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Spinal muscular atrophy (SMA) is a heritable neuromuscular disorder that causes degeneration of the alpha motor neurons from anterior horn cells in the spinal cord, which causes severe progressive hypotonia and muscular weakness. With a carrier frequency of 1 in 40– 50 and an estimated incidence of 1 in 10,000 live births, SMA is the second most common autosomal recessive disorder. Affected individuals with SMA have a homozygous loss of function of the survival motor neuron gene SMN1 on 5q13 but keep the modifying SMN2 gene. The most common mutation causing SMA is a homozygous deletion of the SMN1 exon 7, which can be readily detected and used as a sensitive diagnostic test. Because SMN2 produces a reduced number of full-length transcripts, the number of SMN2 copies can modify the clinical phenotype and as such, becomes an essential predictive factor. Population-based SMA carrier screening identifies carrier couples that may pass on this genetic disorder to their offspring and allows the carriers to make informed reproductive choices or prepare for immediate treatment for an affected child. Three treatments have recently been approved by the Food and Drug Administration (FDA). Nusinersen increases the expression levels of the SMN protein using an antisense oligonucleotide to alter splicing of the SMN2 transcript. Onasemnogene abeparvovec is a gene therapy that utilizes an adeno-associated virus serotype 9 vector to increase low functional SMN protein levels. Risdiplam is a small molecule that alters SMN2 splicing in order to increase functional SMN protein. Newborn screening for SMA has been shown to be successful in allowing infants to be treated before the loss of motor neurons and has resulted in improved clinical outcomes. Several of the recommendations and guidelines in the review are based on studies performed in the United States. [ABSTRACT FROM AUTHOR]

Background: Effects of dopaminergic medication on executive function in patients with Parkinson's disease (PD) are inconsistent. Objective: We examined the effect of dopaminergic medication on executive function in 24 drug-naïve PD patients (de novo group) and in 21 PD patients on chronic dopaminergic medication (chronic medication group). Methods: PD patients without dementia were included in this study. For the de novo group patients, dopaminergic medication was initiated, and the dose was increased to improve motor symptoms. For the chronic medication group patients, dopaminergic medication was adjusted to relieve clinical problems. All participants were tested prior to and at 4-7 months after the drug initiation/adjustment. Executive function was assessed by using the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Motor function was assessed by using the Unified Parkinson's Disease Rating Scale (UPDRS; part III). Improvement in executive function was compared with a simultaneous change in levodopa equivalent doses (LED) of dopaminergic medication and with improvement in motor functions. Results: The mean standardized BADS scores showed no significant improvement in both the groups. In the de novo group, percent improvement in the standardized BADS scores showed a significant positive correlation with the LED, but not with percent improvement in UPDRS part III. In the chronic medication group, percent improvement in the standardized BADS scores was negatively correlated with change in the LED, but not with percent improvement in UPDRS part III. Multiple regression analysis using improvement in the standardized BADS score as a dependent variable and patient's background factors (ie, age, education, disease duration, and motor and executive assessments at baseline) as independent variable showed that improvement in the executive assessment is significantly correlated with the LED only in the de novo group. Conclusion: Effects of dopaminergic drug adjustment on executive function differ according to the patient's clinical stage and depend on LED in de novo stage. [ABSTRACT FROM AUTHOR]

Objectives: To examine the frequency and risk factors of cognitive and anxiety-depressive disorders in patients with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Methods: This was an observational study of 100 ALS/MND patients treated at our hospital outpatient and inpatient departments between January 2009 and April 2010 and 100 matched healthy controls. Subjects were surveyed using Mini Mental State Examination (MMSE), Zung Self-Rating Anxiety Scale (SAS), and Zung Self-Rating Depression Scale (SDS). Patient neurological status was graded by the ALS Functional Rating Scale (ALSFRS). Multivariate linear regression was used to identify factors associated with the MMSE, SAS, SDS, and ALSFRS scores. Results: Patients had significantly lower MMSE scores than controls (P<0.05). MMSE score did not differ by sex or age (<50/≥50 years) (P.0.05). Patients with higher educational level (college and above), shorter disease course (<2 years), and lower ALSFRS score (<20) had significantly higher MMSE scores (all P<0.05). Multivariate analysis revealed that higher education, shorter disease course, and lower ALSFRS score were independent predictors of better cognitive function (higher MMSE score). Patients had significantly higher mean SAS and SDS total scores than controls (both P<0.05), indicating higher subjective anxiety and depression. Female patients, patients with higher education, and those with higher ALSFRS scores had significantly higher SAS and SDS scores (all P<0.05). Age, occupation, diagnostic classification, disease duration, and disease awareness did not influence SAS or SDS scores. Multivariate analysis indicated that lower education and lower ALSFRS were protective factors against anxiety and depression. Conclusion: The frequency of anxiety-depressive disorders was high among patients with ALS/MND. High educational level, short course of disease, and lower ALSFRS were associated with preserved cognitive function. Female sex, higher education, and lower ALSFRS score conferred a greater risk of anxiety and depression. Tailored pharmacotherapy and psychological interventions may help in reducing anxiety and depression in these patients. [ABSTRACT FROM AUTHOR]

Though optic atrophy may be a feature of ATAD3A mutations, Mulla F. Ketogenic diet attenuates cerebellar atrophy progression in a Represent the views of Dove Medical Press, its officers, agents, employees, related entities or the The Application of Clinical Genetics editors. [Extracted from the article]