Publications by authors named "James Berry"

180 Publications

Deep brain stimulation of the nucleus accumbens/ventral capsule for severe and intractable opioid and benzodiazepine use disorder.

Exp Clin Psychopharmacol 2021 Apr;29(2):210-215

Department of Neurosurgery, Department of Neuroscience, RNI, WVUSOM.

Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed for those who are treatment refractory. The objective of this study was to evaluate the safety of deep brain stimulation (DBS) for SUD and the effects of DBS on substance use, substance craving, emotional symptoms, and frontal/executive functions. DBS electrodes were implanted bilaterally within the Nucleus Accumbens/Ventral anterior internal capsule (NAc/VC) of a man in his early 30s with >10-year history of severe treatment refractory opioid and benzodiazepine use disorders. DBS of the NAc/VC was found to be safe with no serious adverse events noted and the participant remained abstinent and engaged in comprehensive treatment at the 12-week endpoint (and 12-month extended follow-up). Using a 0-100 visual analog scale, substance cravings decreased post-DBS implantation; most substantially in benzodiazepine craving following the final DBS titration (1.0 ± 2.2) compared to baseline (53.4 ± 29.5; p < .001). A trend toward improvement in frontal/executive function was observed on the balloon analog risk task performance following the final titration (217.7 ± 76.2) compared to baseline (131.3 ± 28.1, p = .066). FDG PET demonstrated an increase in glucose metabolism in the dorsolateral prefrontal and medial premotor cortices at the 12-week endpoint compared to post-surgery/pre-DBS titration. Heart Rate Variability (HRV) improved following the final titration (rMSSD = 56.0 ± 11.7) compared to baseline (19.2 ± 8.2; p < .001). In a participant with severe, treatment refractory opioid and benzodiazepine use disorder, DBS of the NAc/VC was safe, reduced substance use and craving, and improved frontal and executive functions. Confirmation of these findings with future studies is needed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/pha0000453DOI Listing
April 2021

Ibudilast (MN-166) in amyotrophic lateral sclerosis- an open label, safety and pharmacodynamic trial.

Neuroimage Clin 2021 15;30:102672. Epub 2021 Apr 15.

Sean M Healey & AMG Center for ALS, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Ibudilast (MN-166) is an inhibitor of macrophage migration inhibitory factor (MIF) and phosphodiesterases 3,4,10 and 11 (Gibson et al., 2006; Cho et al., 2010). Ibudilast attenuates CNS microglial activation and secretion of pro-inflammatory cytokines (Fujimoto et al., 1999; Cho et al., 2010). In vitro evidence suggests that ibudilast is neuroprotective by suppressing neuronal cell death induced by microglial activation. People with ALS have increased microglial activation measured by [C]PBR28-PET in the motor cortices. The primary objective is to determine the impact of ibudilast on reducing glial activation and neuroaxonal loss in ALS, measured by PBR28-PET and serum Neurofilament light (NfL). The secondary objectives included determining safety and tolerability of ibudilast high dosage (up to 100 mg/day) over 36 weeks. In this open label trial, 35 eligible ALS participants underwent ibudilast treatment up to 100 mg/day for 36 weeks. Of these, 30 participants were enrolled in the main study cohort and were included in biomarker, safety and tolerability analyses. Five additional participants were enrolled in the expanded access arm, who did not meet imaging eligibility criteria and were included in the safety and tolerability analyses. The primary endpoints were median change from baseline in (a) PBR28-PET uptake in primary motor cortices, measured by standard uptake value ratio (SUVR) over 12-24 weeks and (b) serum NfL over 36-40 weeks. The secondary safety and tolerability endpoints were collected through Week 40. The baseline median (range) of PBR28-PET SUVR was 1.033 (0.847, 1.170) and NfL was 60.3 (33.1, 219.3) pg/ml. Participants who completed both pre and post-treatment scans had PBR28-PET SUVR median(range) change from baseline of 0.002 (-0.184, 0.156) , P = 0.5 (n = 22). The median(range) NfL change from baseline was 0.4 pg/ml (-1.8, 17.5), P = 0.2 (n = 10 participants). 30(86%) participants experienced at least one, possibly study drug related adverse event. 13(37%) participants could not tolerate 100 mg/day and underwent dose reduction to 60-80 mg/day and 11(31%) participants discontinued study drug early due to drug related adverse events. The study concludes that following treatment with ibudilast up to 100 mg/day in ALS participants, there were no significant reductions in (a) motor cortical glial activation measured by PBR28-PET SUVR over 12-24 weeks or (b) CNS neuroaxonal loss, measured by serum NfL over 36-40 weeks. Dose reductions and discontinuations due to treatment emergent adverse events were common at this dosage in ALS participants. Future pharmacokinetic and dose-finding studies of ibudilast would help better understand tolerability and target engagement in ALS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2021.102672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102622PMC
April 2021

Using the Decrease in Trauma Admissions During the COVID-19 Pandemic to Evaluate Compliance With Stay-at-Home and Social Distancing Guidelines.

Cureus 2021 Apr 12;13(4):e14444. Epub 2021 Apr 12.

Neurosurgery, Arrowhead Regional Medical Center, Colton, USA.

Introduction The coronavirus disease 2019 (COVID-19) virus was declared a pandemic on March 10, 2020 by the World Health Organization (WHO) and has massively burdened healthcare systems with cases exponentially rising throughout the United States and the rest of the world. Since implementing precautions to reduce the spread of this disease, emergency departments have seen a decrease in the number of traumas. By evaluating the differences in the number of trauma admissions in different subgroups of patients, we can assess where to target messaging to increase compliance with these precautions. In this study, we aim to analyze the effect of the COVID-19 pandemic on trauma admissions. Methodology This was a retrospective review of the trauma database at our institution, a level 2 trauma center in Southern California, to assess the impact of COVID-19 on the number of traumas. The inclusion criteria were patients activated as traumas, regardless of age. Patients were excluded from the study if they did not have complete information in the trauma database. Data were stratified by date into two groups: (a) COVID period (January to April 2020) and (b) pre-COVID period (January to April 2019). The primary endpoint of this study was to determine whether there was a significant change in the number of patients presenting as trauma during the COVID-19 pandemic. This difference was analyzed and divided into subgroups based on age and trauma type. Results In our review, an average of 279 patients per month presented as trauma from January to April in 2019, and an average of 222 patients per month presented as trauma from January to April 2020 (p = 0.049). We found a significant decrease in the number of patients presenting with the chief complaint of fall and vehicular accident, but a nonsignificant difference in patients presenting as assaults or pedestrian accidents. There was also a significant decrease in the number of traumas in the 18-39 and 65+ age groups and a nonsignificant decrease in the 40-64 age group. It was also noted that the number of trauma admissions in May 2020 increased to 253 compared to 269 in 2019. This increase was most notable in the 18-39 and 40-64 age groups. Discussion As seen in the data, the most notable year-over-year difference was seen in March and April. In California specifically, a stay-at-home order was set in place in March, which was in conjunction with the WHO's declaration of a pandemic. An interesting finding was the significant decrease in patients with traumas in the age groups of 18-39 and 65+ from 2019 to 2020. There was a smaller, nonsignificant decrease in patients aged 40-64. This would be a good group to target with future messaging to increase compliance with health advisories. There was also a notable increase in the number of traumas in May 2020, signaling an end to the cooperation of the majority of people, also indicating that further measures needed to be enacted in all groups. Conclusions COVID-19 has disrupted social structures worldwide. As the pandemic continued, even the observers of stay-at-home and social distancing measures, the 18-39 age group, became fatigued with the guidelines and ventured out into the warming weather and summer activities. This difference in trauma admission due to COVID-19 between subsequent years can highlight the behavioral changes in our patient population and can be further extrapolated to target additional messaging to help reduce the spread of COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.14444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114965PMC
April 2021

Osteopathic Manipulative Treatment to Optimize the Glymphatic Environment in Severe Traumatic Brain Injury Measured With Optic Nerve Sheath Diameter, Intracranial Pressure Monitoring, and Neurological Pupil Index.

Cureus 2021 Mar 11;13(3):e13823. Epub 2021 Mar 11.

Neurosurgery, Arrowhead Regional Medical Center, Colton, USA.

Background Traumatic brain injury (TBI) has a complex pathophysiology that has historically been poorly understood. New evidence on the pathophysiology, molecular biology, and diagnostic studies involved in TBI have shed new light on optimizing rehabilitation and recovery. The goal of this study was to assess the effect of osteopathic manipulative treatment (OMT) on peripheral and central glial lymphatics in patients with severe TBI, brain edema, and elevated intracranial pressure (ICP) by measuring changes in several parameters regularly used in management. Methodology This was a retrospective study at a level II trauma center that occurred in 2018. The study enrolled patients with TBI, increased ICP, or brain edema who had an external ventricular drain placed. Patients previously underwent a 51-minute treatment with OMT with an established protocol. Patients received 51 minutes of OMT to the head, neck, and peripheral lymphatics. The ICP, cerebrospinal fluid (CSF) drainage, optic nerve sheath diameter (ONSD) measured by ultrasonography, and Neurological Pupil Index (NPi) measured by pupillometer were recorded before, during, and after receiving OMT. Results A total of 11 patients were included in the study, and 21 points of data were collected from the patients meeting inclusion criteria who received OMT. There was a mean decrease in the ONSD of 0.62 mm from 6.24 mm to 5.62 mm (P = 0.0001). The mean increase in NPi was 0.18 (P = 0.01). The mean decrease in ICP was 3.33 mmHg (P= 0.0001). There was a significant decrease in CSF output after treatment (P = 0.0001). Each measurement of ICP, ONSD, and NPi demonstrated a decrease in overall CSF volume and pressure after OMT compared to CSF output and ICP prior to OMT. Conclusions This study demonstrates that OMT may help optimize glial lymphatic clearance of CSF and improve brain edema, interstitial waste product removal, NPi, ICP, CSF volume, and ONSD. A holistic approach including OMT may be considered to enhance management in TBI patients. As TBI is a spectrum of disease, utilizing similar techniques may be considered for all forms of TBI including concussions and other diseases with brain edema. The results of this study can better inform future trials to specifically study the effectiveness of OMT in post-concussive treatment and in those with mild-to-moderate TBI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.13823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038899PMC
March 2021

Patient reported outcomes in ALS: characteristics of the self-entry ALS Functional Rating Scale-revised and the Activities-specific Balance Confidence Scale.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Mar 26:1-11. Epub 2021 Mar 26.

Sean M. Healey & AMG Center for ALS, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

This study characterized two patient-reported outcome measures (PROMs): a patient-facing adaptation of the revised amyotrophic lateral sclerosis (ALS) Functional Rating Scale ("self-entry ALSFRS-R") and the Activities-specific Balance Confidence (ABC) Scale. : ALS patients presenting to clinic completed PROMs that included (1) the self-entry ALSFRS-R, (2) the Activities-specific Balance Confidence Scale (ABC Scale), and (3) a question about falls. PROM data were compared to one another and to the traditional ALSFRS-R collected by trained evaluators in clinic ("standard ALSFRS-R"). : Over the data collection period, 449 ALS patients completed at least one of the three PROMs. Self-entry vs. standard ALSFRS-R total scores ( = 183) had high agreement (intraclass correlation (ICC)=0.81, 95% CI = 0.67, 0.88). Self-entry ALSFRS-R total scores were significantly higher than standard ALSFRS-R total scores (2.3 points,  < 0.001). In a subset of participants who contributed data at two timepoints, the average ALSFRS-R decline was not significantly different between methods ( = 49). ABC scores correlated highly with self-entry and standard ALSFRS-R Gross Motor subdomain scores (Pearson's  = 0.72,  < 0.001 and Pearson's  = 0.76,  < 0.001, respectively;  = 130). ABC score was negatively correlated with the number of reported falls within the last month (Spearman's =-0.40;  < 0.001;  = 130). A 10-point decrease in ABC score increased odds of a reported fall by 16%. : In a multidisciplinary clinic setting, self-entry and standard ALSFRS-R scores were similar, but not interchangeable. Self-entry scores were higher than standard ALSFRS-R scores but declined at a similar rate to the standard ALSFRS-R. ABC scores correlated with self-reported fall history and thus may provide useful data for clinical care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21678421.2021.1900259DOI Listing
March 2021

Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs.

Sci Transl Med 2021 Mar;13(585)

Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.

There is a need for replacement heart valves that can grow with children. We fabricated tubes of fibroblast-derived collagenous matrix that have been shown to regenerate and grow as a pulmonary artery replacement in lambs and implemented a design for a valved conduit consisting of three tubes sewn together. Seven lambs were implanted with tri-tube valved conduits in sequential cohorts and compared to bioprosthetic conduits. Valves implanted into the pulmonary artery of two lambs of the first cohort of four animals functioned with mild regurgitation and systolic pressure drops <10 mmHg up to 52 weeks after implantation, during which the valve diameter increased from 19 mm to a physiologically normal ~25 mm. In a second cohort, the valve design was modified to include an additional tube, creating a sleeve around the tri-tube valve to counteract faster root growth relative to the leaflets. Two valves exhibited trivial-to-mild regurgitation at 52 weeks with similar diameter increases to ~25 mm and systolic pressure drops of <5 mmHg, whereas the third valve showed similar findings until moderate regurgitation was observed at 52 weeks, correlating to hyperincrease in the valve diameter. In all explanted valves, the leaflets contained interstitial cells and an endothelium progressing from the base of the leaflets and remained thin and pliable with sparse, punctate microcalcifications. The tri-tube valves demonstrated reduced calcification and improved hemodynamic function compared to clinically used pediatric bioprosthetic valves tested in the same model. This tri-tube valved conduit has potential for long-term valve growth in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.abb7225DOI Listing
March 2021

Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs.

Sci Transl Med 2021 Mar;13(585)

Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.

There is a need for replacement heart valves that can grow with children. We fabricated tubes of fibroblast-derived collagenous matrix that have been shown to regenerate and grow as a pulmonary artery replacement in lambs and implemented a design for a valved conduit consisting of three tubes sewn together. Seven lambs were implanted with tri-tube valved conduits in sequential cohorts and compared to bioprosthetic conduits. Valves implanted into the pulmonary artery of two lambs of the first cohort of four animals functioned with mild regurgitation and systolic pressure drops <10 mmHg up to 52 weeks after implantation, during which the valve diameter increased from 19 mm to a physiologically normal ~25 mm. In a second cohort, the valve design was modified to include an additional tube, creating a sleeve around the tri-tube valve to counteract faster root growth relative to the leaflets. Two valves exhibited trivial-to-mild regurgitation at 52 weeks with similar diameter increases to ~25 mm and systolic pressure drops of <5 mmHg, whereas the third valve showed similar findings until moderate regurgitation was observed at 52 weeks, correlating to hyperincrease in the valve diameter. In all explanted valves, the leaflets contained interstitial cells and an endothelium progressing from the base of the leaflets and remained thin and pliable with sparse, punctate microcalcifications. The tri-tube valves demonstrated reduced calcification and improved hemodynamic function compared to clinically used pediatric bioprosthetic valves tested in the same model. This tri-tube valved conduit has potential for long-term valve growth in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.abb7225DOI Listing
March 2021

In Traditional Medicare, Modest Growth In The Home Care Workforce Largely Driven By Nurse Practitioners.

Health Aff (Millwood) 2021 03;40(3):478-486

Thomas Cornwell is the executive chairman of the Home Centered Care Institute and is the senior medical director of Village Medical at Home, in Chicago, Illinois.

Little is known about the characteristics of the workforce providing home-based medical care for traditional (fee-for-service) Medicare beneficiaries. We found that the number of participating home care providers in traditional Medicare increased from about 14,100 in 2012 to around 16,600 in 2016. Approximately 4,000 providers joined or reentered that workforce annually, and 3,000 stopped or paused participation. The number of home visits that most participants provided each year remained below 200. Only 0.7 percent of physicians in Medicare provided fifty or more home visits annually, with little change over the course of five years. In contrast, the number of home-visiting nurse practitioners almost doubled, and the average number of home visits they made increased each year. Despite generally low overall participation of traditional Medicare providers in home-based care, the workforce has seen modest but steady growth, driven primarily by increasing nurse practitioner participation. Additional stimuli may be necessary to ensure workforce adequacy and stability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1377/hlthaff.2020.00671DOI Listing
March 2021

Anatomic Approach and Outcomes in Children Undergoing Percutaneous Pericardiocentesis.

Pediatr Cardiol 2021 Apr 16;42(4):918-925. Epub 2021 Feb 16.

Division of Pediatric Cardiology, Department of Pediatrics, Masonic Children's Hospital, University of Minnesota, 2450 Riverside Ave, East Building Room MB547, Minneapolis, MN, 55454, USA.

Pericardiocentesis is traditionally performed using a subxiphoid approach. Hepatomegaly or loculated and noncircumferential effusions warrant nonstandard approaches to drain effusions; echocardiographic guidance has made these less traditional, non-subxiphoid approaches feasible. The study is aimed at comparing clinical outcomes of the subxiphoid and non-subxiphoid approaches to percutaneous pericardiocentesis in a pediatric population. This is a retrospective chart review of all children undergoing percutaneous pericardiocentesis from August 2008 to December 2019 at a single-center. A total of 104 patients underwent echocardiography-guided pericardiocentesis during the timeframe. Additionally, fluoroscopy was also used in 80 patients. Hematopoietic stem cell transplantation was the most common underlying diagnosis (n = 53, 50.9%). A non-subxiphoid approach was used in 58.6% (n = 61) of patients. The fifth and sixth intercostal spaces were the most commonly used (n = 17 each). The non-subxiphoid group tended to be older (95.9 vs. 21.7 months, p = 0.006) and weighed more (23.6 vs. 11.2 kgs, p = 0.013) as compared to the subxiphoid group. Non-subxiphoid approach was associated with shorter procedure times (21 vs. 37 min, p = 0.005). No major complications were seen. Five minor complications occurred and were equally distributed in the two groups. Complications were more likely in younger patients (p = 0.047). The technique and anatomic approach to pericardiocentesis, and the location or size of effusion did not influence the risk of complications. Echocardiography-guided percutaneous pericardiocentesis in children was associated with low complication rates in this single-center pediatric experience. The use of a non-traditional, non-subxiphoid approach was associated with shorter procedure times and did not significantly affect complication rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00246-021-02563-8DOI Listing
April 2021

High prevalence of co-occurring substance use in individuals with opioid use disorder.

Addict Behav 2021 03 4;114:106752. Epub 2020 Dec 4.

West Virginia University School of Medicine (WVU SOM), Morgantown, WV 26505, USA; West Virginia Clinical and Translational Science Institute, Morgantown, WV 26505, USA.

Objective: Funding to address the current opioid epidemic has focused on treatment of opioid use disorder (OUD); however, rates of other substance use disorders (SUDs) remain high and non-opioid related overdoses account for nearly 30% of overdoses. This study assesses the prevalence of co-occurring substance use in West Virginia (WV) to inform treatment strategies. The objective of this study was to assess the prevalence of, and demographic and clinical characteristics (including age, gender, hepatitis C virus (HCV) status) associated with, co-occurring substance use among patients with OUD in WV.

Methods: This retrospective study utilized the West Virginia Clinical and Translation Science Institute Integrated Data Repository, comprised of Electronic Medical Record (EMR) data from West Virginia University Medicine. Deidentified data were extracted from inpatient psychiatric admissions and emergency department (ED) healthcare encounters between 2009 and 2018. Eligible patients were those with OUD who had a positive urine toxicology screen for opioids at the time of their initial encounter with the healthcare system. Extracted data included results of comprehensive urine toxicology testing during the study timeframe.

Results: 3,127 patients met the inclusion criteria of whom 72.8% had co-occurring substance use. Of those who were positive for opioids and at least one additional substance, benzodiazepines were the most common co-occurring substances (57.4% of patients yielded a positive urine toxicology screen for both substances), followed by cannabis (53.1%), cocaine (24.5%) and amphetamine (21.6%). Individuals who used co-occurring substances were younger than those who were positive for opioids alone (P < 0.001). There was a higher prevalence of individuals who used co-occurring substances that were HCV positive in comparison to those who used opioids alone (P < 0.001). There were limited gender differences noted between individuals who used co-occurring substances and those who used opioids alone. Among ED admissions who were positive for opioids, 264 were diagnosed with substance toxicity/overdose, 78.4% of whom had co-occurring substance use (benzodiazepines: 65.2%; cannabis: 44.4%; cocaine: 28.5%; amphetamine: 15.5%). Across the 10-year timespan, the greatest increase for the entire sample was in the rate of co-occurring amphetamine and opioid use (from 12.6% in 2014 to 47.8% in 2018).

Conclusions: These data demonstrate that the current substance use epidemic extends well beyond opioids, suggesting that comprehensive SUD prevention and treatment strategies are needed, especially for those substances which do not yet have any evidence-based and/or medication treatments available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.addbeh.2020.106752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934179PMC
March 2021

Fentanyl Quality Assurance Project Prompted Change in Clinical Workflow and Test Configurations.

J Appl Lab Med 2021 Jan;6(1):93-100

Department of Behavioral Medicine and Psychiatry, West Virginia University, Morgantown, WV.

Background: Deaths attributable to fentanyl (FEN, a synthetic opioid) are high in Appalachia and highest in West Virginia. The goal of the study was to determine FEN prevalence among specimens submitted for definitive opioid testing and monitor responses to provider notifications of unexpected FEN findings during Q1 2020.

Methods: All definitive opioid test data were reviewed daily for FEN signatures in Q1 2020. Unexpected FEN results were communicated to providers and monitored for 10 days to record actions taken. Prevalence data were categorized. Behavioral Medicine (BMED) leaders analyzed January data and implemented FEN screening in the clinic. BMED Q1 clinic visits and order volumes for drug screens were reviewed after Q1.

Results: FEN positivity was 11% in Q1; >60% of findings were unexpected. Actions were taken for 54% of notifications in January but only 18% in March. Notifications required 70 hours of combined laboratory effort each month. BMED providers ordered 44% of definitive opioid tests and 69% of definitive FEN tests. Data prompted the addition of FEN to routine drug screen panels in the laboratory, and a 10% random FEN screening rate in the BMED opioid use disorder clinics (COAT).

Conclusions: Prevalence of FEN positivity was higher than initially expected, even for this region in Appalachia. Expanded presence of FEN screening should assist BMED providers with clinical efforts and help identify patients in need of intervention/therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jalm/jfaa173DOI Listing
January 2021

Effect of Ezogabine on Cortical and Spinal Motor Neuron Excitability in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

JAMA Neurol 2021 Feb;78(2):186-196

Department of Neurology, University of California Irvine, Irvine.

Importance: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal motor neuron hyperexcitability using transcranial magnetic stimulation and threshold tracking nerve conduction studies, respectively, although metrics of excitability have not been used as pharmacodynamic biomarkers in multi-site clinical trials.

Objective: To ascertain whether ezogabine decreases cortical and spinal motor neuron excitability in ALS.

Design, Setting, And Participants: This double-blind, placebo-controlled phase 2 randomized clinical trial sought consent from eligible participants from November 3, 2015, to November 9, 2017, and was conducted at 12 US sites within the Northeast ALS Consortium. Participants were randomized in equal numbers to a higher or lower dose of ezogabine or to an identical matched placebo, and they completed in-person visits at screening, baseline, week 6, and week 8 for clinical assessment and neurophysiological measurements.

Interventions: Participants were randomized to receive 600 mg/d or 900 mg/d of ezogabine or a matched placebo for 10 weeks.

Main Outcomes And Measures: The primary outcome was change in short-interval intracortical inhibition (SICI; SICI-1 was used in analysis to reflect stronger inhibition from an increase in amplitude) from pretreatment mean at screening and baseline to the full-dose treatment mean at weeks 6 and 8. The secondary outcomes included levels of cortical motor neuron excitability (including resting motor threshold) measured by transcranial magnetic stimulation and spinal motor neuron excitability (including strength-duration time constant) measured by threshold tracking nerve conduction studies.

Results: A total of 65 participants were randomized to placebo (23), 600 mg/d of ezogabine (23), and 900 mg/d of ezogabine (19 participants); 45 were men (69.2%) and the mean (SD) age was 58.3 (8.8) years. The SICI-1 increased by 53% (mean ratio, 1.53; 95% CI, 1.12-2.09; P = .009) in the 900-mg/d ezogabine group vs placebo group. The SICI-1 did not change in the 600-mg/d ezogabine group vs placebo group (mean ratio, 1.15; 95% CI, 0.87-1.52; P = .31). The resting motor threshold increased in the 600-mg/d ezogabine group vs placebo group (mean ratio, 4.61; 95% CI, 0.21-9.01; P = .04) but not in the 900-mg/d ezogabine group vs placebo group (mean ratio, 1.95; 95% CI, -2.64 to 6.54; P = .40). Ezogabine caused a dose-dependent decrease in excitability by several other metrics, including strength-duration time constant in the 900-mg/d ezogabine group vs placebo group (mean ratio, 0.73; 95% CI, 0.60 to 0.87; P < .001).

Conclusions And Relevance: Ezogabine decreased cortical and spinal motor neuron excitability in participants with ALS, suggesting that such neurophysiological metrics may be used as pharmacodynamic biomarkers in multisite clinical trials.

Trial Registration: ClinicalTrials.gov Identifier: NCT02450552.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2020.4300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684515PMC
February 2021

Moyamoya: An Update and Review.

Cureus 2020 Oct 16;12(10):e10994. Epub 2020 Oct 16.

Neurosurgery, Desert Regional Medical Center, Palm Springs, USA.

This article is a clinical review of Moyamoya disease (MMD) and Moyamoya syndrome (MMS). We review the incidence, epidemiology, pathology, historical context, clinical and radiographic findings, diagnostic imaging modalities, radiographic grading systems, the effectiveness of medical, interventional, and surgical treatment, and some of the nuances of surgical treatment options. This article will help pediatricians, neurologists, neurosurgeons, and other clinical practitioners who are involved in caring for patients with this rare clinical entity. MMD is an intrinsic primary disease process that causes bilateral progressive stenosis of the anterior intracranial circulation with the involvement of the proximal portions of the intracranial internal carotid artery (ICA) extending to involve the proximal portions of the anterior cerebral artery (ACA) and middle cerebral artery (MCA); posterior circulation involvement is very rare. This causes a compensatory response where large numbers of smaller vessels such as the lenticulostriate arteries begin to enlarge and proliferate, which gives the angiographic appearance of a "Puff of Smoke", which is translated into Japanese as "Moyamoya". MMS is a secondary process that occurs in response to another underlying pathological process that causes stenosis of intracranial blood vessels, such as radiation. For example, an external source of radiation causes stenosis of the ICA with a compensatory response of smaller blood vessels, which then enlarge and proliferate in response and has the same "Puff of Smoke" appearance on the diagnostic cerebral angiogram (DCA). Histological findings include an irregular internal elastic lamina with luminal narrowing, hyperplasia of the tunica media, and intimal thickening with vacuolar degeneration in smooth muscle cells in the tunica media. Compensation for diminishing blood supply occurs through angiogenesis, which causes the proliferation and enlargement of smaller collateral blood vessels to increase blood supply to under-perfused areas of the brain. MMD is rare in the United States, with just 0.086 newly diagnosed cases per 100,000 individuals per year, which is approximately one per million new cases annually. Risk factors for MMD include Eastern Asian ancestry and predisposing conditions such as neurofibromatosis and Down's syndrome. Clinically, patients often present with stroke signs and symptoms from cerebral ischemia. The proliferation of collateral blood vessels within the basal ganglia can produce movement disorders. Catheter-based DCA is the current gold standard for obtaining a diagnosis. CT perfusion allows preoperative identification of ischemic vascular territories, which may be amenable to surgical intervention. MRI enables rapid detection of acute ischemic stroke using diffusion-weighted Imaging (DWI) and apparent diffusion coefficient (ADC) sequences to assess for any diffusion restriction. Non-contrast CT of the head is used to rule out acute hemorrhage in the presentation of a progressive neurological deficit. The treatment option for Moyamoya is generally surgical; medical treatment has failed to halt disease progression and neuro-interventional techniques such as attempted stenting of stenosed vessels have failed. Surgical options include direct and indirect cerebrovascular bypass.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.10994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667711PMC
October 2020

Plasma neurofilament light predicts mortality in patients with stroke.

Sci Transl Med 2020 11;12(569)

Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

Given the heterogeneity of stroke brain injury, there is a clear need for a biomarker that determines the degree of neuroaxonal injury across stroke types. We evaluated whether blood neurofilament light (NFL) would fulfill this purpose for patients with acute cerebral infarction (ACI; = 227), aneurysmal subarachnoid hemorrhage (aSAH; = 58), or nontraumatic intracerebral hemorrhage (ICH; = 29). We additionally validated our findings in two independent cohorts of patients with ICH ( = 96 and = 54) given the scarcity of blood biomarker studies for this deadliest stroke type. Compared to healthy individuals ( = 79 and = 48 for the discovery and validation cohorts, respectively), NFL was higher for all stroke types. NFL associated with radiographic markers of brain tissue damage. It correlated with the extent of early ischemic injury in patients with ACI, hemorrhage severity in patients with aSAH, and intracranial hemorrhage volume in patients with ICH. In all patients, NFL independently correlated with scores from the NIH Stroke Scale, the modified Rankin Scale, and the Mini-Mental State Examination at blood draw, which respectively assess neurological, functional, and cognitive status. Furthermore, higher NFL concentrations independently associated with 3- or 6-month functional disability and higher all-cause mortality. These data support NFL as a uniform method to estimate neuroaxonal injury and forecast mortality regardless of stroke mechanism. As a prognostic biomarker, blood NFL has the potential to assist with planning supportive and rehabilitation services and improving clinical trial efficiency for stroke therapeutics and devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.aay1913DOI Listing
November 2020

The human gut microbiota in people with amyotrophic lateral sclerosis.

Amyotroph Lateral Scler Frontotemporal Degener 2021 05 2;22(3-4):186-194. Epub 2020 Nov 2.

Sean M. Healey and AMG Center for ALS, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.

Objective: To characterize the gut microbiota in people with amyotrophic lateral sclerosis (ALS) relative to controls and to test the hypothesis that butyrate-producing bacteria are less abundant in the gastrointestinal tracts of people with ALS (PALS). We conducted a case-control study at Massachusetts General Hospital to compare the gut microbiota in people with ALS to that in controls. Metagenomic shotgun sequencing was performed on DNA extracted from stool samples of 66 people with ALS (PALS), 61 healthy controls (HC), and 12 neurodegenerative controls (NDC). Taxonomic metagenomic profiles were analyzed for shifts in the microbial community structure between the comparator groups using per-feature univariate and multivariate association tests. The relative abundance of the dominant butyrate-producing bacteria and was significantly lower in ALS patients compared to HC. Adjustment for age, sex, and constipation did not materially change the results. The total abundance of 8 dominant species capable of producing butyrate was also significantly lower in ALS compared to HC (p < 0.001). The levels of several butyrate-producing bacteria, which are important for gut integrity and regulation of inflammation, were lower in people with ALS compared to controls. These findings lend support to the inference that the gut microbiota could be a risk factor for ALS. Further investigations are warranted, preferably earlier in the disease with corresponding dietary collection and a longitudinal design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21678421.2020.1828475DOI Listing
May 2021

Smartphone data during the COVID-19 pandemic can quantify behavioral changes in people with ALS.

Muscle Nerve 2021 02 28;63(2):258-262. Epub 2020 Nov 28.

Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, Massachusetts, USA.

Introduction: Passive data from smartphone sensors may be useful for health-care research. Our aim was to use the coronavirus disease-2019 (COVID-19) pandemic as a positive control to assess the ability to quantify behavioral changes in people with amyotrophic lateral sclerosis (ALS) from smartphone data.

Methods: Eight participants used the Beiwe smartphone application, which passively measured their location during the COVID-19 outbreak. We used an interrupted time series to quantify the effect of the US state of emergency declaration on daily home time and daily distance traveled.

Results: After the state of emergency declaration, median daily home time increased from 19.4 (interquartile range [IQR], 15.4-22.0) hours to 23.7 (IQR, 22.2-24.0) hours and median distance traveled decreased from 42 (IQR, 13-83) km to 3.7 (IQR, 1.5-10.3) km. The participant with the lowest functional ability changed behavior earlier. This participant stayed at home more and traveled less than the participant with highest functional ability, both before and after the state of emergency.

Discussion: We provide evidence that smartphone-based digital phenotyping can quantify the behavior of people with ALS. Although participants spent large amounts of time at home at baseline, the COVID-19 state of emergency declaration reduced their mobility further. Given participants' high level of daily home time, it is possible that their exposure to COVID-19 could be less than that of the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mus.27110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898508PMC
February 2021

Rapid Transition of Individual and Group-based Behavioral Outpatient Visits to Telepsychiatry in Response to COVID-19.

J Addict Med 2021 May-Jun 01;15(3):263-265

Department of Behavioral Medicine and Psychiatry, School of Medicine and Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, Department of Neuroscience, School of Medicine, West Virginia University, Morgantown, WV.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ADM.0000000000000748DOI Listing
June 2021

Onset of Mechanochromic Response in the High Strain Rate Uniaxial Compression of Spiropyran Embedded Silicone Elastomers.

Macromol Rapid Commun 2021 Jan 21;42(1):e2000449. Epub 2020 Oct 21.

Department of Chemistry, Duke University, 124 Science Drive, Durham, NC, 27708-0346, USA.

The molecular processes that accompany dynamic mechanical response to large deformations at high strain rate (≈1000 s or higher) underlie the early stages of damage in materials, but understanding of material response in this regime is typically limited to macroscopic constitutive equations. Here, spiropyran mechanophores are embedded in very short, stress-bearing strands in silicone elastomers, and their mechanochromic response to uniaxial compression is explored in a Split Hopkinson Pressure (or Kolsky) Bar. At strain rates of 1000 s , the onset of mechanochromism occurs at lower strains, but higher stresses, than in the same materials under quasi-static loading. Similar to quasi-static loading, however, a negligible effect of mechanophore structure on the critical strain for colorimetric onset is observed. The results suggest that nonequilibrium, inhomogeneous local tension distributions in the elastomers lead to greater stress in individual strands than at the same strains under equilibrium loading, but that within the regions of force concentration, mechanochromic onset is determined primarily by a limiting local strain threshold.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/marc.202000449DOI Listing
January 2021

Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis.

Muscle Nerve 2021 01 30;63(1):31-39. Epub 2020 Oct 30.

Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa.

An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mus.27091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820979PMC
January 2021

Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.

N Engl J Med 2020 09;383(10):919-930

From the Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School (S.P., J.D.B., S.B., M.C., D.D., M.M., J.O., L.P., A.V.S., E.T., P.V., J. Walker, H.Y., R.E.T., M.E.C.), the Biostatistics Center, Massachusetts General Hospital, Harvard Medical School (E.A.M., J. Chan, D.S.), and Spaulding Rehabilitation Hospital, Harvard Medical School (S.P.), Boston, the University of Massachusetts Memorial Medical Center, Worcester (M.A.O.), and Amylyx Pharmaceuticals (J. Cohen, J. Klee, K.L., P.D.Y.) and Harvard University (W.G.), Cambridge - all in Massachusetts; Pentara, Millcreek, UT (S.H., S.P.D., N.E., K.H.); Swedish Neuroscience Institute, Seattle (M.A.E.); Hennepin Healthcare, Minneapolis (S.M.); the Department of Neurology, Oregon Health and Science University, Portland (C.K.); the Department of Neurology, Wake Forest School of Medicine, Winston-Salem, NC (J.B.C.); the Department of Neurology, Ohio State University College of Medicine, Columbus (A.Q.); the Department of Neurology, University of Florida College of Medicine, Gainesville (J. Wymer); the Department of Neurology, University of Michigan, Ann Arbor (S.A.G.); Texas Neurology, Dallas (D.H.); the Department of Neurology, Lewis Katz School of Medicine, Temple University (T.H.-P.), and the Department of Neurology, University of Pennsylvania Perelman School of Medicine (C.Q.) - both in Philadelphia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Disease, University of Texas Health Science Center at San Antonio, San Antonio (C.E.J.); the Brain Science Institute and Department of Neurology, Johns Hopkins University, Baltimore (J.D.R.); the Department of Neurology, University of Kentucky College of Medicine, Lexington (E.J.K.); California Pacific Medical Center and Forbes Norris MDA-ALS Research and Treatment Center, San Francisco (J. Katz, L.J.); Barrow Neurological Institute, Phoenix, AZ (S.L., M.H., G.K., R.R., J.M.S.); the Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis (T.M.M.); the Department of Neurology, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York (S.N.S.); the Department of Neurology, University of South Florida Morsani College of Medicine, Tampa (T.H.V.); the Departments of Neurology and Pathology, Emory University School of Medicine, Atlanta (C.N.F., J.D.G.); Ochsner Health System, New Orleans (K.M.J.); the Department of Neurology, University of Iowa Carver College of Medicine, Iowa City (A.S.); the Department of Neurology, University of California, Irvine, School of Medicine, Irvine (N.A.G.); Neurology Associates, Lincoln, NB (G.L.P.); independent consultant, Nobleboro, ME (P.L.A.); and Statistics Collaborative, Washington, DC (J. Wittes).

Background: Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known.

Methods: In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months. Participants were randomly assigned in a 2:1 ratio to receive sodium phenylbutyrate-taurursodiol (3 g of sodium phenylbutyrate and 1 g of taurursodiol, administered once a day for 3 weeks and then twice a day) or placebo. The primary outcome was the rate of decline in the total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) through 24 weeks. Secondary outcomes were the rates of decline in isometric muscle strength, plasma phosphorylated axonal neurofilament H subunit levels, and the slow vital capacity; the time to death, tracheostomy, or permanent ventilation; and the time to death, tracheostomy, permanent ventilation, or hospitalization.

Results: A total of 177 persons with ALS were screened for eligibility, and 137 were randomly assigned to receive sodium phenylbutyrate-taurursodiol (89 participants) or placebo (48 participants). In a modified intention-to-treat analysis, the mean rate of change in the ALSFRS-R score was -1.24 points per month with the active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% confidence interval, 0.03 to 0.81; P = 0.03). Secondary outcomes did not differ significantly between the two groups. Adverse events with the active drug were mainly gastrointestinal.

Conclusions: Sodium phenylbutyrate-taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Secondary outcomes were not significantly different between the two groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol in persons with ALS. (Funded by Amylyx Pharmaceuticals and others; CENTAUR ClinicalTrials.gov number, NCT03127514.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1916945DOI Listing
September 2020

Engaging ALS patients and caregivers (the ALS research ambassadors) to help design the REFINE-ALS biomarker study.

Amyotroph Lateral Scler Frontotemporal Degener 2021 02 24;22(1-2):147-150. Epub 2020 Aug 24.

Mitsubishi Tanabe Pharma America, Inc., Jersey City, NJ, USA.

In the planning and design of the adicava/daravone indings Biomarkrs From myotrophic ateral clerosis (REFINE-ALS) study, we sought to elicit feedback from patients with ALS and their caregivers to ensure that patient-centric issues would be addressed. Ten ALS Clinical Research Learning Institute (ALS-CRLI) Research Ambassadors participated in 2 meetings. They provided perspectives on patients' interest in the study, the schedule of study visits, and data sharing. The findings were used to help revise the study design, as appropriate. Key concerns identified were (1) the frequency of sample collections, (2) participant travel burden, (3) enrollment criteria, and (4) data reporting and sharing with participants. Several of the identified issues were promptly addressed. The number of visits was reduced, travel optimized, entry criteria clarified, and plans for sharing participants' data with them were codified. The feedback from the Ambassadors was substantive and resulted in constructive patient-centric changes to the study protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21678421.2020.1804939DOI Listing
February 2021

Pathophysiologic Mechanisms of Concussion, Development of Chronic Traumatic Encephalopathy, and Emerging Diagnostics: A Narrative Review.

J Am Osteopath Assoc 2020 Aug 12. Epub 2020 Aug 12.

Pathophysiological mechanisms and cascades take place after a mild traumatic brain injury (mTBI) that can cause long-term sequelae, including chronic traumatic encephalopathy in patients with multiple concurrent TBIs. As diagnostic imaging has become more advanced, microanatomical changes present after mTBI may now be more readily visible. In this narrative review, the authors discuss emerging diagnostics and findings in mTBI through advanced imaging, electroencephalograms, neurophysiologic processes, Q2 biochemical markers, and clinical tissue tests in an effort to help osteopathic physicians to understand, diagnose, and manage the pathophysiology behind mTBI, which is increasingly prevalent in the United States.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7556/jaoa.2020.074DOI Listing
August 2020

Clinical Efficacy of Mesenteric Lift to Relieve Constipation in Traumatic Brain Injury Patients.

J Am Osteopath Assoc 2020 Aug 4. Epub 2020 Aug 4.

Context: Patients with severe traumatic brain injury (TBI) often have multiple autonomic disturbances that interfere with normal gastrointestinal motility. Many of the pharmacologic agents used in the intensive care unit (ICU) also adversely affect gastrointestinal motility. The body is further subjected to excessive levels of sympathetic discharge in states of traumatic injury and extreme stress, which can interfere with the proper absorption of fluids and nutrients.

Objective: To determine whether mesenteric lift, an osteopathic manipulative treatment technique, is effective in relieving constipation in patients with TBI who are intubated in the ICU.

Methods: This retrospective medical record review examined the effect of mesenteric lift on intubated patients with significant TBI who were unable to have a bowel movement within 72 hours of admission. The primary endpoint was the return of normal bowel function within 24 hours. A control group consisted of intubated patients with TBI during the same period who did not receive mesenteric lift.

Results: Of patients who received mesenteric lift, 77% experienced bowel movements (n=27 of 35), compared with 36% (n=16 of 44) in the control group (P=.01).

Conclusion: The application of mesenteric lift to intubated patients with severe TBI in the intensive care unit significantly increased patients' ability to resume normal bowel function and expel waste.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7556/jaoa.2020.094DOI Listing
August 2020

Exploring the use of educational materials for increasing participation in a stretching program: a quality improvement project in people with motor neuron disease.

Eur J Phys Rehabil Med 2021 Feb 3;57(1):78-84. Epub 2020 Aug 3.

Department of Neurology, Harvard Medical School, Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, Boston, MA, USA.

Background: Decreased range of motion is a common secondary complication of motor neuron disease (MND) that can contribute to functional decline and decreased participation in daily activities.

Aim: The purpose of this study was to develop and assess the effectiveness of educational brochures and videos aimed at improving knowledge regarding the importance of a regular stretching program.

Design: This was a quality improvement (QI) project.

Setting: Participants were seen in an outpatient multidisciplinary neuromuscular clinic.

Population: Individuals with motor neuron disease were invited to participate in this QI study.

Methods: Individuals were asked to complete surveys asking questions regarding current stretching program, pain levels, and knowledge of benefits of stretching before and after receiving the stretching brochures or videos.

Results: A total of 53 participants completed the pre-intervention survey, 28 in the brochure group and 25 in the video group. Of those, 86% and 88% completed the post-intervention survey in the brochure and video groups, respectively. The video group increased stretching frequency significantly more than the brochure group (2.04 and 0.62 days/week respectively, P=0.004). Significantly more participants in the video group reported usage of stretches from the educational materials on a regular basis (54% for brochure group and 86% for video group, P=0.024).

Conclusions: Educational brochures and videos are two different strategies to improve knowledge of benefits of stretching for individuals with MND. Both groups increased frequency of stretching. Videos may be better able to improve frequency of stretching when compared to brochures.

Clinical Rehabilitation Impact: The brochures and videos developed for this study can be used by clinicians treating individuals with MND. By improving knowledge regarding the benefits of stretching, individuals with MND may choose to prioritize stretching as a part of their routine. This in turn may help to prevent or address potential joint or muscle length issues or assist patients to incorporate preventative measures into their treatment plans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S1973-9087.20.06245-0DOI Listing
February 2021

Something to despair: Gender differences in adverse childhood experiences among rural patients.

J Subst Abuse Treat 2020 09 5;116:108056. Epub 2020 Jun 5.

West Virginia University, School of Medicine and Rockefeller Neuroscience Institute, Department of Behavioral Medicine and Psychiatry, 930 Chestnut Ridge Road, Morgantown, WV, United States; West Virginia University, School of Medicine, Department of Neuroscience, United States; West Virginia University, School of Medicine, Department of Neurology, United States; West Virginia University, School of Medicine, Department of Radiology, United States.

Existing research has demonstrated that patients in treatment for an opioid use disorder (OUD) have high rates of adverse childhood experiences (ACE) compared to community-based samples. While research has documented important gender differences in ACEs in patients with OUD receiving treatment in urban areas, research has not shown whether these findings would generalize to rural and Appalachian areas, which are known to have lower ACE scores. We conducted a secondary analysis of existing clinical data, utilizing intake assessment data from a rural Appalachian outpatient buprenorphine program. We restricted the sample to patients with an OUD who presented for treatment between June 2018 and June 2019 (n = 173). The clinical intake assessment included a modified 17-item ACE instrument that patients self-administered. More than half (54.3%) of patients reported having experienced 4+ categories of adverse childhood experiences. On average, females endorsed 4.5 categories of adverse experiences, whereas males endorsed 3.3 (p < 0.00); female patients were significantly more likely to have experienced sexual abuse (42.4% versus 10.6%, p < 0.00). Alarmingly, 25.9% of females and 8.2% of males reported being forced to have sex before age 18. Disproportionately high rates of childhood adversities, particularly among females, may partially explain despair in rural Appalachian areas. OUD treatment programs should conduct clinical assessments of trauma and integrate trauma-informed care into drug treatment, especially for female patients residing in rural Appalachia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsat.2020.108056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720246PMC
September 2020

Suppression with Adeno-Associated Virus and MicroRNA in Familial ALS.

N Engl J Med 2020 07;383(2):151-158

From the Horae Gene Therapy Center, Department of Pediatrics, University of Massachusetts Medical School (UMMS) (C.M., G.G., M.B., T.R.F.), and the Department of Neurology, UMMS and UMass Memorial Medical Center (D.M.M.-Y., M.A.O., C.L.D., N.S.W., R.H.B.), Worcester, and the Healey Center for ALS, Department of Neurology (J.D.B., L.M.P., D.G., S.D.L., M.P.F., M.E.C.), and the C.S. Kubik Laboratory for Neuropathology (D.H.O., M.P.F.), Massachusetts General Hospital and Harvard Medical School, Boston.

Two patients with familial amyotrophic lateral sclerosis (ALS) and mutations in the gene encoding superoxide dismutase 1 () were treated with a single intrathecal infusion of adeno-associated virus encoding a microRNA targeting SOD1. In Patient 1, SOD1 levels in spinal cord tissue as analyzed on autopsy were lower than corresponding levels in untreated patients with SOD1-mediated ALS and in healthy controls. Levels of SOD1 in cerebrospinal fluid were transiently and only slightly lower in Patient 1 but were not affected in Patient 2. In Patient 1, meningoradiculitis developed after the infusion; Patient 2 was pretreated with immunosuppressive drugs and did not have this complication. Patient 1 had transient improvement in the strength of his right leg, a measure that had been relatively stable throughout his disease course, but there was no change in his vital capacity. Patient 2 had stable scores on a composite measure of ALS function and a stable vital capacity during a 12-month period. This study showed that intrathecal microRNA can be used as a potential treatment for SOD1-mediated ALS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2005056DOI Listing
July 2020

Longitudinal biomarkers in amyotrophic lateral sclerosis.

Ann Clin Transl Neurol 2020 07 9;7(7):1103-1116. Epub 2020 Jun 9.

Sean M. Healey and AMG Center for ALS, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objective: To investigate neurodegenerative and inflammatory biomarkers in people with amyotrophic lateral sclerosis (PALS), evaluate their predictive value for ALS progression rates, and assess their utility as pharmacodynamic biomarkers for monitoring treatment effects.

Methods: De-identified, longitudinal plasma, and cerebrospinal fluid (CSF) samples from PALS (n = 108; 85 with samples from ≥2 visits) and controls without neurological disease (n = 41) were obtained from the Northeast ALS Consortium (NEALS) Biofluid Repository. Seventeen of 108 PALS had familial ALS, of whom 10 had C9orf72 mutations. Additional healthy control CSF samples (n = 35) were obtained from multiple sources. We stratified PALS into fast- and slow-progression subgroups using the ALS Functional Rating Scale-Revised change rate. We compared cytokines/chemokines and neurofilament (NF) levels between PALS and controls, among progression subgroups, and in those with C9orf72 mutations.

Results: We found significant elevations of cytokines, including MCP-1, IL-18, and neurofilaments (NFs), indicators of neurodegeneration, in PALS versus controls. Among PALS, these cytokines and NFs were significantly higher in fast-progression and C9orf72 mutation subgroups versus slow progressors. Analyte levels were generally stable over time, a key feature for monitoring treatment effects. We demonstrated that CSF/plasma neurofilament light chain (NFL) levels may predict disease progression, and stratification by NFL levels can enrich for more homogeneous patient groups.

Interpretation: Longitudinal stability of cytokines and NFs in PALS support their use for monitoring responses to immunomodulatory and neuroprotective treatments. NFs also have prognostic value for fast-progression patients and may be used to select similar patient subsets in clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.51078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359115PMC
July 2020

Amyotrophic lateral sclerosis care and research in the United States during the COVID-19 pandemic: Challenges and opportunities.

Muscle Nerve 2020 08 5;62(2):182-186. Epub 2020 Jun 5.

Department of Neurology, Duke University, Durham, North Carolina.

Coronavirus disease 2019 has created unprecedented challenges for amyotrophic lateral sclerosis (ALS) clinical care and research in the United States. Traditional evaluations for making an ALS diagnosis, measuring progression, and planning interventions rely on in-person visits that may now be unsafe or impossible. Evidence- and experience-based treatment options, such as multidisciplinary team care, feeding tubes, wheelchairs, home health, and hospice, have become more difficult to obtain and in some places are unavailable. In addition, the pandemic has impacted ALS clinical trials by impairing the ability to obtain measurements for trial eligibility, to monitor safety and efficacy outcomes, and to dispense study drug, as these also often rely on in-person visits. We review opportunities for overcoming some of these challenges through telemedicine and novel measurements. These can reoptimize ALS care and research in the current setting and during future events that may limit travel and face-to-face interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mus.26989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283687PMC
August 2020

Optimizing telemedicine to facilitate amyotrophic lateral sclerosis clinical trials.

Muscle Nerve 2020 09 8;62(3):321-326. Epub 2020 Jun 8.

Department of Neurology, Penn State Health M.S. Hershey Medical Center, Hershey, Pennsylvania.

Amyotrophic lateral sclerosis (ALS) has the largest drug pipeline among neuromuscular diseases, with over 160 companies actively involved in ALS research. There is a growing need to recruit trial participants, but ALS patients often have limited mobility and most ALS trials are conducted in a small number of major centers. These factors effectively limit patient participation, particularly for those in rural areas. The current coronavirus disease 2019 (COVID-19) pandemic has necessitated the more widespread use of telemedicine technology for clinical care, and has prompted consideration of its increased use for clinical trials. In this opinion piece, we describe the current state of telemedicine for recruitment, consenting, and screening of participants for clinical trials. We also summarize the available data on remote administration of outcome measures. Current challenges include validation of outcome measures for remote assessment, as well as technological, regulatory, and licensure barriers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mus.26921DOI Listing
September 2020

Understanding the needs of people with ALS: a national survey of patients and caregivers.

Amyotroph Lateral Scler Frontotemporal Degener 2020 08 12;21(5-6):355-363. Epub 2020 May 12.

Healey Center for ALS, Massachusetts General Hospital, Boston, MA, USA.

: Amyotrophic lateral sclerosis (ALS) has profound effects on people with ALS (PALS) and caregivers. There is a paucity of research detailing and comparing PALS and caregiver day-to-day perspectives of ALS. : A survey developed collaboratively by The ALS Association and a panel of experts in ALS care was designed to broadly sample the experience of PALS and caregivers with respect to physical and emotional symptoms, the efficacy of treatment approaches, and goals for future treatments. Specific physical symptoms assessed consisted of fatigue, pain, weakness, shortness of breath, difficulty sleeping, speech problems, depression and other mood changes, and cognitive changes. PALS, caregivers of living patients with ALS (C-LPALS), and caregivers of deceased patients with ALS (C-DPALS) were contacted by email to participate in a 30-minute online survey. : 887 PALS, 444 C-LPALS, and 193 C-DPALS responded to the survey. In comparison to PALS, C-LPALS perceived that PALS had significantly higher rates of all surveyed symptoms except for pain and weakness. Caregivers self-reported higher stress levels than PALS ( < 0.001). 35% (135/383) of caregivers reported experiencing a devastating or near devastating financial impact of ALS and 64% (247/383) of caregivers felt their own health had worsened. Caregivers were significantly less likely to perceive a positive response to treatment in comparison to PALS ( < 0.001). : PALS and caregivers report a number of symptoms beyond weakness that affect daily life which may be targets of future interventions. There are opportunities to improve services and care for caregivers to reduce the burden of illness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21678421.2020.1760889DOI Listing
August 2020