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.

New Interactive eLearning Format

Take a tour of a new eLearning format we’re working on, and learn the basics of neurologic localization:

Lactic Acid gone to your head?

D-Lactate Encephalopathy and Periodic Ataxia
Posted by Michael Twomey, Drexel MSIV, Class of 2014

Remember that pain in your side during a long hard workout? That’s the buildup of lactic acid or L-lactate which is a way for your body to burn energy when it there isn’t much oxygen around (like when you think it’s a good idea to run 5 miles). This feeling, although uncomfortable, won’t make you loopy–it’s twin brother, however, has no such qualms.

D-lactate is just like normal old lactic acid, only completely different. In fact, it is the mirror image of the molecule that causes us such grief. For those of us who have forgotten organic chemistry, or would rather walk on broken glass than take such a torturous class, think
of it like a pair of gloves. L-lactate would be your left hand glove and D-lactate the right. They look like the same darn thing from a distance (made out of the same leather and thread, and stuffing), but no matter how you rotate them, you could never get them to match up.


Our bodies happen to be finicky. Like the 7 year old fussy eater we all know and (hopefully still) love, the human body can only make and break down L-lactate. Thus, under factory settings, we all have an undetectable level of D-lactate in our blood. Bacteria, however, are wired a bit differently (shocking, I know). Some can take the same sugars that we eat, turn them into D-lactate, and when those buggers are in your intestinal system–this form of lactic acid can enter our blood stream.

Lactobacilli (the bad guys)

It just so happens that high levels of D-lactate effects the brain just as much as it does the rest of our bodies. We aren’t exactly sure the why or how this compound acts on our central nervous system, but it can cause anything from making you unbalanced to putting a patient in a delirious state. Case reports show symptoms of sleepiness, hallucinations, clumsiness, blurred vision, disorientation, dizziness, lethargy, excessive irritability, and abusive behavior. All of which can last up to a few days! The gait can be very unsteady (ataxic) during each episode, and this syndrome is one of the causes of “periodic ataxia”.

To make the diagnosis these patients also had an elevated amount of acid in their blood (something normal Lactic Acid can do as well) and high levels of D-lactate.
So can you blame the next time you trip over the doormat on bacteria? Probably not.
Fortunately the only reports of this syndrome have been found in people with extensive small intestine surgery. It turns out that the bacteria who can make D-lactate tend to live in our large intestine where they almost never see large amounts of sugar. Normally our small intestine is long enough to absorb all of those nutrients and leaving them to digest your Mexican meal instead. People with short bowel syndrome, however, should be aware of this possibility and eat appropriately. Otherwise having meals high in simple sugars could cause you to end up in the hospital with some strange behaviors and a nice long course of antibiotics!

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



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.


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


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


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).


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.


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.


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.

Another reason to take snoring seriously! Sleep apnea linked to strokes.


Sleep apnea, the disorder that causes a person to stop breathing suddenly while sleeping, is already known to increase the risk of high blood pressure, heart failure, and daytime sleepiness.

seep apnea consequences

A new study suggests that the sleep disorder is also linked with small brain lesions and a symptomless form of stroke, known as silent stroke.

In the study, 56 men and women ( aged 44 to 75 years) who’d had a recent stroke or TIA underwent overnight polysomnograms.  91% had sleep apnea.

Furthermore, having more than five episodes of sleep apnea in a night was linked with having multiple extra “silent strokes” on their brain imaging studies.

silent stroke

Silent strokes don’t cause any symptoms as they occur, so a person typically doesn’t know he or she has suffered one, but they can eventually lead to memory loss and difficulties with walking, as their effects accumulate over the years.”

Yet another reason to take the on-line sleepiness test, and if your score is >10 see a sleep specialist and/or get an overnight polysomnogram in a certified sleep laboratory.

CIDP Patient Impoves with Treatment

This 11-year-ol girl had a 4-month history or progressive proximal leg weakness leading to falls and difficulty with stairs. There was no back pain, numbness in the legs or difficulty with badder or bowel control.

Her exam showed leg weakness, absent reflexes and normal sensation.

Her serum CK was normal.  Her EMG showed features of acquired demyelinating neuropathy, most notably absent F-waves.  Her CSF showed a mildly elevated protein level without cells (“albuminocytologic dissociation”).  She was treated with a course of intravenous immune globulin and made a remarkable recovery within 4-weeks.


Chronic inflammatory demyelinating polyneuropathy (CIDP)

CIDP is an acquired immune-mediated inflammatory disorder of the peripheral nervous system, causing demyelination, conduction slowing and conduction block:

Affected nerves fail to respond to stimuli causing progressive muscle weakness, loss of deep tendon reflexes (areflexia), fatigue, and abnormal sensations.

Most cases show evidence of demyelinating neuropathy on electrodiagnostic studies and albuminocytologic dissociation in the cerebrospinal fluid.

Early diagnosis and treatment is important in preventing irreversible axonal loss and improving functional recovery.

However, CIDP is probably under-recognized and under-treated due to its variable presentation and the limitations of clinical, serologic, and electrophysiologic diagnostic criteria.

Consultation with a sub-specialty trained neuromuscular physician is critical.

Monmouth Neuroscience NPH Success Story


Hydrocephalus before (A) and after (B) CSF diversion

Normal pressure hydrocephalus (NPH) is caused by excessive accumulation of cerebrospinal fluid (CSF) and enlargement of the brain’s ventricular system, putting increased pressure on surrounding brain tissue, and leading to a distinctive gait disturbance, urinary incontinence and dementia.

NPH can be effectively treated by a surgical procedure to divert the CSF from the ventricles into the peritoneal cavity via a ventriculoperitoneal shunt.

Early diagnosis and treatment are important for this surgical treatment to be effective.

However NPH is frequently unrecognized or misdiagnosed as arthritis, Parkinson’s disease, Alzheimer’s disease, or “senility”, leading to other ineffective treatments and nursing home confinement.

However, many patients with dementia or gait problems and large ventricles on a brain imaging study will not improve after shunting.  Performing surgery on all such patients, without further selection, can result in ineffective surgery, and more importantly other potential complications like bleeding around the brain (a subdural hematoma).

Therefore selecting the patients with suspected NPH who are most likely to benefit from surgery is of the utmost importance.  Studies have shown that careful evaluation of patients using objective measures during prolonged CSF drainage via a lumbar drain is the most sensitive and specific way to predict which patients will improve with surgery.

The neurologists and neurosurgeons at the Monmouth Neuroscience Center have developed a multidisciplinary hydrocephalus assessment program to evaluate patients with suspected NPH and determine who is most likely to benefit from a shunting procedure.

Here’s one of out recent success stories!

Find out more about:

Normal Pressure Hydrocephalus

Other funny walks and extreme gait apraxia

The Hydrocephalus Program at Monmouth Neuroscience Institute