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Schilder’s disease or myelinoclastic diffuse sclerosis is a rare acute or subacute demyelinating disorder which primarily affects children and young adults.1 2 We report the clinical and neuroradiological follow up of two boys affected by a demyelinating disease with a prolonged relapsing-remitting course, response to corticosteroids, and relatively good long term prognosis.
The first patient presented at the age of 12 with a 2 month history of repeated episodes of headache and blurred vision followed by weakness in the left leg, lasting a few hours. Head CT and bilateral carotid angiography were normal. Two weeks later the left hemiparesis and headache recurred. T2 weighted images on brain MRI disclosed a hyperintense signal in the right parieto-occipital white matter of the centrum semiovale, without a mass effect. Flash visual evoked stimuli elicited a decreased potential on the left side. Motor and sensory nerve conduction were normal. Corticosteroid treatment (prednisone (1mg/kg/day)) reversed the clinical symptoms. At the age of 14, the boy began to have daily headaches. Brain MRI showed the previous white matter lesion, now extending to the parietal, temporal, and occipital areas, with a mass effect and contrast enhancement (figure). Light microscopy of a right parietal stereotactic biopsy disclosed perivascular cuffing with inflammatory cells and ultrastructural examination confirmed a loss of myelinated fibres. Immunohistochemical findings were negative. Five months later the patient had a third episode of left hemiparesis, this time with left sided focal motor and secondarily generalised seizures. Treatment with carbamazepine and cyclophosphamide improved the hemiparesis and controlled the seizures. Brain MRI showed that the mass effect had disappeared, leaving a right parietal, temporal, and occipital lesion. Follow up at the age of 19 showed that, except for a left visual field deficit, the patient had a normal neurological and mental status. He is now receiving azathioprine (75 mg/day).
The second patient was admitted at the age of 4 because of the sudden onset of headache and vomiting with ataxia and drowsiness followed by generalised clonic seizures. Clinical examination on admission showed left hemiparesis, anisocoria (left>right), and dysarthria. Ocular funduscopy was normal. Head CT disclosed a reduced right lateral ventricle and subarachnoid spaces and, 1 week later, a small hypodense area in the right periventricular white matter. A carotid angiogram was normal. At the age of 5 the child had a second episode characterised by high fever, vomiting, sixth nerve bilateral paresis, dysarthria, truncal ataxia, and stupor. Treatment with corticotrophin (35 units daily for 5 days, then every 48 hours for 20 days) induced a rapid clinical improvement. From the ages of 5 to 14 the child had yearly relapses characterised by the sudden onset of left hemiparesis with variable involvement of the cranial nerves and impairment of consciousness associated with inconsistent alteration of white matter on brain CT (widespread hypodensity in the right centrum semiovale with a mass effect on the right ventricle). These attacks regressed spontaneously or after corticosteroid treatment. The last episode, at the age of 14, consisted of right sided paraesthesias of the face and hand, right hemiparesis, dysarthria, and drowsiness. T2 weighted sequences on MRI disclosed multiple focal abnormalities in supratentorial white matter. Corticosteroid treatment induced marked clinical improvement. Follow up at the age of 18 detected only a bilateral paretic nystagmus and hypometric saccades. Mental development was normal. Brain MRI showed that the white matter lesions had partly regressed.
In both patients the following investigations during and between attacks yielded normal findings: CSF examination (absence of oligoclonal bands), CSF lactate and pyruvate; extensive serological and CSF immune screen; extensive viral, bacterial, and parasitic serological and CSF tests; blood lactate and pyruvate, blood ammonia, amino acids in plasma, urine and CSF, gas chromatography-mass spectrometer analysis of organic acid in urine, adrenal function, plasma C26/C22 fatty acid ratio, serum copper, plasma ceruloplasmin, pyruvate dehydrogenase complex and cytochromec oxidase activity in skin fibroblasts; arylsulphatase A, β-galactosidase, β-glucosidase, and galactocerebroside-β-galactosidase activities in leucocytes.
In both cases the overall findings raise the question of myelinoclastic diffuse sclerosis.1 2 A prerequisite for the diagnosis is a normal very long chain fatty acid plasma concentration. Clinical signs include an intracranial hypertension syndrome, mental deterioration, hemiplegia, and visual field defects. The disease has either a monophasic course, rarely rapid and fatal, or a relapsing-remitting course.3 Most patients have neurological sequelae during follow up and few patients fully recover.3 4 Histological studies typically show a demyelinating process similar to that of multiple sclerosis, with an inflammatory perivascular infiltrate, and in severe cases, cystic lesions. Neuroimaging findings tend to parallel the clinical course. Corticosteroids may improve the outcome of the single relapse and possibly of the disease, as they did in our patients. Some patients respond to immunosuppressive therapy.
In both the patients described the association of headache, signs of diffuse and focal brain dysfunction, a relapsing course, and the response to corticosteroids also raise the possibility of an isolated CNS angiitis, a condition primarily affecting middle aged and elderly people. But neither cerebral angiography nor histological examination disclosed a primary vascular disorder. In addition, the early onset and the sporadic occurrence of the disorder rule out another recently described vasculopathy often associated with familial hemiplegic migraine.5
In conclusion, although demyelinating diseases that do not fulfil the classic definition of multiple sclerosis or encephalomyelitis remain difficult to label in children, the two cases we report here seem to fit Schilder’s description of myelinoclastic diffuse sclerosis. Owing to the current lack of knowledge on the causes of this disease strict diagnostic criteria cannot be applied. Some presentations may warrant brain biopsy. The differing clinical and neuroimaging features seen in these patients may help in delineating Schilder’s disease subtypes.