Severe stroke: which medicine for which results?

In face of any severe stroke, the questions for health professionals in charge of the patient are: will the handicap be acceptable for the patient? But can we predict an acceptable handicap for the patient? For his family? When we know that the cognitive disorders, consequences of severe stroke often modify, in a major way, the behaviour of these patients? Given these difficulties for estimate vital and functional prognosis and even more the quality of life of patients with severe stroke, collective reflexions between physicians and nurses are essential, reflexions taking into account preferences and values of patients. Use of resuscitation resources for severe stroke patients implies to offer them the best rehabilitation. So, questions about health pathways for severe stroke are essential: which structures for these patients, which technologies, which medical, medico-social and social supports, which human accompaniment the society can propose to the patients and to their family, so that they have an acceptable quality of life.

[Have centers of rare neurological diseases modified practices and the care of Wilson's disease?]. / Les centres maladies rares en neurologie ont-ils changé les pratiques et la prise en charge de la maladie de Wilson?

Wilson's disease is a particularly rare disease. It is a multisystemic affection related to a genetic abnormality of copper metabolism. Drug treatment is particularly effective if administered at an early stage of the disease and continued throughout life. The French Wilson's disease center, certified for only the one disorder, is easily identifiable by everyone, professionals and patients, which has allowed a rapid increase in the number of patients followed by the center, and considerably reduced the delay between first symptoms and diagnosis. Of its numerous ongoing research projects, it is important to mention the development of a new diagnostic test that would allow the speedy introduction of treatment of both the symptomatic forms and presymptomatic familial forms. Collaborations among professionals permit multidisciplinary care and improve the follow-up of patients in terms of all their medical and social aspects. In addition, the organization of the French Wilson's disease network serves as an exemplar for the implementation of Wilson's disease networks in other European countries and the development of collaborations between Wilson's disease patients'associations across Europe. At present, the center is also working to improve the care of patients presenting with other inherited or acquired pathologies related to copper and other heavy metals.

Corpus callosum abnormalities in Wilson's disease.

INTRODUCTION: Wilson's disease (WD) with neurological presentation is associated with brain lesions classically localised in globus pallidus, putamen, thalamus, mesencephalon, pons and dentate nucleus. Lesions of corpus callosum (CC) have not been studied in a broad population of patients with WD. OBJECTIVE: Evaluation of the frequency of CC lesions in patients with neurological symptoms related to WD. METHOD: The authors included all patients with neurological expression of WD, followed in the French national centre for WD who had a brain MRI between March 2006 and December 2008. The localisation of brain lesions was analysed and the frequency of lesions in CC evaluated. All patients were assessed using the Unified Wilson's Disease Rating Scale. For patients with abnormalities located in CC, a clinical dysconnexion syndrome was investigated. RESULTS: Among 81 patients (45 men, mean age: 34.8 years, from 12 to 74 years) with neurological expression, 42% had white-matter lesions on fluid-attenuated inversion recovery MRI. 23.4% of patients presented CC lesions, limited to the posterior part (splenium). The severity of disability estimated by Unified Wilson's Disease Rating Scale was correlated with the presence of CC lesions on MRI. CONCLUSION: Abnormalities in CC are not unusual (23.4%). Together with lesions of basal ganglia, CC signal changes should suggest the diagnosis of WD.

[Abnormal copper metabolism in adult]. / Anomalies du métabolisme du cuivre chez l'adulte.

Copper is essential for many enzymatic reactions and in neurotransmitter biosynthesis. Its deficiency or its excess has consequences on many organs, especially the liver and the brain. The biochemical tests performed in case of suspicion of copper metabolism disorder are difficult to analyse. They include the measurement of serum ceruloplasmin, serum copper and 24h urinary copper excretion. The interpretation must take into account the clinical features. We distinguish mainly: (1) copper deficiency, acquired in malabsorption or in copper diet deficiency, or related to a genetic disease (Menkes disease); (2) copper overload, acquired or from a genetic origin (Wilson disease); (3) aceruloplasminemia, reducing ferroxidase activity leading to iron overload. It is important to diagnose these diseases as some of them have an effective treatment if it is started early enough.

Elicited repetitive daily blindness: a new phenotype associated with hemiplegic migraine and SCN1A mutations.

OBJECTIVE: Familial hemiplegic migraine (FHM) is a genetically heterogeneous disorder in which three genes, CACNA1A, ATP1A2, and SCN1A, are currently known to be involved. FHM is occasionally associated with other neurologic symptoms such as cerebellar ataxia or epileptic seizures. A unique eye phenotype of elicited repetitive daily blindness (ERDB) has also been reported to be cosegregating with FHM in a single Swiss family. METHODS: We report an additional family in whom the proband had, in addition to FHM, typical ERDB. In this family and the previously reported Swiss family, the whole coding region of the SCN1A gene was screened after exclusion of mutation in CACNA1A and ATP1A2 genes. RESULTS: We identified two novel SCN1A mutations (c.4495T>C/p.Phe1499Leu and c.4467G>C/p.Gln1489His missense substitutions) in exons 24 and 23, respectively, segregating with the disease in all living affected members. Both mutations were absent from 180 healthy Caucasian controls and were located in an intracellular loop highly conserved throughout evolution. CONCLUSION: We report new clinical data supporting cosegregation of familial hemiplegic migraine and the new eye phenotype of elicited repetitive daily blindness and two novel SCN1A mutations as the underlying genetic defect in two unrelated families. SCN1A encodes the voltage-gated sodium channel Nav1.1 that is highly expressed in the CNS including the retina. This remarkably stereotyped new eye phenotype has clinical characteristics of abnormal propagation of the retinal electrical signal that may be a retinal spreading depression. These results suggest that SCN1A mutations, which alter neuronal brain excitability, may occasionally alter retinal cell excitability.

[Wilson disease]. / La maladie de Wilson.

Wilson disease is an autosomal recessive disorder of copper overload. A principal characteristic of this disease is its wide phenotypic and genotypic variability. Its results from mutations of the ATP 7B gene located on chromosome 13, that encodes a hepatic copper transport protein. More than 300 mutations of this gene have been identified. This protein ensures the transport of copper in the hepatocyte, its incorporation with the apoceruloplasmin and its biliary excretion. The clinical manifestations are heterogeneous as well in their presentation, dominated by the neuropsychiatric and hepatic symptoms, as in the age of the first symptoms. Early recognition and initiation of therapy with chelators or zinc are essential for prognosis. Liver transplantation is indicated in cases with fulminant hepatitis, end-stage liver cirrhosis and should be considered in the therapy resistant neurological forms. A regular follow-up with monitoring of adverse effects of treatment and compliance is essential. Any discontinuation of treatments will involve, within a very variable time, but in constant manner, a reappearance or a reaggravation of the signs. Such relapses are often brutal and can be extremely serious, especially since response to subsequent treatment is often poor.

[Meningoradiculitis disclosing T-lymphocyte leukemia in HTLV-1 infection]. / Méningo-radiculite révélatrice d'une leucémie à lymphocytes T au cours d'une infection à HTLV1.

A case of HILV1-associated adult T cell leukaemia/lymphoma (ATLL) in à 21-year olf African woman is reported. The patient presented with lymphomatous meningoradiculopathy. The usual clinical features of ATLL were absent. Lumbar MRI showed a pial enhancement by DTPA-gadolinium of the conus medullaris which extended to the proximal cauda equina. Under systemic chemotherapy coupled with intrathecal chemotherapy the patient progressively improved, and at the second MRI examination complete disappearance of the lumbar enhancement was observed. MRI of the brain using axial and coronal T2-weighted sequences detected multifocal lesions of high-intensity signal in the subcortical white matter. ATLL is unusual in people of African origin. The ATLL-strongyloïdes infestation association has previously been reported, suggesting that parasitic infestation may be an important co-factor leading to the development of ATLL.

Infarction in the territory of the medial branch of the posterior inferior cerebellar artery.

We report 10 cases of cerebellar infarction in the territory of the medial branch of the posterior inferior cerebellar artery (mPICA). Axial sections on MRI through the middle of the medulla and the cerebellum showed the infarction as a triangular area with a dorsal base and a ventral apex directed towards the fourth ventricle. The infarct also involved the lateral and dorsal medulla when the mPICA supplied all or part of these regions. Three clinical patterns were observed: 1) pseudolabyrinthine signs with or without dysmetria and ataxia when the medulla was spared; marked axial lateropulsion was present in most cases; 2) complete or incomplete Wallenberg's syndrome, when the medulla was involved; 3) silent infarction. These syndromes are precisely those previously attributed to PICA occlusion without distinction of the branch involved. No alteration of consciousness was recorded and spontaneous recovery was the rule. Cerebellar infarction in the distribution of the mPICA can be regarded as a benign condition with a good prognosis.

MR Imaging of the cervical cord in juvenile amyotrophy of distal upper extremity.

We report the MR studies of the cervical cord in seven patients presenting juvenile muscular atrophy of distal upper extremity. This illness, also known as monomelic amyotrophy or benign focal amyotrophy, is distinct from the other motor neuron diseases. Seen in young males, it is characterized by muscular atrophy of the hand, and usually of the forearm, most often unilateral. The underlying process, of unknown origin, affects the anterior horn cells in the lower cervical cord. The gradual onset of purely motor disturbances may mimic early amyotrophic lateral sclerosis. This latter diagnosis may be excluded because of clinical stabilization and lack of pyramidal tract involvement. In our series, five MR studies were positive. In three cases we were able to demonstrate focal and unilateral atrophy in the lower cervical cord limited to the anterior horn region. Morphologic MR findings correlated with clinical and electromyographic features. In two other cases the MR-clinical correlation was more complex. No pathologic MR signal was detected on either T1- or T2-weighted images. Although the diagnosis of monomelic muscular atrophy is based on neurologic and neurophysiologic data, MR provides confirmatory evidence as well as useful information contributing to an understanding of this disease.

[Sleep abnormalities and evoked potentials (VEP-BAER-SEP) in progressive supranuclear palsy]. / Etude des anomalies du sommeil et des potentiels évoqués (PEV-PEAp-PES) dans la paralysie supranucléaire progressive (PSP).

Few physiological studies have been performed in PSP. We studied: sleep abnormalities in 36 h polygraphic recordings; changes of PEV after pattern-reversal stimulation, of BAER and of short latency SEP after stimulation of the median nerve. The population was for the 1st group: 18 patients with full typical symptomatology, for the 2nd group: 7 patients with likely diagnose of PSP and for the 3rd group: 10 normal subjects as control sample. All patients of the 1st group had sleep abnormalities: decrease of total sleep time; decrease of the percentage of REM sleep; morphological abnormalities (specially horizontal ocular square wave jerks). Detail is given of the repartition of such abnormalities in the two groups of patients. There is no correlation between sleep abnormalities and the natural history of the disease. The PEV and BAER, abnormalities were present in 50% of the cases. The PES were always normal. The help that can be provided by electrophysiological studies in the diagnose of PSP is discussed (particularly in group 2).

[Neurological manifestations in relation to vitamin E deficiency, caused by a defect of biliary acid synthesis]. / Manifestations neurologiques en rapport avec une carence en vitamine E, par défaut de synthèse des acides biliaires.

A progressive neurological syndrome with cerebellar signs, abnormal proprioception, areflexia and Babinski response was observed in a child with chronic intestinal malabsorption. There was no ophtalmoplegia or retinitis pigmentosa. Electromyography and biopsy showed no axonopathy or myopathy. Two other members of the family were also affected. The serum Vitamin E corrected the serum Vitamin E levels within a few months and led to secondary neurological improvement. The authors underline the importance of searching for Vitamin E deficiency and its cause in patients, especially children, with signs of spino cerebellar degeneration. Substitative therapy may have a favorable influence on the neurological condition even when administered late.