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Paroxysmal movement disorders (PMDs) are rare neurological diseases typically manifesting with intermittent attacks of abnormal involuntary movements. Two main categories of PMDs are recognized based on the phenomenology: Paroxysmal dyskinesias (PxDs) are characterized by transient episodes hyperkinetic movement disorders, while attacks of cerebellar dysfunction are the hallmark of episodic ataxias (EAs). From an etiological point of view, both primary (genetic) and secondary (acquired) causes of PMDs are known. Recognition and diagnosis of PMDs is based on personal and familial medical history, physical examination, detailed reconstruction of ictal phenomenology, neuroimaging, and genetic analysis. Neurophysiological or laboratory tests are reserved for selected cases. Genetic knowledge of PMDs has been largely incremented by the advent of next generation sequencing (NGS) methodologies. The wide number of genes involved in the pathogenesis of PMDs reflects a high complexity of molecular bases of neurotransmission in cerebellar and basal ganglia circuits. In consideration of the broad genetic and phenotypic heterogeneity, a NGS approach by targeted panel for movement disorders, clinical or whole exome sequencing should be preferred, whenever possible, to a single gene approach, in order to increase diagnostic rate. This review is focused on clinical and genetic features of PMDs with the aim to (1) help clinicians to recognize, diagnose and treat patients with PMDs as well as to (2) provide an overview of genes and molecular mechanisms underlying these intriguing neurogenetic disorders.

Involuntary movements develop after 1-4% of strokes and they have been reported in patients with ischemic and hemorrhagic strokes affecting the basal ganglia, thalamus, and/or their connections. Hemichorea-hemiballism is the most common movement disorder following a stroke in adults while dystonia is most common in children. Tremor, myoclonus, asterixis, stereotypies, and vascular parkinsonism are other movement disorders seen following stroke. Some of them occur immediately after acute stroke, some can develop later, and others may have delayed onset progressive course. Proposed pathophysiological mechanisms include neuronal plasticity, functional diaschisis, and age-related differences in brain metabolism. There are no guidelines regarding the management of post-stroke movement disorders, mainly because of their heterogeneity.

The Next Move in Movement Disorders (NEMO) study is an initiative aimed at advancing our understanding and the classification of hyperkinetic movement disorders, including tremor, myoclonus, dystonia, and myoclonus-dystonia. The study has two main objectives: (a) to develop a computer-aided tool for precise and consistent classification of these movement disorder phenotypes, and (b) to deepen our understanding of brain pathophysiology through advanced neuroimaging techniques. This protocol review details the neuroimaging data acquisition and preprocessing procedures employed by the NEMO team to achieve these goals. To meet the study's objectives, NEMO utilizes multiple imaging techniques, including T1-weighted structural MRI, resting-state fMRI, motor task fMRI, and 18F-FDG PET scans. We will outline our efforts over the past 4 years to enhance the quality of our collected data, and address challenges such as head movements during image acquisition, choosing acquisition parameters and constructing data preprocessing pipelines. This study is the first to employ these neuroimaging modalities in a standardized approach contributing to more uniformity in the analyses of future studies comparing these patient groups. The data collected will contribute to the development of a machine learning-based classification tool and improve our understanding of disorder-specific neurobiological factors. Ethical approval has been obtained from the relevant local ethics committee. The NEMO study is designed to pioneer the application of machine learning of movement disorders. We expect to publish articles in multiple related fields of research and patients will be informed of important results via patient associations and press releases.

Individuals with mutations in forkhead box G1 (FOXG1) belong to a distinct clinical entity, termed “FOXG1-related encephalopathy”. There are two clinical phenotypes/syndromes identified in FOXG1-related encephalopathy, duplications and deletions/intragenic mutations. In children with deletions or intragenic mutations of FOXG1, the recognized clinical features include microcephaly, developmental delay, severe cognitive disabilities, early-onset dyskinesia and hyperkinetic movements, stereotypies, epilepsy, and cerebral malformation. In contrast, children with duplications of FOXG1 are typically normocephalic and have normal brain magnetic resonance imaging. They also have different clinical characteristics in terms of epilepsy, movement disorders, and neurodevelopment compared with children with deletions or intragenic mutations. FOXG1 is a transcriptional factor. It is expressed mainly in the telencephalon and plays a pleiotropic role in the development of the brain. It is a key player in development and territorial specification of the anterior brain. In addition, it maintains the expansion of the neural proliferating pool, and also regulates the pace of neocortical neuronogenic progression. It also facilitates cortical layer and corpus callosum formation. Furthermore, it promotes dendrite elongation and maintains neural plasticity, including dendritic arborization and spine densities in mature neurons. In this review, we summarize the clinical features, molecular genetics, and possible pathogenesis of FOXG1-related syndrome.

IntroductionAutism spectrum disorders encompass a heterogeneous group of neurodevelopmental disorders. Autism may be accompanied by other mental and neurological disorders. Comorbidity in autism is the rule rather than the exception (as reflected in DSM-5).ObjectivesTo study comorbidity in patients with childhood autism and hyperkinetic disorder.MethodsSurveyed 102 patients aged 6–7 years who had infantile psychosis before the age of 3 years (F84.02), comorbid with hyperkinetic disorder (F90.0). Methods: clinical, psychological and psychometric (CARS, PEP, bfcrs, CGI, CPRS-R:S (parents’ form)).ResultsIn the surveyed patients, the autism level was 46 points according to CARS. Manifestations of hyperkinetic disorder in patients with F84.02 are found in 72%, which is associated with the severity of catatonic arousal (BFCRS 36 points). The cognitive development of the examined children is characterized by a combination of advancing, normative and delayed levels of development, depending on the type of cognitive dysontogenesis. Low indicators are revealed in involuntary attention, fine motor skills and hand-eye coordination. In patients with F84.02, a secondary hyperkinetic disorder forms upon exit from severe catatonia.ConclusionsExcessive motor activity is combined with impulsiveness and impaired attention in the period of remission. The use of a complex of clinical and psychodiagnostic techniques aimed at assessing voluntary and involuntary attention provides additional data for the diagnosis of ASD and hyperkinetic disorders.

The risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) may be influenced by environmental factors such as maternal obesity before pregnancy. Previous studies investigating those associations have found divergent results. We aim to investigate in a large birth cohort this association further in children with ADHD, ASD and comorbid ADHD and ASD. Our study population consisted of 81,892 mother–child pairs participating in the Danish National Birth Cohort (DNBC). Information about pre-pregnancy weight and height was collected in week 16 of pregnancy; the analysis was divided into groups based on BMI. Children with a clinical diagnosis of ADHD and/or ASD were identified in the Danish health registries at an average age of 13.3 years. Hazard ratios (HRs) were estimated using time-to-event analysis. Compared to normal weight mothers, the risk of having a child with ADHD was significantly increased if the mother was overweight (HR = 1.28 [95% CI 1.15;1.48]), obese (HR = 1.47 [95% CI 1.26;1.71]) or severely obese (HR = 1.95 [95% CI 1.58;2.40]). The same pattern was seen for the combined ADHD and ASD group. Regarding ASD, an increased risk was observed in underweight (HR = 1.30 [95% CI 1.01;1.69]) and obese (HR = 1.39 [95% CI 1.11;1.75]) mothers. Subgroup analysis revealed that the association in the ADHD group could mostly be attributable to the hyperactive group. Maternal obesity before pregnancy is a risk factor for ADHD in children. Maternal obesity as well as underweight may also be associated with an increased risk for ASD.

Sleep-related hypermotor epilepsy (SHE) is a rare epileptic syndrome characterized by nocturnal seizures that predominantly arise during sleep, featuring complex motor behaviors. Pathogenic variants in the nitrogen permease regulator-like 3 ( ) gene and other regulators of the mTOR pathway have been linked to diverse epilepsy phenotypes, including SHE. SHE is challenging to diagnose due to its diverse presentations, overlap with non-epileptic sleep disorders, and semiological similarities to functional/dissociative seizures (FDS). We present the case of a 61-year-old woman with a lifelong history of nocturnal paroxysmal events and focal epilepsy. She experienced stereotyped nocturnal episodes of focal motor seizures with retained consciousness, characterized by hyperkinetic activity and asymmetric posturing. Despite multiple antiseizure medications (ASMs), only carbamazepine (CBZ) provided long-term seizure freedom. Genetic testing revealed a novel heterozygous mutation in the gene. This case highlights the diagnostic challenges of SHE and the importance of genetic testing in drug-resistant epilepsy. The identified mutation shows the genetic complexity of SHE and its implications for treatment.

Adult Attention-Deficit/Hyperactivity Disorder (ADHD) is prevalent but often overlooked and undertreated. Left untreated, it is linked to increased risk of untoward outcomes including unemployment, relationship breakups, substance use, driving accidents and other mental health conditions. Several brief screening tools have been developed for adult ADHD. The most frequently used is the World Health Organization's Adult ADHD Self-Report Scale (ASRS V1.1). Here, we show in two independent population samples (UK: N = 642, USA: N = 579) that the tool resulted in considerable overestimation of ADHD, indicating probable ADHD in 26.0% and 17.3% of participants, as compared to expected prevalence of 2.5%. The estimated positive predictive value was only ~11.5%. Both samples had normal levels of trait impulsivity as assessed using the Barratt Impulsiveness Scale. The data indicate that using the ASRS in general population samples will result in 7–10 times over-identification of ADHD. We use these results to highlight how such tools should most appropriately be used. When being used to determine possible cases (such as for onward referral to an ADHD specialist) they should be complemented by clinical assessment – we give examples of how non-specialists might determine this. When measuring ADHD symptoms dimensionally, researchers should be mindful that the ASRS captures impulsive symptoms other than those due to ADHD. Lastly, we note the need to screen for impulse control disorders (e.g., gambling disorder) when using such tools to measure ADHD, be it for onward referral, or for dimensional research studies. •ADHD commonly persists into adulthood.•We deployed the most widely used screening tool for adult ADHD in two normative samples•The screening tool considerably over-identified probable ADHD, with low positive predictive value.•Key advice is provided about the appropriate use of such tools, to maximise benefits and minimise harms.

Mutations in the ADCY5 gene can cause a complex hyperkinetic movement disorder. Episodic exacerbations of dyskinesia are a particularly disturbing symptom as they occur predominantly during night and interrupt sleep. We present the clinical short- and long-term effects of pallidal deep brain stimulation (DBS) in three patients with a confirmed pathogenic ADCY5 mutation. Patients were implanted with bilateral pallidal DBS at the age of 34, 20 and 13 years. Medical records were reviewed for clinical history. Pre- and postoperative video files were assessed using the “Abnormal Involuntary Movement Scale” (AIMS) as well as the motor part of the “Burke Fahn Marsden Dystonia Rating Scale” (BFMDRS). All patients reported subjective general improvement ranging from 40 to 60%, especially the reduction of nocturnal episodic dyskinesias (80–90%). Objective scales revealed only a mild decrease of involuntary movements in all and reduced dystonia in one patient. DBS-induced effects were sustained up to 13 years after implantation. We demonstrate that treatment with pallidal DBS was effective in reducing nocturnal dyskinetic exacerbations in patients with ADCY5-related movement disorder, which was sustained over the long term.