Hyponatraemia presenting as reversible cerebellar ataxia in Addison’s disease

Abstract

Addison’s disease is a common endocrinopathy often diagnosed in patients presenting with hyponatraemia. Cerebellar ataxia as a presentation of hyponatraemia is extremely rare. A 42-year-old man presented with vomiting, fever, ataxic gait and scanning type of dysarthria. Clinical examination revealed signs suggestive of isolated cerebellar involvement. Patient was found to have severe hyponatraemia and serum cortisol was found to be extremely low while MRI brain was found to be normal. Corticosteroid therapy was initiated and cerebellar ataxia was resolved following normalisation of sodium levels.

Background

Hyponatraemia is known to cause an array of symptoms and clinical signs ranging from simple nausea and vomiting to seizures. Instances of respiratory arrest have also been documented. The presence of cerebellar ataxia in a patient due to reduced sodium levels is unusual and rare in the absence of osmotic demyelination or other organic cerebellar lesions. There are only six cases of reversible cerebellar ataxia due to hyponatraemia which have been described in clinical literature and this particular patient is the only one in whom hyponatraemia was attributed to Addison’s disease.

Case presentation

A 42-year-old man presented to our emergency department with complaints of fever, intermittent vomiting and decreased alertness for 1 week. He also complained of swaying to both sides on walking as well as slurring of speech which was slow in onset and worsened over the last 3 days. His relatives mentioned that he had significant weight loss and darkening of skin for a duration of 1 month. He was not on any chronic medications and was a teetotaller. He was not a vegan by diet and his siblings had no similar complaints. He had no known comorbidities or any history of tuberculosis in a close contact. On examination he was afebrile, drowsy but oriented to time, place and person, slow to respond but obeyed simple commands while having an increased reaction time. He had hyperpigmentation of his palms and oral mucosa (figure 1).

Figure 1.

Hyperpigmentation of mucosa and palmar creases.

Blood pressure recorded at time of presentation was 90/50 mm Hg in supine position. Postural drop of blood pressure could not be elicited as the patient had severe stance ataxia. Detailed nervous system examination revealed bilateral cerebellar signs such as impaired finger–nose test, heel–knee test, gait ataxia and scanning type of dysarthria. He had no signs suggestive of pyramidal tract, sensory system or cranial nerves involvement. He had no neck rigidity or photophobia.

Investigations

Basic investigations revealed haemoglobin of 112 g/L, total white cell count of 4.4×10⁹ cells/L (differential count was normal) and platelet count of 361×10⁹ cells/L. Renal and electrolyte profile showed blood urea nitrogen 3.57 mmol/L, serum creatinine 53.04 µmol/L, sodium 111 mmol/L, potassium 5.5 mmol/L, chloride 83 mmol/L and bicarbonate 16 mmol/L. Erythrocyte sedimentation rate was 68 mm/hour, serum osmolality 230 mOsm/kg, urine osmolarity 270 mOsm/kg and urine spot sodium 153 mmol/L. The 8 am serum cortisol was 1.3 µg/dL (normal range: 8 –18 µg/dL). Liver function tests were also done and found to be normal. Cerebrospinal fluid (CSF) analysis showed no significant findings and MRI brain done showed a normal study. Thyroid function tests were found to be within normal limits. Although serum adrenocorticotropic hormone (ACTH) level is essential to confirm the type of adrenal failure, it was not done for our patient as the clinical sign of hyperpigmentation indicates increased ACTH and melanocyte-stimulating hormone production from the anterior pituitary which is suggestive of primary adrenal failure. However, it is advisable to do serum ACTH level in case of adrenal insufficiency for a case-based learning.

Differential diagnosis

1. Primary adrenal insufficiency: This diagnosis was regarded most likely considering the presentation of darkening of skin and mucous membrane and blood reports confirming low cortisol levels, though the aetiology of primary adrenal insufficiency was at large and needed to be evaluated.

2. Osmotic demyelination (extrapontine): Another important differential diagnosis that was contemplated with regards to low sodium levels and cerebellar involvement but MRI brain showed no cerebellar lesions or any evidence suggesting demyelination.

3. Probable meningoencephalitis: India being a developing country has a high prevalence of meningoencephalitis. This patient presented with fever and neurological signs suggestive of cerebellitis but CSF studies turned out to be normal.

4. Wernicke encephalopathy was also considered which has ataxia as one of the components of the triad but the patient was not confused but rather oriented to time, place and person while being a little drowsy. Also he did not have ophthalmoplegia. It is known that persistent vomiting can cause Wernicke’s encephalopathy in persons who do not consume alcohol.

5. Cerebral venous sinus thrombosis: Although rare case reports have suggested that severe dehydration can cause cerebral venous sinus thrombosis which may also present with neurological deficits, the patient’s neuroimaging ruled out the presence of any cerebral venous sinus thrombosis.

6. Acute intermittent porphyria (AIP): Vomiting and neurological deficits are in favour of AIP but the patient had no abdominal pain nor did imaging show features suggestive of posterior reversible encephalopathy syndrome, which is usually present in patients diagnosed with AIP and having central nervous system involvement.

Treatment

Once the diagnosis of primary adrenal insufficiency was confirmed, the patient was started on steroid replacement therapy (intravenous hydrocortisone 100 mg twice daily). As hydrocortisone is known to have intrinsic mineralocorticoid activity, additional mineralocorticoid replacement was planned based on the patient’s clinical improvement. Serum sodium levels gradually improved in conjunction to improvement in clinical status. Both serum sodium and potassium normalised over 1 week of treatment with steroid and intravenous isotonic saline. Going ahead to evaluate the cause of primary adrenal insufficiency, a CT abdomen was done which revealed an enlarged right adrenal gland with an ill-defined lesion with few non-enhancing areas (figure 2), enlarged left adrenal gland and two necrotic lymph nodes in the anterior abdominal wall (the nodes could not be biopsied due to their small size). A CT thorax was done which showed the presence of fibrotic stranding of the upper lobe of the right lung and few scattered calcified nodules in the upper zones of both lungs. Bronchoscopy was performed and it showed no significant abnormality. Bronchoalveolar lavage was sent for GeneXpert which turned out to be negative.

Figure 2.

CT image showing bilateral enlarged adrenal glands.

After a panel discussion involving the radiologist and infectious disease specialist, it was unanimously concluded that the imaging findings were suggestive of tuberculosis adrenalitis as it is the most common cause of adrenal insufficiency in our country. The possibility of a lymphoma was considered but as the patient had normal blood differentials it was decided that further investigations would be warranted if there was no radiological resolution with antitubercular drugs. The patient was started on antitubercular drugs (2-month intensive phase with isoniazid, rifampicin, ethambutol and pyrazinamide followed by a 4-month continuation phase with isoniazid, ethambutol and rifampicin). With improvement in the sodium concentration, the patient’s cerebellar signs improved and by the 14th day ataxia and dysarthria had completely resolved (video 1).

Video 1.

Download video file ^{(7.8MB, mp4)}

DOI: 10.1136/bcr-2018-227933.video01

Patient having a slow scanning speech on the day of presentation. Patient on day 14 of hospital stay showed normalisation of the speech pattern. Notice the difference in the word ‘Saani-kumdi’.

Outcome and follow-up

Patient is on regular follow-up. He was discharged with oral hydrocortisone 25 mg/day (15 mg in the morning and 10 mg 2 hours after lunch) and antitubercular drugs. He did not have any recurrence of the symptoms and is doing fairly well with his daily activities and work. Serum electrolytes on review showed sodium 138 mmol/L, potassium 4.0 mmol/L, chloride 101 mmol/L and bicarbonate 22 mmol/L. Repeat imaging after 2 months of treatment showed resolution of the ill-defined lesion and non-enhancing areas on the adrenal glands with reduction in size. The above findings reassured us that the probable aetiology of primary adrenal insufficiency was due to tuberculosis.

Discussion

Hyponatraemia is known to have a varied spectrum of clinical presentations predominantly involving the gastrointestinal and central nervous systems.¹ Common gastric symptoms include vomiting, nausea and loss of appetite. It was found that extent of neurological symptoms due to hyponatraemia had a correlation to the concentration of serum sodium levels and is in turn attributed to the swelling of the brain as a result of overhydration of cells. Lower degree of hyponatraemia usually presents with prominent dizziness and lethargy. As hyponatraemia worsens, it sets in weakness, lethargy, restlessness, delirium and confusion. Muscle twitching, tremors and seizures have also been described. Focal neurological deficits such as aphasia, ataxia and generalised rigidity were also documented as rare manifestations of hyponatraemia in the absence of an organic parenchymal lesion of the brain.¹ Hyponatraemia-induced ataxia can be attributed to decreased glutamate uptake in the cerebellum. It has been established that low sodium levels cause increased release of glutamate from brain cells which plays an important role in hyponatraemia-induced ataxia.²

Our patient presented with swaying to sides while walking and also had an ataxic dysarthric speech pattern. Clinical examination was also suggestive of a cerebellar involvement. Extra-pontine myelinolysis, cerebellitis and meningoencephalitis were ruled out. Thus, the features of cerebellar ataxia were attributed to being secondary to hyponatraemia as there was no organic parenchymal lesion of the brain which could correlate with the presentation. The symptoms also resolved following correction of serum sodium levels which was more in favour with the above argument. Rapid improvement of cerebellar signs was against extra-pontine myelinolysis in which the cerebellar signs and symptoms may take months to resolve even after normalisation of sodium levels.³

Cases with similar presentation of reversible cerebellar ataxia as a manifestation of hyponatraemia are rarely described in literature and to our knowledge only six case reports have been published. In each of those cases, the cause of hyponatraemia was attributed to SIADH (paraneoplastic manifestation of carcinoma of lung),⁴ diuretic induced,^{5 6} AIP⁷ and enteric fever.⁵ Our case is the only one where primary adrenal insufficiency was the cause of hyponatraemia. Given the high prevalence of primary adrenal insufficiency, our patient is the only one to have presented with reversible cerebellar ataxia.

Learning points.

• Reversible cerebellar ataxia must be taken into consideration as a manifestation of hyponatraemia.

• It is important to rule out other conditions that can cause cerebellar ataxia such as a cerebrovascular event or cerebellitis before attributing it to hyponatraemia.

• While treating hyponatraemia, it is important to prevent rapid correction as it can cause extra-pontine myelinolysis which can also present with cerebellar signs.