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.

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Concussion’s Axis of Evil

The term concussion is derived from the Latin word “concutere” which means “to shake violently”:

This term is used to describe a head injury associated with a temporary loss of brain function, including impaired consciousness, cognitive dysfunction and/or emotional problems.

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Concussion Center

To fully understand Concussion’s Axis of Evil, one need look no further than the brutal world of professional boxing and it’s neurological complications.

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One of the most savage beatings any fighter every received occurred on July 4, 1919 in Toledo, Ohio, when 24 year old Jack Dempsey destroyed 37 year old Jess Willard to become the Heavyweight Champion of the World.

One can easily spot the effects of concussion in Willard as he sustains blow after blow to the head, and he develops unsteady gait, erratic behavior (failing to avoid punches and protect himself) and ultimately unconsciousness.

New Jersey’s own Harrison S. Martland MD (1883-1954) was the first to report in 1928 that repeated beatings of this kind could lead to a delayed permanent neurologic syndrome referred to as punch drunk syndrome.

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His observations went largely unheeded.

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Muhammad Ali (born as Cassius Marcellus Clay in 1942) was only 22 when he became word heavyweight champion in 1964, almost 40 years after Martland’s paper was published.

Here is with Liberace in 1964:

Almost 10 years after that performance, Prof Corsellis reported further clinical and pathological features of punch drunk syndrome in his 1973 paper “The Aftermath of Boxing”.
Here’s data from one of his cases:

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By the 1980s, reports of abnormal brain CT scans in professional boxers had reached the popular media (Sports Illustrated, 1983):

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By 1983, Muhammad Ali was retired from professional boxing,

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and soon to be diagnosed with “Parkinson’s disease”.

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Here he is on the Today show with Bryant Gumbel in 1991:

Here he is in 2009:

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Obviously, repeated head trauma, and it’s consequences, is not unique to boxing:

concussion9John Grimsley (1962-2008) was a linebacker for the Houston Oilers.  He retired in 1993.  In 2008, aged 45, he was killed by an accidental gun shout wound to the chest.

His brain was examined as part of an ongoing study by Boston University’s Study of Traumatic Encephalopathy.

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concussion10His brain showed the same pathologic changes as the Punch Drunk boxers.

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This syndrome, more commonly referred to as Chronic Traumatic Encephalopathy, is now known to have occurred as a consequence of repeated head trauma in many other sports, including soccer, hockey, horse-racing and wrestling.

College football and amateur soccer players have been shown to have impaired performance on neuropsychologic testing, worse with increasing number of concussions.

Then, there’s the Second Impact Syndrome (SIS).

SIS is said to be a rare, often fatal, traumatic brain injury that occurs when a repeat injury is sustained before symptoms of a previous head injury have resolved.
Although limited to single case reports, and disputed as a discrete syndrome in the scientific literature, SIS cases are young athletes and have become high profile in the media:
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Click here to find out more about this case.

It has become clear that it takes athletes longer to recover from repeated that single concussions:
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This data, as well as SIS cases, has led to a concern that the presence of ongoing concussive symptoms are a significant risk factor for further injury to occur, and that any residual symptoms should mandate restriction for further contact sport in young athletes.

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Finally, it is know that concussions are under-reported by high school players.

A 2004 survey of 1500 varsity football payers in Milwaukee disclosed that although 15% had sustained a concussion during the season only 50% reported it to their coach or trainer.

So there we have it, Concussion’s Axis of Evil:

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And the solution?

The Allies Against Concussion:

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Click here to read more about how we have put these measures into effect at Monmouth Neuroscience Institute.

Click here to find out more about the Matthew J. Morahan III Health Assessment Center for athletes at Barnabas Heath.

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.

DaTscan for Parkinson’s Disease

Parkinson’s disease has always been a clinical diagnosis.

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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.

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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:

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

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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.

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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.

Monmouth Neuroscience NPH Success Story

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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

Extreme Gait Apraxia – Parkinson’s Patient Can’t Walk But Can Ride a Bike!

Apraxia is a disorder of motor planning leading to the loss of ability to carry out a learned purposeful movement, despite having the desire and the physical ability to perform that movements.

For example, patients with dressing apraxia, which can be caused by stroke or dementia, can move their limbs normally, but cannot figure out how to put their clothes on properly:

Patients with gait apraxia, caused by Parkinsonism, NPH or frontal lobe dysfunction, have particular difficulty initiating gait and making turns, often with a tendency to freeze, but a relative preservation of straight-line gait once initiated:

A newspaper article from the UK reported the case of a 58-year-old man with Parkinson’s and severe “gait freezing”. He required visual guides to help him move one foot in front of the other and was unable to turn while walking. After a few steps he would lose his balance and then require his wheelchair.  However, he could still ride his bicycle, flawlessly:

This is extreme gait apraxia – he is able to move his legs and control he balance enough to ride a bike, and yet is unable to do so for the (much easier) task of walking.

Click here to read the full article.

Click here to see more funny walks.

Cortical Basal Ganglionic Degeneration

This post is provided courtesy of K. T. Weber, Drexel University College of Medicine Class of 2013:

Cortical Basal Ganglionic Degeneration (CBGD) is a rare neurodegenerative disorder that affects both the cerebral cortex and basal ganglia, resulting in a rapidly progressive and devastating combination of movement disorder and dementia.

CBGD shares features with other, more common, neurologic illnesses: Like Parkinson’s disease, it often presents asymmetrically, with a tremor, rigidity or dystonia. Like Alzheimer’s disease, there are subtle early cognitive and behavioral changes. However, CBGD progresses more rapidly than these other conditions, ultimately involving the other limbs and causing more cognitive dysfunction. Furthermore the Parkinsonian features of CBGD tend not to respond to dopaminergic medications.

Patient with CBGD, showing rigidity, paucity of movement, and myoclonic jerks in the left arm

One of the distinctive features of CBGD is alien limb phenomenon. Alien limb is characterized by a “loss of agency” in the affected limb. The patient is able to feel sensation in the limb, and movement is preserved, but the patient no longer recognizes the limb as his or her own. This same aLien limb or (more commonly an alien hand) syndrome can also result from separation or dysregulation between the brain’s hemispheres, for example after surgical division of the corpus callosum for severe epilepsy.

Patient with CBGD, showing rigidity, dystonic posturing and Alien limb phenomenon (the patient said the left arm was “moving on it’s own”)

In popular media, Dr. Strangelove struggled with an alien limb that was no longer under his control.

However, the movement disorder is only half the story, and symptoms also include behavioral changes, cognitive decline, and abnormal speech. Behavioral changes may involve personality changes, mood problems, like depression and agitation, or the development of new compulsive behaviors. Language problems often begin with difficulty finding words (“anomia“) and may progress to an inability to speak.

The disorder is currently classified as a “tauopathy” in the same family of diseases as Pick’s disease, progressive supranuclear palsy (PSP), and even Alzheimer’s disease.

Although the diagnosis of CBGD is mostly clinical, there are some diagnostic tests that may helpful, such as asymmetric cortical atrophy on brain imaging or asymmetric slowing on EEG.

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MRI showing right hemispheric atrophy

EEG showing L hemispheric slowing

EEG showing R hemispheric slowing

However, a definitive diagnosis can only be made by examining brain tissue at autopsy.

Pathology of CBGD (A) In the neocortex, ballooned neurons with displaced nuclei and pale cytoplasm (arrow) are common. (B) Immunostaining detects diffuse accumulations of tau protein in a peripheral distribution in a ballooned neuron. (C) Neuron loss and gliosis are often severe in deep nuclei, including the substantia nigra. (D) Diffuse cytoplasmic accumulation of tau protein is seen in neurons of various sizes in the neocortex (arrow, panel D), nucleus basalis (E) and striatum (F), as well as other locations. (Panels A,C from sections stained with H and E, remaining panels from sections immunostained with primary antibodies to tau).

Pathology of CBGD (A) In the neocortex, ballooned neurons with displaced nuclei and pale cytoplasm (arrow) are common. (B) Immunostaining detects diffuse accumulations of tau protein in a peripheral distribution in a ballooned neuron. (C) Neuron loss and gliosis are often severe in deep nuclei, including the substantia nigra. (D) Diffuse cytoplasmic accumulation of tau protein is seen in neurons of various sizes in the neocortex (arrow, panel D), nucleus basalis (E) and striatum (F), as well as other locations. (Panels A,C from sections stained with H and E, remaining panels from sections immunostained with primary antibodies to tau).

There are no effective treatments for CBGD, and therapy is aimed at symptomatic relief. The movement disorder, unlike Parkinson’s disease, does NOT respond well to levadopa, so other medications are used to help control the tremors and stiffness in the limbs. Beta blockers (propanolol), benzodiazepines (clonazepam), and gabapentin may have some efficacy in controlling tremor. Baclofen (a GABA agonist) is used to treat spasticity of many different causes and may provide some relief to patients with CBGD. Additionally, the depression, anxiety and agitation due to degeneration the cortical areas of the brain are critical therapeutic targets, and often respond to the first line therapies, including SSRIs and other antidepressants.

In summary, CBGD is a rare, progressive neurodegenerative disease. Recognizing the constellation of symptoms of CBGD from its more common cousins helps patients by identifying all elements of the disease progression, and can improve quality of life by addressing each of the related symptoms.