[Meningeal tertiary lymphoid organs: Major actors in intrathecal autoimmunity]. / Organes lymphoïdes tertiaires méningés : des acteurs majeurs de l'auto-immunité intrathécale.

Multiple sclerosis (MS) is characterized by an intrathecal synthesis of immunoglobulins synthesized by B-cell clones and by a brain infiltrate of clonal T-cells. The clonal maturation of these lymphocytes takes place in tertiary lymphoid organs (TLO) developed in the intrathecal compartment. TLO are acquired lymphoid organs able to develop in the vicinity of the inflammatory sites, where they mount a complete antigen-driven immune response. We here review TLO pathophysiology in animal models of MS and human MS. Several pieces of evidence suggest that intrathecal TLO may play a major role in the clinical impairment. Potential therapeutic applications are examined.

[Impact of a stroke-unit on rtPA use in a community hospital: a 3-year prospective study]. / Impact de la création d'une unité neurovasculaire sur l'utilisation du rtPA dans l'infarctus cérébral en centre hospitalier général : étude prospective sur trois ans.

INTRODUCTION: Although intravenous thrombolysis has been used for ischemic strokes since 2004 in our community hospital located in Pau (southwest of France), a specifically dedicated stroke-unit (SU) was created only recently in June 2010. We decided to collect prospective data to compare the use and efficacy of intravenous thrombolysis before and after the opening of this dedicated stroke unit. METHODS: Stroke patients with internal carotid artery territory involvement treated with intravenous thrombolysis were compared between two similar periods. The first period (called pre-SU period) stretched from January 2009 to June 2010. The second period (called SU period) stretched from June 2010 to October 2011. We collected prospectively all morbidity/mortality data as well as a modified Rankin score (mRS) three months later. RESULTS: During the pre-SU period, 21 strokes were treated with a mean NIHSS score of 15. Three months later, the mRS score was less than or equal to 2 for five patients, and greater than or equal to 3 for 12. A total of four patients died. In addition, two-thirds of patients (14 of 21) had suffered from notable complications at the initial phase of their stroke. During the SU period, 27 strokes were treated with a mean NIHSS score of 14. At 3 months, the mRS score less than or equal to 2 for 15 patients, and greater than or equal to 3 for nine other patients. A total of three patients died. During this second period, less than 50% of the patients (13 of 27) were not affected by any complication at the initial phase. Statistically, the results also show a better short-term (24 hours with NIHSS) and medium-term (3 months with NIHSS and mRS) clinical outcome for patients treated during the SU period. CONCLUSIONS: Instituting a dedicated stroke-unit helped improve outcome after ischemic strokes treated by intravenous thrombolysis. It also increased the number of patients and reduced the complications at the initial phase.

[Ischemic strokes related to benign primitive cardiac tumours]. / Infarctus cérébraux révélant une tumeur bénigne primitive cardiaque.

BACKGROUND: We report three cases of ischemic cardioembolic strokes related to benign primary cardiac tumours (two fibromas and one fibroelastoma). CASE REPORTS: This is a retrospective study over a five years period (from December 2004 to December 2009) in a French community hospital. Data on hospital strokes were obtained from the informatics department. Three benign primary cardiac tumours were found as the cause of acute neurological manifestations: a 45-year-old woman with a fibroelastoma revealed by a brain infarction, a 29-year-old man with a myxoma revealed by a transient ischemic attack, and a 46-year-old woman with a myxoma revealed by a brain infarction. Rankin scores performed at least 18 months after cardiac tumour surgery were respectively of 0, 0 and 2. CONCLUSION: Our study confirms that this is a rare event even if those tumours seem to have a high embolic potential (myxomas). Anyway, long-term functional outcome seems to be good.

[Mutism and acute behavioral disorders revealing MELAS syndrome]. / Mutisme et troubles du comportement aigus révélant un syndrome MELAS.

INTRODUCTION: MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a rare genetic mitochondrial disease which can cause cerebral (cerebrovascular accident, migraine, mental deterioration..), sensorial (bilateral symmetrical deafness) and peripheral (muscular involvement, neuropathy) disorders potentially associated with diabetes, renal or cardiac disorders, or growth retardation. Eighty percent of the patients have the 3243 A>G mutation in the leucine RNA transfer gene. Clinical manifestations leading to discovery of the mutation can be extremely varied, affecting patients of different age groups. CLINICAL CASE: We report the case of a 49-year-old man who presented acute fits of confusion followed by mutism and praxic disorders. History taking revealed recently diagnosed type 2 diabetes, axonal neuropathy, and bilateral symmetrical deafness requiring hearing aids. The initial MRI showed FLAIR sequences with bi-parietal abnormalities, no signs of recent stroke on the DW/B10000 sequences, and basal ganglia calcifications. Blood tests and morphological findings ruled out a vascular origin. Search for lactic acidosis remained constantly negative in blood samples despite positive cerebrospinal fluid samples (N×3). The 3243 A>G mitochondrial DNA mutation was identified. The neuropsychological evaluation revealed a serious dysexecutive syndrome with a major impact on the patient's self sufficiency. CONCLUSION: Neurocognitive disorders are not common in MELAS syndrome. Brain MRI results and the presence of extra-neurological signs can be helpful for diagnosis.

Relapsing neuromyelitis optica: long term history and clinical predictors of death.

BACKGROUND: Relapsing neuromyelitis optica (RNMO) is an uncommon but devastating inflammatory disorder of the central nervous system. Long term history in a wide series of RNMO is required for better knowledge of the course of the disease and identification of patients at high risk of death. METHODS: Clinical features of patients with RNMO (88 women/eight men) obtained from the geographic Caribbean database (Cuba and French West Indies) were used to determine the progression of disability and to identify clinical predictors of death. RESULTS: Median age at onset of RNMO was 29.5 years (range 11-74). Median duration of disease was 9.5 years (1-40). Median relapse rate was 0.7 attack/patient/year (0.1-3). 66 patients experienced severe visual loss in at least one eye and 46 in both eyes. Median time from onset to unilateral and bilateral severe visual loss was 3 and 15 years, respectively. Median times to reach Kurtzke Disability Status Scale 3, 6 and 8 from onset of RNMO were 1, 8 and 22 years. There were 24 deaths (25%); within 5 years in 63% of cases. A higher attack frequency during the first year of disease (p = 0.009), blindness (p = 0.04) and sphincter signs at onset (p = 0.02) and lack of recovery of first attack (p = 0.003) were independently associated with a shorter time to death. CONCLUSION: RNMO is a very rapidly disabling disease affecting primarily young women. This study has identified clinical features that predict a poor outcome. These findings suggest that early and aggressive immunotherapy might be warranted in RNMO.

[Severe bouts of neuromyelitis optica: dramatic improvement after plasma exchanges]. / Poussées sévères de neuromyélite optique : efficacité spectaculaire des échanges plasmatiques.

Severe relapses are common in neuromyelitis optica (NMO). Plasma exchanges (PE) were successfully used to treat acute demyelinating relapses resistant to corticosteroids. However, little is known about PE efficiency in NMO relapses, particularly in relation with the presence or not of specific antibodies. We here report two patients with NMO (one seropositive and one seronegative) with dramatic improvement after PE on both the optical and spinal involvement.

[Descriptive epidemiology of neuromyelitis optica in the Caribbean basin]. / Epidémiologie descriptive de la neuromyélite optique dans le bassin caraïbéen.

INTRODUCTION: Data on epidemiology of neuromyelitis optica (NMO) remained scarce in the last century, but the recent development of diagnostic criteria now enables inclusion of both monophasic and relapsing NMO in epidemiologic studies. Given the rarity of NMO, multicentric studies are needed to confirm a presumed higher frequency in women and in populations of black/Asian ancestry. The Caribbean basin is a suitable area for collecting a large NMO cohort and to assess the prevalence, incidence, and mortality of this disorder. PATIENTS AND METHODS: This population-based survey of the NMO spectrum in the French West Indies (FWI) and Cuba included 151 cases. RESULTS: Ninety-eight patients (female/male ratio: 9.8) had NMO. Age of onset in NMO patients was 30.9 years. Mean annual incidence of NMO in the French West Indies for the period July 2002 to June 2007 was 0.20/100,000 inhabitants (IC 95% 0.05-0.35). Incidence rates were steady in the FWI during the 1992 to 2007 period. Decreasing mortality in the FWI during the 1992 to 2007 period explained the increasing prevalence which was 4.20/100,000 inhabitants (IC 95% 3.7-5.7) in June 2007. The prevalence of NMO in Cuba on November302004 was 0.52/100,000 inhabitants. (IC 95% 0.39-0.67). Prevalence rates did not differ significantly by ethnic group in Cuba, however, black Cubans exhibited the highest prevalence. DISCUSSION: Epidemiologic studies on NMO in each population are needed to determine whether aggressive therapies can reduce the mortality of this devastating disorder. CONCLUSION: In the Caribbean basin, NMO involves almost exclusively young women; the epidemiologic data confirm its predilection for populations of African ancestry. In the FWI, recent and aggressive therapy has lowered mortality but with an increase in the prevalence of NMO.

[Steroid treatment in four cases of anti-GAD cerebellar ataxia]. / Traitement des ataxies cérébelleuses à anticorps anti-GAD par cures séquentielles de corticoïdes.

INTRODUCTION: Few neurological diseases are linked with anti-glutamic acid decarboxylase antibodies (GAD-ab); stiff man syndrome is an example. Cerebellar ataxia is a new feature of this expanding spectrum. No therapeutic trial is yet available in these diseases. We here report on four patients suffering from cerebellar ataxia linked with GAD-ab and review the data in the literature on this recently described syndrome. METHOD: We conducted an open trial with monthly pulsed steroids. Steroid pulses were given six months followed with placebo for another six months. Main clinical and biological parameters were monitored monthly (International Cooperative Cerebellar Ataxia Rating Scale [ICARS] and GAD-ab). RESULT: The clinical response was found limited and inconstant. Transient decline in GAD-ab level was noted in two patients. Moreover, GAD-ab level was found highly variable and did not correlate with clinical parameters. DISCUSSION: Cerebellar ataxia with GAD-ab is an increasingly described syndrome. Outcome can be severe, leading to definitive cerebellar atrophy. Diagnosis is supported by high level of serum GAD-ab with intrathecal secretion. Experimental data have suggested a direct excitotoxic effect of GAD-ab on Purkinje cells. Response to various treatments is often disappointing. Improvement has been obtained with veinoglobulins in individual patients. A weak clinical and biological response was associated with monthly steroid pulses.

[Neuroradiological aspects of Devic's neuromyelitis optica]. / La neuromyélite optique rémittente: données neuroradiologiques.

INTRODUCTION: Neuromyelitis optica (NMO) is a rare inflammatory and demyelinating disorder of the central nervous system, restricted to optical nerves and spinal cord. The main neuroradiological aspects, now summarized into a complete set of diagnosis criteria, are a normal cerebral MRI at onset and longitudinal involvement of the spinal cord concerning more than 3 vertebral segments. The clinical course and frequency of typical lesions remain unknown. OBJECTIVE: We here report neuroradiological data from patients suffering from NMO. METHODS: Brain and spinal cord MRI were systematically reviewed for 32 afro-Caribbean patients. RESULTS: A typical longitudinal spinal lesion was seen in 44.7 percent with or without edema; a lesion involving less than 3 vertebral segments in 26.3 percent and no lesion in 21.1 percent. Longitudinal study of a few bouts suggested a progressive normalisation of spinal cord appearance. Atrophy was negatively correlated with immunosuppressive treatment. Cerebral lesions usually absent at onset were correlated to the follow-up. In a non-recursive condition, patients completed diagnostic criteria for encephalic and spinal lesions in 82.8 percent and 48.1 percent. CONCLUSION: Radiology of spinal bouts showed multiple aspects besides the typical form. The notion of multiple bouts must be added to the spinal criteria to achieve good sensitivity. A typical extensive spinal lesion is usual in the follow-up, but seen after less then half of the bouts. Requiring such a lesion would delay the diagnosis.

[A new case of cerebellar ataxia with anti-GAD antibodies treated with corticosteroids and initially seronegative]. / Un nouveau cas d'ataxie cérébelleuse à anticorps anti-GAD traité par corticoïdes et initialement séronégatif.

INTRODUCTION: Cerebellar ataxia with antiglutamic acid decarboxylase antibodies (GAD-ab) is an exceptional newly recognized autoimmune disorder. The cerebellar ataxia may occur in isolation or be associated with stiff man syndrome another rare GAD-Ab induced disorder of central nervous system. EXEGESIS: A 38-year-old woman with a past history of Graves disease presented with insidious cerebellar symptoms including ataxic gait, dysmetria, dysarthria, and oscillopsia. A thorough survey of markers of paraneoplastic cerebellar ataxia and collagen diseases was negative. Her serum contained high level of GAD-ab (647.2 U/ml) and MRI evidenced pure cerebellar atrophy leading to diagnosis of autoimmune cerebellar ataxia. Under corticosteroids, cerebellar symptoms partially improved, but serum GAD-ab titre dramatically decreased. CONCLUSION: Testing for GAD-ab may be indicated in patients with idiopathic cerebellar ataxia, particularly mature women with organ-specific autoimmune diseases. Corticosteroids must be started to prevent irreversible cerebellar atrophy.

Visual phenotype of multiple sclerosis in the Afro-Caribbean population and the influence of migration to metropolitan France.

PURPOSE: To describe the visual phenotype of multiple sclerosis (MS) in the Afro-Caribbean population living in Martinique (French West Indies) and to specify the influence of the migration to metropolitan France on ocular impairment. DESIGN: Prospective consecutive observational case series. METHODS: A complete ophthalmologic examination was performed. PARTICIPANTS: A total of 112 patients of Afro-Caribbean origin with MS satisfying McDonald's diagnostic criteria, divided into 53 cases (47.3%), the non-migrant patients (group NM), who had never left the Caribbean basin, and 59 cases (52.7%), the migrant patients (group M), who had lived in metropolitan France for at least 1 year before age 15. RESULTS: MS first manifested as an impairment of the optic nerve in 41 cases (36.6%): 25 cases (47.1%) in group NM and 16 cases (27.1%) in group M. Visual function was recovered in 13/25 cases (52%) in group NM compared to 13/16 cases (81%) in group M. Two-thirds of patients presented with a clinical ocular impairment, which was bilateral in 58.5% of cases in group NM. Fourteen cases (12.5%) met the criteria of neuromyelitis optica, nine cases (17%) in group NM and five cases (8.5%) in group M. In group NM, when the initial visual attack did not regress, the visual Expanded Disability Status Scale (EDSS) score was 5+/-1.5 ; 75% of patients had monocular blindness and 50% binocular. CONCLUSIONS: In the non-migrants (group NM), MS manifested more frequently with an optical neuropathy, the ocular impairment was more severe, and corresponded to neuromyelitis optica in 17% of the cases; a visual presentation and the absence of complete recovery from the first attack represented a factor of poor prognosis. This series is the largest description of the visual phenotype of MS in patients of African origin. The results confirm the preferential impairment of the optic nerve in the black population in the course of the disease. The migration towards an area of high prevalence of MS influences the visual phenotype in terms of a lower incidence and less severe prognosis of ocular impairment.

Plasma exchange in severe spinal attacks associated with neuromyelitis optica spectrum disorder.

BACKGROUND: Plasma exchange (PE) is increasingly undertaken in diseases involving humoral factors and is proven to be beneficial in acute demyelinating diseases. Spinal attacks in relapsing neuromyelitis optica (NMO) and in extensive transverse myelitis (ETM) - a truncated form of NMO with spinal involvement - are usually devastating. OBJECTIVE: We retrospectively studied the outcome of PE-treated versus steroid-only treated spinal attacks in relapsing NMO and ETM. METHODS: We included 96 severe spinal attacks in 43 Afro-Caribbean patients. PE was given as an add-on therapy in 29 attacks. Expanded disability status score (EDSS) was obtained before attack, during the acute and residual stage. We defined the DeltaEDSS as the rise from basal to residual EDSS. RESULTS: The DeltaEDSS was found to be lower in the PE-treated group (1.2 +/- 1.6 vs 2.6 +/- 2.3; P < 0.01). A low basal impairment is associated with a better outcome. Improvement was obtained in both NMO-IgG negative and positive NMO attacks. Minor adverse events manifested in seven PE sessions (24%). CONCLUSION: PE appears to be a safe add-on therapy that may be employed early in severe spinal attacks in the NMO spectrum disorders in order to maximize improvement rate. PE efficiency is independent of NMO-IgG positivity.

Neuromyelitis optica positive antibodies confer a worse course in relapsing-neuromyelitis optica in Cuba and French West Indies.

BACKGROUND: In Caucasian populations neuromyelitis optica (NMO-IgG) antibody has been detected in 27.1% / 78.2% of patients with relapsing-NMO (R-NMO). The prevalence reported for the disease in the Caribbean is 3.1/100,000 in the French West Indies (FWI) and 0.52 /100,000 in Cuba, but the NMO antibody status is unknown. OBJECTIVE: To assess the NMO-IgG antibody status of Cuban/FWI RNMO patients, comparing with European cases tested at the same laboratories. METHODS: Serum NMO-IgG antibodies were assayed in 48 R-NMO patients (Wingerchucks 1999 criteria): Cuba (24)/FWI (24), employing Lennon et als method. We compared the demographic, clinical, disability and laboratory data between NMO-IgG +/- patients. All the data were reviewed and collected blinded to the NMO-IgG status. RESULTS: Seropositivity of the NMO-IgG antibody demonstrated a lower rate in the Caribbean (33.3%), as compared with Caucasian patients from Spain/Italy (62.5%) and France (53.8%). Caribbean patients with NMO-IgG (+) displayed more attacks, more spinal attacks and a higher EDSS than NMO-IgG (-) cases, while brain and spinal cord MRI lesions were more frequent during remission, with more vertebral segments, more gray, white matter and holocord involvement. CONCLUSIONS: NMO IgG positive antibodies in NMO patients had a lower rate in the Caribbean area - where the population has a predominant African ancestry - than in Caucasian Europeans, suggesting the influence of a possible ethnic factor in the pathogenesis of the disease, but they confer a worse course with more attacks, more disability and MRI lesions.