Gender disparity and abuse in functional movement disorders: a multi-center case-control study.

BACKGROUND: To determine gender differences in rates of sexual and physical abuse in functional movement disorders compared to controls and evaluate if the gender disparity of functional movement disorders is associated with abuse history. METHODS: We performed a retrospective case-control study of self-reported trauma data from 696 patients (512 women) with functional movement disorders from six clinical sites compared to 141 controls (98 women) and population data. Chi-square was used to assess gender and disorder associations; logistic regression was used to model additive effects of abuse and calculate the attributable fraction of abuse to disorder prevalence. RESULTS: Higher rates of sexual abuse were reported by women (35.3%) and men (11.5%) with functional movement disorders compared to controls (10.6% of women; 5.6% of men). History of sexual abuse increased the likelihood of functional movement disorders among women by an odds ratio of 4.57 (95% confidence interval 2.31-9.07; p < 0.0001) and physical abuse by an odds ratio of 2.80 (95% confidence interval 1.53-5.12; p = 0.0007). Population attributable fraction of childhood sexual abuse to functional movement disorders in women was 0.12 (0.05-0.19). No statistically significant associations were found in men, but our cohort of men was underpowered despite including multiple sites. CONCLUSIONS: Our study suggests that violence against women may account for some of the gender disparity in rates of functional movement disorders. Most people with functional movement disorders do not report a history of abuse, so it remains just one among many relevant risk factors to consider.

Cost-effectiveness of Erenumab Versus Surgical Trigger Site Deactivation for the Treatment of Migraine Headaches: A Systematic Review.

BACKGROUND: Migraine headache is a common, debilitating condition responsible for astronomical societal burden. The chronicity of migraine headaches necessitates the use of many healthcare services. Preventative treatment remains the desirable option for this patient population. Pharmacologic advances have led to the development of erenumab, a monoclonal antibody calcitonin gene-related peptide receptor antagonist that directly interferes with the known biochemical pathway of migraine initiation. Alternatively, surgical decompression of migraine trigger sites is a historically effective preventative option for certain patients experiencing migraine headaches. As new treatments emerge, the large economic burden of migraine headaches requires cost evaluation against already available preventative modalities. METHODS: Studies evaluating the cost-effectiveness of both erenumab and surgical trigger site deactivation were found using EMBASE and MedLine. Relevant economic data was extracted from this literature and the cost of treatment with erenumab was compared with surgical decompression. RESULTS: The market price of erenumab is $6900/yr. Speculative models predicted a direct annual healthcare cost ranging from $11,404 to $12,988 for patients experiencing episodic migraine. For chronic migraine patients, this range extended to $25,604. Annual indirect costs ranged from $7601 to $19,377. Prospective and model-based studies evaluating surgical trigger site deactivation reported an average 1 time surgical cost between $6956 and $10,303. In episodic migraine, subsequent annual healthcare costs were $900. CONCLUSIONS: Erenumab has potential to be a revolutionary noninvasive preventative treatment for migraine headache. With that said, the cost-conscious option for patients receiving more than 1 year of treatment remains surgical trigger site deactivation.

In vivo assessment of neurodegeneration in Spinocerebellar Ataxia type 7.

Spinocerebellar Ataxia type 7 (SCA7) is a neurodegenerative disease characterized by progressive cerebellar ataxia and retinal degeneration. Increasing loss of visual function complicates the use of clinical scales to track the progression of motor symptoms, hampering our ability to develop accurate biomarkers of disease progression, and thus test the efficacy of potential treatments. We aimed to identify imaging measures of neurodegeneration, which may more accurately reflect SCA7 severity and progression. While common structural MRI techniques have been previously used for this purpose, they can be biased by neurodegeneration-driven increases in extracellular CSF-like water. In a cross-sectional study, we analyzed diffusion tensor imaging (DTI) data collected from a cohort of 13 SCA7 patients and 14 healthy volunteers using: 1) a diffusion tensor-based image registration technique, and 2) a dual-compartment DTI model to control for the potential increase in extracellular CSF-like water. These methodologies allowed us to assess both volumetric and microstructural abnormalities in both white and gray matter brain-wide in SCA7 patients for the first time. To measure tissue volume, we performed diffusion tensor-based morphometry (DTBM) using the tensor-based registration. To assess tissue microstructure, we computed the parenchymal mean diffusivity (pMD) and parenchymal fractional anisotropy (pFA) using the dual compartment model. This model also enabled us to estimate the parenchymal volume fraction (pVF), a measure of parenchymal tissue volume within a given voxel. While DTBM and pVF revealed tissue loss primarily in the brainstem, cerebellum, thalamus, and major motor white matter tracts in patients (p < 0.05, FWE corrected; Hedge's g > 1), pMD and pFA detected microstructural abnormalities in virtually all tissues brain-wide (p < 0.05, FWE corrected; Hedge's g > 1). The Scale for the Assessment and Rating of Ataxia trended towards correlation with cerebellar pVF (r = -0.66, p = 0.104, FDR corrected) and global white matter pFA (r = -0.64, p = 0.104, FDR corrected). These results advance our understanding of neurodegeneration in living SCA7 patients by providing the first voxel-wise characterization of white matter volume loss and gray matter microstructural abnormalities. Moving forward, this comprehensive approach could be applied to characterize the full spatiotemporal pattern of neurodegeneration in SCA7, and potentially develop an accurate imaging biomarker of disease progression.

KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation.

Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although KMT2B-related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease. We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5-37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke Fahn Marsden's Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at 6 months, 1 year and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002 and P = 0.012). At 1 year post-deep brain stimulation, >50% of subjects showed BFMDRS-M and BFMDRS-D improvements of >30%. In the long-term deep brain stimulation cohort (deep brain stimulation inserted for >5 years, n = 8), improvement of >30% was maintained in 5/8 and 3/8 subjects for the BFMDRS-M and BFMDRS-D, respectively. The greatest BFMDRS-M improvements were observed for trunk (53.2%) and cervical (50.5%) dystonia, with less clinical impact on laryngeal dystonia. Improvements in gait dystonia decreased from 20.9% at 1 year to 16.2% at last assessment; no patient maintained a fully independent gait. Reduction of BFMDRS-D was maintained for swallowing (52.9%). Five patients developed mild parkinsonism following deep brain stimulation. KMT2B-related disease comprises an expanding continuum from infancy to adulthood, with early evidence of genotype-phenotype correlations. Except for laryngeal dysphonia, deep brain stimulation provides a significant improvement in quality of life and function with sustained clinical benefit depending on symptoms distribution.

Applicability of long-term electroencephalography in pre-mortem diagnosis of Creutzfeldt-Jakob disease: A case report.

Creutzfeldt-Jakob disease accounts for more than 90% of all sporadic prion disease cases. The molecular MM2 genotype has been divided into cortical and thalamic subtypes based on structures involved and is characterized clinically by progressive dementia without ataxia or typical electroencephalography changes. Proposed diagnostic criteria for MM2 cortical type sporadic Creutzfeldt-Jakob disease include progressive dementia, cortical hyper-intensity on diffusion-weighted magnetic resonance imaging, increased cerebrospinal fluid 14-3-3 protein level, and the exclusion of other types of dementia. The presence of periodic discharges on electroencephalography in MM2 cortical type were reported in 42% of the cases. We are reporting a case of sporadic Creutzfeldt-Jakob disease cortical MM2-type presenting with rapid cognitive decline, who survived 8 months since symptom onset. Brain imaging, cerebrospinal fluid analysis, and long-term electroencephalography monitoring were obtained and diagnosis was confirmed by autopsy. Short-term electroencephalography recording, performed 5 months after symptom onset, demonstrated diffuse background slowing without epileptiform activity. Long-term video electroencephalography monitoring demonstrated generalized slowing, maximum in bilateral frontal areas, which intermittently would become rhythmic (1-2 Hz) without hemispheric predominance. If the findings do not clearly meet the proposed clinical criteria for sporadic Creutzfeldt-Jakob disease, the use of long-term electroencephalography could increase the sensitivity. We question whether the lack of the characteristic findings on electroencephalography in some cases could be due to insufficient time of recording. Application of long-term electroencephalography monitoring increases the sensitivity of electroencephalography and the certainty of pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease.