Degenerative Neurological and Neuromuscular Disease最新文献

Background: Tongue and pharyngeal pressure is an essential factor associated with the swallowing function; however, little is known about the difference in tongue and pharyngeal pressure between neuromuscular diseases. This study aimed to characterize tongue and pharyngeal pressure in myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD), and amyotrophic lateral sclerosis (ALS) patients.

Methods: This study recruited 17 DMD patients, 32 DM1 patients, and 26 ALS patients. They underwent separate measurements of tongue and pharyngeal pressure under videofluoroscopy, swallowing 5 mL of barium water. We measured the largest change in pharyngeal pressure in the hypopharynx and the upper esophageal sphincter (UES) over several swallows.

Results: The mean tongue pressure (TP) was greatest in the DMD group than in the other groups (p<0.01). There was a significant difference in pressure changes in the hypopharynx and UES between the DM1 group and other groups (p<0.01). Significant correlations were observed between pressure change in the UES and the patient's age in the DMD group (R=-0.500, p=0.045) and between pressure change in the hypopharynx and TP in the DM1 group (R=0.421, p=0.016). There was a significant correlation between pressure change in the hypopharynx and disease severity in the ALS group (R=0.435, p=0.030).

Conclusion: Patients with DMD, DM1, and ALS have weakness in the muscles involved in swallowing; however, the results of this study suggested that each disorder has a distinctive profile of impairment in the swallowing function.

Amyotrophic lateral sclerosis (ALS) is the commonest form of motor neuron disease and is a fatal, degenerative, multisystem disorder affecting upper and/or lower motor neurons in the motor cortex, brain stem, and spinal cord. ALS is characterized by progressive atrophy of associated bulbar, limb, thoracic, and abdominal muscles and supporting cells manifesting in a range of muscular symptoms such as weakness and wasting and eventual paralysis; the majority of patients will die from respiratory failure within 2-5 years of onset. Riluzole, a synthetic benzothiazole drug with glutamine antagonist activity, is indicated for the treatment of patients with ALS and is the only drug that has been shown to slow the course of the disease and extend survival in ALS patients. The original analyses, and subsequent meta-analyses, of data obtained from randomized controlled trials (RCTs) suggest that riluzole typically extends survival by 2-3 months and increases the chance of an additional year of survival by ~9%. However, published real-world evidence (RWE) from 10 clinical ALS databases indicates that riluzole therapy may afford much greater extension of survival, and improvements in median survival times of more than 19 months have been reported in the overall ALS patient population. This article will review the available data from RCTs and RWE on riluzole therapy.

Multiple sclerosis (MS) is a progressive, neurodegenerative disease with unpredictable phases of relapse and remission. The cause of MS is unknown, but the pathology is characterized by infiltration of auto-reactive immune cells into the central nervous system (CNS) resulting in widespread neuroinflammation and neurodegeneration. Immunomodulatory-based therapies emerged in the 1990s and have been a cornerstone of disease management ever since. Interferon β (IFNβ) was the first biologic approved after demonstrating decreased relapse rates, disease activity and progression of disability in clinical trials. However, frequent dosing schedules have limited patient acceptance for long-term therapy. Pegylation, the process by which molecules of polyethylene glycol are covalently linked to a compound, has been utilized to increase the half-life of IFNβ and decrease the frequency of administration required. To date, there has been one clinical trial evaluating the efficacy of pegylated IFN. The purpose of this article is to provide an overview of the role of IFN in the treatment of MS and evaluate the available evidence for pegylated IFN therapy in MS.

Multiple sclerosis (MS) therapy has evolved rapidly with an increased availability of several immunomodulating therapies over the past two decades. Disease-modifying therapies have proven to be effective in treating relapse-remitting MS (RRMS). However, clinical trials involving some of the same agents for secondary-progressive and primary-progressive MS (SPMS and PPMS) have been largely negative. The pathogenesis of progressive MS remains unclear, but B-cells may play a significant role in chronic compartmentalized inflammation, likely contributing to disease progression. Biologics targeted at B-cells, such as rituximab, are effective in treating RRMS. Ocrelizumab is a humanized monoclonal antibody to CD20⁺ B-cells that has shown positive results in PPMS with a significant reduction in disease progression. This review aims to discuss in detail the involvement of B-cells in MS pathogenesis, current progress of currently available and investigational biologics, with focus on ocrelizumab, and future prospects for B-cell therapy in PPMS.

Multiple sclerosis (MS) is an autoimmune disease affecting the brain and spinal cord that is associated with chronic inflammation leading to demyelination and neurodegeneration. With the recent increase in the number of available therapies for MS, optimal treatment will be based on a personalized approach determined by an individual patient's prognosis and treatment risks. An integral part of such therapeutic decisions will be the use of molecular biomarkers to predict disability progression, monitor ongoing disease activity, and assess treatment response. This review describes current published findings within the past 3 years in biomarker research in MS, specifically highlighting recent advances in the validation of cerebrospinal fluid biomarkers such as neurofilaments (light and heavy chains), chitinases and chitinase 3-like proteins, soluble surface markers of innate immunity, and oligoclonal immunoglobulin M antibodies. Current research in circulating miRNAs as biomarkers of MS is also discussed. Continued validation and testing will be required before MS biomarkers are routinely applied in a clinical setting.

Background/objective: A Paleolithic diet may improve fatigue and quality of life in progressive multiple sclerosis (MS) patients, but past research has evaluated the effects of this dietary intervention in combination with other treatments such as exercise. Thus, the purpose of this pilot study was to evaluate a modified Paleolithic dietary intervention (MPDI) in the treatment of fatigue and other symptoms in relapsing-remitting MS (RRMS).

Methods: We measured the effects of a MPDI in 17 individuals with RRMS. Of 34 subjects randomly assigned to control (maintain usual diet) and intervention (MPDI) groups, nine subjects (one man) completed the control group and eight subjects (one man) completed the MPDI.

Results: Significant improvements were seen in Fatigue Severity Scale score and also in Multiple Sclerosis Quality of Life-54 and time to complete (dominant hand) 9-Hole Peg Test from baseline in MPDI subjects compared to controls. Increased vitamin K serum levels were also observed in MPDI subjects postprotocol compared to controls.

Conclusion: A Paleolithic diet may be useful in the treatment and management of MS, by reducing perceived fatigue, increasing mental and physical quality of life, increasing exercise capacity, and improving hand and leg function. By increasing vitamin K serum levels, the MPDI may also reduce inflammation.

Neuromuscular ventilatory weakness can be difficult to recognize because the symptoms can be nocturnal, nonspecific, or attributed to other conditions. The presence of respiratory muscle weakness suggests a number of possible heterogeneous conditions, including neurodegenerative, autoimmune, and genetic neuromuscular diseases. In some conditions, disease-modifying management exists, but in the absence of such intervention, supportive respiratory therapy can improve quality of life and survival. In this review, we discuss the differential diagnosis and diagnostic approach to chronic neuromuscular respiratory weakness. We also review the clinical assessment and management of respiratory failure in these conditions.

Multiple sclerosis (MS) is a chronic inflammatory-demyelinating disease of the central nervous system of a putative autoimmune etiology. Although the exact pathogenic mechanisms underlying demyelination and axonal damage in MS are not fully understood, T-cells are believed to play a central role in the pathogenesis of the disease. Daclizumab is a humanized binding monoclonal antibody that binds to the Tac epitope on the α-subunit (CD25) of the interleukin-2 (IL-2) receptor, thus effectively blocking the formation of the high-affinity IL-2 receptor, which is expressed mainly on T-cells. A series of clinical trials in patients with relapsing MS demonstrated a profound effect of daclizumab on inflammatory disease activity and improved clinical outcomes compared with placebo or interferon-β, which led to the recent approval of daclizumab (Zinbryta^™) for the treatment of relapsing forms of MS. Enhancement of endogenous mechanisms of immune regulation rather than inhibition of effector T-cells might explain the effects of daclizumab in MS. These include expansion and improved function of regulatory CD56^bright NK cells, inhibition of the early activation of T-cells through blockade of IL-2 transpresentation by dendritic cells and reduction in the number of intrathecal proinflammatory lymphoid tissue inducer cells. The enhanced efficacy of daclizumab is accompanied by an increased frequency of adverse events and risks of serious adverse events, thus placing it as a second-line therapy and calling for the implementation of a strict risk management program. This review details the mechanisms of action of daclizumab, discusses its efficacy and safety in patients with MS, and provides an insight into the place of this novel therapy in the treatment of MS.

Dementia in Alzheimer's disease (DAD) is more common in adults with Down syndrome (DS), with characteristically an earlier onset. The treatment of DAD is not too dissimilar in the general population and in people with intellectual disabilities. However, the underlying intellectual disability can make the management of DAD more challenging in older adults with DS. This literature review aimed to look at the management of DAD in people with DS. The management of dementia is holistic. This includes treating reversible factors, aiming to slow the cognitive decline, psychological therapies, ensuring that the environment is appropriate, and use of psychotropic medication when necessary to manage behavioral problems, psychotic symptoms, depressive symptoms, and sleep difficulty. Antidementia medications have a role to play but remain limited. The management of DAD in the DS population can be at times challenging, but good clinical practice should involve accurate diagnosis of dementia, treating any reversible additional factors, consideration of psychological and behavioral management, use of antidementia medication, and a multidisciplinary team approach.

The present review is focused on juvenile neuronal ceroid lipofuscinosis (JNCL; Batten disease) due to a mutation in CLN3. Functional vision impairment occurring around 5-6 years of age is the first symptom in more than 80% of patients. Approximately 2 years later (though sometimes simultaneously), obvious signs of cognitive impairment appear. Behavior problems can occur in advance, especially in boys. These include anxious and depressed mood, aggressive behavior, and hallucinations, and even psychotic symptoms. Following the teens, severe dementia is present, including loss of memory, attention, and general reasoning abilities, as well as loss of independent adaptive skills such as mobility, feeding, and communicating. Sleep abnormalities, such as settling problems, nocturnal awakenings, and nightmares, are reported in more than half of patients. The vast majority, if not all, patients develop seizures, starting at approximately 10 years of age. Generalized tonic-clonic seizure occurs as the only type of seizure in approximately half of patients, and in combination with partial seizures in a third of patients. There seems to be no difference in seizure severity according to sex or genotype, and there is great variation in seizure activity among patients. Soon after diagnosis, patients begin to have slight ataxic symptoms, and at adolescence extrapyramidal symptoms (rigidity, bradykinesia, slow steps with flexion in hips and knees) occur with increasing frequency. Chewing and swallowing difficulties emerge as well, and food intake is hampered in the late teens. Disabling periodically involuntary movements may occur as well. A progressive cardiac involvement with repolarization disturbances, ventricular hypertrophy, and sinus-node dysfunction, ultimately leading to severe bradycardia and/or other conduction abnormalities, starts in the mid-teens. Patients are usually bedridden at 20 years of age, and death usually occurs in the third decade of life.