Directions Of Deep Brain Stimulation For Epilepsy And Parkinsons Disease
- 1Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan
- 2Institute of Basic Medical Science, National Cheng Kung University, Tainan, Taiwan
- 3Institute of Medical Informatics, National Cheng Kung University, Tainan, Taiwan
- 4Department of Psychology, National Cheng Kung University, Tainan, Taiwan
Background: Deep brain stimulation is an effective treatment for movement disorders and neurological/psychiatric disorders. DBS has been approved for the control of Parkinson disease and epilepsy.
Objectives: A systematic review and possible future direction of DBS system studies is performed in the open loop and closed-loop configuration on PD and epilepsy.
Methods: We searched Google Scholar database for DBS system and development. DBS search results were categorized into clinical device and research system from the open-loop and closed-loop perspectives.
Results: We performed literature review for DBS on PD and epilepsy in terms of system development by the open loop and closed-loop configuration. This study described development and trends for DBS in terms of electrode, recording, stimulation, and signal processing. The closed-loop DBS system raised a more attention in recent researches.
We overviewed development and progress of DBS. Our results suggest that the closed-loop DBS is important for PD and epilepsy.
Using Cbd For Treating Parkinsons Disease Symptoms
People with PD are already using CBD in various forms for all sorts of symptoms of PD including insomnia, anxiety, tremor, dystonia and pain.
Without clinical trial data however, we do not know whether CBD is safe and effective for a particular symptom, and if it is, what CBD formulation and dosage is best to be used for a particular symptom.
We also dont know the side effect profile of CBD in people with PD. At baseline, people with PD may have various non-motor symptoms that may make them more prone to side effects from CBD, including fatigue and nausea.
If you would like to try CBD for one of your PD symptoms, have a conversation with your movement disorders specialist about it. Your doctor may be willing to oversee your trying it, or may feel that it is too risky for you without evidence that it will help. At the very least, he/she can make sure that there are no drug interactions between CBD and anything else that you take and discuss with you any potential side effects that you need to be aware of.
Stage One: Symptoms Affect Only One Side Of Your Body
The initial phase of Parkinsons disease typically presents with mild symptoms. Some patients will not even detect their symptoms in the earliest phases of this stage. Typical motor symptoms experienced in Stage One include tremors and shaking limbs. Family members and friends may begin to notice other symptoms including tremor, poor posture, and mask face or loss of facial expression.
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The Challenge Of Regulating Cbd Products
Practically, CBD products can be obtained relatively easily at health food stores and online. They are not considered drugs , and therefore are not regulated by the Food and Drug Administration . This can be very problematic because without FDA oversight:
- There is no assurance that what is stated on the package is what is being sold. For example, even if the bottle says it is pure CBD, the product may contain other chemicals from the cannabis plant, or a higher amount of THC than advertised
- The manufacturing process, which is also not regulated, may introduce contaminants
- There is no assurance that the dosage written on the bottle is correct
- Medication interactions between CBD products and other drugs are not clear to consumers
The FDA is aware of the health claims that are made by manufacturers about various products and issues warnings to companies who market CBD products with unsubstantiated health claims.
Clinical Effectiveness Of Zonisamide
Murata et al. incidentally found that ZNS was effective in treating PD patients. Since then, several clinical trials have been performed to explore the effectiveness of ZNS for the treatment of PD. Based on adequate randomized controlled trials , ZNS is efficacious and safe as an adjunctive therapy in patients with PD . Additionally, the 2018 guideline has supported the use of ZNS for motor symptoms, especially for treating motor fluctuations . We review the clinical trials below further details are summarized in Table 2.
Table 2. Clinical trials on zonisamide effectiveness in the treatment of PD.
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Parkinson Disease And The Risk Of Epileptic Seizures
Katharina Gruntz MD
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Claudia Becker PhD
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Boston Collaborative Drug Surveillance Program, Lexington, MA
Boston University School of Public Health, Boston, MA
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Boston Collaborative Drug Surveillance Program, Lexington, MA
Hospital Pharmacy, University Hospital Basel, Basel, Switzerland
Katharina Gruntz MD
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Claudia Becker PhD
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
What Research Is Being Done
The National Institute of Neurological Disorders and Stroke , a component of the National Institutes of Health, is the primary funder of research on the brain and nervous system. NIH is the leading funder of biomedical research in the world.
PSP is one of the diseases being studied as part of the NINDS Parkinsons Disease Biomarkers Program. This major NINDS initiative is aimed at discovering ways to identify individuals at risk for developing Parkinsons disease and related disorders, and to track the progression of these diseases. NINDS also supports clinical research studies to develop brain imaging that may allow for earlier and more accurate diagnosis of PSP.
Genetic studies of PSP may identify underlying genetic causes. Previous studies have linked regions of chromosomes containing multiple genes, including the gene for the tau protein , with PSP. Researchers hope to identify specific disease-causing mutation and are also studying how genetics and environment interaction may work together to contribute to disease susceptibility.
Animal models of PSP and other tau-related disorders, including fruit fly and zebrafish models, may identify basic disease mechanisms and lead to preclinical testing of potential drugs. Other studies in animal models focus on brain circuits affected by PSP, such as those involved in motor control and sleep, which may also yield insights into disease mechanisms and treatments.
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How Is Tremor Diagnosed
Tremor is diagnosed based on a physical and neurological examination and an individuals medical history. During the physical evaluation, a doctor will assess the tremor based on:
- whether the tremor occurs when the muscles are at rest or in action
- the location of the tremor on the body
- the appearance of the tremor .
The doctor will also check other neurological findings such as impaired balance, speech abnormalities, or increased muscle stiffness. Blood or urine tests can rule out metabolic causes such as thyroid malfunction and certain medications that can cause tremor. These tests may also help to identify contributing causes such as drug interactions, chronic alcoholism, or other conditions or diseases. Diagnostic imaging may help determine if the tremor is the result of damage in the brain.
Additional tests may be administered to determine functional limitations such as difficulty with handwriting or the ability to hold a fork or cup. Individuals may be asked to perform a series of tasks or exercises such as placing a finger on the tip of their nose or drawing a spiral.
The doctor may order an electromyogram to diagnose muscle or nerve problems. This test measures involuntary muscle activity and muscle response to nerve stimulation.
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Known Symptoms Like Tremor Spotted In Primary Care Records 10 Years Before Diagnosis
byJudy George, Senior Staff Writer, MedPage Today March 7, 2022
Hearing loss and epilepsy were associated with a future diagnosis of Parkinson’s disease, an observational study of primary care records in East London showed.
Among ethnically diverse primary care patients, epilepsy and hearing loss were linked with a subsequent Parkinson’s diagnosis, reported Alastair Noyce, PhD, of Queen Mary University of London, and co-authors in JAMA Neurology.
Known symptoms associated with Parkinson’s disease, such as tremor and memory problems, were spotted in primary care records years before diagnosis. Tremor was seen up to a decade before and memory symptoms emerged 2 to 5 years before Parkinson’s was diagnosed.
“People see their GPs with symptoms but often don’t get a diagnosis until 5 to 10 years after this,” Noyce said in a statement.
“Tremor, for example, is one of the most recognizable symptoms of Parkinson’s, but was seen 10 years before eventual diagnosis in our study,” he pointed out. “This is too long for patients to wait.”
The primary care setting often is where symptoms that herald the onset of Parkinson’s are first discussed, observed Bhavana Patel, DO, of the University of Florida in Gainesville, and co-authors in an accompanying editorial. “However, little is known regarding the prediagnostic manifestations of Parkinson’s disease that are seen in primary care clinics, particularly in underserved populations,” they wrote.
Disclosures
Primary Source
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Stage Four: Symptoms Are Severe And Disabling And You Often Need Assistance To Walk Stand And Move
Stage Four Parkinsons disease is often called advanced Parkinsons disease. People in this stage experience severe and debilitating symptoms. Motor symptoms, such as rigidity and bradykinesia, are visible and difficult to overcome. Most people in Stage Four arent able to live alone. They need the assistance of a caregiver or home health aide to perform normal tasks.
Symptoms Of Peripheral Neuropathy
The symptoms of PN can be non-specific, and a person therefore may not be able to distinguish on their own whether his/her symptoms are due to PN or another condition. PN, however, often results in specific findings on a neurologic exam, such as decreased sensation to pin prick or vibration or the lack of ability to discern which way a toe is being pointed without looking. Other tests such as Electromyogram and Nerve conduction studies may be necessary to confirm the diagnosis. Small fiber neuropathy which typically causes pain, burning, tingling and/or numbness in the feet, may have normal EMG and NCS and a skin biopsy may be necessary to confirm the diagnosis. With the appropriate examination and supportive tests however, a neurologist should be able to distinguish the symptoms of peripheral neuropathy from other conditions, including PD, that may cause similar symptoms.
There are many known causes of PN including diabetes, vitamin deficiencies, certain infections, and autoimmune diseases. Many of these causes can be treated, so it is important to know if you do have PN and what the cause is. There are those people however, who have the signs and symptoms of PN, but no known cause can be identified.
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What To Do With Deep Brain Stimulation At The End Of Life
Deep brain stimulation uses an Implantable Pulse Generator, usually placed in the infraclavicular area, connected to leads within the brain. There is a remote programmer, and also a charging unit in the case of a rechargeable device, which are given to the patient and their carer. It improves dyskinesias and also has a levodopa sparing effect.37
Deactivation of DBS may lead to increased symptom burden as mentioned in the section above and so awareness of features of PHS should be considered if there is failure at the end of life. Supportive treatment should be given if possible,38 and anticipation of symptoms of distress from rigidity and fever.
After death, deactivation of the device with the patients handheld programmer is required before removing the pulse generator and battery in the case of a cremation.
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Relationship Between Disrupted Neuronal Connectivity And Epileptic Seizures
Epilepsy is considered a disease of network dysfunction.47,48 At a microscopic level, both simple and complex partial seizures involve disruptions in the excitatory interactions between cerebral cortex pyramidal cells.49 From a neurophysiology view, the EEG-graphic representation of an epileptic event is characterized by the paroxysmal onset of hyper-synchronized sharp waves disrupting the neuronal background activity. This activity is often multifocal, reflecting a broader network dysfunction.50,51 Moreover, TMS studies demonstrate similar neurophysiologic features between epilepsy and PD characterized by a state of increased cortical excitability as indicated by reduced intra-cortical inhibition and increased intra-cortical facilitation observed in both patient populations.25,52â55 As mentioned before, in PD, cortical neurons innervating the basal ganglia become hyperexcitable, possibly as a compensatory mechanism following the incremental rise in the output threshold of striatal dopaminergic neurons. As such, it would not be surprising if this putatively maladaptive phenomenon may eventually lead to the generation of epileptiform activity. While epidemiologically, epilepsy-increased comorbidity in patients with PD remains questioned,13,56 our group published the largest case series of patients with PD with concomitant epilepsy57 raising the possibility that epileptic activity in these patients may indeed be under-diagnosed and under-recognized.
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Stage Three: Symptoms Are More Pronounced But You Can Still Function Without Assistance
The third stage is considered moderate Parkinsons disease. In this stage, youll experience obvious difficulty with walking, standing, and other physical movements. The symptoms can interfere with daily life. Youre more likely to fall, and your physical movements become much more difficult. However, most patients at this stage are still able to maintain independence and need little outside assistance.
Which Medications Can Make Confusion And Hallucinations Worse
As PD progresses, non-motor symptoms including psychosis and hallucinations become more prominent both for the patient and caregivers.9 Dopaminergic medication can exacerbate these symptoms and this can be reduced through a last in, first out approach. 27,28 Medications that have an anticholinergic effect also may cause or worsen acute confusion and the anticholinergic burden in the patients medication history should be considered.29
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How Is Psp Diagnosed
Currently there are no tests or brain imaging techniques to definitively diagnose PSP. An initial diagnosis is based on the persons medical history and a physical and neurological exam. Identifying early gait problems, problems moving the eyes, speech and swallowing abnormalities, as well as ruling out other similar disorders is important. Diagnostic imaging may show shrinkage at the top of the brain stem and look at brain activity in known areas of degeneration.
The Increased Interest In Cbd Products As Supplemental Treatment
There is also a very confusing array of CBD products that are available for purchase. These vary in:
- What the manufacturers state is in the product. That is, some formulations of CBD will state on their label that they also contain a small amount of THC or that they contain other cannabis-derived compounds, but not THC. Others state that they are pure CBD.
- The formulation. CBD is available in oils, creams, pills, inhalants and more.
It is not just the Parkinsons disease community that has taken an interest in CBD. There are countless health claims that CBD is helpful for a whole host of conditions. Clinical trial evidence to support the use of CBD however, is minimal. The only FDA-approved indication for CBD is to reduce seizure frequency in certain rare and severe forms of childhood epilepsy. A purified form of CBD, sold under the brand name Epidiolex® was tested in a well-designed clinical trial in order to gain this approval. .
For all the other health claims, there is not enough clinical trial data to allow the FDA to state whether or not CBD is effective. And there definitely is not enough data to support the use of one type or formulation of CBD over another.
This has not dimmed the enthusiasm of millions of CBD users for a wide range of medical conditions.
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Subclinical Or Atypical Epileptic Seizures Could Masquerade As Non
While the non-motor questionnaire and non-motor symptoms scale 73,74 allow improved detection and tracking of NMD-PD, the symptoms often remain under-recognized and under-appreciated by clinicians and caretakers. Recently, six different clinical phenotypes of PD were recognized on the basis of prevalent NMS-PD.75 These non-motor signatures included cognitive impairment, apathy, depression/anxiety, REM behavioral disorder , lower limb pain, and weight loss/olfactory dysfunction. This distinction may help in promoting the incorporation of NMS-PD into routine assessments, emphasizing the importance of these features for an adequate appreciation of the patientâs clinical picture. On the other hand, a rigid categorization may challenge the flexible and consistent monitoring of these dynamic and overall nonspecific symptoms along the disease course.
In the following section, we will focus on clinical features frequently displayed by patients with PD that may signal an ongoing subclinical or non-motor epileptic event masquerading as NMS-PD.
How Is Parkinson Disease Diagnosed
Parkinson disease can be hard to diagnose. No single test can identify it. Parkinson can be easily mistaken for another health condition. A healthcare provider will usually take a medical history, including a family history to find out if anyone else in your family has Parkinsons disease. He or she will also do a neurological exam. Sometimes, an MRI or CT scan, or some other imaging scan of the brain can identify other problems or rule out other diseases.
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What Type Of Pain Occurs With Parkinsons Disease
The types of pain associated with Parkinsons include: aching or burning pain from muscles or skeleton, sharp pain from a nerve or nerve root, numbness or pins and needles pain also radiating from a nerve or nerve root, pulsing or aching pain that results from tightness or ongoing twisting and writhing movements , restlessness caused from akathisia, and sudden, sharp burning pain that occurs for no known reason.
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