Postgrad Med J 1995; 71: 430-442 i) The Fellowship of Postgraduate Medicine, 1995

Short reports

Central pontine myelinolysis: clinical and MRIcorrelates

PJ Martin, CA Young

Department ofNeurology, TheWalton Centre forNeurology andNeurosurgery,Rice Lane, LiverpoolL9 1AE, UKPJ MartinCA Young

Accepted 2 February 1995

SummaryCentral pontine myelinolysis (CPM) is arare condition characterised by spastictetraparesis, pseudobulbar palsy and the'locked-in syndrome'. It is frequentlyfatal. We report a patient who developedCPM secondary to profound hyponat-raemia and who recovered with nodisability. Serial magnetic resonanceimaging (MRI) demonstrated charac-teristic abnormalities within the ponsat the onset of the disease, whereascomputerised tomography was normal.Clinical improvement was followed sixmonths later by progressive resolution ofthe MRI changes, with almost completeresolution after 18 months. Clinical andMRI findings correlate early in the courseof CPM but clinical recovery predatesMRI improvement by several months.

Keywords: central pontine myelinolysis, magneticresonance imaging

Central pontine myelinolysis (CPM) is an in-frequent condition characterised by loss ofmyelin in the central pons, sometimesaccompanied by areas of extra-pontine demye-lination. It was originally described inhyponatraemic patients with a history ofalcohol abuse' but more recently has beendocumented following liver transplantation2and in patients with hypokalaemia. Almostinvariably it occurs in the hospital setting inassociation with correction of the electrolytedisturbance, and it frequently results in death.We report a patient with CPM who made a fullrecovery and in whom serial magneticresonance imaging (MRI) showed progressiveresolution of the initial characteristic pontinechanges.

Case report

A 25-year-old man with a history of alcoholabuse was admitted to a local general hospitalhaving suffered prolonged vomiting followingan alcoholic binge. There was no evidentneurological deficit, but the serum sodium was105 mmol/l. There were no other biochemicalabnormalities apart from elevated liver en-zymes. The hyponatraemia was corrected usinga normal saline infusion (0.9%/; 130 mmol/l).Over the next 48 hours the serum sodium roseto 122 mmol/l, and it rose further to 138 mmol/l

during the ensuing five days. It then remainedwithin the normal range.

Seven days after admission, he developed aprogressive spastic tetraparesis with mixedbulbar and pseudobulbar palsy, dysphagia andanarthria. Computed tomography (CT) of thebrain was normal. He was transferred to aneurological centre and underwent MRI usingstandard Ti- and T2-weighted sequences at1.5 Tesla (Magnetom, Siemens). Ti- and T2-weighted sagittal sections and T2-weightedaxial views revealed extensive signal abnor-malities in the pons, consistent with mye-linolysis (figure, A). There was no evidence ofextra-pontine myelinolysis.The patient's condition gradually improved

over the next four weeks, such that he was ableto walk, speak and swallow. Repeat MRIshowed appearances similar to the original scan(figure, B). Despite the clinical improvement,there was no significant improvement in theradiological findings. He was discharged to hisown home two weeks later.

After a further six months the patient waswalking independently and was fully self-caring. Further MRI showed some resolutionof the abnormality within the pons (figure, C).One year later, the patient was fully recoveredand had returned to work. A further MRI scanshowed almost complete resolution of theprevious pontine abnormalities (figure, D).

Discussion

Originally, CPM was a clinical diagnosis char-acterised by the progressive onset of tetra-paresis and pseudobulbar palsy, with furtherprogression to a 'locked-in' state. The six-month survival rate of CPM is only between 5and 10%.4 Imaging using CT usually fails toreveal any abnormality although sometimesareas of reduced attenuation compatible withmyelin loss are apparent.5 Brainstem evokedpotentials may be of some help in localising thelesion, but not in elucidating its character.5MRI is now the imaging modality of choice,but despite a number of reports of MRIfindings early in the condition,68 there is apaucity of information regarding long-termserial MRI and clinical examinations.9 Thiscase is unusual in that the patient survived withcomplete clinical recovery, and in that serialMRI was undertaken.

Usually CPM occurs in association with arapid rise in serum sodium (more than12 mmol/l a day) although even cautious rever-

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Central pontine myelinolysis 431

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A_

B

D

Figure Series of four TI-weighted MRI scans taken in the sagittal plane. The first sequence (A) was taken sevendays after the onset of neurological symptoms and shows an extensive hypointensity of the central pons compatiblewith myelinolysis. One month later (B) the abnormality was relatively unchanged despite improvement in thepatient's clinical condition. Six months later (C) there was some resolution ofthe low signal area within the pons, andthe abnormality had almost completely resolved a further year later (D).

Central pontine myelinolysis:clinical features

* tetraparesis: usually spastic althoughflaccidity has been described especially soonafter onset

* pseudobulbar palsy: dysarthria, dysphagia,weakness oftongue and palatal movement,exaggerated jaw jerk and emotional lability

* early depression ofconscious level* progression to 'locked-in' state* other brainstem features according to extent

of myelinolysis; failure of ocular movement,absence of pupil reactions

* cerebellar ataxia if cerebellar peduncles orcerebellar hemispheres are involved

* seizures may occur if associated withhyponatraemic encephalopathy

Box 1

sal of hyponatraemia may be a precipitant.'0Certainly, it seems that the rate of correction ofhyponatraemia, rather than the absolutesodium concentration is the most importantfactor in its pathogenesis since chronicallyhyponatraemic patients do not necessarilydevelop CPM, and CPM can even occur withhypernatraemia. It is unclear what role otherfactors (such as hepatic dysfunction) mighthave.The mechanism of myelin loss in CPM is

unclear. Extra-pontine myelinolysis may alsobe a feature, particularly involving the thalamiand the basal ganglia, but there is a particularpredilection for the pons. These areas all have arelatively high grey/white matter interface. It issuggested that the rise in serum sodium exertsan osmotic endothelial injury leading to thelocal release of myelinotoxic factors mainly

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432 Martin, Young

derived from more vascular grey matter."I Theabsence of myelinolysis in pure white mattertracts such as the internal capsule supports thisview. Autopsy studies in early CPM haveshown altered lipid:protein ratios, little in-flammatory reaction, relative sparing of theaxons, and oedema." This latter elementaccounts for the hypointense signals seen onT 1MRI sequences and the hyperintense signalsseen on T2 sequences early in the course ofCPM.

Certain studies in the acute phase of CPMhave shown that the clinical deficit may precedethe appearance ofMRI abnormalities by two orthree weeks,5"13 and that MRI may fail todemonstrate pontine lesions found at aut-opsy.'4"15 Conversely, there are reports of areasof presumed pontine myelinolysis whichremain subclinical in patients with severeelectrolyte imbalance.5 For practical and logis-tical reasons, other studies have failed to obtainMRI in the earliest phase of the disorder.

In the case reported here, the clinicaldeterioration was mirrored within days by themarked neuroradiological abnormality. Thefindings on MRI did not worsen significantlyover the following month suggesting little, ifany, delay of the MRI appearance behind theclinical picture during disease onset. However,on recovery the clinical improvement precededthe resolution of the MRI findings by approx-imately six months. Indeed, useful functionalrecovery was still accompanied by quite pro-nounced MRI abnormalities (figure, C). Onlyafter 18 months was there a major improvementin the MRI appearance.The chronic lesion of CPM is characterised

by intense fibrillary gliosis with astrocyte pro-

Central pontine myelinolysis:postulated causes and associations

* profound hyponatraemia with rapidcorrection (> 12 mmol/l per day)

* absolute correction of hyponatraemia by>25 mmol/l per day

* reversal ofhypokalaemia* chronic liver disease and following liver

transplantation* chronic alcoholism* malnutrition

Box 2

liferation.6 The high proportion of astrocytes,with their abundant cytoplasm, elevates thewater content of the gliotic tissue. Thisexplains the hypointense signals seen on TIsequences and the hyperintense changes on T2images. The persistence ofgliosis and hence theMRI changes, despite clinical improvement,should provide useful diagnostic informationfrom elective MRI after the acute phase of thedisease and may enable studies of the trueincidence of pontine myelinolysis in patientswith electrolyte imbalance.'6MRI is the radiological modality of choice in

suspected CPM. It is usually, but not exclus-ively, abnormal within a few days of symptomonset. Resolution of the MRI changes appearsto follow the clinical improvement, althoughwith a delay of several months. The clinicalpicture probably remains the best guide toprognosis, although MRI can provide usefulconfirmatory data and may be of diagnosticvalue at least six months after recovery.

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13 Brunner JE, Redmond JM, Haggar AM, Kruger DF, EliasSB. Central pontine myelinolysis and pontine lesions afterrapid correction of hyponatraemia: a prospective magneticresonance imaging study. Ann Neurol 1990; 27: 61-6.

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