Bringing the ER to the stroke patient!

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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.

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.

Sleep Apnea Treatment Improves Golf Performance!

 

A new study suggests treating obstructive sleep apnea with continuous positive airway pressure, or CPAP therapy, improves golf performance in middle-aged men.

 

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Up to six months of CPAP treatment was associated with significant improvements in excessive daytime sleepiness.
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CPAP patients also experienced better quality of life and an 11% drop in their average handicap index.

Among the more skilled golfers with baseline handicaps of 12 or less, the average handicap dropped by 31%.

Patients attributed their enhanced performance to improved concentration, endurance and decision making.

Click here to take an on-line test to see if you might have a sleep disoder.

Click here to find out more about sleep disorders in general.

And find out more about the Comprehensive Sleep Medicine Program at Monmouth Neuroscience Institute.

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.

VBP-15 for Duchenne Muscular Dystrophy

Prednisone has been used since the 1970s for delaying the otherwise obligatory progressive motor deterioration seen in  Duchenne Muscular Dystrophy (DMD.

A good deal of data has been acquired over the years.  In fact there are even ongoing studies looking at different dosing regimens.

The drug is typically started between ages 4-6 at a dose of 0.75 mg/Kg.  However, steroid cause may side effects to Duchenne boys, including weight gain and behavioral problems.

How does it work?  We’re not sure, but we think the medication stabilizes muscle membranes and inhibiting cytotoxic T-cells.

Side effects are mediated by binding sites in the cell nucleus which lead to initiation of metabolic pathways :
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The new drug VBP-15 is molecularity very similar to Prednisone, but lacks the 11 beta hydroxy arm, which reduces the metabolic side effects, without affecting the beneficial membrane stabilizing effects:

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VBP-15 has been shown to improve muscle strength and function in an animal model of DMD without the metabolic side effects of Prednisone:

nm4

Clinical trials in humans are expected to begin in 2013-14.

Watch this space for more information.

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.

New Brain Tumor Study at Monmouth Medical Center

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The David S. Zocchi Brain Tumor Center at Monmouth Medical Center is a research site for the ACT IV study – an international clinical trial evaluating the effects of adding an investigational vaccine to standard treatment in patients with glioblastoma, the most commonly diagnosed cancerous brain tumor.

Approximately one-third of patients with glioblastoma express a particular genetic mutation – the Epidermal Growth Factor Receptor protein variant III (EGFRvIII) – which is linked to increased tumor cell growth.  Rindopepimut  is an experimental cancer vaccine that may act to promote anti-cancer effects in patients who have tumors that express this EGFRvIII protein.

Sumul N. Raval, M.D., is the medical director of the Brain Tumor Center and primary investigator for the study at Monmouth Medical Center. “The ACT IV study, evaluates the survival rate, time to disease progression, and quality of life among patients with this genetic mutation (EGFRvIII) when the investigational vaccine rindopepimut is added to standard chemotherapy treatment ” said Dr. Raval.

The study is open to adults with newly diagnosed EGFRvIII-positive glioblastoma. Potential participants will undergo a screening phase, during which tumor tissue is tested for EGFRvIII. Other tests, including brain MRIs, physicals, blood tests, among others, will also be performed to determine eligibility.

Once a patient is accepted into the study, he or she will undergo one of two treatment regimens – both of which include injections of the standard course of chemotherapy treatment, temozolomide. One regimen will add injections of rindopepimut – the vaccine under evaluation – combined with a low dose of GM-CSF to “activate” the immune system. The other regimen will add injections of Keyhole Limpet Hemocyanin – the control injection. Study participants have an equal chance of receiving either treatment regimen, and neither the patient nor the doctor will know which treatment the patient is receiving.

During treatment, patients will be closely monitored and will be asked to visit the clinic site several times per month for standard medical tests, including blood tests and periodic brain imaging. Participants will be contacted every month to evaluate their health and to see what additional treatments are being used to treat their glioblastoma.

Participation in the ACT IV study is voluntary and may last up to five years or longer. Patients should discuss the study and other possible treatment options with their doctor, family and friends before deciding to participate. Taking part in the study may or may not improve the condition of a patient’s glioblastoma. There may be risks associated with study participation, and patients should discuss these risks with the study doctor.

To learn more about the clinical trial, visit www.GlioblastomaStudy.com. For more information on the David S. Zocchi Brain Tumor Center at Monmouth Medical Center, call 1-877-577-9800.

Global warming, bad for MS patients!

uthoff1

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.

ms1

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?

uthoff2

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?

MS, Tysabri and PML

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The disease:

Multiple sclerosis (MS) is an auto-immune disease characterized by episodes of multi-focal inflammation and demyelination of the brain and spinal cord, leading to recurrent and unpredictable neurologic compromise (relapses or exacerbations), usually alternating with periods of disease inactivity (remissions).

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The drug:

Tysabri (natalizumab) is a monoclonal antibody that binds to the cell adhesion molecules involved in the white blood cell movement from the blood stream into the central nervous system across the  “blood-brain barrier”.

Keeping these cells out of the brain and spinal cord can help prevent the immune-mediated inflammation and demyelination that leads to clinical relapses in multiple sclerosis.

Studies have shown that patients taking Tysabri have a 64% reduced risk of disability progression and  >80% fewer exacerbations (relapses) compared to placebo.  More than 1/3 patient who take the drug are clinically free of disease activity.

Tysabri is administered by iv infusion once  a month.

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The problem:

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More than 50% of people have been infected with the JC or John Cunningham) virus (JCV), most during childhood or adolescence, often with no symptoms at all or just a minor febrile illness.

Once infected, the virus then lies dormant in the central nervous system, like a Tojan horse, totally inactive and innocuous.

However, if the infected person becomes immune suppressed, for example from HIV infection (AIDS) or from taking a immune presupposing medication, the virus can become reactivated and lead to a very serious brain infection known as Progressive multifocal leukoencephalopathy (PML).  PML leads to large confluent areas of brain infection and demyelination (below), causing disability and death,

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Large confluent areas of demyelination in PML.

When a few Tysabri patients developed PML during the initial clinical trials, the FDA temporarily pulled the drug, but then re-introduced it with more careful monitoring (the TOUCH porgram).

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I’m taking Tysabri, what’s my risk of PML?

There have now  been >350 cases of PML in MS patients taking Tysabri, and this constitutes an overall risk of about 1.5 cases per 1000 (or 0.15%) of those taking the drug.

The risk is higher for patients who have already been been exposed to (and test positive for) JCV, have taken other immunosupressive drugs, or have taken Tysabri for longer times:

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So, if you take Tysabri but test -ve for JCV, your PML risk is 0.07 per 1000, or 0.007% or 1 in 14,000.

Even if you test positive for JCV but haven’t taken prior immunosupressive meds (like azathioprine, methotrexate or mycophenolate) your PML risk is only 0.6 per 1000 or 0.06% or 1 in 1,700.

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So, what should I do?

If you take Tysabri, you should know your JCV status.  If your negative, you should get re-tested every 6-months since there are false negative results and some people do seroconvert every year.

If (or once) you test positive, you don’t need any further blood tests, but you should carefully weigh the risk benefits of continuing to take Tysabri beyond 2 years, particularly if you have had prior exposure to other immunosupressive drugs.

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Click here to find out more about Tysabri and PML from the MS society.

Foreign Accent Syndrome – Their “Problem” or Yours?

FAS3

Foreign accent syndrome (FAS) is a rare condition which causes affected patients to suddenly speak their native language in a foreign accent.

Cases of FAS were reported as early as 1900.  However, one of the best known historical cases is “Astrid L”, a Norwegian woman who suffered a traumatic brain injury from shrapnel during a WW2 air raid in 1941.  She survived, but found herself mispronouncing vowels in such a way that she seemed to have a German accent, leading to social isolation and stigmatization for the remainder of the war.

Since then, there have been about another 60 FAS cases reported in the literature and media, mostly in patients who have suffered acute neurologic events such as strokes, multiple sclerosis and head injury.

Unlike most neurologic syndromes, FAS has not been localized to a lesion in a particular brain area.

The only thing that can be said is that most affected patients have lesions affecting the dominant hemisphere in or around known language areas.

FLS

Brain imaging studies from a FAS patient: The MRI (left) shows enlargement of the Sylvian fissure from atrophy of the left temporal lobe. The PET scan (right) shows focal hypometabolism in the left temporal lobe.

Many affected patients were initially mute, then developed FAS as they recovered from a non-fluent aphasia:

There are also some cases of FAS that have developed after minor neurologic events, or even without any clearly identifiable neurological cause at all.  Some of these patients have had normal brain imaging, suggesting that the problem can be functional or psychogenic.

This is all further complicated by the fact that different listeners can perceive different accents in a single speaker.

The video clip is a patent with FAS syndrome after brain injury from hemiplegic migraine.  She is said to have a Chinese accent.  Does it sound Chinese or just slurred to you?

The table below is from a FAS case report, where the affected patient’s “foreign accent” was obviously described very differently by observers.

FAS2

This suggests that FAS may not be a true syndrome after all, but simply a listener-bound epiphenomenon.

What does this mean?

Well, we have already explained that most FAS patients have some kind of speech or language problem that changed how they speak.  That explains the association with lesions in the dominant hemisphere.   However the “foreign accent” may actually just something perceived by the listener – the variability of perceived accents is explained by the fact that listeners have different experiences with languages other than their own.

In other words FAS may not be a true syndrome, but simply an epiphenomenon that exists only in the ears of the beholder.