Bruno Barroso

Intrathecal rituximab therapy in multiple sclerosis: review of evidence supporting the need for future trials.

Rituximab has demonstrated a major effect in B-cell lymphoma and in a wide range of autoimmune disorders. Unfortunately, the blood-brain-barrier excludes the disorders restricted to the central nervous system (CNS) from the action of rituximab. The progressive phase of multiple sclerosis (MS) is a prototypical CNS autoimmune disorder characterized by an intrathecal compartmentalization of inflammation resisting all the available immunosuppressive treatments. As a consequence, intrathecal therapeutics are promising new approach in progressive MS. We first review data gathered from animal models and human off-label intrathecal rituximab use in CNS lymphomas, then summarize the recent evidence supporting the need for trials based on the intrathecal use of rituximab in multiple sclerosis. The experience obtained in these settings offers valuable preliminary data for future studies in CNS autoimmunity.

Angiopathie cérébrale réversible du post-partum imputable à la bromocriptine

Resume Introduction Le post-partum est une periode a risque de survenue accrue de complications neuro-vasculaires. La bromocriptine est parfois incriminee dans la survenue d’une angiopathie cerebrale. Observation Une patiente de 26 ans developpa en post-partum un tableau associant cephalees, hypertension arterielle, convulsions et insuffisance renale aigue 8 jours apres avoir debute un traitement par bromocriptine (5 mg/jour) prescrite pour inhiber la lactation. L’angio-IRM cerebrale elimina une thrombose veineuse cerebrale et mit en evidence des hypersignaux corticaux couples a des signes de vascularite intra-crânienne. L’ensemble des symptomes cliniques, ainsi que les anomalies biologiques et radiologiques furent completement reversibles en une semaine apres arret de la bromocriptine. La chronologie des symptomes etait en faveur d’un effet indesirable cerebral et systemique de ce produit. Conclusion L’angiopathie cerebrale liee a la prise de bromocriptine est une entite rare, mais doit inciter les prescripteurs a une surveillance pharmacologique etroite en post-partum.

Stroke thrombolysis in the emergency department as an alternative service for community hospitals lacking a stroke unit.

Objective A significant advancement in the management of acute ischemic stroke has been the use of the recombinant tissue plasminogen activator (rtPA). French guidelines recommend that stroke patients should be treated in stroke units (SU); however, community hospitals experience practical difficulties in treating their patients because SUs are not sufficient in number. Only one SU is available in the Aquitaine area (southwest of France) and it is located in Bordeaux. To improve quality of care and to provide modern stroke therapy, we decided to assess whether thrombolysis was feasible in our community hospital located in Pau, 200 km from Bordeaux. Methods Selected patients were treated with rtPA and observed for 24 h in the emergency department. According to French legislation, rtPA therapy was defined as ‘off-label use’. National Institutes of Health stroke scale (NIHSS) was obtained on admission, immediately after treatment and 24 h after treatment. Results Results from the first 40 patients are reported in this study. They were treated between September 2004 and June 2006. In total, 1169 patients were admitted for stroke during this period. Outcomes and mortality rates were consistent with experience elsewhere. Conclusions According to the local infrastructural criteria and prerequisites described in this study, thrombolysis is a viable and feasible treatment option for stroke patients in emergency departments of French community hospitals. In the absence of an SU, this type of emergency treatment can be used as an alternative until SUs become more numerous throughout the country.

Compartmentalized intrathecal immunoglobulin synthesis during HIV infection - a model of chronic CNS inflammation?

Abstract HIV infects the central nervous system (CNS) during primary infection and persists in resident macrophages. CNS infection initiates a strong local immune response that fails to control the virus but is responsible for by-stander lesions involved in neurocognitive disorders. Although highly active anti-retroviral therapy now offers an almost complete control of CNS viral proliferation, low-grade CNS inflammation persists. This review focuses on HIV-induced intrathecal immunoglobulin (Ig) synthesis. Intrathecal Ig synthesis early occurs in more than three-quarters of patients in response to viral infection of the CNS and persists throughout the course of the disease. Viral antigens are targeted but this specific response accounts for <5% of the whole intrathecal synthesis. Although the nature and mechanisms leading to non-specific synthesis are unknown, this prominent proportion is comparable to that observed in various CNS viral infections. Cerebrospinal fluid-floating antibody-secreting cells account for a minority of the whole synthesis, which mainly takes place in perivascular inflammatory infiltrates of the CNS parenchyma. B-cell traffic and lineage across the blood–brain-barrier have not yet been described. We review common technical pitfalls and update the pending questions in the field. Moreover, since HIV infection is associated with an intrathecal chronic oligoclonal (and mostly non-specific) Ig synthesis and associates with low-grade axonal lesions, this could be an interesting model of the chronic intrathecal synthesis occurring during multiple sclerosis.

Early carotid artery endarterectomy after intravenous thrombolysis therapy

Carotid endarterectomy reduces the risk of stroke in patients with recently symptomatic stenosis.It is also well established that there is a reduction in benefit from CEA with time from the presenting event. Therefore, the procedure should be done early within two-weeks in neurologically stable patients (3,4). According to our results and the small data available in the medical literature, surgery of recently symptomatic severe carotid stenosis previously treated by IVT should not be delayed. There seems to be no higher haemorrhagic risk once this surgery is applied to patients with a stable neurological status and good clinical recovery after lysis. As large series of patients will be difficult to

F - 1 Syndrome de Gougerot-Sjögren primitif de localisation neurologique centrale évoluant sur un mode rémittent avec séquelles

Introduction L’atteinte isolee du systeme nerveux central conduit rarement a la decouverte d’un syndrome de Gougerot-Sjogren primitif. Nous rapportons une observation ayant initialement fait evoquer le diagnostic de neuro-myelite optique. Observations (Dossier 96.33.905) Une patiente de 34 ans fut hospitalisee en novembre 1997 pour une myelite de niveau D6. L’IRM mit en evidence un hypersignal T2 centro-medullaire etendu sur la hauteur de 6 vertebres. Le LCR et la biologie sanguine standard etaient normaux. L’IRM cerebrale etait normale. Deux mois plus tard devant une recidive clinique de niveau cervical, l’IRM montrait la presence d’une lesion supplementaire en regard de C3. En mars 1998 une NORB gauche fut diagnostiquee. Entre janvier et mars 2000 apparurent des douleurs neurogenes des membres inferieurs. Ces episodes regresserent sous corticotherapie. En 2002, elle presenta des cephalees et des troubles de la conscience. L’IRM cerebrale notait des anomalies de signal des noyaux gris centraux. Le LCR avait 44 lymphocytes et une chimie subnormale. La patiente conserva d’importantes sequelles neurologiques de l’episode : ataxie, vessie neurologique, troubles cognitifs, et acuite visuelle abaissee. En mars 2006, devant une nouvelle NORB, une biopsie des glandes salivaires accessoires montra des lesions de sialadenite chronique de grade 4 de Chisholm avec anticorps anti-SSA a 8xN. Le diagnostic de syndrome de Gougerot-Sjogren primitif etait pose. Discussion L’atteinte neurologique du syndrome de Gougerot-Sjogren primitif est presente chez environ 20 % des patients suivis pour cette affection. Les localisations au systeme nerveux central sont beaucoup plus rares que l’atteinte peripherique. La confusion avec le diagnostic de sclerose en plaques est souvent rapportee. Plus rares sont les formes evocatrices de neuro-myelite optique. Conclusion Cette observation reflete les difficultes diagnostiques du syndrome de Gougerot-Sjogren primitif d’expression limitee au systeme nerveux central. Immunosuppresseurs et corticotherapie pourraient ameliorer le pronostic.

Pseudo-migraine avec déficits neurologiques transitoires et lymphocytose du liquide céphalo-rachidien☆

INTRODUCTION: Pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis is a rare syndrome resolving within less than 3 months. CASE REPORT: A young 17-year-old woman without previous medical history was admitted to the hospital because of right motor weakness and language disturbances. The symptoms resolved in a few hours and were followed by severe left headaches with important vegetative signs. Several similar episodes were noted in the previous 10 days. Cranial MRI was normal. EEG showed important slowing of the cerebral electrogenesis. More than 250 lymphocytic cells were found at CSF analysis. Outcome was spontaneously favorable, without similar symptoms after 6-month follow-up. CONCLUSION: Pseudomigraine with lymphocytic pleocytosis seems to be a particular syndrome of unknown origin. This is an elimination diagnosis, generally with a benign course.

Natalizumab is effective in controlling the inflammatory rebound after its discontinuation and failure of an alternative treatment

Progressive multifocal leukoencephalopathy (PML) is the most feared complication when natalizumab (NAT) is used in the treatment of relapsing multiple sclerosis (MS). JC virus serologic status is a currently established risk factor for PML. When seroconversion occurs, NAT discontinuation should be based on a solid rationale to avoid an MS inflammatory resurgence. The JC virus index value may also provide further useful information to help practitioners and patients in their decision process.

Decompressive craniectomy for stroke after intravenous thrombolytic therapy.

Decompressive craniectomy (DC) is a major surgical procedure that can save life of patients with malignant edema after middle cerebral artery (MCA) infarction (1). Intravenous thrombolysis (IVT) is the only approved treatment for patients with acute ischemic stroke within 4·5 hours of symptoms onset (2). Rare previously case studies have already stated that DC in the context of post-IVT treatment might be safe (3,4). We have an additional five cases in which early DC (<48 h) post-IVT was performed. The selection criteria for these patients were the following: thrombolysis for acute supratentorial ischemic stroke; patients age <60 years old; worsening neurologic exam with decrease in the level of consciousness; 24-h post-IVT MRI diffusion-weighted imaging ischaemic volume >145 cm. There were three men and two women aged from 43 to 58 years old. Patients did not present significant disability before stroke, except one who had a mild mental retardation. Surgical procedures consisted of the creation of a large bone flap with a diameter of at least 12 cm, with no resection of the infarcted brain. After surgery, patients were transferred to the intensive care unit. No evidence of major haemorrhagic complication was observed during the procedure. Two patients died in the following days: death was attributed to an acute myocardial infarction in one case, whereas the second patient presented a state of decerebration followed quickly by a brain dead status. At three-months all the three surviving patients were still hospitalized in the rehabilitation department with a modified Rankin Score (mRS) of 4. At six-months, two of them had gone home with a mRS of 3. At that time, the fifth patient had a mRS of 5 after suffering from serious infectious complications. Natural prognosis of malignant edema after MCA infarction is poor with fatality rates series of nearly 80%. In carefully selected patients, IVT does not appear to be an obvious barrier for DC. As large series will be difficult to collect, it is of interest to report small experiences as ours to try to improve patients care.

Postpartum Four-Vessel Cervical Artery Dissection

A postpartum four-vessel cervical artery dissection with no stroke is reported. This transient vasculopathy took place in the autoimmune context of the HELLP syndrome combined with the reversible posterior leucoencephalopathy syndrome. Correlations between the clinical, radiological and biological entities are discussed.