Hand coordination as a quantitative measure of motor abnormality and therapeutic response in Parkinson's disease.

OBJECTIVE: The precision grip-and-lift task (PGLT) has been used to measure hand motor coordination in PD. We designed this study to investigate if the PGLT outcome variables correlate with the UPDRS motor scores and if all PGLT outcome variables are "responsive" to levodopa. METHODS: We used PGLT to assess hand motor coordination in 10 PD and 10 normal controls before and after levodopa. RESULTS: Factor analysis showed that the six PGLT parameters were reduced to two factors, a levodopa-responsive factor and a dopa-resistant factor that explained 74% of the total variance. The levodopa-responsive factor, which correlated significantly with "off" UPDRS motor scores, includes load preparation time, maximum vertical acceleration, maximum grip velocity and maximum grip force. The levodopa-resistant factor, which did not correlate with "off" UPDRS motor scores, included maximum negative load force and tremor during lift. Both dopa-responsive and dopa-resistant factors were altered in PD compared to controls before levodopa. Levodopa improved dopa-responsive, but not dopa-resistant factor in PD. CONCLUSIONS: PGLT can measure two aspects of fine motor performance, both affected by PD but differentially affected by levodopa. SIGNIFICANCE: PGLT can be useful in characterizing the response of motor abnormality in PD therapeutic trials.     

Rest tremor suppression may separate essential from parkinsonian rest tremor

Rest tremor at 4–6 Hz is typical for classical rest tremor (PT) of Parkinson's disease (PD). But rest tremor also appears in other tremor syndromes and may therefore cause a misdiagnosis. In this study we evaluated if suppression of tremor during movement onset is a characteristic feature of Parkinsonian Tremor distinguishing PT from Essential tremor (ET) and if this sign can be reliably diagnosed.Clinically diagnosed patients with PT (n = 44) and ET (n = 22) with rest tremor were included. Video sequences were recorded according to a standardized protocol focusing on the change of tremor amplitude during transition from rest to posture (test 1) or to a target-directed movement (test 2). These videos were assessed for rest tremor suppression by 4 reviewers (2 specialists and 2 residents) blinded to the clinical diagnosis and were compared to the personal assessment of an unblinded movement disorder specialist.Rest tremor suppression was found in 39/44 PD patients and in 2/22 patients with ET during the personal assessment. Rest tremor suppression showed a high sensitivity (0.92–1.00) and an acceptable specificity (0.69–0.95) for PD tremor in both tests. The interrater-reliability of the video-sequences was good to very good (κ 0.73–0.91). Less than 3% of the video sequences were misclassified.We conclude that the assessment of the suppression of rest tremor during movement initiation is a simple and reliable tool to separate PT from rest tremor in ET also suggesting that the mechanisms of rest tremor in these two diseases are different.     

Clinical correlates of action tremor in Parkinson disease

BACKGROUND: Action tremor is often noted in patients with Parkinson disease (PD), yet the clinical correlates of this type of tremor have been the focus of few studies. It is not clear whether this action tremor is a manifestation of the underlying basal ganglia disease. OBJECTIVE: To determine whether the severity of action tremor in PD is associated with age, age at disease onset, disease duration, levodopa dose, severity of rest tremor, or other motor (ie, bradykinesia, rigidity) and nonmotor manifestations of PD. METHODS: Patients with PD (N = 197) were ascertained as part of a familial aggregation study. All patients underwent a neurological examination. Rest tremor was rated with the Unified Parkinson Disease Rating Scale; and action tremor, with the Washington Heights-Inwood Genetic Study of Essential Tremor Rating Scale. RESULTS: Action tremor was present in 184 (93.4%) of 197 patients. Four patients (2%) met criteria for definite essential tremor. The action tremor score was not associated with age, age at onset, or disease duration. The action tremor score was associated with the rest tremor score (r = 0.37; P<.001), and more strongly with the ipsilateral than contralateral rest tremor score. The association between the action tremor score and the rest tremor score was diminished but still significant (r = 0.21, P<.02) even when we excluded these 63 patients with re-emergent tremor. Neither the action nor the rest tremor score was associated with the bradykinesia or rigidity scores, Hoehn and Yahr scale score, or modified Mini-Mental State Examination score. CONCLUSIONS: Action tremor was associated with rest tremor in PD, suggesting that, at least in part, action tremor is a manifestation of the underlying basal ganglia disease. Neither tremor was associated with other motor and nonmotor manifestations of PD. This in turn suggests that tremor in PD may represent an underlying pathophysiological process different from these other manifestations.     

Levodopa response in dementia with lewy bodies: A 1-year follow-up study

PurposeTo evaluate levodopa responsiveness in patients with probable dementia with Lewy bodies (DLB) compared to early Parkinson’s disease (PD) patients.MethodsTwenty four cases with DLB and 21 with PD underwent a baseline assessment with UPDRS (sub-item II and III) and an acute levodopa challenge test. Positive response to acute levodopa test was defined as an improvement of at least 15% in the tapping test, and at least 25% in the walking test and rigidity or tremor score. Subsequently, all patients were treated continuously with levodopa and evaluated after 6 and 12 months by means of UPDRS II/III.ResultsPositive response to the acute levodopa test was observed in 55% of DLB patients (acute DLB responders), and in 90% of PD patients (acute PD responders). Acute DLB responders showed increased latency, and reduction of both duration and amplitude of response to acute levodopa in comparison with acute PD responders. At the 6-month follow-up visit, acute DLB responders showed a greater motor benefit compared with acute DLB non-responders. This improvement was similar to that observed in PD patients. However, at 1-year follow-up acute DLB responders showed a faster worsening of UPDRS III scores compared with acute PD responders, implying a reduction of levodopa efficacy.ConclusionsPositive response to acute levodopa test can occur in DLB patients and may be predictive of long-term benefit of chronic levodopa therapy, although the motor improvement is less impressive than in PD patients.     

Synchronous pattern distinguishes resting tremor associated with essential tremor from rest tremor of Parkinson's disease

Rest tremor associated with essential tremor (ET) is a condition that poses challenges in diagnosing Parkinson's disease (PD). We investigated tremor parameters in PD and ET patients with rest tremor. Fifteen patients with PD and 15 patients with ET underwent electrophysiological examination to evaluate characteristics of muscle bursting in rest postures. Rest tremor amplitude of PD patients was significantly higher than that of patients with ET (p = 0.002), whereas burst duration and frequency were significantly higher in ET than in PD group (p = 0.002, p < 0.001, respectively). Patients with PD, however, showed some overlap of these electrophysiological values with values from patients with ET. By contrast, rest tremor pattern showed no overlap between the two diseases, because all patients with ET presented a synchronous pattern whereas PD patients had an alternating pattern (p < 0.001), a finding that differentiated the patients on an individual basis. The electromyographic pattern of rest tremor may help to differentiate PD from ET.     

Parkinsonism in multiple system atrophy: natural history, severity (UPDRS-III), and disability assessment compared with Parkinson's disease.

We analyzed parkinsonian features in multiple system atrophy (MSA) compared with age- and disease duration-matched Parkinson's disease (PD) patients, and assessed the applicability of the Unified Parkinson's Disease Rating Scale (UPDRS) -III motor scale as a means of rating their severity. Cross-sectional analysis of parkinsonism was done using UPDRS-III, International Cerebellar Atatia Rating Scale, and disability scales (Hoehn and Yahr [H&A], Schwab and England, Katz and Lawton) in 50 unselected MSA patients and in 50 matched PD patients. At symptom onset, falls occurred 10 times more frequently in MSA, whereas limb tremor was 10 times more common in PD. At first visit (10.2 months), hemiparkinsonism and pill-rolling rest tremor were less common in MSA. Hypomimia, atypical rest, postural or action tremor, as well as postural instability were more frequent in MSA. At study examination (62.4 months), parkinsonian signs in MSA patients were more frequently symmetrical and associated with axial rigidity, antecollis and postural instability. A levodopa response of >50% was seen in <10% of MSA patients. Modified H&Y stages (3.2 +/- 1.3 vs. 2.2 +/- 0.78) and UPDRS-III scores (48.14 +/- 19.5 vs. 31.74 +/- 12.9) were significantly (P = 0.0001) higher in MSA. The internal consistency of the UPDRS-III was fair in MSA patients (Cronbach's alpha >0.90), and correlated well with marked dependency on the Schwab and England and Katz and Lawton scales. Factor structure analysis of UPDRS-III in MSA showed five clinically distinct subscores accounting for 74% of the variance, differing from PD by the dependency of the face-speech and limb bradykinesia items and independence of the postural-action tremor from the rest tremor items. There was a significant correlation (R(2) = 0.70, P = 0.001) between ICARS ataxia and UPDRS-III scores in MSA patients. Results confirm a distinct profile of parkinsonism in MSA and greater severity and disability compared with PD. It also indicates that the UPDRS-III provides a useful severity measure of parkinsonism in MSA, albeit contaminated by additional cerebellar dysfunction.     

Ropinirole for the treatment of tremor in early Parkinson's disease.

The effect of Ropinirole on tremor in early Parkinson's disease (PD) was assessed. The results of three multicentre, randomized, double-blind trials comparing ropinirole monotherapy with levodopa, bromocriptine and placebo treatment were analysed retrospectively with respect to improvement of resting tremor and postural/action tremor as measured by items 20 and 21 of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). Improvements in resting tremor were significantly better with ropinirole than placebo. There were no significant differences between the effect of ropinirole and those of levodopa (L-dopa) or bromocriptine on resting tremor. Postural/action tremor was mild in these early therapy studies, and there were no significant differences between treatment groups. These results suggest that ropinirole monotherapy is effective in treating resting tremor in early PD. On the other hand, response of postural/action tremor to dopaminergic treatment in early PD was not significantly better than to placebo at the dosages used in these trials.     

伴有快动眼睡眠行为障碍帕金森患者的震颤特征及多巴反应性

目的研究伴与不伴快动眼睡眠行为障碍(rapid eye movement sleep behavior disorder,RBD)的帕金森病(Parkinson disease,PD)患者的震颤特征及多巴反应性。方法根据2014年国际睡眠障碍分类第三版RBD的临床最低诊断标准,本研究采用RBD筛查问卷(RBD screening questionnaire,RBDSQ)量表来诊断临床很可能RBD(clinically probable RBD,cpRBD),将PD患者分为伴有cpRBD的PD(PD+cpRBD)与不伴有cpRBD的PD(PD-cpRBD)两组。对入组患者进行一般资料的收集,采用修订的H-Y分级、统一帕金森评分量表3.0版运动检查部分(UPDRS-Ⅲ)、MDS-UPDRS震颤量表对患者的运动功能进行评估,并且分别对两组患者首发侧肢体姿势性震颤、动作性震颤及静止性震颤的幅度进行评分,比较两组患者一般资料及震颤特征的差异性。对所有患者行急性左旋多巴冲击试验,将两组患者UPDRS-Ⅲ及MDS-UPDRS震颤量表评分最大改善率进行比较。结果共纳入42例伴有震颤的PD患者,PD+cpRBD组19例,PD-cpRBD组共23例,两组患者在性别、年龄、发病年龄、病程、关期UPDRS-Ⅲ评分及H-Y分级方面均无明显差异(P0.05)。与PD-cpRBD组相比,PD+cpRBD组关期震颤评分明显增高(t=2.379,P=0.022),震颤症状由首发侧肢体进展至对侧肢体的时间短(u=-2.133,P=0.033),首发侧肢体静止性震颤幅度大(u=-2.956,P=0.003),动作性震颤幅度大(u=-2.657,P=0.008)。口服左旋多巴/苄丝肼(200/50 mg)后,PD-cpRBD组的UPDRS-Ⅲ及震颤评分最大改善率均明显高于PD+cpRBD组(UPDRS-Ⅲ最大改善率u=-3.134,P=0.002;震颤评分最大改善率t=-3.189,P=0.003)。结论本研究表明,伴有cpRBD的PD患者震颤程度相对较重,以静止性震颤和动作性震颤为主,由首发侧肢体进展至对侧肢体的时间相对较短,对左旋多巴的反应性较差。     

Clinically deployable Kinesia™ technology for automated tremor assessment

The objective was to design, build, and assess Kinesia?, a wireless system for automated assessment of Parkinson's disease (PD) tremor. The current standard in evaluating PD is the Unified Parkinson's Disease Rating Scale (UPDRS), a qualitative ranking system typically completed during an office visit. Kinesia integrates accelerometers and gyroscopes in a compact patient‐worn unit to capture kinematic movement disorder features. Objectively quantifying PD manifestations with increased time resolution should aid in evaluating efficacy of treatment protocols and improve patient management. In this study, PD subjects performed the tremor subset of the UPDRS motor section while wearing Kinesia. Quantitative kinematic features were processed and highly correlated to clinician scores for rest tremor (r² = 0.89), postural tremor (r² = 0.90), and kinetic tremor (r² = 0.69). The quantitative features were used to develop a mathematical model that predicted tremor severity scores for new data with low errors. Finally, PD subjects indicated high clinical acceptance. © 2009 Movement Disorder Society     

Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation

OBJECTIVE: To assess the effects of high frequency stimulation of the subthalamic nucleus (STN) on axial symptoms occurring in advanced stages of Parkinson's disease (PD). METHODS: The efficacy of STN stimulation on total motor disability score (unified Parkinson's disease rating scale (UPDRS) part III) were evaluated in 10 patients with severe Parkinson's disease. The subscores were then studied separately for limb akinesia, rigidity, and tremor, which are known to respond to levodopa, and axial signs, including speech, neck rigidity, rising from a chair, posture, gait, and postural stability, which are known to respond less well to levodopa. Patients were clinically assessed in the "off" and "on" drug condition during a levodopa challenge test performed before surgical implantation of stimulation electrodes and repeated 6 months after surgery under continuous STN stimulation. A complementary score for axial symptoms from the "activities of daily living" (ADL)-that is, speech, swallowing, turning in bed, falling, walking, and freezing-was obtained from each patient's questionnaire (UPDRS, part II). RESULTS: Improvements in total motor disability score (62%), limb signs (62%), and axial signs (72%) obtained with STN stimulation were statistically comparable with those obtained with levodopa during the preoperative challenge (68%, 69%, and 59%, respectively). When levodopa and STN stimulation were combined there was a further improvement in total motor disability (80%) compared with preoperative levodopa administration. This consisted largely of an additional improvement in axial signs (84%) mainly for posture and postural stability, no further improvement in levodopa responsive signs being found. Axial symptoms from the ADL showed similar additional improvement when levodopa and STN stimulation were combined. CONCLUSION: These findings suggest that bilateral STN stimulation improves most axial features of Parkinson's disease and that a synergistic effect can be obtained when stimulation is used in conjunction with levodopa treatment.     

Fast orthostatic tremor in Parkinson's disease mimicking primary orthostatic tremor.

Leg tremor during standing is a rare feature in idiopathic Parkinson's disease (PD). Tremor during standing usually has a low frequency (range, 4-6 Hz), similar to PD rest tremor frequency, and is improved by levodopa. We describe three cases of fast orthostatic tremor (FoT) of legs and trunk mimicking primary orthostatic tremor (OT) in patients treated with levodopa for PD. Asymmetrical akinetorigid syndrome was accompanied by a rest tremor in two cases. We obtained electrophysiological parameters by electromyographic (EMG) polygraphic recording after 16 hours withdrawal of antiparkinsonian treatment and at the maximal effect of levodopa in order to investigate the effect of dopaminergic stimulation upon such cases of orthostatic tremor in PD. Electrophysiological parameters of orthostatic tremor, especially frequency (range 14-18 Hz), were similar to that seen in POT. Severity of tremor was independent of seriousness and duration of PD. Levodopa had no effect either on the handicap due to OT or on the amplitude and frequency of the EMG OT activity. In contrast, mild improvement of OT was obtained with benzodiazepines in two cases and parkinsonian syndrome was levodopa-sensitive. These findings suggest that FoT in PD would not be directly controlled by the dopaminergic system. However, increased rhythmicities in basal ganglia or in cerebello-thalamic loops at the rapid frequencies range seen in PD could favor the emergence of a primary orthostatic tremor-like tremor in PD patients.     

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.     

Levodopa affects functional brain networks in parkinsonian resting tremor

Resting tremor in idiopathic Parkinson's disease (PD) is associated with an oscillatory network comprising cortical as well as subcortical brain areas. To shed light on the effect of levodopa on these network interactions, we investigated 10 patients with tremor‐dominant PD and reanalyzed data in 11 healthy volunteers mimicking PD resting tremor. To this end, we recorded surface electromyograms of forearm muscles and neuromagnetic activity using a 122‐channel whole‐head magnetometer (MEG). Measurements were performed after overnight withdrawal of levodopa (OFF) and 30 min after oral application of fast‐acting levodopa (ON). During OFF, patients showed the typical antagonistic resting tremor. Using the analysis tool Dynamic Imaging of Coherent Sources, we identified the oscillatory network associated with tremor comprising contralateral primary sensorimotor cortex (S1/M1), supplementary motor area (SMA), contralateral premotor cortex (PMC), thalamus, secondary somatosensory cortex (S2), posterior parietal cortex (PPC), and ipsilateral cerebellum oscillating at 8 to 10 Hz. After intake of levodopa, we found a significant decrease of cerebro‐cerebral coupling between thalamus and motor cortical areas. Similarly, in healthy controls mimicking resting tremor, we found a significant decrease of functional interaction within a thalamus–premotor–motor network during rest. However, in patients with PD, decrease of functional interaction between thalamus and PMC was significantly stronger when compared with healthy controls. These data support the hypothesis that (1) in patients with PD the basal ganglia and motor cortical structures become more closely entrained and (2) levodopa is associated with normalization of the functional interaction between thalamus and motor cortical areas. © 2008 Movement Disorder Society     

Gender differences in patients with Parkinson's disease treated with subthalamic deep brain stimulation.

We investigated gender-differences in clinical phenomenology and response to deep brain stimulation (DBS) of the subthalamic nucleus (STN) in a group of patients with advanced Parkinson's disease (PD). Thirty-eight consecutive patients with PD (22 men and 16 women), bilaterally implanted for DBS of the STN, were evaluated 1 month before and 11 to 14 months after surgery. Gender differences in severity of the disease (HY and UPDRS), ability in the activities of daily living (ADL, UPDRS II), tremor and rigidity (UPDRS III), bradykinesia (UPDRS III and hand tapping test), levodopa-induced dyskinesias (LIDs, UPDRS IV), and levodopa equivalent daily dosage (LEDD) were analyzed before and after intervention. We found a predominantly male population, with no gender-related differences in age at onset, disease progression rate, or severity of disease. Nevertheless, women had more severe LIDs than men, only before the intervention. Bradykinesia was significantly less responsive to any kind of treatment (pharmacologic and neurosurgical) in women than in men. Finally, although STN-DBS induced similar total benefits in both genders, postoperative assessment suggested that the ADL improved more in women than in men. Women and men with advanced PD appear to differ in some clinical features and in response to dopaminergic and STN-DBS treatment.     

Factor structure of parkinsonian signs in the community-dwelling elderly.

Parkinsonian signs are present in 40% of older people. Factor analysis of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease (PD) has identified several principal domains, including rigidity, axial function, and rest tremor. We hypothesized that if Parkinsonian signs in the elderly were due to basal ganglia dysfunction that this same constellation of factors (rigidity, axial function, rest tremor) would emerge in a factor analysis. We carried out factor analysis, using the principal component method with orthogonal (varimax) rotation, on motor UPDRS scores in community-dwelling elderly without PD. A modified (10-item) version of the motor portion of the UPDRS was administered to 1,339 older adults living in the Washington Heights-Inwood community and it was found that Parkinsonian signs were present in 537 (40.1%). Three factors (rigidity, axial function. and rest tremor) were obtained from the factor analysis and, together, explained 67.4% of the variance. A second factor analysis was carried out excluding the 26 participants with rest tremor, and two factors (rigidity, axial function) emerged. These data support the view that Parkinsonian signs in older adults might be due to basal ganglia dysfunction, a possibility that requires further exploration.     

Diagnosing Parkinson's disease using videotaped neurological examinations: validity and factors that contribute to incorrect diagnoses.

Field work is commonly required in movement disorders research. Sending neurologists into the field can be logistically challenging and costly. Alternatively, neurological examinations may be videotaped and reviewed later. There is little knowledge of the validity of the videotaped neurological examination in the diagnosis of Parkinson's disease (PD). We examined the validity of the videotaped Unified Parkinson's Disease Rating Scale (UPDRS) motor examination in the diagnosis of PD, and sought to determine which factors are associated with incorrect diagnoses. PD patients and controls were enrolled in a familial aggregation study between August of 1998 and June of 2000, and as part of that study each was examined by a physician who performed an in-person UPDRS motor examination. Each also underwent a second, videotaped UPDRS motor examination. Based on the review of this videotape, a neurologist, who was blinded to the previous clinical diagnosis, assigned a diagnosis of PD or normal. A total of 211 of 231 PD patients (sensitivity = 91.3%), and 170 of 172 controls (specificity = 98.8%) were correctly identified based on the videotape. True positives had a higher mean rest tremor score (1.7 vs. 0.3; P < 0.001), action tremor score (0.9 vs. 0.3; P < 0.001), bradykinesia score (11.2 vs. 7.4; P = 0.02), and disease of longer mean duration (8.9 vs. 5.8 years; P = 0.001) than false negatives. False negatives did not differ from true positives in terms of age, total dose of levodopa, Hoehn and Yahr score, or rigidity, gait and posture, or facial masking scores (each assessed during the in-person examination). The videotaped UPDRS motor examination is a useful means of diagnosing PD and provides an alternative approach for the diagnosis of PD in field studies. A limitation is that patients with milder PD of shorter duration may not be recognized as PD.     

Replacement of dopaminergic medication with subthalamic nucleus stimulation in Parkinson's disease: Long‐term observation

Stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD), but the medication requirements after implant are poorly known. We performed a long‐term prospective evaluation of 20 patients maintained at stable dopaminergic therapy for 5 years after bilateral STN implants, who were evaluated 6 months, 1 year, 3 years, and 5 years after surgery. We measured, during the entire observation period, the effect of deep brain stimulation on motor and functional outcome measures, the levodopa equivalent daily dose and the total electrical energy delivered. At 5 years, the UPDRS motor score had improved by 54.2% and levodopa equivalent dose was reduced by 61.9%, compared with preimplant. Dopaminergic medication remained stable during the observation period, but energy was progressively increased over time. Rest tremor, rigidity, gait, lower and upper limb akinesia, and total axial score were improved in decreasing order. Postural stability and speech improved transiently, whereas on‐period freezing of gait, motor fluctuations and dyskinesias recovered durably. Functional measures did not show improvement in autonomy and daily living activities after STN implant. Chronic STN stimulation allows to replace for dopaminergic medications in the long‐term at the expense of an increase of the total energy delivered. This is associated with marked improvement of motor features without a matching benefit in functional measures. © 2008 Movement Disorder Society     

Can subthalamic nucleus stimulation reveal parkinsonian rest tremor?

INTRODUCTION: Rest tremor, one of the main symptoms in Parkinson's disease (PD), is dramatically improved following subthalamic nucleus stimulation (STN). Results are often better than after l-dopa treatment. The occurrence of rest tremor after neurosurgery in patients without preoperative tremor is uncommon. AIM: The aim of this work was to investigate the role of subthalamic nucleus stimulation in the appearance of parkinsonian rest tremor. PATIENTS-RESULTS: Thirty PD patients (14%) out of 215 undergoing STN deep brain stimulation had an akinetorigid form of the disease, without preoperative tremor 11 years after onset of the disease. Six of them experienced the appearance of tremor six months after bilateral STN stimulation when the stimulator was switched off in the Off medication state. This de novo parkinsonian tremor was improved by l-dopa treatment and disappeared when the stimulator was turned on. CONCLUSION: This finding suggests that infraclinical parkinsonian tremor is probably present in all PD patients.     

Chronic bilateral pallidal stimulation and levodopa do not improve gait in the same way in Parkinson's disease: a study using a video motion analysis system

Chronic bilateral internal globus pallidus (GPi) stimulation allows control of levodopa induced dyskinesias (LID) and motor symptoms in severe Parkinson's disease (PD). The effect on gait has not been clearly established. Different results have been reported, mostly consisting of clinical data. The aim of this study was to evaluate, by means of a video motion analysis system (optoelectronic VICON system), the influence of bilateral GPi stimulation on gait in PD. Five patients underwent bilateral GPi stimulation. The preoperative and postoperative (3 months after surgery) clinical gait disturbances (items 29 and 30 of the motor UPDRS), as well as spatial and temporal gait measurements (namely cadence, velocity, stride and step times, single and double limb support times, stride and step lengths) were analysed in off condition (the patient had received no treatment for 12 hours or merely the lowest dose of levodopa allowing him to walk for the gait analysis) and in the on drug condition (after administration of 200 mg of levodopa). The gait analysis was performed with the VICON system. In off condition, there was a statistically significant improvement after surgery for UPDRS III and gait (clinically assessed). In on drug condition, there was a significant improvement for LID whereas UPDRS III and clinical assessment of gait were unchanged. The VICON system also showed that surgery improved gait especially in off condition, but also in on drug condition. Our method allowed exact quantification of the influence of surgery on gait characteristics. As compared with levodopa treatment, the effect of stimulation seems to be different. Indeed, the results suggest only limited effects of pallidal stimulation on the control of stride length and rather point to compensatory additional mechanisms. Received: 15 August 2000, Received in revised form: 1 February 2001, Accepted: 10 April 2001     

Motor changes during sertraline treatment in depressed patients with Parkinson’s disease*

Background: Pharmacological interventions to treat depressive symptoms associated with Parkinson’s disease (PD) are limited. Whether selective serotonine re‐uptake inhibitors increase parkinsonism or have clinically significant interactions with antiparkinsonian drugs is unresolved. Purpose: We used a naturalistic approach to prospectively investigate the long‐term effects on motor status of adding sertraline in a large sample of community‐dwelling PD patients with depressive symptoms. Methods: Main outcome measure was the motor part of the Unified PD Rating Scale (UPDRS) at baseline and at 1‐, 3‐, and 6‐month follow‐up. Secondary measures were the change in antiparkinsonian drugs expressed as total levodopa equivalent dose and the scores of the Hospital Anxiety and Depression Scale (HADS). Of the 374 patients included, 310 (82%) completed the study. Results: Treatment with sertraline (mean dose 66.0 ± 29.8 mg) resulted in improvement in all UPDRS domains along with a significant decrease of the HADS scores. A modest but significant increase of the total dose of levodopa, without significant change of total levodopa equivalent dose, was observed. Almost 8% of patients discontinued medication for adverse events, mainly related to the gastrointestinal system. Conclusions: Although worsening of tremor was observed in some patients, active management of depression with sertraline appears to have a positive impact on parkinsonism.