Changes in the relationship between movement velocity and movement distance in primary focal hand dystonia.

The authors examined the relationship between movement velocity and distance and the associated muscle activation patterns in 18 individuals with focal hand dystonia (FHD) compared with a control group of 18 individuals with no known neuromuscular condition. Participants performed targeted voluntary wrist and elbow flexion movements as fast as possible across 5 movement distances. Individuals with FHD were slower than controls across all distances, and this difference was accentuated for longer movements. Muscle activation patterns were triphasic in the majority of individuals with FHD, and muscle activation scaled with distance in a similar manner to controls. Cocontraction did not explain movement slowing in individuals with dystonia, but there was a trend toward underactivation of the 1st agonist burst in the dystonic group. The authors concluded that slowness is a consistent feature of voluntary movement in FHD and is present even in the absence of dystonic posturing. Underactivation of the 1st agonist burst appears to be the most likely reason to explain slowing.

Relationship between ventricular morphology and aqueductal cerebrospinal fluid flow in healthy and communicating hydrocephalus.

OBJECTIVES: Differences in the magnitude of cerebrospinal fluid (CSF) volumetric flow through the cerebral aqueduct between healthy and hydrocephalic patients have been previously reported. However it is not clear whether this is directly related to the pathophysiology or secondary to altered ventricular morphology and hydrodynamics. This work aims to determine the role of anatomic and hydrodynamic factors in modulating the magnitude of CSF flow through the aqueduct. MATERIALS AND METHODS: Twenty subjects (10 healthy and 10 patients with communicating hydrocephalus of different causes) were studied by MRI. Scans included T1-weighted 3D anatomic imaging and velocity-encoded cine phase-contrast scans of transcranial blood and CSF flows as well as CSF flow through the aqueduct. Anatomic MR data were used for quantitation of ventricular volumes, third ventricular width, and gray and white brain tissue volumes. Velocity-encoded imaging was used for quantitation of aqueductal and cervical CSF stroke volumes (SV), aqueductal lumen area, and systolic maximal intracranial volume change. Because data from normal and hydrocephalic patients were aggregated, a battery of statistical methods that accounted for the group effects were used. Partial correlation was used to determine which of these parameters were most significantly associated with aqueductal stroke volume (ASV). Multiple linear regression analyses were employed to identify anatomic and hydrodynamic models with the least amount of variables that are significant predictors of ASV. Finally, the association between the magnitude of ASV and the aqueductal lumen area, and its implication on the CSF flow dynamic characteristics and aqueductal pressure difference was established. RESULTS: Using partial correlations, 5 of the 6 anatomic parameters and none of the hydrodynamic parameters and brain tissue volume were found to be statistically significant. The highest partial correlations were with the total ventricular volume (r = 0.838) and third ventricle width (r = 0.811). These parameters were also found to be significant predictors of ASV in the multiple linear regression analyses with third ventricle volume and group effects as insignificant predictors (F = 28.08, P < 0.0001, R = 0.85). On the other hand, both cervical CSF SV and maximal ICVC were found to be weak predictors of ASV with group effects as the only significant variable of the hydrodynamic model (F = 4.18, P = 0.023, R = 0.33). A combined anatomic-hydrodynamic model including the predictive variables of the anatomic model and the ICVC provides the strongest coefficient of determination (R = 0.873). Pearson correlation analysis revealed a very strong relationship between ASV and the aqueductal lumen area (r = 0.947). CONCLUSIONS: Aqueductal CSF flow is strongly correlated with ventricular morphology, especially with the total ventricular volume and the third ventricle width, but not with the tested hydrodynamic parameters. In addition, ASV is linearly correlated with aqueductal lumen area, suggesting that the aqueductal CSF flow characteristics can be explained by oscillating pressure differences on the order of less than 0.01 mmHg. These findings may explain why a standalone ASV is a poor diagnostic marker and an insensitive indicator of shunt outcome in idiopathic normal pressure hydrocephalus.

Pathways mediating abnormal intracortical inhibition in Parkinson's disease.

Previous studies have used paired-pulse transcranial magnetic stimulation to show that short-interval intracortical inhibition (SICI) is reduced in patients with Parkinson's disease (PD). This study examined whether reduced SICI in PD is caused by an increase in the threshold of inhibitory pathways or a reduction in the threshold of excitatory pathways. Motor-evoked potentials were recorded from a hand muscle in 12 patients with PD (7 patients were tested off and on antiparkinsonian medications) and 12 control subjects. SICI was tested at seven conditioning stimulus intensities (CSIs; 40-100% of resting motor threshold) and at interstimulus intervals (ISIs) of 2, 3, and 4 milliseconds. No differences were found between groups in resting or active motor threshold, SICI threshold, or the extent of SICI at CSIs at or below 80% of resting motor threshold. Significant differences between groups were observed at CSIs of 90% and 100% with an ISI of 3 milliseconds. Antiparkinsonian medication had no effect on SICI. These findings show that the low threshold inhibitory pathways mediating SICI are normal in PD. The suppression of SICI observed at higher CSIs suggests that the threshold of intracortical facilitatory pathways is decreased in PD.

Differential effects of calcium antagonist subclasses on markers of nephropathy progression.

BACKGROUND: Numerous studies suggest that the dihydropyridine calcium antagonists (DCAs) and nondihydropyridine calcium antagonists (NDCAs) have differential antiproteinuric effects. Proteinuria reduction is a correlate of the progression of renal disease. In an earlier systematic review, calcium antagonists were shown as effective antihypertensive drugs, but there was uncertainty about their renal benefits in patients with proteinuria and renal insufficiency. METHODS: A systematic review was conducted to assess the differential effects of DCAs and NDCAs on proteinuria in hypertensive adults with proteinuria, with or without diabetes, and to determine whether these differential effects translate into altered progression of nephropathy. Studies included in the review had to be randomized clinical trials with at least 6 months of treatment, include a DCA or NDCA treatment arm, have one or more renal end points, and have been initiated after 1986. Summary data were extracted from 28 studies entered into two identical but separate databases, which were compared and evaluated by independent reviewers. The effects of each drug class on blood pressure (N= 1338) and proteinuria (N= 510) were assessed. RESULTS: After adjusting for sample size, study length, and baseline value, there were no statistically significant differences in the ability of either class of calcium antagonist to decrease blood pressure. The mean change in proteinuria was +2% for DCAs and -30% for NDCAs (95% CI, 10% to 54%, P= 0.01). Consistently greater reductions in proteinuria were associated with the use of NDCAs compared with DCAs, despite no significant differences in blood pressure reduction or presence of diabetes. CONCLUSION: This analysis supports (1) similar efficacy between subclasses of calcium antagonists to lower blood pressure, and (2) greater reductions in proteinuria by NDCAs compared to DCAs in the presence or absence of diabetes. Based on these findings, NDCAs, alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), are suggested as preferred agents to lower blood pressure in hypertensive patients with nephropathy associated with proteinuria.