Background and purpose
Middle‐aged persons living with HIV (PLHIV) have a heightened risk of more concomitant age‐related comorbidities that are acknowledged as signs of poorer prognosis after ...deep‐brain stimulation of the subthalamic nucleus (STN‐DBS) at younger‐than‐expected ages. To assess the beneficial and adverse effects of STN‐DBS in PLHIV with Parkinson's disease (PD).
Methods
We retrospectively included nine PLHIV with PD who had sustained virological control. Patients were followed up for 7 ± 4 years.
Results
Patients’ mean ages at PD onset and STN‐DBS were 45 ± 15 and 53 ± 16 years, respectively. At STN‐DBS, mean HIV infection and PD durations were 15 ± 12 and 8 ± 4 years, respectively. STN‐DBS significantly improved 1‐year Unified Parkinson's Disease Rating Scale (UPDRS)‐III scores (71%), daily off‐time (63%), motor fluctuations (75%) and daily levodopa‐equivalent dose (68%); mean 5‐year UPDRS‐III score and motor fluctuation improvements remained ~45%. Impulse control disorders (affecting 6/9 patients) fully resolved after STN‐DBS. Postoperative course was uneventful. No serious adverse events occurred during follow‐up.
Conclusion
Our findings indicate that STN‐DBS is a safe and effective treatment for PLHIV with PD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Deep brain stimulation (DBS) has considerable efficacy for the motor dysfunction of idiopathic Parkinson's disease (PD) on patient quality of life. However, the benefit of DBS on voice and speech ...quality remains controversial. We carried out a systematic review to understand the influence of DBS on parkinsonian dysphonia and dysarthria.
A PubMed/MEDLINE and Cochrane systematic review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Population, Intervention, Comparison, Outcome, Timing, and Setting (PICOTS) statements.
Three investigators screened studies published in the literature from inception to May 2022. The following data were retrieved: age, demographic, sex, disease duration, DBS duration, DBS location, speech, and voice quality measurements.
From the 180 studies identified, 44 publications met the inclusion criteria, accounting for 866 patients. Twenty-nine studies focused on voice/speech quality in subthalamic DBS patients, and 6 included patients with stimulation of pallidal, thalamic, and zona incerta regions. Most studies (4/6) reported a deterioration of the vocal parameters on subjective voice quality evaluation. For speech, the findings were more contrasted. There was an important heterogeneity between studies regarding the voice and speech quality outcomes used to evaluate the impact of DBS on voice/speech quality.
The impact of DBS on voice and speech quality significantly varies between studies. The stimulated anatomical region may have a significant role since the stimulation of the pallidal area was mainly associated with voice quality improvement, in contrast with other regions. Future controlled studies comparing all region stimulation are needed to get reliable findings.
Level III: evidence from evidence summaries developed from systematic reviews.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary Background Parkinson's disease is typically treated with oral dopamine replacement therapies; however, long-term treatment leads to motor complications and, occasionally, impulse control ...disorders caused by intermittent stimulation of dopamine receptors and off-target effects, respectively. We aimed to assess the safety, tolerability, and efficacy of bilateral, intrastriatal delivery of ProSavin, a lentiviral vector-based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease. Methods We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. All patients were then enrolled in a separate open-label follow-up study of long-term safety. Three doses were assessed in separate cohorts: low dose (1·9×107 transducing units TU); mid dose (4·0×107 TU); and high dose (1×108 TU). Inclusion criteria were age 48–65 years, disease duration 5 years or longer, motor fluctuations, and 50% or higher motor response to oral dopaminergic therapy. The primary endpoints of the phase 1/2 study were the number and severity of adverse events associated with ProSavin and motor responses as assessed with Unified Parkinson's Disease Rating Scale (UPDRS) part III (off medication) scores, at 6 months after vector administration. Both trials are registered at ClinicalTrials.gov , NCT00627588 and NCT01856439. Findings 15 patients received ProSavin and were followed up (three at low dose, six mid dose, six high dose). During the first 12 months of follow-up, 54 drug-related adverse events were reported (51 mild, three moderate). Most common were increased on-medication dyskinesias (20 events, 11 patients) and on–off phenomena (12 events, nine patients). No serious adverse events related to the study drug or surgical procedure were reported. A significant improvement in mean UPDRS part III motor scores off medication was recorded in all patients at 6 months (mean score 38 SD 9 vs 26 8, n=15, p=0·0001) and 12 months (38 vs 27 8; n=15, p=0·0001) compared with baseline. Interpretation ProSavin was safe and well tolerated in patients with advanced Parkinson's disease. Improvement in motor behaviour was observed in all patients. Funding Oxford BioMedica.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Parkinson's disease is typically treated with oral dopamine replacement therapies. However, long-term use is complicated by motor fluctuations from intermittent stimulation of dopamine receptors and ...off-target effects. ProSavin, a lentiviral vector based gene therapy that delivers local and continuous dopamine, was previously shown to be well tolerated in a Phase I/II first-in-human study, with significant improvements in motor behavior from baseline at 1 year. Here, patients with Parkinson's disease from the open-label trial were followed up in the long term to assess the safety and efficacy of ProSavin after bilateral injection into the putamen. Fifteen patients who were previously treated with ProSavin have been followed for up to 5 years, with some having been seen for 8 years. Eight patients received deep brain stimulation at different time points, and their subsequent assessments continued to assess safety. Ninety-six drug-related adverse events were reported (87 mild, 6 moderate, 3 severe) of which more than half occurred in the first year. The most common drug-related events were dyskinesias (33 events, 11 patients) and on-off phenomena (22 events, 11 patients). A significant improvement in the defined "off" Unified Parkinson's Disease Rating Scale part III motor scores, compared to baseline, was seen at 2 years (mean score 29 · 2 vs. 38 · 4, n = 14, p < 0.05) and at 4 years in 8/15 patients. ProSavin continued to be safe and well tolerated in patients with Parkinson's disease. Moderate improvements in motor behavior over baseline continued to be reported in the majority of patients who could still be evaluated up to 5 years of follow-up.
Spinal Stimulation for Movement Disorders Thiriez, Claire; Gurruchaga, Jean-Marc; Goujon, Colette ...
Neurotherapeutics,
07/2014, Volume:
11, Issue:
3
Journal Article
Peer reviewed
Open access
Epidural spinal cord stimulation (SCS) is currently proposed to treat intractable neuropathic pain. Since the 1970s, isolated cases and small cohorts of patients suffering from dystonia, tremor, ...painful leg and moving toes (PLMT), or Parkinson’s disease were also treated with SCS in the context of exploratory clinical studies. Despite the safety profile of SCS observed in these various types of movement disorders, the degree of improvement of abnormal movements following SCS has been heterogeneous among patients and across centers in open-label trials, stressing the need for larger, randomized, double-blind studies. This article provides a comprehensive review of both experimental and clinical studies of SCS application in movement disorders.
Background This study examined changes in motor function and quality of life (QoL) after subthalamic nuclei deep brain stimulation (STN-DBS) in patients with Parkinson disease (PD) and the role of ...psychosocial predictors on individual changes. Methods Forty-one patients with advanced PD (29 men and 12 women; mean age: 62.0 ± 8.0; disease duration: 14.5 ± 5.7) completed self-report questionnaires before surgery and at 6 and 12 months after surgery. Psychosocial measures assessed coping strategies (Ways of Coping Checklist—Revised), symptoms of depression (Beck Depression Inventory version II), anxiety (State-Trait Anxiety Inventory), and QoL (Parkinson Disease Questionnaire 39 Items, Medical Outcomes Study 36-Item Short-Form Health Survey). Results After surgery, motor function (Unified Parkinson Disease Rating Scale III and IV), global QoL (Parkinson Disease Questionnaire 39 Items) and Physical Component Summary of the Medical Outcome Study Short Form 36-items Health Survey improved, whereas the Mental Component Summary tended to deteriorate. Depression and anxiety were stable. Improvements in motor function and QoL were associated with younger age, shorter duration of illness, higher baseline distress (depression and anxiety), and changes in problem-focused coping. Improvements in mental QoL were associated with a less frequent use of coping focused on seeking social support. Conclusions STN-DBS is associated with major positive changes in PD affecting motor function and QoL. These changes are related to psychological variables, including emotional distress and coping. A better focus on these individual characteristics is necessary to improve care of patients with PD who undertake STN-DBS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established therapy for motor symptoms in patients with pharmacoresistant Parkinson's disease (PD). However, the ...procedure, which requires multimodal perioperative exploration such as imaging, electrophysiology, or clinical examination during macrostimulation to secure lead positioning, remains challenging because the STN cannot be reliably visualized using the gold standard, T2-weighted imaging (T2WI) at 1.5 T. Thus, there is a need to improve imaging tools to better visualize the STN, optimize DBS lead implantation, and enlarge DBS diffusion. METHODS Gradient-echo sequences such as those used in T2WI suffer from higher distortions at higher magnetic fields than spin-echo sequences. First, a spin-echo 3D SPACE (sampling perfection with application-optimized contrasts using different flip angle evolutions) FLAIR sequence at 3 T was designed, validated histologically in 2 nonhuman primates, and applied to 10 patients with PD; their data were clinically compared in a double-blind manner with those of a control group of 10 other patients with PD in whom STN targeting was performed using T2WI. RESULTS Overlap between the nonhuman primate STNs segmented on 3D-histological and on 3D-SPACE-FLAIR volumes was high for the 3 most anterior quarters (mean ± SD Dice scores 0.73 ± 0.11, 0.74 ± 0.06, and 0.60 ± 0.09). STN limits determined by the 3D-SPACE-FLAIR sequence were more consistent with electrophysiological edges than those determined by T2WI (0.9 vs 1.4 mm, respectively). The imaging contrast of the STN on the 3D-SPACE-FLAIR sequence was 4 times higher (p < 0.05). Improvement in the Unified Parkinson's Disease Rating Scale Part III score (off medication, on stimulation) 12 months after the operation was higher for patients who underwent 3D-SPACE-FLAIR-guided implantation than for those in whom T2WI was used (62.2% vs 43.6%, respectively; p < 0.05). The total electrical energy delivered decreased by 36.3% with the 3D-SPACE-FLAIR sequence (p < 0.05). CONCLUSIONS 3D-SPACE-FLAIR sequences at 3 T improved STN lead placement under stereotactic conditions, improved the clinical outcome of patients with PD, and increased the benefit/risk ratio of STN-DBS surgery.
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