Motor evoked potentials in clinically isolated syndrome suggestive of multiple sclerosis.

The aim of the present study was to determine the sensitivity and the profile of motor evoked potentials (MEP) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). We measured the central motor conduction time (CMCT), amplitude ratio (AR), and surface ratio (SR) in tibialis anterior and first dorsal interosseous muscles in 22 patients with CIS. In 12 patients, the triple stimulation technique (TST) was also performed. AR was abnormal in 50% of patients, CMCT in 18% of patients, and TST in 25% of patients. AR had the highest sub-clinical sensitivity and the best positive predictive value. In the absence of clinical pyramidal signs, an early AR decrease seems to result from demyelination inducing excessive temporal dispersion of the MEP, while in territories with clinical pyramidal signs, it seems to result from conduction failure, which suggests that clinical pyramidal signs may be attributable to conduction failure. This study demonstrates that MEP, especially the AR, is sensitive to motor pathway dysfunction right from the early stages of MS.

[Esophageal achalasia, sleep disorders and chorea in a tauopathy without ophthalmoplegia, parkinsonian syndrome, nor dementia (progressive supranuclear palsy?): clinicopathological study]. / Achalasie de l'aesophage, troubles du sommeil et mouvements choréiques au cours d'une taupathie sans ophtalmoplégie, syndrome parkinsonien ni démence (paralysie supranucléaire progressive?): étude clinicopathologique.

CONTEXT: Progressive supranuclear palsy (PSP) is classically characterized by supranuclear ophthalmoplegia, paroxysmal imbalance with backward falling, axial dystonia, rigidity, pseudobulbar palsy and cognitive dysfunction. However, incomplete or atypical clinical presentation has been previously reported, but in all these cases, the patients had at least one of the main clinical features of the disease (ophthalmoplegia, parkinsonian syndrome or cognitive dysfunction). CASE REPORT: A 60-year-old woman presented with nocturnal agitation and choreiform movements. A few months later she developed severe swallowing disorders, caused by achalasia of the upper esophageal sphincter, and responsible for recurrent acute respiratory distress and pneumonia, prevailing to tracheotomy and gastrostomy. She died suddenly two years after the onset of the symptoms. RESULTS: Postmortem examination of brain revealed a tauopathy, with deposition of abnormal phosphorylated tau in threads and in coiled-shaped as well as globose tangles in the brainstem, subthalamic nuclei and hippocampus. Nuclei of the medulla, including the vagus/solitarius complex and the region of the nucleus ambiguous were especially rich in tau positive inclusions. Ultrastructural analysis of globoid-shaped tangles in the brainstem revealed the presence of straight and paired helicoidal filaments compatible with a PSP. CONCLUSIONS: This case contributes to improve knowledge of the clinical phenotypic range of PSP. In this case, the neuropathological lesions accounted for most of the symptoms. However, the early death of the patient was probably related to the particular distribution of the neuropathological lesions. This case suggests that the initial neuropathological changes in PSP is located in the dorsal brainstem.

[Brain magnetic resonance imaging and neuropathology of cortical laminar necrosis]. / Nécrose laminaire corticale: aspects en imagerie par résonance magnétique et étude anatomoclinique.

INTRODUCTION: The most frequent acute and sub-acute complications of chronic alcoholism are delirium tremens, hepatic encephalopathy and Gayet-Wernicke encephalopathy. Morel laminar sclerosis is a rare and less known complication, often reported with Marchiafava-Bignami disease. CASE REPORT: A 57-year-old alcoholic man presented delirium after surgery. Anterograde and retrograde amnesia as well as wrong recognitions appeared progressively and one generalized seizure occurred. He then developed mutism and became bedridden. Magnetic resonance imaging (MRI) showed high-intensity bilateral temporoparietal signals from white matter on T2-weighted images and high-intensity signals from the parietal cortex on T1-weighted images. The patient died four months after the onset of the delirium. Post-mortem examination of the brain showed cortical laminar necrosis with Alzheimer Type II gliosis but without demyelinisation of the corpus callosum. CONCLUSION: Cortical laminar necrosis with chronic ethylism is usually called Morel's laminar sclerosis. Nevertheless, histology is not typical of this diagnosis, because of necrosis especially of the second (and not the third) layer of the cortex, and because of the absence of lesion of the corpus callosum. MRI data are of interest here because they were rarely reported in cases of Morel's laminar sclerosis.

Prospective clinical and electrophysiological follow-up on a multiple sclerosis population treated with interferon beta-1 a: a pilot study.

OBJECTIVE: To analyse transcranial magnetic stimulation (TMS) variables in a prospective six-month follow-up pilot study on patients suffering from relapsing-remitting multiple sclerosis (RRMS), satisfying inclusion criteria for interferon (IFN) beta-1a treatment. BACKGROUND: So far, no predictive factors are available as to the course of RRMS treated with IFN beta-1 a. DESIGN/METHODS: Fifteen RRMS patients were studied before (month 0 (M0)) and after IFN beta-1a onset (M3, M6). The parameters analysed were motor functional score (mFS), Expanded Disability Status Scale (EDSS), and TMS variables - central motor conduction time (CMCT) and amplitude ratio (AR). RESULTS: Four of the six patients with no motor signs at inclusion, subsequently showed signs of pyramidal dysfunction. All had abnormal M0_TMS variables. The number of M0_TMS abnormalities per patient was greatest in the group that showed mFS worsening, and was significantly correlated with M6_EDSS. The M0_CMCT was significantly correlated with M6_EDSS. During follow-up, the number of patients with abnormal TMS variables decreased from 12/15 to 4/15, and the total number of abnormalities decreased from 33.3 to 16.7%. CONCLUSIONS: TMS variables might be predictive of disease progression. The improvement observed here in the TMS variables may reflect an improvement in MS patients undergoing IFN beta treatment.

Onset and underpinnings of white matter atrophy at the very early stage of multiple sclerosis--a two-year longitudinal MRI/MRSI study of corpus callosum.

BACKGROUND: Atrophy of corpus callosum (CC), a white matter structure linking the two hemispheres, is commonly observed in multiple sclerosis (MS). However, the occurrence and processes leading to this alteration are not yet determined. GOAL AND METHODS: To better characterize the onset and progression of CC atrophy from the early stage of MS, we performed a two-year follow-up magnetic resonance imaging/magnetic resonance spectroscopic imaging (MRI/MRSI) exploration of CC in 24 patients with clinically isolated syndrome. These patients were explored using the same protocol at month (M)6, M12 and M24. MRI/MRSI techniques were applied to measure CC volume, and relative concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr) and choline-containing compounds (Cho). A group of matched controls was also explored. RESULTS: Atrophy of CC, not present at baseline, was observed at M12 and progressed over the second year (M24). At baseline, a decrease in relative NAA level was observed in the anterior and posterior body of CC, with normalization during the follow-up period. In the anterior body, an increase in relative Cho level was observed, with normalization at M6. Normal relative Cr levels were observed at all time points in all sub-regions. The rate of CC atrophy was correlated with the change in the Expanded Disability Status Scale (EDSS) during the follow-up period. CONCLUSION: These results suggest that CC atrophy appears over a period of one year after the first acute inflammatory episode, and that this atrophy is accompanied, especially in the anterior body of CC, by a normalization of the relative Cho levels, marker of acute inflammation, and NAA levels, marker of neuronal dysfunction and/or loss.

[Multiple strokes after chickenpox primo-infection in an adult]. / Accidents vasculaires cérébraux multiples et primo-infection varicelleuse chez un adulte.

INTRODUCTION: Chickenpox is considered as a high risk factor for developing stroke in childhood, but descriptions in adult are exceptional (only three cases reported, to our knowledge). CASE REPORT: A 37-year-old man presented with a chickenpox eruption, followed by a right parietal and a left occipital infarcts, associated with multiple lacunae. There was no coagulation disorder, no hypertension or cardiovascular disorder. Cerebral angiography showed an irregular narrowing of the right internal parietal artery and vascular defects in right parietal and left occipital areas. The diagnosis of VZV-related vasculitis was evoked. White cell count, serology and VZV PCR were negative in the cerebrospinal fluid. Clinical improvement was observed after treatment by corticosteroids and aciclovir. CONCLUSION: Chickenpox is a rare cause of cerebral vasculitis. Involvement of both medium and small vessels was present here, contrary to other adult case reports in the literature. Hematogenous dissemination of the virus responsible for cerebral vasculitis seems to be the most probable pathophysiological mechanism.

[Acute tetraparesis of cerebral origin]. / Tétraparésie aiguë d'origine cérébrale.

INTRODUCTION: Thrombolytic treatment in the early stage of ischemic cerebral attacks requires rapid confirmation of the diagnosis and topographic localization. Unusual clinical features can lead to misdiagnosis with the risk of delaying optimal therapeutic management. OBSERVATION: We report the cases of two patients who experienced acute tetraparesis without any associated encephalic sign, consistent with the diagnosis of spinal cord injury. Cervical magnetic resonance imaging (MRI) was normal. Conversely, cerebral MRI displayed in both cases bilateral hemispheric infarction. Two ischemic lesions were revealed in the territory of both anterior cerebral arteries in the first patient, while the second patient had a bilateral infarction in the posterior arms of both internal capsules. CONCLUSION: In case of tetraparesis, emergency spinal cord MRI should be performed to rule out neurosurgical etiologies and ischemia. If negative, cerebral MRI should be performed at the same time to look for early cerebral infarction in both hemispheres and determine the indication for thrombolysis.

Functional MRI study of PASAT in normal subjects.

The paced auditory serial addition test (PASAT) is routinely used to evaluate the cognitive part of the multiple sclerosis functional composite (MSFC) score, the new reference index of patient disability. PASAT is sensitive to subtle cognitive impairment related to MS, although the cognitive components of this test still remain unclear. In order to better characterize brain systems involved during this complex task, functional magnetic resonance imaging (fMRI) experiments were conducted during PASAT in a population of ten normal subjects. The paradigm consisted of a series of 61 single-digit numbers delivered every 3 s. After each number, subjects were asked to overt vocalize the result of the addition of the two last numbers heard. A control task consisting of the repetition of the same series of single-digit numbers was used. Statistical group analysis was performed using the random effect procedure (SPM 99). Cortical activation was observed in the left prefrontal cortex, the supplementary motor area, the lateral premotor cortex, the cingulate gyrus, the left parietal lobe, the left superior temporal gyrus, the left temporal pole, and visual associative areas. fMRI activations underlying PASAT were consistent with an involvement of verbal working memory and the semantic memory retrieval network which could be related to arithmetic fact retrieval. This study on normal subjects could provide a base for the understanding of the potential abnormal cortical activation in MS patients performing this test for a cognitive evaluation.

[Multiple sclerosis associated with neurofibromatosis type I]. / Association neurofibromatose de type I et sclérose en plaques.

Association between neurofibromatosis type 1 (NF-1) and multiple sclerosis (MS) has been very rarely described. We report the case of a 40-year-old woman presenting familial NF-1 who had café au lait spots and cutaneous neurofibromatosis since childhood. Five years earlier, she experienced a first episode of unilateral optic neuritis, recurrent sensory and motor disturbances, then gait ataxia and pyramidal tract dysfunction with progressive walking impairment. Altered evoked potentials, CSF analysis and cerebral MRI findings were consistent with the diagnosis of MS (secondary progressive form after relapsing-remitting phase). We review major demographic, clinical and laboratory data of MS associated with NF-1 and discuss about the potential pathophisiological mechanisms implied.

[Hashimoto's encephalitis and sleep disorders]. / Encéphalite d'Hashimoto et troubles du sommeil.

Hashimoto's encephalitis is a rare cause of encephalitis which is improved by corticosteroid treatment. We report the case of a 42-year-old woman who developed progressive dementia associated with episodes of recurrent discorders of consciousness which rapidly improved with corticosteroids. During these episodes, no sleep activity was recorded on the holter EEG. These discorders were reversible with treatment and a normal EEG sleep pattern reappeared. At physical examination, Hashimoto's encephalitis can mimic Creutzfeld-Jakob disease. Systematic sleep-EEG recordings can be helpful for diagnosis of sleep disorders related Hashimoto's encephalitis. This case illustrates the importance of searching for antithyroid antibodies in patients with unexplained encephalitis.

[Melanocytic meningitis and large congenital melanocytic naevus: neurocutaneous melanosis]. / Méningite mélanocytaire et naevus géant congénital: la mélanose neurocutanée.

Neurological symptoms in a patient with large congenital melanocytic naevus are highly suggestive of cerebromeningeal melanoma metastasis. The presence of melanocytic cells in cerebrospinal fluid confirms this diagnosis If their malignant nature is shared with cutaneous naevocytic cells. Conversely, neurocutaneous melanosis is diagnosed when benign melanocytosis meningitis is found in patients with multiple and/or large congenital melanocytic naevus, whether cutaneous naevus cells are benign or not, or when cerebrospinal fluid cells are malignant with benign cutaneous melanocytic naevus. We report the case of a young man aged 19 presenting with multiple and large congenital melanocytic naevus who experienced transcient neurological signs and increased intracranial pressure. Cerebral neuroimaging evoked meningeal infiltration which benign melanocytic nature was supposed on CSF analysis and confirmed by necropsy findings, only 3 month after neurological onset, leading to neurocutaneous melanosis diagnosis. This rare neuroectodermal dysembryoplasia finds expression in various neurological signs, depending on patient's age and leptomeningeal and/or cerebral proliferation localization. Lumbar puncture, cerebral scanography and MRI may help diagnosis, but only histological examination can prove neurocutaneous melanosis, more often by necropsy because of poor prognosis.

[Acute heart failure in a patient treated by mitoxantrone for multiple sclerosis]. / Insuffisance cardiaque aiguë chez une patiente traitée par mitoxantrone pour sclérose en plaques.

Mitoxantrone is an immunosuppressive drug usually delivered in severe relapsing remitting multiple sclerosis. It can also be used in secondary progressive and progressive relapsing remitting multiple sclerosis. Left ventricular ejection fraction has to be monitored because of the cardiotoxicity risk of mitoxantrone. Acute cardiac side effects in multiple sclerosis have not yet been described. We report the single case of an acute heart failure occurring in a cohort of more than 800 patients treated with mitoxantrone. We discuss about interruption criteria as maximal cumulative dose allowed and left ventricular ejection fraction cut off value.

[Primary leiomyosarcoma of the cavernous sinus associated with Epstein-Barr virus in a kidney graft]. / Leiomyosarcome primitif du sinus caverneux associé au virus Epstein-Barr chez un greffé rénal.

Immunodeficient patients have an increased incidence of neoplasms, whether the immunodeficiency is due to genetic disorder, the acquired immunodeficiency syndrome (AIDS), or immunosuppressive therapy. Leiomyosarcoma (LMS) is a rare neoplasm, even if its incidence has increased because of AIDS. Less than fifteen cases were described after organ transplantation. An intracranial localization is exceptional (five cases in the literature) and was never described after organ transplantation, to our knowledge. Our present report focuses on a 45-year-old immunocompromised patient, who received immunosuppressive therapy for renal transplantation. He suffered from atypical peri-orbital headaches six months after transplantation and a mass involving the cavernous sinus was identified. Surgical biopsy was performed. Histologic examination revealed a LMS. Epstein-Barr virus was identified by quantitative polymerase chain reaction in the LMS. Immunosuppression was reduced, the patient received adriamycin and protontherapy was realized. He died two years after the transplantation because of tumor progression and kidney failure.

["Multiple sclerosis plus": leukoencephalopathies at the frontiers of internal medicine]. / "Sclérose en plaques plus": les leucoencéphalopathies aux frontières de la médecine interne.

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory, demyelinating and probably autoimmune disease affecting the white matter of the central nervous system (CNS). Due to the absence of specific clinical and laboratory markers, diagnosis remains difficult. CURRENT KNOWLEDGE AND KEY POINTS: In particular, no clinical or paraclinical investigation is satisfactory to distinguish definite MS from other autoimmune or inflammatory diseases, especially when they predominantly affect the CNS. Moreover, previous studies have reported that patients with definite MS could present clinical systemic signs suggestive of other inflammatory or autoimmune diseases, and that MS could be associated with other autoimmune diseases. On the other hand, the presence of biological autoimmune abnormalities, including antinuclear antibodies and antiphospholipid antibodies, has been observed, with a high frequency in patients with MS in comparison to control populations. These clinical and laboratory features could therefore represent a new nosological entity characterized by a systemic immune dysregulation more extensive than the CSN target, or a distinct subgroup of MS patients with a classical course of the disease. Because of the impact of the new therapeutic approach to MS, an important issue concerning this aspect that should be addressed is the use of immunomodulatory therapy, especially with interferon beta. It appears necessary to consider these abnormalities before treating MS patients with preventive therapy, in particular in the perspective of new strategies, such as treatment at an early stage of the disease or combination therapies.

A permanent pure amnestic syndrome of insidious onset related to Alzheimer's disease.

A 55-year-old patient experienced a pure amnestic syndrome of insidious onset that worsened progressively. Subsequently, her memory disorder stabilized and remained her only cognitive impairment for several years. She ultimately developed more widespread cognitive decline and terminal dementia. Postmortem examination 18 years after the onset revealed numerous senile plaques and neurofibrillary tangles consistent with Alzheimer's disease. A permanent pure amnestic syndrome of insidious onset may represent a further type of focal cerebral degeneration.

[Rehabilitation of memory: strategies, indications and limits]. / Rééducation de mémoire: stratégies, indications et limites.

The rehabilitation of memory must be defined in terms of patient selection, therapist support and techniques as accurately as for language therapy. Three objectives can be offered for organic amnesia: reorganizing the memory by using alternative intact routes; working with remaining intact memory as the implicit focus, modification of surroundings with 'mnemonics protheses' such as a diary, alarms. The approach must be cognitive for the theoretical support of therapists, but also pragmatic to respect the patient's needs and wishes in the context of family and job. Patient selection must be based not only on rigorous aetiological and neurological grounds but also on an individual and cognitive understanding of each patient.

[Reflex epilepsy with seizures induced by mental calculation, playing chess and scrabble]. / Epilepsie réflexe avec crises induites par le calcul mental, le jeu d'échecs et le jeu de scrabble.

Reflex seizures induced by higher mental activity is rare. We report the case of a young man with myoclonic jerks and generalized tonico-clonic convulsion precipitated by calculation, playing chess and scrabble. Routine EEG, including hyperventilation and photic stimulation, showed no abnormality. Tests stimulation procedures, including spatial tasks, induced focal and generalized EEG spike-wave complex and myoclonic jerks. Valproate was effective in reducing epileptic seizures during a follow-up period of three years. Comparison of our case with previously reported reflex epilepsy with seizures induced by higher mental activity is discussed.

[Familial deficiency of C7 associated with adrenomyeloneuropathy]. / Déficit familial en fraction C7 du complément associé a une adrénomyéloneuropathie.

A 24-year old man presented with recurrent meningitis resulting from familial deficiency of a late component of the complement system (C7). Five years later, he developed gait disturbance, mental impairment and loss of hearing. Adrenomyeloneuropathy was diagnosed by a raised plasma long chain fatty acids level.