The top ten lies doctors tell themselves

The number one thing that I hear over and over again from doctors is, “I’m stuck in assembly line medicine.”…

I’m going to use an example of a specialist who thought she was stuck in middle America, a child psychiatrist, and she discovered that this was not true. Even though she had had a challenging fellowship and then ended up in a very big hospital, where she was told, “There’s absolutely no way as a child psychiatrist, as a pediatric psychiatrist, that you can work outside of the system.” Yet she was so overburdened, and in such a compromised position with the demands that were placed on her, that she felt like she had to explore other options. When she decided that she was going to go out on her own, she was pleasantly surprised to discover that she wasn’t stuck. Not only was she not stuck, she could thrive. And she has a thriving practice where she sees many, many, many children each and every week. And has a waiting list…

Number two is: “I’m not smart enough.”…

I think they lose their confidence. In fact physicians report that their number one issue is self confidence that gets eroded through the process of being trained as a physician. Often we embrace perfectionism in order to make up for that which we feel insecure about, and perfectionism does not help us feel smarter. It just helps us become controlling. Then we feel insecure and not smart enough. You’re absolutely right. You are in the top 1%. You’re not only intelligent. You are brilliant…

Number three. “I have no power.”…

My contract was up,  I was the only breadwinner… And I took my life, and my career into my own hands, and opened my own practice. This was 12 years ago, or 13 years ago now, and it was a simple change in overhead. I changed the structure, I cut out the middlemen, and I literally got my power back by removing all the people in my business life that were sucking my power from me. They’re like little parasites and you’re supporting them with the revenue you’re generating per minute. Sometimes upwards of 85% is going to them. Why not cut them out of the formula?  Which is what I did…

Number four. The thing that gets under my skin more than anything in the world. The thing that I hear more frequently than anything else is, “I’m burned out.” You are not burned out. You have been abused, manipulated, and you have experienced human rights violations in your medical education and training…

So please, I am begging you all to use proper terminology. To stop calling yourself burned out, when you’ve been abused, neglected, manipulated, and have literally survived years of human rights violations.

“I must overwork and overextend myself.” I hear this all the time. Workaholism, alcoholism, self-medicating. These are the top coping strategies that we, as medical professionals, use to deal with unrealistic work demands. We tell ourselves, “In order to get everything done that I have to get done. In order to meet expectations, meet the deadlines, then I have to overwork.” And this is not true. If you believe in it, you are participating in the lie, you’re enabling it. Start to claim yourself. Start to claim your time. Don’t participate. Don’t believe that there is a magic workaround or gimmick that’s going to enable you to stay in a toxic work environment and reshuffle the deck. What happens is in that shuffling process you continue to overcompensate, overdo, overextend yourself—and you’ve moved from overwork on the face of things to complicating your life. This is common. Liberate yourself. You can be free. It’s not about overwork…

And number six. “I can’t get confidential mental health help.” Yes you can. There are so many off-the-grid options. Even locally. Many psychologists and counselors do not even use an electronic medical record. They keep paper charts, and they’re 100% confidential. You can always talk to your pastor, your massage therapist, your friends without worrying about anything going into an EMR. Plus there are therapists, even psychiatrists, who do phone and Skype sessions….

“I’ll go broke.”

Pamela Wible: Number seven.

Sydney Ashland: Believing that in order to pay off debt, maintain your medical license, you have to stay in assembly-line medicine or your big box. I visited, several times recently, with an OB/Gyn who believed this, thought she couldn’t leave her practice because of the tail insurance on her malpractice insurance. She had loans to pay off. She was the breadwinner. Didn’t think she could support her kids and spouse. And guess what? She discovered when she started exploring what it might take to get a small space, to get rid of all of the administrative, middlemen that you talk about, Pamela, in her office, and just provide simple health care for women that her overhead dropped dramatically. From 70% down to 15%, that she got a very reasonably priced space, that actually her risk for malpractice went down because there were fewer people interacting with these patients   Fewer people taking call…

And number eight. “It’s the system.” We spend so much time vilifying and demonizing insurance companies, pharmaceutical companies, clinic managers, hospital CEOs, that we don’t take our own lives back. Once you realize that you have the power to practice medicine on your own terms, you end up way more successful and financially secure. You sometimes realize, along the way, that you are the problem. You have been the main obstacle to your success…

And number nine: “Nobody cares.”

Sydney Ashland: This is another lie. Because there are so many people who want to share your vision. They just need the invitation. So much of the time when we isolate and we don’t communicate, we tell ourselves that nobody cares, because we’re in our little isolated bubble. Once we start to poke our head out, and we start to talk a little bit about our vision, and we get brave enough to invite others to join us, we discover that there’s power in collaboration. That more people cared than we’ve recognized…

And number ten.

Sydney Ashland: “Nothing will ever get better.” I’m here to tell you, you are not terrible. You have not screwed it all up. It doesn’t matter if you’ve lost your license, made unethical or illegal mistakes, or missteps. It can and will get better. You just need help in strategic planning. You need to be willing to embrace change, instead of resisting it. And when you do that, through acts of courage and bravery, usually that start by telling yourself the truth. Not participating in the lies that we tell ourselves, you begin to personally and professionally experience what it’s like to have things get better, not worse. You absolutely can create for yourself, what you want your practice to look like.

http://www.idealmedicalcare.org/blog/top-10-lies-doctors-tell/

Stem cells for autism spectrum disorder

Dawson G, Sun JM, Davlantis KS, Murias M, Franz L, Troy J, Simmons R, Sabatos-DeVito M, Durham R, Kurtzberg J. Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial. Stem Cells Transl Med. 2017 May;6(5):1332-1339.

Abstract

Despite advances in early diagnosis and behavioral therapies, more effective treatments for children with autism spectrum disorder (ASD) are needed. We hypothesized that umbilical cord blood-derived cell therapies may have potential in alleviating ASD symptoms by modulating inflammatory processes in the brain. Accordingly, we conducted a phase I, open-label trial to assess the safety and feasibility of a single intravenous infusion of autologous umbilical cord blood, as well as sensitivity to change in several ASD assessment tools, to determine suitable endpoints for future trials. Twenty-five children, median age 4.6 years (range 2.26-5.97), with a confirmed diagnosis of ASD and a qualified banked autologous umbilical cord blood unit, were enrolled. Children were evaluated with a battery of behavioral and functional tests immediately prior to cord blood infusion (baseline) and 6 and 12 months later. Assessment of adverse events across the 12-month period indicated that the treatment was safe and well tolerated. Significant improvements in children's behavior were observed on parent-report measures of social communication skills and autism symptoms, clinician ratings of overall autism symptom severity and degree of improvement, standardized measures of expressive vocabulary, and objective eye-tracking measures of children's attention to social stimuli, indicating that these measures may be useful endpoints in future studies. Behavioral improvements were observed during the first 6 months after infusion and were greater in children with higher baseline nonverbal intelligence quotients. These data will serve as the basis for future studies to determine the efficacy of umbilical cord blood infusions in children with ASD.

Gesundheit B, Ashwood P, Keating A, Naor D, Melamed M, Rosenzweig JP. Therapeutic properties of mesenchymal stem cells for autism spectrum disorders. Med Hypotheses. 2015 Mar;84(3):169-77.

Abstract

Recent studies of autism spectrum disorders (ASD) highlight hyperactivity of the immune system, irregular neuronal growth and increased size and number of microglia. Though the small sample size in many of these studies limits extrapolation to all individuals with ASD, there is mounting evidence of both immune and nervous system related pathogenesis in at least a subset of patients with ASD. Given the disturbing rise in incidence rates for ASD, and the fact that no pharmacological therapy for ASD has been approved by the Food and Drug Administration (FDA), there is an urgent need for new therapeutic options. Research in the therapeutic effects of mesenchymal stem cells (MSC) for other immunological and neurological conditions has shown promising results in preclinical and even clinical studies. MSC have demonstrated the ability to suppress the immune system and to promote neurogenesis with a promising safety profile. The working hypothesis of this paper is that the potentially synergistic ability of MSC to modulate a hyperactive immune system and its ability to promote neurogenesis make it an attractive potential therapeutic option specifically for ASD. Theoretical mechanisms of action will be suggested, but further research is necessary to support these hypothetical pathways. The choice of tissue source, type of cell, and most appropriate ages for therapeutic intervention remain open questions for further consideration. Concern over poor regulatory control of stem cell studies or treatment, and the unique ethical challenges that each child with ASD presents, demands that future research be conducted with particular caution before widespread use of the proposed therapeutic intervention is implemented.

Hand-held vagus nerve stimulator for migraine

The US Food and Drug Administration (FDA) has cleared the hand-held, noninvasive vagus nerve stimulator (nVS) gammaCore (electroCore LLC) for the treatment of migraine pain in adults, the manufacturer announced earlier today.

The new 510(k) clearance will expand the device's label from just treating episodic cluster headache pain, an indication that the FDA approved in April 2017.

After the portable device is placed over the vagus nerve in the neck, it releases a mild electrical stimulation to the nerve's afferent fibers.

"With the FDA's decision to release gammaCore for migraine, patients now have access to an effective and safe therapy which can be self-administered to acutely treat the pain associated with migraine," Stephen D. Silberstein, MD, professor of neurology and director of the Headache Center at Thomas Jefferson University, Philadelphia, Pennsylvania, said in a news release.

Findings from the randomized, multicenter Prospective Study of nVNS for the Acute Treatment of Migraine (PRESTO) played a major role in the FDA's expanded clearance, notes the manufacturer.

;

PRESTO included 243 patients with episodic migraine. Significantly more members of the group receiving nVNS were pain free at 30 minutes (12.7%) than those receiving a sham treatment (4.2%; P = .01). There was also a greater percentage of the nVNS group who were pain free at 60 minutes (21% vs 10%, respectively; P = .02).

Although between-group differences for being pain free at 120 minutes missed statistical significance (30.4% vs 19.7%, respectively; P = .07), significance for this outcome was found after a post hoc repeated-measures test (odds ratio, 2.3; P = .01).

The secondary endpoint of mild or no pain at 2 hours was also significantly greater in those receiving neuromodulation (40.8% vs 27.6%; P = .03), as was pain reduction at 2 hours (34.8% vs 5.4%; P = .004).

"The PRESTO data suggests that gammaCore was rapidly effective, well-tolerated, and practical for the acute treatment of episodic migraine," principal investigator, Cristina Tassorelli, MD, director of the Headache Science Center at the C. Mondino National Neurological Institute, Pavia, Italy, in a press announcement released in 2017.

"Migraine is the third most common disease in the world, and one of the 10 most disabling diseases, which highlights a need for novel treatment options," Dr Tassorelli added. 

The device will be available commercially for the treatment of migraine headache pain in adults in the second quarter of 2018, according to the manufacturer.

It adds, though, that the safety and effectiveness of the prescription-only device have not been established in the acute treatment of chronic cluster headache or in the prophylactic treatment of chronic or episodic cluster or migraine headache.

This type of therapy is also not indicated for children; pregnant women; patients with active implantable medical devices; those with conditions such as carotid atherosclerosis, hypertension, or bradycardia/tachycardia;  or those with a metallic device, such as a stent, bone plate, or bone screw near the neck. It also shouldn't be used at the same time as the use of a mobile phone or other portable electronic device.

https://www.medscape.com/viewarticle/891930

Brainscope

Hanley D, Prichep LS, Badjatia N, Bazarian J, Chiacchierini R, Curley KC, Garrett J, Jones E, Naunheim R, O'Neil B, O'Neill J, Wright DW, Huff JS. A Brain Electrical Activity Electroencephalographic-Based Biomarker of Functional Impairment in Traumatic Brain Injury: A Multi-Site Validation Trial. J Neurotrauma. 2018 Jan 1;35(1):41-47.

Abstract

The potential clinical utility of a novel quantitative electroencephalographic (EEG)-based Brain Function Index (BFI) as a measure of the presence and severity of functional brain injury was studied as part of an independent prospective validation trial. The BFI was derived using quantitative EEG (QEEG) features associated with functional brain impairment reflecting current consensus on the physiology of concussive injury. Seven hundred and twenty adult patients (18-85 years of age) evaluated within 72 h of sustaining a closed head injury were enrolled at 11 U.S. emergency departments (EDs). Glasgow Coma Scale (GCS) score was 15 in 97%. Standard clinical evaluations were conducted and 5 to 10 min of EEG acquired from frontal locations. Clinical utility of the BFI was assessed for raw scores and percentile values. A multinomial logistic regression analysis demonstrated that the odds ratios (computed against controls) of the mild and moderate functionally impaired groups were significantly different from the odds ratio of the computed tomography (CT) positive (CT+, structural injury visible on CT) group (p = 0.0009 and p = 0.0026, respectively). However, no significant differences were observed between the odds ratios of the mild and moderately functionally impaired groups. Analysis of variance (ANOVA) demonstrated significant differences in BFI among normal (16.8%), mild TBI (mTBI)/concussed with mild or moderate functional impairment, (61.3%), and CT+ (21.9%) patients (p < 0.0001). Regression slopes of the odds ratios for likelihood of group membership suggest a relationship between the BFI and severity of impairment. Findings support the BFI as a quantitative marker of brain function impairment, which scaled with severity of functional impairment in mTBI patients. When integrated into the clinical assessment, the BFI has the potential to aid in early diagnosis and thereby potential to impact the sequelae of TBI by providing an objective marker that is available at the point of care, hand-held, non-invasive, and rapid to obtain.

Courtesy of a colleague

Stuttering

The first email arrived in the morning; the sun was just rising, barely visible through the heavy blinds covering my window. The email was delivered via the automated messaging system on my website; the sender was a complete stranger. Although I had no way of knowing it at the time, this email would be the first of many just like it.

The stranger had sent a short message: Here’s a link to a stuttering specialist in Atlanta, it read. I scrunched my eyes together, puzzled. I don’t live in Atlanta, I thought. But more important, I’m not looking for the help of a stuttering specialist. Why would a stranger assume that I am?

Stuttering is a genetic and neurological speech disability that I’ve carried my whole life. For years, I had difficulty accepting my stutter, but by the time I was in my mid-20s, I began a journey of self-acceptance. I started writing my stutter, and advocating for myself and others who stutter. I hoped that my everyday activism and writing might have a positive impact on the world. This past year alone, I wrote and published a dozen articles and essays about stuttering.

But I wasn’t prepared for the response I received when one particular piece I wrote about stuttering was published in The Washington Post  — placed on the front page of the Sunday health section, no less. After the story’s initial publication, the piece was syndicated and republished in a handful of newspapers all across the United States and Canada. I was delighted, giddy, imagining how many people would read my article and learn more about stuttering, an incredibly complicated speech impediment that only affects 1 percent of the American population.

“You’ve done it,” I whispered to myself, holding the article in print for the first time. “You’ve told the truth. You’re helping people learn.”

But then the emails started coming in — all of them from strangers. Whether they were complimentary of my article or not, most of them insisted on sharing some sort of cure.

My cousin had a stutter, one read, but this SpeechEasy device cured him! By lunchtime, there were a dozen new emails: Have you tried Prozac to cure your stutter? The next day, more: Have you heard thiamine hydrochloride might cure stuttering? Months later, they’re still trickling in: Try out this fluency-shaping program! or, Have you ever tried the Alexander Technique?

Most of these strangers are well-intentioned — a handful impolite — but what they share is the assumption that I’m actively seeking a cure for my stutter. They seem to assume that people with disabilities — which encompasses nearly one-fifth of the American population — are only concerned about finding a cure.

This is simply untrue.

The fact is, for adults, there is no cure for stuttering. Our scientific understanding of stuttering is still incomplete, so for now, researchers seem to agree that early intervention in children is the only way to actually reverse a stutter. Once you reach adulthood, there’s no miracle cure.

In the past, that hasn’t stopped me from trying. For years, I chased every false cure: vitamins claiming fluency, outrageously confident self-cure programs, delayed auditory feedback devices that proved impractical in everyday life. I also tried speech therapy three separate times — in childhood, adolescence, and adulthood — but it was ultimately unsuccessful for me.

I even pursued the most harmful miracle “cure” of them all: drinking alcohol in excess. I discovered this option when I was 15, and perusing a stuttering-focused blog. For years afterward, I struggled with alcohol as a form of disability self-medication. It took more than a decade, but I finally learned that all of these “cures” were ineffective for me. Seeking a magical solution for a lifelong disability did more harm than good.

Eventually, I began to accept my stutter as a permanent part of my speech. I realized that my disability is part of my identity — not a disorder that requires correction. Self-acceptance has been scientifically proven to positively impact the life of a person who stutters. For me, it did just that.

But then came the article, the emails. The messages. The strangers who believed I wanted nothing more than to smother my stutter with pills, devices, and false hope. The more messages I received, the more surprised I became. I had stuttered my entire life. I had been studying and writing about my stutter for years. My graduate thesis had a research component entirely dedicated to stuttering. I have a bookshelf of textbooks, nonfiction research, and self-help books, all about my speech impediment. I wanted to ask these strangers: if there was a miracle cure for stuttering, wouldn’t I know about it already?

Thinking about all this, I grew angry. I complained about the emails to my family. I commiserated with my friends who also stutter. “Can you b-b-b-believe th-th-them?” I demanded.

One night, I was up late working on a project. I turned the TV on, absently watching infomercials. They seemed to be on every channel: commercials for hair-growth serums, weight-loss pills, the perfect shampoo, the perfect shoe rack, the perfect gadget or organizer or device. I started thinking.

Over the past few months, I had been recommended pills and programs from strangers who assumed I needed a cure. I had blamed them for being insensitive, for being unaware, but I should’ve understood all along: It’s our culture that demands perfection. It’s our culture that makes people believe disabilities have to be cured.

I don’t discourage others who are disabled and hope for a cure, I respect their right to pursue whatever it is they want. But this whole experience taught me something about myself: For my own stability and peace of mind, it’s important that I not search for a cure. I hope others too will stop assuming that disability is something that needs to be fixed. And I hope our culture embraces disability for what it’s always been: Just another form of living.

https://www.yahoo.com/lifestyle/disabilities-cured-accepted-001102998.html

Adult-onset Leigh's syndrome

Jabeen SA, Sandeep G, Mridula KR, Meena AK, Borgohain R, Sundaram C. Adult-onset Leigh's disease: A rare entity. Ann Indian Acad Neurol. 2016 Jan-Mar;19(1):140-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782535/#!po=4.16667

Abstract

Leigh syndrome (LS) is a heterogeneous familial or sporadic neurodegenerative disorder. It is typically seen in infancy or childhood, although rare cases of adult onset have been described. The authors describe a 37-year-old woman who presented with protracted gastrointestinal symptoms followed by acute brain stem syndrome with severe metabolic acidosis and who subsequently showed dramatic clinical and neuroradiological improvement.

_____________________________________________________________________

From the article

Adult LD was defined as patients who survived longer than 18 years.   Sakushima et al., extensively reviewed the literature on adult-onset LD and they found that adult LD was rare and its clinical manifestations were different from those of children. They divided the cases into those which fulfilled the Rahman et al., criteria (Rahman's criteria group (RCG)) and those which were diagnosed with the identification of genetic abnormality (laboratory-diagnosed group (LDG)). Adult-onset LD tends to have less incidence of developmental delay, COX deficiency, serum lactate elevation, and basal ganglia lesions. In contrast they have cranial nerve disturbance, pyramidal signs, and cerebellar dysfunction.

A 37-year-old female presented with protracted pain abdomen and vomiting since 3 months; followed by giddiness, headache, and diplopia since 15 days. There was no fever, seizures, limb weakness, or sensory symptoms. Personal and family history was unremarkable. General and other systemic examination was normal. Neurological examination revealed bilateral horizontal gaze palsy with gait ataxia. Rest of the examination was normal. Magnetic resonance imaging (MRI) brain showed dorsal brain stem (midbrain and pons) T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities. In view of recurrent vomiting, clinical and MRI picture, a diagnosis of Wernicke's encephalopathy was made and she was treated with parenteral thiamine. There was marked improvement and she was discharged. Few days later she presented with diplopia, increased swaying while walking, bulbar palsy, breathlessness, and shock. Arterial blood gas (ABG) analysis showed severe metabolic acidosis. Fasting serum lactate was elevated (8 mmol/L; normal: 0.8-2.4 mmol/L). MRI revealed increased brainstem hyperintensities with MR spectroscopy (MRS) of the lesion showing peak lactate.  Cerebrospinal fluid (CSF) lactate was also elevated (4.4 mmol/L; normal: 1.1-2.3 mmol/L). Hemogram and renal and liver function tests were normal. CSF cytology and biochemistry were normal. Further, metabolic work up revealed normal serum copper, ceruloplasmin, and urine copper levels. Serum aquaporin antibodies were negative. A provisional diagnosis of adult-onset LD was considered and patient was treated with mitochondrial cocktail (intravenous thiamine, coenzyme-Q, riboflavin, L-carnitine, and L-arginine) along with ventilator support for respiratory failure. Patient improved dramatically in neurological symptoms and was slowly weaned from the ventilator. Muscle biopsy revealed reduced COX and COX-succinate dehydrogenase (SDH) activity without any evidence of ragged red fibers.  Muscle biopsy was sent to Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India; where muscle deoxyribonucleic acid (DNA) was extracted and sequential analysis for complete mitochondrial genome was done; no pathogenic mutations were observed, however, nuclear part of mitochondrial DNA (mtDNA) of blood was not analyzed. Repeat MRI after 3 months revealed complete disappearance of the hyperintensities. A diagnosis of adult-onset LS was made based on classical radiological appearance, biochemical and histochemical evidence, and excellent response to mitochondrial cocktail. At 1-year follow-up, she was asymptomatic neurologically, but had moderate obstructive sleep apnea with an apnea–hypopnea index of 20/h on overnight polysomnography. Cardiac evaluation which included two-dimensional (2D) echocardiogram, treadmill test, and 24-h Holter monitoring were normal…

The diagnostic criteria by Rahman et al 1996. for LS are as follows:

Progressive neurologic disease with motor and intellectual developmental delay;

Signs and symptoms of brain stem and/or basal ganglia dysfunction;

Elevated lactate levels in the blood and/ or CSF; and

One or more of the following:

     Characteristic features of LS on neuroimaging (symmetric hyperintense lesions in basal
     ganglia or brainstem in T2 sequence),     

     Typical neuropathological changes at postmortem examination, and

     Typical neuropathology in a similarly affected sibling.

The criteria proposed by Sakushima et al., 2011 are:

History of cryptogenic thrive failure or signs of mental retardation, pyramidal signs, cerebellar disturbances, ophthalmoplegia, deafness, dysarthria, or other neurological symptoms are present; and

Bilateral basal ganglia lesions or brainstem lesions with serum or CSF lactate elevation are present (lactate stress test (LST) should be considered when resting lactate levels are normal);

Mitochondrial abnormalities are present in muscle pathology or in biochemical analyses, or known LD gene mutations are present; and

Metabolic disorders, toxins, infection, multiple sclerosis, and Wernicke's encephalopathy can be excluded.

Our patient fulfilled the later criteria as she did not have history of failure to thrive or motor/intellectual delay as required in Rahman et al., criteria. Rather she had recurrent vomiting and brainstem signs…

The major mutations known to occur in LD patients are T8993C, T8993G, T10191C, G13513A, A8344G, and A3243G in mitochondrial genes, and SURF1in the nuclear genome. Currently, there are 24 known mutations in mitochondrial genes and 21 in nuclear genes.  The underlying genetic etiology could not be ascertained in our patient. Recent studies have shown that recognized mtDNA mutations only account for a small proportion of cases of mitochondrial disease.   In addition, nuclear DNA mutations account for a substantial number of mitochondrial disorders which could not be done in our patient due to unavailability. Moreover, mitochondrial respiratory chain analysis in muscle or fibroblasts could not be done in our patient. Adult-onset LD is extremely rare and requires high index of suspicion.

Courtesy of:  https://mitochondrialdiseasenews.com/2016/06/06/adult-onset-leighs-disease-treated-a-case-study/#at_pco=tst-1.0&at_si=5a6f55c5d8785dd3&at_ab=per-2&at_pos=0&at_tot=2

Bleach for autism

Parents are making their children drink industrial bleach to cure them of autism—with the potentially deadly practice linked back to a U.S. cult.

According to British tabloid the Sunday People, six British police forces have probed cases in which children as young as two have been forced to undergo the potentially lethal treatment.

The treatment being administered is CD (Chloride Dioxide) or MMS (Miracle Mineral Solution)—with a secret Facebook group touting its use to desperate parents in the U.K.

The method has been promoted by a controversial U.S. church with a branch in Los Angeles - the secretive Genesis II Church, founded by Jim Humble, a former scientologist.

A 2016 investigation by Eyewitness News and ABC News found an underground network clustered in southern California promoting MMS on Facebook as a cure for ailments including cancer, Parkinsons, and autism in children.

The previous year the BBC exposed a secret conference in which leading figures from the church travelled to the U.K. to promote the use of MMS, which it claims is a non-dangerous religious sacrament.

They believe that autism is caused by pathogens and parasites, which Chloride Dioxide kills. Doctors say that the claims of adherents are groundless, the solution is untested and can cause serious harm.

The solution includes two chemicals – sodium chlorite and hydrochloric acid – that combine to make bleach. It is sold to be used orally or as an enema.

Proponents recommend mixing it with a fruit juice, but medical experts warn that this causes the solution to acidify and produce chlorine dioxide – a potentially lethal bleach used for stripping textiles.

The U.S. Food and Drug Administration warns that the product “used as directed, produces an industrial bleach that can cause serious harm to health.” It is banned in Canada.

The British Food Standards Authority warns against use of MMS, and says it can cause nausea, vomiting, diarrhoea, reduced blood pressure, damage the gut or cause respiratory failure.

There has been one death linked to use of MMS and several cases of those taking it reporting serious injuries.

However, the substance remains available to buy on the internet.

Dr Jeff Foster warned of the potentially deadly consequences of using MMS.

“Autism is a neuro-developmental disease which is not amenable to any form of tablet treatment. ‘It’s developed in the womb or early stages of life. ‘You can’t just reverse it and anyone claiming that does not understand the condition,” he told the People.

"When you have very extreme measures like this to “cure” a condition it’s just a roulette game,’ Dr Foster said. ‘

"Eventually someone will die. It’s only a matter of time."

http://www.newsweek.com/parents-are-making-their-children-drink-bleach-cure-them-autism-793197
Courtesy of a colleague

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Master Mineral Solution - Why has this Product Become so Popular?

This amazingly powerful compound, commonly known as the Miracle Mineral Supplement or MMS,  has been very prominant in the alternative medicinal arena for close to a decade. The reason it has stood the test of time is because it works - & works well!  The man who is responsible for its discovery & bringing it into the mainstream is Jim Humble.

 Who is this man Jim Humble?...

It all begun back in the mid 1990's whilst Jim was on a mining expidition[sic] deep within the jungle's[sic] of the South Americas[sic]. When one of his party was suddenly struck down by the Malaria parasite, Jim struck upon a amazing discovery - a revelation that has since altered the lives of many! Learn more...

What did Mr Humble discover? Chlorine Dioxide Molecule

Upon returning to the States, Jim began testing in earnest - & what he found was that the active component within his simple water purification formulation formula was absolutely deadly against the Malaria parasite - the very same parasite that is responsible for millions of deaths each & every year.   Needless to say, this warranted further investigation! Learn more...

As time progressed, it was becoming increasingly clear that the chlorine dioxide molecule was not only deadly against the malaria parasite, but also a wide range of fungi, bacteria & parasites - interestingly enough viruses as well!

Unfortunately, there is an ever increasing push from various regulatory bodies the world over that are attempting to shut down this product - so the question is how long will this amazingly effective compound will remain available, this is the question...

If you would like to download the first part of Jim Humble's latest book then download it as a .pdf here

The video below features one of Mr Humble's long standing advocates - this is an excellent introduction as to what this potent little compound can do. Be sure to have a watch...

https://www.mms-supplement.com/

Antisense suppression of glial fibrillary acidic protein as a treatment for Alexander disease

Hagemann TL, Powers B, Mazur C, Kim A, Wheeler S, Hung G, Swayze E, Messing A. Antisense suppression of glial fibrillary acidic protein as a treatment for Alexander disease. Ann Neurol. 2017 Dec 11. doi: 10.1002/ana.25118. [Epub ahead of print]

Abstract

OBJECTIVE:

Alexander disease is a fatal leukodystrophy caused by autosomal dominant gain-of-function mutations in the gene for glial fibrillary acidic protein (GFAP), an intermediate filament protein primarily expressed in astrocytes of the central nervous system. A key feature of pathogenesis is overexpression and accumulation of GFAP, with formation of characteristic cytoplasmic aggregates known as Rosenthal fibers. Here we investigate whether suppressing GFAP with antisense oligonucleotides could provide a therapeutic strategy for treating Alexander disease.

METHODS:

In this study, we use GFAP mutant mouse models of Alexander disease to test the efficacy of antisense suppression and evaluate the effects on molecular and cellular phenotypes and non-cell-autonomous toxicity. Antisense oligonucleotides were designed to target the murine Gfap transcript, and screened using primary mouse cortical cultures. Lead oligonucleotides were then tested for their ability to reduce GFAP transcripts and protein, first in wild-type mice with normal levels of GFAP, and then in adult mutant mice with established pathology and elevated levels of GFAP.

RESULTS:

Nearly complete and long-lasting elimination of GFAP occurred in brain and spinal cord following single bolus intracerebroventricular injections, with a striking reversal of Rosenthal fibers and downstream markers of microglial and other stress-related responses. GFAP protein was also cleared from cerebrospinal fluid, demonstrating its potential utility as a biomarker in future clinical applications. Finally, treatment led to improved body condition and rescue of hippocampal neurogenesis.

INTERPRETATION:

These results demonstrate the efficacy of antisense suppression for an astrocyte target, and provide a compelling therapeutic approach for Alexander disease.

_______________________________________________________________

Researchers have successfully used antisense oligonucleotides (ASOs) to block a mutation in experimental mice that causes pathology similar to the genetic defect implicated in Alexander disease, a rare and often fatal leukodystrophy in infants and small children. The findings of the study were published online December 11, 2017 in Annals of Neurology.

ASOs are short, synthetic single-strand nucleic acids — DNA, RNA, or an analog — that bind to and highjack messenger RNA (mRNA) to prevent, reduce, or alter a gene's transcription and expression of a protein.

Several ASOs have shown the ability to target and prevent overproduction of a nerve protein that damages the brain's white matter in Alexander disease (AxD), a progressive disorder that results in imperfect growth or destruction of myelin.

While it can be inherited, AxD is primarily caused by sporadic new mutations in the gene for glial fibrillary acidic protein (GFAP), an intermediate filament protein in astrocytes. When overexpressed, GFAP results in aggregation of abnormal deposits known as Rosenthal fibers, which cripple or destroy astrocytes. About half of all cases occur in infants, who usually die before the age of six.

In the study, the novel ASOs demonstrated the ability to prevent translation of GFAP in wild-type and AxD-mutated mouse models, gradually eliminating downstream levels of the protein. Treatment almost eliminated GFAP in the brains and spinal cords of mice, and resulted in reversal of Rosenthal fiber aggregates as well as markers of microglial and other stress-related responses. Treatment also led to improved body condition and rescue of hippocampal neurogenesis, as well as GFAP clearance from cerebrospinal fluid.

“Our study demonstrates proof of concept,” said senior researcher Albee Messing, VMD, PhD, a professor of neuropathology and director of the Waisman Center at the University of Wisconsin-Madison.

“We believe that GFAP knockdown using antisense technology is a viable approach for treating Alexander disease, but much work remains to be done, including assessing the ability to produce improvements in motor and other behavioral phenotypes,” he told Neurology Today.

That treatment also reduced GFAP in the cerebrospinal fluid of treated animals suggests that GFAP itself could be used as a biomarker to assess ASO efficacy and duration of suppression in patients, Dr. Messing said.

“The results exceeded all of our expectations,” he said. “We are a long way from human application, and I cannot guarantee that this treatment will not cause side effects, but this really is the first positive sign that ASOs might work.”…

“This is the first targeted therapy for Alexander disease, and the idea that we soon might be able to address this gene defect is very exciting,” said Florian Eichler, MD, assistant professor of neurology at Harvard Medical School and director of the leukodystrophy service at Massachusetts General Hospital, who was not involved with the study….

Although the mouse models do not develop leukodystrophy, he said, their pathology is similar to that of adult-onset chronic disease and the lack of white matter problems is secondary to the fact that, for the first time, ASOs were able to target and correct the GFAP mutation.

“Moving forward, clinical trials will be necessary to determine not only if ASOs can target the genetic defect in humans, and what dosages work best, but [also] whether changes in areas of the brain, after delivery, are adequate to prevent symptoms,” Dr. Eichler said…

Amy Waldman, MD, FAAN, assistant professor of neurology and medical director of the Leukodystrophy Center at Children's Hospital of Philadelphia, said the US Food and Drug Administration's recent approval of the ASO nusinersen for spinal muscular atrophy provides precedence for the use of ASOs in humans with neurologic diseases….

However, she said several concerns with the approach still need to be addressed. “The route of administration for the mice was via an intracerebroventricular injection, and such delivery is not feasible for repeated injections of ASOs in humans. There are other methods, but they would add a layer of complexity. In spinal muscular atrophy, for example, ASOs are delivered via a lumbar puncture,” she explained.

“It remains to be seen whether the circulation of ASOs and penetration to various brain structures after a lumbar puncture will be sufficient to reduce GFAP in astrocytes in the frontal white mater, basal ganglia, and brainstem,” Dr. Waldman added.

https://journals.lww.com/neurotodayonline/Fulltext/2018/01250/At_the_Bench_Alexander_Disease__Antisense_Therapy.4.aspx

Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome

Elizabeth A Thiele, Eric D Marsh, MD, Jacqueline A French, MD, Maria Mazurkiewicz-Beldzinska, MD, Selim R Benbadis, MD, Charuta Joshi, MBBS, Paul D Lyons, MD, Adam Taylor, PhD, Claire Roberts, PhD, Kenneth Sommerville, MD on behalf of the show GWPCARE4 Study Group.  Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial.  Lancet 24 January 2018   http://dx.doi.org/10.1016/S0140-6736(18)30136-3

Summary

Background

Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications. No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome. We therefore assessed the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in this population of patients.

Methods

In this randomised, double-blind, placebo-controlled trial done at 24 clinical sites in the USA, the Netherlands, and Poland, we investigated the efficacy of cannabidiol as add-on therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome. Eligible patients (aged 2–55 years) had Lennox-Gastaut syndrome, including a history of slow (<3 Hz) spike-and-wave patterns on electroencephalogram, evidence of more than one type of generalised seizure for at least 6 months, at least two drop seizures per week during the 4-week baseline period, and had not responded to treatment with at least two antiepileptic drugs. Patients were randomly assigned (1:1) using an interactive voice response system, stratified by age group, to receive 20 mg/kg oral cannabidiol daily or matched placebo for 14 weeks. All patients, caregivers, investigators, and individuals assessing data were masked to group assignment. The primary endpoint was percentage change from baseline in monthly frequency of drop seizures during the treatment period, analysed in all patients who received at least one dose of study drug and had post-baseline efficacy data. All randomly assigned patients were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02224690.

Findings

Between April 28, 2015, and Oct 15, 2015, we randomly assigned 171 patients to receive cannabidiol (n=86) or placebo (n=85). 14 patients in the cannabidiol group and one in the placebo group discontinued study treatment; all randomly assigned patients received at least one dose of study treatment and had post-baseline efficacy data. The median percentage reduction in monthly drop seizure frequency from baseline was 43·9% (IQR −69·6 to −1·9) in the cannibidiol group and 21·8% (IQR −45·7 to 1·7) in the placebo group. The estimated median difference between the treatment groups was −17·21 (95% CI −30·32 to −4·09; p=0·0135) during the 14-week treatment period. Adverse events occurred in 74 (86%) of 86 patients in the cannabidiol group and 59 (69%) of 85 patients in the placebo group; most were mild or moderate. The most common adverse events were diarrhoea, somnolence, pyrexia, decreased appetite, and vomiting. 12 (14%) patients in the cannabidiol group and one (1%) patient in the placebo group withdrew from the study because of adverse events. One patient (1%) died in the cannabidiol group, but this was considered unrelated to treatment.

Interpretation

Add-on cannabidiol is efficacious for the treatment of patients with drop seizures associated with Lennox-Gastaut syndrome and is generally well tolerated. The long-term efficacy and safety of cannabidiol is currently being assessed in the open-label extension of this trial.

Funding

GW Pharmaceuticals.

Leigh syndrome and MRPS34

Lake NJ, Webb BD, Stroud DA, Richman TR, Ruzzenente B, Compton AG, Mountford HS, Pulman J, Zangarelli C, Rio M, Bodaert N, Assouline Z, Sherpa MD, Schadt EE, Houten SM, Byrnes J, McCormick EM, Zolkipli-Cunningham Z, Haude K, Zhang Z, Retterer K, Bai R, Calvo SE, Mootha VK, Christodoulou J, Rötig A, Filipovska A, Cristian I, Falk MJ, Metodiev MD, Thorburn DR. Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome. Am J Hum Genet. 2017 Aug 3;101(2):239-254.

Abstract

The synthesis of all 13 mitochondrial DNA (mtDNA)-encoded protein subunits of the human oxidative phosphorylation (OXPHOS) system is carried out by mitochondrial ribosomes (mitoribosomes). Defects in the stability of mitoribosomal proteins or mitoribosome assembly impair mitochondrial protein translation, causing combined OXPHOS enzyme deficiency and clinical disease. Here we report four autosomal-recessive pathogenic mutations in the gene encoding the small mitoribosomal subunit protein, MRPS34, in six subjects from four unrelated families with Leigh syndrome and combined OXPHOS defects. Whole-exome sequencing was used to independently identify all variants. Two splice-site mutations were identified, including homozygous c.321+1G>T in a subject of Italian ancestry and homozygous c.322-10G>A in affected sibling pairs from two unrelated families of Puerto Rican descent. In addition, compound heterozygous MRPS34 mutations were identified in a proband of French ancestry; a missense (c.37G>A [p.Glu13Lys]) and a nonsense (c.94C>T [p.Gln32∗]) variant. We demonstrated that these mutations reduce MRPS34 protein levels and the synthesis of OXPHOS subunits encoded by mtDNA. Examination of the mitoribosome profile and quantitative proteomics showed that the mitochondrial translation defect was caused by destabilization of the small mitoribosomal subunit and impaired monosome assembly. Lentiviral-mediated expression of wild-type MRPS34 rescued the defect in mitochondrial translation observed in skin fibroblasts from affected subjects, confirming the pathogenicity of MRPS34 mutations. Our data establish that MRPS34 is required for normal function of the mitoribosome in humans and furthermore demonstrate the power of quantitative proteomic analysis to identify signatures of defects in specific cellular pathways in fibroblasts from subjects with inherited disease.

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Scientists have developed a new strategy for diagnosing mitochondrial diseases and identified the Mrps34 gene as a cause for Leigh syndrome.

The study, “Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome,” was published in The American Journal of Human Genetics.

Diagnosing mitochondrial diseases is often a hard task, and while genetic screening of a person’s entire genome has helped, additional strategies are in need to identify the most difficult cases.

Now, a team of scientists at the Murdoch Children’s Research Institute (MCRI) in Australia found a new cause underlying Leigh syndrome, the most common form of childhood mitochondrial disease.

They found mutations in a gene called Mrps34 in six patients with Leigh syndrome from different parts of the world, including Australia, France, and the United States. The findings were only possible with researchers applying a different technique called quantitative proteomics.

“A key approach was using quantitative proteomics. This process involves sampling all the proteins in a cell at once to identify any problems with the cellular machinery,” Nicole Lake, a Murdoch PhD student and the study’s first author, said in a press release. “Using this technique, you get a snapshot of what’s happening in cells.”

The MRPS34 is a component of mitochondrial ribosomes, called mitoribosomes, which are the protein synthesis machinery responsible for the production of proteins involved in the mitochondrial oxidative phosphorylation (OXPHOS) system. This system, located in the inner membrane of our mitochondria, is where the majority of the energy used by cells is produced.

Researchers performed quantitative proteomics in skin cells extracted from the six patients as well as in healthy skin cells, called controls. They found that the mutations led to a reduction in MRPS34 protein levels. Examining the mitoribosome profile by quantitative proteomics showed that its assembly was impaired, with half of its members falling apart.

These results establish the Mrps34 gene as an important cause for mitochondrial diseases and that employing quantitative proteomics  could help improve the diagnosis of these fatal diseases.

“This approach will therefore help to end the diagnostic odyssey for families with children suspected of mitochondrial and other inherited diseases,” said Murdoch chief investigator and Prof. David Thorburn, the study’s lead author.

“Early diagnosis improves the chance for early intervention. It can also provide the opportunity to enroll patients with mitochondrial diseases into clinical trials to test many new promising therapies that are in the pipeline, but not yet proven,” Thorburn added.

Sean Murray, CEO of the Australian Mitochondrial Disease Foundation (AMDF) said he was thrilled to see “an outcome like this, as it has been partly supported by the hard work of AMDF fund-raisers through activities such as our ‘Bloody Long Walks’ and demonstrates the value of researchers engaging with the patient community.”

https://mitochondrialdiseasenews.com/2017/08/09/researchers-develop-method-may-help-diagnose-mitochondrial-diseases/#at_pco=tst-1.0&at_si=5a6a32d06783351e&at_ab=per-2&at_pos=0&at_tot=2

Mitochondrial disease and medical child abuse

Justina Pelletier, a Connecticut teenager with mitochondrial disease, was admitted to Boston Children’s Hospital in 2013 on the advice of a metabolic geneticist at nearby Tufts Medical Center so she could see her longtime gastroenterologist, who had recently transferred to Boston. But the hospital — without consulting the Tufts geneticist — decided the girl’s problem was psychiatric rather than mito.

When her parents tried to get Justina transferred to Tufts, Boston Children’s called the authorities, claiming they were harmfully interfering in her care. A juvenile court judge agreed, and Justina’s parents lost custody. After more than 16 months in state custody, much of it in a locked psychiatric ward, the traumatized teen was returned to her family — still in a wheelchair, and still sick from her disease.

In another well-documented case involving Boston Children’s, Jessica and Sean Hilliard of Attleboro, Massachusetts, asked the hospital to test their 3-year-old son for mitochondrial disease, which often runs in families, after he showed symptoms of the rare disorder; his older sister had died of mito there in 2011. A hospital pediatrician accused the parents of inventing their son’s medical issues, after which they transferred the boy’s care to Tufts, where he received several diagnoses, including mito.

Yet, that didn’t stop Boston Children’s from calling a Tufts child-abuse specialist, who reported the Hilliards for “overmedicalization.” The state intervened, but backed off only after the parents took their son off of his medications. During the ensuing six-week hospitalization, the boy’s condition worsened, until the treatments were restored. Authorities eventually dropped all charges…

Those two cases generated lots of publicity. But in recent years, the U.S. mitochondrial disease community has been hit with hundreds of other false accusations of medical child abuse. MaryBeth Hollinger of MitoAction says the problem is getting worse.

“This issue comes up over and over,” said Hollinger, director of education, support and advocacy at the Boston-based nonprofit organization. “Munchausen syndrome by proxy is a real thing and it happens extremely rarely. But this new term ‘medical child abuse’ is really a game changer. It’s basically Munchausen by proxy but with no boundaries — and it often includes medical neglect, which I find ironic.”…

“We need medical professionals, but the way I see it, the families are experts on their child in a way the doctor isn’t,” Hollinger explained. “We are not all the same, even if we have the same genetic mutations.”

She added: “Child protective agencies are out there, and they work quite closely with the doctors. But they’re overworked and they know nothing about rare diseases. So, if some doctor or school says ‘I think they’re overdoing it,’ Child Protective Services will ask the name of this disease. They’re already aligning themselves — and not in your ballpark.”

Hollinger said she’s spoken with close to 100 families that faced similar situations.

“We may get calls for a different reason, but in the course of the conversation, a lot of times you uncover that they also went through accusations of medical child abuse,” she said. “So even though they didn’t call us about this, it sort of comes up. This is why they’re afraid.”…

Eichner [Maxine Eichner], who in July 2015 wrote a New York Times opinion piece on the subject, said that for every real case of medical abuse, there are at least two false positive cases. Her research led her to conduct an online poll that attracted 95 respondents in 30 states who had been falsely accused of overmedicating their children.

“My guess is that’s just the tip of the iceberg,” said Eichner, who joined MitoAction’s medical child abuse task force at the urging of her daughter, whose mito symptoms began at the age of 10, when she had her first migraine. Ultimately, the disease caused the girl to miss nearly two years of school.

Eichner said she and her husband were lucky not to have been charged with medical child abuse during the eight years they searched for answers.

“When I started to look into the science, I was horrified. All throughout our history, many doctors had jumped to the conclusion that it was either in her head, or that I was part of the problem,” she said. “My husband and I are both attorneys and we advocate for ourselves. What has happened with so many of these parents, in my view, is horrifying and completely unconstitutional. It violates parents’ right to choose medical care in their kids’ best interests.”…

Eichner said that despite advocacy and lobbying on this issue by MitoAction and other groups, “I don’t see any huge progress having been made in these past years.”

In her New York Times op-ed, Eichner also quoted Mark Korson, MD, the geneticist who treated Justina Pelletier at Tufts, as saying that such false charges have “snowballed” nationally. In Michigan, one of the few states that compile such figures, an average 51 accusations of medical abuse were filed against caretakers every year between 2010 and 2013; extrapolating this to the entire U.S. population, Eichner wrote, translates into more than 1,600 charges annually.

Some of the diagnostic criteria doctors use for medical child abuse are parents seeking care from more than one medical provider, and more than one organ system being affected. “Mito diseases invariably involve both of these,” she said. “It affects more than [one] organ system, and because of that parents seek more than one medical expert.”  …

“We want to make sure that the physicans who treat these children are educated [about mitochondrial disease],” she said. “We also want to make sure the parents understand how to best communicate with their medical team so that it’s clear that when they’re asking questions or seeing multiple doctors, they’re really just trying to get answers to this disease that has so many unknowns — and that there are no negative intentions.”

Yet Hollinger spoke of a general lack of awareness, noting that “most doctors were never taught anything about mitochondrial disease.” Because the disease involves energy production, it varies greatly from one person to the next.

“You can have two siblings in the same family,” she said. “Little sister A can have severe neurological issues and can’t walk, and big sister B, with the exact same mutation, might not have seizures, but have severe gastrointestinal issues. People just don’t understand.”

In addition, she said, “depending on how your energy systems are going, the symptoms can totally vary — not just week to week or day to day, but even minute to minute.”

For all these reasons, Hollinger advised parents to watch what they say around doctors and nurses, and to think twice before posting photos of their children on Facebook or Twitter.

“You have to really be careful about what you share, and how it could impact your child down the line,” she said. “I would definitely say no photos. What law enforcement does is use social media to see if you are guilty or not. It is the most important aspect of their investigation. They consider social media your crime scene. Any picture that could embarrass your child at less than 18 years old is considered abusive.”

https://mitochondrialdiseasenews.com/2018/01/12/false-child-abuse-charges-trouble-mito-parents/

See:  http://childnervoussystem.blogspot.com/2016/07/medical-child-abuse-revisited-2.html

Oculomotor and vestibular findings in Gaucher disease type 3

Bremova-Ertl T, Schiffmann R, Patterson MC, Belmatoug N, Billette de Villemeur T, Bardins S, Frenzel C, Malinová V, Naumann S, Arndt J, Mengel E, Reinke J, Strobl R and Strupp M (2018) Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings. Front. Neurol. 8:711. doi: 10.3389/fneur.2017.00711

Objectives: To evaluate the function of the oculomotor and vestibular systems and to correlate these findings with the clinical status of patients with Gaucher disease type 3 (GD3). The goal of this cross-sectional and longitudinal study was to find oculomotor biomarkers for future clinical trials.

Methods: Twenty-six patients with GD3 were assessed for eligibility and 21 were able to perform at least one task. Horizontal and vertical reflexive saccades, smooth pursuit, gaze-holding, optokinetic nystagmus, and horizontal vestibulo-ocular reflex (VOR) were examined by video-oculography/video-head impulse test and compared concurrently with 33 healthy controls. The Scale for the Assessment and Rating of Ataxia (SARA), the modified Severity Scoring Tool (mSST), and Grooved Pegboard Test (GPT) were administered to assess overall neurological function. Eleven patients were also re-assessed after 1 year.

Results: Nine out of 17 patients exhibited gaze-holding deficits. One patient had upbeat nystagmus. Three patients presented with bilateral abducens palsy in combination with central oculomotor disorders, suggesting a bilateral involvement of the abducens nucleus. Horizontal angular VOR gain was reduced in all patients (0.66 ± 0.37) compared with controls (1.1 ± 0.11, p < 0.001). Most strongly correlated with clinical rating scales were peak velocity of downward saccades (SARA: ρ = −0.752, p < 0.0005; mSST: ρ = −0.611, p = 0.003; GPT: ρ = −0.649, p = 0.005) and duration of vertical saccades (SARA: ρ = 0.806, p < 0.001; mSST: ρ = 0.700, p < 0.0005; GPT: ρ = 0.558, p = 0.02) together with the VOR gain (SARA: ρ = −0.63, p = 0.016; mSST: ρ = −0.725, p = 0.003; GPT: ρ = −0.666, p = 0.004). Vertical smooth pursuit gain decreased significantly at follow-up.

Interpretation: This study shows neuronal degeneration of the brainstem and cerebellum with combined involvement of both supranuclear and nuclear oculomotor structures and the vestibular system in GD3. We also identified oculomotor parameters that correlate with the neurological status and can be used as biomarkers in future clinical trials.

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From the article

This study evaluated the comprehensive ocular motor and vestibular function of a sizable international cohort of patients with GD3. It related this function to their overall clinical state in a systematic and standardized manner.

The major findings in this study are as follows:

First, gaze-holding function was compromised in some patients, which might indicate a cerebellar dysfunction, mainly of the flocculus, and/or dysfunction of the neuronal integrator (17).

Second, PV of downward saccades and duration of vertical saccades as well as gains in horizontal aVOR correlated significantly with the patients’ clinical status assessed by SARA, mSST, and the GPT. Therefore, these easily quantifiable oculomotor and vestibular parameters may be used as biomarkers for future studies.

Third, horizontal aVOR was impaired in all patients and showed consistent patterns over time in patients evaluated longitudinally.

Fourth, longitudinal analysis did not show significant changes over time, except for a deterioration of vertical smooth pursuit.

Topo-anatomical findings suggest that multiple areas in the brainstem and cerebellum are involved in patients with GD3: pontine paramedian reticular formation (PPRF), rostral interstitial nucleus of the medial longitudinal fascicle (riMLF), motoneurons of the abducens nucleus, cerebellum (mainly the flocculus), and the vestibular system. For typical clinical ocular motor findings in patients with GD3, see Video S1 in Supplementary Material of patient 9 on the webpage...

In conclusion, our findings suggest a widespread neuronal dysfunction, both at brainstem and cerebellar levels. The deficits seen in the oculomotor and vestibular examination, particularly those that progressed over time, can be used as biomarkers in future clinical trials. Future studies evaluating the voluntary saccades, including also absolute number of performed saccades or intersaccadic intervals, should be planned to assess the reliability of these biomarkers. The otolith function examined by VEMP holds promise as another vestibular biomarker, as was shown previously. Also, a compact binocular testing battery to minimize the effect of fatigue should be performed in clinical trials in the future. Our clinical experience also suggests performing the VOG as early as possible prior to the other clinical tests.

Neuro-development and psychological Issues in congenital heart defects

Antonio F. Corno,Elisabeth M. W. J. Utens   Editorial: Neuro-Development and Psychological Issues in Congenital Heart Defects. Front. Pediatr., 12 January 2018 | https://doi.org/10.3389/fped.2017.00297 (links in online article to references)

The operative mortality in infants with congenital heart defects has dramatically decreased in the past few decades to less than 3% in all databases of Europe and North America. As a result, attention has been moved from the survival to the quality of life. Surviving children often experience neurodevelopmental deficits and behavioral, emotional, and social problems, which can have a profound impact on their quality of life. This Research Topic focused on recent studies conducted in this field, to predict, evaluate, and manage the neurodevelopmental and psychological outcomes after congenital heart surgery.

Moon et al. studied 180 adolescents, analyzing the relationship between parental rearing behavior, resilience, and depressive symptoms. They demonstrated that parental rearing behaviors, such as emotional warmth, rejection, punishment, control, and overprotection have a significant influence on the resilience of the adolescents. They suggested that parenting attitudes, gender, age, and severity of the defects should be taken into consideration when developing intervention programs to increase the resilience and reduce the depression in these adolescents.

In another study on children and adolescents with congenital heart defects, Meentken et al. did an extensive review of post-traumatic stress, with a particular focus on stress related to medical interventions and treatment due to their underlying congenital heart defects, particularly for invasive interventions. The authors concluded that children with congenital heart defects present with an elevated risk of developing posttraumatic stress. Therefore, early screening of psychological problems and, if indicated, referral for psychological treatment should be made early on in this group of patients.

Pike et al. evaluated memory deficits in 80 adolescents and young adults with congenital heart defects, more than a decade following their last surgery in comparison to 76 healthy controls. Long after surgery, the group with congenital heart defects demonstrated significant verbal, attention, and working memory deficits over the control group. To enhance patient memory/self-care, the authors recommend to reduce anxiety, improve self-efficacy, and use of visual patient education material.

Buratti et al. studied 184 children, adolescents, and their parents, where heart malformations were divided in mild, moderate, and severe. Irrespective of the severity of the cardiac malformation, a strong association was found between the parent’s ratings of cognitive problems and the children’s and adolescents’ results on intelligence (Wechsler) scales, with this association present for all ages.

Helm et al. conducted a survey into transition in Germany in 1828 patients with congenital heart defects after they had turned 18 years of age. Their survey revealed that after age 18, many young adult patients had not been transferred to certified adult congenital heart defects providers and about 1/3 were not in continuous care at a specific adult congenital heart defects clinic/heart center. These observations regarding the adult certification were particularly disappointing and indicative of a large information gap and inadequate education in the current clinical practice.

Kolaitis et al. performed an extensive literature review into parental mental health at the time of the diagnosis of congenital heart defect, following cardiac surgery, and at long-term, assessing the need for psychological care. Their review confirmed that parents of children with congenital heart defects, and especially the mothers, are at higher risk for a variety of mental health problems at all different time periods of their children’s illness.

In a literature review, Hövels-Gürich identified that the factors influencing the neurodevelopment in infants undergoing cardiac surgery are not only related to the methods of cardiopulmonary bypass, procedure specific risk factors, and postoperative management but also patient specific risk factors, family and environmental factors.

Ryberg et al. investigated 228 children who underwent either surgery or interventional cardiology procedure. Their research demonstrated that socioeconomic status of the families and the severity of diagnosis had a significant influence on the full scale IQ of the children.

Kasmi et al. focused on neurodevelopment and psychiatric outcomes in a specific group of patients: those born with transposition of the great arteries. The authors conducted a detailed systematic review. They describe the results within a life-span perspective, putting particular emphasis on adolescent/young adult neuropsychological outcomes, describing potential mechanisms by which pediatric neurodevelopmental impairments can have negative influences into adulthood and also interventions to improve the clinical outcomes.

In response to an increased need for patient information congenital heart defects, Etnel et al. designed a pilot project developing an online, evidence-based information portal, with information on aortic and pulmonary valve disease, supported by both patients and physicians. If successful, this information portal will be further developed and expanded to include all common congenital heart defects, translated into other languages, and developing into a public information portal to serve patients’ relatives and the general public at large.

The studies and reviews collected in this Research Topic demonstrate that the success obtained by substantially reducing the mortality in the repair of congenital heart defects has not been followed by corresponding improvement in the quality of life.

While surgery does provide patients with a better life style related to their physical health, with less cyanosis, heart failure, and better exercise tolerance, much progress is still needed to improve the neurodevelopment outcomes and psychological health of these patients. We are now beginning a new era of research and clinical efforts to prevent and reduce the negative impact of congenital heart defects. Improved psychosocial interventions that caregivers, social workers, and behavior health providers can deliver to support patients and their families are urgently needed.

CGRP and PTX3 as predictors of efficacy of onabotulinumtoxin type A in chronic migraine

Domínguez C, Vieites-Prado A, Pérez-Mato M, Sobrino T, Rodríguez-Osorio X, López A, Campos F, Martínez F, Castillo J, Leira R. CGRP and PTX3 as Predictors of Efficacy of Onabotulinumtoxin Type A in Chronic Migraine: An Observational Study. Headache. 2018 Jan;58(1):78-87.

Abstract

OBJECTIVE:

The aim of this study is to find a relation between several biomarkers in peripheral blood and outcome after treatment with onabotulinumtoxin A (OnabotA).

BACKGROUND:

OnabotA is an effective treatment in chronic migraine (CM). Different studies have tried to find predictors of response to treatment, either with clinical characteristics, neuroimaging features, or molecular biomarkers; however, it is still not possible to predict the individual outcome.

METHODS:

We measured serum levels of biomarkers of inflammation (IL-6, IL-10, TNF-α, and hs-CRP), endothelial dysfunction (PTX3 and sTWEAK), blood-brain barrier disruption (cFN), brain damage (S100b, NSE), and trigemino-vascular activation (CGRP) by ELISA in a group of CM patients treated with OnabotA and healthy controls. After 24 weeks, patients were classified in two groups according to their outcome considering variations in headache frequency: nonresponders (nonimprovement or improvement <50%) and responders (improvement >50%). We compared baseline levels of biomarkers between these groups.

RESULTS:

Sixty-two patients diagnosed with CM (IHS 2013 criteria) who fulfilled criteria for treatment with OnabotA and 24 healthy controls were included. Fifteen patients did not respond to treatment (24.2%) and 47 were responders (75.8%). Pentraxin 3 (PTX3) serum levels (1455.4 ± 487.5 pg/mL versus 720.3 ± 334.1 pg/mL, P < .0001) and calcitonin gene-related peptide (CGRP) serum levels (133.1 ± 86.6 ng/mL versus 58.2 ± 91.7 ng/mL, P = .004) were significantly higher in responders than nonresponders. Serum basal levels of PTX3 >1000 pg/mL (AUC 0.908; 95% CI: 0.827-0.990) and CGRP >50 ng/mL (AUC 0.800; 95% CI: 0.652-0.947) were associated with good response to OnabotA treatment.

CONCLUSIONS:

These results show that molecular markers of trigeminovascular activation (CGRP) and endothelial dysfunction (PTX3) are associated with response to OnabotA and may act as new biomarkers for the selection of treatment in chronic migraineurs.

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“A new era is beginning for migraine treatment with anti-CGRP antibodies, and these biomarkers could be helpful in the future to tailor a personal treatment for each patient,” said the lead study author Clara Domínguez, MD, of the Universidade de Santiago de Compostela in Santiago de Compostela, Spain.

CGRP, which has been found to be elevated during migraine attacks, is thought to induce neural inflammation and vasodilation of blood vessels, and plays a role in central sensitization. Prior studies have also found that botulinum toxin blocks the release of CGRP.

This study was the first to report a relationship between PTX3 levels and treatment response to onabotulinum toxin A, the study authors said. PTX3, an inflammatory protein, has been associated with endothelial dysfunction in coronary artery disease and atherosclerosis. The identification of PTX3 as a marker for responders is important as it points to the role of the vascular endothelium in migraine pathophysiology and in botulinum toxin's mechanism of action, Dr. Domínguez explained.

“PTX3 constitutes a very specific biomarker of endothelial dysfunction, which is one of the main mechanisms in the pathophysiology of migraine,” Dr. Domínguez said.

Botulinum toxin appears to reduce headaches by acting on meningeal fibers, inhibiting mechanical nociception, and by blocking the release of neurotransmitters such as glutamate, CGRP, and substance P. Botulinum toxin is a safe and effective treatment to prevent pain and frequency of migraines in chronic migraineurs, Dr. Dominguez noted, but it is not effective in all migraineurs. Studies have tried to find factors that predict response to botulinum toxin, including molecular markers and clinical factors, but results have been inconsistent. Therefore, choosing candidates for botulinum toxin has been based on poor response to oral medications or adverse effects…

The only significant difference in clinical characteristics between responders and nonresponders was age. Responders tended to be younger, with a median age of 39.4, compared to nonresponders, whose median age was 51.6. The authors expressed surprise that there was no significant difference in response based on other characteristics such as frequency or intensity of migraine, sex, weight, or medications.

“The study is important because it focuses on personalized medicine, looking at biomarkers for migraines,” said Matthew Robbins, MD, associate professor of neurology at Albert Einstein College of Medicine, who was not involved with the study. “We're faced with choosing treatments based on their side effect profile rather than their individual merits. Before you go down the road of getting a series of injections or before you take a medication, it would be great to have more scientific information,” he said.

The study was also helpful in narrowing in on important biomarkers, he said. “What's new in this study is that they used a broad panel of different potential biomarkers.” But he added that it's too preliminary to consider testing for these biomarkers. “It's probably quite an expensive thing to do,” he said.

The study results are limited by the small sample size of patients, however, and they came from a selected clinical population, Dr. Robbins continued. The study was not a randomized controlled trial, so the results could have been an association. “It could be that people who got better had higher levels in the first place and maybe they were more likely to improve with any therapy,” said Dr. Robbins, adding that the placebo response is high in botulinum toxin therapy.

https://journals.lww.com/neurotodayonline/Fulltext/2018/01110/In_the_Clinic_Migraine__Migraine_Biomarkers_Offer.8.aspx

It is ok to think that every child matters however a lot of them do not

Disability advocate Natalie Weaver has slammed Twitter for not clamping down on an account that used an image of her severely disabled child in a pro-abortion tweet.

”Just received an email that Twitter doesn't think a person using my child's image as the poster child to ABORT & to weed out all the "defectives" in utero is a violation. Why? Bc they won't recognize hate toward ppl w/ disabilities in their regulations/reports,” Weaver tweeted on Monday.

Weaver had reported a tweet by the @OBSIDIANSMOAK account that used an image of her 9-year-old daughter Sophia. “It is ok to think that every child matters however a lot of them do not hence the amnio test which should be a mandatory test and if it proves negative and the woman does not want to abort then all bills accrued after that is on her and the father,” said a post accompanying the tweet. Sophia suffers from Rett syndrome, a rare neurological disorder that affects a child’s ability to eat, speak, walk and breathe. She was also born with an unknown syndrome that has caused facial deformities.

picture: http://wncn.com/2017/05/31/with-medicaid-cuts-looming-nc-mom-takes-fight-for-medically-fragile-daughter-to-dc/

 “I would like for Twitter to find obsidiansmoak in violation of hate towards people (children) w/ disabilities,” Weaver told Fox News, via email. “I would like for them to remove the tweet that uses my daughter's image as the poster disabled child to abort.”

The mom, who is the co-founder of Advocates for Medically Fragile Kids NC, is urging Twitter to tighten its rules regarding hate speech against people with disabilities. “I would like twitter to also add 'hate towards people with disabilities' to their violation reporting categories,” she said.

The circulation of Sophia’s image in a pro-abortion tweet has sparked anger from a host of users on Twitter.

As a result of her disabilities, Sophia requires extensive care.  “She’s an amazing little girl,” Weaver told Fox News.

http://www.foxnews.com/tech/2018/01/22/mom-slams-twitter-after-abortion-troll-uses-her-disabled-daughters-image.html

picture: https://twitter.com/nataliew1020/status/930826213391785984

Topiramate use early in pregnancy and the risk of oral clefts

Hernandez-Diaz S, Huybrechts KF, Desai RJ, Cohen JM, Mogun H, Pennell PB, Bateman BT, Patorno E. Topiramate use early in pregnancy and the risk of oral clefts: A pregnancy cohort study. Neurology. 2017 Dec 27. pii:10.1212/WNL.0000000000004857. doi:10.1212/WNL.0000000000004857. [Epub ahead of print]

Abstract

OBJECTIVE:

To assess the relative risk of oral clefts associated with maternal use of high and low doses of topiramate during the first trimester for epilepsy and nonepilepsy indications.

METHODS:

This population-based study nested in the US 2000-2010 Medicaid Analytic eXtract included a cohort of 1,360,101 pregnant women with a live-born infant enrolled in Medicaid from 3 months before conception through 1 month after delivery. Oral clefts were defined as the presence of a recorded diagnosis in claims during the first 90 days after birth. Women with a topiramate dispensing during the first trimester were compared with those without any dispensing and with an active reference group of women with a lamotrigine dispensing during the first trimester. Risk ratios (RRs) were estimated with generalized linear models with fine stratification on the propensity score of treatment to control for potential confounders. Stratified analyses by indication of use and dose were conducted.

RESULTS:

The risk of oral clefts at birth was 4.1 per 1,000 in the 2,425 infants born to women exposed to topiramate compared with 1.1 per 1,000 in the unexposed group (RR 2.90, 95% confidence interval [CI] 1.56-5.40). The RR among women with epilepsy was 8.30 (95% CI 2.65-26.07); among women with other indications such as bipolar disorder, it was 1.45 (95% CI 0.54-3.86). The median daily dose for the first prescription filled during the first trimester was 200 mg for women with epilepsy and 100 mg for women without epilepsy. For topiramate monotherapy, the RR for oral clefts associated with doses ≤100 mg was 1.64 (95% CI 0.53-5.07) and for doses >100 mg it was 5.16 (95% CI 1.94-13.73). Results were similar when lamotrigine was used as a reference group.

CONCLUSION:

The increased risk of oral clefts associated with use of topiramate early in pregnancy was more pronounced in women with epilepsy, who used higher doses.
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Dr. Hernandez-Diaz told Neurology Today that this risk had been previously described in women using the drug for epilepsy, but the question of whether this risk extended to “women receiving topiramate at lower daily doses (around 100mg versus 200mg) for indications such as bipolar disorders or migraine headaches was controversial.”

Using a cohort of more than 1.3 million pregnancies, the researchers found “maternal use of topiramate during the first trimester was associated with an approximately eight-fold increased risk of oral clefts in women with epilepsy; the increased risk in women taking topiramate at lower doses for other indications was under two-fold,” she said.

These findings “further support avoiding high doses of topiramate in women of childbearing age to prevent exposures early in pregnancy unless the benefits outweigh and justify these risks,” Dr. Hernandez-Diaz told Neurology Today…

The study was “well-designed” and its findings confirm earlier reports, Kimford J. Meador, MD, FAAN, professor in the department of neurology & neurological sciences at Stanford University School of Medicine, told Neurology Today. Significantly, he said, these findings expand to women who use topiramate for migraine, weight loss, and other conditions, at typically lower dosages.

“In addition, this study demonstrates for the first time a dose-dependent effect of topiramate on a malformation. A teratogen is expected to exhibit a dose-dependent effect, but prior studies have not shown this for topiramate due to limited sample size or restricted dosage range,” he said…

Still, there were some notable limitations, the commentators said. For example, as discussed by the authors, prescriptions filled do not necessarily mean adherence to medication. Additionally, Dr. Sperling [Michael R. Sperling, MD, FAAN, the Baldwin Keyes professor of neurology and vice chair for research in the department of neurology at Sidney Kimmel Medical College of Thomas Jefferson University and director of the Jefferson Comprehensive Epilepsy Center] said, “the population contains patients from lower socioeconomic levels who probably have higher levels of stress than more financially secure individuals, and this population suffers a moderately high rate of substance abuse and smoking, as well as significant rates of use of other medications including antipsychotic drugs. These factors should randomize between populations, but whether interactions between topiramate and other substances/drugs might pose a particular risk might affect that relative risk, though not the main conclusions of the study.”

https://journals.lww.com/neurotodayonline/Fulltext/2018/01110/In_the_Clinic_Drug_Safety__Dose_Dependent_Response.10.aspx