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BackgroundSeveral earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias inherent to study design. Moreover, information is lacking on whether sex-related differences exist in expressing other dystonia-associated features and dystonia spread.ObjectiveTo provide accurate information on the relationship between sex differences, motor phenomenology, dystonia-associated features and the natural history of IAOD.MethodsData of 1701 patients with IAOD from the Italian Dystonia Registry were analysed.ResultsWomen predominated over men in blepharospasm, oromandibular, laryngeal and cervical dystonia; the sex ratio was reversed in task-specific upper limb dystonia; and no clear sex difference emerged in non-task-specific upper limb dystonia and lower limb dystonia. This pattern was present at disease onset and the last examination. Women and men did not significantly differ for several dystonia-associated features and tendency to spread. In women and men, the absolute number of individuals who developed dystonia tended to increase from 20 to 60 years and then declined. However, when we stratified by site of dystonia onset, different patterns of female-to-male ratio over time could be observed in the various forms of dystonia.ConclusionsOur findings provide novel evidence on sex as a key mediator of IAOD phenotype at disease onset. Age-related sexual dimorphism may result from the varying exposures to specific age-related and sex-related environmental risk factors interacting in a complex manner with biological factors such as hormonal sex factors.

Background: Parkinson's disease (PD) is a chronic, progressive neurodegenerative condition that gradually worsens motor function and leads to postural instability and, eventually, falls. Several factors may influence the frequency of future falls, such as slowness, freezing of gait, loss of balance, and mobility problems, cognitive impairments, and the number of previous falls. The TED bracelet is an advanced technological wearable device able to predict falls. Aims: This principal aim is to investigate the feasibility of a full-scale research project that uses the TED bracelet to identify whether individuals with PD are at risk of falling. Methods: This study will involve a pilot prospective observational study design; the subjects will include 26 patients suffering from mild PD and 26 others with no PD and no gait problems. Data will be collected from the TED bracelet and then compared to a paper-based fall diary. The enrolled participants will have a scheduled outpatient evaluation to collect both clinical and instrumental data as well as biological samples. Discussion: This pilot study could then be implemented in a larger form to further evaluate the effectiveness of the TED device. Finally, it will help further develop gait monitoring systems for people with Parkinson's disease and other neurodegenerative diseases that can affect physical function and mobility, such as dementia and Alzheimer's. Conclusions: Preventing falls and their complications could lead to major advancements in the quality of home care for patients with PD, which would significantly impact the quality of life of both these patients and their caregivers.

T cells are key mediators of both humoral and cellular adaptive immune responses, and their role in Parkinson’s disease (PD) is being increasingly recognized. Several lines of evidence have highlighted how T cells are involved in both the central nervous system and the periphery, leading to a profound imbalance in the immune network in PD patients. This review discusses the involvement of T cells in both preclinical and clinical studies, their importance as feasible biomarkers of motor and non-motor progression of the disease, and recent therapeutic strategies addressing the modulation of T cell response.

Management of motor complications (MC) represents a major challenge in the long-term treatment of Parkinson’s disease (PD) patients. In this context, the role of peripheral adaptive immunity may provide new insights, since neuroinflammatory mechanisms have been proved crucial in the disease. The aim of this study was to analyze the transcription factors genes involved in CD4 + T cells development to uncover specific molecular signatures in patients with (PMC) and without (WMC) motor complications. mRNA levels of CD4 + T lymphocytes transcription factor genes TBX21, STAT1, STAT3, STAT4, STAT6, RORC, GATA3, FOXP3, and NR4A2were measured from 40 PD patients, divided into two groups according to motor complications. Also, 40 age- and sex-matched healthy controls were enrolled. WMC patients had higher levels of STAT1and NR4A2(p = 0.004; p = 0.003), whereas in PMC we found higher levels of STAT6(p = 0.04). Also, a ROC curve analysis confirmed STAT1and NR4A2as feasible biomarkers to discriminate WMC (AUC = 0.76, 95%CI 0.59–0.92, p = 0.005; AUC = 0.75, 95%CI 0.58–0.90, p = 0.007). Similarly, STAT6detected PMC patients (AUC = 0.69, 95%CI 0.52–0.86, p = 0.037). These results provide evidence of different molecular signatures in CD 4 + T cells of PD patients with and without MC, thus suggesting their potential as biomarkers of MC development.

Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with a wide spectrum of motor, cognitive, and neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and XPR1. Our study aimed at screening the coding regions of these genes in a series of 177 unrelated probands that fulfilled the diagnostic criteria for primary brain calcification regardless of their family history. Sequence variants were classified as pathogenic, likely pathogenic, or of uncertain significance (VUS), based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying either pathogenic or likely pathogenic variants (n= 34, 19.2%) or VUS (n= 11, 6.2%). SLC20A2provided the highest contribution (16.9%), followed by XPR1and PDGFB(3.4% each), and PDGFRB(1.7%). A total of 81.5% of carriers were symptomatic and the most recurrent symptoms were parkinsonism, cognitive impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic individuals, respectively), with a wide range of age at onset (from childhood to 81 years). While the pathogenic and likely pathogenic variants identified in this study can be used for genetic counseling, the VUS will require additional evidence, such as recurrence in unrelated patients, in order to be classified as pathogenic.

In its classic presentation, Hashimoto's encephalopathy is an acute‐subacute complex neuropsychiatric syndrome with cognitive impairment, hallucinations, myoclonus, tremor or ataxia, associated with elevated anti‐thyroid antibodies. Corticoids and immunotherapy are dramatically effective. However, in some cases, not all the associated features are presented and this delays diagnosis and appropriate treatment. We describe a man with abrupt onset of recurrent auditory seizures resulting in refractory non‐convulsive status epilepticus. The patient was diagnosed with an autoimmune encephalopathy with elevated serum and CSF anti‐thyroid antibodies. None of the antiepileptic drugs were successful, however, following immune‐modulating therapy, the refractory non‐convulsive status epilepticus dramatically improved, as did the patient overall. We suggest that Hashimoto's encephalopathy should be suspected in otherwise healthy patients with unexplained new‐onset focal recurrent auditory seizures which do not respond to antiepileptic drugs. The presence of anti‐thyroid antibodies in the CSF supports this diagnosis.