Anatomical categorization of isolated non-focal dystonia: novel and existing patterns using a data-driven approach.

According to expert consensus, dystonia can be classified as focal, segmental, multifocal, and generalized, based on the affected body distribution. To provide an empirical and data-driven approach to categorizing these distributions, we used a data-driven clustering approach to compare frequency and co-occurrence rates of non-focal dystonia in pre-defined body regions using the Dystonia Coalition (DC) dataset. We analyzed 1,618 participants with isolated non-focal dystonia from the DC database. The analytic approach included construction of frequency tables, variable-wise analysis using hierarchical clustering and independent component analysis (ICA), and case-wise consensus hierarchical clustering to describe associations and clusters for dystonia affecting any combination of eighteen pre-defined body regions. Variable-wise hierarchical clustering demonstrated closest relationships between bilateral upper legs (distance = 0.40), upper and lower face (distance = 0.45), bilateral hands (distance = 0.53), and bilateral feet (distance = 0.53). ICA demonstrated clear grouping for the a) bilateral hands, b) neck, and c) upper and lower face. Case-wise consensus hierarchical clustering at k = 9 identified 3 major clusters. Major clusters consisted primarily of a) cervical dystonia with nearby regions, b) bilateral hand dystonia, and c) cranial dystonia. Our data-driven approach in a large dataset of isolated non-focal dystonia reinforces common segmental patterns in cranial and cervical regions. We observed unexpectedly strong associations between bilateral upper or lower limbs, which suggests that symmetric multifocal patterns may represent a previously underrecognized dystonia subtype.

Effects of ventral intermediate nucleus deep brain stimulation across multiple effectors in essential tremor.

OBJECTIVE: Essential tremor (ET) prominently affects the upper-limbs during voluntary movements, but can also affect the lower-limbs, head, and chin. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of thalamus improves both clinical ratings and quantitative measures of tremor, no study has quantified effects of DBS on tremor across multiple body parts. Our objective was to quantify therapeutic effects of DBS across multiple body parts in ET. METHODS: We performed quantitative assessment of tremor in ET patients who had DBS for at least one year. We assessed tremor on and off VIM-stimulation using triaxial accelerometers on the upper-limbs, lower-limbs, head and chin during seated and standing tasks. RESULTS: VIM-DBS significantly reduced tremor, but there was no statistical difference in degree of tremor reduction across the measured effectors. Compared to healthy controls, ET patients treated with DBS showed significantly greater tremor power (4-8 Hz) across all effectors during seated and standing tasks. CONCLUSIONS: VIM-DBS reduced tremor in ET patients. There was no significant difference in the degree of tremor reduction across the measured effectors. SIGNIFICANCE: This study provides new quantitative evidence that VIM-DBS is effective at reducing tremor across multiple parts of the body.

High rates of fatigue and sleep disturbances in dystonia.

BACKGROUND: Nonmotor symptoms in dystonia are increasingly recognized to impair the quality of life. The primary objective of this study was to determine the prevalence of fatigue and sleep disturbances in dystonia and to ascertain their impact on quality of life using standardized questionnaires. METHODS: Dystonia patients presenting to a Botulinum toxin clinic were prospectively administered Fatigue Severity Scale (FSS), Multidimensional Fatigue Inventory (MFI), Epworth Sleepiness Scale (ESS) and Parkinson's Disease Sleep Scale (PDSS) for assessment of fatigue and sleep disturbances. Health-related Quality of life (HRQOL) was determined using MOS SF-36 scale and depressive symptoms were assessed using the Beck Depression Inventory II. RESULTS: Ninety-one patients with dystonia participated (66 women, 25 men, mean age 60 ± 17 years). Nine subjects had generalized dystonia, 18 segmental dystonia and 64 had focal dystonia. Moderate to severe fatigue was present in 43% of the cohort (FSS), excessive daytime somnolence in 27% (ESS) and other sleep disturbances in 26% (PDSS). FSS and MFI scores correlated significantly with HRQOL even when controlled for depression and sleep disturbances. Excessive daytime somnolence and nocturnal sleep disturbances correlated significantly with the HRQOL; however, these effects were not seen for daytime somnolence when controlled for depression. Psychometric testing found adequate reliabilities and convergent validities for both fatigue and sleep scales. CONCLUSION: Fatigue and sleep disturbances revealed high prevalence rates in this large, first of its dystonia study. They negatively impacted the quality of life even when controlled for comorbid depression.

Impaired presynaptic inhibition in the motor cortex in Parkinson disease.

OBJECTIVE: Intracortical inhibition in the motor cortex may be measured with short interval intracortical inhibition (SICI), likely mediated by GABA(A) receptors, and long interval intracortical inhibition (LICI), likely mediated by GABA(B) receptors. Separate neuronal populations mediate SICI and LICI, and LICI inhibits SICI, likely through GABA(B) mediated presynaptic inhibition. The purpose of this study was to test the hypothesis that cortical presynaptic inhibition in Parkinson disease (PD) is impaired. METHODS: Eleven patients with PD were studied at rest both OFF and ON dopaminergic medications and the results were compared to nine healthy, age-matched controls. Motor evoked potentials were recorded from the first dorsal interosseous muscle and a triple-stimulus transcranial magnetic stimulation paradigm was used to evaluate SICI in the presence of LICI. The interstimulus interval (ISI) for SICI was 2 msec and LICI was studied at 100 (LICI(100)) and 150 msec (LICI(150)) ISIs. RESULTS: There was no difference in SICI between the controls and PD ON and PD OFF groups. LICI(100) was stronger than LICI(150) and both were reduced in the PD ON and OFF groups. LICI(100) led to a much greater reduction in SICI in the control group compared to both the PD OFF and ON groups. LICI(150) caused no significant change in SICI with no significant difference between the controls and PD OFF and PD ON groups. CONCLUSIONS: The inhibitory effect of long interval intracortical inhibition on short interval intracortical inhibition, likely representing presynpatic inhibition in the motor cortex, is decreased in Parkinson disease and may be a nondopaminergic feature of the disease.

Subthalamic nucleus stimulation modulates afferent inhibition in Parkinson disease.

BACKGROUND: Peripheral sensory stimulation at the wrist inhibits the motor cortex as measured by transcranial magnetic stimulation at interstimulus intervals of approximately 20 ms (short latency afferent inhibition [SAI]) and 200 ms (long latency afferent inhibition [LAI]). Previous studies suggested that reduced SAI in Parkinson disease (PD) reflects adverse effect of dopaminergic medications and reduced LAI may be related to nondopaminergic manifestations of PD. We hypothesize that subthalamic nucleus (STN) deep brain stimulation (DBS) may correct these deficiencies. METHODS: We studied the effects of STN DBS on SAI and LAI in seven PD patients and age-matched controls. PD patients were studied in an off medication followed by an on medication session, with the stimulator switched on or off in random order in each session. RESULTS: In the on medication session, SAI was reduced in the stimulator off condition and was restored by STN DBS. LAI was partially normalized by STN DBS in the medication on condition. CONCLUSIONS: Subthalamic nucleus (STN) stimulation improves short latency afferent inhibition, suggesting that it could normalize pathways that are adversely affected by dopaminergic medications. The effect of STN stimulation on long latency afferent inhibition suggests that it may influence nondopaminergic pathways involved in sensorimotor integration.