Neurology AND Movement disorders [keywords]
- Paroxysmal movement disorders: An update. [JOURNAL ARTICLE]
- Rev Neurol (Paris) 2016 Aug 23.
Paroxysmal movement disorders comprise both paroxysmal dyskinesia, characterized by attacks of dystonic and/or choreic movements, and episodic ataxia, defined by attacks of cerebellar ataxia. They may be primary (familial or sporadic) or secondary to an underlying cause. They can be classified according to their phenomenology (kinesigenic, non-kinesigenic or exercise-induced) or their genetic cause. The main genes involved in primary paroxysmal movement disorders include PRRT2, PNKD, SLC2A1, ATP1A3, GCH1, PARK2, ADCY5, CACNA1A and KCNA1. Many cases remain genetically undiagnosed, thereby suggesting that additional culprit genes remain to be discovered. The present report is a general overview that aims to help clinicians diagnose and treat patients with paroxysmal movement disorders.
- Does Cognitive Impairment Affect Rehabilitation Outcome in Parkinson's Disease? [Journal Article]
- Front Aging Neurosci 2016.:192.
The cognitive status is generally considered as a major determinant of rehabilitation outcome in Parkinson's disease (PD). No studies about the effect of cognitive impairment on motor rehabilitation outcomes in PD have been performed before.This study is aimed to evaluate the impact of cognitive decline on rehabilitation outcomes in patients with PD.We retrospectively identified 485 patients with PD hospitalized for a 4-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT) between January 2014 and September 2015. According to Mini Mental State Examination (MMSE), patients were divided into: group 1-normal cognition (score 27-30), group 2-mild cognitive impairment (score 21-26), group 3-moderate or severe cognitive impairment (score ≤ 20). According to Frontal Assessment Battery (FAB), subjects were divided into patients with normal (score ≥13.8) and pathological (score <13.8) executive functions. The outcome measures were: Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Disability Scale (PDDS), Six Minutes Walking Test (6MWT), Timed Up and Go Test (TUG) and Berg Balance Scale (BBS).All scales had worse values with the increase of cognitive impairment and passing from normal to pathological executive functions. After rehabilitation, all the outcome measures improved in all groups (p < 0.0001). Between groups, the percentage of improvement was significantly different for total UPDRS (p = 0.0009, best improvement in normal MMSE group; p = 0.019, best improvement in normal FAB group), and BBS (p < 0.0001, all pairwise comparisons significant, best improvement in patients with worse MMSE score; p < 0.0001, best improvement in patients with pathological FAB). TUG (p = 0.006) and BBS (p < 0.0001) improved in patients with pathological FAB score, more than in those with normal FAB score.Patients gain benefit in the rehabilitative outcomes, regardless of cognition. Our data suggest that rehabilitation could be effective also in Parkinsonian subjects with cognitive impairment, as well as with dysexecutive syndrome.
- Neurometabolic disorders are treatable causes of dystonia. [JOURNAL ARTICLE]
- Rev Neurol (Paris) 2016 Aug 22.
A broad range of rare inherited metabolic disorders can present with dystonia. For clinicians, it is important to recognize dystonic features, but it can be complicated by the mixed and complex clinical picture seen in many neurometabolic patients. Careful phenotyping is the first step towards the diagnosis of the underlying condition and subsequent targeted treatment, further supported by imaging, biochemical diagnostics and the availability of modern diagnostic techniques such as next generation sequencing. As several neurometabolic disorders are treatable causes of dystonia, these should have priority in the diagnostic process. In the symptomatic treatment of dystonia, several therapeutic options are available. Awareness for the occurrence and optimal treatment of dystonia and other movement disorders in neurometabolic conditions is important because these symptoms can have a substantial impact on the quality of life and daily functioning; this effect is not only exerted by the dystonia itself, but also by the frequently associated non-motor features. In this paper, the highlights and key concepts of neurometabolic forms of dystonia are discussed, with a focus on phenomenology, the diagnostic approach, the most important neurometabolic aetiologies, co-occurring non-motor features and therapeutic options.
- Narcolepsy Following Yellow Fever Vaccination: A Case Report. [Journal Article]
- Front Neurol 2016.:130.
Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the pediatric age group probably linked to the use of the Pandemrix influenza vaccine in 2009, has increased awareness that different environmental factors can "trigger" narcolepsy with cataplexy in a genetically susceptible population. Here, we describe the case of a 13-year-old boy with narcolepsy following yellow fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy. Polysomnography showed rapid sleep onset with rapid eye movement (REM) latency of 47 min, significant sleep fragmentation and a mean sleep latency of 1.6 min with sleep onset REM in four out of four nap periods. Together with the clinical history, these findings are diagnostic of narcolepsy type 1. The envelope protein E of the yellow fever vaccine strain 17D has significant amino acid sequence overlap with both hypocretin and the hypocretin receptor 2 receptors in protein regions that are predicted to act as epitopes for antibody production. These findings raise the question whether the yellow fever vaccine strain may, through a potential molecular mimicry mechanism, be another infectious trigger for this neuro-immunological disorder.
- NALCN channelopathies: Distinguishing gain-of-function and loss-of-function mutations. [JOURNAL ARTICLE]
- Neurology 2016 Aug 24.
To perform genotype-phenotype analysis in an infant with congenital arthrogryposis due to a de novo missense mutation in the NALCN ion channel and explore the mechanism of pathogenicity using a Caenorhabditis elegans model.We performed whole-exome sequencing in a preterm neonate with congenital arthrogryposis and a severe life-threatening clinical course. We examined the mechanism of pathogenicity of the associated NALCN mutation by engineering the orthologous mutation into the nematode C elegans using CRISPR-Cas9.We identified a de novo missense mutation in NALCN, c.1768C>T, in an infant with a severe neonatal lethal form of the recently characterized CLIFAHDD syndrome (congenital contractures of the limbs and face with hypotonia and developmental delay). We report novel phenotypic features including prolonged episodes of stimulus-sensitive sustained muscular contraction associated with life-threatening episodes of desaturation and autonomic instability, extending the severity of previously described phenotypes associated with mutations in NALCN. When engineered into the C elegans ortholog, this mutation results in a severe gain-of-function phenotype, with hypercontraction and uncoordinated movement. We engineered 6 additional CLIFAHDD syndrome mutations into C elegans and the mechanism of action could be divided into 2 categories: half phenocopied gain-of-function mutants and half phenocopied loss-of-function mutants.The clinical phenotype of our patient and electrophysiologic studies show sustained muscular contraction in response to transient sensory stimuli. In C elegans, this mutation causes neuronal hyperactivity via a gain-of-function NALCN ion channel. Testing human variants of NALCN in C elegans demonstrates that CLIFAHDD can be caused by dominant loss- or gain-of-function mutations in ion channel function.
- Treatment of Medically Refractory Essential Tremor. [Comment, Editorial]
- N Engl J Med 2016 Aug 25; 375(8):792-3.
- Verbal Memory Decline following DBS for Parkinson's Disease: Structural Volumetric MRI Relationships. [Journal Article]
- PLoS One 2016; 11(8):e0160583.
Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory.Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes.A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data.A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03).Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes.
- Correlation of Quantitative Motor State Assessment Using a Kinetograph and Patient Diaries in Advanced PD: Data from an Observational Study. [Journal Article]
- PLoS One 2016; 11(8):e0161559.
Effective management and development of new treatment strategies for response fluctuations in advanced Parkinson's disease (PD) largely depends on clinical rating instruments such as the PD home diary. The Parkinson's kinetigraph (PKG) measures movement accelerations and analyzes the spectral power of the low frequencies of the accelerometer data. New algorithms convert each hour of continuous PKG data into one of the three motor categories used in the PD home diary, namely motor Off state and On state with and without dyskinesia.To compare quantitative motor state assessment in fluctuating PD patients using the PKG with motor state ratings from PD home diaries.Observational cohort study on 24 in-patients with documented motor fluctuations who completed diaries by rating motor Off, On without dyskinesia, On with dyskinesia, and asleep for every hour for 5 consecutive days. Simultaneously collected PKG data (recorded between 6 am and 10 pm) were analyzed and calibrated to the patient's individual thresholds for Off and dyskinetic state by novel algorithms classifying the continuous accelerometer data into these motor states for every hour between 6 am and 10 pm.From a total of 2,040 hours, 1,752 hours (87.4%) were available for analyses from calibrated PKG data (7.5% sleeping time and 5.1% unclassified motor state time were excluded from analyses). Distributions of total motor state hours per day measured by PKG showed moderate-to-strong correlation to those assessed by diaries for the different motor states (Pearson's correlations coefficients: 0.404-0.658), but inter-rating method agreements on the single-hour-level were only low-to-moderate (Cohen's κ: 0.215-0.324).The PKG has been shown to capture motor fluctuations in patients with advanced PD. The limited correlation of hour-to-hour diary and PKG recordings should be addressed in further studies.