Bringing the ER to the stroke patient!

mobile stroke

We are trying to do a better job educating our patients about the warning signs of stroke, and that if they think they might be having a stroke they should act FAST and call 911 to get to the ER as soon as possible.

Stroke

However, despite these efforts only 5% of US stroke patients get to the ER in time to receive clot busting therapy to treat their stroke.  Furthermore, the quicker the drug is given, the better the outcome, TIME IS BRAIN!

time is brain

We would like to see patients getting treated within one hour of the onset of their stroke, but because of the time it takes to get to the hospital and get evaluated in the ER this is rarely possible.

A pilot study in Texas is looking at getting stroke therapy administered faster by bringing the ER to the stroke patient.

mobile stroke

The project brings a mobile CT scanner and a stroke neurologist (via telemedicine) to the patient in a specially equipped ambulance.  The investigators hope to see stroke patients getting treated faster and improved outcomes.

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Gene therapy trial for Duchenne Muscular Dystrophy

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Duchenne and Becker muscular dystrophy are both caused by mutations in the same dystrophin gene.

How it this possible?

Well, the genetic code which is translated to from proteins “talks” in words made of three letters (base pairs).

dmd dna

A gene mutation that deletes only one or two base pairs, or worse still signals the end of the word (known a “premature stop codon”) will result it a very abnormal dysfunctional gene product, leading to complete deficiency of functioning dystrophin, and the more severe Duchenne Muscular Dystrophy.

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Normal muscle bx (a) vs Duchenne muscular dystrophy (b) with complete absence of dystrophin (d)

However a gene mutation (deletion) that removes base pairs in a multiples of three is called an in-frame mutation, and causes a (sometimes only minor) qualitative change in the dystrophin protein, leading to the milder Becker’s muscular dystrophy.

Ataluren (also known as PTC124) is a small molecule designed to overcome premature stop codons.

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Put simply, the idea is that it might convert some Duchenne boys in to a milder form (more like Becker’s) of muscular dystrophy by allowing them to produce some more normal dystrophin.

The drug can only help boys affected with premature stop codons confirmed by DNA testing.

The drug is currently undergoing Phase III trialsClick here for more information.

Petadolex for Migraine Prophylaxis: The Facts

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Posted by Sonia Jasuja, MSIV Drexel University College of Medicine

As a current student of traditional Western Medicine, I have been trained to turn towards modern pharmacology and away from natural remedies, for the most part.  However, as someone who has suffered from severe skin allergies all my life, I know how desperate patients can get in order to find something that really works! When Western Medicine fails us, where can we turn?

During my clinical Neurology rotation at Monmouth Medical Center, I saw another issue that plagues patients: Migraine.  While there have been great advances in the prevention and treatment of migraine, some patients are still left with debilitating pain. It was during this rotation that I first heard about Petadolex, or Petasites hybridus (aka Butterbur).

What is it? Butterber is an herbal plant that has been used for medicinal purposes, including migraine and headache, allergies, asthma, and many more. Most herbal remedies use the root extract in the form of a pill. It has properties that relieve spasms and decrease inflammation.1

Is it safe? Yes- studies have determined that Petasites is safe to use for the prophylaxis of migraine. The dose that was cited to have moderate efficacy is 150mg daily.2

Side effects are very mild and include burping, stomach upset, diarrhea, fatigue and itching.3

One important thing to keep in mind- make sure to only buy Petasites hybridus that is certified and labeled, “PA free”. “PA” stands for pyrrolizidine alkaloids, which cause adverse effects in the liver, lungs and circulatory system. PA’s can cause cancer.3

You should not take Petasites if you are pregnant or breast-feeding, have liver disease, or if you are allergic to ragweed, marigolds, daisies or other related herbs. 3

Does it work? Probably, but we still need more information! In 2006, Agosti et al. published “Effectiveness of Petasites hybridus preparations in the prophylaxis of migraine: A systematic review”. Of the two studies that were looked at, the systematic review showed that there is only moderate evidence for the effectiveness of Petasites at the dose of 150mg/day for a period of 3-4 months. The review also thoughtfully pointed out that confounding factors still need to be accounted for. These factors would include things like which migraine treatments have been successful or unsuccessful in the past, and any use of addictive or hormonal substances, such as nicotine or estrogens.2

The review article states that the overall effect size of the 150mg extract dose is approximately 15% percent lower migraine frequency rate per month compared to placebo.2

The bottom line.  If you have frequent or debilitating headaches, you should see you doctor for an evaluation.  You may need some diagnostic testing, and there are probably some very effective conventional medications you can try.  However, if you are still having frequent headaches despite that, Petasites might be worth a try.

REFERENCES

1. Brind’Amour, Katie. “Migraine Herbal Home Remedies From Around the World.”Healthlines RSS News. Healtline Editorial Team, 16 Apr. 2013. Web. 16 Nov. 2013.

2. R. Agosti, R.K. Duke, J.E. Chrubasik, S. Chrubasik, Effectiveness of Petasites hybridus preparations in the prophylaxis of migraine: A systematic review, Phytomedicine, Volume 13, Issues 9–10, 24 November 2006, Pages 743-746, ISSN 0944-7113, http://dx.doi.org/10.1016/j.phymed.2006.02.008.

3. “Butterbur Information | Evidenced-Based Supplement Guide.” MedicineNet. MedicineNet.com, n.d. Web. 16 Nov. 2013.

High altitude sickness and the size of your brain?

Posted by David Cuthbert, MSIV, Drexel University College of Medicine

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Every year thousands of people flock to several world locations with one common goal in mind – to push their bodies well beyond what nature has so far intended by climbing to dangerously high altitudes.

For whatever reason this appeals to some people.  Those people are eager to overcome the restrictions set by Mother Nature, despite the obvious dangers.

As a kid I loved the move Cliffhanger with Sylvester Stallone.  I remember watching that film and thinking that the only real dangers associated with extreme altitude were obvious – falling (please see video clip # 1), Slyvester Stalone wanting to use you as a human sled (watch video clip #1 again), the cold, or John Lithgow going crazy and wanting to use a helicopter to kill you for money (please see video clip #2).

But apparently those aren’t the only dangers, and medical school has taught me some pretty interesting stuff.

In fact there are a whole variety of medical syndromes that can occur at high altitude that don’t involve John Lithgow, and being that this is a neurology blog, this piece will focus on the neurological high altitude medical syndromes.  And in particular, will place emphasis on one terribly interesting study.

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Elevated intracranial pressure at high altitude may be a function of brain size?

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The “Tight Fit Hypothesis”, and the story of one extremely curious neurosurgeon.

The neurological syndromes of high altitude sickness are thought to be a spectrum of illness ranging from high altitude headache (HAH), to acute mountain sickness (AMS), to the most severe – high altitude cerebral edema (HACE).

The exact pathophysiologic mechanisms leading to these conditions are still somewhat unclear but several theories have been proposed and tested – all of which related to hypoxia and elevated intracranial pressure (ICP).

It is thought that in the milder end of this spectrum (HAH) the symptoms are solely contributed from hypoxia, and as disease severity progresses, and the patient comes closer to HACE – the pathogenesis is more attributable to raised ICP.

But what I find even more interesting than just the development of these syndromes – is the fact that there is great variability between who develops them.  For some people, no matter how acclimatized they are they simply cannot go to a certain altitude without great risk of HACE and subsequent death.  While others require little acclimatization, and are capable to trekking to the summit of Mt. Everest without necessitating the use of supplemental oxygen.  This leads one to ask, what are the factors present that allow someone this ability to tolerate high altitude?

One answer (with considerable evidence to support it) lies within their genetics.  The discovery of a transcription factor called “Hypoxia Inducible Factor”, or HIF, confirmed this.  HIF is a transcription factor that contributes to the regulation of several metabolic pathways, and allows both production of a higher concentration of hemoglobin, and greater sensitivity of the carotid body to hypoxia.  Another older, and forgotten theory looks to further explain this increased altitude tolerance through anatomic differences.

In 1985 Ross suggested that the “random nature of cerebral mountain sickness” can be explained by “more compliant systems”.  In other words, if a person has larger sized ventricles, and/or more atrophic brain, they will in turn be less susceptible to altitude sickness because the compliance will leave them better equipped to tolerate the raise intracranial pressure.

Interestingly enough, there existed someone crazy enough to test this hypothesis.  Someone not only willing to hike to these ungodly altitudes, but also willing to screw a bolt in his head to measure his own intracranial pressure.  This person was Brian Cummings, an avid outdoorsman, who also just so happened to be a neurosurgeon.

Cummings and a team of ten undertook an expedition to the Kishtwar region of northern India to try to put this hypothesis to the test.  However the data obtained from the experiment was destroyed in a fire.  Or so everyone thought!  Then recently Cummings wife (Cummings has since passed away) found the data from the experiment, allowing it to have since be published.

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Mountain rage within Kishtwar region of northern India.

In this experiment the “tight fit” hypothesis was tested by using 10 subjects.  These subjects had computed tomographic scans of their brains to measure their ventricular size.  After which a scoring system was used to measure symptomatology related to high altitude neurological syndromes while at high altitudes.  Also, three lucky volunteers had their intracranial pressures measured – allowed via screwing a pressure monitor through a burr hole in their heads .  This stayed in place while trekking through Northern India Himalaya’s.  Cummings himself participated in the study, and also had a pressure monitor placed.

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Dr. Cummings manipulating ICP monitor

The results of the study showed that the three subjects with the smallest ventricles suffered the most from Acute Mountain Sickness, and reported the worst headaches of the group.  Meanwhile patients with larger to normal sized ventricles reportedly had significantly less clinical findings related to AMS:

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Regarding the intracranial pressure monitoring, of the 3 subjects to be observed, one had large ventricles, one with normal size, and one with small ventricles.  The only one to experience headache, was the patient with the highest observed rise in ICP, and was also the subject with the smallest ventricles.

Therefore the results of this experiment support Ross’s “tight fit” hypothesis, and provide a potential anatomic explanation to compliment other genetic mechanisms to explain why some people are more prone to developing high altitude neurologic syndromes.

Obviously, the small study size cannot definitively explain this susceptibility, nor can it exclude other mechanisms as contributing as well. Nevertheless this experiment is considerably important to those who wish to conquer the hypoxic environment of Mother Nature’s higher altitudes.

It allows an explanation for those that are less able to adapt, and maybe even one day provide a means of testing their ability to acclimatize prior to their summit attempt.  And while that very well may never happen, this study at the very least is a great story about the incredible strength of the human spirit.

Dr. Cummings showed incredibly determination while searching for answers regarding the human ability to adapt to their environment, and fortunately now his work can live on.

Brain-to-Brain Interfacing: Next Step… Mind Control

Post written by Anne Verlangieri, MS IV at Drexel University College of Medicine, Class of 2014

Obi

Step aside Obi-Wan Kenobi, this is not the mind control you’re looking for. A recent study conducted by researchers at Harvard University has demonstrated a method for non-invasive, functional linkage of brain activity from human volunteers and Sprague-Dawley rats. The method, dubbed brain-to-brain interface (BBI), utilizes electroencephalographic steady-state-visual-evoked potentials (SSVEP) and transcranial focused ultrasound (FUS). The goal of the process is to allow human volunteers to use visual stimuli to elicit motor responses from the tail’s of rats. To understand how BBI works, we’ll need some background on the SSVEP and FUS segments.

SSVEP

Numerous neurophysiological studies have shown that there is increased neural activity elicited by a visual stimulus with directed attention. In other words, observer attention on a specific visual stimuli is more important that the stimulus itself, in producing measurable spikes in neural activity. SSVEP utilizes EEG based brain-to-computer interfacing (BCI), to take advantage of this idea. In practice, a human volunteer is equipped with an EEG and instructed to gaze on a designated visual stimulus. The EEG reads the pre-synchronized neural activity, linking the volunteer’s brain with an SSVEP computer.

FUS

Transcanial focused ultrasound has been used clinically as a non-invasive therapy for certain brain disorders, (ex. Deep brain stimulation in Parkinson’s Disease) as well as thermal ablation of brain tumors. This technology allows for region-specific brain stimulation, and when set at low acoustic energy, has been shown to excite or suppress rabbit motor/visual cortices; effectively creating a computer-to-brain interface (CBI).

How BBI works

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(Figure 1. The schematics of the implemented brain-to-brain interface (BBI). The implementation consists of steady-state visual evoked potential (SSVEP)-based brain-to-computer interface (BCI: on the left column) and focused ultrasound (FUS)-based computer-to-brain interface (CBI) segments (on the right column). [doi:10.1371/journal.pone.0060410.g001]

The set-up shown in figure 1, demonstrates how SSVEP and FUS are utilized to link the human volunteer and with the rat’s brain. The volunteer is instructed to look at a specific visual target, creating an increase in EEG bandwidth corresponding to that specific visual stimulation frequency. A SSVEP detector reads the increase in EEG bandwidth and triggers the activation’s of the FUS, which stimulates specific motor area’s of the rats brain, resulting in a twitch in the rat’s tail. Here’s the experiment in action:

What can we do with this technology?

Certainly, the possible applications of BBI are far reaching. The studies authors proposed that this technology could one day be used for indirect sensory/somatomotor communication allowing an increased degree of understanding during verbal communications between speaker and listener.
Other’s have suggested “Hive mind” like problem solving, via a linked think-tank. And of course there is the potential for further human-to-animal interaction; pet owners would jump at the chance to know just what Fido is thinking.
Another recent study used this technology for one student to control another student playing a video game at a remote location.
Regardless of the application, it will be important to look at the legal, ethical, and privacy concerns involving technology that has the potential to transmit thought from one individual to another. The study is free to download and read here.

Global warming, bad for MS patients!

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Wilhelm Uhthoff (1853-1927) a German neuro-ophthalmologist described an optic neuritis patient in 1890 who would develop episodes of temporary vision loss during physical exercise.

This condition, subsequently known as Uhthoff’s phenomenon, was later found to be caused by a rise in body temperature.

More than half of all multiple sclerosis (MS) patients spontaneously report being sensitive to environmental heat.

When specifically asked, as many as 70% MS patients report that high temperatures worsened their MS.

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Increased temperature blocks action potentials in compromised (demyelinated) neurons resulting in slower conduction velocities and/or temporary failure of conduction altogether (conduction block).

This explains the temporary exacerbations in neurologic dysfunction that underlie Uhthoff’s phenomenon.

So what can you do?

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Drugs like Ampyra (dalfampridine or 4-aminopyridine) improve conduction across demyelinated neurons, and can improve Uhthoff’s phenomenon, but these drugs are not currently FDA approved for this indication, and used off label can cost as much as $1200/month.  It might be cheaper to move to Alaska or buy a window box AC unit?