George Huntington, On Chorea

Huntington

George Huntington (1850-1916) was a medical practitioner in Dutchess County New York.

His father and grandfather had both been doctors, and his family had lived on Long Island since 1797.

He gave his classic presentation, “On Chorea”, at the Meiga and Mason Academy of Medicine in Middleport Ohio in 1972, and this was subsequently published in the Medical and Surgical Reporter of Philadelphia on April 13, 1872.

This took place just one year after he graduated from his medical training at Columbia University.

He later explained his interest in the condition that now bears his name:

Over 50 years ago, in riding with my father on his rounds, I saw my first case of the “disorder”, which is the way the natives always referred to the dreaded disease.  I recall it as vividly as though it had just occurred but yesterday.  It made a most enduring impression on my boyish mind, an impression which was the very first impulse to my choosing chorea as my virgin contribution to the medical lore.  Driving with my father through a wooded road leading from East Hampton to Amagansett we suddenly came upon two women both bowing, twisting, grimacing.  I stared in wonderment, almost in fear.  What could it mean?  My father paused to speak with them and we passed on.  Then my Gamaliel-like instruction began; my medical instruction had its inception.  From this point on my interest in the disease has never wholly ceased.

Huntington’s disease (HD) is now know to be caused by a genetic mutation.  It is inherited in an autosomal dominant fashion, so that any child of an affected person typically has a 50% chance of inheriting the disease.  The mutation is a triplet repeat, so the genetics of HD lead to anticipation, a phenomenon whereby the disease may begin earlier and more severely in each successive generation.

HD can present at any age, but most often begins around 35-44 years with psychiatric disturbance such as depression or forgetfulness.  Neurological manifestations such as unsteady gait and the  jerky body movements (chorea) noted by George Huntington come later, followed by a progressive dementia.

Genetic testing is available, but pre-symptomatic testing for family members, who are at increased risk for the disease, is controversial since there is no treatment for HD.

Find out more about HD from the Huntington’s Disease Society of America.

Gamma knife tremor patient comes back to get the other side done!

Our first tremor patient treated with gamma knife radiosurgery recently came back, one year later, to have the other side treated.
He has essential tremor, which was affecting both arms.
He had undergone treatment to the left brain for right sided tremor last year.
He was so pleased with his results, he recently came to have the right brain treated to address the left sided tremor.
Here is his most recent video.
Note the action and postural tremor on the left (untreated) side, and the fact that he has almost not residual tremor on the right (treated) side.

Click here to find out more about Gamma knife radiosurgery for tremor at the Monmouth Neuroscience Institute.

A “bionic” spoon for tremor patients

A new small handheld device for tremor patients was shown to stabilize a spoon and allow affected patients to eat without spilling their food in a recently published pilot study:

The device, which is similar to an electric toothbrush, consists of a detachable spoon, a motion-generating platform, a controller/sensor, and a rechargeable battery.  It detects the frequency of the patient’s tremor, and then counteracts that motion, to keep the spoon stable.

Patients in the study still had tremor, but they were less likely to spill their food when eating with the spoon.

The device is now commercially available, and costs around $295.

Lytico-Bodig Syndrome, You Might Get it From Eating Bats

Posted by Daniel Rubio, Drexel University College of Medicine Class of 2014

“A man” obsessing over “bats”…

“A man” eating “bats”…


The patients above are displaying symptoms resulting from a disease known as Lytico-Bodig Syndrome (LBS), a neurologic disease resembling amyotrophic lateral sclerosis (ALS/Lou Gehrig’s Disease), Parkinson’s disease, and Alzheimer’s disease.  The country with the greatest number affected is the US territory of Guam.  In fact, between the 1940-1960 it was the leading cause of death among the Chamorro people, a tribe found on the island of Guam.  The afflicted were usually between the ages of 25-40 years of age.

What’s up with the bats?

Although yet to be proven, it is believed that the high incidence of LBS is due to the consumption of fruit bat, a cultural delicacy on the island.  These fruit bats feed on specific fruits containing high concentrations of an altered amino acid called beta-N-methylamino-L-alanine (BMAA). BMAA is a known neurotoxin and is believed to be the cause of LBS.  BMAA is a protein building block that is incorporated into neuronal proteins to produce an abnormal form that creates clumps with neurons resulting in their dysfunction and death.

I don’t eat bat though?

I addition to the high concentrations found in the fruit bats on the island of Guam, multiple sources have been proposed leading to BMAA exposure within the United States.  Certain bacteria in fresh and salt waters produce BMAA; and, fish and crustaceans will concentrate BMAA within their tissues when they consume the bacteria as part of their normal diet.  It is believed that human consumption of fish and crustaceans in at-risk areas might increase the incidence of neurodegenerative diseases, like Alzheimer’s, Parkinson’s, and Lou Gehrig’s.  This association has been seen in many areas within the United States, especially around the gulf regions and around large bodies of water.  Click here for more details about this.

Am I more lytico or bodig?

Presenting symptoms exist along the continuum of lytico-bodig.  Patients on the lytico spectrum present more like ALS/Lou Gehrig’s disease.  These patients have muscle wasting/atrophy and accompanying weakness, paralysis of mouth and tongue, and an inability to swallow resulting in choking to death.  Over time, paralysis involves the breathing muscles requiring mechanical ventilation to help the patient breath and to prevent choking on secretions.  Lytico patients remain aware of their deterioration.  The form of LBS is fatal in all cases.

On the other end of the spectrum, patients with bodig presentations look more like Parkinson’s disease and Alzheimer’s disease patients.  Bodig patients present with “freezing” with progressive immobility with loss of starting purposeful movement and loss of spontaneous movement.  Progressive dementia with loss of speech and irrational behavior, including violence and rapid fluctuations in mood, are common.  Over time, patients are left in stiff and immobile postures with inability to speak and swallow.

How would I know if I had LBS?

Currently Lytico-Bodig syndrome is diagnosed based upon appropriate history and physical exam by a neurologist.  Definite LBS is declared in post-mortem autopsy.  However, there is research being done to develop rapid tests using cerebral spinal fluid analysis.

What can I do if I have LBS?

Treatment is mainly supportive as is based upon symptoms present, whether it’s Parkinson’s, Alzheimer’s, ALS, or a combination of the three spectrums of diseases.   The more the symptoms resemble Lytico, the greater the mortality: in patients with predominantly lytico-type symptoms the disease is practically 100% fatal.

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.

Do you take an antidepressant medicine? – If the answer is yes, you should know about serotonin syndrome

Post written by Dr. Hadi Razjouyan, PGY III Internal Medicine Resident at Monmouth Medical Center

pills

Introduction

Serotonin syndrome is a rare and potentially life-threatening toxic state caused by excessive serotonergic activity in the nervous system.
It was first described in 1960s in studies of antidepressant medications and classically consists of a triad of mental status changes, abnormalities of muscle tone, and autonomic hyperactivity. However, clinical manifestations can be diverse and nonspecific, leading to misdiagnosis. Most reported cases are in patients using multiple serotonergic drugs, or who have had considerable exposure to a single serotonin-augmenting drug:

serotonin1

Medications that may contribute to serotonin syndrome. (Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician. 2010 May 1; 81(9):1139-42).

Epidemiologic features

It can happen in all age groups.
Its incidence is rising as the number and use of available serotonergic drugs are increased in clinical practice.

Mechanism

Potential mechanisms include increased serotonin synthesis or release; reduced serotonin uptake or metabolism; and direct serotonin receptor activation. Addition of drugs that inhibit the cytochromes (e.g. CYP 2D6 and/or 3A4) to therapeutic regimens of selective serotonin reuptake inhibitors (SSRIs) could be another mechanism.
The majority of cases are iatrogenic from synergistic medication use, although cases of self-poisoning with serotonergic agents also occur.

Diagnosis

Diagnosis can be made using the Hunter Serotonin Toxicity Criteria:

serotonin2

Hunter’s rules for diagnosis of serotonin syndrome. (Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician. 2010 May 1; 81(9):1139-42).

Symptoms can include anxiety, restlessness, confusion, sweating, muscle spasm or rigidity, rapid back and forth eye movement, shaking, fever, rapid heart rate, vomiting and diarrhea.

Symptoms can develop rapidly, within minutes of taking the drug, however, most patients present within couple of hours after a medication change or overdose.

Differential Diagnosis

The primary differential diagnosis of serotonin syndrome includes malignant hyperthermia, neuroleptic malignant syndrome, and anticholinergic syndrome. A complete history of the drugs or substances is helpful in ruling out these conditions. It is necessary to rule out initiation or change of dosage of dopaminergic drugs and other possibilities, such as infection, metabolic disorder, substance intoxication, or withdrawal. Other potential diagnoses include heat stroke, overdose of sympathomimetic drugs, delirium tremens, meningitis, encephalitis, thyroid storm, sepsis, or tetanus.

Treatment

First, Recognize the disease
Next, Stop the offending agent(s)
In the meantime, Supportive care (treat hyperthermia, autonomic dysfunction)
Benzodiazepines may be used to treat agitation and tremor.
Sometimes may administer serotonin antagonists, cyproheptadine or chlorpromazine.
Patients with moderate or severe cases of serotonin syndrome require hospitalization.
Critically ill patients may require neuromuscular paralysis, sedation, and intubation.

Prognosis

If serotonin syndrome is recognized and complications are managed appropriately, the prognosis is favorable. The severity of the disease can range from mild to life-threatening situation. However, most cases are mild and do not require hospitalization and generally resolve within 1 to 3 days by withdrawal of the offending agent and supportive care. Patients with moderate and severe cases may require hospitalization.

Prevention

Awareness of physicians and patients of the potential for toxicity from serotonergic drugs.
Always tell any doctor who prescribes you about all medications, herbal products and street drug you take.
When starting new medicine, have the pharmacist check for drug interaction
Avoiding the combined use of serotonin-augmenting drugs.
If you are already on medicine, do not take a new herbal or over-the-counter medicine without first checking with your doctor

Warning

If you have any symptoms of serotonin syndrome, please call your primary care physician and inform him/her of your suspicion before taking any steps.

Deep Brain Stimulation for Essential Tremor

Essential-tremor-is-characterized-by-sporadic-and-postural-tremor-on-hands

We have already blogged about “benign” essential tremor.

xx

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:

xx

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:

xx

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

xx

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:

xx

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

xx

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.

xx

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

xx

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

xx

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).

xx

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.

xx

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.

xx

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.

DaTscan for Parkinson’s Disease

Parkinson’s disease has always been a clinical diagnosis.

512px-Sir_William_Richard_Gowers_Parkinson_Disease_sketch_1886_2.svg

And most patients who present with the typical unilateral rest tremor, associated with cogwheeling and rigidity are easily distinguished from essential tremor on clinical grounds (click here to review the differences).

However, some atypical cases can cause diagnostic uncertainty.   A 2009 study from the UK found that almost 50% of patients with tremor who were taking Sinemet (a medication used for Parkinson’s) prescribed by their primary care physicians, when examined by an experienced neurologist actually had essential tremor or some other diagnosis.

Autopsy studies have shown that almost 1/3 of patients diagnosed with Parkinson’s by neurologists during life actually had alternate pathological diagnoses at autopsy such as progressive supranuclear palsy or Cortico Basal Gangionic degeneration.

xx

A new radiological study, may help end some of this diagnostic uncertainty in difficult cases.

The DaTscan uses single-photon emission computed tomography (SPECT) after an injection of Ioflupane I-123 to demonstrate abnormal dopamine uptake in the basal ganglia in patients with Parkinson’s disease:

DAT

On the left an essential tremor patient showing symmetric dopamine uptake. On the right, a Parkinson’s patient showing asymmetrically reduced dopamine uptake.

xx

Here’s a patient we recently saw, with a right sided rest and re-emergent postural tremor. On the right half of the screen we have shown an image from his DaTscan, showing reduced dopamine uptake in the left basal ganglion, and confirming the diagnosis of Parkinson’s.

xx

So who should get a DaTscan?

If you have already received a diagnosis of Parkinson’s from an expert, and are responding well to dopaminergic therapy, a DaTscan would not add any new information and would therefore be unnecessary. However, if the expert is not sure of the diagnosis – is it essential tremor or Parkinson’s, for example– or where a potentially risky procedure is being considered (e.g. deep brain stimulation surgery), it may be reasonable for your doctor to recommend a DaTscan.

DaTscans are now available through the radiology department at Monmouth Medical Center.

MMC Free Education Event, May 1

125th-annv-logo-blue-and-gray

Join us for a FREE education event

WHEN – Wednesday May 1, 2013 1-2pm

WHERE – SCAN Adult Learning Center

Dr Neil Holland, Chief of Neurology and Medical Director of the Neuroscience Institute

strokeTIA RAPID EVALUATION CENTER

Essential-tremor-is-characterized-by-sporadic-and-postural-tremor-on-handsTREMOR

CALL 732 542 1326 To Register!

Click here for directions