Better functional outcomes for medical therapy alone in unruptured brain AVMs

A deeper look at the data from a randomized trial of unruptured brain arteriovenous malformations (AVMs), known as ARUBA, shows that outcomes (death or stroke) among those treated with interventional therapy compared with medical therapy were worse than previously known. Data from the new five year-analysis were presented here on Saturday at the AAN Annual Meeting.

The investigators examined functional impairment as defined by a modified Rankin Scale score (mRS) of 2 or greater at the time of death or stroke. They also compared the frequency of functional impairment and its association with both the score on the Spetzler-Martin Grading Scale and primary outcome events in both the medical therapy and interventional groups. The Spetzler-Martin Grading Scale assesses features of intracranial AVMs to determine operability of AVMs on a scale of 1 to 6; a grade of 6 describes inoperable lesions.

They found that after a median follow-up of 42 months the risk of functional impairment after a primary outcome event was significantly lower (HR 0.26, 95%CI 0.12-0.57) for patients randomized to medical management compared with interventional treatment, which included neurosurgery, embolization, or stereotactic radiotherapy, or a combination of those interventions chosen by the participating center. The Spetzler-Martin Grade and primary outcome events were not associated in the medical arm (p=0.80), but were associated with increasing grades in the interventional arm (p=0.0002).

"Enough details exist now to show that the adverse events in the interventional arm occurred for the most part very early — often the day of initiation — while those in the medical arm occurred later, some of them much later, and not clustered in time," said J.P. Mohr, MD, FAAN, the Daniel Sciarra professor of neurology at Columbia University and the trial's co-principal investigator. "More important, the few outcomes in the medical arm were clinically mild compared with the more serious ones from intervention."

"At five years follow-up, the trial looks like it justifies watchful waiting, hoping that either no spontaneous hemorrhage will occur in this lifetime condition or that if it does the effect will be clinically mild," at which time intervention can be tried to eliminate the AVM, Dr. Mohr said.

Commenting on the study, Dileep Yavagal, MD, FAAN, director of interventional neurology at the University of Miami, said the findings dovetail with his own experience. He agreed that "watchful waiting is the better management strategy" for these AVMs.

The "one clear exception" to watchful waiting, he said, would be cases with "feeding-artery" aneurysms that are more than 4-5 mm in size associated with the AVMs. In those cases, interventional treatment may be indicated to treat the aneurysms even if we do watchful waiting for the AVMs."

Issam Awad, MD, FACS, director of neurovascular surgery at the University of Chicago, said, however, that the problem with the study is "that most patients with unruptured AVMs undergo treatment decisions to purchase a natural risk over a life expectancy horizon of several decades and not merely 42 months."

Another issue, he said, is that all the treatments were combined, without the benchmarking of therapeutic objectives or outcomes. 

Dr. Mohr said he would like the neurologic community to focus not so much on problems associated with intervention but on the success of medical management in ARUBA's patients. "We prefer to focus attention on those who did not have the intervention," he said. "Their benign outlook is the least arguable of all the findings."​

http://journals.lww.com/neurotodayonline/blog/NeurologyTodayConferenceReportersAANAnnualMeeting/pages/post.aspx?PostID=27&cid=MR-eJP-AANNTCR-AnnualMeetingDay2-Neurology-WNT-NoPromo

When adults shun modern medicine and a child pays the price

Hi. I'm Art Caplan from the Division of Medical Ethics at the New York University (NYU) Langone Medical Center.

Little Ezekiel Stephan is dead, and that is a tragedy. It's a tragedy for his parents and for his community. The little boy died of meningitis in a small town up in Manitoba, Canada. It should not have happened. It could have been prevented because the little boy could have been treated.

His parents chose, out of loving concern for him, to pursue alternative medicine. In this case, they knew the boy was sick. They fed him smoothies made out of maple syrup, horseradish, and other ingredients. They went to the natural foods store where the father worked and got some immune-boosting agent to give to him. They basically tried to do everything outside of mainstream medicine to help their son. They even had a friend, who was a nurse, come by, who said, "I'm not sure what's wrong with Ezekiel, but I think you should take him to the doctor, because it could be meningitis."

They didn't do it.

Why were they so afraid of mainstream medicine? What led to their opposition? I don't know. Appropriately, authorities in Canada have put the parents on trial. Now the parents are claiming that they are being persecuted for their beliefs in non–mainstream medicine. They even suggest that they are being persecuted because they did not vaccinate their little child against meningitis.

I don't think they're being persecuted. The trial is appropriate. But I don't think it's appropriate to punish these parents. They lost their son. They clearly loved their son. By their own lights, one could say they tried to do right by their son.

Something that every doctor needs to tell parents who might be interested in alternative treatment is, "If your family member stays sick for more than a few days and looks seriously ill, you must take that family member to a doctor, to a hospital. No issue and no argument about it. They have to go." Ezekiel was stiff from the meningitis. They could not get him into the car easily. When he finally went through respiratory arrest, he was in pain and suffering—he was obviously very ill.

Remember, all that is being required is a diagnosis. Then we can argue about whether there is a treatment, whether the treatment should be forced, or what should be done. Every parent should have a duty to take their child to the hospital no matter whether they are pursuing mainstream medicine, alternative medicine, or some cultural belief that does not recognize Western medicine. We might consider lobbying to pass laws that say, "When your child is very sick for more than a couple of days, you must bring them to the doctor."

That is what I would advise telling families. Pursue the philosophies you like—whether you want to pray, use horseradish smoothies, or whatever you are going to do. But if that does not work, and somebody is very sick for more than 36 hours—particularly a child—you'd better take that child or your family member to the hospital. One can believe what one wants, but when it comes to kids or family members who are too incapacitated to say what they would want, they must go to a physician. They must go to a hospital.

http://www.medscape.com/viewarticle/861547?src=WNL_bom_160418_MSCPEDIT&uac=60196BR&impID=1065407&faf=1

Autism poem

Benjamin Giroux was given an assignment to write a poem called “I Am” for his fifth grade class. The poem follows a template: each student was given the first two words of every line — I am, I see, I feel, etc. — and then asked to fill the rest in. Benjamin used the assignment to describe what it feels like to live on the autism spectrum, and his finished poem moved his parents to tears.

Benjamin’s parents shared his poem on the National Autism Association’s Facebook page, where it’s quickly amassed over 11,000 likes and 6,235 shares. His dad, Sonny Giroux, tells the Huffington Post they decided to share the poem for two reasons: so other parents with kids on the spectrum could understand what their children are going through, and so Benjamin could understand that others accept him and feel the same way he does.

“I… wanted to show Benjamin that he is not, odd, alone, or isolated and that his diagnosis is something to embrace and not something to hold him back,” Sonny explained to the Huffington Post. “Each like, share and comment he’s received since has made him feel like not only he does fit in and belong in this world, but has also moved him beyond words that he’s touched so many.”

When I first read Benjamin’s poem, it took my breath away. Not only is he an immensely talented poet at only 10 years old, but he also managed to capture his unique life experience and feelings in a way that’s so universal. Everyone — whether they’re on the autism spectrum or not — can identify with feeling like a castaway, an outsider, afraid of what others think.

Benjamin connected with thousands of people, but he also made everyone who reads his poem understand what it’s like to live with autism in completely new way. When we consider other’s experiences and find the ways we’re all the same, that creates compassion and understanding — that’s what makes the world a better place. Benjamin inspired thousands of people to walk in his shoes. He’s an immensely talented and beautiful soul, and it’s exciting to think of the many ways kids like him are going to change the world.

I am odd, I am new

I wonder if you are too

I hear voices in the air

I see you don’t, and that’s not fair

I want to not feel blue

I am odd, I am new

I pretend that you are too

I feel like a boy in outer space

I touch the stars and feel out of place

I worry what others might think

I cry when people laugh, it makes me shrink

I am odd, I am new

I understand now that so are you

I say I “feel like a castaway”

I dream of a day that that’s okay

I try to fit in

I hope that someday I do

I am odd, I am new.

http://www.scarymommy.com/10-year-old-writes-poem-about-life-with-autism/

Courtesy of my daughter

A doctor, not a martyr

Dear doctor,

I need you to be healthy. When I come to you for help, I need your “A” game. I need you sleep enough. Eat healthy food. Not too much. Mostly vegetables. I need you to exercise regularly and take time to take care of your own physical, emotional and spiritual needs. I need to you use the bathroom when you need to. I need you to stop and take a deep breath when you are frustrated. I need you to deal with your relationships in healthy ways. Get the help you need to be healthy. Take time for yourself. Find quiet space for creativity. Enjoy the sun on your cheeks on occasion.

I need you to laugh with your loved ones. Be there physically and emotionally, even when they don’t need you, and there is no crisis. I need you to accept yourself as human, be gentle and loving to yourself, don’t beat yourself up when you make mistakes. Learn from mistakes and move on. Don’t repeat them. I need you to be at your best. If you don’t take care of your own needs, how can you take care of mine? And for how long can you keep it up? I need you to be healthy so that you can do what you are here to do — practice medicine, in the best way that you can.

Oh, I know you think you can do it all. You’ve been “doing it all” for years. Your colleagues and friends “do it all. “ Work days and nights and days again without sleep. Watch a video of your child’s first steps and tell yourself you will see the next ones in person. Consider lunch a granola bar eaten in the hallway while walking to the next ward. It’s a big deal that you stoop long enough to pump breastmilk for the nanny to give to your baby. This makes your colleagues uncomfortable not because you are breastfeeding but rather because you are tending to your own bodily need when they are ignoring theirs.

If you are lucky, you have that spouse at home taking care of everything. And he/she will think that your occasional time together and last-minute but sincere gestures are enough. For awhile. And then what. I know you think you can’t make time for exercise. The EMR is inefficient and charts have to get done. Besides, let’s just admit there are things about your work that are just plain fun and it’s easy to want to jump right in. Then a week or a month or a year goes by, and you realize that you really don’t exercise very much anymore. Or see friends outside of work. You text them, that counts. You remember to call your mother, so you must be doing something right most of the time.

Patients need you. You can’t walk away from that. There are millions of reasons why you don’t take care of yourself, get burned out at sky-high rates, commit suicide, get divorced, have health problems. If you don’t prioritize your own health, no one will. You’re a physician in one of the most affluent countries on the globe. If you don’t vote with your actions, who can?

When I come into your ED with chest pain, or bring my father in for surgery, or my son in to deal with the fracture, I want your best. No more stinking, wrinkled 30-hour old scrubs. No more bags under the eyes. No more neglected relationships, no more constantly working late, no more being overweight and out of shape. We all need you. Change your habits. Change the system. Do what it takes, we all have a lot riding on you. You signed up to be a doctor, not a martyr.

Sincerely,

Your next patient

Kathy Stepien, MD
http://www.kevinmd.com/blog/2016/04/signed-doctor-not-martyr.html
Courtesy of Doximity

Ultrasound echomyography in facial palsy

Sauer M, Guntinas-Lichius O, Volk GF. Ultrasound echomyography of facial

muscles in diagnosis and follow-up of facial palsy in children. Eur J Paediatr

Neurol. 2016 Mar 26. pii: S1090-3798(16)00054-4. doi: 10.1016/j.ejpn.2016.03.006.

[Epub ahead of print]

Abstract

BACKGROUND:

Ultrasonography is a reliable, non-invasive and painless tool for quantitative assessment of the static and dynamic changes of the facial muscles in adult patients with facial palsy. Therefore it would also be worthwhile to establish the method for quantitative analysis of facial muscles in children with facial palsy to improve and expand the diagnostics for paediatric facial palsy.

METHODS:

Eight children, aged 1-18 years, with facial palsy of different aetiology were scanned and their ultrasound-images analysed. Bilateral scans of the frontal, orbicularis oculi, zygomaticus major, orbicularis oris, depressor anguli oris, depressor labii inferioris, and mentalis muscle were performed at rest and if possible during contraction. Muscle cross-section area, muscle thickness and echo intensity were measured.

RESULTS:

All muscles of our investigation protocol for adults could also be reliably identified in children. On the paralyzed side of the face a reduction of muscle size in rest and contraction and higher echo intensity could be convincingly detected. Based on these observations, we were able to make well-founded treatment decisions and avoid painful electrophysiological examinations.

CONCLUSION:

Ultrasonography of facial muscles is also feasible in children and facilitates diagnostics in children with facial palsy.

Courtesy of:  http://www.mdlinx.com/neurology/medical-news-article/2016/04/13/quantitative-sonography-children-facial-palsy-mimic/6605121/?category=sub-specialty&page_id=2&subspec_id=317

Volk GF, Pohlmann M, Sauer M, Finkensieper M, Guntinas-Lichius O. Quantitative

ultrasonography of facial muscles in patients with chronic facial palsy. Muscle

Nerve. 2014 Sep;50(3):358-65

Abstract

INTRODUCTION:

In this study we introduce quantitative facial muscle ultrasound as a diagnostic tool for patients with chronic unilateral facial palsy.

METHODS:

Muscle area, thickness, and echo intensity of 6 facial muscles (frontalis, orbicularis oculi, orbicularis oris, depressor anguli oris, depressor labii inferioris, and mentalis) and of 2 chewing muscles (temporalis and masseter, as controls) were measured in 20 patients with chronic facial palsy.

RESULTS:

Aside from 1, all facial muscles were significantly smaller on the paralyzed side. With exception of frontalis and orbicularis oculi muscles, all other facial muscles showed significantly higher echo intensity on the affected side. Muscle size and echo intensity of the chewing muscles showed no side-to-side asymmetry.

CONCLUSIONS:

Quantitative ultrasound of facial muscles helps to better characterize their status in patients with chronic facial palsy in the phase of denervation and during regeneration.

Volk GF, Pohlmann M, Finkensieper M, Chalmers HJ, Guntinas-Lichius O.

3D-Ultrasonography for evaluation of facial muscles in patients with chronic

facial palsy or defective healing: a pilot study. BMC Ear Nose Throat Disord.

2014 Apr 25;14:4.

Abstract

BACKGROUND:

While standardized methods are established to examine the pathway from motorcortex to the peripheral nerve in patients with facial palsy, a reliable method to evaluate the facial muscles in patients with long-term palsy for therapy planning is lacking.

METHODS:

A 3D ultrasonographic (US) acquisition system driven by a motorized linear mover combined with conventional US probe was used to acquire 3D data sets of several facial muscles on both sides of the face in a healthy subject and seven patients with different types of unilateral degenerative facial nerve lesions.

RESULTS:

The US results were correlated to the duration of palsy and the electromyography results. Consistent 3D US based volumetry through bilateral comparison was feasible for parts of the frontalis muscle, orbicularis oculi muscle, depressor anguli oris muscle, depressor labii inferioris muscle, and mentalis muscle. With the exception of the frontal muscle, the facial muscles volumes were much smaller on the palsy side (minimum: 3% for the depressor labii inferior muscle) than on the healthy side in patients with severe facial nerve lesion. In contrast, the frontal muscles did not show a side difference. In the two patients with defective healing after spontaneous regeneration a decrease in muscle volume was not seen. Synkinesis and hyperkinesis was even more correlated to muscle hypertrophy on the palsy compared with the healthy side.

CONCLUSION:

3D ultrasonography seems to be a promising tool for regional and quantitative evaluation of facial muscles in patients with facial palsy receiving a facial reconstructive surgery or conservative treatment.

Stuttering mice

The closest thing to a stuttering mouse has been created by scientists who gave rodents a genetic mutation that causes the speech disorder in humans.

Mouse pups recorded in the first week of life squeaked with more pauses and displayed more repetitive, halting patterns in the noises they produced when they carried the mutation.

But the mutated mice had no other obvious language problems and squeaked out the same rich repertoire of ultrasonic syllables – defined by abrupt changes in pitch – as normal mice.

Researchers at Washington University in St Louis worked on the mice to see whether some of the characteristics of human stuttering, or stammering, can be reproduced in rodents. The research aims to help scientists unpick the biological pathways that underpin stammering, and give them a ready way to test drugs and other potential treatments.

These mice aren’t stuttering but they show a lot of features that are similar to a human that stutters, so this is an incredibly powerful research tool,” said Terra Barnes, whose study is published in Current Biology. “This is a huge first step towards an animal model of stuttering.”

“Once you have an animal model for the condition, you can do a lot of things you can’t do with humans. We can find the neural correlates of stuttering, identify the underlying biological mechanisms, and maybe work out how to fix it,” she added.

In the past, stammering has been blamed on anxiety, stress and even bad parenting, but the primary driver for the disorder is now considered biological, with stress potentially exacerbating the condition. In 2008, scientists at Oxford University identified changes in the brain that appear to disrupt the neural pathways needed for fluent speech.

Two years later, a team led by Dennis Drayna at the National Institute on Deafness and other Communication Disorders in Maryland, found mutations in a gene called Gnptab that appeared to cause stuttering in some people. The discovery was a surprise, because the gene is only considered important for general housekeeping duties, such as digesting waste inside the bodies’ cells.

To find out whether rodents can be made to stutter, or at least display some aspects of the condition, Barnes, Drayna and other colleagues created mice that carried the Gnptab mutations. They then recorded the noises the mice made until they were eight days old. Mouse pups make spontaneous sounds when they are taken from their mothers, but also when they are in pain, meet another mouse, or want to attract a mate.

Each recording session lasted 3.5 minutes. The mutated mice produced nearly a third fewer sounds, with longer pauses between the noises they made. Within bouts of vocal activity, the mutated mice squeaked out more single syllables than their natural littermates. The pauses are similar to the hesitations that can break up the smooth flow of speech in people who stutter, while the repetition of syllables also mirrors human stammering.

While speech remains a uniquely human skill, the patterns of speech are built on simple building blocks. To speak clearly, people have to control the timing of their breath, the fine muscles in the tongue and mouth, and be able to initiate the movements. “Those kinds of things may be shared all the way from mice to people,” said Tim Holy, a senior author on the study.

The modified mice could help researchers work out how mutations in the Gnptab gene give rise to stammering and shed light on the related mystery of how the mutation, which would affect every cell in the body, leads to a condition as specific as stuttering...

“Twin studies have long supported the view that there is a genetic element in stuttering. It also tends to run in some families: Charles Darwin stuttered, as did his Grandfather, Erasmus,” said Robin Lickley, a reader in speech and hearing sciences at Queen Margaret University in Edinburgh. “The genetic mutations probably affect the neurological processes that support speech production. So they probably conspire to create a neurological condition.”

https://www.theguardian.com/science/2016/apr/14/stuttering-mouse-experiment-sheds-light-on-common-human-speech-disorder

Myasthenia gravis and stem cell transplantation

Adam Bryant, MD; Harold Atkins, MD, FRCPC; C. Elizabeth Pringle, MD; David Allan, MD, MSc; Grizel Anstee, MD; Isabelle Bence-Bruckler, MD, FRCPC; Linda Hamelin, MScN; Michael Hodgins, MD; Harry Hopkins, RPh, FCSH; Lothar Huebsch, MD, FRCPC, Sheryl McDiarmid, MBA; Mitchell Sabloff, MD, FRCPC; Dawn Sheppard, MD, MSc, FRCPC; Jason Tay, MD, MSc, FRCPC; Christopher Bredeson, MD, MSc, FRCPC. Myasthenia Gravis Treated With Autologous Hematopoietic Stem Cell Transplantation.  JAMA Neurology. Online.

Abstract

Importance  Some patients with myasthenia gravis (MG) do not respond to conventional treatment and have severe or life-threatening symptoms. Alternate and emerging therapies have not yet proved consistently or durably effective. Autologous hematopoietic stem cell transplant (HSCT) has been effective in treating other severe autoimmune neurologic conditions and may have similar application in MG.

Objective  To report 7 cases of severe MG treated with autologous HSCT in which consistent, durable, symptom-free, and treatment-free remission was achieved.

Design, Setting, and Participants  This retrospective cohort study reports outcomes at The Ottawa Hospital, a large, Canadian, tertiary care referral center with expertise in neurology and HSCT, from January 1, 2001, through December 31, 2014, with a median follow-up of 40 months (range, 29-149 months). Data collection and analysis were performed from February 1 through August 31, 2015. All patients with MG treated with autologous HSCT at The Ottawa Hospital were included. All had persistent severe or life-threatening MG-related symptoms despite continued use of intensive immunosuppressive therapies.

Interventions  Autologous hematopoietic stem cell grafts were mobilized with cyclophosphamide and granulocyte colony-stimulating factor, collected by peripheral blood leukapheresis, and purified away from contaminating lymphocytes using CD34 immunomagnetic selection. Patients were treated with intensive conditioning chemotherapy regimens to destroy the autoreactive immune system followed by graft reinfusion for blood and immune reconstitution.

Main Outcomes and Measures  The primary outcome was MG disease activity after autologous HSCT measured by frequency of emergency department visits and hospitalizations and Myasthenia Gravis Foundation of America (MGFA) clinical classification, MGFA therapy status, and MGFA postintervention status. Safety outcomes included all severe autologous HSCT–related complications.

Results  Seven patients underwent autologous HSCT, 6 for MG and 1 for follicular lymphoma with coincident active MG. Mean (SD) ages at MG diagnosis and at autologous HSCT were 37 (11) and 44 (10) years, respectively. Five patients (71%) had concurrent autoimmune or lymphoproliferative illnesses related to immune dysregulation. All patients had distinct clinical and electromyographic evidence of MG (MGFA clinical classification IIIb-V). All patients achieved durable MGFA complete stable remission with no residual MG symptoms and freedom from any ongoing MG therapy (MGFA postintervention status of complete stable remission). Three patients (43%) experienced transient viral reactivations, and 1 (14%) developed a secondary autoimmune disease after autologous HSCT, all of which resolved or stabilized with treatment. There were no treatment- or MG-related deaths.

Conclusions and Relevance  Autologous HSCT results in long-term symptom- and treatment-free remission in patients with severe MG. The application of autologous HSCT for this and other autoimmune neurologic conditions warrants prospective study.