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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.

Natalizumab (Tysabri(®)) is highly efficacious in controlling disease activity in relapsing multiple sclerosis (MS) patients. As it is one of the more recent therapies for MS, there remains a need for long-term safety and efficacy data of natalizumab in a clinical practice setting. The Tysabri observational program (TOP) is an open-label, multicenter, multinational, prospective observational study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from Europe, Canada and Australia. The objectives of this study are to collect long-term safety and efficacy data on disease activity and disability progression. We report here the interim results of the 563 patients included in TOP between December 2007 and 2012 from Belgium. This patient cohort was older at baseline, had longer disease duration, higher neurological impairment, and a higher baseline annualized relapse rate, when compared to patients included in the pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was comparable. The annualized relapse rate on treatment was reduced by 90.70 % (p < 0.0001) with a cumulative probability of relapse of 26.87 % at 24 months. The cumulative probabilities of sustained disability improvement and progression at 24 months were 25.68 and 9.01 %, respectively. There were no new safety concerns over the follow-up period. Two cases of progressive multifocal leukoencephalopathy were diagnosed. Our results are consistent with other observational studies in the post-marketing setting.

Mucormycosis is a rare opportunistic fungal infection. Rhinocerebral form of the disease mainly affects diabetic or immunocompromised patients. Mucormycosis have specific tropism for blood vessels leading to mucorthrombosis and less often to mycotic aneurysms. We report on a patient initially presenting with a severe sphenoid sinusopathy, who progressively evolved to cavernous sinus syndrome, internal carotid aneurysm followed by spontaneous thrombosis, chronic meningitis and ultimately fatal hypertensive hydrocephalus. Necropsy revealed a purulent infiltrate containing thin-walled, aseptate, right-angle branching, hyphae consistent with mucormycosis. His only relevant previous medical history was a transsphenoidal surgery for pituitary macroadenoma 21 years before. We hypothesize that post-surgical mucosal changes in the sphenoid sinus have been a favoring factor for delayed and invasive mucor infection.

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.

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.

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.

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 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.

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.

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.

We amplified the mRNA for cytokines in peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) cells from 18 multiple sclerosis (MS) patients and 21 other neurological patients, using the reverse transcription polymerase chain reaction (RT-PCR). Radioactive hybridization of the amplified DNA allowed quantitation of mRNA levels. Expression of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 mRNA was elevated in CSF cells from MS patients. IFN-gamma and IL-10 mRNA levels were higher in MS patients than in other inflammatory neurological diseases. mRNA coding for transforming growth factor (TGF)-beta was detectable in the majority of cases, with higher expression in CSF cells of MS and other inflammatory neurological diseases than in noninflammatory controls, and higher expression in PBMC of MS patients than in all other cases. In many MS patients both proinflammatory and immunoregulatory cytokine messages were detected in the CSF compartment without correlation with the clinical activity of the disease. In contrast, mRNA for the costimulatory molecule B7.1 was only detected in the CSF cells of some MS patients, who showed clinical signs of acute relapse at the time of the spinal tap.

Anti-GQ1b antibodies were assayed by an enzyme-linked immunosorbent assay in sera from patients with non-neurological disorders (N = 20), and with various neurological disorders (N = 59), including nine cases of Miller Fisher syndrome, 16 cases of Guillain-Barré syndrome and one case of acute post-infectious ophthalmoparesis. Such antibodies were found in most cases (8 out of 9) of Miller Fisher syndrome, and at very high titres, in one case of Guillain-Barré syndrome characterised by an initial ophthalmoparesis, and in the case of isolated post-infectious ophthalmoparesis. The latter was characterised by a long-lasting occurrence of these antibodies. Anti-GQ1b antibodies are specific for an immune-mediated neuropathy of the cranial, especially oculomotor, nerves.

Cytomegalovirus (CMV) infections are common and severe complications of HIV infection. The virus involves the nervous system, causing encephalitis, polyradiculomyelitis and peripheral neuropathies. Due to their limited sensitivity, traditional virological approaches, such as virus isolation or antigen detection in the CSF are useful only in limited instances, e.g. CMV polyradiculopathy. The aetiological diagnosis of these disorders relies on the analysis of cerebrospinal fluid by PCR and quantitative PCR may be important to establish the extent of CNS lesions and to monitor the efficacy of antiviral treatments. CMV is susceptible to various antivirals, including ganciclovir, foscarnet and cidofovir. CMV infections of the nervous system, in particular encephalitis, however, show only a poor response to standard treatments. Drug combination treatments i.e. ganciclovir plus foscarnet, are currently under evaluation in clinical trials.

Serum and cerebrospinal fluid (CSF) of 13 patients have been examined to confirm and precise the diagnosis of herpes simplex virus encephalitis (HSVE). By amplifying the DNA with a nested polymerase chain reaction (PCR), we could demonstrate the herpetic origin of these cases of encephalitis. DNA of HSV type 1 or type 2 was directly identified and differentiated, by the use of both type-specific primes in the same reaction. The primer sequences were chosen in the glycoprotein D region for HSV type 1, and in the glycoprotein G region for HSV type 2. Only one case was due to the latter. In all but one cases, an immunoaffinity-mediated capillary blotting study was also performed. This technique showed the occurrence of oligoclonal CSF-specific IgG bands, while the antigen-driven immunoblotting demonstrated intrathecal production of oligoclonal anti HSV antibodies. In most of the cases, repeated CSF analysis allowed us to study the sequential detection of viral DNA and of intrathecal synthesis of virus-specific IgG in relation to the clinical course. All the patients were treated with acyclovir. In one case, a relapse was clinically suspected, but the PCR remained negative.

A clinically definite diagnosis of multiple sclerosis was done in a 61 year-old woman who displayed severe cerebellar and pyramidal tract involvement. Symptoms developed 5 years before with unsteadiness of gait and difficulties in walking. Diagnosis was supported by evoked potentials studies and magnetic resonance imaging. However, the cerebrospinal fluid (CSF) analysis was very unusual. CSF albumin and IgG concentrations were normal, as well as the IgG index. In contrast, the IgA level and the IgA index were markedly increased and the local synthesis of IgA was estimated at 31.36 mg/l. Reduction by dithiotreitol did not change the IgA level. On affinity immunoblots, oligoclonal IgA bands were not detected but oligoclonal IgG bands were present. The strong local production of IgA in this patient seems to be therefore polyclonal.

We describe the clinical, radiological, neurophysiological and biological characteristics of 4 patients suffering from tropical spastic paraparesis due to a HTLV-I infection. Patient 1 immigrated in Europe at the age of 16 from Caribbean islands. Patient 2 was a White male Caucasian who lived during several years with a prostitute also native of Caribbean islands. Patient 3 was a Black male Zaïrian and Patient 4 was a female of mixed race who lived many years in Zaäire and in Senegal. All the 4 patients presented with walking difficulties, a spastic paraparesis, urinary disturbances and often, severe constipation. The diagnosis was based on a positive ELISA test for HTLV-I antibodies, confirmed in 2 cases each by Western blots and detection of the viral genome by the Polymerase Chain Reaction. In all cases, CSF pleocytosis and CSF-restricted oligoclonal IgG bands were observed. MRI of the spinal cord showed a global atrophy in 3 cases. Cerebral MRI revealed unusual extensive, progressive and symmetric lesions of the white matter in Patient 1, and some patchy periventricular lesions in Patient 4; this examination was normal in the two other cases. Sensory evoked potentials indicated abnormalities of central conduction velocities at the level of the posterior columns. The pathogenesis of tropical spastic paraparesis is briefly discussed.

The authors describe the clinical and biological data of seven patients with anti-Hu antibodies. Six of them displayed a small cell lung carcinoma (SCLC), but no cancer was detected in the 7th patient in spite of an extensive workup. The clinical heterogeneity of the anti-Hu syndrome is emphasized. The major symptoms were linked to a severe sensory neuropathy in three cases, to cerebellitis in two cases, to dysautonomia in one case, and to gastro-intestinal pseudo-obstruction in one case. One patient also displayed EMG abnormalities characteristic of the Lambert-Eaton myasthenic syndrome. Two patients developed opsoclonus or ocular flutter associated with severe confusion in the late stage of their disease. In four patients, the neurological signs and symptoms preceded the discovery of the SCLC, and in two cases the initial detection of anti-Hu antibodies prompted the successful search for this tumor. Immunopathological events injuring the peripheral and central nervous system are briefly discussed.

The incidence of tuberculosis (TB) is expected to increase substantially during the next 10 years as well as its extrapulmonary manifestations, often in association with the HIV panepidemic. TB meningitis displays some clinical and radiological characteristics but the "gold standard" for diagnosis remains the identification of Mycobacterium tuberculosis in the CSF by direct staining of culture. Direct staining, however, is rarely successful and culturing of M. Tuberculosis can take 4 to 8 weeks. Other techniques may be helpful, such as the detection of an intrathecal synthesis of antimycobacterial antibodies, or the detection in the CSF of the mycobacterial genome by the polymerase chain reaction (PCR). DNA amplification, and especially the "nested" amplification protocol, may represent a major step forward and find its place as a sensitive, specific and rapid test in the routine diagnostic laboratory.

The authors report 3 observations of dural arterio-venous fistula cured by combined neuroradiological and neurosurgical intervention. In the first case, the shunt affected the left lateral sinus. Repeated embolizations failed whilst intracranial hypertension developed, as a consequence of flux in the opposite lateral sinus and in the sagittal sinus. Surgical intervention, consisting in isolation of the transverse sinus, led to complete cure, after a one month delay. In the second case, the shunt was adjacent to the sagittal sinus, right parietal, and had led to an intracerebral haematoma, by rupture of an arterialized cortical vein. Embolizations alone could not cure the fistula which therefore had to be excised. In the third case, the shunt was located in the falx, at the parieto-occipital junction, and was responsible for arterialization of cerebral veins in the right parieto-occipital region. For this reason, after failure of endovascular treatment, the fistula was coagulated, with subsequent complete cure. These three cases illustrate the different types of drainage of such arterio-venous fistula, and their corresponding neurological symptoms and signs, complications and risks, that required a radical-not only clinical, but also anatomical-cure. This aim was achieved when embolizations were accompanied by direct surgical attack.

The serum and CSF of two women with a severe subacute pancerebellar syndrome contained high titers of antibodies directed against antigens present in the perikaryon of Purkinje cells. In Western blots performed on human Purkinje cells extracts these antibodies reacted with two groups of proteins the molecular weights of which were estimated to 34-38 and 62 kilodaltons (anti-Yo antibodies). Complementary investigations revealed a tubar adenocarcinoma in the first case, an ovarian carcinoma in the second. The tubar tumoral cells also contained the protein of the highest molecular weight. Compared to the serum, the CSF contained a higher proportion of anti-Yo antibodies per mg IgG, and a fraction of the latter was likely synthesized intrathecally. These antibodies may be involved in the almost total disappearance of the Purkinje cells, as observed at autopsy of both cases.

A 21-year-old woman developed hyperemesis gravidarum, complicated by Wernicke's encephalopathy and central pontine myelinolysis. For the latter, time course of the lesions on magnetic resonance imaging suggests a pathogenetic role for hypophosphatemia rather than for hyponatremia.

As beta-2 transferrin is almost specific to the cerebrospinal fluid, its detection in rhinorrhea or otorrhea fluids demonstrates the occurrence of CSF fistula. We describe a highly sensitive method based on immunoaffinity-mediated capillary blotting for the detection of this cathodic isoform of transferrin in minute amounts (3 microliters) of rhinorrhea or otorrhea fluids. Application of this method in a series of 10 patients with CSF fistula is reported.

The authors report a case of compression of the peroneal nerve by an intraneural ganglionic cyst. The chief complaint is generally a lateral upper leg pain occasionally associated with foot drop and swelling of the upper tibiofibular joint. In our case, the disease was revealed by a tentative intraarticular injection of betamethasone. Early microsurgical treatment remains the only way to avoid permanent motor sequellae.

A case of Streptococcus suis meningitis is observed in a 39-year-old and previously healthy meat factory worker. Neurological recovery was incomplete despite adequate and sustained antimicrobial therapy. Early deafness was demonstrated by brainstem auditory evoked potentials. Death due to aspiration pneumonia, cardiac arrest and subsequent cerebral anoxia occurred late in the course of the illness.

We report four patients with Behçet's disease characterized by initial and predominant neurological signs and symptoms. In three cases, a clinical picture of relapsing meningoencephalitis preceded the appearance of the classical signs of the disease for several months or years; in the fourth case, an acute febrile aseptic meningitis coincided with the development of bipolar aphthosis and uveitis. Disease activity was linked to a blood inflammatory syndrome and neutrophilic leucocytosis. Acute phases were associated with CSF mixed pleocytosis and high protein content. Brain CT scans and MRI were very effective to detect lesions which are mainly located in the brain stem and basal ganglia. High-dose corticosteroids and, in cases of relapses, immunosuppressive drugs were required to treat these severe forms of Behçet's disease.

Otitis media in a 43 year-old male patient was followed by signs of chronic meningitis with persistent headaches, moderate pleiomorphic lymphocytosis of CSF without hypoglycorrhachia and unilateral impairment of cranial nerves XI to II. These signs were accompanied by widespread inflammation with general deterioration of the patient's condition. After a time the tentorium of cerebellum showed thickening and significant contrast uptake in conjunction with necrotizing granulomatous inflammation, indicating tentorial pachymeningitis. Swift and complete remission was obtained with a corticoid-cyclophosphamide combination. After reviewing the other possible causes of chronic meningitis, the authors proposed a diagnosis of Wegener's disease of auricular origin in view of the compatibility of all the data. A few cases of cranial pachymeningitis of indeterminate origin are described in the literature. Only this patient was treated with a corticoid-cyclophosphamide combination. The remarkable efficacy of this double therapy confirms the diagnostic hypothesis of Wegener's granulomatosis.

The authors describe three patients with a chronic sensory-motor polyneuropathy associated with a monoclonal IgM gammopathy. In each case, the M-component was shown to display an antibody activity against the Myelin-Associated Glycoprotein (MAG) in a western blot technique. Sera from the three patients stained specifically the myelin sheaths of normal human peripheral nerves after incubation with rabbit anti-IgM. Motor conduction velocities were very low in each case. Morphological studies of the sural nerve from one patient revealed a moderate loss of myelinated fibres, some onion-bulbs but also a microangiopathy and signs of axonal degeneration.

The authors report a case of Wegener's granulomatosis unusual for its initial signs. The first evidence of disease consisted in pains in the lower limbs, probably caused by inflammatory processes involving the fascia. Biochemical, radiological and histological examinations allowed the diagnosis to be made.

The authors describe various applications of an immunoblot technique which allows the qualitative determination of the specific antibody activity of oligoclonal IgG intrathecally synthesized in infectious diseases of the nervous system. After dilution of sera to the same IgG concentration as the paired CSF samples, 10 microliters of both fluids are applied side by side on agarose gel plates and isoelectrically focused. Precipitated IgG or specific IgG antibodies are then blotted onto a nitrocellulose sheet previously coated with either a rabbit anti-IgG antiserum or the antigen under study, respectively. The immunoblot is successively incubated with biotinylated anti-IgG antiserum and with the streptavidin-biotin-peroxidase complex before staining with 4 chloro-1-naphthol. This method was applied to samples from patients with subacute sclerosing panencephalitis, herpetic encephalitis, meningoradiculitis due to Herpes Zoster, neuro-AIDS, neurobrucellosis, meningoradiculitis or encephalomyelitis due to Borrelia burgdorferi, and tuberculous meningitis. In each case, specific oligoclonal IgG antibodies, superimposed or not on a diffuse polyclonal synthesis were detected in the CSF, but not, or more faintly, in the corresponding serum. This was taken as evidence for an intra-thecal synthesis of these antibodies. In contrast, when a "mirror effect" was observed, i.e. similar oligoclonal bands in both serum and CSF after dilution at the same IgG concentration, an intra-thecal synthesis was ruled out.

During a period of 30 months, we studied the proportions of B and T cells, and of T cell subpopulations, in 924 blood samples from 213 MS patients. The disease was clinically stable in 88 patients (271 samples), relapsing progressive in 50 (349 samples), slowly progressive in 71 (262 samples) and in acute, selfremitting relapses for 31 patients (42 samples). By comparison with controls, untreated MS patients displayed a slightly higher percentage of B-cells (p less than 0.05) and a striking decrease of the mean percentage of CD8 + cells (p less than 0.001). Within the MS group, patients with an active disease presented a more marked decrease of the number of CD8 + cells and an increase of the CD4/CD8 ratio (p less than 0.01). However, 13 out of the 88 clinically stable patients had persistently high CD4/CD8 ratios, whereas such a high ratio was observed only in 60% of samples collected during an acute relapse. Eighty patients with a progressive form of the disease were chronically treated by immunosuppressive drugs, usually cyclophosphamide (N = 69). This treatment induced within one year a marked decrease of the absolute number of B and CD4 + cells, and a return to normal values of the CD4/CD8 ratio.