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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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Deep Brain Stimulation May Increase Dementia Risk in Some Parkinson’s Patients, Study Suggests

deep brain stimulation

Parkinson’s disease patients with mild cognitive impairment who undergo deep brain stimulation are at a higher risk of cognitive decline and dementia, a long term “real-life”study suggests.

The study, “Longterm outcome of cognition, affective state, and quality of life following subthalamic deep brain stimulation in Parkinson’s disease,” was published in the Journal of Neural Transmission.

Subthalamic nucleus-deep brain stimulation (STN-DBS) is a surgical treatment for Parkinson’s motor symptoms where a device that generates electrical impulses is implanted into specific regions of the patient’s brain.

Increasing evidence suggests that STN-DBS significantly improves motor symptoms as well as some non-motor symptoms, such as sensory issues and sleep disturbances. However, some reports point to a potential decline in cognition in Parkinson’s patients following STN-DBS.

Researchers here investigated the cognitive status of 104 Parkinson’s patients who received STN-DBS for nine years, from 1997 and 2006, at a single center in Germany.

Neuropsychological data from before the surgery were available for 79 of the patients, of whom 37, diagnosed with Parkinson’s for more than 11 years, were followed long term for a median of 6.3 years after surgery. During this time, they underwent several neuropsychological and motor tests.

In the remaining 42 patients, no follow-up was possible due to patients’ death (21 of the cases), loss of contact (nine patients) and patients’ refusal to undergo follow-up (12 patients).

Researchers measured patients’ dementia rate (using the Mattis dementia rating scale) and cognitive status, focusing on five domains — memory, executive function, language, attention, and working memory — mood (depression and anxiety), and quality of life using the Parkinson’s Disease Questionnaire and the 36-item Short-Form Health Survey.

Motor function was assessed using several motor tests, including the Unified Parkinson Disease Rating Scale motor subscore (UPDRSm) and Hoehn and Yahr Stage, a widely used clinical rating scale, with broad categories of motor function in Parkinson’s.

Prior to the surgery, 28 patients (75.7%) had mild cognitive impairment, while nine patients (24.3%) had normal cognitive function. Moreover, no patients showed signs of Parkinson’s-related dementia.

Patients in the two groups — with and without mild cognitive impairment — showed no differences in age, disease duration, response to treatment, and dosage with levopoda, motor function, and education. Mood and quality of life were also similar.

Patients’ verbal intelligence, measured by a multiple choice word test, and memory were lower in the mild cognitive impairment group.

After undergoing STN-DBS, 18.9%, or seven, of the patients had no cognitive impairment, while the remaining patients (41%) were diagnosed with either mild cognitive impairment (15 patients) or dementia (15 patients).

Mild cognitive impairment has been previously identified as a risk factor for dementia in Parkinson’s patients. Twenty-eight patients categorized as having mild cognitive impairment before STN-DBS developed dementia within 6.3 years after surgery.

Researchers observed a trend, although not statistically significant, between mild cognitive impairment before STN-DBS and progression to dementia according to the patients’ age, sex, and education at the beginning of the study.

Compared with non-demented Parkinson’s patients, those with dementia had longer disease duration (15 years versus 20.2 years, respectively) and more severe motor impairments (UPDRSm score of 23.7 versus 36.1), with demented patients showing a faster progression of several typical Parkinson’s symptoms — bradykinesia (slowness of movement), rigidity, impaired speech, posture, gait, and postural stability.

In general, researchers observed a decline in cognition, including memory and language, in all STN-DBS-treated patients in the 6.3 years after surgery. However, partial working memory (also referred to as short-term memory) was preserved and slightly improved in some cases.

Disease duration, but not age, at the time of DBS surgery had a significant relation to the risk of developing dementia.

“This observational, ‘real-life’ study provides long-term results of cognitive decline in STN-DBS-treated patients with presurgical [mild cognitive impairment] possibly predicting the conversion to dementia,” the researchers wrote.

“Although, the present data is lacking a control group of medically treated PD [Parkinson’s disease] patients, comparison with other studies on cognition and PD do not support a disease-modifying effect of STN-DBS on cognitive domains,” they concluded.

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Deep Brain Stimulation Technique Lessens Parkinson’s Dyskinesia, Study Finds

deep brain stimulation, dyskinesia

Using a parameter called interleaving stimulation (ILS) in deep brain stimulation (DBS) eased dyskinesia — involuntary, jerky movements — in patients with Parkinson’s, according to a new study.

In contrast, the benefits in people with tremor or dystonia — abnormal muscle tone — or in mitigating DBS-induced adverse side effects were not as evident.

The study, “Interleaving Stimulation in Parkinson’s Disease, Tremor, and Dystonia,” was published in the journal Stereotactic and Functional Neurosurgery.

DBS is a surgical treatment for Parkinson’s motor symptoms that involves implanting a device to stimulate specific brain regions using electrical impulses generated by a battery-operated neurostimulator.

ILS is a variant of DBS that enables alternating stimulation with two contacts on different brain regions set with specific measures — amplitude, or wave height, and pulse width. ILS may be applied to lessen stimulation-induced adverse side effects and to simultaneously target different brain regions to ease specific symptoms.

Researchers assessed the applications and outcomes of ILS in clinical practice for patients with Parkinson’s, tremor, and dystonia. The team conducted a review through June 2015, by searching the electronic database at Toronto Western Hospital for all patients receiving DBS and ILS.

ILS was preformed in 50 patients — 27 with Parkinson’s (19 men), seven with tremor (three men), and 16 with dystonia (three men). Mean age at diagnosis was 48 for patients with Parkinson’s, 48.6 for people with tremor, and 23.8 for those with dystonia. Age at surgery was 58, 57.8 and 37.8, respectively.

Pre- and post-operative assessments (at six months) were performed with validated scales, including the Unified Parkinson’s Disease Rating Scale part III (motor section), the Fahn-Tolosa-Marin Tremor Rating Scale for patients with tremor, and the Toronto Western Spasmodic Torti-collis Rating Scale and the Burke-Fahn-Marsden Dystonia Rating Scale specifically for those with dystonia.

Twenty-nine patients underwent ILS to manage stimulation-induced adverse effects, mainly to reduce the volume of activated tissue (the amount of brain tissue that is stimulated by electrical activity in DBS). Nineteen participants — 14 with Parkinson’s, two with tremor and three with dystonia — experienced a reduction of symptoms, while 10 (seven with Parkinson’s, one with tremor and two with dystonia) saw no change.

Overall, the benefit of using ILS was predominantly noted in the lessening of dyskinesia — the involuntary, jerky movements — in patients with Parkinson’s disease, and occurred soon after the switch. The average duration of ILS in the six Parkinson’s patients who continued on this approach was 206 days.

Six additional patients also experienced easing of dyskinesia but discontinued the therapy due to worsened pain or mood, temporary benefit, and worsened motor function.

Of the nine Parkinson’s patients receiving ILS for other stimulation-induced adverse effects, only one who tried ILS for dysarthria (slurred or slow speech) continued the treatment with further improvement in parkinsonism.

Three patients with tremor and five with dystonia were receiving ILS for stimulation-induced adverse events. Among these, the approach had mixed results, with only three participants with dystonia showing improvements.

A total of 21 participants tried ILS to improve DBS clinical effectiveness (six Parkinson’s; four tremor; 11 dystonia). Of these, all six Parkinson’s patients and three with dystonia demonstrated benefits. Of the patients with Parkinson’s (mean ILS duration 420 days), four had ILS to reduce tremor, one to lower bradykinesia (slowness of movement), and one to lessen freezing of gait. ILS was not effective in people with tremor and only two patients with dystonia continued with the treatment.

“We identified 2 reasons for attempting ILS: to mitigate adverse effects and to improve disease signs and symptoms,” researchers wrote. “The most impressive finding was improvement of dyskinesias with ILS …  In tremor and dystonia, marginal effects in terms of mitigation of adverse effects and improvement of clinical outcomes were evident,” they added.

“Overall, ILS appears to have limited benefits in the treatment of other stimulation-induced adverse effects potentially due to minimal adjustment of the VAT [volume of activated tissue] and would unlikely be effective to salvage a misplaced electrode,” they concluded.

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Wireless Pacemaker-like Device May Offer Real-time Treatment for Parkinson’s, Study Reports

neuromodulator for Parkinson's

A new neuromodulator — a wireless pacemaker-like device — may provide real-time treatment to patients with diseases such as Parkinson’s by monitoring abnormalities and delivering corrective electrical signals to the brain.

The device was described in the study, “A wireless and artefact-free 128-channel neuromodulation device for closed-loop stimulation and recording in non-human primates,” published in the journal Nature Biomedical Engineering.

Recent studies have shown that closed-loop neuromodulation systems could improve deep brain stimulation for treating Parkinson’s disease and other motor disorders. These systems deliver and adjust therapeutic electrical stimulation in response to a patient’s neural state in real time.

Up to this point, it has been difficult, both medically and economically, to apply closed-loop neuromodulation systems in patients with movement disorders, and it hasn’t been clear how to implement strategies for these treatments. Previous attempts were short term, using systems that were not fully implantable.

“In order to deliver closed-loop stimulation-based therapies, which is a big goal for people treating Parkinson’s and epilepsy and a variety of neurological disorders, it is very important to both perform neural recordings and stimulation simultaneously, which currently no single commercial device does,” study author Samantha Santacruz, PhD, now an assistant professor at the University of Texas, said in a press release.

To enable advanced research in closed-loop neuromodulation, “there is a need for a flexible research platform, for testing and implementing these various closed-loop paradigms, that is also wireless, compact, robust and safe,” the researchers wrote in the study.

The researchers, from the University of California, Berkeley and Cortera Neurotechnologies, introduce a new device in this study that allows simultaneous recording and stimulation of the brain. The WAND — wireless artifact-free neuromodulation device — is a miniaturized, autonomous neural interface capable of closed-loop sensing and stimulation while fully canceling stimulation artifacts — recorded electrical signals coming from the device. With this WAND, electrodes are surgically implanted inside the brain, with chips contained in a chassis attached to the outside of the head.

Existing devices can detect neural biomarkers electrical signatures indicative of abnormal brain processes and stimulate the brain in a closed-loop neuromodulation system, but they contain a low number of recording and stimulating channels. WAND improves on these limitations by incorporating a large number of recording and stimulation channels and a wireless data rate to support a large number of streaming channels. The technology also automatically adjusts stimulation parameters.

“The process of finding the right therapy for a patient is extremely costly and can take years. Significant reduction in both cost and duration can potentially lead to greatly improved outcomes and accessibility,” said Rikky Muller, PhD, an assistant professor of electrical engineering at University of California, Berkeley. “We want to enable the device to figure out what is the best way to stimulate for a given patient to give the best outcomes. And you can only do that by listening and recording the neural signatures.”

In a study of non-human primates, WAND enabled long-term recordings of local brain activity and the real-time cancellation of stimulation artifacts. The researchers proved that the closed-loop system device was causing changes in brain activity by using stimulation to create a functional change in the primates’ behavior during a routine task. To this end, the device enables neuroscientific discovery and preclinical investigations of stimulation-based therapeutic interventions.

“While delaying reaction time is something that has been demonstrated before, this is, to our knowledge, the first time that it has been demonstrated in a closed-loop system based on a neurological recording only,” Muller said. “In the future, we aim to incorporate learning into our closed-loop platform to build intelligent devices that can figure out how to best treat you, and remove the doctor from having to constantly intervene in this process.”

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Focused-ultrasound Lesion Surgery Can Treat Tremors and Improve Life Quality, Study Says

tremors and surgery

Treating tremor in Parkinson’s patients using non-invasive and focused-ultrasound lesion surgery is associated with better quality of life when compared to deep brain stimulation, although both approaches are equally effective in easing this disease symptom, a review study reports.

The study, “Outcomes in Lesion Surgery versus Deep Brain Stimulation in Patients with Tremor: A Systematic Review and Meta-analysis,” was published in the journal World Neurosurgery.

At least 50 percent of people with Parkinson’s, essential tremor (ET) or multiple sclerosis (MS) given oral medications as a first-line treatment for tremor — defined as an involuntary, uncontrollable muscle contraction; most commonly in the hands — do not tolerate these medications over the long term.

Current alternatives include deep brain stimulation (DBS) and lesion surgery (LS), which induces lesions on targeted areas using a heated electrode or focused ultrasound. Prior comparisons have shown that while the two techniques are equally effective in suppressing tremor, DBS led to a greater improvement in function.

But LS with focused ultrasound is gaining in popularity, and one study suggested that it may significantly improve tremor and quality of life.

Researchers at Harvard Medical School conduced a systematic review and a meta-analysis — a type of statistical study that combines the results of various studies — to determine which strategy is most effective in diminishing tremor severity and improving life quality and function in people with Parkinson’s, ET, or MS.

Three online databases were searched for results of randomized clinical trials published up to Jan. 1, 2018, and that included adults treated with either LS or DBS, or serving as controls. Both DBS and LS studies targeted unilateral or bilateral thalamus, pallidum or subthalamic nucleus, all of which are implicated in motor function.

Thirteen Parkinson’s trials were among the 15 included in this study, and the primary outcome for all but one was change in upper limb tremor severity, as assessed with the unified Parkinson’s disease rating scale (UPDRS) part III. Changes in quality of life, cognitive function and neuropsychiatric function were also assessed with variable measures.

A total of 1, 508 patients (mean age range, 48.4 to 70.8) were included, and in addition to the 13 studies involving only Parkinson’s patients, one study looked at people with Parkinson’s, ET and MS, while the remaining study was in people with severe ET.

Four of the 15 trials — involving 125 patients — directly compared DBS to LS. The others compared either LS or DBS with controls.

Results showed that DBS and LS were not significantly different across all analyzed outcomes, which is in line with current guidelines, the researchers noted. All but one trial showed both these types of surgery eased tremor severity. Quality of life findings showed variability in outcomes, which was driven by disease duration. Specifically, longer disease duration correlated with a greater likelihood of surgery and better quality of life.

A subgroup analysis that looked specifically at LS using focused ultrasound revealed that this approach was associated with a significant improvement in quality of life compared to DNS, although changes in tremor severity were similar.

“Policy makers, healthcare providers, and patients could therefore consider focused-ultrasound [LS] as a potential choice for tremor control, based on currently available evidence,” the researchers wrote.

However, results from more studies directly comparing DBS with focused-ultrasound LS are needed, they advised.

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Transient Cerebral Swelling a Common Side Effect of Deep Brain Stimulation, Study Suggests

brain edema DBS

Swelling of brain areas close to where the electrodes that deliver deep brain stimulation (DBS) are placed is a common and transient side effect of this treatment in Parkinson’s disease patients, a study suggests.

Long-term impact of this adverse reaction and potential related complications are still unknown and warrant further analysis, researchers say.

The study, “Peri-lead edema after DBS surgery for Parkinson’s disease: a prospective MRI study” was published in the European Journal of Neurology.

DBS is a surgical treatment in which thin wires are implanted in strategic brain areas (those that control complex movements) to deliver electrical impulses generated by a battery-operated device.

Studies have shown that DBS can be beneficial in treating a variety of neurological diseases, particularly Parkinson’s. DBS has been accepted as an effective therapy to reduce motor symptoms such as tremors, lower the necessary daily dose of medication and improve Parkinson’s patients’ quality of life.

The most common adverse events associated with DBS include hemorrhage, infection, and failure of the implant’s components. However, some studies have also reported rare events of cerebral swelling (edema) surrounding DBS electrodes a few days after the surgery.

To gain binsight on the prevalence of this complication, Italian researchers evaluated the progression of 19 Parkinson’s patients who had undergone DBS therapy.

Surgeries were uneventful in all patients, with no complications being reported. However, after surgery, two patients experienced small hemorrhages close to the placed electrodes without any other brain tissue alterations reported.

All patients were evaluated by magnetic resonance imaging (MRI) between days 7 and 20 after surgery.

Researchers found that all patients showed some degree of MRI signal alteration along the placed electrodes, which was consistent with edema. The analysis also revealed small symptomatic hemorrhage in four additional patients, raising the total number of hemorrhagic patients to six (31.57%).

Researchers failed to find any correlation between edema volume and patients’ age, gender, disease duration, or side of the brain in which DBS electrodes had been implanted.

Patients who had hemorrhages also showed tissue swelling on the side of the brain opposite the bleeding.

Most patients were asymptomatic, but six had transient confusional state — disorientation in space and time plus mild signs of frontal lobe dysfunction, which included disinhibition, inattentiveness, and slightly impaired speech with poor word retrieval. Patients did not show any new motor deficits after surgery.

Two symptomatic patients were treated with a short corticosteroid treatment, but no significant effect on symptoms was noted. Still, both patients recovered in two to four weeks.

At a mean time period of 40.64 days after surgery, MRI signs returned to normal values in eight  patients. Superficial edema was still detected in three patients. At follow-up, no patient had detectable bleeding around the DBS electrodes.

To further explore the prevalence of brain edema associated with DBS, the team retrospectively evaluated computed tomography (CT) imaging data of 77 patients who had undergone DBS surgery from January 2013 to February 2017.

Hemorrhage around DBS electrodes was detected in four (5.19%) patients and edema in six (7.78%) patients. In nine patients evaluated by CT scans on days 1, 2, and 3 after surgery, edema was present in two who also had hemorrhage, and another patient.

“Our prospective MRI study confirms that [transient] edema is a common finding in STN-DBS [subthalamic nucleus] implanted patients for Parkinson’s disease and that it is asymptomatic in most patients,” researchers said. “The reason of the extremely high incidence of our finding is likely due to the timing of imaging (average 10 days) from surgery.”

They stated their opinion that edema near the electrode sites “is a normal and constant finding in patients undergoing STN-DBS lead placement. Its recognition is biased mainly because it is mostly asymptomatic and also because of the lack of early routine MRI scans in DBS patients.”

The team suggested that to avoid overtreatment and complications, “no corticosteroid treatment should be administered to patients whose MRI shows … edema in the first 7 to 60 days from surgery.”

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Black Doggy Goes to the Doctor

“Why can’t I go?” asked my granddaughter, whom I call Boo.
“The doctor is trying to fix my brain and it won’t be any fun,” I replied as 3-year-old Boo looked at me curiously. I had undergone deep brain stimulation two weeks earlier for my Parkinson’s disease, and was scheduled to have my unit turned on and programmed.
It was a two-day drive down to Arizona where my movement disorder specialist was, then two days driving back home to southern Oregon.
The day before I left, Boo informed me that she still wanted to go with me to the specialist. Boo also told her mother the same thing when she came to pick her up. (I watched her every day while her parents were at work.) When her mommy said no, her little lips began to quiver and tears welled.
“Boo, the ride is really long and you really wouldn’t like it. How about the next time Grammy goes to her regular doctor here, you can come with me, OK?” I asked her.
That appeased my granddaughter for the time being and she left for home.
Later that evening, my husband and I drove over to Boo’s to say goodbye to the family because we were leaving in the morning. As we got ready to go back home, my son said, “Boo, isn’t there something you wanted to give Grammy to take with her to the doctor?”
Her face lit up and she ran to her room.
“She was still upset when we got home today about not being able to go with you to the doctor,” her mom told me as we waited for Boo to return. And then, here she came around the corner with Black Doggy. Black Doggy is Boo’s prized and favored little friend. Boo cannot sleep without Black Doggy. Boo cannot live without Black Doggy. Boo gave me Black Doggy.
“You can take Black Doggy with you to take care of you,” she told me as she handed him over.
I fought back tears. “Oh … but what will you do when you go to bed?”
“I’ll use Brown Doggy,” she said. My son winked at me and nodded his head.
“OK,” I said. I then asked, “Do you want to have Black Doggy’s picture taken with the doctor?”
Boo was beside herself. “Yeah, Grammy! Yeah!”
I gave Boo another big hug and we left. OK, so how was I going to pull this off without feeling utterly ridiculous? Who cares? Anything for Boo.
Two mornings later, I saw my doctor. Re-entering the exam room after doing some tests, my husband sat waiting and holding Black Doggy and the camera.
“OK,” he said as he stood up, “this is for Boo.”
“Oh, the grandchild! We can do that,” my doctor laughed and then smiled for the camera, holding Black Doggy.
Boo was so pleased with her picture. Sometimes all it takes to make things better is a stuffed black doggy.
***
Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

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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

DBS Linked to Distinct Motor and Cognitive Pathways in Brain, Finding That May Improve Its Use

deep brain stimulation

The benefits of deep brain stimulation (DBS) on motor function in Parkinson’s patients are mediated by a different brain pathway than the one involved in the procedure’s unwanted cognitive effects, according to a new study.

This finding may help improve the effectiveness and safety of DBS use in patients with Parkinson’s disease.

The research, “Functional segregation of basal ganglia pathways in Parkinson’s disease,” was published in the journal Brain.

DBS is an efficient alternative surgical procedure to treat Parkinson’s motor symptoms, such as tremor, rigidity, stiffness and slowed movement, in patients with an inadequate response to medications.

The treatment targets the subthalamic nucleus (STN), a brain region that is hyperactive in Parkinson’s patients. Besides its role in motor control, the STN is also involved in cognitive processes such as decision-making.

Prior research has shown that the STN is part of a brain pathway linking the striatum — a key region in movement and cognition — to the thalamus, which relays motor and sensory signals. This pathway is affected by loss of the neurotransmitter dopamine in the striatum due to Parkinson’s.

The STN is also involved in a brain pathway connecting motor-related areas in the cerebral cortex with the globus pallidus, a major component of the basal ganglia, which is mainly implicated in the control of movement and posture. The STN has been proposed to act through this pathway to delay, and thereby optimize, behavioral responses.

Although researchers suggest that DBS may alter the activity of both these brain pathways, no study had assessed the treatment’s effects on cognition and movement control in an integrated perspective.

A research team from Charité – Universitätsmedizin Berlin, in Germany, combined behavioral experiments with clinical observations, brain mapping and computer-based modeling. The study involved 20 Parkinson’s patients (18 men, mean age 63) undergoing STN-DBS, and 20 controls given a tracking task that required normal (automatic) and controlled reach movements.

Improvements in motor function — such as in movement velocity — were independent from unwanted cognitive effects, such as premature actions taken in situations requiring deliberation and decision-making. These motor and cognitive effects were independently mediated by the striatum-thalamus and the cortex-globus pallidus pathways, respectively.

“Our findings integrate with previous reports regarding cognitive and clinical implications of distinct pathway effects in Parkinson’s,” the researchers wrote.

Besides a better understanding of the neuronal networks affected by Parkinson’s, the findings also shed light on the workings of DBS.

“Only an improved understanding of the treatment’s mechanism of action will allow us to make [DBS] more effective,” Wolf-Julian Neumann, MD, the study’s first author, said in a press release.

As such, the results “may inspire new innovative pathway-specific approaches to reduce side effects and increase therapeutic efficacy of neuromodulation in patients with Parkinson’s,” the researchers wrote.

The team is now planning to use measurements of neural activity to differentiate patients and healthy individuals.

“This will allow us to adapt brain stimulation treatments according to the needs of the individual patient and in real time,” said Andrea A. Kühn, MD, the study’s senior author. “It is an important step on the way to developing an intelligent, personalized and demand-adapted treatment.”

The post DBS Linked to Distinct Motor and Cognitive Pathways in Brain, Finding That May Improve Its Use appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Magnetic Gene in Fish May Help Develop New Treatment Strategies for Parkinson’s, Study Says

magnetic gene in fish

A fish that can sense the Earth’s magnetic field while it swims could help scientists understand how the human brain works and eventually unlock strategies to help control movement impairments in patients with Parkinson’s disease and other neurological disorders, a study reports.

The study, “Wireless control of cellular function by activation of a novel protein responsive to electromagnetic fields,” was published in the journal Scientific Reports.

The freshwater glass catfish, also known as Kryptopterus bicirrhis, is capable of sensing and responding to the Earth’s electromagnetic fields.

Michigan State University (MSU) researchers were able to identify this “navigational gene,” called the electromagnetic-perceptive gene, or EPG. The protein produced by the EPG senses both static and alternating magnetic waves, allowing the fish to swim away in response to magnetic fields.

The team injected a virus containing the EPG into motor neurons located in one of the main regions of the brain involved in motor function, called the right primary motor cortex, of 10 adult rats. Five control rats were injected with a virus that had a fluorescent protein called GFP instead of the EPG.

Remote wireless magnetic stimulation of EPG-expressing rats induced large muscle responses compared with control rats.

“We’ve found a noninvasive way to activate this gene once injected in the brain cells of mice and regulate movement in their limbs,” Galit Pelled, PhD, a medical bioengineering professor at MSU’s Institute for Quantitative Health Science and Engineering and the study’s lead author, said in a press release.

These findings suggest that the same strategy “could work similarly in humans,” he said.

In the future, a Parkinson’s disease patient with tremors could receive an injection of the EPG gene in a specified brain region. A magnet that emits electromagnetic waves could then activate the gene to help control, or ideally stop, the tremors.

“Technology is getting better and better every year, so this magnet could be built into anything,” Pelled said.

Deep brain stimulation, an established treatment for advanced Parkinson’s patients, is a surgical procedure that involves implanting a neurostimulator in the brain, which sends electrical impulses to specific brain regions.

However, this technique is highly invasive involving drilling a hole in the skull for electrode implantation. This process can damage neurons and other cells and even increase the levels of inflammatory factors.

Engineering stem cells to express the EPG gene and introducing them into the brain of Parkinson’s patients is the goal of Assaf Gilad, PhD, the study’s co-author and a professor of biomedical engineering and radiology.

“Stem cells are very good carriers of genes so if someone has Parkinson’s, we can introduce these stem cells into the brain as a therapy,” he said. “This type of treatment could not only help the brain, but could work in other parts of the body too, like the heart, and help those with heart issues.”

Researchers are now trying to understand the underlying mechanisms that allow the EPG gene to respond to magnetic waves.

“The mechanism of the gene is still unknown,” Gilad said. “But once we understand how it really works, it could open the door to even more possibilities.”

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Source: Parkinson's News Today