Tremor Patient Markedly Improved 6-months After Gamma Knife Radiosurgery

This 73-year-old left-handed man had complained of progressively worsening tremor for more than 25 years.    He had become unable to write or (actually more of a concern to him) use chop sticks.

He was evaluated in the multidisciplinary tremor clinic at Monmouth Neuroscience Institute in March 2013.  We determined that he had already failed to respond to, or had side effects from, the oral medications usually used to treat tremor.  He was not a good candidate for deep brain stimulation because of previous bran surgery and cognitive impairment.

He  underwent gamma knife radiosurgery to the R thalamus in April 2013.  There were no side effects.

He started to see significant improvement in L sided tremor during the fall of 2013, and by October was able to use chop sticks again!

Click here to find out more about the program.
Click here for contact information.

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Deep Brain Stimulation for Essential Tremor

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We have already blogged about “benign” essential tremor.

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Here is a recap of the patient featured in one of those previous posts. He has a long history of worsening essential tremor, which has not responded to oral medications, and has made it impossible for him to hold a cup or write with a pen:

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He decided to undergo deep brain stimulation, a procedure where tiny electrodes are placed into deep nuclei inside the brain. When these electrodes are activated, they cause an interruption in the brain circuits which cause tremor:

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Here he is, after surgery, with the electrodes switched off:

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Here he is with the electrodes to both sides of the brain switched on, see how much better his tremor is, particularly on the right side:

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He can write and hold a cup for the first time in >10 years.

These same pathways can be inactivated by gamma knife radiosurgery in tremor patients who cannot undergo deep brain stimulation because of blood thinners, dementia or some other medical problem.

A new kind of stem cell treatment for Parkinson’s Disease?

ParkinsonsResearch

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First, what is Parkinson’s Disease?

Parkinson’s disease (PD) is a degenerative disorder of the central nervous system, characterized by the death of dopamine-generating cells in the substantia nigra, leading to neurologic symptoms including tremor, rigidity, slowness of movement and difficulty with walking.  Traditionally a clinical diagnosis, uncertain cases can now be more readily confirmed using a DaTscan.

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Early PD, showing L>R rest tremor, awkward movement of the L hand, rest tremor walking, and increased tone in the L arm:

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More advanced PD, showing stooped posture, rest tremor, slow hesitant gait and difficulty turning, and poor postural reflexes (risk of falls).

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How is it usually treated?

Modern treatments are effective at managing the early motor symptoms of the disease, by:

1. Taking extra dopamine, in the form of the precursor drug L-Dopa,

2. Taking MAO-B or COMT inhibitors, which inhibit the breakdown of dopamine, or

3.  Taking synthetic dopamine agonist drugs, which bypass dopamine, and bind directly to the dopamine receptors.

Patient with moderately severe PD, fist untreated (left panel), then after taking L-Dopa medication (right panel).

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Then what happens?

Unfortunately, as the disease progresses, patients develop motor complications characterized by involuntary movements called dyskinesias and fluctuations in the response to medication.  As this occurs, PD patients a can change from phases with good response to medication and few symptoms (“on” state, center panel in video below), to phases with no response to medication and significant motor symptoms (“off” state, left panel in video below), then to dyskinesias (right panel in video below).  It becomes harder and harder to keep the patient “on” (middle panel) with medical treatment.

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What about surgery for PD?

Deep brain stimulation (DBS) surgery to implant a medical device called a brain pacemaker in to the subthalamanic nucleus or globus pallidus can still be an option for PD patients with significant motor fluctuations, as long as they do not have dementia.

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So, we still need more treatment options! What about stem cells?

Current therapies do improve motor symptoms, but they become less effective with time, and do not address the non-motor features of the disease, including dementia, speech and swallowing difficulties, and the gait/balance problems.

In the hope of finding a better treatment, investigators have been trying to replace dopamine deficiency in the brains of PD patients by introducing embryonic stem cell transplants since the 1980s. Some patients improved, but results were very variable, with many patients showing no benefit, and others developing uncontrolled dyskinesias.

One of the problems is that these foreign transplanted cells are attacked by the PD patient’s immune system. There is also a concern that the implanted embryonic stem cells may undergo a transformation in the PD patient’s brain and grow into cancerous tumors.

However, there’s a brand new study about to start at the Scripps Research Institute in La Jolla California: 8 PD patients have undergone removal of small patches of their own skin, which have been turned into a new kind of stem cell that acts like embryonic stem cells, called induced pluripotent stem cells (IPS), and can then be injected back in to the brain.  The main advantage of IPS cells over embryonic stem cells is that they are less prone to rejection by the patients’ immune systems, because the transplanted cells come from the individuals themselves.

Ultimately, the hope is that implanted the stem cells will replace the degenerated cells in the patients’ brains, and start producing dopamine in a more physiologic way, treating all of the effects of PD without the side effects of oral medications.

Only time will tell if this IPS treatment is effective, or if we need some other stem cell strategy to treat PD.  We do know that a lot of PD patients and their families and friends are waiting with baited breath.

Find out more about the IPS for PD study here.

Find out more about stem cell therapy for PD from the Michael J. Fox Foundation.

Stereotactic radiosurgery for obsessive compulsive disorder, Phineas Gage meets the Jetsons.

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Small studies have shown that gamma knife stereotactic radiosurgery can relieve symptoms in as many as 50% of patients with obsessive-compulsive disorder (OCD) who got no help from conventional behavioral or medical therapies.

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What is OCD?

OCD is an anxiety disorder in which people have unwanted and repeated fearful thoughts (obsessions) that drive them to perform repeated behaviors (compulsions) to temporarily relieve the associated anxiety.

Examples of OCD include excessive hand washing or cleaning, repeated checking and nervous obsessive rituals like such as opening and closing a door a certain number of times before entering or leaving a room.

Anxiety from OCD and the resultant obsessive ritualistic behaviors can be alienating and time-consuming, leading to emotional and financial distress.

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Symptoms of OCD can be ameliorated by medications, such as serotonin reuptake inhibitors, and behavioral therapy.  However, many severely affected patients remain unable to function normally despite these interventions, leading them to look for more effective or permanent solutions to this difficult problem.

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Surgery for psychiatric disorders.

Phineas Gage (1923-1960) survived an accident in which a pole impaled his head going through his left cheek, destroying his eye, through the frontal part of his brain, and back out the right top part of his skull.
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Before the accident, he was described by his friends as a friendly, calm, caring man.  After the accident, he became bad mannered, aggressive, foul-mouthed, and anti-social to the point where he could no longer hold a job and none of his friends wanted to associate with him anymore.

His skull was saved and later analyzed to plot the trajectory of this pole through his skull, finding that the rod mostly damaged the middle region of the frontal lobes.

This and other cases of medial frontal lobe lesions causing similar changes in behavior led to the conclusion that this part of the brain’s function is related to normal social  social behavior

Surgical frontal lobotomy was first performed in the 1935, and lobotomized patients showed a decrease in agitation, anxiety, and depression.  Walter Freeman and James Watts spread the technique of lobotomy across America in the 1930 and 40s, and it became considered as a quick fix for dealing with overcrowded insane asylums.

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Ultimately the procedure was conducted using an “ice pick” inserted into the frontal lobe through the orbit under a brief period of unresponsiveness induced by ECT.

However, with the advent of psychotherapeutic drugs and increasing evidence for the horrors and limited therapeutic effects of lobotomy, the surgery lost popularity, almost becoming completely extinct.

Nevertheless, the important influence of the frontal lobes on social behavior was not forgotten, and more recent PET studies have further reinforced the influence of this brain region area in OCD:

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PET study showing increased activity in the frontal lobes in a OCD patient compared to a normal control.

There has been a limited comeback of psychosurgery, initially the form of less invasive non destructive  surgical techniques like the anterior cingulotomy (designed just to sever the connections between the frontal lobes and the underlying subcortical structures) still used for patients with severe OCD and depression refractory to conventional therapies.

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Gamma knife for OCD.

Activated deep brain stimulation electrodes placed into the anterior limb of the internal capsule can also interrupt the circuits than connect the frontal lobes to the rest of the brain and ameliorate OCD behavior:

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Gamma knife radiosurgery can create permanent lesions in these same regions of the brain, leading to Permanent lesions resulting in long-lasting benefit to OCD patients without the need for implanted hardware.

A recent study published in Neurosurgery by Kondziolka et al (click here for link) demonstrated the long-term benefit of bilateral gamma knife lesioning to the internal capsule in three patients with OCD intractable to conventional medical therapies.

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Gamma knife radiosurgery for OCD. Left – MRI showing the lesions resulting from the procedure. Right – clinical improvement in na OCD rating score in all three patients after surgery (lower score = better).

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Where can you get help and more information?

The International OCD Foundation has a website with more information on medical therapies, psychosurgery, DBS and gammaknife radiosurgery for OCD.