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Parkinson’s Patients with Poorer Quality of Life May Benefit the Most from Deep Brain Stimulation, Study Finds

dbs oucome quality of life

Individuals with Parkinon’s disease who have worse quality of life due to their disease-related impairments may benefit most from treatment with deep-brain stimulation.

The study with that finding, “Quality of life predicts outcome of deep brain stimulation in early Parkinson disease,” was published by the journal Neurology.

Deep-brain stimulation (DBS) is an invasive surgical technique in which thin wires are implanted in the brain to deliver electric pulses to specific areas, such as the subthalamic nucleus (STN), to ease motor symptoms in patients for whom standard medications are not effective.

Studies have shown that DBS can effectively help manage motor symptoms and reduce the necessary daily dose of medication, improving quality of life in those with advanced or early-stage Parkinson’s.

In a previous Phase 4 clinical trial (NCT00354133) called the EARLYSTIM study, researchers evaluated the long-term impact of STN-DBS as an add-on to best medical treatment regarding quality of life in patients with Parkinson’s disease for a period of more than two years.

The study enrolled patients younger than 61 who had a good response to levodopa therapy, but who still had developed motor complications. Among the participants, 124 were treated with DBS-STN and best medical treatment, while 127 patients received the best medical treatment only.

In the most recent study researchers reviewed the trial data to understand which factors contributed to the detectable changes in disease-specific quality of life, as measured using the 39-item Parkinson’s Disease Questionnaire summary index (PDQ-39-SI). The self-reported questionnaire assesses Parkinson’s-specific health across eight quality-of-life dimensions.

The analysis revealed that quality of life over the two years of follow-up correlated with the initial value of the PDQ-39-SI in both treatment groups. Still, this association was more pronounced among patients who were treated with STN-DBS.

Patients with very mild impairment due to Parkinson’s, corresponding to PDQ-39-SI values lower than 15, were found not to benefit from STN-DBS as compared to patients treated with standard care alone. In contrast, patients treated with STN-DBS who had PDQ-39-SI sores higher than 15 (worse quality of life) at the beginning of the study experienced better quality of life changes.

“In patients with very low baseline ratings on the PDQ-39-SI, the natural progression of impairment of [quality of life] may outweigh the improvement achieved by STN-DBS,” researchers wrote. “On the other hand, some patients with very modest impairment of their [quality of life] seem to have less to gain from STN-DBS,” they added.

Patients’ cognitive status before the treatment, as determined by the Mattis Dementia Rating Scale (MDRS), was not predictive of change in quality of life in either treatment group. However, higher scores for depression and poorer mood correlated with larger improvements in quality of life among patients in the STN-DBS group.

These findings “may indicate that these patients have a potential for nonmotor improvement to gain from surgery,” researchers suggested.

Changes in quality of life during the two years of follow-up were independent of patient age, disease duration, duration of motor complications, severity of parkinsonian motor manifestation under levopoda therapy, or treatment complications.

Supported by these findings, the team believes that “baseline impairment of quality of life is (…) a reasonable aspect to consider for the decision to treat with STN-DBS.”

“The subjective individual suffering as measured with the PDQ-39-SI should be taken into account as a predictive factor for outcome when selecting patients with early motor complications for STN-DBS,” researchers concluded.

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Study Highlights Importance of Personalized Parkinson’s Treatment

DBS IJLI Apokyn comparative study

Invasive treatment approaches for advanced Parkinson’s disease have differential effects on disease-associated motor and non-motor symptoms, a real-life observational study shows.

These findings suggest that selection of a treatment should be based on each patient’s particular clinical profile, researchers say.

The study, “EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson’s disease,” was published in Movement Disorders.

Parkinson’s is a progressive neurological disease mostly recognized for its motor symptoms, such as tremor, bradykinesia (impaired body movement control), and muscular rigidity. In advanced cases, oral therapies may not be sufficient to control these motor symptoms and patients often require device-aided therapies.

There are three well-established, safe, and effective treatments to improve quality of life and alleviate motor and non-motor symptoms of Parkinson’s disease: deep brain stimulation, intrajejunal levodopa infusion (IJLI), and Apokyn (apomorphine) infusion (APO).

In deep brain stimulation, electrodes are surgically implanted in certain areas of a patient’s brain. Through electrical signals received from a small device, the electrodes will stimulate these brain areas to produce dopamine — the chemical compound (neurotransmitter) lacking in Parkinson’s disease.

IJLI is one of the most influential therapies used in patients with moderate to late-stage Parkinson’s disease, shown to have positive effects on both motor and non-motor symptoms and quality of life. This approach uses a portable infusion pump that continuously dispenses levodopa gel through a tube inserted into the intestine.

Apokyn is an engineered therapy that mimics dopamine’s ability to stimulate nerve cells. Unlike other dopamine agonist agents, Apokyn is administrated by injection or continuous infusion using a pump.

Despite the demonstrated efficacy of these therapies, there is little information comparing their impact.

An international group of researchers, on behalf of the EUROPAR and the Non-motor Parkinson’s Disease Study Group of the International Parkinson’s Disease and Movement Disorders Society, compared the differential effects of DBS applied to the subthalamic nucleus (STN), IJLI, and APO in patients with advanced Parkinson’s disease.

The study included 101 Parkinson’s patients who underwent bilateral STN-DBS, 33 who received IJLI, and 39 patients who received APO treatment. Patients had a mean age of 62.3 years and had been diagnosed with the disease for a mean of 12.1 years.

Six months after receiving the treatment, patients were evaluated to determine changes in Parkinson’s symptoms.

Significant improvements concerning non-motor symptoms and motor-related complications were noted in the three groups of patients six months after receiving the treatment, as determined by the Nonmotor Symptom Scale (NMSS) and Unified Parkinson’s Disease Rating Scale-motor complications (UPDRS-IV), respectively.

Significant changes in quality of life, as assessed by the Parkinson’s Disease Questionnaire-8 Summary Index (PDQ-8 SI), were also reported by all treatment groups during follow-up.

IJLI and APO treatments were found to effectively prevent disease worsening during the follow-up period, according to Hoehn and Yahr scores, which rate severity of symptoms in Parkinson’s disease.

STN-DBS treatment reduced the amount of daily levodopa use by approximately 52%. As expected, levodopa equivalent daily dose remained stable in infusion therapies.

The three treatment approaches were found to have similar effects on dyskinesia (involuntary movements)/motor fluctuation ratios. In contrast, they had different effects on patients’ non-motor symptoms.

A more detailed analysis showed that STN-DBS had a significant positive effect on sleep and fatigue, mood and cognition, perceptual problems and hallucinations, urinary symptoms, and sexual function.

IJLI had a positive effect on sleep, mood, and cognition, and gastrointestinal symptoms, while APO therapy significantly improved patients’ mood and cognition, lessened occurrence of perceptual problems and hallucinations, as well as improved attention and memory.

In general, STN-DBS and IJLI seemed to improve non-motor symptom burden, and APO therapy was favorable for neuropsychological and neuropsychiatric symptoms and improved quality of life.

Patients who underwent IJLI treatment had more frequent non-serious adverse events (abdominal pain and gastrointestinal symptoms) immediately after the procedure, compared to those in the other two groups.

“Distinct effect profiles were identified for each treatment option,” researchers said. “This study highlights the importance of holistic assessments of motor as well as non-motor aspects of Parkinson’s that could provide a means to personalize treatment options to patients’ individual disease profiles.”

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DBS Effectively Reduces Tremor in Parkinson’s Patients, Regardless of Stimulated Brain Area, Study Shows

Parkinson's tremor

Deep brain stimulation (DBS) can effectively reduce tremor in people with Parkinson’s disease, regardless of the brain region stimulated, according to a recent review study.

The review, “STN vs. GPi deep brain stimulation for tremor suppression in Parkinson disease: A systematic review and meta-analysis,” was published in the journal Parkinsonism & Related Disorders.

Tremor is a main symptom of Parkinson’s disease, strongly affecting patients’ quality of life. It is estimated that 47-90% of Parkinson’s patients have an action tremor and 76-100% have a resting tremor.

Reduction of tremors is an important goal in Parkinson’s treatment, and could have a significant impact in patients’ well-being and everyday life. However, tremor is difficult to treat and often does not respond to anti-tremor medications.

Deep brain stimulation — electric stimulation in strategic brain areas through surgically implanted thin wires in the brain — is used to treat people with advanced Parkinson’s disease whose motor symptoms, such as tremors, are not reduced with medication.

Several studies have shown that DBS eases motor symptoms, reduces the necessary daily dose of medication, and improves patients’ quality of life.

Currently, the main approved targets for DBS in Parkinson disease are the subthalamic nucleus (STN) and the globus pallidus interna (GPi), areas of the brain involved in motor function.

While recent studies have found no significant differences between the therapeutic effects of the stimulation of both targets, many clinicians maintain an older preference for STN over GPi, due to a supposedly greater reduction in tremors and in medication.

However, evidence supporting STN-DBS superiority in tremor suppression is limited.

Researchers have conducted a systematic review of all randomized clinical studies comparing the therapeutic effects of STN-DBS and GPi-DBS on tremors in Parkinson’s patients, published before March 2017.

Their search identified five suitable longitudinal randomized control trials with five years follow-up data. The data included the two DBS targets, STN and GPi, and tremor sub-scores of the Unified Parkinson’s Disease Rating Scale (UPDRS) before and after DBS, and with or without dopaminergic medication.

Their analysis showed that deep brain stimulation significantly reduced tremor symptoms in Parkinson’s patients, and that these effects were observed regardless of medication status.

When looking at the two targets of deep brain stimulation, researchers found that both methods reduced tremor severity in Parkinson’s patients, with no significant differences between them. These results support that DBS of each target promotes similar long-term benefits on tremor.

However, analysis of therapeutic effects on tremor over the course of five years showed that STN-DBS was more effective to reduce tremors after two and five years than at the first six months. In turn, GPi-DBS showed a more stable degree of effectiveness on tremors over time.

“Although both targets were effective, practitioners should be aware that it is possible one target could appear superior in studies depending on the duration of follow-up,” researchers wrote.

They also noted that when Parkinson’s patients present with tremor as the primary complaint, or as an issue adversely affecting quality of life, selection of deep brain stimulation target should focus on the presence of other problems “such as cognitive impairment, speech difficulties, presence of mood disorders, and presence of impulse control disorders.”

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Source: Parkinson's News Today

Deep Brain Stimulation is a Long-term, Effective, Safe Treatment for Parkinson’s, New Studies Show

deep brain stimulation

Subthalamic deep brain stimulation (STN-DBS) seems to be a long-term, effective, and safe therapeutic option for patients with advanced Parkinson’s disease, new studies report.

STN-DBS is a non-destructive surgical treatment for Parkinson’s, in which a battery-operated device that generates electrical impulses is implanted to specific regions of the patient’s brain. Since its implementation, it has become an accepted and effective therapeutic option to treat the motor symptoms associated with Parkinson’s and other complications caused by prolonged dopaminergic treatment in advanced forms of the disease.

However, research documenting the long-term effects of STN-DBS on the clinical state of patients with advanced Parkinson’s disease is still scarce. Now, researchers presented two studies during the IAPRD World Congress 2018, held August 19-22 in Lyon, France, where they revealed the effects of STN-DBS after long-term follow-up.

In the study, “Subthalamic deep brain stimulation for advanced Parkinson’s disease beyond the 5-year follow-up,” (abstract e-book, page 11) Russian researchers evaluated the long-term safety and effectiveness of STN-DBS in a group of patients for at least seven years after surgery.

The study enrolled 33 patients with advanced Parkinson’s disease who had undergone STN-DBS surgery with a minimum follow-up period of five years. Several parameters, including motor function, disease impact on daily activities and quality of life, were assessed using the UPDRS-2,3,4, the Schwab & England scale and the PDQ-39 questionnaire, respectively.

After a follow-up period of seven years, there was a significant improvement in patients’ motor functions (42% in UPDRS-3, 24% in UPDRS-2 and 58% in UPDRS-4), ability to perform regular daily activities (23% in Schwab & England scale) and quality of life (9% in PDQ-39 questionnaire).

In addition, researchers also found that 41% of patients who underwent STN-DBS reduced their intake of levodopa and three even completely withdrew from the medication in the course of the study.

“In advanced PD-patients, STN-DBS could provide significant improvement in OFF-state [when medications fail to suppress disease symptoms] and diminish dopaminergic medication up to seven postoperative years,” the authors wrote.

In another study, “Long-term effect of subthalamic deep brain stimulation in young- and late-onset Parkinson’s disease: 10-year follow-up study,” (abstract e-book, page 13) Korean researchers evaluated the long-term safety and effectiveness of STN-DBS in patients with young disease onset (YOPD) and compared it to those who developed the condition later (LOPD) for a follow-up period of 10 years.

The study analyzed motor symptoms (UPDRS scores) of 24 patients with advanced Parkinson’s disease (13 YOPD and 11 LOPD) who underwent STN-DBS between March 1, 2002 and March 31, 2007 at the Asan Medical Center in Seoul, South Korea.

Ten years after STN-DBS, the reduction in the scores of levodopa equivalent dose (a rough technique to compare different medications, LED) and levodopa-induced dyskinesia (measures levodopa side effects, LID) were significantly lower in YOPD compared to LOPD patients.

Levodopa-induced dyskinesia improvement remained statistically significant until five years after the surgery in both groups, but after 10 years, its severity increased substantially in LOPD patients.

However, the decrease in motor symptoms (measured by UPDRS scores), visual hallucinations and adverse effects did not differ between the two groups.

“This study shows that STN DBS showed higher effect on LED reduction in LOPD and LID improvement in YOPD at 10 years after DBS surgery. These results may have clinical implications for tailored application of STN DBS in patients with PD,” the authors wrote.

Altogether, these data suggest that STN-DBS is a long-term beneficial treatment option for patients with advanced Parkinson’s disease.

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Source: Parkinson's News Today