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Central pontine myelinolysis (CPM) develops due to acute hypernatremia from a normal baseline serum sodium in the setting of electrolyte abnormalities induced by topiramate use. Topiramate is a commonly used medication with several indications including migraines, myoclonic jerks and seizures. It has been reported to cause renal tubular acidosis and severe electrolyte abnormalities, which in turn predispose patients to neuropathology via renal concentration defects and osmotic shifts. Our patient is a 55-year-old woman with a history of multiple sclerosis and myoclonus on topiramate for several years who presented with weakness and was found to be profoundly hypokalemic. She went on to develop changes in mental status, motor deficits and evidence of CPM on MRI during her hospitalisation. Surprisingly, the patient never had hyponatremia; however, she had an acute rise in serum sodium from a normal baseline after fluid resuscitation with normal saline for hypotension during her admission.

Central pontine myelinolysis (CPM) is commonly associated with osmotic stress and rapid correction of hyponatraemia. It has rarely been reported in conjunction with malignancies. We report a case where CPM was not only associated with a new diagnosis of diffuse large B-cell lymphoma but was also a key presenting feature.

Central pontine myelinolysis is characterised by focal osmotic demyelination within the pons. Its clinical presentation varies, but may include acute paralysis, dysarthria and dysphagia. The cause is traditionally associated with overzealous correction of hyponatraemia in patients who are malnourished, alcoholic or chronically ill. However, it may develop in the context of normal serum sodium, since rapid gradient shifts in brainstem osmolalities can occur in other ways. We present an unusual example of central pontine myelinolysis caused by osmotic shifts secondary to hyperglycaemia in a person with type 1 diabetes mellitus and with consistently normal serum sodium concentrations.

Osmotic demyelination syndrome commonly affects the pons and infrequently involves the extrapontine region. We report a patient with severe hyponatraemia who developed osmotic demyelination syndrome as a consequence of rapid sodium correction. The condition manifested as acute severe parkinsonism, bilateral ptosis and gaze impairment. MRI revealed typical features of central pontine and extrapontine myelinolysis. The patient improved gradually after treatment with a combination of levodopa, intravenous immunoglobulin and dexamethasone. However, it is important to emphasise that the improvement of neurological symptoms is not necessarily causal with these experimental therapies.

A diagnosis of demyelination carries important therapeutic and prognostic implications. In most cases the diagnosis is made clinically, and involvement of the histopathologist is largely confined to postmortem confirmation and clinicopathological correlation. However, every now and then, accurate diagnosis of the presence or cause of demyelination before death hinges on the histopathological assessment. Recognition of demyelination depends on an awareness of this as a diagnostic possibility, and on the use of appropriate tinctorial and immunohistochemical stains to identify myelin, axons and inflammatory cells. In biopsy specimens, the critical distinction is usually from ischaemic or neoplastic disease, and the types of demyelinating disease most likely to be encountered are multiple sclerosis, acute‐disseminated encephalomyelitis, progressive multifocal leucoencephalopathy and extrapontine myelinolysis. Interpretation of the pathology has to be made in the context of the clinical, radiological and biochemical findings. Freezing of a small amount of fresh tissue allows for later virological studies, and electron microscopy is occasionally helpful for demonstration of viral particles.

Central pontine myelinolysis (CPM) was described by Adams and colleagues in 1959 as a disease affecting alcoholics and the malnourished.1 The concept was extended from 1962 with the recognition that lesions can occur outside the pons, so-called extrapontine myelinolysis (EPM). In 1976 a link between these disorders and the rapid correction of sodium in hyponatraemic patients was suggested, and by 1982 substantially established. In this review we discuss the clinical, pathological, and aetiological features of the disease, the dilemma facing clinicians treating patients with severe hyponatraemia, and treatment opportunities. ### Clinical manifestations #### Central pontine myelinolysis (CPM) Nothing has been added to the clinical description of CPM since the original report. The patient has usually gone through a biphasic clinical course, initially encephalopathic or presenting with seizures from hyponatraemia, then recovering rapidly as normonatraemia is restored, only to deteriorate several days later. The initial signs of the CPM, which reflect this second phase, include dysarthria and dysphagia (secondary to corticobulbar fibre involvement), a flaccid quadriparesis (from corticospinal tract involvement) which later becomes spastic, all from involvement of the basis pontis (fig 1); if the lesion extends into the tegmentum of the pons pupillary, oculomotor abnormalities may occur. There may be an apparent change in conscious level reflecting the “locked-in syndrome” that a large lesion in this site is particularly liable to produce. If lesions of EPM are also present the clinical picture may be very confusing, as added to the above, or even preceding, can be a variety of apparently psychiatric and behavioural changes and movement disorders (outlined below). Figure 1 A reminder of the anatomy of the pons; although included to clarify the anatomical terms, a small lesion is in fact present, illustrating how easily such lesions may be missed on cursory pathological examination. To summarise: “…whenever a patient who is gravely ill with alcoholism and malnutrition or …

An HIV positive black African woman presented with widespread lymphadenopathy and pancytopenia that had been ascribed to tuberculosis. Lymph node biopsy showed both Kaposi's sarcoma and multicentric Castleman's disease. Despite antiretroviral therapy and chemotherapy the patient deteriorated, developing confusion and dysphasia. A cranial magnetic resonance scan showed central pontine myelinolysis. Despite supportive therapy the patient died.

Central pontine myelinolysis (CPM) is a demyelinating disorder of central nervous system which involves central portion of the pons and sometimes extrapontine areas also. It is commonly reported in settings of hyponatraemia or its rapid correction, but in the last few years it has also been reported in patients with diabetes in the absence of electrolyte disturbances or correction of serum osmolality. Here we report a case of a 20-year-old female patient, with a known history of type 1 diabetes mellitus, who presented with acute onset spastic quadriparesis with dysarthria and mild ataxia which evolved over 2 weeks. Her MRI brain showed well-defined, bilateral symmetric hyperintense lesion involving central pons showing area of diffusion restriction which was consistent with CPM. Patient was treated conservatively and improved over a period of few weeks. To diagnose more number of cases, we should not overlook CPM in patients with diabetes.

A 31-year-old man was admitted to hospital with of anorexia, binge eating, and self induced vomiting. On admission, he showed a pronounced low weight and disturbance of the body image and was diagnosed as having anorexia nervosa. In addition, electrolyte abnormalities, mainly hypokalaemia, and increased serum renin and aldosterone concentrations were recorded, suggesting pseudo-Bartter syndrome as a complication. Under frequent monitoring of the serum potassium and sodium concentrations, serum electrolytes were gradually corrected, but brain magnetic resonance imaging revealed reversible central pontine myelinolysis (CPM). Although attention has been mainly paid to the association of CPM with rapid correction of hyponatraemia and abnormal osmolality, this case report strongly suggested the involvement of hypokalaemia in the pathogenesis of CPM.

A 40-year-old man was diagnosed with pancreatitis following cholecystectomy. During hospitalisation, he reported bilateral acute vision loss. His best-corrected visual acuity (BCVA) was counting fingers in the right eye and 20/200 in the left eye. Ocular fundus examination and optical coherence tomography revealed a slight alteration in the retinal nerve fibres in the nasal macular region. Automated perimetry revealed bilateral visual field defects affecting both temporal and nasal hemifields in a predominantly nasal distribution, and brain MRI confirmed symmetrical lesions within both lateral geniculate nuclei. BCVA was gradually recovered, reaching 20/20 within 6 weeks.

A 40-year-old man, a chronic alcoholic, presented with left-sided weakness of 2 days duration. Clinical examination revealed stable vitals and left hemiparesis. Routine biochemical examination was normal except for raised liver enzymes. CT of the brain was normal. A working diagnosis of anterior circulation stroke was made and the patient was started on antiplatelets and statins. The following day, he developed difficulty swallowing and quadriparesis. MRI revealed T2/fluid-attenuated inversion recovery hyperintensity with corresponding T1 hypointensity involving the central pons, crossing the midline and sparing the periphery (figure 1A–C). Diffusion-weighted imaging (DWI) showed restricted diffusion (figure 1D). MR angiography was normal (figure 2). Figure 1 (A) Axial T2-weighted image showing hyperintensity involving the basis pontis, crossing the midline and sparing the periphery. (B) Axial fluid-attenuated inversion recovery image showing non-suppression of the T2 hyperintense lesion. (C) Axial T1-weighted image showing corresponding hypointensity in the basis pontis. (D) Diffusion-weighted image showing restricted diffusion (apparent diffusion coefficient (ADC) map not available). Figure 2 MR angiogram of the patient is normal. A …

Parkinsonism as well as dystonic signs are rarely seen in central pontine myelinolysis and extrapontine myelinolysis. A 51year old woman developed central pontine myelinolysis and extrapontine myelinolysis with parkinsonism after severe vomiting which followed alcohol and drug intake, even though marked hyponatraemia had been corrected gradually over six days. Parkinsonism resolved four months after onset, but she then exhibited persistent retrocollis, spasmodic dysphonia, and focal dystonia of her left hand. Although the medical literature documents three similar patients, this patient is different as dystonic symptoms only developed four months after parkinsonian signs had resolved.

A 44-year-old female is described who developed persistent upper extremity and orolingual dystonia several weeks after suspected onset of central pontine myelinolysis (CPM), later confirmed by characteristic pontine lesions on MRI. No foci of the extrapontine myelinolysis were evident. This case confirms that dystonia may be a late and persistent sequela of CPM and may occur in the absence of visible lesions outside the brainstem.

A 25-year-old man presented with progressive impairment of consciousness, ocular bobbing and tetraparesis. Since the age of 3 he had received substitution therapy for central diabetes insipidus after surgical treatment of a craniopharyngioma. Accidental disruption of his intranasal desmopressin treatment 1 day before admission led to an increase of serum sodium of 29 mmol/L in less than 24 h. Initial MRI and cerebrospinal fluid examination were unobtrusive. Despite extensive symptomatic treatment the patient developed …

Central pontine myelinolysis (CPM), which is a component of the osmotic demyelination syndrome (ODS), is a frequent neurological complication that follows rapid correction of hyponatraemia. However, there are other predisposing risk factors (chronic alcoholism, hypokalaemia) that perpetuate the development of ODS. We report a case of a 39-year-old woman with a history of chronic alcoholism who presented to us with progressive neurological deficits (paraparesis, paresthesias). She was initially detected to have coexisting hypokalaemia which was eventually rectified with potassium supplementation. However, she continued to experience progressive worsening of her neurological symptoms despite adequate potassium supplementation. Therefore, a neurological opinion was sought for and she was diagnosed with CPM based on a background of chronic alcoholism and malnutrition; an MRI of the brain showed a hyperintense signal in the central pontine region. Following the diagnosis of CPM, she was rehabilitated with occupational and physiotherapy.

Amiddle aged man with a history of alcoholism and psychotic troubles was admitted to the emergency department with drowsiness that had been developing over the previous week. He had been treated with a carboxamide of valproic acid, citalopram, cyamemazine (neuroleptic), alimemazine (another antihistamine) and oxazepam. As well as chronic alcoholism, he had also suffered from recent compulsive water …

Patients with chronic alcoholism are commonly admitted to hospital and given intravenous fluids as part of the treatment of alcohol withdrawal. These patients are predisposed to chronic severe hyponatraemia because of a variety of mechanisms including psuedohyponatraemia, hypovolaemia, “beer” potomania syndrome, cerebral salt wasting syndrome, and reset osmostat syndrome.1 If hyponatraemia (serum sodium concentration < 136 mmol/l) is present it is important to correct this slowly, at a rate of less than 8 mmol/l/day to minimise the risk of developing osmotic demyelination syndrome, the general term for central pontine and extrapontine myelinolysis.2 A 42 year old man with chronic alcoholism presented with confusion. He had no significant medical history and was not taking any regular medications. On the day of admission his serum sodium concentration was 105 mmol/l at 5 pm. His serum was hypo-osmolar at 212 mmol/kg and his urine sodium concentration was 22 mmol/l, suggesting hypovolaemia. Over the next 11 hours he was given 1 litre of intravenous 0.9% saline with 40 mmol potassium chloride, followed by another litre over the subsequent 24 hours, as well as intravenous multivitamins (Pabrinex) and oral chlordiazepoxide. His …

A 48 year old man presented with a four day history of lethargy, dizziness, and an unsteady gait with recurrent falls, on a background of chronic alcohol misuse. The patient was taking desmopressin for nocturnal enuresis and bendroflumethiazide for hypertension, which were both stopped on admission. On physical examination he appeared clinically euvolaemic and he had no focal neurological deficit. Vital signs were within normal limits. Serum biochemistry showed sodium of 110 mmol/L (normal range 137-145; 1 mmol/L=1mEq/L) and potassium of 2.6 mmol/L (normal range 3.5-5.5 mmol/L). A computed tomogram of the brain that was performed to rule out traumatic brain injury was unremarkable. Fluids were subsequently restricted and he was started on parenteral thiamine, oral chlordiazepoxide, and intravenous 0.9% sodium chloride with potassium supplementation. Twenty four hours later, serum sodium was 119 mmol/L and serum potassium was 3.3 mmol/L. Serum sodium eventually reached 130 mmol/L on day 4. Seven days after admission he developed delirium and on examination had bilateral pyramidal weakness, more pronounced on the right. Reflexes were generally brisk, with bilateral extensor plantar responses. He also developed mild dysarthria but there was no dysphagia. A repeat computed tomogram of the brain was normal. Magnetic resonance imaging of the brain was subsequently performed to obtain better images of the brainstem and posterior fossa (fig 1⇓). Fig 1 Axial T2 weighted magnetic resonance imaging of the head ### 1 What does the magnetic resonance imaging scan show and what is the most likely diagnosis? #### Short answer A hyperintense triangular lesion in the central pons with peripheral sparing. In the clinical context of spastic quadriparesis, this is consistent with central pontine …

Case report A 56-year-old gentleman was referred to the A&E department following an episode of loss of consciousness. His medical and surgical history was unremarkable except for a background history of alcohol dependency. Serological tests revealed a serum sodium concentration of 118 mEq/l. The patient developed acute pseudobulbar palsy less than 24 h after admission and an urgent MRI of the brain was requested. Central pontine myelinolysis is an acute non-inflammatory demyelinating disorder first described …

A 50-year-old woman was brought to the emergency department with complaints of altered mental status, her serum sodium at that time was 103 mmol/l. Slow correction of hyponatraemia was started but despite every effort serum sodium rise was rapid. Although the patient improved initially, after 4 days she presented with features of parkinsonism. MRI brain was done and it was suggestive of features of EPM. She responded well to levodopa plus carbidopa therapy.

A 47-year-old patient with a history of chronic alcoholism was admitted to our hospital with sudden loss of consciousness, respiratory failure and severe hypernatraemia (173 mEq/l); he had no other alterations in routine laboratory analyses. During admittance he experienced mental status fluctuations and developed a spastic tetraparesis, a bilateral Babinski sign and a bilateral facial paresis (locked in status). Brain MRI (figure 1) showed symmetric lesions in the pons and thalami with …