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ADAR1 variants are associated to rare and heterogenous neurological conditions, including Aicardi-Goutieres syndrome type 6, bilateral striatal necrosis, and dyschromatosis symmetrica hereditaria. Movement disorders (MDs) commonly occur in ADAR1-related diseases although a complete overview on the phenomenology has not been provided yet. Here, a cohort of 57 patients with ADAR1-related diseases, including 3 unpublished patients and 54 previously reported cases, was reviewed. Data on demographics, clinical features of MDs, genetics and biomarkers were collected and descriptive statistics, group analysis for genotype and logistic regression were run. Manifestations of MD characterized the onset of ADAR1-related disease in 60% of patients. Specifically, dystonia occurred in 39% of cases, even as severe status dystonicus, while prevalence of other MDs was lower. Patients often presented brain lesions (>90%) and progressive disease course (43%), fatal in some cases. Clinical presentation and outcome differed among patients with distinct genotype. This review shows that phenomenology of MDs in ADAR1-related diseases is wide and heterogeneous, although a severe motor syndrome (often characterized by dystonia) secondary to brain lesions represents the most common manifestation. Waiting for future development of disease-modifying treatments, an appropriate symptomatic intervention is crucial for ADAR1 patients. Accordingly, a deeper knowledge of phenomenology is fundamental.

Multiple sclerosis (MS) is an inflammatory immune-mediate disorder of the central nervous system (CNS), primarily affecting the myelin sheath and followed by neurodegeneration. Synaptic alterations are emerging as critical determinants of early neurodegeneration in MS. Inflammation-induced alterations of synaptic transmission and plasticity have been investigated in vitro and also in human MS using transcranial magnetic stimulation (TMS) techniques. Specific inflammatory cytokines alter glutamatergic and GABAergic transmission, resulting in synaptic hyperexcitability. In both experimental autoimmune encephalomyelitis (EAE) and MS, excitotoxic damage and neurodegeneration are found even in the early phases of disease, conversely inflammation persists in the progressive phases. Inflammatory cytokines also affect synaptic plasticity, as both long-term potentiation (LTP) and long-term depression (LTD) are altered in EAE and in MS patients. In particular, inflammation profoundly subverts plasticity and influence both clinical recovery after a relapse and disease course. Regulation of neuronal activity by cytokines plays important roles in the neuro-immune crosstalk involved in inflammation-associated excitotoxic neuronal damage, and in the chance of developing compensatory plasticity. Innate and adaptive immunity interact with the CNS in MS, in line with the concept that cytokines and chemokines, in concert with neurotransmitters and neuropeptides, represent a major communication system in the CNS.