Dual target deep brain stimulation for complex essential and dystonic tremor - A 5-year follow up.

BackgroundEssential tremor (ET) is characterized by action tremor of the upper limbs, head tremor and voice tremor. Dystonic tremor (DT) is produced by muscle contractions in a body affected by dystonia. Deep brain stimulation (DBS) of ventral intermediate nucleus of the thalamus (VIM) is the most well-known advanced treatment for medication-refractory tremor. However, decline in efficacy overtime has led to explore other targets. This study aimed to measure the efficacy of bilateral dual targeting ViM/caudal Zona Incerta (cZI) stimulation on tremor control. A secondary aim was to evaluate if there was a difference in the efficacy between ET and DT.Methods36 patients were retrospectively recruited at the Walton NHS Foundation Trust, Liverpool, UK. Patients were assessed pre-operatively, and then at 1-year, 3-years, and 5-years post-operatively with the following scales: Fahn-Tolosa-Marin tremor rating (FTMTR) scale, EuroQol-5D, and Hospital Anxiety and Depression Scale.ResultsBilateral ViM-cZI DBS significantly improved overall tremor score by 45.1% from baseline to 3-years post-operatively (p  0.001).ConclusionsOur study found that bilateral ViM-cZI DBS treatment had a favourable effect on motor symptoms sustained over the 5-years in tremor patients, especially in ET group. There was limited effect on mood and QoL with similar trends in outcomes for both tremor types

The long-term outcomes of epilepsy surgery

<div><p>Objective</p><p>Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K.</p><p>Methods</p><p>This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom.</p><p>Results</p><p>We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1–27). Kaplan-Meier estimates showed that 47% (95% CI 40–58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31–45) at 10 years after surgery. 74% (95% CI 69–80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64–77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years.</p><p>Conclusion</p><p>The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections.</p></div

Genetic regulation of gene expression in the epileptic human hippocampus

Epilepsy is a serious and common neurological disorder. Expression quantitative loci (eQTL) analysis is a vital aid for the identification and interpretation of disease-risk loci. Many eQTLs operate in a tissue- and condition-specific manner. We have performed the first genome-wide cis-eQTL analysis of human hippocampal tissue to include not only normal (n = 22) but also epileptic (n = 22) samples. We demonstrate that disease-associated variants from an epilepsy GWAS meta-analysis and a febrile seizures (FS) GWAS are significantly more enriched with epilepsy-eQTLs than with normal hippocampal eQTLs from two larger independent published studies. In contrast, GWAS meta-analyses of two other brain diseases associated with hippocampal pathology (Alzheimer’s disease and schizophrenia) are more enriched with normal hippocampal eQTLs than with epilepsy-eQTLs. These observations suggest that an eQTL analysis that includes disease-affected brain tissue is advantageous for detecting additional risk SNPs for the afflicting and closely related disorders, but not for distinct diseases affecting the same brain regions. We also show that epilepsy eQTLs are enriched within epilepsy-causing genes: an epilepsy cis-gene is significantly more likely to be a causal gene for a Mendelian epilepsy syndrome than to be a causal gene for another Mendelian disorder. Epilepsy cis-genes, compared to normal hippocampal cis-genes, are more enriched within epilepsy-causing genes. Hence, we utilize the epilepsy eQTL data for the functional interpretation of epilepsy disease-risk variants and, thereby, highlight novel potential causal genes for sporadic epilepsy. In conclusion, an epilepsy-eQTL analysis is superior to normal hippocampal tissue eQTL analyses for identifying the variants and genes underlying epilepsy

A structural magnetic resonance imaging review of clinical motor outcomes from deep brain stimulation in movement disorders

Abstract Patients with movement disorders treated by deep brain stimulation do not always achieve successful therapeutic alleviation of motor symptoms, even in cases where surgery is without complications. Magnetic resonance imaging (MRI) offers methods to investigate structural brain-related factors that may be predictive for clinical motor outcomes. This review aimed to identify features which have been associated with variability in clinical post-operative motor outcomes in patients with Parkinson’s disease, dystonia, and essential tremor from structural MRI modalities. We performed a literature search for articles published between January 01, 2000, and April 01, 2022, and identified 5197 articles. Following screening through our inclusion criteria, we identified 60 total studies (39 = Parkinson’s disease, 11 = dystonia syndromes and 10 = essential tremor). The review captured a range of structural MRI methods and analysis techniques used to identify factors related to clinical post-operative motor outcomes from deep brain stimulation. Morphometric markers, including volume and cortical thickness were commonly identified in studies focused on patients with Parkinson’s disease and dystonia syndromes. Reduced metrics in basal ganglia, sensorimotor and frontal regions showed frequent associations with reduced motor outcomes. Increased structural connectivity to subcortical nuclei, sensorimotor and frontal regions were also associated with greater motor outcomes. In patients with tremor, increased structural connectivity to the cerebellum and cortical motor regions showed high prevalence across studies for greater clinical motor outcomes. In addition, we highlight conceptual issues for studies assessing clinical response with structural MRI and discuss future approaches towards optimising individualised therapeutic benefits. Although quantitative MRI markers are in their infancy for clinical purposes in movement disorder treatments, structural features obtained from MRI offer powerful potential to identify candidates who are more likely to benefit from deep brain stimulation and provide insight into the complexity of disorder pathophysiology.</jats:p

Bilateral globus pallidus internus (GPi) deep brain stimulation for cervical dystonia: Effects on motor and non-motor symptoms within 5 years follow.

BackgroundCervical Dystonia ("CD") is a movement disorder characterised by sustained muscle contractions in the neck, causing involuntary posturing. Deep brain stimulation ("DBS") of the globus pallidal internus (GPi) is advanced treatment for pharmaco-refractory patients. As CD is a rare disease, cohort studies are often limited to patients of heterogenous disease profile, small sample size or short follow-up. This study firstly aimed to measure the efficacy of GPi-DBS on motor and non-motor symptoms of CD. A secondary aim was to evaluate if clinical factors - such as age, disease duration and baseline disease severity - influence variability of motor outcomes.Methods37 idiopathic CD patients were recruited from movement disorders clinics at The Walton NHS Foundation Trust, Liverpool, UK. Patients were assessed pre-operatively, and 1 year, 3 years and 5 years post-operatively with the following clinical scales: Toronto Western Spasmodic Torticollis Rating Scale ("TWSTRS"), Hospital Anxiety and Depression Scale and EuroQuol-5D.ResultsGPI-DBS significantly improved overall TWSTRS scores by 57% from baseline to 5Y FU (p ConclusionWe concluded that GPi-DBS is an effective treatment for motor symptoms and pain in CD. There was limited effect on mood and QoL, and no clinical predictive factors of outcome were identified

High frequency spinal cord stimulation for chronic back and leg pain

Background: High frequency stimulation (HFS) may provide pain relief without the paresthesias typical of traditional low-frequency Spinal cord stimulation (SCS). Methods: A consecutive single-center series of patients was retrospectively reviewed to evaluate safety and efficacy of HF10 therapy. In this 24-month study, 62 patients with variables pathologies (44 patients with back failure surgery syndrome (FBSS), 18 patients with chronic peripheral neuropathic pain in the lower limbs (NeppL) were included to be treated with HF10. Pain outcomes were compared from preoperative baseline and at the conclusion of each study period. Clinical features, outcomes and complications were reviewed. Results: 62 patients completed this study. All patients had a successful trial before the definitive implantation of a spinal cord stimulator at the low dorsal level. The mean follow-up period was 11 months, ranging from 6 to 24 months. 6 patients showed no change from baseline visual analogue scale (VAS) after permanent implant and 2 had improved during the trial but was aggravated after the permanent implant placement. At 1 month, 63% of implanted HF10 therapy subjects were responders and 77% at 6 months. The average baseline, trial and postoperative Visual Analogue Scale (VAS) was 8.1, 3.6 and 4.2 respectively. When compared to the baseline, the average reduction achieved during the VAS trial was 4.5 points, accounting for a 56% pain reduction. The long-term failure rate was 22%. Conclusions: This study generated preliminary evidence showing improved VAS current pain scores in absence of paresthesias and increase patient satisfaction with HF10 spinal cord stimulatio

Kaplan-Meier analysis of time to first seizure.

<p>Kaplan-Meier analysis of time to first seizure.</p