Narayanan Krishnamurthi

Deep brain stimulation amplitude alters posture shift velocity in Parkinson's disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is now widely used to alleviate symptoms of Parkinson’s disease (PD). The specific aim of this study was to identify posture control measures that may be used to improve selection of DBS parameters in the clinic and this was carried out by changing the DBS stimulation amplitude. A dynamic posture shift paradigm was used to assess posture control in 4 PD STN-DBS subjects. Each subject was tested at 4 stimulation amplitude settings. Movements of the center of pressure and the position of the pelvis were monitored and several quantitative indices were calculated. The presence of any statistically significant changes in several normalized indices due to reduced/no stimulation was tested using the one-sample t test. The peak velocity and the average movement velocity during the initial and mid phases of movement towards the target posture were substantially reduced. These results may be explained in terms of increased akinesia and bradykinesia due to altered stimulation conditions. Thus, the dynamic posture shift paradigm may be an effective tool to quantitatively characterize the effects of DBS on posture control and should be further investigated as a tool for selection of DBS parameters in the clinic.

Comparison of Parkinson Disease Patients Who Fell Once with Patients Who Fell More than Once (Recurrent Fallers)

Falls are a major risk for Parkinson disease patients (PD). Single falls, in older peoplemay be related to the underlying disease or may be accidental. Recurrent falls are more likely to be related to the underlying disease. We followed 401persons with PD for a year, 205 of whom, 51.0%, fell: 161 fell once and 44 fell more than once (recurrent fallers). Recurrent fallers had PD significantly longer, 12.6 ± 7.0 versus 5.9 + 4.5 years, had significantly higher, worse, motor Unified Parkinson Disease Rating Scale (UPDRS) scores” 31.2 ± 12.7 versus 19.7 + 8.3. The major difference between recurrent and single fallers was an inability of recurrent fallers to stand on one leg for < 3 seconds: 95% versus 11%, odds ratio 178 CI 95% 39.5 – 801.2 single fallers who are unable to stand on one foot for < 3 seconds may be at risk for recurrent falls. Gait and balance training focused on improving a patient’s ability to stand on one leg may decrease the risk of recurrent falls in PD.

Distinguishing the tremor of Parkinson's disease from essential tremor: Finger displacement

Although, the tremor of Parkinsons disease (PD) usually, but not always, differs from essential tremor (ET), there is no simple bedside test to distinguish PD from ET. We believe we have made such an observation. We studied 50 consecutive tremor-dominant PD patients (mean age: 63.4 years; mean disease duration: 4.9 years) and 35 consecutive ET patients (mean age: 64.1 years; mean disease duration: 12.5 years). Among PD patients, 31 had a bilateral tremor and among ET patients, 29 patients had a bilateral tremor. Patients sat opposite the examiner and pointed both index fingers at the examiners index fingers. Then they closed their eyes. Within 15 s, one or rarely both of the patients index fingers moved, was displaced, either upward or laterally. Finger displacement occurred only with bilateral simultaneous pointing with the patients eyes closed. All the tremor-dominant PD patients exhibited displacement of an index finger. In 46 patients, it occurred on the side of dominant tremor, in 4, it occurred bilaterally. In 31 of 35 ET patients, no displacement occurred. In 4 of 35 ET patients, it occurred unilaterally on the side of dominant tremor. Odds ratio of distinguishing PD from ET: 89.62 at 95% confidence limits (5.31–1513.4), p = 0. 0018. Sensitivity 100% (0.91–1), specificity 89% (0.72–0.96). Finger displacement can distinguish the tremor of PD from ET. The unilateral movement with eyes closed suggests the tremor of PD unlike ET may impact circuits involving the parietal and supplementary motor cortices.

A Simple Question About Falls to Distinguish Balance and Gait Difficulties in Parkinson's Disease

ABSTRACT Although gait and balance difficulties often occur together in Parkinsons disease (PD) patients, it is believed that they are actually two separate symptoms. However, there are no simple tests to distinguish them. We have developed the self-administered Barrow Neurological Institute (BNI) question to distinguish between gait and balance issues in PD and it was tested in 102 consecutive PD patients. The responses were compared with those of the walking and balance question (item # 2.12) of the Movement Disorder Society-sponsored revision of the Unified Parkinsons Disease Rating Scale (MDS-UPDRS), and the MDS-UPDRS motor examination and its subsets such as gait and postural stability (PS). Fifty-five patients reported balance difficulty on the BNI question and 64 reported walking and balance difficulty on the MDS-UPDRS question. Of the patients who reported balance difficulty on the BNI question, 74.5% had a PS score ≥2 and 25.4% fell at least three times per month. Of the patients who reported walking and balance difficulty on the MDS-UPDRS question, only 59.4% had a PS score ≥2 and only 10.9% fell three or more times per month. These statistically significant results suggest that the BNI question is better able to detect balance difficulty and its associated falls in PD and can be a supplement to the MDS-UPDRS or a stand-alone question to evaluate balance difficulty and its associated falls in PD.

A System for Real-Time Feedback to Improve Gait and Posture in Parkinson's Disease

For people with Parkinsons disease (PD), gait and postural impairments can significantly affect their ability to perform activities of daily living. Presentation of appropriate cues has been shown to improve gait in PD. Based on this, a treadmill-based system and experimental paradigm were developed to determine if people with PD can utilize real-time feedback (RTFB) of step length or back angle (uprightness) to improve gait and posture. Eleven subjects (mean age 67 ± 8 years) with mild-to-moderate PD (Hoehn and Yahr stage I-III) were evaluated regarding their ability to successfully utilize RTFB of back angle or step length during quiet standing and treadmill walking tasks during a single session in their medication-on state. Changes in back angle and step length due to feedback were compared using Friedman nonparametric tests with Wilcoxon Signed-Rank tests for post-hoc comparisons. Improvements in uprightness were observed as an increase in back angle during quiet standing (p = 0.005) and during treadmill walking (p = 0.005) with back angle feedback when compared to corresponding tasks without feedback. Improvements in gait were also observed as an increase in step length (p = 0.005) during step length feedback compared to tasks without feedback. These results indicate that people with mild-to-moderate PD can utilize RTFB to improve upright posture and gait. Future work will investigate the long-term effects of this RTFB paradigm and the development of systems for clinical or home-based use.

Finger displacement in Parkinson disease: up? down? sideways?

We previously reported that patients with tremor preponderant Parkinson disease (PD) displayed upward or lateral displacement of their more tremulous finger when they pointed both their index fingers at a target and closed their eyes for 15 seconds. In this study, we examined the phenomenon in 104 PD patients: 72 patients without tremor and 32 with minimal tremor to see if the displacement is related to the disease or the tremor. Sixty-eight of the 72 patients without tremor, 94%, exhibited finger displacement suggesting the phenomenon is related to the disease. None of the 104 patients were demented: mini-mental status examination (MMSE) score 29.0 ± 0. 75. Ninety patients displayed upward displacement (56 patients) or lateral or medial displacement (34 patients). MMSE score of the 90 patients: 29.2 ± 0.74 with no score < 28. Eight patients (6 without tremor) displayed downward displacement. MMSE score of the 8 patients: 27.5 ± 0.35 with 5 having MMSE score of 27. Although not significant the results suggest that patients with downward displacement and lower MMSE score may be evolving a dementia. Upward displacement with eyes closed for 15 seconds requires an ability to “remember” the position of the finger in space and to alter tone to overcome gravity. Downward displacement implies an inability to “remember” the position of the finger in space an inability to overcome the effects of gravity. This may be more likely in patients who are evolving a dementia. Two patients, with PD-like symptoms, and specific anatomical abnormalities are also presented as they illustrate the anatomy of finger displacement.

Is there room for non-dopaminergic treatment in Parkinson disease?

Although levodopa and dopaminergic drugs remain the mainstay of therapy for the motor symptoms of Parkinson disease (PD), they fail to address many of the non-motor symptoms of PD including orthostatic hypotension, freezing of gait (FOG) and difficulty with balance, drug-induced paranoia and hallucinations, and drug-induced dyskinesias. Droxidopa, a drug that increases norepinephrine, treats orthostatic hypotension, cholinomimetic drugs sometimes help with FOG and difficulty with balance, pimavanserin, a drug that blocks serotonin receptors, treats paranoia and hallucinations, and anti-glutaminergic drugs treat dyskinesias. Thus, there are ample opportunities for non-dopaminergic drugs in PD.

Attractor-shape descriptors for balance impairment assessment in Parkinson's disease

In this paper, we propose a computational framework using high-dimensional shape descriptors of reconstructed attractors of center-of-pressure (CoP) tracings collected from subjects with Parkinsons disease while performing dynamical posture shifts, to quantitatively assess balance impairment. Using a dataset collected from 60 subjects, we demonstrated that the proposed method outperforms traditional methods, such as dynamical shift indices and use of chaotic invariants, in assessment of balance impairment.In this paper, we propose a computational framework using high-dimensional shape descriptors of reconstructed attractors of center-of-pressure (CoP) tracings collected from subjects with Parkinsons disease while performing dynamical posture shifts, to quantitatively assess balance impairment. Using a dataset collected from 60 subjects, we demonstrated that the proposed method outperforms traditional methods, such as dynamical shift indices and use of chaotic invariants, in assessment of balance impairment.

Characterization of balance control through dynamic posture shifts

The control of posture is achieved by complex integrated visual, vestibular, and somatosensory systems. Neurological disorders such as Parkinsons disease (PD) and aging may affect these systems resulting in compromised balance control and subsequent increase in risk of falling. Typically, balance control is evaluated with static posturography and dynamic posturography involving applied or volitional perturbation. In this study, we have utilized dynamic posture shifts that mimic everyday reaching tasks to distinguish balance performance among young, elderly, and people with PD. A total of 57 subjects were recruited: young (21 subjects; 19-32 years), elderly (22 subjects; 50-75 years), and PD (17 subjects; 53-72 years). The dynamic posture shift task involves subjects moving their Center-of-Pressure (CoP) from a center (quiet standing position) to different outward targets (leaning position) then back to center, and hold their CoP inside the targets for about 2 seconds. During these movements, their CoP was displayed in real-time as a circular cursor on a monitor at eye level. Many balance indices were calculated from stabilogram obtained from CoP data of each target presentation. Of them, the path length during movement phase was significantly different (p <; 0.05) across all the three groups. The peak velocity, movement time, and movement velocity was significantly different between young and PD and elderly and PD groups (p <; 0.05). These results suggest that these measures can be utilized to evaluate balance control for different conditions, specifically to monitor changes due to any exercise training and medical treatment.

A Shoe Mounted System for Parkinsonian Gait Detection and Real-Time Feedback

Conditions like Parkinson’s disease (PD) remain largely a mystery in the way that they affect individuals even under today’s modern medical practices. One of the main secondary effects associated with PD can be seen in issues with the individual’s gait and is referred to as Freezing of Gait (FoG). The symptom often responds poorly and sometimes paradoxically to treatment with dopaminergic medication that is traditionally used to treat the other symptoms of PD. However, a linkage found that FoG, during walking, results when the sequence effect is superimposed on a reduced step length. Prior research has focused on the development of technologies that use audio or visual feedback to help the individual adjust their gait. These systems may not be deployable in real-world environments since people rely on sight and sound for navigation. This research proposes the development of a system to measure step length in real-time and to provide haptic feedback to offset the progression of FoG episodes.