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ISSN / EISSN : 0028-3878 / 1526-632X
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Lena Carolyn O'Flynn,
Background and Objectives: Laryngeal dystonia (LD) is isolated task-specific focal dystonia selectively impairing speech production. The first choice of LD treatment is botulinum neurotoxin (BoNT) injections into the affected laryngeal muscles. However, whether BoNT has a lasting therapeutic effect on disorder pathophysiology is unknown. We investigated short- and long-term effects of BoNT treatment on brain function in LD patients.Methods: A total of 161 subjects participated in the functional MRI study. Statistical analyses examined central BoNT effects in LD patients who were stratified based on the effectiveness and duration of treatment.Results: LD patients who were treated and benefited from BoNT injections had reduced activity in the left precuneus compared to BoNT-naïve and treatment non-benefiting patients. Additionally, BoNT-treated patients with adductor LD had decreased activity in the right thalamus, whereas BoNT-treated abductor LD patients had reduced activity in the left inferior frontal cortex. No statistically significant differences in brain activity were found between patients with shorter (1-5 years) and longer (13-28 years) treatment durations. However, patients with intermediate treatment duration of 6 to 12 years showed reduced activity in the right cerebellum compared to patients with both shorter and longer treatment durations and reduced activity in the right prefrontal cortex compared to patients with shorter treatment duration.Discussion: Our findings suggest that the left precuneus is the site of short-term BoNT central action in LD patients, whereas the prefrontal-cerebellar axis is engaged in the BoNT response in patients with intermediate treatment duration of 6-12 years. Involvement of these structures points to indirect action of BoNT treatment on the dystonic sensorimotor network via modulation of speech motor sequence planning and coordination.
Acute vision loss related to cerebral or retinal ischemia is a time-sensitive emergency with potential treatment options including intravenous or intraarterial thrombolysis and mechanical thrombectomy. However, patients either present in delayed fashion or present to an emergency department that lacks the subspecialty expertise to recognize and treat these conditions in a timely fashion. Moreover, healthcare systems in the United States are becoming increasingly reliant on telestroke and teleneurology services for acute neurologic care, making accurate diagnosis of acute vision loss even more challenging due to critical limitations to the remote video evaluation, including the inability to perform routine ophthalmoscopy. The COVID-19 pandemic has led to a greater reliance on telemedicine services and helped to accelerate the development of novel tools and care pathways to improve remote ophthalmologic evaluation, but these tools have yet to be adapted for use in the remote evaluation of acute vision loss. Permanent vision loss can be disabling for patients and efforts must be made to increase and improve early diagnosis and management. Herein, the authors outline the importance of improving acute ophthalmologic diagnosis, outline key limitations and barriers to the current video-based teleneurology assessments, highlight opportunities to leverage new tools to enhance the remote assessment of vision loss, and propose new avenues to improve access to emergent ophthalmology subspeciality.
, Irina Podkorytova, Marisara Dieppa,
Insular epilepsy is a great mimicker and can be mistaken for seizures originating from other areas of the brain or as non-epileptic spells. The semiology of insular epilepsy can include, but is not limited to, auditory illusions, paresthesias, gastric rising, laryngeal constriction, and hyperkinetic movements. These arise from both the functions of the insula itself and its extensive connections with other regions of the brain. Noninvasive workup can be negative or non-localizing due to the insula’s location deep within the lateral sulcus. Stereotactic EEG can therefore be an important tool in cases of insular epilepsy so that patients may be appropriately diagnosed and evaluated for potential surgical treatment. We present two cases of epilepsy with non-localizing scalp EEG and challenging semiologies, the workup undertaken to identify them as cases of insular epilepsy, and subsequent surgical treatment and outcomes.
Rachel C Kenney, , Lisena Hasanaj, Binu Joseph, Abdullah Abu Al-Hassan, Lisanne J. Balk, Raed Behbehani, , , Elliot Frohman, et al.
Background and Objectives: Recent studies have suggested that inter-eye differences (IEDs) in peripapillary retinal nerve fiber layer (pRNFL) or ganglion cell+inner plexiform (GCIPL) thickness by spectral-domain optical coherence tomography (SD-OCT) may identify people with a history of unilateral optic neuritis (ON). However, this requires further validation. Machine learning classification may be useful for validating thresholds for OCT IEDs and for examining added utility for visual function tests, such as low-contrast letter acuity (LCLA), in the diagnosis of people with multiple sclerosis (PwMS) and for unilateral ON history.Methods: Participants were from 11 sites within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. pRNFL and GCIPL thicknesses were measured using SD-OCT. A composite score combining OCT and visual measures was compared individual measurements to determine the best model to distinguish PwMS from controls. These methods were also used to distinguish those with history of ON among PwMS. ROC curve analysis was performed on a training dataset (2/3 of cohort), then applied to a testing dataset (1/3 of cohort). Support vector machine (SVM) analysis was used to assess whether machine learning models improved diagnostic capability of OCT.Results: Among 1,568 PwMS and 552 controls, variable selection models identified GCIPL IED, average GCIPL thickness (both eyes), and binocular 2.5% LCLA as most important for classifying PwMS vs. controls. This composite score performed best, with AUC=0.89 (95% CI 0.85, 0.93), sensitivity=81% and specificity=80%. The composite score ROC curve performed better than any of the individual measures from the model (p<0.0001). GCIPL IED remained the best single discriminator of unilateral ON history among PwMS (AUC=0.77, 95% CI 0.71,0.83, sensitivity=68%, specificity=77%). SVM analysis performed comparably to standard logistic regression models.Conclusions: A composite score combining visual structure and function improved the capacity of SD-OCT to distinguish PwMS from controls. GCIPL IED best distinguished those with history of unilateral ON. SVM performed as well as standard statistical models for these classifications.Classification of Evidence: The study provides Class III evidence that SD-OCT accurately distinguishes multiple sclerosis from normal controls as compared to clinical criteria.
, Jori O. Ruuskanen, Jussi O.T. Sipilä, , Päivi Rautava,
Objective: Usage of oral anticoagulants (OAC) or adenosine diphosphate inhibitors (ADPi) is known to increase the risk of bleeding. We aimed to investigate the impact of OAC and ADPi therapies on short-term outcomes after traumatic brain injury (TBI).Methods: All adult patients hospitalized for TBI in Finland during 2005–2018 were retrospectively studied using a combination of national registries. Usage of pharmacy-purchased OACs and ADPis at the time of TBI was analyzed with the pill-counting method (Social Insurance Institution of Finland). The primary outcome was 30-day case-fatality (Finnish Cause of Death Registry). The secondary outcomes were acute neurosurgical operation (ANO) and admission duration (Finnish Care Register for Health Care). Baseline characteristics were adjusted with multivariable regression including age, sex, comorbidities, skull or facial fracture, OAC/ADPi treatment, initial admission location, and the year of TBI admission.Results: The study population included 57,056 persons (mean age 66 years) of whom 0.9% used direct oral anticoagulants (DOAC), 7.1% Vitamin K antagonists (VKA), and 2.3% ADPis. Patients with VKAs had higher case-fatality than patients without OAC (15.4% vs. 7.1%; adjHR 1.35, CI 1.23–1.48; p<0.0001). Case-fatality was lower with DOACs (8.4%) than with VKAs (adjHR 0.62, CI 0.44–0.87; p=0.005) and was not different from patients without OACs (adjHR 0.93, CI 0.69–1.26; p=0.634). VKA usage was associated with higher neurosurgical operation rate compared to non-OAC patients (9.1% vs. 8.3%; adjOR 1.33, CI 1.17–1.52; p<0.0001). There was no difference in operation rate between DOAC and VKA. ADPi was not associated with case-fatality or operation rate in the adjusted analyses. VKAs and DOACs were not associated with longer admission length compared with the non-OAC group, whereas the admissions were longer in the ADPi group compared with the non-ADPi group.Conclusion: Preinjury use of VKA is associated with increases in short-term mortality and in need for ANOs after TBI. DOACs are associated with lower fatality than VKAs after TBI. ADPis were not independently associated with the outcomes studied. These results point to relative safety of DOACs or ADPis in patients at risk of head trauma and encourage to choose DOACs when oral anticoagulation is required.Classification of evidence: This study provides Class II evidence that among adults with TBI, mortality was significantly increased in those using VKAs but not in those using DOACs or ADPis.
Young Min Choe, Hyewon Baek, Hyo Jung Choi, Min Soo Byun, Dahyun Yi, Bo Kyung Sohn, Chul Ho Sohn,
Background and Objectives: Although enlarged perivascular spaces (EPVS) have been suggested as an emerging measure of small vessel disease (SVD) in the brain, their association with cognitive impairment is not yet clearly understood. We aimed to examine the relationship between each EPVS in the basal ganglia (BG-EPVS) and centrum semiovale (CSO-EPVS) with cognition in a memory clinic population.Methods: Participants with diverse cognitive spectrum were recruited from a university hospital memory clinic. They underwent comprehensive clinical and neuropsychological assessments and brain MRI. BG-EPVS and CSO-EPVS were measured on T2-weighted MRI, and then dichotomized into low and high degrees for further analyses. Other SVD markers were assessed using validated rating scales.Results: A total of 910 participants were included in this study. A high degree of BG-EPVS was significantly associated with poorer scores on executive function domain, but not with other cognitive domains, when age, sex, education, MRI scanner type, and cognitive diagnosis were controlled as covariates. However, the association between BG-EPVS and executive function was no longer significant after controlling for other markers of SVD, such as lacunar infarcts and periventricular white matter hyperintensities, as additional covariates. CSO-EPVS did not have a significant relationship with any cognitive scores regardless of the covariates.Discussion: Our findings from a large memory clinic population suggest that EPVS, regardless of topographical location, may not be used as a specific SVD marker for cognitive impairment, although an apparent association was observed between a high degree of BG-EPVS and executive dysfunction before controlling other SVD markers that share a common pathophysiological process with BG-EPVS.
, , Céline Lager, Capucine de Lattre, Yann Gary, Elisabeth Keroulle, Brigitte Feuillerat, Hervé Caudan, Zoé Sancelme, Arnaud Isapof, et al.
Background: Cerebral palsy is a life-long condition that causes heterogeneous motor disorders. Motor rehabilitation interventions must be adapted to the topography of the symptoms, ambulatory capacity and age of the individual. Current guidelines do not differentiate between the different profiles of individuals with cerebral palsy, which limits their implementation.Objectives: To develop evidence-based, implementable guidelines for motor rehabilitation interventions for individuals with cerebral palsy according to the age, topography of the cerebral palsy and ambulatory capacity of the individual, and to determine a level of priority for each intervention.Methods: We used a mixed methods design that combined a systematic review of the literature on available motor rehabilitation interventions with expert opinions. Based on the French National Authority for Health methodology, recommendations were graded as strong, conditional or weak. Interventions were then prioritized by the experts according to both the evidence and their own opinions on relevance and implementability to provide a guide for clinicians. All recommendations were approved by experts who were independent from the working group.Results: Strong recommendations as first-line treatments were made for gait training, physical activities and hand-arm bimanual intensive therapy for all children and adolescents with cerebral palsy. Moderate recommendations were made against passive joint mobilizations, muscle stretching, prolonged stretching with the limb fixed, and neurodevelopmental therapies for all children and adolescents with cerebral palsy. Strong recommendations as first-line treatments were made for gait training for all adults with cerebral palsy and moderate recommendations as moderate importance interventions for strengthening exercises and ankle-foot orthoses for motor impairment of the feet and the ankles.Discussion: These guidelines, which combine research evidence and expert opinion, could help individuals with cerebral palsy and their families to co-determine rehabilitation goals with health professionals, according to their preferences.
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