A Case of Unilateral Brachial Plexus Injury Caused by First-Rib Stress Fractures Presenting With an Uncontrollable Involuntary Movement of the Neck.

Stress fracture of the first rib is a rare but an important cause of brachial plexopathy. Here, we describe a patient with a unilateral brachial plexus injury presenting with involuntary neck movements. A 22-year-old man with cervical involuntary movements for 10 months was diagnosed with tardive dyskinesia. After admission, he abruptly noticed that he could not lift his right arm. The electrophysiological study revealed weakness of the right deltoid and brachioradialis, but normal findings in the other muscles innervated by the right C5 segment. Chest computed tomography showed fractures of the first rib on both sides, with callus formation. Based on the involvement of muscles innervated by the right axillary and radial nerves and presence of callus at the first rib, a diagnosis of right posterior cord entrapment was made. In the present case, intermittent strong contraction of muscles due to dyskinesia may have caused the stress fractures.

A case of chorea-acanthocytosis with significant improvement of symptoms at one year with deep brain stimulation: case report and literature review.

Chorea-acanthocytosis (ChAc) is a rare, neurodegenerative disorder caused by mutations in the VPS13A gene. In this article, we report on a 32-year-old man diagnosed with ChAc, with involuntary movements of the mouth and trunk, drooling of the mouth, slurred speech, and abnormal vocalizations as the main clinical manifestations. Three weeks after implantation of globus pallidus internal (GPi)-deep brain stimulation (DBS), the patient's symptoms improved significantly. For example, articulation is clear, involuntary trunk movements and salivation have largely disappeared, and abnormal vocalizations have been significantly reduced. After 1 year of follow-up, the improvement in involuntary movement symptoms is essentially the same as before. As far as we know, we are the first to report the relief of involuntary vocalizations in a patient with GPi-DBS treatment, and that salivation and involuntary trunk movements have almost disappeared, and all other symptoms are significantly relieved, which is rare in previous cases. All of the above proves that the treatment of our case with DBS was very successful and that longer term follow-up is critical. We also hope that our case will provide new references and therapeutic ideas for the future treatment of patients with ChAc.

Anti-contactin-associated protein 1 antibody-positive nodopathy presenting with central nervous system symptoms.

Contactin-associated protein 1 (Caspr1) is widespread in both the peripheral and central nervous systems (CNS). However, anti-Caspr1 antibody-positive nodopathy associated with CNS symptoms has not previously been reported. In this case, a 69-year-old man presented with polyneuropathy and memory loss. The patient had negative myoclonus, positive myoclonus, and pseudoathetosis in the upper limbs, and we detected anti-Caspr1 antibodies in the serum and cerebrospinal fluid. Therefore, anti-Caspr1 nodopathy was diagnosed. After rituximab treatment, all symptoms of polyneuropathy, involuntary movements, and memory impairment improved. In conclusion, anti-Caspr1 antibodies might also affect the CNS; therefore, CNS symptoms of anti-Caspr1 nodopathy require attention.

Pseudohypoparathyroidism type 1B with involuntary movements: a case report and literature review.

Pseudohypoparathyroidism (PHP) is a rare disorder characterized by convulsions, tetany, and sensory abnormalities caused by hypocalcemia due to parathyroid hormone (PTH) resistance. Only few patients present with involuntary movements. We report the case of a 7-yr-old girl with PHP and involuntary movements triggered by running. Initially, she was suspected of having paroxysmal kinesigenic dyskinesia and was treated with carbamazepine (CBZ). Involuntary movements were reduced. However, 2 months post-treatment, she experienced convulsions during a fever. Blood tests and brain computed tomography revealed hypocalcemia, hyperphosphatemia, elevated intact PTH, and calcifications in the frontal cortex and basal ganglia. The patient showed no features of Albright's hereditary osteodystrophy. The involuntary movements disappeared after the discontinuation of CBZ and initiation of calcium and active vitamin D preparations. Methylation-specific multiplex ligation-dependent probe amplification for the GNAS region and microsatellite analysis of chromosome 20 led to the diagnosis of PHP1B caused by epimutation. In 15 reported cases, with or without intracranial calcification, PHP-associated involuntary movements disappeared or became less severe with treatment for hypocalcemia; in eight of 11 cases, they were triggered by exercise or movement. PHP-associated hypocalcemia can trigger exercise-induced involuntary movements owing to lowered serum ionized calcium levels. In such patients, early blood tests are vital for the differential diagnosis of PHP.

[Fatal Familial Insomnia With Significant Correlations Between Involuntary Movements and Postural Changes:Report of One Case].

Fatal familial insomnia,an autosomal dominant prion disease,is rare.We reported the clinical symptoms,examination results,diagnosis,treatment,and prognosis of a patient who was diagnosed with fatal familial insomnia.Furthermore,we described the unique clinical manifestations that involuntary movements and laryngeal stridor were significantly correlated with postural changes,aiming to provide reference for the clinical diagnosis,treatment,and research of the disease in the future.

Suppression of presynaptic corticostriatal glutamate activity attenuates L-dopa-induced dyskinesia in 6-OHDA-lesioned Parkinson's disease mice.

A common adverse effect of Parkinson's disease (PD) treatment is L-dopa-induced dyskinesia (LID). This condition results from both dopamine (DA)-dependent and DA-independent mechanisms, as glutamate inputs from corticostriatal projection neurons impact DA-responsive medium spiny neurons in the striatum to cause the dyskinetic behaviors. In this study, we explored whether suppression of presynaptic corticostriatal glutamate inputs might affect the behavioral and biochemical outcomes associated with LID. We first established an animal model in which 6-hydroxydopamine (6-OHDA)-lesioned mice were treated daily with L-dopa (10 mg/kg, i.p.) for 2 weeks; these mice developed stereotypical abnormal involuntary movements (AIMs). When the mice were pretreated with the NMDA antagonist, amantadine, we observed suppression of AIMs and reductions of phosphorylated ERK1/2 and NR2B in the striatum. We then took an optogenetic approach to manipulate glutamatergic activity. Slc17a6 (vGluT2)-Cre mice were injected with pAAV5-Ef1a-DIO-eNpHR3.0-mCherry and received optic fiber implants in either the M1 motor cortex or dorsolateral striatum. Optogenetic inactivation at either optic fiber implant location could successfully reduce the intensity of AIMs after 6-OHDA lesioning and L-dopa treatment. Both optical manipulation strategies also suppressed phospho-ERK1/2 and phospho-NR2B signals in the striatum. Finally, we performed intrastriatal injections of LDN 212320 in the dyskenesic mice to enhance expression of glutamate uptake transporter GLT-1. Sixteen hours after the LDN 212320 treatment, L-dopa-induced AIMs were reduced along with the levels of striatal phospho-ERK1/2 and phospho-NR2B. Together, our results affirm a critical role of corticostriatal glutamate neurons in LID and strongly suggest that diminishing synaptic glutamate, either by suppression of neuronal activity or by upregulation of GLT-1, could be an effective approach for managing LID.

A Case of Diabetic Chorea Secondary to Appetite Loss Due to COVID-19 Vaccination.

A 76-year-old woman with type 2 diabetes mellitus was admitted to our hospital with a complaint of involuntary movements of the limbs and face. Brain MRI demonstrated a bilateral high signal of putamen on the T1 weighted image, and she was diagnosed with diabetic chorea. She took a second dose of the COVID-19 vaccine 28 days before admission and lost her appetite. Consequently, her HbA1c level on admission decreased from 13.5% to 10.0% in 28 days. This case suggests that diabetic chorea could be induced by the rapid amelioration of a hyperglycemic state due to appetite loss after COVID-19 mRNA vaccination.

Axon terminal hypertrophy of striatal projection neurons with levodopa-induced dyskinesia priming.

Background: A rat model of levodopa-induced dyskinesia (LID) showed enlarged axon terminals of striatal direct pathway neurons in the internal segment of the globus pallidus (GPi) with excessive gamma-aminobutyric acid (GABA) storage in them. Massive GABA release to GPi upon levodopa administration determines the emergence of LID. Objectives: We examined whether LID and axon terminal hypertrophy gradually develop with repeated levodopa treatment in Parkinsonian rats to examine if the hypertrophy reflects dyskinesia priming. Methods: 6-hydroxydopamine-lesioned hemiparkinsonian rats were randomly allocated to receive saline injections (placebo group, 14 days; n = 4), injections of 6 mg/kg levodopa methyl ester combined with 12.5 mg/kg benserazide (levodopa-treated groups, 3-day-treatment; n = 4, 7-day-treatment; n = 4, 14-day-treatment; n = 4), or injections of 6 mg/kg levodopa methyl ester with 12.5 mg/kg benserazide and 1 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin for 14 days (8-OH-DPAT-treated group; n = 4). We evaluated abnormal involuntary movement (AIM) scores and axon terminals in the GPi. Results: The AIM score increased with levodopa treatment, as did the hypertrophy of axon terminals in the GPi, showing an increased number of synaptic vesicles in hypertrophied terminals. Conclusion: Increased GABA storage in axon terminals of the direct pathway neurons represents the priming process of LID.

Disappearance of hemichorea as the initial presentation of moyamoya disease after revascularization surgery regardless of residual hypoperfusion evaluated by quantitative N-isopropyl-p-123I-iodoamphetamine SPECT.

BACKGROUND AND IMPORTANCE: Although hypoperfusion of the basal ganglia or the frontal subcortical matter is suspected, the pathology of chorea in moyamoya disease remains unclarified. Herein, we report a case of moyamoya disease presenting with hemichorea and evaluate pre- and postoperative perfusion using single photon emission computed tomography with N-isopropyl-p-123I-iodoamphetamine (123I-IMP SPECT). CLINICAL PRESENTATION: An 18-year-old woman presented with choreic movement of her left limbs. Magnetic resonance imaging revealed an ivy sign, and 123I-IMP SPECT demonstrated decreased cerebral blood flow (CBF) and cerebral vascular reserve (CVR) values in the right hemisphere. The patient underwent direct and indirect revascularization surgery to improve cerebral hemodynamic impairment. The choreic movements entirely resolved immediately after surgery. Although CBF and CVR values in the ipsilateral hemisphere demonstrated by quantitative SPECT increased, these did not reach the normal values threshold. CONCLUSION: Choreic movement in moyamoya disease may be related to cerebral hemodynamic impairment. Further studies are required to elucidate its pathophysiological mechanisms.

A Case of Drug-Resistant Myoclonus Improved by Only Slight Adjustment to the Hemodialysis Setting.

Myoclonus, a rare complication in patients with end-stage renal disease, is typically ameliorated through hemodialysis. The present case concerns an 84-year-old male with chronic renal failure undergoing hemodialysis, presenting involuntary movements in his limbs, which gradually worsened from the initiation of hemodialysis without constant elevation of serum blood urea nitrogen and electrolytes levels. Surface electromyography revealed characteristic findings consistent with myoclonus. He was diagnosed with subcortical-nonsegmental myoclonus related to hemodialysis, and the myoclonus was significantly alleviated after slightly increasing the post-dialysis target weight even though drug treatment was ineffective. This case suggests that drug-resistant myoclonus in patients with renal failure may be improved by adjusting hemodialysis settings, even in cases of atypical dialysis disequilibrium syndrome.

Dramatic Responses to Low-Dose Pramipexole in Painful Legs and Moving Toes Syndrome.

Painful legs and moving toes syndrome (PLMTS) is a rare movement disorder characterized by spontaneous abnormal, involuntary toe movements and unilateral or bilateral lower extremity pain that predominantly affects women in middle age or later. The background etiology of PLMTS includes peripheral neuropathy, a history of trauma, and nerve root damage, but the cause of the disease is often undetermined. The pain usually occurs first and is often more distressing to the patient than abnormal toe movement. Spontaneous resolution is rare, and symptomatic therapies include the oral administration of anticonvulsants, antidepressants, and various pain relievers, as well as other therapeutic interventions, including botulinum toxin injection and epidural block, but their effectiveness is uncertain. We report a case of PMLTS in which low doses of pramipexole, a non-ergot dopamine agonist, dramatically improved both abnormal toe movement and leg pain, which are documented by videography.

Neurological insights on two siblings with GM3 synthase deficiency due to novel compound heterozygous ST3GAL5 variants.

BACKGROUND: ST3GAL5 encodes GM3 synthase (ST3 beta-galactoside alpha-2,3-sialyltransferase 5; ST3GAL5), which synthesizes GM3 by transferring sialic acid to lactosylceramide. GM3, a sialic acid-containing glycosphingolipid known as ganglioside, is a precursor to the biosynthesis of various more complex gangliosides that are active in the brain. Biallelic variants in ST3GAL5 cause GM3 synthase deficiency (GM3SD), a rare congenital disorder of glycosylation. GM3SD was first identified in the Amish population in 2004. CASE: We report two siblings diagnosed with GM3SD due to novel compound heterozygous ST3GAL5 variants. The novel ST3GAL5 variants, detected by whole-exome sequencing in the patients, were confirmed to be pathogenic by GM3 synthase assay. The clinical courses of these patients, which began in infancy with irritability and growth failure, followed by developmental delay and hearing loss, were consistent with previous case reports of GM3SD. The older sibling underwent deep brain stimulation for severe involuntary movements at the age of 9 years. The younger sibling suffered from acute encephalopathy at the age of 9 months and subsequently developed refractory epilepsy. DISCUSSION: Reports of GM3SD outside the Amish population are rare, and whole-exome sequencing may be required to diagnose GM3SD in non-Amish patients. Since an effective treatment for GM3SD has not yet been established, we might select deep brain stimulation as a symptomatic treatment for involuntary movements in GM3SD.

De novo Huntington′s disease due to paternal intermediate alleles: a case report and literature review / 中华神经科杂志

Objective:To report the clinical manifestation and genetic characteristics of a case of de novo Huntington′s disease due to paternal intermediate alleles. Methods:Clinical data and imaging features of a middle-aged female, who complained of unstable walking without positive family history and was admitted to Xuanwu Hospital, Capital Medical University on September 20, 2022, were retrospectively analyzed. The serum samples of the patient and her parents were used to screen HTT gene dynamic mutation in accordance with the principle of informed consent and voluntary. And the relevant literatures were reviewed. Results:This is a 38-year-old female with progressive course, who presented as ataxia, involuntary movement at the end of extremities, dystonia, and cognitive impairment. Imaging results showed atrophy of bilateral caudate nuclei, as well as decreased glucose metabolism of bilateral caudate nuclei, putamen and partial cortex. Genetic testing showed the abnormal expansion of polymorphic trinucleotide (CAG) repeats in HTT gene and confirmed the diagnosis of Huntington′s disease. The CAG repeat length of the patient was 17/47 (pathopoiesis), of the father was 17/35 (intermediate alleles), and of the mother was 17/17 (normal). Conclusions:Paternal intermediate alleles may cause the first case of Huntington′s disease in a family. Importantly, HTT gene screening should be performed for the patient and parents when the diagnosis of Huntington′s disease is clinically possible despite negative family history, to prevent the misdiagnosis.

Late-onset, first-ever involuntary movement after successful surgical revascularization for pediatric moyamoya disease - Report of two cases.

Background: A small number of children with Moyamoya disease develop involuntary movements as an initial presentation at the onset, which usually resolves after effective surgical revascularization. However, involuntary movements that did not occur at the onset first occur after surgery in very rare cases. In this report, we describe two pediatric cases that developed involuntary movements during the stable postoperative period after successful surgical revascularization. Case Description: A 10-year-old boy developed an ischemic stroke and successfully underwent combined bypass surgery. However, he developed chorea six months later. Another 8-year-old boy developed a transient ischemic attack and successfully underwent combined bypass surgery. However, he developed chorea three years later. In both cases, temporary use of haloperidol was quite effective in resolving the symptoms, and involuntary movements did not recur without any medication during follow-up periods of up to 10 years. Conclusion: Postoperative first-ever involuntary movement is very rare in pediatric moyamoya disease, and the underlying mechanisms are still unclear, but a temporary, reversible imbalance of excitatory and inhibitory circuits in the basal ganglia may trigger the occurrence of these rare symptoms. Careful follow-up would be mandatory.

ACUTE CHOREO-DYSTONIA IN A NEWLY DIAGNOSED PATIENT WITH DIABETES MELLITUS: A CASE REPORT AND REVIEW OF LITERATURE.

Introduction: Diabetes mellitus is a disease with diverse macrovascular and microvascular consequences. One of the unusual effects of hyperglycemia is involuntary movement, termed hyperglycemia-induced involuntary movement. This could range from hemibalismus, chorea, choreo-atethosis, tremors to dystonia. Chorea associated with dystonia is a less commonly reported manifestation. When it is focal, it can be misdiagnosed as stroke or seizure disorder. To the best our knowledge, there is hitherto no case report in sub-Saharan Africa describing the occurrence of focal choreo-dystonia in type 2 Diabetes Mellitus. Case presentation: Here, we present a case of a middle-aged Nigerian woman with focal choreo-dystonia of the right upper limb accompanying the diagnosis of type 2 diabetes. Achieving euglycemia with insulin resulted in complete resolution of the choreo-dystonia. Conclusion: Doctors in resource-constrained settings should be aware of this presentation to avoid misdiagnosis and to provide prompt and goal-oriented management with a view to reducing morbidity and attendant health-care costs.

A new era in the diagnosis and treatment of tardive dyskinesia.

Tardive dyskinesia (TD) is a heterogeneous, hyperkinetic movement disorder induced by dopamine-receptor blocking agents that presents a unique challenge in the treatment of psychosis. Although acceptance of TD as a serious consequence of antipsychotic treatment was resisted initially, subsequent research by many investigators in psychopharmacology contributed to a rich store of knowledge on many aspects of the disorder. While basic neuroscience investigations continue to deepen our understanding of underlying motor circuitry, past trials of potential treatments of TD focusing on a range of theoretical targets were often inconclusive. Development of newer antipsychotics promised to reduce the risk of TD compared to older drugs, but their improved tolerability unexpectedly enabled an expanding market that paradoxically both increased the absolute number of patients at risk and diminished attention to TD which was relegated to legacy status. Fortunately, development and approval of novel vesicular monoamine transporter inhibitors offered evidence-based symptomatic treatment of TD for the first time and rekindled interest in the disorder. Despite recent progress, many questions remain for future research including the mechanisms underlying TD, genetic predisposition, phenomenological diversity, whether new cases are reversible, how to implement best practices to prevent and treat TD, and whether the development of novel antipsychotics free of the risk of TD is attainable. We owe our patients the aspirational goal of striving for zero prevalence of persistent symptoms of TD in anyone treated for psychosis.

Unique, Not Psychogenic Movements: Painful Leg and Moving Toes Syndrome.

A 74-year-old woman visited our department for distally predominant unpleasant pain in the bilateral feet for several months. She had a history of chronic lumbago. Neurological examinations showed normal findings other than involuntary movements. A nerve conduction study, electroencephalography, and brain MRI revealed unremarkable findings, while spinal MRI revealed mild lumbar spinal stenosis. Given the typical unique movements, i.e., bilateral toe movements, which are asynchronous and consist of extension, flexion, and, rarely, abduction, she was diagnosed with painful leg moving toes syndrome. Administration of duloxetine produced partial pain relief and reduced movements. We considered that clinicians should be aware of this unique movement disorder in order to avoid misdiagnosis with psychogenic conditions.

Efficacy and safety of valbenazine in Japanese patients with tardive dyskinesia: A multicenter, randomized, double-blind, placebo-controlled study (J-KINECT).

AIM: Valbenazine is approved in the US for treatment of tardive dyskinesia (TD); however, efficacy/safety data in Asian populations are lacking. We assessed the efficacy/safety of valbenazine in Japanese patients. METHODS: This phase II/III, multicenter, randomized, double-blind, placebo-controlled study (NCT03176771) included adult psychiatric patients with TD, who were randomly allocated to receive placebo or valbenazine (once-daily 40- or 80-mg) for a 6-week, double-blind period, after which the placebo group was switched to valbenazine for a 42-week extension. The primary endpoint was change from baseline in Abnormal Involuntary Movement Scale (AIMS) total score at Week 6; clinical global impression of improvement of TD (CGI-TD) was also assessed. RESULTS: Of 256 patients, 86, 85, and 85 were allocated to the 40-mg valbenazine, 80-mg valbenazine, and placebo groups, respectively. Least-squares mean (95% confidence interval) change from baseline in AIMS score at Week 6 was -2.3 (-3.0 to -1.7) in the valbenazine 40-mg group, -3.7 (-4.4 to -3.0) in the 80-mg group, and -0.1 (-0.8 to 0.5) in the placebo group; both treatment groups showed statistically significant improvements vs. placebo. Patients switched to valbenazine at Week 6 showed similar improvements in AIMS scores, which were maintained to Week 48. Improvements in CGI-TD scores were observed for both treatment groups vs. placebo. Incidence of adverse events was highest in the 80-mg group; common events included nasopharyngitis, somnolence, schizophrenia worsening, hypersalivation, insomnia, and tremor. CONCLUSION: The efficacy/safety profile of valbenazine was similar to that of previous clinical trials, supporting its use for TD treatment in Japanese patients.

Simultaneous assay of urine sepiapterin and creatinine in patients with sepiapterin reductase deficiency.

OBJECTIVES: Sepiapterin reductase deficiency (SRD) causes central nervous system symptoms due to dopamine and serotonin depletion because sepiapterin reductase plays an important role in tetrahydrobiopterin biosynthesis. SRD cannot be detected by newborn screening because of the absent hyperphenylalaninemia. To diagnose SRD biochemically, confirmation of reduced monoamine metabolites and elevated sepiapterin in the cerebrospinal fluid (CSF) has been considered necessary, because a past study showed no elevation of urine sepiapterin. Recently, however, the elevation of urine sepiapterin in SRD was reported. METHODS: We developed a fast method to measure sepiapterin and creatinine simultaneously using high-performance liquid chromatography with fluorescence and ultraviolet detection. Urine sepiapterin and creatinine were measured in three SRD patients, two SRD carriers, four SRD siblings, and 103 non-SRD patients. RESULTS: In the three SRD cases, concentrations of urine sepiapterin were 1086, 914, and 575 µmol/mol creatinine (upper limit: 101.7 µmol/mol creatinine), and were markedly higher than those in other groups. CSF sepiapterin concentration was also measured in one SRD case and it was 4.1 nmol/L (upper limit: 0.5 nmol/L). CONCLUSIONS: The simultaneous determination of urine sepiapterin and creatinine appears helpful for the diagnosis of SRD. This assay system can also be used to measure sepiapterin in the CSF.