RÉSUMÉ
BACKGROUND: Most patients with myasthenia gravis (MG) need long-term immunosuppressive therapy. However, conventional agents may have intolerable side effects, take too long or fail to achieve disease control. Rituximab (RTX) has emerged as an off-label treatment for refractory MG, but data on its use are still sparse. METHODS: We conducted a retrospective nationwide study contacting all Austrian neurologists to provide anonymized data of all adult MG patients treated with RTX and minimum follow-up of 3 months. The Myasthenia Gravis Foundation of America Postintervention Status scale was used to assess outcomes. RESULTS: 34 (60.7%) of a total of 56 patients were women. Median (IQR) age at diagnosis of MG and start of RTX were 41.5 (24.3; 65.8) and 47.5 (33; 71) years, respectively. Antibodies (ab) against acetylcholine receptor (AchR) and muscle-specific tyrosine kinase (MuSK) were present in 69.6% and 25% of patients, respectively (seronegative: 5.4%). Before RTX, 47 (83.9%) patients had had plasma exchange, immune adsorption or immunoglobulins. Three months after RTX, 14 of 53 (26.4%) patients were in remission. At last follow-up after a median of 20 (10; 53) months, remission was present in 42.9% of patients and another 25% had minimal manifestations. Remission was more frequent in patients with MuSK ab vs. those with AchR ab (71.4% vs. 35.9%, p = 0.022). RTX was safe. The presence of MuSK ab independently predicted remission after RTX. CONCLUSION: In this retrospective study on RTX for MG, the largest to date, RTX appeared safe, efficacious and fast acting. Benefit from RTX was greatest in MuSK ab + MG.
Sujet(s)
Facteurs immunologiques/usage thérapeutique , Myasthénie/traitement médicamenteux , Rituximab/usage thérapeutique , Résultat thérapeutique , Adulte , Sujet âgé , Autriche , Études de cohortes , Relation dose-effet des médicaments , Femelle , Humains , Modèles logistiques , Mâle , Adulte d'âge moyen , Récepteurs à activité tyrosine kinase/immunologie , Récepteurs cholinergiques/immunologieRÉSUMÉ
BACKGROUND AND OBJECTIVES: Multifocal motor neuropathy (MMN) is a rare neuropathy and detailed descriptions of larger patient cohorts are scarce. The objective of this study was to evaluate epidemiological, clinical, and laboratory features of MMN patients and their response to treatment in Austria and to compare these data with those from the literature. METHODS: Anonymized demographic and clinical data about MMN patients until 31.12.2017 were collected from registered Austrian neurologists. Exploratory statistics on clinical and laboratory features as well as treatment regimens and responses were performed. RESULTS: 57 Patients with MMN were identified, resulting in a prevalence of 0.65/100.000. Mean age of onset was 44.1 ± 13.1 years, the diagnostic delay 5.5 ± 8.4 years. In 77% of patients, symptom onset was in the upper limbs, and in 92%, it occurred in distal muscles. Proximal onset was never observed in the lower limbs. At the final follow-up, the majority of patients had atrophy (88%) in affected regions. Definite motor conduction blocks (CB) were found in 54 patients. Anti-GM1-IgM antibodies were present in 43%. Treatment with intravenous immunoglobulins improved muscle strength and INCAT score initially, but at last follow-up, both scores deteriorated to values before treatment. DISCUSSION: The findings of the present study corroborate the previous findings in MMN. Onset typically occurs in the upper limbs and mostly distal, CBs are found in the majority of cases, while anti-GM1-IgM antibodies are detected in only approximately 40%. Our study underlines that the initial good response to treatment fades over time.
Sujet(s)
Maladies du motoneurone/épidémiologie , Maladies du motoneurone/thérapie , Adolescent , Adulte , Âge de début , Sujet âgé , Autriche/épidémiologie , Autoanticorps/métabolisme , Femelle , Études de suivi , Ganglioside GM1/immunologie , Humains , Immunoglobuline M/métabolisme , Mâle , Adulte d'âge moyen , Maladies du motoneurone/physiopathologie , Neurologues , Prévalence , Enquêtes et questionnaires , Jeune adulteRÉSUMÉ
Rituximab (RTX) has emerged as an attractive off-label treatment option for patients with myasthenia gravis (MG) refractory to other immune therapies. However, data on long-term outcome after RTX for MG are still scarce. Here we present the 10-year outcomes [median (range) 10.1 (6.7-11.2) years] with respect to efficacy, safety, costs of inhospital care, and impact on childbearing potential in all four MG patients treated by one of the authors with RTX. In all patients, RTX led to sustained clinical improvement and eventual tapering of other immune therapies. RTX was well tolerated, and complications were not observed. After the start of RTX, annual costs for hospital admissions were markedly reduced compared to costs in the year preceding RTX. Under close clinical observation, two patients had uncomplicated pregnancies giving birth to a healthy child. With regard to its efficacy, excellent tolerance, lack of complications, low frequency of repeat infusions and pending patent expiry in many countries, RTX appears to compare favourably with other immune therapies used for MG. Multicentre trials and registries are urgently needed to further address long-term safety issues and clarify the efficacy and role of RTX in managing MG.
Sujet(s)
Hospitalisation/économie , Facteurs immunologiques/usage thérapeutique , Myasthénie/traitement médicamenteux , Myasthénie/économie , Comportement procréatif/physiologie , Rituximab/usage thérapeutique , Adulte , Autoanticorps/sang , Études de cohortes , Femelle , Humains , Immunoglobulines par voie veineuse , Adulte d'âge moyen , Myasthénie/immunologie , Myasthénie/psychologie , Récepteurs à activité tyrosine kinase/immunologie , Récepteurs cholinergiques/immunologie , Résultat thérapeutiqueSujet(s)
Hormones corticosurrénaliennes/usage thérapeutique , Faiblesse musculaire/traitement médicamenteux , Polyradiculonévrite inflammatoire démyélinisante chronique/traitement médicamenteux , Congénères de la testostérone/administration et posologie , Haltérophilie/traumatismes , Pied/anatomopathologie , Main/anatomopathologie , Humains , Mâle , Faiblesse musculaire/complications , Faiblesse musculaire/diagnostic , Polyradiculonévrite inflammatoire démyélinisante chronique/complications , Polyradiculonévrite inflammatoire démyélinisante chronique/diagnostic , Résultat thérapeutique , Jeune adulteRÉSUMÉ
Mononeuritis multiplex is characterized by an asymmetric pattern with affection of the peripheral nervous system; this form of polyneuropathy is often seen in non-systemic vasculitis. We present a case of multiplex neuropathy in a patient with histologicaly verified Hailey-Hailey disease. With the exception of this comorbidity--in its characteristic form presenting additionally with a superinfected subdermal node--we did not find any other possible etiologic factor possibly causative of multiplex neuritis. The diagnosis was confirmed by electrophysiological testing. To our knowledge, this is the first case report indicating a possible relationship between Hailey-Hailey disease and multiplex neuritis. There exists only one related study in the literature, which was conducted in Columbia--our patient's home country. This study delineates a clinically similar dermal disease (pemphigus foliaceus) in patients from rural Colombia (El Bagre). The authors detected anti-neuronal antibodies which were interpreted to be responsible for the pathognomonic burning sensations.
Sujet(s)
Mononeuropathies/diagnostic , Mononeuropathies/génétique , Pemphigus chronique bénin familial/diagnostic , Pemphigus chronique bénin familial/génétique , Climat tropical , Adulte , Analgésiques/usage thérapeutique , Anti-inflammatoires/usage thérapeutique , Autriche , Colombie , Humains , Mâle , Mononeuropathies/traitement médicamenteux , Pemphigus chronique bénin familial/traitement médicamenteux , Résultat thérapeutiqueRÉSUMÉ
Inherited peripheral neuropathies (IPN) are one of the most frequent inherited causes of neurological disability characterized by considerable phenotypic and genetic heterogeneity. Based on clinical and electrophysiological properties, they can be subdivided into three main groups: HMSN, dHMN, and HSN. At present, more than 50 IPN genes have been identified. Still, many patients and families with IPN have not yet received a molecular genetic diagnosis because clinical genetic testing usually only covers a subset of IPN genes. Moreover, a considerable proportion of IPN genes has to be identified. Here we present results of WES in 27 IPN patients excluded for mutations in many known IPN genes. Eight of the patients received a definite diagnosis. While six of these patients carried bona fide pathogenic mutations in known IPN genes, two patients had mutations in genes known to be involved in other types of neuromuscular disorders. A further group of eight patients carried sequence variations in IPN genes that could not unequivocally be classified as pathogenic. In addition, combining data of WES and linkage analysis identified SH3BP4, ITPR3, and KLHL13 as novel IPN candidate genes. Moreover, there was evidence that particular mutations in PEX12, a gene known to cause Zellweger syndrome, could also lead to an IPN phenotype. We show that WES is a useful tool for diagnosing IPN and we suggest an expanded phenotypic spectrum of some genes involved in other neuromuscular and neurodegenerative disorders. Nevertheless, interpretation of variants in known and potential novel disease genes has remained challenging.
Sujet(s)
Exome/génétique , Variation génétique/génétique , Neuropathies périphériques/diagnostic , Neuropathies périphériques/génétique , Analyse de séquence d'ADN/méthodes , Adulte , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Mâle , Adulte d'âge moyen , Résultat thérapeutique , Jeune adulteRÉSUMÉ
BACKGROUND: Despite the high prevalence of lumbosacral transitional vertebrae (LSTV), little is known about the segmental innervation in this condition. METHODS: The authors performed a prospective comparative clinical evaluation and an intraoperative electromyographic (EMG) investigation on patients with six lumbar vertebral bodies (6LVB) and on patients with five lumbar vertebrae (5LVB). First, clinical pain distribution in 80 patients (46 patients with 6LVB, 34 patients with 5LVB) with degenerative lumbar diseases were analysed between patient groups. Intraoperative EMG monitoring of five lower-limb muscles was performed. Compound muscle action potentials were obtained from 100 nerve roots of our 80 patients. RESULTS: The EMG results compared fairly to the clinical findings: 40 CMAPs from 5LVB and 60 CMAPs from 6LVB patients were compared with each other within L3 to S levels. First, there was no difference between groups in the pattern of radicular pain and myotomal innervation at the level L3/4 and L4/5 (p=0.39-1.0). Second, the nerve root stimulated at the L5/6 level compares to the S1 root in 5LVB patients; the only difference was found in a coinnervation of the biceps femoris muscle that is less frequent in 6LVB patients (p=0.02). Third, the nerve root at the L6/S level corresponds to the S1 as well as to the S2 root in 5LVB patients. CONCLUSION: Intraoperative EMG monitoring of surgically decompressed nerve roots was found to be the ideal means of unequivocal determination of segmental innervation in LSTV patients.
Sujet(s)
Électromyographie , Vertèbres lombales/malformations , Région lombosacrale/malformations , Surveillance peropératoire , Potentiels d'action/physiologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Stimulation électrique , Femelle , Humains , Déplacement de disque intervertébral/anatomopathologie , Déplacement de disque intervertébral/chirurgie , Vertèbres lombales/anatomopathologie , Vertèbres lombales/chirurgie , Région lombosacrale/anatomopathologie , Région lombosacrale/chirurgie , Mâle , Adulte d'âge moyen , Muscles squelettiques/physiopathologie , Blocage neuromusculaire , Procédures de neurochirurgie , Études prospectives , Radiculopathie/étiologie , Radiculopathie/anatomopathologie , Racines des nerfs spinaux/physiologie , Sténose du canal vertébral/anatomopathologie , Sténose du canal vertébral/chirurgie , Jeune adulteRÉSUMÉ
Multifocal motor neuropathy (MMN) is a chronic, pure motor, asymmetric neuropathy for which intravenous immunoglobulin (IVIg) is widely regarded as first-line treatment. Rituximab is a monoclonal antibody against CD20+ cells that causes prolonged B cell depletion, a well-tolerated therapy currently explored in several immune-mediated neurologic disorders. We report three patients with MMN, who had become increasingly less responsive to IVIg but showed sustained clinical improvement following rituximab monotherapy. We provide a review of the literature on rituximab for MMN and conclude that rituximab may represent an efficacious, well-tolerated and cost-effective therapeutic option for MMN patients with declining response to IVIg.
Sujet(s)
Anticorps monoclonaux/administration et posologie , Immunosuppression thérapeutique/méthodes , Immunosuppresseurs/administration et posologie , Maladies du motoneurone/traitement médicamenteux , Neuropathies périphériques/traitement médicamenteux , Adulte , Anticorps monoclonaux/effets indésirables , Anticorps monoclonaux/économie , Anticorps monoclonaux d'origine murine , Antigènes CD20/immunologie , Axones/effets des médicaments et des substances chimiques , Axones/immunologie , Axones/anatomopathologie , Lymphocytes B/effets des médicaments et des substances chimiques , Lymphocytes B/immunologie , Numération cellulaire , Prolifération cellulaire/effets des médicaments et des substances chimiques , Analyse coût-bénéfice , Résistance aux substances/effets des médicaments et des substances chimiques , Résistance aux substances/immunologie , Humains , Immunoglobulines par voie veineuse/usage thérapeutique , Facteurs immunologiques/administration et posologie , Facteurs immunologiques/effets indésirables , Facteurs immunologiques/économie , Immunosuppresseurs/effets indésirables , Immunosuppresseurs/économie , Mâle , Maladies du motoneurone/immunologie , Maladies du motoneurone/physiopathologie , Motoneurones/effets des médicaments et des substances chimiques , Motoneurones/immunologie , Motoneurones/anatomopathologie , Nerfs périphériques/effets des médicaments et des substances chimiques , Nerfs périphériques/immunologie , Nerfs périphériques/physiopathologie , Neuropathies périphériques/immunologie , Neuropathies périphériques/physiopathologie , Rituximab , Résultat thérapeutiqueRÉSUMÉ
In generalized myasthenia gravis (MG), a wide array of immunosuppressive and immunomodulating treatments is being used in clinical practice, but most drugs lack evidence from randomized controlled trials supporting their use. Furthermore, many patients develop serious side effects or do not respond sufficiently to these drugs. We report three patients with generalized MG who were treated with rituximab, a monoclonal antibody against CD20+ cells that causes prolonged B cell depletion. In all three patients, treatment with rituximab led to a sustained clinical improvement and discontinuation or reduction of prednisolone and other drugs. Rituximab was well tolerated. Therapy with rituximab was guided by the total count of peripheral B lymphocytes. Reviewing the anecdotal literature on rituximab for MG, we conclude that preliminary data on the efficacy and safety of rituximab are encouraging and that further studies in MG seem warranted.
Sujet(s)
Anticorps monoclonaux/usage thérapeutique , Facteurs immunologiques/usage thérapeutique , Myasthénie/traitement médicamenteux , Adulte , Anti-inflammatoires/usage thérapeutique , Anticorps monoclonaux d'origine murine , Lymphocytes B/effets des médicaments et des substances chimiques , Association de médicaments , Femelle , Humains , Adulte d'âge moyen , Prednisolone/usage thérapeutique , Rituximab , Indice de gravité de la maladie , Facteurs temps , Résultat thérapeutique , Jeune adulteRÉSUMÉ
Even with mild neurological signs, patients with botulism frequently complain of autonomic symptoms. This study aimed at the evaluation of sudomotor and cardiovascular reflex functions by quantitative autonomic testing (QAT), which may identify patients with autonomic involvement but otherwise benign clinical presentation. Five patients with food-borne botulism were subjected to a structured questionnaire on autonomic symptoms, cardiac and neurological examination, and QAT after a median of 2 weeks (baseline) and 12 weeks (follow-up) post intoxication. For calculation of haemodynamic and cardiovascular autonomic parameters, we used the Task Force((R)) Monitor (Version 2.1, CNSystems, Graz, Austria). Cardiovagal function was assessed by Ewing's test battery. Autonomic complaints were more pronounced than neurological symptoms. Baseline tests revealed widely abnormal sudomotor function and marked impairment of heart rate variation and blood pressure response to standing. Prominent features of cardiovascular failure were high resting heart rate, supine hypertension, orthostatic hypotension, and impaired baroreflex function. Three patients reported inability to keep up with their routine amount of physical work. Based on the baseline QAT results, these three patients were instructed to engage in physical activity but avoid physical strain until there was considerable improvement. On follow-up, fatigue was the most frequent residual complaint, sympathetic skin responses were present, and cardiovascular QAT results were significantly improved and did not differ from those of ten control subjects. QAT identified autonomic involvement in botulism patients with otherwise benign neurological presentation. Comprehensive evaluation of autonomic failure may provide useful information for the management of botulism.
Sujet(s)
Maladies du système nerveux autonome/microbiologie , Maladies du système nerveux autonome/physiopathologie , Système nerveux autonome/microbiologie , Système nerveux autonome/physiopathologie , Botulisme/complications , Botulisme/physiopathologie , Activités de la vie quotidienne , Adulte , Animaux , Troubles du rythme cardiaque/étiologie , Troubles du rythme cardiaque/physiopathologie , Maladies du système nerveux autonome/diagnostic , Évaluation de l'invalidité , Tolérance à l'effort/physiologie , Femelle , Réflexe psychogalvanique , Humains , Mâle , Souris , Souris de lignée BALB C , Adulte d'âge moyen , Examen neurologique , Barorécepteurs/physiopathologie , Syndrome de Shy-Drager/étiologie , Syndrome de Shy-Drager/physiopathologie , Enquêtes et questionnaires , Maladies des glandes sudoripares/étiologie , Maladies des glandes sudoripares/physiopathologie , Jeune adulteSujet(s)
Artérite à cellules géantes/complications , Artérite à cellules géantes/traitement médicamenteux , Insuffisance vertébrobasilaire/complications , Insuffisance vertébrobasilaire/traitement médicamenteux , Hormones corticosurrénaliennes/usage thérapeutique , Sujet âgé de 80 ans ou plus , Association de médicaments , Fibrinolytiques/usage thérapeutique , Artérite à cellules géantes/diagnostic , Héparine/usage thérapeutique , Humains , Angiographie par résonance magnétique , Mâle , Méthylprednisolone/usage thérapeutique , Résultat thérapeutique , Insuffisance vertébrobasilaire/diagnosticRÉSUMÉ
We report on 2 patients with cerebral vasculitis and stroke due to Lyme neuroborreliosis (LNB). Both patients had a prodromal stage involving headaches, and showed meningeal enhancement in addition to ischemic infarctions on brain magnetic resonance imaging and diffuse vasculitis on vascular imaging. Serological and cerebrospinal (CSF) fluid studies confirmed the diagnosis of active LNB. Ceftriaxone for 3 weeks led to an excellent recovery and improvements in the CSF examination findings. Stroke physicians should be aware of this rare presentation of LNB. A review of the current knowledge on cerebral vasculitis due to LNB is provided.
Sujet(s)
Borrelia burgdorferi , Neuroborréliose de Lyme/complications , Accident vasculaire cérébral/microbiologie , Vascularite du système nerveux central/microbiologie , Adolescent , Adulte , Sujet âgé , Antibactériens/usage thérapeutique , Anticorps antibactériens/sang , Anticorps antibactériens/liquide cérébrospinal , Borrelia burgdorferi/immunologie , Encéphalopathie ischémique/microbiologie , Ceftriaxone/usage thérapeutique , Angiographie cérébrale , Enfant , Enfant d'âge préscolaire , Femelle , Céphalée/microbiologie , Humains , Neuroborréliose de Lyme/traitement médicamenteux , Neuroborréliose de Lyme/anatomopathologie , Angiographie par résonance magnétique , Mâle , Adulte d'âge moyen , Accident vasculaire cérébral/traitement médicamenteux , Accident vasculaire cérébral/anatomopathologie , Résultat thérapeutique , Vascularite du système nerveux central/traitement médicamenteux , Vascularite du système nerveux central/anatomopathologie , Jeune adulteSujet(s)
Athétose/induit chimiquement , Agents de maintien de la densité osseuse/effets indésirables , Chorée/induit chimiquement , Diphosphonates/effets indésirables , Hypocalcémie/induit chimiquement , Tétanie/induit chimiquement , Sujet âgé de 80 ans ou plus , Tumeurs osseuses/traitement médicamenteux , Tumeurs osseuses/secondaire , Humains , Mâle , Tumeurs de la prostate/anatomopathologieRÉSUMÉ
A 35-year-old female ingested a lethal dose of potassium cyanide in a suicide attempt. She survived following antidote therapy and intensive care. Following artificial coma she presented with an agitative state for several days followed by akinetic mutism, buccofacial and ideomotoric aphasia. Severe rigid-akinetic syndrome, dysarthria, dysphagia and generalized dystonia developed weeks later. MRI revealed lesions in the caudate and lentiform nuclei, precentral cortex, and cerebellum. SPECT by [123-I] 2 beta-carbomethoxy-3-beta-(4-iodophenyl)-Tropan on two occasions revealed progressive loss of dopamine transporter suggestive of nigral neuronal apoptosis. Striatal and frontal hypometabolism and hypoperfusion were found by FDG-PET and HMPAO SPECT.
Sujet(s)
Mutisme akinétique/induit chimiquement , Mutisme akinétique/diagnostic , Cocaïne/analogues et dérivés , Imagerie par résonance magnétique , Tomographie par émission de positons , Cyanure de potassium/intoxication , Tomographie par émission monophotonique , Adulte , Dystonie/induit chimiquement , Dystonie/diagnostic , Femelle , Fluorodésoxyglucose F18 , Humains , Tentative de suicide , Examétazime de technétium (99mTc)RÉSUMÉ
We describe MR changes that occurred 3 and 6 weeks after a suicide attempt with cyanide. The toxicity of cyanide causes damage, primarily to the basal ganglia, and those changes were visible as altered signal intensity on the first MR images. Extensive areas of hemorrhagic necrosis were seen 6 weeks later. Our case shows pseudolaminar necrosis along the central cerebral cortex 3 weeks after cyanide poisoning, showing that the sensorimotor cortex is also a site for toxic necrosis because of its high oxygen dependency.