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BMJ Neurology Open 2024Dystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with...
BACKGROUND
Dystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with tremor. Genetic and phenotypic heterogeneity leads to variable clinical presentation.
METHODOLOGY
Next-generation sequencing technologies are being currently used in the workup of patients with inherited dystonia to determine the specific cause in the individuals with autosomal dominant, recessive, X-linked or mitochondrial inheritance patterns. Calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene variants are rare in dystonias.
RESULTS
We here present a 20-year-old man with a history of delayed milestones, flexor posturing, dysarthria, dysphagia and a negative family history from consanguineous parents. Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. MRI of the brain was unremarkable. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene (CHR19: NM_023035.2, c. 1602G>A; p. Met534Ile). Segregation analyses in both the parents revealed wild-type CACNA1A gene suggesting de novo nature of the variant with a likely pathogenic classification.
CONCLUSION
Dystonia is one of the clinical phenotypes that can be associated with CACNA1A gene mutations and we recommend that this gene either be included in the dystonia panel offered or tested when the initial primary genetic result is negative.
PubMed: 38912174
DOI: 10.1136/bmjno-2024-000710 -
Journal of Radiology Case Reports 2024Traumatic intracranial ICA dissections are not commonly seen in children. Dissection resulting in perfusion deficit warrants intervention. Here we encountered a patient...
BACKGROUND
Traumatic intracranial ICA dissections are not commonly seen in children. Dissection resulting in perfusion deficit warrants intervention. Here we encountered a patient who experienced traumatic ICA dissection, treated by endovascular stenting.
METHODS
A 10-year-old female presented with aphasia and right sided weakness following trauma. Imaging showed deficit in the left MCA territory without core. Further imaging showed dissection of the left supraclinoid ICA, confirmed by digital subtraction angiography.
RESULTS
A Neuroform Atlas stent was placed without complication. All dysarthria and weakness had resolved on follow-up 5 months post-stenting.
CONCLUSIONS
Acute stroke symptoms in children can result in lasting deficits if not treated quickly. Medical management is regarded to be first line, depending on presentation. Endovascular stenting may provide a promising means to treat pediatric ICA dissections involving perfusion deficits and mitigate permanent ischemic changes.
Topics: Humans; Female; Stents; Child; Carotid Artery, Internal, Dissection; Endovascular Procedures; Angiography, Digital Subtraction; Cerebral Infarction; Reperfusion
PubMed: 38910586
DOI: 10.3941/jrcr.v18i1.5217 -
Medicine Jun 2024This study aimed to characterize the risk factors, etiology, clinical manifestations, anatomical characteristics, stroke mechanisms, imaging features, and prognosis of... (Observational Study)
Observational Study
This study aimed to characterize the risk factors, etiology, clinical manifestations, anatomical characteristics, stroke mechanisms, imaging features, and prognosis of bilateral medial medullary infarction (BMMI). A retrospective analysis was conducted on 11 patients with BMMI who met the inclusion criteria at the Affiliated Hospital of Xuzhou Medical University from January 2013 to January 2023. The patients' imaging and clinical features were analyzed and summarized. Eleven patients (7 male, 4 female), aged 46 to 62 years, met the inclusion criteria. Common clinical presentations included dysarthria (90.9%), dysphagia (90.9%), quadriplegia (81.8%), and so on. Within 72 hours of onset, 8 cases presented with quadriplegia, 2 cases with hemiplegia, and 1 case without limb paralysis. The main risk factor for BMMI was hypertension, followed by diabetes. "Heart appearance" infarcts occurred in 4 cases (36.4%), while "Y appearance" infarcts occurred in 7 cases (63.6%). Among the patients, 3 had unilateral vertebral artery stenosis or occlusion, 5 had bilateral vertebral artery stenosis or occlusion, 2 had normal vertebral basilar artery, and 1 did not undergo cerebrovascular examination. All patients received standardized treatment for cerebral infarction. The prognosis was poor, with 81.8% of patients having an unfavorable outcome, including 1 death, 9 cases of disability, and only 1 patient achieving self-care ability after recovery. BMMI is more prevalent in males aged 45 to 60 years. The main risk factors are hypertension and diabetes. Atherosclerosis is the primary etiological subtype. The main clinical manifestations are dyskinesia, dizziness, quadriplegia, and dysarthria. The prognosis of BMMI is poor. The specific imaging features of "heart appearance" or "Y appearance" infarcts aid in the diagnosis of BMMI.
Topics: Humans; Male; Female; Middle Aged; Retrospective Studies; Medulla Oblongata; Brain Stem Infarctions; Risk Factors; Prognosis; Quadriplegia; Hypertension
PubMed: 38905383
DOI: 10.1097/MD.0000000000038336 -
Clinical Medicine Insights. Case Reports 2024Cerebral infarct associated with varicella-zoster virus (VZV) has been reported in the literature, while isolated central dizziness due to lateral medullary infarct...
BACKGROUND
Cerebral infarct associated with varicella-zoster virus (VZV) has been reported in the literature, while isolated central dizziness due to lateral medullary infarct (LMI) following VZV infection is rarely reported.
CASE REPORT
We report the case of a 65-year-old man who presented to the neurology department because of herpes zoster on the right trigeminal nerve distribution. At 12 hours after admission, he developed transient vertigo along with nausea and unsteady walking and left-sided spontaneous horizontal nystagmus, gaze-evoked nystagmus, and upbeat nystagmus. The other usual signs of LMI including Horner syndrome, dysarthria, swallowing difficulty, and hemibody sensory change were absent. Video head impulse indicated decreased head impulse gain of the vestibulo-ocular reflex for the bilateral horizontal, anterior, and posterior semicircular canals with abnormal saccade waves. Suppression head impulse paradigm showed few downward saccades reflecting anti-compensatory saccades after the end of the head impulse back to the head-fixed target and decreased vestibulo-ocular reflex gain values of bilateral semicircular canals. Brain magnetic resonance imaging (MRI) showed a small infarct in the far dorsolateral portion of the left rostral medulla. The cerebrospinal fluid was positive for VZV DNA.
CONCLUSIONS
In patients with VZV infection who develop dizziness, the possibility of cerebral infarct should be considered. Patients with facial herpes zoster and neurological symptoms always be screened for stroke using MRI and lumbar puncture should be performed and acyclovir administered empirically.
PubMed: 38895742
DOI: 10.1177/11795476241262213 -
Neuropsychopharmacology Reports Jun 2024Anticholinergic toxicity is a common occurrence in the emergency room, making it crucial for emergency clinicians to have a good understanding of this toxidrome. The...
Anticholinergic toxicity is a common occurrence in the emergency room, making it crucial for emergency clinicians to have a good understanding of this toxidrome. The neuropsychiatric effects of anticholinergic agents and anabolic steroids (ASs) can manifest as symptoms like anxiety, agitation, dysarthria, confusion, seizures, visual hallucinations, bizarre behavior, delirium, psychosis, and coma. When dealing with a conscious patient who has ingested an anticholinergic substance, a detailed history of ingestion can aid clinicians in making an accurate diagnosis. However, the lack of information about the substances consumed can complicate diagnosis. In cases where the exposure is unknown, clinicians should consider anticholinergic poisoning in patients showing signs of altered mental status and physical examination findings consistent with anticholinergic toxicity. We report four cases presenting a range of symptoms, including neuropsychiatric manifestations, following the ingestion of the same bodybuilding powders with anticholinergic properties. All four patients consumed yellow and white powders at the same time and in the same place. Laboratory analysis revealed that yellow powder and white powder contained ASs and cyproheptadine, respectively.
PubMed: 38889254
DOI: 10.1002/npr2.12460 -
Radiology Case Reports Aug 2024A 79-year-old woman with a history of resection of the ascending colon cancer presented with conscious disturbance, dysarthria, nausea, and dizziness. Computed...
A 79-year-old woman with a history of resection of the ascending colon cancer presented with conscious disturbance, dysarthria, nausea, and dizziness. Computed tomography (CT) revealed striking high-density lesions in the left cerebellum and left frontal lobe with slight perifocal edema. These lesions were suspected the coexistence of spontaneous cerebellar hemorrhage and frontal lobe metastasis, or multiple brain metastases with massive hematoma. Because of the mass effect of the cerebellar lesion and impaired consciousness, she underwent emergency resection of the cerebellar lesion which was found to be composed of grayish abnormal soft solid tissue and did not include an obvious hematoma mass. The pathological findings were consistent with brain metastasis from colon cancer. This is an impressive rare case of intraoperative solid brain metastasis with a clearly homogenous hyper-dense CT appearance mimicking intracerebral hematoma.
PubMed: 38872752
DOI: 10.1016/j.radcr.2024.05.011 -
Radiology Case Reports Aug 2024Situs inversus is a rare congenital abnormality characterized by mirror-image transposition of the major visceral organs and vessels. Few reports have discussed the use...
Situs inversus is a rare congenital abnormality characterized by mirror-image transposition of the major visceral organs and vessels. Few reports have discussed the use of mechanical thrombectomy in acute ischemic stroke with situs inversus. We present such a case, to raise awareness and deepen the knowledge on these cases. A 44-year-old man was admitted to our hospital with sudden-onset dysarthria and left-sided paresis. Computed tomography (CT) angiography revealed situs inversus and occlusion in the internal carotid artery. First, intravenous tissue plasminogen activator was administered, followed by immediate reperfusion with mechanical thrombectomy. We achieved thrombolysis in cerebral infarction grade 3. After the procedure, the patient fully recovered. Prompt diagnosis is crucial for rapid recanalization in patients with vascular anomalies such as situs inversus.
PubMed: 38872738
DOI: 10.1016/j.radcr.2024.05.012 -
Molecular Genetics and Metabolism Jun 2024The late-onset GM2 gangliosidoses, comprising late-onset Tay-Sachs and Sandhoff diseases, are rare, slowly progressive, neurogenetic disorders primarily characterized by...
The late-onset GM2 gangliosidoses, comprising late-onset Tay-Sachs and Sandhoff diseases, are rare, slowly progressive, neurogenetic disorders primarily characterized by neurogenic weakness, ataxia, and dysarthria. The aim of this longitudinal study was to characterize the natural history of late-onset GM2 gangliosidoses using a number of clinical outcome assessments to measure different aspects of disease burden and progression over time, including neurological, functional, and quality of life, to inform the design of future clinical interventional trials. Patients attending the United States National Tay-Sachs & Allied Diseases Family Conference between 2015 and 2019 underwent annual clinical outcome assessments. Currently, there are no clinical outcome assessments validated to assess late-onset GM2 gangliosidoses; therefore, instruments used or designed for diseases with similar features, or to address various aspects of the clinical presentations, were used. Clinical outcome assessments included the Friedreich's Ataxia Rating Scale, the 9-Hole Peg Test, and the Assessment of Intelligibility of Dysarthric Speech. Twenty-three patients participated in at least one meeting visit (late-onset Tay-Sachs, n = 19; late-onset Sandhoff, n = 4). Patients had high disease burden at baseline, and scores for the different clinical outcome assessments were generally lower than would be expected for the general population. Longitudinal analyses showed slow, but statistically significant, neurological progression as evidenced by worsening scores on the 9-Hole Peg Test (2.68%/year, 95% CI: 0.13-5.29; p = 0.04) and the Friedreich's Ataxia Rating Scale neurological examination (1.31 points/year, 95% CI: 0.26-2.35; p = 0.02). Time since diagnosis to study entry correlated with worsening scores on the 9-Hole Peg Test (r = 0.728; p < 0.001), Friedreich's Ataxia Rating Scale neurological examination (r = 0.727; p < 0.001), and Assessment of Intelligibility of Dysarthric Speech intelligibility (r = -0.654; p = 0.001). In summary, patients with late-onset GM2 gangliosidoses had high disease burden and slow disease progression. Several clinical outcome assessments suitable for clinical trials showed only small changes and standardized effect sizes (change/standard deviation of change) over 4 years. These longitudinal natural history study results illustrate the challenge of identifying responsive endpoints for clinical trials in rare, slowly progressive, neurogenerative disorders where arguably the treatment goal is to halt or decrease the rate of decline rather than improve clinical status. Furthermore, powering such a study would require a large sample size and/or a long study duration, neither of which is an attractive option for an ultra-rare disease with no available treatment. These findings support the development of potentially more sensitive late-onset GM2 gangliosidoses-specific rating instruments and/or surrogate endpoints for use in future clinical trials.
PubMed: 38870773
DOI: 10.1016/j.ymgme.2024.108512 -
NPJ Parkinson's Disease Jun 2024Approximately 90% of Parkinson's patients (PD) suffer from dysarthria. However, there is currently a lack of research on acoustic measurements and speech impairment... (Review)
Review
Approximately 90% of Parkinson's patients (PD) suffer from dysarthria. However, there is currently a lack of research on acoustic measurements and speech impairment patterns among Mandarin-speaking individuals with PD. This study aims to assess the diagnosis and disease monitoring possibility in Mandarin-speaking PD patients through the recommended speech paradigm for non-tonal languages, and to explore the anatomical and functional substrates. We examined total of 160 native Mandarin-speaking Chinese participants consisting of 80 PD patients, 40 healthy controls (HC), and 40 MRI controls. We screened the optimal acoustic metric combination for PD diagnosis. Finally, we used the objective metrics to predict the patient's motor status using the Naïve Bayes model and analyzed the correlations between cortical thickness, subcortical volumes, functional connectivity, and network properties. Comprehensive acoustic screening based on prosodic, articulation, and phonation abnormalities allows differentiation between HC and PD with an area under the curve of 0.931. Patients with slowed reading exhibited atrophy of the fusiform gyrus (FDR p = 0.010, R = 0.391), reduced functional connectivity between the fusiform gyrus and motor cortex, and increased nodal local efficiency (NLE) and nodal efficiency (NE) in bilateral pallidum. Patients with prolonged pauses demonstrated atrophy in the left hippocampus, along with decreased NLE and NE. The acoustic assessment in Mandarin proves effective in diagnosis and disease monitoring for Mandarin-speaking PD patients, generalizing standardized acoustic guidelines beyond non-tonal languages. The speech impairment in Mandarin-speaking PD patients not only involves motor aspects of speech but also encompasses the cognitive processes underlying language generation.
PubMed: 38866758
DOI: 10.1038/s41531-024-00720-3 -
MedRxiv : the Preprint Server For... Jun 2024Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron disease that causes progressive muscle weakness. Progressive bulbar dysfunction causes dysarthria...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron disease that causes progressive muscle weakness. Progressive bulbar dysfunction causes dysarthria and thus social isolation, reducing quality of life. The Everything ALS Speech Study obtained longitudinal clinical information and speech recordings from 292 participants. In a subset of 120 participants, we measured speaking rate (SR) and listener effort (LE), a measure of dysarthria severity rated by speech pathologists from recordings. LE intra- and inter-rater reliability was very high (ICC 0.88 to 0.92). LE correlated with other measures of dysarthria at baseline. LE changed over time in participants with ALS (slope 0.77 pts/month; p<0.001) but not controls (slope 0.005 pts/month; p=0.807). The slope of LE progression was similar in all participants with ALS who had bulbar dysfunction at baseline, regardless of ALS site of onset. LE could be a remotely collected clinically meaningful clinical outcome assessment for ALS clinical trials.
PubMed: 38853969
DOI: 10.1101/2024.05.31.24308140