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Deep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson’s disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics, behavioral tasks and mathematical modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A computational model highlights that a decrease in pyramidal neuron activity induced by DBS or by a stimulation of cortical somatostatin interneurons can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation. Deep brain stimulation (DBS) is a symptomatic treatment of Parkinson’s disease (PD) that benefits only a minority of patients. Here, the authors show that activation of cortical somatostatin interneurons alleviates motor symptoms in a mouse model of PD and may constitute a less invasive alternative than DBS.

IntroductionRecreational use of nitrous oxide (N2O) is a growing practice in France and all around the world and is often associated with neurological complications. We report detailed clinical and paraclinical presentations of 12 patients with combined degeneration of the spinal cord and peripheral neuropathies in relation to N2O consumption, possibly favored by lockdowns due to SARS-CoV-2 pandemic.ResultsWith variable levels of consumption, the 12 patients presented spinal cord and/or peripheral nerve damage, with mostly motor and ataxic symptoms, motor axonal nerve damage, and medullary T2-weighted hyperintensities on MRI. There was a clear improvement in symptoms after vitamin B12 substitution, although some sequelae remained, particularly sensory.DiscussionWe report detailed clinical, electrophysiological, radiological, and biological consequences of N2O abuse in 12 patients. Our data support the clinical and paraclinical observations reported in the literature. The mechanisms of neurological N2O toxicity are still debated. There is currently no precise recommendation on the therapeutic management. The clinical evolution after vitamin B12 substitution seems sufficient but could depend on early management. Effective messages targeting at risk population, but also the health professionals involved, seem crucial as does a better legal framework for this growing practice.

Injection of botulinum toxin into each splenius capitis muscle at baseline and week 12 was more effective than placebo in reducing the severity of essential head tremor over 18 weeks. Effects waned at 24 weeks.

Chronic Levodopa therapy, the gold-standard treatment for Parkinson’s Disease (PD), leads to the emergence of involuntary movements, called levodopa-induced dyskinesia (LID). Cerebellar stimulation has been shown to decrease LID severity in PD patients. Here, in order to determine how cerebellar stimulation induces LID alleviation, we performed daily short trains of optogenetic stimulations of Purkinje cells (PC) in freely moving LID mice. We demonstrated that these stimulations are sufficient to suppress LID or even prevent their development. This symptomatic relief is accompanied by the normalization of aberrant neuronal discharge in the cerebellar nuclei, the motor cortex and the parafascicular thalamus. Inhibition of the cerebello-parafascicular pathway counteracted the beneficial effects of cerebellar stimulation. Moreover, cerebellar stimulation reversed plasticity in D1 striatal neurons and normalized the overexpression of FosB, a transcription factor causally linked to LID. These findings demonstrate LID alleviation and prevention by daily PC stimulations, which restore the function of a wide motor network, and may be valuable for LID treatment. Here, the authors studied how cerebellar stimulation alleviates levodopa-induced dyskinesia (LID). They demonstrated that Purkinje cell opto-stimulation is sufficient to prevent LID development and can normalize brain activity in a wide motor network in mice.

123 I-FP-CIT SPECT enables the detection of presynaptic dopaminergic denervation. It allows to differentiate degenerative parkinsonian syndromes from secondary parkinsonian syndromes or essential tremor, and patients with suspected dementia with Lewy bodies from those with other dementia subtypes. The aim of our study was to evaluate the appropriateness of 123 I-FP-CIT SPECT prescriptions, identify prescriber profiles and analyze changes in prescriptions over a decade in the Neurology department of Avicenne University hospital. This retrospective study included all patients who underwent 123 I-FP-CIT SPECT between February 2009 and May 2019 (n = 723). Clinical and paraclinical data were compared between three groups based on the relevance of 123 I-FP-CIT SPECT prescription: “inappropriate”, “uncertain” and “relevant”. We showed that inappropriate indications accounted for 37.5% of 123 I-FP-CIT SPECT requests. Hospital neurologists and neurologists with mixed practice accounted for 74.1% of 123 I-FP-CIT SPECT requests, hospital movement disorders specialists being more likely to prescribe appropriately (67.1%) than hospital non-movement disorders specialists (33.3%). Following the replacement of the neuro-oncology team with a team including movement disorders specialists, the percentage of relevant SPECT 123I-FP-CIT prescriptions rose from 37.5% to 81.0%. These observations suggest that seeking the expertise of a movement disorders specialist would be more relevant than the systematic prescription of 123 I-FP-CIT SPECT.

Clinical assessments for Parkinson’s disease depend on clinician-administered scales, which have limitations in sensitivity and real-world applicability. Wearable inertial sensors offer a promising approach for objective and continuous monitoring of PD motor symptoms. This study aimed to evaluate the feasibility and accuracy of a magneto-inertial wearable device in detecting key PD motor manifestations—tremor, akinesia, and dyskinesia—on an individual movement basis. Ten PD patients undergoing pre-surgical evaluation for deep brain stimulation were included in a pilot multicentric study. Participants performed a Levodopa challenge test while wearing an inertial measurement unit on the most affected wrist and ankle. MDS-UPDRS Part III and video recordings were obtained to compare sensor performance to expert evaluations. Algorithms analyzed acceleration and angular velocity data to detect tremor, akinesia and dyskinesia. The sensor demonstrated high sensitivity (100%) and specificity (≥ 93%) for tremor and akinesia detection, with an overall accuracy exceeding 94%. Performance metrics were less promising for dyskinesia detection. Levodopa significantly reduced tremor (p = 0.0247) and increased dyskinesia (p = 0.0169), confirming sensor responsiveness to pharmacological effects. Magneto-inertial wearable device showed promising accuracy for the objective assessment of PD motor symptoms in a controlled environment. These findings support further validation in real-life conditions.

Krabbe disease usually presents as a severe leukodystrophy in early infancy and childhood. From a series of 11 patients and 30 cases previously reported in the literature we describe the clinical, radiological, electrophysiological and genetic features of adult Krabbe disease. Patients diagnosed after the age of 16 years were included in this study. They were further divided into three groups depending on age at symptoms onset: (1) childhood onset cases ( n  = 7); (2) adolescence onset cases ( n  = 6) and adult onset cases ( n  = 28). Overall, 96 % of patients in the adult-onset group presented with signs of pyramidal tracts dysfunction. Spastic paraparesis or tetraparesis became prominent in all cases. A peripheral neuropathy was present in 59 % of cases and was most often demyelinating (80 %). Other clinical signs encompassed dysarthria (31 %), cerebellar ataxia (27 %), pes cavus (27 %), deep sensory signs (23 %), tongue atrophy (15 %), optic neuropathy (12 %), cognitive decline (12 %). Cerebrospinal fluid protein concentration was moderately increased in 54 % of patients. Patients in the adolescent- and childhood-onset groups had similar presentations but were more likely to display optic neuropathy (33 % and 57 %) and cerebellar ataxia (50 % and 57 %). In the adult-onset group, the disease progressed slowly over more than 10 years, but a rapid course was observed in two patients. Abnormalities of brain MRI was similar in the three groups and included high signals of cortico-spinal tracts (94 % of cases), hyper-intensities of optic radiations (89 %) and hyper-intensities or atrophy of the posterior part of the corpus callosum (60 %). No clear genotype-phenotype relationship could be demonstrated.

Anticipatory actions require to keep track of elapsed time and inhibitory control. These cognitive functions could be impacted in Parkinson’s disease (iPD). To test this hypothesis, a saccadic reaction time task was used where a visual warning stimulus (WS) predicted the occurrence of an imperative one (IS) appearing after a short delay. In the implicit condition, subjects were not informed about the duration of the delay, disfavoring anticipatory behavior but leaving inhibitory control unaltered. In the explicit condition, delay duration was cued. This should favor anticipatory behavior and perhaps alter inhibitory control. This hypothesis was tested in controls ( N  = 18) and age-matched iPD patients ( N  = 20; ON and OFF L-DOPA). We found that the latency distribution of saccades before the IS was bimodal. The 1 st mode weakly depended on temporal information and was more prominent in iPD. Saccades in this mode were premature and could result of a lack of inhibition. The 2 nd mode covaried with cued duration suggesting that these movements were genuine anticipatory saccades. The explicit condition increased the probability of anticipatory saccades before the IS in controls and iPD ON but not iPD OFF patients. Furthermore, in iPD patients the probability of sequences of 1 st mode premature responses increased. In conclusion, the triggering of a premature saccade or the initiation of a controlled anticipatory one could be conceptualized as the output of two independent stochastic processes. Altered time perception and increased motor impulsivity could alter the balance between these two processes in favor of the latter in iPD, particularly OFF L-Dopa.

Dopamine modulates striatal synaptic plasticity, a key substrate for action selection and procedural learning. Thus, characterizing the repertoire of activity-dependent plasticity in striatum and its dependence on dopamine is of crucial importance. We recently unraveled a striatal spike-timing-dependent long-term potentiation (tLTP) mediated by endocannabinoids (eCBs) and induced with few spikes (~5–15). Whether this eCB-tLTP interacts with the dopaminergic system remains to be investigated. Here, we report that eCB-tLTP is impaired in a rodent model of Parkinson’s disease and rescued by L-DOPA. Dopamine controls eCB-tLTP via dopamine type-2 receptors (D 2 R) located presynaptically in cortical terminals. Dopamine–endocannabinoid interactions via D 2 R are required for the emergence of tLTP in response to few coincident pre- and post-synaptic spikes and control eCB-plasticity by modulating the long-term potentiation (LTP)/depression (LTD) thresholds. While usually considered as a depressing synaptic function, our results show that eCBs in the presence of dopamine constitute a versatile system underlying bidirectional plasticity implicated in basal ganglia pathophysiology. Dopamine tightly regulates plasticity at corticostriatal synapses. Here, the authors report that endocannabinoid dependent LTP induced with few spikes in the striatum is impaired in a rodent model of Parkinson’s disease, requires dopamine through presynaptic D2 receptors located on corticostriatal inputs.