Real-life clinical use of natalizumab and fingolimod in Austria.

OBJECTIVES: To compare the efficacy of natalizumab or fingolimod in a nationwide observational cohort using prospectively collected data. MATERIALS AND METHODS: We included all patients starting treatment with natalizumab or fingolimod documented in the Austrian MS Treatment Registry (AMSTR) from 2011 and staying on therapy for at least 24 months. We used propensity scores for several matching methods and as a covariate in multivariate models to correct for the bias of this non-randomized registry study. RESULTS: The study cohort includes 588 patients with RRMS. Ten patients did not produce a propensity score in the common support region, thus leaving 578 cases for final analyses, 332 in the fingolimod and 246 in the natalizumab group. Mean annualized relapse rates (ARR) during the 24 months observation period were 0.19 under fingolimod and 0.12 under natalizumab treatment (P = .005). No statistical significant differences were found analysing the log-transformed ARR, probability for experiencing a relapse, EDSS progression and EDSS regression. The hazard ratio for switching treatment from fingolimod comparing with natalizumab was 0.36 (95% CI: 0.247-0.523), P < .001. CONCLUSIONS: The generalized linear model (GLM) for relapse count as Poisson distributed dependent variable and propensity score as covariate showed a statistically significant reduction for the mean relapse count in the natalizumab group compared with fingolimod. This effect was smaller in the analyses of log-transformed ARR with propensity score matching, loosing statistical significance although showing the same direction for the effect. We assume that the GLM was the more sensitive model analysing this question.

Health-related quality of life in multiple sclerosis: temperament outweighs EDSS.

BACKGROUND: The influence of personality on health-related quality of life in patients with multiple sclerosis has been the focus of previous studies showing that introversion and neuroticism were related with reduced health related quality of life. However, no data exist on the impact of temperament on quality of life in this patient group. METHODS: Between April 2014 and March 2016 139 multiple sclerosis patients were recruited from a specialized outpatient clinic of the general hospital of Vienna. Health-related quality of life was measured by "The Multiple Sclerosis International Quality of Life Questionnaire (MusiQol)", temperament by "Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Questionnaire - Münster version" (briefTEMPS-M), and disability by the "Expanded disability status scale". All patients underwent a diagnostic psychiatric semi-structured interview (MINI). RESULTS: Known predictors (like disease duration, EDSS, psychiatric co-morbidities, immunomodulatory treatments) explain the proportion of variation in the outcome of MusiQol global index score in 30.9% in multi-variable linear regression analysis. It increased respectively to 40.3, 42.5, and 45.8% if adding the depressive, cyclothymic, or hyperthymic temperament to the list of variables. An increase of depressive and cyclothymic temperament scores significantly reduced global index score of MusiQol (p = 0.005, p = 0.002, respectively), while the hyperthymic temperament significantly raised it (p < 0.001). CONCLUSION: In MS patients, the depressive and cyclothymic temperament predict a lower and hyperthymic temperament an increased health-related quality of life, independent of current disability status, immunomodulatory treatments, and affective co-morbidities.

What to expect after natalizumab cessation in a real-life setting.

BACKGROUND: To minimize the risk of progressive multifocal leucoencephalopathy (PML), treatment with natalizumab is often stopped after 2 years, but evidence upon rebound of disease activity is limited and controversial. OBJECTIVE: To evaluate effects of natalizumab discontinuation on clinical disease activity within twelve months after cessation. METHODS: We retrospectively analyzed data of 201 patients with MS who discontinued natalizumab between 2007 and 2012. Mean change scores of annualized relapse rate (ARR) and expanded disability status scale (EDSS) were calculated for detection of rebound disease activity after twelve months. RESULTS: Natalizumab exposure did not exceed 2 years in 50.2% of patients, and the most common reasons for discontinuation were a long treatment period and concern of PML (56%). A total of 11.9% experienced a rebound phenomenon within twelve months. Mean ARR prenatalizumab was lower (P = 0.001, 95% CI -1.0-0.000) and treatment response to natalizumab poorer (P < 0.001, 95% CI 0.4-1.3) in patients with rebound compared to those without, but rebound was not associated with brief exposure to natalizumab (P = 0.159, 95% CI -9.3-1.5). 86.1% of patients switched to another therapy. Patients without rebound were found more often in the group starting an alternative treatment early (P = 0.013). CONCLUSION: Our data suggest that rebound of MS disease activity affects a subgroup of patients (11.9%), especially those with low disease activity before natalizumab therapy and a longer treatment gap after its withdrawal.

[Contribution of spinal cord biopsy to the differential diagnosis of longitudinal extensive transverse myelitis]. / Biopsie bei tumorverdächtiger spinaler Raumforderung: Fallstrick Neuromyelitis optica.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are characterized by recurrent optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM) as well as the serological detection of antibodies to aquaporin-4 (AQP4-ab). However, longitudinal extensive spinal cord lesions are not pathognomonic for NMOSD as they can also occur in systemic autoimmune diseases or mimic spinal cord tumors. OBJECTIVES/METHODS: We report a female patient who initially presented with a subacute spinal syndrome and a longitudinal spinal cord lesion on magnetic resonance imaging (MRI). As the brain MRI showed only unspecific white matter lesions and the cerebrospinal fluid was normal, a spinal cord biopsy was performed to exclude malignancies and revealed inflammatory demyelinating changes. In addition, after several deep vein thromboses and the detection of antiphospholipid antibodies, an antiphospholipid syndrome (APS) was diagnosed. Many years after the spinal cord biopsy, AQP4-ab were tested and found to be positive. We discuss the important differential diagnoses of LETM, give an overview of previously reported NMOSD cases in which a spinal cord biopsy was performed and highlight the crucial role of AQP4-ab testing for the differential diagnosis of longitudinal spinal cord lesions. RESULTS/CONCLUSIONS: Considering possible serious sequelae of spinal biopsy procedures, testing for AQP4-ab is mandatory in patients with unclear longitudinally extensive spinal cord lesions and should be performed preoperatively in all cases. In light of the heterogeneity of available assays, different detection methods should be used in doubtful cases. The relationship between NMO and APS needs further clarification; however, AQP4 IgG testing is recommended in patients presenting with APS and myelitis, optic neuritis or brainstem encephalitis.

Iron Rims in Patients With Multiple Sclerosis as Neurodegenerative Marker? A 7-Tesla Magnetic Resonance Study.

Introduction: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system, characterized by inflammatory-driven demyelination. Symptoms in MS manifest as both physical and neuropsychological deficits. With time, inflammation is accompanied by neurodegeneration, indicated by brain volume loss on an MRI. Here, we combined clinical, imaging, and serum biomarkers in patients with iron rim lesions (IRLs), which lead to severe tissue destruction and thus contribute to the accumulation of clinical disability. Objectives: Subcortical atrophy and ventricular enlargement using an automatic segmentation pipeline for 7 Tesla (T) MRI, serum neurofilament light chain (sNfL) levels, and neuropsychological performance in patients with MS with IRLs and non-IRLs were assessed. Methods: In total 29 patients with MS [15 women, 24 relapsing-remitting multiple sclerosis (RRMS), and five secondary-progressive multiple sclerosis (SPMS)] aged 38 (22-69) years with an Expanded Disability Status Score of 2 (0-8) and a disease duration of 11 (5-40) years underwent neurological and neuropsychological examinations. Volumes of lesions, subcortical structures, and lateral ventricles on 7-T MRI (SWI, FLAIR, and MP2RAGE, 3D Segmentation Software) and sNfL concentrations using the Simoa SR-X Analyzer in IRL and non-IRL patients were assessed. Results: (1) Iron rim lesions patients had a higher FLAIR lesion count (p = 0.047). Patients with higher MP2Rage lesion volume exhibited more IRLs (p <0.014) and showed poorer performance in the information processing speed tested within 1 year using the Symbol Digit Modalities Test (SDMT) (p <0.047). (2) Within 3 years, patients showed atrophy of the thalamus (p = 0.021) and putamen (p = 0.043) and enlargement of the lateral ventricles (p = 0.012). At baseline and after 3 years, thalamic volumes were lower in IRLs than in non-IRL patients (p = 0.045). (3) At baseline, IRL patients had higher sNfL concentrations (p = 0.028). Higher sNfL concentrations were associated with poorer SDMT (p = 0.004), regardless of IRL presence. (4) IRL and non-IRL patients showed no significant difference in the neuropsychological performance within 1 year. Conclusions: Compared with non-IRL patients, IRL patients had higher FLAIR lesion counts, smaller thalamic volumes, and higher sNfL concentrations. Our pilot study combines IRL and sNfL, two biomarkers considered indicative for neurodegenerative processes. Our preliminary data underscore the reported destructive nature of IRLs.

A novel mutation in the MFSD8 gene in late infantile neuronal ceroid lipofuscinosis.

Neuronal ceroid lipofuscinoses (NCL) are lysosomal storage disorders and constitute the most common group of progressive neurodegenerative diseases in childhood. Most NCLs are inherited in a recessive manner and are clinically characterised by a variable age at onset, epileptic seizures, psychomotor decline, visual impairment and premature death. To date, eight causative genes have been identified to underlie various clinical forms of NCL. We performed a genome-wide linkage analysis followed by sequencing the recently described NCL gene MFSD8 in three affected and three unaffected members of a consanguineous Egyptian family with an autosomal recessively inherited progressive neurodegenerative disorder. The clinical picture of the patients was compatible with a late infantile NCL (LINCL); however, impairment of the visual system was not a cardinal symptom in the respective family. By linkage analysis, we identified two putative loci on chromosome 1p36.11-p35.1 and 4q28.1-q28.2. The latter locus (4q28.1-q28.2) contained the MFSD8 gene, comprising a novel homozygous missense mutation in exon 5 (c.362a>g /p.Tyr121Cys), which segregated with the disease in the three affected sibs. We describe a novel mutation in the previously identified MFSD8 gene in a family with a common phenotype of LINCL, but no clinical report of vision loss. Our results enlarge the mutational and perhaps the nosological spectrum of one of the recently identified subtypes of NCL, called CLN7.

Disruption of nigrostriatal and cerebellothalamic pathways in dopamine responsive Holmes' tremor.

Holmes' tremor is an unusual combination of rest, postural and kinetic tremor of the extremities. Medical treatment of this condition still remains unsatisfactory. The case of a 20-year-old female patient is reported who developed right-sided Holmes' tremor 9 months after a left-sided, cavernoma induced midbrain/pontine haemorrhage at the age of 16 years. Beta-CIT single photon emission computed tomography revealed abolished dopamine transporter activity in the left basal ganglia and striatum, in accordance with missing ipsilateral tegmento-frontal connectivity (medial forebrain bundle), demonstrated by diffusion tensor MRI. Tractography showed reduced fibre connectivity of the superior and middle cerebellar peduncles on the lesioned side. Administration of pramipexole and L-DOPA led to a clinically significant reduction in tremor severity. In conclusion, our results support the notion that Holmes' tremor was a result of diminished striatal dopaminergic input in our patient.

Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1 alpha,25-dihydroxyvitamin D3 and cytokines.

The effects of 1 alpha,25-dihydroxyvitamin D3/calcitriol on the expression of Fc receptors (FcR) for IgA (Fc alpha R), IgE (Fc epsilon RII), and IgG (Fc gamma R) on human peripheral blood monocytes and the cell lines U937, THP-1, and Mono Mac-6, in combination with various cytokines, was examined by flow cytometry. On both monocyte-derived macrophages and the myelomonocytic cell lines, Fc alpha R/CD89 expression was induced by calcitriol alone and additively in combination with tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor. Constitutive and interleukin-4 (IL-4)-driven Fc epsilon RII/CD23 expression was markedly diminished on calcitriol-treated U937 cells and monocytes. Fc epsilon RII was also triggered by IFN-gamma, TNF-alpha, and IL-6 on all the cell lines, an effect blocked by calcitriol. On monocytes, the basal level and IFN-gamma-induced Fc gamma RI/CD64 expression was down-regulated by calcitriol and IL-4. The expression of Fc gamma RII/CD32 on monocytes was strongly suppressed by calcitriol. Transforming growth factor-beta induced Fc gamma RIII/CD16 on monocytes, an effect opposed by calcitriol. The ability of calcitriol-treated monocytes to phagocytose IgG-sensitized ox erythrocytes was diminished. Our results demonstrate that calcitriol, alone or in combination with cytokines, modulates Fc alpha R, Fc epsilon RII, Fc gamma RI, and Fc gamma RII expression on human mononuclear phagocytes, as well as Fc gamma R-mediated phagocytosis.

Asymmetric ending of secondarily generalized seizures: a lateralizing sign in TLE.

The authors investigated whether asymmetric ending of the clonic phase of secondarily generalized tonic clonic seizures (SGTCS) has lateralizing value concerning the hemisphere of seizure onset. They studied 70 patients with mesial temporal lobe epilepsy who underwent epilepsy surgery. Asymmetric ending of the clonic phase occurred in 43% of patients. The last clonic movement appeared on the upper extremity ipsilateral to the hemisphere of seizure onset in 83%.

Postictal nose wiping: a lateralizing sign in temporal lobe complex partial seizures.

We report postictal nose wiping as a postictal symptom of localizing and lateralizing significance in focal epilepsy. We reviewed videotapes of 444 focal seizures in 101 patients who underwent prolonged video and EEG monitoring during presurgical epilepsy evaluation, and observed postictal nose wiping in 51.3% of 76 patients with temporal lobe epilepsy. The hand used to perform postictal nose wiping was ipsilateral to the side of seizure origin in 86.5% of all seizures and in 97.3% of all patients. We conclude that postictal nose wiping is a common, easily assessed symptom after focal seizures of temporal lobe origin that provides reliable lateralizing information on the side of seizure onset.

Clinical seizure lateralization in mesial temporal lobe epilepsy: differences between patients with unitemporal and bitemporal interictal spikes.

OBJECTIVE: To compare the reliability of clinical seizure lateralization in temporal lobe epilepsy patients with unitemporal and bitemporal independent interictal spikes and unilateral hippocampal atrophy or sclerosis (HA/HS) on MRI scan. PATIENTS AND METHODS: We studied 11 patients with unitemporal and 10 patients with bitemporal interictal spikes. We calculated a spike ratio by dividing the number of spikes ipsilateral to the side of HA/HS by those occurring contralaterally. RESULTS: Clinical seizure lateralization was correct, i.e., ipsilateral to the side of HA/HS, significantly more often in the unitemporal group. Spike ratios were significantly higher in seizures that were lateralized correctly as compared with both incorrectly and nonlateralized seizures. Within the individual patients, a significant positive correlation between spike ratios and the proportion of correctly lateralized seizures was found. We identified three categories of symptoms according to lateralization accuracy. Category 1 symptoms (version, postictal paresis, and early ictal vomiting/retching) lateralized to the side of HA/HS in 100% of patients in the uni- and bitemporal groups. Category 2 symptoms (dystonic posturing, mouth deviation, postictal dysnomia/dysphasia, and ictal speech) provided a 100% correct lateralization in the unitemporal but not in the bitemporal patients. Category 3 symptoms (nonversive early head turning and unilateral upper extremity automatisms) yielded erroneous lateralization in both patient groups. CONCLUSIONS: We conclude that reliable clinical seizure lateralization in mesial temporal lobe epilepsy can only be achieved in patients with unitemporal interictal spikes, whereas clinical lateralization in patients with bitemporal spikes must be viewed cautiously.

Ictal urinary urge indicates seizure onset in the nondominant temporal lobe.

The authors describe six patients with medically refractory temporal lobe epilepsy whose seizures were characterized by an aura of ictal urinary urge. All seizures originated in the nondominant temporal lobe as evidenced from interictal spikes, ictal EEG, and MRI. Ictal SPECT, which was obtained in two patients, showed a hyperperfusion of the insular cortex, indicating a critical role of the insula for the generation of this symptom. Ictal urinary urge represents a new lateralizing sign indicating a seizure onset in the nondominant temporal lobe.

Genital automatisms in complex partial seizures.

OBJECTIVE: To determine which brain region is responsible for the generation of sexual automatisms. METHODS: Ninety consecutive patients with medically refractory focal epilepsy (74 with temporal lobe and 16 with frontal lobe epilepsy) referred to an epilepsy monitoring unit were studied. The occurrence of the following sexual automatisms was assessed during prolonged video-EEG monitoring: 1) repeatedly grabbing or fondling the genitals and 2) pelvic or truncal thrusting or similar movements. RESULTS: Five patients repeatedly fondled or grabbed their genitals during or immediately after some of their seizures. All five had temporal lobe epilepsy, as evidenced from prolonged video-EEG monitoring, high-resolution MRI, and good to excellent outcome after epilepsy surgery. Sexual automatisms did not occur with frontal lobe epilepsy. CONCLUSION: Sexual automatisms cannot be related exclusively to frontal lobe seizures. As previously proposed, apparently sexual hypermotoric pelvic or truncal movements are common in frontal lobe seizures, but this study suggests that discrete genital automatisms, like fondling and grabbing the genitals, are more common in seizures evolving from the temporal lobe.

Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset.

UNLABELLED: Peri-ictal SPECT provides unique information on the dynamic changes in regional cerebral blood flow (rCBF) that occur during seizure evolution and, thus, could be useful in clarifying the poorly understood interplay of the interictal and ictal states in human focal epilepsy. The regional hyperperfusion observed on ictal SPECT is generally believed to be a consequence of electrical seizure activity. However, recent studies using invasive long-term cortical CBF monitoring have demonstrated that rCBF changes occur up to 20 min prior to ictal electroencephalography (EEG) onset. Because of apparent technical difficulties, no preictal SPECT studies have been reported so far. Therefore, we present our results on two patients with temporal lobe epilepsy in whom preictal SPECT scans were performed fortuitously under continuous video-EEG monitoring control. METHODS: Technetium-99m-hexamethyl propyleneamine oxime was injected 11 min (Patient 1) and 12 min (Patient 2) before clinical and EEG seizure onset, as documented from simultaneous video-EEG monitoring in two patients with temporal lobe epilepsy. We obtained accurate anatomical reference of CBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. RESULTS: Whereas interictal SPECT showed a hypoperfusion of the temporal lobe ipsilateral to the seizure focus, on preictal SPECT, a significant increase in rCBF in the epileptic temporal lobe could be observed. These rCBF changes were not accompanied by any significant changes of the ongoing EEG. CONCLUSION: Our study provides evidence that rCBF is increased in the epileptic temporal lobe several minutes before EEG seizure onset. Thus, rCBF changes observed on peri-ictal SPECT scan cannot be considered a mere consequence of EEG seizure activity but may rather reflect a change in neuronal activity precipitating the transition from the interictal to the ictal state.

Health-related quality of life (HRQOL), activity of daily living (ADL) and depressive mood disorder in temporal lobe epilepsy patients.

We determined the interrelations of chronological age, age at seizure onset, duration of seizure disorder, cognitive functioning (IQ), scales of activities of daily living, depressive mood disorder and measures of health-related quality of life (HRQOL). Furthermore, we investigated the association of the laterality of seizure onset zone and absence/presence of hippocampal atrophy and/or sclerosis (HA/HS) with measures of HRQOL, activities of daily living (ADL) and depressive mood disorder. In the setting of pre-surgical epilepsy evaluation, a sample of 56 patients with temporal lobe epilepsy (TLE) was studied using the Bonner Skalen für Epilepsie (BPSE) and the depression inventory D-S of von Zerssen. Patients reported high levels of dependency on others and poor coping capabilities. Our data also showed specific ADL-behaviour suggesting social withdrawal and isolation. Our results indicate emotional impairment as a major problem in TLE, because 45% of our patients scored in the depressive range of the D-S depression scale. Depression score was found to be a powerful predictor of self-reported quality of life after adjusting for seizure-related variables, demographic variables and cognitive functioning (IQ). The only scale showing a significant laterality effect was ADL-home. No relationship between the dependent measures of HRQOL, ADL-social, ADL-cultural, depressive mood disorder and laterality of the epileptogenic zone or absence/presence of HA/HS was found. HRQOL and depressive mood disorder are strongly interrelated indicating that patients with depressive symptoms report lower quality of life and specific patterns of ADL. HRQOL, ADL and depressive mood disorder are largely independent of biological markers such as laterality of seizure onset zone and absence/presence of HA/HS in TLE.

Autonomic symptoms during epileptic seizures.

Autonomic symptoms frequently occur during epileptic seizures either as an accompaniment to other seizure symptoms or as the predominant seizure manifestation. They do not represent simple reactions to motor manifestations of seizures, but are mediated by an activation of the central autonomic network. Autonomic symptoms can be divided into cardiovascular changes, respiratory manifestations, gastrointestinal symptoms, cutaneous manifestations, pupillary symptoms, genital and sexual manifestations as well as urinary symptoms. Due to a hemispheric-specific representation of the central autonomic network, certain autonomic symptoms may provide lateralizing and sometimes localizing information on the seizure onset zone, although some of these signs may appear as a result of discharge spreading. Autonomic symptoms indicating a seizure onset in the non-dominant hemisphere include ictal vomiting and retching, spitting automatisms and ictal urinary urge. Autonomic symptoms range from subtle seizure manifestations which become apparent only during meticulous seizure analysis, to severe, sometimes life-threatening events. Cardiovascular and respiratory autonomic symptoms are discussed as the mechanisms underlying sudden unexplained death in epilepsy. When autonomic symptoms represent the sole seizure manifestation, they can pose problems for differential diagnosis of various non-epileptic conditions. Finally, autonomic seizure symptoms open a unique window on the functional organization of the central autonomic network and on brain function in general. (Published with videosequences.)

[The postictal state. A clinically oriented observation of patients with epilepsy]. / Der postiktale Zustand. Eine klinisch orientierte Betrachtung bei Patienten mit Epilepsie.

UNLABELLED: Epileptic seizures are followed by dynamic alterations in neurologic function in the postictal period which have received little attention by clinicians over a long period of time. We therefore retrospectively studied videotapes of 160 patients with focal epilepsy who underwent presurgical evaluation, for the occurrence of postictal symptoms to determine whether these phenomena have any localizing or lateralizing value in defining the seizure onset zone. RESULTS: (1) We found postictal paresis in 22 of 160 patients (18.8%) in each case contralateral to the hemisphere of seizure onset. (2) 'Perservative' automatisms which start during the ictus and continue in the postictal period occurred in 25.2% of 135 patients with temporal lobe epilepsy but not in patients with frontal lobe epilepsy. (3) Sexual automatisms defined as manipulations of the genitals were found exclusively in patients with temporal lobe epilepsy (in 5.9% of 135 patients). (4) Postictal 'Nose-wiping' was evident in 51.3% of 76 temporal lobe epilepsy patients but only in 12.0% of 25 extratemporal lobe epilepsy patients and was performed with the hand ipsilateral to the hemisphere of seizure onset in 86.5% of all temporal lobe seizures. (5) Postictal language disturbances were observed only in patients with temporal lobe epilepsy (34% of 97 patients) and pointed to a seizure onset in the dominant hemisphere in 80.8%. We conclude that postictal phenomena can provide reliable information for the localization of the seizure onset zone in patients with complex partial seizures. Thus, more attention should be given to the postictal state during presurgical epilepsy monitoring.

Clinical symptoms in psychogenic seizures.

PURPOSE: To develop a classification system of psychogenic seizures based on characteristic clinical symptom clusters and sequences in order to facilitate the correct differential diagnosis of epileptic seizures. METHODS: We analysed the symptoms: clonic movements, hypermotor movements, trembling and tonic posturing of the upper/lower extremities, pelvic thrusting, stiffening of the body, version, side-to-side-head movements, non-versive head-turning and falling to the floor. We did this in a series of 16 patients with psychogenic seizures documented with prolonged video EEG monitoring. Nine patients (7 with frontal lobe epilepsy and 2 with primary generalised epilepsy with tonic, clonic seizures) served as a control group. RESULTS: We classified psychogenic seizures into 3 groups, namely (1) atonic psychogenic seizures, (2) psychogenic motor seizures and (3) psychogenic hypermotor seizures characterised by (1) falling to the ground, (2) trembling in the upper/lower extremities and (3) pelvic thrusting in combination with beating and kicking. While version exclusively occurred in epileptic seizures (incidence = 20%) and side-to-side head movements were only observed during psychogenic seizures (incidence = 8%), all other analysed symptoms were observed in both psychogenic and epileptic seizures. CONCLUSION: Our classification scheme should be useful in terms of permitting a more comprehensive clinical assessment of psychogenic seizures and their underlying psychiatric disorders. Furthermore, the differential diagnosis of psychogenic seizures should be considerably improved.

Celiac disease with cerebral and peripheral nerve involvement mimicking multiple sclerosis.

OBJECTIVES: Due to the similarity in the clinical presentation, morphology, and course, celiac disease (CD) may be mixed up with other immunological disorders, such as multiple sclerosis (MS). CASE REPORT: In a 43-year-old Caucasian male with a history of diarrhea and colics since young age, progressive sensory disturbances developed since age 18 years. At age 34, he was diagnosed as relapsing-remitting MS upon an inflammatory CSF-syndrome and non-specific white matter lesions and treated with interferon beta-1b during the next 8 years without effect. At age 35, axonal polyneuropathy and ataxia were diagnosed. Despite normal anti-gliadin, endomysial, and transglutaminase antibodies, CD was diagnosed at age 41, based upon the history, polyneuropathy, positivity for HLA-DQ2 and HLA-DQ8, the white matter lesions, and a beneficial response of the gastrointestinal problems and polyneuropathy to gluten-free diet. CONCLUSIONS: CD may mimic MS and may be present despite the absence of anti-gliadin, endomysial or transglutaminase antibodies. CD should be considered if there is a gastrointestinal problem, polyneuropathy, and ataxia, even if CSF and MRI findings are suggestive of MS.

Contemporary treatment options for relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, encompassing both neuroinflammatory as well as prominent neurodegenerative aspects. A significant proportion of MS patients will develop neurological disability over time and up until recently licensed drugs could not satisfactorily halt this process. However, in the last years MS treatment has raised a stage of rapid progress. Several new drugs with significantly improved efficacy have entered the therapeutic field and several others are currently undergoing phase III clinical trials. In this review, we will summarize efficacy data as well as safety and tolerability issues of currently licensed drugs for relapsing-remitting MS and will give a short update on new drugs currently undergoing late-stage clinical trials.