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Susac syndrome is a rare vasculopathy of unknown aetiology, affecting prominently young women and electively targeting brain (encephalopathy), retina (visual field defects), and cochlea (hearing loss), of which optimal treatment has yet to be established. We report clinical, CSF and MRI features together with the long-term outcome in a monocentric series of eight consecutive patients with unusual sex ratio (5 male; 3 female), to define the best diagnostic/therapeutic strategy. Six patients presented with the classical clinical triad within less than 6 months after symptoms onset; two did not suffer from sensorineural hearing loss. All but one received a treatment combining high doses of methylprednisolone and cyclophosphamide intravenously. The first two patients had very delayed diagnosis (6-4 months) resulting in severe cognitive sequelae. The third one had only mildly delayed diagnosis (2 months) with subsequent behaviour impairment and severe right hypoacousia. All three were unable to return to work. The last five patients who had early diagnosis and undelayed aggressive treatment were able to resume their professional activities.

Clinical trials have shown that natalizumab is highly effective for treating relapsing forms of multiple sclerosis (MS). The purpose of this analysis was to conduct a targeted review of data from country-specific observational studies and registries of natalizumab-treated patients with relapsing MS in order to more fully investigate the longer-term effectiveness and safety of this disease-modifying therapy in real-world clinical practice settings. A PubMed search was conducted on March 13, 2014, using the terms (natalizumab AND multiple sclerosis) AND (observational OR registry OR post-marketing OR clinical practice). Only English-language papers that reported effectiveness (in terms of effects on relapses, disability progression, and magnetic resonance imaging findings) and/or safety results from studies were included. Data from 22 studies/registries were included. Annualized relapse rates decreased by 73%-94% from baseline across the studies, with improvement maintained for up to 5 years during natalizumab treatment. Natalizumab effectiveness was also demonstrated via assessment of disability progression (Expanded Disability Status Scale), radiological measures, and no-evidence-of-disease-activity measures (clinical, radiological, and overall). Results were similar among patient groups stratified by level of disease activity. Safety outcomes were consistent with natalizumab's known safety profile. Data from country-specific observational studies and registries varying in size and scope support the effectiveness and safety of natalizumab in a broad range of patients in clinical practice., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Accumulating data highlight proinflammatory processes leading to MS relapses. Whether anti-inflammatory mechanisms are concomitantly activated is unclear. The ectonucleotidase CD39 has been described as a novel T regulatory cell (Treg) marker. The purpose of this study was to explore whether regulatory mechanisms are activated during MS relapses and reinforced by intravenous methylprednisolone (ivMP)., Methods: Blood samples were collected from stable and relapsing MS patients and healthy controls. We used FOXP3 methylation-specific qPCR and CD4(+)CD25(high)FOXP3(+) analysis to quantify Tregs. Cytokine mRNA expression levels were measured in peripheral blood mononuclear cells (PBMCs) and in CD4(+) T cells. CD39 expression was determined by flow cytometry in monocytes, NK, T and B cells. CD39 enzymatic activity was assessed by ATP luminometry., Results: The proportion of Tregs was similar in relapsing MS patients and healthy controls. CD39 mRNA level was higher in PBMCs of relapsing MS patients than in controls. The proportion of CD39-expressing Tregs was higher in MS patients. IvMP decreased the overall proportion of Tregs while it increased CD39 mRNA levels, the proportions of CD39-expressing Tregs and monocytes as well as CD39 ectonucleotidase activity., Conclusions: Our data suggest that immunoregulatory mechanisms are ongoing in MS patients, particularly during relapses, and strengthened by ivMP., (© The Author(s), 2015.)

Background: Multiple sclerosis (MS) likely results from an imbalance between regulatory and inflammatory immune processes. CD39 is an ectoenzyme that cleaves ATP to AMP and has been suggested as a novel regulatory T cells (Treg) marker. As ATP has numerous proinflammatory effects, its degradation by CD39 has anti-inflammatory influence. The purpose of this study was to explore regulatory and inflammatory mechanisms activated in fingolimod treated MS patients., Methods and Findings: Peripheral blood mononuclear cells (PBMCs) were isolated from relapsing-remitting MS patients before starting fingolimod and three months after therapy start. mRNA expression was assessed in ex vivo PBMCs. The proportions of CD8, B cells, CD4 and CD39-expressing cells were analysed by flow cytometry. Treg proportion was quantified by flow cytometry and methylation-specific qPCR. Fingolimod treatment increased mRNA levels of CD39, AHR and CYP1B1 but decreased mRNA expression of IL-17, IL-22 and FOXP3 mRNA in PBMCs. B cells, CD4+ cells and Treg proportions were significantly reduced by this treatment, but remaining CD4+ T cells were enriched in FOXP3+ cells and in CD39-expressing Tregs., Conclusions: In addition to the decrease in circulating CD4+ T cells and CD19+ B cells, our findings highlight additional immunoregulatory mechanisms induced by fingolimod.

Purpose of Review: Infectious neuropathies are heterogeneous neuropathies with multiple causes. They still represent an important world health burden and some of them have no current available therapy., Recent Findings: Leprosy incidence has decreased by 50% during the last years, but leprosy-related neuropathies still cause severe disability. The pure neuritic leprosy is a diagnostic challenge that may require nerve biopsy or nerve aspiration cytology. The treatment itself may lead to a 'reversal reaction', which further causes injuries to the nerve. HCV-related neuropathies may be related or not to the presence of cryoglobulins. The absence of vasculitis, the most frequent form is a peripheral sensory neuropathy involving small nerve fibers, and more accurately diagnosed by pain-related evoked potentials. HIV-related neuropathy has become the major neurological complication of HIV infection. Both HIV-induced neuropathy and antiretroviral toxic neuropathy are clinically indistinguishable. The existence of an isolated chronic polyneuropathy due to Borrelia burgdorferi remains highly controversial. Lastly, an active infectious ganglioneuritis caused by varicella zoster virus, producing shingles, is the most frequent infectious neuropathy in the world and may cause various neurological complications. Zoster sine herpete remains frequently undiagnosed., Summary: Recent data have improved our knowledge and diagnostic tools of infectious neuropathies. Treatment of the injured nerves is not yet available, and prevention and rapid diagnosis remain the main priorities for the clinician.

The concomitant production of IL-17A and IL-9, both Th17 cytokines, has not been compared in MS patients. We show that IL-17A but not IL-9 expression by CD3(+) cells was increased during a MS relapse. Co-expression of IL-17A and IL-9 was marginal. In addition to Th1 and Th2 cytokines, IL-17A, IL-6 and IL-23p19 were down-regulated by ivMP, but Foxp3 was not, while an increase in IL-10, TGF-β1 and IL-27p28 mRNA was observed. This change in the Th17, Treg and IL-10 balance could be an additional mechanism by which corticosteroids shorten the duration of a MS relapse and promote recovery., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We describe a patient who had four relapses of Miller Fisher syndrome over a period of 20 years. The classical triad - ophthalmoparesis, ataxia and areflexia - was present during the first two attacks; ataxia was not observed during the third episode. The final recurrence was characterized by signs suggestive of a central involvement of the oculomotor pathways, subclinical slowing of the visual-evoked potentials, and peripheral vestibular hyporeactivity. Brain imaging was normal, but high levels of anti-GQ1b IgG antibodies were detectable during the second relapse and persisted after the fourth recurrence despite complete clinical recovery., (Copyright © 2011 S. Karger AG, Basel.)

Neurosarcoidosis is a diagnostic challenge, especially in the absence of systemic involvement, even when cerebral biopsies show noncaseating granulomas. We report a patient with a pineal germinoma associated with a extensive peri- and intra- tumoural granulomatous reaction, who was first diagnosed as possible neurosarcoïdosis. A second patient was initially considered as suffering from Multiple Sclerosis. Brain biopsy showed typical granulomas and gallium scintigraphy revealed other locations of the disease. Unfortunately, he developed a severe, steroid-induced, epidural lipomatosis at the Th3-Th8 levels and died unexpectedly after surgical decompression. Granulomatous inflammation in a tissue obtained by biopsy from a midline lesion should be always considered for the differential diagnosis of germinoma. Corticosteroid-sparing immunosuppressant drugs should be used early in neurosarcoïdosis.

Background: There is no specific serum-based biomarker for the diagnosis or prognosis of relapsing-remitting multiple sclerosis (RRMS)., Objective: We investigated whether levels of IgM antibodies to Glc(alpha1,4)Glc(alpha) (GAGA4) or to a panel of four glucose-based glycans could differentiate MS from other neurological diseases (OND) or predict risk of early relapse following first presentation (FP) of RRMS., Methods: Retrospective analysis of 440 sera samples of three cohorts: A) FP-RRMS (n = 44), OND (n = 44); B) FP-RRMS (n = 167), OND (n = 85); and C) FP (n = 100). Anti-GAGA4 IgM levels were measured by enzyme immunoassay in cohort-A and cohort-B. Cohort-C IgM antibodies to glucose-based glycan panel were measured by immunofluorescence., Results: FP-RRMS had higher levels of anti-GAGA4 IgM than OND patients (cohort-A, P = 0.01; cohort-B, P = 0.0001). Sensitivity and specificity were 27% and 97% for cohort-A; and 26% and 90% for cohort-B, respectively. In cohort-C, 58 patients experienced early relapse (<24 months), 31 had late relapse (> or =24 months), and 11 did not experience second attack during follow-up. Kaplan-Meier curves demonstrated decrease in time to next relapse for patients positive for the antibody panel (P = 0.02, log rank)., Conclusions: Serum anti-GAGA4 IgM discerns FP-RRMS patients from OND patients. Higher levels of serum anti-alpha-glucose IgM in FP patients predict imminent early relapse.

Lyme disease is a multisystemic disorder caused by an epizootic organism of the spirochete group, called Borrelia burgdorferi, which is transmitted to humans by ticks of the genus Ixodes. Lyme neuroborreliosis may occur during the early dissemination phase, most often as a painful meningo-radiculitis and very rarely as a radiculo-myelitis, whereas encephalomyelitis is observed in the late phase. We report the case of a patient with an early subacute poliomyelitis-like syndrome closely matching the selective involvement of the anterior horns and roots of the cervical spinal cord seen on magnetic resonance imaging. This condition improved with appropriate antibiotics.

We report the case of a 23-year-old male patient who suddenly developed right hemiparesis, cerebellar ataxia, dysarthria, and bilateral dysmetria. Brain magnetic resonance (MR) examination demonstrated hyperacute ischaemic lesions within the pons. CSF analysis revealed a high protein content, lymphocytic pleocytosis, and oligoclonal IgG bands not present in the serum. Elevated IgM and IgG anti-Borrelia burgdorferi antibodies were shown in both serum and CSF samples, associated with an intrathecal synthesis of these antibodies. Ischaemic CNS lesions have been rarely observed as the first manifestation of Lyme neuroborreliosis. The putative mechanism for parenchymal ischaemia is the local extension of inflammatory changes from meninges to the wall of penetrating arterioles.

We report two new cases of mitoxantrone-related leukemia occurring in two patients with multiple sclerosis (MS), 14 and 18 months after the last infusion of the drug. One patient was successfully treated. We were able to collect 29 other cases in the literature. Most of them were single reports but some were described within cohorts of mitoxantrone-treated MS patients. The incidence rate was 0.65% from all cohorts totalizing 2299 patients. Acute promyelocytic leukemia with the translocation t(15;17) was over-represented in the MS population in comparison with cancer patients also treated with mitoxanrone. The occurrence of leukemia was dose-independent and appeared with a mean delay of 20 months after the end of the treatment.

Transient neuroimaging features indicating primary cortical and secondary subcortical white matter cytotoxic oedema have been described in association with prolonged or intense seizures. We describe the unusual condition of recurrent ictal cortical blindness due to focal occipital status epilepticus, in the context of chronic hepatic failure. There was a close association between the onset and disappearance of clinical, electrophysiological and magnetic resonance imaging abnormalities.

Objective: To study cerebrospinal fluid (CSF) and serum samples from 34 consecutive patients suspected of having varicella-zoster virus (VZV) infection of the central nervous system (CNS)., Population and Methods: The patients were divided into three groups. The first group consisted of 27 patients with a rash in one to three dermatomes and clinical suspicion of meningitis and radiculitis; among them, three subgroups were distinguished according to the affected dermatome: ophthalmicus (n = 9), oticus (n = 11) and cervico-thoraco-lumbar zoster (n = 7). Four cases of zoster sine herpete (ZSH) were included in the second group: these patients presented with either radiculitis (n = 2) or meningoencephalitis (n = 2), without cutaneous eruption. The third group consisted of three patients with a generalised rash and encephalitis. A polymerase chain reaction (PCR) for VZV DNA and antigen-driven immunoblots for oligoclonal anti-VZV antibodies were carried out on all CSF samples., Results: PCR of the CSF was positive in 44% of the patients from the first group, mainly within the first 7 days after eruption. In addition, intrathecal synthesis of anti-VZV antibodies was detected in 37% of patients, always after an interval of 7 days (p<0.0001). Among the four patients with ZSH, a positive VZV PCR was detected in three patients and CSF-specific oligoclonal anti-VZV antibodies in two. PCR was also positive in the CSF of two of the three patients with generalised rash and encephalitis; local production of anti-VZV antibodies was seen in a second CSF sample in one patient, and was also present in the third patient., Conclusion: Amplification of VZV DNA by PCR in the CSF and antigen-driven immunoblots have important diagnostic value in suspected VZV infection, although their presence depends on the timing of the CSF sampling. VZV is thought to be a causative agent in unexplained cases of meningitis associated with radiculitis or focal CNS symptoms, even in the absence of skin manifestations. In such patients, rapid diagnosis by this combined approach permits early antiviral treatment.

L-2-Hydroxyglutaric (L-2-HG) aciduria is a rare inherited metabolic disease usually observed in children. Patients present a very slowly progressive deterioration with cerebellar ataxia, mild or severe mental retardation, and various other clinical signs including extrapyramidal and pyramidal symptoms, and seizures. The disease is characterized by increased levels of L-2-HG in body fluids such as urine and cerebrospinal fluid. We report on two sisters from consanguineous parents, in whom L-2-HG aciduria was diagnosed at an adult age. Although magnetic resonance imaging and spectroscopic findings were severely abnormal in both, they experienced a different clinical course. The older sister presented with severe mental retardation, recurrent epileptic seizures, and progressive deterioration in her ability to walk and to talk; she is now confined to a wheelchair with severe speech deficit. In contrast, the younger sister only had a few epileptic seizures in childhood and moderate mental retardation, is still able to walk, and performs manual work, and has a social life in a specialized institution for moderately mentally handicapped persons. For the two patients, a complete deletion of exon 9 was demonstrated in a gene located on chromosome 14q22.1, which most probably encodes for L-2-hydroxyglutarate dehydrogenase. The pathological findings observed in this metabolic disorder could therefore be related to a toxic effect of L-2-hydroxyglutarate on the central nervous system, although the presence of other toxic metabolites cannot be excluded.

Amphiphysin, a synaptic vesicle protein, is an auto-immune target in rare cases of paraneoplastic neurological disorders. We report two additional cases with distinct neurological syndromes and paraneoplastic anti-amphiphysin antibodies. The first patient, a 59-year-old man, presented with cerebellar and cranial nerve dysfunction and small cell lung carcinoma. The second, a 77-year- old woman, presented with left brachial plexopathy followed by sensorimotor neuropathy and breast carcinoma., (Copyright 2006 S. Karger AG, Basel.)

Mitoxantrone is an approved drug for patients with worsening relapsing-remitting, secondary progressive and progressive relapsing multiple sclerosis (MS). From a cohort of 820 MS patients, 52 (6%) were treated with this drug between December 1991 and April 2003. Mitoxantrone was administered at a dose of 12 mg/m(2) once a month for three months and then at three-month intervals to reach a total cumulative dose of 144 mg/m(2). The left ventricular ejection fraction was checked by radionuclide ventriculography prior to treatment and every six months. Treatment was stopped if the ejection fraction was below 50% in two consecutive ventriculographies performed one to three months apart. Cardiotoxicity during the course of the treatment was not observed. However, three patients developed congestive heart failure 24, 39 and 80 months after the last dose of mitoxantrone. Other cardiac causes were excluded. Two of these patients had been treated previously with cyclophosphamide. All patients first recovered on medical treatment, but two worsened a few months later. One patient remained severely symptomatic in spite of optimal medical treatment. Although mitoxantrone is generally well tolerated and reduces progression of disability and clinical exacerbations, our observation of a delayed cardiotoxicity makes necessary a long-term follow-up of MS patients treated with this drug.

Between June 1995 and November 1998, 228 patients with relapsing-remitting Multiple Sclerosis started treatment with glatiramer acetate (Copaxone) 20 mg once daily in the frame of a "compassionate use" protocol in 15 Belgian centers. Following an average treatment period of 5.8 years, treating neurologists were requested to fill in follow-up forms indicating neurological disability status and side effects during the previous 6 months. These data were available for 134 patients. In this group, the Expanded Disability Status Scale (EDSS) improved in 26.3% of patients. An additional 36.8% of patients remained neurologically stable. The Ambulation Index (AI) showed similar results: 12.5% of patients improved, 50% of patients remained stable, and 37.5% worsened. Only 10% of patients dropped out due to several reasons. The adverse events occurring in the period preceding the follow-up survey were non-serious and consistent with the current product information of glatiramer acetate. Among the 94 patients no longer followed-up in the compassionate program, reasons for lost to follow-up were obtained for 63; most of them (41) had stopped GA treatment or switched to another disease-modifying treatment. Overall these results are very similar to the ones reported in the extension study of the pivotal trial (Johnson et al., 2000), and indicate that patients treated with glatiramer acetate have a better outcome than expected on the basis of the natural course of the disease. Despite limitations of the study design, this report confirms the sustained efficacy of glatiramer acetate in reducing the disease progression in patients with relapsing-remitting multiple sclerosis treated in day-to-day clinical practice.

New criteria for the diagnosis of multiple sclerosis (MS) were published as the result of an internationally formed committee. To increase the specificity of diagnosis and to minimize the number of false diagnoses, the committee recommended the use of both clinical and paraclinical criteria, the latter involving information obtained from magnetic resonance imaging, evoked potentials, and cerebrospinal fluid (CSF) analysis. Although rigorous magnetic resonance imaging requirements were provided, the "new criteria paper" fell short in terms of guidelines as to how the CSF analysis should be performed and simply equated the IgG index with isoelectric focusing, without any justification. The spectrum of parameters analyzed and methods for CSF analysis differ worldwide and often yield variable results in terms of sensitivity, specificity, accuracy, and reliability, with no decided "optimal" CSF test for the diagnosis of MS. To address this question specifically, an international panel of experts in MS and CSF diagnostic techniques was convened and the result was this article, representing a consensus of all the participants. These recommendations for establishing a standard for the evaluation of CSF in patients suspected of having MS should greatly complement the new criteria in ensuring that a correct diagnosis of MS is being made.

We describe clinical and magnetic resonance (MR) features in a 69-year-old, Caucasian woman presenting with an unusual meningeal onset of cerebral schistosomiasis. Magnetic resonance work-up demonstrated supra- and infratentorial lesions with prominent brainstem involvement contrasting with the paucisymptomatic clinical presentation. Because of a recent stay in Uganda, including swimming in Lake Victoria, a diagnosis of neuroschistosomiasis was suggested. Serological tests and rectal biopsy confirmed the putative diagnosis. The patient was successfully treated with praziquantel at a dose of 50 mg/kg/day for 15 days. Brain MRI abnormalities improved dramatically within two months.

We report the serial MR imaging and neuropathologic findings in a patient with fibrocartilaginous embolism to the spinal cord, presumptively originating from vertebral body endplates. Extensive increased T2 signal intensity, minimal contrast enhancing foci, concomitant vertebral body bone marrow infarction, and terminal cord hemorrhagic necrosis were the main MR imaging features. Pathologic examination of the cord demonstrated arteriolar occlusions by chondrocytic thrombi resulting in hemorrhagic necrosis.

Cerebrospinal fluid (CSF) TAU protein and Amyloid beta42 were able to distinguish between 28 mild cognitive impairment (MCI) patients and both 38 normal aged and 17 anxious and depressed elderly patients, with good sensitivity/specificity when the two measures were combined. These biological markers are independent predictors of the presence of Alzheimer disease (AD), in addition to memory performance. Low Amyloid beta42 level was predictor of a fast progression of MCI patients to full blown dementia. The TAU protein level tended to correlate with memory performance, presumably in relation with the extent of the bilateral medio-temporal damage in early AD.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

We report two cases of paraneoplastic limbic encephalitis (PLE) that differed in their clinical patterns, the underlying tumours, and the associated paraneoplastic antibodies. The first patient was a young adult male, with anti-MA-2 antibodies and testicular tumour. The clinical picture was restricted to limbic involvement. The second patient was a 56-year old, female heavy smoker; with seizures and depression, but also vertigo and diplopia. A low level of serum anti-Hu antibodies led to the detection of a small cell lung carcinoma by total body PET-scanning. In both cases, intrathecal synthesis of CSF oligoclonal IgG bands and of the corresponding paraneoplastic antibodies was demonstrated.

Reelin is a large extracellular glycoprotein that is defective in reeler mutant mice and plays a well-established role during brain development in human as well as rodents. In the adult brain, Reelin is expressed in a subset of GABAergic interneurons. Its role in disease states is not clearly defined, although it is implicated in autism and psychoses such as schizophrenia. In this report, we show that Reelin immunoreactive proteins can be detected in the human cerebrospinal fluid (CSF) with monoclonal antibodies directed against the N- and C-terminal regions of the protein. In CSF, Reelin is present as different products due to processing at two main sites; preservation at -20 degrees C increases processing further. CSF Reelin originates from the brain tissue and not from plasma. The protein was detected in comparable concentrations in children and adults, and the signal varied largely from subject to subject with no obvious correlation with age or neurological disease state.

Background: Oligoclonal free kappa bands are present as frequently as oligoclonal IgG bands in the cerebrospinal fluid (CSF) from patients with definite multiple sclerosis (MS) and can even occur in the absence of oligoclonal IgG. As such, they too are markers of an ongoing intrathecal immune process., Objectives: To determine how frequently oligoclonal free kappa bands are detectable in the CSF from patients with clinical signs and symptoms suggestive of MS in the absence of CSF restricted oligoclonal IgG., Methods: An immunoaffinity mediated immunoblotting technique specific for free kappa chains was used, after isoelectric focusing of paired CSF and serum samples from 33 patients with clinical signs and symptoms suggestive of MS but without CSF oligoclonal IgG. CSF data were correlated with MRI results in the context of the new diagnostic criteria from McDonald et al., Results: Eighteen CSF samples contained oligoclonal free kappa bands (54%), mainly from patients with motor dysfunction (83%) and optic neuritis (64%). All patients with a positive MRI according to Barkhof's criteria (n = 6) had free kappa bands in their CSF., Conclusions: (1) Oligoclonal free kappa bands in the CSF are related to the dissemination of MS lesions; (2) such bands should be looked for in oligoclonal IgG negative CSF, and (3) the presence of free kappa bands in the CSF may be a substitute for oligoclonal IgG in the McDonald's criteria for diagnosis of MS.

Introduction: Paraneoplastic choreo-athetoses are rare. We report a case of anti-Hu syndrome with choreo-athetosis., Case Report: A 48-year-old woman developed a small-cell lung carcinoma revealed by an anti-Hu syndrome. The neurological features included choreo-athetosis predominating in the upper limbs, chronic sensorimotor axonal polyneuropathy, and opsoclonus. The cerebrospinal fluid was acellular and contained several oligoclonal IgG bands, not found in the corresponding serum. Magnetic resonance imaging revealed bilateral high-intensity lesions on T2/FLAIR sequence in the corona radiata. Moderate transitory improvement of the paraneoplastic neurological syndrome was observed after several carboplatin-etoposid cycles., Conclusion: A paraneoplastic origin must be considered in all cases of unexplained choreo-athetosis. Paraneoplastic choreo-athetosis is most often associated with other neurological symptoms. The most frequent associated tumor is a small-cell lung carcinoma with anti-CRMP5 and/or anti-Hu antibodies. Our patient developed paraneoplastic choreo-athetosis related to an anti-Hu syndrome in the absence of anti-CRMP5/CV2 antibodies. Paraneoplastic choreo-athetosis might result from a central lesion, and/or from proprioceptive deafferentation subsequent to peripheral neuropathy.

Quantitative and qualitative techniques for assessment of the intrathecal humoral immune response in human African trypanosomiasis were compared, and their diagnostic potential for detection of the meningo-encephalitic stage of the disease was evaluated. Total and trypanosome specific immunoglobulin G (IgG) and IgM intrathecal synthesis were studied in paired cerebrospinal fluid (CSF) and blood samples of 38 trypanosomiasis patients and in three controls using Reiber's formulae. The presence of CSF-specific oligoclonal IgG and of trypanosome-specific antibodies was determined using iso-electric focusing followed by immunoblotting and antigen-driven immunoblots. The intrathecal IgG fraction (16% positive) and oligoclonal IgG detection (24% positive) were insensitive for detection of an intrathecal humoral immune response. Trypanosome-specific IgG synthesis, reflected by the IgG antibody index (AI) (26% positive), was confirmed by the presence of oligoclonal specific IgG (47% positive), but the latter was more sensitive. Although the detection technique failed for oligoclonal IgM, the intrathecal IgM fraction (42% positive) and the IgM AI (32% positive) indicated that the meningo-encephalitic stage of the disease is characterized by a dominant intrathecal IgM response, which was higher than the IgG response. The highest combination of diagnostic sensitivity and specificity for the meningo-encephalitic stage of trypanosomiasis was observed for quantitative IgM determinations.

Background: In carotid artery dissections, local and ischemic manifestations usually occur within days or weeks. In some cases, persistent extracranial aneurysms cause thromboembolic complications even years after the initial event. The management of these aneurysms is still controversial., Case Description: We report the case of a 74 year old woman with a stroke due to a long standing giant dissecting aneurysm of the internal carotid artery. Medical management was insufficient to stop ongoing embolization. She was finally successfully treated with stenting., Conclusion: Carotid artery aneurysms can become symptomatic even after many years of silence. Once medical therapy fails, endovascular treatment can avoid recurrent embolization.

Polymerase chain reaction assays are a powerful tool for detecting the presence of infectious genomes in the cerebrospinal fluid. Positive results always mean a current or pending infection of the central nervous system. Subacute (>7 days) or chronic infections induce an intrathecal humoral immune response and the appearance of oligoclonal IgG antibodies directed against the causal infectious agent. This local synthesis may be observed even in cases of severe systemic immunodeficiency. The use of polymerase chain reactions in combination with the detection of a specific intrathecal immune response should represent the most reliable strategy for the diagnosis of viral and chronic infections of the central nervous system. The authors describe their experience, using this approach, in herpetic encephalitis, acute and recurrent herpetic meningitis, varicella zoster-induced neurological diseases, cytomegalovirus encephalitis, progressive multifocal leukoencephalitis and tuberculous meningitis.

A father and his daughter displayed strictly similar focal brain dysplasia at MR examination, characterized by regional medial posterior laminar sub-cortical grey matter heterotopia. To our knowledge, no family presenting such anomalies has yet been described. LIS1 and DCX gene defects were excluded. Collecting patients with such inherited dysplasia should improve our knowledge of the genetic basis of cortical malformations.

Diagnosis of central nervous system (CNS) involvement in human African trypanosomiasis is crucial in determination of therapy. Cerebrospinal fluid (CSF) and serum immunoglobulin concentrations, blood-CSF barrier dysfunction, pattern of intrathecal immunoglobulin synthesis, trypanosome-specific antibody synthesis, and CSF lactate concentrations were analyzed in 272 patients with Trypanosoma brucei gambiense infection. As part of the 2- or 3-class immune response, the predominant intrathecal IgM synthesis was the most sensitive (95%) marker for inflammation of the brain. We propose to replace the World Health Organization (WHO) criteria (white blood cell count >5 cells/microL and presence of trypanosomes in CSF) with a new approach for stage determination in trypanosomiasis: CNS involvement is diagnosed only in patients with >20 cells/microL or with intrathecal IgM synthesis, independent of the presence of trypanosomes in CSF. Compared with the use of these new criteria, the WHO criteria incorrectly classified 49 of 234 patients in the meningoencephalitic stage and 7 of 38 patients in the hemolymphatic disease stage. We also show that trypanosomiasis-related immunoglobulin patterns are of value in differential diagnosis.

A group of neurologists and clinical neurochemists representing twelve countries worked towards a consensus on laboratory techniques to improve the quality of analysis and interpretation of cerebrospinal fluid (CSF) proteins. Consensus was approached via a virtual Lotus Notes-based TeamRoom. This new approach respecting multicultural differences, common views, and minority opinions, is available in http://www.teamspace.net/ CSF, presenting the implicit, complementary version of this explicit, printed consensus. Three key recommendations were made: CSF and (appropriately diluted) serum samples should be analyzed together in one analytical run, i.e., with reference to the same calibration curve. Results are evaluated as CSF/serum quotients, taking into account the non-linear, hyperbolic relation between immunoglobulin (Ig)- and albumin-quotients rather than using the linear IgG index or IgG synthesis rate. Controls should include materials with values within the reference ranges (IgM: 0.5-1.5 mg/l; IgA: 1-3 mg/l; IgG: 10-30 mg/l and albumin: 100-300 mg/l). The physiological, methodological and clinical significance of CSF/serum quotients is reviewed. We confirmed the previous consensus on oligoclonal IgG, in particular the usefulness of the five typical interpretation patterns. The group compared current external and internal quality assurance schemes and encouraged all members to maintain national or local traditions. Values for acceptable imprecision in the CSF quality assurance are proposed.

Concurrent radionecrosis within the spinal cord and the bone marrow at the same thoracic level was observed 8 years after localized therapeutic irradiation in a patient who had undergone repeated cycles of radiotherapy, glucocorticoid treatment, and chemotherapy for a non-Hodgkin's lymphoma. Mechanisms combining radiotoxic potentialization by glucocorticoids/alkylating agents and delayed radiation-induced vasculitis involving the common arterial pathways to the spinal cord and to the vertebrae were speculated to have acted in a synergistic way.

The complex pathogenesis of multiple sclerosis includes inflammation and potentially disabling focal lesions that are associated with heterogeneous, often destructive pathologic changes disseminated throughout the white matter of the central nervous system. Genetic and environmental factors may trigger the movement of autoreactive T cells, from the systemic circulation into the central nervous system through disruption of the blood-brain barrier. In the brain, local factors may enhance the immune reaction, resulting in the proliferation of pro-inflammatory CD4+ type 1 T cells, and ultimately in immune-mediated injury of oligodendrocytes and myelin. The exposed axon segments may be susceptible to further injury from soluble mediators such as cytokines, chemokines, complement and proteases, resulting in irreversible axonal lesions. Partial remyclination may occur by differentiation of resident oligodendrocyte precursor cells. Decreases in the volume of the brain and spinal cord, indicating atrophy, correlate with both the loss of axons and the occurrence of extensive demyelination, and are markers of the degenerative phase of the disease. Besides classical motor and sensory signs and symptoms, cognitive impairment is frequently observed and increases the burden of the disease.

A double-blind clinical trial of mitoxantrone versus methylprednisolone was performed in 49 patients with relapsing, secondary multiple sclerosis. Patients were randomized to receive 13 infusions of mitoxantrone 12 mg/m2 (n = 28), or 13 infusions of 1 g of methylprednisolone (n = 21), over 32 months. Twenty-four patients completed the trial. There were no statistical differences between the two groups of patients at study entry. A significant improvement in the Expanded Disability Scale Score (EDSS) was observed in the mitoxantrone group after one year of treatment (p < 0.0022). The total number of relapses, the mean number of relapses/patient/year, and the total number of gadolinium-enhanced lesions on bi-annual MRI scans were significantly decreased in the mitoxantrone group throughout the study period. Nausea, vomiting, and alopecia were more frequent in the mitoxantrone-treated patients. Mitoxantrone has a role in the treatment of MS patients with frequent exacerbations and rapid disease progression.

The association of an acute encephalopathy, neurosensory hearing loss and retinal branch artery occlusions in a 35 year old man as well as the absence of systemic disease suggest the diagnosis of Susac's syndrome. This is the eighth male case described, the syndrome being more frequently reported in females.

In normal conditions, albumin and immunoglobulin (Ig)G in the cerebrospinal fluid (CSF) originate from the blood, and there is no antibody production within the central nervous system. Up to 20% of CSF proteins are intrathecally synthesized, but the major fraction is blood-derived. The CSF/serum albumin quotient (QAlb) is the best marker of the blood-CSF barrier function. The corresponding immunoglobulin quotients (QIGG, QIGA, QIGM) are not linearly related to QAlb and their correlations are defined by an hyperbolic equation. This equation is used to discriminate between a blood-derived and a locally produced fraction of immunoglobulins in case of an intrathecal humoral immune response. The detection of CSF-specific oligoclonal IgG is more sensitive than the quantitative comparison between QIGG and QAlb. A further step is the determination of antibody indices and the detection of specific oligoclonal antibodies by antigen-driven immunoblots. CSF analysis remains a cornerstone for the diagnosis of various neurological disorders, including multiple sclerosis and infectious diseases of the central nervous system.

The MR monitoring of a patient with acute spontaneous intracranial hypotension successfully treated by epidural blood patch revealed strikingly different time course of the initially concomitant cranial and spinal subdural fluid collections. This undescribed feature suggested different pathophysiological mechanisms for the disorder in the two locations and should be kept in mind when imaging patients with the condition.

Toxocara canis causes the visceral larva migrans syndrome in which central nervous involvement is rare. We report the case of a 40-year-old woman presenting with a subacute weakness of the right leg and dysaesthesiae in the right Th8-Th10 dermatomas. Spinal magnetic resonance imaging examination showed abnormal hyperintensity within the spinal cord. Cerebrospinal fluid analysis revealed eosinophilic pleocytosis. Antibody titres to Toxocara canis were higher in the cerebrospinal fluid than in the serum. Treatment using mebendazole led to a complete clinical recovery, normalization of cerebrospinal fluid parameters and improvement in spinal magnetic resonance imaging abnormalities.

We report on a case of biopsy-proven progressive multifocal leukoencephalopathy (PML) in a patient without obvious immunodeficiency. Analysis of the cerebrospinal fluid revealed the simultaneous presence of JC virus DNA and of locally produced, anti-JC virus antibodies. The intrathecal humoral immune response increased throughout the course of the disease, whereas the detection of the JC genome became ultimately negative in spite of the continuous extension of the lesions with fatal outcome.

Using serial magnetic resonance imaging, we monitored an unique lesion of the brain in a 15-year-old girl with clinically definite and laboratory-supported remitting-relapsing multiple sclerosis. During initial phases of the disease course, cystic necrosis around the plaque was observed. Later, remyelination of the central core of the lesion was speculated, as similarities in signal intensity between the core and the normal appearing white matter were partially recovered both on the T1- and the T2-weighted images.