Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6–12 months of treatment. Long-term results in a ...large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3–4 years after surgery. The primary outcome measure was the change in the ‘off’ medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3–4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the ‘off’ medication UPDRS-III score at 3–4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the ‘on’ time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3–4 years showed a significant worsening in the ‘on’ medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3–4 years in a large cohort of patients with severe Parkinson's disease.
To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery.
This was a prolonged ...follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation.
Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group.
This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.
Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into ...the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-18Ffluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.
Objective – To compare potential clinical value of plateau pressure (Ppl), resistance to outflow (Rout), pulse‐pressure amplitude (PplA) and rate of pressure increase (vP), taken from the constant ...rate lumbar infusion test (LIT), as predictors for the outcome of shunt surgery.
Methods – Recordings from preoperative LIT in 55 patients were scrutinized for the values of Ppl, PplA, vP and Rout. Gait, memory, spatial capacity and reaction ability were tested before and 6 months after shunt surgery.
Results – Forty‐three (78%) of the patients improved. There were no statistically significant differences in Ppl, Rout, PplA or vP between improved and not improved patients. Five patients with Ppl below 22 mmHg (the cut off level) improved after shunting, while 16 and eight patients with Rout below the cut off levels of 18 and 14 mmHg/ml/min improved. PplA correlated with Ppl and Rout (r = 0.74 and 0.63, respectively). In the group of patients with high PplA (≥20 mmHg) as many as 93% improved but a high PplA did not recruit more improved patients than Ppl or Rout alone.
Conclusion – v
P
or PplA does not add useful information to Ppl for selecting patients with suspected NPH for surgery. Rout calculations from LIT does not provide advantage over using the steady‐state plateau pressure for selecting patients for surgery and may increase the risk of missing patients who should benefit from surgery.
Objective – To evaluate the effect of bilateral deep‐brain stimulation (DBS) in the subthalamic nucleus (STN) on balance performance in patients with severe Parkinson's disease (PD), when tested ...without anti‐parkinsonian medication.
Material and methods – Thirty‐one patients (median age 65 years, range 50–77) were included. Assessments were made after 10–12 h withdrawal of medication, before and 6 and 12 months after surgery. Postoperative evaluations were performed with DBS on and off. Balance performance was evaluated with the Berg Balance Scale (BBS). Motor symptoms and postural stability (item 30) were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS III).
Results – DBS in STN improved balance performance as well as postural stability and motor symptoms significantly (P ≤ 0.001). Seventy per cent of the patients improved their total score of the BBS with DBS on compared with DBS off. Thus, at 6 months their median improvement was 6 points (q1–q3, 4–11) and at 12 months 4 points (2.5–16).
Conclusion – DBS in STN improves balance performance in patients with severe PD.
Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human ...fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-l-$^{18}$Ffluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the "on-off" phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.
BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of ...rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 μg rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD. TRIAL REGISTRATION. Clinical Trials.gov NCT00866502. FUNDING. Newron Sweden AB (former NeuroNova AB) and Swedish Governmental Agency for Innovation Systems (VINNOVA).
Abstract The aim was to investigate if functional balance performance in patients with Parkinson's disease (PD) was affected by long-term (3 years) treatment with bilateral subthalamic nucleus (STN) ...high-frequency stimulation. Thirty-five patients were consecutively included, and 28 patients completed the study (mean age 62 years, SD 6.5). The Berg Balance Scale (BBS) was assessed preoperatively and 1 and 3 years postoperatively (with and without anti-PD medication and with the STN stimulation turned OFF or ON). Although the balance performance of patients with PD decreased over time, the functional balance performance was still positively affected by STN stimulation alone 3 years after surgery.
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