The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide. To prevent severe infection, mass COVID-19 vaccination campaigns with several vaccine types are currently ...underway. We report pathological and immunological findings in 8 patients who developed vaccine-induced immune thrombotic thrombocytopenia (VITT) after administration of SARS-CoV-2 vaccine ChAdOx1 nCoV-19. We analyzed patient material using enzyme immune assays, flow cytometry and heparin-induced platelet aggregation assay and performed autopsies on two fatal cases. Eight patients (5 female, 3 male) with a median age of 41.5 years (range, 24 to 53) were referred to us with suspected thrombotic complications 6 to 20 days after ChAdOx1 nCoV-19 vaccination. All patients had thrombocytopenia at admission. Patients had a median platelet count of 46.5 x109/L (range, 8 to 92). Three had a fatal outcome and 5 were successfully treated. Autopsies showed arterial and venous thromboses in various organs and the occlusion of glomerular capillaries by hyaline thrombi. Sera from VITT patients contain high titer antibodies against platelet factor 4 (PF4) (OD 2.59±0.64). PF4 antibodies in VITT patients induced significant increase in procoagulant markers (P-selectin and phosphatidylserine externalization) compared to healthy volunteers and healthy vaccinated volunteers. The generation of procoagulant platelets was PF4 and heparin dependent. We demonstrate the contribution of antibody-mediated platelet activation in the pathogenesis of VITT.
In view of the importance of neurosyphilis and the difficulties encountered in diagnosing it, the S1 guideline "Neurosyphilis" has been published by the German Society for Neurology (DGN) in ...accordance with the stipulations of the Association of the Scientific Medical Societies in Germany (AWMF). The present article is an abridged translation of that German guideline.
(a) Neurosyphilis can manifest as early neurosyphilis (meningitis, meningovascular neurosyphilis or syphilitic gummas) or late neurosyphilis (tabes dorsalis, general paresis). (b) The following diagnostic criteria help to establish the presence of probable neurosyphilis (always point iv, accompanied by any two of points i to iii): (i) subacute or chronic neuro-psychiatric symptoms; (ii) increased cerebrospinal fluid (CSF) cell count or signs of blood-CSF barrier disruption; (iii) positive effect of anti-neurosyphilis antibiotic therapy on clinical course and CSF findings; (iv) positive TPHA/TPPA or FTA test in serum. (c) The diagnosis of neurosyphilis is confirmed by the subsequent detection of intrathecal production of antibodies against
. (d) In neurosyphilis, treatment with intravenous penicillin or ceftriaxone for 14 days is recommended. (e) The following parameters can be used to assess a therapeutic effect: clinical findings, serum VDRL, and CSF cell count.
The German guideline on the diagnosis and treatment of neurosyphilis is a practical tool to support clinicians in diagnosing and treating patients with neurosyphilis. This article is an abridged translation of this guideline (Klein MW, J.; Angstwurm, K.; Esser, S.; Hahn, K.; Matschke, M.; Scheithauer, S.; Schoefer, H.; Sturzenegger, M.; Wildemann, B. Neurosyphilis, S1-Leitlinie. Deutsche Gesellschaft für Neurologie, Leitlinien für Diagnostik und Thearpie in der Neurologie 2020).
Parkinson's disease (PD) is a neurodegenerative disorder that leads to a progressive decline in motor function. Growing evidence indicates that PD patients also experience an array of sensory ...problems that negatively impact motor function. This is especially true for proprioceptive deficits, which profoundly degrade motor performance. This review specifically address the relation between proprioception and motor impairments in PD. It is structured around 4 themes: (a) It examines whether the sensitivity of kinaesthetic perception, which is based on proprioceptive inputs, is actually altered in PD. (b) It discusses whether failed processes of proprioceptive-motor integration are central to the motor problems in PD. (c) It presents recent findings focusing on the link between the proprioception and the balance problems in PD. And (d) it discusses the current state of knowledge of how levodopa medication and deep brain stimulation affect proprioceptive and motor function in PD. The authors conclude that a failure to evaluate and to map proprioceptive information onto voluntary and reflexive motor commands is an integral part of the observed motor symptoms in PD.
Infectious diseases are an important consideration in autoimmune conditions such as multiple sclerosis. Infective episodes may trigger relapses and significantly deteriorate the course of the ...disease. Some immunotherapies may cause increased rates of infection-related adverse events. Thus, infection and vaccine-related issues should be included in the individualized patient-specific treatment strategy and counseling before starting therapy and regularly on treatment. Clinical and epidemiological studies as well as pharmacovigilance data repeatedly demonstrated the safety of the great majority of vaccines in multiple sclerosis patients. Moreover, studies have shown that vaccinations with killed/inactivated vaccines do not increase the short-term risk of relapse or deterioration in multiple sclerosis, whereas infections have been shown to provoke relapses. The available evidence indicates reduced humoral vaccination efficacy on treatment with MS drugs acting on the S1P receptor, natalizumab, and B-cell depleting therapies. Recent data for cladribine tablets suggest the potential of effective immunization in the interval of the two treatment courses and after completion of therapy. Regardless of treatment, vaccine efficacy may be optimized with proper timing of application. Multiple sclerosis patients receiving highly effective therapies should be vaccinated according to general recommendations for healthy adults. Immunization against COVID-19 is highly recommended for all multiple sclerosis patients regardless of age and comorbidities. Preliminary data show the potential of adequate responses in patients treated with cladribine tablets.
Abstract Objectives The clinical spectrum of amyotrophic lateral sclerosis (ALS) is characterized by a considerable variation. Different phenotypes have been described by previous studies. We ...assessed clinical variability and prognostic relevance of these phenotypes in a prospective, population-based cohort of ALS patients in Rhineland-Palatinate, Germany. Methods Incident ALS cases, diagnosed between October 2009 and September 2012, were prospectively enrolled and classified according to established ALS phenotype classification (bulbar, classic, flail arm, flail leg, pyramidal, respiratory). Survival probability was described using Kaplan–Meier method. Moreover, the influence of an additional frontotemporal dementia (FTD) was analysed. Results Phenotypes of all 200 patients were determined. Bulbar and classic phenotypes accounted for 75% of all cases. Deterioration of functional impairment during disease progression was lowest in flail leg and pyramidal variants, and most pronounced in bulbar and classic phenotypes. A poor survival prognosis was observed for bulbar, classic or respiratory phenotypes. Patients with an additional FTD showed an even worse outcome. Conclusions Results suggest that ALS is a heterogeneous disease, as ALS phenotypes differ in disease progression and survival time. Patients classified as suffering from bulbar, classic and respiratory ALS, as well as those with an additional FTD, show a marked reduction of survival time.
We investigated how humans with hereditary cerebellar degeneration spinocerebellar ataxia (SCA) type 6 and 8, n = 9 and age- and sex-matched healthy controls (n = 9) adapted goal-directed arm ...movements to an unknown external force field. We tested whether learning could be generalized to untrained regions in the workspace, an aspect central to the idea of an internal model, and if any learning could be retained. After removal of the force field, SCA patients showed little or no learning-related aftereffects indicating that repeated force-field exposure never led to successful force compensation. In contrast, healthy control subjects quickly adapted their movements to the new force field. The difference in force adaptation was significant for movements to targets that required both the shoulder and elbow joint (P < 0.001). Moreover, the generalization of learned movements to targets outside the learned workspace was prevented by the cerebellar degeneration (P < 0.01). Retention of force adaptation was significantly lower in SCA patients (P = 0.003). The severity of ataxia in SCA patients correlated negatively with the extent of learning (r = -0.84, P = 0.004). Our findings imply that progressive loss of cerebellar function gradually impairs force adaptation. The failure to generalize learning suggests that cerebellar degeneration prevents the formation of an internal representation of the limb dynamics.
The possibility to survive with amyotrophic lateral sclerosis (ALS) varies considerably and survival extends from a few months to several years. A number of demographic and clinical factors ...predicting survival have been described; however, existing data are conflicting. We intended to predict patient survival in a population-based prospective cohort of ALS patients from variables known up to the time of diagnosis.
Incident ALS patients diagnosed within three consecutive years were enrolled and regularly followed up. Candidate demographic and disease variables were analysed for survival probability using the Kaplan-Meier method. The Cox proportional hazard regression model was used to assess the influence of selected predictor variables on survival prognosis.
In the cohort of 193 patients (mean age 65.8, standard deviation 10.2 years), worse prognosis was independently predicted by older age, male gender, bulbar onset, probable or definite ALS according to El Escorial criteria, shorter interval between symptom onset and diagnosis, lower Functional Rating Scale, diagnosis of frontotemporal dementia, and living without a partner.
Taking into account these predictor variables, an approximate survival prognosis of individual ALS patients at diagnosis seems feasible.
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