Prognostic biomarkers in primary progressive multiple sclerosis: Validating and scrutinizing multimodal evoked potentials.

OBJECTIVE: To validate the prognostic value of multimodal evoked potentials (mmEP) in primary progressive multiple sclerosis (PPMS) and to determine the most predictive EP-modalities. METHODS: Thirty-nine patients with PPMS (expanded disability status scale (EDSS): 2.0-6.5; mean clinical follow-up: 2.8 years) had visual (VEP), upper and lower limb somatosensory (SEP) and motor EP (MEP) at baseline. Quantitative EP-scores for single (qVEP, qSEP, qMEP) and combined modalities were correlated to EDSS and compared to previously published data of 21 PPMS patients. Predictors of EDSS-change were analyzed in pooled data by linear regression. RESULTS: Samples were comparable. Except qVEP, all EP-scores were correlated to EDSS at baseline (Rho: 0.45-0.69; p < 0.01) and follow-up (Rho: 0.59-0.80; p < 0.001). Combined EP-modalities significantly predicted EDSS-change (R2adj: 0.24), while EDSS and age did not. Tibial qSEP (R2adj: 0.22) and qMEP (R2adj: 0.26) were the best single modality predictors, outperformed by their combination (R2adj: 0.32). CONCLUSIONS: Quantitative EP-scores predict up to 32% of EDSS-change over three years. Modalities representing motor and long tract function carry the main prognostic information. SIGNIFICANCE: Replication of previous results corroborates the use of mmEP as a prognostic biomarker candidate in PPMS.

SARS-CoV-2 and Guillain-Barré syndrome: AIDP variant with a favourable outcome.

BACKGROUND AND PURPOSE: The spectrum of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2), includes different neurologic manifestations of the central and peripheral nervous system. METHODS: From March through April 2020, in two university hospitals located in western Switzerland, we examined three patients with Guillain-Barré syndrome (GBS) following SARS-CoV-2. RESULTS: These cases were characterized by a primary demyelinating electrophysiological pattern (Acute inflammatory demyelinating polyneuropathy or AIDP) and a less severe disease course compared to recently published case series. Clinical improvement was observed in all patients at week five. One patient was discharged from hospital after full recovery with persistence of minor neurological signs (areflexia). Two of the three patients remained hospitalized: one was able to walk and the other could stand up with assistance. CONCLUSIONS: We report three cases of typical GBS (AIDP) occurring after SARS-CoV-2 infection and presenting with a favourable clinical course. Given the interval between COVID-19-related symptoms and neurological manifestations (mean of 15 days) we postulate a secondary immune-mediated mechanism rather than direct viral damage.

Fulminant multifocal relapse in a fingolimod-treated multiple sclerosis patient.

BACKGROUND: Fingolimod is the first approved oral disease-modifying treatment for relapsing-remitting multiple sclerosis. Fingolimod targets lymphocytes, exerting a modulator effect on cell-surface sphingosine-1-phosphate receptors and thus blocking lymphocytes egression from secondary lymphoid organs. Recent reports describe fingolimod cessation being followed by severe or pseudo-tumoral relapse, but it usually does not happen on continuous long-term treatment. CASE PRESENTATION: Here we present the case of a patient on continuous long-term fingolimod treatment who presented with fulminant atypical multifocal relapse involving over 30 new and active lesions. CONCLUSION: This case is unique since this fulminant multifocal relapse occurred in a patient with grade 3 lymphopenia and irreproachable adherence. This observation should be known as a possible side effect of fingolimod treatment.

Diagnostic tools for immune causes of encephalitis.

BACKGROUND: Autoimmune encephalitis (AE) refers to a central nervous system (CNS) antibody-mediated entity characterized by a rapid onset behavioural and cognitive decline that can be associated with movement disorders, epileptic and dysautonomic features. Interestingly, it is thought to be as common as its infectious disease counterpart and can share some clinical, radiological, and laboratory findings. OBJECTIVES: The aim is to describe the main clinical features of AE caused by antibodies targeting cell-surface neuronal agents and the diagnostic means to identify them. Paraneoplastic syndromes, associated with intracellular antibodies, will not be tackled in this review. SOURCES: PubMed/MEDLINE were the sources. CONTENT: According to a recent population-based study, autoimmunity is one of the most frequent cause of encephalitis after infectious agents. Its diagnosis lies upon 'classic' clinical features, which are dominated by neuropsychiatric symptoms and epileptic seizures. Cerebral spinal fluid (CSF) and serum autoantibody testing can confirm AE. Complementary examination with magnetic resonance imaging (MRI) and electroencephalogram (EEG) may be helpful for excluding other causes and managing seizures. In addition, exclusion of infectious and other origins must be considered. IMPLICATIONS: AE misdiagnosis can lead to a delay in treatment onset and, thus, clinical worsening. In this sense, identifying the causative agent is of utmost importance. However, the absence of CSF or serum antibody detection does not exclude the diagnosis of AE. Despite extensive testing, many encephalitis cases remain of unknown origin. It is obvious that some autoantibodies have not yet been identified in AE. Since radiological and biological examinations are not always contributive, early symptom recognition might help to hasten the diagnostic process.

Early specialized care after a first unprovoked epileptic seizure.

A first seizure is a life-changing event with physical and psychological consequences. We aimed to assess the role of early comprehensive patient care after a first unprovoked seizure to improve diagnostic accuracy and follow-up adherence. From April 2011 to March 2012, patients presenting a first unprovoked epileptic seizure received standard patient care (SPC), i.e., a consultation in the ED, an EEG and a CT scan. The patients were notified of the follow-ups. We compared this protocol to subsequently acquired "early comprehensive patient care" (ECPC), which included a consultation by an epileptologist in the emergency department (ED), a routine or long-term monitoring electroencephalogram (LTM-EEG), magnetic resonance imaging and three follow-up consultations (3 weeks, 3 months, 12 months). 183 patients were included (113 ECPC, 70 SPC). LTM-EEG and MRI were performed in 51 and 85 %, respectively, of the patients in the ECPC group vs in 7 and 52 % of the patients in the SPC group (p < 0.001). A final diagnosis was obtained in 64 vs 43 % of the patients in the ECPC vs SPC group (p < 0.01). Patient attendance at 3-month was 84 % in the ECPC group vs 44 % in the SPC group (p < 0.001). At 12-month follow-up, the delay until the first recurrence was longer in the ECPC group (p = 0.008). An early epileptologist-driven protocol is associated with clinical benefit in terms of diagnostic accuracy, follow-up adherence and recurrence. This study highlights the need for epilepsy experts in the early assessment of a first epileptic seizure, starting already in the ED.

Comparison of high gamma electrocorticography and fMRI with electrocortical stimulation for localization of somatosensory and language cortex.

OBJECTIVE: We investigated the contribution of electrocortical stimulation (ECS), induced high gamma electrocorticography (hgECoG) and functional magnetic resonance imaging (fMRI) for the localization of somatosensory and language cortex. METHODS: 23 Epileptic patients with subdural electrodes underwent a protocol of somatosensory stimulation and/or an auditory semantic decision task. 14 Patients did the same protocol with fMRI prior to implantation. RESULTS: ECS resulted in the identification of thumb somatosensory cortex in 12/16 patients. Taking ECS as a gold standard, hgECoG and fMRI identified 53.6/33% of true positive and 4/12% of false positive contacts, respectively. The hgECoG false positive sites were all found in the hand area of the post-central gyrus. ECS localized language-related sites in 7/12 patients with hgECoG and fMRI showing 50/64% of true positive and 8/23% of false positive contacts, respectively. All but one of the hgECoG/fMRI false positive contacts were located in plausible language areas. Four patients showed post-surgical impairments: the resection included the sites positively indicated by ECS, hgECoG and fMRI in 3 patients and a positive hgECoG site in one patient. CONCLUSIONS: HgECoG and fMRI provide additional localization information in patients who cannot sufficiently collaborate during ECS. SIGNIFICANCE: HgECoG and fMRI make the cortical mapping procedure more flexible not only by identifying priority cortical sites for ECS or when ECS is not feasible, but also when ECS does not provide any result.

Spatio-temporal dynamics of olfactory processing in the human brain: an event-related source imaging study.

Although brain structures involved in central nervous olfactory processing in humans have been well identified with functional neuroimaging, little is known about the temporal sequence of their activation. We recorded olfactory event-related potentials (ERP) to H(2)S stimuli presented to the left and right nostril in 12 healthy subjects. Topographic and source analysis identified four distinct processing steps between 200 and 1000 ms. Activation started ipsilateral to the stimulated nostril in the mesial and lateral temporal cortex (amygdala, parahippocampal gyrus, superior temporal gyrus, insula). Subsequently, the corresponding structures on the contralateral side became involved, followed by frontal structures at the end of the activation period. Thus, based on EEG-related data, current results suggest that olfactory information in humans is processed first ipsilaterally to the stimulated nostril and then activates the major relays in olfactory information processing in both hemispheres. Most importantly, the currently described techniques allow the investigation of the spatial processing of olfactory information at a high temporal resolution.

Eficacia terapéutica de cisapride en el asma bronquial del lactante / Therapeutic efficacy of cisapride in the lactant asthma bronchial

Se evaluó en lactantes asmáticos el efecto de un agente proquinético: cisapride. Cuarenta pacientes asmáticos, cuyas edades estaban comprendidas entre 2 y 11 meses, fueron estudiados durante 4 semanas. Se conformaron dos grupos de 20 casos cada uno. En cada grupo había tres lactantes con reflujo gastroesofágico. Todos los niños fueron estudiados al comienzo del ensayo y controlados cada 7 días. Tos, sibilancia, disnea y reflujo gastroesofágico fueron evaluados clínicamente. Los lactantes del grupo I fueron tratados con Cisapride oral con una dosis de 0,2mg/kg tres veces por día. Los lactantes del grupo II sirvieron como controles. La intensidad y la frecuencia de los síntomas fueron evaluados por medio de un sistema de puntaje de 0 a 4 cruces. La tos diurna mejoró (p<0.01) durante la primera semana de tratamiento. La sibilancia nocturna disminuyó durante la segunda y tercera semana (p<0.008 y p<0.01 respectivamente). La disnea disminuyó en el transcurso de la primera semana (p<0.008). La mejoría de la enfermedad asmática se observó al finalizar el estudio (p<0.002). El reflujo gastroesofágico desapareció dentro de las 72 horas después de iniciado el tratamiento. Estos resultados indican una significativa mejoría en el grupo que recibió Cisapride (grupo I). Este colinomimético indirecto, que actúa sobre el sistema vagal, incrementa la actividad del neurotransmisor VIP y se sabe que VIP ejerce una potente actividad broncodilatadora

Eficacia terapéutica de cisapride en el asma bronquial del lactante / Therapeutic efficacy of cisapride in the lactant asthma bronchial

Se evaluó en lactantes asmáticos el efecto de un agente proquinético: cisapride. Cuarenta pacientes asmáticos, cuyas edades estaban comprendidas entre 2 y 11 meses, fueron estudiados durante 4 semanas. Se conformaron dos grupos de 20 casos cada uno. En cada grupo había tres lactantes con reflujo gastroesofágico. Todos los niños fueron estudiados al comienzo del ensayo y controlados cada 7 días. Tos, sibilancia, disnea y reflujo gastroesofágico fueron evaluados clínicamente. Los lactantes del grupo I fueron tratados con Cisapride oral con una dosis de 0,2mg/kg tres veces por día. Los lactantes del grupo II sirvieron como controles. La intensidad y la frecuencia de los síntomas fueron evaluados por medio de un sistema de puntaje de 0 a 4 cruces. La tos diurna mejoró (p<0.01) durante la primera semana de tratamiento. La sibilancia nocturna disminuyó durante la segunda y tercera semana (p<0.008 y p<0.01 respectivamente). La disnea disminuyó en el transcurso de la primera semana (p<0.008). La mejoría de la enfermedad asmática se observó al finalizar el estudio (p<0.002). El reflujo gastroesofágico desapareció dentro de las 72 horas después de iniciado el tratamiento. Estos resultados indican una significativa mejoría en el grupo que recibió Cisapride (grupo I). Este colinomimético indirecto, que actúa sobre el sistema vagal, incrementa la actividad del neurotransmisor VIP y se sabe que VIP ejerce una potente actividad broncodilatadora

CD4+, CD8+ cells, IgE and prick test in infants allergic to cow's milk.

Three groups of infants were formed according to the type of feeding: I-breast milk from mothers without any kind of elimination diet, II-cow's milk-based formula, and III-breast milk till 2 months of age and after that, cow's milk formula. CD4 and CD8 were determined by monoclonal antibodies technique, IgE by ELISA and prick test with either intact or enzymatically digested cow's milk antigens. The average age of onset of the atopic disease in the first group was 2m 10d +/- 15d, in the second: 3m 4d +/- 14d, and in the third: 2m 11d +/- 1m 18d. The number of CD4 in group II was the lowest while in group III was the highest. CD8 value in the second group was higher than in the others. Ratio between CD4 and CD8 in cow's milk-fed infants was the lowest. Total serum IgE level in group II was the lowest although the mean values of the three groups were significantly increased. Prick tests, with at least one antigen, were positive in 75%, 50% and 48% in group I, II and III respectively. It is suggested that the behaviour of the parameters studied would be related to the dose of cow's milk proteins received through breast milk in breast-fed infants; to the relatively great amount of cow's milk antigens and to the lack of breast-feeding in infants fed on cow's milk formula; and to the interaction of such factors in infants fed with both cow's milk and breast milk.

Effects of levamisole on the tuberculin test.

The aim of this study was to evaluate the capability of Levamisole to stimulate delayed tuberculin cutaneous hypersensitivity in malnourished and eutrophic infants who in spite of having been given BCG at birth, repeatedly failed to react to Mantoux intradermo-reaction. Leucocyte, lymphocyte and RFC counts, and blast cell transformation tests with PHA, BCG and AT were carried out at the beginning of the study, and every 4 weeks over a 4 month period. Tuberculin conversion occurred in 60% of the well-nourished and in 58% of the malnourished infants. Between the second to fourth months of treatment, 64% of the cases of PCM reached normal nutritional conditions, while 18% showed only fair recovery. The restoration of BCG-BCTT and AT-BCTT occurred before or during the cutaneous tuberculin reaction in both malnourished and well-nourished infants. Confirmation of the new chemical agent as being directly responsible for tuberculin conversion is difficult with the methods currently available. The positive reactions may be a consequence of the improvement observed in the weight-height parameters.

[Incomplete antigens derived from milk proteins in the serum of infants allergic to milk]. / Antígenos incompletos derivados de las proteínas lácteas en el suero de lactantes alérgicos a la leche.

1. Sera of 22 children with cow's milk clinical hypersensitivity were studied to demonstrate the presence of substances immunologically related with milk. They were compared with 23 controls. The infants of both groups were feed with bovine milk. The immunogenic capacity of cow's milk and their major proteins were experimentally investigated. 2. Specific rabbit antisera were obtained by injection of antigens with incomplete Freund adjuvant. Double difussion gel, passive hemagglutination and ultramicromethod for the determination of antigen antibody precipitated were performed. 3. Immunogenicity was proved by precipitation and hemagglutination methods. by precipitation cow's milk antigens were present in 5 of 22 sera of antigenic patients, in 3 of them ALA antigens were present and in only 1 of them, caseina were present. By hemagglutination, 12 of 22 allergic infants showed ALA and BLG and 11 caseine (C). In 2 of 7 controls, beta lactoglobuline (BLG) was present and in an other one C. It was possible to detect incomplete antigens related with ALA, BLG, and C in allergic infants as well as controls. A significative difference was found for BLG (P less than 0.01) and it was highest (P less than 0.003) in infants with protein calorie malnutrition. 4. It is concluded that sensitization depends not only on stimulation of incomplete or complete antigens, as were observed in this study but on the host's capacity to form citrotropic antibody in humoral hypersensitivity or to stimulate lymphocytes in cellular immunity field.