[Telemedicine and fibrinolysis in Franche-Comté]. / Télémédecine et fibrinolyse de l'ischémie cérébrale en Franche-Comté

INTRODUCTION: The aim of our study was to compare the efficacy and safety of intravenous thrombolysis of cerebral ischemia as it has been established in a distant hospital (DH) through telemedicine tools or in neurovascular unit of the University Hospital of Besançon. METHOD: Our work was conducted retrospectively at the University Hospital of Besançon from 1 January 2003 to December 31, 2009. RESULTS: Fibrinolysis was introduced at the university hospital in 98/161 patients (61%) and a DH in remote 63/161 patients (39%). A favorable neurological outcome (Rankin 0/1) was observed in 27/98 patients (27.5%) treated at University Hospital and in 25/63 (39.5%) patients in a DH. There was no significant difference between the two subgroups. Symptomatic hemorrhagic transformation occurred in 5/98 (5%) patients treated at University Hospital and in 1/63 (1.5%) patients treated in DH. There was no significant difference between the two subgroups. CONCLUSION: Our study shows that fibrinolysis remotely using the tools of telemedicine has, from 2003 to 2009, in Franche-Comté deal effectively and without risk of a significant proportion of patients.

CSF biomarkers in posterior cortical atrophy.

OBJECTIVE: To describe CSF biomarker profiles in posterior cortical atrophy (PCA), which induces high-order visual deficits often associated with Alzheimer disease (AD) pathology, and relate these findings to clinical and neuropsychological assessment. METHODS: This prospective observational study included 22 patients with PCA who underwent CSF biomarker analysis of total tau (t-tau), phosphorylated tau on amino acid 181 (p-tau181), and amyloid ß (Aß(42)). At group level, the CSF profiles of patients with PCA were compared to those of patients with typical AD and patients with other dementia (OD). Individually, the clinical presentation of patients with PCA was correlated to their CSF profile to assess the predictability of clinical features for diagnosis of underlying AD pathology. RESULTS: At group level, the PCA biomarker profile was not different from that of the AD group, but very different from that of the OD group (p < 0.001). More than 90% of patients with PCA had CSF profiles consistent with AD. All patients with PCA with either isolated higher-order visual deficit (n = 8) or visual deficit associated with memory impairment (n = 11) had CSF profiles consistent with AD. Only one of the 3 patients with PCA with asymmetric motor signs fulfilled biological CSF criteria for AD. CONCLUSIONS: PCA syndrome is usually associated with CSF biomarkers suggestive of AD, as shown by previous neuropathologic studies. This does not apply in case of motor signs suggesting associated corticobasal syndrome. CSF biomarkers help to discriminate AD from non-AD processes associated with this condition.

L-2-hydroxyglutaric aciduria: identification of ten novel mutations in the L2HGDH gene.

L-2-hydroxyglutaric aciduria (L-2-HGA) is a metabolic disease with an autosomal recessive mode of inheritance. It was first reported in 1980. Patients with this disease have mutations in both alleles of the L2HDGH gene. The clinical presentation of individuals with L-2-HGA is somewhat variable, but affected individuals typically suffer from progressive neurodegeneration. Analysis of urinary organic acids reveals an increased signal of 2-hydroxyglutaric acid, mainly as the L-enantiomer. L-2-HGA is known to occur in individuals of various ethnic backgrounds, but up to now mutation analysis has been mainly focused on patients of Turkish and Portuguese origin. This led us to confirm the diagnosis on the DNA level and undertake the corresponding mutation analysis in individuals of diverse ethnicity previously diagnosed with L-2-HGA on the basis of urinary metabolites and clinical/neuroimaging data. In 24 individuals from 17 families with diverse ethnic and geographic origins, 13 different mutations were found, 10 of which have not been reported previously. At least eight of the patients were compound heterozygotes. The identification of two mutations (c.751C > T and c.905C > T in exon 7) in patients with different origins supports the view that they occurred independently in different families. In contrast, the mutation c.788C > T was detected in all six Venezuelan patients originating from the same Caribbean island of Margarita, but not in other patients, thus rendering a founder effect likely. None of the mutations was found in the control population, indicating that they are most probably causative. Mutation analysis may improve the quality of diagnosis and prenatal diagnosis of L-2-HGA.

[Limbic encephalitis with severe sleep disorder associated with voltage-gated potassium channels (VGKCs) antibodies]. / Encéphalite limbique avec anticorps anticanaux potassiques voltage dépendants et troubles sévères du sommeil.

INTRODUCTION: Voltage-gated potassium channels (VGKCs) antibodies are associated with neuromyotonia, limbic encephalitis and Morvan syndrome. CASE REPORT: We report the case of a patient who, after three weeks of fever, presented an anamnestic syndrome, associated with confusion and partial seizures. MRI showed left hyperintensity of mesial temporal structures on Flair images and right hippocampal atrophy on T1 weighted sequences. Laboratory tests only showed high level of anti-TPO antibodies. Thus, the patient was considered as having Hashimoto's encephalopathy. She was treated with intravenous methylprednisolone with no improvement of symptoms. On the contrary, the patient suffered from insomnia, deep diurnal drowsiness and complete disappearance of REM sleep. Episodes of hypothermia and severe hyponatremia were recorded. Serum VGKC antibodies were found at high level. After intravenous immunoglobulin treatment followed by methylprednisolone, we noted remarkable improvement of clinical status. Polysomnography showed reappearence of REM sleep. CONCLUSION: This case report broadens the spectrum of clinical manifestations associated with VGKC antibodies and suggests that VGKC are implicated in regulation of sleep. The potential pathophysiological mechanisms linking sleep disturbances and VGKC antibodies are discussed.

[Fatal giant cell arteritis with severe bilateral involvement of the vertebral arteries]. / Maladie de Horton d'évolution fatale avec atteinte sévère bilatérale des artères vertébrales.

With steroid therapy, it is commonly considered that prognosis is good in giant cell arteritis. However serious or even fatal complications may occur. Here we report the case of a patient who developed fatal giant cell arteritis with severe stenosis of both vertebral arteries and right carotid siphon. Several similar cases have been reported in the literature. Initially diagnosis may be difficult because neurological manifestations are intermittent and classical signs of giant cell arteritis may be lacking. In such condition the reason of poor outcome is unknown and therapy remains empiric.

Atypical MELAS syndrome associated with a new mitochondrial tRNA glutamine point mutation.

The authors studied a 47-year-old patient who presented with an association of deafness, acute cerebral stroke-like episode, leukoencephalopathy, and extensive basal ganglia calcifications. Late onset and neuroradiologic findings were atypical for MELAS syndrome (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Strokelike episodes). A heteroplasmic G to A transition at nucleotide 4332 in the tRNA glutamine gene was identified in the patient's muscle mitochondrial DNA. The pathogenicity of the mutation was shown in single muscle fibers by the correlation between high mutation load and cytochrome c oxidase defect.

Interferon gamma, IL2, IL4, IL10 and TNFalpha secretions in multiple sclerosis patients treated with an anti-CD4 monoclonal antibody.

In order to better understand the mechanisms of action of a monoclonal anti-CD4/BF5 antibody(mAb), cytokine secretions were studied in 14 multiple sclerosis (MS) patients treated in a phase 1 trial. Secretion patterns of IFNgamma, IL2, IL4, IL10 and TNFalpha by peripheral blood mononuclear cells were studied before (DO) and after (D30) the treatment. We decided to undertake this study because in a previous one we observed no variations in serum levels of TNFalpha, IFNgamma, IL1, IL6. Results showed significant reductions in IFNgamma, IL2 and TNFalpha secretions after treatment. The anti-CD4 mAb seemed to act on both Th1- and Th2-cells but with preferential action on Th1-cells. Results on Th2-cells were less obvious even though a significant decrease in IL10 was observed. There was no correlation between any of the immunological markers studied and disease activity. This study demonstrates that pharmacological modifications of the CD4 receptor can induce variations in several cytokine secretion levels. It also stresses the role played by Th1- and Th2-cells in the etiopathogenesis of MS.

[Isolated spastic paraparesis disclosing Krabbe disease in adult age]. / Paraparésie spastique isolée révélant une maladie de Krabbe à l'âge adulte.

A 25-year-old woman developed a slowly progressive spastic paraparesis a few weeks after delivering of her first child. A cerebral MRI showed bilateral areas of hyperintensity in T-2 weighted images in the centrum semi-ovale, internal capsule, midbrain and occipital white matter. A profound deficiency of galactosyl/ceramidase activity was demonstrated in leukocytes (< 5 p. 100 of controls) and in cultured fibroblasts. The diagnosis of the adult form of Krabbe's disease was thus retained. We summarize the clinical symptoms and neuroradiological signs of this disorder and discuss the causative factors of its clinical heterogeneity.

[Open therapeutic trial of anti-T CD4 monoclonal antibody in multiple sclerosis]. / Essai thérapeutique ouvert d'un anticorps monoclonal anti-T CD4 dans la sclérose en plaques.

Twenty-one patients with active multiple sclerosis (16 progressive and 5 recurrent forms) were treated with murine monoclonal anti-T CD4/BF5 antibodies in an open trial. Tolerance was relatively good; 11 patients had side effects including facial swellings, skin eruptions and trembling which occurred only at the first infusion. Treatment had to be stopped in one female patient. Nine months after initiating treatment, no relapse had occurred in any of the 5 patients with a recurrent form and improvement was observed in 3 patients with a progressive form. At the end of the treatment period, there was a clear drop in the number of CD3+ cells and particularly in CD4+ cells, a decrease which was less after one month. All the patients who had side effects showed an increased level of serum IL6 and alpha TNF. These findings demonstrate that this type of long-term treatment is possible in patients with multiple sclerosis and suggest that in another trial it would be important to evaluate the effect in recurrent forms.

Treatment of multiple sclerosis with anti-CD4 monoclonal antibody. A preliminary report on B-F5 in 21 patients.

Twenty-one patients with definite active multiple sclerosis (MS) were treated with a monoclonal anti-T CD4/B-F5 (murine IgG1) antibody for 10 days. Side effects were observed in 11 patients during the first infusion. These side effects were accompanied by and probably related to a transient increase in IL6 and TNF alpha serum levels. This problem led to treatment interruption in one patient. Neither clinical improvement nor deterioration was observed in the course of treatment. EDSS improvement (> 1 point) occurred in six patients one month post-treatment. One month after the end of treatment total lymphocytes and CD3+ and CD4+ cells were significantly decreased. Cytokine analysis performed in serum and in CSF before and after treatment showed no induced modifications. Ten patients developed xenogenic antibodies. It is of interest that the patients with relapsing-remitting forms were relapse-free at the 6th month post-therapy.

[Contribution of MRI to the topography of oculomotor disorders in multiple sclerosis]. / Apport de l'I.R.M. au diagnostic topographique des troubles oculomoteurs dans la sclérose en plaques.

Magnetic resonance imaging (MRI) was performed in 20 patients with multiple sclerosis and abnormal electro-oculographic examination. All but 2 patients showed MRI abnormalities in the infratentorial region: hypersignal on T2-weighted sequences and/or images of atrophy. Usually, each patient had multiple abnormalities, which could prevent anatomico-oculographic correlations. With oculomotor disorders of cerebellar origin, correlations between clinical findings and MRI images were satisfactory, but with disorders due to brainstem lesions correlations were not so good, as shown by the results in 9 patients with internuclear ophthalmoplegia.

Adrenoleukodystrophy. Value of contrast-enhanced MR imaging.

In its early stage adrenoleukodystrophy (ALD) is characterized by hypodensity at CT and signal abnormalities at RMI (low-intensity signal on T1-weighted sequences, high-intensity signal on T2-weighted sequences) in the white matter of the parieto-occipital region and the splenium of the corpus callosum. These CT and RMI abnormalities are suggestive of ALD in children with progressive alteration of the superior brain functions, but they are not specific of the disease. The authors present two cases of ALD and underline the almost pathognomonic value of contrast-enhanced ribbons found at the periphery of low-intensity signal plaques after gadolinium injection. These areas of blood-barrier disruption on a background of inflammation and active demyelination appear, on T2-weighted sequences, as ribbons of low-intensity signal within plaques of high-intensity signal. MRI is also superior to CT in detecting abnormalities located in the posterior fossa, notably lesions of the auditory fibres.

[Predominant involvement of the central nervous system in a secondary form of borreliosis]. / Atteinte prédominante du système nerveux central au cours d'une forme secondaire de borreliose.

The clinical features of a patient with a secondary stage of Borrelia Burgdorferi infection are reported. Severe symptoms and signs of central nervous involvement were present.