Diana M. Dimitrova

Direction-specific postural instability in subjects with Parkinson's disease

The purpose of this study was to determine whether and why subjects with Parkinsons disease (PD) have greater instability in response to specific directions of perturbations than do age-matched control subjects and how instability is affected by stance width. This study compared postural responses to 8 directions of surface translations in PD subjects and age-matched control subjects while standing in a narrow and wide stance. PD subjects were tested in their practical OFF state. A postural stability margin was quantified as the difference between peak center of pressure (CoP) and peak center of mass (CoM) displacement in response to surface translations. The control subjects maintained a consistent stability margin across directions of translations and for both narrow and wide stance by modifying rate of rise of CoP responses. PD subjects had smaller than normal postural stability margins in all directions, but, especially for backwards sway in both stance widths and for lateral sway in narrow stance width. The reduced stability margin in PD subjects was due to a slower rise and smaller peak of CoP in the PD subjects than in control subjects. Lateral postural stability was compromised in PD subjects by lack of trunk flexibility and backwards postural stability was compromised by lack of knee flexion, resulting in excessive displacements of the body CoM. Stability margins in PD subjects were related to their response on the pull test in the Unified Parkinsons Disease Rating Scale. Thus, PD patients have directionally specific postural instability due to an ineffective stiffening response and inability to modify their postural responses for changing postural demands related to direction of perturbation and initial stance posture. These results suggest that the basal ganglia, in addition to regulating muscle tone and energizing postural muscle activation, also are critical for adapting postural response patterns for specific biomechanical conditions.

Can stooped posture explain multidirectional postural instability in patients with Parkinson’s disease?

To determine the effects of the stooped posture of patients with Parkinson’s disease (PD) on postural stability, we compared the kinetic, kinematic, and electromyographic responses of seven subjects with PD and 11 control subjects to eight directions of surface translations. Control subjects were studied in an upright posture and in a stooped posture that mimicked the posture of the PD subjects. When control subjects adopted a stooped posture, peak center of pressure displacements slowed and decreased, reducing stability margins toward values observed in PD subjects. Stooped control subjects, however, responded to translations with large joint angle displacements, whereas PD subjects exhibited small joint angle displacements. Stooping in control subjects did not lead to abnormally directed horizontal forces under each foot or antagonistic muscle co-activation at the hip and trunk, as seen in PD subjects. Upright and stooped control subjects never fell during the trials, whereas PD subjects fell in 16% of the trials. We conclude that stooped posture is a destabilizing posture, but it does not account for abnormal postural responses in PD.

Using modafinil to treat fatigue in Parkinson disease: a double-blind, placebo-controlled pilot study.

Background: Fatigue is a major nonmotor symptom in Parkinson disease (PD). It is associated with reduced activity and lower quality of life. Objective: To determine if modafinil improves subjective fatigue and physical fatigability in PD. Methods: Nineteen PD patients who reported significant fatigue in the Multidimensional Fatigue Inventory (MFI) participated in this 8-week study. Subjects took their regular medications and were randomly assigned to the treatment group (9 subjects, modafinil 100-mg capsule BID) or placebo group (10 subjects). We used the MFI to measure subjective fatigue and used finger tapping and intermittent force generation to evaluate physical fatigability. Subjects also completed the Epworth Sleepiness Scale (ESS) and the Center of Epidemiological Study-Depression Scale. Results: There were no significant differences at baseline and at 1 month in finger tapping and ESS between the modafinil and placebo groups. At 2 months, the modafinil group had a higher tapping frequency (P < 0.05), shorter dwell time (P < 0.05), and less fatigability in finger tapping and tended to have lower ESS scores (P < 0.12) than the placebo group. However, there was no difference between groups over time for any dimension of the MFI. Conclusions: This small study demonstrated that although modafinil may be effective in reducing physical fatigability in PD, it did not improve fatigue symptoms.

Abnormal force patterns for multidirectional postural responses in patients with Parkinson’s disease

This study tests the hypothesis that the basal ganglia are involved in optimizing postural responses for changes in perturbation direction and stance width. We compared the patterns of horizontal and vertical ground reactive forces under each leg in response to eight directions of surface translation in Parkinson’s disease (PD) subjects and age-matched control subjects standing with both narrow and wide stance. Although passive reactive forces were larger, active forces were weaker and in abnormal directions for subjects with PD. Unlike the control subjects, who corrected their postural equilibrium in response to lateral and diagonal-lateral perturbations primarily with their loaded limbs, the PD subjects used both legs more symmetrically to recover equilibrium. PD subjects also did not change the magnitude or direction of reactive forces when initial stance width changed. These results support the hypothesis that the basal ganglia are important for optimizing automatic postural response patterns for changes in perturbation direction and for initial stance conditions.

Polyneuronal Innervation of Single Muscle Fibers in Cat Eye Muscle: Inferior Oblique

Single muscle fibers with multiple axonal endplates (multiply innervated fibers) are normally present in adult extraocular muscles (EOMs), while most other mammalian skeletal muscles contain fibers with a single myoneural junction. Recent findings by others led us to investigate for the presence of polyneuronal innervation (innervation of a single muscle fiber by >1 motoneuron) in the inferior oblique (IO) muscle of pentobarbital anesthetized cats. The IO muscle nerve branches, as they coursed through the orbit, were further divided for independent or simultaneous electrical stimulation with bipolar electrodes. Four of five established tests for polyneuronal innervation gave positive results. The sum of the twitch (1) and tetanic (2) tensions in response to individual nerve branch stimulation was greater than that for simultaneous (whole) nerve stimulation. The summed electromyographic (EMG) responses (3) gave a similar positive result. The result for crossed tetanic potentiation (4) was negative for polyneuronal innervation while the crossed fatigue (5) test was positive. These results are consistent with recent studies. That the EOMs exhibit polyneuronal innervation further explains the eye-movement systems functional integrity during some neuromuscular disorders as well as its ability to operate with precision after the loss of numerous motoneurons.

Effect of expectancy and personality on cortical excitability in Parkinson's disease

Our previous studies in Parkinsons disease have shown that both levodopa and expectancy of receiving levodopa reduce cortical excitability. We designed this study to evaluate how degree of expectancy and other individual factors modulate placebo response in Parkinsons patients. Twenty‐six Parkinsons patients were randomized to 1 of 3 groups: 0%, 50%, and 100% expectancy of receiving levodopa. All subjects received placebo regardless of expectancy group. Subjects completed the NEO‐Five Factor Inventory, General Perceived Self‐Efficacy Scale, and Perceived Stress Scale. Cortical excitability was measured by the amplitude of motor‐evoked potential (MEP) evoked by transcranial magnetic stimulation. Objective physical fatigue of extensor carpi radialis before and after placebo levodopa was also measured. Responders were defined as subjects who responded to the placebo levodopa with a decrease in MEP. Degree of expectancy had a significant effect on MEP response (P < .05). Subjects in the 50% and 100% expectancy groups responded with a decrease in MEP, whereas those in the 0% expectancy group responded with an increase in MEP (P < .05). Responders tended to be more open to experience than nonresponders. There were no significant changes in objective physical fatigue between the expectancy groups or between responders and nonresponders. Expectancy is associated with changes in cortical excitability. Further studies are needed to examine the relationship between personality and placebo effect in Parkinsons patients.

P02.186. CAST (Centella asiatica selected triterpenes): stability, safety, and effect on diabetic neuropathy (DN)

Methods The stability of CAST was monitored throughout the study using reversed phase high performance liquid chromatography. CAST or placebo capsules were administered to 33 DN subjects, in a randomized double-blind, placebocontrolled study. The dose of CAST was escalated from 60 mg to 240 mg/day over the first 12 weeks, followed by a stable dose of 240 mg/day for the remaining 40 weeks. The primary outcome was total symptom score (TSS), while secondary outcomes were nerve conduction studies, neurological disability score (NDS) and qualitative sensory testing (QST).

P06.5 The effects of rTMS of different frequency and intensity on cortical excitability and finger tapping in PD

respectively. There was no statistically significant difference in SSRI group in HRV parameters. Conclusions: Though rTMS and SSRI are effective antidepressants, their effect on HRV are different. rTMS modulates the cardiac autonomic tone towards increasing the parasympathetic activity and decreasing the sympathetic activity whereas SSRI did not modulate the neurocardiac regulation. Further studies with large sample size, biochemical and imaging studies would throw more light into the mechanism of such modulation.