Dystonic Posturing Research Articles

Distinguishing seizures in autoimmune limbic encephalitis from mesial temporal lobe epilepsy with hippocampal sclerosis: Clues of a temporal plus network

ObjectiveDiagnosing autoimmune limbic encephalitis (ALE) in adults with new-onset seizures can be challenging, especially when seizures represent the predominant manifestation and MRI findings are not straightforward. By comparison with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), this study aimed to identify ictal electro-clinical features that might help clinicians recognize ALE-related seizures. MethodsThis retrospective, multi-centre study analysed the ictal semiology and EEG correlate of 116 video-EEG-captured seizures in 40 ALE patients and 45 ones recorded in 21 MTLE-HS subjects. The proportion of patients presenting each clinical feature on at least one occasion was compared between the study groups. Latent class analysis (LCA) was also performed. ResultsIctal features were overall more numerous in ALE than in MTLE-HS (33 vs 22), and LCA confirmed the intrinsic variability of ALE-related seizures. Hyperventilation served as a trigger only in ALE (4/40). Awareness impairment (p = 0.032), limb dystonic posturing (p = 0.009) and manual automatisms (p < 0.001) were significantly less common in ALE cases. Conversely, piloerection was observed only in ALE subjects, although it did not reach statistical significance (p = 0.289), as was the case for déjà-vu (p = 0.084), and sensory symptoms (p = 0.079). Regarding EEG, the type of ictal pattern differed significantly (p = 0.007). SignificanceThis study shows that, despite the wide overlap with MTLE-HS, some ictal electro-clinical features could help clinicians suspect the autoimmune origin of adult-onset seizures. Moreover, autoimmune limbic seizures apparently shared similarities with ‘temporal plus’ epilepsy, which could partly account for the poor surgical outcomes and provide an interesting conceptual framework for future research.

Heterozygous KCNJ10 Variants Affecting Kir4.1 Channel Cause Paroxysmal Kinesigenic Dyskinesia.

More than 60% of paroxysmal kinesigenic dyskinesia (PKD) cases are of uncertain variants. The aim was to elucidate novel genetic contribution to PKD. A total of 476 probands with uncertain genetic causes were enrolled for whole-exome sequencing. A method of case-control analysis was applied to identify the candidate genes. Whole-cell patch-clamp recording was applied to verify the electrophysiological impact of the identified variants. A mouse model with cerebellar heterozygous knockout of the candidate gene was developed via adeno-associated virus injection, and dystonia-like phenotype inducement and rotarod tests were performed. In vivo multiunit electrical recording was applied to investigate the change in neural excitability in knockout mice. Heterozygous variants of potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) clustered in PKD patients were compared with those in the control groups. Fifteen variants were detected in 16 of 522 probands (frequency = 3.07%). Patients with KCNJ10 variants tended to have a milder manifestation compared to those with PRRT2 (proline-rich transmembrane protein 2) variants. KCNJ10 variants partially altered the transmembrane location of inwardly rectifying potassium channel 4.1 (Kir4.1). The Kcnj10 expression is consistent with the natural course of PKD. Variants resulted in different degrees of reduction in cell Kir4.1 currents, and mice with heterozygous conditional knockout of Kcnj10 in the cerebellum presented dystonic posture, together with poor motor coordination and motor learning ability in rotarod tests. The firing rate of deep cerebellar nuclei was significantly elevated in Kcnj10-cKO mice. We identified heterozygous variants of KCNJ10 in PKD. Impaired function of Kir4.1 might lead to abnormal neuronal excitability, which attributed to PKD. © 2024 International Parkinson and Movement Disorder Society.

CANVAS For A Diagnosis: Can You Hear The Hooves Of Zebras?

Abstract Background A 75year old male presented to a Movement Disorder Service with complex multimorbidity including: chronic pain, type 2 diabetes mellitus, hypoventilatory obesity syndrome, biliary calculus, moderate aortic stenosis, marked orthostatic hypotension, pulmonary hypertension, coronary artery bypass grafting, permanent pacemaker for complete atrioventricular block, carpal tunnel release bilaterally, polypharmacy and bilateral cataracts. History elucidated a distal to proximal sensory loss over 20years and neuropathic pain without nerve conduction confirmation; and progressively ataxic gait over several years. He also complained of hypophonia, bruxism, excessive daytime somnolence, passages, transitions, visual agnosia, textural illusion, oscillopsia, irritability, inflexibility, hoarding, impulsivity, disorganisation, inattention, apathy, depression and aspontaneity. He was intolerant of nocturnal continuous positive airway pressure device. Epworth score was 21. Methods Examination demonstrated: marked orthostatic hypotension, preserved cognition, hypersomnolence, dyspraxic dysgraphia, palmar and antecubital agraphaesthesia, downbeat horizontal nystagmus at eccentric gaze positions, square wave jerks, bidirectionally impaired head impulse test, dysmetric saccades, asymmetric cerebellar signs in upper and lower limbs, rightward Pisa syndrome, kinesigenic dystonic axial posturing, rightward laterocollis and equivocal Babinski/Oppenheim reflexes. Gait assessment demonstrated sensory and cerebellar ataxic features with marked apraxia. No pes cavus. Results Computed tomography of brain had Fazekas 1 small vessel disease, Medial temporal atrophy score 1, Koedam 1 and age-commensurate cerebral and cerebellar atrophy. RFC1 gene testing confirmed biallelic intronic AAGGG repeat expansion disorder. Conclusion Cerebellar Ataxia Neuropathy and Vestibular Areflexia Syndrome (CANVAS) should be considered in patients with presentations from mid-life of progressive sensory ataxic neuropathy, altered vestibular ocular reflex, gaze evoked nystagmus and prominent dysautonomia. CANVAS is a rare autosomal recessive genetic disorder with a protean presentation. Referral to Genetics Services should be undertaken for family counselling. Keeping an open mind in complex, multimorbid patients to a potentially unifying diagnosis is important to guide prognostication. The rumble of hooves in the distance is not always that of horses.

Limited cerebellar gradient extension in temporal lobe epilepsy with dystonic posturing.

Dystonic posturing (DP) is a common semiology in temporal lobe epilepsy (TLE). We aimed to explore cerebellar gradient alterations in functional connectivity in TLE patients with and without DP. Resting-state functional MRI data were obtained in 60 TLE patients and 32 matched healthy controls. Patients were further divided into two groups: TLE with DP (TLE + DP, 31 patients) and TLE without DP (TLP-DP, 29 patients). We explored functional gradient alterations in the cerebellum based on cerebellar-cerebral functional connectivity and combined with independent component analysis to evaluate cerebellar-cerebral functional integration and reveal the contribution of the motor components to the gradient. There were no obvious differences in clinical features and postoperative seizure outcomes between TLE + DP and TLE-DP patients. Patients and controls all showed a clear unimodal-to-transmodal gradient transition in the cerebellum, while TLE patients demonstrated an extended principal gradient in functional connectivity compared to healthy controls, which was more limited in TLE + DP patients. Gradient alterations were more widespread in TLE-DP patients, involving bilateral cerebellum, while gradient alterations in TLE + DP patients were limited in the cerebellum ipsilateral to the seizure focus. In addition, more cerebellar motor components contributed to the gradient alterations in TLE + DP patients, mainly in ipsilateral cerebellum. Extended cerebellar principal gradients in functional connectivity revealed excessive functional segregation between unimodal and transmodal systems in TLE. The functional connectivity gradients were more limited in TLE + DP patients. Functional connectivity in TLE patients with dystonic posturing involved more contribution of cerebellar motor function to ipsilateral cerebellar gradient. Dystonic posturing contralateral to epileptic focus is a common symptom in temporal lobe epilepsy, and the cerebellum may be involved in its generation. In this study, we found cerebellar gradients alterations in functional connectivity in temporal lobe epilepsy patients with and without contralateral dystonic posturing. In particular, we found that TLE patients with dystonic posturing may have more limited cerebellar gradient in functional connectivity, involving more contribution of cerebellar motor function to ipsilateral cerebellar gradient. Our study suggests a close relationship between ipsilateral cerebellum and contralateral dystonic posturing.

Obsessive-compulsive disorder as a first manifestation of Ataxia with Oculomotor Apraxia type 2 due to a novel mutation of SETX gene.

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disorder presenting with cerebellar ataxia, sensory-motor axonal neuropathy, oculomotor apraxia, cerebellar atrophy and high alpha-fetoprotein (AFP) serum level. AOA2 is due to coding mutations of the SETX gene, mapped to chromosome 9q34. Seldom noncoding mutations affecting RNA processing have been reported too. To date psychiatric symptoms have never been reported in AOA2. A 19 years-old man came to our attention for progressive gait ataxia debuted five years earlier. His past medical history was unremarkable, while his parents were consanguineous. On neurological examination, he had bilateral horizontal gaze-evoked nystagmus with hypometric saccades and saccadic horizontal smooth pursuit, appendicular ataxia, limbs and trunk myoclonic involuntary movements with hands' dystonic postures and dance of the tendons. Psychological evaluation described intrusive and obsessive thoughts experienced by the patient, then diagnosed as obsessive-compulsive disorder. Blood tests detected an elevated AFP level. Brain MRI showed cerebellar atrophy, while electroneuromyography revealed an axonal sensory-motor polyneuropathy. In the suspicion of a pathology belonging to the autosomal recessive cerebellar ataxias (ARCA) spectrum disorder, a direct search of point mutations by whole-exome sequencing was performed revealing a novel biallelic variant in SETX gene (c.6208+2dupT), which was classified as likely pathogenic. The present case expands the genotypic and phenotypic spectrum of AOA2, reporting a novel likely pathogenic SETX mutation (c.6208+2dupT) and highlighting an early psychiatric involvement in AOA2, suggesting the need for psychiatric assessment in these neurologic patients.

Phenotype Distinctions in Mice Deficient in the Neuron-Specific α3 Subunit of Na,K-ATPase: Atp1a3tm1Ling/+ and Atp1a3 +/D801Y.

ATP1A3 is a Na,K-ATPase gene expressed specifically in neurons in the brain. Human mutations are dominant and produce an unusually wide spectrum of neurological phenotypes, most notably rapid-onset dystonia parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). Here we compared heterozygotes of two mouse lines, a line with little or no expression (Atp1a3tm1Ling/+) and a knock-in expressing p.Asp801Tyr (D801Y, Atp1a3 +/D801Y). Both mouse lines had normal lifespans, but Atp1a3 +/D801Y had mild perinatal mortality contrasting with D801N mice (Atp1a3 +/D801N), which had high mortality. The phenotypes of Atp1a3tm1Ling/+ and Atp1a3 +/D801Y were different, and testing of each strain was tailored to its symptom range. Atp1a3tm1Ling/+ mice displayed little at baseline, but repeated ethanol intoxication produced hyperkinetic motor abnormalities not seen in littermate controls. Atp1a3 +/D801Y mice displayed robust phenotypes: hyperactivity, diminished posture consistent with hypotonia, and deficiencies in beam walk and wire hang tests. Symptoms also included qualitative motor abnormalities that are not well quantified by conventional tests. Paradoxically, Atp1a3 +/D801Y showed sustained better performance than wild type on the accelerating rotarod. Atp1a3 +/D801Y mice were overactive in forced swimming and afterward had intense shivering, transient dystonic postures, and delayed recovery. Remarkably, Atp1a3 +/D801Y mice were refractory to ketamine anesthesia, which elicited hyperactivity and dyskinesia even at higher dose. Neither mouse line exhibited fixed dystonia (typical of RDP patients), spontaneous paroxysmal weakness (typical of AHC patients), or seizures but had consistent, measurable neurological abnormalities. A gradient of variation supports the importance of studying multiple Atp1a3 mutations in animal models to understand the roles of this gene in human disease.

Clinical Response of Levodopa in CTNNB1-Related Dystonia

Abstractβ-catenin, which is encoded by the CTNNB1 gene, is essential for the development and functioning of the brain. There are a few documented cases of dystonia related to CTNNB1. Here, we report the case of an 11-year-old Spanish boy referred for movement disorders and gait disturbance. He had motor developmental delay and achieved unassisted walking at 3 years, with a tiptoe gait and valgus foot posture requiring ankle-foot orthoses. Blood tests showed elevated creatine kinase levels (1684 U/L, normal range 62–235). Molecular analysis revealed a deletion in exons 3-9 of the DMD gene, leading to the diagnosis of Becker muscular dystrophy. By age 8, he presents frequent falls due to a dystonic posture of the feet and abnormal movements in the upper and lower limbs. Whole-exome sequencing revealed a novel heterozygous, de novo pathogenic frameshift variant in the CTNNB1 gene (NM_001098209.1):p.Thr297fs/ c.889dupA. Treatment with levodopa/carbidopa (5.3 mg/kg/day) led to a partial clinical improvement, including a decrease in dystonia, measured by the Burke-Fahn-Marsden Dystonia Rating Scale, and choreic movements in all four limbs. We suggest that levodopa contributes to motor improvement in patients with CTNNB1-related dystonia, supporting its inclusion in the differential diagnosis of childhood dopa-responsive dystonia.

Pick's Disease Presenting as Tremulous Parkinsonism with Limited Levodopa Response-A Rare Cause of Corticobasal Syndrome.

Corticobasal syndrome is a clinical diagnosis and common pathological causes are corticobasal degeneration, progressive supranuclear palsy and Alzheimer's disease. We would like to highlight a rare but important differential of corticobasal syndrome. A 78-year-old female had a 4-year history of predominantly right-hand rest tremor, worsening of handwriting but no change in cognition. The clinical examination showed right upper limb postural and kinetic tremor, mild wrist rigidity and reduced amplitude of right-sided finger tapping. She was initially diagnosed as idiopathic Parkinson's disease. Five years after onset of symptoms, she demonstrated bilateral myoclonic jerks and right upper limb dystonic posturing. She could not copy movements with the right hand. The magnetic resonance imaging (MRI) revealed disproportionate atrophy in the parietal lobes bilaterally. The clinical diagnosis was changed to probable corticobasal syndrome. She passed away 11 years from onset of symptoms at the age of 85 years. She underwent a post-mortem. The anterior and posterior frontal cortex, anterior cingulate, temporal neocortex, hippocampus and amygdaloid complex demonstrated considerable tau-related pathology consisting of a dense background of neuropil threads, and rounded, paranuclear neuronal inclusions consistent with Pick bodies. The immunostaining for three microtubule binding domain repeats (3R) tau performed on sections from the frontal and temporal lobes, basal ganglia and midbrain highlighted several inclusions whilst no 4R tau was observed. She was finally diagnosed with Pick's disease. Pick's disease can rarely present with clinical features of corticobasal syndrome.

Bedside clinical assessment of patients with common upper limb tremor and algorithmic approach.

The diagnostic approach for patients with tremor is challenging due to the complex and overlapping phenotypes among tremor syndromes. The first step in the evaluation of tremor is to identify the tremulous movement and exclude the tremor mimics. The second step is to classify the tremor syndrome based on the characteristics of tremor from historical clues and focused examination (Axis 1). Comprehensive tremor examinations involve the assessment of tremor in different conditions (rest, action or mixed, position or task-specific), distribution of tremor (upper limb, lower limb, head, jaw), positive signs for functional tremor (FT) if suspected (distractibility, entrainment, co-contraction), and associated neurological signs including parkinsonism, dystonic posture, cerebellar/brainstem signs, neuropathy, and cognitive impairment. A pivotal feature in this step is to determine any distinct feature of a specific isolated or combined tremor syndrome. In this review, we propose an algorithm to assess upper limb tremors. Ancillary testing should be performed if clinical evaluation is unclear. The choice of investigation depends on the types of tremors considered to narrow down the spectrum of etiology (Axis 2). Laboratory blood tests are considered for acute onset and acute worsening of tremors, while structural neuroimaging is indicated in unilateral tremors with acute onset, nonclassical presentations, and a combination of neurological symptoms. Neurophysiological study is an important tool that aids in distinguishing between tremor and myoclonus, etiology of tremor and document specific signs of FT. Treatment is mainly symptomatic based depending on the etiology of the tremor and the patient's disabilities.

236 Bilateral Intrathalamic Infusion of rAAVrh8-Hexa/Hexb in a Phase 1/2 Clinical Trial for Gene Therapy in Infantile and Juvenile Tay-Sachs and Sandhoff Disease; Surgical Technique

INTRODUCTION: Tay-Sachs (TSD) and Sandhoff (SD) diseases are rare,monogenic and severe neurodegenerative disorders due to Hexosaminidase A deficiency. We performed the first-in-human bilateral thalamic (BiTh) delivery of rAAVrh8-HEXA/HEXB in 8 children in a Phase 1/2 clinical trial. METHODS: Stereotactic infusion cannula placement was performed using ROSA robotic platform. Bilateral trajectories were planned via the trans-frontal route..Head stabilization was accomplished using radiolucent horse-shoe head rest and radiolucent pin-skull clamps. Flexible infusion cannulas were placed through small drill holes using ROSA guidance. Cannula stabilization was achieved using a construct which combined the Navigus brain biopsy platform and flexible cannula bolt. Insertion accuracy was verified with intraoperative CT images. Patients received one of the three doses in each thalamus: 180 mcl (5.87E + 12vg), 360 mcl (1.17E + 13vg) or 720 mcl (2.35E + 13vg). Drug infusion rate was 4 mcl/minute and completed in 90-360 minutes depending on drug dosage. RESULTS: Eight patients received treatment; 5 infants (6, 11, 13, 17, and 20 months) and 3 juvenile (5, 6, 12 years). Duration of follow up was 2-28 months. Outcome assessments included safety, CSF biochemistry, MRI/MRS/DTI, and neurodevelopmental observations. Surgery and drug infusions were well-tolerated. Post-infusion MRIs showed signal enhancement volume coverage in thalamus from 8%-44% parallel to escalating doses. The only surgery related complication was superficial wound dehiscence in two patients. Infants showed partial stabilization or improvement, including in oral feeding and myelination. In juveniles, dystonic posturing worsened after dosing in all 3 patients treated. Two patients died much later from reasons unrelated to surgery or drug infusion. CONCLUSIONS: Surgery for BiTh infusion of rAAVrh8-HEXA/HEXB for gene therapy in infants with TSD and SD is well-tolerated. Patients respond well to treatment with some stabilization or improvement.

Three-Dimensional Gait Analysis as a Biomarker for GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia

BackgroundGTP-cyclohydrolase 1-deficient dopa-responsive dystonia (GTPCH1-deficient DRD) typically presents in childhood with dystonic posture of the lower extremities, gait impairment, and a significant response to levodopa. We performed three-dimensional gait analysis (3DGA) to quantitatively assess the gait characteristics and changes associated with levodopa treatment in patients with GTPCH1-deficient DRD. MethodsThree levodopa-treated patients with GTPCH1-deficient DRD underwent 3DGA twice, longitudinally. Changes were evaluated for cadence; gait speed; step length; gait deviation index; kinematic data of the pelvis, hip, knee, and ankle joints; and foot progression angle. ResultsLevodopa treatment increased the cadence and gait speed in one of three patients and increased the gait deviation index in two of three patients. The kinematic data for each joint exhibited different characteristics, with some improvement observed in each of the three patients. There was consistent marked improvement in the abnormal foot progression angle; one patient had excessive external rotation of one foot, another had excessive bilateral internal rotation, and the other had excessive internal rotation of one foot and excessive external rotation of the opposite foot, all of which improved. ConclusionThe 3DGA findings demonstrate that the gait pathology and recovery process in GTPCH1-deficient DRD vary from case to case. Changes in the foot progression angle and gait deviation index can enable the effects of treatment to be more easily evaluated.

Paroxysmal Dystonic Posturing Mimicking Nocturnal Leg Cramps as a Presenting Sign in an Infant with DCC Mutation, Callosal Agenesis and Mirror Movements.

Background/Objectives: Pathogenic variants in the deleted in colorectal cancer gene (DCC), encoding the Netrin-1 receptor, may lead to mirror movements (MMs) associated with agenesis/dysgenesis of the corpus callosum (ACC) and cognitive and/or neuropsychiatric issues. The clinical phenotype is related to the biological function of DCC in the corpus callosum and corticospinal tract development as Netrin-1 is implicated in the guidance of developing axons toward the midline. We report on a child with a novel inherited, monoallelic, pathogenic variant in the DCC gene. Methods: Standardized measures and clinical scales were used to assess psychomotor development, communication and social skills, emotional and behavioural difficulties. MMs were measured via the Woods and Teuber classification. Exome sequencing was performed on affected and healthy family members. Results: The patient's clinical presentation during infancy consisted of paroxysmal dystonic posturing when asleep, mimicking nocturnal leg cramps. A brain magnetic resonance imaging (MRI) showed complete ACC. He developed typical upper limb MMs during childhood and a progressively evolving neuro-phenotype with global development delay and behavioural problems. We found an intrafamilial clinical variability associated with DCC mutations: the proband's father and uncle shared the same DCC variant, with a milder clinical phenotype. The atypical early clinical presentation of the present patient expands the clinical spectrum associated with DCC variants, especially those in the paediatric age. Conclusions: This study underlines the importance of in-depth genetic investigations in young children with ACC and highlights the need for further detailed analyses of early motor symptoms in infants with DCC mutations.

Alternating hemiplegia of childhood misdiagnosed as hysteria: a case report

BackgroundAlternating hemiplegia of childhood (AHC) is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia, and frequently accompanied by dystonic posturing, choreoathetosis movements, anomalous ocular motions, and a gradual deterioration in cognitive function. The principal etiology of this disorder is traced back to mutations in the ATP1A3 gene.Case presentationHere, we report a 16-year-old girl with recurrent hemiplegia since her infancy. This patient has experienced paroxysmal limb weakness and aphasia for over 15 years, and has kept seeking medical attention but without receiving effective treatment. A misdiagnosis of hysteria persisted for over 4 years until the patient’s admission to our hospital. Whole-exome sequencing identified a known pathogenic heterozygous c.2270T>C (p.Leu757Pro) mutation in her ATP1A3 gene. Notably, her clinical manifestations, including pathological emotional responses and autonomic dysfunction, differed from the established profile associated with the same ATP1A3 mutation, which typically present with intellectual disability, a rostrocaudal symptom gradient, choreoathetosis, and dysarthria. The patient was finally diagnosed with AHC and treated with flunarizine thus significantly ameliorated hemiplegic episodes.ConclusionsThis case enhances our understanding of the intricate clinical manifestations of AHC, which require careful differentiation from various diseases such as epilepsy, hysteria, and paroxysmal dyskinesias. In the diagnosis of patients presenting with suspected symptoms, adhering to a systematic approach for localizing and diagnosing neurological disorders is crucial to prevent misdiagnosis and inappropriate treatments. Additionally, when AHC is suspected in a patient, genetic testing should be considered as part of the diagnostic approach.

Multifractal characteristics of neuronal activity of the &lt;i&gt; globus pallidus &lt;/i&gt; in patients with dystonia

Dystonia is a movement disorder characterized by involuntary muscle contractions resulting in anomalous postures, often accompanied by dystonic tremors. Among the indicative dystonic postures is an involuntary tonic tilt or rotation of the head. Currently, the etiology and pathogenesis of the disease remain theories. Currently, only low-frequency (theta-alpha) oscillations in the globus pallidus are regarded as the possible biomarker of pathological activity in dystonia. In many patients with dystonia, the absence of rhythmic neuronal activity in the basal ganglia renders this biomarker unusable for surgical treatment of the disease. Additionally, the mechanisms underlying the rearrangement of temporary patterns of neural activity that result in pathological symptoms remain unclear. We propose that the appearance of these pathological rhythms is associated with the reduction of dynamic complexity in the pattern of neural activity within the globus pallidus. We aim to use multifractal analysis in this study to evaluate changes in the globus pallidus neural activity pattern’s dynamic complexity and their correlation with the clinical manifestations of dystonia. The study examined the electrical activity of the globus pallidus in 23 patients receiving deep brain stimulation (DBS) treatment. We used the microelectrode registration technique and local field potential (LFP) registration during intraoperative neuron monitoring to precisely identify the specific locations of the external and internal segments of the globus pallidus (GPe and GPi). In four patients, an additional postoperative recording of local field potentials (LFP) was conducted while performing DBS and vibrational impact on the neck muscles. A neurologist evaluated the patients to determine the severity of the disease using the Burke-Fahn-Mardsen Dystonia Rating Scale (BFMDRS). The LEAD DBS software package was employed for postoperative reconstruction of the DBS stimulating electrode positions and for simulating the optimal stimulation zone, selected by the neurologist (i.e., volume of tissue activated, VTA). Subsequently, we identified the region that presented the most significant variation in multifractal spectrum parameters following DBS to understand its correlation with the optimal VTA. A total of 745 local potential records were analyzed, with 433 in GPe and 312 in GPi. The severity of dystonia was found to be correlated with the parameters of the multifractal spectrum (rho: –0.5630882, p=0.005149 for GPe and rho: –0.5180609, p=0.01133 for GPi). Moreover, as the dystonia severity increased along the BFMDRS scale, the multifractal spectrum became narrower and more asymmetric. In post-surgery recordings, we observed changes in the shape of the multifractal spectrum during DBS stimulation or vibration. In particular, when exposed, the multifractal spectrum significantly widened, and its symmetry was restored. We identified the region with the greatest alteration in the width of the multifractal spectrum following DBS and discovered that this region considerably intersected or fully matched the neurologist’s chosen zone for optimal DBS stimulation. We demonstrated that multifractal analysis can serve as an ancillary approach to evaluate the extent of proprioceptive feedback impairment and as a biomarker of dystonia. The noteworthy and substantial correlation with dystonia severity underscores the considerable potential of multifractal spectrum features as a biomarker of dystonia. Additionally, the overlapping areas with the most significant DBS impact and the widest variation in the multifractal spectrum in DBS can be used as a tool for identifying the most favorable region for DBS stimulation.

Differential diagnosis of chorea (guidelines of the German Neurological Society)

IntroductionChoreiform movement disorders are characterized by involuntary, rapid, irregular, and unpredictable movements of the limbs, face, neck, and trunk. These movements often initially go unnoticed by the affected individuals and may blend together with seemingly intended, random motions. Choreiform movements can occur both at rest and during voluntary movements. They typically increase in intensity with stress and physical activity and essentially cease during deep sleep stages. In particularly in advanced stages of Huntington disease (HD), choreiform hyperkinesia occurs alongside with dystonic postures of the limbs or trunk before they typically decrease in intensity.Summary or definition of the topicThe differential diagnosis of HD can be complex. Here, the authors aim to provide guidance for the diagnostic process. This guidance was prepared for the German Neurological Society (DGN) for German-speaking countries.RecommendationsHereditary (inherited) and non-hereditary (non-inherited) forms of chorea can be distinguished. Therefore, the family history is crucial. However, even in conditions with autosomal-dominant transmission such as HD, unremarkable family histories do not necessarily rule out a hereditary form (e.g., in cases of early deceased or unknown parents, uncertainties in familial relationships, as well as in offspring of parents with CAG repeats in the expandable range (27–35 CAG repeats) which may display expansions into the pathogenic range).ConclusionsThe differential diagnosis of chorea can be challenging. This guidance prepared for the German Neurological Society (DGN) reflects the state of the art as of 2023.

Methodology of botulinum therapy in the treatment of dystonic scoliosis in generalized dystonia (clinical case)

Dystonic scoliosis as one of the forms of generalized dystonia is a highly disabling form of dystonia, which can lead to damage to internal organs (lungs, heart) and the peripheral nervous system, including the spinal cord. Almost always, those muscles that are involved in the formation of a dystonic posture in generalized dystonia have not been studied in terms of the effectiveness of treatment with botulinum toxin type A and are not reflected in the instructions. As a result, there is no understanding of the general motor interaction with differentiation into targeted and non-targeted muscles, administration doses and control methods.The aim of the work was to evaluate the efficacy and tolerability of high doses of botulinum toxin type A in dystonic scoliosis, as well as to present the introduction of botulinum toxin type A using ultrasound and electromyographic control. We have described a clinical case of a 19-year-old patient suffering from generalized dystonia with S-shaped dystonic scoliosis of the III degree. Deep brain stimulation was recommended as a treatment for the patient. During the waiting period for the timing of the operation, we attempted symptomatic therapy using the drug incobotulotoxin A. Over the next year and a half, 700 units of botulinum toxin type A were administered under ultrasound and electromyographic control every 3–4 months. As a result, treatment of trunk dystonia in the patient during the observation period led to a clinically significant decrease in the degree of curvature (from 37° to 27°, from III to II degree of scoliosis) in the absence of undesirable effects of the drug, including generalized muscle weakness. According to the repeated conclusion of the council of neurosurgeons, surgical intervention is not indicated for the patient due to the positive effect of the introduction of botulinum toxin type A.

Brief potentially ictal rhythmic discharges on intraoperative electrocorticography predict a good outcome of focal cortical dysplasia after surgical resection: a case report

BackgroundFocal cortical dysplasia (FCD) is a common cause of drug-resistant epilepsy. Electroencephalography (EEG) biomarkers that predict good postoperative outcomes are essential for identifying patients with focal epilepsies.Case presentationWe report the case of a 21-year-old female with seizure onset at the age of 9, characterized by left-hand dystonic posturing and impaired awareness, which evolved to bilateral tonic-clonic seizures, evaluated in a neurological referral center in Lima, Peru. During 6-h video-EEG, interictal EEG revealing focal brief potentially ictal rhythmic discharges (BIRDs) over the right frontal central region, lasting less than 10 s. The ictal features were characterized by low-voltage fast activity over the same area. Brain magnetic resonance imaging (MRI) demonstrated a focal lesion of focal cortical dysplasia type II in the right frontal lobe. The patient underwent a lesionectomy guided by electrocorticography, which showed continuous polyspikes. BIRDs showing a brief burst of spikes lasting longer than 0.5 s, were also identified on intraoperative electrocorticography (ECoG) and helped define the extent of resection. The patient obtained an Engel Outcome Class IA at 6 years of follow-up.ConclusionsThe atypical BIRDs on ECoG can be used as a prognostic biomarker for prolonged seizure-freedom outcome in patients with epilepsy. Additional reports are needed in developing countries with and without brain MRI lesions to advance outpatient presurgical evaluations despite limited resources.

Neuropathic Tremor in Guillain-Barré Syndrome.

Neuropathic Tremor (NT) is a postural/kinetic tremor of the upper extremity, often encountered in patients with chronic neuropathies such as paraprotein-associated and hereditary neuropathies. To describe the clinical and electrophysiological features of NT in a previously underrecognized setting- during recovery from Guillain-Barré Syndrome (GBS). Patients with a documented diagnosis of GBS in the past, presenting with tremor were identified from review of clinical records. Participants underwent structured, videotaped neurological examination, and electrophysiological analysis using tri-axial accelerometry-surface electromyography. Tremor severity was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale. We describe the clinical and electrophysiological features of 5 patients with GBS associated NT. Our cohort had a fine, fast, and slightly jerky postural tremor of frequency ranging from 8 to 10 Hz. Dystonic posturing and overflow movements were noted in 4/5 patients. Tremor appeared 3 months-5 years after the onset of GBS, when patients had regained near normal muscle strength and deep tendon jerks were well elicitable. Electrophysiological analysis of tremor strongly suggested the presence of a central oscillator in all patients. NT is not limited to chronic inflammatory or hereditary neuropathies and may occur in the recovery phase of GBS. The tremor is characterized by a high frequency, jerky postural tremor with dystonic posturing. Electrophysiological evaluation suggests the presence of a central oscillator, hypothetically the cerebellum driven by impaired sensorimotor feedback.

1001 A Case of Unusual Nocturnal Movements Consistent with Paroxysmal Hypnogenic Dyskinesia

Abstract Introduction Paroxysmal hypnogenic dyskinesia (PHD) is a rare subset of paroxysmal dyskinesias characterized by recurring involuntary dystonic or choreoathetoid movements that occur during sleep or immediately after an arousal from sleep. These episodes often occur without loss of consciousness or trigger and lack association with epileptiform electroencephalography (EEG) activity. Report of case(s) A 61-year-old male with obstructive sleep apnea compliant with PAP was referred for abnormal nighttime movements for the past 9 years. The episodes were characterized by stereotyped involuntary dystonic posturing involving his upper extremities or his entire body lasting up to 15 seconds. The onset of the events occurred invariable during nighttime sleep and resulted in awakenings from sleep. He denied dream enactment as well as other symptoms suggestive of sleep-related movement disorders or parasomnias. Sleep deprived EEG demonstrated left temporal slowing during wakefulness and drowsiness and captured a typical event that occurred during NREM stage II sleep and had no ictal correlate. An MRI of the brain was unremarkable. During overnight polysomnogram, his current PAP settings were found to be effective, and three episodes of body stiffening consistent with his typical events were captured. These episodes were found to occur after awakening from REM sleep and lasted less than 10 seconds each. There was no EEG correlate, and REM atonia was preserved throughout. The patient was started on oxcarbazepine for the nocturnal movements, which reduced the frequency of events from 12 to 4 events per night. Oxcarbazepine was tapered and discontinued due to side effects and incomplete control of the events. Genetic testing for epilepsy syndromes is pending. Conclusion PHD is a rare syndrome of involuntary movements which begin during sleep or cause awakenings from sleep and can be misdiagnosed as a sleep disorder. It is crucial for the sleep physician to be aware of possible neurological causes of sleep-related movement disorders. Furthermore, our patient’s partial response to oxcarbazepine may further support that PHD may have an epileptic origin although not well characterized. Support (if any) Advancing Innovation in Residency Education (AIRE) Pilot Program Training Grant

Seronegative Isaac Syndrome Presenting as Focal Limb Stiffness Responsive to Plasma Exchange Therapy (P8-8.015)

<h3>Objective:</h3> N/A <h3>Background:</h3> Isaac syndrome is an autoimmune disorder of peripheral nerve hyperexcitability characterized by neuromyotonia, myokymia, muscles stiffness, pseudomyotonia, and pseudotetany frequently accompanied by dysautonomia and neuropathic pain. Approximately 50% of cases are associated with antibodies against contactin-associated protein-like 2 (CASPR2) or less commonly leucine-rich glioma inactivated protein 1 (LGI1), both components of the voltage-gated potassium channel (VGKC) complex. Paraneoplastic, genetic, and toxic etiologies must be considered. Management includes membrane-stabilizing drugs as well as immunotherapy in more severe cases. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 50-year-old woman presented with one year of left neck, shoulder, and upper extremity pain and stiffness that began one month after an upper respiratory illness. Her exam was notable for anterocollis, left shoulder elevation, impaired left shoulder abduction beyond 35–40 degrees, tonically contracted left biceps, and marked tenderness to palpation of the affected muscles. Symptomatic management with diazepam, lorazepam, baclofen, mexiletine, and trihexyphenidyl was ineffective. EMG demonstrated widespread neuromyotonic discharges throughout the proximal greater than distal left upper extremity, cervical and thoracic paraspinals, and right deltoid. Laboratory studies including CASPR2, LGI1, VGKC, GAD-65, and amphiphysin antibodies were unremarkable. Comprehensive screening for occult malignancy was unrevealing. She received partial benefit from carbamazepine, levetiracetam, cyclobenzaprine, and onabotulinumtoxinA injections, but symptoms remained debilitating. She was treated with IVIg 1g/kg Q2 weeks for three months with symptom progression to the jaw and lower extremities. She was started on plasmapheresis QOD for ten days every four weeks with rapid improvement in symptoms. <h3>Conclusions:</h3> We report a case of seronegative Isaac syndrome initially presenting with focal limb stiffness and dystonic posturing that was exquisitely responsive to plasmapheresis. This case highlights the need to consider peripheral nerve hyperexcitability syndromes in patients presenting with focal limb stiffness or painful dystonia and provides additional support for plasmapheresis as an effective treatment option for patients with debilitating symptoms. <b>Disclosure:</b> Dr. Khalil has received personal compensation in the range of $0-$499 for serving as a Resident and Fellow Council Member with American Association of Neuromuscular &amp; Electrodiagnostic Medicine. Dr. Khalil has received personal compensation in the range of $0-$499 for serving as a MS Mentorship Forum Participant with Foundation of the Consortium of Multiple Sclerosis Centers. Dr. Bradshaw has nothing to disclose.