Example: Stimulation Of The Vagus Nerve To Treat Alzheimer Disease
Alzheimer disease is the most common cause of dementia, affecting more than 5 million individuals in the United States. AD clinical decline and pathological processes occur gradually. Dementia is the end stage of many years of accumulation of pathological changes, which begin to develop decades before the earliest clinical symptoms occur. A pre-symptomatic phase occurs first, in which individuals are cognitively normal but some have AD pathological changes. This is followed by a second prodromal phase of AD, commonly referred to as mild cognitive impairment . The final phase in the evolution of AD is dementia, defined as impairments that are severe enough to produce loss of function.
Until recently, a definitive diagnosis of AD could only be made at the autopsy or by brain biopsy of an individual, by identifying amyloid plaques and neurofibrillary tangles in the association regions of the individual’s brain, particularly in the medial aspect of the temporal lobe. Additional evidence of AD from an individual’s autopsy or biopsy would include the presence of the following: the granulovacuolar degeneration of Shimkowicz, the neuropil threads of Braak, and neuronal loss with synaptic degeneration.
Amyloid precursor protein is a membrane protein that is concentrated in the synapses of neurons. APP is the precursor molecule whose proteolysis generates ß-amyloid , a peptide whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of AD patients.
Why Is This So Important
While this procedure does not provide a cure for Parkinsons disease, there is now a less invasive option for patients suffering with medication-induced dyskinesia or severe motor deficits, said UVA Health neurosurgeon Jeff Elias, MD. Being only one of 37 medical centres in the United States that are capable of providing this non-invasive procedure, UVA Health is offering pioneering research in the battle against Parkinsons. By offering an entirely new and non-invasive treatment, focused ultrasound is opening new doors for Parkinsons research and patients.
While this procedure does not provide a cure for Parkinsons disease, there is now a less invasive option for patients suffering with medication-induced dyskinesia or severe motor deficits
Chairman of the Focused Ultrasound Foundation, Neal F. Kassell, MD addressed the FDAs decision stating that, the Foundation has long considered the brain to be a vanguard target for focused ultrasound, and this ruling by the FDA is a huge win for both providers and patients,
Signs & Symptoms: Is It Essential Tremor Or Parkinsons
In order to start managing your condition and receive the treatment you need, you should be aware of the most common signs and symptoms as well as the key differences between essential tremor andParkinsons. After all, the first step in getting care as early on as possible is self-awareness that you might be suffering from one of these conditions.
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Limitations Side Effects And Long
Baltuch cautions, however, that focused ultrasound thalamotomy is not without risk or side effects, there are limitations, and there are not yet long-term studies.
- Side effects: Side effects include difficulty walking or unsteadiness following the procedure, along with tingling or numbness in the lips or fingers. Most issues resolve within months.
- Limitations: Currently, only one side of the body can be treated. Earlier forms of surgical ablation sometimes resulted in speech difficulties, so for now, the FDA has limited treatment to one side of the brain. The side that controls the patient’s dominant hand is usually targeted. INSIGHTEC is exploring bilateral treatment in medical centers outside the U.S. In addition, while treatment can reduce or eliminate tremors on one side of the body, it does not stop other symptoms of Parkinson’s or slow disease progression.
- Long-term studies: Because five- and 10-year studies have not yet been conducted, “We dont yet long-term effectiveness” of focused ultrasound thalamotomy for tremor-dominant Parkinson’s and essential tremor, says Baltuch. “The published data show that this may not be as effective in tremor reduction as, potentially, deep brain stimulation can. And, although it’s non-invasive, you’re still making a thermal lesion .”
How Can I Be Assessed For Suitability For This Treatment
Patients with various types of tremor, as well as Parkinsons Disease and dystonia, may be assessed for suitability for Neuravive.
Typically the assessment includes:
- Diagnostic confirmation of the type of movement disorder
- Measurement of skull density on CT, and brain morphology on MRI
- Assessment with the standard rating scales
- Consideration of quality of life issues
- Assessment of other health problems which may be relevant
The assessment team includes a neurologist, neurosurgeon, neuroradiologist, and sometimes a rehabilitation physician and neuropsychologist.
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Environmental Factors And Exposures
Exposure to pesticides and a history of head injury have each been linked with PD, but the risks are modest. Never having smoked cigarettes, and never drinking caffeinated beverages, are also associated with small increases in risk of developing PD.
Low concentrations of urate in the blood is associated with an increased risk of PD.
Different medical drugs have been implicated in cases of parkinsonism. Drug-induced parkinsonism is normally reversible by stopping the offending agent. Drugs include:
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Causes: Parkinsons Vs Essential Tremor
The cause is largely unknown for both Parkinsons and essential tremor. However, there are theories about what may cause these conditions.
In regards to essential tremor, John Hopkins Medicine notes that there is a theory that the condition may be caused by miscommunication between the cerebellum and other parts of the brain. There is also believed to be a genetic predisposition for developing essential tremor. You may be 50% more likely to develop essential tremor if your parent has the condition.
It is also important to note that certain factors can also cause other types of tremors. For example, according to the National Institute of Neurological Disorders and Stroke, certain medications, thyroid overactivity, and toxins like lead and mercury can produce tremors that might be confused with this condition.
In regards to what causes Parkinsons disease, the direct cause as to why specific individuals develop Parkinsons is unknown. However, what happens within the body that causes Parkinsons symptoms to manifest, is the gradual loss of brain cells that are responsible for producing dopamine. When this happens, it can interfere with normal body movement, leading to patients to exhibit the common symptoms of Parkinsons.
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Dementia With Lewy Bodies
- Dementia with Lewy bodies is a progressive, neurodegenerative disorder in which abnormal deposits of a protein called alpha-synuclein build up in multiple areas of the brain.
- DLB first causes progressive problems with memory and fluctuations in thinking, as well as hallucinations. These symptoms are joined later in the course of the disease by parkinsonism with slowness, stiffness and other symptoms similar to PD.
- While the same abnormal protein is found in the brains of those with PD, when individuals with PD develop memory and thinking problems it tends to occur later in the course of their disease.
- There are no specific treatments for DLB. Treatment focuses on symptoms.
Action Versus Resting Tremors
Almost all tremors are either considered action tremors or resting tremors. Action tremors are tremors that happen the most when you contract a muscle or try to hold a certain position.
Resting tremors, on the other hand, happen when a body part is at rest. Resting tremors are frequently related to PD, but action tremors are more likely to suggest other conditions.
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What Is The Treatment Process
Multielectrode Transcranial Electrical Stimulation
Multielectrode tES is an improved version of tES with shared mechanism but multielectrode montages. Currently, multielectrode tES consists of multitarget tES and high-definition tES . Multitarget can modulate multiple regions of interest , while hd-tES aims to achieve higher focality by minimizing the electrodes size and multiplying return electrodes . These two techniques are usually incorporated as a combination in experiments. In PD studies, up to date, only multitarget tDCS and hd-tDCS have been tested in clinical population.
However, skepticism still exists in the assumption that multitarget tDCS would improve FOG performance, as a subsequent clinical trial with a subject population of 70 PD patients revealed the opposite results. After 2 weeks of intense treatment containing 10 stimulation sessions and 5 weeks of mild treatment with 5 stimulation sessions, despite some secondary performance improvements, no significant differences in FOG provoking test and FOG severity score were found .
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Outlook For Closed Loop Transcranial Electrical Stimulation
Although closed-loop tES studies toward PD are few, adaptive stimulation schemes have gained vast attention since they can deliver individual- or circumstance-specific modulation. Self-adaptive individualized closed-loop scheme can achieve higher efficacy and closed-loop tES schemes in the future might also be able to automatically switch on when symptoms occur, like closed-loop DBS.
Another serious technical problem for closed loop tES is the time delay between detection of changes in brain conditions and the response to stimulus. For symptoms with a short provoking duration, the time delay in response might just miss the period of symptoms and become ineffective. Future studies might employ machine learning to predict the occurrence of symptoms so that more precise stimulation could be provided. In addition, using a brain machine interface can provide a quicker stimulation response. For example, in a chronic pain study that used BMI in mice to monitor and stimulate the brain, the time delay between characteristics detected and stimulation response was minimized thus, the pain could be released even when recognizing acute pain signals .
Many studies have proposed numerous novel adaptive tACS and tDCS systems that proved to be safe and tolerable in healthy people . Building on these results, investigators could adopt those technologies in future closed loop tES studies in clinical PD populations.
Treatments For Essential Tremor
According to Harvard.edu, there are several actions that can be taken to help manage your essential tremor and minimize how they impact your daily life. First, lets cover treatment options:
As each patient is different, you and your doctor will need to decide what the best course of action is for you. You must weigh the pros and cons of each treatment option based on your lifestyle and how you think theyll impact your quality of life.
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What Are The Costs Involved With The Assessment For This Treatment
Consultations with the neurologist and neurosurgeon take place in their consulting suites and are billed at their standard specialist rates. This information, together with the likely Medicare rebates, will be provided to you before your booking is confirmed. In order to be certain that you receive a Medicare rebate, please ensure that you obtain a referral from your GP or neurologist.
The assessment process includes dedicated CT and MRI scans, both of which are undertaken at specific radiology clinics. The prices may vary according to which clinic, and this information will be provided to you at around the time of your initial enquiry.
A New Era For Parkinson’s Disease Treatment
“A diagnosis of Parkinson’s disease no longer automatically portends a future of extremely limited physical capabilities. Thanks to the commitment of researchers like Dr. Eisenberg and Dr. Fishmanand clinical trial participants like Steve Squirestreatment has expanded to include non-invasive options that significantly reduce certain symptoms within minutes and transform the lives of people who had been living with debilitating symptoms,” said Bert W. O’Malley, MD, President and CEO of the University of Maryland Medical Center.
“Our school of medicine researchers have established themselves as world leaders in pioneering MRI-guided focused ultrasound for many devastating brain diseases, including Parkinson’s and essential tremors,” said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “The stellar work of Dr. Eisenberg and Dr. Fishman has led to a new era in which this breakthrough modality has now become the standard of care for patients looking for less invasive treatments for their symptoms.”
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Fda Approval Of Focused Ultrasound Device Provides Patients With Novel Treatment Option Without Requiring Incision
A non-invasive ultrasound treatment for Parkinsonâs disease that was tested in a pivotal trial led by University of Maryland School of Medicine researchers is now broadly available at the University of Maryland Medical Center . The device, called Exablate Neuro, was approved in November by the US Food and Drug Administration to treat advanced Parkinsonâs disease on one side of the brain.
The approval was based on findings from the UMSOM clinical trial and effectively expands access to focused ultrasound beyond clinical trial participation.
When Its Not Parkinsons: Non
Everyone has some amount of tremor. Physiologic tremors are common, barely noticeable amounts of shakiness that worsen when people are stressed, anxious, or have had too much caffeine. As long as the tremors are not significant and do not affect your day-to-day activities, they may be completely normal.
Even tremors that are not normal are not always caused by Parkinsons. They can be caused by a range of other conditions, which together are known as movement disorders.
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When To See Your Doctor
Its easy to assume these problems have other causes, and they often do. But any of these non-motor symptoms can have a big impact on your overall quality of life.
Having one or more doesnt necessarily mean you have Parkinsons disease or that youll eventually develop it. But its worth consulting with your doctor.
Tell your doctor if youre concerned about having Parkinsons disease. Although theres no cure, there are medications to help control symptoms.
Potential Applications And Therapeutic Effects Of Nibs In Pd
There has been cumulative evidence supporting beneficial effects of TMS and tDCS in PD. However, several limitations have obscured the evidence-based generalizability of these results. Main limitations are wide methodological heterogeneity in study designs and exploratory designs with small sample sizes in the majority of the studies. As TMS research is significantly more advanced in terms of number of studies and Class I multicenter initiatives, TMS and tDCS therapeutic evidence will be revised separately.
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Transcranial Electrical Stimulation Combined With Drug
Since one limitation of pharmacologic therapy is side effects, it is intriguing to discuss whether the combination of tES and drugs would optimize improvements and lessen side effects at the same time.
In contrast to tDCS experiments where medication is controlled as baseline, in the study of Ferrucci et al., tDCS was provided as a supplementary intervention of levodopa to eliminate L-dopa-induced cognitive and motor impairments. M1 tDCS, cerebellar tDCS, and sham sessions are randomized for each subject, and each session was at least 1 month separated from another. Anodal tDCS was applied for 20 min in 5 consecutive days in each active stimulation session. Although no other cognitive or motor improvements were observed, both M1 and cerebellar tDCS led to a decrease in levodopa-induced dyskinesias in PD patients .
Example: Stimulation Of The Vagus Nerve To Treat Postoperative Cognitive Dysfunction And/or Postoperative Delirium
Postoperative cognitive dysfunction is a loss in cognitive function after surgery. The loss may include memory, the ability to learn, the ability to concentrate, and/or the ability to reason and comprehend. The cognitive decline may be subtle, such that psychological testing is needed to detect it, or it may be profound and obvious.
POCD does not refer to delirium that may occur immediately after surgery, but instead refers to cognitive loss that may persist weeks, months, or permanently after the surgery. However, postoperative cognitive dysfunction and postoperative delirium are not mutually exclusive. They may in fact have risk factors, mechanisms, and treatment options in common. Accordingly, background information pertaining to POD is presented below, after first discussing POCD and disclosing methods for treating POCD.
The pathophysiology of POCD has been investigated in view of the above clinical findings and in the context of cellular responses to surgery in general .
However, the site of transcutaneous vagal stimulation that XIONG et al suggest is the external auditory canal. This may not be as effective as stimulating at the site where vagus nerve stimulators are ordinarily implanted, namely, in the neck. Furthermore, XIONG et al do not suggest stimulation parameters that should be used. Accordingly, methods are disclosed here to better treat POCD patients. The methods counteract inflammation by any of the mechanisms shown in FIG. 8.
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