- Pathogenesis of Wilson disease. [Journal Article]
- HCHandb Clin Neurol 2017; 142:43-55
- Wilson disease is an autosomal-recessive disorder originating from a genetic defect in the copper-transporting ATPase ATP7B that is required for biliary copper secretion and loading of ceruloplasmin ...
Wilson disease is an autosomal-recessive disorder originating from a genetic defect in the copper-transporting ATPase ATP7B that is required for biliary copper secretion and loading of ceruloplasmin with copper. Impaired ATP7B function in Wilson disease results in excessive accumulation of copper in liver, brain, and other tissues. Toxic copper deposits may induce oxidative stress, modify expression of genes, directly inhibit proteins, and impair mitochondrial function, leading to hepatic, neuropsychiatric, renal, musculoskeletal, and other symptoms. Hepatocyte dysfunction initially manifests as steatosis and later may progress to other hepatic phenotypes such as acute liver failure, hepatitis, and fibrosis. In the brain, copper accumulates in astrocytes, leading to impairment of the blood-brain barrier and consequent damage to neurons and oligodendrocytes. Basal ganglia and brainstem are the brain regions with highest susceptibility to copper toxicity and their lesions lead to various combinations of movement and psychiatric disorders. This chapter will give an overview of the essential requirement of copper for biologic processes and the molecular mechanisms employed by cells to maintain their copper levels in a proper range. We will specify the physiologic functions of ATP7B and the consequences of its dysfunction and summarize the current knowledge on the pathogenesis of liver and neuropsychiatric disease. Finally, we will describe the consequences of copper overload in Wilson disease in other tissues.
- Multicenter observational study of abobotulinumtoxinA neurotoxin in cervical dystonia: The ANCHOR-CD registry. [Journal Article]
- JNJ Neurol Sci 2017 May 15; 376:84-90
- CONCLUSIONS: This study confirmed the beneficial effect of abobotulinumtoxinA on CD in routine clinical practice as measured by improvements in TWSTRS and PGIC. No new safety concerns were identified.
- TPK1 mutation induced childhood onset idiopathic generalized dystonia: Report of a rare mutation and effect of deep brain stimulation. [Journal Article]
- JNJ Neurol Sci 2017 May 15; 376:42-43
- Quantitative biomechanical assessment of trunk control in Huntington's disease reveals more impairment in static than dynamic tasks. [Journal Article]
- JNJ Neurol Sci 2017 May 15; 376:29-34
- Postural instability is common in individuals with Huntington's disease (HD), yet little is known about control of the trunk during static and dynamic activities. We compared the trunk motion of 41 i...
Postural instability is common in individuals with Huntington's disease (HD), yet little is known about control of the trunk during static and dynamic activities. We compared the trunk motion of 41 individuals with HD and 36 controls at thoracic and pelvic levels during sitting, standing, and walking using wearable iPod sensors. We also examined the ability of individuals with HD to respond to an auditory cue to modify trunk position when the pelvis moved >8° in sagittal or frontal planes during sitting using custom software. We found that amplitude of thoracic and pelvic trunk movements was significantly greater in participants with HD, and differences were more pronounced during static (i.e. sitting, standing) than dynamic (i.e. walking) tasks. In contrast to the slow, smooth sinusoidal trunk movements of controls, individuals with HD demonstrated rapid movements with varying amplitudes that continuously increased without stabilizing. Ninety-seven percent of participants with HD were able to modify their trunk position in response to auditory cues. Our results demonstrate that wearable iPod sensors are clinically useful for rehabilitation professionals to measure and monitor trunk stability in persons with HD. Additionally, auditory cueing holds potential as a useful training tool to improve trunk stability in HD.
- The PRIAMO study: urinary dysfunction as a marker of disease progression in early Parkinson's disease. [Journal Article]
- EJEur J Neurol 2017 Apr 20
- CONCLUSIONS: This is the first prospective longitudinal study involving a large cohort of PD patients demonstrating the relevance of urinary dysfunction as an early marker of higher motor and non-motor disability as well as lower health-related quality of life. These findings support a role for urinary dysfunction as an early marker of more severe disease progression.
- MEIS1 variant as a determinant of autonomic imbalance in Restless Legs Syndrome. [Journal Article]
- SRSci Rep 2017 Apr 20; 7:46620
- Restless Legs Syndrome (RLS) is a genetically complex neurological disorder in which overlapping genetic risk factors may contribute to the diversity and heterogeneity of the symptoms. The main goal ...
Restless Legs Syndrome (RLS) is a genetically complex neurological disorder in which overlapping genetic risk factors may contribute to the diversity and heterogeneity of the symptoms. The main goal of the study was to investigate, through analysis of heart rate variability (HRV), whether in RLS patients the MEIS1 polymorphism at risk influences the sympathovagal regulation in different sleep stages. Sixty-four RLS patients with periodic leg movement index above 15 per hour, and 38 controls underwent one night of video-polysomnographic recording. HRV in the frequency- and time- domains was analyzed during nighttime sleep. All RLS patients were genotyped, and homozygotes for rs2300478 in the MEIS1 locus were used for further analysis. Comparison of the sympathovagal pattern of RLS patients to control subjects did not show significant differences after adjustments for confounding factors in frequency-domain analyses, but showed an increased variability during N2 and N3 stages in time-domain analyses in RLS patients. Sorting of RLS patients according to MEIS1 polymorphism reconfirmed the association between MEIS1 and PLMS, and showed a significant increased sympathovagal balance during N3 stage in those homozygotes for the risk allele. RLS patients should be considered differently depending on MEIS1 genotype, some being potentially at risk for cardiovascular disorders.
- Restless legs syndrome and tension-type headache: a population-based study. [Journal Article]
- JHJ Headache Pain 2017; 18(1):47
- CONCLUSIONS: The prevalence of RLS was higher among individuals with TTH than among those with non-headache. Some clinical presentations varied in accordance with the presence of RLS among participants with TTH.
- Driving with a neurodegenerative disorder: an overview of the current literature. [Review]
- JNJ Neurol 2017 Apr 19
- Driving is important for employment, social activities, and for the feeling of independence. The decision to cease driving affects the quality of life and has been associated with reduced mobility, s...
Driving is important for employment, social activities, and for the feeling of independence. The decision to cease driving affects the quality of life and has been associated with reduced mobility, social isolation, and sadness. Patients with neurodegenerative disorders can experience difficulties while driving due to their cognitive, motor, and behavioral impairments. The aim of this review is to summarize the available literature on changes in driving competence and behavior in patients with neurodegenerative disorders, with a particular focus on Huntington's (HD), Parkinson's (PD), and Alzheimer's disease (AD). A systematic literature search was conducted in the PubMed/Medline database. Studies using on-road or simulated driving assessments were examined in this review. In addition, studies investigating the association between cognitive functioning and driving were included. The review identified 70 studies. Only a few publications were available on HD (n = 7) compared to PD (n = 32) and AD (n = 31). This review revealed that driving is impaired in patients with neurodegenerative disorders on all levels of driving competence. The errors most commonly committed were on the tactical level including lane maintenance and lane changing. Deficits in executive functioning, attention, and visuospatial abilities can partially predict driving competence, and the performance on neuropsychological tests might be useful when discussing potential driving cessation. Currently, there is no gold standard to assess driving ability using clinical measures such as neuropsychological assessments, so more studies are necessary to detect valid screening tools and develop useful and reliable evidence-based guidelines.
- A polysomnographic study in parkinsonian patients treated with intestinal levodopa infusion. [Journal Article]
- JNJ Neurol 2017 Apr 19
- Sleep disorders are very common in advanced Parkinson's disease (PD) and have a significant negative impact on the quality of life of patients. Questionnaire-based studies suggest that sleep quality ...
Sleep disorders are very common in advanced Parkinson's disease (PD) and have a significant negative impact on the quality of life of patients. Questionnaire-based studies suggest that sleep quality might improve following levodopa-carbidopa intestinal gel (LCIG) infusion. The objective of this study was to evaluate the impact of LCIG infusion and subsequent oral medication changes on polysomnography (PSG) and sleep symptoms in advanced PD patients. Eleven PD patients underwent PSG at baseline and after 3.8 ± 1.2 months of LCIG treatment. LCIG infusion therapy was halted during PSG. Patients were assessed with the Unified-PD-rating-Scale and completed the PD-Sleep-Scale-version-2 (PDSS-2), the Epworth Sleepiness Scale and the RBD single question. Subjective sleep quality improved in all patients. PSG showed a reduction of the number of awakenings in sleep, a trend towards a lower apnea-hypopnea index and no change in sleep latency, total sleep time and sleep efficiency. There was a positive correlation between the number of awakenings and PDSS-2 scores for "difficulty staying asleep", "muscle cramps of arms or legs" and "urge to move arms or legs". Motor complications and activities of daily living improved with LCIG. Subjective sleep quality improved significantly and the PSG study showed a less fragmented sleep pattern in advanced PD patients treated with LCIG infusion.
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- Treatment of Leukoencephalopathy With Calcifications and Cysts With Bevacizumab. [Journal Article]
- PNPediatr Neurol 2017 Mar 23
- CONCLUSIONS: Further studies in a cohort of patients are warranted to investigate the efficacy of VEGF inhibition as a treatment for leukoencephalopathy with calcifications and cysts.