Sunday, May 31, 2015

A trilogy on consciousness

Peterson A, Cruse D, Naci L, Weijer C, Owen AM. Risk, diagnostic error, and
the clinical science of consciousness. Neuroimage Clin. 2015 Feb 20;7:588-97.
In recent years, a number of new neuroimaging techniques have detected covert awareness in some patients previously thought to be in a vegetative state/unresponsive wakefulness syndrome. This raises worries for patients, families, and physicians, as it indicates that the existing diagnostic error rate in this patient group is higher than assumed. Recent research on a subset of these techniques, called active paradigms, suggests that false positive and false negative findings may result from applying different statistical methods to patient data. Due to the nature of this research, these errors may be unavoidable, and may draw into question the use of active paradigms in the clinical setting. We argue that false positive and false negative findings carry particular moral risks, which may bear on investigators' decisions to use certain methods when independent means for estimating their clinical utility are absent. We review and critically analyze this methodological problem as it relates to both fMRI and EEG active paradigms. We conclude by drawing attention to three common clinical scenarios where the risk of diagnostic error may be most pronounced in this patient group.

Naci L, Cusack R, Anello M, Owen AM. A common neural code for similar
conscious experiences in different individuals. Proc Natl Acad Sci U S A. 2014
Sep 30;111(39):14277-82.

The interpretation of human consciousness from brain activity, without recourse to speech or action, is one of the most provoking and challenging frontiers of modern neuroscience. We asked whether there is a common neural code that underpins similar conscious experiences, which could be used to decode these experiences in the absence of behavior. To this end, we used richly evocative stimulation (an engaging movie) portraying real-world events to elicit a similar conscious experience in different people. Common neural correlates of conscious experience were quantified and related to measurable, quantitative and qualitative, executive components of the movie through two additional behavioral investigations. The movie's executive demands drove synchronized brain activity across healthy participants' frontal and parietal cortices in regions known to support executive function. Moreover, the timing of activity in these regions was predicted by participants' highly similar qualitative experience of the movie's moment-to-moment executive demands, suggesting that synchronization of activity across participants underpinned their similar experience. Thus we demonstrate, for the first time to our knowledge, that a neural index based on executive function reliably predicted every healthy individual's similar conscious experience in response to real-world events unfolding over time. This approach provided strong evidence for the conscious experience of a brain-injured patient, who had remained entirely behaviorally nonresponsive for 16 y. The patient's executive engagement and moment-to-moment perception of the movie content were highly similar to that of every healthy participant. These findings shed light on the common basis of human consciousness and enable the interpretation of conscious experience in the absence of behavior.

Graham M, Weijer C, Peterson A, Naci L, Cruse D, Fernández-Espejo D,
Gonzalez-Lara L, Owen AM. Acknowledging awareness: informing families of
individual research results for patients in the vegetative state. J Med Ethics.
2014 Jul 30.

Recent findings in cognitive neuroscience have revealed that some patients previously diagnosed as being in a vegetative state may retain some degree of covert awareness. However, it is unclear whether such findings should be disclosed to the families of these patients. Concerns about the preservation of scientific validity, reliability of results and potential harms associated with disclosure suggest that individual research results should be disclosed only under certain conditions. In the following paper, we offer four criteria for the disclosure of individual research results. Because the results of functional neuroimaging studies to detect covert awareness in vegetative patients are scientifically valid, informative and reasonably reliable and have considerable potential benefit for the patient, researchers have an obligation to disclose such results to family members. Further work is needed to develop educational materials for families and to systematically study the impact of disclosure on the families themselves.

Sudden onset of (symptoms of) Chiari malformation after mild trauma

Spina A, Boari N, Gagliardi F, Donofrio CA, Mortini P. Sudden onset of Chiari
malformation type 1 in a young child after trauma. Childs Nerv Syst. 2015 May 10.
[Epub ahead of print]

Chiari 1 malformation is a rare craniovertebral junction malformation accounting up to 1 case in every 1000 newborns per year. It is characterized by herniation of cerebellar tonsils below the foramen magnum sometimes with syringomyelia. Usually, patients have a long history of slowly progressive neurological symptoms. Uncommonly, Chiari 1 malformation could present with a sudden onset, also after trauma. Few cases are reported about young children.
The authors report a case of a 6-month child with symptoms at onset after a mild trauma. The pertinent literature is reviewed.
Symptoms of Chiari 1 malformation are usually slowly progressive. Few cases have been reported of the sudden onset of symptoms, some of these after trauma. In young children, the clinical setting could be insidious and potentially lethal. A sudden onset of Chiari 1 malformation must be considered as a consequence of trauma, usually after performing a brain MRI. Management of these cases is still controversial, and surgery may be indicated in managing symptoms; however, it seems to not affect clinical outcome.

Saturday, May 30, 2015

Why doctors quit

I was reminded of this exchange upon receiving my med-school class’s 40th-reunion report and reading some of the entries. In general, my classmates felt fulfilled by family, friends and the considerable achievements of their professional lives. But there was an undercurrent of deep disappointment, almost demoralization, with what medical practice had become.

The complaint was not financial but vocational — an incessant interference with their work, a deep erosion of their autonomy and authority, a transformation from physician to “provider.”

As one of them wrote, “My colleagues who have already left practice all say they still love patient care, being a doctor. They just couldn’t stand everything else.” By which he meant “a never-ending attack on the profession from government, insurance companies, and lawyers . . . progressively intrusive and usually unproductive rules and regulations,” topped by an electronic health records (EHR) mandate that produces nothing more than “billing and legal documents” — and degraded medicine.

Courtesy of a colleague

Friday, May 29, 2015

An unbiased view of sleep

Implicit biases -- those stereotypes about gender, race, age and ethnicity that you might never own up to but which nevertheless color your reactions to people and situations -- are laid down early, and they are surprisingly hard to break.

In a study published Thursday in Science, psychologists from Northwestern University note that although a systematic retraining session can begin to undo implicit biases, its impact is fragile and fleeting. With just a nudge -- a news report, a personal interaction that supports a long-held implicit bias or just the passage of time -- the effects of training aimed at countering such unconscious prejudice disappear.

The new research finds, however, that adding sleep to the mix -- and subtly reinforcing the retraining during subsequent sleep -- helped stamp out implicit bias robustly and enduringly in experimental subjects. When participants slept soundly after viewing a series of images designed to counter implicit bias, and got a subtle reminder of that learning during their sleep, their implicit biases were more clearly unlearned. And those prejudices stay unlearned for longer, the study found.


Thanks to:

Xiaoqing Hu , James W. Antony, Jessica D. Creery, Iliana M. Vargas, Galen V. Bodenhausen, Ken A. Paller.  Unlearning implicit social biases during sleep.  Science Vol. 348 no. 6238 pp. 1013-1015


Palliative medicine

One morning, my patient’s wife told me that he had decided against any more aggressive procedures...

I stared at the sign still hanging behind his bed, NPO (from the Latin “nil per os,” or “nothing by mouth”) in bold black letters warning his caregivers that he wasn’t allowed to eat or drink.
I told the medical student I was working with that we were going on a field trip — to the liquor store.
“Won’t we get in trouble?” he asked.
I hoped not. But I had promised my patient a beer when it was all done, and that was a promise I could keep. So that afternoon, we trooped to the liquor store across the street form the hospital and bought a cold bottle of Guinness Extra Stout, which the medical student tucked inside the pocket of his short white coat. We giggled about the bulge the smuggled beverage made in his coat as we rode the elevator back up to the patient’s room...
“I figured I’d get you that Guinness I promised,” I said. I held it up to the patient’s wife first, who nodded encouragingly, and then turned around and showed my patient. He smiled – a Guinness man after all. It was only after I struggled with the cap that I realized none of us had a bottle opener. My medical student saw me casting about, grabbed the beer and expertly flicked the bottle on the side of the table. We all laughed in surprise as drops of beer ran over the side of the bottle and onto his hands. The room smelled like a party.
“Is that O.K.?” I asked.
My patient gave me a thumbs-up. I wished that I had known him better. “Cheers,” he said.
“Bottoms up,” I replied.
Thanks to:

Thursday, May 28, 2015

Ventriculomegaly in NF1

An earlier post from the child-neuro list-serve with today's addition
The patient’s younger sister, who has Beckwith-Weidemann, as well as NF1, had an MRI done at 9 ½ years of age when growth hormone therapy was being considered which showed  that ventriculomegaly with some transependymal flow had emerged since an MRI 4 years earlier .   Low positioning of the cerebellar tonsils and an increased size of the supracerebellar cistern suggested a component of craniocervical junction outflow obstruction.  The patient was asymptomatic.   A repeat MRI done 3 ½  months later shows fundamental stability of findings.  Her older brother had a follow-up MRI in 9/14, the fifth since the discovery of his ventriculomegaly  3 ½ years ago,  which showed stable ventriculomegaly.

Unexplained emergence of ventriculomegaly in a NF1 patient 2014-07-03 12:13:00

An 11 ½ yo boy with NF1 (father and sister also have NF1) was found at 2 years of age to have optic pathway enlargement which was most pronounced in the chiasm, with slight extension into the optic tracts, right greater than left with abnormal enhancement, also eccentric to the right. 10 MRIs later, this has remained unchanged. There were multiple foci of T2/FLAIR increased signal within the deep cerebellar white matter, pons, midbrain, basal ganglia and thalami. At 9 years of age, surprisingly, there had emerged mild to moderate ventriculomegaly involving the lateral, right greater than left, and third ventricles compared to an MRI done 2 ½ years previously. There was no evident explanation for this. There was no intervention. 4 MRIs later, these findings have remained unchanged. The focus of attention on the most recent MRI was a focal area of increased T2/FLAIR signal in the left lateral margin of the third ventricle/hypothalamus measuring 7 x 8 x 9 mm, which had minimally changed in size and conspicuity for 4 MRIS.

He did well academically in 5th grade. He does receive intramuscular leuprolide acetate tor precocious puberty

Wednesday, May 27, 2015

Tell me why

Six years ago I went to the hospital for an ultrasound. I had recently suffered a second trimester miscarriage and needed to know that the Rainbow Baby that I was carrying was alive.

She was.

But with fluid separating her skin from her body – a condition called “diffuse fetal hydrops” – and with heart holes, the doctor told me that she had a zero percent chance of survival.

Let’s hold that a moment: zero percent.

He said she had a zero percent chance. He said that I should have an amniocentesis, not for her as she had no chance of surviving, but to know what was going on so that we would be prepared for a similar situation should it happen with a future pregnancy.

Gulp. Zero percent.

So I did. I went back in the hospital with my husband by my side, and had the amnio, which ultimately revealed the presence of an extra chromosome. Down syndrome. By the time our baby was born, her diffuse fetal hydrops had “miraculously” resolved itself, as had her heart holes. Moxie Eleanor Xuan Mai was born with no health issues whatsoever.

Tell me why now. Tell me why it’s OK for the doctor to give a sentence like “zero percent.”

Tell me why he can get away with this, when if I had believed him and followed through on his recommendation to terminate her life, I would have ended the life of a perfectly healthy child – not that there is anything wrong with a child being born unhealthy. It’s simply that by his own reasoning – health – he was completely, utterly and profoundly wrong.

Tell me why doctors can say “zero percent” and not be held accountable.

Tell me how many other babies are aborted based on a doctor saying “zero percent.”

- See more at:

SIDS and altitude

Babies born at a higher altitude faced a greater risk of sudden infant death syndrome (SIDS), according to the results of a large population-based study.

David Katz, MD, of the University of Colorado School of Medicine in Aurora, and colleagues found an adjusted increased risk of SIDS (odds ratio 2.30, 95% CI 1.01-5.24) for babies born where the mother resided at an altitude >8,000 feet compared with those born at <6,000 feet of mother's residence


Katz D, Shore S, Bandle B, Niermeyer S, Bol KA, Khanna A. Sudden Infant Death
Syndrome and Residential Altitude. Pediatrics. 2015 May 25. pii: peds.2014-2697.
[Epub ahead of print]

Dyslexia in Kids Not Caused by Vision Problems (Surprise!)

Alexandra L. Creavin, of the School of Social and Community Medicine at the University of Bristol in the England, and colleagues reported no association between severe reading impairment (SRI) and strabismus ("squinting"), motor fusion (eye coordination), sensory fusion at a distance, refractive error (need for glasses), amblyopia ("lazy eye"), convergence (focus), accommodation, or contrast sensitivity (eye chart)...

The authors state that ophthalmic intervention should not be the main focus of dyslexia management, and "intensive interventions involving instructions on phonics, word analysis, and reading fluency comprehension" may produce better results.
"There is a lack of robust epidemiologic evidence to suggest that [ophthalmic] therapies are effective in improving outcomes for those with dyslexia," they concluded.


Creavin AL, Lingam R, Steer C, Williams C. Ophthalmic Abnormalities and
Reading Impairment. Pediatrics. 2015 May 25. pii: peds.2014-3622. [Epub ahead of

Tuesday, May 26, 2015

Dragon lady

According to an Anglo-Dutch research team in the Hague, the Netherlands, a 52-year-old woman presented at a psychiatric clinic in 2011 plagued with something utterly bizarre – even to the experienced doctors.

For the entirety of her life she’d seen human faces metamorphose into the faces of dragons, with this same hallucination happening multiple times each day. ‘She could perceive and recognise actual faces, but after several minutes they turned black, grew long, pointy ears and a protruding snout, and displayed a reptiloid skin and huge eyes in bright yellow, green, blue, or red,’...

‘She saw similar dragon-like faces drifting towards her many times a day from the walls, electrical sockets, or the computer screen, in both the presence and absence of face-like patterns, and at night she saw many dragon-like faces in the dark.’

Read more:

See:  Blom JD, Sommer IE, Koops S, Sacks OW. Prosopometamorphopsia and facial
hallucinations. Lancet. 2014 Nov 29;384

Friday, May 22, 2015

How the Biggest Fabricator in Science Got Caught

Yoshitaka Fujii falsified 183 papers before statistics exposed him...

Carlisle compared the findings from 168 of Fujii’s “gold standard” clinical trials from 1991 to 2011 (an eyebrow-raising average of about eight papers a year) with what other investigators had previously reported, and what would be expected to occur by chance. He looked at factors ranging from patient height and blood pressure at the start of a study to rates of side effects associated with the drugs Fujii was reportedly testing.

Using these techniques, Carlisle concluded in a paper he published in Anaesthesia in 2012 that the odds of some of Fujii’s findings being experimentally derived were on the order of 10-33, a hideously small number. As Carlisle dryly explained, there were “unnatural patterns” that “would support the conclusion that these data depart from those that would be expected from random sampling to a sufficient degree that they should not contribute to the evidence base.” In other words: If it seems too good to be true, math will tell you it probably is.

Thursday, May 21, 2015

An Upper Midwest Make-a-Wish

Thanks again to a colleague

Located in Hudson WI, SHOT for HOPE is a 501 (c) (3) charity that was founded in 2012 by Eric and Missy Steingraber. They both have a passion for hunting and believe that "a family that hunts together, stays together". Their mission is to bring outdoors enthusiasts together to support children with a life threatening illness or life altering disability and to raise awareness, support and funding to be able to give a child a chance to experience the outdoors and a chance to go on a hunt of their dreams.

Teen Drinking Linked to Brain Changes

All of the participants had an MRI scan two to six times between the ages of 12 and 24 and were followed for up to 8 years, the investigators reported.

Over time, neocortical gray matter decreased in all participants, they found, but was significantly greater in the drinkers, especially in the frontal, lateral frontal, and temporal cortices (at P=0.019, P=0.013, and P=0.001, respectively.)

Similarly, white matter regions grew in volume in both groups, but growth was attenuated in the heavy drinkers compared with the nondrinkers in the pons and the corpus callosum (at P=0.001 and P<0.001, respectively.)

Squeglia LM, Tapert SF, Sullivan EV, Jacobus J, Meloy MJ, Rohlfing T,
Pfefferbaum A. Brain Development in Heavy-Drinking Adolescents. Am J Psychiatry.
2015 May 18: [Epub ahead of print]

Great experiments

R. Rossen, H. Kabat, J.P. Anderson. Acute arrest of cerebral circulation in man.
Arch. Neurol Psychiatry, 50 (1943), pp. 510–528
In order to study the effect of acute cerebral anoxia in man, a new technic was devised, which used the Kabat-Rossen-Anderson apparatus. This procedure is essentially an adaptation to the human subject of the method devised by one of us for producing arrest of cerebral circulation by means of a cervical pressure cuff. Acute arrest of circulation in the human brain was studied in 11 schizophrenic patients and in 126 normal young male subjects. No deleterious effects were observed from repeated tests on these subjects...
The Kabat-Rossen-Anderson apparatus has been designed to induce temporary arrest of circulation in the human brain without affecting the respiratory tract. This is accomplished by means of a specially designed inflatable cervical pressure cuff, held down to the lower third of the neck. The pressure in the cuff rises to 600 mm. of mercury within one-eighth second. The subject himself, as well as the physician, controls the deflation of the cuff, which can be accomplished within a fraction of a second. The apparatus allows full observation of the sitting subject at all times for accurate recording. The reactions of the subject may readily be recorded by means of devices such as the electrocardiograph and the electroencephalograph. The sudden inflation of the cuff to a high pressure causes occlusion of the vessels to the brain before the next heart beat, so that engorgement of the cerebral vessels is prevented.
The pressure cuff has been improved in the course of this investigation, so that the earlier experiments on the schizophrenic patients and normal subjects are valuable chiefly for their qualitative observations.
The procedure has been applied repeatedly to the same subjects, with no injurious effects. Periods of acute arrest of cerebral circulation for as long as one hundred seconds appear to be well tolerated and are followed by rapid and uneventful recovery.
See also below Breathholding spells April 15, 2015.

Retinoblastoma diagnosis

Julie Fitzgerald told WREX that she first noticed something odd about her son Avery’s eye a couple months before the photo was taken — when light would shine at a certain angle she thought she could see something in his pupil.

She couldn’t figure out what exactly she was looking at, however, so she decided to scour the Internet for answers.

That’s how she learned about a woman whose family photo led to a cancer diagnosis after the flash turned one of her relative’s pupils white instead of red in the image.

Her husband Patrick told her it was probably nothing and that she shouldn’t assume the worst after reading the article. Fitzgerald couldn’t shake a growing sense of concern about Avery, however, so she picked up her phone and took a photo.

“I did not want to take the picture because I had this dreaded feeling in the pit of my stomach,” she told WREX. “And I took the picture and boom. His whole pupil was just white and that’s when I knew.”

Wednesday, May 20, 2015

16p11.2 deletion is associated with auditory processing delays

4 patients at Gillette Children's Specialty Healthcare have this deletion.


Jenkins J 3rd, Chow V, Blaskey L, Kuschner E, Qasmieh S, Gaetz L, Edgar JC,Mukherjee P, Buckner R, Nagarajan SS, Chung WK, Spiro JE, Sherr EH, Berman JI,Roberts TP. Auditory Evoked M100 Response Latency is Delayed in Children with 16p11.2 Deletion but not 16p11.2 Duplication. Cereb Cortex. 2015 Feb 11. pii:bhv008. [Epub ahead of print] PubMed PMID: 25678630.


Individuals with the 16p11.2 BP4-BP5 copy number variant (CNV) exhibit a range of behavioral phenotypes that may include mild impairment in cognition and clinical diagnoses of autism spectrum disorder (ASD). To better understand auditory processing impairments in populations with this chromosomal variation, auditory evoked responses were examined in children with the 16p11.2 deletion, 16p11.2 duplication, and age-matched controls. Stimuli consisted of sinusoidal binaural tones presented passively while children underwent recording with magnetoencephalography (MEG). The primary indicator of auditory processing impairment was the latency of the ∼100-ms "M100" auditory response detected by MEG, with the 16p11.2 deletion population exhibiting profoundly delayed M100 latencies relative to controls. This delay remained even after controlling for potential confounds such as age and cognitive ability. No significant difference in M100 latency was observed between 16p11.2 duplication carriers and controls. Additionally, children meeting diagnostic criteria for ASD (16p11.2 deletion carriers) exhibited nonsignificant latency delays when compared with the corresponding CNV carriers not meeting criteria for ASD. Present results indicate that 16p11.2 deletion is associated with auditory processing delays analogous to (but substantially more pronounced than) those previously reported in "idiopathic" ASD.

More news regarding 16p11.2.

Autism genes activate during fetal brain development
February 20, 2015 source: UC San Diego Health System

Scientists at the University of California, San Diego School of Medicine have found that mutations that cause autism in children are connected to a pathway that regulates brain development. The research, led by Lilia Iakoucheva, PhD, assistant professor in the Department of Psychiatry, is published in the February 18 issue of Neuron. The researchers studied a set of well–known autism mutations called copy number variants or CNVs. They investigated when and where the genes were expressed during brain development. “One surprising thing that we immediately observed was that different CNVs seemed to be turned on in different developmental periods,” said Iakoucheva. Specifically, the scientists noted that one CNV located in a region of the genome known as 16p11.2, contained genes active during the late mid–fetal period. Ultimately, they identified a network of genes that showed a similar pattern of activation including KCTD13 within 16p11.2 and CUL3, a gene from a different chromosome that is also mutated in children with autism.

Lin GN, Corominas R, Lemmens I, Yang X, Tavernier J, Hill DE, Vidal M, Sebat J, Iakoucheva LM. Spatiotemporal 16p11.2 Protein Network Implicates Cortical Late Mid-Fetal Brain Development and KCTD13-Cul3-RhoA Pathway in Psychiatric Diseases. Neuron. 2015 Feb 18;85(4):742-754.


The psychiatric disorders autism and schizophrenia have a strong genetic component, and copy number variants (CNVs) are firmly implicated. Recurrent deletions and duplications of chromosome 16p11.2 confer a high risk for both diseases, but the pathways disrupted by this CNV are poorly defined. Here we investigate the dynamics of the 16p11.2 network by integrating physical interactions of 16p11.2 proteins with spatiotemporal gene expression from the developing human brain. We observe profound changes in protein interaction networks throughout different stages of brain development and/or in different brain regions. We identify the late mid-fetal period of cortical development as most critical for establishing the connectivity of 16p11.2 proteins with their co-expressed partners. Furthermore, our results suggest that the regulation of the KCTD13-Cul3-RhoA pathway in layer 4 of the inner cortical plate is crucial for controlling brain size and connectivity and that its dysregulation by de novo mutations may be a potential determinant of 16p11.2 CNV deletion and duplication phenotypes

Tuesday, May 19, 2015


Orthorexia:  An Unhealthy Obsession with Healthy Foods

Children and teens who show signs of this eating disorder have obsessive concerns about eating foods that are clean, unprocessed, organic, pesticide and preservative free, low in fat, sugar or salt – to the point that it impacts their everyday activities. For instance, if your daughter turns down an opportunity to go out to eat with her friends because she is worried that she will not be able to follow her strict dietary guidelines, this is a good time to ask some questions...

What’s troubling about orthorexia is that the side effects can mimic the more well-known eating disorders, such as anorexia or bulimia. The symptoms are serious, chronic, and go beyond a lifestyle choice. Maintaining an obsession with healthy food may cause a serious reduction in calories because “acceptable” food might not be available and if dietary restrictions are too severe, malnutrition can result. Malnutrition and weight loss for children and teens is highly concerning because this is a period of time when they should be growing. When too few calories are consumed, this cannot occur properly. Losing weight can lead to a slower metabolism, stunted growth, delayed puberty, hair loss, dry skin, absent menstrual cycles, and changes in body temperature.


Multiple sclerosis confers distance running advantage

Kayla Montgomery, 18, was found to have multiple sclerosis three years ago. Defying most logic, she has gone on to become one of the fastest young distance runners in the country — one who cannot stay on her feet after crossing the finish line.
Because M.S. blocks nerve signals from Montgomery’s legs to her brain, particularly as her body temperature increases, she can move at steady speeds that cause other runners pain she cannot sense, creating the peculiar circumstance in which the symptoms of a disease might confer an athletic advantage.
But intense exercise can also trigger weakness and instability; as Montgomery goes numb in races, she can continue moving forward as if on autopilot, but any disruption, like stopping, makes her lose control.

Identical triplets

 A special delivery and a first for the doctors and nurses at Corpus Christi Medical Center-Bay Area, identical girl triplets were born last night. Two of the babies are conjoined.

Sylvia Torres gave birth to all three babies Saturday night at 10:52pm. The chances of having identical triplet girls, 2 of which are conjoined, is a one in fifty million chance.

Monday, May 18, 2015

Respiration and SUDEP

Summary: There is increasing evidence that periictal respiratory disturbances are an important contributor to the pathophysiological changes leading to sudden unexpected death in epilepsy (SUDEP). In patients with SUDEP occurring in epilepsy monitoring units, respiratory disturbances occurred early in the postictal period and frequently preceded terminal bradycardia and asystole. Periictal hypoxemia and hypercapnia are observed in about one-third of patients undergoing video-EEG telemetry. Pulmonary edema is frequently observed at autopsy in cases of SUDEP and may be relevant as a contributing cause in a subset of SUDEP. Animal studies support the notion that periictal respiratory disturbances are crucial to the pathophysiology of SUDEP. Serotonergic neurons modulate the excitability of the neuronal network generating the respiratory rhythm. Ictal and periictal impairment of serotonergic and glutaminergic neurons involved in the arousal system may also predispose to SUDEP by impeding the patient's ability to reposition the head and facilitate ventilation after a seizure. Periictal functional impairment of serotonergic neurons seems to be important in the pathophysiology of SUDEP and a potential target for pharmacotherapy aimed at SUDEP risk reduction.

Kennedy JD, Seyal M. Respiratory pathophysiology with seizures and
implications for sudden unexpected death in epilepsy. J Clin Neurophysiol. 2015

Another Tourette tale

The day before the race in Charlotte, her father, Mike, an Air Force pilot, picked her up as if she were a little girl and carried her up 17 flights of stairs because she was too terrified to get inside the elevator at their hotel. All closed spaces paralyze her with anxiety and fear: her face goes flush, her heart races, her whole body becomes hot. The first time she encountered the hotel elevator, she took the stairs and wore herself out. The second time, her father wouldn’t let her exhaust herself before the race. As he climbed, he held her close while she cracked jokes and tried to get her heart to slow down.

A couple months later, Amaris’ mother, Kristen, explained how someone so unnaturally talented could also be so fragile. Kristen is perceptive and protective of her children, and she’s had plenty of reason to think about the struggle between Amaris’ body and brain. “When she runs,” Kristen says, “I think she’s running from disorder.”

When Amaris was three years old, her parents would sometimes find her lying on the floor, face up and stiff, the muscles in her body clenched all at once. Her eyes would be wide open and focused to one side; her face would be red from holding her breath. Then, after a few minutes, she’d get up and continue playing as if nothing had happened.


Now we know

Elucidating the neurobiology of the adolescent brain is fundamental to our understanding of the etiology of psychiatric disorders such as schizophrenia and addiction, the symptoms of which often manifest during this developmental period. Dopamine neurons in the ventral tegmental area (VTA) are strongly implicated in adolescent behavioral and psychiatric vulnerabilities, but little is known about how adolescent VTA neurons encode information during motivated behavior.
We recorded daily from VTA neurons in adolescent and adult rats during learning and maintenance of a cued, reward-motivated instrumental task, and extinction from this task.
During performance of the same motivated behavior, identical events were encoded differently by adult and adolescent VTA neurons. Adolescent VTA neurons with dopamine-like characteristics lacked a reward anticipation signal and showed a smaller response to reward delivery compared to adults. After extinction, however, these neurons maintained a strong phasic response to cues formerly predictive of reward opportunity.
Anticipatory neuronal activity in the VTA supports preparatory attention and is implicated in error prediction signaling. Absence of this activity, combined with persistent representations of previously rewarded experiences, may provide a mechanism for rash decision making in adolescents.

See: Yunbok Kim, Nicholas W Simon, Jesse Wood, Bita Moghaddam.  Reward anticipation is encoded differently by adolescent ventral tegmental area neurons.  Biological Psychiatry.  Publication stage: In Press Accepted Manuscript

Sunday, May 17, 2015

Kissing cousins

And the consensus about health risks appears to be shifting. In 2002, the National Society of Genetic Counselors (NSGC) published the findings of a task force set up to look specifically at the risks for offspring of first cousins. They estimated that health risks for those children were about 1.7 percent to 2.8 percent higher than for children born to unrelated parents. They concluded that “There is a great deal of stigma associated with cousin unions in the United States and Canada that has little biological basis.”

See: RL Bennett, AG Motulsky, A Bilttles, L Hudgins, et al.  Genetic Counseling and Screening of Consanguineous Couples and Their Offspring:  Recommendations of the National Society of Genetic Counselors. Journal of Genetic Counseling. 2002;11: 97-119.

Saturday, May 16, 2015


In 2010, the Institute of Medicine issued a report stating that waste accounted for thirty per cent of health-care spending, or some seven hundred and fifty billion dollars a year, which was more than our nation’s entire budget for K-12 education. The report found that higher prices, administrative expenses, and fraud accounted for almost half of this waste. Bigger than any of those, however, was the amount spent on unnecessary health-care services. Now a far more detailed study confirmed that such waste was pervasive...

Another powerful force toward unnecessary care emerged years after Arrow’s paper: the phenomenon of overtesting, which is a by-product of all the new technologies we have for peering into the human body. It has been hard for patients and doctors to recognize that tests and scans can be harmful. Why not take a look and see if anything is abnormal? People are discovering why not. The United States is a country of three hundred million people who annually undergo around fifteen million nuclear medicine scans, a hundred million CT and MRI scans, and almost ten billion laboratory tests. Often, these are fishing expeditions, and since no one is perfectly normal you tend to find a lot of fish. If you look closely and often enough, almost everyone will have a little nodule that can’t be completely explained, a lab result that is a bit off, a heart tracing that doesn’t look quite right...

What’s more, the value of any test depends on how likely you are to be having a significant problem in the first place.. .

Overtesting has also created a new, unanticipated problem: overdiagnosis. This isn’t misdiagnosis—the erroneous diagnosis of a disease. This is the correct diagnosis of a disease that is never going to bother you in your lifetime.

Friday, May 15, 2015

Colorado Rancher Suffers Traumatic Brain Injury, Becomes Accidental Genius

For most of her life, Leigh Erceg was an athlete who loved NASCAR, a bubbly tomboy who worked on a ranch in remote northwestern Colorado. She had boyfriends and a degree in physical education and zero interest in math or art.

A few years ago, Erceg, 47, suffered a traumatic brain injury and now she is a gifted artist and poet. She enjoys spending time puzzling over mathematical equations. She can “see” sounds and “hear” colors when she listens to music, although she is extremely sensitive to light.
She remembers nothing about her prior life. She doesn’t even recognize her own mother.
Erceg’s condition is so incredibly rare that it took numerous scientific studies and brain scans to diagnose her with what is called “savant syndrome.”

Laughter is the best medicine

Benefits of laughter include reduced anger, anxiety, depression, and stress; reduced tension (psychological and cardiovascular); increased pain threshold; reduced risk of myocardial infarction (presumably requiring hearty laughter); improved lung function; increased energy expenditure; and reduced blood glucose concentration. However, laughter is no joke—dangers include syncope, cardiac and oesophageal rupture, and protrusion of abdominal hernias (from side splitting laughter or laughing fit to burst), asthma attacks, interlobular emphysema, cataplexy, headaches, jaw dislocation, and stress incontinence (from laughing like a drain). Infectious laughter can disseminate real infection, which is potentially preventable by laughing up your sleeve.

Ferner RE, Aronson JK. Laughter and MIRTH (Methodical Investigation of
Risibility, Therapeutic and Harmful): narrative synthesis. BMJ. 2013 Dec 12;347

Rocket docs

Confession:  I was a 3 year MD (University of Texas Medical Branch 1979)
"In response to complaints that medical education costs too much, takes too long, teaches the wrong things, and distorts the physician workforce, schools are reconfiguring themselves in a variety of ways -- with revamped curriculums, new teaching styles, individually shaped courses of study, and shortened study periods.
A handful of medical schools, notably Mercer University in Georgia, University of California at Davis, and Texas Tech, are allowing students to complete their course of study in 3 years instead of the traditional 4, with the expectation that they will go into primary care specialties...

OHSU students are finishing the first year of the school's "competency-based" course of study, which teaches them how to search out data and use information systems to care for individual patients and populations. Once they master certain milestones of learning, they advance to the next level. That means some students will complete medical school in less than 4 years."

See also:  But today, says Mangrulkar, the 2-plus-2 model doesn't work. For one thing, there's too much medical science for anyone to learn in 2 years – and most information can be quickly accessed from a smartphone or tablet. At the same time, medicine is constantly in flux. What Michigan and many other schools are trying to do instead is prepare doctors for the inevitable changes they'll see over their practice lives...

"We shouldn't even try to predict what that system's going to be like," he says. "Which means we need to give students the tools to be adaptable, to be resilient, to problem solve, push through some things, accept some things, but change other things."

Treatment of globoid cell leukodystrophy

Hawkins-Salsbury JA, Shea L, Jiang X, Hunter DA, Guzman AM, Reddy AS, Qin EY,
Li Y, Gray SJ, Ory DS, Sands MS. Mechanism-based combination treatment
dramatically increases therapeutic efficacy in murine globoid cell
leukodystrophy. J Neurosci. 2015 Apr 22;35(16):6495-505.

Globoid cell leukodystrophy (GLD, Krabbe disease) is a lysosomal storage disease (LSD) caused by a deficiency in galactocerebrosidase (GALC) activity. In the absence of GALC activity, the cytotoxic lipid, galactosylsphingosine (psychosine), accumulates in the CNS and peripheral nervous system. Oligodendrocytes and Schwann cells are particularly sensitive to psychosine, thus leading to a demyelinating phenotype. Although hematopoietic stem-cell transplantation provides modest benefit in both presymptomatic children and the murine model (Twitcher), there is no cure for GLD. In addition, GLD has been relatively refractory to virtually every experimental therapy attempted. Here, Twitcher mice were simultaneously treated with CNS-directed gene therapy, substrate reduction therapy, and bone marrow transplantation to target the primary pathogenic mechanism (GALC deficiency) and two secondary consequences of GALC deficiency (psychosine accumulation and neuroinflammation). Simultaneously treating multiple pathogenic targets resulted in an unprecedented increase in life span with improved motor function, persistent GALC expression, nearly normal psychosine levels, and decreased neuroinflammation. Treating the primary pathogenic mechanism and secondary targets will likely improve therapeutic efficacy for other LSDs with complex pathological and clinical presentations.

Li Y, Sands MS. Experimental therapies in the murine model of globoid cell
leukodystrophy. Pediatr Neurol. 2014 Nov;51(5):600-6.

Globoid cell leukodystrophy or Krabbe disease, is a rapidly progressive childhood lysosomal storage disorder caused by a deficiency in galactocerebrosidase. Galactocerebrosidase deficiency leads to the accumulation of galactosylsphingosine (psychosine), a cytotoxic lipid especially damaging to oligodendrocytes and Schwann cells. The progressive loss of cells involved in myelination results in a dysmyelinating phenotype affecting both the central and peripheral nervous systems. Current treatment for globoid cell leukodystrophy is limited to bone marrow or umbilical cord blood transplantation. However, these therapies are not curative and simply slow the progression of the disease. The Twitcher mouse is a naturally occurring biochemically faithful model of human globoid cell leukodystrophy that has been used extensively to study globoid cell leukodystrophy pathophysiology and experimental treatments. In this review, we present the major single and combination experimental therapies targeting specific aspects of murine globoid cell leukodystrophy.
Literature review and analysis.
The evidence suggests that even with the best available therapies, targeting a single pathogenic mechanism provides minimal clinical benefit. More recently, combination therapies have demonstrated the potential to further advance globoid cell leukodystrophy treatment by synergistically increasing life span. However, such therapies must be designed and evaluated carefully because not all combination therapies yield such positive results.
A more complete understanding of the underlying pathophysiology and the interplay between various therapies holds the key to the discovery of more effective treatments for globoid cell leukodystrophy.

Thursday, May 14, 2015

"Benign" infantile seizures

Kenjiro Kikuchi, Shin-ichiro Hamano, Norimichi Higurashi, Ryuki Matsuura, Kotoko Suzuki, Manabu Tanaka, Motoyuki Minamitani.  Difficulty of early diagnosis and requirement of long-term follow-up in benign infantile seizures.  To appear in: Pediatric Neurology.  Accepted Date: 28 March 2015
To investigate whether benign infantile seizures can be diagnosed in the acute phase.

We retrospectively investigated the medical records of 44 patients initially diagnosed as having acute phase benign infantile seizures. All patients were followed for ≥12 months and we reviewed patients’ psychomotor development and presence or absence of seizure recurrence at the last visit. Patients were divided into the following three groups according to the final diagnosis: benign infantile seizures, benign infantile seizures associated with mild gastroenteritis, and non-benign infantile seizures. We defined benign infantile seizures associated with mild gastroenteritis and benign infantile seizures as those associated with normal psychomotor development and no seizure recurrence 3 months after onset of the first seizure, whereas non-benign infantile seizures were associated with delayed psychomotor development and/or seizure recurrence after 3 months of onset of the first seizure. We analyzed the clinical features in the acute phase and compared them between the groups.

The median age at onset was 7.6 months. A final diagnosis of benign infantile seizures associated with mild gastroenteritis was made in 3 patients. In the remaining 41 patients, the final diagnosis was benign infantile seizures in 30 (73.2%) and non-benign infantile seizures in 11 (26.8%). In the non-benign infantile seizure group, intellectual disability was diagnosed in 8 patients and seizure recurrence in 6. There were no significant differences in clinical features between the groups in the acute phase, such as seizure type or seizure duration.

About 30% of patients initially diagnosed as having benign infantile seizures did not experience a benign clinical course. Our findings suggest that clinical features in the acute phase are not helpful for predicting benign outcomes in benign infantile seizures and that only long-term follow-up can discriminate benign infantile seizures from non-benign infantile seizures.

Wednesday, May 13, 2015

Dummheit--the return of measles

Evans RG. Dummheit. Healthc Policy. 2015 Feb;10(3):14-22.

Immunizing against influenza is tricky; against measles is not. Influenza comes in many constantly evolving strains, but one measles shot in childhood confers lifelong immunity. Unlike the flu, measles was wiped out. Its return represents an outbreak not of disease, but of stupidity. The matrix of stupidity is, however, reinforced by strong strands of malice, as when Andrew Wakefield's fraudulent 1998 paper linked the MMR vaccine to autism. The fraud was unmasked and the vaccine-autism link disproven, but the evil influence continues. Measles offers an illustration of Virchow's insights that medicine is a social science and that politics is medicine writ large. It is this "inconvenient truth" that is being suppressed by muzzling the Chief Public Health Officer (CPHO) and attacking public health for addressing "social determinants."

ADHD and genetics

A sharp general linear decrease in the levels of hyperactive/impulsive symptoms was observed from ages 8 to 16 years in this population-based sample of twins. A less pronounced decrease was observed for inattention symptoms. Important interindividual differences were detected (faster or slower decreases vs persistence, or even increases in inattention symptoms for a subset of children). These interindividual differences in the developmental course of symptoms were mostly explained by genetic influences, mostly independent from those influencing the baseline level of symptoms. Developmental models will be crucial in identifying genetic variants and specific environmental influences explaining why some children remit from ADHD, whereas others persist. The confirmation of large genetic influences on the developmental course of ADHD symptoms is important for both clinicians and patients. For clinicians, the maintenance or increase in symptoms (a decline being normative in the population) might represent a marker of vulnerability reflecting genetic liability and warrant closer follow-up. It also raises the question of the necessity to inform patients and their relatives about the higher risk of persistence in families of index cases with persistent symptoms.

Pingault JB, Viding E, Galéra C, Greven CU, Zheng Y, Plomin R, Rijsdijk F.
Genetic and Environmental Influences on the Developmental Course of
Attention-Deficit/Hyperactivity Disorder Symptoms From Childhood to Adolescence.
JAMA Psychiatry. 2015 May 6. doi: 10.1001/jamapsychiatry.2015.0469. [Epub ahead
of print]

Concussion and school performance

Ransom DM, Vaughan CG, Pratson L, Sady MD, McGill CA, Gioia GA. Academic
Effects of Concussion in Children and Adolescents. Pediatrics. 2015 May 11. pii:
peds.2014-3434. [Epub ahead of print]



The aim of this work is to study the nature and extent of the adverse academic effects faced by students recovering from concussion.


A sample of 349 students ages 5 to 18 who sustained a concussion and their parents reported academic concerns and problems (eg, symptoms interfering, diminished academic skills) on a structured school questionnaire within 4 weeks of injury. Postconcussion symptoms were measured as a marker of injury severity. Results were examined based on recovery status (recovered or actively symptomatic) and level of schooling (elementary, middle, and high school).


Actively symptomatic students and their parents reported higher levels of concern for the impact of concussion on school performance (P < .05) and more school-related problems (P < .001) than recovered peers and their parents. High school students who had not yet recovered reported significantly more adverse academic effects than their younger counterparts (P < .05). Greater severity of postconcussion symptoms was associated with more school-related problems and worse academic effects, regardless of time since injury (P < .001).


This study provides initial evidence for a concussion's impact on academic learning and performance, with more adverse effects reported by students who had not yet recovered from the injury. School-based management with targeted recommendations informed by postinjury symptoms may mitigate adverse academic effects, reduce parent and student concerns for the impact of the injury on learning and scholastic performance, and lower the risk of prolonged recovery for students with active postconcussion symptoms.


Tuesday, May 12, 2015

Death by organ donation

Nair-Collins justifies harvesting organs from living persons, in part, by attacking the legitimacy of the concept of “brain death” that is utilized in some cases to define a person as dead even though some basic life functions remain operative.

“Patients who have been accurately diagnosed with ‘brain death’ according to accepted standards are able to engage in a large variety of integrative, feedback-driven biological functions that work together to maintain the internal physiologic stability for the organism as a whole and can do so over very long periods of time,” Nair-Collins told the Register.

“This includes things like getting a fever in response to an infection, healing wounds, regulating the amount of salt and water in the blood, absorbing nutrients through the gut and generating waste products and exchanging oxygen and carbon dioxide through the lungs,” he added. “Some of these patients also show increased blood pressure and heart rate in response to surgical incision. And, finally, more dramatic examples include sexual maturation in children and gestation of a fetus in pregnant women. ... For these reasons, many scholars, including myself, have concluded that ‘brain-dead’ patients are biologically alive.”

If this scientific criticism of brain-death diagnoses is accurate, then it follows that organ removal causes the biological death of the donor.

“In other words, we do not follow the dead-donor rule in practice now,” Nair-Collins added.
But stopping the procurement of organs from “brain-dead” donors, on the grounds that they are really still alive, would exacerbate the organ shortage for transplant, he said. So, he said, doctors alternatively could “make exceptions to the dead-donor rule ... but to explicitly acknowledge that organ donation causes the biological death of these patients.”...

Truog highlighted problems of the modern definitions of brain and cardiac death, citing instances where people are pronounced dead — “dead enough for skin incision and organ procurement,” for example — and then recovered, on their own or with intervention. Such examples illustrate that the definitions of death are “convoluted” and “torture our commonsense understanding of what it means to be dead.” As well, he added, “Current practices violate the dead-donor rule — they’re perfectly ethical, but not because they’re conforming with the dead-donor rule.”

Widespread acknowledgement of these problems associated with the dead-donor rule “destroy the public’s trust in the organ-transplantation process, and this will lead to the unnecessary death of many patients. But we’ve got to come up with other ways of talking about it because we need to save the lifesaving enterprise of organ transplantation,” Truog said.

“What about procuring organs before death?” he asked. “We’ll call it DPD — donation prior to death.”

Read more:


For those who may have seen the cult classic film Freaks (1932), an article describes medical aspects of the movie:

In a circus in which several people with significant physical deformities make their living as sideshow attractions, a voluptuous trapeze artist and her brawny lover attempt to take advantage of a midget in order to take possession of his fortune. When the beauty’s intentions are unmasked and this humiliating lover’s deception is discovered by the little fellow, the revenge of all his handicapped colleagues culminates in a horrifying dramatic ending for the unscrupulous trapeze artist and her strongman lover...

Both ‘normal’ and ‘handicapped’ performers work in a circus. Hans, one of the midgets in the circus, falls in love with the beautiful trapeze artist, Cleopatra. She apparently loves him in return, but in truth what she really wants is Hans’ money because her secret lover is Hercules, the strongman of the circus...

Various characters who have these types of malformations appear in Freaks: Above all we highlight Prince Randian, “The Living Torso” (1881-1934) (Figure 11), a native of British Guyana who had all four extremities missing since birth. Married and having fathered 5 children, he starred in one of the most impressive scenes in the film, in which he was able to roll a cigarette and light it calmly using only his lips...

Frances O’Connor (1914-1982) (Figure 13), also known as the “Living Venus de Milo”, who made up for the congenital absence of her arms by having an extreme ability with her feet, which enabled her to eat, drink, write and even dress herself...

See more at



Fetal alcohol syndrome prevention

Will free pregnancy tests in bar restroom prevent fetal alcohol syndrome? The state of Alaska is hoping it will. In fact, with alcohol use during pregnancy being among the top preventable causes of developmental disabilities and birth defects, the state is even funding a special, two-year pilot project being conducted by the University of Alaska Anchorage...

The $400,000 project’s supporters believe it could yield significant results considering the millions of dollars that Alaska puts out for social services and health care for a patient with fetal alcohol syndrome. Officials state that over 120 babies born in the state every year are afflicted with fetal alcohol symptoms.

Sunday, May 10, 2015

Don't fall for cancer envy

Sadly some cancer charities have openly attacked the amount of funding and attention breast cancer receives instead of finding a way to communicate their own message.

This was best illustrated when a UK group, Pancreatic Cancer Action, devised a campaign that shocked many and was labelled ‘cancer envy.’

The ad may have had the best intentions but all it did was raise outrage by showing pancreatic cancer patients, many of them close to death, saying "I wish I had breast cancer."

The point may have been to highlight the grim prognosis of those suffering from the deadliest form of cancer — one that kills four in five sufferers within a year of diagnosis — but all it did was upset people including the families of those lost to breast cancer.
In 2011 the leading cause of the 43,221 cancer deaths in Australia was lung cancer (8,114), bowel cancer (3,999) prostate cancer (3,294) breast cancer (2,937) and pancreatic cancer (2,416.) But it’s brain cancer that kills more children in Australia than any other disease and is the biggest cancer killer of people under 40. In 2011 there were 1,272 deaths attributed to the condition.

Syndrome X

Layla Qualls looks like a happy, 9- to 10-month-old baby— but she’s actually three years old. The Oklahoma girl was diagnosed with Syndrome X, which means she will never age.
Researchers from the University of California Los Angeles studied Layla as one of seven children found worldwide with Syndrome X to understand the extremely rare condition, reported. They hoped to find the condition’s genetic blueprint to see which genes are slowing down the aging process.

A woman who died last week at the age of 20 never aged.

Brooke Greenberg, of Reisterstown, Md., puzzled medical professionals for years because she still looked and acted like a toddler. Doctors eventually dubbed her extremely rare condition "Syndrome X."

“While the outside world may have noticed Brooke’s physical stature and been puzzled by her unique development state, she brought joy and love to her family,” Rabbi Andrew Busch, who delivered the eulogy at the funeral, told the Daily News Monday.

“Her parents, three sisters and extended family showered her with love and respected her dignity throughout her entire life.”

See also:

"Best practice" guidelines

For all their talk about evidence-based medicine, a lot of doctors don't follow the clinical guidelines set by leading medical groups...

So, even in the midst of good science and a clear consensus on what should be done, a lot of physicians don't follow the "best practice" guidelines.

Now, imagine what happens when the science isn't clear...

"There's really a lot more ambiguity about what is the right thing — what's appropriate [and] what's not appropriate," says Dr. Albert Wu, an internist and professor at the Johns Hopkins Bloomberg School of Public Health.

In cases like these, Wu says, doctors are more likely to follow their gut instincts. And when that happens, fear often comes into play.

Imagine, for example, that a healthy, 40-year-old woman walks into your office and asks about a mammogram.

"If that woman were to develop breast cancer or to have breast cancer, you can imagine what might happen to you if you didn't order the test," Wu says. "Maybe you'd get sued."

Doctors often hear stories like this, he says, and that can affect their judgment.

"Emotion and recent events do influence our decision-making," he says. "We are not absolutely rational, decision-making machines."

See:  Oliver D. Schein, M.D., M.P.H., Joanne Katz, Sc.D., Eric B. Bass, M.D., M.P.H., James M. Tielsch, Ph.D., Lisa H. Lubomski, Ph.D., Marc A. Feldman, M.D., M.P.H., Brent G. Petty, M.D., and Earl P. Steinberg, M.D., M.P.P. for the Study of Medical Testing for Cataract Surgery.  The Value of Routine Preoperative Medical Testing before Cataract Surgery,  N Engl J Med 2000; 342:168-175

Saturday, May 9, 2015

Rett syndrome and the immune system

UVA’s discovery suggests that immune cells bearing a mutation in the Rett gene, MeCP2, cannot perform their normal function and are instead amplifying the disease. By identifying a new role of the immune system in the disorder, through cells known as "macrophages," the UVA team has opened up an exciting new pathway to targeting the disease therapeutically...

"These immune cells may be functioning OK when there is no problem, but the moment there is any sort of problem in any tissue, to respond they need this gene," said Jonathan Kipnis, PhD, of the UVA Department of Neuroscience. "And without this gene, macrophages not only do not respond properly. They respond abruptly, and they start to produce molecules that are further damaging the tissue. ... Cells which are supposed to maintain tissue are killing that tissue."

Cronk JC, Derecki NC, Ji E, Xu Y, Lampano AE, Smirnov I, Baker W, Norris GT,
Marin I, Coddington N, Wolf Y, Turner SD, Aderem A, Klibanov AL, Harris TH, Jung
S, Litvak V, Kipnis J. Methyl-CpG Binding Protein 2 Regulates Microglia and
Macrophage Gene Expression in Response to Inflammatory Stimuli. Immunity. 2015
Apr 21;42(4):679-91.

Taking a stand

From a colleague.

The patient could not stand up from a seated position without using her hands to boost herself up. Others could do it easily, but not this young and otherwise robust woman. It wasn’t really a new problem, the young woman told her mother. She couldn’t even remember when she’d first started to use her arms to help her body go from sitting to standing.

Indeed, she had never given it much thought until a couple of weeks earlier, when the family had gotten together at her mother’s home in South Carolina. She’d gotten up out of her chair to get something when her sister announced, with a touch of surprise, ”Hey, I do that too!” Her sister, it turned out, also used her arms in order to stand up.

Friday, May 8, 2015

A microdeletion tale

A 5 ½ year old girl had undergone evaluation for hypotonia, cognitive and motor handicap and subependymal nodular heterotopia. She had a muscle biopsy performed on July 19, 2005. Muscle histology and histochemistry were unremarkable. She had oxidative metabolism enzymology performed through Horizon Medical Medicine (now Medical Neurogenetics). There was a mild decrease in Complex IV (cytochrome C oxidase) activity. Dr. John Shoffner’s note indicated, “However, before making a diagnosis of Complex IV (cytochrome C oxidase) deficiency, I would want to see cytochrome C oxidase deficient muscle fibers on histochemistry. If the histochemistry is normal, this result is probably related to freezing of the muscle sample. The report from the muscle biopsy reads ‘cytochrome C oxidase activities are maintained.’” I was in contact with Dr. Shoffner who suggested that she have further studies, likely including a repeat muscle biopsy, done through Medical Neurogenetics in order to reassess this issue. She was then seen by Dr. John Shoffner on March 18, 2009.

Comparative genomic hybridization had shown loss of material involving 5q14.3 to 5q15. This result was deemed to be of uncertain significance. It was deemed possible that this represented a benign inherited copy number variant. The report of the comparative genomic hybridization indicated, “No genes of known clinical significance have been mapped to this region.” The mother had comparative genomic hybridization showing no abnormality. It was not possible to obtain comparative genomic hybridization from the father.

In the March 3, 2009, issue of Neurology, an article appeared reporting periventricular heterotopias, mental retardation, and epilepsy associated with 5q14.3-q15 deletion. (Cardoso C, Boys A, Parrini E, Mignon-Ravix C, McMahon JM, Khantane S, Bertini E, Pallesi E, Missirian C, Zuffardi O, Novara F, Villard L, Giglio S, Chabrol B, Slater HR, Moncla A, Scheffer IE, Guerrini R. Periventricular heterotopia, mentalretardation, and epilepsy associated with 5q14.3-q15 deletion. Neurology. 2009 Mar 3;72(9):784-92.) Accordingly, Dr. John Shoffner then gave a diagnosis of the now recognized syndrome associated with the 5q14.3-q15 deletion. Further studies were unnecessary.

Postscript: Later the patient developed problems with foot pain. An MRI of the spine showed approximately 1 cm Tarlov cysts dorsal to the S2 vertebral body, one on the left and two on the right. These were new since the earlier spine MRI of July 19, 2005. She underwent S2-S3 osteoplastic laminotomies for repair of the bilateral Tarlov cysts of exiting S2 and S3 nerve roots. The “crinkly” foot pain remitted, at least for an extended interval of time. However, her life was rendered miserable by iatrogenic urinary incontinence.

Pediatric polysomnography revisited

Strong evidence supports tonsil and adenoidectomy in the context of obstructive sleep apnea (OSA) in children. However, whether a polysomnogram (PSG) is indicated for either preoperative or postoperative evaluation of OSA is not yet established. Although expert opinion suggests that a PSG study is needed to justify the need for tonsil and adenoidectomy, the expert opinion exists in the absence of controlled, randomized studies. Moreover, some experts opine that PSG is indicated both before and after tonsil and adenoidectomy. Certainly, greater clarity surrounding the indications for obtaining PSG studies is needed…
In most sleep laboratories, the cost of an overnight study, including professional fees, exceeds 3000 US dollars. Charges to the patient or the payer are generally well in excess of costs. Thus, there ought to be clear justification to undertake a relatively costly, and inconvenient, diagnostic study. Certainly, in the presence of concerns such as central hypoventilation syndrome or recurrent airway obstruction that does not lead to overt hypoxemia, a PSG may be both instructive and justified. However, when clinical outcomes are apparent and the results of the PSG are largely confirmatory, obtaining the test might not be completely justified…
Given the broad distribution of the PSG testing, it might be time for a well designed trial that can effectively test the hypothesis that PSG testing improves specific, well defined, outcomes in the context of children with OSA, the most common indication for procuring a study. A trial wherein children with clinical evidence of OSA are randomly assigned to either empiric treatment or to undergo PSG testing would provide significant information surrounding the value and utility of PSG. Such data would meaningfully inform the management of many children worldwide.
See:  Cornfield DN, Bhargava S. Sleep medicine: pediatric polysomnography revisited. Curr Opin Pediatr. 2015 Jun;27(3):325-8.

Thursday, May 7, 2015

Traumatic brain injury

Ten days after the accident, doctors and hospital clergy sat down with Hyland and his wife, Cindy, and said they wished they had better news, but Blake had suffered a traumatic brain injury, damaging his temporal and frontal lobes. They said he would never be the same.

"I remember grabbing Cindy's hand in that room," Hyland said. "We said we really appreciate their diagnosis. They're professionals. But our God is greater than that. And that our son will walk out of this hospital one day. They said, 'We hope you prove us wrong.'"
The day after giving his father a kiss, Blake opened his eyes. Little by little, he learned to speak and move again. It's now been 15 months, and the Blake, now 16, is set to return to the 10th grade in Waco in the fall. He still has trouble with his short-term memory and he has some trouble getting around, but he says he wouldn't change what happened to him.
"For him to be cognitively back to where he is, it's a miracle," Hyland told ABC News.
See also:  (cited below under "Ten Years After Terri Schiavo, Death Debates Still Divide Us: Bioethicist"  April 2, 2015 in the comment from April 7, 2015)

Infantile epileptic encephalopathy benefitted by carbamazepine and phenytoin

Pisano T, Numis AL, Heavin SB, Weckhuysen S, Angriman M, Suls A, Podesta B,
Thibert RL, Shapiro KA, Guerrini R, Scheffer IE, Marini C, Cilio MR. Early and
effective treatment of KCNQ2 encephalopathy. Epilepsia. 2015 Apr 16.


To describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the first year of life.

We identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data.

Seizure onset was between 1 and 4 days of age with daily tonic asymmetric, focal and clonic seizures in nine patients and status epilepticus in the remaining six. Electroencephalography (EEG) showed multifocal epileptiform abnormalities in nine patients and a burst-suppression pattern in six. All patients were trialed with adequate daily doses of several AEDs before they reached seizure freedom. Six patients (40%) achieved seizure control within 2 weeks of carbamazepine (CBZ) administration and five (33%) were seizure-free with phenytoin (PHT). The last four patients (27%) were successfully treated with topiramate (TPM) (two patients), levetiracetam (LEV) (one), and a combination of LEV with TPM (one). Most patients reached seizure freedom within the first year of life and remained seizure-free thereafter. Twelve patients had moderate-to-severe developmental delay at follow-up. However, the two patients whose seizures ceased within a few days of onset showed only mild cognitive impairment.

Our findings suggest that drugs acting on sodium channels including CBZ and PHT should be considered as first-line treatment in patients with KCNQ2 encephalopathy. Voltage-gated sodium and potassium channels co-localize at the neuronal membrane. Therefore, the efficacy of drugs acting as sodium-channel blockers could be linked to their modulating effect on both channels. The type of KCNQ2 mutation might influence AED response as well as developmental outcome. Early recognition of KCNQ2 encephalopathy followed by the most appropriate and effective treatment may be important for reducing the neurodevelopmental impairment associated with this disorder.