PINK1 mutations in sporadic early-onset Parkinson's disease.

Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.     

Effect of exercise on repetitive nerve stimulation studies: new appraisal of an old technique.

Repetitive nerve stimulation (RNS) is a simple and rapid method for evaluation of neuromuscular transmission defects. Although the effect of exercise in conjunction with RNS is well recognized, it has not been standardized in actual patient and control groups. In a prospective study over a period of 1 year, the authors evaluated the effect of exercise in conjunction with RNS in comparison with conventional 3-Hz RNS at rest in the clinical setting. Fifty-four patients who were referred for possible neuromuscular transmission disorders, in addition to 35 healthy control subjects, were studied. Amplitude and area decremental responses with RNS at rest and after 20 seconds of maximal exercise at 1-minute intervals up to 3 minutes were evaluated. The use of RNS with exercise resulted in additional diagnostic yield of up to 36.4% compared with conventional 3-Hz RNS at rest. The standardized use of exercise with RNS is advocated for increasing its diagnostic yield in the neurophysiologic laboratory.     

Electrophysiological evidence of cerebellar fiber system involvement in the Miller Fisher syndrome

BackgroundIn the Miller Fisher syndrome (MFS), ataxia may be due involvement of Ia afferents and the cerebellum. Transcranial magnetic stimulation (TMS) over the cerebellum is known to interfere transiently with normal function.MethodsIn this study, we utilized a previously described TMS protocol over the cerebellum in combination with ballistic movements to investigate cerebellar dysfunction in MFS patients.ResultsThe agonist (biceps) reaction time in MFS patients during a motor cancellation task was not significantly reduced during the initial TMS study. However, during the repeat TMS study, significant reduction was seen for all patients, in tandem with clinical recovery. There was significant correlation between anti-GQ1b IgG titers and change in agonist reaction time between the initial and repeat TMS studies.ConclusionsTMS likely affected horizontally orientated parallel fibers in the cerebellar molecular layer. During disease onset, antibody binding may have interfered with facilitation of reaction time during motor cancellation tasks seen in normal subjects. Normalization of reaction time facilitation corresponded to resolution of antibody-mediated interference in the molecular layer.Our study has provided evidence suggesting parallel fiber involvement in MFS, and suggested a role of anti-GQ1b IgG antibody in these changes.     

Piribedil and bromocriptine in Parkinson's disease: a single-blind crossover study

INTRODUCTION: Clinicians switch from one dopamine agonist to another for various reasons. However, each change may inadvertently result in certain potential risks such as decreased medication efficacy or new side-effects. OBJECTIVE: We evaluated the tolerability of a switch of bromocriptine to piribedil using two conversion ratios as a primary outcome measure, with motor function as a secondary outcome measure, in patients with mild to moderate Parkinson's disease (PD). METHODS: Twenty consecutive patients with mild to moderate PD (Hoehn and Yahr, stage II-III) on treatment with stable doses of bromocriptine and levodopa were randomized to two groups of 10 patients each, to receive piribedil based on 1:5 or 1:10 conversion ratios. Blinded evaluations were performed: 1) United Parkinson's Diseased Rating Scale (UPDRS) scores both in 'on' and 'off', 2) Open-ended interviews for adverse events, 3) Epworth Sleepiness Scale, 4) Purdue Pegboard assessment during 'on' and 'off', 5) Hand-arm movement test during 'on' and 'off', and 6) Walking test during 'on' and 'off'. RESULTS: Major adverse events included 'sleep attacks' in one patient and minor side-effects included giddiness, nausea, hallucinations, sleepiness and lethargy. However, these were mild and 19 (95%) of the 20 patients completed the study. There was a significant improvement in both the UPDRS 'off' total and motor scores at 1 month compared with baseline for the group on 1:10 ratio. The walking times during the 'off' state at 1 and 2 months were significantly better compared with baseline in the 1:5 group. There were otherwise no significant differences in the rating tests during both 'off' and 'on' states before and after the bromocriptine switch. CONCLUSIONS: We demonstrated that patients with mild to moderate PD who were on relatively low doses of bromocriptine can be safely switched to piribedil based on a conversion ratio of either 1:5 or 1:10. However, the higher conversion ratio has to be carried out with caution in patients with daytime somnolence.     

Decrement in area of muscle responses to repetitive nerve stimulation

Measurement of the decremental muscle response to repetitive nerve stimulation (RNS) has low yields for the diagnosis of neuromuscular transmission defects compared with single fiber electromyography (SFEMG). We compared area and amplitude of muscle responses to RNS in 87 patients and 30 controls, using SFEMG as the reference standard. Decrement of response area provided additional diagnostic yields of 5.3% to 30% depending on the muscle examined and disease severity, and is recommended as a diagnostic adjunct to measurement of amplitude decrement during RNS.     

Pectoral nerve conduction studies: technique in healthy subjects and evaluation of brachial plexopathy

OBJECTIVE: To define the optimal nerve conduction study (NCS) technique of the pectoral nerves and evaluate its clinical utility. DESIGN: Prospective electrophysiologic study with healthy controls. SETTING: Electrophysiologic laboratory in a large general hospital. PARTICIPANTS: Thirty healthy controls and 10 patients with cervical root or brachial plexus pathologies. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Correlation of pectoral NCS with electromyography and magnetic resonance imaging. RESULTS: For pectoral NCS, the mean values +/- standard deviation of onset latency, amplitude, and interside amplitude ratio (ratio of smaller over larger amplitude) were 2.01+/-0.22 ms, 11.75+/-2.21 mV, and .95+/-.04 mV, respectively. Subject age correlated significantly with both onset latency (r=.46, P<.001) and amplitude (r=-.34, P<.008). All 5 patients with brachial plexopathy had amplitude ratios below the normal limit of controls (.87). However, this was not seen for all 5 patients with cervical spondylotic radiculopathy. CONCLUSIONS: The pectoral NCS technique is feasible in healthy subjects. It is useful when differentiating brachial plexopathy from cervical root lesions.