A prospective study on gait dominant normal pressure hydrocephalus.

OBJECT: We characterize idiopathic normal pressure hydrocephalus (NPH) following treatment with lumbar puncture (LP) and shunt placement through clinical evaluation and quantitative ProtoKinetics Zeno walkway assessments. We evaluate the symptomology by determining gait characteristics altered by treatment. METHODS: Patients at Barrow Neurological Institute (BNI) who underwent a LP, removing 30-32 mL cerebrospinal fluid) followed by ventriculoperitoneal shunt placement in February 2015 to February 2017 were analyzed for gait impairments. Inclusion in the study required a diagnosis of NPH, no conflicting comorbidities, and pre-LP, post-LP, and 6-month post-shunt assessments. Analyses of gait and balance data recorded by physical therapists and the ProtoKinetics Zeno Walkway at pre-LP, post-LP, and post-shunt were performed. RESULTS: A total of 28 patients were included and one-way analysis of variance and Tukey-Kramer HSD was performed. Among the 15 clinical assessments, nine were significantly altered. Using the ProtoKinetics Zeno Walkway, 7 out of 10 characteristics recorded were considered significantly different among the three data sets. Furthermore, there were more significant differences between pre-LP assessments and post-shunt assessments in comparison to differences between pre-LP assessments and post-LP assessments. CONCLUSIONS: Our results indicate that certain gait characteristics better fit NPH than others. By focusing on the features that are caused by NPH and alleviated by LP and/or shunt placement, a more definitive NPH diagnosis can be attained. Additionally, our findings confirm a cumulative effect of continuous drainage via shunt placement may lead to increased improvement in NPH symptoms over LP results.

Downward finger displacement distinguishes Parkinson disease dementia from Alzheimer disease.

Purpose/Aim of the study: To study finger displacement in patients with Parkinson disease dementia (PDD) and in patients with Alzheimer disease (AD). METHODS: We examined 56 patients with PDD and 35 with AD. Patients were examined during their regular outpatient clinic visit. Finger displacement was measured by observers not actively involved in the study using a creative grid ruler for all PDD and AD patients. Finger displacement was examined by asking patients to point their index fingers toward the grid ruler with the nails facing upward. Patients were asked to maintain the pointing position for 15 s. After 15 s, patients were asked to close their eyes for another 15 s while maintaining the same position. A positive result was downward index finger displacement of ≥5 cm within the 15-second time window with eyes closed. RESULTS: Of the 56 PDD patients, 53 had bilateral finger displacement of >5 cm. In comparison, of the 35 AD patients, only 1 patient had minimal displacement. CONCLUSIONS: Results of the non-invasive finger displacement test may provide insight, on an outpatient basis, of the integrity of subcortical-cortical circuits. Downward finger displacement, especially bilateral downward displacement, may signal the extensive disruption of subcortical-cortical circuits that occurs in PDD patients. ABBREVIATIONS: AChE: acetylcholinesterase; AD: Alzheimer disease; DLB: dementia with Lewy bodies; ET: essential tremor; MDS-UPDRS: Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale; MMSE: Mini-Mental State Examination; PD: Parkinson disease; PDD: Parkinson disease dementia.

Motor Subtypes of Parkinson's Disease Can Be Identified by Frequency Component of Postural Stability.

Parkinson's disease (PD) can be divided into two subtypes based on clinical features-namely tremor dominant (TD) and postural instability and gait difficulty (PIGD). This categorization is important at the early stage of PD, since identifying the subtypes can help to predict the clinical progression of the disease. Accordingly, correctly diagnosing subtypes is critical in initiating appropriate early interventions and tracking the progression of the disease. However, as the disease progresses, it becomes increasingly difficult to further distinguish those attributes that are relevant to the subtypes. In this study, we investigated whether a method using the standing center of pressure (COP) time series data can separate two subtypes of PD by looking at the frequency component of COP (i.e., COP position and speed). Thirty-six participants diagnosed with PD were evaluated, with their bare feet on the force platform, and were instructed to stand upright with their arms by their sides for 20 s (with their eyes open and closed), which is consistent with the traditional COP measures. Fast Fourier transform (FFT) and wavelet transform (WT) were performed to distinguish between the motor subtypes using the COP measures. The TD group exhibited larger amplitudes at the frequency range of 3-7 Hz when compared to the PIGD group. Both the FFT and WT methods were able to differentiate the subtypes. COP time series information can be used to differentiate between the two motor subtypes of PD, using the frequency component of postural stability.

Dynamical Properties of Postural Control in Obese Community-Dwelling Older Adults †.

Postural control is a key aspect in preventing falls. The aim of this study was to determine if obesity affected balance in community-dwelling older adults and serve as an indicator of fall risk. The participants were randomly assigned to receive a comprehensive geriatric assessment followed by a longitudinal assessment of their fall history. The standing postural balance was measured for 98 participants with a Body Mass Index (BMI) ranging from 18 to 63 kg/m², using a force plate and an inertial measurement unit affixed at the sternum. Participants' fall history was recorded over 2 years and participants with at least one fall in the prior year were classified as fallers. The results suggest that body weight/BMI is an additional risk factor for falling in elderly persons and may be an important marker for fall risk. The linear variables of postural analysis suggest that the obese fallers have significantly higher sway area and sway ranges, along with higher root mean square and standard deviation of time series. Additionally, it was found that obese fallers have lower complexity of anterior-posterior center of pressure time series. Future studies should examine more closely the combined effect of aging and obesity on dynamic balance.

Polestriding Intervention Improves Gait and Axial Symptoms in Mild to Moderate Parkinson Disease.

OBJECTIVE: To evaluate the effects of 12-week polestriding intervention on gait and disease severity in people with mild to moderate Parkinson disease (PD). DESIGN: A-B-A withdrawal study design. SETTING: Outpatient movement disorder center and community facility. PARTICIPANTS: Individuals (N=17; 9 women [53%] and 8 men [47%]; mean age, 63.7±4.9y; range, 53-72y) with mild to moderate PD according to United Kingdom brain bank criteria with Hoehn & Yahr score ranging from 2.5 to 3.0 with a stable medication regimen and ability to tolerate "off" medication state. INTERVENTIONS: Twelve-week polestriding intervention with 12-week follow-up. MAIN OUTCOME MEASURES: Gait was evaluated using several quantitative temporal, spatial, and variability measures. In addition, disease severity was assessed using clinical scales such as Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale, and Parkinson's Disease Questionnaire-39. RESULTS: Step and stride lengths, gait speed, and step-time variability were improved significantly (P<.05) because of 12-week polestriding intervention. Also, the UPDRS motor score, the UPDRS axial score, and the scores of UPDRS subscales on walking and balance improved significantly after the intervention. CONCLUSIONS: Because increased step-time variability and decreased step and stride lengths are associated with PD severity and an increased risk of falls in PD, the observed improvements suggest that regular practice of polestriding may reduce the risk of falls and improve mobility in people with PD.

Accuracy of Patient and Care Partner Identification of Cognitive Impairments in Parkinson's Disease-Mild Cognitive Impairment.

BACKGROUND: Criteria for Parkinson's disease-mild cognitive impairment require a caregiver or patient complaint or clinician observation of cognitive decline and objective evidence of cognitive deficit in at least 1 of 5 cognitive domains. This study examines the accuracy of Parkinson's disease-mild cognitive impairment patient and care partner reports of specific cognitive difficulties. METHODS: A total of 42 Parkinson's disease-mild cognitive impairment patients and their care partners reported the absence or presence of deficits in each cognitive domain during an interview. A deficit in each domain was defined by scores ≤ 1.5 standard deviations below the mean on corresponding cognitive tests. RESULTS: Sensitivity, specificity, and positive and negative predictive values were modest for patient and care partner reports across all domains. Patients' and care partners' accuracy in observing objectively identified deficits was poor across all domains (≤ 60% agreement; κ ≤ .07). Patient and care partner reports showed moderate agreement in all domains except attention (≥ 74% agreement; κ ≥ .43). CONCLUSIONS: Parkinson's disease-mild cognitive impairment patients and their care partners may not be accurate in identifying specific cognitive deficits. Thus, even patients (and care partners) who correctly report having a cognitive deficit may misidentify the specific deficit. The finding supports the value of International Parkinson and Movement Disorder Society Parkinson's disease-Mild Cognitive Impairment Level II assessment and cautions against relying on subjective report or screening in research in which the nature of cognitive deficit identification or treatment is paramount. Overreliance on patient and care partner reports of specific impairments may distort epidemiologic estimates of mild cognitive impairment subtypes and misdirect cognitive rehabilitation at incorrect domains. © 2016 International Parkinson and Movement Disorder Society.

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.

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

Although, the tremor of Parkinson's 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 examiner's index fingers. Then they closed their eyes. Within 15 s, one or rarely both of the patient's index fingers moved, was displaced, either upward or laterally. Finger displacement occurred only with bilateral simultaneous pointing with the patient's 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.

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.

Effects of protective step training on proactive and reactive motor adaptations in Parkinson's disease patients.

The aim of this study was to investigate to what extent PD affects the ability to walk, respond to balance perturbations in a single training session, and produce acute short-term effects to improve compensatory reactions and control of unperturbed walking stability. Understanding the mechanism of compensation and neuroplasticity to unexpected step perturbation training during walking and static stance can inform treatment of PD by helping to design effective training regimens that remediate fall risk. Current rehabilitation therapies are inadequate at reducing falls in people with Parkinson's disease (PD). While pharmacologic and surgical treatments have proved largely ineffective in treating postural instability and gait dysfunction in people with PD, studies have demonstrated that therapy specifically focusing on posture, gait, and balance may significantly improve these factors and reduce falls. The primary goal of this study was to assess the effectiveness of a novel and promising intervention therapy (protective step training - i.e., PST) to improve balance and reduce falls in people with PD. A secondary goal was to understand the effects of PST on proactive and reactive feedback responses during stance and gait tasks. Multiple-baseline, repeated measures analyses were performed on the multitude of proactive and reactive performance measures to assess the effects of PST on gait and postural stability parameters. In general, the results indicate that participants with PD were able to use experiences with perturbation training to integrate and adapt feedforward and feedback behaviors to reduce falls. The ability of the participants with PD to adapt to changes in task demands suggests that individuals with PD could benefit from the protective step training to facilitate balance control during rehabilitation.

A simple question about falls to distinguish balance and gait difficulties in Parkinson's disease.

Although gait and balance difficulties often occur together in Parkinson's disease (PD) patients, it is believed that they are actually two eparate 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 Parkinson's 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.

Motor Learning Deficits in Parkinson's Disease (PD) and Their Effect on Training Response in Gait and Balance: A Narrative Review.

Parkinson's disease (PD) is a neurological disorder traditionally associated with degeneration of the dopaminergic neurons within the substantia nigra, which results in bradykinesia, rigidity, tremor, and postural instability and gait disability (PIGD). The disorder has also been implicated in degradation of motor learning. While individuals with PD are able to learn, certain aspects of learning, especially automatic responses to feedback, are faulty, resulting in a reliance on feedforward systems of movement learning and control. Because of this, patients with PD may require more training to achieve and retain motor learning and may require additional sensory information or motor guidance in order to facilitate this learning. Furthermore, they may be unable to maintain these gains in environments and situations in which conscious effort is divided (such as dual-tasking). These shortcomings in motor learning could play a large part in degenerative gait and balance symptoms often seen in the disease, as patients are unable to adapt to gradual sensory and motor degradation. Research has shown that physical and exercise therapy can help patients with PD to adapt new feedforward strategies to partially counteract these symptoms. In particular, balance, treadmill, resistance, and repeated perturbation training therapies have been shown to improve motor patterns in PD. However, much research is still needed to determine which of these therapies best alleviates which symptoms of PIGD, the needed dose and intensity of these therapies, and long-term retention effects. The benefits of such technologies as augmented feedback, motorized perturbations, virtual reality, and weight-bearing assistance are also of interest. This narrative review will evaluate the effect of PD on motor learning and the effect of motor learning deficits on response to physical therapy and training programs, focusing specifically on features related to PIGD. Potential methods to strengthen therapeutic effects will be discussed.

Effects of Obesity and Fall Risk on Gait and Posture of Community-Dwelling Older Adults.

Epidemiological studies link increased fall risk to obesity in older adults, but the mechanism through which obesity increases falls and fall risks is unknown. This study investigates if obesity (Body Mass Index: BMI>30 kg/m2) influenced gait and standing postural characteristics of community dwelling older adults leading to increased risk of falls. One hundred healthy older adults (age 74.0±7.6 years, range of 56-90 years) living independently in a community participated in this study. Participants' history of falls over the previous two years was recorded, with emphasis on frequency and characteristics of falls. Participants with at least two falls in the prior year were classified as fallers. Each individual was assessed for postural stability during quiet stance and gait stability during 10 meters walking. Fall risk parameters of postural sway (COP area, velocity, path-length) were measured utilizing a standard forceplate coupled with an accelerometer affixed at the sternum. Additionally, parameters of gait stability (walking velocity, double support time, and double support time variability) were assessed utilizing an accelerometer affixed at the participant's sternum. Gait and postural stability analyses indicate that obese older adults who fell have significantly altered gait pattern (longer double support time and greater variability) exhibiting a loss of automaticity in walking and, postural instability as compared to their counterparts (i.e., higher sway area and path length, and higher sway velocity) further increasing the risk of a fall given a perturbation. Body weight/BMI is a risk factor for falls in older adults as measured by gait and postural stability parameters.

Falls When Standing, Falls When Walking: Different Mechanisms, Different Outcomes in Parkinson Disease.

Our retrospective study of falls and resultant trauma in consecutive Parkinson disease (PD) patients seen in one year at the Muhammad Ali Parkinson Clinic found that multiple-fallers could be divided into patients who fell mainly when walking or those who fell mainly when standing. Patients who fell when walking were more likely to visit an emergency room or be admitted to a hospital. Of 455 consecutive patients who were evaluated over a one-year period, 51 were excluded because they had atypical Parkinson disorders, had multiple risk factors for falling, or were demented. Unified Parkinson Disease Rating Scales and Zeno Walkway results were compared among non-fallers, single-fallers, and multiple-fallers. Among multiple-fallers, comparisons were made between patients who fell mainly when standing and those who fell mainly when walking. Most patients (197, 49%) did not fall, 142 (35%) fell once, and 65 (16%) fell more than once. Multiple-fallers differed significantly from single-fallers and non-fallers: they had PD significantly longer (p<0.001), were more severely affected (p<0.001), and took shorter steps (p<0.001). Of 65 multiple-fallers, 26 (40%) fell mainly when standing, 28 (43%) fell mainly when walking, and 11 (17%) fell equally often when standing or walking. Falls when walking resulted in more severe injuries. Patients who fell mainly when standing did not realize they could fall when standing; engaged in inappropriate weight shifting, bending, reaching, and multitasking; and failed to use their assistive devices. Such patients would benefit from being counseled about falling when standing. Patients who fell mainly when walking were aware they could fall, despite using an assisted device, and were more likely to have freezing of gait (FOG). They were more likely to sustain a severe injury, and were more likely to be admitted to an emergency room or hospital. Such patients would benefit from reducing, if possible, FOG.

Nicotine Bitartrate Reduces Falls and Freezing of Gait in Parkinson Disease: A Reanalysis.

Objective: Determine if NC001, an oral formulation of nicotine that reduces levodopa-induced dyskinesias (LIDs) in MPTP-Parkinson monkeys, could reduce falls, freezing of gait (FOG), and LIDs in Parkinson disease (PD) patients. Methods: Previously collected data from a study analyzing the effects of NC001 on LIDs in PD patients were reanalyzed. Because indirect-acting cholinergic drugs are sometimes helpful in reducing falls, we hypothesized that NC001, a direct-acting cholinergic agonist, could reduce falls in PD. The original 12-center, double-blind, randomized trial enrolled 65 PD patients. NC001 or placebo was administered 4 times per day for 10 weeks, beginning at 4 mg/day and escalating to 24 mg/day. Assessments included the Unified Dyskinesia Rating Scale (UDysRS) and Parts II-III of the original Unified Parkinson's Disease Rating Scale (UPDRS). Results: Randomization (1:1) resulted in 35 patients on NC001 and 30 on placebo at baseline. Thirty and 27 patients, respectively, had data available for an intent-to-treat analysis. NC001 was safe and well-tolerated. After 10 weeks, NC001 patients (14/30) had a significant reduction in falls vs. placebo patients (3/27) (p = 0.0041) as assessed by UPDRS Part II. NC001 patients (12/30) also had significantly reduced FOG vs. placebo patients (4/27) (p = 0.0043). NC001 patients, compared with placebo patients, had a significant improvement (p = 0.01) in UDysRS ambulation subtest (40% vs. 3%, respectively). Although NC001 patients had a greater reduction in dyskinesias on the UDysRS than placebo patients (30% vs. 19%, respectively), this was not significant (p = 0.09). Conclusions: NC001 significantly improved two refractory symptoms of PD, falls and FOG. The reduction in falls and FOG is attributed to selective stimulation of nicotinic receptors. Clinical Trial Registration: Conducted under IND 105, 268, serial number 0000. ClinicalTrials.gov identifier NCT00957918.

Pain-pressure threshold in patients with Parkinson's disease with and without dyskinesia.

The objective of this study was to determine if Parkinson's disease (PD) patients with dyskinesia have a lower pain pressure threshold (PPT) than patients without dyskinesia and healthy controls. This was an outpatient, controlled study. We studied 25 healthy controls, 25 PD patients without dyskinesia and 25 PD patients with dyskinesia. A J Tech Pain Track algometer was used to measure PPT. No differences were found in PPT between controls and PD patients with or without dyskinesia. Patients and control women had a lower PPT than men. In conclusion, the presence of dyskinesia in PD patients does not appear to decrease PPT.

Are dementia and depression in Parkinson's disease related?

INTRODUCTION: Depression and dementia are common problems in PD. As the depression and dementia of PD share many symptoms such as apathy, anhedonia, anergia, and agitation, it is reasonable to ask if they are related. METHODS: 106 consecutive PD patients, unselected for depression or dementia were evaluated for depression using the Hamilton Depression Scale (Ham-D21). They were also evaluated using a modified neuropsychiatric inventory (NPI). Following the above, 100 consecutive PD patients were evaluated for dementia using Folstein's Mini Mental Status Examination (MMSE). They were also evaluated using the modified NPI. RESULTS: 29 of the first series of patients, 27%, were depressed, score of > or =14 on the Ham-D21. 8 of the second series of consecutive patients, 18%, were demented, score < or =24 on the MMSE. Depressed and demented patients were significantly more likely to suffer from apathy, anhedonia, mood lability, daytime drowsiness, paranoia, and hallucinations. Demented patients were significantly older, had PD longer, were more disabled and more likely to be depressed. COMMENT: The commonality of certain symptoms in demented and depressed patients suggests that dementia and depression in PD may be related and that, in PD depression may be a fore-runner of dementia. Five year follow-up of these patients supports this suggestion.

Are freezing of gait (FOG) and panic related?

We studied 109 consecutive patients who were unselected for freezing of gait (FOG), anxiety, depression, or panic attacks. All patients completed a panic assessment, the Hamilton Anxiety Scale and the Hamilton Depression Scale. Patients were divided into those with FOG or no FOG based on their answer to the FOG question on the Activities of Daily Living part of the UPDRS. Patients with FOG were more disabled, had more "wearing off", dyskinesia, leg dystonia, and postural instability. They were also more anxious and more likely to panic. FOG, in many patients, is increased by anxiety and panic.

Parkinson's disease outcomes after intraoperative CT-guided "asleep" deep brain stimulation in the globus pallidus internus.

OBJECTIVE: Recent studies show that deep brain stimulation can be performed safely and accurately without microelectrode recording ortest stimulation but with the patient under general anesthesia. The procedure couples techniques for direct anatomical targeting on MRI with intraoperative imaging to verify stereotactic accuracy. However, few authors have examined the clinical outcomes of Parkinson's disease (PD) patients after this procedure. The purpose of this study was to evaluate PD outcomes following "asleep" deep brain stimulation in the globus pallidus internus (GPi). METHODS: The authors prospectively examined all consecutive patients with advanced PD who underwent bilateral GPi electrode placement while under general anesthesia. Intraoperative CT was used to assess lead placement accuracy. The primary outcome measure was the change in the off-medication Unified Parkinson's Disease Rating Scale motor score 6 months after surgery. Secondary outcomes included effects on the 39-Item Parkinson's Disease Questionnaire (PDQ-39) scores, on-medication motor scores, and levodopa equivalent daily dose. Lead locations, active contact sites, stimulation parameters, and adverse events were documented. RESULTS: Thirty-five patients (24 males, 11 females) had a mean age of 61 years at lead implantation. The mean radial error off plan was 0.8 mm. Mean coordinates for the active contact were 21.4 mm lateral, 4.7 mm anterior, and 0.4 mm superior to the midcommissural point. The mean off-medication motor score improved from 48.4 at baseline to 28.9 (40.3% improvement) at 6 months (p < 0.001). The PDQ-39 scores improved (50.3 vs 42.0; p = 0.03), and the levodopa equivalent daily dose was reduced (1207 vs 1035 mg; p = 0.004). There were no significant adverse events. CONCLUSIONS: Globus pallidus internus leads placed with the patient under general anesthesia by using direct anatomical targeting resulted in significantly improved outcomes as measured by the improvement in the off-medication motor score at 6 months after surgery.

Cocaine abusers have an overexpression of alpha-synuclein in dopamine neurons.

Alpha-synuclein is a presynaptic protein that has been implicated as a possible causative agent in the pathogenesis of Parkinson's disease. The native protein is a major component of nigral Lewy bodies in Parkinson's disease, and full-length alpha-synuclein accumulates in Lewy neurites. Here we present evidence that alpha-synuclein levels are elevated in midbrain dopamine (DA) neurons of chronic cocaine abusers. Western blot and immunoautoradiographic studies were conducted on postmortem neuropathological specimens from cocaine users and age-matched drug-free control subjects. The results demonstrated that alpha-synuclein levels in the DA cell groups of the substantia nigra/ventral tegmental complex were elevated threefold in chronic cocaine users compared with normal age-matched subjects. The increased protein levels in chronic cocaine users were accompanied by changes in the expression of alpha-synuclein mRNA in the substantia nigra and ventral tegmental area. Although alpha-synuclein expression is prominent in the hippocampus, there was no increase in protein expression in this brain region. The levels of beta-synuclein, a possible negative regulator of alpha-synuclein, also were not affected by cocaine exposure. Alpha-synuclein protein levels were increased in the ventral tegmental area, but not the substantia nigra, in victims of excited cocaine delirium who experienced paranoia, marked agitation, and hyperthermia before death. The overexpression of alpha-synuclein may occur as a protective response to changes in DA turnover and increased oxidative stress resulting from cocaine abuse. However, the accumulation of alpha-synuclein protein with long-term cocaine abuse may put addicts at increased risk for developing the motor abnormalities of Parkinson's disease.