Progressive Neurological Disorder Research Articles

CHRONIC CEREBRAL ISCHEMIA. MODERN VIEW OF THE PROBLEM

Introduction. Chronic cerebral ischemia (CCI) is considered a syndrome that develops as a result of a slowly progressive reduction in cerebral blood flow. This reduction occurs due to the gradual accumulation of ischemic and secondary degenerative changes in the brain, which are caused by repeated ischemic episodes resulting from the development of atherosclerosis and arterial hypertension. These changes lead to impairment of brain functions, manifested by progressive neurological, neuropsychological, and mental disorders.
 The aim. To analyze the problems of pathogenesis, diagnosis, and treatment of CCI from the sources of modern literature in order to optimize the treatment of this group of patients.
 Materials and methods. Bibliosemantic, comparative and method of system analysis.
 Results. The pathogenetic mechanisms underlying CCI remain controversial due to the heterogeneity of causes and the complexity of the neuropathology associated with the disease. However, one common reason that can be named is dysregulation of cerebral blood flow, that results in chronic cerebral hypoperfusion, which can lead to the development of vascular cognitive impairment and dementia. Detection of biological markers in the patients' blood in combination with neuropsychological testing, neurophysiological (CEP P300, EEG) and neuroimaging (CT, MRI, Doppler Ultrasound of the head and neck) methods, which confirms the morphological substrate of vascular disease (leukoareosis, focal changes, multi-infarct condition, cerebral atrophy) and provides the possibility of choosing an effective pathogenetically-justified treatment.
 Conclusions. The rating of effectiveness of treatment in CCI is complicated considering difficulties in the selection of the efficiency criteria due to the significant differences in the methodology and research formats, as well as problem of a significant medication-related burden in the case of comorbidities. In this regard, the main direction in therapy is combined neuroprotection, which allows to optimize the possibilities of this strategy and to increase its clinical significance in angioneurology.

M6A modification and its role in neural development and neurological diseases.

N6-methyladenosine (m6A) methylation, the most prevalent post-transcriptional modification in eukaryotes, represents a highly dynamic and reversible process that is regulated by m6A methyltransferases, m6A demethylases and RNA-binding proteins during RNA metabolism, which affects RNA function. Notably, m6A modification is significantly enriched in the brain and exerts regulatory roles in neurogenesis and neurodevelopment through various mechanisms, further influencing the occurrence and progression of neurological disorders. This study systematically summarizes and discusses the latest findings on common m6A regulators, examining their expression, function and mechanisms in neurodevelopment and neurological diseases. Additionally, we explore the potential of m6A modification in diagnosing and treating neurological disorders, aiming to provide new insights into the molecular mechanisms and potential therapeutic strategies for neurological disorders.

Sleep Disorders in Patients with Neurologic Disease.

This article provides an overview of the growing body of evidence showing bidirectional relationships between sleep and various neurologic disorders. Mounting evidence demonstrates that disrupted sleep can negatively impact various neurologic disease processes, including stroke, multiple sclerosis, epilepsy, neuromuscular disorders including amyotrophic lateral sclerosis, and headache syndromes. Abnormal sleep can also be a precursor to Alzheimer disease and neurodegenerative disease states such as Parkinson disease and dementia with Lewy bodies. Interventions to improve sleep and treat obstructive sleep apnea may play a vital role in preventing neurologic disease development and progression. Sleep disorders are common among patients with neurologic disorders. To provide comprehensive care to patients with neurologic conditions, neurologists must ask patients about sleep issues that may warrant further diagnostic testing, treatment, and sleep medicine referral when indicated.

Multicohort cross-sectional study of cognitive and behavioural digital biomarkers in neurodegeneration: the Living Lab Study protocol

Introduction and aimsDigital biomarkers can provide a cost-effective, objective and robust measure for neurological disease progression, changes in care needs and the effect of interventions. Motor function, physiology and behaviour...

Integrating a Standardized Self-Report Tool into Geriatric Medicine Practice during the COVID-19 Pandemic: A Mixed-Methods Study.

Specialized geriatric services care for older adults (≥ 65 years of age) with dementia and other progressive neurological disorders, frailty, and mental health conditions were provided both virtually and in person during the pandemic. The objective of this study was to implement a software-enabled standardized self-report instrument - the interRAI Check-Up Self-Report - to remotely assess patients. A convergent, mixed-methods research design was employed. Staff found the instrument easy to use and the program-level metrics helpful for planning. Most patients urgently needed a geriatrician assessment (72%) and had moderate to severe cognitive (34%) and functional impairments (34%), depressive symptoms (53%), loneliness (57%), daily pain (32%), and distressed caregivers (46%). Implementation considerations include providing ongoing support and facilitating intersectoral collaboration. The Check Up enhanced the geriatric assessment process by creating a system to track all needs for immediate and future care at both the patient and program level.

Automated Vowel Articulation Analysis in Connected Speech Among Progressive Neurological Diseases, Dysarthria Types, and Dysarthria Severities.

Although articulatory impairment represents distinct speech characteristics in most neurological diseases affecting movement, methods allowing automated assessments of articulation deficits from the connected speech are scarce. This study aimed to design a fully automated method for analyzing dysarthria-related vowel articulation impairment and estimate its sensitivity in a broad range of neurological diseases and various types and severities of dysarthria. Unconstrained monologue and reading passages were acquired from 459 speakers, including 306 healthy controls and 153 neurological patients. The algorithm utilized a formant tracker in combination with a phoneme recognizer and subsequent signal processing analysis. Articulatory undershoot of vowels was presented in a broad spectrum of progressive neurodegenerative diseases, including Parkinson's disease, progressive supranuclear palsy, multiple-system atrophy, Huntington's disease, essential tremor, cerebellar ataxia, multiple sclerosis, and amyotrophic lateral sclerosis, as well as in related dysarthria subtypes including hypokinetic, hyperkinetic, ataxic, spastic, flaccid, and their mixed variants. Formant ratios showed a higher sensitivity to vowel deficits than vowel space area. First formants of corner vowels were significantly lower for multiple-system atrophy than cerebellar ataxia. Second formants of vowels /a/ and /i/ were lower in ataxic compared to spastic dysarthria. Discriminant analysis showed a classification score of up to 41.0% for disease type, 39.3% for dysarthria type, and 49.2% for dysarthria severity. Algorithm accuracy reached an F-score of 0.77. Distinctive vowel articulation alterations reflect underlying pathophysiology in neurological diseases. Objective acoustic analysis of vowel articulation has the potential to provide a universal method to screen motor speech disorders. https://doi.org/10.23641/asha.23681529.

Using artificial intelligence to learn optimal regimen plan for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurological disorder with no specific curative medications. Sophisticated clinical skills are crucial to optimize treatment regimens given the multiple coexisting comorbidities in the patient population. Here, we propose a study to leverage reinforcement learning (RL) to learn the clinicians' decisions for AD patients based on the longitude data from electronic health records. In this study, we selected 1736 patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We focused on the two most frequent concomitant diseases-depression, and hypertension, thus creating 5 data cohorts (ie, Whole Data, AD, AD-Hypertension, AD-Depression, and AD-Depression-Hypertension). We modeled the treatment learning into an RL problem by defining states, actions, and rewards. We built a regression model and decision tree to generate multiple states, used six combinations of medications (ie, cholinesterase inhibitors, memantine, memantine-cholinesterase inhibitors, hypertension drugs, supplements, or no drugs) as actions, and Mini-Mental State Exam (MMSE) scores as rewards. Given the proper dataset, the RL model can generate an optimal policy (regimen plan) that outperforms the clinician's treatment regimen. Optimal policies (ie, policy iteration and Q-learning) had lower rewards than the clinician's policy (mean -3.03 and -2.93 vs. -2.93, respectively) for smaller datasets but had higher rewards for larger datasets (mean -4.68 and -2.82 vs. -4.57, respectively). Our results highlight the potential of using RL to generate the optimal treatment based on the patients' longitude records. Our work can lead the path towards developing RL-based decision support systems that could help manage AD with comorbidities.

Unmasking the Mystery of A Hidden Syrinx: Case Report of Progressive Paralysis in A 20-Year-Old Male with Intact Pain and Temperature Sensations

Syringomyelia is a progressive neurological disorder in which a fluid-filled cyst known as syrinx forms within the spinal cord. The case of a 20-year of adult is presented with lower limb stiffness and difficulty in walking for last 3 years. For the last 1 year, he also developed stiffness of upper limbs. Upon examination, he had a spastic gait with no ataxia. There was muscle wasting of both upper and lower limbs, with fasciculation. Tone was increased with reduced power and hyperreflexia bilaterally in all four limbs with positive ankle clonus and upgoing plantars bilaterally. Sensory system, cerebellum and higher motor functions were intact. MRI scan revealed an abnormal intramedullary multifocal T2WI hyper intense signal in cervical and thoracic spinal cord consistent with syrinx and he was diagnosed with Syringomyelia. This case is an uncommon presentation of Syringomyelia presenting with predominantly upper motor neuron lesion without sensory involvement

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.

Dementia: recognition and cognitive testing in community and primary care settings.

Dementia is an umbrella term used to describe a group of symptoms characterised by behavioural changes, as well as loss of cognitive and social functioning brought about by progressive neurological disorders. There are approximately 944 000 people living with dementia in the UK and estimates indicate this will increase to over 2 million by 2051. Dementia, if left undiagnosed, can have an insidious and harmful impact on the people and their families who are affected by it. A timely diagnosis can be made when a person with a possible dementia comes to the attention of clinicians due to concerns about changes in their cognition, behaviour, or functioning. Community nurses are well-placed to observe changes in their older patients, which may be indicative of early dementia. This paper uses a case study to illustrate possible early signs of dementia and discusses the recognition and initial cognitive tests that can be used in a primary care setting.

Modulation of immunity by tryptophan microbial metabolites.

Tryptophan (Trp) is an essential amino acid that can be metabolized via endogenous and exogenous pathways, including the Kynurenine Pathway, the 5-Hydroxyindole Pathway (also the Serotonin pathway), and the Microbial pathway. Of these, the Microbial Trp metabolic pathways in the gut have recently been extensively studied for their production of bioactive molecules. The gut microbiota plays an important role in host metabolism and immunity, and microbial Trp metabolites can influence the development and progression of various diseases, including inflammatory, cardiovascular diseases, neurological diseases, metabolic diseases, and cancer, by mediating the body's immunity. This review briefly outlines the crosstalk between gut microorganisms and Trp metabolism in the body, starting from the three metabolic pathways of Trp. The mechanisms by which microbial Trp metabolites act on organism immunity are summarized, and the potential implications for disease prevention and treatment are highlighted.

The Crosstalk between Gut Microbiota and Nervous System: A Bidirectional Interaction between Microorganisms and Metabolome.

Several studies have shown that the gut microbiota influences behavior and, in turn, changes in the immune system associated with symptoms of depression or anxiety disorder may be mirrored by corresponding changes in the gut microbiota. Although the composition/function of the intestinal microbiota appears to affect the central nervous system (CNS) activities through multiple mechanisms, accurate epidemiological evidence that clearly explains the connection between the CNS pathology and the intestinal dysbiosis is not yet available. The enteric nervous system (ENS) is a separate branch of the autonomic nervous system (ANS) and the largest part of the peripheral nervous system (PNS). It is composed of a vast and complex network of neurons which communicate via several neuromodulators and neurotransmitters, like those found in the CNS. Interestingly, despite its tight connections to both the PNS and ANS, the ENS is also capable of some independent activities. This concept, together with the suggested role played by intestinal microorganisms and the metabolome in the onset and progression of CNS neurological (neurodegenerative, autoimmune) and psychopathological (depression, anxiety disorders, autism) diseases, explains the large number of investigations exploring the functional role and the physiopathological implications of the gut microbiota/brain axis.

N-methyl-D-aspartate receptor hypofunction as a potential contributor to the progression and manifestation of many neurological disorders.

N-methyl-D-aspartate receptors (NMDA) are glutamate-gated ion channels critical for synaptic transmission and plasticity. A slight variation of NMDAR expression and function can result in devastating consequences, and both hyperactivation and hypoactivation of NMDARs are detrimental to neural function. Compared to NMDAR hyperfunction, NMDAR hypofunction is widely implicated in many neurological disorders, such as intellectual disability, autism, schizophrenia, and age-related cognitive decline. Additionally, NMDAR hypofunction is associated with the progression and manifestation of these diseases. Here, we review the underlying mechanisms of NMDAR hypofunction in the progression of these neurological disorders and highlight that targeting NMDAR hypofunction is a promising therapeutic intervention in some neurological disorders.

ANESTHETIC MANAGEMENT OF A SHORT UROLOGICAL PROCEDURE IN A PATIENT WITH MULTISYSTEM ATROPHY - CEREBELLAR TYPE: A CASE REPORT

Multisystem atrophy cerebellar type (MSA-C) is a rare, fatal, and progressive neurological disorder characterized by features of atypical parkinsonism and autonomic dysfunction. This condition poses numerous challenges in the perioperative period to the anesthesiologist for the safe conduct of anesthesia. Here, we report a case of 65-year-old male patient with the diagnosis of MSA-C who was posted for a short urological procedure. General anesthesia is usually preferred for MSA-C patients due to the autonomic dysfunction. However, after considering the risks of general anesthesia in MSA-C, we administered a low-dose spinal anesthetic. The patient was hemodynamically throughout the surgery and the post-operative period was uneventful.

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.

The role of DNA methylation in progression of neurological disorders and neurodegenerative diseases as well as the prospect of using DNA methylation inhibitors as therapeutic agents for such disorders.

This review aims to describe the role of DNA methylation in inhibiting and progressing neurological and neurodegenerative disorders and therapeutic approaches. A Systematic search of PubMed, Web of Science, and Cochrane Library was conducted for all qualified studies from 2000 to 2022. For the current need of time, we have focused on the DNA methylation role in neurological and neurodegenerative diseases and the expression of genes involved in neurodegeneration such as Alzheimer's, Depression, and Rett Syndrome. Finally, it appears that the various epigenetic changes do not occur separately and that DNA methylation and histone modification changes occur side by side and affect each other. We focused on the role of modification of DNA methylation in several genes associated with depression (NR3C1, NR3C2, CRHR1, SLC6A4, BDNF, and FKBP5), Rett syndrome (MECP2), Alzheimer's, depression (APP, BACE1, BIN1 or ANK1) and Parkinson's disease (SNCA), as well as the co-occurring modifications to histones and expression of non-coding RNAs. Understanding these epigenetic changes and their interactions will lead to better treatment strategies. This review captures the state of understanding of the epigenetics of neurological and neurodegenerative diseases. With new epigenetic mechanisms and targets undoubtedly on the horizon, pharmacological modulation and regulation of epigenetic processes in the brain holds great promise for therapy.

Vanishing white matter disease: a case of combined saposin deficiency

Vanishing white matter disease (VWMD) is an autosomal recessive neurodegenerative disease often present during childhood and is exacerbated by trauma and other stressors. VWMD is caused by EIF2B gene mutation, which encodes eukaryotic initiation factor 2 B (EIF2B), a transcription factor activated by insulin that is a major protein synthesis regulator during the integrated stress response. Autosomal recessive combined saposin deficiency is a metachromatic leukodystrophy, a progressive neurological disorder characterized by motor delay, regression of gained skills, and nerve demyelination. Here, we present the case of an 11-year-old Hispanic male presenting with ataxia, dysphagia, and global developmental delay which was found to have VWMD on imaging. A genetic panel reveals the PSAP gene, a novel presentation in the setting of VWMD.

Loss of Vision in a Division I Basketball Player

We present a case report of a 20-year-old cis female division 1 collegiate basketball athlete who presented to her team physician with concerns for bilateral temporal, throbbing headache and sudden-onset, non-traumatic, right eye irritation and blurred vision. She was found to have optic neuritis and ultimately diagnosed with multiple sclerosis (MS). Although MS is the most common progressive neurologic disease of young adults there is limited research on athletes with MS. While the pathogenesis of MS remains unknown, current science identifies MS as a multifactorial condition influenced by both environmental and genetic factors. MS has a female predominance and presents most often between the ages of 20 to 45 years old. Since musculoskeletal and/or neurological symptoms are often the first sign of MS it is necessary for healthcare professionals caring for athletes to be familiar with the diagnosis, management and prognosis of MS. This case presents several key themes that aim to assist clinicians caring for athletes with MS. MS can present similar to sports-related injuries (e.g., concussions, overtraining, psychosocial stressors, musculoskeletal injuries) therefore diagnosis in the athletic population is easily missed. Without a healthcare team familiar with the immediate and future needs of the athlete, subpar preliminary and continuous treatment may result in devastating health changes and career ending consequences in athletes. Treatment goals must also align with the patient's athletic goals. Additionally, this case highlights unforeseen ethical and clinical obstacles including the repercussions of the COVID-19 pandemic that must be considered by clinicians involved in the medical care of athletes.

Benzoic-D5 acid as D2 receptor agonist in the treatment of rotenone induced Parkinson’s disease in mice

Parkinson's disease is a progressive neurological disorder that affects movement. It is caused by the degeneration of dopamine-producing neurons in the brain. There is no cure for Parkinson's disease, but there are treatments available that can help manage the symptoms. Medications such as levodopa, dopamine agonists and Amantadine (Amd) can help to increase dopamine levels in the brain. Sodium benzoate (Benzoic-D5) is used as preservative in foods due to its antimicrobial potential. Benzoic-D5 showed a pivotal role in ameliorating the symptoms of Parkinson’s disease (PkD) in animal model. The current study is designed to probe the anti-Parkinson potential of Benzoic-D5 in the rotenone (ROT)-induced PkD mice. Behavioral studies showed improvement in sensory-motor functions, and neuromuscular strength in wire hanging test, grip strength, vertical rod test, and swim test. Evaluation of biochemical markers suggested increase in catalase (CAT) and superoxide dismutase (SOD), but decreases in the malondialdehyde (MDA) activity. Dopamine, dihydroxyphenyl acetic acid (DOPAC), and homovanillic acid (HVA) levels were improved in Benzoic-D5-treated animals. Moreover, there were down regulation of pro-inflammatory markers like TNF-α, NF-Kβ, and up regulation of anti-inflammatory IL-4 in the RT-PCR analysis. In molecular docking Benzoic-D5 showed strong binding affinity with an active site of Dopamine D2 receptor. Afterwards, ADMET analysis points to the selected drug’s acceptable properties. Conclusively, in vivo, and in silico studies propose that Benzoic-D5 possesses potentials to ameliorate symptoms of PkD. Binding energy data of Benzoic-D5 (-6.2), shows promising results compared to ROT (-6.0), and Amd (5.8).

Progressive myoclonus and neuroregression – a dreadful combination

Progressive myoclonic epilepsy (PME) is a gradually progressive neurological disorder characterized by the development of progressive myoclonus, ataxia, and cognitive impairment with other neurodeficits. There are a wide variety of PMEs, such as Lafora body disease (LBD), neuronal ceroid lipofuscinoses, Unverricht-Lundborg disease, myoclonic epilepsy with ragged-red fiber syndrome, sialidoses, dentato-rubro-pallidal atrophy, storage diseases, and some of the inborn errors of metabolism, among others. Although the modern genetic tests are helpful in discerning underlying etiology, the clinical differentiation is often possible with historical background and clinical examination. We report a case of PME, where we suspected LBD on basis of clinical history and examination, which was confirmed with skin biopsy and next-generation sequencing.