Advanced MRI scans may help treat essential tremors and Parkinson's disease

Researchers at UT Southwestern Medical Center have recently developed MRI techniques used to more precisely target a small area in the brain linked to Parkinson's disease and essential tremor. This may lead to better outcomes without surgery and with less risk of negative effects of treatment of tremors and Parkinson's disease.

The study have been published in the journal Brain.

The research describes recently refined MRI methods designed to allow neuroradiologists to zero in on a pea-sized region in the brain's thalamus involved in movement. Using the images, doctors then can use high-intensity focused ultrasound (HIFU) to ablate, or burn away, problem tissue, says Bhavya R. Shah, M.D., first author of the study and an assistant professor of radiology and neurological surgery at UT Southwestern's Peter O'Donnell Jr. Brain Institute.

"The benefit for patients is that we will be better able to target the brain structures that we want," Shah says. "And because we're not hitting the wrong target, we'll have fewer adverse effects." The procedures are already Food and Drug Administration-approved for use in patients, and UTSW plans to begin employing them to treat patients when its Neuro High Intensity Focused Ultrasound Program opens this fall.

Adverse effects from imprecise targeting include problems walking or slurring words. While such effects are usually temporary, they can be permanent in 15 to 20 percent of cases, says Dr. Shah.

According to the National Institutes of Health, essential tremor affects up to 10 million Americans and Parkinson's disease impacts more than 1 million. Both are neurologic diseases thought to have genetic links. The first line of treatment for the involuntary trembling or shaking seen with these diseases is medication. However, approximately 30 percent of patients do not respond well to drugs, according to the study.

In the late 1990s, neurosurgeons began using a procedure called deep brain stimulation, opening the skull to permanently implant metal electrodes that could then be stimulated via a battery pack.

About a decade ago, a new MRI-guided procedure emerged that uses high-intensity ultrasound waves to heat and eliminate a small section of the thalamus linked to the disorders. MRI-guided HIFU is currently approved for treatment of essential tremor and tremors seen in Parkinson's disease patients. The outpatient procedure does not require opening the skull, and the patient is awake while it is performed, says Dr. Shah. "No cuts. No anesthesia. No implanted devices."

A challenge in both procedures has been locating the precise area inside the brain's thalamus to treat - the pea-sized ventral intermediate nucleus, says Dr. Shah.

Traditionally, doctors have relied on either landmarks or maps of the brain drawn from cadavers to help them pinpoint the correct location. However, every brain is different, Dr. Shah says, and tiny errors can lead to damage in surrounding tissue, or to missing portions of the correct target.

Three newly refined MRI techniques are better at delineating the target tissue, according to the study.

The most widely studied and perhaps most promising imaging method is called diffusion tractography, says Dr. Shah. It creates precise brain images by taking into account the natural water movement within tissues.

The other methods described are quantitative susceptibility mapping - which creates contrast in the image by detecting distortions in the magnetic field caused by substances such as iron or blood - and fast gray matter acquisition TI inversion recovery - which operates much like a photo negative, turning the brain's white matter dark and its gray matter white in order to provide greater detail in the gray matter.

Dr. Shah and his team plan to participate in a multicenter clinical trial with collaborators at the Mayo Clinic in Rochester, Minnesota, testing the diffusion tractography method in patients.

 

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Causes and treatment for internal vibrations

Internal vibrations, also known as internal tremors, can affect people with Parkinson's disease, multiple sclerosis, or essential tremor. Internal tremors are not harmful, but they be can be worrying and may interfere with a person's daily life.

 

Internal tremors are shaking sensations felt inside the body. They occur without visible movement, which external tremors produce.

A person may experience internal tremors in the trunk, arms, legs, or internal organs.

In this article, we look at the causes and treatment of internal tremors.

Causes

Internal tremors can occur in the trunk or the limbs.

People with Parkinson's disease (PD), multiple sclerosis (MS), or essential tremor (ET) may experience internal and external tremors.

The causes of internal tremors are not well understood, and current research is limited. However, doctors tend to believe that these tremors stem from the same neurological causes of external tremors.
A study published in 2017 found a link between tremors and social anxiety. Some researchers have also suggested that internal tremors may produce physical movement too slight to detect.

Authors of a 2016 study have suggested that internal tremors are early, unusual symptoms of movement disorders, such as PD. Other researchers have proposed that anyone can experience internal tremors, but they are more pronounced in people with PD, MS, and ET.
Below, find more information about PD, MS, and ET, the three most common causes of internal tremors.

Parkinson's disease

PD is a neurological disease that results from the loss of dopamine-producing brain cells. It usually occurs in people over 60 years old.
People with PD may experience some of the following symptoms:

• slowness of movement
• external tremors, including visible trembling in the hands, limbs, face, and jaw
• internal tremors
• stiffness of the arms, legs, and trunk
• poor coordination and balance

These symptoms may progress quickly or slowly, and they can make daily activities difficult. Tremors are not always the most evident symptom of PD, though many people with the condition have tremors.
Initially, a person may only experience a tremor in one limb. As the condition progresses, the tremor can spread to both sides of the body. Strong emotions and stress can make tremors worse.

Treatments for PD

There is no cure for PD. It is a chronic condition that progresses over time. However, there are several treatment options.
A doctor may prescribe a combination of levodopa and carbidopa to replenish the brain's dopamine supply. This can help to treat advanced PD.
Other drug-related options include bromocriptine, pramipexole, and ropinirole.
A doctor may recommend surgery for people who do not respond to medication. The primary type is called deep brain stimulation (DBS).
During the procedure, a surgeon implants electrodes in a person's brain. These stimulate targeted areas to alleviate some symptoms of PD. DBS can also reduce the need for certain drugs, and this may especially benefit people experiencing unpleasant side effects.

Multiple sclerosis (MS)

Damage to the nerves characterizes multiple sclerosis.

MS is a chronic condition that affects the central nervous system (CNS).
Many experts believe that in a person with MS, the immune system attacks and damages the body's nerves.
This can affect many parts of the body, and it can have a significant impact on a person's quality of life.
Symptoms of MS usually develop between the ages of 20 and 40. They can include:

• blurred or double vision
• color blindness
• blindness in one eye
• muscle weakness
• poor coordination and balance
• a sensation of numbness or pins and needles
• pain
• speech difficulties
• internal and external tremors
• dizziness

Around half of the people with MS also experience difficulty with:

• memory
• attention
• concentration
• judgment

A person may also experience tremor.

Treatment of MS

There is currently no cure for MS, and its severity varies from person to person.
Disease-modifying therapies (DMTs)
In the past, doctors considered MS untreatable, but new drugs and treatment options are changing the outlook.
Current guidelines from the American Academy of Neurology (AAN) advise doctors to start prescribing a type of medication known as disease-modifying therapy (DMT) as soon as possible after a diagnosis.
With early use, these drugs appear to reduce the numbers of flares that a person experiences in relapsing-remitting MS (RRMS), and they may slow the progression of the disease.
Examples include:

• injectable interferon beta-1a and 1-b, such as Avonex and Extavia
• injectable glatiramer acetate, for example, Copaxone and Glatopa
• oral medications, such as siponimod (Mayzent) and fingolimod (Gilenya)
• infusions, including alemtuzumab (Lemtrada) and ocrelizumab (Ocrevus)

Mitoxantrone is an older DMT that can have severe adverse effects. A doctor will only prescribe it if a person has severe symptoms and if the possible benefits outweigh the risks for the individual.
Anyone who has been using mitoxantrone for some time should ask their doctor about newer drugs that may be safer and more effective.
Flares and symptoms
A person will take a DMT regularly, whether they are experiencing a relapse or not.
When flares occur, a doctor may prescribe:

• steroid injections to reduce inflammation and help manage severe symptoms
• specific medications to help with specific symptoms, such as weakness and muscle spasms

A doctor may prescribe muscle relaxers or tranquilizers for people with sustained muscle stiffness and spasticity.
Treatment for tremor
Drugs to help relieve tremor include:

• isoniazid, for example, Laniazid or Nydrazid
• clonazepam, for instance, Klonopin, Rivotril or Syn-Clonazepam

Non-drug therapies
Exercise, occupational therapy, and physical therapy can also help. A doctor can advise on an exercise plan to suit an individual's needs.
They may also advise on assistive devices that may help, such as a walking cane.
The symptoms and progress of MS vary widely between individuals. Each person will make a treatment plan with their doctor to suit their needs.

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Essential tremor

ET is the most common type of abnormal tremor.
The condition is sometimes associated with mild degeneration of some of the cerebellum. This is the part of the brain that receives information needed to regulate the quality of a person's movements.
The cerebellum receives this information from other parts of the brain, the spinal cord, and the body's sensory systems.
People with ET may experience unintentional, rhythmic movements, most commonly a hand tremor. The tremor may also affect the head, tongue, limbs, trunk, and the ability to speak.
Symptoms can develop at any age, but they usually become noticeable in people over the age of 40. Triggers of ET can include:

• stress and anxiety
• heightened emotions
• fever
• feeling physically tired
• low blood sugar

The tremor usually appears on both sides of the body, but it is often more noticeable in the dominant hand.

Treatment of ET

While there is no cure for ET, medications can help to reduce symptoms. These can include beta-blockers or anti-convulsants.
Some people with ET find physical, occupational therapy, and DBS helpful. Treatment plans often involve reducing triggers, such as caffeine and other stimulants.

Treatment

A doctor will prescribe treatment for internal tremors according to the cause.

There are currently no diagnostic tests for internal tremors. However, anyone experiencing a tingling sensation, shaking, muscle weakness, or poor coordination should speak with a doctor.
For people with internal tremors, doctors may recommend treatments similar to those for other movement or neurological disorders.
However, the severity of internal tremors can vary from person to person, and some may find that no treatment is necessary.
When PD, MS, or ET is responsible for internal tremors, doctors will aim to treat the underlying condition.
Treatments for internal tremors can include:

• reducing anxiety and stress
• avoiding dietary stimulants, such as caffeine
• avoiding intense exercise and heat

For some people, doctors may recommend DBS or medications similar to those for PD, MS, and ET.

Outlook
While internal tremors are not harmful, they can be disconcerting and may interfere with daily activities.
PD, MS, and ET are the most common causes of internal tremors. For many people, treatments for tremors will be similar to treatments for these neurological conditions.
Avoiding known triggers, such as stress or stimulants, can also help.

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Mesh electronics could make brain stimulation the new therapeutic norm

Implantable brain electrodes have been around for quite some time now, both for diagnosing and treating neuropsychiatric conditions like Parkinson’s disease. However, one limitation of conventional probes is their size and rigidity, compared to the soft, gelatinous consistency of the brain.

A new research paper offers a revolutionary solution: mesh electronics, which allows personalized electronics that mimic the neuron’s shape, size and texture, to be created for any brain-related disorder.

A traditional deep brain stimulation electrode (top panel) provokes an immune response in the brain while a mesh electronic interface (bottom panel) does not. The size and rigidity of the DBS electrode result in chronic inflammation causing glial scarring between brain tissue and electrode, degrading the neural interface. Mesh electronics evade the immune response due to cellular and sub-cellular features and bending stiffness resembling the brain itself.

Why are implantable electrodes needed?

All neuroscientists agree that the foundation of cognition is the brain, including thinking, emotions, memory, judgment and decision-making. The same applies to all kinds of brain disorders, according to researcher. She became interested in this field after witnessing a 500 ms pulse of electricity conferring an impulsive risk-taker with the momentary ability to make a safer choice, without even knowing how it occurred. The alteration of cognitive thinking, in other words, happened below the level of consciousness.

However, it is difficult for scientists to trace behaviors to specific neurons or brain areas that are dysfunctional, though this could help discover where illnesses such as addiction, Alzheimer’s or Parkinson’s disease originate. Therapy for these conditions is currently limited to drugs and electrical stimulation via implantable electrodes.

Medical treatment is mostly with neuroactive drugs like L-dopa in Parkinson’s disease, which stills the quivering movements that make voluntary actions so difficult. However, the off-target or nonselective inhibition of L-dopa actions causes severe and even unacceptable side effects, on various body systems, including nausea, depression or arrhythmia.

The failure of drug treatment is an indication for electrode implantation to provide Deep Brain Stimulation (DBS). These work by sending automated pulses of electrical energy to paired implants, each about the size of a pencil, which is huge with respect to the brain. These FDA-approved electrodes must be implanted while the patient is awake and able to guide the surgeons during their calibration of the required current intensity that will stop the tremors.

Describing the effect of DBS, researcher  marvels, “Almost instantly, you can see the person regain control of their limbs.” However, these electrodes aren’t quite foolproof either, causing inadvertent stimulation of other brain areas at times, which causes disturbing adverse effects such as speech impediments. Just as bad, the brain has an active and vigilant immune system composed of neuroglial cells, which eventually disrupts the electrode’s efficient functioning by smothering it in a protective glial covering. This may also grow so large as to mechanically affect or even kill neighboring neurons. The limited device life caused by unnecessary continuous operation, and the lack of feedback which hampers operational efficiency, are other limitations. While many of these are being individually overcome, the rigid and imprecise neural interface is a basic restriction on further progress.

Implantable rigid electrodes vs mesh electronics

The increased rigidity of even the softest conventional probes causes several problems: chronic inflammation and scarring, mismatched stiffness which leads to a movement of the probe and neuron away from each other relatively quickly, and hinders tracking of the same neuron or circuit; and the solid probe lies uneasily on the quite differently shaped brain surface. This topological difference pushes neurons away from their rightful place, while also preventing repair of broken synaptic connections and blocking the free movement of chemicals in the brain environment.

Neuron-like electronics (red) mimic the shape, size, and flexibility of neurons (green), enabling them to maintain symbiosis with native brain tissue

This is where Lieber has made a huge difference with ultra-flexible mesh electronics, which promise to deliver what he calls “precision electronic medicine”. These hardly activate an immune response, but remain very close to the cells they are intended to spy on. As such, they offer a way to obtain reliable information on the communication between individual neurons or its breakdown. This could help elucidate cross-talk between specific subsets of neurons. It is also necessary if any degree of precise regulation is to be achieved via feedback circuits, which requires a two-way transmission of information through the neural device. All this could produce a more accurate and detailed map of the brain circuitry. This could potentially open the door to the successful treatment of any brain disorder.
Moreover, Lieber’s mesh electrodes have a peculiar benefit in their ability to guide developing neurons to the right place, such as injured areas as following a stroke. They could potentially encourage directed neuronal migration to rebuild injured or degenerated areas, and integrate these cells into the right circuits, using differentially modulated successive pulses of electricity.

The risk – and the future

Lieber envisages other mind-blowing advances: special electrodes could be designed to provide precise control over prosthetic or paralyzed limbs, and this could serve as an efficient substitute for damaged brain connections, as well as autocalibration of the signal based on live feedback. He says, “If you could actually interact in a precise and long-term way and also provide feedback information, you could really communicate with the brain in the same way that the brain is communicating within itself.”

Other major would-be players in this field include Neuralink from Elon Musk, which aims at assisting paralyzed patients by providing a mind-computer interface so they can use their computers; Facebook which is looking at texting via word imaging; and Kernel from Brian Johnson, which is focused on increasing cognitive abilities. Lieber emphasizes that his desire is to help people who are sick – and even to prevent the aging-related decline in memory if possible. However, strict ethical control is mandatory lest such mind-altering power be misused. While the benefits are obvious, such as helping people overcome addiction or obsessive-compulsive disorder, the downside is equally plain – the patient’s thoughts are laid open to scrutiny, despite being the innermost stronghold of a person. Secondly, it raises the risk of putting memory, learning ability and other  desirable mental traits up on sale, for people who would like to enhance their brain capability.

Meanwhile, scientists like Lieber and Patel continue to refine mesh electronics, by increasing the number of electrodes that can be implanted, designing live feedback systems to enable continuous recalibration, and improving the processing of the voluminous data collected by the electrodes. They urge a blending of multiple disciplines to help advance neurotechnology to the point where it breaches the limit of machine-mind interface. Patel says, “The next frontier is really the merging of human cognition with machines.”

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Parkinson's disease: Popular western medicine Apomorphine now launched in Bengaluru

In a boon to patients in the middle stages of Parkinson’s Disease, a private hospital in Bengaluru, in association with UK-based specialty pharmaceutical company, has launched Apomorphine for the first time in India. Apomorphine, available both as injections and infusion pumps, has been popular in the West for over 15 years in the management of Parkinson’s, but Indian patients could not benefit from it until now because of a lack of regulatory approvals. Now, it will be given on compassionate grounds to a select number of patients.

This powerful new drug stimulates the production of dopamine by nerve cells in the brain, providing quick and effective relief to patients and improving their quality of life. A Parkinson’s Disease and Movement Disorders Specialist,  where the drug will be available, said, “Currently in India, patients of Parkinson’s have only two options: either oral treatment for the early stages of the disease, or very expensive Deep Brain Stimulation (DBS) surgery for advanced stages. There was no treatment for the middle stages of the disease. Most patients in India cannot afford DBS. This procedure is also not a choice for all ages or stages of Parkinson’s Disease.”
“Introduction of apomorphine in India has given an important medical option to doctors in the middle stages of the management of Parkinson’s Disease,” Dr.  said. Dr.  said once the Drug Controller General of India approves the drug it will be available at other hospitals. The prevalence of Parkinson’s Disease in India is 300-400 out of 100,000, which is expected to double by 2030.

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Brain implant gives patients control over Parkinson's disease

Parkinson's disease can be challenging even in its early stages.

But one Texas woman has been able to regain control of her life.

She was diagnosed with the neurological disease five years ago at age 40.

Her tremors and muscle stiffness got so bad, she couldn't cook or even wash her hair.

So, last October she decided on deep brain stimulation.

"A lot of times, these patients are trapped in their bodies because they can't do things they want to do," said the Dr. "This surgery allows them to go back to a more normal life."

During the surgery, electrodes are implanted into the brain while another device, like a pacemaker, goes near the collarbone. It sends impulses to the brain which block the abnormal nerve signals that cause tremors.

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