Case Report/Series

Case Presentation:

We report the case of 36 year old white Caucasian female who used to work as a driving instructor and living with her parents.

She has a diagnosis of congenital adrenal hyperplasia (21 hydroxylase deficiency) and is on long term corticosteroid replacement (prednisolone 4 mg once daily and fludrocortisone

100 mcg once daily) and she is under the care of an endocrinologist.

She was referred for psychiatric evaluation with “anxiety and depressive symptoms” and failure to respond to antidepressant treatment which was prescribed by her General Practitioner.

During the psychiatric assessment, she reported long history of recurrent episodes of elevated mood and depression dating back to her late teens with clear description of distinct periods of mood elevations lasting for few weeks and longer periods of persistent low mood. There was no history of psychotic symptoms and no family history of mental illness.

She was diagnosed with bipolar affective disorder and failed to achieve remission of symptoms on two different antipsychotic medications (quetiapine and olanzapine) and anticonvulsant medication (sodium valproate) before starting lithium carbonate.

The introduction of lithium and gradual titration resulted in significant improvement in her symptoms and mood stability. However, few months later, she reported relapse in her symptoms (mainly reporting features of bipolar depression) despite adequate lithium levels.

She agreed on the introduction of lamotrigine as an adjunctive medication to lithium. The initial dose of lamotrigine was 25 mg daily for two weeks in line with dose recommendation from manufacturer and drug guides.

On the same day of lamotrigine introduction, the patient started to experience visual hallucinations that she never had before (please see patient’s perspective for detailed description of her hallucinations).

With the dose of lamotrigine increased to 50 mg daily after the initial two weeks, she started to report worsening of these abnormal perceptions which developed into more complex visual and auditory hallucinations.   

More importantly, there was no evidence of accompanying manic symptoms or severe depressive symptoms to explain these symptoms and also no alcohol or drug use.

Following a psychiatric review, the dose of lamotrigine was reduced to 25 mg which resulted in immediate reduction in the intensity of the abnormal perceptions. When the lamotrigine was eventually stopped after one week, there was complete cessation of abnormal perceptions.

Lamotrigine was never re-started again and she was maintained on a combination of lithium and quetiapine with good effect.

Investigation:

We used the Naranjo Adverse Drug Reaction Probability Scale (1) to determine the likelihood of whether an adverse drug reaction is related to this specific drug or may be related to other factors. This tool examine factors such as the temporal association of drug administration and event occurrence, alternative causes for the event, drug levels, dose – response relationships and previous patient experience with the medication.

The probability of the adverse drug reaction is concluded from the total score (Definite if the overall score is 9 or greater, Probable for a score of 5-8, Possible for 1-4 and Doubtful if the score is 0).

Questionnaire

1. Are there previous conclusive reports on this reaction? Yes (+1)

2. Did the adverse events appear after the suspected drug was given? Yes (+2)

3. Did the adverse reaction improve when the drug was discontinued or a specific antagonist was given?

Yes (+1)

4. Did the adverse reaction appear when the drug was re-administered? Do not know or not done (0)

5. Are there alternative causes that could have caused the reaction? No  (+2)

6. Did the reaction reappear when a placebo was given? Do not know or not done (0)

7. Was the drug detected in any body fluid in toxic concentrations?

No (0)

8. Was the reaction more severe when the dose was increased or less severe when the dose was decreased?

Yes (+1)

9. Did the patient have a similar reaction to the same or similar drugs in any previous exposure?

No (0)

10. Was the adverse event confirmed by any objective evidence? Do not know or not done (0)

Scoring 7 (Probable Adverse drug reaction)

Discussion:

Lamotrigine is a phenyltriazine derivative used as an anticonvulsant drug with established mood stabilising properties. In the United Kingdom, it is recommended for use in bipolar affective disorder according to the guidelines from the National Institute of Health and Care Excellence (2) and the British Association for Psychopharmacology (3).

We performed a literature search to find similar case reports. We searched the following databases using the keywords (lamotrigine AND hallucinations): Complementary Medicine (AMED), British Nursing Index BNI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (EMBASE), Health Business Elite (HMIC), Medline, PsycINFO and Health Management Information Consortium (HMIC).

The search returned 57 results. Only 8 articles discussed hallucinations and other psychiatric symptoms as side effects associated with lamotrigine and therefore were included in this review.

Psychotic symptoms have been reported with the use of lamotrigine (both as an anticonvulsant or mood stabiliser) but this reaction is mainly seen in patients with history of epilepsy. One study reported 4.8% incidence of psychiatric and behavioural side effects with lamotrigine in 546 patients with epilepsy. (4)

Another study on paediatric patients showed that reversible visual and auditory hallucinations were reported in one patient among 9 patients with epilepsy who received lamotrigine treatment (mean age 5 years). (5) 

Villari et al published a literature review on psychiatric symptoms related to lamotrigine and included case reports documenting full acute psychotic episodes hallucinations and affective switching in patients with and without history of epilepsy.(6)

They found one case report on hallucination with lamotrigine in bipolar patient without epilepsy. In patients with epilepsy, they reported two cases reports and one case series (total number of patients 9) developing psychotic symptoms following lamotrigine and one randomised controlled trial in which four out of 216 patients stopped lamotrigine due to psychotic symptoms (including hallucinations and delusions).

The authors concluded that majority of the case reports concluded that these symptoms were lamotrigine-induced due to the temporal association with lamotrigine treatment and favourable outcome following drug withdrawal. It also appeared that more case reports were from patients with epilepsy, suggesting lower incidence in patients without this condition.

Chistyakova and Amos (7) reported a case of delirium associated with lamotrigine use. The dose of lamotrigine was increased from 200 to 400 mg over two weeks prior to her admission. The patient reported visual and auditory hallucination with confusion. She took an accidental overdose of her medication (200 mg of fluoxetine and 2800 mg of lamotrigine) due to her confusion and medications were stopped.

The authors concluded that delirium may result from lamotrigine toxicity or drug interaction with fluoxetine.

Uher and Jones in 2006 (8) reported a case of a 42-year-old woman with bipolar affective disorder with comorbid alcohol abuse and no history of  neurological illness.

The patient tolerated an initial dose of lamotrigine 50 mg/day but following a dose increase to 100 mg/day, she reported vivid dream-like experiences and subsequently she reported visual hallucinations. These symptoms subsided over a few days when the dose was decreased to 50 mg/day.

The authors suggested a causal association through this dose dependent effect but also pointed out that the concurrent alcohol abuse may have been a contributing factor.

They also highlighted the paucity of case reports documenting this rare adverse reaction and identified two similar case reports in their references (which we were unable to get their full text) and a third paper reporting hallucination in 2 out of 108 patients with epilepsy on a combination of lamotrigine and sodium valproate (9)

Hallucination with lamotrigine when combined with valproic acid was also reported in a case report by Roberts et al (10) in 14 year old girl with epilepsy when it was added to valproic acid and it was suggested that this adverse effect may be due to an interaction between the two medications causing lamotrigine half-life to triple with valproic acid.

Learning points:

• Lamotrigine is an anticonvulsant with an established role in management of bipolar affective disorder, particularly for the treatment and prevention of depressive episodes.
• However, it appears to be associated with variable incidence of psychiatric symptoms which should be known to the prescriber and patient.

• These adverse effects are mainly seen in patients with history of epilepsy but can occur in patients with mental health problem without epilepsy.
• Different mechanisms for inducing these psychiatric symptoms have been suggested, including idiosyncratic reaction, lamotrigine toxicity as a result of concomitant use of another drug that affect lamotrigine metabolism (e.g., valproic acid) and delirium.

• Examples of these psychiatric symptoms including affective switches in depressed patients with bipolar disorder, hallucinations in depressed patients, delirium and psychotic symptoms (mainly hallucinations and delusions) in patients with or without epilepsy.

• Reversible and severe psychiatric disturbances associated with lamotrigine therapy are rarely reported in literature and more research is needed to identify population at risk.
• Patient education about these rare but frightening side effects is essential to improve medication adherence and better outcome of the management of the mental disorder.

Patient perspective:

“The first hallucination I had was one hour roughly after taking lithium and lamotrigine. It was the Pope which appeared as bright light on my wall. He was wearing a white gown and he had gold jewellery. The picture was so clear and very detailed. I’m not religious and this image would not be something I would think of.

Every day on lamotrigine I had black spots moving quickly around the walls. They were in size of about an inch, 20-30 moving around at one time. Like spiders but without legs. I was really scared at first because I hate spiders. It was very unsettling and I changed my whole bed, away from my wall, and had trouble sleeping.

There was another night when I had similar to the black dots, where instead I had smaller black dots like bees moving into the corner of my room. They were all slightly moving as if they were getting their places. There were hundreds of them.

The scariest incident that happened was hearing voices downstairs. I was so sure that people had broken into the house; I went downstairs armed with razors. I was going to cut DNA from the burglars to give to the police as evidence. When I checked the house, there was no one there.

When I was taking lamotrigine with the lithium, it made me very unsettled, more anxious and mentally unstable. I was so tiered for not sleeping and my decisions irrational. It wasn’t a pleasant place to be for me personally.”

A 44-yr-old patient with history of ileal Crohn’s disease was admitted to our Department because of asthenia, subclinical jaundice, painful hepatomegaly, fluid retention and ascites. In 2008 the patient was diagnosed with bladder cancer and was treated by surgical resection of the cancer and intravesical chemotherapy with mitomicyn C. In 2010 he was given azathioprine (AZA) at 2 mg/kg for Crohn’s disease and 3 months later he developed an increase in serum alkaline phosphatase, gamma-glutamyl transpeptidase and transaminases. He was then started on 1.5 mg/kg 6-mercaptopurine (6-MP) once daily. After 9 months he stopped 6-MP because of nausea, vomiting and abnormal liver function tests; 6-MP was therefore discontinued until the normalisation of markers of liver function. Two months later, when the transaminases were within the normal range, he received 6-thioguanine (6-TG) 25 mg a day, that was progressively increased to 80 mg a day. Three months later, the patient was referred to our Department with painful hepatomegaly, ascites and asthenia. Laboratory tests on admission revealed an elevation in AST 198 U/l and ALT 209 U/l. Total bilirubin was 3 mg/dl (direct bilirubin 1.5 mg/dl), LDH 784 U/l, alkaline phosphatase 191 U/l and ammonia 112 umol/l. Virological markers (HBsAg, HBcAb, anti HCV, HBV DNA) were negative. Patient was apyrexial, showed normal blood pressure (130/80 mmHg), tachycardia (110 bpm) and 97% SaO2 on room air. Physical examination revealed right hypochondrial tenderness, abdominal distension and shifting dullness, suggesting the presence of ascites. The rest of the physical examination was unremarkable. An echo-Doppler evaluation revealed thin linear suprahepatic veins and confirmed the presence of ascites. A CT scan of the abdomen showed hepatomegaly with dishomogeneous enhancement after dye injection (mosaic pattern). There was no evidence of any venous thrombosis or splenomegaly (Figure 1A); 6-TG was withdrawn empirically and the patient was started on therapy with albumin 25 g/day and spironolactone 200 mg/day. The average serum Na+ level during diuretic treatment was 134 mEq/l. An abdominal paracentesis of two litres was necessary, due to the progressive increase of ascites.

FIGURE 1A. CT scan of the abdomen on admission: Dishomogeneous enhancement of the liver after dye injection (mosaic pattern) (arrow). Suprahepatic veins are not detectable.

FIGURE 1B. Histological pattern of the liver biopsy specimen: marked centrilobular congestion (arrows) with hepatocyte dropout. There is no evidence of centrolobular veins thrombosis.

A routine laboratory investigation of ascitic fluid showed < 500 leukocytes/µL and < 250 polymorphonuclear leukocytes (PMNs)/µL. The ascitic fluid total protein level was 2.1 g/dl and serum-ascites albumin gradient (SAAG) was > 1.1 g/dL. No neoplastic cells were found. A transjugular liver biopsy was then performed, showing marked centrilobular hemorrhage with hepatocyte necrosis. There was mild ductular reaction, with no evidence of centrilobular vein thrombosis. The histologic diagnosis confirmed veno-occlusive disease (VOD) (Figure 1B). Screening for thrombophilia was also done, showing low levels of serum protein C and protein S. There was no mutation of JAK-2 V617F. The patient was then treated with a hyposodic diet, mild hydric restriction, enoxaparin,spironolactone, lactulose and omeprazole. He was discharged two weeks later, and after 3 months a complete regression of ascites and hepatomegaly occurred, and echography of the liver was unremarkable (Figure 2A and 2B).

FIGURE 2A. Echography of the liver at follow up. No evidence of ascites.

FIGURE 2B. Echography of the liver at follow up. No evidence of ascites. Suprahepatic veins are detectable (arrow)

Discussion

Although VOD was known among complications of 6-TG in childhood, this case-report emphasises the occurrence of VOD in adults with Crohn’s disease, as first described by Kane et al. in 2004¹. The thiopurine drugs were developed more than 50 years ago, and 6-MP was first used as a drug in 1952². Since then, 6-MP and 6-TG have been widely used to treat acute lymphoblastic leukemia in children. VOD mimicking Budd-Chiari like disease was then described as a frequent complication of 6-TG in pediatric patients given the drug for lymphoblastic leukaemia. Later on, in 1976, Griner et al. described the cases of two adult male patients with acute leukaemia developing a fatal Budd-Chiari-like disease while receiving 6-TG³. Since patients were given 6-TG plus cytosine arabinoside, authors were unable to ascribe this complication solely to 6-TG³. VOD exclusively related to 6-TG was first described by Gill et al., who observed a clinically reversible liver VOD developing in a young man with acute lymphocytic leukemia after 10 month administration of 6-TG⁴. Furthermore, sinusoidal obstruction was also reported in a patient with psoriasis treated with 6-TG and other cytotoxic therapy⁵. In 2006, a European 6-TG Working Party established that 6-TG should be considered a rescue drug in stringently defined indications in inflammatory bowel diseases (IBD). The indication for administration of 6-TG should only include its use for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Moreover, 6-TG must be withdrawn in case of overt or histologically proven hepatotoxicity⁶. Although Ansari et al ⁷ found no nodular regenerative hyperplasia (NRH) in the liver of patients given 6-TG, Dubinsky et al.⁸ described NHR as a common finding in 6-TG-treated patients with inflammatory bowel disease in the absence of VOD. By contrast, in our case report we showed histological pattern of VOD and, in accord with Gisbert et al.⁹, would suggest that 6-TG should not be administered out of a clinical trial setting. Given that the proportion of patients with Crohn’s disease achieving an improvement of symptoms during 6-TG treatment is similar to that after methotrexate¹⁰ or infliximab⁶, these drugs should therefore be considered as second line therapy in patients intolerant or resistant to azathioprine and 6-mercaptopurine.

Introduction

Metastatic carcinoma to the sinonasal tract is rare. We describe a patient with an aggressive follicular variant of papillary thyroid carcinoma who presented with an unusual metastasis to sphenoid sinus.

Case report

A 44 year old Hispanic woman presented at Queens Hospital Center in June 1988 with airway obstruction and was found to have a 10x12 cm firm mass in the left thyroid lobe, and palpable left supraclavicular node. She had no prior history of radiation, and no family of thyroid cancer. She underwent a total thyroidectomy with a modified radical neck dissection. Pathology revealed a follicular variant of papillary thyroid carcinoma: non-tall cell variant. Six of fifty (6/50) lymph nodes were positive. Post-surgery, patient received Iodine-131 ablation therapy (93 mCi) and was placed on thyroid hormone suppressive therapy. Non-stimulated thyrogen total body scan a week after therapy was negative. Thyrogen was not available at that time.

The patient was non-compliant with thyroxine and thyroid stimulating hormone (TSH) was often elevated (13-80 mlU/ml). However, the serum thyroglobulin remained less than 5.0 ng/ml and antithyroglobulin antibody was negative. A repeat total body scan (with 5 mCi I131) 6 months later and 4 years later with thyroxin withdrawal (TSH 36 mIU/ml and 48 mIU/ml respectively) was negative, and patient was continued on thyroxine suppression therapy.

Five years after initial presentation, the patient developed urinary retention and lower extremity weakness. A myelogram revealed block at T1-T2. Patient underwent laminectomy. Pathology revealed metastatic follicular variant of papillary thyroid carcinoma. Since iodine containing contrast was used during the myelogram, I131 iodine therapy was not given. External radiation of 2000 CGY to C7-T5 was administered.

A total body scan 8 weeks post laminectomy (when 24 hour urine iodine < 100 microgram/litre, and TSH was 38 mIU/ml after thyroid hormone withdrawal) was negative, the thyroglobulin level was 5 ng/ml and negative antithyroglobulin antibody (at that period of time, positron emission tomography (PET) scan was not an available option). For the next 2 years of follow up, the patient was maintained on thyroxin suppression therapy, this time with good compliance (TSH 0.1 mIU/ml, thyroglobulin less than 5 ng/ml and negative antithyroglobulin antibody). She did not show up for follow up lumbar computerised tomography (CT).

Seven years after the initial presentation, she complained of headache and double vision, and a three month history of amenorrhea. The thyroglobulin at this time was elevated (20 ng/ml). Chest X-ray was positive for two nodules in the right lung. Magnetic resonance imaging (MRI) revealed a soft tissue mass in the sphenoid sinus, eroding the basi-sphenoid and extending into the nasopharynx (Fig. 1 ABCD). The mass also eroded the sella floor displacing the pituitary gland upwards (arrows). Bone scan revealed focal abnormalities in the upper thoracic spine, ethmoid bones and base of the skull. At that period of time, PET scan was not an available option. Pituitary function testing revealed TSH 0.1 mIU/ml, free T4 level 1.2 mIU/ml.  AM cortisol 5.3 mcg/dl, prolactin 182 ng/ml, ACTH 12 pg/ml, FSH 11.5 mIU/ml, LH 4.0 mIU/ml, and Estradiol 20 pg/ml.

Figure 1: A-T1 weighted midline sagittal MRI scan without contrast. B-T1 weighted midline sagittal MRI scan with contrast. C-T2 weighted axial MRI scan through the lesion. D-Axial CT scans without (on the left) and with (on the right) contrast. Note: The large destructive and enhancing lesion (*) in the sphenoid sinus associated with destruction of the basisphenoid, clivus and sellar floor. Note the normal pituitary gland (arrow) is displaced upwards out the sellaturcica.

Biopsy of the sphenoid sinus mass confirmed that it was metastatic papillary thyroid cancer, follicular variant. The tumour cell nuclear DNA was diploid and P53 and K167 were negative (Impat, NY). The patient was placed on hydrocortisone replacement and continued on thyroxine suppression therapy. Three months later the patient suffered a cardiorespiratory arrest and expired.

Discussion

Metastasis to the sphenoid sinus is rare from any tumour, and from papillary thyroid cancer it is extremely rare. An extensive world literature review revealed only 4 cases of spread to sphenoid sinus region from papillary thyroid cancer_.^1-4

Renal cell carcinoma is the most common tumour of paranasal sinus metastasis, 41.8%. The average age is 58 years, with slight predominance of males. The most common presentation was epistaxis, 31%. The most common causes of sphenoid metastasis are gastrointestinal and renal tumours⁵_.

Von Eiselsberg et  al. in 1893 described one case of metastasising thyroid carcinoma to sphenoid sinus.⁶ Harmer et al., 1899, reported a case of medullary thyroid carcinoma metastasis to sphenoid/ ethmoid sinus and nose. ⁷ Barrs et al. in 1979 reported a case of metastasis of follicular thyroid carcinoma to sphenoid sinus and sphenoid bone.⁸ Chang et al. in 1983 described a case of metastatic carcinoma of the thyroid to the sphenoid sinus.⁹ Renners et al. in 1992 reported one case of metastasis of follicular thyroid carcinoma to the paranasal sinuses, including the sphenoid sinus. ¹⁰Yamasoba et al. in 1994 reported a case with follicular thyroid carcinoma metastasising to sinonasal tract which also included sphenoid sinus.¹¹ In the same year, Cumberworth et al. reported a case of metastasis of a thyroid follicular carcinoma to the sinonasal cavity which head CT showed sphenoid, ethmoid, frontal and maxillary sinuses. ¹²In 1997, Altman et al. described a case of follicular metastatic thyroid carcinoma to paranasal sinuses which included the sphenoid sinus. ¹³ The reported cases of thyroid cancer metastasis to sphenoid sinus are in table 1. Four cases were papillary thyroid carcinoma (included follicular variant of papillary thyroid carcinoma), six cases were follicular thyroid carcinoma, 1 case was medullary thyroid carcinoma and 1 case was unspecified thyroid carcinoma. 

Table 1: Cases of thyroid metastases to the sphenoid sinus

Pathologic lesions involving the sphenoid sinus include inflammatory disease, mucocele, chordoma, nasopharyngeal carcinoma, plasmacytoma, primary sphenoid sinus carcinoma, adenocystic carcinoma, pituitary adenoma, and giant cell granuloma. Benign disease often presents with a more gradual obstruction and disturbance of vision. This contrasts with the acute and progressive disturbances of vision in all cases reported with malignant lesions of the sphenoid sinus.¹⁴

Our patient presented with complaints of double vision for 6 months and headache. After imaging with MRI and given her previous history of metastatic thyroid cancer, the most likely diagnosis was metastases to the sphenoid sinus from the thyroid cancer, which was confirmed by tissue biopsy. Since this patient had evidence of bone metastasis, it is likely that the tumour first metastasised to the bone and then ruptured into the sphenoid sinus. The tumour appears to have eroded the sellar floor, extending into and displacing the pituitary gland, causing secondary hypoadrenalism.

In our patient, low thyroglobulin proved to be an unreliable marker because it was low when the patient had metastasis of the tumour in the spine. These tumours are more aggressive and today, PET scanning has proved more reliable in following them, a modality that was not available at the time for our patient. The possible explanations for negative total body scans in patients with metastatic differentiated thyroid cancer are a) technical limitations of the scan in detecting the tumour cells, and b) failure of the tumour tissue to trap iodine.

There are several unusual aspects in this patient’s presentation. Firstly, the initial presentation was unusual, since this tumour was very aggressive with rare sites of distant metastases. Perhaps the long periods of hypothyroidism when patient was noncompliant promoted the aggressive nature of this tumour. Secondly, the failure of known tumour markers, i.e. serum thyroglobulin and total body scan to identify these metastases. Thirdly, our patient’s tumour cell nuclear DNA was diploid. Investigations have shown that the DNA ploidy pattern as determined by flow cytometry is an important and independent prognostic variable.^15-17 Fortunately, aggressive follicular variant papillary cancer of thyroid (non-tall cell type) is very uncommon.

Generally, total body scan negative with low stimulated thyroglobulin is an excellent prognostic sign. Our patient demonstrates that we need to remain vigilant for the unusual tumour especially when the initial presentation showed so much bulky disease. The need for additional tumour markers will help to identify aggressive well differentiated thyroid carcinoma cases.

Acknowledgement

Appreciation is extended to Ms. Deborah Goss and Mr. Timothy O’Mara, librarians, in helping with literature search and preparing the manuscript. No other financial sources or funding involved in the formation of manuscript. No potential financial conflicts of interest. 

Introduction

Diabetic patients with peripheral neuropathy are predisposed to foot injury. In Asian countries, a common culture among patients with peripheral neuropathy is to immerse their feet in hot water baths, with a belief that it will “improve circulation” and hence “cure the numbness”. We hereby report three cases of severe burn injuries of the feet presented to our hospital over a span of six months due to the above belief.

Case Report

The first patient was a 53-year old Malay gentleman with poorly controlled diabetes mellitus for six years, complicated with peripheral neuropathy, diabetic nephropathy and right eye cataract (latest HbA1C 8.1%), treated with oral anti-diabetic agents. He had a habit of using hot footbaths for numbness of both feet. Two weeks prior to presentation, due to increased feeling of numbness, he immersed his right foot into a self-prepared tub of hot water with added salt, followed by application of traditional sea cucumber gel. That evening, he noticed blistering of his right foot. Despite advice for admission, he chose to do the dressing as an outpatient in a local clinic. He presented two weeks later due to a worsening wound. At presentation, 4% full thickness burn of his right foot was noted, complicated by secondary infection (Figure 1). He underwent wound debridement, and subsequent split skin grafting. He had a prolonged hospitalization of five weeks due to secondary pseudomonas wound infection requiring parenteral antibiotics.

Figure 1. Right lower limb upon presentation to our hospital

The second patient was a 26-year old Indian gentleman with type I diabetes mellitus for nine years, complicated with diabetic nephropathy and peripheral neuropathy. His wife usually prepared hot water footbaths for him to improve his feet circulation. He developed 5% full thickness burn when he immersed his right foot into a pail of boiling water, not knowing that his wife had not added cold water into the footbath. He presented himself after two days and was hospitalized for two weeks. He recovered after wound debridement and split skin grafting.

The third patient was a 17-year old Chinese lady with poorly controlled type I diabetes mellitus for eight years, complicated with diabetic nephropathy (latest HbA1C 10.0%). She used hot water steam therapy with an aim to cure her recent onset of left foot drop, but was unaware of the temperature of the water. She developed blisters on her left foot, but only presented herself two weeks later when she developed left foot gas gangrene.  She had a prolonged hospital stay of eight weeks with recurrent hospital acquired infections, including Methicillin-resistant Staphylcoccus aureus (MRSA). Despite multiple wound debridement, she required amputation of her left fifth toe (Figure 2).

Figure 2. Left lower limb post Ray amputation

Discussion

Peripheral neuropathy is a known complication of diabetes mellitus. More than 50% of patients who are over 60 years old have this complication.^{1, 2} Thermal injury to the feet in patients with neuropathy has been reported after walking barefoot on hot surfaces³ and after application of hot water bottles or heating pads during winter months.^{4, 5} The use of thermal footbath as a cause of burn injury is mostly due to patient-misuse or ignorance of correct usage.^{6, 7} In contrast, in Asian countries, a common culture among patients with peripheral neuropathy is to immerse their feet in self-prepared hot water without checking the water temperature,⁸ with a belief that it will “improve circulation” and hence “cure the numbness”. This practice has led to accidental burn injuries as described in our case reports.

There are a few reasons why patients with diabetic peripheral neuropathy end up with such a severe complication after the use of thermal footbath. Firstly, the temperature of the thermal bath may be underestimated. The time to develop full thickness burn reduces exponentially with just minimal increments in water temperature.⁹ Secondly, lack of pain despite the burn can prolong exposure to the heat source. In addition, concomitant peripheral vascular disease and endothelial function can limit vasodilatation to conduct heat away hence further aggravate the thermal insult.

Another important contributing factor of complicated wounds are the delays in seeking treatment as the result of lack of pain despite the burn injury. In a study done by Memmel et al on 1794 patients (of which 130 were diabetics) who presented with burn injuries, the majority of non-diabetic burn patients (63%) presented within 48 hours of injury, but only 40% of diabetic patients sought treatment within that time frame. Significantly more patients with diabetes presented after two weeks compared to those without diabetes. As burn injuries are highly susceptible to secondary infection, any delay in presentation further complicates and prolongs hospital stay.^10,11 Not surprisingly, our two patients who presented two weeks after their burn injury had a prolonged and complicated hospital course compared to our second patient who presented soon after the burn injury. Increased susceptibility to infection and delayed wound healing from poor circulation contribute to prolonged recovery and poorer clinical outcomes in patients with diabetes mellitus, with some needing amputation as noted in our third patient.

As a healthcare provider we play a role in preventing this misfortune. Routine screening for the presence of peripheral neuropathy and vascular disease should be done during clinic visits to identify high-risk patients. Specific education regarding avoidance of thermal footbath and consequences of this highly preventable injury should be incorporated into standard diabetic foot care education. If patients choose to immerse their feet in hot water, temperature of the water should always be measured with a thermometer and immersion time should be limited. If a wound develops, they should present early to hospital for immediate treatment.

Conclusion

Thermal footbath for therapeutic purposes is commonly practiced in Asian culture. Our case reports highlight the serious consequences of this practice in diabetic patients with peripheral neuropathy. More public awareness and patient education is needed to prevent these injuries and to avoid the high cost of prolonged hospital stay and losses to the patient.

Introduction:

We report a case of worsening psychiatric symptoms in a patient who was serendipitously diagnosed with Primary Hyperparathyroidism.

Behavioural change in form of aggression sometimes occurs as a component of psychiatric disorders such as psychosis, attention deficit hyperactivity disorder, autistic spectrum condition, conduct disorder and various mood disorders. It may also present as a psychiatric manifestation of an endocrine disorder such as Primary Hyperparathyroidism (PHPT)^1,2.

PHPT is rare in children and adolescents with an incidence of 2-5 in 100000 ³. It is characterized by hypercalcaemia and elevation of parathyroid hormone. Children with PHPT may present with non-specific complaints such as behavioural change and deteriorating school performance.

Patients who present with non-renal symptoms have a longer duration of symptoms prior to diagnosis of PHPT^4,6. It seems probable that it takes much longer for diagnosis to be made in those with pre-existing mental disorder. When left undiagnosed and untreated, PHPT can be a serious disease with significant morbidity.

The finding of elevated serum calcium levels in young people is often fortuitous as they often present with non-specific symptoms^3,4. A significant number of hyperparathyroidism cases with neuropsychiatric manifestation have been reported in patients without recorded pre-existing psychiatric diagnosis ^3-6.

This case report highlights the need for clinicians to always consider endocrine disorder as a differential diagnosis when treating patients with psychiatric symptoms which are poorly responsive to standard treatment. It also demonstrates the relevance of an integrated approach in healthcare delivery including the importance of good communication between primary and tertiary care clinicians.

Case Report:

A 15yr old Caucasian male known to Child & Adolescent Mental Health Service (CAMHS) for management of his behavioural problems presented in crisis as a consequence of physical aggression, suicidal ideation and homicidal thoughts.

His first contact with CAMHS had been at the age of 10 when he was referred for management of his frequent aggressive outbursts. He had always been boisterous but had no previous history of significant emotional or behavioural difficulties. His developmental history was unremarkable and there were no features indicative of any neurodevelopmental disorder. There was no family history of mental illness.

His biological parents were involved in an acrimonious divorce at the time of his first referral to CAMHS so it was felt that this conflict may have contributed to his presentation.

He was referred a Child Psychotherapist for weekly sessions as the initial assessment suggested significant weakness in his attachment and identification which manifested in the instability and immaturity of mood and behaviour.

The family described minimal improvements in his capacity for self-control having had three years of psychotherapy. His behaviour remained challenging but manageable within the community until six months prior to him being re-referred by his General Practitioner (GP) for urgent psychiatric assessment.

Following parental divorce, his mum remarried but her new marriage was also turbulent and the couple had to separate. During this period of increased psychosocial stresses within his family, the patient’s behaviour escalated to a point that he was regarded as a significant risk to himself and others. It was thought that the separation between his mother and step-father might have triggered this deterioration.

The night before his urgent referral to CAMHS, he set a trap for his mother; he had put a rope around some curtains on the floor and was planning to throw another curtain over her. He also had a knife and hockey stick with him at the time. As his mother stepped into the room, he put the curtain over her head and attempted to hit her with the hockey stick. He was promptly restrained by his father, who had come to visit, before he could do much damage.

He presented as unpredictable and aggressive but would often deny recollection of any reported outbursts. He was very upset when incidents were talked about as he believed he had no control whatsoever over this behaviour – it was clear how upsetting his behaviour was to him.

He displayed uncontrollable rage on many occasions. It was usually directed at his mother and home furniture, and might last up to two hours. He appeared to seek immediate gratification and was clearly hypersensitive to his setting with a significant degree of paranoia and irritability.

He repeatedly stated that he had thoughts of wanting to kill his mother and himself especially when angry. He did not appear able to accept any responsibility for his actions, blaming his temper outbursts on his older sibling. We heard she was extremely frightened of him; he had on two occasions broken down her door.

When he came out of these rages he would become very tearful and profoundly apologetic. These difficulties had been noticed at school where his grades had been falling. He told teachers he felt suicidal and would sometimes go into the school toilet to cry especially when he thought about his inability to control himself.

Physical examination at this point was unremarkable. The Community Psychiatrist commenced him on Fluoxetine and referred him to an in-patient psychiatric unit for further psychiatric evaluation including a forensic assessment.

He was diagnosed with Asperger’s Syndrome and Attention Deficit Hyperactivity Disorder in the inpatient unit and was prescribed risperidone and methylphenidate. His GP was asked to arrange a baseline blood test, consisting of full blood count (FBC), liver function test (LFT), urea & electrolytes (U&E) and thyroid function test (TFT). There was no request for blood glucose level or serum calcium.

The GP asked for a serum calcium level estimate purely out of ‘habit’. The laboratory result showed a high level of calcium 3.89mmol/L (normal range 2.2-2.6). Based on this significantly elevated serum calcium level, a referral was sent to the Paediatric Endocrinologist.

At the Endocrinology Clinic, he described a twelve month history of generalised aches and pains in association with emotional lability. A history of fracture of his right wrist and left hallux occurring within 18 months prior to presentation was also obtained. The X-ray report showed presence of a radiolucent area in his right femur. An assay of his parathyroid hormone, Sestamibi scan and ultrasound scan of his neck were done.

The elevated parathyroid hormone level, increased serum calcium, history of fractures and X-ray features indicated the diagnosis of Primary Hyperparathyroidism. The endocrinologist was of the opinion that his PHPT has been present for a number of years. He was referred for parathyroidectomy.

His serum calcium level dropped to 2.47mmol/L two days post surgery. As calcium level normalised, his symptoms improved remarkably and his psychotropic medications were discontinued. Since then, he has successfully commenced college full time and has succeeded in obtaining good grades in his chosen courses.

Discussion:

Psychiatric symptoms cause significant impairment in children and adolescents. Having additional symptoms of hyperparathyroidism would exacerbate the psychiatric symptoms and increase the degree of impairment. This patient presented with neuropsychiatric symptoms and evidence of end organ damage which is similar to those in published reports^3,4.

Research shows that diagnosis of primary hyperparathyroidism is often delayed in young people but we suspect that it may even be more delayed in those with a pre-existing psychiatric disorder as the symptoms may be more likely to be attributable to the psychiatric condition.

It is possible that the behavioural problems in this patient may have co-existed independently of each other, but the rapid resolution of the psychiatric symptoms suggests that they may have been exacerbated by hyperparathyroidism.

Our findings in this case are similar to those reported by Spivak and colleagues’ which showed that early diagnosis of hypercalcaemia can prevent unnecessary and potentially harmful treatment with psychotropic medications⁷.

Psychiatric diagnoses are usually formed from identification of collective symptoms some of which may occur in other medical conditions. Adopting a multidisciplinary team approach is most helpful in the management of complex psychiatric cases. This approach may encourage clinicians to take a holistic view in management of children.

It is important for clinicians to be familiar with common psychiatric symptoms and medical conditions that may mimic or cause them because the presence of non-specific symptoms in PHPT poses a significant emotional burden for affected children and their families. It is a potentially treatable condition which if not diagnosed early could lead to impaired psychosocial well-being and damage of vital organs. Parathyroidectomy has been shown to improve general health, quality of life and cognitive functioning in patients with PHPT⁸.

The outcome for this particular young person could have included further episodes of in-patient hospitalisation or involvement with the juvenile justice system as a consequence of further violent episodes. The achievement of adolescent milestones and his education could have been severely disrupted and may have resulted in labelling detrimental to his future.

In the current economic climate and because of the rarity of Primary Hyperparathyroidism, we do not advocate routine serum calcium estimation in all behavioural problems but clinicians should have lower threshold for screening for this condition especially in patients with worsening symptoms despite conventional treatment.

In conclusion, Primary Hyperparathyroidism should be considered in the differential diagnosis in young people with worsening neuropsychiatric symptoms which are unresponsive to standard psychiatric treatment.

Introduction

Patients who present to physicians with altered mental health and behaviour may prematurely be diagnosed to have psychiatric illness. Psychiatric manifestations commonly accompany acute medical illnesses. As a rule of thumb, organic causes need to be ruled out before making a psychiatric diagnosis. A delay in arriving at a diagnosis could lead to prolonged psychiatric symptoms and unnecessary use of psychotropic medications. Prognosis and recovery will vary depending on the type of accompanying medical illness.  Below, two cases are presented which varied significantly in terms of the sequelae.

Case 1

A female patient in her late 20’s was referred from primary care as she reported a sudden onset of “hearing voices”. The patient disclosed that she was bullied at work 6 months prior to this episode which resulted in change of job role and bullying has been dealt with. She described that the voices were talking about world politics and wanted her join MI5. She also believed that there were evil scientists who could read her mind through telepathy and felt that there were cameras and bugs planted in her house by a plumber. She became suspicious that her neighbours were spying on her. Her sleep was disturbed and she heard a ‘tick-tock ‘sound. This led to her checking pipes and walls to find the origin of the sounds.  She believed that people were throwing things on to her bed and became very distressed - to the extent that the police were called on many occasions. She believed that people had been using telepathy on her and that aliens were invading the world. She was so distressed that she attempted to end her life by drinking bleach on one occasion and  trying to cut her wrist on another.

There is no previous history of mental illness and no mental illness in the family.

Her medical history revealed that she had had mastoid surgery four years ago. Three weeks prior to the psychotic episode noted above, she had an ear infection with discharge from her ear. She presented to the general practitioner with psychotic symptoms at the same time. A CT scan of the brain was normal. A 2 week course of antibiotics in the form of Co-amoxiclav was given by the general practitioner. Her psychiatric manifestation resolved completely on follow up at two months without any psychotropics or Benzodiazepines, The patient was then kept under ‘wait and watch’ for six months in order to monitor any re-emergence  of psychotic symptoms. She did not report any further episodes of ear infections during this period of follow up. Her diagnosis was Diseases of middle ear and mastoid (H65-H75).

Case 2

A 31 year old lady was referred to secondary mental health services from a Neurology team, presenting with psychotic symptoms following a viral encephalitis infection. A diagnosis of Herpes Simplex viral (HSV) encephalitis was confirmed by lumbar puncture and a CT scan by the Neurology team. She had made a gradual recovery from the encephalitis over a period of one month. She developed psychotic symptoms 2 weeks later, where she believed that doctors were trying to kill her and that she had been raped, with no evidence that this had occurred at any time. Her distress worsened which led to her informal admission to an inpatient mental health unit. A close assessment on the ward showed her to display an intermittent picture of worsening gait. A neuropsychiatry assessment confirmed that this lady had acquired brain injury following Herpes encephalitis. Single photon emission computed tomography (SPECT) showed extensive brain injury consistent with HSV. This lady presented with several acute episodes of psychosis where she complained of hearing voices and believed that people were trying to harm her. Her mood was labile and variably responsive to Olanzapine initially with a control of her psychotic symptoms as well as mood behaviour. She was diagnosed as suffering from Organic Delusional (Schizophrenia-like) Disorder (ICD 10 F06.2), with a picture of Paranoid Schizophrenia secondary to viral encephalitis. A maternal aunt was said to have suffered from Schizophrenia. Later on she had frequent relapses of psychosis and Quetiapine was initiated. As her symptoms did not respond to two different anti-psychotics, she was started on Clozapine which gave her reasonable stability. However, she still needs support while walking andhas been transferred to a suitable neuropsychiatric rehabilitation placement to maximise her independence and manage her ongoing needs.

Discussion

 The two cases above display infective neurological diseases characterised by psychiatric presentations and greatly differing prognosis. The first case was an example of a chronic recurrent ear infection which was likely to have involved inner ear, mastoid or temporal lobe but has subsided without any long term sequelae. This was promptly treated with antibiotics at an early stage with complete recovery and there was no evidence of brain injury on imaging. The psychiatric manifestation was dramatically acute in this case and this could be partly attributable to stress at work. In particular there was neither previous history of mental illness nor a family history of psychiatric disorders.

In the second case, there was evidence of significant brain injury resulting in both physical and psychiatric sequelae following herpes encephalitis. Furthermore, this patient has a family history of schizophrenia which might have influenced the manifestation of the Mental Disorder.

There is significant evidence to suggest that childhood neurological viral infections increase the risk of psychotic illness ¹. In both cases there was no suggestion of such illness in the childhood history. A recent study investigated whether HSV1 exposure was associated with structural brain abnormalities in individuals who, because of genetic or other factors, were deemed at high risk of developing psychosis. The results suggested that a history of HSV1 infection is associated with volumetric gray matter reductions in individuals at high risk for developing psychosis ². In our second case, SPECT imaging confirmed grey matter loss and with the strong genetic risk would have led to the psychiatric illness.  

The relationship between bacterial infections and psychotic illness in less well understood. Schizophrenic illnesses are often multifactorial in origin following a complex interplay between genetic and environmental factors such as infections. While there are various reports of Neurosyphilis, Mycoplasma Pneumoniae and Cryptococcal meningitis causing psychotic illness, specific bacteria could not be isolated in the first case presented ^3-7. The improvement with antibiotics simply suggests that this could be a bacterial infection.

In summary, these cases clearly show the importance of identifying and treating medical illness presenting with psychiatric symptoms at the earliest to prevent long term complications. 

Case Report

A 34 week preterm, small for gestational age, third born male neonate to a non consanguinous married couple with father having short extremities was admitted in our NICU prematurely with respiratory distress.

On examination the baby was tachypneic with grunt and lower chest indrawing. The baby  was also found to have a narrow thorax, short fingers with postaxial polydactyly in both upper limbs and right lower limb, with syndactyly in right upper and lower limb (figures 1,2,3). The cardiovascular, respiratory, abdominal and neurological examination were unremarkable with no facial dysmorphism. The fundus examination was inconclusive.

The antenatal scan showed all long bones short in configuration. The liver function tests were normal except for mild elevation of alkaline phosphatase. The Ultrasound abdomen showed hepatomegaly and no evidence of any other mass lesions. The urine examination was negative for proteinuria and haematuria. The chest x ray showed short ribs, high position of clavicle and features of hyaline membrane disease (Figure 4).

The baby was put on continuous positive airway pressure and given surfactant through an endotracheal tube twice for two consecutive days, but as the condition deteriorated, with hypercarbia and hypoxia as evident on arterial blood gases, the baby was electively ventilated with minimal settings. The baby improved and hence was extubated. After a few hours of being extubation the baby gradually developed respiratory distress and started to deteriorate. Hence the baby was reintubated. The condition of baby was explained to attenders and as the attenders were not willing to continue the treatment, the baby was discharged from hospital against medical advice and later we were informed that the baby expired within few hours after discharge from the hospital.

Fig 1 : showing long narrow thorax and short upper extremities

Fig 2 : showing postaxial polydactyly with syndactyly in upper extremity

Fig 3 : showing polydactyly with syndactyly in lower extremity

Fig 4 : chest xray showing long narrow thorax  and short and horizontally oriented ribs with irregular costochondral junctions and bulbous and irregular anterior ends

Discussion

Jeune syndrome or asphyxiating thoracic dystrophy is a rare autosomal recessive skeletal dysplasia characterised by a small chest and short ribs which restrict the growth and expansion of the lungs¹. The inheritance is autosomal recessive and a locus has been identified on chromosome 15q13 ². Other symptoms may include shortened bones in the arms and legs, unusually shaped pelvic bones, and extra fingers and/or toes (polydactyly)³ . It is estimated to occur in 1 per 1,00,000 -1,30,000 (again is this 130,000?) live births^4.. The diagnosis is based on clinical and radiological findings. Our patient fulfills the diagnostic criteria for Jeune syndrome. The most consistent and characteristic findings were the abnormalities of the thoraxand limbs. Jeune syndrome was first described in 1955 by Jeune in two siblings with severely narrow thorax⁵. It is known to be genetically heterogeneous.

Several complications of asphyxiating thoracic dystrophy have been described in the literature. The respiratory problems are the main concern. A large percentage of the children with asphyxiating thoracic dystrophy die as a result of these problems. Percentages up to 80% have been mentioned in literature^6,7. In our case the baby experienced respiratory distress on day one of life needing ventilator support. The thoracic malformation tends to become less pronounced with age⁸. A possible explanation could be the improved mechanical properties of the chest wall with growth.

Clinically, Jeune syndrome is characterized by a small, narrow chest and variable limb shortness. Associated congenital abnormalities can be postaxial polydactyly of both hands and/or feet (20%). Typical radiographic findings include a narrow, bell-shaped thorax with short, horizontally oriented ribs and irregular costochondral junctions, elevated clavicles, short iliac bones with a typical trident appearance of the acetabula, relatively short and wide long bones of the extremities, and hypoplastic phalanges of both hands and feet with cone-shaped epiphyses⁹. The reported case has long narrow chest, short and horizontally oriented ribs with irregular costochondral junctions and bulbous and irregular anterior ends with post axial polydactyly in both upper extremities and right lower limb with left lower limb being normal.

Jeune syndrome is sometimes compatible with life, although respiratory failure and infections are often fatal during infancy. The severity of thoracic constriction widely varies. For those patients who survive infancy, the thorax tends to revert to normal with improving respiratory function. This suggests that the lungs have a normal growth potential and the respiratory problems are secondary to restricted rib cage deformity ¹⁰.

Trigeminal Neuralgia (TN) is relatively rare in Multiple Sclerosis (MS) affecting approximately 2% of patients¹. The severity of the pain is indistinguishable whether TN is an isolated impairment or is associated with MS. However, when associated with MS, TN is often bilateral, affecting younger patients and is more refractory to medical treatment ². 

Several pharmacological agents are reported to be effective in TN associated with MS. Topiramate^3,4, gabapentin⁵ and lamotrigine⁶ were all reported to benefit patients with TN associated with MS in small uncontrolled trials. Several other drugs such as phenytoin, misoprostol and amitriptyline are routinely tried in patients with TN despite the lack of convincing evidence of their efficacy⁷.

In 2008, Both the American Academy of Neurology and the European Federation of Neurological Societies launched joint Task Force general guidelines for the management of TN. After systematic review of the literature the Task Force came to a series of evidence-based recommendations ⁸. Carbamazepine and oxcarbazepine had the strongest evidence of efficacy and were recommended as the first line treatment. An earlier Cochrane systematic review reached the same conclusion. ⁹.

Case report

A 62 year old female patient had been suffering from MS for about 20 years. The MS presented with trigeminal neuralgia from the outset and this was then followed by pyramidal lower limbs’ weakness and sphincteric dysfunction. The patient started to use a wheelchair 10 years ago but she became totally wheelchair dependent about 6 years later.

Trigeminal neuralgia remained active throughout the 20 years. Carbamazepine (300 mg daily) provided the patient with a satisfactory control of TN. Despite having occasional break through TN pain; the patient declined having higher doses of carbamazepine as excessive sedation was an unacceptable side effect.

Recently; the patient was admitted to hospital in two separate occasions complaining of increasing malaise and confusion. Plasma sodium levels were found to be low in both occasions (first presentation 118 mmol/l and second admission 114 mmol/l). Clinical evaluation confirmed Syndrome of Anti Diuretic Hormone Secretion (SIADH) as the cause of the hyponatremia and in the absence of any other explanation for the SIADH; carbamazepine was thought to be the main reason and was duly discontinued.

Unfortunately, TN attacks came back with vengeance. During the following 6 months, therapeutic trials using gabapentine, topiramate and amitriptyline failed to show any beneficial effect on either the severity or the frequency of the TN attacks. All three drugs were duly discontinued.

The patient was started on eslicrbazepine 400 mg on a single daily dose. This dose lead to almost complete eradication of the TN attacks. The control of TN and the plasma sodium levels remained stable a year following the initiation of the therapy.

Comments

Hyponatremia, defined as a sodium level < 135 mmol/l is a common side effect of carbamazepine and oxcarbazepine therapy. The incidence of hyponatremia secondary to carbamazepine therapy ranges between 4.8 and 40 % depending on the population studied^10,11. In most cases, hyponatremia is asymptomatic and continuation of the carbamazepine use is possible whilst a close eye is kept on the plasma sodium level¹⁰. In rare occasions hyponatremia is symptomatic and discontinuation of carbamazepine is warranted. Administration of demeclocycline to normalise the sodium level was suggested by some authors¹² However, the long term use of demeclocycline is associated with several complications and this approach is hardly a standard practice.

Clinicians often face a dilemma when carbamazepine is the only agent able to control a specific clinical problem. With many antiepileptics available, it is unusual to face such a problem in epileptic patients. Trigeminal neuralgia on the other hand can be extremely difficult to control and carbamazepine was found to have a unique ability to manage such unpleasant condition even before its antiepileptic effects were noticed on 1962¹³.

Eslicarbazepine is promoted as an alternative to carbamazepine when side effects occurs on otherwise responsive patients to its favourable antiepileptic effects¹⁴. Hyponatremia is rare in eslacarbazepine users with only an incidence of less than 1% in the small populations studied^15,16.  Frequency of hyponatraemia increased with increasing eslicarbazepine dose. In patients with pre-existing renal disease leading to hyponatraemia, or in patients concomitantly treated with medicinal products which may themselves lead to hyponatraemia¹⁷.

Our patient showed the same favourable response to eslicarbazepine as she experienced with carbamazepine. However, hyponatremia did not occur with eslicarbazepine therapy. This enabled our patient to continue with pharmacological management and avoid surgical interventions.

With the exception of epilepsy, no reports are available commenting on the use of eslicarbazepine on the wide range of conditions that carbamazepine is traditionally used for such as mental health problems and neuropathic pain. When patients are well controlled on carbamazepine whatever the indication is, the occurrence of side effects such as hyponatremia is often managed by an automatic replacement with another agent. We feel that in such patients a therapeutic trial of eslicarbazepine might be appropriate especially if the control on carbamazepine was robust or if the benefits of carbamazepine therapy were clearly superior to other pharmacological agents potentially useful for the targeted clinical condition.

Case Presentation: Reflex Anoxic Seizures and Anaesthesia

Reflex anoxic seizures (‘RAS’) may present, as potentially life threatening events, but these are often preventable. They are most common in preschool children (but can occur in any age) and more so in females.  As a cause of seizures they are not rare; one study estimated a frequency of 8 in 1000 preschool children¹, but they are often misdiagnosed. The pathophysiology of RAS is vagally mediated – a noxious stimulus causes a supranormal vagal discharge resulting in bradycardia and then astystole². This then results in cerebral under perfusion and hypoxia. During this time the patient is often noted to become very pale with dusky lips, initially flaccid and then tonic with rigid extension and clenched jaws. They may then have a generalised convulsion, often with rolling eyes and urinary incontinence. The patient spontaneously recovers (the whole episode lasting around 30 to 60 seconds) and will feel somnolent, often remaining pale for a while.

From this description it can be easily understood how such an event can be misdiagnosed as epilepsy; however it is not associated with the uncontrolled neuronal discharge of epilepsy and if monitored by EEG this is absent². It may also be mistaken as breath-holding attacks (where intra-thoracic pressure restricts cerebral perfusion) or Stokes- Adams attacks (where there is abnormal electrical function of the heart).

The noxious stimuli responsible can be many different things. Ocular pressure², venepuncture³, anaesthetics⁴, accidental trauma and fear have all been implicated. If these stimuli cannot be prevented, management is normally just supportive (positioning, protection from trauma, oxygen) and allowing the fit to self-resolve[U1] . Further management can involve atropine⁵ (either acutely of preventatively), maintenance anticonvulsants⁶ (though these often just stop the fitting but not the syncope) and even pacemaker [U2] insertion⁷.

The case we encountered was that of a 20 year old female student, presenting for a planned day case removal of a molar tooth. She was otherwise fit and well with no other past medical history, only taking the combined oral contraceptive pill. Her history with RAS started at age 1, when she was admitted to hospital following two seizures. The seizures occurred every few months and she was provisionally diagnosed as suffering from epilepsy, with prophylactic treatment started. However, as she grew older she was able to describe how the attacks were not associated with a preceding aura, but rather an unpleasant stimulus (such as accidental injury). A new diagnosis of RAS was made and the antiepileptics were stopped without the seizures becoming more frequent. As she entered late childhood and adolescence the frequency of the seizures became less, but (atypically) they did not stop entirely.  On preassessment she reported being seizure free for just over a year and was anxious that today could precipitate another.

After consideration, we decided to proceed with anaesthesia with the following measures. The patient was kept calm by having a clear explanation of what to expect before coming to theatre, and then was reassured by an affable theatre team (who had been informed of her condition). Atropine was drawn up and available if vagal over stimulation occurred, as was suxamethonium in case of emergency airway intervention. For cannulation, cold spray was used along with distraction. Induction was with propofol (under full monitoring) and anaesthesia was maintained with sevoflurane/nitrous oxide via LMA. To prevent pain as a potential trigger, fentanyl (at induction) and paracetamol (after induction) were given and local anaesthetic (lidocaine) was administered before any surgery. Emergence was kept as smooth as possible by removing the LMA prior to any gagging and coughing and manually supporting the airway until she was awake.

With these measures the procedure was uneventful and the patient could be discharged home as planned. We hope this case report will help improve awareness and understanding of RAS, and the steps that can be taken peri-operatively to help ensure safe anaesthesia.

Introduction:

Ganglioneuroma is a rare, benign, neuroblastic tumour that originates from the neural crest cells. Ganglioneuroma, ganglioneuroblastoma and neuroblastoma are three maturational manifestations of a common neoplasm in the progressive order of loss of differentiation. Ganglioneuromas may be found anywhere along the line of the embryonic neural crest, from clivus to sacrum and are very rare in the pelvis. Less than twenty cases have been described in the literature with various presentations based upon location including extradural, retroperitoneal, spinal, thoracic and one solely intradural medullary location. Ganglioneuromas may stay asymptomatic for a long period and  give rise to no pressure symptoms either due to slow growth leading to progressive increase in size accompanied by adaptive changes. Ganglioneuromas demonstrate long-term disease-free survival even with an incomplete surgical removal. Here we present a case of a girl aged 11 years with pelvic ganglioneuroma.

Case Report:

A girl aged eleven years was brought from a remote hilly area in Pakistan by her mother to the city hospital many miles away. She had noticed that her daughter’s lower abdomen had progressively enlarged over last few months. Her menstrual cycle was normal so the mother was concerned that despite not being pregnant, her daughter had a distended abdomen as if she was pregnant She had a good appetite and unaltered bowel and bladder function. She had no heartburn, regurgitation, nausea, vomiting, heamatemesis or melaena. She denied any bleeding par rectum, shortness of breath, cough, loss of consciousness or convulsions. Her past medical history was mundane. She had not had any surgery in the past and was not taking any medication. Examination revealed a smooth, large, fixed hard mass in the right lower abdomen and pelvis. It was palpable in the pelvis on rectal examination which was otherwise normal.  Liver or spleen was not palpable and she had no ascites. Her chest was clear, heart sounds were normal and there were no neurological abnormalities. Laboratory tests including FBC, LFT, U&E and Creatinine were normal. Her MRI  scan was not of a good quality due to limitation of resources and technology at place of her diagnosis, but it showed an 11.4 x 11.8cm solid, well-defined mass arising from pelvis and extending up to the umbilicus. The mass showed intermediate low signals on T1 and hyper intense signals on T2 images (Fig. 1). Mid line surgical exploration was undertaken which showed a large, solid, retroperitoneal mass arising from sacral nerves within the pelvis. Mass was lying in front of great vessels, overlapping the confluence of common iliac vessels. The left ureter was displaced laterally while the right ureter was lying over the mass. The mass was excised completely. Post operative course was uneventful and patient was discharged home on the fifth post operative day.

Figure1: MRI showing showing a large soft tissue mass.

Macroscopically, the specimen was a 13x13x5cm rounded well-encapsulated mass (Fig. 2). Upon sectioning in vitro, mass was seen to be solid, whorled and grey white. Microscopically, groups and singly scattered ganglion cells were seen with surrounding neural tissue. There was no evidence of atypia, mitosis or necrosis. Features were suggestive of a ganglioneuroma. (Figure 3) The patient was well at two months follow up and required no further treatment.

Figure2: Photograph of the resected specimen shows a well-encapsulated ovoid mass.

Figure 3 Microscopy showing scattered ganglion admist neuronal cells

Discussion:

Neuroblastoma, ganglioneuroblastoma and ganglioneuromas are tumours of  sympathetic nervous system that arise from the neural crest cells.¹ These tumours differ only in their progressive degree of cellular and extracellular maturity, with ganglioneuroma being the most mature hence well differentiated and neuroblastoma being the least.² Ganglioneuroma are rare, benign and slow growing. They may occur spontaneously or as a down grading from therapy for Neuroblastoma with either chemotherapy or radiation.³ International Neuroblastoma Pathology Classification (INPC) has been devised after studying 552 such tumours. Out of 300 with favourable prognosis three groups were identified as; ganglioneuroma maturing (GN-M), ganglioneuroblastoma intermixed (GNB-I) and ganglioneuroblastoma nodular with favourable subset (GNB-N-FS). These are resectable in 91% cases in one or more surgical sessions. In contrast, the remaining 252 tumours had unfavourable prognosis and were called ganglioneuroblastoma nodular unfavourable subset (GNB-N-US). This group was not amenable to surgical resection and usually already had metastasis at the time of presentation.⁴

Ganglioneuromas although are mostly sporadic, may be associated with Neurofibromatosis (Von Recklinghausens Disease) and  Multiple Endocrine Neoplasia type II (MEN).¹ Ganglioneuroma usually presents before the second decade and rarely after the sixth.² The median age at diagnosis has been reported to be approximately 7 years. There is a slight female preponderance.⁵ The common locations are the posterior mediastinum, and the retroperitoneal space. Retroperitoneal pelvic location is very rare and only few case histories have been reported.¹

Although retroperitoneal ganglioneuromas are usually asymptomatic, some patients may get compression symptoms, diarrhea, hypertension, virilization and myasthenia gravis owing to release of certain peptides.¹ Radiological examination may localize the lesion. MRI may show low intensity on T1-weighted images and heterogenous hyper intensity on T2-weighted images with gradual increasing enhancement on dynamic images.⁶

Surgical excision is sufficient for treatment of ganglioneuromas. Chemotherapy or radiotherapy has no role in the treatment. Even with an incomplete excision, close follow up alone may be adequate. If any progression of the tumour is seen then repeat laparotomy may be indicated.²

Conclusion:

Although pelvic ganglioneuroma is a very rare lesion, it should be considered in the differential diagnosis of any abdomeno-pelvic mass. As it is a slow growing tumour, gross total surgical removal with preservation of organ function is a feasible surgical option.

CASE PRESENTATION

A 67 year old Caucasian male presented to our institution with a one day history of uncontrollable movements. The patient was being evaluated by a psychiatrist, neurologist and a neuro-opthalmologist for a three month history of severe anxiety, gait instability and palinopsia, respectively. The patient had progressively worsened over the prior two weeks and at the time of presentation reported visual hallucinations with increased confusion. His involuntary movements escalated to the point where it appeared that he was having seizures.

His medical history was significant for gouty arthritis, hypertension, and major depression. His surgical history was notable for an open reduction and internal fixation of his left hip 6 years prior. There was no history of any blood or blood product transfusion. He was an insurance executive and did not have significant occupational exposures. His social and family history was unremarkable. His medications upon arrival included captopril, atenolol, bupropion, lamotrigine, clonazepam, folic acid, and ibuprofen.

On admission he was arousable, well nourished, afebrile, haemodynamically stable but disorientated. His cardiopulmonary, abdominal and integumentary examinations were unremarkable. Neurological examination was significant for bilateral symmetric hyperreflexia, diffuse cogwheel rigidity without a resting or postural tremor, and multi-focal dysrhythmic generalised myoclonus. No neck tenderness or nuchal rigidity was noted. A CT of the head without contrast in the causality department was negative for haemorrhage or any acute intracranial pathology.

His initial assessment showed confusion, hallucinations, myoclonus with medication induced delirium. Lewy body dementia, occipital lobe epilepsy, peduncular hallucinosis and prion disease were all considered in the differential diagnosis. On admission, laboratory data including a CBC, CMP, serum ammonia level, cardiac enzymes, urinalysis, and coagulation profile were unremarkable. A toxicology screen for illicit drugs and heavy metals was negative. The initial lumbar spinal fluid (CSF) analysis was only notable for mild proteinorachia of 57 mg/dL. Gram stain, India-ink stain, acid-fast bacilli (AFB), bacterial & fungal cultures, as well as PCR for viral nucleic acid (herpes, Varicella-Zoster, Epstein-Barr virus, arboviruses, and cytomegalovirus virus) were all negative. MRI with contrast was remarkable only for periventricular ischemic changes consistent with small vessel disease. The patient’s bupropion and lamotrigine were discontinued upon admission, and his clonazepam was increased with resolution of the myoclonus after 24 hours.

The admission EEG showed diffuse slowing with no epileptiform discharges or triphasic waves. Due to progressive neurologic deterioration, he was followed with serial electroencephalograms. On hospital day 5, he became unresponsive and the subsequent EEG revealed non-convulsive status epilepticus (NCSE). Temporary resolution of his seizures was achieved with lorazepam and pentobarbital infusions. After 3 days of almost complete suppression, the pentobarbital was discontinued without NCSE recurrence. On hospital day 15 the EEG again displayed NCSE. A ketamine drip was added to his drug regimen with only brief improvement. Pentobarbital had been restarted and progressively titrated up to the maximal dose without achieving burst suppression. Despite being on the maximal dose of pentobarbital, ketamine, valproic acid, levetiracetam, and topiramate he continued to display NCSE (Figure 1A).

At this point (hospital day 16), therapeutic hypothermia was initiated and continued for 48 hours. The patient’s core body temperature was maintained between 32-33 °C followed by slow rewarming to normothermia over the following 48 hours. Near complete suppression of epileptiform activity was observed on the EEG (Figure 1B). Ketamine and pentobarbital were successfully weaned off during the following days and phenobarbital was introduced without recurrence of NCSE.

Figure 1A.  Electroencephalogram from hospital day 15. Refractory non-convulsive status epilepticus while on ketamine, levetiracetam, valproic acid, topiramate and pentobarbital.

DISCUSSION

Creutzfeldt-Jakob disease is the archetype of prion mediated neurodegenerative disorders. There are 4 types of CJD; sporadic, familial, iatrogenic and variant⁴. The sporadic type accounts for 85 per cent of all cases of CJD⁴. The diagnosis of CJD and transmissible spongiform encephalopathy (TSE) can be elusive. The World Health Organisation’s diagnostic criteria for CJD require at least one of the following: (1) Neuropathological confirmation,  (2) confirmation of protease-resistant prion protein (PrP) via immunohistochemistry or Western blot,  or (3) presence of scrapie-associated fibrils⁴. However, newer and less invasive means for diagnosis have been explored in recent literature. CSF analysis for protein 14-3-3, tau protein, S100B protein and neuron-specific enolase have demonstrated sensitivities of 93 per cent, 89 per cent, 87 per cent and 78 per cent, respectively⁵. In addition, the use of MRI fluid-attenuated inversion recovery (FLAIR) and diffusion weighted imaging (DWI) techniques have yielded sensitivities of 91-92 per cent and specificities of 94 -95 per cent respectively, especially when utilised early in the disease state⁶. In our case, the initial MRI was unremarkable and only the repeated MRI, performed three weeks after admission, revealed basal ganglia signal intensities consistent with CJD.

One of the most studied and well characterised tools used to support the diagnosis of CJD is the EEG. The typical pattern observed in the early stages of CJD is frontal intermittent rhythmic delta activities (FIRDA). As the disease progresses, characteristic periodic sharp wave complexes (PSWC) can be observed, usually 8 to 12 weeks after the onset of symptoms⁷. However, the reported sensitivity of EEG is relatively low, ranging from 22 to 73 per cent, and is largely dependent of the subtype of CJD⁸. In our case, the patient presented with NCSE, which is an uncommon presentation of an uncommon disease. In a retrospective review of 1,384 patients with probable or definite CJD, only 0.007 per cent or 10 patients presented with NCSE². Our patient did not demonstrate EEG findings consistent with CJD until late in his hospital course. Hence, CJD must be considered as a diagnosis in a patient who presents with refractory non-convulsive status epilepticus without overlooking the more common causes⁹.

The last important observation is the potential utility of therapeutic hypothermia in patients with refractory NCSE. Therapeutic hypothermia has long been known to suppress epileptiform discharge^10,11. However, the safety and efficacy have not been broadly studied in human subjects. Corry and colleagues conducted a small study examining the effects of therapeutic hypothermia on 4 patients with refractory status epilepticus. The results were promising in that therapeutic hypothermia was successful in aborting seizure activity in all 4 patients and effectively suppressed seizure activity in 2 of the 4 patients after re-warming¹². We were able to observe similar result in achieving temporary resolution of NCSE with therapeutic hypothermia in combination with antiepileptic medication in our patient. 

Case Report

A 69 year old male with hypertension, body mass index 24 kg/m², neck circumference 16 inches, and moderate COPD, on home oxygen, presented to his pulmonary clinic appointment with worsening complaints of fatigue, leg cramps, and intermittent shortness of breath with chest discomfort.  A remote, questionable history of syncope five to ten years ago was elicited.  His vital signs were: temperature 98.8⁰F, blood pressure 119/76 mmHg, pulse 92/min and regular, and respirations 20/min.  Physical exam was significant for crowded oropharynx with a Mallampati score of four, distant breath sounds with a prolonged expiratory phase on lung exam with a normal cardiac exam.  Laboratory investigation showed normal complete blood counts, haemoglobin 15 g/dL, and normal chemistries.  Compared to his previous studies, a pulmonary function study showed stable parameters with a FEV1 1.47 L   (69%), FVC/FEV1 ratio 0.44 (62%), and a DLCO/alveolar volume ratio of 2.12 (49%).  A room air arterial blood gas revealed pH 7.41, PCO2 44 mmHg, and PO2 61 mmHg, with 92% oxygen saturation.  A six minute treadmill exercise test performed to assess the need for supplemental oxygen showed that he required supplemental oxygen at 1L/min via nasal cannula to eliminate hypoxemia during exercise.  His chest radiograph was significant for hyperinflation and prominence of interstitial markings.  A high resolution computed tomography of the chest demonstrated severe centrilobular and panacinar emphysema only.  A baseline electrocardiogram (EKG) showed normal sinus rhythm with an old anterior wall infarct (Figure 1).   Echocardiography of the heart revealed a normal left ventricle with an ejection fraction of 65%.  Right ventricular systolic function was normal although elevated mean pulmonary arterial pressure of 55 mmHg was noted.  A diagnostic polysomnogram performed for evaluation of daytime fatigue and snoring at night revealed mild OSA with an AHI of 6/hr. with sleep time spent with oxygen saturation below 90% (T-90%) of 19%.  The EKG showed normal sinus rhythm.  A full overnight polysomnogram for continuous positive airway pressure (CPAP) titration performed for treatment of sleep disordered breathing was sub-optimal,  however it demonstrated an apnoea–hypopnea index (AHI) of 28 during REM (rapid eye movement) sleep, and a T-90% of 93%.  The associated electrocardiogram showed Wenckebach second degree AV heart block during REM sleep usually near the nadir of oxygen desaturation.   On a repeat positive airway pressure titration study, therapy with Bilevel pressures (BPAP) of 18/14 cmH₂0 corrected the AHI and nocturnal hypoxemia to within normal limits during Non REM (NREM) and REM sleep.  His electrocardiogram remained in normal sinus rhythm .A twenty-four hour cardiac holter monitor revealed baseline sinus rhythm and confirmed the presence of second degree AV block of the Wenckebach type.  A one month cardiac event recording showed normal sinus rhythm with frequent episodes of second degree AV block.  These varied from Type I progressing to Type II with a 2:1 and 3:1 AV block, during sleep.  Progression to complete heart block was noted with the longest pause lasting 3.9 seconds during sleep.  The patient underwent an electrophysiology study with placement of a dual chamber pacemaker.  He was initiated on BIPAP therapy.  Subsequently, the patient was seen in clinic with improvements in his intermittent episodes of shortness of breath, fatigue, and daytime sleepiness.

Figure 1- Patient’s baseline EKG, normal sinus rhythm. Figure 2 -Progression to Mobitz Type II block 5:07 am. Figure 3 and 4- Sinus pauses, longest interval 11:07 pm 3.9 seconds (Figure 4).

Discussion

In healthy individuals, especially athletes, bradycardia, Mobitz I AV block, and sinus pauses up to 2 seconds are common during sleep and require no intervention⁵. Cardiac rhythm is controlled primarily by autonomic tone.  NREM sleep is accompanied by an increase in parasympathetic, and a decrease in sympathetic, tone. REM sleep is associated with decreased parasympathetic tone and variable sympathetic tone.  Bradyarrhythmias in patients with OSA are related to the apnoeic episodes and over 80% are found during REM sleep.   During these periods of low oxygen supply, increased vagal activity to the heart resulting in bradyarrhythmias may actually be cardioprotective by decreasing myocardial oxygen demand.  This may be important in patients with underlying coronary heart disease. 

Some studies have found that Mobitz I AV block may not be benign.  Shaw⁶ et al studied 147 patients with isolated chronic Mobitz I AV block.  They inserted pacemakers in 90 patients, 74 patients were symptomatic and 16 patients received a pacemaker for prophylaxis.  Outcome data included five-year survival, deterioration of conduction to higher degree AV block, and new onset of various forms of symptomatic bradycardia.  They concluded that survival was higher in the paced groups and that risk factors for poor outcomes in patients with Mobitz I included age greater than 45 years old, symptomatic bradycardia, organic heart disease, and the presence of a bundle branch block on EKG.

The Sleep Heart Health Study⁷ found a higher prevalence of first and second-degree heart block among subjects with sleep-disordered breathing (SDB) than in those without (1.8% vs. 0.3% and 2.2 vs. 0.9%, respectively). Gami et al⁸observed thatupon review of 112 Minnesota residents who hadundergone diagnostic polysomnography and subsequentlydied suddenly from a cardiac cause, sudden death occurred between the hours of  midnight and 6:00 AM in 46% of those with OSA, as compared with 21% of those without OSA.   In a study of twenty-three patients with moderate to severe OSA who were each implanted with an insertable loop recorder, about 50% were observed to have frequent episodes of bradycardia and long pauses (complete heart block or sinus arrest) during sleep⁹.  These events showed significant night-to-night intra individual variability and their incidence was under-estimated, only 13%, by conventional short-term EKG Holter recordings. 

Physiologic factors predisposing patients with OSA to arrhythmias include alterations in sympathetic and parasympathetic nervous system activity, acidosis, apnoea’s, and arousal^{2, 10, 11}.  Some patients with OSA may have an accentuation of the ‘Diving Reflex’.  This protective reflex consists of hypoxemia-induced sympathetic augmentation to muscles and vascular beds associated with increased cardiac vagal activity which results in increased brain perfusion, bradycardia and decreased cardiac oxygen demand.  In patients with cardiac ischemia, poor lung function (i.e. COPD), or both, it may be difficult to differentiate between these protective OSA-associated Bradyarrhythmias and those which may lead to sudden death.  It has been well established that patients with COPD are at higher risk for cardiovascular morbidity¹² and arrythmias¹³.  Fletcher¹⁴ and colleagues reported that the effects of oxygen supplementation on AHI, hypercapnea and supraventricular arrhythmias in patients with COPD and OSA were variable.  Out of twenty obese men with COPD studied, in most patients oxygen eliminated the bradycardia observed during obstructive apnoea’s and eliminated AV block in two patients.  In some patients supplemental oxygen worsened end-apnoea respiratory acidosis however this did not increase ventricular arrhythmias. 

CPAP therapy has been demonstrated to significantly reduce sleep–related Bradyarrhythmias, sinus pauses, and the increased risk for cardiac death ^{9, 15}.   Despite this, in certain situations placement of a pacemaker may be required.  These include persistent life-threatening arrhythmias present in patients with severe OSAS on CPAP, arrhythmias in patients who are non-compliant with CPAP, and in patients who may have persistent sympathovagal imbalance and hemodynamic fluctuations resulting in daytime bradyarrhythmias¹⁶.

Our case is interesting since it highlights the importance of recognizing the association between OSA, COPD, and life-threatening cardiac arrhythmias.  Primary care providers should note the possible association of OSA-associated bradyarrhythmias with life-threatening Type II bradyarrhythmias and pauses.  Since bradyarrhythmias related to OSA are relieved by CPAP, one option would be to treat with CPAP and observe for the elimination of these arrhythmias using a 24hour holter or event recorder¹⁷.  Compliance with CPAP is variable and if life-threatening bradycardia is present, placement of a permanent pacemaker may be preferred¹⁸. 

Our patient is unusual because most studies showing a correlation with the severity of OSA and magnitude of bradycardia have included overweight patients without COPD¹⁹. This patient’s electrocardiogram revealed a Type II AV block at 5am (Figure 2).  This is within the overnight time frame where patients with OSA have been observed to have an increased incidence of sudden death. Figures 3 and 4 show significant sinus pauses.   In selected cases where patients have significant co-morbidities (i.e. severe COPD with OSA), in addition to treatment with positive airway pressure, electrophysiological investigation with placement of a permanent pacemaker may be warranted.

INTRODUCTION:

Even though it is commonly seen in Graves' disease, TPP is not related to the etiology, severity, and duration of thyrotoxicosis. ¹

The pathogenesis of hypokalaemic periodic paralysis in certain populations with thyrotoxicosis is unclear. Transcellular distribution of potassium is maintained by the Na+/K+–ATPase activity in the cell membrane, and it is mainly influenced by the action of insulin and beta-adrenergic catecholamines.² Hypokalemia in TPP results from an intracellular shift of potassium and not total body depletion. It has been shown that the Na+/K+–ATPase activity in platelets and muscles is significantly higher in patients with TPP.³ Hyperthyroidism may result in a hyperadrenergic state, which may lead to the activation of the Na+/K+–ATPase pump and result in cellular uptake of potassium.^{2, 4, 5} Thyroid hormones may also directly stimulate Na+/K+– ATPase activity and increase the number and sensitivity of beta receptors.^{2, 6} Patients with TPP have been found to have hyperinsulinemia during episodes of paralysis. This may explain the attacks after high-carbohydrate meals.⁷

CASE REPORT:

A 19 year old male patient presented to our emergency room with sudden onset weakness of lower limbs. He was not able to stand or walk. Power of 0/5 in both lower limbs and 3/5 in upper limbs was noticed on examination.  Routine investigations revealed to have severe hypokalemia with a serum potassium of 1.6 meq/l (normal range 3.5-5.0 meq/l), a serum phosphorus level of 3.4 mg/dl (normal range 3-4.5 mg/dl) and mild hypomagnesemia with serum magnesium level of 1.5mg/dl (normal range 1.8-3.0 mg/dl). ECG showed hypokalemic changes with prolonged PR interval, increased P-wave amplitude and widened QRS complexes. He was managed on intravenous as well oral potassium and history revealed weight loss, increased appetite and tremors from past 4 months. He had a multinodular goiter and radioactive iodine uptake scan (Iodine 131) showed a toxic nodule (Toxic nodule shows increased iodine uptake while the rest of the gland is suppressed) with no exophthalmos, sensory or cranial nerve deficits. Thyroid function tests revealed thyrotoxicosis with free T4 of 4.3ng/dl (normal range 0.8-1.8ng/dl), T3 of 279 ng/dl (normal range = 60 - 181 ng/dl) and a TSH level of <0.15milliunits/L (normal range = 0.3 - 4 milliunits/L). He was managed on intravenous  potassium & propanolol. The patient showed dramatic improvement of his symptoms. The patient was discharged home on carbamazole with the diagnosis of TPP secondary to toxic nodular goiter.

In this case there was a significant family history as one of  his elder brother had a sudden death (cause not known) and his mother was primary hypothyroid on levothyroxin replacement therapy.

DISCUSSION :

TPP is seen most commonly in Asian populations, with an incidence of approximately 2% in patients with thyrotoxicosis of any cause.^1,8,9,10 The attacks of paralysis have a well-marked seasonal incidence, usually occurring during the warmer months.¹ Pathogenesis of hypokalaemia has been explained by some authors to be due to an intracellular shift of body potassium, which is catecholamine mediated.^11,12 Shizume and his group studied total exchangeable potassium which revealed that patients with thyrotoxic periodic paralysis were not significantly different from controls when the value was related to lean body mass.¹¹ The paralytic symptoms and signs improve as the potassium returns from the intracellular space back into the extracellular space.¹³ The diurnal variation in potassium movement where there is nocturnal potassium influx into skeletal muscle would explain the tendency for thyrotoxic periodic paralysis to occur at night.¹⁴ Hypophosphataemia and hypomagnesaemia are also known to occur in association with thyrotoxic periodic paralysis.^{14,15,16,17,18} The correction of hypophosphataemia without phosphate administration supports the possibility of intracellular shift of phosphate.¹⁶ Electrocardiographic findings supportive of a diagnosis of TPP rather than sporadic or familial periodic paralysis are sinus tachycardia, elevated QRS voltage and first-degree AV block (sensitivity 97%, specificity 65%).²⁰ In addition to ST-segment depression, T-wave flattening or inversion and the presence of U waves are typical of hypokalaemia.

The management is to deal with the acute attack as well as treatment of the underlying condition to prevent future attacks. Rapid administration of oral or intravenous  potassium chloride can abort an attack and prevent cardiovascular and respiratory complications.⁴ A small dose of potassium is the treatment of choice for facilitating recovery and reducing rebound hyperkalaemia due to release of potassium and phosphate from the cells on recovery.^1,2,3 Rebound hyperkalaemia occurred in approximately 40% of patients with TPP, especially if they received >90 mmol of potassium chloride within the first 24 hours.⁴ Another mode of treatment is to give propranolol, a nonselective b-blocker, which prevents the intracellular shift of potassium and phosphate by blunting the hyperadrenergic stimulation of Na+/K+–ATPase.²⁰  Hence, initial therapy for stable TPP should include propranolol.^21,22,23  The definitive therapy for TPP includes treatment of hyperthyroidism with antithyroid medications, surgical thyroidectomy, or radioiodine therapy.

Case report

A 78 year old man was admitted for re-fashioning of a prolapsing colostomy. Nine months previously he had undergone a juxtarenal aortic aneurysm repair complicated by ischaemic colitis, for which he had a sigmoid colectomy and a further laparotomy for refashioning of the stoma.

His past medical history consisted of anaemia, stable angina, superficial bladder cancer, Stage 4 chronic kidney disease, type 2 diabetes mellitus and osteoarthritis. He weighed 77 kg and his exercise tolerance was 100 yards, with the aid of a stick. His medications included doxazosin, quinine sulphate, perindopril, simvastatin, ferrous sulphate, isosorbide mononitrate and aspirin.

On examination, he was apyrexial with a blood pressure of 170/70 mm Hg, a heart rate of 65 bpm, a respiratory rate of 14 bpm and Sa0₂ of 98% on room air. Serum laboratory tests showed a prothrombin time of 13.4 sec (normal range 9.0 – 13.0 sec), haemoglobin 10.2 g/dL (13.0 – 16.7 g/dl), platelets 131 x10⁹/L (150 – 400 x10⁹/L), sodium 139 mmol/L, potassium 4.2 mmol/L, urea 15.7 mmol/L (2.5 – 7.0 mmol/L), creatinine 196 umol/L (50 – 130 umol/L) and eGFR 29 ml/min/1.73m² (>60ml/min/1.73m²).

His preoperative pulmonary function tests showed an FVC of 2.78L (93.8% predicted), a reduced FEV1 of 1.66L (75.2% predicted) and FEV/FVC of 59.87%. His ECG showed normal sinus rhythm. A CPEX test taken 12 months previously showed moderately reduced peak aerobic capacity, with a peak V0₂ of 11 ml/kg/min and an anaerobic threshold (AT) of 7 ml/kg/min.

In the anaesthetic room, the patient was connected to standard monitoring in accordance with AAGBI Guidelines and venous access secured with an 18 g biovalve cannula. Following pre-oxygenation, anaesthesia was induced using fentanyl 200 mcg, midazolam 2 mg, propofol 120 mg and atracurium 50 mg. Tracheal-intubation was achieved (grade 1 view) using an 8.0 mm cuffed endotracheal tube (lo-contour). A TAP block was administered following induction using ultrasound guidance (Sonosite ‘micromax’). A 50 mm insulated Stimi-Plex needle was used to inject a total of 40 ml levobupivacaine 0.375% bilaterally. Anaesthesia was maintained using a mixture of air, oxygen and sevoflurane (1.3 – 2.3 ETAA range). Intravenous (IV) paracetamol 1 g was given intraoperatively. The prolapsing colon was dissected through a circumstomal incision. A 10 cm length of colon was resected after ligation and division of the mesenteric vessels. The new end colostomy was fashioned with interrupted mucocutaneous sutures. Blood loss was minimal and there were no intraoperative complications. The duration of surgery was 1.5 hrs.

The patient spent 30 minutes in the postoperative recovery unit. He was awake, orientated and pain free throughout this period and clinical observations were stable. The patient remained pain-free on the ward and did not require any postoperative opioids. He was medically fit for discharge the following day.

Discussion

There are no previous case reports to our knowledge describing the use of TAP blocks in a patient with such poor CPEX testing preoperatively (AT = 7 ml/kg/min). CPEX testing has been shown to be an independent predictor of morbidity, mortality and length of hospital stay after major abdominal surgery.¹ The anaerobic threshold marks the onset of anaerobic metabolism as a result of inadequate oxygen delivery. It is not affected by patient effort and therefore provides a reliable patient specific measurement of functional capacity.² An AT of at least 11 ml/kg/min is recommended to safely undertake major surgery.² A combination of an AT of <11 ml/kg/min with ECG evidence of myocardial ischaemia is associated with high mortality and poor outcome. ³One study showed a mortality of 42% in those with ischaemic heart disease (IHD) and an AT <11 ml/kg/min, compared with just 4% in those with no IHD.⁴

Postoperative morbidity and mortality most often occurs in patients with pre-existing cardiorespiratory disease and a reduced functional capacity, due to their inability to withstand the additional physiological demands placed upon them by major surgery. Many of these patients develop features of organ hypoperfusion due to poor cardiorespiratory reserve.⁵

Our patient had an AT of 7 ml/kg/min and poor respiratory reserve (exercise tolerance of 100 yards, FEV/FVC 59.87% of predicted) but underwent uneventful intra-abdominal surgery with a good recovery and short length of hospital stay. Contributing factors may have been the anaesthetic technique used, as well as the surgical approach via a parastomal incision. Good intraoperative and postoperative control of cardiovascular parameters, temperature and pain are well known to reduce the surgical stress response and postoperative morbidity, and to improve postoperative outcome.⁶ Our patient was cardiovascularly stable throughout the perioperative period. His pain was well controlled with no opioid requirements due to the use of bilateral TAP blocks, and this probably contributed to his uneventful recovery, with no critical care requirement.

CPEX testing is not universally accepted as a useful preoperative assessment tool. In studies assessing it as a reliable predictor of outcome, there is heterogeneity in the degree of clinician blinding used. Blinding was used in some studies,¹ whilst in other instances, clinicians were aware of the CPEX results and changed their management accordingly. This obscures the true relationship between patient outcome and CPEX-derived measures of risk.⁷

TAP blocks were first described in 2001⁸ and have been shown to significantly reduce postoperative morphine consumption following abdominal surgery by up to 70%. They reduce pain scores at rest and during mobilisation in the early postoperative period (0-6 hours), and in the first 24 hours.⁹ The reduced requirement for morphine also leads to a reduction in postoperative nausea, vomiting and sedation.⁹ It may be possible that the ultrasound guided TAP block confers advantages in procedures with moderate surgical trauma to minimize pain and reduce opioid usage, thereby promoting faster recovery and discharge.⁸ TAP blocks were the chosen method of analgesia in our patient as they would elicit the least physiological disturbance, but would provide good postoperative analgesia, without opioid-related side effects. This was particularly beneficial, as his pre-existing renal impairment put him at increased risk of opiate toxicity. TAP blocks eliminate somatic pain relating to the surgical incision but do not treat visceral pain. However, our patient tolerated a 10 cm bowel resection with bilateral TAP blocks and intravenous paracetamol. A similar effect has been observed in other studies but the mechanisms behind it are unclear. One theory is that there is an analgesic effect due to high systemic levels of local anaesthetic.¹⁰

The use of CPEX testing to determine fitness for surgery should be interpreted with caution as newer anaesthetic and surgical techniques develop. Our patient had IHD and an AT which showed a significantly increased level of risk. However, a combination of regional anaesthesia and a cardio stable general anaesthetic with minimally invasive surgery, allowed a rapid and uneventful recovery with no opioid requirements and a short length of hospital stay.

Introduction

Thyrotoxic periodic paralysis (TPP) is an uncommon disorder characterised by simultaneous thyrotoxicosis, hypokalaemia, and paralysis that occurs primarily in males of South Asian descent.¹ Many affected patients do not have obvious symptoms and signs of hyperthyroidism and hence may be misdiagnosed or overlooked on presentation.² We hereby report a male patient who presented to us with weakness of all four limbs. The patient was evaluated and diagnosed to be having TPP.

Case History

A 30-year-old male patient, who was an agriculturist by profession, presented with weakness of all four limbs of one-day duration. The weakness first appeared in his lower limbs and then in the upper limbs. There were no sensory symptoms or bladder involvement. He was not a known hypertensive, diabetic or thyrotoxic patient. He was not on any medication for any significant illness.

On general physical examination, there was no pallor, icterus, cyanosis, clubbing, lymphadenopathy or pedal oedema. Multinodular goitre was noted on thyroid examination. There was no exopthalmos, lid lag, pretibial myxoedema or other signs of thyrotoxicosis.  Thyroid bruit was absent.  Pulse rate was 96/minute, blood pressure of 140/80mmHg, and respiratory rate 18/minute. On central nervous system examination, the higher mental functions and cranial nerve examination were within normal limits. Motor system examination showed the presence of flaccid quadriparesis with areflexia. Sensory system examination was within normal limits. Cardiovascular and respiratory system examination were normal.

Investigations revealed: haemoglobin (Hb) -13.1 gm%, total count (TC) - 11,400/cmm, platelet count - 49,000/cmm, random blood sugar (RBS) - 110mg/dl, blood urea - 29 mg/dl, serum creatinine - 0.8 mg/dl. Serum electrolyte profile showed sodium - 143 mEq/L, potassium - 2.2mEq/L, chloride - 112mEq/L. Serum calcium and magnesium levels were within normal limits. Electrocardiogram (ECG) was normal. Human Immunodeficiency Virus (HIV) ELISA was non reactive. Bone marrow biopsy and ultrasonography of abdomen were normal. Fine Needle Aspiration Cytology (FNAC) of thyroid showed features of hyperplastic colloid goitre. Ultrasonography of thyroid showed hyperechoic small nodules in both lobes as well as isthmus suggestive of multinodular goitre. Thyroid profile was: total T3 - 2.34 (normal: 0.60 - 1.81ng/ml), total T4 - 13.9 (normal: 4.5 - 10.9 mcg/dl), thyroid-stimulating hormone (TSH) - 0.01 (normal: 0.35 - 5.5IU/ml). Antithyroid antibodies and antiplatelet antibodies were negative. Nerve conduction study was normal. A final diagnosis of TPP with idiopathic thrombocytopenia was made.

The patient was administered 40mmol potassium chloride intravenously.  He was treated with tablet carbimazole 10mg three times a day and tablet propanolol 10mg twice a day. The patient’s weakness in all four limbs improved dramatically within an hour after potassium chloride administration. As he had persistent thrombocytopenia during his stay in hospital, he was commenced on tablet prednisolone (1mg/kg body weight). His platelet count normalized in one month after which the steroid dose was tapered and stopped.

Discussion

TPP is an uncommon disorder characterised by simultaneous thyrotoxicosis, hypokalaemia and paralysis that occurs primarily in males of South Asian descent. The overall incidence of TPP in Chinese and Japanese thyrotoxic patients is 1.8% and 1.9% respectively.^{3, 4} Sporadic cases have been reported in non-Asian populations such as Caucasians, Afro-Americans, American Indians and Hispanics. With population mobility and admixture, TPP is becoming more common in Western countries. Many affected patients are in the age group of 20 - 40 years and do not have obvious symptoms and signs of hyperthyroidism.⁵ The attack is characterised by recurrent, transient episodes of muscle weakness that range from mild weakness to complete flaccid paralysis. The proximal muscles are affected more severely than distal muscles.  Attacks usually first involve the lower limbs, and progress to the girdle muscles and subsequently the upper limbs. Sensory function is not affected. Although patients can present with quadriparesis that resembles Guillain-Barre Syndrome or transverse myelitis, the bladder and bowel functions are never affected. Patient may experience recurrent episodes of weakness that last from a few hours up to 72 hours with complete recovery between the attacks. In the majority of patients, deep tendon jerks are markedly diminished or absent although some patients may have normal jerks.

Patients with TPP usually experience the attacks a few hours after a heavy meal or in the early morning hours upon waking. More than two-thirds present to the emergency department between 2100 and 0900 hours; hence it was initially described as nocturnal palsy or night palsy.⁶ It has been shown that plasma glucose and insulin responses to meals are markedly higher in the evening than in the morning in control subjects. Such a phenomenon suggests a possible mechanism for the nocturnal preponderance of TPP. Another explanation could be the circadian rhythmicity of many hormones reaching their peak levels during sleep. Hypokalaemia is considered to be the most consistent electrolyte abnormality in TPP and a hallmark of the syndrome along with hyperthyroidism. It has been demonstrated that hypokalaemia is a result of potassium shift into cells and that it is not caused by total body potassium depletion.⁷ Patients with thyrotoxic periodic paralysis have an underlying predisposition for activation of Na+/K+-ATPase activity either directly by thyroid hormones or indirectly via adrenergic stimulation, insulin or exercise. Increased Na+-K+ ATPase activity is postulated to contribute to hypokalaemia.⁸

The majority of cases of hyperthyroidism associated with thyrotoxic periodic paralysis are due to Graves disease although other conditions including thyroiditis, toxic multinodular goitre, toxic adenoma, TSH secreting pituitary tumour, ingestion of T4 and inadvertent iodine excess have also been implicated.⁹ Assaying of thyroid function in patients with hypokalaemic paralysis distinguishes thyrotoxic periodic paralysis from other forms of hypokalaemic periodic paralysis. Thyrotoxic periodic paralysis occurs only in the presence of hyperthyroidism and is abolished when thyroid hormones are normalised.

Immediate therapy with potassium supplementation and beta-adrenergic blockers can prevent serious cardiopulmonary complications and may hasten recovery of periodic paralysis.¹⁰ Potassium chloride is given intravenously and/or orally. Regular potassium supplementation as prophylaxis against further paralysis when the patient has normal serum potassium level is ineffective. Effective control of hyperthyroidism is indicated to prevent recurrence of paralysis.

Conclusion

To conclude, although the association of thyrotoxicosis and periodic paralysis has been well known, TPP is often not recognised when first seen because of lack of familiarity with the disorder and partly because of the subtleness of thyrotoxicosis. When a young male of South Asian descent is initially seen with severe lower limb weakness or paralysis, TPP should be considered in the differential diagnosis and investigated for its presence since it is a curable disorder that resolves when euthyroid state is achieved.

Introduction

Lactic acidosis is an important cause of metabolic acidosis in hospitalised patients. This usually occurs either due to over production or under utilisation of lactate¹ . Most cases of lactic acidosis are due to marked tissue hypoperfusion or hypoxia in systemic shock.

Asymptomatic lactic acidosis has been reported previously during acute severe asthma and attributed to fatiguing respiratory muscles, hypoxaemia and liver ischaemia. It has also been linked to β2 agonist therapy in asthma, although lactic acidosis causing increasing dyspnoea in the asthmatic patient has only been recorded rarely.

Case presentation

We present a case of lactic acidosis in a patient with acute severe asthma who did not have any overt signs of sepsis or tissue hypoperfusion.

Mr IL was a 49 years old male who was known to have moderate asthma. He had multiple previous admissions to hospital with exacerbation of asthma but had never required an intensive care admission and had never been intubated. His other comorbidities included atrial fibrillation, ischaemic heart disease and depression.

His usual medications included salbutamol, budesonide and salmeterol inhalers, aspirin, atorvastatin and digoxin. He was a mechanic by trade with no obvious occupational sensitisation. He had no pets at home. He was a smoker with a 20 pack year history. Recent lung function tests showed an FEV1/FVC of 0.68 with a post bronchodilator FEV1 of 4.17 L (95% predicted).

He was admitted with a 1 week history of worsening shortness of breath, dry cough and wheeze. His baseline blood tests including full blood count, C reactive protein, liver and renal function were normal. Chest radiograph was unremarkable. Arterial blood gas showed no evidence of hypoxia or acidosis.He was treated as acute severe asthma with back to back nebulisers, intravenous hydrocortisone and magnesium sulphate resulting in gradual improvement in bronchospasm and peak expiratory flow rate.

Despite optimal treatment, his breathing started to deteriorate. Arterial blood gas at this time showed lactic acidosis with normal oxygenation (Table 1). There was no clinical or biochemical evidence of haemodynamic compromise or sepsis. A presumptive diagnosis of lactic acidosis secondary to salbutamol was made. The nebulisers were withheld and he has transferred to high dependency unit for closer monitoring. The acidosis completely resolved in the following 12 hours on stopping salbutamol and the patient made an uneventful recovery.

Table 1: Serial Arterial Blood Gases (On admission, 4 hours later and on stopping salbutamol)

* Salbutamol witheld

Discussion

Lactate is a product of anaerobic glucose metabolism and is generated from pyruvate. Normal plasma lactate concentration is 0.5-2 meq/L. Most cases of lactic acidosis are due to marked tissue hypoperfusion or hypoxia in systemic shock² .

Lactic acidosis can occur in acute severe asthma due to inadequate oxygen delivery to the respiratory muscles to meet an elevated oxygen demand³ or due to fatiguing respiratory muscles⁴ . A less recognised cause of lactic acidosis is treatment with salbutamol. The mechanism of this complication is poorly understood.

Salbutamol is the most commonly used short acting βagonist. Stimulation of β adrenergic receptors leads to a variety of metabolic effects including increase in glycogenolysis, gluconeogenesis and lipolysis⁵ thus contributing to lactic acidosis.

Table 2 shows an assortment of previously published case reports and case series of lactic acidosis in the context of acute asthma.

Table 2: Details of etiology and consequences of lactic acidosis in previously published case reports 

Conclusion

In this case, the patient developed lactic acidosis secondary to treatment with salbutamol nebulisers. The acidosis resolved spontaneously without any specific treatment.

Lactic acidosis secondary to β agonist administration may be a common scenario which can be easily misinterpreted and confuse the clinical picture. Acidosis itself results in hyperventilation which could be mistaken for failure to treat the  response. This may in turn lead to inappropriate intensification of treatment.

INTRODUCTION:

Hypertension is common but, with early detection and treatment, it is rare to see malignant hypertension. We report a patient who presented with signs suggestive of thrombotic thrombocytopenic purpura and severe hypertension, which resolved with the treatment of hypertension.

CASE REPORT:

A 34 year old African American male presented to the emergency department (ED) having experienced nausea, vomiting and diarrhoea for two days.  He denied haematochezia, meleana or sick contacts at home.  He complained of blurred vision without photophobia, headache and mild chest discomfort.  His past medical history was unremarkable.  The patient did not have any significant family history. Smoking history was significant for a pack of cigarettes daily for seven years.  He reported occasional alcohol intake, and denied use of recreational drugs.  On presentation, this patient’s blood pressure was 201/151 mmHg, with a mean of 168 mmHg.  Pulse 103 beats per minute, respirations 20 per minute and temperature 98.4F.  Physical examination was otherwise unremarkable, including absence of focal neurological deficits.

Blood tests showed: Haemoglobin 12.6 g/dl, White cell count 13.9 g/dl, Platelets 67000, Sodium 136, Potassium 3.4, BUN 24, Creatinine 2.56 and LDH 556. Chest x-ray showed cardiomegaly.  A non-contrast computed tomography scan of the brain did not show any sign of stroke (haemorrhage).  Urinalysis was positive for proteins 4+, a large amount of blood, 0-2 white blood cells/high power field (HPF) and 0-2 red blood cells/HPF.

Figure 1

The patient’s initial treatment whilst in the ER consisted of a Labetalol drip.  His mean arterial pressure decreased to approximately 115 mmHg during the first hour, and his chest pain and headache improved with the control of elevated mean arterial pressure.  Furthermore, over the next 24 - 48 hours, the patient’s blood pressure was brought down to 138/86 mmHg and his blurred vision improved significantly.  Subsequently, intravenous medications were switched to an oral regimen.  Blood peripheral smear from the day of admission was significant for the schistocytes (Figure 1) suggesting ongoing haemolysis.  Renal ultrasound was unremarkable.  His cardiac ultrasound revealed an enlarged left ventricle, however no valvular abnormality was seen.  Serum calcium and thyroid stimulating hormone levels were normal, as were urine catecholamines and vanillylmandelic acid level.  On two week follow up in the outpatient clinic, the patient’s platelet count and creatinine had returned back to baseline and peripheral smear did not reveal any schistocytes as the blood pressure came under better control. [Table 1]

Table 1

DISCUSSION:

Malignant hypertension is a medical emergency with an incidence of 1% in hypertensive patients¹and is more common in the African American population².  Depending on the clinical presentation, it must be differentiated from thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), glomerulonephritis and vasculitis.

Suspicion for TTP was initially high in this patient because of haemolysis, thrombocytopaenia, central nervous system (CNS) manifestations and renal insufficiency.  However, TTP did not explain the presence of elevated blood pressure^3,4nor the improvement in symptoms and signs with the management of this, which clearly supports our diagnosis.  Rapidly progressive glomerulonephritis did not explain the CNS symptoms, and a normal prothrombin time and activated partial thromboplastin time ruled against disseminated intravascular coagulation⁵.  The patient did not have a history of preceding diarrhoea⁶, which could possibly direct towards haemolytic uraemic syndrome (HUS)⁴.  There was no history of prosthetic valves, nor clinical evidence of vasculitis. The patient’s symptoms of severe hypertension, haemolysis, thrombocytopaenia and renal failure were consistent with malignant hypertension, and treating the hypertension⁷gradually resolved the thrombocytopaenia, haemolysis and renal failure⁸. 

CONCLUSION:

This case report highlights that malignant hypertension is a medical emergency which can present with features resembling a wide variety of diseases, including TTP and HUS.  Using appropriate management to control the elevation in blood pressure can help reveal the underlying diagnosis.

A 73 year old lady presented for assessment of her recurrent right sided pleural effusion. She had a history of gallstones and underwent open cholecystectomy.  One month after surgery the patient had recurrent pleural effusion requiring thoracocentesis on a monthly basis. On the chest x-ray, the pleural effusion was seen exclusively on the right side occupying the whole right hemithorax. 

The pleural fluid was transudative on multiple occasions and there was no evidence of malignant cells. Her echocardiography revealed preserved cardiac function. An abdominal ultrasound showed findings of cirrhosis and splenomegaly consistent with portal hypertension.

Image 1

Computerised tomography (CT) of the chest and abdomen revealed a large right-sided pleural effusion and minimal ascites (Image 1). An ultrasound guided paracentesis was performed with difficulty and only 17cc of fluid.was obtained.  The abdominal fluid showed similar consistency as the pleural fluid. The blood workup at the same time was unremarkable.

Image 2

Intra-peritoneal administration of 99mTc-sulphur colloid was attempted but failed in the absence of ascites. Computed tomography with three dimensional reconstruction at the diaphragmatic level revealed a defect in the posterior aspect of the right hemidiaphragm (Image 2 black arrow) and also revealed irregular contours of the liver, an indirect sign of diaphragmatic defect (Image 2 white arrow).

The patient declined any surgical intervention at that point including the option of pleurodesis. She was started on diuretics and a low salt diet with significant improvement. 

Discussion:

Pleural effusion due to hepatic cirrhosis and ascites is well known, but hepatic hydrothorax in the absence of ascites is a rare complication. We report a case of liver cirrhosis with a large and recurring right sided pleural effusion that had an apparent abdominal source in the absence of ascites. We review the characteristics and treatment for hepatic hydrothorax in the absence of ascites.

Hepatic hydrothorax is defined as the presence of significant pleural effusion in a cirrhotic patient without primary pulmonary or cardiac disease¹. Postulated mechanisms for the development of pleural effusions in patients with hepatic cirrhosis include: hypoalbuminemia and decreased oncotic pressure leakage of the plasma from the hypertensive azygos vein, lymphatic leak from the thoracic duct, passage of ascitic fluid to the pleural space by way of lymphatic channels in the diaphragm, and transfer of peritoneal fluid directly via diaphragmatic defects².

The usual unilaterality of hepatic hydrothorax could be attributed to a congenital factor, but not to physiologic mechanisms³. The most likely explanation appears to be that ascitic fluid passes through congenital or acquired fenestrations in the diaphragm directly into the pleural space². The description of hepatic hydrothorax in the absence of ascites is very rare¹. The flow of the ascitic fluid into the pleural space equaled the rate of ascites production in patients with this entity³.

The composition of pleural fluid from hepatic hydrothorax is similar to that of ascitic fluid. Pleural effusions associated with portal hypertension are always transudative¹. Nuclear scans can be performed to establish the diagnosis of hepatic hydrothorax with fairly high accuracy. Intra-peritoneal administration of 99mTc-human serum albumin or 99mTc-sulphur colloid can be used to demonstrate the communication between the peritoneal and pleural space. Recent advances in radiological imaging have enabled investigators to examine in detail the diaphragmatic defects responsible for the development of hepatic hydrothorax¹.

The management is challenging and frequently associated with poor outcomes in most cases. Dietary restriction of sodium intake and the addition of diuretics is the initial approach. Thoracocentesis can be performed in patients with dyspnoea due to hepatic hydrothorax for immediate relief of symptoms. When thoracocentesis is required too frequently in patients on maximal sodium restriction and optimal diuretics, alternative treatment options must be considered^{1, 3}.

Over the last few years, new insights into the pathogenesis of this entity have lead to improved treatment modalities such as portosystemic shunts (TIPS) and video-assisted thoracoscopy (VATS) for closure of diaphragmatic defects. Both, though temporary  measures, are perhaps the best available bridging to liver transplantation in selected patients with refractory hepatic hydrothorax^{2, 3}.

Introduction

It is often forgotten that smoking inducescytochrome P450 (CYP) 1A2, resulting in altered concentrations and required doses of drugs metabolized by this route.  Conversely, upon cessation of smoking, concentrations of these drugs can rise to toxic levels unless appropriate dose adjustments are made.  Medical staff, and others involved with smoking cessation counselling, need to be aware of this if potential harm to patients is to be avoided.  Here, we describe a patient who developed tonic clonic seizures due to Theophylline toxicity, having ceased smoking 2 weeks earlier.

Case Report

Our patient is a 76-year-old lady who presented to A&E feeling generally unwell, with a two day history of dizziness.  Her medical history included atrial fibrillation, which was treated with Digoxin 62.5mcg, and Chronic Obstructive Pulmonary Disease, for which she took a combination inhaler of 25mcg Salmeterol Xinafoate and 250mcg Fluticasone Propionate, 2 puffs twice a day, plus Theophylline MR 175mg twice daily.  She had successfully given up smoking 2 weeks prior to admission, having smoked 100 cigarettes per day over the previous 40 years.  On admission, she was in atrial fibrillation, well controlled with a heart rate of 90 beats per minute, and normotensive, with no evidence of postural hypotension.  Respiratory system examination revealed prolonged expiration, in keeping with COPD, but the rest of the examination was unremarkable.  Routine blood investigations, including full blood count, urea, creatinine and electrolytes, liver function tests and C-reactive protein, were all normal apart from a serum potassium level of 3.0mmol/l (NR 3.5-5.0mmol/l).  Theophylline concentrations were not tested at this point.  A chest X-ray showed hyper-inflated lung fields in keeping with Chronic Obstructive Pulmonary Disease.

The patient was admitted for observation, and treated with Trimethoprim for a presumed urinary tract infection on the basis of urinalysis, which was positive for leukocytes and nitrites.

Two days following admission, the patient developed facial spasms and twitching of her muscles of her upper limbs. Over the next 24 hours, the patient had two witnessed tonic-clonic seizures, which were terminated with intravenous Lorazepam. An urgent CT (Computed Tomography) scan of the brain was performed.  This showed changes in keeping with small vessel disease only, nothing to account for new onset of seizures. Following a post-ictal period, the patient recovered, but then the following day had a further two tonic-clonic seizures.  It was at this point that a blood Theophylline concentration was requested.

The Theophylline concentration was reported as 41.6mcg/ml (NR 10-19.9mcg/ml), more than twice the upper safe therapeutic concentration.  A search of the laboratory system revealed that this patient’s Theophylline concentration had been within the therapeutic range when last checked 2 months prior to admission, while she was still smoking.

The Theophylline was immediately stopped and the patient closely monitored at the Medical High Dependency Unit for further fits, arrhythmias or electrolyte disturbances.  Other causes of seizures had been investigated and excluded.

The patient’s neurological symptoms improved dramatically following cessation of Theophylline, with no further twitching, muscle spasms or seizures.  Within three days her Theophylline concentration returned to a safe level, but the drug was not recommenced. Unfortunately, however, the patient died from sepsis two weeks following her admission without having left hospital.

Discussion

Theophylline has largely fallen out of favour as a treatment for airways disease due to its very narrow therapeutic index.  Even within the therapeutic range, side effects frequently occur. These side effects range from mild, including tremor and gastrointestinal disturbance, to serious and potentially life threatening, such as seizures and cardiac arrhythmias. Following acute overdose, hypokalemia, hyperglycemia, hypercalcemia, hypophosphatemia, and acidosis commonly occur.

Theophylline is mainly metabolised in the liver by demethylation or oxidation using the cytochrome P450 system.  The 8-hydroxylation of Theophylline to 1,3-dimethyluric acid (1,3-DMU) via cytochrome P450 1A2 is the major pathway.

The cytochrome P450 enzyme CYP1A2 mediates the rate-limiting step in the metabolism of Theophylline¹, andthe polycyclic aromatic hydrocarbons found in cigarette smoke are potent inducers of this enzyme².  For this reason, smokers may need up to double the dose of Theophylline to achieve therapeutic effect compared with non-smokers³.

The relationship between smoking cessation and Theophylline has also been the subject of many studies.  Lee et al demonstrated that stopping smoking for 1 week resulted in a 37.6% decrease in clearanceand a 35.8% increase in the half-life of Theophylline, and that the dose needs to be reduced by one fourth to one third after brief abstinence from tobacco to prevent potentially toxic concentrations⁴.  For this reason, careful monitoring of plasma Theophylline concentration should be considered essentialfor optimal dosing in patients following smoking cessation. The study by Faber et al recommends that the dose of CYP1A2 substrates such as Theophylline should automatically be reduced by 10% on cessation of heavy smoking and thereafter be guided by plasma concentration monitoring^5.

We found one report in which Theophylline toxicity resulted in a patient’s death following a similar presentation to the one described above⁶.  This highlights the close attention that must be paid to drug concentration monitoring by physicians when advising patients to quit smoking.

Theophylline is not the only drug which needs to be considered when patients stop smoking. Other examples are Clozapine, Olanzapine, Haloperidol and Flecanide to name a few. These drugs are also substrates for CYP1A2⁷.

Conclusion

When advising patients to stop smoking, it is essential that physicians routinely review the drugs that the patient is taking to look for those that may require dose adjustments. In the case of Theophylline, careful monitoring of Theophylline concentrations, for instance weekly in the first few weeks following smoking cessation, is essential to avoid potentially life-threatening complications.  

The authors declare that they have no conflict of interest. 

Introduction  A hydatid cyst is the larval stage of a small tapeworm, Echinococcus granulosus. This is an emerging zoonotic parasitic disease throughout the world, thought to cause an annual loss of US $193,529,740.¹ Hydatid cysts are more prevalent in Australia, New Zealand, South America, Russia, France, China, India, the Middle East and Mediterranean countries.^2,3,4 They are most commonly (about 50-75%) seen in children and young adults.^4,5,6 The liver is the most common organ involved (77%), followed by the lungs (43%).^7,8,9,10 However, some researchers report that the lung is the most common organ involved in children, possibly due to bypass of the liver by lymphatics, and higher incidental findings in the lungs when children are assessed for other respiratory infections.^8,11,12,13 Hydatid cysts have been reported in the brain (2%),^{3,4,5,7,8,14,15} heart (2%),^8,10,13,16 kidneys (2%),^9,10,11 orbit (1%),^17,18 spinal cord (1%),^3,19 spleen,⁴ spine,^3,8 spermatic cord²⁰ and soft tissues.⁸ However, in the Mediterranean region, the incidence of brain hydatid cysts have been reported higher (7.4-8.8%).²¹ Surgery remains the treatment of choice, although recently some new modalities have been described.^5,8,22 Careful removal of the lesion is of considerable importance, otherwise fatal complications are inevitable.^23,24,25 We describe the case of a 6 year old boy who came to our department with various neurological manifestations. The main purpose of this study is to demonstrate the unusual symptoms of the patient and the enormity of the operated cyst, which was fully resected without rupture. Case Report A 6-year-old boy was referred to our Neurosurgery Department with a four week history of ataxia and left sided weakness. His vital signs were normal and his Glasgow Coma Scale (GCS) was 15. The symptoms had started about six months ago with numbness and parasthesia of the toes. Subsequently he developed intermittent nausea and vomiting. He then started to develop left sided weakness and finally ataxia. He also had a few focal convulsions but did not complain of headache. Fundoscopy revealed bilateral frank papilloedema. On examination, the patient had nystagmus and a positive Romberg’s test. Laboratory data showed mild leucocytosis without any significant rise in eosinophils, and liver enzymes were normal. The enzyme-linked immunosorbent assay (ELISA) for hydatid cysts was negative. Plain chest X-ray and ultrasound scan of the abdomen and pelvis were also normal. Brain computed tomography (CT scan) of the frontal and parietal lobes demonstrated a single large, spherical, well-defined, thin-walled homogenous cyst, with an inner density similar to that of cerebrospinal fluid (CSF), and a wall which did not show enhancement [fig 1(a)]. This cystic structure caused a mass effect and a midline shift towards the left, as well as hydrocephalus, possibly due to obstruction. Magnetic resonance imaging (MRI) of the brain showed cystic signal intensity similar to that of CSF, without ring enhancement or oedema [fig 2].   Fig 1 (a): Pre-operative unenhanced CT scan which shows a large CSF density cystic lesion on the right side causing mass effect and midline shift to the left. There is no peri-lesional oedema. Fig 1 (b): Post-operative CT scan of the lesion shows a large void which can lead to dangerous collapse. Mild haematoma is also seen. Fig 2 (a): T1-weighted axial MRI of the brain demonstrates a cyst density similar to CSF. Fig 2 (b): T2-weighted MRI shows no ring enhancement or oedema. The periventricular hyperintensity of the left side is probably due to obstructive hydrocephalus. Fig 3: This shows the cyst removed in toto after operation. The cyst appears creamy and smooth. After summation of all the above data, the diagnosis of a hydatid cyst was made and a right frontotemporoparietal craniotomy was performed. A large cystic structure (14×14×12 cm) was delivered with utmost care to avoid rupture and spillage [fig 3]. A hydatid cyst was confirmed by pathology reports.  A post-operative CT scan showed a large space without any residual matter [fig 1(b)]. Post-operatively, albendazole 15 mg/kg was started and continued for four weeks. The patient showed marked improvement in his neurological deficit and was discharged after one week with close follow-up. Discussion/Review Of Literature Life CycleHydatidosis is caused by Echinococcus granulosus, which occurs mainly in dogs. Humans who act as intermediate hosts get infected incidentally by ingesting eggs from the faeces of the infected animal. The eggs hatch inside the intestines and penetrate the walls, entering blood vessels and eventually reach the liver where they may form cysts or move on towards the lungs. Even after pulmonary filter, a few still make it to the systemic circulation and can lodge in almost any part of the body, including the brain, heart and bones.^{2,3,8,14,16,26} Brain hydatid cysts are relatively rare and only account for up to 2% of total cases.^4,5,7  The actual percentage may be higher than what we have in literature, due to under-reporting. Brain hydatid cysts can be primary (single) or secondary (multiple).^2,3,4,5,7 The latter are thought to arise from the multiple scolices released from the left side of the heart following cyst rupture in the heart^2,3,5,27 or due to spontaneous, traumatic or surgical rupture of a solitary cranial cyst.^3,5 Cysts mostly involve the territory of the middle cerebral artery^4,7 but other regions like intraventricular, posterior fossa and the orbit have also been reported.^15,17,18,28 The wall of the cyst consists of an inner endocyst (germinal layer) and outer ectocyst (laminated layer). The host reacts to the cyst forming a pericyst (fibrous capsule), which provides nutrients to the parasite. In the brain, due to minimal reaction, the pericyst is very thin. The endocyst produce scolices which bud into the cyst cavity and may sediment within the hydatid cavity, commonly known as hydatid sand.^3,14,29,30 Presentation and DiagnosisMost hydatid cysts are acquired in childhood and are manifested during early adulthood.^8,29 Cysts develop insidiously, usually being asymptomatic initially, and present with protean clinical and imaging features.^3,5,6 In previous studies the most common presenting symptoms were headache and vomiting.^{4,5,7,14,15,28} Also in the literature, patients reported ataxia, diplopia, hemiparesis, abducens nerve palsy and even coma.^5,7,15,28 Surprisingly, in the present study the patient did not have a headache and presented with parasthesia and numbness of the toes. Later he developed left sided weakness, convulsions and finally ataxia, which correlate with previous studies. Diagnosis of a hydatid cyst can sometimes be confused with other space occupying lesions of the brain, especially abscesses, neoplasms and arachnoid cysts.^14,31  In this study the patient had bilateral frank papilloedema which is also mentioned in earlier reports.^4,28  The Casoni and Weinberg tests, indirect haemagglutination, eosinophilia and ELISA are used in diagnosing hydatid cysts, but as brain tissue evokes minimal response many results tend to be false negatives.^2,5,8,25  In our case also, serology for hydatid cyst was negative. CT scan and MRI are used frequently in diagnosing the cystic lesions.^{3,8,14,23,32,33}  However, MRI is considered superior in demonstrating the cyst rim.^{5,8,11,21,32,34}  On CT scan, a solitary cyst appears as well-defined, spherical, smooth, thin-walled and homogeneous, with an inner density similar to CSF, and non-enhancing walls.^11,29,32The wall may appear iso-dense to hyper-dense on CT scan^3,8, and rarely, may become calcified.^11,29,32 There is usually no surrounding brain parenchymal oedema, which if exists along with ring enhancement, indicates inflammation and infection. ^{7,11,32,33,34,35} Ring enhancement and peri-lesional oedema differentiates brain abscesses and cystic neoplasms from uncomplicated hydatid cysts.^3,8 These findings can in fact sometimes cause dilemma and misdiagnosis and lead to catastrophic events.¹⁴ The cyst shows low signal intensity on T1-weighted, and high signal intensity on T2-weighted MRI.² MRI may also show peri-lesional oedema not seen on regular CT scan imaging.⁷ MRI may prove superior in determining exact cyst location, presence of super-added infections and cystic contents, and also in surgical planning and ruling out other diagnostic possibilities.^14,33 We strongly recommend MRI for better evaluation of cystic brain lesions. Spontaneous cystic rupture can lead to different appearances depending on which layers have been obliterated, and produce some specific signs.³ When only the endocyst ruptures, cyst contents are held by the outer pericyst giving a peculiar water lily sign, which is pathognomic.^3,8 TreatmentThough still in infancy, medical therapy for small or inoperable brain hydatid cysts has been promising. Albendazole alone or in combination with other compounds, such as praziquantel, has been reported with favourable results as an adjunct and, in certain circumstances, as the primary mode of treatment.^2,36,37,38 It is reported that albendazole results in the disappearance of up to 48% of cysts and a substantial reduction in size of the cysts in another 28%.² The duration of the treatment is four weeks or more, and recently many authors have favoured a prolonged therapy. The change in levels of cyst markers such as alanine, succinate, acetate and lactate, measured before and during treatment on Proton Magnetic Resonance Spectroscopy (MRS), correlate well with shrinkage and resolution of cyst findings on conventional MRI and help in evaluating the efficacy of chemotherapy.³⁹ Cysts may drain into ventricles or rupture completely, causing spillage of contents into the subarachnoid space, leading to fatal anaphylactic shock, meningitis or local recurrence.^3,5,22,25 Surgery is the mainstay for treating intracranial hydatid cysts and the aim is to excise the cysts entirely without rupture, which can otherwise lead to catastrophic events as described earlier ^2,3,14,25. The Dowling-Orlando technique remains the preferred method, in which the cyst can be delivered by lowering the head of the operating table and instilling warm saline between the cyst and the surrounding brain.⁴⁰ Even minimal spillage can cause deleterious effects (1 ml of hydatid sand contains 400,000 scolices).¹⁴ The thin cyst wall, periventricular location and micro-adhesions to the parenchyma are the main problems encountered during the surgical procedure.^1,22 The large cavity remaining after the cystic removal can lead to many serious complications, such as cortical collapse, hyperpyrexia, brain oedema and cardio-respiratory failure.⁵ Recurrence remains a major concern, which is managed by both antihelminthic chemotherapy and surgery. In a study conducted by Ciurea et al, 25% of the patients had recurrence, which highlights the need for long term follow up.²³ In the present study, due to the huge size of the cyst and progressive neurological deficit, it was not wise to completely rely on medical therapy. Surgery was performed and post-operatively albendazole was started as an adjunct. We recommend that for treating brain hydatid cyst, the size of the cyst, multiplicity, location and neurological deficit must all be taken into consideration. 

Introduction                                                                                                                              

Myocardial ischemia from coronary artery vasospasm can lead to variety of presentation including stable angina, unstable angina, myocardial infarction and sudden death ¹. Although, pathognomic clinical scenario includes symptom of chest pain, transient ST-segment elevation on the electrocardiogram(ECG), and vasospasm on a coronary angiography, atypical presentations have also been reported ². Various known physiological factors including stress, cold, hyperventilation and pharmacological agents including cocaine, ethanol, 5-Fluouracil, and triptans can precipitate a vasospastic attack. ^3-7.We report a case of ST-segment elevation due to right coronary artery vasospasm, in patient with hypoxic respiratory failure, and successful treatment with calcium channel blockers.

A 75 year old woman with a history of prosthetic mitral valve replacement, atrial fibrillation & TIA on warfarin was scheduled for TURBT to be done under spinal anaesthetic. Warfarin was stopped one day prior to admission and heparin infusion commenced on admission, with target APTT 2.5 times the normal. Heparin was stopped 4 hours prior to the spinal anaesthetic, which was difficult due to ankylosing spondylitis and needed four attempts. However, after an atraumatic tap and good sensory motor block, surgery was commenced without incident. Post-operatively, the patient developed a lower respiratory tract infection for which co-amoxyclav was commenced. On the fourth day post-op, the patient developed sudden onset, right leg weakness and paraesthesia, with right lower limb power 3/5, decreased tone and absent reflexes, leading to the diagnosis of a spinal haematoma post spinal anaesthesia. However on further examination, she was also noted to be anaemic with a drop in haemoglobin to 6g/dl, with an INR of 3.4 and an acute renal impairment with a serum creatinine of 120. In addition, bruising in the right flank, abdominal pain and a right iliac fossa mass were also noted. An urgent MRI was booked, but as the patient was haemodynamically unstable, a CT scan was deemed more appropriate, which showed a retroperitoneal bleed into the right illio-psoas. This was confirmed with a spinal MRI done subsequently, which also ruled out any spinal haematoma. The patient was treated conservatively with 5units PCV and 3units FFP. Her clotting profile gradually normalised as did her renal function and her right sensory-motor deficit continues to improve.   

                                                 Discussion: Retroperitoneal bleed The predilection for bleeding into the retroperitoneal space has not been fully explained but a unique weakness of the vascular and connective tissue has been suggested.² It is also most commonly seen in association with patients on anticoagulation therapy or haemodialysis, or with bleeding abnormalities,³ and may represent one of the most serious and potentially lethal complications of anticoagulation therapy. The incidence of retroperitoneal haematoma has been reported at 0.6-6.6% of patients undergoing therapeutic anticoagulation.^{4, 5, 6} Warfarin, unfractionated and low-molecular weight heparin have all been implicated.⁷ The risk of bleeding during unfractionated heparin therapy has been estimated to be two- to five fold greater than that with warfarin.⁸ However, it is nonetheless important to note that the therapeutic index of warfarin is narrow ⁹ and anticoagulant control is easily deranged by drugs (such as antibiotics) and co-morbid factors such as renal or hepatic dysfunction. Frequent INR measurement is the best way to avoid haemorrhagic complications. Patients report lower abdominal or hip pain radiating to the groin or anterior thigh. Bleeding into the psoas muscle causes spasm and hip flexion and, as it extends, flank or thigh bruising may appear. Femoral nerve compression reduces quadriceps power and causes loss of knee jerk and paraesthesia in the area of cutaneous supply. CT scan is the investigation of choice¹⁰ but ultrasound is also sensitive and is more rapidly available. Delay in diagnosis is potentially fatal because severe haemorrhage can supervene. Locally the haematoma may cause ureteric obstruction and acute renal failure, or femoral nerve compression.¹¹ (Both of which were seen in the case reported). Treatment options are surgery ¹² and conservative management consisting of treating the anaemia associated with the bleed and correcting the coagulopathy.¹³ Options to treat the coagulopathy would mainly depend on how quickly correction is required, to what range and how long normal clotting indices would be safe in a patient on therapeutic or treatment anticoagulation. Fresh frozen plasma (FFP at a dose 15ml/kg) is given for rapid but short-lived correction with the usual risks of transfusion of blood products. Vitamin K (>2.5mg) is given for a slower but more prolonged correction (leaving patients with artificial valves at risk of thromboembolic events and valve failure). Over-anticoagulation due to warfarin can be reversed completely and immediately by infusion of a complex concentrate of factors 2, 7, 9 and 10.¹⁴ Spinal haematoma The true incidence of spinal haematoma is unknown and due to its rarity it is very difficultto evaluate risk factors prospectively and any properly poweredstudy would require many thousands of patients to investigatethis. Therefore, data on the incidence of spinal haematoma followingneuraxial blockade are mainly based on audit studies and casereports. Tryba¹⁵ reported that the incidence of spinal haematoma afterepidural and spinal anaesthesia is 1 in 150,000 and 1 in 220,000, respectively. The insertion and removal of an epidural catheter appeared to be of far greater importance in the genesis of a spinal hematoma.^{16, 17} The incidence of spontaneous spinal haematomais rarer still and is estimated at 1 patient per 1,000,000 patientsper year. ¹⁸ Central neuraxial blockade has a low incidence of major complications, many of which resolve within 6 months. ¹⁹  The symptoms of an acute spinal hematoma include a sharp irradiating back pain of radicular character, and sensory and motor deficits which outlast the expected duration of the anaesthetic. Not all of these symptoms have to be present at the same time. The clinical suspicion can only be confirmed by means of an emergency CT-scan (with myelography) or magnetic resonance imaging.²⁰ The only treatment of a compressing spinal hematoma is an emergency decompressive laminectomy with evacuation of the hematoma. Final neurologic outcome depends on^{21, 22} the speed with which the hematoma develops; the severity of the preoperative neurologic deficit; the size of the hematoma; and most importantly, the time span between hematoma formation and surgical decompression. Complete recovery of neurologic function is possible if surgery is performed within 8 hours of the onset of the paraplegia. Conclusion The aim of this report is in no way to undermine the importance of Alderman’s advice to suspect the spine as an area of bleeding in patients on anticoagulant therapy. The above case is a reminder to consider retroperitoneal bleeding as one of the differential diagnoses of spinal haematoma in an anticoagulated patient who develops sudden onset spinal pain, with or without neurological deficit post spinal anaesthetic. The presenting symptoms are similar and early management is equally important in terms of associated morbidity when management is delayed.