Mandar Jog

Methylphenidate improves fatigue scores in Parkinson disease: A randomized controlled trial

Fatigue is a common nonmotor symptom in idiopathic Parkinson disease (IPD) that can prominently affect everyday function. This study was a randomized, double‐blind, placebo‐controlled trial evaluating methylphenidate for the treatment of fatigue in patients with IPD maintained on their regular medications. Thirty‐six patients were randomized to receive either methylphenidate (10 mg three times per day; n = 17) or placebo (n = 19) for 6 weeks. Primary outcomes were the change from baseline on two separate self‐report fatigue questionnaires: the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI). Secondary outcomes included the Unified Parkinson Disease Rating Scale (UPDRS) motor score and the five individual domains of the MFI. Fourteen patients in the methylphenidate group and 16 patients in the control group remained on the intervention for the entire study period. In the treatment arm, mean FSS score was reduced by 6.5 points (from a baseline of 43.8) and mean MFI score was reduced by 8.4 points (from a baseline of 51.0). Both these reductions were significant (P < 0.04). Smaller reductions in the placebo group were nonsignificant. Mean UPDRS motor score did not change significantly in either group. Analysis of MFI subscores showed a significant reduction in General Fatigue in the methylphenidate group (P < 0.001). Overall, adverse effects of medication were more frequent in the placebo group. In conclusion, methylphenidate was effective in lowering fatigue scores in patients with IPD following a 6‐week treatment period.

Sublingual Atropine for sialorrhea secondary to parkinsonism: A pilot study

Sialorrhea is a relatively common symptom in idiopathic Parkinsons disease and related conditions for which most of the accepted treatments are either highly invasive or may cause substantial systemic side effects. This study describes an open‐label pilot study of sublingual atropine drops for the treatment of sialorrhea in 7 patients (6 with Parkinsons disease, 1 with progressive supranuclear palsy). Participants demonstrated statistically significant declines in saliva production, both objectively and subjectively. Self‐reported drooling severity showed a significant decline between baseline and 180 minutes, t(6) = 3.240 P < 0.025 (η2 = 0.636), and between baseline and 1 week, t(6) = 4.583 P < 0.005 (η2 = 0.778). Objectively measured saliva production decreased significantly between baseline and the 1‐week follow‐up, t(6) = 2.711 P < 0.05 (η2 = 0.551). Delirium occurred in 1 patient (concurrent with a urinary tract infection), and 2 patients experienced worsening of hallucinations (active hallucinosis was concealed by both individuals to allow participation in the trial). The remaining trial participants did not experience any anticholinergic side effects. This trial shows that, in selected patient populations, sublingual atropine is a simple and inexpensive treatment for sialorrhea associated with parkinsonism.

Tetrode technology: advances in implantable hardware, neuroimaging, and data analysis techniques

The technical advances in hardware and software for multiunit recordings have made it easier to gather data from a large number of neurons for behavioral correlations. This paper discusses several such advances in implantable hardware, magnetic resonance imaging of electrodes in situ, and data analysis software for multiple simultaneous signals.

Dopaminergic modulation of timing control and variability in the gait of Parkinson's disease

The basal ganglia have been implicated in timing control, yet the nature of timing disturbances in Parkinsons disease (PD) is poorly understood. We evaluated the influence of timing cues on spatiotemporal aspects of gait control and its variability, and the impact of dopaminergic treatment on timing. Three separate groups: 19 PD (OFF state); 24 PD (ON state); and 30 control participants were tested. Participants walked on a computerized carpet at four randomized and metronome‐controlled rates: self‐paced, 60, 80, or 100 steps/min. To our knowledge, this is the first study to demonstrate that medicated PD patients had poorer timing control than patients withdrawn from medication and healthy participants when modulating timing to an external stimulus. Increased step‐to‐step timing variability and deficits in mean temporal gait characteristics revealed that the medicated PD group (in contrast to nonmedicated PD group) performed least like healthy participants. This was observable in externally‐cued conditions, but not during self‐paced gait. Similar to previous research, step length contributed to overall slowness in PD, while temporal characteristics of gait did not. Interestingly, healthy participants increased stride length with each increase in cue rate, whereas both PD groups locked their step length regardless of temporal demand. Step‐to‐step variability differences between PD and healthy (e.g. step and double‐support time measurements) may be indicative of specific basal ganglia involvement in temporal control of gait.

Spike source localization with tetrodes

The paper presents in detail a method for approximating the spatial position of neural spike activity from tetrode recordings. The method uses a nonlinear mapping of a set of tetrode tip amplitudes into three-dimensional (3D) space, followed by a self-organizing map clustering technique. Viewed as a spike sorting method, it performs better than tetrode peak amplitudes and it is roughly equivalent with amplitude ratios. The techniques appeal to physical location may be of advantage in many investigations.

Femoral neuropathy in renal transplantation

Acute femoral neuropathy after renal transplantation is an uncommon and rarely recognized complication. Recovery of the nerve is usual. Although rare, five cases have come to our attention in the past twenty years. A detailed clinical and electrophysiological analysis with a six month follow-up is presented. A review of sixteen other reported cases is also provided. The possible pathophysiology including direct compression and nerve ischemia, is discussed. We believe that nerve ischemia, possibly caused by a steal phenomenon, occurs in all cases following the anastomosis of the graft renal artery to the internal iliac artery, with a superimposed component of compression in some cases. The severity of ischemia probably determines the degree of recovery.

Gum chewing improves swallow frequency and latency in Parkinson patients: a preliminary study.

Background: Reduced swallowing frequency affects secretion management in Parkinson disease (PD). Gum chewing increases saliva flow and swallow frequency. This study uses chewing gum to modify swallow frequency and latency between swallows in patients with PD. Objectives: 1) Assess the frequency and latency of swallow at baseline (BL), during gum chewing (GC), and post gum chewing (PGC) for participants with PD (stage 2–4) nonsymptomatic for prandial dysphagia; and 2) assess carryover after gum is expectorated. Methods: Twenty participants were studied across 3 tasks, each of 5 minutes in duration: BL, GC, and PGC. Respiratory and laryngeal signals were continuously recorded using PowerLab (version 5.5.5; ADI Instruments, Castle Hill, Australia). Frequency and latency of swallow events were calculated. Results: Differences (analysis of variance) are reported for frequency (p < 0.000001) and latency (p < 0.000001). Swallow frequency (mean ± SD) increased during GC (14.95 ± 3.02) compared with BL (3.1 ± 2.85) and PGC (7.0 ± 2.57). Latency in seconds (mean ± SD) decreased during GC (24.1 ± 4.174) and increased with BL (131.8 ± 59.52) and PGC (mean = 60.74 ± 25.25). Intertask comparisons (t test) found differences in swallow frequency and latency between tasks: BL vs GC (p < 0.0001, p < 0.0001), BL vs PGC (p < 0.0011, p < 0.0009), and GC vs PGC (p < 0.0001, p < 0.0002), respectively. Post hoc analysis showed carryover to 5.317 minutes. Conclusions: Modifying sensorimotor input by chewing gum alters frequency and latency of swallowing and may be an effective strategy for secretion management in Parkinson disease. Classification of evidence: This study provides Class III evidence that chewing gum increases swallow frequency and decreases latency of swallowing in an experiment in patients with stage 2 to 4 Parkinson disease who are nonsymptomatic for significant prandial dysphagia.

Movement patterns of peak-dose levodopa-induced dyskinesias in patients with Parkinson's disease.

The present study characterized involuntary movements associated with levodopa-induced dyskinesias (LID) in patients with Parkinsons disease. We used amplitude, proportional energy, frequency dispersion and sample entropy to determine whether LID movement patterns are truly random, as clinical description seems to suggest, or possess some underlying pattern that is not visible to the naked eye. LID was captured using a magnetic tracker system, which provided 3D rendering of whole-body LID. Patients were instructed to maintain a standing position, with arms extended in front of them. We compared the measurements of the dyskinetic PD group (DPD) with 10 patients without dyskinesias (NDPD) and 10 control subjects. In comparison to the other two groups, movement patterns from the DPD group had significantly higher amplitude, confirming the presence of dyskinesias. In addition, higher frequency components in the power spectrum of velocity were detected, suggestive of higher velocity in LID movement. Furthermore, there was a concentration in narrow frequency bands, which suggested stable oscillatory activity. Finally, sample entropy revealed more regularity in the DPD group. Although not statistically significant, we found that the amplitude from the NDPD group had a tendency to be smaller than those of controls. As well, the spectra were often more dispersed for the NDPD group. In conclusion, the present results suggest that LID cannot be considered as purely random movement since they possess some deterministic pattern of motion. This may provide a way for patients to adapt to these involuntary movements while performing voluntary motor acts.

Computing spike directivity with tetrodes

The ability of neurons to generate electrical signals is strongly dependent on the evolution of ion-specific pumps and channels that allow the transfer of charges under the influence of electric fields and concentration gradients. This paper presents a novel method by which flow of these charge fluxes may be computed to provide directivity of charge movement. Simulations of charge flow as well as actual electrophysiological data recorded by tetrodes are used to demonstrate the method. The propagation of charge fluxes in space in data from simulation and actual recordings during action potential can be analyzed using signals recorded by tetrodes. Variation in spike directivity can be estimated by computing singular value decomposition of the estimated 3D trajectory data. The analysis of the spike model can be accomplished by performing simulations of presumed equivalent moving charges recorded by the tetrode tips. For in vivo spike recordings, the variation of spike directivity could be obtained using several spikes of selected neurons considering the charge movement model (CMM). The relationship between computer simulation results and tetrode data recordings is examined. The paper concludes by showing that the method for calculating directivity in actual spike recordings is robust. The method allows for improved filtering of data and more importantly may shed light on furthering the study of spatio-temporal encoding in neurons.

Capturing whole-body mobility of patients with Parkinson disease using inertial motion sensors: Expected challenges and rewards

While many studies have reported on the use of kinematic analysis on well-controlled, in-laboratory mobility tasks, few studies have examined the challenges of recording dynamic mobility in home environments. This preliminary study evaluated whole body mobility in eleven patients with Parkinson disease (H&Y 2–4). Patients were recorded in their home environment during scripted and non-scripted mobility tasks while wearing a full-body kinematic recording system using 11 inertial motion sensors (IMU). Data were analyzed with principal component analysis (PCA) in order to identify kinematic variables which best represent mobility tasks. Results indicate that there was a large degree of variability within subjects for each task, across tasks for individual subjects, and between scripted and non-scripted tasks. This study underscores the potential benefit of whole body multi-sensor kinematic recordings in understanding the variability in task performance across patients during daily activity which may have a significant impact on rehabilitation assessment and intervention.