Onset Of Dystonia Research Articles

A Rare Case of Asymmetric Progressive Supra Nuclear Palsy Diagnosed In vivo with Magnetic Resonance/Positron Emission Tomography.

PSP and CBD are usually multi system sporadic disorders characterized by tau inclusions in neurons and glia. The clinical and neuroimaging features are different .However in some cases overlapping of features are noted. Here we present a case of a 65 years old female patient, presenting a 3 years history of insidious onset of asymmetric right upper and lower limb dystonia, followed by slowness, falls and injuries to the back, Parkinsonism, urinary incontinence and cognitive dysfunction and upward gaze palsy. MRI findings were suggestive of moderate cerebral and cerebellar atrophy with prominent ventricular system, reduced antero-posterior midline midbrain diameter, at the level of superior colliculus on axial imaging (morning glory sign was positive) on the left side. PET showed asymmetric hypo metabolism noted in the left superior and middle frontal gyrus, superior temporal and mid temporal gyrus in addition to striatum and thalamus, as well as midbrain, pons and right cerebellar hemisphere. Overall MR/PET was suggestive of unilateral PSP (left) and it corroborated with clinical history of unilateral dystonia and supranuclear gaze palsy. Based on MRI the differential considered was also CBD, but PET showed metabolic activity in the motor cortex. Additionally based on the hummingbird sign and morning glory sign a rare diagnosis of unilateral PSP could be made which also corroborated with the clinical picture.The case report emphasizes the utility of PETMRI simultaneously in situations like these to pick atypical variants or cases with overlapping pathology to reach a diagnosis with in vivo imaging methods.

Novel SERAC1 Variant Presenting With Adult-Onset Extrapyramidal Dystonia-Parkinsonism Phenotype: A Case Report.

To report a novel likely pathogenic variant in the SERAC1 gene associated with early adult-onset parkinsonism and progressive dystonia. Clinical, biochemical, and imaging assessments were performed on 2 affected adult brothers with a genetically unsolved progressive neurologic disorder followed by whole-genome sequencing. A homozygous likely pathogenic variant in the SERAC1 gene (c.[129-2A > C], p.[(?)];[(?)]) was discovered. We describe a novel homozygous variant in the serine active site-containing protein 1 gene (SERAC1) in 2 brothers with a progressive extrapyramidal movement disorder of early onset parkinsonism and dystonia. Previous variants have been associated with a severe 3-methylglutaconic aciduria with dystonia, deafness, hepatopathy, encephalopathy and Leigh-like syndrome, or juvenile onset complicated spastic paraparesis. Our cases expand the phenotype of SERAC1 variants, with an adult-onset presentation of dystonia-parkinsonism.

Altered brain state during episodic dystonia in tottering mice decouples primary motor cortex from limb kinematics.

Episodic Ataxia Type 2 (EA2) is a rare neurological disorder caused by a mutation in the CACNA1A gene, encoding the P/Q-type voltage-gated Ca2+ channel important for neurotransmitter release. Patients with this channelopathy exhibit both cerebellar and cerebral pathologies, suggesting the condition affects both regions. The tottering (tg/tg) mouse is the most commonly used EA2 model due to an orthologous mutation in the cacna1a gene. The tg/tg mouse has three prominent behavioral phenotypes: a dramatic episodic dystonia; absence seizures with generalized spike and wave discharges (GSWDs); and mild ataxia. We previously observed a novel brain state, transient low-frequency oscillations (LFOs) in the cerebellum and cerebral cortex under anesthesia. In this study, we examine the relationships among the dystonic attack, GSWDs, and LFOs in the cerebral cortex. Previous studies characterized LFOs in the motor cortex of anesthetized tg/tg mice using flavoprotein autofluorescence imaging testing the hypothesis that LFOs provide a mechanism for the paroxysmal dystonia. We sought to obtain a more direct understanding of motor cortex (M1) activity during the dystonic episodes. Using two-photon Ca2+ imaging to investigate neuronal activity in M1 before, during, and after the dystonic attack, we show that there is not a significant change in the activity of M1 neurons from baseline through the attack. We also conducted simultaneous, multi-electrode recordings to further understand how M1 cellular activity and local field potentials change throughout the progression of the dystonic attack. Neither putative pyramidal nor inhibitory interneuron firing rate changed during the dystonic attack. However, we did observe a near complete loss of GSWDs during the dystonic attack in M1. Finally, using spike triggered averaging to align simultaneously recorded limb kinematics to the peak Ca2+ response, and vice versa, revealed a reduction in the spike triggered average during the dystonic episodes. Both the loss of GSWDs and the reduction in the coupling suggest that, during the dystonic attack, M1 is effectively decoupled from other structures. Overall, these results indicate that the attack is not initiated or controlled in M1, but elsewhere in the motor circuitry. The findings also highlight that LFOs, GSWDs, and dystonic attacks represent three brain states in tg/tg mice.

Transient dystonia correlates with parkinsonism after 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine in nonhuman primates.

Unilateral internal carotid artery 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion in non-human primates produces transient contralateral hemi-dystonia followed by stable contralateral hemi-parkinsonism; the relationship between dystonia and parkinsonism remains unclear. We hypothesized that transient dystonia severity following MPTP correlates with parkinsonism severity. In male Macaca nemestrina (n = 3) and M. fascicularis (n = 17) we administered unilateral intra-carotid MPTP, then correlated validated blinded ratings of transient peak dystonia and delayed parkinsonism. We also correlated dystonia severity with post-mortem measures of residual striatal dopamine and nigral neuron counts obtained a mean 53 ± 15 days following MPTP, after resolution of dystonia but during stable parkinsonism. Median latency to dystonia onset was 1 day, and peak severity 2.5 days after MPTP; total dystonia duration was 13.5 days. Parkinsonism peaked a median of 19.5 days after MPTP, remaining nearly constant thereafter. Peak dystonia severity highly correlated with parkinsonism severity (r[18] = 0.82, p < 0.001). Residual cell counts in lesioned nigra correlated linearly with peak dystonia scores (r[18] = -0.68, p=<0.001). Dystonia was not observed in monkeys without striatal dopamine depletion (n = 2); dystonia severity correlated with striatal dopamine depletion when residual nigral cell loss was less than 50% ([11] r = -0.83, p < 0.001) but spanned a broad range with near complete striatal dopamine depletion, when nigral cell loss was greater than 50%. Our data indicate that residual striatal dopamine may not reflect dystonia severity. We speculate on mechanisms of transient dystonia followed by parkinsonism that may be studied using this particular NHP MPTP model to better understand relationships of transient dystonia to nigrostriatal injury and parkinsonism.

Early Onset Dystonia: Complaints about Executive Functioning, Depression and Anxiety.

Early Onset Dystonia (EOD) is thought to result from basal ganglia dysfunction, structures also involved in non-motor functions, like regulation of behavior, mood and anxiety. Problems in these domains have been found in proxy-reports but not yet in self-reports of EOD patients. The main questions are whether proxy-reports differ from those of patients and how problems relate to everyday social functioning. Subjective complaints about executive problems (BRIEF) and symptoms of depression and anxiety (CBCL) were obtained through a cross-sectional questionnaire study conducted on 45 EOD patients. Scores were in the normal range in patients and proxies. Proxy-rated behavior regulation was correlated with the estimated number of friends and quality of relations. Proxy-reported scores of depression correlated with the quality of relations and were higher than self-reports of adolescent/young adult patients. EOD patients and proxies do not seem to experience problematic regulation of behavior, mood and anxiety. Still, our study revealed two important aspects: (1) all measures were related to the estimated quality of relations with others, relating questionnaires to everyday social functioning; (2) proxies reported more symptoms of depression than patients. This may indicate overestimation by proxies or higher sensitivity of proxies to these symptoms, implying underestimation of problems by patients.

RARE CASE REPORT -AUTOIMMUNE LGI1 LIMBIC ENCEPHALITIS IN ELDERLY

Autoimmune encephalitis is one of the main causes of noninfectious encephalitis. Can be broadly classied into non-paraneoplastic, paraneoplastic and vasculitis associated encephalopathy. It can be triggered by tumors and infections. Autoimmune encephalitis presents with variety of clinical features such as acute onset behavioral changes, psychiatric symptoms, memory loss, movement disorders, dystonia, mutism and seizures. Neuronal antibodies are directed against cell surface Ag(CSAab) ,synaptic antigen (SyAab), intraneuronal Ag(INAab). Anti LG1 and CASPR2 encephalitis are usually non-neoplastic autoimmune encephalopathy where antibodies are directed against proteins associated with Voltage gated k channel. About 50% patients with anti-VGKC encephalitis do not present antibodies against LGI1 or CASPR-2. Anually 1 case is detected amongst 100000 patients. This is a case report of a patient presented to Geriatrics OPD and the series of evaluation which led to diagnosis and treatment outcome.

Deep brain stimulation effect in genetic dyskinetic cerebral palsy: The case of ADCY5- related disease.

Cerebral Palsy (CP) represents a frequent cause of disability in childhood. Early in life, genetic disorders may present with motor dysfunction and diagnosed as CP. Establishing the primary, genetic etiology allows more accurate prognosis, genetic counselling, and planning for symptomatic interventions in homogeneous etiological groups. Deep brain stimulation (DBS) is recommended in refractory movement disorders, including isolated pediatric dystonias. For dystonia evolving in more complex associations in genetic CP, the effect of DBS is still understudied and currently only sporadically described. To report the effect of DBS applied to the globus pallidus pars interna (GPi) in children with complex movement disorders caused by pathogenic ADCY5 variants, diagnosed as dyskinetic CP previous to genetic diagnostic. We conducted a retrospective study on evolution of treatment with DBS in ADCY5-related disease. A standardized proforma including the different type of movement disorders and associated neurological signs was completed at each follow-up time, based on video recordings, as well as functional assessments used in children with CP. Four children (mean of age, 13 ± 2.9 years) received GPi-DBS. The same de novo pathogenic missense variant (c.1252C > T, p.R418W) was identified in three out of four and a splice site variant (c.2088 + 2G > T) in one subject. Developmental delay and overlapping features including axial hypotonia, chorea, dystonic attacks, myoclonus, and cranial dyskinesia were present. The median age at DBS was 9 years and follow-up with DBS, 2.6 years. We identified a pattern of clinical response with early suppression of dystonic attacks, followed by improvement of myoclonus and facial dyskinesia. Effect on chorea was delayed and more limited. Two patients gained notable functional benefit related to sitting, standing, gait, use of upper limbs and speech. ADCY5-related disease may benefit from GPi-DBS. The most significant clinical response relates to the early and sustained benefit on dystonic attacks and a variable but still positive response on the other hyperkinetic features. Genetic etiology of CP will contribute to further elucidate genotype-phenotype correlations and to refine DBS indication as network-related symptomatic interventions.

Clinico-Etiological Spectrum and Functional Outcomes of Children with Pre-Status Dystonicus and Status Dystonicus (SD): A Descriptive Study.

Status dystonicus (SD) is a life-threatening movement disorder emergency characterized by increasingly frequent and severe episodes of generalized dystonia, requiring urgent hospital admission. The diverse clinico-etiological spectrum, high risk of recurrence, and residual disabilities complicate functional outcomes. We aim to describe the clinico-etiological spectrum, radiology, therapeutic options, and follow-up of patients with pre-status dystonicus (pre-SD) and SD. A cross-sectional retrospective study was carried out in a tertiary care referral center. The clinical, laboratory, and radiology data of all patients aged less than 18 years with pre-SD and SD from January 2010 to December 2020 were collected. The Dystonia Severity Assessment Plan (DSAP) scale for grading severity and the modified Rankin Scale (mRS) for assessing outcome were used at the last follow-up visit. Twenty-eight patients (male:female: 2.1:1) experiencing 33 episodes of acute dystonia exacerbation were identified. The median age at the onset of dystonia and SD presentation was 8.71 (range: 0.25-15.75) and 9.12 (range: 1-16.75) years, respectively. Four patients experienced more than one episode of SD. The etiological spectrum of SD includes metabolic (Wilson's disease-13, L-aromatic amino acid decarboxylase deficiency-one, and Gaucher's disease-one), genetic (neurodegeneration with brain iron accumulation-three and KMT2B and THAP 1 gene-related-one each), structural-three, post-encephalitic sequelae (PES)-four, and immune-mediated (anti-NMDA receptor encephalitis-one). Five patients had pre-SD (DSAP grade 3), and 23 patients had established SD (DSAP grade 4-17 and DSAP grade 5-six). The Rapid escalation of chelation therapy precipitated SD in 11 patients with Wilson's disease. Febrile illness or pneumonia precipitated SD in nine patients. Twenty-three episodes of SD required midazolam infusion in addition to anti-dystonic medications. The median duration of hospital stay was 10 days (range: 3-29). Twenty-three patients had resolution of SD but residual dystonia persisted, while two patients had no residual dystonia at follow-up. Three patients succumbed owing to refractory SD and its complications. Early identification of triggers, etiology, and appropriate management are essential to calm the dystonic storm.

DYT30 due to VPS16 Mutation: An Etiology of Childhood-Onset Generalized Dystonia.

DYT30 due to VPS16 Mutation: An Etiology of Childhood-Onset Generalized Dystonia.

A Rare Cause of Paroxysmal Movement Disorder Associated with TBC1D24 Gene Mutation in Two Siblings.

A Rare Cause of Paroxysmal Movement Disorder Associated with TBC1D24 Gene Mutation in Two Siblings.

Childhood-Onset Choreo-Dystonia Due to a Recurrent Novel Homozygous Nonsense HPCA Variant: Case Series and Literature Review.

Biallelic variants in HPCA were linked to isolated dystonia (formerly DYT2) in 2015. Since then, the clinical spectrum of HPCA-related disorder has expanded up to including a complex syndrome encompassing neurodevelopmental delay, generalized dystonia with bulbar involvement, and infantile seizures. We report four individuals with a new phenotype of childhood-onset choreo-dystonia belonging to two unrelated Iranian pedigrees and harboring a novel homozygous nonsense pathogenic variant NM_002143.3:c.49C>T p.(Arg17*) in HPCA. Although the families are both Iranian, haplotype analysis of the exome data did not reveal a founder effect of the variant. A systematic review of articles on HPCA and dystonia published since the disease gene discovery (PubMed; search on July 09, 2022; search strategy "HPCA AND dystonia", "HPCA AND movement disorder", "hippocalcin AND dystonia", and "hippocalcin AND movement disorder"; no language restriction) resulted in 18 references reporting 10 cases from six families. HPCA-related dystonia was isolated or in various combinations with neurodevelopmental delay, intellectual disability, seizures, cognitive decline, and psychiatric comorbidity. Onset of dystonia ranged from infancy to early adulthood. Dystonia started in the limbs or neck and became generalized in most cases. Brain MRI was unremarkable in nearly all cases where performed. There was poor or no response to common antidystonic medications in most cases. Our case series expands the pheno-genotypic spectrum of HPCA-related disorder by describing childhood-onset choreo-dystonia as a new phenotype, reporting on a recurrent novel pathogenic nonsense variant in HPCA, and suggesting that exon 2 of HPCA might be a mutational hotspot.

Alternating hemiplegia of childhood: a distinct clinical entity and ATP1A3-related disorders: A narrative review.

Alternating Hemiplegia of Childhood (AHC) is a rare disorder with onset in the first 18 months of life characterized by stereotyped paroxysmal manifestations of tonic and dystonic attacks, nystagmus with other oculomotor abnormalities, respiratory and autonomic dysfunctions. AHC is often associated with epileptic seizures and developmental delay. Hemiplegic paroxysm is the most remarkable symptom, although AHC includes a large series of clinical manifestations that interfere with the disease course. No cure is available and the treatment involves many specialists and therapies. Flunarizine is the most commonly used drug for reducing the frequency and intensity of paroxysmal events. Mutations in ATP1A2, particularly in ATP1A3, are the main genes responsible for AHC. Some disorders caused by ATP1A3 variants have been defined as ATP1A3-related disorders, including rapid-onset dystonia-parkinsonism, cerebellar ataxia, pes cavus, optic atrophy, sensorineural hearing loss, early infant epileptic encephalopathy, child rapid-onset ataxia, and relapsing encephalopathy with cerebellar ataxia. Recently, the term ATP1A3 syndrome has been identified as a fever-induced paroxysmal weakness and encephalopathy, slowly progressive cerebellar ataxia, childhood–onset schizophrenia/autistic spectrum disorder, paroxysmal dyskinesia, cerebral palsy/spastic paraparesis, dystonia, dysmorphism, encephalopathy, MRI abnormalities without hemiplegia, and congenital hydrocephalus. Herewith, we discussed about historical annotations of AHC, symptoms, signs and associated morbidities, diagnosis and differential diagnosis, treatment, prognosis, and genetics. We also reported on the ATP1A3-related disorders and ATP1A3 syndrome, as 2 recently established and expanded genetic clinical entities.

243 Mood disorder affects age at onset of adult-onset cervical dystonia

IntroductionMood disorder is common in cervical dystonia (CD) and may precede the onset of dystonia. There is controversy as to whether mood disorder is part of the primary process or secondary to the disability.We assessed the characteristics of CD patients in relation to a past history of mood disorder.MethodsWe collected demographic data, medical history of mood disorder, and prospectively measured prevalence of mood disorder using the BAI and BDI.ResultsIn 193 patients (128 women and 65 men) mean age at onset of CD was 43.9 years with mean duration, 17.5 years. Men had earlier age at onset of CD than women(p=0.0037). 53/128 (41%) women with a history of a mood disorder had a significantly earlier median age at onset than 75/128 (59%) women without a history of mood disorder (p=0.005). 33(26%) women with mood disorder prior to CD also had an earlier age at onset than the 75(59%) without such a history (p=0.0154). A history of mood disorder was more common in women(41%) than men(31%). 54/128(42%) women and 21/65(32%) men had current mood disorder symptoms.ConclusionsThe significant differences in the age at onset in women with, and without, a history of mood disorder strongly indicates that anxiety and depression are primary non-motor (and premotor) symptoms of CD.ihedinachindukwe@gmail.com

Longitudinal Follow-Up of Mood in Cervical Dystonia and Influence on Age at Onset.

Anxiety and depression are highly prevalent conditions in cervical dystonia and considered intrinsic to the disease mechanism. Psychiatric symptoms do not appear to be influenced by botulinum toxin therapy. Studies focusing on changes in mood disorder during the course of the disease are limited in this chronic, lifelong disorder. To assess the longitudinal prevalence of mood disorder, pain, and quality of life in patients with cervical dystonia attending a botulinum toxin clinic. Patients involved in phase I of our study were invited to be involved in reassessment using the Beck Depression Inventory, Second Revision; Beck Anxiety Index; Cervical Dystonia Impact Profile-58 (CDIP-58); and the Toronto Western Spasmodic Torticollis Rating Scale-2 Pain Scale (TWSTRS2-Pain). A total of 53 participants took part after a mean study interval duration of 24months. There were no significant differences between the 2 study time points in the prevalence of anxiety (P= 0.2919) and depressive symptoms (P= 0.5). Self-reported quality of life by CDIP-58 (P= 0.96) and pain by TWSTRS2-Pain (P= 0.9321) were unchanged. Men and women with significant symptoms of mood disorder had an earlier age of onset of cervical dystonia (P= 0.008). Anxiety and depressive symptoms persist in cervical dystonia, seem to be unrelated to pain severity, and need to be specifically targeted to improve quality of life. The relationship between mood disorder and age of onset suggest that mood disorder may be part of the disease pathophysiology.

EP296: Familial MECP2 variants: a report of 4 affected families highlighting the variable phenotypic spectrum and implications for genetic counseling

Pathogenic variants in MECP2 cause a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT; 312750). Although historically this was considered an X-linked dominant diagnosis with male lethality, it is now known that males can also be affected, with a disease spectrum ranging from severe neonatal encephalopathy to intellectual disability (ID). Other features commonly seen in RTT are inconsistently present in males. A qualified genotype-phenotype correlation exists, with variants that are known to cause RTT in females most often leading to more severe phenotypes in males. Additionally, whereas pathogenic MECP2 variants identified in affected females with classic and atypical RTT are most often de novo variants, pathogenic variants in males may be either de novo or maternally inherited. Here we report 4 novel families with pathogenic MECP2 variants. In all 4 families, the affected probands were male and maternal inheritance was identified. Family 1: The proband is a now 8-year-old male with mild global developmental delay, epilepsy, ataxia, and hypotonia. He also has significant anxiety. Epilepsy gene panel identified a hemizygous pathogenic variant in MECP2 (c.491C>T; p.Ala140Val); targeted testing confirmed maternal inheritance. His mother has no significant medical issues or learning issues, but endorses a history of anxiety. He has four clinically unaffected siblings; one brother has been tested and is negative. His other brother and sisters have not been tested. Family 2: The proband is a now 47-year-old male with mild-moderate intellectual disability. Genetic testing was initiated after MRI performed in the context an episode of confusion and shaking concerning for a panic attack revealed signal abnormalities in the bilateral cerebral peduncles possibly concerning for Fragile X Associated Tremor Ataxia Syndrome (FXTAS). He also experienced a motor regression and onset of dystonia after an episode of rhabdomyolysis in his mid 40’s and has not returned to baseline. Trio exome sequencing identified a maternally inherited hemizygous pathogenic variant (c.499C>T; p.Arg167Trp) in MECP2. Cascade testing identified that his sister and niece also both carry the familial MECP2 variant. His sister has a history of learning difficulties, significant anxiety, obsessive compulsive disorder, and has developed progressive spasticity with hyperreflexia and sustained clonus over time. His niece also has anxiety, obsessive compulsive disorder, and bipolar disorder. Family 3: The proband is a now 37-year-old male with mild intellectual disability and autism spectrum disorder. He also has a history of anxiety and depression. Trio exome sequencing identified a maternally inherited hemizygous pathogenic variant (c. 1136_1151del16; p.Pro379HfsX25) in MECP2. Testing was initiated after the onset of abnormal movements in his thirties suggestive of dystonia. Exam was notable for kyphosis and shuffling gait. His mother reports a history of anxiety, but no learning or cognitive concerns and no other neurologic symptoms. He has one clinically unaffected sister who has not yet been tested. Exome sequencing also identified a de novo, heterozygous c.1672C>T (p.Arg558Cys) variant of uncertain significance in ALDH18A1, though it is unclear whether or not this is contributing to his phenotype. Family 4: The proband is a now 8-year-old male who initially presented for evaluation due to concern for global developmental delay, hypotonia, and macrocephaly. Family history was unremarkable. MRI identified prominent perivascular spaces. Trio exome sequencing identified a maternally inherited likely pathogenic hemizygous variant (c.1244delC; p.Pro415LeufsX6) in MECP2. The proband’s younger brother subsequently presented with expressive language delay and was also macrocephalic. Targeted testing confirmed the presence of the familial MECP2 variant. These 4 familial reports of pathogenic MECP2 variants add to the data provided by previous publications describing the phenotypic spectrum in affected males and supporting that many of the variants may be maternally inherited. Affected male probands in all cases presented with developmental delay and/or intellectual disability. Only 1/4 probands had epilepsy. Anxiety was present in 3/4. Cascade testing identified carrier female relatives with a prominent neuropsychiatric phenotype in one family. Anxiety was also reported in the mothers of two other families, without any other cognitive or neurologic features. Although two families harbored pathogenic missense variants previously known to be associated with an X-linked intellectual disability phenotype, two families with mildly affected male probands and unaffected female carrier mothers had novel, predicted loss of function variants that would have been expected to result in a RTT phenotype. These families highlight the clinical variability that can be seen with pathogenic MECP2 variants and challenge reported genotype-phenotype correlations, providing important information for genetic counseling.

EP202: A new pathologic KMT2B variant associated with childhood onset dystonia presenting as variable phenotypes among family members

KMT2B-related dystonia (DYT-KMT2B) is an autosomal dominant disease resulting in a complex movement disorder. KMT2B is expressed ubiquitously throughout human tissues, with the greatest expression within the cerebellum. Additionally, KMT2B-dystonia patients have reduced KMT2B expression. To date, less than eighty affected individuals of varying genotypes have been identified. DYT-KMT2B typically presents in early childhood with lower extremity dystonia in the first decade. DYT-KMT2B is known to progress into generalized dystonia with associated dysphagia, spasticity, dysarthria, and dysphonia, generally two to eleven years after symptom onset.

EP257: A homozygous nonsense variant in DNAJC30 causes Leigh-like phenotypes

A single exon protein coding gene, DNAJC30, encodes a chaperone protein which enriches in neurons, involves in ATP biosynthesis, and is a regulator of mitochondrial respiration. Here, we report a 12-year-old boy of Guatemalan ancestry who had acute dystonia onset at age 10. Brain MRI showed bilateral basal ganglion and thalamic hyperintensities. He developed bilateral optic atrophy and rapidly progressive vision loss. He also was diagnosed with autism spectrum disorder. Whole exome sequencing analysis of his peripheral blood sample revealed a homozygous nonsense variant, c.24G>A (p.W8X), in the DNAJC30 gene.

Functional movement disorder gender, age and phenotype study: a systematic review and individual patient meta-analysis of 4905 cases

Functional movement disorder (FMD) is a common manifestation of functional neurological disorder presenting with diverse phenotypes such as tremor, weakness and gait disorder. Our current understanding of the basic epidemiological...

CHARACTERISTIC UPPER LIMB DYSTONIA PATTERN AS A CORRELATE TO THE 'EYE OF TIGER' MRI SIGN.

Childhood onset dystonia are generally genetic. NBIA is one of the commonest cause. We present ve cases with a characteristic upper limb dystonia in patients of suspected PKAN with MRI Brain showing classical 'Eye of tiger' sign.

Mental health and behaviour in children with dystonia: Anxiety, challenging behaviour and the relationship to pain and self-esteem

<h2>Abstract</h2><h3>Purpose</h3> To ascertain whether young people with dystonia are more likely than the general population to have mental health and/or behavioural difficulties, and to explore factors that may contribute to these difficulties. <h3>Method</h3> Using a quasi-experimental design, 50 young people with dystonia aged 7–17 and their carers were recruited from the Evelina London Children's Hospital. Young people completed the Beck Youth Inventories and the Strengths and Difficulties Questionnaire. Carers completed the Strengths and Difficulties Questionnaire-Parent version and the Paediatric Pain Profile. Important medical factors, such as age of onset, motor severity and manual function were obtained from medical records. <h3>Results</h3> One sample z tests showed young people with dystonia self-reported significantly higher levels of anxiety (<i>p</i> < .001) and prosocial difficulties (<i>p</i> < .01), with 48% experiencing clinically significant anxiety levels. They experienced significantly lower levels of anger, disruptive behaviour and conduct problems (all <i>p</i> ≤ .01). Carers reported significantly higher rates of emotional problems, hyperactivity and peer problems, and significantly lower prosocial behaviours (all <i>p</i> ≤ .01). Pearson's correlation coefficients showed lower levels of self-esteem were related to higher levels of anxiety (p = .015). High levels of pain were related to parent-rated conduct problems (p = .004). Age of dystonia onset and motor severity did not correlate with any of the psychological or behavioural measures. <h3>Interpretation/conclusions</h3> Our study suggests high rates of anxiety and behaviours that challenge in children with dystonia. Screening in movement clinics would be helpful in early identification and signposting for support.