Degenerative Neurological and Neuromuscular Disease最新文献

The advent of interferon therapy for the treatment of multiple sclerosis (MS) was a massive advancement in the field and changed the course of the disease. While the exact mechanism of interferon therapy in MS is unknown, disease control is likely mediated by reducing Th1 and Th17 cells while increasing regulatory T cells and altering the cytokine profile. Interferon therapy not only gave physicians and patients an evidence-based treatment option to treat MS by decreasing relapses and the accrual of disability but it also provided valuable insight into disease pathophysiology that allowed for the development of further treatments. Currently, there are 18 disease-modifying therapies available for the treatment of MS with varying efficacies, routes of administration, and mechanisms. As treatment options in the field have evolved, interferon therapy is less commonly prescribed as first-line therapy, because the newer therapies are more effective and better tolerated. That being said, interferons still have a place in the field in both clinical practice and clinical trial research. In this review, we will summarize the safety and efficacy of interferon therapy and discuss its current place in MS care.

Dysphagia after multiple sclerosis (MS) is a common disabling symptom which can lead to serious complications. Regular screening and assessment of dysphagia in patients with MS are important. Using valid and reliable instruments to measure dysphagia in MS patients is a crucial component in clinical practice and of research quality. There are various strategies to diagnose and assess the dysphagia in patients with MS. Screening strategies are for early diagnosis of the dysphagia. Clinical, non-instrumental strategies are used to verify the presence and to determine the severity and cause of dysphagia. Instrumental strategies are complementary to clinical examination to provide objective data on the various aspects of swallowing dysfunctions. This review revealed a few validated tools for dysphagia assessment in MS. The Dysphagia in Multiple Sclerosis Questionnaire (DYMUS) and the Mann Assessment of Swallowing Ability (MASA) are the only validated MS-specific dysphagia tools. Further development of valid and reliable MS-specific screening and assessment tools that can be administered rapidly and scored easily to detect dysphagia and evaluate clinical outcomes in adults with MS is imperative. Until then, validation and metric evaluation of the screening and assessment tools currently available are required.

Neurologic and neuropsychiatric diseases are associated with great morbidity and mortality. Prostaglandins (PGs) are formed by sequential oxygenation of arachidonic acid in physiologic and pathologic conditions. For the production of PGs cyclooxygenase is a necessary enzyme that has two isoforms, that are named COX-1 and COX-2. COX-1 produces type 1 prostaglandins and on the other hand, COX-2 produces type 2 prostaglandins. Recent studies suggest PGs abnormalities are present in a variety of neurologic and psychiatric disorders. In a disease state, type 2 prostaglandins are mostly responsible and type 1 PGs are not so important in the disease state. In this review, the importance of prostaglandins especially type 2 in brain diseases has been discussed and their possible role in the initiation and outcome of brain diseases has been assessed. Overall the studies suggest prostaglandins are the agents that modulate the course of brain diseases in a positive or negative manner. Here in this review article, the various aspects of PGs in the disease state have discussed. It appears more studies must be done to understand the exact role of these agents in the pathophysiology of brain diseases. However, the suppression of prostaglandin production may confer the alleviation of some brain diseases.

Alzheimer's disease is the leading cause of dementia. However, neither Alzheimer's disease nor Alzheimer's dementia are an inevitable consequence of aging. This review provides an overview of the issues involved in a diagnosis of Alzheimer's disease before an individual meets the criteria for Alzheimer's dementia. It examines how Alzheimer's disease diagnosis rates can be improved, the implications of an early diagnosis for the individual, carer and society, and the importance of risk reduction to prevent or delay progression. Although no disease-modifying agents capable of reversing the initial pathological changes are currently available, it may be possible to prevent or delay the development of dementia in a proportion of the population by modifying exposure to common risk factors. In other individuals, diagnosing the disease or risk of disease early is still valuable so that the individual and their carers have time to make choices and plan for the future, and to allow access to treatments that can help manage symptoms. Primary healthcare professionals play a pivotal role in recognising individuals at risk, recommending lifestyle changes in mid-adult life that can prevent or slow down the disease, and in timely diagnosis. Early intervention is the optimal strategy, because the patient's level of function is preserved for longer.

Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon disorder of neuromuscular transmission with distinctive pathophysiological, clinical, electrophysiological and laboratory features. There are two forms of LEMS. The paraneoplastic (P-LEMS) form is associated with a malignant tumor that is most frequently a small cell lung carcinoma (SCLC), and the autoimmune (A-LEMS) form is often related to other dysimmune diseases. Approximately 90% of LEMS patients present antibodies against presynaptic membrane P/Q-type voltage-gated calcium channels (VGCC). These antibodies are directly implicated in the pathophysiology of the disorder, provoke reduced acetylcholine (ACh) at the nerve terminal and consequently lead to muscle weakness. LEMS is clinically characterized by proximal muscle weakness, autonomic dysfunction and areflexia. In clinically suspected cases, diagnoses are confirmed by serological and electrodiagnostic tests. The detection of P/Q-type VGCC antibodies is supportive when there is clinical suspicion but should be carefully interpreted in the absence of characteristic clinical or electrodiagnostic features. Typical electrodiagnostic findings (ie, reduced compound motor action potentials (CMAPs), significant decrements in the responses to low frequency stimulation and incremental responses after brief exercise or high-frequency stimulation) reflect the existence of a presynaptic transmission defect and are key confirmatory criteria. Diagnosis requires a high level of awareness and necessitates the initiation of a prompt screening and surveillance process to detect and treat malignant tumors. In clinically affected patients without cancer and after cancer treatment, symptomatic treatment with 3,4-diaminopyridine or immunosuppressive agents can significantly improve neurologic symptoms and the quality of life. We present a detailed review of LEMS with special emphasis on the pathophysiological mechanisms, clinical manifestation and diagnostic procedure.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor neuron, which selectively affects it both at central (first motor-neuron) and peripheral level (second motor-neuron). The disease shows up at a mean age of 56 years and the most affected are males. Although ALS may start as a bulbar or spinal disease, with the progression of the disease typically both become evident. Pharmacological approved treatments for ALS are still limited and include riluzole and edaravone which improve survival over time. Despite this, ALS leads to progressive muscle involvement and requires a complex multidisciplinary approach to manage increasing disability which goes beyond motor neurons. Sialorrhea is, amongst others, one of the most disabling symptoms in ALS. The complexity in managing saliva is due to a muscular spasticity and to a scarce palatino-lingual muscles control, rather than to an overproduction of saliva. These features could increase the risk of aspiration pneumonia and limit the use of noninvasive mechanical ventilation. We reviewed the treatment for sialorrhea in ALS patients that are available at this time, emphasizing pros and cons for each approach. Our purpose is to create a practical tool for the diagnosis, in order to facilitate the quantification and management of sialorrhea in everyday practice.

Therapies targeting mutant huntingtin DNA, mRNA, and protein have a chance at becoming the first disease-modifying treatments for Huntington's disease, a fatal inherited neurodegenerative disorder for which only symptom management treatments are available today. This review focuses on evidence addressing several key questions pertinent to huntingtin-lowering, ranging from the functions of wild-type huntingtin (wtHTT) that may be disrupted by huntingtin-lowering treatments through the various ways huntingtin can be lowered, the tolerability of wtHTT-lowering in mice and primates, what has been found in the Ionis Pharmaceutical safety trial of a huntingtin-lowering therapy, and to the question of how much mutant huntingtin may need to be lowered for a therapy to be clinically effective. We conclude that adverse consequences of lowering wtHTT in animals appear to be brain region-specific, and/or dependent upon the animal's stage of development and the amount by which huntingtin is lowered. Therefore, safe approaches to huntingtin-lowering in patients may be to lower huntingtin only moderately, or lower huntingtin only in the most affected brain regions, or lower huntingtin allele-selectively, or all of the above. Many additional questions about huntingtin-lowering remain open, and will only be answered by upcoming clinical trials, such as whether the delivery approaches currently planned will be adequate to get the treatment to the necessary brain regions, and whether non-allele-selective huntingtin-lowering will be safe in the long run. Meantime, there is a role for preclinical research to address key knowledge gaps, including the effects of non-allele-selective huntingtin-lowering on protein trafficking and viability at the cellular level, the tolerability of wtHTT-lowering in the corticostriatal connections of the primate brain, and the effects of this lowering on the functioning of neurotransmitter systems and the transport of neurotrophic factors to the striatum.

Bowel dysfunction in patients with multiple sclerosis (MS) is highly prevalent. Constipation and fecal incontinence can coexist and alternate, impacting on the patient's quality of life and social interactions, as well as burdening the caregivers. The cost for the health care providers is also significant, with increased number of hospital admissions, treatment-related costs, and hospital appointments. The origin is multifactorial, and includes alteration of neurological pathways, polypharmacy, behavioral elements, and ability to access the toilet. Every patient with MS should be sensitively questioned about bowel function, and red flag symptoms should prompt adequate investigations. Manipulation of life style factors and establishment of a bowel regime should be attempted in the first place, and if this fails, other measures such as biofeedback and transanal irrigation should be included. A stoma can improve quality of life, and is not necessarily a last-ditch option. Antegrade colonic enemas can also be an effective option, whilst neuromodulation has not proved its role yet. Effective treatment of bowel dysfunction improves quality of life, reduces incidence of urinary tract infection, and reduces health care costs.

Purpose: Duchenne muscular dystrophy (DMD) is an X-linked recessive pediatric disorder that ultimately leads to progressive muscle degeneration. It has been known that cell-based therapies were used to promote muscle regeneration. The main purpose of this study was to investigate the effects of allogeneic Wharton jelly-derived mesenchymal stem cells therapy in Duchenne muscular dystrophy.

Patients and methods: Four ambulatory and five nonambulatory male patients were assessed as having acceptance criteria. Gene expression and immunohistochemical analysis were performed for dystrophin gene expression. The fluorescent in situ hybridization method was used for detection of chimerism and donor-recipient compatibility. Complement dependent lymphocytotoxic crossmatch test and detection of panel reactive antigen were performed. All patients were treated with 2 × 10⁶ cells/kg dose of allogeneic Wharton jelly-derived mesenchymal stem cells via intra-arterial and intramuscular administration. Stability was maintained in patient follow-up tests, which are respiratory capacity tests, cardiac measurements, and muscle strength tests.

Results: The vastus intermedius muscle was observed in one patient with MRI. Chimerism was detected by fluorescent in situ hybridization and mean gene expression was increased to 3.3-fold. An increase in muscle strength measurements and pulmonary function tests was detected. Additionally, we observed two of nine patients with positive panel reactive antigen result.

Conclusion: All our procedures are well tolerated, and we have not seen any application-related complications so far. Our main purpose of this study was to investigate the effects of allogeneic mesenchymal stem cell therapy and determine its suitability and safety as a form of treatment in this untreatable disorder.