BackgroundWe report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanità and the competent Ethics Committees and was monitored by an external Safety Board.MethodsSix non-ambulatory patients were treated. Three of them received 3 unilateral hNSCs microinjections into the lumbar cord tract, while the remaining ones received bilateral (n = 3 + 3) microinjections. None manifested severe adverse events related to the treatment, even though nearly 5 times more cells were injected in the patients receiving bilateral implants and a much milder immune-suppression regimen was used as compared to previous trials.ResultsNo increase of disease progression due to the treatment was observed for up to18 months after surgery. Rather, two patients showed a transitory improvement of the subscore ambulation on the ALS-FRS-R scale (from 1 to 2). A third patient showed improvement of the MRC score for tibialis anterior, which persisted for as long as 7 months. The latter and two additional patients refused PEG and invasive ventilation and died 8 months after surgery due to the progression of respiratory failure. The autopsies confirmed that this was related to the evolution of the disease.ConclusionsWe describe a safe cell therapy approach that will allow for the treatment of larger pools of patients for later-phase ALS clinical trials, while warranting good reproducibility. These can now be carried out under more standardized conditions, based on a more homogenous repertoire of clinical grade hNSCs. The use of brain tissue from natural miscarriages eliminates the ethical concerns that may arise from the use of fetal material.Trial registrationEudraCT:2009-014484-39.

† The COVID19 pandemic is causing an unprecedented public health crisis impacting healthcare systems, healthcare workers and communities. The COVID-19 Pandemic Health System REsilience PROGRAM (REPROGRAM) consortium is an international not-for-profit think-tank established to champion the safety of healthcare workers, policy development and advocacy for global pandemic preparedness and action Specialty section: This article was submitted to Dementia and Neurodegenerative Diseases, a section of the journal Frontiers in Neurology

Instrumental guidance may improve the outcome of botulinum toxin injections into the spastic forearm muscles of stroke patients.

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Summary Purpose:  To assess the visual system excitability of photosensitive patients with idiopathic generalized epilepsy (IGE) with the paired‐pulse flash‐evoked potential (paired F‐VEP) technique. Methods:  We studied 19 photosensitive patients with IGE (16 women) showing a photoparoxysmal electroencephalographic (EEG) response (PPR). Twenty‐two normal subjects of similar age and sex acted as controls (17 women). We recorded F‐VEPs from occipital and central electrodes. Stimuli were single flashes, intermingled to flash pairs at the interstimulus interval (ISI) of 333, 125, 62.5, 50, 33, and 16.5 msec (i.e., at the internal frequency of 3, 8, 16, 20, 30, and 60 Hz). Recordings were done both with closed and open eyes. The single F‐VEP was split into a “main complex” and a “late response,” which were measured separately. As to paired stimuli, the “test” F‐VEP emerged from electronic subtraction of the single F‐VEP to the paired F‐VEP. Grouped data were analyzed by means of nonparametric analyses of variance (ANOVAs). Key Findings:  In patients, the single F‐VEP showed some enhanced components in its early “main complex.” Then, the “test” F‐VEP behaved differently than controls, particularly if recorded with closed eyes, when the normal inhibition was abolished at given ISIs, corresponding to an internal frequency of 16–30 Hz. In patients with a posterior PPR, impaired inhibition was evident over the occipital region only, but in those with a widespread PPR, it also involved the central areas. Significance:  The paired F‐VEP technique documents a defective inhibition in the visual system of photosensitive patients with IGE, whose features and timing likely underlie the PPR origin.