Degenerative Neurological and Neuromuscular Disease最新文献

Three aspects of poststroke cognitive impairment and dementia are discussed in this review: prevalence; diagnosis; and treatment. The aim is to increase awareness of poststroke cognitive impairment in order to further stimulate strategies to recognize the condition and to prevent its progression. Approximately two-thirds of all middle-aged and elderly stroke patients develop cognitive impairment, and one in three develops dementia. The standard reference for diagnosis is a detailed neuropsychological examination. Short screening tests have been used for both clinical and research purposes, but their sensitivity is limited and there is no consensus as to which test is the most appropriate. The treatment of poststroke cognitive impairment and dementia is based on effective treatment of vascular risk factors, including lifestyle modification when needed.

Alzheimer's disease (AD) is the major cause of dementia in the elderly and an unmet clinical challenge. A variety of therapies that are currently under development are directed to the amyloid cascade. Indeed, the accumulation and toxicity of amyloid-β (Aβ) is believed to play a central role in the etiology of the disease, and thus rational interventions are aimed at reducing the levels of Aβ in the brain. Targeting β-site amyloid precursor protein-cleaving enzyme (BACE)-1 represents an attractive strategy, as this enzyme catalyzes the initial and rate-limiting step in Aβ production. Observation of increased levels of BACE1 and enzymatic activity in the brain, cerebrospinal fluid, and platelets of patients with AD and mild cognitive impairment supports the potential benefits of BACE1 inhibition. Numerous potent inhibitors have been generated, and many of these have been proved to lower Aβ levels in the brain of animal models. Over 10 years of intensive research on BACE1 inhibitors has now culminated in advancing half a dozen of these drugs into human trials, yet translating the in vitro and cellular efficacy of BACE1 inhibitors into preclinical and clinical trials represents a challenge. This review addresses the promises and also the potential problems associated with BACE1 inhibitors for AD therapy, as the complex biological function of BACE1 in the brain is becoming unraveled.

In the text that follows, we review the main clinical features, genetic characteristics, and treatment options for Parkinson's disease (PD), considering the age at onset. The clinical variability between patients with PD points at the existence of subtypes of the disease. Identification of subtypes is important, since a focus on homogenous group may lead to tailored treatment strategies. One of the factors that determine variability of clinical features of PD is age of onset. Young-onset Parkinson's disease (YOPD) is defined as parkinsonism starting between the ages of 21 and 40. YOPD has a slower disease progression and a greater incidence and earlier appearance of levodopa-induced motor complications; namely, motor fluctuations and dyskinesias. Moreover, YOPD patients face a lifetime of a progressive disease with gradual worsening of quality of life and their expectations are different from those of their older counterparts. Knowing this, treatment plans and management of symptoms must be paid careful attention to in order to maintain an acceptable quality of life in YOPD patients.

As the population ages, the prevalence of dementia is increasing. Distressing behavioral problems are often part of the illness. This review considers the available evidence for cognitive effects related to music, evidence for the efficacy of music in the management of behavioral problems in dementia, and evidence about the effects of different types of music, their mode of delivery, and any adverse effects. Live music may be more beneficial than recorded. The effect of music may not be lasting, but there is evidence of benefit in studies, which to date are mostly not of high quality.

Background: Post-poliomyelitis syndrome is a clinical condition that can affect poliomyelitis survivors with the onset of new symptoms several years after the acute disease. These symptoms include new muscular weakness, fatigue, pain, onset or aggravation of muscle atrophy, muscle cramps, onset or aggravation of pre-existing difficulties in accomplishing daily life activities, cold intolerance, sleep disorders, dysphonia or dysphagia, and respiratory deficiency. The treatment of post-poliomyelitis syndrome requires a multiprofessional health team because the rehabilitation procedures include lifestyle changes, physiotherapy, avoidance of secondary complications, and physical exercise. As physical exercise is prescribed by physical education professionals, the assessment of knowledge about post-poliomyelitis syndrome among these professionals is very relevant. The aim of this study was to evaluate poliomyelitis and post-poliomyelitis syndrome knowledge among physical education professionals in Brazil.

Methods: We invited participants with an academic degree in physical education (n = 217) to participate in this study. A self-administered survey (30 questions) was designed to probe knowledge about poliomyelitis and post-poliomyelitis syndrome. From the survey, we created a questionnaire to evaluate the performance of the professionals. The questionnaire was composed of 20 questions and a score was provided, varying from 0 (totally uninformed) to 20 (well informed).

Results: Approximately 73% of surveyed participants had never heard of post-poliomyelitis syndrome, and only 19.4% had received information about the disease. Among those surveyed, 61.8% did not know whether restriction of physical activities was warranted for people with poliomyelitis sequelae, and only 32.3% knew that physical exercise (especially intense exercise) should be limited for patients with sequelae of paralytic poliomyelitis.

Conclusion: The findings of the present study indicate a critical need for improvement of knowledge about post-poliomyelitis syndrome among Brazilian physical education professionals.

The diagnosis of movement disorders including Parkinsonian syndromes and essential tremor is mainly clinical. The most common diagnostic errors for Parkinson's disease include misdiagnoses such as Parkinson plus syndromes and cases of essential tremor. In this article, we discuss the clinical utility of DaTscan™ (123I-Ioflupane injection) and its diagnostic value in Parkinson's disease and the other Parkinsonian syndromes. Single photon emission computed tomography with 123I-Ioflupane can be useful to assist in the diagnosis of uncertain cases of Parkinsonism. An accurate diagnosis can aid clinicians in making correct decisions that are related to the overall management and treatment of Parkinson's disease, avoiding common therapeutic errors.

Pseudobulbar affect is a disorder resulting from neurologic damage manifesting as sudden, stereotyped affective outbursts that are not reflective of internal emotion. A literature review was completed to examine the current understanding of the epidemiology, characterization, diagnosis, pathophysiology, and treatment of pseudobulbar affect. This review revealed that it is common in neurodegenerative disorders but is poorly recognized, placing significant impacts on patients and their families. The disorder appears to result from a disruption of the cortico-limbic-subcortical-thalamic-pontocerebellar network involved in emotional expression and regulation with resulting disruptions of neurotransmitter systems. Effective treatment is available with agents such as selective serotonin reuptake inhibitors and dextromethorphan combined with quinidine, but further well-designed comparative studies are needed. Advances in technology such as neuroimaging may enhance knowledge about the pathophysiology of this disorder, and help guide future interventions.

Taiep (tremor, ataxia, immobility, epilepsy, paralysis) mutants show a significant increase in myelin thickness from 10 to 30 days of age but then demonstrate a decrease in myelin thickness from 1 to 6 months. The severity of the demyelination in the optic nerve suggests that visual deficits may exist in the taiep mutants. Animals were trained on a discrimination task, in which responses to a light stimulus (the S^D period) were reinforced on a fixed ratio (FR)-1 schedule, and responses in the absence of the light stimulus (the S^Δ period) were not reinforced. Following training, the light intensity presented during the S^D period was gradually reduced between sessions until -6.0 candela/m² was reached. Both groups of animals - taiep mutants and control Sprague Dawley rats - successfully recognized and responded in the presence of the stimulus near perfectly by the final day of training, suggesting that taiep mutants demonstrated normal learning, at least under this paradigm. Despite the severe demyelination of the taiep optic nerve, no visual deficits were detected as both groups of animals performed similarly as the light intensity decreased. Though the myelin loss of the optic nerve may have negatively affected signal transduction, this did not result in an increase in visual threshold.

Background: The degree of hippocampal magnetic resonance imaging (MRI) volume loss in Alzheimer's disease (AD) is commonly accepted as a marker of disease severity, yet remains expensive, unavailable, or not tolerated by many patients.

Aim: To examine whether the presence of one or more apolipoprotein E (ApoE) e4 alleles is associated with smaller hippocampal MRI volumes in a population of early AD patients.

Methods: A total of 88 consecutive patients attending a community-based memory disorders clinic who had both mild dementia on the Clinical Dementia Rating scale and Diagnostic and Statistical Manual of Mental Disorders criteria for probable AD were recruited. We examined the relationship between ApoE e4 allele load and hippocampal atrophy on MRI volumes.

Results: There was no association between the ApoE e4 load and hippocampal volume in this cohort.

Conclusion: This study suggests that the presence of one or more ApoE e4 alleles cannot be used to estimate pathological disease load in early AD.

Depression in Parkinson's disease (PD) is common, and it appears to worsen the motor and cognitive progression of the disease, and limits the patient's quality of life. In this paper, we review the pharmacotherapy of depression in people with PD. We find that evidence is sparse when it comes to this patient population. There is some evidence that older tricyclic antidepressants (nortriptyline and desipramine) may be effective in this population. There is also growing evidence that newer antidepressants like paroxetine and venlafaxine may be effective. We will also review a number of other promising medication treatments. What is apparent is the need for more research identifying the most effective medications for treating depression in this population. We provide recommendations that fall in line with current evidence-based practice for managing depression in the general population. Also, we suggest that collaborative models of depression care may be a promising approach to support the identification and effective treatment of those with PD also suffering from depressive disorders.