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Archive for the ‘Neurosurgery’ Category

Thursday, September 20th 2012

The MRIs Aren’t Large Enough Or The People Aren’t Small Enough

David Washington has encountered a hurdle to getting the medical treatment he needs to return to work as a mechanic: He can’t find an imaging device large enough to accommodate his 630 pounds.

The 57-year-old Mr. Washington hurt his back at work last year, but said surgeons won’t operate without a magnetic resonance imaging, or MRI, scan to evaluate his injury.

“I’ve been looking for an MRI for a year,” he said, a saga that has included fruitless phone calls to imaging equipment makers such as Siemens AG and General Electric Co., and a two-hour trip from his home in Wheaton, Md., to a Virginia clinic only to find he was too large for their equipment.

The above from a WSJ piece looking at how the growth in American obesity is impacting patient’s ability to get medical imaging. A hat-tip to The Atlantic for the link.

I don’t have the data for, but I imagine neurosurgeons utilize MR imaging as much as any other specialty. MRIs in particular are a problem for those morbidly obese patients. More than once in my training care on a brain tumor or a spinal cord injury has required patient transfer away from the acute care hospital to an outside facility for lower quality open MRI because the patient’s weight precluded the use of any of the many MRI machines at the hospital of presentation. It is a real world problem that delays care. Now there are more applicable and likely real world reasons that the very large should be working diligently to reduce their weight; this is a rare concern but, still, it’s something else to consider. I’m not sure the solution is larger machines but smaller people.

Monday, July 23rd 2012

Research At Your Peril

A physician can’t employ novel, potentially dangerous, treatments on you, even with your permission, without crossing off Institutional Review Board approval. The IRB critique process is designed to weight the risk/benefit of the proposed study and assure appropriate informed consent of the subjects. And in the case of new drugs or devices, the physician can’t do it without running through the Food & Drug Administration.

And so the confusion out at UC-Davis right now, involving the chair of neurosurgery, is likely to grab some attention.

In 2008, [UC-Davis neurosurgery chair Dr. J. Paul Muizelaar and his colleague Dr. Rudolph J. Schrot] proposed treating a glioblastoma patient with bacteria applied to an open wound to “attack the tumor,” then later withholding antibiotics and letting the bacteria do its work.

Schrot contacted the FDA but ultimately was cautioned that animal studies were needed first.

Back at UC Davis, IRB chairman [Dr. John] Anderson…was also skeptical. Anderson told Schrot in an email that denying this patient the treatment would be “likely devastating to this family,” but that he believed the FDA and UC Davis “won’t allow this product to be used in humans without further testing,” internal documents reveal.

Despite the initial roadblock, Muizelaar and Schrot “strongly believed that the intervention with intentional wound infection was promising for patients who otherwise faced certain death,” according to [a letter from Harris A. Lewin UC-Davis' vice chancellor of research]


Between October 2010 and March 2011, the physicians went forward with three procedures on humans with malignant brain tumors, surgically introducing probiotics into their open head wounds.


Schrot got IRB permission to move forward on Patient No. 1 with a “one-time procedure” that was “not associated with any research aim,” the letter states.

University documents show that the physicians believed they had been given the go-ahead for all three surgeries, but officials later determined that they had been misinformed or were misunderstood by the doctors.

Muizelaar and Schrot stressed to The Bee that all three patients, in consultation with their families, gave their consent.


In the case of Patient No. 1, the investigation found, Schrot had made an “incorrect statement” about restrictions on the bacteria’s use, leading IRB staff to incorrectly conclude that such review was not necessary, Lewin told the FDA.

As for Patients 2 and 3, the university found that treating them with an “unapproved biologic” amounted to human-subjects research – and thus required prior review and approval.

The idea of infections stemming cancer progression is hardly unprecedented and is reported in the literature for everything from lung cancer to bone cancers. Indeed, even intentional infections in cancer patients have a history. And, although two recent relatively large retrospective studies from 2009 and 2011 failed to show post operative infections improved survival in GBM, the issue remains equivocal with more anecdotal reports supporting the idea that infections may promote an immunologic response against the tumor itself.

Much of the issue seems to center on the idea of these bacteria as a ‘biologic’. If what Drs. Muizelaar and Schort did constituted ‘research’ of a biologic then there is likely real trouble ahead and much, if not all, of UC-Davis’ federal research funds, from all sources, could be at risk. It probably bodes well that if the University thought there was something wrong going on here that they self reported it and potentially did so in a relatively timely fashion.

I’m not going to jump to conclusions here. Although two patients seems to have had poor outcomes, potentially related to the treatment, it seems very plausible that this is a matter of bureaucratic misunderstanding. I understand the idea behind IRBs and the reasoning of a level of paternalism that most bioethicists feel patients need,

Arthur Caplan, director of medical ethics at New York University’s Langone Medical Center, said that desperate people are especially vulnerable and need added protections.

“If you’re dying, you’re kind of like reaching out to anything that anybody throws in front of you,” said Caplan, who recently left the University of Pennsylvania’s Center for Bioethics to assume the New York post.

“That’s why so many people over the years are pursuing quack cures in Mexico and all kinds of questionable treatments,” he said, speaking in general terms. “They’re not able to think straight because they’re at death’s door.”

Caplan said that institutional review boards are often misunderstood, with many people believing that such strenuous oversight is “a lot of bureaucracy to get in the way of trying something to save lives.”

In reality, he said, the committees are an essential safeguard for research subjects, who may not get an unbiased view on a researcher’s consent form of the study’s risks vs. benefits.

Maybe the informed consent portion should be the sole purview of the IRB. It is true that the ‘informed’ in informed consent can be a matter of contention, there is very often a wide discrepancy in information between a provider and patient. However, if Drs. Murzelaar and Schort, provided a reasonable view of the risks versus very potential benefits to these patients, even if the use of the bacteria actually under law fell to the FDA for permission, I would be inclined to step back, take a very libertarian view and think much unnecessarily is being made of the situation.

I’m sure fuller details are to follow. It is unfortunate that this is playing out so publicly at present.

Thursday, May 31st 2012

Therapeutic Effects of Intra-Arterial Delivery of Bone Marrow Stromal Cells in Traumatic Brain Injury of Rats

No where in medicine are the dreams for stem cells bigger than in treatment of diseases of the central nervous system. From neurodegenerative diseases to strokes to traumatic brain and spine injuries considerable work has been done. Specific attention being paid to autologous adult bone marrow stem cells which do not carry the risk of cancer, rejection and are readily available. Previous work has documented their ability to cross the blood brain barrier and to differentiate from BMSCs into microglia and neural cells. In a recent edition of Neurosurgery a group from the Hokkaido University Graduate School of Medicine presented BMSC use in a rat model of TBI.

Osanai, Toshiya, Satoshi Kuroda, Taku Sugiyama, Masahito Kawabori, Masaki Ito, Hideo Shichinohe, Yuji Kuge, Kiyohiro Houkin, Nagara Tamaki, and Yoshinobu Iwasaki. “Therapeutic Effects of Intra-Arterial Delivery of Bone Marrow Stromal Cells in Traumatic Brain Injury of Rats – In Vivo Cell Tracking Study by Near-Infrared Fluorescence Imaging.” Neurosurgery 70:435-444, 2012.

A link to the article is here.

The group induced “traumatic” lesions in 12 Sprague-Dawley rats by exposing a unilateral sensorimotor area with craniotomy and applying a freezing 7mm cylinder (cooled in liquid nitrogen) to the dura over the area causing an underlying lesion and significant post injury motor dysfunction.

Of the 12 rats 6 were then injected with an extimated 2 x 10^6 bone marrow stem cells in 200 microliters of saline through the ipsilateral internal carotid and 6 were injected similiarly with 200 microliters of saline. The injections occured 7 days post injury. The group derived the BMSC non-autologous bone marrow from the femurs of other Sprague-Dawley rats after death. These were labeled with PKH26 prior to implantation and with fluroscent cell markers for optical imaging.

The outcomes were functional recovery, in vivo optical imaging and histological examination after euthanasia.

Optical imaging showed that in the ipsilateral side to the injury the injected BMSC left the vasculature and began engrafting into the damaged cortex as quickly as 1-3 hours after injection.

After death of the animals histological examination of the brain showed that the PKH26 labeled cells were primarily to be found in the damaged hemisphere and 22% showed NeuN and 18% showed GFAP implying that the BMSC were differentiating into neural elements.

The implanted animals showed statistically better motor improvement at 2 and 3 weeks post implantation.

More importantly than showing functional recovery this paper’s biggest showing is a clinically, real world applicable method of stem cell administration, within a time frame that would be reasonable for clinicians and patient’s suffering traumatic brain injury.

Tuesday, May 22nd 2012

Metastatic Brain Tumors

In a patient with a known history of cancer, what percentage of new intracranial lesions will be metastatic?

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Wednesday, May 16th 2012

Plavix Coming Off Patent

If I was a cardiologist or a primary care physician or a neurologist I might love Plavix. As a neurosurgery resident I have a decidedly different view.

We know that anticoagulation therapy is associated with larger intracranial bleeds in trauma as well as worse outcomes. And we should have no doubt that antiplatelet therapy carries a similar risk. Indeed, Plavix is probably associated with worse outcomes in traumatic brain injury, although the data is scarcer for a drug like Plavix as compared to say warfarin.

Don’t get me wrong, cerebrally I know that the data supports its use whole heartedly. These are, typically, patients whom Plavix has helped save from further heart or brain attacks. The risk they face from such far outweighs the risk of an intracranial bleed. That said, it is hard to put aside what I see everyday; that is trauma patients with large bleeds associated with antiplatelet or anticoagulant use.

Well, Plavix, one of my largest scourges, is coming off patent.

The drug is set to lose its patent protection on Thursday. Faced with an expected influx of cheaper generic alternatives, Bristol-Myers Squibb, which sells Plavix in the United States under a partnership with Sanofi-Aventis, has said it no longer plans to actively promote the drug.

“This is one of the behemoth drugs that really defined the drug industry in the ’90s,” said Catherine J. Arnold, an analyst for Credit Suisse.

I’ll take comfort in the fact that the cheaper costs of generics typically does not actually lead to increased use of a drug. For me that would be a horror scenario. And I’ll keep telling myself that, despite my very limited view point, these are drugs that actually do far more good than harm.

Thursday, May 10th 2012

Hospital Bacteremia

What are the two most common organisms grown in hospital acquired bacteremia?

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Wednesday, May 9th 2012

Electromyographic Thresholds After Thoracic Screw Stimulation Depend on the Distance of the Screw From the Spinal Cord and not on Pedicle Cortex Integrity


Since Dawson demonstrated it in humans in 1946-1947 monitoring SSEPs during spinal surgery has become the norm rather than an exceptional available tool. It has spread from high risk deformity correction surgeries, such as scoliosis, to more mundane and typical procedures like fusions for trauma or degenerative disease.

Neuromonitoring during spinal surgery has become a huge industry and while population sized reports show a 50% decrease in neurological complications since monitoring came into wide use not all monitoring appears created equal and prospective studies trying to tease out the benefit of costly neuromonitoring have been inconclusive at best.

One of the newer additions to neuromonitoring is evoked EMG. And here is where the paper by Montes, et al out of the Hospital Ramon y Cajal in Madrid. In evoked EMG you stimulate something, usually the pedicle screw in spinal fusions, and see if the stimulation is conducted to neural tissue. The lower the level of stimulation required supposedly the closer the screw is to damaging a neural element (the spinal cord or a nerve, etc). One of the primary fears when placing these pedicle screws is placing the screw so that it is out of bone and in the spinal canal. It is a long held belief with EMG in neuromonitoring that stimulating the screw might give you evidence if you’ve broken through the bone medially. If the stimulation of the screw evoked a response at a low enough threshold then you removed the screw and replaced.

In an animal model the pediatric orthopedic practice in Spain wanted to see if there was a relationship between the stimulation needed to evoke a motor response in each screw and the integrity of the medial wall of the pedicle.

Montes, et al used a porcine model. They placed a total of 18 viable screws in the thoracic columns of anesthetized pigs. The placed screws were measured and found 8mm from the spinal cord. With leads in the intercostal muscles the screws were stimulated in this position, 8mm from the cord with the medial pedicle bone intact, and the threshold at which stimulation of the muscle was achieved was recorded. The team then placed different materials in the canal, between the medial border of the pedicle (and the screw) and the dural sac. This organic material included bone, fat and muscle. With these interspersed tissues the EMG thresholds were again recorded. The team then removed the screws, took off some medial pedicle bone creating a “breach” and then replaced the screw so that it was 2mm from the spinal cord. EMG thresholds recorded the team then repeated the thresholds with fat, bone and muscle between the screw and the dural sac.


The only association with the threshold for stimulation was the distance from the spinal cord.

The tissues between the screw made no difference. So whether the medial pedicle wall was intact or not had no effect at what stimulation there was a response in the muscle.

It is true that other in vitro studies have shown that stimulation relates to the impedence from the screw to the neural elements (ie the tissues between the screw and the spinal cord) and the authors provide no answer for the discrepancy.

Taken alone these findings argue against somewhat the usefulness of evoked EMG in spinal fusion surgery in some ways. EMG cannot really give us a high sensitivty for breach of the pedicle cortex.

All EMG leaves us with is to have a very high tolerance for borderline thresholds on stimulation. The screws that should be replaced are those that have very, very low thresholds on EMG implying that they are touching or nearly touching neural elements. That in and of itself may still be of some use as its probably that proximity, more than the violation of the bone, that most puts patient at risk for injury (ie, even if there is no intervening tissue between the screw and the cord the fact that there’s some distance is safe in and of itself).

Wednesday, May 9th 2012

Spinal Dysraphism

What is the major maternal risk factor for spinal dysraphism?

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Tuesday, May 8th 2012

Carotid Endarterectomy Occlusion Order

What is the order of clamp placement during carotid endarterectomy?

A. External, internal, common
B. Internal, common, external
C. External, common, internal
D. Common, external, internal
E. Common, internal, external

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Monday, May 7th 2012

Nerve Tumor

The H&E micrograph above represents what?

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