Chronic Progressive Neurological Disorder Research Articles

The Early Initiation Advantages of Physical Therapy in Multiple Sclerosis-A Pilot Study.

(1) Background: Multiple sclerosis (MS), a chronic progressive neurological disorder which affects the central nervous system (CNS), can result in disorders of all the functions controlled by the CNS: motor, sensory, cognitive and emotional. Physical therapy (PT), conducted through proprioceptive neuromuscular facilitation (PNF) techniques, can be customized to the individual patient's needs and has the potential to improve the patient's evolution. This study aims to establish if PT based on PNF techniques has a beneficial role in MS treatment. (2) Methods: We performed a prospective study on 40 patients who were diagnosed with MS and previously treated only with MS drug treatment (DT). These patients have participated in a PT program throughout one year. At the beginning and at the end of our study, after one year, we have assessed the following parameters: timed walk for 25 feet (Timed 25-Foot Walk test- T25FW test), dexterity of the upper limbs (9-Hole Peg Test-9HPT), disability level (Expanded Disability Status Scale-EDSS) and cognitive function (Paced Auditory Serial Addition Test-PASAT. (3) Results: In subjects in the early stages of MS, lower limb mobility improved significantly, T25FW decreasing from 6.46 to 5.80 (p < 0.001) and upper limb ability increased significantly in the dominant hand, 9HPT decreasing from 17.73 to 16.97 (p = 0.006) and not significantly in the non-dominant hand, 9HPT decreasing from 17.73 to 17.50 (p = 0.255). Furthermore, among these subjects, cognitive performance improved; their PASAT increased from 52.14 to 54.14 (p = 0.036), while the level of disability of these subjects improved only slightly, the EDSS scale evolving from 3.08 to 2.91 (p = 0.650). (4) Conclusions: In patients with early forms of MS, combining DT with a PT program based on PNF techniques results in: regaining muscle strength in the lower limbs, improving coordination while walking, correcting dexterity in the upper limbs and increasing the ability to concentrate.

Caregivers’ Burden in Parkinson’s Disease: A Study on Related Features and Attachment Styles

Abstract Parkinson’s disease (PD) is a chronic progressive neurological disease clinically characterized by motor and non-motor symptoms, with an increasing impact on the quality of life not only for the patient but also for the caregivers. Twenty-six primary caregivers (female = 19; mean age = 57.04, SD = 10.64) of PD patients were consecutively recruited. Several psychological aspects were verified through clinical screening tests: EQ-5D and PQoL CARER for quality of life, Hospital Anxiety and Depression Scale (HADS), Caregiver Burden Inventory (CBI), Family Strain Questionnaire (FSQ), and Adult Attachment Questionnaire. We found that the burden was generally higher in cohabiting female caregivers of patients with dementia as compared with not cohabiting caregivers. Severe burden emerged in 7.7% of the participants according to the PQoL. The mean score of this scale was higher in cohabiting caregivers. Finally, according to the CBI, 19.2% of the participants suffered from severe burden, with mean scores of the CIB-S and CIB-E subscales higher in cohabitants. Our study highlights the need to investigate more thoroughly the burden of caregivers of PD patients and its associated factors, and to pay more attention to the physical and psychological health of caregivers to improve their quality of life.

Palliative physiotherapy in community settings for people with terminal illness

ObjectivesThe need for palliative care is constantly growing worldwide. Palliative care is typically provided by a multidisciplinary team in community-based facilities. As part of this team, physiotherapists can effectively address...

Amyotrophic lateral sclerosis, a neurodegenerative motor neuron disease with retinal involvement

AbstractAmyotrophic lateral sclerosis (ALS) is a chronic progressive neurological disease that predominantly affects the brain, the brainstem and the spinal cord; therefore, the neurological involvement is far from the visual pathway. Moreover, ophthalmological symptoms are scarce or absent. Consequently, there are few studies that analyse visual changes in these patients, and they sometimes produce contradictory results.Since the retina is considered a window to the rest of the central nervous system, it could serve as a biomarker of neuronal damage that would help diagnose and monitor each patient's progression, and it also assesses the effectiveness of different treatments.All neurodegenerative diseases have common pathophysiological mechanisms although some of them may predominate over others. In addition to environmental and genetic factors, in ALS glial activation and the accumulation of protein aggregates mechanisms stand out. Furthermore, asymmetric central nervous system involvement has been described in ALS.This SIS course analyses whether changes occur in the anterior visual pathway in ALS patients at both functional and anatomical levels. Furthermore, it examines the evolution of these changes as the pathology progresses in order to determine whether there is a detectable progression of the disease in the anterior visual pathway. In addition, it is also analyses whether these retinal changes have a histological correlation using animal's models.The retina is sensitive enough to detect changes in neuromuscular diseases with a spinal onset, as in the case of ALS. On one hand, in ALS patients, optic coherence tomography (OCT) is the best ophthalmological exploratory method that has shown first significant changes in the anterior visual system, showing a thickening in OCT parameters in early stages, with subsequent thinning, allowing the assessment of disease progression. These retinal changes correlate with neurological disability, duration of the disease and pulmonary function tests. In addition, there is an asymmetric involvement in the retina, as in the central nervous system, by visual evoked potentials and OCT.On the other hand, histopathologically, there is an accumulation of protein aggregates with characteristic ubiquitin‐reactive inclusions, which are positive for P62 and negative for TDP‐43, both in one patient and in animal models. | Moreover, in 120‐day‐old TG(SOD1G93A) ALS mice retinas, there are signs of microglial activation (neuroinflammation) and a decrease in the number of retinal ganglion cells (neurodegeneration) in the late stages of the disease. Microglial cells are in an M1 or pro‐inflammatory activation phenotype, which is neurotoxic to retinal ganglion cells and could help cause this neuronal loss. These microglial changes have also been described in the spinal cord of TG(SOD1G93A) ALS mice. Microglial activation, an accumulation of protein aggregates and decreases in retinal ganglion cells could explain the thickness changes found by OCT in ALS patients at the macular and papillary level.

Perceived facilitators, needs, and barriers to health related quality of life in people with multiple sclerosis: a qualitative investigation

BackgroundMultiple sclerosis (MS) is a chronic progressive neurological disease that influences an individual's physical, mental, emotional, and social functioning, otherwise known as health-related quality of life (HRQOL). To fully capture the impacts of MS on HRQOL, perspectives from the lived experience should be investigated.ObjectiveThe purpose of this study was to describe, in people with relapsing–remitting multiple sclerosis (RRMS), (1) the health and wellness needs and facilitators perceived to influence HRQOL, (2) determine which health needs are not being met, and (3) identify barriers to meeting health and wellness needs.MethodsParticipants with RRMS were recruited from a more extensive study for this cross-sectional, qualitative investigation guided by phenomenological theory. Semi-structured interviews were conducted until data saturation was reached (n = 15). The data were analyzed using a thematic analysis approach.ResultsFive themes emerged as facilitators of HRQOL; mental/emotional health, knowledge about MS, family/peer support, lifestyle behaviors, and social engagement. Identified barriers to achieving better HRQOL included limited access to specialized care, lack of communication/ empathy from providers, lack of comprehensive care, challenges caused by MS symptoms, and difficulty navigating the healthcare and insurance landscape.ConclusionsStudy participants described mental health and lifestyle behaviors as the primary promoters of overall HRQOL. Access to dietary guidelines, exercise instruction, and education about living healthy with MS were also identified as positive contributors to overall QOL. When these positive contributors are limited or absent, HRQOL was reported to decrease.

The Social Support Needs of Family Caregivers of Patients With Multiple Sclerosis: A Qualitative Study

Objective: Multiple sclerosis (MS) is one of the most common chronic progressive neurological diseases. It is the non-traumatic cause of neurological disability in adults. This disease increases the patient’s need for care due to the progressive course of disease that intensifies the symptoms over time. Family caregivers of these patients have different challenges and needs for caregiving. The present study aims to investigate the supportive needs of family caregivers of patients with MS in Iran. Materials &amp; Methods: This is a qualitative study conducted in MS Association of Isfahan, Iran in 2018-2019 for 8 months. Participants were selected by a purposive sampling method who included 8 patients, 13 family caregivers, and 4 treatment staff. Semi-structured interviews were used to survey the supportive needs of caregivers. Interviews took about 30-60 minutes. Sampling and data collection were saturated after 25 interviews. We used Guba and Lincoln’s criteria (credibility, dependability, transferability, and conformability) to evaluate and validate the data. The contract content analysis technique was used to analyze the data. Results: The results of analysis yielded 795 initial codes. After merging these codes based on common features, 562 codes were remained. The supportive needs of family caregivers of MS patients were presented in three main categories (creating interaction opportunities to reduce isolation, empathetic interaction with peers and treatment staff, and financial support) and nine sub-categories. Conclusion: Most of the family caregivers of MS patients in Iran do not receive adequate social and systemic supports from health care providers and do not have access to support resources. Policymakers and health caregivers should provide the required supporting programs for these caregivers so that they can optimally play their role in caregiving MS patients, especially at home, while receiving appropriate social and systemic supports.

Microbiota shaping - the effects of probiotics, prebiotics, and fecal microbiota transplant on cognitive functions: A systematic review.

BACKGROUNDDementia is a chronic progressive neurological disease affecting millions of people worldwide, and represents a relevant economic burden for healthcare systems. Although its pathogenesis is still unknown, recent findings have reported that a dysregulated gut-brain axis communication, a fundamental relationship mediated by several host and microbial molecules, is associated with cognitive disorders. In addition, gut microbiota manipulation reduces neuroinflammation, improving cognitive function by restoring the functional gut-brain axis.AIMTo better define the effects of probiotics, prebiotics, synbiotics, and fecal microbiota transplant (FMT) on cognitive function.METHODSWe performed a literature search of human randomized clinical trials to examine the effects of the administration of probiotics, prebiotics, synbiotics, or FMT on cognition outcomes in healthy or sick people of every age, sex, and nationality. We systematically searched Embase, Medline/PubMed, Cochrane Library, central and clinicaltrials.gov databases with a combination of comprehensive terms related to cognition and gut microbiota manipulation. Then we carefully reviewed and synthesized the data by type of study design and setting, characteristics of the studied population, kind of intervention (strain type or mixture type, dosage, and frequency of administration), control treatment, inclusion and exclusion criteria, follow-up duration, and cognitive or memory outcomes.RESULTSAfter examining the titles and abstracts, the initial literature screening identified 995 articles, but we added 23 papers in our systematic review. The analyses of these selected studies highlighted that both probiotic supplementation and FMT improved cognitive function regardless of the type and posology of administration and the adopted cognitive tests and questionnaires. We found that most of the studies conducted in healthy people showed a significant positive effect of the intervention on at least one of the performed cognitive tests. Regarding unhealthy subjects, while FMT and especially probiotic administration had multiple beneficial effects on different cognitive functions, supplementation with prebiotics did not provide any cognitive improvement.CONCLUSIONProbiotic supplementation and FMT may represent a promising strategy to restore gut eubiosis and enhance the cognitive functions of healthy people and patients with neurological disorders.

Presumptive Primary Cerebral T-Cell Lymphoma in a White-Tailed Deer (Odocoileus virginianus)

Primary central nervous system (CNS) lymphomas are rare in humans and even more uncommon in animals. We report the clinical, pathological and immunohistochemical features of a presumptive primary cerebral T-cell lymphoma (PCTCL) in an aged female white-tailed deer (Odocoileus virginianus) that had chronic progressive neurological disease characterized by ataxia, claudication and eventual circling. The animal was euthanized due to poor prognosis. Grossly, a 2.5cm dark red, friable nodule effaced the cortical neuroparenchyma of the left anterior cingulate cortex (LACC). Microscopically, the meningeal vasculature and adjacent grey and white matter cortical neuroparenchyma of the LACC were infiltrated by a poorly demarcated, unencapsulated and densely cellular round cell neoplasm with a consistent angiocentric pattern. The neoplasm was associated with extensive regions of haemorrhage and liquefactive necrosis. Neoplastic cells immunolabelled for CD3 antigen and had high proliferative activity, as indicated by Ki-67 labelling. Based on the cytohistomorphological and immunohistochemical features and absence of metastasis, a diagnosis of PCTCL was determined. This case indicates that PCTCL should be considered in the differential diagnosis of neurological disease and intracranial, intra-axial CNS masses in deer.

The Novel Coronavirus Infection (COVID-19) and Nervous System Involvement: Mechanisms of Neurological Disorders, Clinical Manifestations, and the Organization of Neurological Care.

The new coronavirus SARS-CoV-2 and the disease it causes COVID-19 involves not only respiratory system damage, but can also lead to disorders of the central and peripheral nervous system, as well as the muscular system. This article presents published data and our own observations on the course of neurological disorders in COVID-19 patients. There is a relationship between the severity of COVID-19 and the severity and frequency of neurological manifestations. Severe neurological disorders are mostly seen in severe cases of COVID-19 and include acute cerebrovascular accidents (aCVA), acute necrotizing encephalopathy, and Guillain–Barré syndrome. Factors potentially complicating the course of COVID-19 and increasing the development of neurological complications include arterial hypertension, diabetes mellitus, and chronic cardiac and respiratory system diseases. Questions of the possible effects of human coronaviruses on the course of chronic progressive neurological diseases are addressed using multiple sclerosis (MS) as an example. We discuss the management of patients with aCVA and MS depending on the risk of developing coronavirus infection.

Changing Behaviour towards Aerobic and Strength Exercise (BASE): Design of a randomised, phase I study determining the safety, feasibility and consumer-evaluation of a remotely-delivered exercise programme in persons with multiple sclerosis

BackgroundMultiple sclerosis is a chronic progressive neurological disease. Evidence attests to the benefits of exercise, guidelines for exercise in multiple sclerosis are available. Remote-delivery of exercise adherence programmes based on the exercise guidelines require urgent testing. AimsThe design, and outcomes of Behaviour towards Aerobic and Strength Exercise in MS (BASE-MS), a remotely-delivered exercise training study based principles of behaviour change, will further evaluate the remote-delivery of the current exercise guidelines. MethodsBASE is a 4-month clinically relevant randomised controlled trial to explore the delivery of a remotely supervised, guidelines-based exercise programme for persons with multiple sclerosis, underpinned by principles of health behaviour change. Initially, 72 persons with mild to moderate multiple sclerosis will be randomised in a 1:1:1 allocation to receive the BASE programme, or act as controls continuing usual care. On programme completion, exercise participants will be further randomised to an optimised adherence treatment or usual adherence. Our online survey assesses the primary outcome of exercise participation, and secondary outcomes of symptoms, and correlates of behaviour change at baseline, month four, month five and month eleven. Online surveys will capture coach and participant feedback to identify the contexts, mechanisms and outcomes of BASE implementation. ConclusionsThe research and clinical landscape for MS management must remain in-step with public health and health communication. BASE tests the remote-delivery of the current exercise guidelines for exercise in persons with MS. Safety, feasibility and evaluative outcomes will provide rich data for future remote-delivery of exercise in neurological conditions.

The economic benefit of timely, adequate, and adherence to Parkinson's disease treatment: the Value of Treatment Project 2.

Parkinson's disease (PD) is a chronic progressive neurological disorder with a high psychosocial and economic burden. As part of the European Brain Council (EBC)-led Value of Treatment project, this study aimed to capture the economic benefit of timely, adequate, and adherence to PD treatment. The EBC Value of Treatment Initiative combined different stakeholders to identify unmet needs in the patients' journey according to Rotterdam methodology. The economic evaluation focused on three major topics identified as major gaps: start of treatment; best treatment for advanced disease; and adherence to treatment. Two separate healthcare systems (Germany and the UK) were chosen. Cost-effectiveness was determined by using decision-analytical modelling approaches. Effectiveness was expressed as quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratio (ICER). Treatment intervention in PD was found to be cost-effective regardless of the initial health state of the patient receiving the treatment. Cost savings were between -€1000 and -€5400 with 0.10 QALY gain and -€1800 and -€7600 with 0.10 QALY gain for Germany and the UK, respectively. Treatment remains cost-effective within the National Institute for Health and Care Excellence thresholds. Availability of adequate treatment to more patients was also found to be cost-effective, with an ICER of €15,000-€32,600 across country settings. Achieving the target adherence to treatment would generate cost-savings of €239,000-€576,000 (Germany) and €917,000-€2,980.000 (UK) for every 1,000 patients treated adequately. The analyses confirmed that timely, adequate, and adherence to PD treatment will not only improve care of the patients but is also cost-effective across healthcare systems. Further studies with a distinct identification of gaps in care are necessary to develop better and affordable care.

Met5]-enkephalin preserves diffusion metrics in EAE mice

Multiple sclerosis is a chronic progressive neurological disorder that has few distinctive biomarkers associated with disease progression or response to therapy. This research investigated whether non-invasive imaging correlated with animal behavior and morphological indicators of disease in response to serum levels of [Met5]-enkephalin. Using the experimental autoimmune encephalomyelitis (EAE) model, adult female C57BL/6 J mice were randomized to receive daily injections of 0.1 mg/kg naltrexone (NTX) (= low dose naltrexone, LDN), 10 mg/kg Opioid Growth Factor (OGF) (chemically termed [Met5]-enkephalin) or saline beginning at the time of disease induction. Daily composite behavior scores were recorded over a 30-day period based on tail tone, gait, righting reflex, and limb strength. Prior to disease onset (day 7), and at peak disease (day 18), mice were imaged and tissues (blood and spinal cord) collected at day 30 for serum analyses of OGF and morphology. Serum OGF levels of EAE mice treated with saline were significantly reduced from baseline and from normal mice. Longitudinal cohort data demonstrated an increase in fractional anisotropy in all cohorts by day 18. There was a significant decrease in radial diffusivity in the saline group seen at day 18 whereas the axial diffusivity was not altered amongst treatment groups. Treatment with OGF or LDN resulted in mean diffusivity rates that were comparable to baseline (normal) levels at days 7 and 18. Luxol fast blue staining of the lumbar spinal cords demonstrated a 16 % reduction in myelin staining in saline treated EAE animals when compared to OGF and LDN treated EAE mice. Immunohistochemistry with Olig2 (pan-oligodendrocyte marker) and myelin basic protein (MBP) revealed that OGF and LDN treatment restored the area (%) of MBP and number of oligodendrocytes to that of normal spinal cord (∼75 %). Saline treated EAE mice had more demyelination and fewer oligodendrocytes than normal mice. Collectively, these data suggest that a panel of biomarkers including imaging, serum biomarker levels, and behavior correlate with progression of disease, and may begin to validate use of specific non-invasive markers for MS.

Music therapy in Parkinson's disease

Objectives: Parkinson's disease (PD) is a chronic progressive neurologic disorder involving degeneration of the dopaminergic system. Its clinical manifestations include motor and nonmotor symptoms. Several nonpharmacologic therapies, such as music therapy (MT), have recently been developed in order to improve the clinical manifestations of this disease. The aim of this narrative literature review is to analyze the scientific evidence for the therapeutic effects of music in PD.

Work-related exposure to organic solvents and the risk for multiple sclerosis\u2014a systematic review

PurposeMultiple sclerosis (MS) is a chronic progressive neurological disorder. Several environmental factors have been discussed as possible causing agents, e.g. organic solvents, whose impact on the disease is analysed in this review.MethodsSystematic search strategies were used to identify high-quality studies of workers exposed to organic solvents, published up to September 30, 2019, in databases, such as PubMed, Cochrane library and Scopus. The exposure was in most studies obtained by questionnaires, supplemented with telephone interviews. The diagnosis MS was mainly detemined following a thorough neurological examination. Finally, fourteen case–control studies and two cohort studies met the inclusion criteria and were included in the meta-analysis. Random effects models were used to pool the results of the studies.ResultsThe odds ratios from the 14 case–control studies included in the meta-analysis ranged from 0.12–4.0. Five case–control studies and one cohort study showed a significant association between the development of multiple sclerosis and exposure to organic solvents. The results from the other nine case–control studies and from one of the two cohort studies did not reach statistical significance. The pooled data from the 14 case–control studies gave an OR of 1.44 (95% CI 1.03–1.99), which shows a moderately increased risk of developing MS after exposure to organic solvents.ConclusionsThe final interpretation of the result is that organic solvents may be slightly associated with an increased risk to develop MS. In addition, other factors, e.g. genetic markers and smoking, may contribute to the development of the disease.

Gait Training Methods and ChangesiIn Gait Parameters in Parkinson`s Disease (Literature Review)

Parkinson’s disease is a chronic progressive neurological disorder that can impact function to a variable degree. Changes in gait parameters are the most common signs of Parkinson’s disease. Patients with Parkinson’s disease walk with a reduced step length, step time, walking velocity and walking cadence, increased stride cycle time, coefficient of variation of the step amplitude and step time and increased risk to fall. So, various gait training methods are applied. The effect of rhythmic auditory stimulation on gait in Parkinson’s disease patients is analysed. We can use various kinds of music, metronome, scansion and clapping as a rhythmic auditory stimulation.One of gait training methods in Parkinson’s disease patients is treadmill training. There are attempts to combine treadmill training with transcranial magnetic stimulation and virtual reality. We can use Nordic walking method and because walking technique requires straight posture, trunk rotation, bigger step and heel stride. More often robot–assisted gait training is used in patients with Parkinson’s disease gait training. The effect of dual–tasking and walking with music methods for gait and balance training in patients with Parkinson’s disease is also analysed. This method requires participants to perform primary and secondary tasks at the same time. The secondary task can be cognitive or motor. Dual–tasking is widely analysed because opinions about applying this method are very controversial. Walking with music method is more often analysed in scientific literature. This method could not be compared to rhythmic auditory stimulation method because the latter requires precise walking to rhythm and walking with music method is oriented to emotional component (music is chosen according patients’ music taste). As these methods are applied, we can see an increase in chosen walking and maximal walking velocities, step length and time, distance covered, and decrease in the coefficient of variation of the step time and turning time.Keywords: Gait impairments, walking velocity, rhythmic auditory stimulation.

MiR-124 and the Underlying Therapeutic Promise of Neurodegenerative Disorders.

Neurodegenerative disorders (NDDs) are a group of chronic progressive neurological diseases based on primary neurodegeneration. The common pathological characteristics of various NDDs are neuronal degeneration, deletion, glial cell proliferation, and hypertrophy at specific locations in the nervous system. Proliferation and hypertrophy of microglia are manifestations of inflammation. MicroRNAs (miRNAs) have emerged as pivotal regulators of glial cells. MiRNAs are small non-coding molecules that regulate gene expression. Altered expression of miRNAs has been associated with several NDD pathological processes, among which regulation of the inflammatory response is key and a research hotspot at present. At the same time, miRNAs are also biological markers for diagnosis and potential targets for treating NDDs. MiR-124 is highly conserved and enriched in the mammalian brain. Emerging studies have suggested that miR-124 is closely related to the pathogenesis of NDDs and may be an effective treatment strategy to reduce inflammation associated with NDDs. In this review, we describe a summary of general miRNA biology, implications in pathophysiology, the potential roles of miR-124 associated with inflammation, and the use of miRNA as a future biomarker and an application for NDD therapy.

The Bu Shen Yi Sui Formula Promotes Axonal Regeneration via Regulating the Neurotrophic Factor BDNF/TrkB and the Downstream PI3K/Akt Signaling Pathway.

Axonal damage is recognized as an important pathological feature in the chronic progressive neurological disorder multiple sclerosis (MS). Promoting axonal regeneration is a critical strategy for the treatment of MS. Our clinical and experimental studies have shown that the Bu Shen Yi Sui formula (BSYS) promotes axonal regeneration in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, but the exact mechanism has not been thoroughly elucidated to date. In this study, we investigated the effects of BSYS and its two decomposed formulas—the Bu Shen formula (BS) and the Hua Tan Huo Xue formula (HTHX)—on brain-derived neurotrophic factor (BDNF)/TrkB and related signaling pathways to explore the mechanism by which axonal regeneration is promoted in vitro and in vivo. Damaged SH-SY5Y cells incubated with low serum were treated with BSYS-, BS-, and HTHX-containing serum, and EAE mice induced by the myelin oligodendrocyte glycoprotein (MOG)35–55 peptide were treated with BSYS. The results showed that the BSYS-containing serum markedly increased cell viability and increased the levels of growth associated protein (GAP)-43, phosphorylated (p)-cAMP-response element binding protein (CREB), BDNF, TrkB, and p-PI3K. The BS and HTHX treatments also induced the protein expression of GAP-43 and p-extracellular signal-regulated kinase (ERK) in the cells. Furthermore, the effects of BSYS on cell viability, GAP-43, p-CREB, and neurite outgrowth were clearly inhibited by LY294002, a specific antagonist of the PI3K signaling pathways. The addition of U0126 and U73122, antagonists of the ERK and PLCγ pathway, respectively, significantly inhibited cell viability and GAP-43 protein expression. Moreover, BSYS treatment significantly increased the expression of the 68-, 160-, and 200-kDa neurofilaments (NFs) of proteins and the BDNF, TrkB, PI3K, and Akt mRNA and proteins in the brain or spinal cord of mice at different stages. These results indicated that BSYS promotes nerve regeneration, and its mechanism is mainly related to the upregulation of the BDNF/TrkB and PI3K/Akt signaling pathways. BS and HTHX also promoted nerve regeneration, and this effect involved the ERK pathway.

Advance care planning in progressive neurological diseases: lessons from ALS

BackgroundThere is increasing awareness of the need for an integrated palliative care approach in chronic progressive neurological diseases. Advance care planning (ACP) is an integral part of this approach. As a systematically organized and ongoing communication process about patients’ values, goals and preferences regarding medical care during serious and chronic illness, ACP aims to involve patients in decision-making before they become cognitively and communicatively incapable. However, it remains underutilized in daily neurological practice except for speciality clinics such as ALS centers. Our aim was to study ACP in the tertiary ALS center Amsterdam and to investigate patients’ reflections on it. Subsequently we used this knowledge to formulate recommendations for integration of ACP in the care of patients with other chronic progressive neurological diseases.MethodsNon-participating observations of all appointments of patients with amyotrophic lateral sclerosis (ALS) or progressive muscular atrophy (PMA) with the treating physician, in various stages of disease, during 6 consecutive months, followed by single in-depth interviews, and an inductive analysis.ResultsTwenty-eight Dutch patients participated, varying in age, gender, disease onset and severity of physical decline. ACP started directly when the diagnosis was given, by means of a general outlook on the future with progressive disability and immediate introduction to a customized multidisciplinary team. During follow-up ACP was realized by regular appointments in which monitoring of the patient’s status and clear communication strategies formed the basis of tailor-made discussions on treatment options. Patients accepted this policy as careful professional guidance.ConclusionsACP is a professional communication process throughout the whole course of progressive disease. It is feasible to integrate ACP into follow-up of patients with ALS and PMA from diagnosis onwards. Supported by recent literature, we argue that such a well-structured approach would also enhance the quality of care and life of patients with other chronic progressive neurological diseases.

Passing the sniff test

Parkinson's Disease Parkinson's disease (PD) is a chronic progressive neurological disorder that largely affects movement. There is currently no diagnostic test. Trivedi et al. collected sebum samples from PD patients and unaffected volunteers to identify volatile metabolites that may serve as PD biomarkers. The research team included a woman with a sensitive sense of smell who reported to be able to detect PD by odor. In blinded studies, she identified the “musky” samples that belonged to the PD patients with high accuracy, which guided mass spectrometry to identify the volatile compounds that constituted a signature PD scent. These studies may pave the way for development of the first PD-specific diagnostic test. ACS Cent. Sci. 10.1021/acscentsci.8b00879 (2019).

The Role of Palliative Care in Chronic Progressive Neurological Diseases-A Survey Amongst Neurologists in the Netherlands.

Background: Chronic progressive neurological diseases like high grade glioma (HGG), Parkinson's disease (PD), and multiple sclerosis (MS) are incurable, and associated with increasing disability including cognitive impairment, and reduced life expectancy. Patients with these diseases have complex care needs. Therefore, timely advance care planning (ACP) is required. Our aim was to investigate timing and content of discussions on treatment restrictions, i.e., to initiate, withhold, or withdraw treatment in patients with HGG, PD, and MS, from the neurologists' perspective.Methods: We performed a national online survey amongst consultants in neurology and residents in The Netherlands. The questionnaire focused on their daily practice concerning timing and content of discussions on treatment restrictions with patients suffering from HGG, PD or MS. We also inquired about education and training in discussing these issues.Results: A total of 125 respondents [89 neurologists (71%), 62% male, with a median age of 44 years, and 36 residents (29%), 31% male with a median age of 29 years] responded. Initial discussions on treatment restrictions were said to take place during the first year after diagnosis in 28% of patients with HGG, and commonly no earlier than in the terminal phase in patients with PD and MS. In all conditions, significant cognitive decline was the most important trigger to advance discussions, followed by physical decline, and initiation of the terminal phase. Most discussed issues included ventilation, resuscitation, and admission to the intensive care unit. More than half of the consultants in neurology and residents felt that they needed (more) education and training in having discussions on treatment restrictions.Conclusion: In patients with HGG discussions on treatment restrictions are initiated earlier than in patients with PD or MS. However, in all three diseases these discussions usually take place when significant physical and cognitive decline has become apparent and commonly mark the initiation of end-of-life care. More than half of the responding consultants in neurology and residents feel the need for improvement of their skills in performing these discussions.