Radiosurgical treatment of medically refractory Parkinson’s tremor

Introduction. In spite of medication treatment being today the basic form of treatment for Parkinson’s disease, surgical methods may be preferable to improve symptoms of the disease. Radiosurgery is one of them, but in Russia, to date, there are no publications summarizing data about the experience of using this method throughout the country.The study objective is to evaluate the effect of radiosurgical thalamotomy (destruction of the intermediate ventral nucleus of the thalamus) on the severity of tremor in patients with Parkinson’s disease, as well as to estimate the frequency of complications of this intervention, the frequency of different variants of radiological and clinical-neurological response.Materials and methods. One hundred and one (101) patients with medically refractory Parkinson’s tremor received Gamma Knife radiosurgery in our centre over a 10‑year period, of whom 10 patients were treated bilaterally. Pre-treatment evaluation was done using tremor assessment scales and video recordings of tremor intensity. Gamma Knife radiosurgery was provided with Leksell Gamma Knife 4C and Leksell Gamma Knife Perfexion (Elekta AB, Sweden) preceded by magnetic resonance tractography the day before treatment. The same planning protocol was used for all patients, the target was ventral intermediate nucleus and the prescription dose of 130 Gy was delivered with a 4 mm isocenter. After treatment, patients were evaluated radiologically and neurologically at regular 6‑month intervals, as well as through telephone interviews and video recordings.Results. Ninety-two (92) patients were included in the analysis of the results of radiosurgical treatment. Median follow-up time after radiosurgery was 26 months, from 6 to 113 months. Tremor reduction was achieved in 76 % of the patients, 61 % of whom had almost complete tremor arrest. Decreased tremors were observed from 1 to 6 months after treatment, with a mean of 4 months. Three (3) patients experienced tremor resurgence after 3–7 years. Complications were observed in 6.5 % of patients and were transient in character. Some of the patients developed severe depression. Only 1 patient had a serious complication in the form of thalamic haemorrhage (at 22 months after treatment). Ten (10) patients who were treated bilaterally all showed considerable clinical improvement and absence of complications.Conclusion. Gamma Knife radiosurgery is a safe and effective functional neurosurgical procedure for tremor correction to improve patients’ quality of life, especially when deep brain stimulation is not accessible. Patients with severe medically refractory tremors are good candidates for Gamma Knife treatment, which showed high efficacy and a low risk of complications.

COVID-19 Attributed Cases and Deaths are Statistically Higher in States and Counties with 5th Generation Millimeter Wave Wireless Telecommunications in the United States.

COVID-19-attributed case and death rates for the U.S.A. were analyzed through May 2020 in three ways – for all 50 states, the country’s largest counties, and the largest counties in California – and found to be statistically significantly higher for states and counties with compared to those without 5G millimeter wave (mmW) technology. 5G mmW index was a statistically significant factor for the higher case and rates in all three analyses, while population density, air quality and latitude were significant for only one or two of the analyses. For state averages, cases per million were 79% higher (p = 0.012), deaths per million were 94% higher (p = 0.049), cases per test were 68% higher (p = 0.003) and deaths per test were 81% higher (p = 0.025) for states with vs. without mmW. For county averages, cases per million were 87% higher (p = 0.005) and deaths per million were 165% higher (p = 0.012) for counties with vs. without mmW. While higher population density contributed to the higher mean case and death rates in the mmW states and counties, exposure to mmW had about the same impact as higher density of mmW states on mean case and death rates and about three times as much impact as higher density for mmW counties on mean case and death rates. Based on multiple linear regression, if there was no mmW exposure, case and death rates would be 18-30% lower for 5G mmW states and 39-57% lower for 5G mmW counties. This assessment clearly shows exposure to 5G mmW technology is statistically significantly associated with higher COVID-19 case and death rates in the U.S.A. The mechanism–should this be a causal relationship–may relate to changes in blood chemistry, oxidative stress, an impaired immune response, an altered cardiovascular and/or neurological response.

Efficacy and Safety of Regimens Used for the Treatment of POEMS Syndrome- a Systematic Review

Introduction: POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy/edema, myeloma protein, skin changes) is a rare disorder associated with plasma cell neoplasia where an overproduction of proinflammatory cytokines such as vascular endothelial growth factor (VEGF) upregulates vasculogenesis and increases vascular permeability resulting in multiple symptoms of the disease e.g. edema and hemangioma. Although the limited-stage disease can be treated with radiotherapy, treatment for the more advanced disease remains unclear. Here we offer a systematic review of the efficacy and safety of treatment regimens used to treat POEMS syndrome in the adult population. Methods: Databases i.e. PubMed, Embase, Web of Science, and clinicaltrials.gov were searched since inception through May 15th, 2020, following the PRISMA guidelines. Out of 421 studies, 8 articles (5 prospective clinical trials, and 3 retrospective studies) were included. Phase I clinical trials, abstracts, case reports, case series, and review articles were excluded. Results: A total of 171 patients (21-79 years of age) were evaluated in 8 clinical studies. Immunomodulator Based Regimens: In the 5 clinical studies (N=96) where lenalidomide (Len) plus dexamethasone (Dex) were used, the hematological (heme) complete response (CR) ranged from 20% to 46%. Heme CR was defined as the absence of monoclonal immunoglobulins in serum or urine. VEGF CR defined as normalization of serum VEGF levels ranged from 35% to 80%. Neurological response defined as the improvement in the overall neuropathy limitations scale (ONLS) by at least one score ranged from 0% to 95%. These studies reported 2-3 year progression-free survival (PFS) and overall survival (OS) of 59% to 92% and 90% to 100%, respectively. In the study by Suichi et al. (N=5), VEGF CR was reported to be 80%. However, no neurological improvement was seen in these patients. Proteasome Inhibitor Based Regimens: In the study by He et al. (N=20) bortezomib in combination with cyclophosphamide and Dex yielded heme, VEGF, and neurological responses in 76%, 88%, and 95% of the patients, respectively. No grade ≥3 treatment-related adverse effects (TRAE) were seen. Conventional Chemotherapy Based Regimens: In the phase II trial conducted by Misawa et al. (N=25) the reduction in serum VEGF levels, as well as clinical response as measured by improvement in muscle strength, was higher in the thalidomide arm as compared to the placebo arm. Grade ≥3 TRAE reported in the treatment arm were cardiac arrest, heart failure, and dehydration in 1 (8%) patient each. In the study by Li et al. (N=31) melphalan (Mel) in combination with Dex achieved heme, VEGF, and neurological response rates of 81%, 100%, and 100%, respectively. Twenty percent of the patients experienced grade ≥3 TRAE. Conclusion: Immunomodulator and chemotherapy based regimens appear to have a reasonable safety and efficacy profile. Lenalidomide and melphalan based therapies were most effective. Proteasome inhibitors based regimens yielded efficacious results without significant toxicity. More studies with existing and newer combinations with autologous stem cell transplantation are warranted. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Anthracene-Based Down-Converting Copolymers for Non-Invasive Optogenetic Techniques

<p>The down-conversion of high energy light with a fluorescent material may provide sufficient emission intensity to invoke a measurable neurological response in optogentically-active neurons. This work describes the use of anthracene-containing copolymers for use as a fixed emission material in optogenetic electrophysiology to demonstrate the feasibility of this technique. An anthracene-modified methacrylate was synthesized and copolymerized with methyl methacrylate to produce glassy copolymers with physical properties like those of poly(methyl methacrylate) (PMMA). The fluorescence in both solution and solid states are like those of pure anthracene and overlap fully with the absorption spectrum of channelrhodpsin-2. Scintillation is observed but is weak compared to fluorescence. The copolymers were found to be non-toxic to neuronal cultures. Whole cell patching measured the voltage changes of neurons under UV-irradiation in the absence and presence of a copolymer film. Increased frequencies and amplitudes of electrical events were observed in the presence of the polymers. </p> <div> <hr> </div>

Anthracene-Based Down-Converting Copolymers for Non-Invasive Optogenetic Techniques

<p>The down-conversion of high energy light with a fluorescent material may provide sufficient emission intensity to invoke a measurable neurological response in optogentically-active neurons. This work describes the use of anthracene-containing copolymers for use as a fixed emission material in optogenetic electrophysiology to demonstrate the feasibility of this technique. An anthracene-modified methacrylate was synthesized and copolymerized with methyl methacrylate to produce glassy copolymers with physical properties like those of poly(methyl methacrylate) (PMMA). The fluorescence in both solution and solid states are like those of pure anthracene and overlap fully with the absorption spectrum of channelrhodpsin-2. Scintillation is observed but is weak compared to fluorescence. The copolymers were found to be non-toxic to neuronal cultures. Whole cell patching measured the voltage changes of neurons under UV-irradiation in the absence and presence of a copolymer film. Increased frequencies and amplitudes of electrical events were observed in the presence of the polymers. </p> <div> <hr> </div>

FM2-5 Shell shock or neurasthenia? The queen square experience in the first world war

ObjectivesThe neurological response to psychological trauma during the Great War changed between the initial engagements, the final offensive and the later reflections of the Southborough enquiry.DesignAt Queen Square, neurasthenia was a recorded diagnosis from 1890 and, for the next 30 years, between 4%–8% of all admissions were so described. The term ‘shell shock’ was first used in 1914 but the diagnosis burgeoned until, by 1918, it amounted to 25% of all admissions.SubjectsEarly in the war, affected soldiers were rapidly evacuated to the UK, but attitudes changed after the Somme, because of the need to expedite return to the frontline. The use of ‘Electrical Therapy’ at Queen Square was an example of this imperative (Linden 2013).ResultsReview of the case records suggests that ‘Shell Shock’ became an increasingly pejorative term as the condition was seen as a ‘contagious psychological response of the weak.’ The records show it was largely restricted to the lower ranks whilst officers were generally considered to have neurasthenia requiring a more gentle psychotherapeutic approach, occasionally involving transfer to specialist facilities.ConclusionsUltimately, at Queen Square, the diagnosis and management of acute traumatic neurosis was driven by the needs of war but also by popular prejudice.

Repurposing a Histamine Detection Platform for High-Throughput Screening of Histidine Decarboxylase

Histidine decarboxylase (HDC) is the primary enzyme that catalyzes the conversion of histidine to histamine. HDC contributes to many physiological responses as histamine plays important roles in allergic reaction, neurological response, gastric acid secretion, and cell proliferation and differentiation. Small-molecule modulation of HDC represents a potential therapeutic strategy for a range of histamine-associated diseases, including inflammatory disease, neurological disorders, gastric ulcers, and select cancers. High-throughput screening (HTS) methods for measuring HDC activity are currently limited. Here, we report the development of a time-resolved fluorescence resonance energy transfer (TR-FRET) assay for monitoring HDC activity. The assay is based on competition between HDC-generated histamine and fluorophore-labeled histamine for binding to a Europium cryptate (EuK)-labeled anti-histamine antibody. We demonstrated that the assay is highly sensitive and simple to develop. Assay validation experiments were performed using low-volume 384-well plates and resulted in good statistical parameters. A pilot HTS screen gave a Z′ score > 0.5 and a hit rate of 1.1%, and led to the identification of a validated hit series. Overall, the presented assay should facilitate the discovery of therapeutic HDC inhibitors by acting as a novel tool suitable for large-scale HTS and subsequent interrogation of compound structure–activity relationships.

Non Stress Test – An Update

Non stress test is a time tested, convenient and reliable test of antenatal fetal surveillance. It accurately predicts those fetus that do not require acute or premature obstetric intervention and thereby prevents pregnancies from being subjected to unnecessary iatrogenic risks and avoids unnecessary medical, financial and emotional burden. The principle of non stress test is that the heart rate of a fetus with adequate oxygenation and normal neurological response will temporarily accelerate with fetal movement. Loss of reactivity is commonly associated with a fetal sleep cycle but may result from any cause of central nervous system depression, fetal acidosis or maternal drug intake and requires further evaluation for an extended period or evaluation with other techniques like biophysical profile or amniotic fluid testing or umbilical artery Doppler study as per the overall clinical scenario. A correctly performed NST, using standard technique with proper interpretation may be of great value in planning further management.

Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage: a meta-analysis

ObjectiveThe efficacy of intra-arterial vasodilators (IADs) for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) remains debatable. The objective of this meta-analysis was to pool estimates of angiographic and neurological response, clinical outcome, and mortality following treatment of vasospasm with IADs.MethodsWe searched PubMed, Embase, Scopus, Clinicaltrials.gov, Cochrane database, and CINAHL in December 2015 and August 2016. Studies reporting angiographic and neurological response, clinical outcome, and mortality following IAD treatment of vasospasm in 10 or more adults with aSAH were included. All established IADs were allowed. Two authors independently selected studies and abstracted the data. Mean weighted probabilities (MWP) were calculated using random effects model.ResultsInclusion criteria were met by 55 studies (n=1571). MWP for immediate angiographic response to IAD treatment was 89% (95% CI 83% to 94%), post-IAD neurological improvement 57% (95% CI 49% to 65%), good outcome 66% (95% CI 60% to 71%), and mortality was 9% (95% CI 7% to 12%). After adjusting for publication bias, MWP for mortality was 5% (95% CI 4% to 7%). When transcranial Doppler (TCD) was used along with clinical deterioration for patient selection, rates of neurological response (64%) and good outcome (72%) were better. IADs were not superior to controls (balloon angioplasty or medical management).ConclusionIAD treatment leads to a robust angiographic response and fair (but lower) rates of neurological response and good clinical outcome. Mortality was lower than the average reported in the literature. Rates of neurological response and good outcome were better when TCD was used for patient selection. Carefully designed studies are needed to compare IADs against medical management and balloon angioplasty.