When the physician becomes a patient

I first suspected something was wrong in 2013 when my marathon times increased by more than an hour. A lifelong runner, I suddenly had slow and heavy legs. I was always tired, and I had inexplicably gained  weight.

A battery of tests that summer indicated perfect health. Yet symptoms continued: By fall, I had difficulty focusing my left eye. In late January 2014 I realized during a morning jog that I could no longer smell the honeysuckle along my route.

And then it happened. One February night my husband, David, awoke to find me convulsing beside him in bed. He was unable to rouse me.
 

After I awoke, David said he thought I had had a seizure. I had no memory of it, but when I noticed the aches in my body, the twisted bedding and my rumpled pajamas, I knew my husband was right.
 

Only this time, I wondered. Days after my seizure, an M.R.I. scan revealed a bifrontal meningioma, a tumor that affects the brain’s lining and can lead to memory loss, personality changes and seizures. Though these tumors are rarely cancerous, my symptoms were worsening. Surgery was my only option.

 

All the fears and concerns I had been hearing over all those years from patients and families now took on a new dimension, and the same questions arose: How risky is the procedure? Will brain surgery leave lasting effects? Can we try medication instead?
 

Now I was the one asking those questions, and the usual data and statistics did not provide much relief.
 

I routinely tell parents that a young brain’s plasticity helps it heal and change more easily than an adult brain. But my brain was more than 60 years old.
 

And the possibility that I could die in surgery loomed large. More frightening, however, was the possibility of surviving the surgery, but no longer being the same person. I had seen this in patients who developed encephalitis, and it is truly heartbreaking. They grieve the loss of their former selves.

Surgeons removed the tumor from my brain during a four-hour procedure. The mass arose from my cribriform plate, compressing my left optic nerve and affecting the pituitary gland. It was about two inches in diameter, and had been growing for at least 10 years, possibly even 20.

The seizures are now gone, and I no longer have vision problems. But my surgery has had other lasting effects...

When I recently met with two parents to discuss their child’s ongoing seizures — the patient had undergone surgery to remove a portion of a brain tumor, yet seizures continued, so a second surgery to remove the entire mass was needed — the couple asked about risks, alternative options and medications. I answered, and they asked again.

Not so long ago, I might have inwardly grumbled when I heard the same questions repeated. Now, I answered as calmly and thoroughly the fourth time as I did the first.

These days, parents’ questions have even more weight. I pause and listen when they relay what they learned on the Internet about their child’s condition. I might have dismissed this before, but now I understand: They are desperate for information and some sense of control.

For many physicians, facts, figures and data are king. For me, feeling truly vulnerable for the first time has transformed my life and practice. I understand better than ever that patients and families do not want to be treated like a number or a diagnosis, to have their feelings dismissed or their fears treated casually. They need a physician, but they also need an advocate, an ally and a partner.

 

And that is why I tell my story. I want them to know they are not alone on this journey. After all, for the rest of my life, I will be both a physician and a patient.

http://well.blogs.nytimes.com/2015/06/25/sharing-my-story-with-patients/?_r=0

Chronic Lyme disease

Infectious disease specialists agree that “chronic Lyme disease” does not exist, and that Lyme disease from a tick bite can be cured with a short course of antibiotics.

Add “chronic Lyme disease” to the list of conditions doctors say are nothing more than hype.
Lyme disease is a bacterial illness carried by ticks. The Infectious Diseases Society of America (IDSA) maintains that it is easily diagnosed and usually curable with a short course of antibiotics. The IDSA represents 9,000 U.S. doctors.

But a growing number of Americans are saying their Lyme disease symptoms persist well beyond the three-week course of antibiotic treatment. They complain of muscle aches, headaches, and fatigue. They have found doctors to treat them with more antibiotics, but not without controversy.Patients who describe general symptoms such as achiness and fatigue plead for doctors' help. Those who are diagnosed with fibromyalgia and chronic fatigue syndrome sometimes have the same reaction. But in the case of Lyme disease, doctors aim to cure the illness with long-term antibiotics, not just manage symptoms.

Medical boards in states such as New York have questioned doctors who prescribe antibiotics for “post-treatment Lyme disease syndrome,” as the CDC describes the condition. Organizations such as LymeDisease.org are battling to have the IDSA treatment guidelines removed from the National Guideline Clearinghouse, a branch of the U.S. Department of Health and Human Services.

“The people behind pushing this ‘syndrome’ (including numerous people who have chronic fatigue and other conditions that are difficult to diagnose and treat, and who are therefore looking for answers) have gained remarkable political power,” Dr. Otto Yang told Healthline. Yang is an infectious disease specialist at the University of California, Los Angeles (UCLA).
 
A bill to shield doctors in New York from the retribution of government regulators for treating chronic Lyme disease patients with antibiotics is sitting on Gov. Andrew Cuomo’s desk now.

Doctors promoting the bill say their patients have “chronic Lyme disease,” an ongoing condition caused by the original infectious tick bite. They choose to treat it with antibiotics beyond the stated IDSA guidelines. Some of these doctors place patients on antibiotics intravenously for six months or even longer, Dr. Daniel Cameron told Healthline.

Cameron serves as president of the International Lyme and Associated Diseases Society (ILADS). He declined to say how many members the organization has. ILADS is the engine behind the chronic Lyme disease movement.

Although the widely accepted Western blot test used by most doctors to test for Lyme disease may come back negative, Cameron says patients can get tested elsewhere and receive a positive result.  For example, a company called IGeneX offers testing using the Western blot, but says their technique is more sensitive. It has two extra protein “bands” to better detect an ongoing Lyme disease infection, Cameron said. The president and CEO of IGeneX, Nick Harris, was one of the founders of ILADS.

Cameron authored a 2010 article “Proof that Chronic Lyme Disease Exists” in the journal Interdisciplinary Perspectives on Infectious Disease. In it he laid out research showing that some people with Lyme disease have symptoms for six years or longer after completing the standard treatment. Thinking problems, arthritis, and nerve damage can be debilitating for these patients.

In the article, Cameron quotes the Dr. Mark S. Klempner trials as showing that such patients have a quality of life equivalent to that of someone with osteoarthritis or congestive heart failure. But the Klempner trials, published in the New England Journal of Medicine, also concluded that prolonged antibiotic use (for 90 days) was so ineffective that the data and safety monitoring board recommended the trials be discontinued.

“States have been lobbied to cover treatment of this syndrome, since it is not recognized by insurance as a real disease,” Yang said. But Cameron said insurers often do pay for the treatment....

“In some cases, people may have serious illnesses that do not get diagnosed because they think this is the answer,” Yang told Healthline. “Also note that many people feel better on antibiotics, but the mind is powerful, and it is well known that the placebo effect is generally 40 to 50 percent when the evaluation of a treatment is subjective (e.g. fatigue, mood, insomnia, appetite ... anything that depends on human perception).”

Cameron told Healthline that those bitten by a tick may not only be suffering from Lyme disease, but from other co-infections as well. Testing for co-infections is not easy...

Cameron said the idea that patients are being needlessly treated with medications that cause uncomfortable side effects does not take into account the whole picture. “There are plenty of side effects from antibiotics, but there are plenty of problems if you don’t get well and are living with a chronic disease. Loss of job. Loss of education,” he said.

Cameron said people come to him who are in so much pain they cannot work and are also having relationship problems due to their illness. Most get better, he said, some in a month and some in a year. He said doctors who stop prescribing antibiotics after three weeks are missing an opportunity to help a patient.

Dr. Amesh Adalja, an infectious diseases specialist and an assistant professor at the University of Pittsburgh, says there is no scientific evidence to suggest an ongoing infection in patients with lingering Lyme disease symptoms. He said all infections require a recovery time beyond when the antibiotics run out. He said that continuing antibiotic treatment after a few weeks for people who have Lyme disease carries “a lot of risk and no real benefit.”

Adalja said the positive test results that some laboratories produce are just a way to support a doctor’s diagnosis. “It is not a valid way of approaching this,” he said. The CDC also warns against prolonged antibiotic use because it can drive the growth of bacteria that are resistant to antibiotic medications.

Oral antibiotics can cause gastrointestinal upset, and those who take antibiotics intravenously are subject to line infections. Last year, the CDC issued a call to action to halt unnecessary prescribing of antibiotics.

Yang said Lyme disease is a “very well understood condition, with close parallels to another old and well understood disease, syphilis, which is caused by a related bacterium.”

http://www.healthline.com/health-news/you-do-not-have-chronic-lyme-disease-091514#3
See Alternatively diagnosed chronic Lyme syndrome  6/26/15
Inspired by seeing a 7 year old patient who has had years of oral antibiotic therapy after testing by IGeneX was positive for Lyme, bartonella and babesia.  At one time, the patient was receiving azithromycin, augmentin, tinidazole, trimethaprim/sulfamethoxazole, Malarone and nystatin simultaneously under the direction of a Lyme literate physician.

Dravet syndrome and birthday parties

Meet the little girl who has not had a birthday party for four years - because excitement could kill her.

Isla Smith, four, has Dravet syndrome, a rare form of epilepsy where the potentially lethal seizures can be triggered by excitement, as well as temperature, water and what time the youngster eats.

She was diagnosed with the condition aged just 14 months and since then her parents, Claire and Jason, and her sister Ruby, eight, have had to tailor their lives to fit around her unusual condition.

For poor Isla this means she cannot have birthday parties for fear of the excitement causing a seizure.

Any one of the seizures could be her last having put too much pressure on her heart.

Claire, 37, an administrator from Dewsbury, Yorkshire, said: “I have to push it to the back of my mind, but every big seizure Isla has I can’t help but worry that it will be the last one.

“She could have a seizure and be gone. She’s a ticking time bomb that could go off at any time.

“We would love Isla to just be a normal four-year-old and enjoy life like she should.

“Isla’s birthdays are always a big milestone for us, especially last year as I never thought she would get to see her fourth, but unfortunately we have to keep these as low key as possible.

“Her sister Ruby has seen things that an eight-year-old shouldn’t see.

“It got to the point where Isla was having so many seizures we couldn’t protect her from it any more.

“We struggle to go out and about with Isla because she’s so unpredictable. We can’t even go shopping because she might have a seizure in Sainsbury’s. It takes over your life.

“Ruby finds it hard to do her own thing. It’s not the life we wanted for her. It’s out of our control.”...

“They tried different medications but they seemed to be making it worse. We were going back every couple of weeks.

“We kept calling the ambulance and they would ask what was wrong but we couldn’t tell them.”

At nine months old Isla had a seizure that lasted three hours. She was put into an induced coma and suffered brain damage.

She reverted back to being a newborn and could not even suck a dummy.

As a result Isla does not walk or talk and is fed through a gastrostomy. She is also fitted with a portacath to enable instant IV access, as when she has a seizure her veins start to collapse.

A genetic test eventually revealed Isla had a mutation of the SCN1A gene, which links to Dravet Syndrome...

Last year, aged three, Isla took a turn for the worse.

Claire said: “We didn’t know if she was going to live or not. It was very scary.

“They told us to get the family to say goodbye because they didn’t think she would make the next 36 hours.

“Thankfully she pulled through but it took six months to get her back to how she was, and a lot of hard work.

“She had to go through a drug-wean programme as she was in PICU in Sheffield for six weeks and was addicted to the drugs.”

Isla is now on three different drugs to keep her condition under control, but she still has seizures.

http://www.mirror.co.uk/news/uk-news/girl-aged-4-sick-celebrate-6448543
Courtesy of a colleague

A case of the Willeys

Eventually, two pediatricians, one allergist, one cardiologist and no less than six neurologists later, Kennedy was diagnosed with Dravet syndrome. This was not good news. For parent or child, Dravet can be a terrifying diagnosis.

The prognosis is anything but encouraging, the mortality rate is exceptionally high — 15-20% — with most dying suddenly while asleep, and seizures are severe, lifelong, and generally bring a host of developmental, behavioral and medical issues affecting every aspect of the child’s life.

Most children with Dravet are given anti-epileptic medications, even though Dravet does not tend to be responsive to medications. After reading story after story of children for whom medications made little to no difference, Kennedy’s mother, Dawn, felt there had to be a better way.

Through a series of fortunate events (apologies to Lemony Snicket), she was led back to her chiropractor and DAN! (Defeat Autism Now!) doctor who was eager to help, and the two struck up a collaborative relationship. Over time, they came to believe that Kennedy, like so many other medically complex children, had a “compromised gut” and if her gut were healed her health could be greatly improved. They started her on the Specific Carbohydrate Diet (SCD) and eventually transitioned to the Gut and Psychology Syndrome (GAPS) diet.

The results of her diet change approached the miraculous. Dawn estimates that Kennedy’s symptoms improved about 98%, with a huge reduction in frequency, duration, and intensity of her seizures. In addition, they no longer occurred randomly throughout the day, but typically occurred only when she was asleep. Children with Dravet’s are expected to regress from age two onwards due to the tremendous stress the seizures put on the developing nervous system.

Kennedy, however, has been beating the odds. She is now seven years old and generally lives a full “normal” life with her family in California. She attends a regular school, took surfing lessons in Costa Rica, plays tennis and the piano, and loves to swim and ride her bike...

But life is always a little precarious with a severe chronic illness, and recently the Willey family came face to face with their worst nightmare. Last week Kennedy experienced an increase in seizures. The seizures began “clustering” requiring medical attention. On Thursday, April 21, she was taken to her local hospital, but they decided she needed to transfer to a larger hospital: Children’s Hospital of California (CHOC) – Orange County...

That was when Dawn had had enough. She says she ran in and stepped in front of the nurse who was trying to do as the doctor had ordered. The next thing they knew a neurologist came into the room yelling about getting a court order if they continued interfering with Kennedy’s care. At 11 p.m. that night, a representative from Child Protection Services allegedly knocked on their door and interviewed the underslept, overstressed parents about their “medical neglect” until 1 a.m...

After the CPS visit, the Willeys knew they had to get Kennedy away from CHOC... They formulated a plan to move her to UCSF in San Francisco and hired an independent medical advocate and two attorneys...

They realized that they were fighting for Kennedy’s life. Carl asked the PICU pediatrician if he thought Kennedy was stable enough to be airlifted to another hospital and he said yes.

Carl met with the pediatrician saying, “I beg you to save my daughter’s life and release her. You have the power to do this because you are in charge on my daughter’s floor.” 

After hours of battle, the doctor finally agreed to release Kennedy. The transfer would happen the next morning. However, delay after delay kept them at the hospital till mid-afternoon, and before they left, Kennedy was given a final high dose of medications, taking her to toxic levels. Kennedy finally arrived in San Francisco on Wednesday (April 29th) and has reportedly been receiving excellent care since then. She is eating real food and smiling again.

One might think that this would mean the Willeys could breathe a sigh of relief, with their nightmare finally over.

Unfortunately, that does not seem to be the case. Last night (April 30th) Kennedy’s pediatrician at UCSF came to the Willeys and told them that CHOC had called CPS in San Francisco accusing the Willeys of “severe medical neglect,” saying that among other ridiculous charges they had “denied all meds.”

The representative from CPS in San Francisco interviewed the Willeys and agreed with everyone at UCSF that the Willeys were exceptional parents, CHOC’s complaint was “totally unfounded,” constituting blatant harassment, and the case would be closed.

The Willeys hope this may finally be the end of their nightmare, but they wonder about the next unsuspecting family? ...

The Willeys just want to have the freedom to choose their own medical care and treatment plan without being threatened by CPS because of over-zealous medical authorities who believe their treatments are the only ones available. They do not believe that doctors should try to coerce parents into accepting their methods and pharmaceutical products when other options are available.

 - See more at: http://healthimpactnews.com/2015/cps-threatens-to-kidnap-7-year-old-in-california-when-parents-try-to-transfer-to-different-hospital/#sthash.JlNMfgyI.dpuf

http://medicalkidnap.com/2015/05/01/cps-threatens-to-kidnap-7-year-old-in-california-when-parents-try-to-transfer-to-different-hospital/

US Dietary Guidelines for Americans

The expert report underpinning the next set of US Dietary Guidelines for Americans fails to reflect much relevant scientific literature in its reviews of crucial topics and therefore risks giving a misleading picture, an investigation by The BMJ has found. The omissions seem to suggest a reluctance by the committee behind the report to consider any evidence that contradicts the last 35 years of nutritional advice.

Issued once every five years, the guidelines have a big influence on diet in the US, determining nutrition education, food labeling, government research priorities at the National Institutes of Health, and public feeding programs, which are used by about a quarter of Americans each year. The guidelines, which were first issued in 1980, have also driven nutrition policy globally, with most Western nations subsequently adopting similar advice.

The guidelines are based on a report produced by a dietary guidelines advisory committee—a group of 11-15 experts who are appointed to review the best and most current science to make nutrition recommendations that both promote health and fight disease. The committee’s latest report was published in February and is under review by the government’s health and agricultural agencies, which will finalize the guidelines in the fall.

Concern about this year’s report has been unprecedented, with some 29 000 public comments submitted compared with only 2000 in 2010. In recent months, as government officials convert the scientific report into the guidelines, Congress has sought to intervene. In June, it proposed a requirement that the guidelines be based exclusively on “strong” science and also that they focus on nutritional concerns without consideration of sustainability. Other debated topics include newly proposed reductions in consumption of sugar and red meat...

The BMJ has also found that the committee’s report used weak scientific standards, reversing recent efforts by the government to strengthen the scientific review process. This backsliding seems to have made the report vulnerable to internal bias as well as outside agendas.

The 2015 report states that the committee abandoned established methods for most of its analyses. Since its inception, the guideline process has suffered from a lack of rigorous methods for reviewing the science on nutrition and disease, but a major effort was undertaken in 2010 to implement systematic reviews of studies to bring scientific rigor and transparency to the review process. The US Department of Agriculture set up the Nutrition Evidence Library (NEL) to help conduct systematic reviews using a standardized process for identifying, selecting, and evaluating relevant studies.

However, in its 2015 report the committee stated that it did not use NEL reviews for more than 70% of the topics, including some of the most controversial issues in nutrition.4 Instead, it relied on systematic reviews by external professional associations, almost exclusively the American Heart Association (AHA) and the American College of Cardiology (ACC), or conducted an hoc examination of the scientific literature without well defined systematic criteria for how studies or outside review papers were identified, selected, or evaluated.

Use of external reviews by professional associations is problematic because these groups conduct literature reviews according to different standards and are supported by food and drug companies. The ACC reports receiving 38% of its revenue from industry in 2012, and the AHA reported 20% of revenue from industry in 2014. Potential conflicts of interest include, for instance, decades of support from vegetable oil manufacturers, whose products the AHA has long promoted for cardiovascular health. This reliance on industry backed groups clearly undermines the credibility of the government report...

The overall lack of sound science and proper methods in the 2015 report could be seen as a reluctance to depart from existing dietary recommendations. Many experts, institutions, and industries have an interest in keeping the status quo advice, and these interests create a bias in its favor. Abandoning the NEL review methods, as the 2015 committee has done, opens the door not only for bias but also for influence from outside agendas and commercial interests, and all of these can be observed in the report.

For example, a bias towards the longstanding view that saturated fats are harmful can be seen in the report’s designation of them, together with sugar, as a new category it calls “empty calories.” The report repeatedly mentions the need to reduce “sugar and solid fats,” because, “both provide calories, but few or no nutrients.” Yet this pairing is unsupported by nutrition science. Unlike sugar, saturated fats are mostly consumed as an inherent part of foods such as eggs, meat, and dairy, which together contain nearly all of the vitamins and minerals needed for good health.

Not following the NEL methods has also allowed outside agendas to enter into the report, most clearly in the form of the new consideration for environmental sustainability. Although, as the report states, the environmental effects of food and drink production are considerable, they are outside the committee’s formal mandate to provide the federal government with the “current scientific evidence on topics related to diet, nutrition, and health.” In a new development for 2015, the USDA hired a food policy analyst focused on environmental issues to oversee the guideline committee’s work, reflecting a new agenda in the process.

Teicholz N. The scientific report guiding the US dietary guidelines: is it scientific? BMJ. 2015 Sep 23;351:h4962.   http://www.bmj.com/content/351/bmj.h4962
Courtesy of:  http://www.medpagetoday.com/PrimaryCare/DietNutrition/53701?xid=nl_mpt_DHE_2015-09-25&eun=g906366d0r

Rhabdomyolysis

On the morning of Sept. 8, 18-year-old Paul Houle Jr. lined up in his nose tackle position at the year's first football practice, feeling healthy and ready to take on the season ahead.

By 8 p.m., Houle was in an emergency room at a nearby hospital. His heart, liver and kidneys were all shutting down.

"Doctors told me that if I had not said anything and gone to practice the next day, I very easily could have died," Houle told The Huffington Post over the phone.

Houle, a senior at Tabor Academy in Marion, Massachusetts, had come down with an acute condition called rhabdomyolysis after participating in two football practices in the sweltering heat, Cape Cod-based health care news service One Cape Health News first reported. The condition is a known risk for amateur athletes engaging in physically strenuous summer workouts.

Houle was dehydrated and overheated from participating in two practices in one day, and the muscles in his body had begun to break down and release a protein into his bloodstream that was causing his vital organs to fail.

Houle was dehydrated and overheated from participating in two practices in one day, and the muscles in his body had begun to break down and release a protein into his bloodstream that was causing his vital organs to fail.

Houle told HuffPost that after the day's second practice, he felt back pain whenever he took a deep breath.

"I thought I was just sore and a little out of shape because the practice was hard. I didn’t think much of it," he said. "Later, when I was at the hospital, they let me know that my back pain was actually my kidneys failing."

Back at his dorm room after practice, Houle said he showered and took a short nap. When he woke up, he checked his Apple Watch's heart rate monitor for the first time that day. He knew something was wrong immediately. The watch indicated his heart rate was 145 beats per minute, a full 60 to 80 beats higher than an average resting heart rate. He didn't know it then, but a rapid heart rate is a symptom of rhabdomyolysis.

In fact, he actually thought the watch was broken. He had never considered its heart rate monitor to be anything more than a gimmick.

"I thought it was a neat little feature, but didn’t see myself really using it," he said. "What I thought was so tiny and not important turned out to be a life-changing decision."

The school's athletic trainer also thought the watch was broken when Houle told him about his abnormally high heart rate reading. But after being examined by both the trainer and the school's nurse, he was immediately driven to the emergency room. Once at the hospital, Houle was diagnosed with rhabdomyolysis and began receiving treatment, but the condition's effects still caused him to lose control of his muscles...

As a senior proctor at his boarding school, Houle lives alone in a single room. He would have had difficulty finding help late at night once the rhabdomyolysis had rendered him immobile. He credits the Apple Watch for quickly compelling him to seek the help he needed to prevent his body from fully shutting down.

http://www.huffingtonpost.com/entry/paul-houle-apple-watch_5601878de4b08820d91a4688?utm_hp_ref=sports&ir=Sports&section=sports

Autism and the endoplasmic reticulum

By identifying a key signalling defect within a specific membrane structure in all cells, researchers believe they have found both a possible reliable biomarker for diagnosing certain forms of autism and a potential therapeutic target.

J. Jay Gargus, MD, and Ian Parker, MD, University of California at Irvine Center for Autism Research & Translation, Irvine, California, and colleagues examined skin biopsies of patients with fragile X syndrome and tuberous sclerosis 1 and 2.

They discovered that a cellular calcium signalling process involving the inositol trisphosphate receptor was very much altered.

This IP3R functional defect was located in the endoplasmic reticulum, which is among the specialised membrane compartments in cells called organelles, and may underpin cognitive impairments -- and possibly digestive and immune problems -- associated with autism.

There are no current, reliable diagnostic biomarkers for autism spectrum disorder (ASD). Genetic research has identified hundreds of genes that are involved, which impedes diagnosis and, ultimately, drug development. There simply may be too many targets, each with too small an effect.

Many of these genes associated with ASD, however, have been found to be part of the same signalling pathway, and multiple defects in this pathway may converge to produce a large functional change.

The researchers detected such a convergence in the IP3R calcium channel in an organelle called the endoplasmic reticulum. According to Dr. Gargus, diseases of the organelles are an emerging field in medicine, with several well-recognised neurological ailments linked to the mitochondria and lysosomes.

The IP3R controls the release of calcium from the ER. In the brain, calcium is used to communicate information within and between neurons, and it activates a host of other cell functions, including ones regulating learning and memory, neuronal excitability and neurotransmitter release - areas known to be dysfunctional in ASD.

http://dgnews.docguide.com/researchers-find-biomarker-autism-may-aid-diagnostics?overlay=2&nl_ref=newsletter&pk_campaign=newsletter

Schmunk G, Boubion BJ, Smith IF, Parker I, Gargus JJ. Shared functional defect
in IP(3)R-mediated calcium signaling in diverse monogenic autism syndromes.
Transl Psychiatry. 2015 Sep 22;5:e643.

Abstract

Autism spectrum disorder (ASD) affects 2% of children, and is characterized by impaired social and communication skills together with repetitive, stereotypic behavior. The pathophysiology of ASD is complex due to genetic and environmental heterogeneity, complicating the development of therapies and making diagnosis challenging. Growing genetic evidence supports a role of disrupted Ca²⁺ signaling in ASD. Here, we report that patient-derived fibroblasts from three monogenic models of ASD-fragile X and tuberous sclerosis TSC1 and TSC2 syndromes-display depressed Ca²⁺ release through inositol trisphosphate receptors (IP₃Rs). This was apparent in Ca²⁺ signals evoked by G protein-coupled receptors and by photoreleased IP₃ at the levels of both global and local elementary Ca²⁺ events, suggesting fundamental defects in IP₃R channel activity in ASD. Given the ubiquitous involvement of IP₃R-mediated Ca²⁺ signaling in neuronal excitability, synaptic plasticity, gene expression and neurodevelopment, we propose dysregulated IP₃R signaling as a nexus where genes altered in ASD converge to exert their deleterious effect. These findings highlight potential pharmaceutical targets, and identify Ca²⁺ screening in skin fibroblasts as a promising technique for early detection of individuals susceptible to ASD.

DNR orders adversely affect survival

Fendler TJ, Spertus JA, Kennedy KF, Chen LM, Perman SM, Chan PS; American Heart Association’s Get With the Guidelines–Resuscitation Investigators. Alignment of Do-Not-Resuscitate Status With Patients' Likelihood of Favorable Neurological Survival After In-Hospital Cardiac Arrest. JAMA. 2015 Sep 22-29;314(12):1264-71.

Importance After patients survive an in-hospital cardiac arrest, discussions should occur about prognosis and preferences for future resuscitative efforts.
Objective To assess whether patients’ decisions for do-not-resuscitate (DNR) orders after a successful resuscitation from in-hospital cardiac arrest are aligned with their expected prognosis.
Design, Setting, and Participants Within Get With The Guidelines–Resuscitation, we identified 26 327 patients with return of spontaneous circulation (ROSC) after in-hospital cardiac arrest between April 2006 and September 2012 at 406 US hospitals. Using a previously validated prognostic tool, each patient’s likelihood of favorable neurological survival (ie, without severe neurological disability) was calculated. The proportion of patients with DNR orders within each prognosis score decile and the association between DNR status and actual favorable neurological survival were examined.
Exposures Do-not-resuscitate orders within 12 hours of ROSC.
Main Outcomes and Measures Likelihood of favorable neurological survival.
Results Overall, 5944 (22.6% [95% CI, 22.1%-23.1%]) patients had DNR orders within 12 hours of ROSC. This group was older and had higher rates of comorbidities (all P < .05) than patients without DNR orders. Among patients with the best prognosis (decile 1), 7.1% (95% CI, 6.1%-8.1%) had DNR orders even though their predicted rate of favorable neurological survival was 64.7% (95% CI, 62.8%-66.6%). Among patients with the worst expected prognosis (decile 10), 36.0% (95% CI, 34.2%-37.8%) had DNR orders even though their predicted rate for favorable neurological survival was 4.0% (95% CI, 3.3%-4.7%) (P for both trends <.001). This pattern was similar when DNR orders were redefined as within 24 hours, 72 hours, and 5 days of ROSC. The actual rate of favorable neurological survival was higher for patients without DNR orders (30.5% [95% CI, 29.9%-31.1%]) than it was for those with DNR orders (1.8% [95% CI, 1.6%-2.0%]). This pattern of lower survival among patients with DNR orders was seen in every decile of expected prognosis.
Conclusions and Relevance Although DNR orders after in-hospital cardiac arrest were generally aligned with patients’ likelihood of favorable neurological survival, only one-third of patients with the worst prognosis had DNR orders. Patients with DNR orders had lower survival than those without DNR orders, including those with the best prognosis.

Courtesy of:  http://www.medpagetoday.com/Cardiology/Arrhythmias/53689?xid=nl_mpt_DHE_2015-09-24&eun=g906366d0r

Wrong diagnosis

Most Americans who go to the doctor will get a diagnosis that is wrong or late at least once in their lives, sometimes with terrible consequences, according to report released Tuesday by an independent panel of medical experts.

This critical type of health-care error is far more common than medication mistakes or surgery on the wrong patient or body part. But until now, diagnostic errors have been a relatively understudied and unmeasured area of patient safety. Much of patient safety is focused on errors in hospitals, not mistakes in diagnoses that take place in doctors’ offices, surgical centers and other outpatient facilities.

The new report by the Institute of Medicine, the health arm of the National Academy of Sciences, outlines a system-wide problem that experts say affects an estimated 12 million adults each year.

"Diagnostic errors are a significant contributor to patient harm that has received far too little attention until now," said Victor Dzau, institute president, in a statement...

Diagnostic errors result from a variety of causes, the committee found. They include inadequate collaboration among clinicians, patients and their families; limited feedback to clinicians about the accuracy of their diagnoses; and a health-care culture that discourages transparency and disclosure of errors.

One example cited in the report was about a woman, identified only as Carolyn, who arrived in the emergency room with chest pain and other classic symptoms of a heart attack. But her tests were normal, and the clinician told her she had acid reflux. A nurse even told her to stop asking questions of the doctor.

The woman was released a few hours later, feeling embarrassed about making a fuss. But over the next two weeks, she became sicker. She returned to the emergency department and clinicians told her she had had a heart attack caused by a blocked artery.

The report also said that health information technology may be contributing to diagnostic errors...

 Doctors often don’t know when they have made the wrong diagnosis, said Tejal Gandhi, president of the National Patient Safety Foundation, and an internal medicine doctor for 15 years. Often the scenario involves a physician missing something and a patient, who doesn't get better, seeking a second opinion. Something that was missed is picked up, and the first doctor never hears about it, said Kavita Patel, a healthy policy expert at the Brookings Institution's Center for Health Policy and a practicing primary care doctor at Johns Hopkins Medicine.

The report said health-care organizations need to put systems in place to identify diagnostic errors and near misses. They also need to adopt a non-punitive culture so open discussion and feedback can take place. That could be empowering for frontline workers like medical assistants to act as a check and balance, looking for gaps and raising flags, even if it's "something doctors won't like but will appreciate when they avoid a near miss," she said.

https://www.washingtonpost.com/news/to-your-health/wp/2015/09/22/most-americans-who-go-to-the-doctor-will-get-a-wrong-or-late-diagnosis-at-least-once-in-their-lives-study-says/

Alexander disease

Mahajnah, Muhammad; Abu-Rashid, Muhammad; Lerman-Sagie, Tally; Goikhman, Igor; Zelnik, Nathanel.  Alexander Disease in Israel: Megalencephaly and Leukoencephalopathy and Its Differential Diagnosis.  Journal of Pediatric Neurology (J PEDIATR NEUROL), 2015; 13 (3): 121-5.

Alexander disease (AD) is a rare leukodystrophy caused by overexpression of glial fibrillary acidic protein and heat shock proteins, which accumulate in the astrocytes and appear as Rosenthal fibers. Clinically, there are three main phenotypes: infantile, juvenile, and adult forms, with a highly variable clinical course. The classical, and most common phenotype, is the infantile form, which occurs during the first 2 years of life. The diagnosis of AD is based on clinical findings and, supported by magnetic resonance imaging, should be suspected in infants with leukoencephalopathy associated with progressive megalencephaly. In this article, we report two additional patients. Their mutations were already reported; however, while one of them is a common hotspot of the severe infantile-onset phenotype, the other is uncommon and was not yet reported in early infantile-onset AD. To the best of our knowledge, these are the first cases of AD reported from Israel. AD was reported anecdotally in a few other Middle Eastern countries but, since they are usually de novo sporadic mutations, they are not affected by consanguineous marriages, and do not tend to cluster in isolated ethnic populations.

Ebrahimi-Fakhari D, Wahlster L, Hoffmann GF, Kölker S. Emerging role of
autophagy in pediatric neurodegenerative and neurometabolic diseases. Pediatr
Res. 2014 Jan;75(1-2):217-26.

Abstract

Pediatric neurodegenerative diseases are a heterogeneous group of diseases that result from specific genetic and biochemical defects. In recent years, studies have revealed a wide spectrum of abnormal cellular functions that include impaired proteolysis, abnormal lipid trafficking, accumulation of lysosomal content, and mitochondrial dysfunction. Within neurons, elaborated degradation pathways such as the ubiquitin-proteasome system and the autophagy-lysosomal pathway are critical for maintaining homeostasis and normal cell function. Recent evidence suggests a pivotal role for autophagy in major adult and pediatric neurodegenerative diseases. We herein review genetic, pathological, and molecular evidence for the emerging link between autophagy dysfunction and lysosomal storage disorders such as Niemann-Pick type C, progressive myoclonic epilepsies such as Lafora disease, and leukodystrophies such as Alexander disease. We also discuss the recent discovery of genetically deranged autophagy in Vici syndrome, a multisystem disorder, and the implications for the role of autophagy in development and disease. Deciphering the exact mechanism by which autophagy contributes to disease pathology may open novel therapeutic avenues to treat neurodegeneration. To this end, an outlook on novel therapeutic approaches targeting autophagy concludes this review.
 

Rodriguez D. Leukodystrophies with astrocytic dysfunction. Handb Clin Neurol.
2013;113:1619-28.

Abstract

Astrocytic dysfunctions have been recently identified in four leukosdystrophies without peripheral nervous system myelin involvement. Alexander disease, the first primary genetic astrocytic disorder identified, is due to dominant GFAP mutations. The presence of Rosenthal fibers throughout the CNS is the pathological hallmark of this disease. Neurological degradation, megalencephaly, and typical MRI pattern are characteristic of infantile sporadic patients. Nevertheless, clinical and MRI expression is large, including late onset forms which can be familial. Spongiform or cystic white matter CNS degeneration is present in the other three recessive disorders. The visualization of a white matter cystic breakdown on MRI has led to the identification of CACH/VWM and MLC diseases. CACH/VWM is due to mutations in one of the five subunits of EIF2B which compromise the astrocytic lineage. The clinical spectrum is large, from antenatal to adult forms, and several extraneurological organs can be affected. Mutations in MLC1, which is mainly expressed in astrocyte endfeet, produce megalencephaly, whereas the mild clinical course contrasts with severe MRI features. An increased concentration of NAA in the urine is sufficient to diagnose Canavan disease, which is due to mutations of the ASPA gene. These disorders highlight the role of astrocytes in myelination or myelin maintenance.

Permission for preservation

Wall SP, Plunkett C, Caplan A. A Potential Solution to the Shortage of Solid
Organs for Transplantation. JAMA. 2015 Jun 16;313(23):2321-2.

In the United States, the majority of deaths occur unexpectedly, outside hospitals or in emergency departments. Rarely do these deaths provide opportunities for organ donation. In Europe, unexpected deaths provide substantial numbers of transplantable organs through uncontrolled donation after circulatory determination of death (UDCDD). UDCDD considers decedents candidates for donation even when death is unexpected, regardless of location, as long as preservation begins after all life-sustaining efforts have been exhausted.

United States policy currently promotes organ recovery from 3 sources; neurologic deaths, controlled circulatory deaths, and live donors for kidneys and partial livers.

However, these approaches are incapable of meeting increasing US demand for transplants. During controlled donation after circulatory determination of death (CDCDD), the time from cessation of life support to circulatory arrest often exceeds 60 minutes. Prolonged hypotension leads to irreparable organ damage, thus limiting the effect of CDCDD on organ supply. Live donation primarily affects kidney supply; it is unlikely that altruistic donation will ever meet demand. Although many changes in public policy regarding cadaveric donation are debated (markets and presumed consent), none is likely to become law or make substantial differences in organ supply.

UDCDD requires initiation of organ preservation soon after death. If the warm ischemic time, which represents the time organs receive inadequate circulation to sustain cellular function, exceeds an organ-specific threshold, organs are not viable. European programs initiate organ preservation without requiring explicit consent, a concept the US public will not allow despite supporting UDCDD.  Therefore, some US programs restricted eligibility to deceased persons who had previously registered for organ donation. However, UDCDD programs in the United States experienced recruitment problems by restricting eligibility to previously registered organ donors.

A decision to preserve organs is less complex and consequential than the decision to donate. The capacity required to permit preservation is lower than that required to authorize donation. Grieving persons could be asked to provide permission to preserve when providing authorization for donation would be beyond their current capacity. Immediately following death, family members would be asked only for permission to begin organ preservation, thereby keeping open the option to donate later. The decision to begin organ preservation does not commit the family to a decision to donate, but it does maintain donation as an option.

 

The second step of the proposed 2-step authorization process is authorization to donate. Family members and loved ones initially need time to process the fact that death has occurred. Later they need the opportunity to weigh the pros and cons of donation against the decedent’s and family’s values.

 

The proposed schema of “permission for preservation” followed by later consideration of donation serves to protect the decedent’s values and family members’ autonomy when it comes to making a decision to donate. Moreover, this proposed approach also may increase the likelihood that families will authorize organ donation. The importance of “decoupling” pronouncement of death and requests for organ donation is well established. When conversations about organ donation occur several hours after the decedent’s death, in a private setting, with a transplant professional, families are much more likely to authorize donation. If organ preservation is permitted at or close to the time of death, family members can later take the time they need to process death, talk extensively with each other and transplant professionals, and come to a thoughtful decision.

 

See:  http://www.medscape.com/viewarticle/850071?src=wnl_edit_bom_weekly&uac=60196BR&impID=831611&faf=1

Intracranial hypertension and optic sheath diameter assessment

Jose E. Irazuzta, Javed Akhtar, Martha E. Brown. Bedside Optic Nerve Sheath Diameter Assessment in the Identification of Increased Intracranial Pressure in Suspected Idiopathic Intracranial Hypertension.  Pediatric Neurology in press.

Abstract

Objective

To assess if the bedside assessment of the optic nerve sheath diameter (ONSD) could identify elevated intracranial pressure (ICP) in patients suspected of having Idiopathic Intracranial Hypertension (IIH).

Methods

Single-center, prospective, rater- blinded study performed in a freestanding pediatric teaching hospital

Patients 12-18 years of age scheduled for an elective lumbar puncture with the suspicion of IIH were eligible to participate. ONSD was measured via ultrasonography (US) prior to performing a sedated, lumbar puncture for measuring CSF opening pressure. Abnormal measurements were predefined as: ONSD ≥ 4.5 mm and a CFS opening pressure > 20 cmH₂O.

Results

13 patients participated in the study, ten of them with elevated ICP. ONSD was able to predict or ruled out elevated ICP in all patients.

Conclusions

Noninvasive assessment of the ONSD could be of value to identify patients with elevated ICP when IIH is suspected. 

From the paper:  The sedation of an often anxious and obese adolescent is not without risks. It is possible that further clinical follow up and response to treatment can be assessed using ONSD and avoid need of further lumber punctures. Although a relationship exists between increased ICP and ONSD but at this time ONSD cannot be solely used for diagnostic purpose. Our study highlights the need of a large, perhaps multi-center study with a control arm to validate the use of ONSD in the diagnostic work up of children with suspected IIH. It is not unforeseeable that in the near future the diagnosis of IIH may not require the direct measurement of an opening pressure obtained from an invasive lumbar puncture in a symptomatic patient but instead it could be identified through the use of non-invasive ultrasonography.
 

Dummheit 2

Medical organizations and the media have come down hard on the remarks about so-called risks of vaccines during CNN telecast of a Republican presidential candidates' debate Wednesday.

In the course of the TV show Donald Trump suggested that autism was linked to vaccines, while Ben Carson, a neurosurgeon, and Rand Paul, who trained as an ophthalmologist but is not currently certified, favored changes in the currently recommended vaccine schedule.

 

In recent years it has seemed that the visibility of the scientifically unsupported link to autism has died down and the infectious disease outbreaks linked to low vaccination rates, plus new studies refuting the association, have added to a sense of greater public acceptance of scientific evidence on the value of vaccines...

I was outraged by Trump's comments and the responses of the two GOP candidates who are doctors -- Rand Paul and Ben Carson. Their responses were pandering to the population who ascribe to the delusions of vaccine caused autism. Their comments undermine the public health of the United States and are irresponsible for a future presidential candidate...

I was very disappointed by politicians making statements about the unsupported link between autism and vaccines. Because vaccines have been so effective, we as a society have become complacent about these deadly infectious diseases. From a public health perspective, we absolutely have to vaccinate as many children as possible to protect them and to protect others who for medical reasons cannot get vaccinated....

This is not a major setback for childhood immunization, but it does create temporary confusion. The American Academy of Pediatrics and many others have responded promptly and forcefully, rejecting the misguided notion that vaccines are associated with autism which now has been disproven many times over. In addition, the so-called "stretched out schedule" also has been shown to be unproven and that it sadly leaves children unprotected for longer than necessary...

The vaccine schedule is the result of a great deal of thought. It makes sense to get protection for any given child at the earliest possible opportunity and thus, the schedule is loaded on the front end, i.e. lots of vaccines early in life. The development of combination vaccines to decrease the number of injections is a good thing and has the potential to decrease the number of injections necessary to have compliance with the carefully thought out vaccine schedule. This effort is proceeding and has already decreased the number of injections a child should receive to be up to date.''...

So much money (millions) has gone into researching the vaccine-ASD link, to the detriment of research for discovering other causes (which could be preventable) or interventions to improve the quality of lives for people with ASD. I am disappointed that the GOP continues to harp on this false science, because much of the public believes them. Dr. Carson should be especially ashamed that he has not kept current with the evidence-base for vaccines and ASD.

http://www.medpagetoday.com/InfectiousDisease/Vaccines/53635?xid=nl_mpt_DHE_2015-09-19&eun=g906366d0r

Transparency 2

A re-analysis of data from the heavily criticized Study 329 involving the antidepressant paroxetine (Paxil) turned up more cases of suicidality in young people than previously reported -- a finding that suggests greater need for reporting of patient-level data by pharmaceutical companies, researchers said.

While the original 2001 publication of the study reported five cases of suicidality -- and subsequent analyses by drugmaker GlaxoSmithKline (GSK) and FDA during litigation found nine and 10 cases, respectively -- Jon Jureidini, PhD, MBBS, of the University of Adelaide in Australia, and colleagues found a total of 12 cases when they went through the 93 patient-level case reports made available to them by GSK.

"There were several of, what looks like to the impartial observer, deliberate attempts to play down the adverse effect profile," Jureidini said during a press call with editors from the BMJ, where the study was published. "We can't be definite about that, but that's what it looks like."

Study 329 has long been a subject of controversy in child and adolescent psychiatry. Published in 2001 in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) after being rejected by JAMA, it was criticized in letters to the editor, and the FDA never approved Paxil in adolescents based on the data.

Only fluoxetine (Prozac) and escitalopram (Lexapro) are officially indicated for use in adolescents, but antidepressants are often used off-label in this population. All antidepressants carry a black box warning about increased suicidality in people under age 25.

Data manipulation in the study also played a key role in federal regulators' legal action against GSK, which ultimately ended up paying a $3 billion fine for illegal off-label marketing of drugs, including Paxil being promoted for young people.

Despite all of these problems, the paper remains part of the literature. JAACAP editors declined to retract it after an internal investigation found no evidence of wrongdoing, Peter Doshi, PhD, of the University of Maryland in Baltimore and an associate editor at BMJ, noted in an accompanying feature article.

 

Brown University of Providence, R.I., where lead author of the JAACAP paper Martin Keller, MD, is an emeritus professor, never confirmed having made an internal investigation at all, Doshi said.

As part of a settlement with the New York Attorney General's office, GSK publicly disclosed all Clinical Study Reports (CSRs) from Study 329, but they left out Appendix H, which contained individual patient-level data.

After negotiations with GSK, Jureidini and colleagues were able to get access to 77,000 pages worth of individual patient reports, but they weren't allowed to print or download those records and could only make manual notations.

They scrutinized 93 patient case reports, out of the original 275 patients (34%).

Overall they found paroxetine wasn't effective at treating depression in adolescents (neither was the comparator imipramine; neither drug was better than placebo)....

And for the specific adverse event of suicidality, the researchers found a total of 12 cases among 93 children that had case reports -- far higher than the five reported in the Keller study, they said.

"It's hard to think there wasn't some mischief being done when a severe suicide attempt requiring hospitalization was coded as 'emotional liability,'" Jureidini said during the press call about one of the specific cases they reviewed and re-classified....

"Our re-analysis of Study 329 showed considerable variations in the way adverse events can be reported, demonstrating several ways in which the analysis and presentation of safety data can influence the apparent safety of a drug," they wrote in the paper.

In an emailed statement, GSK emphasized its participation in giving the researchers access to patient-level data.

"This reflects our commitment to data transparency," the statement said. "We publish the results of all our studies regardless of whether they are positive or negative and we are the only pharmaceutical company to be part of the AllTrials campaign. We have also led the way in giving external researchers access to the very detailed patient-level data behind our studies, granting access to more than 50 research teams around the world so they can independently use our data in their research."...

Doshi noted that GSK has had access to their paper since March and has not disputed the findings.

http://www.medpagetoday.com/Psychiatry/GeneralPsychiatry/53583

Medicalization of suicide

On September 16, the American College of Physicians sent the following letter to California Governor Jerry Brown asking him to veto the End of Life Option Act (ABX2-15), which would legalize physician-assisted suicide.

Dear Governor Brown,

 

The American College of Physicians (ACP), the largest medical specialty organization and the second-largest physician group in the United States, writes to urge you to veto "The End of Life Option Act." This is a physician-assisted suicide bill. ACP does not support the legalization of physician-assisted suicide (PAS) and does not support PAS as an appropriate action (see the ACP Ethics Manual and position paper). Terms such as "end of life option" and "aid-in-dying" used in the bill are confusing and obscure what is at stake when physicians are asked to facilitate suicide. We are deeply sympathetic to the concerns and fears patients and their families have at the end of life. However, PAS is not the answer and in fact, ACP sees it as abandonment of the dying patient. It is not the role of the physician to give individuals control over the cause and timing of death -- the medicalization of suicide.

The physician must always act in the best interests of the patient as healer, comforter, and trusted advisor. PAS undermines trust in patient-physician relationships and trust in the profession of medicine. Proponents of PAS claim it is an act of compassion in keeping with the physician's role as comforter. However, this argument incorrectly assumes that physicians can only provide comfort for certain patients through facilitating suicide. In fact, physicians can and do provide comfort to dying patients. It is a lack of awareness of these services and a perceived concern that patients will not have access to this care that helps drive interest in PAS as an option. We need to ensure that all patients have access to palliative care and hospice services at the end of life rather than promote suicide...

Patients often fear pain at the end of life, but physicians have an ethical obligation to treat pain with competence and compassion. Aggressive management of pain at the end of life is ethically acceptable, even when the risk of hastening death is foreseeable, if the intent is to relieve pain: the ACP Ethics Manual states that "...the physician may appropriately increase medication to relieve pain, even if this action inadvertently shortens life." The option of aggressive pain control has been consistently supported by U.S. courts, including the U.S. Supreme Court, and PAS has been distinguished from the right to refuse treatment by the courts as well (see especially Washington v. Glucksberg, 117 S.Ct. 2258 (1997) and Vacco v. Quill, 117 S.Ct. 2293 (1997))...

We also note the paradox of access to PAS where there is no general right to healthcare. In Oregon, the irony of difficulties getting coverage for palliative services and pain drugs under the state's Medicaid program -- but no problem receiving PAS paid for as a covered service -- has been noted (Toffler William L. A doctor-assisted disaster for medicine. Wall Street Journal. August 18, 2015:A1). PAS is especially troubling in an environment of cost control in healthcare and continuing disparities in care.

 

We hope you will join ACP in advocating that society should encourage those who seek suicide with a physician's help to instead be provided with full access to the care and compassion that can alleviate their suffering. No Californian, or any other American, should have to fear an undignified or pain-filled life or death.

Providing greater access to palliative and hospice care needs our full attention. In this way, physicians can fulfill their mission and give dying patients and their families the care, compassion, and comfort they need and deserve.

We hope that you will veto this bill.

ACP President Wayne Riley, MD, MPH, MBA, MACP
President, American College of Physicians (ACP)

http://www.medpagetoday.com/PublicHealthPolicy/Ethics/53601?xid=nl_mpt_DHE_2015-09-18&eun=g906366d0r

A story that I hope ends up being true

“Every person contributes,” he says. “You don’t have to join the Peace Corps to do something worthwhile. I don’t like it when her friends act like her job isn’t as important to the world as theirs.” He tells me about his 21-year-old daughter. She recently graduated from college and got her first job in communications, and he’s proud of her. “Do you have kids?” he asks.

 

He is 44 years old and battling anaplastic myeloma. I’m not sure of the precise ways in which it’s different from regular myeloma, but I know it’s bad. After two failed bone marrow transplants, he’s been admitted for salvage chemotherapy, but it has been complicated by respiratory syncytial virus and parainfluenza pneumonias and now increasing fevers with progressing pulmonary infiltrates for which his hematology team asked for infectious diseases consultation. That’s when I meet him...

 

We recommend a few more tests, trying to balance the benefits of figuring it out vs the risks of further invasive procedures. We suggest empirical broad-spectrum treatments to cover all the usual suspects, but we don’t get any new answers and his condition seems to be worsening—continued coughing, increasing infiltrates on another chest CT, new frontal lobe strokes on a head MRI done for changes in his neurologic examination. He recognizes things are not going well and asks to go home.

I almost don’t see him that last day because it’s hard to face him with no answers.

 

“Yes, I have kids,” I say, “a 12-year-old daughter and a 9-year-old son.” And that simple response opens the door. The vast space between helpless physician and suffering patient, the one where shame and disappointment can live and grow, is bridged in an instant, and for the next several precious minutes, I realize how glad I am that I came. The smells and sounds of the bone marrow transplant unit disappear, and we talk. He tells me about his twin daughters and how different they are from each other. We talk about the challenges of raising kids in the time of social media and iPhones. He explains what it means to work as an economist. I assume too simplistically that it’s all about math, but he describes it is more about theories, about “telling a story that you hope ends up being true.” “Math for me was a means to an end,” he describes, “but I never really understood math in the way a mathematician does.” I hear admiration in his voice as he describes his friend in Haiti “who has one of those minds. One that thinks and understands like a mathematician.” He makes his profession sound like one he sort of fell into “when I decided not to become a lawyer and just kept going on to get more degrees in economics,” culminating with his PhD. “There are only about 50 people in the country who do what I do,” he says, though with humility that wants you believe he chose it because there wasn’t much competition. He insists you have to be “way more brilliant” to be a doctor than an economist, but I don’t think either of us believes this.

 

I am surprised to look at my watch and realize 20 minutes has passed. As I reluctantly become the doctor again, I ask if I can examine him and slide back into the usual routine. I listen to his lungs with my stethoscope and hear the same wet-sounding crackles and wheezes throughout his lower lobes that have been there for days … the ones we have not been able to fix. “I hear you may get to go home soon,” I say. “Yes,” he replies, a smile spreading across his face. “Even if I’m too tired to do much, I like to just lie down and watch my kids run around.”

 

“That sounds wonderful,” I say. “We suggested a couple of oral antibiotics to your team that they could prescribe when you leave to cover most of the usual bugs. They should help protect you while your immune system is so impaired.” As the words leave my lips I realize I am also telling a story that I hope ends up being true. He seems to understand we’ve found no unifying diagnosis that we can treat to make him better. But still he says, “Thanks. Thank you for coming and talking with me.” Not “Thank you for fixing my infection with your medicine.” Not “Thank you for figuring out the obscure diagnosis that nobody else could find.” And certainly not “Thank you for curing my cancer.” We have done none of these things. He thanks me for coming into the room. And in these simple words of gratitude, he reminds me of the healing power of care, conversation, explanation, and reassurance. Of why, even when we don’t have the answers, we should still go into the room.

 

I am home putting away dishes later that night when I feel a rush of gratitude for that simple conversation. It hits me suddenly, as I place a clean drinking glass in my cupboard, the gift of those small moments. All those things he could have been—angry, depressed, disengaged, hopeless—he wasn’t. And all those things I could have been—ashamed, helpless, avoidant, exhausted—I left outside the door. Something about our conversation felt like forgiveness. At a time in his life when fear and self-focus would be expected, he was still so fully and remarkably looking out—sharing, wondering, teaching. And he brought me with him for a few moments. While modern medicine was failing both of us, he treated me as a human, not as a doctor, and led us to that place where the power to heal remained.

 

Stead W. A PIECE OF MY MIND. A Story I Hope Ends Up Being True. JAMA. 2015 Aug
11;314(6):563-4.

Courtesy of  http://www.medpagetoday.com/PatientCenteredMedicalHome/PatientCenteredMedicalHome/53613?isalert=1&uun=g906366d4529R5793688u&xid=NL_breakingnews_2015-09-17#./53567?&_suid=1442527889007013833902190756714

Cryonics and connectomics

I woke up on Saturday to a heartbreaking front-page article in the New York Times about a terminally ill young woman who chooses to freeze her brain. She is drawn into a cottage industry spurred by “transhumanist” principles that offers to preserve people in liquid nitrogen immediately after death and store their bodies (or at least their heads) in hopes that they can be reanimated or digitally replicated in a technologically advanced future.

Proponents have added a patina of scientific plausibility to this idea by citing the promise of new technologies in neuroscience, particularly recent work in “connectomics”—a field that maps the connections between neurons. The suggestion is that a detailed map of neural connections could be enough to restore a person’s mind, memories, and personality by uploading it into a computer simulation.

Science tells us that a map of connections is not sufficient to simulate, let alone replicate, a nervous system, and that there are enormous barriers to achieving immortality in silico. First, what information is required to replicate a human mind? Second, do current or foreseeable freezing methods preserve the necessary information, and how will this information be recovered? Third, and most confounding to our intuition, would a simulation really be “you”?

I study a small roundworm, Caenorhabditis elegans, which is by far the best-described animal in all of biology. We know all of its genes and all of its cells (a little over 1,000). We know the identity and complete synaptic connectivity of its 302 neurons, and we have known it for 30 years.

If we could “upload” or roughly simulate any brain, it should be that of C. elegans. Yet even with the full connectome in hand, a static model of this network of connections lacks most of the information necessary to simulate the mind of the worm. In short, brain activity cannot be inferred from synaptic neuroanatomy...

The presence or absence of a synapse, which is all that current connectomics methods tell us, suggests that a possible functional relationship between two neurons exists, but little or nothing about the nature of this relationship—precisely what you need to know to simulate it...

But what is this replica? Is it subjectively “you” or is it a new, separate being? The idea that you can be conscious in two places at the same time defies our intuition. Parsimony suggests that replication will result in two different conscious entities. Simulation, if it were to occur, would result in a new person who is like you but whose conscious experience you don’t have access to.

That means that any suggestion that you can come back to life is simply snake oil. Transhumanists have responses to these issues. In my experience, they consist of alternating demands that we trust our intuition about nonexistent technology (uploading could work) but deny our intuition about consciousness (it would not be me).

No one who has experienced the disbelief of losing a loved one can help but sympathize with someone who pays $80,000 to freeze their brain. But reanimation or simulation is an abjectly false hope that is beyond the promise of technology and is certainly impossible with the frozen, dead tissue offered by the “cryonics” industry. Those who profit from this hope deserve our anger and contempt.

http://www.technologyreview.com/view/541311/the-false-science-of-cryonics/

Ventriculomegaly contraindicating fetal surgery in myelomeningocele

Fetuses with enlarged ventricles may be less likely than their counterparts to benefit from surgery in the womb to treat spina bifida, according to a study published in the Journal of Neurosurgery: Pediatrics.

Researchers found that fetuses with enlarged ventricles were more likely to require a second surgery to relieve a life-threatening build-up of pressure within the brain. Given the risks that fetal surgery poses for mother and newborn, the findings indicate that, in these cases, it may be better to wait until after birth to perform the corrective spinal surgery.

In 2011, the Management of Myelomeningocele (MOMS) study showed that surgically correcting the spinal defect while the fetus is in the womb greatly reduces the need to divert fluid away from the ventricles to relieve hydrocephalus.

In the current analysis of data from the original MOMS study, Noel B. Tulipan, MD, Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues found that fetuses who had larger ventricles were equally as likely to require placement of a shunt during the first year after birth, regardless of when they underwent the spinal repair surgery.

“These results indicate that physicians should proceed with caution before recommending in utero surgery for a fetus with enlarged ventricles,” said Rosemary Higgins, MD, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health (NIH), Bethesda, Maryland.

The original MOMS study found that infants who had undergone the surgery before birth were more likely to walk without crutches or other devices. At 30 months of age, the fetal surgery group also had higher scores in tests of mental and motor development. However, as with any surgery, the procedure presented risks. Babies who underwent surgery in the uterus were more likely to be born preterm than were those who had the surgery after birth. In addition, mothers in the fetal surgery group were at risk for having the surgical scar on the uterus tear or rupture during subsequent pregnancies.

“A major rationale for performing the surgery is to avoid having to place a shunt later on,” explained Dr. Higgins. “If it’s likely that a second surgery will be needed anyway, then it doesn’t appear that the potential benefits of an initial fetal surgery outweigh the risks.”

For the current analysis, researchers tabulated the results in a single, composite outcome, to highlight the differences between treatment and control groups. The primary combined outcome for this analysis was whether a child had died, had a shunt placed in the first year after birth, or met the study’s criteria for when to place a shunt.

Dr. Higgins explained that when the researchers began the original study, there were no formal recommendations for shunt placement, so the researchers developed a set of objective criteria to guide the treatment of patients in the study.

Of the women who took part in the study, 91 were randomised to the prenatal surgery group and 92 to the postnatal group. Of these, 72.5% in the prenatal surgery group and 97.8% in the postnatal surgery group met the criteria for inclusion in the primary outcome. Overall, 44% of children in the prenatal surgery group had a shunt placed, compared with 83.7% in the postnatal group.
When the women were first enrolled in the study, the researchers took magnetic resonance imaging scans of the fetuses’ brains. Irrespective of whether they were in the prenatal or postnatal surgery group, children with the largest ventricles were more likely to require a shunt than those with smaller ventricles.

For the prenatal surgery group, shunts were eventually placed in 20% of those with ventricles <10 mm, 45.2% with ventricles from 10 to <15 mm, and 79% with ventricle size ≥15 mm. For the postnatal surgery group, shunts were placed in 79.4%, 86%, and 87.5%, respectively.
The researchers concluded that fetuses with ventricles smaller than 10 mm are the ideal candidates for fetal surgery, while there appears to be no benefit, in relation to shunting, for fetuses with ventricles ≥15 mm. Cases in between should be evaluated carefully before deciding whether to refer them for fetal surgery, the authors concluded.

http://dgnews.docguide.com/mri-scan-may-identify-best-candidates-fetal-spina-bifida-surgery?overlay=2&nl_ref=newsletter&pk_campaign=newsletter

Tulipan N, Wellons JC 3rd, Thom EA, Gupta N, Sutton LN, Burrows PK, Farmer D,
Walsh W, Johnson MP, Rand L, Tolivaisa S, D'alton ME, Adzick NS;  for the MOMS
Investigators. Prenatal surgery for myelomeningocele and the need for
cerebrospinal fluid shunt placement. J Neurosurg Pediatr. 2015 Sep 15:1-8. [Epub
ahead of print]

Abstract

OBJECT The Management of Myelomeningocele Study (MOMS) was a multicenter randomized trial comparing the safety and efficacy of prenatal and postnatal closure of myelomeningocele. The trial was stopped early because of the demonstrated efficacy of prenatal surgery, and outcomes on 158 of 183 pregnancies were reported. Here, the authors update the 1-year outcomes for the complete trial, analyze the primary and related outcomes, and evaluate whether specific prerandomization risk factors are associated with prenatal surgery benefit. METHODS The primary outcome was a composite of fetal loss or any of the following: infant death, CSF shunt placement, or meeting the prespecified criteria for shunt placement. Primary outcome, actual shunt placement, and shunt revision rates for prenatal versus postnatal repair were compared. The shunt criteria were reassessed to determine which were most concordant with practice, and a new composite outcome was created from the primary outcome by replacing the original criteria for CSF shunt placement with the revised criteria. The authors used logistic regression to estimate whether there were interactions between the type of surgery and known prenatal risk factors (lesion level, gestational age, degree of hindbrain herniation, and ventricle size) for shunt placement, and to determine which factors were associated with shunting among those infants who underwent prenatal surgery. RESULTS Ninety-one women were randomized to prenatal surgery and 92 to postnatal repair. The primary outcome occurred in 73% of infants in the prenatal surgery group and in 98% in the postnatal group (p < 0.0001). Actual rates of shunt placement were only 44% and 84% in the 2 groups, respectively (p < 0.0001). The authors revised the most commonly met criterion to require overt clinical signs of increased intracranial pressure, defined as split sutures, bulging fontanelle, or sunsetting eyes, in addition to increasing head circumference or hydrocephalus. Using these modified criteria, only 3 patients in each group met criteria but did not receive a shunt. For the revised composite outcome, there was a difference between the prenatal and postnatal surgery groups: 49.5% versus 87.0% (p < 0.0001). There was also a significant reduction in the number of children who had a shunt placed and then required a revision by 1 year of age in the prenatal group (15.4% vs 40.2%, relative risk 0.38 [95% CI 0.22-0.66]). In the prenatal surgery group, 20% of those with ventricle size < 10 mm at initial screening, 45.2% with ventricle size of 10 up to 15 mm, and 79.0% with ventricle size ≥ 15 mm received a shunt, whereas in the postnatal group, 79.4%, 86.0%, and 87.5%, respectively, received a shunt (p = 0.02). Lesion level and degree of hind-brain herniation appeared to have no effect on the eventual need for shunting (p = 0.19 and p = 0.13, respectively). Similar results were obtained for the revised outcome. CONCLUSIONS Larger ventricles at initial screening are associated with an increased need for shunting among those undergoing fetal surgery for myelomeningocele. During prenatal counseling, care should be exercised in recommending prenatal surgery when the ventricles are 15 mm or larger because prenatal surgery does not appear to improve outcome in this group. The revised criteria may be useful as guidelines for treating hydrocephalus in this group.

Visual attention and migraine

Villa TR, Agessi LM, Moutran AR, Gabbai AA, Carvalho DS. Visual Attention in
Children With Migraine: The Importance of Prophylaxis. J Child Neurol. 2015 Aug
31. pii: 0883073815601498. [Epub ahead of print]

Abstract

This study aimed to compare the visual attention performance of children newly diagnosed with migraine, children undergoing migraine prophylaxis, and a healthy control group. Eighty-two children aged 8 to 12 years were divided into 3 groups: untreated migraine (n = 30), migraine prophylaxis (n = 22), and control (n = 30). All were subjected to a visual attention assessment with the Trail Making Test parts A and B, Letter-Cancellation Test, and the Brazilian Visual Attention Test 3rd edition. Although performance in attention tasks was within the normal range in all groups, children with untreated migraine performed significantly worse in some visual attention tests than did the control children or children undergoing migraine prophylaxis. The migraine prophylaxis group performed as well as the control group. The deregulation of the neurochemical mechanisms underlying the physiopathology of migraine might induce visual attention deficits, but an effective prophylactic treatment might reverse migraine symptoms.

Courtesy of  http://www.mdlinx.com/neurology/medical-news-article/2015/09/17/children-migraine-prophylaxis-visual-attention/6307156/?category=sub-specialty&page_id=1&subspec_id=317

Voluntary movement after paralysis

39-year-old man who had been completely paralyzed for four years was able to voluntarily control his leg muscles and take thousands of steps in a “robotic exoskeleton” device during five days of training — and for two weeks afterward— a team of UCLA scientists reports this week.

This is the first time that a person with chronic, complete paralysis has regained enough voluntary control to actively work with a robotic device designed to enhance mobility.

In addition to the robotic device, the man was aided by a novel noninvasive spinal stimulation technique that does not require surgery. His leg movements also resulted in other health benefits, including improved cardiovascular function and muscle tone.

The new approach combines a battery-powered wearable bionic suit that enables people to move their legs in a step-like fashion, with a noninvasive procedure that the same researchers had previously used to enable five men who had been completely paralyzed to move their legs in a rhythmic motion. That earlier achievement is believed to be the first time people who are completely paralyzed have been able to relearn voluntary leg movements without surgery. (The researchers do not describe the achievement as “walking” because no one who is completely paralyzed has independently walked in the absence of the robotic device and electrical stimulation of the spinal cord.)

In the latest study, the researchers treated Mark Pollock, who lost his sight in 1998 and later became the first blind man to race to the South Pole. In 2010, Pollock fell from a second-story window and suffered a spinal cord injury that left him paralyzed from the waist down.

At UCLA, Pollock made substantial progress after receiving a few weeks of physical training without spinal stimulation and then just five days of spinal stimulation training in a one-week span, for about an hour a day.

“In the last few weeks of the trial, my heart rate hit 138 beats per minute,” Pollock said. “This is an aerobic training zone, a rate I haven’t even come close to since being paralyzed while walking in the robot alone, without these interventions. That was a very exciting, emotional moment for me, having spent my whole adult life before breaking my back as an athlete.”

“It will be difficult to get people with complete paralysis to walk completely independently, but even if they don’t accomplish that, the fact they can assist themselves in walking will greatly improve their overall health and quality of life,” said V. Reggie Edgerton, senior author of the research and a UCLA distinguished professor of integrative biology and physiology, neurobiology and neurosurgery.

The procedure used a robotic device manufactured by Richmond, California-based Ekso Bionics which captures data that enables the research team to determine how much the subject is moving his own limbs, as opposed to being aided by the device.

“If the robot does all the work, the subject becomes passive and the nervous system shuts down,” Edgerton said.

The data showed that Pollock was actively flexing his left knee and raising his left leg and that during and after the electrical stimulation, he was able to voluntarily assist the robot during stepping; it wasn’t just the robotic device doing the work.

“For people who are severely injured but not completely paralyzed, there’s every reason to believe that they will have the opportunity to use these types of interventions to further improve their level of function. They’re likely to improve even more,” Edgerton said. “We need to expand the clinical toolbox available for people with spinal cord injury and other diseases.”

http://newsroom.ucla.edu/releases/completely-paralyzed-man-voluntarily-moves-his-legs-ucla-scientists-report

Iron 'ElectriRx' Man: Overground Stepping in an Exoskeleton Combined with Noninvasive Spinal Cord Stimulation after Paralysis

Gad, Parag ; Gerasimenko, Yury ; Zdunowski, Sharon ; Sayenko, Dimitry ; Haakana, Piia ; Turner, Amanda ; Lu, Daniel ; Roy, Roland ; Edgerton, V Reggie

37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EBS)

We asked whether coordinated voluntary movement of the lower limbs could be regained in an individual having been completely paralyzed (>4 yr) and completely absent of vision (>15 yr) using a novel strategy – transcutaneous spinal cord stimulation at selected sites over the spinal vertebrae with just one week of training. We also asked whether this stimulation strategy could facilitate stepping assisted by an exoskeleton (EKSO, EKSO Bionics) that is designed so that the subject can voluntarily complement the work being performed by the exoskeleton. We found that spinal cord stimulation enhanced the level of effort that the subject could generate while stepping in the exoskeleton. In addition, stimulation improved the coordination patterns of the lower limb muscles resulting in a more continuous, smooth stepping motion in the exoskeleton. These stepping sessions in the presence of stimulation were accompanied by greater cardiac responses and sweating than could be attained without the stimulation. Based on the data from this case study it appears that there is considerable potential for positive synergistic effects after complete paralysis by combining the overground stepping in an exoskeleton, a novel transcutaneous spinal cord stimulation paradigm, and daily training.

 

Courtesy of Doximity