Predictive and diagnostic measures for kernicterus spectrum disorder: a prospective cohort study.

BACKGROUND: Kernicterus spectrum disorder (KSD) resulting from neonatal hyperbilirubinemia remains a common cause of cerebral palsy worldwide. This 12-month prospective cohort study followed neonates with hyperbilirubinemia to determine which clinical measures best predict KSD. METHODS: The study enrolled neonates ≥35 weeks gestation with total serum bilirubin (TSB) ≥ 20 mg/dl admitted to Aminu Kano Hospital, Nigeria. Clinical measures included brain MRI, TSB, modified bilirubin-induced neurologic dysfunction (BIND-M), Barry-Albright Dystonia scale (BAD), auditory brainstem response (ABR), and the modified KSD toolkit. MRI signal alteration of the globus pallidus was scored using the Hyperbilirubinemia Imaging Rating Tool (HIRT). RESULTS: Of 25 neonates enrolled, 13/25 completed 12-month follow-up and six developed KSD. Neonatal BIND-M ≥ 3 was 100% sensitive and 83% specific for KSD. Neonatal ABR was 83% specific and sensitive for KSD. Neonatal HIRT score of 2 was 67% sensitive and 75% specific for KSD; this increased to 100% specificity and sensitivity at 12 months. BAD ≥ 2 was 100% specific for KSD at 3-12 months, with 50-100% sensitivity. CONCLUSIONS: Neonatal MRIs do not reliably predict KSD. BIND-M is an excellent screening tool for KSD, while the BAD or HIRT score at 3 or 12 months can confirm KSD, allowing for early diagnosis and intervention. IMPACT: The first prospective study of children with acute bilirubin encephalopathy evaluating brain MRI findings over the first year of life. Neonatal MRI is not a reliable predictor of kernicterus spectrum disorders (KSD). Brain MRI at 3 or 12 months can confirm KSD. The modified BIND scale obtained at admission for neonatal hyperbilirubinemia is a valuable screening tool to assess risk for developing KSD. The Barry Albright Dystonia scale and brain MRI can be used to establish a diagnosis of KSD in at-risk infants as early as 3 months.

Multiple motor disorders in cerebral palsy.

AIM: To characterize motor disorders in children and young people with cerebral palsy (CP). METHOD: This was a cross-sectional study of 582 children and young people with CP (mean age 9 years 7 months; range 11 months-19 years 9 months; standard deviation 4 years 11 months; 340 males) attending a rehabilitation clinic at a specialized children's hospital (May 2018-March 2020). Data on motor disorders, topography, functional classifications, and non-motor features, such as epilepsy, intellectual disability, and sensory impairments, were collected using the Australian Cerebral Palsy Register CP Description Form. RESULTS: Fifty-five per cent (n = 321) of children and young people with CP presented with multiple motor disorders, often affecting the same limb(s). The most common motor disorders were spasticity and dystonia (50%), spasticity only (36%), and dystonia only (6%), but 18 different combinations were identified, including choreoathetosis, ataxia, and generalized hypotonia with increased reflexes. Children with spasticity only had less severe functional deficits (p < 0.001) and lower rates of associated intellectual disability (p < 0.01) and epilepsy (p < 0.001) than those with both spasticity and dystonia. INTERPRETATION: Multiple motor disorders in children and young people with CP are common and associated with more severe functional impairment. Accurate assessment of motor disorders is essential to guide prognosis and ensure personalized evidence-based interventions. WHAT THIS PAPER ADDS: More than half of children and young people with cerebral palsy presented with multiple motor disorders. Dystonia was identified in 60% of study participants. Dystonia was associated with more severe functional impairments and rates of non-motor features.

Os odontoideum and craniovertebral junction instability secondary to dystonia: case series and review of the literature.

INTRODUCTION: Os odontoideum refers to a rounded ossicle detached from a hypoplastic odontoid process at the body of the axis. The aetiology has been debated and believed to be either congenital or acquired (resulting from trauma). Os odontoideum results in incompetence of the transverse ligament and thus predisposes to atlantoaxial instability and spinal cord injury. METHODS/RESULTS: Three cases of children with severe dystonic cerebral palsy presenting with myelopathic deterioration secondary to atlantoaxial instability due to os odontoideum are presented. This observation supports the hypothesis of os odontoideum being an acquired phenomenon, secondary to chronic excessive movement with damage to the developing odontoid process. CONCLUSION: In children with cerebral palsy and dystonia, pre-existing motor deficits may conceal an evolving myelopathy and result in delayed diagnosis of clinically significant atlantoaxial subluxation.

Femur Fractures in 5 Individuals With Pantothenate Kinase-associated Neurodegeneration: The Role of Dystonia and Suggested Management.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, neurodegenerative disorder that manifests with progressive loss of ambulation and refractory dystonia, especially in the early-onset classic form. This leads to osteopenia and stress on long bones, which pose an increased risk of atraumatic femur fractures. The purpose of this study is to describe the unique challenges in managing femur fractures in PKAN and the effect of disease manifestations on surgical outcomes. METHODS: A retrospective case review was conducted on 5 patients (ages 10 to 20 y) with PKAN with a femur fracture requiring surgical intervention. Data regarding initial presentation, surgical treatment, complications, and outcomes were obtained. RESULTS: All patients were non-ambulatory, with 4 of 5 patients sustaining an atraumatic femur fracture in the setting of dystonia episode. One patient had an additional contralateral acetabular fracture. Postoperatively, 4 of the 5 patients sustained orthopaedic complications requiring surgical revision, with 3 of these secondary to dystonia. Overall, 4 required prolonged hospitalization in the setting of refractory dystonia. CONCLUSION: Femur fractures in PKAN present distinct challenges for successful outcomes. A rigid intramedullary rod with proximal and distal interlocking screws is most protective against surgical complications associated with refractory dystonia occurring during the postoperative period. Multidisciplinary planning for postoperative care is essential and may include aggressive sedation and pain management to decrease the risk of subsequent injuries or complications. LEVEL OF EVIDENCE: Level IV.

TMEM151A variants associated with paroxysmal kinesigenic dyskinesia.

TMEM151A, located at 11q13.2 and encoding transmembrane protein 151A, was recently reported as causative for autosomal dominant paroxysmal kinesigenic dyskinesia (PKD). Here, through comprehensive analysis of sporadic and familial cases, we expand the clinical and mutation spectrum of PKD. In doing so, we clarify the clinical and genetic features of Chinese PKD patients harboring TMEM151A variants and further explore the relationship between TMEM151A mutations and PKD. Whole exome sequencing was performed on 26 sporadic PKD patients and nine familial PKD pedigrees without PRRT2 variants. Quantitative real-time PCR was used to assess the gene expression of frameshift mutant TMEM151A in a PKD patient. TMEM151A variants reported to date were reviewed. Four TMEM151A variants were detected in four unrelated families with 12 individuals, including a frameshift mutation [c.606_607insA (p.Val203fs)], two missense mutations [c.166G > A (p.Gly56Arg) and c.791T > C (p.Val264Ala)], and a non-pathogenic variant [c.994G > A (p.Gly332Arg)]. The monoallelic frameshift mutation [c.606_607insA (p.Val203fs)] may cause TMEM151A mRNA decay, suggesting a potential pathogenic mechanism of haploinsufficiency. Patients with TMEM151A variants had short-duration attacks and presented with dystonia. Our study provides a detailed clinical description of PKD patients with TMEM151A mutations and reports a new disease-causing mutation, expanding the known phenotypes caused by TMEM151A mutations and providing further detail about the pathoetiology of PKD.

Development and Validation of the Dystonia-Pain Classification System: A Multicenter Study.

BACKGROUND: Dystonia is associated with disabling nonmotor symptoms like chronic pain (CP), which is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain management. OBJECTIVE: The aim was to develop a CP classification and scoring system for dystonia. METHODS: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia-PCS). The classification of CP as related or unrelated to dystonia was followed by the assessment of pain severity score, encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of different spatial distribution were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to validated pain, mood, QoL, and dystonia scales (Brief Pain Inventory, Douleur Neuropathique-4 questionnaire, European QoL-5 Dimensions-3 Level Version, and Burke-Fahn-Marsden Dystonia Rating Scale). RESULTS: CP was present in 81 of 123 recruited patients, being directly related to dystonia in 82.7%, aggravated by dystonia in 8.8%, and nonrelated to dystonia in 7.5%. Dystonia-PCS had excellent intra-rater (Intraclass Correlation Coefficient - ICC: 0.941) and inter-rater (ICC: 0.867) reliability. In addition, pain severity score correlated with European QoL-5 Dimensions-3 Level Version's pain subscore (r = 0.635, P < 0.001) and the Brief Pain Inventory's severity and interference scores (r = 0.553, P < 0.001 and r = 0.609, P < 0.001, respectively). CONCLUSIONS: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help improve clinical trial design and management of CP in patients affected by this disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Hypertrophic olivary degeneration associated with bilateral vocal cord adductor dystonia.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare condition caused by lesions within the dentato-rubro-olivary pathway, resulting in ocular nystagmus and palatal myoclonus (oculopalatal tremor) but not usually dystonia. Dystonia is an uncommon association, and we present the first reported association of hypertrophic olivary degeneration with bilateral vocal cord dystonia. CASE PRESENTATION: A 33 year old male presented initially with acute hydrocephalus on the background of previous ventriculoperitoneal (VP) shunting for previously treated medulloblastoma. After revision of the VP shunt, the patient developed progressive hiccups and stridor leading to respiratory failure requiring intubation. Ocular pendular nystagmus and palatal myoclonus at 3 Hz was observed. Flexible nasendoscopy (FNE) demonstrated bilateral tonic adduction of the vocal folds with 3 Hz coarse supraglottic, pharyngeal and palatal rhythmic myoclonus. MRI imaging demonstrated T2 hyperintensity within the bilateral inferior olivary nuclei consistent with stage 3 radiological HOD. CONCLUSIONS: Dystonia is a rarely reported phenomenon in HOD but is not unexpected with the inferior olivary nucleus implicated in dystonic disorders. We report the association of HOD with bilateral vocal cord adductor dystonia, a potentially life threatening condition.

Elective and Emergency Deep Brain Stimulation in Refractory Pediatric Monogenetic Movement Disorders Presenting with Dystonia: Current Practice Illustrated by Two Cases.

BACKGROUND: Dystonia is characterized by sustained or intermittent muscle contractions, leading to abnormal posturing and twisting movements. In pediatric patients, dystonia often negatively influences quality of life. Pharmacological treatment for dystonia is often inadequate and causes adverse effects. Deep brain stimulation (DBS) appears to be a valid therapeutic option for pharmacoresistant dystonia in children. METHODS: To illustrate the current clinical practice, we hereby describe two pediatric cases of monogenetic movement disorders presenting with dystonia and treated with DBS. We provide a literature review of similar previously described cases and on different clinical aspects of DBS in pediatric dystonia. RESULTS: The first patient, a 6-year-old girl with severe dystonia, chorea, and myoclonus due to an ADCY5 gene mutation, received DBS in an elective setting. The second patient, an 8-year-old boy with GNAO1-related dystonia and chorea, underwent emergency DBS due to a pharmacoresistant status dystonicus. A significant amelioration of motor symptoms (65% on the Burke-Fahn-Marsden Dystonia Rating Scale) was observed postoperatively in the first patient and her personal therapeutic goals were achieved. DBS was previously reported in five patients with ADCY5-related movement disorders, of which three showed objective improvement. Emergency DBS in our second patient resulted in the successful termination of his GNAO1-related status dystonicus, this being the eighth case reported in the literature. CONCLUSION: DBS can be effective in monogenetic pediatric dystonia and should be considered early in the disease course. To better evaluate the effects of DBS on patients' functioning, patient-centered therapeutic goals should be discussed in a multidisciplinary approach.

Spastic dystonia: Still a valid term.

Hypertonia in childhood may arise because of a variable combination of neuronal and non-neuronal factors. Involuntary muscle contraction may be due to spasticity or dystonia, which represent disorders of the spinal reflex arch and of central motor output respectively. Whilst consensus definitions for dystonia have been established, definitions of spasticity vary, highlighting the lack of a single unifying nomenclature in the field of clinical movement science. The term spastic dystonia refers to involuntary tonic muscle contraction in the context of an upper motor neuron (UMN) lesion. This review considers the utility of the term spastic dystonia, exploring our understanding of the pathophysiology of dystonia and the UMN syndrome. An argument is advanced that spastic dystonia is a valid construct that warrants further exploration. WHAT THIS PAPER ADDS: There is no single universally accepted definitions for terms commonly used to describe motor disorders. Spasticity and dystonia are phenomenologically and pathophysiologically distinct entities. Spastic dystonia represents a subset of dystonia, but with pathophysiological mechanisms more in common with spasticity.

Perampanel as a novel treatment for subcortical myoclonus in myoclonus-dystonia syndrome.

BACKGROUND: Myoclonus-dystonia (MD) is a syndrome characterized by subcortical myoclonus and milder dystonia. The main causative gene is the epsilon sarcoglycan gene (SGCE), but other genes may be involved. Response to medications is variable, with poor tolerability limiting their use. CASE PRESENTATION: We present the case of a patient with severe myoclonic jerks and mild dystonia since childhood. At first neurological visit at the age of 46 years old, she presented brief myoclonic jerks predominating in the upper limbs and neck, mild at rest and elicited by action, posture and tactile stimulus. Myoclonus was accompanied by mild neck and right arm dystonia. Neurophysiological tests suggested subcortical origin of myoclonus, brain MRI was unremarkable. Myoclonus-dystonia was diagnosed, and genetic testing identified a novel mutation in SGCE gene (c.907delC) in heterozygosis. Over time she assumed a large variety of anti-epileptics without beneficial effect on myoclonus and low tolerability. Add-on treatment with Perampanel was started, with a beneficial effect. No adverse events were reported. Perampanel is the first selective non-competitive AMPA receptor antagonist approved in add-on for focal and generalized tonic-clonic seizures. To our knowledge, this is the first trial of Perampanel in MD. CONCLUSIONS: We presented the case of a patient with MD due to SGCE mutation who was treated with Perampanel with beneficial effects. We propose Perampanel as a novel treatment for myoclonus in MD.

Spasticity and movement disorders in cerebral palsy.

PURPOSE: To review the neurosurgical treatments of children with movement disorders associated with cerebral palsy (CP) during the previous decades, up to the present day. METHODS: An extensive literature review was undertaken to identify important publications about this subject. My experience treating children with these disorders over the past three decades was included in the individual sections. RESULTS: Peripheral neurotomies have been developed for children with focal spasticity. For those with spastic paraparesis, selective lumbar rhizotomies were developed, and for those with spastic quadriparesis, intrathecal baclofen infusions were developed. Both effectively alleviate spasticity in the affected extremities. Generalized dystonia associated with CP has been treated with deep brain stimulation with mild improvement, but treatment with intrathecal baclofen and intraventricular baclofen improve those movements markedly. No effective treatment has been reported for children with athetoid CP. For those with choreiform CP, deep brain stimulation may be effective but intrathecal baclofen does not appear to be. CONCLUSION: Treatment of children with movement disorders associated with CP increased slowly in the 1970s and 1980s but accelerated rapidly in the 1990s with the introduction of lumbar dorsal rhizotomies and intrathecal baclofen. In the last 30 years, tens of thousands of children with spasticity and movement disorders associated with CP have been treated by pediatric neurosurgeons, and their care has become an integral component of current pediatric neurosurgical practice.

Debunking the Puzzle of Eyelid Apraxia: The Muscle of Riolan Hypothesis.

PURPOSE: Apraxia of eyelid opening (AEO) has been defined by the presence of an intermittent nonparalytic bilateral loss of the volitional ability to open the eyes or to maintain the eyelids in a sustained elevated position. It is not known whether the condition represents an apraxia, a dystonia, or a freezing phenomenon, and several different nomenclatorial terms have been suggested for this condition including the so-called AEO (scAEO), blepahrocolysis, focal eyelid dystonia, and so on. The primary goal of this review is to attempt to clarify the pathogenetic mechanisms underlying scAEO as a clinical phenomenon. This review also addresses the issue of whether scAEO is part of the spectrum of blepharospasm (BSP) which includes BSP, dystonic blinks and other dystonic eyelid conditions, or whether it is a separate phenomenologically heterogeneous disease with clinical features that merely overlap with BSP. METHODS: A literature review was conducted in PubMed, MEDLINE, PubMed Central (PMC), NCBI Bookshelf, and Embase for several related keywords including the terms "apraxia of eyelid opening," "pretarsal blepharospasm," "blepharocolysis," "eyelid freezing," "eyelid akinesia," "levator inhibition," "blepharospasm-plus," as well as "blepharospasm." The clinical findings in patients with scAEO who fulfilled the classic diagnostic criteria of the disease that were originally set by Lepore and Duvoisin were included, while patients with isolated blepharospasm or dystonic blinks (DB) were excluded. In addition, electromyographic (EMG) studies in patients with scAEO were reviewed in detail with special emphasis on studies that performed synchronous EMG recordings both from the levator muscle (LPS) and the pretarsal orbicularis oculi muscle (OO). RESULTS: The apraxia designation is clearly a misnomer. Although scAEO behaves clinically as a hypotonic freezing phenomenon, it also shares several cardinal features with focal dystonias. The authors broadly categorized the EMG data into 3 different patterns. The first pattern (n = 26/94 [27.6%]) was predominantly associated with involuntary discharges in the OO muscle and has been termed pretarsal blepharospasm (ptBSP). The commonest pattern was pattern no. 2 (n = 53/94 [56.38%]), which was characterized by involuntary discharges in the OO muscle, together with a disturbed reciprocal innervation of the antagonist levator muscle and is dubbed disturbed reciprocal innervation (DRI). This EMG pattern is difficult to discern from the first pattern. Pattern no. 3 (n = 15/94 [15.9%]) is characterized by an isolated levator palpebrae inhibition (ILPI). This levator silence was observed alone without EMG evidence of contractions in the pretarsal orbicularis or a disturbed reciprocal relation of both muscles. CONCLUSION: EMG evidence shows that the great majority (84%) of patients show a dystonic pattern, whereas ILPI (16%) does not fit the dystonic spectrum. The authors propose that a spasmodic contraction of the muscle of Riolan may be the etiological basis for levator inhibition in patients with ILPI. If this is true, all the 3 EMG patterns observed in scAEO patients (ptBSP, DRI, and ILPI) would represent an atypical form of BSP. The authors suggest coining the terms Riolan muscle BSP ( rmBSP ) for ILPI, and the term atypical focal eyelid dystonia ( AFED ) instead of the term scAEO, as both terms holistically encompass both the clinical and EMG data and concur with the authors' theorem.

Hyperkinetic movement disorders following SARS-CoV-2 infection and vaccination - an update.

The aim of this review was to summarise current knowledge regarding hyperkinetic movement disorders related to SARS-CoV-2 infection and vaccination in terms of phenomenology, epidemiology, pathogenesis and treatment. After a thorough review of the PubMed and Google Scholar databases (2020-2022), we identified myoclonus and ataxia sometimes accompanied by opsoclonus (AMS) as the two most frequent COVID-19 sequelae, with chorea, tremor and dystonia being very rare. The pathogenesis seems to be variable, but in the majority of AMS cases it was autoimmunological, with good response and recovery after corticosteroids or intravenous immunoglobulins infusions. Vaccination may be complicated by hyperkinetic movement disorders (e.g. tremor, dystonia), but this is very rare. Patients with Deep Brain Simulation depletion should not be postponed due to lockdowns as this may result in fatal outcomes.

[Methods and results of neurosurgical treatment of cerebral palsy]. / Metody i rezul'taty neirokhirurgicheskogo lecheniya detskogo tserebral'nogo paralicha.

Treatment of spastic syndrome and muscular dystonia in patients with cerebral palsy is a complex clinical problem. Effectiveness of conservative treatment is not high enough. Modern neurosurgical techniques for spastic syndrome and dystonia are divided into destructive interventions and surgical neuromodulation. Their effectiveness is different and depends on the form of disease, severity of motor disorders and age of patients. OBJECTIVE: To evaluate the effectiveness of various methods of neurosurgical treatment of spasticity and muscular dystonia in patients with cerebral palsy. MATERIAL AND METHODS: We To evaluate the effectiveness of various methods of neurosurgical treatment of spasticity and muscular dystonia in patients with cerebral palsy.analyzed literature data in the PubMed database using the keywords «cerebral palsy¼, «spasticity¼, «dystonia¼, «selective dorsal rhizotomy¼, «selective neurotomy¼, «intrathecal baclofen therapy¼, «spinal cord stimulation¼, «deep brain stimulation¼. RESULTS: Effectiveness of neurosurgery was higher for spastic forms of cerebral palsy compared to secondary muscular dystonia. Destructive procedures were the most effective among neurosurgical operations for spastic forms. Effectiveness of chronic intrathecal baclofen therapy decreases in follow-up due to secondary drug resistance. Destructive stereotaxic interventions and deep brain stimulation are used for secondary muscular dystonia. Effectiveness of these procedures is low. CONCLUSION: Neurosurgical methods can partially reduce severity of motor disorders and expand the possibilities of rehabilitation in patients with cerebral palsy.

Early onset disease, anarthria, areflexia, and dystonia can be the distinctive features of SPG64, a very rare form of hereditary spastic paraplegias.

Hereditary spastic paraplegias (HSP) are a group of inherited, neurodegenerative disorders characterized by progressive gait impairment, lower extremity spasticity and increased patellar reflexes. More than 80 types of HSP have been defined to date. In complicated forms, lower limb spasticity and gait impairment is accompanied by an additional neurological finding. Autosomal recessive (AR) HSPs are usually identified in complicated forms and occur more frequently in countries where consanguineous marriage is more widespread. Next generation sequencing techniques, developed in the last decade, have led to the identification of many new types of HSP and reduced the "diagnostic odyssey." Whole exome sequencing (WES) can diagnose up to 75% of undiagnosed HSP patients. Targeted genetic analysis with good clinical phenotyping gives the best diagnostic yields for rare diseases. Clinical heterogeneity is prominent in AR complicated HSP. However, some clinical features complicating the disease or magnetic resonance imaging findings, including thin corpus callosum or white matter abnormalities, can help to distinguish some types. AR spastic paraplegia type 64 (SPG64) is a very rare HSP, caused by a mutation in the ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) gene, first described in 2014. To date only nine patients from five families have been reported. We present two siblings with a novel pathogenic variant in ENTPD1, diagnosed by WES, as the sixth published family. We propose that early onset in childhood, cognitive impairment, dysarthria/anarthria, dystonia and areflexia may be the distinctive features of SPG64 and more clinical evidence from families with pathogenic ENTPD1 variants is warranted.

COVID-19-related delays of botulinum toxin injections have a negative impact on the quality of life of patients with dystonia and spasticity: a single-center ambulatory care study.

BACKGROUND: Botulinum toxin A (BoNT-A) is considered a safe and effective treatment for spasticity and dystonia. Individual interinjection intervals are critical for the maintenance of the effect. In Austria, BoNT outpatient clinics were shutdown from November to December 2020 during COVID-19 control measures, leading to rescheduling of BoNT-A injections. This survey aimed at investigating the influence of injection delays on symptoms, physical functioning, and quality of life (QoL) of the affected patients. METHODS: Between April and July 2021, 32 outpatients (21 females, mean age: 63.4 ± 12.1 years) treated ≥ 12 months at the BoNT outpatient clinic Horn-Allentsteig (Austria) and experienced ≥ 2 week injection delays, completed a structured face-to-face questionnaire. RESULTS: Indications were dystonia (34%), spasticity (63%), and hyperhidrosis (3%). Injections were delayed by 10 weeks (median, range: 2-15). Muscle cramps increased in 95% of patients with spasticity, muscle twitches in 91% of those with dystonia, and pain in 9% and 60% for dystonia and spasticity, respectively. Overall, 75% reported functional worsening, and deterioration in QoL by 62.6% ± 16.8 (mean ± SD). The impact on QoL correlated with the subjective global improvement induced by BoNT-A (Rs: 0.625; p < 0.001). For 75%, long-term assurance of BoNT-A therapy was very important, and 81% felt their patient rights not respected. CONCLUSIONS: COVID-19-related delays in BoNT-A injections illustrate the importance of this therapy for symptom relief, functional outcome, and QoL in patients suffering from involuntary muscle hyperactivity. BoNT-A therapy is essential and has to be guaranteed even in circumstances such as the COVID-19 pandemic.

The Italian tremor Network (TITAN): rationale, design and preliminary findings.

INTRODUCTION: The recently released classification has revised the nosology of tremor, defining essential tremor (ET) as a syndrome and fueling an enlightened debate about some newly conceptualized entities such as ET-plus. As a result, precise information of demographics, clinical features, and about the natural history of these conditions are lacking. METHODS: The ITAlian tremor Network (TITAN) is a multicenter data collection platform, the aim of which is to prospectively assess, according to a standardized protocol, the phenomenology and natural history of tremor syndromes. RESULTS: In the first year of activity, 679 patients have been recruited. The frequency of tremor syndromes varied from 32% of ET and 41% of ET-plus to less than 3% of rare forms, including focal tremors (2.30%), task-specific tremors (1.38%), isolated rest tremor (0.61%), and orthostatic tremor (0.61%). Patients with ET-plus were older and had a higher age at onset than ET, but a shorter disease duration, which might suggest that ET-plus is not a disease stage of ET. Familial aggregation of tremor and movement disorders was present in up to 60% of ET cases and in about 40% of patients with tremor combined with dystonia. The body site of tremor onset was different between tremor syndromes, with head tremor being most commonly, but not uniquely, associated with dystonia. CONCLUSIONS: The TITAN study is anticipated to provide clinically relevant prospective information about the clinical correlates of different tremor syndromes and their specific outcomes and might serve as a basis for future etiological, pathophysiological, and therapeutic research.

Fatigue is related to depression in idiopathic dystonia.

INTRODUCTION: Dystonia is a movement disorder presented with involuntary muscle contraction causing abnormal posture, movement, or both. Besides motor symptoms, patients may also report non-motor symptoms such as pain, anxiety, apathy, depression, sleep problems, fatigue, and cognitive impairment. The etiology of fatigue in patients with dystonia is not yet well understood. AIM: To evaluate the presence of fatigue, depression, anxiety, sleep disorders, and daily sleepiness in patients with focal and segmental dystonia and to determine which of these non-motor symptoms influence the occurrence and severity of fatigue. PATIENTS AND METHODS: Patients were surveyed for symptoms of fatigue, depression, anxiety, night-time sleep problems, and daily sleepiness using the Fatigue Assessment Scale, Beck Depression Inventory II, Beck Anxiety Inventory, Pittsburgh Sleep Questionnaire Index, and Epworth Sleepiness Scale. Demographic data (sex, age, and disease duration) were collected from patient medical records. On statistical analysis, we used SPSS for Windows 10. The level of significance was set at p<0.05. RESULTS: Sixty patients (43 female and 17 male) with focal or segmental dystonia were evaluated. Fatigue was reported by 67.2% of patients. Fatigue (general, physical, and mental fatigue) was found to correlate with depression, anxiety, and sleep problems. Daily sleepiness correlated only with mental fatigue. Disease duration, age, and gender did not influence the symptoms of fatigue. Multiple regression analysis showed that depression mostly predicted symptoms of general, physical, and mental fatigue. CONCLUSION: Depression mostly predicted symptoms of general, physical, and mental fatigue in patients with focal and segmental dystonia.

The Signature of Primary Writing Tremor Is Dystonic.

BACKGROUND: It has been debated for decades whether primary writing tremor is a form of dystonic tremor, a variant of essential tremor, or a separate entity. We wished to test the hypothesis that primary writing tremor and dystonia share a common pathophysiology. OBJECTIVES: The objective of the present study was to investigate the pathophysiological hallmarks of dystonia in patients affected by primary writing tremor. METHODS: Ten patients with idiopathic dystonic tremor syndrome, 7 with primary writing tremor, 10 with essential tremor, and 10 healthy subjects were recruited. They underwent eyeblink classic conditioning, blink recovery cycle, and transcranial magnetic stimulation assessment, including motor-evoked potentials and short- and long-interval intracortical inhibition at baseline. Transcranial magnetic stimulation measures were also recorded after paired-associative plasticity protocol. RESULTS: Primary writing tremor and dystonic tremor syndrome had a similar pattern of electrophysiological abnormalities, consisting of reduced eyeblink classic conditioning learning, reduced blink recovery cycle inhibition, and a lack of effect of paired-associative plasticity on long-interval intracortical inhibition. The latter 2 differ from those obtained in essential tremor and healthy subjects. Although not significant, slightly reduced short-interval intracortical inhibition and a larger effect of paired-associative plasticity in primary writing tremor and dystonic tremor syndrome, compared with essential tremor and healthy subjects, was observed. CONCLUSIONS: Our initial hypothesis of a common pathophysiology between dystonia and primary writing tremor has been confirmed. Primary writing tremor might be considered a form of dystonic tremor. © 2021 International Parkinson and Movement Disorder Society.

Leber hereditary optic neuropathy and dystonia overlapping mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes due to m.14459G>A mutation.

OBJECTIVE: To report a Chinese family with combined m.14459G>A mutation and m.6064A>T mutation of which the female proband presenting unique Leber hereditary optic neuropathy and dystonia (LDYT) overlapping mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) phenotype. METHODS: Clinical information of the pedigree was collected. We performed muscle biopsy and whole-length mitochondrial DNA (mtDNA) sequencing on the proband. The activity of respiratory chain complexes in immortalized lymphoblasts was determined. RESULTS: The current 23-year-old proband suffered from vision decline at age 15 and developed seizures and dystonia with bilateral lesions in precentral gyri at age 18. When she was 21, the lesions in bilateral putamen were found with elevated cerebrospinal fluid lactate. Her mother had optic atrophy; one of her brother died at age 4 with respiratory distress; and the other 8-year-old brother was asymptomatic. Muscle biopsy of the proband was unremarkable. The mtDNA sequencing revealed a heteroplasmic m.14459G>A mutation and a previously unreported m.6064A>T mutation. The respiratory chain complex I activity in the proband's immortalized lymphoblasts was 50% less than the normal control; while there was no statistical difference between the proband and the normal control in the activity of complex IV. CONCLUSIONS: We presented the first case exhibiting LDYT and MELAS phenotype with m.14459G>A mutation, and the decreased complex I activity contributed to the pathogenicity. Our study expanded the clinical spectrum of m.14459G>A mutation.