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.

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Epilepsy surgery and functional MRI

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Epilepsy surgery is an option for patients with intractable partial onset seizures that are not controlled by oral medications.  Epilepsy monitoring is used to localize the seizure focus, often a lesion or abnormal area of brain located in the temporal lobe.  That part of the brain is then carefully removed to prevent future seizures:

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A patient with a brain abnormality in the R temporal lobe (top) undergoes brain surgery to remove that area of brain and prevent future seizures.

Epilepsy surgery is very effective and yet still underutilized for treating seizures.

Left temporal lobe resections are more risky that right-sided cases, because the left hemisphere controls language functions in most (even left handed) patients.  Surgeons have to be very careful planning seizure surgery on the left side to be sure that they do not damage brain critical for speech and language and leave the patient with aphasia.

That’s where functional magnetic resonance imaging (fMRI) comes in.  fMRI goes beyond the conventional imaging of brain structure, and can actually localize regional brain functions by detecting changes in regional blood flow in response actual or imagined activity.

fMRI is increasingly being used to evaluate candidates for epilepsy surgery by identifying important functional regions within the brain, including unpredictable patterns of functional reorganization, to prevent unexpected post-operative deficits.  Click here for a link to a paper with illustrative cases.

Osteoporosis from epidural steroid injections

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Epidural steroid injections are often offered to patients as a conservative treatment for back or leg pain from herniated discs.

We have already highlighted the lack of outcome studies to support this intervention in an earlier post on radiculopathy.

Data from a new study now indicates that epidural steroids may actually be harmful, and increase the risk of osteoporosis with spinal compression fractures.

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Monmouth’s New Onset Seizure Center Opens in June!

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New onset seizures can be isolated events or the harbinger of future epilepsy.

Decisions about starting medications and restricting driving are complicated, and are best made by neurology sub-specialists (“epileptologists“) after a detailed evaluation that usually includes an electroencephalogram (EEG) and brain magnetic imaging study (MRI).

Monmouth Neuroscience Institute is pleased to announce the opening of the region’s first New Onset Seizure Center in June 2013.

Patients who come to the emergency room with their first seizure can be stabilized and then sent home with instructions to follow-up in New Onset Seizure Center, an integral part our Certified Epilepsy Center within one week.

All patients coming to the center they will undergo an EEG, MRI of the brain and a visit with one of our board certified fellowship-trained epilepsy experts during a single visit.

This avoids hospitalization and hasty decisions about medical management.

Click here to find out more about the center.

Monmouth Stroke Service Success Story: Great outcome after emergent carotid endartercomy

Case presentation prepared by Drs N. Nachimuthu and M Chan, Residents, Dept of Internal Medicine, Monmouth Medical Center

Introduction:

When feasible, administration of tissue plasminogen activator (tPA) is the standard of care for treatment of acute ischemic stroke to improve outcomes. Treated patents may be found on subsequent work up to have significant stenosis of one or both carotid arteries. Carotid endarterectomy (CEA) has been shown to be more effective than medical therapy for preventing subsequent strokes in patients with symptomatic stenosis. However, the timing of CEA after ischemic stroke with or without administration of tPA remains controversial, particularly in patients with critical stenosis or unstable symptoms.

To better illustrate this dilemma, we present the case of a 43 year old male who presented with symptoms of acute stroke, was given tPA within the recommended time frame, but was subsequently found to have high grade carotid stenosis and fluctuating symptoms. We follow with a review and discussion of recent literature showing that in select cases, CEA can be done early with no increase in perioperative complications or adverse events.

Case report:

A 43 year old man presented to our Emergency Room after he was found to be restless in bed by his wife at 12:30am on the day of admission. He was also unable to express himself and was noted to have had a right sided facial droop. He was last observed to be asymptomatic 1 hour and 45 mins earlier when he was getting ready for bed at 10:45pm.

The patient arrived at the ER at 1:15am and a code stroke was immediately called. Initial examination revealed aphasia, disorientation, and right-sided facial droop, with a NIH stroke score of 5. There was no motor weakness and the rest of the neurologic exam was unremarkable. Vital signs were stable and within normal limits. A stat CT scan was done which did not show any hemorrhage or findings of ischemia:
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After the CT scan, the patient initially showed some improvement in speech and orientation with the NIH stroke score dropping to 2. It seemed that treatment with tPA might not be necessary.

However, at 2am the patient’s symptoms again worsened acutely. Repeat NIH stroke score was 6 at 1:50am. tPA was given at 2:10am, 3 hours and 25 mins from last known normal.

Following tPA administration, the patient seemed to be improving again and was admitted to the ICU for close observation. However, a few hours later, at 6am, the patient again worsened. He had new right sided weakness and worsening of his aphasia and right facial droop. Given the fluctuating course of the patient’s symptoms he underwent a repeat stat CT of the head to rule out a bleed. This was negative. A CT angiogram of the head and neck was done at the same time, and this showed severe stenosis (almost total occlusion) of the left internal carotid artery:

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At this point, our multidisciplinary stroke team suggested that he undergo emergent carotid endarterectomy to prevent further deterioration of his neurologic status. This was a controversial decision, but after discussing the risks and benefits of the procedure, the patient consented and a carotid endarterectomy was done urgently and completed at 12:05am on the second hospital day, or 21 hours and 55 mins from administration of tPA.

Intraoperatively, the patient was found to have left internal carotid artery narrowing secondary to hemorrhagic plaque and dissection:

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The patient experienced no intraoperative complications. Post-operatively, he was started on Lovenox at 1mg/kg every 12 hours. He did develop a hematoma on the site of the CEA, and Lovenox and antiplatelets were immediately stopped. Aspirin at 325mg daily was resumed after a day and Plavix 75mg daily was resumed the next day, after the hematoma had shown signs of resolution. The patient experienced no further complications.

He underwent a repeat CT scan after surgery, more than a day from symptom onset, which did show an evolving left hemispheric stroke:

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However, clinically, in the hours following CEA, his right sided weakness improved.

By the time the patient was discharged to a rehabilitation facility, he had only mild aphasia, a residual right facial droop, but no motor deficits.

Discussion:

Many vascular surgeons suggest waiting 6-8 weeks after acute stroke before considering CEA, because of fear or bleeding or extension of cerebral infarction during the surgery. However, this delay can lead to recurrent stroke or complete occlusion of the carotid artery.  Moreover, more recent studies have shown that urgent early CEA can be performed on patients with evolving symptoms without additional risks.

We feel that our patient’s near complete recovery was the direct result of early CEA, done despite the recent stroke and potential hemorrhagic complications associated with the use of tPA.

These types of complicated medical decisions can only be made after discussion between neurologists, intensivists and vascular surgeons in a multidisciplinary stroke center.

Click here to find out more about Monmouth’s Certified Stroke Center.

Back pain? Could it be coming from inside your head?

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Most people agree that emotional stress or psychological factors can make any pain, including back pain pain worse.

However, the concept of “stress-related” or psychosomatic back pain, which is primarily caused by psychological and emotional factors, is usually harder to grasp.

It is important to make affected patients understand that even though psychological factors may be causing the physical symptoms, the symptoms are not imaginary

Instead, the unresolved emotional tension is pushed out of awareness into the unconscious mind, which then causes changes in the body’s nervous system, leading to muscle tension, spasm and the back pain experienced by the patient.  This chronic pain can lead to insomnia, fatigue, disability and then depression in a viscous feedback cycle:

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This syndrome can be hard to recognize for 2 reasons:

First, the pain may actually start with an identifiable incident that caused lower back sprain or strain, but then continue as the result of emotional factors long after any physical  injury should have  healed.

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Second, MR imaging studies are so sensitive, that when used inappropriately they may demonstrate incidental “findings” such as a “disc bulge” or “degenerative disc disease”, and the pain becomes attributed to this even when stress is the actual culprit.

The end result is that the affected patient gets sent for endless cycles of physical therapy, then epidural injections and even surgery.  Despite these measures, many patients continue in chronic pain.

If the back pain can be correctly identified as stress related in the first place, then the patient can be encouraged to “think psychological, not physical”,  and get some psychotherapy to address the unconscious issues.

Obviously, this approach is very different than the way most physicians manage patients with back pain.

Perhaps it’s time for a game change?

Click here to find out more.

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.