Thursday, June 29, 2017

Sentenced to death by the European Court on Human Rights

You’ve probably never heard of Charlie Gard.

He’s a terminally ill 10-month-old baby who has now been s– an Orwellian organization if ever there has been one – which determined that while his parents wanted to take him to the United States for a long-shot potentially life-saving treatment, they could not. Instead, the Court ruled, the Great Ormond Street Hospital for Children would withdraw all life support, killing Charlie. What was the Court’s justification? Charlie had to “die with dignity.”

Charlie suffers from a mitochondrial disease that destroys the muscles and the brain. There was no available treatment in the United Kingdom, and so Charlie’s parents, Chris Gard and Connie Yates, raised $1.6 million to fly him to the United States for an experimental treatment. But the hospital argued that the treatment wouldn’t help Charlie, and would prolong his suffering, and that they knew better than the parents who had to suffer through his illness and care for him every single day. Thus, the hospital argued that it would be in Charlie’s best interest to die.

UK courts agreed. The Gards appealed to the EU. And now the court has ruled against them, with the ECHR stating, “Charlie would suffer significant harm if his present suffering was prolonged without any realistic prospect of improvement, and the experimental therapy would be of no effective benefit.”

The hospital issued its own perverse statement:

Our thoughts are with Charlie’s parents on receipt of this news that we know will be very distressing for them. Today’s decision by the European Court of Human Rights marks the end of what has been a very difficult process and our priority is to provide every possible support to Charlie’s parents as we prepare for the next steps.

Despite the hospital’s statement that it would not immediately change his standard of care, his parents now report that the hospital will withdraw his life support on Friday. His parents announced:

We begged them to give us the weekend. Friends and family wanted to come and see Charlie for the last time. But now there isn’t even time for that. Doctors said they would not rush to turn off his ventilator but we are being rushed. Not only are we not allowed to take our son to an expert hospital to save his life, we also can’t choose how or when our son dies.

There are several levels to the perversity here.

First, for all the talk of the evils of the American system of healthcare, at least we promote freedom of choice – and give as many options to people for their care as they can afford. As the doctor who offered experimental treatment stated in court, if Charlie had become ill at “any institution in the US,” they would immediately begin the treatment. But in the UK, a socialized medicine country where individual needs come secondary to the preservation of the “system,” there is less concern with parental rights. In the United States, we are so interested in the freedom to obtain care that we insist on releasing a legally brain-dead girl to her mother, so long as her mother wishes to keep her hooked up to a ventilator; in the UK, they are insistent on withdrawing the opportunity for life-saving care because it’s better to kill the child than keep it alive. While this case became a court proceeding, every single day the NHS makes decisions about how to ration care. Bernie Sanders tweets about how nobody should be denied care because they can’t afford it – but that’s what happens all the time under socialized medicine – and you don’t even have the capacity to raise the money to fund the care yourself.

Second, a government-run system breeds a shift in control. In the United States, the case of Charlie Gard is a major scandal; in the EU, it’s apparently no big deal. That’s because we in the United States like to think that we control our lives and that as parents, our priorities matter more than those of doctors who do not raise our children. But once you give up control over life and death decisions to an impersonal government, it’s nearly impossible to take back that control. This case could have been easy: the hospital could have released the child. The hospital didn’t do so because it believed that it had the final say. And why shouldn’t it? It always has the final say.

Third, allowing the government to control the value of life means devaluing life. It has been a fundamental hallmark of Western civilization that life ought to be preserved, in spite of pain, in spite of suffering – that death is no solution to suffering. But that notion has been stripped away in favor of the secularist standard of “healthy living” – and so in Europe, euthanasia is now available to people who are not terminal, but merely suffer from depression or anorexia. Better to "die with dignity" than live with pain, in the new math. That's a far cry from the original Hippocratic Oath which overtly stated, "Neither will I administer a poison to anybody when asked to do so, nor will I suggest such a course," or even the Tufts Medical School version, which stated, "Above all, I must not play at God."

Those who value life want to keep choices about their life in their own hands, rather than turning such control over to an impersonal government agency that guarantees you coverage that it chooses for you. Charlie Gard’s story isn’t merely a travesty of justice and an insult to decency. It’s a warning for people who think that bureaucracies are as interested in preserving your health care priorities as you are.

Prenatal, perinatal and neonatal risk factors for perinatal arterial ischaemic stroke

Li C, Miao JK, Xu Y, Hua YY, Ma Q, Zhou LL, Liu HJ, Chen QX. Prenatal, perinatal and neonatal risk factors for perinatal arterial ischaemic stroke: a systematic review and meta-analysis. Eur J Neurol. 2017 Jun 24. doi:10.1111/ene.13337. [Epub ahead of print]

The aim of the present study was to perform a meta-analysis of published data to determine the significance of clinical factors and exposures to the risk of perinatal arterial ischaemic stroke (PAIS) and provide guidance for clinical diagnosis and treatment. A comprehensive literature search of the PubMed, Embase, MEDLINE and Cochrane Library databases for relevant observational studies (cohort/case-control) from March 1984 to March 2016 was undertaken. Two review authors independently examined the full text records to determine which studies met the inclusion criteria and evaluated risk factors for PAIS. Risk ratios, odds ratios and 95% confidence intervals were estimated. A total of 11 studies were included in the analyses. Intrapartum fever >38°C, pre-eclampsia, oligohydramnios, primiparity, forceps delivery, vacuum delivery, fetal heart rate abnormalities, abnormal cardiotocography tracing, cord abnormalities, birth asphyxia, emergency caesarean section, tight nuchal cord, meconium-stained amniotic fluid, umbilical arterial pH <7.10, Apgar score at 5 min <7, resuscitation at birth, hypoglycaemia, male gender and small for gestational age were identified as risk factors for PAIS. This systemic review and meta-analysis provides a preliminary evidence-based assessment of the risk factors for PAIS. Patients with any of the risk factors identified in this analysis should be given careful consideration to ensure the prevention of PAIS. Future studies focusing on the combined effects of multiple prenatal, perinatal and neonatal risk factors for PAIS are warranted.

The physicians performed a meta–analysis of published data to ascertain the significance of clinical factors and exposures to the risk of perinatal arterial ischaemic stroke (PAIS) and provide guidance for clinical diagnosis and treatment. They provided a preliminary evidence–based assessment of the risk factors for PAIS. Patients with any of the risk factors identified in this analysis needed to be given careful consideration to ensure the prevention of PAIS. Future investigations focusing on the combined effects of multiple prenatal, perinatal and neonatal risk factors for PAIS were warranted.


From March 1984 to March 2016, the physicians undertook a comprehensive literature search of the PubMed, Embase, MEDLINE and Cochrane Library databases for relevant observational studies (cohort/case-control).

To determine which studies met the inclusion criteria, 2 review authors independently examined the full-text records and assessed risk factors for PAIS.

They estimated risk ratios, odds ratios, and 95% confidence intervals.


The physicians included 11 studies in the analyses.

Factors identified as risk for PAIS were intrapartum fever >38°C, pre-eclampsia, oligohydramnios, primiparity, forceps delivery, vacuum delivery, fetal heart rate abnormalities, abnormal cardiotocography tracing, cord abnormalities, birth asphyxia, emergency caesarean section, tight nuchal cord, meconium-stained amniotic fluid, umbilical arterial pH <7.10, Apgar score at 5 min <7, resuscitation at birth, hypoglycaemia, male gender and small for gestational age.

Wednesday, June 28, 2017

The consequence of a reversal sign

Following an uncomplicated post-dates pregnancy, delivery was accomplished by cesarean section for sustained fetal bradycardia.  Apgars scores were 1.5.5 and 1, 5 and 10 minutes. The initial blood gas was 6.42 and cord gas was 6.76.  Lactate was 17.2.  Head cooling was performed.  He experienced neonatal seizures.

Exponential apparent diffusion images at 4 days of age showing the disparity between the cerebellum and the supratentorial brain, a reversal sign.  See Kavanagh EC. The reversal sign. Radiology. 2007 Dec;245(3):914-5.

Apparent coefficient diffusion showing the disparity between the cerebellum and the supratentorial brain, a reversal sign.

Axial T2 propellar imaging at 15 months showing extensive diffuse damage to the supratentorial brain.

Axial T2 FLAIR imaging at 15 months.

Tuesday, June 27, 2017

Cognitive outcome after epilepsy surgery in children

Sibilia V, Barba C, Metitieri T, Michelini G, Giordano F, Genitori L, Guerrini R. Cognitive outcome after epilepsy surgery in children: A controlled longitudinal study. Epilepsy Behav. 2017 Jun 9;73:23-30.

To analyze the determinants of cognitive outcome two years after surgery for drug-resistant epilepsy in a cohort of 31 children when compared to a control group of 14 surgical candidates who had yet to undergo surgery two years after the first neuropsychological assessment.
Controlled longitudinal study including three evaluations of IQ (Intelligence Quotient) scores or GDQ (General Developmental Quotient) for each group depending on the patient's age: prior to surgery (T0), one year (T1) and two years (T2) after surgery for the surgical group; baseline (T0) and one year (T1) and 2years (T2) after the first evaluation for the control-group. At follow-up, 25 children (80%) of the surgical group were seizure free, while seizure outcome was unsatisfactory in the remaining six (20%). To analyze language, visuomotor skills, memory, reading, visual attention, and behavior, we selected 11 school age children in the surgical group and nine controls. We reported performance prior to (T0) and one year after surgery (T1).
There was a significant correlation between earlier age at seizure onset and lower IQ/GDQ at T0 (r=0.39; p=0.03) in the overall cohort. IQ/GDQ scores did not significantly differ between the surgical and control groups when analyzed at T0 and T2. However, they evolved differently with an improved developmental trajectory becoming identifiable only in the surgical group (F1,31=5.33 p=0.028; η2=0.15). There was also a significant increase of forward digit span (Z=2.33; p=0.02) and Rey recall scores (Z=1.97; p=0.049) in the surgical school age subgroup at T1 versus T0.
We identified significantly different developmental trajectories in operated versus non- operated children with improved IQ/GDQ scores in operated children only. We also observed a significant increase of digit span scores and Rey recall scores a year after surgery. Further studies including larger samples with longer follow-ups are needed to confirm these preliminary findings.

Courtesy of Mendeley

Monday, June 26, 2017

Bioequivalence between generic and branded lamotrigine in people with epilepsy

Michel Berg, Timothy E. Welty, Barry E. Gidal, Francisco J. Diaz, Ron Krebill, Jerzy P. Szaflarski, Barbara A. Dworetzky,; John R. Pollard,; Edmund J. Elder Jr,; Wenlei Jiang, Xiaohui Jiang, Regina D. Switzer, Michael D. Privitera.  Bioequivalence Between Generic and Branded Lamotrigine in People With Epilepsy.  The EQUIGEN Randomized Clinical Trial. JAMA Neurol. Published online June 26, 2017.

Key Points

Question  Are branded-to-generic and generic-to-generic lamotrigine switches bioequivalent in people with epilepsy?

Findings  In this randomized clinical trial involving 50 adults with epilepsy, bioequivalence between branded and generic lamotrigine products was established for 2 key pharmacokinetic measures (area under the concentration–time curve and maximal concentration).

Meaning  Branded and generic lamotrigine products can be substituted with an expectation of bioequivalence.

Importance  Switching between generic antiepileptic drugs is a highly debated issue that affects both clinical care and overall health care costs.

Objective  To evaluate the single-dose pharmacokinetic bioequivalence of 3 (1 branded and 2 generic drugs) on-market, immediate-release lamotrigine drug products.

Design, Setting, and Participants  The Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy (EQUIGEN) single-dose study is a crossover, prospective, sequence-randomized, replicate pharmacokinetic study conducted at 5 US academic epilepsy centers. Fifty adults (≥18 years) with epilepsy who were taking concomitant antiepileptic drugs and not currently receiving lamotrigine were enrolled between July 18, 2013, and January 19, 2015. Every participant was randomly assigned to 1 of 3 equivalent sequences, each comprising 6 study periods, during which they had blood draws before and after medication administration. Forty-nine participants were included in intention-to-treat analyses.

Interventions  Participants received a single 25-mg dose of immediate-release lamotrigine at the start of each period, with the branded and the 2 most disparate generic products each studied twice. Lamotrigine was selected as the antiepileptic drug of interest because of its wide use, publications indicating problems with generic switches, and complaints to the US Food and Drug Administration regarding generic products. Both participants and study personnel were blinded to the specific generic products selected.

Main Outcomes and Measures  The primary outcome was bioequivalence between products. Maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC) were compared, and average bioequivalence (ABE) was established if the 90% CIs of the ratios of the 2 products were within equivalence limits (80%-125%).

Results  Of the 50 randomized participants, 49 (98%) received all 3 lamotrigine products and completed at least 3 pharmacokinetic assessments and 46 (92%) completed all 6 pharmacokinetic assessments. Among the 49 participants, 28 (57%) were men and 21 (43%) were women, 42 (86%) self-identified as white, and 46 (16) years was the mean (SD) age. The 3 drug products were considered bioequivalent because the 90% CIs were within equivalence limits (lowest and highest CI limits for Cmax, 92.6% and 110.4%; for AUC0-96, 96.9% and 101.9%). Replicate testing demonstrated no significant differences in within-subject variability across the 3 products (likelihood ratios, χ22 for log-transformed variables: AUC0-96, 2.58; Cmax, 0.64; and AUC0-∞, 4.05; P ≥ .13) and that the 3 products were also bioequivalent according to scaled ABE and individual bioequivalence criteria with no subject × formulation interaction (Cmax, 0.00; AUC0-96, 0.54; and AUC0-∞, 0.36; P ≥ .76).

Conclusions and Relevance  This study provides evidence that the disparate lamotrigine products studied are bioequivalent when tested in people with epilepsy taking concomitant antiepileptic drugs.

Trial Registration Identifier: NCT01733394

From the article 

To inform the debate about generic AED equivalence, we performed a single-dose replicate study (among people with epilepsy taking concomitant AEDs) comparing bioequivalence between disparate generic lamotrigine products and bioequivalence of each generic product to branded lamotrigine. Confidence intervals comparing the extent (AUC) and rate (Cmax) of absorption of these tested products were all well within the FDA ABE range, thus establishing bioequivalence. This study provides further support to the bioequivalence found in 2 recently reported long-term–dose studies, especially because single-dose study designs are considered more sensitive to PK differences than are long-term–dose studies.

Most of the published literature concerning the therapeutic implications of branded-to-generic or generic-to-generic substitutions is uncontrolled or comprises retrospective studies that did not account for confounding factors (eg, adherence and participant bias). This study’s prospective replicate design enabled us to determine the within-subject variations over time in the PK profile for the 3 products and to explore subject × formulation interaction. Replicate testing demonstrated variability of approximately 8% (AUC) and 15% (Cmax) within each of the individual products. The finding that biological variation was similar for the branded and both generic products suggests that this variation may account for some of the differences reported when switching among branded and generic products.

Biological factors are presumed to have similar effects regardless of the product (branded or generic) taken by the participant. Establishing the amount of variation from these factors for the branded product is important for understanding how much variation among generic products is acceptable. That is, if there is a wide variation in the PK measures from a replicate study of the branded product, then similar wide variations among generic products should be acceptable. By contrast, if the differences in a replicate study of the branded product are small, then wider variations among generic products may be unacceptable.

Within-subject variability is one of the factors proposed to characterize narrow therapeutic index drugs, which are required to meet reference-scaled bioequivalence limits using the scaled ABE method. The PK results for the products tested in our study fell well within scaled ABE bounds. Individual bioequivalence was also established with this set of lamotrigine data given that individual bioequivalence analyses reduced to scaled ABE analyses because there was no subject × formulation interaction…

Despite the inclusion of participants with multiple clinically relevant variables, the 3 lamotrigine products tested demonstrated essentially identical PK profiles and were all well within the FDA bioequivalence standards. In fact, our results fell within the standards for narrow therapeutic index drugs and showed no evidence of differences in within-subject variability between the 3 products.

Courtesy of a colleague

Perisylvian, including insular, childhood epilepsy: Presurgical workup and surgical outcome

Freri E, Matricardi S, Gozzo F, Cossu M, Granata T, Tassi L. Perisylvian, including insular, childhood epilepsy: Presurgical workup and surgical outcome. Epilepsia. 2017 Jun 23. doi: 10.1111/epi.13816. [Epub ahead of print]

To report the presurgical workup, surgical procedures, and outcomes in a series of pediatric patients with drug-resistant epilepsy involving the perisylvian/insular regions.
We retrospectively assessed 16 pediatric patients affected by drug-resistant focal epilepsy involving perisylvian/insular regions, who consecutively underwent tailored resective surgery. All patients underwent a detailed presurgical workup, which included the analysis of the anatomoelectroclinical correlations with scalp electroencephalography (EEG) and/or with stereo-electroencephalography (SEEG), brain magnetic resonance imaging (MRI), and comprehensive cognitive and neuropsychological evaluations. After surgery, all patients underwent serial clinical and laboratory evaluations.
Focal motor seizures restricted to perioral area, associated with symptoms related to the surrounding areas (as auditory hallucinations, unpleasant paresthesia, fear, and epigastric sensation), characterized the ictal semiology in 75% of patients. In 50%, autonomic manifestations were present and in 56% subjective manifestations were reported. The 50% of the patients underwent SEEG with insular sampling to better define the epileptogenic zone. In all patients, the insular cortex was always part of the epileptogenic zone, and tailored resections also involved, with variable degree, the frontal, parietal, and temporal opercula. Preoperatively, the neuropsychological assessment revealed impairments in specific cognitive functions and mild or moderate cognitive compromise in 88% of the patients. Postoperatively, one patient had permanent slight hemiparesis. At the most recent follow-up (median 39 months), seizure outcome was satisfactory in 69% of patients: seven patients were completely seizure-free (Engel class Ia), two were free of disabling seizure (class Ic), and two had rare disabling seizures (class II). The cognitive functioning remained unchanged in 62%, and improved in 38%.
The assessment of perisylvian/insular epilepsy in children is particularly challenging. However, tailored resections based on a careful presurgical evaluation, including SEEG recording, may lead to a good seizure control and to a better overall outcome.

The clinicians conducted this study to describe the presurgical workup, surgical procedures, and outcomes in a series of pediatric patients with drug–resistant epilepsy involving the perisylvian/insular regions. In children, the evaluation of perisylvian/insular epilepsy was particularly challenging. However, tailored resections based on a careful presurgical evaluation, including SEEG recording, could lead to a good seizure control and to a better overall outcome.


In this study, 16 pediatric patients affected by drug-resistant focal epilepsy involving perisylvian/insular regions, who consecutively underwent tailored resective surgery were retrospectively evaluated.

For this study, all patients underwent a detailed presurgical workup, which involved the analysis of the anatomoelectroclinical correlations with scalp electroencephalography (EEG) and/or with stereo-electroencephalography (SEEG), brain magnetic resonance imaging (MRI), and comprehensive cognitive and neuropsychological evaluations.

All patients underwent serial clinical and laboratory evaluations after surgery.


Focal motor seizures restricted to perioral area characterized the ictal semiology in 75% of patients associated with symptoms related to the surrounding areas (as auditory hallucinations, unpleasant paresthesia, fear, and epigastric sensation).

Autonomic manifestations were present in 50%, and in 56% subjective manifestations were reported.
In this study, the 50% of the patients underwent SEEG with insular sampling to better define the epileptogenic zone.

The insular cortex was always part of the epileptogenic zone, and tailored resections also involved, with variable degree, the frontal, parietal, and temporal opercula in all patients.

The neuropsychological assessment demonstrated impairments in specific cognitive functions and mild or moderate cognitive compromise in 88% of the patients preoperatively.

1 patient had permanent slight hemiparesis postoperatively.

Seizure outcome was satisfactory in 69% of patients at the most recent follow-up (median 39 months): 7 patients were completely seizure-free (Engel class Ia), 2 were free of disabling seizure (class Ic), and 2 had rare disabling seizures (class II).

In 62%, the cognitive functioning remained unchanged and improved in 38%.

Sunday, June 25, 2017

Haleigh Poutre

Haleigh Poutre (born February 24, 1994) is an American woman who became the subject of a legal controversy regarding the removal of life support for patients in persistent vegetative states. In 2006, 11-year-old Poutre awoke from a coma shortly before she was scheduled to be removed from life support. Poutre had a severe brain injury thought to be caused by abuse by her adoptive mother…

Following criminal charges, the department of social services took custody of 11 year old Haleigh. Eight days after she was admitted to the hospital, Harry Spence, the commissioner of the Massachusetts Department of Social Services, sought to remove Haleigh from life support. Physicians involved in the case asserted that Haleigh was in a vegetative state, and "virtually brain dead." On Oct. 5, 2005, a judge approved the request. Jason Strickland, Haleigh's stepfather, appealed the decision.  Although Jason Strickland had never legally adopted Haleigh, he opposed the decision on the basis that he was the de facto parent.

Complicating the issue was the criminal case against Jason Strickland. If Haleigh died, the state could bring murder charges against Strickland. But if she lived, even in a vegetative state, the charges brought against Strickland were significantly less severe. Many perceived the actions of Strickland to be an attempt at evading homicide charges.

On January 17, 2006, the Massachusetts Supreme Court ruled in favor of the Department of Social Services that life support could be removed.  On January 18, 2006, as physicians were preparing to remove life support, Haleigh regained consciousness. In the presence of Harry Spence, social workers asked Haleigh to identify a series of items in front of her and she successfully completed the task. The order to remove life support was cancelled.

A number of Right to Life groups got involved with Haleigh Poutre's case and many noted parallels between this case and the high profile Terri Schiavo case which ended in her death earlier that year. Schiavo's family contacted Mitt Romney regarding the case. The family runs the Terri Schindler Schiavo Foundation Center for Health Care Ethics Inc. Schiavo's father, Bob Schindler Sr., commented that there have been many similar cases and his foundation's goal is "essentially to guard against this rush to judgment."

Haleigh Poutre, the brain-damaged girl at the center of a passionate end-of-life debate, was transferred yesterday from a pediatric intensive-care unit to a Brighton rehabilitation center, two days after the state's top child-protection official saw her pick up a Curious George stuffed animal and a yellow duck on command.

''It's her incredible will to live," said Harry Spence, commissioner of the state Department of Social Services, which has had custody of the 11-year-old girl since she was brought, badly beaten, to a hospital last September and lapsed into a coma.

Spence, who has been criticized for seeking to remove her life support as soon as eight days after her hospitalization, said he visited Haleigh for the first time ''out of some sense of responsibility."

He said he wanted to see the girl whose fate he will help determine. ''I needed to put myself in the place of a parent," he said.

During his 30-minute visit Tuesday evening at Baystate Medical Center in Springfield, Spence said he noticed her eyes tracking his movements some of the time. He said that, except for her arms, her body did not move.

In a telephone interview yesterday, Spence emphasized that he is not a physician and that he cannot evaluate the significance of these signs.

Many neurologists say that patients with extensive brain injuries often, despite significant recovery, end up with severe disabilities. Still, Spence said his first instinct, after seeing Haleigh, was to say, ''We've got to start this child in rehab."

Spence's comments offered the most vivid account of the condition of Haleigh, whose story has drawn national attention to end-of-life issues, as well as to the agency's failure to protect her against abuse at home. Haleigh's adoptive mother and stepfather were charged with her near-fatal beating in September.

Spence again defended the agency's decision to move quickly to remove Haleigh's life support.

Doctors had said she was in a vegetative state, and ''virtually brain dead." On Oct. 5, a juvenile court judge approved the request, but the stepfather appealed to the Supreme Judicial Court to keep her alive. Many in his hometown of Westfield saw that as a way for him to avoid further charges.

The week before the SJC ruled on Jan. 17 that life support could be removed, DSS ordered a new round of tests on Haleigh after her biological mother visited and described the girl as being responsive. Based on the new tests, doctors told DSS officials that there was ''not a chance" of recovery, Spence said.

But a day after the high court's ruling, doctors told DSS that they had noticed significant improvements in Haleigh, saying, in effect, ''Oops, we're seeing something," Spence said. Haleigh was off the ventilator and had begun to show increasing responsiveness.

On Tuesday, Spence said, he went to Haleigh's room at Baystate and noticed a quiet brown-haired girl lying in bed. In front of her, he said, there were three objects: a yellow duck, a Curious George stuffed animal, and a yellow block. He said a DSS social worker accompanied him, and she said, ''Haleigh, this is Harry."

''Give him the yellow duck," the social worker said, according to Spence's recollection.

Haleigh picked up the yellow duck, he said.

''Where's Curious George?" the social worker asked Haleigh.

Haleigh then picked up the stuffed animal, Spence said.

''It's an astounding case," he said.

Haleigh did not appear to be grimacing or making sounds suggesting she was in pain, he said.

Spence said he remains hopeful that she will continue to move and that she will express herself more. He reiterated that his agency has suspended any efforts to remove life support.

He said that he has asked several pediatric neurologists to further evaluate Haleigh at her new home, Franciscan Hospital for Children in Brighton.

Some neurologists say Haleigh's actions suggest she may have moved into a ''minimally conscious state," in which patients are aware of their surroundings and can respond to commands.

That condition could sometimes strengthen arguments to withdraw life support, because such patients can feel pain, some medical ethicists said. Patients in a vegetative state, on the other hand, are oblivious to the agony that is part of their life.

''Suffering requires consciousness," said Dr. Robert L. Fine, a medical ethicist at Baylor University Medical Center in Dallas.

Children are more likely than adults to significantly recover from severe brain injuries, and some neurologists say they would want to wait at least a year before concluding that a child had stagnated in that state with no hope for a better life.

''I wouldn't give up before a year," said Dr. Douglas Katz, medical director of the traumatic brain injury program at Braintree Rehabilitation Hospital.

Katz said many patients in a minimally conscious state can track movements with their eyes and even pick up objects. But only when they begin to pick up objects and use them appropriately are they believed to have gained a higher level of consciousness.

At best, however, these patients generally stay ''extremely disabled," Katz said.

In 2008, Haleigh was released from Brighton rehabilitation hospital to live as a foster child with Keith and Becky Arnett in Southwick, Massachusetts. She was adopted by the Arnetts in 2010 at the age of 16 and attended a special education program in the Southwick public school system. She remains substantially disabled and relies on a wheelchair, but is able to feed herself and use a letterboard to communicate.  Regarding the attack, Haleigh's adoptive father reports that she knows she was hurt, but is unable to remember any specifics about the event.

Substantial article correction strengthens findings

A 2016 study in New England Journal of Medicine has received a substantial correction, which affected several aspects of the article.

Typically, an error that affects so much of a paper would undermine the results (and possibly lead to a retraction). But in this case, the revised dose calculations actually strengthened the findings, according to the first author.

The NEJM study aimed to clarify whether patients with a neuromuscular disease called myasthenia gravis benefit from a surgical procedure to remove the thymus. About half of the patients received surgery plus the steroid prednisone, while the rest only received the steroid. The researchers found patients who received the surgery fared better.

Shortly after the paper was published in August 2016, the authors discovered an error in the calculation of the average prednisone dose. According to Gil Wolfe, the first author of the paper, when the researchers corrected the error:

“The recalculation didn’t reverse any of the findings; it actually strengthened them, making thymectomy look even better.”

In other words, people who had surgery needed less prednisone overall, and the authors found the doses went down faster in the surgery group than they initially thought.

Here’s the correction notice for “Randomized Trial of Thymectomy in Myasthenia Gravis,” which explains the calculation error:

“Randomized Trial of Thymectomy in Myasthenia Gravis (Original Article, N Engl J Med 2016;375:511-522). An error in calculating the time-weighted average of the doses of prednisone led to incorrect point estimates for the primary and secondary outcomes. For patients whose prednisone dose was tapered and then stopped before month 36 and who remained off prednisone, the time-weighted dose calculations did not account for the months during which the patients were not receiving the medication. As a result, the time-weighted prednisone doses for such patients were overestimated. The errors affected several parts of the article: the Abstract, the Results section, the Discussion, Figure 1B, and Table 2. The Supplementary Appendix was also affected. The direction of change of the primary and secondary outcomes and the overall conclusions of the trial are not altered from the original published version. The article is correct at”

Wolfe, professor and chair of the Department of Neurology at the University at Buffalo School of Medicine and Biomedical Sciences, the State University of New York, told us:

“We wanted prednisone data for the full 36 months patients were followed. But for patients who went down to 0 mg of the drug during the study, the time-weighted dose calculation stopped before 36 months.”

Wolfe explained that when the authors recalculated the drug dose over the three year study period, the revised numbers made the surgery option look even better than the original numbers had.

Wolfe said that the recalculation only affected the prednisone dose data, not the data on disease severity, patient quality of life, or complications from surgery or prednisone.

A spokesperson for NEJM told us the journal never considered a retraction:

“In the process of looking at the computer program that did the analysis for this trial, the study statisticians found that that the amount of prednisone was miscounted. They reviewed the published article and found that they needed to make changes in dose reported for each group.”
Courtesy of Doximity
Courtesy of a colleague

Friday, June 23, 2017

Variability in preferred management of electrographic seizures in neonatal hypoxic Ischemic encephalopathy

Melanie A. McNally, MD, Adam L. Hartman, MD.  Variability in Preferred Management of Electrographic Seizures in Neonatal Hypoxic Ischemic Encephalopathy.  Pediatric Neurology.  In press.

Seizures occur commonly in neonates and growing evidence suggests they may cause added harm in neonates with hypoxic ischemic encephalopathy (HIE). However, specific recommendations about when and how to treat seizures in this context are lacking. The objective of this study was to determine the scope of practice nationally regarding management of non-status epilepticus electrographic-only seizures (ESzs) in neonates with HIE.

Study Design
A case-based survey was distributed to members of the Child Neurology Society. Providers were asked about their preferred management strategy for sequential clinical scenarios.

177 child neurologists responded to the survey. 77% of providers would treat 20 seconds or less of electrographic seizure activity. In a neonate with mild HIE and an ESz, there was no agreement among providers regarding whether to start maintenance therapy in addition to a one-time anti-seizure drug (ASD) load. In a neonate with moderate HIE on phenobarbital (PB) for early electro-clinical seizures, the majority of providers would escalate treatment for ongoing ESzs and would do so by increasing PB dosing. In a neonate with severe HIE complicated by status epilepticus on PB who subsequently develops recurrent ESzs, providers varied significantly in their management preferences. For all three cases, 75-85% of providers would not change their management preferences based on the presence or absence of a clinical correlate with the electrographic seizure.

We found marked variability among providers regarding preferred management of non-status epilepticus ESzs after HIE. Our results identified specific aspects of ESz management in neonatal HIE where there is limited consensus. These discrepancies may serve as opportunities for future investigation.

This study was meant to determine the scope of practice nationally about management of non–status epilepticus electrographic–only seizures (ESzs) in neonates with hypoxic ischemic encephalopathy (HIE). Among providers regarding preferred management of non–status epilepticus ESzs, the physicians found marked variability after HIE. The outcomes recognized specific aspects of ESz management in neonatal HIE where there is the limited consensus. For the future investigation, these discrepancies probably served as opportunities.


The authors distributed a case-based survey to members of the Child Neurology Society.
They asked providers about their preferred management strategy for sequential clinical scenarios.


A total of 177 child neurologists responded to the survey and 77% of providers would treat 20 seconds or less of electrographic seizure activity.

There was no agreement among providers regarding whether to start maintenance therapy in addition to a one-time anti-seizure drug (ASD) load in a neonate with mild HIE and an ESz.

The majority of providers would escalate treatment for ongoing ESzs and would do so by increasing PB dosing in a neonate with moderate HIE on phenobarbital (PB) for early electro-clinical seizures.
In their management preferences, providers varied significantly in a neonate with severe HIE complicated by status epilepticus on PB who subsequently develops recurrent ESzs.

Based on the presence or absence of a clinical correlate with the electrographic seizure, 75-85% of providers would not change their management preferences for all 3 cases.

Courtesy of:

Thursday, June 22, 2017

Chromosome 15q duplication syndrome

Inspired by a patient

Verrotti A, Sertorio F, Matricardi S, Ferrara P, Striano P. Electroclinical features of epilepsy in patients with InvDup(15). Seizure. 2017 Apr;47:87-91. doi: 10.1016/j.seizure.2017.03.006. Epub 2017 Mar 9.

InvDup(15) syndrome is one of the most common chromosomal abnormalities associated with epilepsy. Here we review the seizure types described in InvDup(15) patients and the main electroclinical, therapeutic, and prognostic aspects of the syndrome.
A literature search of PubMed, MEDLINE, and EMBASE was performed to identify papers examining InvDup(15) syndrome and epilepsy.
About 65% of the InvDup(15) patients described in the literature had multiple seizure types with a predominance (40.4%) of tonic-clonic seizures. Age at seizure onset was before 10 years in more than half of them. Patients suffered from a variety of EEG abnormalities, generalized spike activity being the most frequent. Brain MRI was unremarkable in the majority of patients. Treatment was with several anticonvulsant drugs used as mono- or polytherapy. Valproic acid was the most common treatment against generalized seizures and was often effective, although drug resistance was a major concern in a large number of cases. Finally, more than 30% of the children suffered from infantile spasms, and status epilepticus was described in nearly 20% of patients, occasionally resulting in death.
Seizures are very common in InvDup(15) patients, who suffer from a variety of seizure types. Information about EEG and brain MRI findings, seizure treatment, and prognosis is often poor. The overall prognosis is fair. Prospective studies of larger samples are needed, to gain further insights into the natural history of InvDup(15) syndrome.

Luchsinger K, Lau H, Hedlund JL, Friedman D, Krushel K, Devinsky O. Parental-reported pain insensitivity in Dup15q. Epilepsy Behav. 2016 Feb;55:124-7. doi: 10.1016/j.yebeh.2015.10.007. Epub 2016 Jan 13.

Parents of children with chromosome 15q duplication syndrome (Dup15q) have anecdotally reported high pain threshold as a feature of the disorder. The purpose of this study was to document parental-reported estimates of the frequency of high pain tolerance and the stimuli that fail to evoke a normal pain response. We sent an online survey to 840 families with children with Dup15q to explore the frequency and clinical manifestations of high pain threshold. There were 216 respondents (25.7%). A high pain threshold was reported in 87% of children at some time. There was a trend (p=0.06) for high pain threshold to be more commonly observed among children with the isodicentric (85.6%) and other genetic variants (95%) than interstitial (69.6%) duplications. There was no association between reports of high pain threshold and reports of an intellectual disability (91% of cases), autism spectrum disorder (83% of cases), or self-injurious behavior (40% of cases). Reports included many dramatic cases such as severe burns, broken bones, and electrical traumas, which were associated with little or no evidence of a painful stimulus. A high pain threshold is reported in other disorders associated with intellectual disability and autism; the underlying mechanism in Dup15q and other disorders remains undefined.

Boronat S, Mehan WA, Shaaya EA, Thibert RL, Caruso P. Hippocampal abnormalities in magnetic resonance imaging (MRI) of 15q duplication syndromes. J Child Neurol. 2015 Mar;30(3):333-8.

Patients with 15q duplication syndromes, including isodicentric chromosome 15 and interstitial duplications, usually present with autism spectrum disorder, intellectual disability, and frequently epilepsy. Neuroimaging studies in these patients are typically reported as normal, but nonspecific findings such as thinning of the corpus callosum and increased pericerebral spaces have been reported. A review of brain magnetic resonance imaging (MRI) studies of 11 individuals seen at the Massachusetts General Hospital Dup15q Center was performed. Hippocampus morphology was specifically reviewed, as a recent neuropathologic study has found frequent hippocampal heterotopias and dysplasias in these disorders. Two subjects had unilateral hippocampal sclerosis and 6 had bilateral hippocampal malformations. Hypoplasia of the corpus callosum was present in 2 subjects. 

Wednesday, June 21, 2017

Evaluation of sport-related concussion

McCrea M, Meier T, Huber D, Ptito A, Bigler E, Debert CT, Manley G, Menon D, Chen JK, Wall R, Schneider KJ, McAllister T. Role of advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion: a systematic review. Br J Sports Med. 2017 Jun;51(12):919-929.

To conduct a systematic review of published literature on advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion (SRC).
Computerised searches of Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Scopus and Cochrane Library from 1 January 2000 to 31 December 2016 were done. There were 3222 articles identified.
In addition to medical subject heading terms, a study was included if (1) published in English, (2) represented original research, (3) involved human research, (4) pertained to SRC and (5) involved data from neuroimaging, fluid biomarkers or genetic testing collected within 6 months of injury. Ninety-eight studies qualified for review (76 neuroimaging, 16 biomarkers and 6 genetic testing).
Separate reviews were conducted for neuroimaging, biomarkers and genetic testing. A standardised data extraction tool was used to document study design, population, tests employed and key findings. Reviewers used a modified quality assessment of studies of diagnostic accuracy studies (QUADAS-2) tool to rate the risk of bias, and a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to rate the overall level of evidence for each search.
Results from the three respective reviews are compiled in separate tables and an interpretive summary of the findings is provided.
Advanced neuroimaging, fluid biomarkers and genetic testing are important research tools, but require further validation to determine their ultimate clinical utility in the evaluation of SRC. Future research efforts should address current gaps that limit clinical translation. Ultimately, research on neurobiological and genetic aspects of SRC is predicted to have major translational significance to evidence-based approaches to clinical management of SRC, much like applied clinical research has had over the past 20 years.

Courtesy of:

Tuesday, June 20, 2017

Frontal lobotomy 2

20,000 Lobotomies in the United States

Medscape: The story that I wanted to focus on was "turning the mind inside out"—the chapter that addressed lobotomies and how they developed. From my perspective, what was most shocking about this topic is that lobotomies were still being performed, I believe, until about 1970. Is that correct?

Dr Offit: That's right.

Medscape: That is kind of amazing, in a terrible way. And it started with a couple of experiments with chimps, Becky and Lucy, in 1935. Can you tell our readers a little bit about those experiments and why the procedure jumped to humans so quickly?

Dr Offit: The experiment was done originally by two Yale physiologists, named Fulton and Jacobson. They found that when they tried to teach chimps how to get food with sticks, there was one chimp who was good at it and a chimp who wasn't particularly good at it. And when the chimp who wasn't good at it wasn't able to get the food, she would do such things as throw her feces at the researchers and jump up and down.

What they were really interested in was trying to understand the role of the frontal lobe in memory. So they then did an experiment where they essentially severed the chimp's frontal lobe from the rest of the brain. And they found that the chimp who used to get very anxious about not being able to perform the task wasn't anxious anymore. It was as if, as they said, "[s]he had joined a happiness cult." And so they had created a surgical procedure to eliminate anxiety.

When they presented that finding at a neurology meeting, there was a neurologist from Portugal named Egas Moniz, who said, "Well, sure. Let's do this in people." And then he did just that. He would essentially try to sever the frontal lobe from the rest of the brain, either surgically or just by infusing alcohol. He claimed that the results were great. He called it a "leukotomy," when, across the Atlantic Ocean, it was ultimately called a "lobotomy," for which he won a Nobel Prize.

But it is important to put this in context. This was the 1930s, when people who had severe mental disorders were hospitalized. At that time, more people in the United States were hospitalized with mental disorders than for all other diseases combined. The state institutions were bursting at the seams. The level of sanitation and hygiene in these institutions was woeful. The number of physicians versus the number of patients was also woeful in those settings. So, people were desperate to do something—anything—to make it better.

At the time, they had electroshock therapy, insulin shock therapy, and metrazol shock therapy. But these were all "therapies of despair," and somehow lobotomy seemed more reasonable—the idea that you can actually surgically make things better. Psychosurgery was born.

Over the years, we did 20,000 lobotomies in this country—7000 by one man, a Philadelphian, named Walter Jackson Freeman, who trained at my own institution, the University of Pennsylvania School of Medicine.

He eventually developed the drive-through lobotomy, where he would essentially insert an icepick into the upper inner aspect of the eye, the orbit.

He eventually developed the drive-through lobotomy, where he would essentially insert an icepick into the upper inner aspect of the eye, the orbit. He took a small hammer and drilled the icepick about 3 inches into the brain. He first did it on one side, and then he did it on the other side. He did it without anesthesia. He did it without sterilization. And it would take him only 5-7 minutes to do it.
He could do 20 or 25 procedures in a day. And that's what he did. It was a tough time.

Medscape: I'm sure it was amazing to you that he continued doing that for so long. And from what I read, so much of the problem was that he included a very short period of follow-up when he reported his results. He didn't give complete or totally factual information when he presented his data.

Dr Offit: Yes; he appealed to the sense of desperation at the time. People wanted to believe him and were willing to ignore some of the warnings that were starting to surround lobotomies, and one of those people was Joe Kennedy.

Medscape: Remind us of that story.

Dr Offit: Joseph Kennedy was the father of John F. Kennedy and Robert F. Kennedy. He was also the father of Rosemary Kennedy, who today would be considered mildly developmentally delayed. Even though he'd been warned against lobotomy, he wanted to believe that there was a quick and easy way to make his daughter like his other children, who were bright, active, and politically ambitious. And Rosemary wasn't. She could read, she could write, she could go to parties. But she would occasionally get angry and flap her arms up and down. He wanted all that to go away.

So, that's what Walter Freeman was able to appeal to—the sense of wanting to believe that he could do a magic trick. As it ended up, after the procedure, Rosemary was pretty much vegetative for the rest of her life. And neither of her parents really visited her for the last 25 years of her life. The only person who visited her was John F. Kennedy, during a sort of whistle-stop tour, when he was traveling through Wisconsin.

Functional neuroimaging of high-risk 6-month-old infants predicts a diagnosis of autism at 24 months of age

Emerson RW, Adams C, Nishino T, Hazlett HC, Wolff JJ, Zwaigenbaum L, Constantino JN, Shen MD, Swanson MR, Elison JT, Kandala S, Estes AM, Botteron KN, Collins L, Dager SR, Evans AC, Gerig G, Gu H, McKinstry RC, Paterson S, Schultz RT, Styner M; IBIS Network, Schlaggar BL, Pruett JR Jr, Piven J. Functional neuroimaging of high-risk 6-month-old infants predicts a diagnosis of autism at 24 months of age. Sci Transl Med. 2017 Jun 7;9(393).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors that typically emerge by 24 months of age. To develop effective early interventions that can potentially ameliorate the defining deficits of ASD and improve long-term outcomes, early detection is essential. Using prospective neuroimaging of 59 6-month-old infants with a high familial risk for ASD, we show that functional connectivity magnetic resonance imaging correctly identified which individual children would receive a research clinical best-estimate diagnosis of ASD at 24 months of age. Functional brain connections were defined in 6-month-old infants that correlated with 24-month scores on measures of social behavior, language, motor development, and repetitive behavior, which are all features common to the diagnosis of ASD. A fully cross-validated machine learning algorithm applied at age 6 months had a positive predictive value of 100% [95% confidence interval (CI), 62.9 to 100], correctly predicting 9 of 11 infants who received a diagnosis of ASD at 24 months (sensitivity, 81.8%; 95% CI, 47.8 to 96.8). All 48 6-month-old infants who were not diagnosed with ASD were correctly classified [specificity, 100% (95% CI, 90.8 to 100); negative predictive value, 96.0% (95% CI, 85.1 to 99.3)]. These findings have clinical implications for early risk assessment and the feasibility of developing early preventative interventions for ASD.
"Our study shows that early brain development biomarkers could be very useful in identifying babies at the highest risk for autism before behavioral symptoms emerge," said senior author Joseph Piven, MD, the Thomas E. Castelloe Distinguished Professor of Psychiatry at the University of North Carolina-Chapel Hill. "Typically, the earliest an autism diagnosis can be made is between ages two and three. But for babies with older autistic siblings, our imaging approach may help predict during the first year of life which babies are most likely to receive an autism diagnosis at 24 months."…
Despite much research, it has been impossible to identify those at ultra-high risk for autism prior to 24 months of age, which is the earliest time when the hallmark behavioral characteristics of ASD can be observed and a diagnosis made in most children.

For this Nature study, Piven, Hazlett, and researchers from around the country conducted MRI scans of infants at six, 12, and 24 months of age. They found that the babies who developed autism experienced a hyper-expansion of brain surface area from six to 12 months, as compared to babies who had an older sibling with autism but did not themselves show evidence of the condition at 24 months of age. Increased growth rate of surface area in the first year of life was linked to increased growth rate of overall brain volume in the second year of life. Brain overgrowth was tied to the emergence of autistic social deficits in the second year…

The researchers then took these data -- MRIs of brain volume, surface area, cortical thickness at 6 and 12 months of age, and sex of the infants -- and used a computer program to identify a way to classify babies most likely to meet criteria for autism at 24 months of age. The computer program developed the best algorithm to accomplish this, and the researchers applied the algorithm to a separate set of study participants.

The researchers found that brain differences at 6 and 12 months of age in infants with older siblings with autism correctly predicted eight out of ten infants who would later meet criteria for autism at 24 months of age in comparison to those infants with older ASD siblings who did not meet criteria for autism at 24 months.

"This means we potentially can identify infants who will later develop autism, before the symptoms of autism begin to consolidate into a diagnosis," Piven said.

If parents have a child with autism and then have a second child, such a test might be clinically useful in identifying infants at highest risk for developing this condition. The idea would be to then intervene 'pre-symptomatically' before the emergence of the defining symptoms of autism.

Research could then begin to examine the effect of interventions on children during a period before the syndrome is present and when the brain is most malleable. Such interventions may have a greater chance of improving outcomes than treatments started after diagnosis.

"Putting this into the larger context of neuroscience research and treatment, there is currently a big push within the field of neurodegenerative diseases to be able to detect the biomarkers of these conditions before patients are diagnosed, at a time when preventive efforts are possible," Piven said. "In Parkinson's for instance, we know that once a person is diagnosed, they've already lost a substantial portion of the dopamine receptors in their brain, making treatment less effective."

Piven said the idea with autism is similar; once autism is diagnosed at age 2-3 years, the brain has already begun to change substantially.

"We haven't had a way to detect the biomarkers of autism before the condition sets in and symptoms develop," he said. "Now we have very promising leads that suggest this may in fact be possible."

Courtesy of a colleague

Monday, June 19, 2017

Vagal nerve stimulation in Dravet syndrome

Maxine Dibué-Adjei, Maxine Dibué-Adjei, Igor Fischer, Hans-Jakob Steiger, Marcel Alexander Kamp.  Efficacy of Adjunctive Vagus Nerve Stimulation in Patients with Dravet Syndrome: A Meta-Analysis of 68 Patients.  Seizure.  In press.


•13 studies comprising 68 patients report efficacy of VNS in Dravet syndrome.
•52.9% of DS patients experienced a ≥50% reduction of seizures.
•Average seizure reduction, assessed in n = 28 patients was 50.8%.


Dravet Syndrome (DS) is a severe epileptic encephalopathy of childhood involving intractable seizures, recurrent status epilepticus and cognitive decline. Because DS is a rare disease, available data is limited and evidence-based treatment guidelines are lacking. Vagus nerve stimulation (VNS) is an established neurostimulation treatment for intractable epilepsy, however little evidence is published on its efficacy in patients with DS.

We performed a meta-analysis of all peer-reviewed English language studies reporting seizure outcomes of patients with DS treated with adjunctive vagus nerve stimulation. The primary and secondary outcome measures were ≥50% reduction of seizures or of the most-debilitating seizure type and seizure reduction per patient.

13 studies comprising 68 patients met the inclusion criteria of which 11 were single-center retrospective case series, one was a multi-center retrospective analysis and one was a case report. 52.9% of patients experienced a ≥50% reduction of seizures and the average seizure reduction, which could only be assessed in n = 28 patients was 50.8%. 7 out of 13 studies reported additional benefits of VNS, however this could not be assessed systematically.

Vagus nerve stimulation appears to reduce seizure frequency in patients with DS. Based on this preliminary analysis, controlled trials of VNS in this rare condition using patient-centric outcome measures are indicated. 

Texas spine surgery

Now serious allegations are being raised about another North Texas spine doctor. [See] Former patients filing lawsuits and complaints with the State allege their lives have been ruined by a surgeon putting profits over patient care.

A picture may be worth a thousand words, but not every picture tells the whole story.

Pictures of a smiling Steven Pennington of Royce City, for example, mask his torture. The back pain that plagued him for 20 years and now the images of his headstone tell a final story. On July 22, 2015, Pennington took that pain to his grave.

The autopsy blames "sudden cardiac death," which occurred during his second back surgery. Pennington's family blames something else: an orthopedic surgeon once touted as Collin County's best -- Dr. Stephen Courtney.

The family has filed a lawsuit against Dr. Courtney for "gross negligence" and for trying to profiteer off Pennington by using his own surgical implants during surgery.
Dr. Courtney is co-founder of Eminent Spine. The company slogan on the website video is "Bad to the Bone."

The company designs and delivers surgical hardware such as the "Copperhead," the "King Cobra," the "Diamondback," and the "Python."

According to a video on the business' site, Dr. Courtney, "uses the product every day, on every patient."

“Eminent Spine offers quality products at a significantly lower cost that benefits everyone in healthcare, from the doctors and hospitals to the patients themselves,” the site said.

But according to multiple lawsuits and complaints on file with the Texas Medical Board, it is those devices that are being improperly and unnecessarily implanted in patient's spines.

Bryan Taylor of Collinsville hurt his back in November 2014. He was diagnosed with a herniated disc and received a steroid injection.

After a few weeks, still in pain, Taylor was referred to Dr. Courtney who, according to the suit, wanted to operate using the Python.

Federal Drug Administration (FDA) guidelines recommend that a patient should receive "six months of non-operative treatment" prior to performing surgery. Medical records show Taylor received only two months.

FDA guidelines also say the Python should be secured in place with "supplemental fixation" so it won't slip. According to his attorney, Kelly Liebbe, supplemental fixation was not used.

"Obviously, he didn't follow the standard of care what the FDA clearance told him to do," Liebbe alleged.

Liebbe showed WFAA an x-ray of Bryan's back and how the Python "spacer" in Taylor's back allegedly shifted after surgery.

"This is four months later. You can see the spacers are now tilted to the right, which indicates the spacer is moving, migrating out of place," Liebbe said.

Out of place, causing Taylor intense pain.

"I knew something wasn't right," Taylor said.

According to Taylor's lawsuit, a few weeks later, Dr. Courtney operated on Taylor's back again by re-installing the Python. Again without fixing it in place.

"Every time I had a surgery, he kept saying that this is what I need, and it's going to make it better and I trusted him," Taylor said. "It got to the point [where] I needed something to happen."

In June 2015, Dr. Courtney performed a third surgery on Taylor. It did not help, he said, who then sought the help of a second surgeon who removed Dr. Courtney's device.

Alan Tarrant of Plano also trusted Dr. Courtney, even after three failed surgeries involving Courtney implants, the Python and the Cottonmouth, which he said broke off in his spine rendering him permanently impaired.

Tarrant said he has been in constant pain, unable to work or bend, or sit for longer than a few minutes.

"I'm 48 years old and disabled," Tarrant said. "I've got nothing to look forward to, just going backwards, never getting better."

WFAA has identified other former patients with similar complaints against Courtney. And WFAA has learned of multiple complaints filed against Courtney with the Texas Medical Board dating back to 2012.

So far, none of the complaints has resulted in disciplinary action.

Records obtained by WFAA indicate Dr. Courtney is currently under investigation by the board…

WFAA made repeated attempts to contact Dr. Courtney. He did not respond.

In legal filings in lawsuits, his attorneys have denied all allegations of negligence and gross negligence...

All four patients suing Dr. Courtney had their procedures done and his devices implanted at Baylor Scott & White Medical Center Frisco.

Since those surgeries, Baylor Frisco has started following the lead of several major hospital chains across the country, in most cases, prohibiting surgeons from using their own implants on patients.

The Texas Medical Board has declined to comment on their investigation into the Courtney complaints.

Records show Dr. Courtney has now opened his own hospital, Eminent Medical Center, in Richardson.

Epileptic encephalopathies

Germain B, Maria BL. Epileptic Encephalopathies. J Child Neurol. 2017 Jan 1:883073817697846. doi: 10.1177/0883073817697846. [Epub ahead of print]

Epileptic encephalopathies encompass a heterogeneous group of epilepsy syndromes that manifest with cognitive, behavioral, and neurologic deficits, seizures that are often intractable and multiform, aggressive electroencephalographic paroxysmal activity, and sometimes early death. As more is learned about the etiologies and manifestations of epileptic encephalopathies, progress has been made toward better treatment options. However, there is still a great need for further randomized controlled trials and research to help create clinically effective therapies. The 2015 Neurobiology of Disease in Children symposium, held in conjunction with the 44th annual meeting of the Child Neurology Society, aimed to (1) describe the clinical concerns involving diagnosis and treatment, (2) review the current status of understanding in the pathogenesis of epileptic encephalopathy, (3) discuss clinical management and therapies for epileptic encephalopathy, and (4) define future directions of research. This article summarizes the presentations and includes an edited transcript of question-and-answer sessions.

From the manuscript

Infantile spasms

As far as current treatment for spasms is concerned, there is no clear consensus as to what treatment regimen is best. Seventy percent of providers are seeing fewer than 10 patients per year with new-onset spasms, which stresses the importance of having a consortium to identify treatment options. The aim of treatment is to stop clinical spasms and hypsarrhythmia, which in turn will help prevent future developmental regression. Most first-line medications, such as adrenocorticotropic hormone and vigabatrin, will stop spasms fairly quickly. Adrenocorticotropic hormone can stop spasms within a week and vigabatrin sometimes within a month. The relapse rate is about a quarter to a third of patients with spasms…

Oral prednisolone is also thought to help, but there is really no consensus as to whether adrenocorticotropic hormone or oral prednisolone is more effective. Several studies have looked at this, but have drawn different conclusions. The Pediatric Epilepsy Research Consortium protocol for adrenocorticotropic hormone is based on a study done by Baram in 1996 in which she looked at 29 infants randomly assigned to receive adrenocorticotropic hormone or prednisone. Of those treated with adrenocorticotropic hormone, 87% responded, compared with 29% who received prednisone. The protocol is a high dose of adrenocorticotropic hormone at 150 µg/m2 divided twice a day for the first 2 weeks and then tapered quickly. However, adrenocorticotropic hormone is very expensive. Each vial costs $28,000. In addition, parents must be taught to administer it by intramuscular injection, and it is typically given in an inpatient setting because the child was just diagnosed with spasms through an EEG or MRI…

Dr Koh concluded by providing current data collected by the Pediatric Epilepsy Research Consortium on spasms. The consortium of 38 pediatric epilepsy centers has enrolled about 230 patients with new-onset infantile spasms under the age of 2. The main goal is to identify numbers of children with the presenting information, etiologies, and short-term outcomes to provide baseline data for a larger comparative effectiveness trial. The etiologies found are similar to those identified by the UKISS group, in that about 64% of their patients did have a known etiology. The most common etiologies found were genetic or metabolic issues such as trisomy 21 and hypoxic-ischemic encephalopathy.

After 3 months of freedom from spasms, it seemed that the adrenocorticotropic hormone group had a much better response rate, especially compared with participants who received second-line medications, which were associated with a very low response rate. Those who had no developmental problems prior to spasms or those with mild developmental delay seemed to do better than those who had moderate or severe developmental delay prior to onset of spasms. In terms of etiology, those who had cryptogenic or unknown neurologic issues or etiologies with genetic or metabolic issues such as trisomy 21 did much better compared with those who had cortical dysplasia, who did not do as well. Those who had high-dose adrenocorticotropic hormone had a better response rate than those who had a low-dose form.


Ninety-three percent were diagnosed with Lennox-Gastaut syndrome within 1 year of seizure onset; 59% had normal development prior to seizure onset, with 11 patients having normal posterior rhythm on EEG. Only 11.8% had prior West syndrome. A detailed genetic analysis was performed, and it was found that de novo mutations were enriched in specific gene sets, including genes regulated by the fragile X protein. However, it was found that clinical phenotype could not predict a responsible gene. Because various genetic pathways resulted in epileptic encephalopathy, researchers explored the interrelationship between these mutations. They found that about three-fourths of the genetic defects in the cryptogenic group were associated with a protein involved in synaptic regulation, which will hopefully help to further progression of treatment methods.

First-line evaluation of Lennox-Gastaut syndrome, following clinical history and physical examination, includes brain MRI, EEG, and routine laboratory studies. If there are no abnormalities consistent with etiology, a chromosomal microarray may be done, which has a 12% to 13% yield. Urine organic acids, amino acids, and metabolic screening may yield an etiology in only about 1 in 50 to 100 patients. Targeted next-generation sequencing of epileptic encephalopathy panels has a high yield of about 12% to 13%. The Epilepsy Phenome/Genome Project is then suggesting whole exome sequencing be performed in those remaining…

ESES in Landau-Kl3effner

Dr Hirsch reviewed previous studies of electrical status epilepticus in sleep, including studies of sleep homeostasis and genetic studies. It has been demonstrated that the role of sleep was disturbed, mostly in the down-scale of the slow activity usually observed during sleep related to spike-and-wave activity. In genetic studies, a relation between this group of diseases and autism has been shown. In a study conducted by Dr Hirsch and colleagues in 2010, 10% to 50% of these patients had a mutation of GRIN2A, which is related to cortical oscillation and maturation and can be attributed to acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction, as well as idiopathic focal epilepsy with rolandic spikes.

With regard to treatment, studies have proven efficacy of benzodiazepines, steroids, and immunoglobulins. Use of personalized therapy with memantine in patients with GRIN2A mutation and early-onset epileptic encephalopathy has also been demonstrated and showed while there was no effect on the EEG, there was an effect on seizures. In a study by Downes and colleagues in 2015, subpial transections had no effect on patients with Landau-Kleffner syndrome.

Autoimmune encephalopathies

In conclusion, studies reveal that pediatric forms of autoimmune encephalitis are generally similar to those seen in adults. Encephalopathy, seizures, and cognitive and behavioral changes are common, and children are often apyrexic at presentation. They do not always have high cerebrospinal fluid cell counts, and not all of them have MRI abnormalities, making these features less helpful. They can be diagnosed by specific antibody, although lack of known antibody should not rule out a high suspicion of an autoimmune form and the appropriate treatment. Coexisting or previous infections are becoming quite common, and they do not rule out an autoimmune etiology for the patient’s present symptoms. Also, some antibodies, such as the voltage-gated potassium channel-complex antibodies, are not always directly pathogenic and may be a biomarker for inflammatory, potentially treatable, disease.


To summarize, the cannabinoid system has significant representation in multiple brain regions, making it a promising target for therapeutics, but mechanisms are complex. Clinical data are available for some indications but data for epilepsy are still sparse and often poorly conducted; more research is needed. Extensive literature on potential toxicity highlights the need for safety monitoring, especially in children and adolescents. Regulatory measures are inconsistent and evolving, with differences at the state and federal level. Increased use of complementary and alternative medicine indicates an unmet therapeutic need and highlights the need to ask patients and families about this subject. Lastly, if patients and families are choosing to use complementary and alternative medicines, a standardized approach to assess safety and efficacy should be developed.