Treatment of central pontine myelinolysis with therapeutic plasmapheresis

Abstract

Central pontine myelinolysis (CPM) is a demyelinating disease of the brainstem but rarely found in other cerebral regions. Signs of pseudobulbar palsy with dysphagia and dysarthria, paraparesis or quadriparesis are first symptoms, which usually appear within 2–6 days after correction of hyponatraemia. CPM is also associated with chronic alcohol abuse or liver transplantation. Magnetic resonance imaging confirms the diagnosis of CPM. The disease has a poor prognosis and no effective treatment is established. The lesions are characterised by a loss of oligodendrocytes and myelin with preserved neuronal cell bodies and axons. The histological similarity of CPM lesions with lesions from other demyelinating disorders, like multiple sclerosis, may lead to the assumption that these lesions have the same pathogenetic pathway. However, the background remains unclear. In three cases with CPM we did extensive therapeutic plasmapheresis immediately after confirmation by magnetic resonance imaging (figure). A 29-year-old female patient with chronic alcohol abuse was admitted to hospital with nausea and diarrhoea. Hyponatraemia (107 mmol/L) was rapidly corrected with isotonic saline. 3 days later she had pseudoflabby tetraparesis, absent deep-tendon reflexes in the extremities, and abnormal bulbar movements. Plasmapheresis started with daily sessions over 4 days changing to twice a week for a further 3 weeks. In total 24 700 mL plasma was exchanged with albumin and cristalloid solutions. Tetraplegia resolved within 2 months. Silent signs of ataxia remained after 1 year. In a second case a 20-year-old female patient with anorexia nervosa (21 kg) was admitted to the hospital with diarrhoea and a sporadic seizure. Hyponatraemia (106 mmol/L) was slowly adjusted over 5 days to normal values. She then became somnolent and a complete spastic tetraparesis occurred together with dysarthria, dysphagia, and bulbar movement disorders. 5243 mL plasma was withdrawn in five plasmapheresis sessions. Equal amounts of albumin and cristalloid solutions were infused. One month later she was able to walk with assistance. The mental status test showed an impaired intermediate-term memory. In the third case a 30-year-old female patient with pneumonia and a history of chronic alcoholic abuse was referred to our hospital. After 2 weeks of treatment with cephalasporine mild hyponatraemia was corrected slowly over 5 days. At the third day of infusion therapy the patient became lethargic and the extremities were flaccid, with reduced deep-tendon reflexes. The neurological examination showed a pseudobulbar palsy with persistent nystagmus, dysphagia, dysarthria and tetraparesis. Therapeutic plasmapheresis was done over 7 weeks. 18 270 mL plasma was exchanged with albumin and cristalloids. Mild ataxia improved to total remission after 12 months. The pontine lesions appeared unchanged in the magnetic resonance imaging even 6 months after treatment in all patients. We suppose that osmotic stress may release myelinotoxic compounds, which then cause the irreversible demyelination. Therapeutic plasmapheresis may reduce high-molecular myelinotoxic substances and therefore lead to clinical improvement. However, immediate therapeutic plasmaheresis should be considered as a safe and effective method to improve the clinical outcome of patients with CPM.