A pilot study: Microlesion effects and tremor outcome in the ventrointermediate deep brain stimulation (VIM-DBS).

OBJECTIVES: To perform a pilot study to investigate the relationship between the microlesion effect (MLE) seen in deep brain stimulation (DBS) of the ventralis intermedius nucleus (VIM) and subsequent tremor response and DBS parameter settings. PATIENTS AND METHODS: Nineteen thalami in 12 patients (11 essential tremor and 1 Parkinson's disease), who underwent unilateral (n=5) and bilateral VIM-DBS (n=7) were assessed at pre- and 24-h post-operation, at their initial DBS activation, and at 6-month follow-up. The severity of tremor was rated (from 0 to 4) for each activity including hand at rest, outstretched, wing beating, finger-nose-finger, dot approximation and spiral drawing (total score ranging from 0 to 24). The difference of total tremor score before and 24-h after electrode implants (MLE) was segregated into 3 groups based on immediate (24h) post-operative tremor improvement: (1) minimal (none or mild, 0-2), (2) moderate (>2-4), and (3) marked (>4). At the initial activation (23.4+/-3.7 days post-operation), the mean OFF tremor scores were still marginally better in marked than the minimal and moderate MLE groups. RESULTS: At 6 months, 14 of 19 thalami (74%) were eligible for follow-up analysis. The "OFF" stimulation MLE disappeared in all groups. There was no significant difference of mean ON tremor scores among the groups; however, DBS parameter settings, including amplitude and pulse width, trended to be mildly lower in those with a marked MLE. CONCLUSION: MLE has minimal long term clinical effect except for possibly allowing for lower DBS settings.

Motor overflow and mirror dystonia.

Motor overflow is an unintentional muscle contraction which accompanies, but is anatomically distinct from the primary dystonic movement. This phenomenological nosology has not been systematically studied in focal hand dystonia (FHD). We conducted a prospective, case-control study to characterize motor overflow and mirror dystonia in patients with FHD. We compared the performance of 30 patients with FHD and 40 healthy controls on a variety of motor tasks, such as writing, drawing a spiral, straight line and a sine wave, repetitive wrist flexion-extension, finger tapping, hand grasping, hand pronation-supination, and a finger-to-nose task with each hand. The assessments were videotaped, the edited video segments were randomized, and an independent investigator who was "blind" to the subject's diagnosis rated the ipsilateral and contralateral overflow and mirror dystonia twice, 6 months apart. Using the mean of the two ratings, ipsilateral overflow was identified in 8.5 +/- 2.1 (28%) patients and in 1.5 +/- 0.7 (4%) controls (p < 0.001), contralateral overflow in 2.5 +/- 0.7 (8%) patients and in 1.5 +/- 0.7 (4%) of controls (p = 0.138), and mirror movement in 20.0 +/- 0.0 (67%) of patients and in 15.5 +/- 4.9 (39%) of controls (p = 0.001). There was a statistically significant correlation of dystonia and overflow score (Pearson's r 0.713, p < 0.001). The relatively high frequency of ipsilateral overflow and mirror dystonia in patients with FHD has both pathophysiological and therapeutic implications. In this study, the severity of dystonia was significantly correlated with motor overflow in multiple tasks.

Brain magnetic resonance imaging (MRI) in parkinsonian disorders.

Magnetic resonance imaging (MRI) is increasingly integrated into neurological diagnostics. In addition to functional MRI, a large number of sequences (T1W, T2W, PD, T2W gradient echo, diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI)), investigate CNS abnormalities. Objective quantification techniques (T1W voxel-based morphometry) can also discern subtle anatomical differences. Parkinsonian conditions such as Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration and manganese-induced parkinsonism can clinically overlap, yet have very different prognoses and treatments. Relatively little radiographic interest has focused on movement disorders. Nevertheless in the past decade, a variety of findings, often subtle and routinely overlooked, have emerged to help the clinician differentiate these conditions. This review will summarize and discuss MRI findings in parkinsonian conditions. Most data concern either structural abnormalities or the imaging sequelae of abnormal iron deposition, common in some parkinsonian conditions.

Applause sign in Parkinsonian disorders and Huntington's disease.

The applause sign has been previously reported to be indicative of neurodegenerative disorders, such as progressive supranuclear palsy (PSP). In order to determine the sensitivity, specificity, and positive predictive value, we tested it in patients with PSP, Parkinson's disease (PD), multiple system atrophy (MSA), corticobasal degeneration (CBD), and Huntington's disease (HD). Subjects were asked to clap three times after demonstration by the examiner. The performance was scored as follows: 3 = claps only three times; 2 = claps four times; 1 = claps 5 to 10 times; 0 = claps >10 times. The clap test was videotaped and rated. Patients with CBD, MSA, and PSP showed significant differences in clap scores compared with normal controls. The test differentiated patients with CBD from those with PD (P < 0.005) and HD (P < 0.005), but failed to discriminate patients with PSP from other parkinsonian groups. The specificity of the applause sign is 100% in distinguishing parkinsonian patients from normal subjects with the highest sensitivity in CBD patients. We concluded that the applause sign is highly specific for parkinsonian disorders but it is not a specific sign for PSP; it appears to be most sensitive for CBD.

Weight change in Parkinson and Alzheimer patients taking atypical antipsychotic drugs.

Atypical antipsychotics (AA) are generally associated with weight gain. We determined body mass index (BMI) change in Parkinson's disease (PD) before and after taking AA and compared against PD controls and Alzheimer's disease (AD) patients on AA. In 66 consecutive PD subjects started on AA who had accurate weights for more than 6 months before and after initiation of AA, we compared weight change before and after AA use, against a control group of sixty-one sex-matched PD subjects, and against twenty-eight AD subjects taking AA. A linear regression model was created to compare weight changes. Fifty-nine PD subjects had complete data, quetiapine (n=53) and clozapine (n=6). The mean BMI change in the period before starting AA was 0.00 kg/m(2)/month over 1.95+/-1.41 years. After starting AA, subjects lost 0.03 kg/m(2)/month (95% CI 0.62-1.21, P<0.0001), comparing PD before AA to the same PD patients after AA. In 61 PD controls, the mean BMI loss was 0.01 kg/m(2)/month (95% CI 0.15-0.94, P=0.007) comparing PD on AA vs. PD controls. The BMI for 28 AD subjects on AA increased 0.01 kg/m(2)/month (95% CI 0.26-0.83, P<0.0001), comparing PD on AA vs. AD on AA. The weight loss seen in the PD/AA group, compared to AD, suggest uniquely altered weight homeostasis in PD.

Focal hand dystonia, mirror dystonia and motor overflow.

Focal hand dystonia (FHD) is a syndrome of sustained muscle contraction, frequently causing twisting and repetitive movements or abnormal postures of the hand. Motor overflow, defined as unintentional muscle contraction that accompanies but is anatomically distinct from the primary dystonic movement, is a frequent but often unrecognized feature of FHD. In this series of eight patients with FHD, we describe two patterns of motor overflow, termed "ipsilateral overflow" and "contralateral overflow", and contrast it with the phenomenon termed "mirror dystonia". These findings extend the phenomenology and provide evidence for widespread abnormalities of motor control in patients with focal hand dystonia.

Tetrabenazine for hyperglycemic-induced hemichorea-hemiballismus.

We reported a 74-year-old woman with new-onset diabetes mellitus who presented with the sudden onset of mild left hemiparesis and marked left hemichorea-hemiballismus. Brain CT scan and MRI showed T1W, T2W, and DWI lesions in the right putamen and caudate, which have been previously reported in cases of hyperglycemic-induced hemichorea-hemiballismus (HIHH). The patient dramatically responded to tetrabenazine within a day. Subsequent dose reductions lead to a reemergence of symptoms. Tetrabenazine improves a variety of hyperkinetic movement disorders but, to our knowledge, its use has never been reported for HIHH.

Magnetic resonance imaging: implication in acute ischemic stroke management.

Multimodality magnetic resonance imaging (MRI) techniques, including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), fluid-attenuated inversion recovery (FLAIR), T2 susceptibility imaging, and magnetic resonance angiography (MRA), quickly provide accurate information about ischemic penumbra (DWI/PWI mismatch), tissue perfusion, and vascular localization in acute stroke setting. These techniques help physicians to select the proper candidates for thrombolysis and/or neuroprotective treatment to salvage tissue at risk (mismatch) and monitor acute stroke patients after treatment. Recent and ongoing trials demonstrate the benefit of treating acute stroke patients depending on tissue at risk of infarction rather than timing of onset. These techniques will extend timing to salvage ischemic brain tissue beyond the 3-hour window. MRI is a powerful tool for managing acute stroke patients and helps elucidate the pathophysiology of cerebral ischemia in a given patient.