Music Improves Parkinson’s Gait

Post prepared by Quoc-Sy Kinh Nguyen Drexel University College of Medicine Class of 2014

Walking through the park

Parkinson’s disease is a progressive, neurodegenerative disorder that affects 1% of people over the age of 60.
It is a clinical diagnosis that requires 2 out of 3 of the following signs: resting tremors, rigidity, and bradykinesia.
Although there is no cure, there are certain medications that can slow down the process: Levodopa is currently the most effective medical treatment for Parkinson’s, but long-term use can lead to levodopa-induced dyskinesias (LID), which include chorea, athetosis, and dystonia. This condition is difficult to treat and significantly affects a patient’s quality of life.

Fortunately, once LID has developed, lowering the dosage of levodopa may help. Medications such as amantadine and atypical neuroleptics can also be used to alleviate the symptoms of LID. Though a bit more invasive, deep brain stimulation is another alternative.

Ultimately, LID is caused by chronic levodopa therapy. Therefore, if one can avoid its use or lower the dosage of levodopa while still treating symptoms of Parkinson’s, then this whole ordeal can be circumvented. To avoid developing LID, one can initially take dopamine agonists such as pramipexole to delay the need for levodopa. As the disease progresses, dopamine agonists become less effective, and levodopa must then be introduced. Once it is introduced, taking levodopa at a lower dosage may decrease the risk of developing LID. In practical terms, one must lower the threshold to symptomatic relief of Parkinson’s by levodopa.

In the pilot study “Ambulosono: A Sensorimotor Contingency-Based Musical Walking Program For People Living With Parkinson’s Disease,” researchers aimed to do just that.

They used the accelerometer of the fourth-generation iPod to monitor differences in stride length among Parkinson’s patients tied to a music program.

The patients were told to do long-distance, large-stride walking every day, with the iPod strapped in a pouch above the patients’ knees, connected by wireless headphones. It was set up to have continuous music playback when a certain stride length was reached. The music playlist consisted of musical cues that have reported effectiveness in activating the limbic and other associated motor networks.

The researchers followed 42 patients with Parkinson’s over a period of 320 days with a cumulative walking distance of 3500 km and 700 hours of music playback. They found significant improvements in stride length (10–30%) and walking speed (10–20%), as well as improvements in other functional areas, like arm swinging, facial expression, long-term fear and anxiety of using escalators, and activity avoidance resulting from depression and anxiety.

This novel approach of employing current accessible technology in the functional improvement of Parkinson’s disease reduces the burden linked to taking levodopa. While this is a small study and further investigations are still needed, it provides a different perspective of Parkinson’s treatment that has the potential to greatly improve patients’ quality of life by decreasing exposure to medications and their many side effects.

“Frozen Addicts” – An Unusal Twist on Drug-Induced Parkinsonism

The term “frozen addicts” was coined by Californian neurologist Dr William Langston after he had encountered an outbreak of akinetic rigid Parkinsonism in 6 drug users in Santa Clara County California:

The story actually starts in 1947 with Hoffman-La-Roche chemist Dr Albert Ziering, who first synthesized synthetic opioid  Desmethylprodine 1,3-Dimethyl-4-phenyl-4-propionoxypiperidine (MPPP).  The drug was never developed or marketed.

The story continues with chemist Barry Kidston, who in the 1970s synthesized MPPP using Dr Ziering’s recipe and a home chemistry set.  However, a few days after injecting himself with a sample from a newly synthesized batch of drug, Kidston became frozen, unable to speak or walk.  He was taken to the hospital by his parents, misdiagnosed with catatonic schizophrenia, and treated with electroconvulsive therapy for months.  He was ultimately diagnosed him with Parkinson’s disease, and improved with L-dopa treatment.  Soon after, researchers analyzed the tainted drugs, and concluded that it was comprised of both MPPP and a similar compound, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).  Kidston died of cocaine overdose shortly afterwards.  His autopsy showed loss of dopaminergic cells in the substantia nigra, the hallmark of Parkinson’s disease.  The case was written up in the Journal Psychiatry Research in 1979.


In July 1982, a 42 year old named George Carillo was hospitalized in San Jose frozen like a statue in a bent twisted position.


Then a neurologist in Watsonville, only 30 miles away, reported 2 drug-addict brothers in their 20s  both with advanced symptoms of Parkinson’s.

Ultimately seven addicts came down with these same symptoms.


A sample of tainted heroin was ultimately analyzed, and one of the toxicologists involved remembered reading about the Kidston case in Psychiatry Research.

William Langston, the neurologist who first treated Carillo, looked the case report up and found that Kidston had prepared drugs based on a 1947 paper by Albert Ziering.  But when Langston he went to the Stanford University library to read that original paper, he found that it had been cut out of the journal.  Some enterprising college chemist was cooking up MPPP and selling it as heroin, but like Kidston had made a mistake in his recipe and produced MPTP instead.

Once inside the brain, MPTP is metabolized into 1-methyl-4-phenylpyridinium which is toxic to dopamine producing neurons in the substantia nigra.

Since then MPTP has been used to develop an animal model of Parkinson’s disease, and this has allowed researchers to investigate surgeries to repair the injured region of the brain, new techniques using electrical stimulation, and more recently stem cell replacement of damaged cells.

These Frozen Addicts have also posed a question that we have yet to answer. If a street-drug impurity can trigger on form of Parkinson’s, could other “idiopathic” cases also have a chemical source? Recent studies have found that ingestion of the pesticide Rotenone can bring on Parkinson-like symptoms in mice. Loss of motor control, stiffening of muscles, and even loss of facial expression have been noted among the rare side effects of the high blood pressure medication, Reserpine, and the heartburn drug, Metoclopramide.

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.

GDNF and Parkinson’s Disease


We have already blogged about the difficulties in treating advanced Parkinson’s Disease, and the need for new strategies including stem cell therapy.

Another therapeutic approach is use of a trophic factor to replenish or prevent the loss of those dopamine producing cells in the first place.

Glial cell-derived neurotrophic factor (GDNF) has been considered a potential therapy for Parkinson’s Disease for many years.


GDNF has been known to protect and restore these cells in animal models of Parkinson’s Disease since the 1990s.

However, human studies have shown mixed results so far:

Early small open label studies of GDNF infusions into the putamen showed promising results:

These results were not confirmed in a larger double blind study, although this study has been criticized for early termination and other issues:

Furthermore, subsequent studies have confirmed the clinical benefits of GDNF infusions in Parkinson’s patients, and have even shown a sustained benefit after the infusions were discontinued in one patient.

There are ongoing trials of direct infusions of GDNF into the putamen in the UK using a novel infusion pump:

Another potential approach is to use gene therapydelivering a virus that carries the DNA to make GDNF directly into the putamen by a single injection. The “infected” neurons will make GDNF on their own to treat the disease.

So, at this point the jury is still out on GDNF and Parkinson’s, watch this space for more information!

Living The Dream? The Medical Mysteries of REM Sleep

A dream is a succession of images, ideas, emotions, and sensations that occur involuntarily in the mind during REM sleep.

So during REM sleep our subconscious minds are supposed to be active, while we lie unaware with our bodies perfectly still. However, two unusual phenomena can occur during REM sleep:


1. Lucid dreams

A lucid dream is when a person is aware they are dreaming, and may have some control over their own actions in the dream or even the characters and the environment of the dream.

This is different from simply having a passive memory of a dream, which can sometimes happen if we awake directly from REM sleep.

when a person recognizes he or she is dreaming while in a dreaming state and often manipulates events within the dream.”Read more at:

Sound like Inception? It should, the screenplay was inspired by the phenomenon of lucid dreaming:


Scenes from the Matrix have also been compared to the mind control techniques used by lucid dreamers:


Stephen LaBerge is a psychophysiologist who did research on lucid dreaming at Stanford University in the 1970s.

He found that subjects who could control their dreams had more volitional (and not random) eye movements during REM sleep.

He now runs the Lucidity Institute, which aims to train people how to achieve lucid dreaming:

Proponents of lucid dreaming claim they can control their dreams to enjoy fantasies and over come nightmares.

This might have been a skill that would helped those ill fated victims of Freddy Kruger in Nightmare on Elm Street Part 3: Dream Warriors:

Click here to listen to a RadioLab podcast about Lucid Dreaming.


2. REM Sleep Behavior Disorder

REM sleep behavior disorder (RBD) is in a sense the opposite of lucid dreaming. Affected patients lose the motor inhibition that is a typical feature of normal REM sleep, and regain the motor strength to “act out” their unconscious dreams. This is an uncommon disorder, and can be associated with underlying neurodegenerative disorders like Parkinson’s Disease.

Or, if you prefer the Disney interpretation of RBD:

RBD video clips courtesy of Matthew J. Davis.


The medical mysteries of REM sleep:

So, during REM sleep our conscious minds and bodies are supposed to be switched off, while our subconscious brain performs a scandisk generating passive dreaming. If our conscious brain somehow switches on during this time we experience lucid dreaming. Of our bodies switch on, and we start unconsciously reacting to these dreams we have REM sleep behavior disorder. If both were to happen simultaneously, we’d be awake!