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Archivos de La Sociedad Espanola de... Jun 2024Benign essential blepharospasm (BEB) is the most common adult-onset focal facial dystonia and its treatment of choice is periodic application of botulinum toxin (BtA)....
BACKGROUND
Benign essential blepharospasm (BEB) is the most common adult-onset focal facial dystonia and its treatment of choice is periodic application of botulinum toxin (BtA). It has a higher incidence in middle and late adulthood, especially in women between 40 and 60 years of age.
OBJECTIVE
To carry out the translation and cross-cultural adaptation of the CDQ24 questionnaire in its Spanish version in patients diagnosed with BEB who have been treated with BtA in an ophthalmologic center in Bogotá - Colombia.
MATERIALS AND METHODS
Pilot test of validation study and adaptation of a scale assembled in a prospective cohort of the CDQ24 instrument to Spanish in adult patients with primary blepharospasm treated with botulinum toxin in Bogota, Colombia.
RESULTS
We obtained a sample of 26 patients to whom the instrument was applied after translation and retranslation of the original document, composed of 19 (73%) women with a median age of 64.5 years; the average time to answer the survey was 4.93 min. The internal consistency of the scale evaluated by Cronbach's Alpha had a total score of 0.78. Criterion validity between the CDQ24 scale and the WHOQOL-BREF quality of life scale was determined by determining correlation between the Emotional Well-Being and Phsychological domains of both scales.
CONCLUSIONS
The translation and cross-cultural adaptation of the CDQ-24 scale into Spanish allowed the applicability of the instrument to the Spanish-speaking population during the pilot test, which allows us to continue the relevant studies in the study population.
PubMed: 38878820
DOI: 10.1016/j.oftale.2024.04.013 -
Movement Disorders Clinical Practice Jun 2024
PubMed: 38877772
DOI: 10.1002/mdc3.14137 -
Parkinsonism & Related Disorders Jun 2024Patients with classic-onset corticobasal syndrome (CBS) present with asymmetric limb apraxia and parkinsonism. We have, however, observed patients who initially present...
INTRODUCTION
Patients with classic-onset corticobasal syndrome (CBS) present with asymmetric limb apraxia and parkinsonism. We have, however, observed patients who initially present with speech and/or language (SL) problems and several years later develop CBS (i.e., SL-onset CBS). We aimed to compare clinical, neuroimaging and pathological characteristics of classic-onset CBS with SL-onset CBS.
METHODS
We conducted a retrospective cohort study of 62 patients who met criteria for CBS (17 presented with classic-onset CBS and 45 had SL-onset CBS). We compared demographics, clinical characteristics, and grey and white matter volume loss with SPM12 between groups and assessed pathology and corticobasal degeneration (CBD) pathological lesion counts in patients who had died and undergone autopsy.
RESULTS
Median age at CBS diagnosis was 66.4 years in classic-onset CBS and 73.6 years in SL-onset CBS. Classic-onset CBS had higher frequencies of dystonia, myoclonus, and alien limb phenomenon, while SL-onset CBS had a higher frequency of vertical supranuclear gaze palsy. Both groups showed smaller frontoparietal volumes than controls, with SL-onset CBS having greater volume loss in the left supplementary motor area than classic-onset CBS. All three classic-onset CBS cases with autopsy (100 %) had CBD pathology while 8/21 of SL-onset CBS cases (38 %) had CBD. Pathological lesion burden (including astrocytic plaques) did not differ between classic-onset and SL-onset CBS.
CONCLUSION
Classic-onset and SL-onset CBS appear to be different syndromes, with the former being a more profuse motor syndrome. The more widespread volume loss in SL-onset CBS likely reflects longer disease course.
PubMed: 38875956
DOI: 10.1016/j.parkreldis.2024.107025 -
Frontiers in Neurology 2024Laryngeal dystonia is a task-specific focal dystonia of laryngeal muscles that impairs speech and voice production. At present, there is no cure for LD. The most common...
BACKGROUND
Laryngeal dystonia is a task-specific focal dystonia of laryngeal muscles that impairs speech and voice production. At present, there is no cure for LD. The most common therapeutic option for patients with LD involves Botulinum neurotoxin injections.
OBJECTIVE
Provide empirical evidence that non-invasive vibro-tactile stimulation (VTS) of the skin over the voice box can provide symptom relief to those affected by LD.
METHODS
Single-group 11-week randomized controlled trial with a crossover between two dosages (20 min of VTS once or 3 times per week) self-administered in-home in two 4-week blocks. Acute effects of VTS on voice and speech were assessed in-lab at weeks 1, 6 and 11. Participants were randomized to receive either 40 Hz or 100 Hz VTS.
MAIN OUTCOME MEASURES
Primary: (CPPS) of the voice signal to quantify voice and speech abnormalities, and (PSE) ranked by participants as a measure of voice effort (scale 1-10). Secondary: during continuous speech, the (CAPE-V) inventory as a measure of overall disease severity and the 30-item self report.
RESULTS
Thirty-nine people with a confirmed diagnosis of adductor-type LD (mean [SD] age, 60.3 [11.3] years; 18 women and 21 men) completed the study. A single application of VTS improved voice quality (median CPPS increase: 0.41 dB, 95% CI [0.20, 0.61]) and/or reduced voice effort (PSE) by at least 30% in up to 57% of participants across the three study visits. Effects lasted from less than 30 min to several days. There was no effect of dosage and no evidence that the acute therapeutic effects of VTS increased or decreased longitudinally over the 11-week study period. Both 100 and 40 Hz VTS induced measurable improvements in voice quality and speech effort. VTS induced an additional benefit to those receiving Botulinum toxin. Participants, not receiving Botulinum treatment also responded to VTS.
CONCLUSION
This study provides the first systematic empirical evidence that the prolonged use of laryngeal VTS can induce repeatable acute improvements in voice quality and reductions of voice effort in LD.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov ID: NCT03746509.
PubMed: 38872829
DOI: 10.3389/fneur.2024.1403050 -
BMJ Case Reports Jun 2024We present a rare case of low titre GAD65 antibody-associated autoimmune encephalitis and status epilepticus in a young woman. She initially presented with left arm...
We present a rare case of low titre GAD65 antibody-associated autoimmune encephalitis and status epilepticus in a young woman. She initially presented with left arm dystonic movements, contractures and status epilepticus. Due to the concern of autoimmune encephalitis and seizures, the patient received intravenous immunoglobulin empirically. After the detection of low serum GAD65 antibodies, the patient underwent immunomodulation therapy with significant improvement. This case demonstrated that in autoimmune encephalitis, it is important to monitor serum GAD65 antibodies levels and consider immunotherapy, despite mildly elevated serum levels. The patient's history of left arm dystonic movements without impaired awareness may have been due to limb dystonia, a presenting symptom of stiff person syndrome (SPS), despite SPS more commonly affecting axial muscles. This case further demonstrates that GAD65 antibody-related syndromes can manifest with different neurological phenotypes including co-occurrence of epilepsy with possible focal SPS despite low GAD65 antibodies titres.
Topics: Humans; Female; Glutamate Decarboxylase; Immunoglobulins, Intravenous; Autoantibodies; Adult; Status Epilepticus; Encephalitis; Immunotherapy; Hashimoto Disease
PubMed: 38871638
DOI: 10.1136/bcr-2024-260503 -
Journal of Pharmacy Practice Jun 2024Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic...
Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic drug monitoring (TDM). PTH has been observed to induce a variety of Adverse drug reactions (ADRs) including ataxia, dystonia, nystagmus, dyskinesia, etc. Phenytoin-induced ataxia is an uncommonly observed ADR of Phenytoin whose reports are extremely limited. Herein, we present a case report of a 16-year-old Asian patient with a past history of epilepsy that was admitted to a tertiary care hospital due to the development of ataxia, giddiness, and vomiting when taking Phenytoin in addition to Oxcarbazepine, Clobazam, and Levetiracetam to treat seizures. On admission, Magnetic resonance imaging (MRI) findings revealed bilateral variable cerebrospinal fluid (CSF) lesions in the parieto-occipital region of the periventricular area (periventricular leukomalacia). Additionally, serum Phenytoin levels were observed to be in the toxic range (40 μg/mL) due to which physicians confirmed the ADR to be due to Phenytoin toxicity. Thus, the Phenytoin drug was discontinued in the patient gradually and he was continued on clobazam, oxcarbazepine, and brivaracetam which led to reversal of the ADR in the patient. In this case, ataxia resulted from Phenytoin overdose, as confirmed by MRI and serum tests suggesting that TDM of Phenytoin is essential to prevent ADRs. Given the scarcity of ataxia cases caused by Phenytoin, awareness is lacking within the scientific community. Our aim is to provide insights to promote better monitoring and patient-centered treatment outcomes for epileptic patients.
PubMed: 38871356
DOI: 10.1177/08971900241262379 -
Operative Neurosurgery (Hagerstown, Md.) Jun 2024Deep brain stimulation (DBS) has developed into an effective therapy for several disease states including treatment-resistant Parkinson disease and medically intractable...
BACKGROUND AND OBJECTIVES
Deep brain stimulation (DBS) has developed into an effective therapy for several disease states including treatment-resistant Parkinson disease and medically intractable essential tremor, as well as segmental, generalized and cervical dystonia, and obsessive-compulsive disorder (OCD). Dystonia and OCD are approved with Humanitarian Device Exemption. In addition, DBS is also approved for the treatment of epilepsy in the anterior nucleus of the thalamus. Although overall considered an effective treatment for Parkinson disease and epilepsy, a number of specific factors determine the treatment success for DBS including careful patient selection, effective postoperative programming of DBS devices and accurate electrode placement. Furthermore, invasiveness of the procedure is a rate limiter for patient adoption. It is desired to explore a less invasive way to deliver DBS therapy.
METHODS
Here, we report for the first time the direct comparison of endovascular and parenchymal DBS in a triplicate ovine model using the anterior nucleus of the thalamus as the parenchymal target for refractory epilepsy.
RESULTS
Triplicate ovine studies show comparable sensing resolution and stimulation performance of endovascular DBS with parenchymal DBS.
CONCLUSION
The results from this feasibility study opens up a new frontier for minimally invasive DBS therapy.
PubMed: 38869291
DOI: 10.1227/ons.0000000000001226 -
The Journal of Pharmacology and... Jun 2024Mutations in the gene, which encodes the abundant brain G-protein Gα, result in neurologic disorders characterized by developmental delay, epilepsy, and movement...
Mutations in the gene, which encodes the abundant brain G-protein Gα, result in neurologic disorders characterized by developmental delay, epilepsy, and movement abnormalities. There are over 50 mutant alleles associated with disorders; the R209H mutation results in dystonia, choreoathetosis, and developmental delay without seizures. Mice heterozygous for the human mutant allele ( ) exhibit hyperactivity in open field tests but no seizures. We developed self-complimentary adeno-associated virus vectors (scAAV9) expressing two splice variants of human Gα isoforms 1 (GA, ) and 2 (GB, ). Bilateral intra-striatal injections of either scAAV9- or scAAV9- significantly reversed mutation-associated hyperactivity in open field tests. overexpression did not increase seizure susceptibility, a potential side-effect of vector treatment. This represents the first report of successful preclinical gene therapy for encephalopathy applied Further studies are needed to uncover the molecular mechanism that results in behavior improvements after scAAV9-mediated Gα expression and to refine the vector design. mutations cause a spectrum of developmental, epilepsy, and movement disorders. Here, we show that intra-striatal delivery of scAAV9- to express the wild-type Gα protein reduces the hyperactivity of the mouse model, which carries one of the most common movement disorder-associated mutations. This is the first report of a gene therapy for encephalopathy applied on a patient-allele model.
PubMed: 38866563
DOI: 10.1124/jpet.124.002117 -
Journal of Psychiatric Research Jun 2024Deep brain stimulation (DBS) has been reported as a therapy option for the motor dysfunction of severe tardive dystonia (TD). The major psychiatric diseases, however,...
BACKGROUND
Deep brain stimulation (DBS) has been reported as a therapy option for the motor dysfunction of severe tardive dystonia (TD). The major psychiatric diseases, however, are contraindications to DBS treatment in TD patients.
METHODS
Six severe, medically refractory TD patients undergoing bilateral anterior capsulotomy combined with bilateral subthalamic nucleus (STN)-DBS treatment were studied retrospectively at two time points: pre-operation, and 1-3 years post-operation. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to assess the dystonia and disability. Depressive, anxiety, psychiatric symptoms, and Quality of Life (QoL) were evaluated using the 17-item Hamilton Depression Scale (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive and Negative Syndrome Scale (PANSS), and 36-item Short-Form Health Survey (SF-36), respectively.
RESULTS
After receiving the combination treatment for 25 ± 11.6 months (range, 12-41 months), significant clinical symptom improvements were reported in TD patients. BFMDRS motor and disability scores were ameliorated by 78.5 ± 32.0% (p = 0.031) and 76.5 ± 38.6% (p = 0.031), respectively. The HAMD-17 and HAMA-14 scores were reduced by 60.3 ± 27.9% (p = 0.007) and 60.0 ± 24.6% (p = 0.009), respectively. Furthermore, the PANSS scores of the comorbidity schizophrenia TD patients decreased by 58.1 ± 6.0% (p = 0.022), and the QoL improved by 59.7 ± 14.1% (SF-36, p = 0.0001). During the research, there were no notable adverse effects or problems.
CONCLUSION
Bilateral anterior capsulotomy combined with bilateral STN-DBS may be an effective and relatively safe treatment option for severe TD comorbid with major psychiatric disorders.
PubMed: 38865864
DOI: 10.1016/j.jpsychires.2024.06.011 -
Frontiers in Network Physiology 2024Abnormal neuronal synchrony is associated with several neurological disorders, including Parkinson's disease (PD), essential tremor, dystonia, and epilepsy. Coordinated...
BACKGROUND
Abnormal neuronal synchrony is associated with several neurological disorders, including Parkinson's disease (PD), essential tremor, dystonia, and epilepsy. Coordinated reset (CR) stimulation was developed computationally to counteract abnormal neuronal synchrony. During CR stimulation, phase-shifted stimuli are delivered to multiple stimulation sites. Computational studies in plastic neural networks reported that CR stimulation drove the networks into an attractor of a stable desynchronized state by down-regulating synaptic connections, which led to long-lasting desynchronization effects that outlasted stimulation. Later, corresponding long-lasting desynchronization and therapeutic effects were found in animal models of PD and PD patients. To date, it is unclear how spatially dependent synaptic connections, as typically observed in the brain, shape CR-induced synaptic downregulation and long-lasting effects.
METHODS
We performed numerical simulations of networks of leaky integrate-and-fire neurons with spike-timing-dependent plasticity and spatially dependent synaptic connections to study and further improve acute and long-term responses to CR stimulation.
RESULTS
The characteristic length scale of synaptic connections relative to the distance between stimulation sites plays a key role in CR parameter adjustment. In networks with short synaptic length scales, a substantial synaptic downregulation can be achieved by selecting appropriate stimulus-related parameters, such as the stimulus amplitude and shape, regardless of the employed spatiotemporal pattern of stimulus deliveries. Complex stimulus shapes can induce local connectivity patterns in the vicinity of the stimulation sites. In contrast, in networks with longer synaptic length scales, the spatiotemporal sequence of stimulus deliveries is of major importance for synaptic downregulation. In particular, rapid shuffling of the stimulus sequence is advantageous for synaptic downregulation.
CONCLUSION
Our results suggest that CR stimulation parameters can be adjusted to synaptic connectivity to further improve the long-lasting effects. Furthermore, shuffling of CR sequences is advantageous for long-lasting desynchronization effects. Our work provides important hypotheses on CR parameter selection for future preclinical and clinical studies.
PubMed: 38863734
DOI: 10.3389/fnetp.2024.1351815