Description
Osmotic demyelination syndrome (ODS), also known as central pontine myelinolysis (CPM) and extrapontine myelinolysis, is a neurological disorder characterised by the destruction of myelin sheaths in the brain due to rapid changes in osmolality, particularly associated with the rapid correction of hyponatraemia. ODS can occur in the pons (CPM) or other parts of the brain (extrapontine myelinolysis). The condition is most common in adults, particularly those with a history of chronic alcoholism, malnutrition, or liver transplantation. The term “osmotic” refers to the shift in fluid balance, “demyelination” refers to the loss of myelin sheaths, and “syndrome” signifies the collection of symptoms that arise from these changes.
Pathogenesis
ODS primarily affects the central nervous system (CNS), specifically targeting the myelin sheaths that insulate nerve fibres, which are essential for rapid signal conduction. The pathogenesis involves rapid correction of chronic hyponatraemia, leading to a sudden shift in osmotic balance. This shift causes cellular stress and damage, particularly in oligodendrocytes, which are responsible for myelin production. The breakdown of the blood-brain barrier and subsequent infiltration of inflammatory cells further exacerbate demyelination. Anatomically, the pons is frequently affected due to its unique vulnerability to osmotic shifts, but other regions such as the basal ganglia and thalamus can also be involved.
Subtypes
ODS is divided into two main subtypes based on the location of demyelination:
- Central Pontine Myelinolysis (CPM): Demyelination primarily in the pons.
- Extrapontine Myelinolysis (EPM): Demyelination occurs in areas outside the pons, such as the basal ganglia, thalamus, and cortex.
Epidemiology, Risk Factors & Associations
- Most common in adults.
- No significant gender predilection.
- Greatest risk factors:
- Chronic alcoholism (50% of cases)
- Malnutrition
- Liver transplantation (20%)
- Rapid correction of hyponatraemia
- Most common associations:
- Chronic liver disease
- Electrolyte imbalances
- Severe burns
Clinical Features
- Acute or subacute onset of symptoms following rapid correction of hyponatraemia.
- Dysarthria and dysphagia.
- Quadriparesis or paraparesis.
- Altered mental status ranging from confusion to coma.
- Movement disorders, including parkinsonism.
- Locked-in syndrome in severe cases, where patients are aware but unable to move or communicate verbally due to extensive pontine involvement.
Complications
- Permanent neurological deficits.
Pathological Features
Histopathology
- Macroscopic: Symmetrical, well-demarcated areas of demyelination.
- Microscopic: Loss of myelin with relative preservation of axons, gliosis, and presence of foamy macrophages.
Radiological Features
General Features
- Best seen on MRI with T2-weighted and FLAIR sequences.
- Predominantly in the central pons involving the transverse pontine fibres.
- The ventrolateral pons and the pontine portion of the corticospinal tracts are typically spared.
- Sites of extrapontine myelinolysis include:
- Basal ganglia and cerebral white matter
- Peripheral cortex, hippocampi and lateral geniculate bodies – less commonly.
- Extrapontine myelinolysis occurs in conjunction with central pontine myelinolysis; however, it may also be seen in isolation.
- Pitfalls: Misdiagnosis as stroke, tumour, or infection without proper clinical correlation.
MRI
- T1: Hypointense or isointense lesions in the pons.
- T2/FLAIR: Symmetrical hyperintense lesions in the central pons with sparing of the outermost lateral pontine fibres giving a trident or bat-wing appearance.
- DWI/ADC: May show restricted diffusion in acute phases.
- T1 Gad+: Typically no enhancement.
- SWI/GRE: Not typically used.
- In-Out-Phase: Not applicable.
CT
- Non-contrast: May show hypoattenuation in the pons but less sensitive than MRI.
- C+ Arterial: Not typically used.
- C+ Venous: Not typically used.
Grading and Staging
No specific grading or staging system for ODS. Severity is assessed based on the extent of neurological impairment and radiological findings.
Diagnosis
- Clinical history and presentation, particularly rapid correction of hyponatraemia.
- Confirmation by MRI findings showing characteristic demyelination patterns.
Differential Diagnosis
Image-based
- Brainstem Stroke: Typically presents acutely with focal neurological deficits, with hyperintense areas on DWI but different distribution.
- Multiple Sclerosis: Demyelinating lesions scattered throughout the CNS, often with periventricular and corpus callosum involvement.
- Metabolic Encephalopathies: Diffuse cerebral involvement, less specific to pons.
- Infections (e.g., Progressive Multifocal Leukoencephalopathy): Viral inclusions on biopsy, different clinical context and distribution.
- Tumours: Mass effect, enhancement, and usually lack symmetry.
Clinically-based
- Hyponatraemia-related Encephalopathy: Symptoms resolve with correction of sodium levels without imaging evidence of demyelination.
- Wernicke’s Encephalopathy: Triad of ophthalmoplegia, ataxia, and confusion, associated with thiamine deficiency, typically with periventricular lesions on MRI.
- Alcohol Withdrawal Syndrome: Symptoms of agitation, tremor, and hallucinations, responding to benzodiazepines, without demyelinating lesions on imaging.
Management
- Referral to neurology.
- Slow and controlled correction of hyponatraemia to prevent ODS.
- Supportive care for neurological deficits.
- Rehabilitation for motor and speech impairments.