Background and ObjectivesTo determine the real-world use of rituximab in autoimmune encephalitis (AE) and to correlate rituximab treatment with the long-term outcome.MethodsPatients with NMDA receptor (NMDAR)-AE, leucine-rich glioma-inactivated-1 (LGI1)- AE, contactin-associated protein-like-2 (CASPR2)-AE, or glutamic acid decarboxylase 65 (GAD65) disease from the GErman Network for Research on AuToimmune Encephalitis who had received at least 1 rituximab dose and a control cohort of non–rituximab-treated patients were analyzed retrospectively.ResultsOf the 358 patients, 163 (46%) received rituximab (NMDAR-AE: 57%, CASPR2-AE: 44%, LGI1-AE: 43%, and GAD65 disease: 37%). Rituximab treatment was initiated significantly earlier in NMDAR- and LGI1-AE (median: 54 and 155 days from disease onset) compared with CASPR2-AE or GAD65 disease (median: 632 and 1,209 days). Modified Rankin Scale (mRS) scores improved significantly in patients with NMDAR-AE, both with and without rituximab treatment. Although being more severely affected at baseline, rituximab-treated patients with NMDAR-AE more frequently reached independent living (mRS score ≤2) (94% vs 88%). In LGI1-AE, rituximab-treated and nontreated patients improved, whereas in CASPR2-AE, only rituximab-treated patients improved significantly. No improvement was observed in patients with GAD65 disease. A significant reduction of the relapse rate was observed in rituximab-treated patients (5% vs 13%). Detection of NMDAR antibodies was significantly associated with mRS score improvement. A favorable outcome was also observed with early treatment initiation.DiscussionWe provide real-world data on immunosuppressive treatments with a focus on rituximab treatment for patients with AE in Germany. We suggest that early and short-term rituximab therapy might be an effective and safe treatment option in most patients with NMDAR-, LGI1-, and CASPR2-AE.Class of EvidenceThis study provides Class IV evidence that rituximab is an effective treatment for some types of AE.
-Conventional anti-Parkinsonian dopamine replacement therapy is often complicated by side effects that limit the use of these medications. There is a continuing need to develop nondopaminergic approaches to treat Parkinsonism. One such approach is to use medications that normalize dopamine depletion-related firing abnormalities in the basal ganglia-thalamocortical circuitry. In this study, we assessed the potential of a specific T-type calcium channel blocker (ML218) to eliminate pathologic burst patterns of firing in the basal gangliareceiving territory of the motor thalamus in Parkinsonian monkeys. We also carried out an anatomical study, demonstrating that the immunoreactivity for T-type calcium channels is strongly expressed in the motor thalamus in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. At the electron microscopic level, dendrites accounted for Ͼ90% of all tissue elements that were immunoreactive for voltage-gated calcium channel, type 3.2-containing T-type calcium channels in normal and Parkinsonian monkeys. Subsequent in vivo electrophysiologic studies in awake MPTP-treated Parkinsonian monkeys demonstrated that intrathalamic microinjections of ML218 (0.5 l of a 2.5-mM solution, injected at 0.1-0.2 l/min) partially normalized the thalamic activity by reducing the proportion of rebound bursts and increasing the proportion of spikes in non-rebound bursts. The drug also attenuated oscillatory activity in the 3-13-Hz frequency range and increased gamma frequency oscillations. However, ML218 did not normalize Parkinsonism-related changes in firing rates and oscillatory activity in the beta frequency range. Whereas the described changes are promising, a more complete assessment of the cellular and behavioral effects of ML218 (or similar drugs) is needed for a full appraisal of their anti-Parkinsonian potential.
Deep brain stimulation of the internal globus pallidus (GPi) is a major treatment for advanced Parkinson's disease. The effects of this intervention on electrical activity patterns in targets of GPi output, specifically in the thalamus, are poorly understood. The experiments described here examined these effects using electrophysiological recordings in two Rhesus monkeys rendered moderately parkinsonian through treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), after sampling control data in the same animals. Analysis of spontaneous spiking activity of neurons in the basal ganglia-receiving areas of the ventral thalamus showed that MPTP-induced parkinsonism is associated with a reduction of firing rates of segments of the data that contained neither bursts nor decelerations, and with increased burst firing. Spectral analyses revealed an increase of power in the 3- to 13-Hz band and a reduction in the γ-range in the spiking activity of these neurons. Electrical stimulation of the ventrolateral motor territory of GPi with macroelectrodes, mimicking deep brain stimulation in parkinsonian patients (bipolar electrodes, 0.5 mm intercontact distance, biphasic stimuli, 120 Hz, 100 μs/phase, 200 μA), had antiparkinsonian effects. The stimulation markedly reduced oscillations in thalamic firing in the 13- to 30-Hz range and uncoupled the spiking activity of recorded neurons from simultaneously recorded local field potential (LFP) activity. These results confirm that oscillatory and nonoscillatory characteristics of spontaneous activity in the basal ganglia receiving ventral thalamus are altered in MPTP-induced parkinsonism. Electrical stimulation of GPi did not entrain thalamic activity but changed oscillatory activity in the ventral thalamus and altered the relationship between spikes and simultaneously recorded LFPs.
Physical examination, interviews with patients and the results of rating scales for movement disturbances are the basis for the assessment of Parkinson's disease (PD). However, subjectivity in the assessment of the symptoms and the short period of observation are disadvantageous. This paper presents the results of a study to assess the feasibility of using accelerometer data, acquired from smart clothes, to estimate the severity of tremor in patients with PD. Algorithms were implemented to estimate the severity of rest and postural tremor of hands from accelerometer data features. The system developed consists of a pullover with eight integrated accelerometers and a computer. The newly developed system for the detection and assessment of tremor was tested with PD patients. System-based estimates were compared with clinical scores derived via visual inspection of video recordings taken while patients performed a series of standardized motor tasks. A quantifiable objective data acquisition by means of a portable wireless system could evaluate the motor disorders better.
IntroductionHuman multimodal vestibular cortical regions are bilaterally anterior insulae and posterior opercula, where characteristic vestibular-related cortical potentials were previously reported under acoustic otolith stimulation. Galvanic vestibular stimulation likely influences semicircular canals preferentially. Galvanic stimulation was compared to previously established data under acoustic stimulation.Methods14 healthy right-handed subjects, who were also included in the previous acoustic potential study, showed normal acoustic and galvanic vestibular-evoked myogenic potentials. They received 2,000 galvanic binaural bipolar stimuli for each side during EEG recording.ResultsVestibular cortical potentials were found in all 14 subjects and in the pooled data of all subjects (“grand average”) bilaterally. Anterior insula and posterior operculum were activated exclusively under galvanic stimulation at 25, 35, 50, and 80 ms; frontal regions at 30 and 45 ms. Potentials at 70 ms in frontal regions and at 110 ms at all of the involved regions could also be recorded; these events were also found using acoustic stimulation in our previous study.ConclusionGalvanic semicircular canal stimulation evokes specific potentials in addition to those also found with acoustic otolith stimulation in identically located regions of the vestibular cortex. Vestibular cortical regions activate differently by galvanic and acoustic input at the peripheral sensory level.SignificanceDifferential effects in vestibular cortical-evoked potentials may see clinical use in specific vertigo disorders.
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