Possible case of peripheral osmotic demyelination syndrome

Abstract

Central pontine myelinolysis (CPM) is an uncommon neurological syndrome that is usually related to the rapid restoration of a previous hyponatraemia. Although the most frequent location of CPM injury is the pons, it is now designated osmotic demyelination syndrome (ODS) because, as well as in the brainstem, these injuries can be observed in other parts of the central nervous system (CNS)–for example, the thalamus, subthalamic nucleus, external geniculate body, putamen, globus pallidum, internal capsule, white matter of cerebellum and the deep layers of the brain cortex. However, an exhaustive search of the literature (MEDLINE 1967–2007) has revealed no case report of peripheral nervous system (PNS) demyelination secondary to severe hyponatraemia.

BACKGROUND

Central pontine myelinolysis (CPM) is an uncommon neurological syndrome that is usually related to the rapid restoration of a previous hyponatraemia. Although the most frequent location of CPM injury is the pons, it is now designated osmotic demyelination syndrome (ODS) because, as well as in the brainstem, these injuries can be observed in other parts of the central nervous system (CNS)–for example, the thalamus, subthalamic nucleus, external geniculate body, putamen, globus pallidum, internal capsule, white matter of cerebellum and the deep layers of the brain cortex. However, an exhaustive search of the literature (MEDLINE 1967–2007) has revealed no case report of peripheral nervous system (PNS) demyelination secondary to severe hyponatraemia.

Experimental models of hyponatraemia have shown a marked fall in brain levels of several organic osmolytes during the first few hours after the metabolic insult, followed by a slow restoration over several days.¹ The rapid correction of hyponatraemia can lead to low brain concentrations of amino acids and creatine, even after serum sodium correction, producing a net shrinkage of the brain. A high sodium concentration without adequate concentrations of organic osmolytes may predispose the brain to osmotic injury.

CASE PRESENTATION

We present the case of a 35-year-old woman with a history of active alcohol abuse and no previous polyneuropathy. Three months before hospital admission, she presented with an intermittent diffuse encephalopathy, changes in behaviour and consciousness, and visual hallucinations. One week before admission, she became unable to walk and suffered a marked deterioration in consciousness, with an elevated consumption of up to 6–10 litres of liquids daily. A full evaluation on her admission to the Emergency area included analytical screening for the most frequent toxic metabolic encephalopathies and brain CT. Results indicated that the sole cause of her neurological deterioration was a plasma sodium concentration of 97 mg/dl with simultaneous urinary hypo-osmolarity. She was diagnosed with hyponatraemic encephalopathy and treated with oral liquid restriction and intravenous infusion of 0.9% normal saline or 7% hypertonic saline. After 2 days, her serum sodium was 135 mg/dl, an estimated rate of increase of 0.79 meq/l per hour.

Over the next few days, she developed a progressive flaccid tetraparesis (2–3/5 in distal vs. 4/5 in proximal muscle groups), with normal ankle and knee reflexes, bilateral Babinski signs and mild distal amyotrophies in both upper and low extremities. Neuropsychological examination at this time showed an anarthric mutism with acceptable comprehension of verbal language, affective lability but relatively normal mental status. She had poor left conjugate gaze and no perimetric defects. Low cranial nerve examination was consistent with bilateral velopalatine paralysis. A continuous myoclonic left facial jerk was observed. The remainder of the neurological examination was normal.

INVESTIGATIONS

Basic haematological and coagulation studies and biochemical determinations (basal glycaemia, renal function, transaminases, electrolytes, ammonia, albumin, thyroid function, hepatitis and HIV serologies, drug screening, immunological studies (antinuclear and anti-ganglioside antibodies) and porphyrins) were all normal or negative. Figure 1 depicts axial T2-weighted MRI sequences obtained, showing pontine demyelination. In the neurophysiological examination, compound muscle action potentials (CMAPs) in the lower bilateral tibial, superficial peroneal, median, ulnar, radial, musculocutaneous and circumflex nerves showed normal amplitudes and morphologies. Motor nerve velocities were bilaterally slow (peroneal nerves velocities <38 m/sec; ulnar nerves velocities <44 m/sec), with increased latencies (peroneal and median nerve distal latencies both >5 ms). Conduction blocks (CBs) with amplitude drop >80% were detected in the proximal tracts of the nerve trunks of the upper extremities other than typical compression sites or Erb’s point. Sensory nerve conduction velocity and sensory nerve action potentials were normal in all studied nerves

Figure 1. Pontine demyelination in axial T2 MRI sequences.

These findings were interpreted as suggesting bilateral and symmetrical motor demyelinating polyneuropathy in the lower and upper extremities.

OUTCOME AND FOLLOW-UP

A repeat neurophysiological study by the same examiner 3 weeks later showed an improvement in altered parameters and CNS symptoms. Skin temperature during examinations was not measured but was reported to be normal by the examiner.

DISCUSSION

We present an uncommon case of classic ODS with CNS damage and simultaneous acute demyelinating polyneuropathy. We hypothesise that a peripheral osmotic demyelination might have been the main pathogenic mechanism for the acute polyneuropathy. This hypothesis is supported by: the close chronological correlation of the central and peripheral symptoms produced by the metabolic event; the absence of axonal damage (suggesting absence of critical illness or porphyric polyneuropathies, the two main differential diagnoses) and the absence of other causes of peripheral demyelination–for example, parainfection or immunological disorder.

Critical illness polyneuropathy was our principal differential diagnosis. However, the neurophysiological data, including the normality of CMAPs, the presence of proximal CBs and the prolonged latencies, cannot be explained by this entity, suggesting that another mechanism must be implicated.

Although osmotic injury has been reported only in brain neurons, there is theoretically no reason why myelin pods in the PNS should not suffer similar damage. In this respect, it has been observed that high concentrations of anaesthetic in close contact with nerve roots or peripheral nerves can cause transient or permanent CBs, probably by an osmotic mechanism.² Moreover, cases of demyelinating neuropathy secondary to a metabolic insult have previously been reported. Thus, diabetes mellitus can be associated with chronic inflammatory demyelinating polyneuropathy.³ Finally, there have been observations of the same mechanism underlying both peripheral and central demyelination. For example, immunological demyelination can simultaneously affect the CNS and PNS.⁴

Nevertheless, an exhaustive search of the literature (MEDLINE 1967–2007) revealed no case of peripheral demyelinating neuropathy secondary to hyponatraemia or simultaneous with classic ODS. Lampl⁵ reviewed 174 cases of CPM in alcoholic patients published between 1986 and 2002. None showed the symptoms of the present patient, although most of them had not undergone a neurophysiological study.

In conclusion, it appears that severe osmotic stress may be able to damage central and peripheral myelin in the same way. A proportion of ODS cases may therefore have a subclinical peripheral neuropathy of osmotic aetiology. A systematic neurophysiological screening of an adequate sample of patients with ODS is required to test this hypothesis.

LEARNING POINTS

• The osmotic demyelination syndrome (ODS) occurs with rapid correction of low sodium and causes damage to the brain.

• No case of osmotic demyelination syndrome affecting the peripheral nervous system has been described.

• In the case described here central ODS was associated with new onset demyelinating peripheral neuropathy.