Timed Motor Tests Research Articles

Can Quantitative Muscle Strength and Functional Motor Ability Differentiate the Influence of Age and Corticosteroids in Ambulatory Boys with Duchenne Muscular Dystrophy?

Background: In the absence of a curative treatment for Duchenne Muscular Dystrophy (DMD), corticosteroid therapy (prednisone, deflazacort) has been adopted as the standard of care, as it slows the progression of muscle weakness and enables longer retention of functional mobility. The ongoing development of novel pharmacological agents that target the genetic defect underlying DMD offer hope for a significant alteration in disease progression; however, substantiation of therapeutic efficacy has proved challenging. Identifying functional outcomes sensitive to the early, subtle changes in muscle function has confounded clinical trials. Additionally, the alterations in disease progression secondary to corticosteroid therapy are not well described making it difficult to ascertain the benefits of novel agents, often taken concurrently with corticosteroids.Objective: The purpose of this study was to examine outcome responsiveness to corticosteroid therapy and age at the onset of a natural history study of ambulatory boys with DMD.Methods: Eighty-five ambulatory boys with DMD (mean age 93 mo, range 49 to 180 mo) were recruited into this study. Fifty participants were on corticosteroid therapy, while 33 were corticosteroid naïve at the baseline assessment. Within each treatment group boys were divided in two age groups, 4 to 7 years and 8 and greater years of age. The Biodex System 3 Pro isokinetic dynamometer was used to assess muscle strength. Motor skills were assessed using the upper two dimensions (standing/walking, running & jumping) of the Gross Motor Function Measure (GMFM 88) and Timed Motor Tests (TMTs) (10-meter run, sit to stand, supine to stand, climb 4-stairs). Two way analysis of variance and Pearson correlations were used for analysis.Results: A main effect for age was seen in select lower extremity muscle groups (hip flexors, knee extensors and ankle dorsiflexors), standing dimension skills, and all TMTs with significantly greater weakness and loss of motor skill ability seen in the older age group regardless of treatment group. Interaction effects were seen for the walking, running, and jumping dimension of the GMFM with the naïve boys scoring higher in the younger group and boys on corticosteroid therapy scoring higher in the older group. The TMT of climb 4-stairs demonstrated a significant treatment effect with the boys on corticosteroid therapy climbing stairs faster than those who were naïve, regardless of age. Examination of individual items within the upper level GMFM dimensions revealed select motor skills are more informative of disease progression than others; indicating their potential to be sensitive indicators of alterations in disease progression and intervention efficacy. Analysis of the relationship between muscle group strength and motor skill performance revealed differences in use patterns in the corticosteroid versus naïve boys.Conclusion: Significant muscle weakness is apparent in young boys with DMD regardless of corticosteroid treatment; however, older boys on corticosteroid therapy tend to have greater retention of muscle strength and motor skill ability than those who are naive. Quantification of muscle strength via isokinetic dynamometry is feasible and sensitive to the variable rates of disease progression in lower extremity muscle groups, but possibly most informative are the subtle changes in the performance characteristics of select motor skills. Further analysis of longitudinal data from this study will explore the influence of corticosteroid therapy on muscle strength and further clarify its impact on motor performance.

DAT imaging and clinical biomarkers in relatives at genetic risk for LRRK2 R1441G Parkinson's disease.

The objective of this study was to study motor and nonmotor symptoms and striatal dopaminergic denervation, as well as the relationship between them, in a cohort of asymptomatic relatives of patients with Parkinson's disease (PD) with the R1441G-leucine-rich repeat kinase 2 mutation. Asymptomatic relatives of patients with PD and this mutation were tested for the presence of the mutation and evaluated for striatal, putamenal, and caudate dopaminergic transporters using (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single-photon emission computed tomography binding ratios. Clinical and neuropsychological evaluations including timed motor tests, a smell identification test, and global cognition, attention, executive, visuospatial, and memory functions as well as depression, constipation, and rapid eye movement sleep behavior disorder were also assessed. Twenty-seven carriers and 19 noncarriers were studied. Compared with noncarriers, mutation carriers had significantly lower (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropan mean striatal (P = 0.03), mean putamenal (P = 0.01), and lowest putamenal (P = 0.01) binding ratios. Multiple linear regression analysis showed that the carrier status and the execution of timed tests significantly predicted striatal (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane binding. The proportion of variation accounted for by the regression model of these variables was 69% for the putamen and 53% for the caudate nucleus. Asymptomatic carriers of the R1441G-leucine-rich repeat kinase 2 mutation have evidence of dopaminergic nigrostriatal denervation, mainly in the putamen, which is associated with a decline in the execution of complex motor tests. These tests could be early indicators of the ongoing dopaminergic deficit in this group at risk of PD.

P.11.15 Recombinant human insulin-like growth factor-I (IGF-I) therapy in Duchenne Muscular Dystrophy (DMD): A 6-month prospective randomized controlled trial

Glucocorticoids (GC) delay motor decline in DMD, but cause significant endocrine adverse effects. IGF-I offers potential as a therapeutic agent; it may improve or preserve muscle function and counter GC effects of growth failure and insulin resistance. To determine if IGF-I therapy (1) improves or preserves muscle function and (2) improves linear growth in DMD. Prospective randomized controlled trial of IGF-I therapy in pre-pubertal, ambulatory, GC-treated DMD boys (n = 17) compared to controls (GC alone, n = 21). IGF-I 160 mcg/kg was given daily subcutaneously for 6 months. Primary motor outcome was 6-min walk distance (6MWD), and endocrine outcomes were height velocity and change in height SD score (ΔHtSDS). Other outcomes included changes in timed motor tests, cardiopulmonary function, insulin sensitivity and safety. The difference of 6MWD between control and IGF-I groups at 6 months was 8.5 ± 7.0 m (mean ± SEM, p > 0.5). There were no significant differences between groups for changes in cardiopulmonary and other motor functional outcomes. Height velocity in IGF-I treated subjects was double that of controls at 6 months (6.5 ± 0.4 vs. 3.3 ± 0.3 cm/yr, p In this first study of IGF-I therapy in DMD boys, 6 months of daily IGF-I significantly increased height velocity and HtSDS compared to controls, but there was no difference in motor functional outcomes.

GW24-e0014 Analysis on clinical evaluation of parkinson’s disease with interated traditional chinese and western medicine therapy: a multicenter, randomized, double-blind, placebo controlled trial

ObjectivesObjective Sensitive clinical evaluation items for detecting the early stages of PD could improve development of new treatments. The aim of this study was to analyse on clinical evaluation of...

A historical justification for and retrospective analysis of the systematic application of light therapy in Parkinson’s disease

For the past 40 years the primary purpose of therapeutics for Parkinson's disease (PD) has been to replace deficient dopamine (DA) in the nigrostriatal dopamine (NSD) system. Even in the presence of limited efficacy, abundant side effects and impoverished quality of life, the involvement of other systems in the aetiology and treatment of this disorder has been sorely neglected and the excessive use of DA replacement therapy (DART) continues on a global basis. Recent scientific work suggests that the retina plays a major role in NSD function and intimates light therapy in the management of PD. After a thorough review of historical evidence supporting this contention, a retrospective, open-label study on 129 PD patients, whereby they were monitored for a period extending for a few months to eight years, was carried out. Primary motor and non-motor symptoms were monitored using an objectified global rating scale and timed motor tests that were assessed at regular intervals for the duration of the study. Thirty-one patients with other neurological disorders (OND) served as controls to determine whether any therapeutic effects seen with light were generalizable across other conditions. Patients were classified as compliant (COM), semi-compliant (SCOM), or early quit (EQUIT; prematurely discontinued treatment). EQUIT patients showed deterioration, while the COM group improved on most parameters. The SCOM patients were not as good as the COM group. The OND group showed significant improvement in depression and insomnia, but exposure to light did not improve motor function. The total drug burden of PD patients maintained on light was less with fewer side effects than SCOM or EQUIT groups. These results confirm the value of the strategic application of light therapy with controlled doses of DART in PD and warrants further controlled investigation. That the symptomatic improvement continued as long patients remained in the program suggests that exposure to light, under a strict daily regimen, combined with controlled DART, actively slows or arrests the progressive degenerative process underlying PD.

SMA CARNI-VAL TRIAL PART II: A Prospective, Single-Armed Trial of L-Carnitine and Valproic Acid in Ambulatory Children with Spinal Muscular Atrophy

BackgroundMultiple lines of evidence have suggested that valproic acid (VPA) might benefit patients with spinal muscular atrophy (SMA). The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and l-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2–8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children.MethodsThis study involved 33 genetically proven type 3 SMA subjects ages 3–17 years. Subjects underwent two baseline assessments over 4–6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend), timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP), handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores.ResultsTwenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful.ConclusionsThis study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA.Trial RegsitrationClinicaltrials.gov NCT00227266

Timed motor tests can detect subtle motor dysfunction in early Parkinson's disease

Early diagnosis of Parkinson's disease (PD) is important for putative neuroprotective therapies to be initiated in the earliest stage of the disease. We investigated whether a previously validated timed motor test (TMT) battery could detect subtle motor dysfunction in early PD patients and even in clinically unaffected limbs of strictly hemiparkinsonian patients. We assessed 107 PD patients (symptom duration <or=2 years; dopa-naive) and 100 healthy, age-matched controls with eight simple TMTs based on aspects of (a) walking, (b) writing, (c) single and double-handed pegboard performance, (d) finger tapping, and (e) diadochokinesis. We evaluated the ability of individual and combined TMTs to discriminate patients from controls using ROC curves. Second, we investigated whether these TMTs could identify motor dysfunction of the clinically unaffected limb in 42 strictly hemiparkinsonian patients. The pegboard dexterity test had the best ROC curve (AUC 0.97; 95% sensitivity, 89% specificity) for patients versus controls. It retained reasonable accuracy when testing the clinically unaffected limb of hemiparkinsonian patients versus the mean of right and left-hand scores in controls (AUC 0.73). The pegboard dexterity test is a sensitive and inexpensive instrument to detect motor dysfunction in early PD. Therefore, it may be worth evaluating as a diagnostic tool in everyday clinical practice to assess patients with early symptomatic PD, or as part of a more elaborate screening battery in a defined population at risk.

GM1 ganglioside in Parkinson's disease: Results of a five year open study

Previous work demonstrated that short-term (i.e., 16 weeks) use of GM1 ganglioside resulted in significant symptom reduction in Parkinson's disease (PD) patients. As GM1 use may have long-term benefit for PD patients, the present study was conducted to evaluate the long-term safety and efficacy of GM1 in PD patients. Twenty-six patients who concluded a previous randomized double blind placebo controlled trial of GM1 volunteered for this open-extension study. At the end of 5 years of GM1 use, patients generally had lower Unified Parkinson's Disease Rating Scale (UPDRS) motor scores (assessed during a practically defined “off” period) than at baseline prior to randomization into the original study. A similar result was found for UPDRS Activities of Daily Living scores. Performance of timed motor tests also remained mostly stable over the 5 year observation period. No consistent clinically significant changes in blood chemistry, hematologic indices or urine chemistry were noted over the course of this study. These results suggest that long-term GM1 use by PD patients is safe and may provide some clinical benefit for PD patients. Additional study is required to more completely assess the degree to which GM1 treatment may be a symptomatic and/or disease-modifying agent for treatment of PD.

Periodic Salbutamol in Facioscapulohumeral Muscular Dystrophy: A Randomized Controlled Trial

Payan CA, Hogrel JY, Hammouda EH, Lacomblez L, Ollivier G, Doppler V, Eymard B, Attarian S, Pouget J, Desnuelle C, Laforêt P. Periodic salbutamol in facioscapulohumeral muscular dystrophy: a randomized controlled trial. Objective To evaluate the effects on muscle strength of salbutamol administered for 6 months using a periodic regimen in patients presenting with facioscapulohumeral muscular dystrophy (FSHD). Design Placebo-controlled double-blind randomized study. Setting Three clinical centers involved in neuromuscular disorders. Participants Ambulatory patients (N=112), 56 per group, with genetically confirmed FSHD, age 18 to 60 years. Interventions Salbutamol (sustained released formulation) administered orally at a daily dose of 16mg using a periodic dosage regimen (3wks on, 1wk off). Main Outcome Measures Muscle strength was assessed with quantitative muscle testing (QMT), manual muscle testing (MMT), and timed motor tests. Patients were evaluated at baseline, and 3 and 6 months later. Plasma drug assays were carried out at each visit. Results There was no significant change with periodic use of salbutamol in the total composite QMT z-score, MMT score, or timed motor tests. Salbutamol was well tolerated. Lack of efficacy did not seem to be related to plasma concentrations, which were within the expected range. Conclusions Results from this study and previous controlled trials preclude at present the use of salbutamol as routine treatment for FSHD, even if we cannot exclude improvement from anabolic effects with a longer duration of treatment.

Comparison of a timed motor test battery to the Unified Parkinson's Disease Rating Scale‐III in Parkinson's disease

The most widely used scale currently available for the clinical evaluation of motor dysfunction in Parkinson's disease (PD)-the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) -is time-consuming, subjective, and has suboptimal sensitivity. A brief timed motor test (TMT) battery could possibly overcome these drawbacks. Two hundred eighty-eight PD patients (disease duration 3.1 years; preceding dopaminergic treatment initiation) were assessed with the UPDRS-III and nine TMTs based on aspects of (a) walking, (b) writing, (c) single and double-handed pegboard performance, (d) finger tapping, and (e) rapid alternating forearm movements. We investigated validity, reliability, responsiveness, and feasibility. Completing the TMT battery took less than 5 minutes. The TMT correlated well with UPDRS-III and disease duration. Two factors explained 61% of the TMT variance, the first represented mainly upper extremity function, the second mainly axial/lower extremity function. Cronbach's alpha was equal for the TMT and the UPDRS-III (0.8). Test-retest reliability of the TMT sumscore was 0.93 to 0.89 for measurements separated by 3 up to 24 months, whereas UPDRS-III correlations were 0.88 to 0.84. At group level, a trial using "change from baseline" as endpoint requires only 75% of the patients needed with the UPDRS-III when applying the TMT battery, and 57% using the pegboard dexterity test. At patient level, TMT and UPDRS-III were equally responsive. The TMT battery described here is valid, reliable, and feasible. Compared to the UPDRS-III, it is more objective and more sensitive to change. Therefore, it could be a useful tool for both practical and scientific purposes. (c) 2008 Movement Disorder Society.

Impact of Prophylactic Thoracolumbosacral Orthosis Bracing on FunctiQnal Activities and Activities of Daily Living in the Pediatric Spinal Cord Injury Population

Background/Objective: The purpose of this study is to assess the impact of a thoracolumbosacral orthosis (TLSO) on children with spinal cord injuries (SCI) in terms of functional independence and time requirements for performance of functional activities and to ascertain the children's preference for TLSO use.Methods: Fourteen subjects with thoracic SCI, ages 6 to 14 years, were studied. All subjects had previously been prescribed and were using a TLSO to prevent the progression of scoliosis. Functional activities included in the Functional Independence Measure and 6 additional wheelchair and transfer skills were scored by level of assistance required. The timed motor test (TMT) included 6 activities involving dressing, transfers, and wheelchair propulsion. Subjects completed the activities of the functional activities scale (FAS) and TMT while wearing a TLSO and without a TLSO. Subjects were asked their preference for wearing or not wearing the TLSO during each of the activities.Results: For the TMT, subjects were slower with a TLSO when donning a shirt or pants, with even and uneven transfers and hallway propulsion (P < 0.05). The majority of subjects preferred not wearing the TLSO during the TMT activities. Lower functional activity scores were recorded while wearing a TLSO for upperextremity dressing (P < 0.05), lower-extremity dressing, bladder management, transferring to bed, and reaching for objects on the floor. Subjects preferred not wearing a TLSO for the following activities: lowerextremity dressing, bladder management, reaching for an object on the floor, and transfer from a supine to a sitting position.Conclusions: Wearing a TLSO adversely affected independence level and time requirements for selected functional activities. Subjects preferred not wearing a TLSO while performing the activities. Activities that required hip flexion, such as donning pants or transitioning from a supine to a sitting position were restricted by the TLSO. Future studies with larger sample sizes should explore the relationships between functioning with a TLSO as related to a patient’s age, level of injury, and TLSO design.

Bilateral subthalamotomy in Parkinson's disease: initial and long-term response

We conducted an open label pilot study of the effect of bilateral subthalamotomy in 18 patients with advanced Parkinson's disease. In seven patients, the first subthalamotomy pre-dated the second by 12-24 months ('staged surgery'). Subsequently, a second group of 11 patients received bilateral subthalamotomy on the same day ('simultaneous surgery'). Patients were assessed according to the CAPIT (Core Assessment Program for Intracerebral Transplantation) protocol, a battery of timed motor tests and neuropsychological tests. Evaluations were performed in the 'off' and 'on' drug states before surgery and at 1 and 6 months and every year thereafter for a minimum of 3 years after bilateral subthalamotomy. Compared with baseline, bilateral subthalamotomy induced a significant (P < 0.001) reduction in the 'off' (49.5%) and 'on' (35.5%) Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at the last assessment. A blind rating of videotape motor exams in the 'off' and 'on' medication states preoperatively and at 2 years postoperatively also revealed a significant improvement. All of the cardinal features of Parkinson's disease as well as activities of daily living (ADL) scores significantly improved (P < 0.01). Levodopa-induced dyskinesias were reduced by 50% (P < 0.01), and the mean daily levodopa dose was reduced by 47% at the time of the last evaluation compared with baseline (P < 0.0001). Dyskinesias occurred intraoperatively or in the immediate postoperative hours in 13 patients, but were generally mild and short lasting. Three patients developed severe generalized chorea that gradually resolved within the next 3-6 months. Three patients experienced severe and persistent postoperative dysarthria. In two, this coincided with the patients exhibiting large bilateral lesions also suffering from severe dyskinesias. No patient exhibited permanent cognitive impairment. The motor benefit has persisted for a follow-up of 3-6 years. This study indicates that bilateral subthalamotomy may induce a significant and long-lasting improvement of advanced Parkinson's disease, but the clinical outcome was variable. This variability may depend in large part on the precise location and volume of the lesions. Further refinement of the surgical procedure is mandatory.

Test-retest reliability of UPDRS-III, dyskinesia scales, and timed motor tests in patients with advanced Parkinson's disease: an argument against multiple baseline assessments.

The primary objective of this study was to assess the intra-rater reliability of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) in patients with advanced Parkinson's disease (PD). The secondary objective was to assess the intra-rater reliability of standard timed motor tests and dyskinesia scales to determine the necessity of multiple baseline core evaluations before surgery for PD. We carried out two standardized preoperative core evaluations of patients with advanced PD scheduled to undergo deep brain stimulation. Patients were examined in the defined off and on conditions by the same rater. UPDRS-III, timed tests, and dyskinesia scores from the two evaluations were compared using Wilcoxon Signed Ranks tests and intraclass correlation coefficients (ICC). Differences in UPDRS-III scores for the two visits were clinically and statistically nonsignificant, and the ICC was 0.9. Similarly, there were no significant differences in timed motor tests or dyskinesia scores, with a median ICC of 0.8. The results indicate that previous findings of high test-retest reliability of UPDRS-III in early untreated PD patients can now be extended to those with advanced disease complicated by motor fluctuations. In addition, test-retest reliability of dyskinesia scales and timed motor tests was high. Taken together, these findings challenge the need for multiple baseline assessments as currently stipulated in core assessment protocols for surgical intervention in PD.

Timed Motor Test For Wheelchair Users: Initial Development and Application in Chiloren With Spinal Cord Injury

Objective: The objective of this study was to describe the development and preliminary results of reliability testing of the timed motor test (TMT), a performance-based measure of functional status for children with a spinal cord injury (SCI) who use a manual wheelchair. This study will also provide pilot data using the TMT to examine the impact of thoracolumbosacral orthoses (TLSO) on function in children with a SCI.Study Design: Cross-sectional observational study.Methods/Participants: This study enrolled 11 subjects with SCI. The TMT consisted of donning a shirt, donning pants, even transfers, uneven transfers, and propelling a wheelchair 80 feet and up a ramp of 45 feet. Nine subjects completed the TMT with and without a TLSO, and 6 subjects ( 4 of whom also completed the TMT with and without a TLSO) completed the reliability testing.Results: Except for donning pants, the intertester and intratester reliability of the TMT was fair-to-good with intradass correlation coefficients (ICCs) of 0.60 or greater. When wearing a TLSO, participants were slower at donning a shirt, donning pants, performing even and uneven transfers, and hallway propulsion (P < 0.05). There was a preference for not wearing a TLSO for dressing and transfer skills.Conclusion: ln general, the TMT for wheelchair users had fair-to-good intertester and intratester reliability. Based on these pilot data, there was an increase in time to complete several functional tasks because of the use of a TLSO as measured by the TMT in children with a SCI.

MRI directed bilateral stimulation of the subthalamic nucleus in patients with Parkinson’s disease

Objective: Bilateral chronic high frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has emerged as an appropriate therapy for patients with advanced Parkinson’s disease refractory to medical therapy....

Gait dynamics in Parkinson's disease: relationship to Parkinsonian features, falls and response to levodopa

Objectives: Patients with Parkinson's disease (PD) have an increased risk of falling that has yet to be fully explained. To better understand the gait disturbance in PD and the factors that contribute to falls, we quantitatively evaluated: (1) the relationship between gait variability (a marker of fall risk in other populations), fall history, and other parkinsonian features, and (2) the effects of levodopa on these relationships. Methods: The average stride time and stride-to-stride variability were measured using force-sensitive insoles during comfortable walking. Fall frequency, motor control, function, and mental health were measured using the Unified Parkinson's Disease Rating Scale (UPDRS), the Mini-Mental State Exam (MMSE), and the timed motor tests of the Core Assessment Program for Intracerebral Transplantations (CAPIT) in 32 subjects with idiopathic PD, in an “off” (unmedicated) state and again in an “on” (medicated) state. Results: Average stride time was not associated with any UPDRS or CAPIT measure and was similar in fallers and non-fallers in “off” and “on” states (p>0.27). Stride time variability was significantly associated with fall frequency as well as with total scores on the CAPIT and the UPDRS, ADL abilities, and motor function. Stride time variability and falls were not related to tremor, rigidity or bradykinesia in the “off” state. 41% of subjects reported one or more falls. Stride time variability was 8.8±7.9% in fallers and 4.2±1.3% in non-fallers (p<0.009). Stride time variability significantly improved in response to levodopa, both in fallers and non-fallers, but remained increased in fallers (vs. non-fallers). Conclusions: The patho-physiology responsible for impaired stride-to-stride regulation of gait timing is apparently independent of other cardinal features of PD, i.e., tremor, rigidity, or bradykinesia, but is responsive to levodopa. Stride-to-stride variability is especially impaired among PD subjects with a history of falls, suggesting, for the first time, the possibility of exaggerated impairment of internal clock function in PD fallers.

Deep brain stimulation of the subthalamic nucleus for control of extrapyramidal features in advanced idiopathic parkinson's disease: one year follow-up.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) with a quadripolar electrode was carried out in 9 patients with advanced idiopathic Parkinson's disease (PD) affected with severe diurnal motor fluctuations. The effect of bilateral STN stimulation was evaluated by clinical methods in all patients after 3 and 12 months. Assessment was based on the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests, the Schwab and England Activities of Daily Living and a diary chart to document motor fluctuations. Alterations in parkinsonian signs, motor performance and functional outcome were recorded postoperatively (1) under temporary complete withdrawal of both STN stimulation and medication; (2) in the presence of STN stimulation only; and (3) in the presence of both STN stimulation and medication. The results were compared with the preoperative data assessed in defined on-phase and defined off-phase. STN stimulation on (compared to STN stimulation off) results in a significant improvement in UPDRS motor scores: after 3 months from 50.5 +/- 14.3 to 27.8 +/- 5.8, and after 12 months from 49.4 +/- 14.1 to 27.1 +/- 7.1 (p < 0.01). There was a significant decrease in the average duration of off-periods from 8.82 +/- 2.47 hours to 1.00 +/- 1.06 hours (p < 0.001), a marked increase in on-periods without dyskinesia from 4.62 +/- 2.72 to 14.62 +/- 1.51 hours (p < 0.01), and a sharp drop in on-periods with dyskinesia from 2.87 (+/- 4.18) to 0.25 (+/- 0.97) hours (p < 0.05), which remained stable up to 12 months (off-periods: 1.25 +/- 1.58 hours, p < 0.001; on-periods without: 13.87 +/- 1.95 hours, p < 0.001; and on-periods wth dyskinesia: 0.37 +/- 1.06 hours, p < 0.05). However, our first PD patient with an implanted DBS electrode within the STN died from cardiac infarction two days after surgery. This sudden death was not linked either to surgery nor to stimulation - and happened by chance. Our findings confirm that STN stimulation is a suitable functional neurosurgical procedure for the modulation and control of PD signs associated with severe motor fluctuations, in that they demonstrate a beneficial effect which was fully sustained over a one year follow-up period. Subthalamic nucleus, deep brain stimulation, Parkinson's disease.

Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson's disease.

The aim of this study was to compare, retrospectively, the value of chronic bilateral stimulation of the internal globus pallidus (GPi) and the subthalamic nucleus (STN) in patients with young onset Parkinson's disease. We selected 13 consecutive patients with similar characteristics at the time of surgery: age at onset < 40 years, disabling motor fluctuations (Hoehn and Yahr stage 4 or 5 in off-drug phases) and levodopa-induced dyskinesias (LID). Eight patients were operated on in the STN and five in the GPi. The Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests and a LID scale were compared in on- and off-drug conditions before surgery and 6 months after surgery on stimulation using the chronic electrical parameters found to improve best the motor state of the individual patient, without adverse effects. In off-drug phases, the motor score of the UPDRS was improved by 71% with STN stimulation and by 39% with GPi stimulation on average. This difference was statistically significant (P < 0.05). Whereas rigidity and tremor showed good improvement in both groups, the decrease in the akinesia score was more pronounced in the STN group. In the STN group, the improvement of all motor symptoms was very close, or equal, to the best levodopa response. Thus the levodopa test was predictive of outcome. The improvement in off-drug period motor handicap allowed a decrease in the levodopa-equivalent dose only in the STN group (-56%). The voltage, frequency and pulse width used for chronic stimulation were lower in the STN group. In the on-drug phases there was a marked improvement in LID in the GPi group, as measured by the dyskinesias score during an acute levodopa test, whereas there was only a small decrease in the STN group (P < 0.05). However, in the long term, the reduction of levodopa dosage in the STN group led to an indirect reduction of LID similar to that in the GPi group during activities of everyday life. In conclusion, the overall results favour the neurosurgical treatment of Parkinson's disease by stimulating the STN rather than the GPi.

A study of medial pallidotomy for Parkinson's disease: clinical outcome, MRI location and complications.

We have studied the effects of unilateral ventral medial pallidotomy in 26 patients with medically intractable Parkinson's disease with marked drug-induced dyskinesias. Preoperatively, all patients were assessed during one 5-day admission according to the Core Assessment Programme for Intracerebral Transplantation (CAPIT) protocol, including rating in the 'practically defined off' and 'best on' states before and during a single-dose levodopa challenge. Motor performance was assessed with subset categories of the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests and a standard dyskinesia rating scale. Pallidotomy was performed under stereotaxic CT guidance with intra-operative extracellular microelectrode recording made from the basal ganglia. All patients were re-assessed 3 months postoperatively and a subgroup (n = 9) have so far also been re-assessed after 1 year. Pre- and postoperative performance scores were compared in order to determine which categories of performance improved postoperatively. Significance was accepted at P < 0.005 in order to take into account the multiple number of comparisons performed. Patient medication was compared pre- and postoperatively and the morbidity associated with surgery was also recorded. The most significant improvement postoperatively was the diminution of 'on' dyskinesias contralaterally (67%, P = 0.0001); however, ipsilateral (45%, P = 0.0006) and axial (50%, P = 0.0008) dyskinesias also improved. Contralateral to pallidotomy, the median 'off' motor UPDRS score improved by 27% (P = 0.001) and a significant improvement was also observed in contralateral rigidity by 25% (P = 0.001). There were trends towards improvement in contralateral tremor (33%, P = 0.016) and bradykinesia (24%, P = 0.013) scores. Ipsilateral rigidity improved by 22% (P = 0.005), but other ipsilateral motor scores did not alter significantly. The 'off' gait/postural instability score and 'off' walking time showed marginally significant improvements by 7% (P = 0.007) and 29% (P = 0.014), respectively. On medication, no significant postoperative improvements in parkinsonism were detected. Anti-parkinsonian medication increased by 11% postoperatively. In the subgroup who were available for assessment 1 year postoperatively, responses were generally maintained. Two (7.7%) of the 26 patients had fatal complications (one cerebral haemorrhage and one haemorrhagic infarct) directly related to surgery. Among the remaining 24 patients, four (15.4% of the total 26) had major complications (two persisting and two transient). Ten patients (38.5%) had minor complications. The majority of the complications (major and minor) occurred in the earlier operated patients and the complication rate subsequently declined with increasing operative experience. The remaining 10 patients (38.5%) had no significant side-effects. One of these 10 patients died from an incidental malignant glioma 6 months postoperatively. These findings confirm that levodopa-induced dyskinesias are dramatically reduced following ventral medial pallidotomy and constitute the principal indication for pallidotomy. Improvements in underlying parkinsonism were of smaller magnitude. Pallidotomy may also offer some patients an opportunity to increase antiparkinsonian medication. Patient selection for medial pallidotomy should, therefore, be based largely on anticipated improvements in levodopa-induced dyskinesias, but this must be balanced against the associated morbidity and mortality.

Usefulness of pallidotomy in advanced Parkinson's disease.

OBJECTIVE: The combined effect of posteroventral pallidotomy and optimal medical treatment was assessed in 22 patients with levodopa sensitive Parkinson's disease. METHODS: Timed motor tests, video recordings, and computer assisted...