[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: Surveys of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) have shown that this procedure is roughly twice more common in men than in women. Here, we investigate possible differences between women and men undergoing STN DBS, with respect to health-related quality of life. MATERIALS AND METHODS: Forty-nine consecutive patients (18 women) received STN DBS. The impact of PD and its surgical treatment was compared between women and men, before and at mean of 19 ± 11 months after surgery, using the Unified Parkinson Disease Rating Scale (UPDRS) and the Parkinson's Disease Questionnaire-39 (PDQ-39). RESULTS: Duration of disease at surgery and off-medication scores of the motor part of the UPDRS were similar in women and men. At baseline, women had lower doses of dopaminergic medication than men, experienced more disability due to dyskinesias, had more sensory symptoms and perceived more difficulties in mobility. Following DBS, both men and women showed equal and significant (P < 0.001) improvement in off-medication scores on the UPDRS III. On the PDQ-39, women expressed improvement in ADL to a greater extent than men. Moreover, women but not men showed a positive effect on mobility, stigma and cognition as well as on the summary score of PDQ-39. CONCLUSIONS: Although STN DBS results in equal degree of motor improvement between women and men, health-related quality of life seems to improve to a greater extent in women.
[Show abstract][Hide abstract] ABSTRACT: Treatment options in advanced Parkinson's disease (PD) include subcutaneous apomorphine, pallidal or subthalamic nucleus Deep Brain Stimulation (DBS), or levodopa/carbidopa intestinal gel (LCIG/Duodopa). In this study, we describe the outcome of 12 PD patients with PD related complications started on LCIG, with respect to their quality of life measured by a disease specific validated scale-the PDQ39, together with diaries recording time spent "On," "Off," "Dyskinetic," or "Asleep." At the time of latest follow up, improvements were observed in both the PDQ39 Summary index as well as diary reports of PD symptom control following introduction of LCIG, supporting its use in well selected patients. The use of a trial period of LCIG via naso-jejunal administration allows objective evaluation of improvement in PD symptom control in advance of the placement of the more invasive percutaneous jejunostomy procedure. The decision to embark on LCIG, apomorphine or DBS should be supported by input from centres with experience of all 3 approaches. Since LCIG is an expensive option, development of the most appropriate future commissioning of this therapy in the absence of Class 1 evidence requires careful scrutiny of the outcomes of its use in a broad range of published series.
[Show abstract][Hide abstract] ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinson's disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology and Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording. Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6) mm. There were no haemorrhagic complications. At a median follow-up period of 12 months, there was a mean improvement in the off-medication motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition, there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre-operatively, to 1.56 (SD 1.92) post-operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinson's disease Questionnaire 39 summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity.
Journal of neurology, neurosurgery, and psychiatry 04/2011; 82(4):358-63. · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with Parkinson's disease (PwPD) have a slow, shuffling gait, marked by sporadic freezing of gait (FoG) during which effective stepping ceases temporarily. As these gait problems are not commonly improved by medical and surgical treatments, alternative approaches to manage these problems have been adopted. The aim of this study was to evaluate the effect of real and virtual visual cues on walking in PD. We assessed 26 mid-stage PwPD, on and off medication, on a laboratory-based walking task which simulated real world challenges by incorporating FoG triggers and using appropriate placebo conditions. Cueing interventions were presented via virtual reality glasses (VRG rhythmic, visual flow and static placebo cues), and as transverse lines (TL) on the walkway. Objective measures of gait (task completion time; velocity, cadence, stride length; FoG frequency) and self-rated fear of falling (FoF) were recorded. Cueing intervention affected task completion time only off medication. Whereas placebo VRG cues provided no improvement in walking, visual flow VRG cues marginally reduced the task completion time. TL on the floor elicited more substantial improvements in gait with reduced cadence, increased stride length and reduced FoG frequency. VRG rhythmic cueing impaired overall walking. Notably, a final no-intervention condition yielded quicker task completion, greater walking velocity, increased stride length and less frequent FoG. Although the VRG produced modest improvements only in the visual flow condition, their flexibility is an advantage. These results endorse the use of TL and justify further testing and customisation of VRG cues for individual PwPD.
Journal of Neurology 01/2011; 258(6):991-1000. · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The local strength of pathological synchronization in the region of the subthalamic nucleus (STN) is emerging as a possible factor in the motor impairment of Parkinson's Disease (PD). In particular, correlations have been repeatedly demonstrated between treatment-induced suppressions of local oscillatory activity in the beta frequency band and improvements in motor performance. However, a mechanistic role for beta activity is brought into question by the difficulty in showing a correlation between such activity at rest and the motor deficit in patients withdrawn from medication. Here we recorded local field potential (LFP) activity from 36 subthalamic regions in 18 patients undergoing functional neurosurgery for the treatment of PD. We recorded directly from the contacts of the deep brain stimulation (DBS) electrodes as they were introduced in successive 2 mm steps, and assessed phase coherence as a measure of spatially extended, rather than local, oscillatory synchronization. We found that phase coherence in the beta frequency band correlated with the severity of Parkinsonian bradykinesia and rigidity, both in the limbs and axial body. Such correlations were frequency and site specific in so far as they were reduced when the lowermost contact of the DBS electrode was above the dorsal STN. Correlations with limb tremor occurred at sub-beta band frequencies and were more lateralized than those between beta activity and limb bradykinesia and rigidity. Phase coherence could account for up to ∼25% of the variance in motor scores between sides and patients. These new data suggest that the strength of spatially extended oscillatory synchronization, as well as the strength of local synchronization, may be worthwhile incorporating into modelling studies designed to inform surgical targeting, post-operative stimulation parameter selection and closed-loop stimulation regimes in PD. In addition, they strengthen the link between pathological synchronization and the different motor features of Parkinsonism.
[Show abstract][Hide abstract] ABSTRACT: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limiting its beneficial effect. Here we prospectively examined the short- and long-term speech response to STN-DBS in a consecutive series of patients to identify clinical and surgical factors associated with speech change.
Thirty-two consecutive patients were assessed before surgery, then 1 month, 6 months, and 1 year after STN-DBS in 4 conditions on- and off-medication with on- and off-stimulation using established and validated speech and movement scales. Fifteen of these patients were followed up for 3 years. A control group of 12 patients with PD were followed up for 1 year.
Within the surgical group, speech intelligibility significantly deteriorated by an average of 14.2%±20.15% off-medication and 16.9%±21.8% on-medication 1 year after STN-DBS. The medical group deteriorated by 3.6%±5.5% and 4.5%±8.8%, respectively. Seven patients showed speech amelioration after surgery. Loudness increased significantly in all tasks with stimulation. A less severe preoperative on-medication motor score was associated with a more favorable speech response to STN-DBS after 1 year. Medially located electrodes on the left STN were associated with a significantly higher risk of speech deterioration than electrodes within the nucleus. There was a strong relationship between high voltage in the left electrode and poor speech outcome at 1 year.
The effect of STN-DBS on speech is variable and multifactorial, with most patients exhibiting decline of speech intelligibility. Both medical and surgical issues contribute to deterioration of speech in STN-DBS patients. Classification of evidence: This study provides Class III evidence that STN-DBS for PD results in deterioration in speech intelligibility in all combinations of medication and stimulation states at 1 month, 6 months, and 1 year compared to baseline and to control subjects treated with best medical therapy.
[Show abstract][Hide abstract] ABSTRACT: Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale-Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale-Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2-6 and 9-15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2-6 months and 25.7% at 9-15 months. At 9-15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia, and 31.3% showed an improvement of 20% or more in disability. Global quality of life ratings showed a median improvement of 83.3% at 9-15 months. Severity of dystonia preoperatively and disease duration predicted improvement in severity of dystonia at 2-6 months; this failed to reach significance at 9-15 months. The study confirms that dystonia in neurodegeneration with brain iron accumulation improves with bilateral pallidal deep brain stimulation, although this improvement is not as great as the benefit reported in patients with primary generalized dystonias or some other secondary dystonias. The patients with more severe dystonia seem to benefit more. A well-controlled, multi-centre prospective study is necessary to enable evidence-based therapeutic decisions and better predict therapeutic outcomes.
[Show abstract][Hide abstract] ABSTRACT: It is unclear how subthalamic nucleus activity is modulated by the cerebral cortex. Here we investigate the effect of transcranial magnetic stimulation (TMS) of the cortex on oscillatory subthalamic local field potential activity in the 8-35 Hz (alpha/beta) band, as exaggerated synchronization in this band is implicated in the pathophysiology of parkinsonism. We studied nine patients with Parkinson's disease (PD) to test whether cortical stimulation can modulate synchronized oscillations in the human subthalamic nucleus. With patients at rest, single-pulse TMS was delivered every 5 s over each primary motor area and supplementary motor area at intensities of 85-115% resting motor threshold. Subthalamic local field potentials were recorded from deep brain stimulation electrodes implanted into this nucleus for the treatment of PD. Motor cortical stimulation suppressed beta activity in the subthalamic nucleus from approximately 0.2 to 0.6 s after TMS (repeated measures anova; main effect of time, P < 0.01; main effect of side, P = 0.03), regardless of intensity. TMS over the supplementary motor area also reduced subthalamic beta activity at 95% (P = 0.05) and 115% resting motor threshold (P = 0.01). The oscillatory activity decreased to 80 +/- 26% of baseline (averaged across sites and stimulation intensities). Suppression with subthreshold stimuli confirmed that these changes were centrally driven and not due to peripheral afference. The results may have implications for mechanisms underlying the reported therapeutic benefits of cortical stimulation.
European Journal of Neuroscience 10/2008; 28(8):1686-95. · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the effect of electrode contact location on efficacy of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for primary generalised dystonia (PGD). Subjects and
A consecutive series of 15 patients with PGD (10 females, mean age 42 years, seven DYT1) who underwent bilateral GPi DBS, were assessed using the Burke-Fahn-Marsden (BFM) dystonia scale before and 6 months after surgery. The position of the stimulated electrode contact(s) was determined from the postoperative stereotactic MRI. Contralateral limb and total axial BFM subscores were compared with the location of the stimulated contact(s) within the GPi.
The mean total BFM score decreased from 38.9 preoperatively to 11.9 at 6 months, an improvement of 69.5% (p<0.00001). Cluster analysis of the stimulated contact coordinates identified two groups, distributed along an anterodorsal to posteroventral axis. Clinical improvement was greater for posteroventral than anterodorsal stimulation for the arm (86% vs 52%; p<0.05) and trunk (96% vs 65%; p<0.05) and inversely correlated with the y coordinate. For the leg, posteroventral and anterodorsal stimulation were of equivalent efficacy. Overall clinical improvement was maximal with posteroventral stimulation (89% vs 67%; p<0.05) and inversely correlated with the y (A-P) coordinate (r = -0.62, p<0.05).
GPi DBS is effective for PGD but outcome is dependent on contact location. Posteroventral GPi stimulation provides the best overall effect and is superior for the arm and trunk. These results may be explained by the functional anatomy of GPi and its outflow tracts.
Journal of neurology, neurosurgery, and psychiatry 01/2008; 78(12):1314-9. · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe intermittent or sustained severe involuntary tongue protrusion in patients with a dystonic syndrome. Speech, swallowing, and breathing difficulties can be severe enough to be life threatening. Causes include neuroacanthocytosis, pantothenate kinase-associated neurodegeneration, Lesch-Nyhan syndrome, and postanoxic and tardive dystonia. The pathophysiology of intermittent severe tongue protrusion remains unknown. Tongue protrusion dystonia is often unresponsive to oral drugs but may benefit from botulinum toxin injections into the genioglossus muscle. Bilateral deep brain pallidal stimulation was beneficial in two cases.
[Show abstract][Hide abstract] ABSTRACT: The authors recorded forearm H reflex reciprocal inhibition and clinical outcome in eight patients with primary torsion dystonia before and 1, 3, and 6 months after pallidal deep brain stimulation (DBS). There was progressive increase in reciprocal inhibition after surgery, which correlated with clinical improvement. The authors conclude that pallidal DBS for dystonia results in functional reorganization of the nervous system, which includes a long-term increase in spinal inhibition.
[Show abstract][Hide abstract] ABSTRACT: To determine which thalamic subnuclei are involved in symptomatic unilateral movement disorders due to localized thalamic infarction, and the clinical characteristics of these abnormal movements.
The authors studied 22 patients with thalamic infarcts for their clinical presentation and the topography of the lesions, using three-dimensional T1-weighted MRI sequencing and stereotaxic analysis of the lesions.
Patients were divided into four groups: 1) absence of abnormal involuntary movements (AIM) (nine patients); 2) isolated dystonic posture (two patients); 3) myoclonic dystonia (five patients); and 4) tremor or myoclonus (six patients). In patients with AIM, thalamic lesions were contralateral to the abnormal movements, involving the thalamogeniculate territory, centered on the ventral intermediate (Vim) and ventral caudal (Vc) nuclei. No significant difference in the volumes or center of mass of the lesions was found between patients with tremor and myoclonus and patients with dystonia, although the central nucleus and the internal part of the Vim nucleus were more consistently damaged in dystonic patients.
Movement disorders related to thalamic lesions included: 1) myoclonic dystonia with predominating myoclonus and "thalamic" hand associating dystonic posture and slow, pseudo-athetoid movements, both related to lesions in the Vim and Vc nuclei of the thalamus; and 2) postural and action tremor, also related to lesions in the Vim, similar to tremor associated with midbrain lesions, as a result of abnormal functioning of the cerebello-thalamic pathways.
[Show abstract][Hide abstract] ABSTRACT: Severe dyskinesias or ballism can occur following hemorrhagic events in the subthalamic nucleus (STN), and it has recently been established that the STN plays a major role in the pathophysiology of the motor dysfunction of Parkinson's disease (PD) and that STN inhibition improves parkinsonian dysfunction. Deep brain stimulation of the STN in PD patients is therefore currently being evaluated as a therapy. High-frequency stimulation of the STN in PD patients can induce intense dyskinesias that are similar to those induced by levodopa. These may occur with a variable latency and resemble all types of levodopa-induced dyskinesias (LIDs). They can be decreased by reducing the levodopa dosage, which is permitted by the antiparkinsonian effect of stimulating the STN. STN stimulation has been shown to improve all types of LIDs, with the most dramatic effect being that on off-period dystonia. The improvement in LIDs may relate to the decrease in drug dosage, while the off-period dystonia is likely improved by the simultaneous administration of levodopa and STN stimulation. It is thought that the STN is an important node in a network, which can produce dyskinesias when disturbed by a lesion, and is particularly sensitive for the induction of these abnormal movements.