Should a psychotic or manic episode be considered an early manifestation of Multiple Sclerosis? A multiple case study.

BACKGROUND: Early manifestations of Multiple Sclerosis (MS) can be atypical and misleading, and several case report studies have highlighted that MS onset sometimes takes the form of a psychotic or manic episode. METHODS: All neurologists belonging to the French Multiple Sclerosis Observatory network were contacted by email and were asked to find patients with MS who presented with a history of psychiatric episode(s) near MS onset. RESULTS: Seventeen patients were selected that met the criteria of presenting with psychotic or manic symptoms either before the diagnosis of MS (N=8), or at the time of the first neurological episode or shortly after (N=9). Patients with a history of a psychiatric episode occurring before the first neurological episode were diagnosed on average 7 years later than patients with either a first neurological or a mixed (both neurological and psychiatric) episode. However, psychiatric symptoms in the first group and the first neurological symptoms of MS in the second group occurred at a similar age. CONCLUSION: Based on this multiple case study, we question whether past psychotic or manic episode should be considered equivalent to a first manifestation of MS.

[Difficulties experienced at work by patients with multiple sclerosis]. / Difficultés ressenties au travail par les patients atteints de sclérose en plaques.

AIM: Multiple sclerosis (MS) is a disease of the central nervous system that affects young adults at a time when they launch into the workforce. The disease often has a great impact on working life. The objective of this survey was to identify the problems faced by people with multiple sclerosis in the context of their work. METHODS: To describe the difficulties experienced at work by patients with multiple sclerosis, we carried out in 2010 a regional survey including neurology and functional rehabilitation centers. RESULTS: Two hundred and seven MS patients of working age responded to the survey. The employment rate was 67.6%. Among difficulties expressed by patients, physical and mental fatigue appeared as the issues affecting work. For 41% of respondents, preventive measures at work could help maintain or resume employment. CONCLUSION: Problems of fatigability put forward by MS patients are elements that can predict a loss of employment.

[Cerebrotendinous xanthomatosis: a multicentric retrospective study of 15 adults, clinical and paraclinical typical and atypical aspects]. / Étude rétrospective multicentrique de 15 cas adultes de xanthomatose cérébrotendineuse : aspects cliniques et paracliniques typiques et atypiques.

INTRODUCTION: Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an autosomal recessive inheritance, is secondary to deficiency of sterol 27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms include clinical or infraclinical xanthomas affecting the skin and tendons, early cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of the dentate nuclei and periventricular white matter hyperintensities. The diagnosis is based on an increased cholestanol level in serum, confirmed by the presence of a mutation in the CYP27A1 gene. Treatment is based on chenodeoxycholic acid. METHOD: We report a retrospective multicentric study of 15 cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical, molecular and MRI findings were recorded in all patients. RESULTS: The average age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood in 73% of patients and in adulthood in 27%. All patients with a pediatric onset were diagnosed during adulthood (age range 28-65years). Clinical symptoms variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline, epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8), psychiatric disorders, cataract and xanthomas. One patient had an atypical presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in all: findings consisted in T2-weighted hyperintensity of the dentate nuclei (47%), periventricular leuoencephalopathy (73%) which preferentially involved the posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%), hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients. The most frequent mutation was 1183C>T (n=5/15). Under treatment with chenodeoxycholic acid, eight patients improved initially, followed by stabilization in five of them, and worsening in the others. Four patients died. CONCLUSION: Patients with the xanthoma-neurological disorder association should be tested for cerebrotendinous xanthomatosis. The disease often begins in childhood with a diagnostic delay but also in adulthood. Involvement of the dentate nuclei is specific but not sensitive and the supratentorial leucoencephalopathy is not specific but with an antero-posterior gradient. A vascular distribution and involvement of the corpus callosum are possible. Serum cholestanol assay is very reliable: an elevated level provides the diagnosis, which must nevertheless be confirmed by molecular biology.

[Optic neuropathy and meningioma: a diagnostic trap]. / Méningiome et neuropathie optique : un piège diagnostique.

INTRODUCTION: Meningiomas are benign primary meningeal tumors. Their diagnosis may be incidental or in response to a work-up for neurological or ophthalmological symptoms. PATIENTS AND METHODS: The clinical course of five patients with ophthalmological symptoms leading to the diagnosis of meningioma is described. RESULTS: The case reports consist of five women (48 to 54 years old - mean 52 years at the onset of symptoms), all suffering from a progressive unilateral decrease in visual acuity with a normal initial fundus examination and ipsilateral visual field changes. Ancillary testing, in particular MRI and CT-scans, had to be repeated to make the diagnosis of meningioma, which was delayed from 18 months to 4 years. DISCUSSION: The clinical presentation of these five cases was that of a retrobulbar optic neuropathy, which biased the work-up towards an inflammatory disease of the central nervous system such as multiple sclerosis. However, the atypical character of the neuropathy, which did not respond to intravenous steroids, caused the diagnosis to be questioned and radiological examinations repeated. The iso-intense appearance of meningiomas on T1 MR imaging and only slightly hyperintense appearance on T2 may result in a diagnostic delay if the exam is not performed and interpreted by an experienced professional. Gadolinium contrast, fat suppression and centration on the anterior visual pathways are essential to a proper MRI examination. CONCLUSION: When confronted with a progressive, painless optic neuropathy unresponsive to steroid treatment, the diagnosis of meningioma of the anterior visual pathways must be considered. This diagnosis is enabled by a targeted MRI of the anterior visual pathways.

A new peroxisomal disease with impaired phytanic and pipecolic acid oxidation.

Phytanic acid (PA) accumulates in patients with adult Refsum disease (ARD) and with peroxisomal disorders. In three related patients with ARD, PA levels were moderately increased in plasma, whereas phytanic oxidation was severely deficient in the fibroblasts. Two of these patients had a significant increase of pipecolic acid in plasma, a finding not reported in ARD, and a fourth related patient, a brother, died at age 17 from a progressive neurologic disorder with unusual clinical and neuropathologic (a spongy degeneration of the white matter) abnormalities for ARD. The first step of L-pipecolic acid degradation occurs in peroxisome. In these patients, the accumulation of PA could have resulted from an impaired capacity to degrade pristanic acid rather than PA. The activity of pristanic oxidase, measured in fibroblasts, was normal, as were two other peroxisomal enzymes, lignoceric acid oxidase and dihydroxyacetone phosphate transferase. Since both mitochondria and peroxisomes are involved in PA alpha-oxidation, we propose that these four related patients presented various phenotypical variants of a novel peroxisomal disease with impairment of PA and pipecolic acid oxidation.