Highlighting the Dystonic Phenotype Related to GNAO1.

BACKGROUND: Most reported patients carrying GNAO1 mutations showed a severe phenotype characterized by early-onset epileptic encephalopathy and/or chorea. OBJECTIVE: The aim was to characterize the clinical and genetic features of patients with mild GNAO1-related phenotype with prominent movement disorders. METHODS: We included patients diagnosed with GNAO1-related movement disorders of delayed onset (>2 years). Patients experiencing either severe or profound intellectual disability or early-onset epileptic encephalopathy were excluded. RESULTS: Twenty-four patients and 1 asymptomatic subject were included. All patients showed dystonia as prominent movement disorder. Dystonia was focal in 1, segmental in 6, multifocal in 4, and generalized in 13. Six patients showed adolescence or adulthood-onset dystonia. Seven patients presented with parkinsonism and 3 with myoclonus. Dysarthria was observed in 19 patients. Mild and moderate ID were present in 10 and 2 patients, respectively. CONCLUSION: We highlighted a mild GNAO1-related phenotype, including adolescent-onset dystonia, broadening the clinical spectrum of this condition. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Autistic spectrum disorder, epilepsy, and vagus nerve stimulation.

PURPOSE: In individuals with a comorbid autistic spectrum disorder and medically refractory epilepsy, vagus nerve stimulation may offer the potential of seizure control and a positive behavioral side effect profile. We aimed to examine the behavioral side effect profile using longitudinal and quantitative data and review the potential mechanisms behind behavioral changes. METHODS: We present a case report of a 10-year-old boy with autistic spectrum disorder and epilepsy, who underwent vagus nerve stimulation subsequent to unsuccessful treatment with antiepileptic medication. RESULTS: Following vagus nerve stimulation implantation, initial, if temporary, improvement was observed in seizure control. Modest improvements were also observed in behavior and development, improvements which were observed independent of seizure control. CONCLUSIONS: Vagus nerve stimulation in autistic spectrum disorder is associated with modest behavioral improvement, with unidentified etiology, although several candidates for this improvement are evident.

Botulinum Neurotoxin Injections in Children with Self-Injurious Behaviors.

Self-injurious behaviors are repetitive, persistent actions directed toward one's body that threaten or cause physical harm. These behaviors are seen within a broad spectrum of neurodevelopmental and neuropsychiatric conditions, often associated with intellectual disability. Injuries can be severe and distressing to patients and caregivers. Furthermore, injuries can be life-threatening. Often, these behaviors are challenging to treat and require a tiered, multimodal approach which may include mechanical/physical restraints, behavioral therapy, pharmacotherapy, or in some cases, surgical management, such as tooth extraction or deep brain stimulation. Here, we describe a series of 17 children who presented to our institution with self-injurious behaviors in whom botulinum neurotoxin injections were found helpful in preventing or lessening self-injury.

Function and dysfunction of the dystonia network: an exploration of neural circuits that underlie the acquired and isolated dystonias.

Dystonia is a highly prevalent movement disorder that can manifest at any time across the lifespan. An increasing number of investigations have tied this disorder to dysfunction of a broad "dystonia network" encompassing the cerebellum, thalamus, basal ganglia, and cortex. However, pinpointing how dysfunction of the various anatomic components of the network produces the wide variety of dystonia presentations across etiologies remains a difficult problem. In this review, a discussion of functional network findings in non-mendelian etiologies of dystonia is undertaken. Initially acquired etiologies of dystonia and how lesion location leads to alterations in network function are explored, first through an examination of cerebral palsy, in which early brain injury may lead to dystonic/dyskinetic forms of the movement disorder. The discussion of acquired etiologies then continues with an evaluation of the literature covering dystonia resulting from focal lesions followed by the isolated focal dystonias, both idiopathic and task dependent. Next, how the dystonia network responds to therapeutic interventions, from the "geste antagoniste" or "sensory trick" to botulinum toxin and deep brain stimulation, is covered with an eye towards finding similarities in network responses with effective treatment. Finally, an examination of how focal network disruptions in mouse models has informed our understanding of the circuits involved in dystonia is provided. Together, this article aims to offer a synthesis of the literature examining dystonia from the perspective of brain networks and it provides grounding for the perspective of dystonia as disorder of network function.

Tics and TikTok: Functional Tics Spread Through Social Media.

BACKGROUND: Functional movement disorder is a subtype of functional neurologic symptom disorder a syndrome of involuntary physical, neurologic-type symptoms that are incongruous with "organic" disease. Throughout history, there have been outbreaks of functional symptoms in communities; until recently, spread had been confined to groups of people who shared a physical location. However, in the era of social media, a new mode of dissemination may have arisen. CASES: We describe six teenage girls, each with the explosive onset of tic-like movements. Mean age of onset was 14.2 years. The presence of features incongruous with Tourette syndrome on history and examination prompted the diagnosis of functional tics. All patients reported exposure to a specific social media personality before symptom onset. CONCLUSIONS: Our series suggests that social media may contribute to the spread of functional neurologic symptom disorder, in a way previously requiring physical proximity.

Botulinum Neurotoxin Injections in Childhood Opisthotonus.

Opisthotonus refers to abnormal axial extension and arching of the trunk produced by excessive contractions of the paraspinal muscles. In childhood, the abnormal posture is most often related to dystonia in the setting of hypoxic injury or a number of other acquired and genetic etiologies. The condition is often painful, interferes with ambulation and quality of life, and is challenging to treat. Therapeutic options include oral benzodiazepines, oral and intrathecal baclofen, botulinum neurotoxin injections, and deep brain stimulation. Management of opisthotonus within the pediatric population has not been systematically reviewed. Here, we describe a series of seven children who presented to our institution with opisthotonus in whom symptom relief was achieved following administration of botulinum neurotoxin injections.

A case of treatable encephalopathy, developmental regression, and proximal tremor.

Tyrosine hydroxylase (TH) deficiency is an autosomal recessive condition first described as a progressive, early-onset hypokinetic-rigid and dystonic syndrome that was responsive to levodopa. Here we present a child with developmental regression, proximal tremor, and encephalopathy found to have tyrosine hydroxylase deficiency in whom treatment resulted in acquisition of developmental milestones.

Increased Incidence of Functional (Psychogenic) Movement Disorders in Children and Adults Amid the COVID-19 Pandemic: A Cross-sectional Study.

BACKGROUND AND OBJECTIVES: Functional (psychogenic) movement disorders (FMDs) are conditions in which affected patients develop abnormal movements that are incongruous with known, organic, movement disorders, often associated with psychological stressors. METHODS: In this case series, electronic medical records of all patients who presented to our adult and pediatric tertiary care movement disorders clinics between March 1 and October 30, 2020, and during the same period in 2019 were reviewed. All patients diagnosed with functional (psychogenic) movement disorder were included if they satisfied diagnostic criteria. RESULTS: Among 550 new patients referred for evaluation at our tertiary care movement disorders centers, 45 (8.2%) received a diagnosis of FMD; 75.6% were female, in comparison to the prior year during which time 665 new patients were evaluated and 5.1% were diagnosed with FMD. This represents a 60.1% increase (90.1% in pediatric cohort, 50.9% in adult cohort) in new patients diagnosed with FMD during the COVID-19 pandemic. CONCLUSIONS: Within our patient population, there has been increased incidence of FMDs in the setting of the COVID-19 pandemic, possibly reflecting increased psychological and other stressors during this period.

Effective Treatment of Geniospasm: Case Series and Review of the Literature.

Background: Geniospasm is a rare genetic disorder characterized by paroxysmal rhythmic or irregular movements of the chin and lower lip due to repetitive contractions of the mentalis muscle. Pathophysiology is poorly understood, and optimal treatment has not been established. Methods: Geniospasm was characterized in a series of patients after evaluation in our clinics, and a comprehensive review of all cases in the medical literature was performed. Results: We evaluated four patients (1 female) in four families with geniospasm, aged 4 months to 9 years. Bothersome symptoms were present in one patient, who was treated with regular injections of onabotulinumtoxinA, with complete resolution of symptoms and no adverse effects. 9 patients in the literature have had similar outcomes. Conclusions: Limited data exist with regard to the effective treatment of geniospasm. Several treatments have been used historically, with variable outcomes. Our results, together with those of prior reported cases, demonstrate benefit of the use of botulinum toxin injections for management of this condition.