Extrapontine Lesions Research Articles

Osmotic demyelination syndrome: novel risk factors and proposed pathophysiology.

Osmotic demyelination syndrome (ODS) is non-inflammatory demyelination in response to an osmotic challenge. It can be pontine or extrapontine in presentation. To retrospectively review cases involving ODS and define the spectrum of causes, risk factors, clinical and radiological presentations, and functional outcomes. The study utilised data from 15 patients with a mean age of 53.6 years. Malnutrition (9; 60%) and chronic alcoholism (10; 66.7%) were the most common associated disorders. Two (13.3%) patients had severe hyponatraemia (<120 mmol/L). The average highest single-day change was 5.1 mmol/L. Radiologically, 14 (93.3%) had pontine and 6 (40%) had extra-pontine lesions. Hypokalaemia (14; 93.3%) and hypophosphataemia (9; 60%) were commonly associated. Common clinical manifestations include altered consciousness/encephalopathy (9; 60%), dysphagia (4; 26.7%) and limb weakness (4; 26.7%). At 3months, two (14.3%) had died and six (40%) were functionally independent (modified Rankin scale 0-2). We found that ODS occurred despite appropriate correction rates of hyponatraemia. Factors such as malnutrition, chronic alcoholism, hypokalaemia and hypophosphataemia are thought to play a role in its pathogenesis. Approximately half of the patients survived and became functionally independent.

Hyponatremia, osmotic demyelination syndrome, and the importance of the patient’s history

Central pontine myelinolysis (CPM), first described in 1959, is a symmetrical non-inflammatory demyelinating disease with loss of oligodendrocytes that occurs most often following a rapid correction of severe hyponatremia (i.e., &lt;120 mmol/L). It presents as a biphasic disease with initial seizure or encephalopathy, followed by clinical improvement and subsequent rapid deterioration with bulbar dysfunction, oculomotor dysfunction, various degree of paresis, and even locked in syndrome. Its occurrence is rare (≈0.6% of severe hyponatremia), it is diagnosed clinically and confirmed with brain imaging, ideally with magnetic resonance image, and it is reversible in approximately half the patients. Lesions are classically identified in the pons but extra pontine lesions (in basal ganglia, cerebellar white matter, thalamus, and hippocampus) have also been identified. The most commonly accepted molecular mechanism involves brain cell volume regulation with a rapid shift of osmole following brain edema which establishes during the chronic hyponatremic phase. For these reasons, osmotic demyelination syndrome (ODS) is a better term. The most identified risk factor is severe hyponatremia, but other electrolyte abnormalities can contribute, in particular, if the patient is an alcoholic or malnourished. This diagnosis should also be suspected in post-op patients with nausea and headache non-responsive to antiemetic and analgesic drugs. An essential step is an appropriate medical history, a list of medications, physical examination, and basic initial lab tests with the goal of identifying possible easily reversible causes of hyponatremia. Correction of severe hyponatremia with neurological symptoms should be done using rapid boluses of hypertonic saline solution in rapid succession with goals of increasing serum sodium by 5-6 mEq/L in the first two hours, which should be stopped if the level has risen by 10 mEq/L in the first five hours, and with the overall correction goal not to exceed 15-20 mEq/L in 48 hrs. This method has been shown safe in all hospital settings studied. Serial measurements of electrolyte levels and neurological examinations are recommended, as are correction of all electrolyte abnormalities, in&#x0D; particular magnesium and potassium. Thiamine should be given to all patients with chronic alcohol use who present with hyponatremia and encephalopathy.

Extra-pontine lesions of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) (P4.074)

Extra-pontine lesions of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) (P4.074)

Osmotic demyelination syndrome in Intensive Care Unit.

Dyselectrolytemia, especially hyponatremia is a common occurrence in hospitalized patients, and a number of dreaded complications arise out of the disorder itself and its treatment. Osmotic demyelination syndrome develops secondary to rapid correction of hyponatremia. As the disease is rare and available literature from Intensive Care Units are limited, we report our retrospective observation over 5 years. Overall incidence was 2.5% with altered sensorium and hypokalemia as most common symptom and associated factor respectively. Isolated pontine involvement was in 41% and combined pontine, and extra-pontine lesions were found in 23% of cases. All patients received supportive therapy; out of which 2 died and complete neurological recovery was seen in 24% of patients. Our findings suggest that a well organized supportive therapy and multidisciplinary approach is of more concern than many available therapeutic modalities which are still to be proved.

More often striatal myelinolysis than pontine? A consecutive series of patients with osmotic demyelination syndrome

Introduction: Osmotic demyelination syndrome (ODS) is increasingly recognized to involve extrapontine locations in addition to the better-known central pontine myelinolysis.Aims: This study describes clinical and radiological features of consecutive patients with ODS detected over 1 year.Methods: Patients fulfilling clinical and radiological criteria for ODS were prospectively enrolled and were followed with serial assessments during hospital stay and up to 253 days after discharge.Results: Eight patients (five females) aged 24–89 years were enrolled, comprising 0·06% of all admissions to the general medical and neurology services. All had preceding hyponatraemia and hypokalaemia of various aetiologies. One patient developed ODS after postpartum pituitary haemorrhage, which has been reported only rarely. Sodium levels were corrected at maximal rates exceeding 8 mmol/l/day. Neurological symptoms attributed to ODS began 3–15 days after clinical improvement following sodium correction in four patients; the remainder did not show any intervening lucent interval. Fifty per cent were stuporous at admission, 50% had seizures, 62·5% had symmetric parkinsonism, and 75% had prominent primitive reflexes. Stretch reflexes were absent in 25% and normal or brisk in the remainder. Magnetic resonance imaging (MRI) showed symmetric striatal lesions in all patients, with concomitant pontine involvement in only 25%. Four patients had poor outcomes (modified Rankin score >3), with prognosis dependent on the presence of severe systemic illness, liver dysfunction, encephalopathy, seizures, and degree of disability upon discharge from hospital. Patients with parkinsonism responded to dopaminergic therapy, with chorea, dystonia, and depression as later developments. This series is remarkable for the high incidence of extrapontine lesions, much more common than pontine involvement.

Teaching Neuro Images : Neuroradiologic findings in pontine and extrapontine myelinolysis

A 58-year-old woman presented with subacute onset of tetraparesis, anarthria, and dysphagia after rapid correction of hyponatremia caused by repeated vomiting. Brain MRI showed pontine and extrapontine lesions typical for the osmotic demyelination syndrome (figure, A and B). The pontine …

Secondary tics after osmotic demyelination syndrome involving both the striatum and the cerebral cortex

Although some reports have associated parkinsonism, dystonia, and chorea with the extrapontine lesions of osmotic demyelination syndrome (ODS), to our knowledge delayed-onset tic disorder has not been reported. Thus, we report a rare secondary tic associated with ODS involving both the striatum and the cerebral cortex. We can hypothesize that aberrant neuronal plasticity after the initial insult in both basal ganglia and motor cortical areas could be implicated in the pathogenesis of delayed-onset tics.

Central Pontine and Extrapontine Myelinolysis that Developed during Alcohol Withdrawal, without Hyponatremia, in a Chronic Alcoholic

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are osmotic demyelination syndrome. A 45-year-old man with a history of alcoholism visited the ER with dysarthria and dysphagia for 2 days. These symptoms occurred 3 days after he had stopped drinking alcohol. The neurological symptoms progressed to anarthria, pseudobulbar palsy and gait disturbance. During admission, the electrolyte studies were within the normal range. Diffusion-weighted images revealed high signal intensities in the pons, thalamus and basal ganglia. Apparent diffusion coefficient image showed low signal intensities in the pontine lesion, but isosignal intensities in the extrapontine lesion. The symptoms gradually improved after 1 month with only conservative treatment. The 1 month-follow-up MRI showed significant reduction of the previous extrapontine lesions. These findings suggest that cytotoxic edema is central to the pathogenesis of CPM, but vasogenic edema plays an important role in the pathogenesis of EPM occurring during alcohol withdrawal.

Differential diagnosis of white matter diseases in the tropics: An overview.

In hospitals in the tropics, the availability of magnetic resonance imaging (MRI) facilities in urban areas and especially in teaching institutions have resulted in white matter diseases being frequently reported in a variety of clinical settings. Unlike the west where multiple sclerosis (MS) is the commonest white matter disease encountered, in the tropics, there are myriad causes for the same. Infectious and post infectious disorders probably account for the vast majority of these diseases. Human immunodeficiency virus (HIV) infection tops the list of infective conditions. Central nervous system (CNS) tuberculosis occasionally presents with patchy parenchymal lesions unaccompanied by meningeal involvement. Human T cell leukemia virus (HTLV) infection and cystic inflammatory lesions such as neurocysticercosis are important causes to be considered in the differential diagnosis. Diagnosing post infectious demyelinating disorders is equally challenging since more than a third of cases seen in the tropics do not present with history of past infection or vaccinations. Metabolic and deficiency disorders such as Wernicke's encephalopathy, osmotic demyelinating syndrome associated with extra pontine lesions and Vitamin B12 deficiency states can occassionaly cause confusion in diagnosis. This review considers a few important disorders which manifest with white matter changes on MRI and create diagnostic difficulties in a population in the tropics.

Cerebellar peduncular myelinolysis in a patient receiving hemodialysis

Here, we report the observation of extrapontine lesions, in addition to the pontine lesions previously documented in a diagnosed case of hemodialysis-associated osmotic demyelination syndrome due to end-stage renal disease. The patient exhibited lesions on bilateral middle cerebellar peduncles, and had been receiving regular hemodialysis as treatment for end-stage renal disease. He presented with progressive gait disturbance and postural instability. Accompanying symptoms included peduncular hallucinations and mild cognitive dysfunction. Brain MRI revealed high signal intensity in the area of bilateral cerebellar peduncles on the diffusion and T2-weighted images, with a decreased signal intensity noted on the ADC map. The ataxic form of osmotic myelinolysis syndrome is quite rare. The involvement of the cerebellar peduncles in extrapontine myelinolysis in a patient with end stage renal disease has not, to our knowledge, been previously reported. Here, we describe the MRI findings and clinical features associated with this unique case, and include a review of the relevant literature.

MR imaging of seven presumed cases of central pontine and extrapontine myelinolysis

MRI was performed in seven patients with presumed central pontine and extrapontine myelinolysis. The underlying diseases were diabetes, lung cancer, Wilson disease, trauma, alcoholism, renal insufficiency and hemodialysis. CPM was found in four cases (in two of them extrapontine lesions were considered as resulting from Wilson disease), CPM and EPM in three patients. The localization of extrapontine changes included cerebellum, cerebral peduncles, caudate and lentiform nuclei, internal capsules, white matter and cortex of the cerebrum.

Central pontine myelinolysis

Central pontine myelinolysis (CPM) was initially associated with alcoholism. Subsequently other factors, including rapid reversal of hyponatraemia and extreme serum hypoosmolality associated with severe burns, have been identified as other important factors in its pathogenesis. Extra-pontine lesions have also been described. CPM may be found at autopsy, either having been overlooked during life or as an incidental finding. Its precise incidence is not known but the ability to diagnose it during life has been helped by modern neuroimaging, particularly magnetic resonance imaging (MRI) of the brain stem. In the past the prognosis for CPM was thought to be invariably fatal. It is clear now that with the greater general awareness of the disorder and the ability to diagnose it during life that some degree of recovery is possible. However, the number who do recover and the degree of recovery is not known. We report a 40-year-old man who developed CPM presenting with quadriparesis and inability to speak and swallow. There were risk factors for CPM and the diagnosis was confirmed by MRI scanning. He made a complete recovery although he remains ataxic. We are reporting this case as we believe it is important to make clinicians aware of the potential for recovery of CPM. While no specific treatment has been shown to influence the degree and rate of recovery of the demyelination, the fact that the quadriplegia and bulbar paralysis can recover fully is of considerable importance. In particular, it means that when the diagnosis is made, complete and vigorous nursing and medical care is warranted.

Movimientos anormales en un caso de mielinólisis extrapontina. Revisión de la literatura

We present a case of extra-pontine myelinolysis caused by acute hypernatraemia in which a complex picture of late onset extrapyramdial features, choreodystonia and parkinsonism developed. Repeated physical examinations, neurophysiological and neuroimaging studies using magnetic resonance all indicated an extra-pontine site of the lesions, which symmetrically affected the striate and to a lesser extent both thalami. We review the relevant literature available and analyze the cases described as having abnormal movements associated with a myelinolytic syndrome. Extra-pontine myelinolysis is a cause of acquired dystonia, chorea and parkinsonism, generally of late onset and with varying response to treatment. The association of hypernatraemia, hyperglycaemia and liver transplant seem to predispose to the development of extra-pontine lesions.

Pontine and Extrapontine Myelinolysis

Neurologic disorders developing after correction of severe, symptomatic hyponatremia were studied in 14 patients. None had a hypoxic event or other identifiable cause for the neurologic illness. Neurologic deterioration began about 3 days after correction and often followed a period of improvement in hyponatremic encephalopathy. Although the symptoms were as mild as transient confusion in 1 patient, they were more severe in the others. Typically, spastic quadriparesis, pseudobulbar palsy, and impairment in the level of consciousness progressed for up to 7 days. Improvement generally began 2 weeks after correction and continued for up to a year in some patients. Routine spinal fluid analysis was usually normal, but myelin basic protein concentration was elevated in all patients in whom it was measured. Electroencephalograms commonly showed nonfocal slowing. Brainstem auditory evoked potential latencies were prolonged in some patients. Brain imaging was normal in the initial week of illness, while later scans, obtained in 9 patients, showed central pontine and/or symmetric extrapontine lesions. The clinical manifestations and distribution of lesions seen on imaging demonstrate that neurologic illness following correction of hyponatremia is due to myelinolysis. Although this neurologic disorder typically followed an elevation in serum sodium > 18 mEq/L/24 hr, it sometimes followed a rise as slow as 10 mEq/L/24 hr and 21 mEq/L/48 hr. Whenever possible, the rate of correction of hyponatremia should be kept below these values in order to minimize the risk of myelinolysis.