Tuesday, July 31, 2018

Medical mayhem 10

Monday morning, investigators filed nearly 70 additional charges against a former pediatrician, Johnnie "Jack" Barto, accusing him of sexually abusing 29 more victims.

Barto was first charged in January 2018 with sexually assaulting a 12-year-old patient. Then in March and again in April, he was charged on separate, similar allegations of abuse of his relatives, who were children.

Investigators accused the 70-year-old of sexually assaulting patients at Laurel Pediatric Associates and Conemaugh Hospital.

The alleged abuse dates back to the late 1980s and the victims include boys and girls of all ages, as young as a two-week-old baby girl.

Barto is accused of inappropriately touching the victim's breasts and genitals. His charges include involuntary deviate sexual intercourse, aggravated indecent assault, indecent assault and endangering the welfare of children.

"Dr. Barto used his power and authority as a pediatrician and abused them in those instances to feed his own sick desires," said Attorney General Josh Shapiro.

Investigators said Barto waited for the victims' guardians to leave the exam room or would use his body to hide the assaults. On occasion, parents would notice Barto's actions and confront him during the victims' exam, however, investigators said Barto would claim the assaults were part of a standard medical exam.

Barto's medical license was revoked on January 22, 2018.

Shapiro said this investigation is ongoing and thanked the victims for their courage coming forward.


A woman who brutally stabbed her 13-year-old son to death was sentenced to at least 37 years
in prison Friday.

In the rare role of a murder defendant who pleaded guilty while acting as her own attorney, Donna
Marie Anderson stretched the sentencing in Redwood City into a three-hour marathon.

She peppered San Mateo County Superior Court Judge Mark Forcum with objections in a bid to
cleanse a presentencing report of suggestions that she "fiercely and savagely" attacked her son 
in crime that "caused the entire family to be traumatized and irreparably damaged."

At one point, she made a belated and bizarre attempt to shield the child she murdered, objecting to the report's recounting of how she had her son, Stephen Burns, convert with her to Judaism. This violated their freedom of religion and privacy, she said.

"I feel strongly about protecting the constitutional rights of the victim," Anderson, a bright but
troubled physician, said as tearful relatives muttered in disbelief.

Anderson also objected to a prosecutor's report stating "the victim must have suffered immense
horror and pain" as his mother stabbed him 15 times with a knife at his grandparents' Burlingame
home in February.

"It's speculation," Anderson said, saying the prosecutor cannot "know the exact feeling of the

After patiently hearing more than 20 objections and motions, Forcum sentenced the 49-year-old
Anderson to 37 years to life in prison for murdering Stephen and attempting to murder her exhusband, Frank Burns Jr., when he ran to help their son.

"Dr. Anderson, your cruel, callous and premeditated acts robbed Stephen of the gift of life," 
Forcum said. "I have been struck by the absolute lack of what I consider genuine remorse."

Chief Deputy District Attorney Steve Wagstaffe lauded the judge's patience with Anderson's
frequent interruptions during four months of hearings, in which the woman was deemed mentally
competent to act as her own attorney and ultimately pleaded guilty.

While homicide prosecutions can take as long as three years, Wagstaffe said Forcum's gentle
handling of the defendant gave "the gift . . . of a quick closure to the victim's family."

As she has since taking over her representation, Anderson was obsessed with control and legal 
trivia -- agreeing to allow a TV camera in the courtroom, for example, but requesting to see the cameraman's press credentials.

While Anderson quibbled over the report's depiction that killing one's own child is "the most
heinous of crimes," a woman relative in the audience said: "She's making us suffer."

Yet Anderson seemed oblivious to the question that a dozen distraught family members in court 
had hoped she would answer: Why would a mother kill her own son, a boy described as a loving, witty, trusting child?

"I regret that circumstances came into my life (and) that on Feb. 24 I was unable to make a better
decision than to kill my son and attempt to kill Mr. Burns," the mother said, in the closest she 
came to an apology.

Saying that "women are expected to break down and cry," Anderson explained that her legal 
duties required keeping her emotions in check. "I do request that the audience not misinterpret
my professional demeanor . . . (as evidence) that I'm not a human being."

In an early jailhouse interview, Anderson said she quit her job in Minnesota and journeyed to the
Bay Area where Stephen was visiting relatives in an act of mercy -- to spare him from being
kidnapped by child pornographers.

The probation report described the obstetrician as a woman who had grown increasingly 
paranoid and delusional, often quitting jobs and moving when employers or relatives urged her to seek psychological treatment.

Against Anderson's objections, grief-stricken family members finally had their say Friday.

Stephen's aunt, Jamile McConnell, said she believed that Anderson killed Stephen because he  
had begun to question her mental stability and was planning to stay in the Bay Area with relatives.

"I don't believe that Donna killed Stephen in an act of mercy," the aunt said. "I believe she killed 
him out of rage and anger."


Courtesy of a colleague

Monday, July 30, 2018

RASopathies: personality and social skills

Bizaoui V, Gage J, Brar R, Rauen KA, Weiss LA. RASopathies are associated with a distinct personality profile. Am J Med Genet B Neuropsychiatr Genet. 2018 Jun;177(4):434-446.

Personality is a complex, yet partially heritable, trait. Although some Mendelian diseases like Williams-Beuren syndrome are associated with a particular personality profile, studies have failed to assign the personality features to a single gene or pathway. As a family of monogenic disorders caused by mutations in the Ras/MAPK pathway known to influence social behavior, RASopathies are likely to provide insight into the genetic basis of personality. Eighty subjects diagnosed with cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, and Noonan syndrome were assessed using a parent-report BFQ-C (Big Five Questionnaire for Children) evaluating agreeableness, extraversion, conscientiousness, intellect/openness, and neuroticism, along with 55 unaffected sibling controls. A short questionnaire was added to assess sense of humor. RASopathy subjects and sibling controls were compared for individual components of personality, multidimensional personality profiles, and individual questions using Student tests, analysis of variance, and principal component analysis. RASopathy subjects were given lower scores on average compared to sibling controls in agreeableness, extraversion, conscientiousness, openness, and sense of humor, and similar scores in neuroticism. When comparing the multidimensional personality profile between groups, RASopathies showed a distinct profile from unaffected siblings, but no difference in this global profile was found within RASopathies, revealing a common profile for the Ras/MAPK-related disorders. In addition, several syndrome-specific strengths or weaknesses were observed in individual domains. We describe for the first time an association between a single pathway and a specific personality profile, providing a better understanding of the genetics underlying personality, and new tools for tailoring educational and behavioral approaches for individuals with RASopathies.

Pierpont EI, Hudock RL, Foy AM, Semrud-Clikeman M, Pierpont ME, Berry SA, Shanley R, Rubin N, Sommer K, Moertel CL. Social skills in children with RASopathies: a comparison of Noonan syndrome and neurofibromatosis type 1. J Neurodev Disord. 2018 Jun 18;10(1):21.

Gene mutations within the RAS-MAPK signaling cascade result in Noonan syndrome (NS), neurofibromatosis type 1 (NF1), and related disorders. Recent research has documented an increased risk for social difficulties and features of autism spectrum disorder (ASD) among children with these conditions. Despite this emerging evidence, the neuropsychological characteristics associated with social skills deficits are not well understood, particularly for children with NS.

Parents of children with NS (n = 39), NF1 (n = 39), and unaffected siblings (n = 32) between the ages of 8 and 16 years were administered well-validated caregiver questionnaires assessing their child's social skills, language abilities, attention-deficit hyperactivity disorder (ADHD) symptoms and anxiety.

With respect to overall social skills, average ratings of children in both clinical groups were similar, and indicated weaker social skills compared to unaffected siblings. Although ratings of social skills were outside of normal limits for more than four in ten children within the clinical groups, most of the deficits were mild/moderate. Fifteen percent of the children with NS and 5% of the children with NF1 were rated as having severe social skills impairment (< - 2SD). Independent of diagnosis, having fewer ADHD symptoms or better social-pragmatic language skills was predictive of stronger social skills.

Amidst efforts to support social skill development among children and adolescents with RASopathies, neuropsychological correlates such as social language competence, attention, and behavioral self-regulation could be important targets of intervention.

Fingolimod treatment of mucolipidosis IV.

Weinstock L, Furness AM, Herron S, Smith SS, Sankar S, DeRosa SG, Gao D, Mepyans ME, Scotto Rosato A, Medina DL, Vardi A, Ferreira NS, Cho SM, Futerman AH, Slaugenhaupt SA, Wood LB, Grishchuk Y. Fingolimod Phosphate Inhibits Astrocyte Inflammatory Activity in Mucolipidosis IV. Hum Mol Genet. 2018 May 16. doi: 10.1093/hmg/ddy182. [Epub ahead of print]

Mucolipidosis IV (MLIV) is an orphan neurodevelopmental disease that causes severe neurologic dysfunction and loss of vision. Currently there is no therapy for MLIV. It is caused by loss of function of the lysosomal channel mucolipin-1, also known as TRPML1. Knockout of the Mcoln1 gene in a mouse model mirrors clinical and neuropathological signs in humans. Using this model, we previously observed robust activation of microglia and astrocytes in early symptomatic stages of disease. Here we investigate the consequence of mucolipin-1 loss on astrocyte inflammatory activation in vivo and in vitro and apply a pharmacological approach to restore Mcoln1-/- astrocyte homeostasis using a clinically approved immunomodulator, fingolimod. We found that Mcoln1-/- mice over-express numerous pro-inflammatory cytokines, some of which were also over-expressed in astrocyte cultures. Changes in the cytokine profile in Mcoln1-/- astrocytes are concomitant with changes in phospho-protein signaling, including activation of PI3K/Akt and MAPK pathways. Fingolimod promotes cytokine homeostasis, down-regulates signaling within the PI3K/Akt and MAPK pathways, and restores the lysosomal compartment in Mcoln1-/- astrocytes. These data suggest that fingolimod is a promising candidate for preclinical evaluation in our MLIV mouse model, which, in case of success, can be rapidly translated into clinical trial.

In the nearly five decades since Mucolipidosis Type IV, or ML4, was first identified, children with the disease have had little promise of ever having a “normal” life.

ML4 generally strikes their nervous system early and hard. Most never learn to walk or talk and have a maximum mental capacity of about 18 months. By their teen years, the disease steals their eyesight, and by their 20s, their life is at stake.

But just in the past few months, research using an already FDA-approved drug is giving parents like Randy and Caroline Gold of Atlanta hope.

In the nearly five decades since Mucolipidosis Type IV, or ML4, was first identified, children with the disease have had little promise of ever having a “normal” life.

ML4 generally strikes their nervous system early and hard. Most never learn to walk or talk and have a maximum mental capacity of about 18 months. By their teen years, the disease steals their eyesight, and by their 20s, their life is at stake.

But just in the past few months, research using an already FDA-approved drug is giving parents like Randy and Caroline Gold of Atlanta hope. 

“I think that this drug is the first of many treatments that will be available to kids with ML4,” Randy Gold said. “We are incredibly excited because it is the first opportunity to treat a kid affected by ML4.”

Gold is president of the Mucolipidosis Type IV Foundation, an international nonprofit focused on funding research directed at understanding the genetic disease and developing treatments.

The Golds’ 10-year-old daughter, Eden, was diagnosed with ML4 in 2009. The couple haven’t been shy about soliciting donations for the foundation to help fund research or talking about their experiences caring for Eden.

They’ve been on the front lines since 2010 doing what they could to not only improve Eden’s life but the lives of all kids with ML4. They first shared their story here last summer…

As this year’s ML4 International Research Conference approached late last month, Randy Gold reached out again, excited about the promise of this new research.

He knows the drug is not going to instantly turn Eden into a “typical” kid; that she is not going to wake up tomorrow and get herself dressed for school.

And yet, it’s hard not to be excited about this first treatment.

“We’re certain more treatments will have to follow,” Gold said. “Unfortunately, this drug is not one and done.”…

With funding from the foundation, researchers began testing the drug a year ago in mice cells, then expanded to do more advanced testing to validate their findings. The results were published in the May issue of The Journal of Human Molecular Genetics.

Further testing is now being done in a bigger study of live mice, with study results expected late this year.

“This is the first time with this disease that we have a drug that shows a level of rescue, taking a cell and returning it to a healthier state,” Oberman said. “If the results from the mouse study are as positive as we hope, it could mean a clinical trial in kids with ML4 in 2019, giving us the first opportunity to treat these kids with something that the FDA agrees will have a positive impact on them. It’s not a cure, but it will treat a major symptom of this disease, neurological inflammation. I can’t tell you now what it will look like in each individual child, but we know this is treating something that is a significant part of this disease.”


Sunday, July 29, 2018

MAST1 mutations

Inspired by a patient

Abstract Number: (223)  ACMG Annual Clinical Genetics Meeting 2018

De novo variants in MAST1 are associated with a novel neurodevelopmental disorder characterized by microcephaly and brain malformations

Topic: Clinical Genetics

First Author: Wei Shen, PhD, University of Utah

Presenting Author: Wei Shen, PhD, University of Utah

Co-Authors: T. Tvrdik, University of Utah; T. Tidwell, ARUP Laboratories; L. Botto, University of Utah; J. Bale, University of Utah; A. Andrews, University of Utah; D. Ball, University of Utah; F. Filloux, University of Utah; C. Van Orman, University of Utah; K. Dent, University of Utah; J. Palumbos, University of Utah; C. Miller, ARUP Laboratories; S. Brown, ARUP Laboratories; P. Krautscheid, ARUP Laboratories; J. Carey, University of Utah; R. Mao, University of Utah; P. Bayrak-Toydemir, ARUP Laboratories/University of Utah School of Medicine

Human MAST1 encodes microtubule associated serine/threonine kinase 1, which is predominately expressed in the brain. In mouse, MAST1 interacts with syntrophin through the PDZ domain. To date, no human disease association has been established for MAST1. de Ligt (2012) and Gilissen (2014) reported a de novo MAST1 variant, c.3530C>G, p.Pro1177Arg, in an individual with microcephaly, global developmental delay, intellectual disability, partial agenesis of corpus callosum and an arachnoid cyst in the posterior fossa. Several additional de novo missense variants of MAST1 have been reported in the large cohort studies of individuals with developmental disorders, intellectual disability, and cerebral palsy. However, clinical descriptions of these individuals are not available. 

Here we report 3 unrelated patients with overlapping neurological phenotypes and de novo missense variants in MAST1 identified by clinical exome sequencing. Two patients had de novo missense variants that alter the same amino acid Pro1177 as the variant reported by Gilissen (2014) (Patient 1: c.3530C>T, p.Pro1177Leu; Patient 2: c.3529C>T, p.Pro1177Ser). Patient 3 carried a different de novo variant c.3889G>T, p.Asp1297Tyr. All 3 patients had microcephaly, severe global developmental delay, and intellectual disability with absent speech or speech delay. In Patient 1, brain MRI showed hypoplasia of corpus callosum and cerebellar vermis, and periventricular white matter loss. In Patients 2 and 3, brain MRI demonstrated partial agenesis of corpus callosum and pontocerebellar hypoplasia. Patient 2 also exhibited delayed myelination, whereas Patient 3 had an arachnoid cyst over the posterior left frontal lobe. 

We compiled the previously reported MAST1 de novo variants. All 8 variants are missense alterations not observed in the population variant databases. Three missense variants alter the same codon Pro1177. Computational analysis predicted that all 8 MAST1 missense variants would impact protein function. Functional consequences of these MAST1 missense variants are under nvestigation. 

Our results support that MAST1 de novo variants are associated with an emergent autosomal dominant neurodevelopmental disorder characterized by microcephaly, global developmental delay, intellectual disability, and brain malformations.

A tuberous sclerosis potpourri

Gupta N, Henske EP. Pulmonary manifestations in tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018 Jul 28. doi: 10.1002/ajmg.c.31638. [Epub ahead of print]


Tuberous sclerosis complex has manifestations in many organ systems, including brain, heart, kidney, skin, and lung. The primary manifestations in the lung are lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH). LAM affects almost exclusively women, and causes cystic lung destruction, pneumothorax, and chylous pleural effusions. LAM can lead to dyspnea, oxygen dependence, and respiratory failure, with more rapid disease progression during the premenopausal years. In contrast, MMPH affects men and women equally, causing small nodular pulmonary deposits of type II pneumocytes that rarely progress to symptomatic disease. Here, we review the clinical features and pathogenesis of LAM and MMPH.


Tuberous sclerosis complex has manifestations in many organ systems, including brain, heart, kidney, skin, and lung. The primary manifestations in the lung are lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH). LAM affects almost exclusively women, and causes cystic lung destruction, pneumothorax, and chylous pleural effusions. LAM can lead to dyspnea, oxygen dependence, and respiratory failure, with more rapid disease progression during the premenopausal years. In contrast, MMPH affects men and women equally, causing small nodular pulmonary deposits of type II pneumocytes that rarely progress to symptomatic disease. Here, we review the clinical features and pathogenesis of LAM and MMPH.

Bissler JJ, Budde K, Sauter M, Franz DN, Zonnenberg BA, Frost MD, Belousova E, Berkowitz N, Ridolfi A, Christopher Kingswood J. Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2. Nephrol Dial Transplant. 2018 Jul 19. doi: 10.1093/ndt/gfy132. [Epub ahead of print]


A reduction in renal angiomyolipoma volume observed with everolimus (EVE) treatment in patients with tuberous sclerosis complex (TSC) has been postulated to translate to clinical benefit by reducing the risk of renal hemorrhage and chronic renal failure.

The long-term effects of EVE on renal function (4years of treatment) were examined in patients treated with EVE in the Phase 3 EXIST-1 and EXIST-2 studies. Patients in EXIST-1 had TSC and subependymal giant cell astrocytoma (SEGA), and patients in EXIST-2 had renal angiomyolipoma and a definite diagnosis of TSC or sporadic lymphangioleiomyomatosis. EVE was administered at 4.5 mg/m2/day, with adjustment to achieve target trough levels of 5-15 ng/mL in EXIST-1 and at 10 mg/day in EXIST-2. Estimated glomerular filtration rate (eGFR) and creatinine levels were assessed at baseline, at Weeks 2, 4, 6, 8, 12 and 18, then every 3 months thereafter. Proteinuria was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.

A total of 111 patients from EXIST-1 and 112 patients from EXIST-2 were included in this analysis. Respective mean ages at EVE initiation were 10.5 [standard deviation (SD) 6.45] and 33.2 (SD 10.29) years, and 3.6% and 37.5% of patients had undergone prior renal intervention. Mean baseline eGFR was 115 and 88 mL/min/1.73 m2 in EXIST-1 and EXIST-2, respectively. Overall, mean eGFR remained stable over time in both studies, with an decline in renal function mostly confined to some patients with severely compromised renal function before treatment. Patients with prior renal intervention exhibited low eGFR values throughout the study. The incidence of proteinuria increased after initiating treatment with EVE and was mostly Grade 1/2 in severity, with Grade 3 proteinuria reported in only two patients. Measurements of proteinuria were limited by the use of urine dipstick tests.

The use of EVE does not appear to be nephrotoxic in patients with SEGA or renal angiomyolipoma associated with TSC and may preserve renal function in most patients. 

Li S, Zhang Y, Wang Z, Yang Y, Gao W, Li D, Wei J. Genotype-phenotype correlation of patients with tuberous sclerosis complex-associated renal angiomyolipoma: a descriptive study. Hum Pathol. 2018 Jul 20. pii:S0046-8177(18)30284-3. doi: 10.1016/j.humpath.2018.07.017. [Epub ahead of print]


TSC2 gene mutation was repeatedly reported associated with a more severe phenotype in patients of tuberous sclerosis complex (TSC). Our current study aims to further explore whether there is such a correlation in patients with TSC-associated renal angiomyolipoma (TSC-RAML). TSC1/TSC2 gene mutation was screened by high throughput sequencing in 25 TSC-RAML patients from two medical centers. Clinical data were also carefully collected. Linear-regression analysis and student t-test were conducted by IBM SPSS Statistics Version 21.0 to analyze the genotypic-phenotypic relationship. The results indicated a high level of TSC gene mutation (80%, 20/25) in TSC-RAML patients, with higher frequency of TSC2 mutation (68%, 17/25) than TSC1 mutation (12%, 3/25). Seven novel mutation sites were detected in this study. In general, there were no significant correlations between tumor size and age (r=0.134, P=0.522), hemoglobin (r=0.255, P=0.219) and serum creatinine (r=0.043, P=0.839). Patients with larger tumor size have higher risk of bleeding. Specially, it was higher level of hemoglobin in patients with TSC1 mutation than ones with TSC2 mutation and without TSC mutation (P<0.05). However, no difference was found in either tumor size or serum creatinine by TSC mutation genes (P>0.05). Furthermore, no difference was found in tumor size, hemoglobin and serum creatinine by TSC mutation types (P>0.05). In conclusion, TSC-RAML is TSC2 mutation dominant, with the individual differences varying greatly. No definite genotype-phenotype correlation exists in patients with TSC-RAML, and it needs to be further explored.

Saturday, July 28, 2018

Sleep disordered breathing and ventilatory support in children with Down syndrome

Trucco F, Chatwin M, Semple T, Rosenthal M, Bush A, Tan HL. Sleep disordered breathing and ventilatory support in children with Down syndrome. Pediatr Pulmonol. 2018 Jul 10. doi: 10.1002/ppul.24122. [Epub ahead of print]


Obstructive sleep apnoea (OSAS) in children with Down syndrome (DS) is now well recognized, but other forms of sleep disordered breathing (SDB) in this population are less well described. Anecdotally, respiratory support for SDB treatment in this population is not easily tolerated. We aimed to characterize the types of SDB in children with DS referred to a tertiary respiratory center and to assess the effectiveness and adherence to respiratory support.

Retrospective study of DS patients <18 years old under follow-up at a tertiary respiratory center. Anthropometrics, comorbidities, sleep study results, and details of respiratory support were collected. Satisfactory adherence to oxygen (O2 ), Continuous Positive Airway Pressure (CPAP), or bilevel noninvasive ventilation (NIV) was defined as use >4 h/night for >50% nights.

Sixty patients were included, median age 1.5 (0.7-5.3) years; 49 (82%) had congenital heart disease, 16 (27%) pulmonary hypertension, 28 (47%) gastroesophageal reflux, 38 (63%) swallowing impairment; 16/17 who underwent CT scanning had evidence of aspiration. Forty-two had SDB: 27 (61%) OSAS (10 mild, 5 moderate, 12 severe), 11 (25%) central apnoeas, 19 (32%) nocturnal hypoventilation. Twenty-six had baseline saturations <95%. Lower SpO2 correlated with pulmonary hypertension (r2  = 0.1, P = 0.04). Thirty-nine (65%) patients started respiratory support (14 O2 , 18 CPAP, 7 NIV) and 22 (56%) have regularly used it. After a 1.9 years follow up 11/24 had satisfactory adherence to CPAP/NIV (average use 8 h/night).

Our results confirm the high prevalence of OSAS in children with DS. A significant number also have low baseline saturations, central apnoeas, and nocturnal hypoventilation. Contrary to popular belief, more than half of children with DS had satisfactory adherence to respiratory support.

Courtesy of:  https://www.mdlinx.com/journal-summaries/cpap-down-syndrome-non-invasive-ventilation/2018/07/12/7527976?spec=neurology&rcid=45

Friday, July 27, 2018

Blood test may accurately diagnose traumatic brain injury, need for CT scan

Jeffrey J Bazarian, Peter Biberthaler, Robert D Welch, Lawrence M Lewis, MD, Pal Barzo, Viktoria Bogner-Flatz, P Gunnar Brolinson, Andras Büki, James Y Chen, Robert H Christenson, Dallas Hack, J Stephen Huff, Sandeep Johar, J Dedrick Jordan, Bernd A Leidel, Tobias Lindner, Elizabeth Ludington, David O Okonkwo, Joseph Ornato, W Frank Peacock, Kara Schmidt, Joseph A Tyndall, Arastoo Vossough, Andy S Jagoda’ Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study.  Lancet Neurology. 24 July 2018.  https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(18)30231-X.pdf


More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI.

This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9–15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT.

Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931–0·995) and an NPV of 0·996 (0·987–0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative.

These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted.

Banyan Biomarkers and US Army Medical Research and Materiel Command.

"We see this test not as a substitute for head CT scan, but as an accurate and objective way to help emergency care providers decide which patients really need one," Jeffrey Bazarian, MD, MPH, professor, Department of Emergency Medicine, University of Rochester Medical Center, New York, told Medscape Medical News.

"Our results suggest that this blood test holds potential for ruling out the need for head CT scan among head-injured patients presenting to EDs, in whom a head CT scan is felt to be clinically indicated; in fact, up to a third of head CT scans done in the acute setting of TBI could be avoided, with very low false-negative rates," he said…

The "diagnostic modality of choice" in evaluating patients for traumatic intracranial injuries is a head CT scan, which accounts for approximately 20 million CT scans performed annually in the United States.

"[T]he widespread use of head CT scanning has been questioned due to potential adverse effects of radiation exposure, unnecessary [ED] resource use, and cost," the authors state.

Moreover, the prevalence of CT-detected intracranial injury in patients with mild TBI is typically less than 10%.

Previous research has suggested the potential for blood-based brain injury biomarkers to predict the absence of intracranial injury after TBI and aid in reducing unnecessary head CT scans….

S100B, a well-established biomarker for TBI, is already in clinical use in Europe; however, to date, no blood-based brain biomarker tests have been approved by the US Food and Drug Administration for clinical use in the United States…

Two novel brain proteins that have been advanced are UCH-L1 and GFAP, but preliminary investigations into these "promising" biomarkers have been limited by small cohort sizes, variability in blood sample acquisition timing, and retrospective determination of cutoff values…

When the researchers conducted a sensitivity analysis comparing the diagnostic accuracy of the combined biomarker test with each protein individually, they found that the combination of both proteins outperformed each marker separately on the primary outcomes…

"We were pleasantly surprised to see that 97.6% of patients with a CT-detected intracranial injury, like hemorrhage, tested positive, and 99.7% of patients with a negative test had a normal head CT scan," he said.


IV lidocaine in the treatment of children and adolescents with status migraine

Ayulo MA Jr, Phillips KE, Tripathi S. Safety and Efficacy of IV Lidocaine in the Treatment of Children and Adolescents With Status Migraine. Pediatr Crit Care Med. 2018 Jun 19. doi: 10.1097/PCC.0000000000001629. [Epub ahead of print]


To evaluate the safety and efficacy of IV lidocaine in treating children and adolescents with status migraine.

Retrospective observational study.

Single center PICU.

Children and adolescents admitted with status migraine.

IV lidocaine.

Thirty-three lidocaine infusions were administered to 28 patients with status migraine. Two patients were excluded from analysis, leaving 31 infusions administered to 26 patients for analysis. Patients' ages ranged from 10 to 19 years with an average of 14.9 ± 2.4 years. Mean duration of hospitalization was 4.6 ± 1.5 days. Lidocaine was administered as a bolus (2.9 ± 0.18 mg/kg) in 80.6% (95% CI, 63.7-90.8%) of the patients, followed by an infusion, which was started at a mean rate of 1.29 ± 0.2 mg/kg/hr with mean maximum dose of 1.56 ± 0.27 mg/kg/hr. The highest lidocaine drip was 2.25 mg/kg/hr and lowest 1.125 mg/kg/hr. Lidocaine was interrupted in one patient secondary to side effects: chest pain and anxiety. On average, it took 16.3 ± 12.9 hours for 50% reduction in pain scores (range, 1.3-40.4 hr) and 19.3 ± 19.3 hours for complete resolution (0.8-72.1). 90.3% of cases (95% CI, 75.1-96.6%) experienced pain resolution with 51.6% (95% CI, 34.8-68%) encountering a relapse of pain. Mean pain scores at the time of discharge were 1 ± 1.6 (median, 0). Both mean reported highest and lowest scores dropped over the course of the 5 days from 5.1 ± 1.9 and 2.1 ± 2.4 on day 1 to 1.0 ± 1.4 and 0 on day 5 of therapy. One-way analysis by analysis of variance for high pain score by day was statistically significant with a p value of less than 0.01.

In the appropriate patient population, IV lidocaine may be a safe and effective treatment for children and adolescents with status migraine. Larger prospective studies need to be done not only to evaluate safety and efficacy but also the analgesic longevity of IV lidocaine post discharge.

Courtesy of:   https://www.neurologyadvisor.com/headache-migraine-advisor/status-migraine-children-adolescents-intravenous-lidocaine/article/783430/

Thursday, July 26, 2018

Soccer headers

Soccer players who head the ball more often may be more likely to have balance problems than players who do not head the ball as often, according to a preliminary study released today that will be presented at the American Academy of Neurology’s Sports Concussion Conference in Indianapolis July 20 to 22, 2018.

“Soccer headers are repetitive subconcussive head impacts that may be associated with problems with thinking and memory skills and structural changes in the white matter of the brain,” said study author John Jeka, PhD, of the University of Delaware in Newark, Del. “But the effect of headers on balance control has not been studied.”

For the study, 20 soccer players recruited from the community in Newark took a balance test where they walked along a foam walkway with their eyes closed under two conditions: with galvanic vestibular stimulation (GVS) and without GVS. For GVS, electrodes placed behind each ear stimulate the nerves that send messages from the balance system in the inner ear to the brain. So the stimulator can make you feel like you are moving when you are not. In this case, it made participants feel like they were falling sideways.

The soccer players, who had an average age of 22, also completed questionnaires about how many times they had headed the ball during the past year. The number of headers over a year for each participant ranged from 16 to 2,100, with an average of 451 headers. Those numbers were calculated by asking participants for the average number of headers during a practice and game, the average number of practices and games per week, and the average number of months per year that the player participated.

The study found that the players with the largest number of headers had the largest balance responses to GVS in both foot placement and hip adduction during the walking test, which indicated that they had vestibular processing and balance recovery problems. Researchers found for every 500 headers, foot placement response increased about 9 millimeters and hip adduction response increased about 0.2 degrees.

“Soccer players must have good balance to play the game well, yet our research suggests that headers may be undermining balance, which is key to all movement, and yet another problem now linked to headers,” said study author Fernando V. Santos, PT, of the University of Delaware. “It is important that additional research be done to look more closely at this possible link with balance and to confirm our findings in larger groups of people.”

A limitation of the study was that participants relied on memory when reporting how many times they headed the ball.

The study was supported by the National Institutes of Health.


Genetic teasers 2

An 11 months old boy with infantile spams

He was found to have a likely pathogenic variant, c.251G>A in the SPATA5 gene. This gene is associated with autosomal recessive epilepsy, hearing loss, and intellectual disability. Typically, affected individuals have two pathogenic genetic changes/variants in this gene (one inherited from each parent). Given that only one variant was identified in him, this finding is likely not related to his diagnosis of epilepsy (testing included sequencing and deletion/duplication analysis). However, this result indicates that he is a carrier of SPATA-related epilepsy, hearing loss, and intellectual disability.

He was also found to have a variant of unclear significance, c.225C>G, in the KCNQ3 gene, which is associated with autosomal dominant familial neonatal seizures. This variant has not been previously reported in any affected individuals, but is present in population databases. According to the report, it has a higher allele count than what is expected for a pathogenic variant. At this time the significance of this finding in him is unknown. Another variant of unclear significance, c.815C>T, was identified in the NEDD4L gene, which is associated with autosomal dominant periventricular heterotopia. There is preliminary evidence that suggests that it may also be associated with autosomal dominant early infantile epileptic encephalopathy. This variant has not been reported in affected individuals and is not present in population databases.

See:  http://childnervoussystem.blogspot.com/2016/08/genetic-teasers.html

Wednesday, July 25, 2018

Back to sleep

The parents of a four-month-old boy who suffocated in February at the motel where the family was living have been charged with murder in connection with his death.

William Herring, 42, and Brianna Brochhausen, 22, were living at the Hilltop Motel in the 100 block of Route 68 in Springfield Township, N.J., at the time of the incident.

They were each charged with murder and conspiracy to commit murder.

A charge of endangering the welfare of a child was initially filed March 9, but authorities decided to upgrade the charges following their investigation.

Herring and Brochhausen were taken into custody Monday by the New Jersey State Police.

A first appearance was held Tuesday in Superior Court in Mount Holly. A detention hearing will be held later this week.

Paramedics and Springfield Township police officers were called to the motel on the night of February 14.

Police said Herring and Brochhausen were frustrated because their son, Hunter, would not stop crying and decided he needed to be placed in a "time out."

Officials said the pair put the baby face down on the bed and pulled a comforter over him then went outside to smoke cigarettes.

When they returned to the room approximately 10 minutes later, they discovered Hunter was not breathing.

Hunter was taken to Virtua Hospital in Mount Holly and immediately transferred to the Pediatric Intensive Care Unit at Children's Hospital of Philadelphia, where he had minimal brain activity and was breathing with the assistance of a respirator.

He died March 3 after life support was removed.

"The thoughtless actions of these individuals ended up costing a defenseless 4-month-old infant his life," said New Jersey State Police Superintendent Colonel Callahan. "I commend the detectives of our Homicide South Unit and Criminal Investigation Office for their commitment and dedication to finding justice for Baby Hunter."

Philadelphia Deputy Chief Medical Examiner Albert Chu declared the cause of Hunter's death to be "complications of suffocation," and the manner of death to be homicide.


Shades of Questcor 6

Trevor Foltz splashes in the pool in his grandparents' backyard. His brother and sister join in the fun, as does their father.

Their mother, Danielle, watches from a nearby lawn chair. She's like a hawk, keeping a close eye on Trevor and the rest of her brood.

It was 10 years ago in this backyard when a similar moment of revelry was shattered. Trevor, then a toddler, was running around, having the time of his life, his mom keeping steady watch.

Trevor suddenly came over, placed his hand on her knee and looked directly into her eyes. He tried to speak but couldn't say a word. Then his head twitched ever so slightly to the right. Their gazes locked. Mom's heart wrenched.

It was so mild that Danielle told herself it must have been her imagination. She didn't tell her husband, Jonathan, or anyone else. But moments later, it happened again: Trevor coming to her, resting his hands on her knees, looking into her eyes.

Trevor's condition soon became obvious to all. The Foltzes were eating dinner with friends a few days later when Trevor had one seizure, then another and another.

"Some heartache transcends language," Danielle recalled. "This is one of them."'

The Foltzes had been there before. At 7 months, Trevor was diagnosed with infantile spasms, a rare and catastrophic form of epilepsy. The diagnosis was devastating, forcing the family to cancel an overseas move and fight for their son's life.

It also thrust them into the unregulated world of America's drug prices.

Trevor's doctors said he needed a "miracle drug" known as Acthar. But between Trevor's birth and diagnosis, the price of the drug had shot up from $1,600 a vial to more than $23,000 a vial -- making him one of the first children caught up in one of medicine's most controversial price hikes.

After the initial diagnosis, the Foltzes wrestled with their insurance company for days to get Trevor treated with Acthar. Eventually, the treatment was fully covered, at a cost of more than $125,000. And the drug worked. The tremors stopped.

But more than a year later, on that day in the backyard, the seizures had returned. Another round of treatment was in order.

Again, the Foltzes ran into red tape. The insurer was balking at spending another $125,000, and Trevor's parents worried whether he would get the precious vials of medicine needed to give him a shot at a normal life.

A decade on, the pain is still raw. Still palpable. Still real.

"It feels like we're pawns," says Trevor's father, Jonathan. The drugmaker, he says, "is allowed to take advantage of us, and we have to move on and go about the challenge of living."

"It seems very backwards, from the top down -- and we're at the bottom."…

But we rarely hear about the anatomy of a price hike, especially one that climbed for more than a decade in the face of a federal investigation and protests from top medical associations.

I wanted to know how a drug invented in the 1930s could go from $40 a vial in 2000 to $39,000 in 2018 -- essentially from the cost of a coffee maker to the price of a new car with leather seats. With a treatment regimen requiring at least three vials over the course of several weeks, this drug costs more than many people's homes.

The sharp jump in Acthar's price outraged families, doctors, pharmacists and hospitals -- and led Danielle Foltz to testify before Congress against the increase.

It ultimately resulted in a $100 million settlement between the government and the drugmaker -- as well as revelations that Medicare has spent nearly $2 billion covering Acthar prescriptions for seniors while the drugmaker paid millions to prescribing doctors.

The exorbitant price also forced doctors and hospitals to question whether a $20 alternative would work just as well.

I first heard about Acthar from the epilepsy community; my own son has an uncontrolled seizure disorder. Parents would often cry when describing the cost of Acthar and the struggle to get the medicine for their child.

Please tell this drug's story. Our story.

Imagine holding a vial worth more than your minivan, your hand trembling for fear of dropping it, while you administer a shot with a 1-inch needle to your seizing, screaming baby.

I spent the past year canvassing the epilepsy community, talking to scores of people, including 10 parents whose children struggle with infantile spasms and more than a dozen doctors who treat them…

The skyrocketing cost of Acthar led to huge increases in revenues for the drugmakers, Questcor and Mallinckrodt, not because of any breakthrough in treatment, critics say, but as a result of higher prices, aggressive marketing and an alleged effort to thwart all competition.

That allegation is what led to the government's case against Mallinckrodt, which purchased Questcor in 2014. Mallinckrodt settled without any admission of wrongdoing.

"This was a particularly egregious situation where they raised prices extraordinarily, but then they sought to buy out a potential competitor to make sure those prices were going to stick as long as possible," said Mike Moiseyev, the deputy director of the Federal Trade Commission's Bureau of Competition, who helped build the government's case.

Questcor had purchased Synacthen, a synthetic version of Acthar, and then made sure it never entered the US market, the government alleged. "When Questcor deprived [babies] of an imminent alternative in the form of Synacthen, they truly became victims of that scheme," Moiseyev said.
And though Mallinckrodt says it will cover the cost of Acthar if insurance can't, some doctors say high-priced drugs are raising health care costs for all of us in the form of higher premiums, co-pays and hospital visits.

From months of reporting, the magnitude of the controversy became clear. Parents are distraught and angry. Neurologists are perplexed and frustrated. Mallinckrodt maintains that it is acting "responsibly and ethically" and has made only "modest price adjustments in the mid-single digit percentage range" since purchasing the drug.

"H.P. Acthar Gel makes a significant difference in the lives of very sick patients with unmet medical needs. We are proud of the drug and the important investment we are making in it," Mallinckrodt told CNN in a statement.

Still, the drug's price has continued to rise. It's now nearly $39,000 a vial -- an increase of $7,000 since Mallinckrodt purchased Questcor and 97,000% since Questcor first acquired Acthar in 2001. By 2015, Mallinckrodt was reporting net sales from Acthar of $1 billion…

Even at some top medical centers like Johns Hopkins, Acthar isn't offered as a first-line treatment due to its exorbitant price tag.

"We have found oral prednisolone to be equally effective, as have several other researchers," said Dr. Eric Kossoff, director of Hopkins' pediatric neurology residency program.

Dr. Eli Mizrahi, president of the American Epilepsy Society, said Acthar's high cost is a constant worry. Simply put, he said, paying tens of thousands of dollars a vial is not viable in the long run.
"It's a concern because it's a barrier to care," Mizrahi said. "I'd like to hear why the drug is so expensive and what [the drugmaker is] doing to bring the cost down."

"For many pediatric neurologists, ACTH is not a treatment option," said Dr. John Mytinger, a pediatric neurologist at Nationwide Children's Hospital in Columbus, Ohio. "This may be because the clinician believes that prednisolone is just as good as ACTH and/or the expense of ACTH cannot be justified."…

But those were nothing compared with the rise in price of Acthar.

Questcor Pharmaceuticals had paid a mere $100,000 for the rights to the drug in 2001.

The company first raised the price from $40 to $750 a vial shortly after acquiring it. The price doubled over the next few years. Then, on August 27, 2007, the price shot up overnight from $1,600 to $23,000 a vial.

The hike was so dramatic that the Epilepsy Foundation, the American Epilepsy Society, the American Academy of Neurology and the National Association of Epilepsy Centers fired off a letter demanding answers.

The Epilepsy Foundation was especially shocked. The drug's previous manufacturer almost took Acthar off the market in the mid-1990s after federal regulators found major problems at a factory. But the Epilepsy Foundation pleaded for the drugmaker to keep producing it for babies with infantile spasms…

Its new owner, Questcor, would make Acthar the centerpiece of its business, stoking controversy with the massive price hike in 2007. It would ride the price increase to record profits and eventually a mega deal, getting bought out by Mallinckrodt for $5.6 billion in cash and stock in 2014.
Not bad for a company that paid $100,000 for the drug…

Dr. Stephen Schondelmeyer has followed the price of Acthar ever since it skyrocketed overnight in 2007. He's the director of the PRIME Institute, a research organization that studies economic and policy issues related to pharmaceuticals.

"It wasn't because of competition. It wasn't because of research and development costs," he said. "The company saw an opportunity to raise the price, and they did it."

How can the company keep raising the price, even after settling the monopoly case?

"When you have a unique position in a marketplace," Schondelmeyer said, "you can charge whatever you want."

He called the 97,000% drug hike, from 2000 to today, "one of the highest price changes ever" in the history of the United States…

The city of Rockford, Illinois, also sued Mallinckrodt after the city got stuck with a nearly $500,000 bill to cover the costs of Acthar for two infants of city employees. The half-million-dollar charge nearly blew through the city's $3.5 million allocation for prescription drugs for city employees.

"The tale of how a 65-year-old brand medication could rise in price from $40 per vial in 2001 to over $35,000 per vial by 2015 is a story of, perhaps, the most egregious monopolistic conduct and unfair trade practice in US history," the city of Rockford alleged.


Tuesday, July 24, 2018

Drowning in epilepsy

Bain E, Keller AE, Jordan H, Robyn W, Pollanen MS, Williams AS, Donner EJ. Drowning in epilepsy: A population-based case series. Epilepsy Res. 2018 Jun 20;145:123-126.


The risk of drowning is reported to be 15-19 times greater in people with epilepsy compared to the general population. Despite this disproportionate burden, there is limited data about the circumstances surrounding drowning deaths in people with epilepsy. This population-based case series characterizes drowning deaths in people with epilepsy.

Postmortem data from coroner-ordered autopsies conducted in Ontario between 2014 and 2016 were screened for cases of drowning in people with a history of seizures. Demographic information, epilepsy characteristics, and circumstances surrounding death were extracted from post mortem reports. The incidence of drowning in people with epilepsy was calculated using government estimates of the Ontario population and the number of people with epilepsy.

Twenty-five people with epilepsy drowned during the three-year study period, giving an estimated incidence of 1.5 per 10,000 epilepsy person-years (95% CI: 0.98, 2.23). Decedents were mostly young (mean age 36 years) and without physical or developmental disability. Approximately one-third had psychiatric comorbidities. Epilepsy severity ranged from well-controlled to drug refractory. Only 3 people had alcohol or illicit drugs detected on toxicological analysis. Forty-four percent of deaths were the result of an unwitnessed drowning in a bathtub.

This population-based case series confirms people with epilepsy drown at a rate nearly ten times greater than the general population (1.5 per 10,000 epilepsy person-years compared to the estimated provincial average of 0.13 per 10,000). Drowning deaths in people with epilepsy most often occur in the bathtub. These deaths are only rarely associated with intoxication. People with epilepsy should receive counseling on the increased risk of drowning, including information regarding the significant risk associated with bathtub use, the potential protective roles of anti-epileptic drug (AED) adherence and supervision when in or around water, and the fact that all people with epilepsy remain at an increased risk of drowning regardless of their apparent seizure control.

Incidence of sudden unexpected death in epilepsy in children is similar to adults

Keller AE, Whitney R, Li SA, Pollanen MS, Donner EJ. Incidence of sudden unexpected death in epilepsy in children is similar to adults. Neurology. 2018 Jul 10;91(2):e107-e111.


To determine the incidence of sudden unexpected death in epilepsy (SUDEP) in children in Ontario, Canada.

Cases of suspected pediatric SUDEP occurring between January 1, 2014, and December 31, 2015, in Ontario, Canada, were eligible for inclusion. Potential cases were identified through 3 sources: a national pediatrician surveillance program, child neurologist report, and screening of provincial forensic autopsies. Cases were classified as definite, definite plus, probable, possible, and near/near plus according to criteria described by Nashef et al. (Epilepsia 2012). Overall crude pediatric SUDEP incidence and the incidence of definite or probable pediatric SUDEP were calculated using estimates of the prevalence of pediatric epilepsy in Canada drawn from government survey data and the number of children living in Ontario. Capture-recapture analysis was used to estimate the number of missing cases and determine an adjusted definite/probable SUDEP incidence.

Seventeen cases of pediatric SUDEP resulted in an overall incidence of 1.17 (95% confidence interval 0.68-1.88) per 1,000 pediatric epilepsy person-years. The definite/probable incidence, including definite (n = 11), definite plus (n = 2), or probable (n = 3) SUDEP cases, was 1.11 (0.63-1.79). Capture-recapture analysis indicated an estimated 21 (16-39) definite/probable SUDEP cases occurred during the study period, giving an adjusted incidence of definite/probable SUDEP of 1.45 (0.90-2.22) per 1,000 pediatric epilepsy person-years.

SUDEP may be more common in children than widely reported, with the incidence rate of definite/probable SUDEP in children being similar to rates reported in adults.

Causes of mortality in early infantile epileptic encephalopathy

Radaelli G, de Souza Santos F, Borelli WV, Pisani L, Nunes ML, Scorza FA, da Costa JC. Causes of mortality in early infantile epileptic encephalopathy: A systematic review. Epilepsy Behav. 2018 Aug;85:32-36


Early infantile epileptic encephalopathy syndrome (EIEE), also known as Ohtahara syndrome, is an age-dependent epileptic encephalopathy syndrome defined by clinical features and electroencephalographic findings. Epileptic disorders with refractory seizures beginning in the neonatal period and/or early infancy have a potential risk of premature mortality, including sudden death. We aimed to identify the causes of death in EIEE and conducted a literature survey of fatal outcomes.

We performed a literature search in MEDLINE, EMBASE, and Web of Science for data from inception until September 2017. The terms "death sudden," "unexplained death," "SUDEP," "lethal," and "fatal" and the medical subject heading terms "epileptic encephalopathy," "mortality," "death," "sudden infant death syndrome," and "human" were used in the search strategy. The EIEE case report studies reporting mortality were included.

The search yielded 1360 articles. After screening for titles and abstracts and removing duplicate entries, full texts of 15 articles were reviewed. After reading full texts, 11 articles met the inclusion criteria (9 articles in English and 2 in Japanese, dated from 1976 to 2015). The review comprised 38 unique cases of EIEE, 17 of which had death as an outcome. In all cases, the suppression-burst pattern on electroencephalographies (EEGs) was common. Most cases (55%) involved male infants. The mean (standard deviation [SD]) age at onset of seizure was 19.6 ± 33 days. The mean (SD) age at death was 12.9 ± 14.1 months. Most infants (58.8%) survived less than one year. The cause of death was described only in eight (47%) patients; the cause was pneumonia/respiratory illness or sudden unexpected death in epilepsy (SUDEP).

The results show EIEE as a severe disease associated with a premature mortality, evidenced by a very young age at death. Increasing interest in the detection of new molecular bases of EIEE is leading us to a better understanding of this severe disease, but well-reported data are lacking to clarify EIEE-related causes of death.

A vaccine story

A Delaware teen getting ready to leave for college got the health scare of his life when he lost feeling in his legs following a vaccine injection.

The family of Jaire Pritchett asked for prayers over the weekend when his legs became paralyzed after getting an immunization required of his college for students living at dorms.

Jaire’s father, Greg, posted updates regarding his son’s condition on Facebook.
“Need your prayers for my kid Jaire Pritchett’s is in the ER after getting some immunization. He was told that was needed before he started college. Now he cannot feel his legs and cannot walk. #prayers,” Greg wrote.

In a follow-up post the concerned father, who works as a martial arts trainer, was pleased to report his son was doing much better after being hospitalized for several hours. 

While omitting the name of the college, Greg later explained Jaire had received Pfizer’s Trumenba Meningitis B vaccine, which he claimed was “mandated by his college.” 

Greg indicates doctors had to flush the vaccine out of Jaire’s system due to his severe adverse reaction, and says Jaire’s mom refused to allow their son to take the vaccine’s recommended second dose.

“After 24 hrs he could not feel his legs and could not walk. Now he is able to stand and walk and has full feeling,” Greg Pritchett wrote on Facebook Sunday. “The doctors had to flush the vaccine out of his body. Thanks so much for all the calls and messages and most of all prayers.”

In a Sunday Facebook update, Jaire called it one of the scariest experiences of his life and claimed he’d heard from others who’d experienced the same thing: 

“One of the scariest things I faced but I’m ok now laying in bed resting I thank everyone that’s said a prayer for me🙏🏽 and this didn’t just happened to me I had a couple people tell me that got that new shot and the same thing happened to them 💯 doctors think they look up everything and know everyone but the one thing u don’t know is inside a person body and how they are feeling💯 but I’m blessed to be able to walk again #25strong.”

While headaches, nausea, fatigue and fainting are listed as possible side effects of Trumenba on the vaccine’s package insert, paralysis was not listed as an adverse reaction in clinical trials. The insert does, however, indicate that 269 out of 15,227 test subjects (1.8%) had experienced “serious adverse events,” but does not go into detail on what those side effects were.

Mr. Greg Pritchett told Infowars a doctor at the hospital confirmed his son’s reaction was vaccine-related and advised the family against re-administering the vaccine. Mr. Pritchett said most of his family was already skeptical of vaccines, but that the incident has prompted more family members to question them.

Jaire’s story should caution parents to conduct their own research instead of blindly following the orders of school administrators and health professionals.


Cerebral cysticercosis

The parents of an 8-year-old girl suffering from severe headaches and epileptic seizures for months were both relieved and horrified when doctors told them her diagnosis: 100 tapeworm eggs were inside her brain.

Doctors at Fortis Hospital in New Delhi, India, told India Today the larvae traveled to the girl's brain through her bloodstream, causing massive swelling. By the time she was hospitalized, the young girl, who has not been identified, was nearly unconscious.

"Her brain scan showed more than a 100 white dots, formed due to tapeworm eggs," Dr. Praveen Gupta, director of neurology at Fortis Hospital, told the newspaper. "When eggs reach the brain through the nervous system they cause neurocysticercosis, which is characterised by a severe headache, epileptic seizures and confusion."

A tapeworm infection is typically caused by the ingestion of food or water contaminated with the parasites.

"If you ingest certain tapeworm eggs, they can migrate outside your intestines and form larval cysts in body tissues and organs," according to the Mayo Clinic. If you ingest tapeworm larvae, however, they develop into adult tapeworms in your intestines."

According to the Centers for Disease Control and Prevention (CDC), the likely culprit in this girl's case was the Taenia solium, also known as a "pork tapeworm" because the infection is typically caused by eating raw or undercooked meat.

"Infection with T. solium tapeworms can result in human cysticercosis, which can be a very serious disease that can cause seizures and muscle or eye damage," the CDC explains.

Gupta said they first focused on reducing the swelling of the girl's brain before administering drugs.

"Her treatment began by reducing her swelling with decongestants and later steroids and gradually the cysts (tapeworm eggs) were treated by starting anthelmintic therapy with albendazole under observation. Later the steroids and antihelminthic therapy were weaned off," Gupta described, adding that the treatment appeared to be a success.

The girl's parents told India Today they were surprised at how quickly their daughter's health bounced back, revealing that she's already returned to school.

"We had absolutely no idea that our healthy and cheerful daughter could ever get such a dreadful disease. But I think we are extremely lucky to have reached here and get right treatment," the girl's father told the newspaper.


Epilepsy and driving

A Savage man admitted in court Monday, July 23, that he shouldn't have been driving the night he had a seizure in early December 2016 and ran head-on into another vehicle on Interstate 494, leaving three dead, including a toddler.

Patrick Hayes made the admission in Hennepin County District Court when he pleaded guilty to five counts for causing the fatal wrong-way crash, authorities say…

During his guilty plea, Hayes admitted that there had been a change in his epilepsy medication while he was still living in Texas that made him more prone to seizures, the attorney's office said. His medication was changed a second time when he moved to Minnesota, increasing his chances for a seizure even more. That made his decision to drive the evening of Dec. 2, 2016, "grossly negligent," according to the attorney's office.

Hayes wound up having a seizure behind the wheel and blacking out, so he doesn't remember the crash, according to his testimony in court Monday, the attorney's office said.

He was driving his tan Chevy Malibu westbound on I-494 in Bloomington near the Minneapolis-St. Paul International Airport when he suddenly pulled over to the right shoulder, made a U-turn, and started heading eastbound in the west lane just east of the 24th Avenue exit.

He eventually collided head-one with a blue Jeep Cherokee. Payton Bailey, 2, was among the passengers in the Jeep. The toddler died about a week after the crash. His mother, Dylan Bailey, and grandmother, Dawn Chiodo, were also in the vehicle, the attorney's office reported. Both died the night of the wreck.

The family members had just left the airport, where they'd picked up Olivia and Jennifer Nord…
Hayes was observed suffering a seizure at the scene of the crash and was given anti-seizure medication, court documents say. A blood test revealed no alcohol in his system at the time. 

He'd failed to disclose his condition when he applied for Minnesota driver's licences during the past five years — a requirement under state law, according to court documents.

A review of Hayes' medical records indicates he has suffered from epilepsy since he was 16 years old. Investigators also discovered that Hayes had been involved in three previous crashes since 2014, at least one of which involved a seizure, court documents say.


PANDAS stories

Vanessa Baier's 4-year-old daughter Alexia was in full-on crisis.

"I just kept thinking, 'What's going on with my child?'" Vanessa Baier told "20/20" while fighting back tears.

Alexia had been breaking out into erratic, explosive behavior that would appear completely out of left field.

"It was just swings that were very dramatic and uncalled for, for the situation," her father, Brian Baier, told "20/20."

"There have been times where [her tantrum] was an hour and a half, two hours," Vanessa Baier said.

Alexia, now 8, wasn't always so volatile. Her mother, a special-needs teacher; her father, an accountant; and their oldest daughter, Kyla, had all welcomed a very typical baby girl to their loving home outside Chicago.

"She had such a fun personality. She was always laughing, smiling," Vanessa Baier said.

And as Alexia began attending preschool, her mom said her daughter was excited and loved her new friends and teachers.

"She was on track. She was even advanced in different areas. She was just a typical 4-year-old," AJ McCree, the school's principal, told "20/20."

But in the winter of 2014, Alexia got sick. A doctor diagnosed her with strep throat.

"That was the first time she ever had strep throat," Vanessa Baier said. "No big deal, just run-of-the-mill strep throat."

Alexia was prescribed a typical course of antibiotics, but as the infection disappeared, her bubbly personality began to change.

"It was less than two days later. It was defiance and OCD [behavior]. She just all of a sudden seemed angry," her mother said.

"It really came to my attention that something was off when Lexi would start to destroy the classroom," McCree said, referring to Alexia. "It was a lot of screaming, a lot of hitting and kicking adults."…

"We're trying to team together to try to figure out what's going on, but at the same time it's like this just isn't making sense," Vanessa Baier said. "I don't know how to de-escalate my own child."

This was especially troubling to Vanessa Baier because de-escalating children in crisis is part of her responsibility as a special-needs teacher.

But things became dire when Alexia's prolonged tantrums turned into threats toward her family and herself.

"Telling my 6-year-old (Kyla), 'You have to stay in your bedroom because I don't know what your sister is capable of,' is heartbreaking. She knew the whole time. She had told me, 'Something's wrong with Alexia's brain.' She knew," Vanessa Baier said. "'Something happened because this is not my sister.'"

Vanessa Baier said Alexia knew something was wrong too.

"She would cry and say, 'Mommy, why can't I be good? I just want to be good.' That broke my heart," she said…

Alexia had unbuckled her car seat and started rummaging through her mother's purse. Vanessa Baier pulled over and turned to her daughter.

"As I picked my head up, she was stabbing me in the eye with my mascara wand. I was scared. I was scared for all of our safety," Vanessa Baier said. "This isn't normal, you know. Four-year-olds don't unbuckle their seat belts in the car to stab their mommy in the eye with a mascara wand all over a milkshake."

She called her husband, who was at work.

"He immediately dropped what he was doing and left work. I said, 'You need to stay on the phone this entire time, just in case. If something happens, you need to call 911,'" Vanessa Baier said. "I didn't feel that I was safe, that Kyla was safe or that Alexia was even safe from herself."

Out of options, the desperate parents did what had been previously unthinkable to them: They had Alexia admitted to a psychiatric hospital.

"[It was] the hardest nine days of my life," Vanessa Baier said through tears. "We could only see her for an hour a day. She was allowed to call us once a day. ... For a 4-year-old, those phone calls that she got once a day, she spent crying to me, 'Why did you leave me? I need you. I need you to come back.'"…

About 400 miles away from the Baiers, another family's child was suffering in suburban Minnesota.

Natalie and Brian Barnes' son Parker had been having seizures and dealing with debilitating anxiety, rage and depression for months.

"I would liken it to an abduction. Something came in the window and stole our child and left behind this shell. Our kid is gone!" Brian Barnes told "20/20."

The Barnes family's lives changed in April 2017 when Parker, the oldest of four children, was just 10. He was a rambunctious and outgoing boy. But midway through fourth grade, Parker began acting differently, with odd tics and strange moodiness.

Then one day, his brother Stetson was heading to the family's upstairs bathroom and ran into Parker.

"I'm like, 'Mom! Dad! He's going to stab himself!'" Stetson told "20/20."

"I ran up to the bathroom and there he stood with a knife in his hand," Natalie Barnes told "20/20."

"Bawling uncontrollably," Brian Barnes said.

"He was, like, in a trance, and I just grabbed the knife…

An emergency room doctor recommended that Parker be evaluated by a psychiatrist, and just like the Baier family, the Barneses checked Parker into a psychiatric hospital.

"That was a nightmare," Parker, now 12, told "20/20." "That was like a prison for children 'cause all the children didn't want to see their families, because they were all so like angry or mean or something."

As Parker was evaluated, one doctor became struck by one factor in his case. She learned that Parker's symptoms had first begun months earlier, when he had been diagnosed with strep throat.

"She said he might have something called PANDAS, and we're like, 'PANDAS?'" Natalie Barnes said…

Brian and Natalie Barnes took Parker to more than a dozen doctors in Minnesota looking for a remedy for PANDAS, showing them videos of his erratic behavior. They got limited results.

"I would have to say most the time they would go, 'Hmm.' Nobody ever said, 'O.M.G., I can't believe he's doing that. Let's figure it out!'" Brian Barnes said.

Their quest for better treatment took them to Dr. Beth Latimer, a pediatric neurologist in Washington D.C. who takes on the PANDAS cases that many other doctors don't.

"I have felt tremendous amount of responsibility for these kids," Latimer told "20/20." "I've seen people move from one side of the country to the other. Parents get divorced because they can't deal with the trauma of this illness."…

As a young girl, Kathryn Ulicki, now 12, suddenly started exhibiting bizarre behavior.

Rather than breaking out into screaming fits or convulsions, Kathryn suddenly feared that she would suffer an allergic reaction or be poisoned from food. So one day, she just stopped eating.

"I had no idea what was going on," Michael Ulicki, her father, told "20/20."

Kathryn had a longstanding allergy to sesame, but this level of paranoia when it came to eating was new. Kathryn said she wanted to eat and drink but feared that she would have an allergic reaction.

"I was, like, scared to swallow my own saliva, so I would just spit the whole entire day," Kathryn told "20/20."

It's not clear whether Kathryn had an undetected strep infection or whether the onset of symptoms was triggered by a different infection, according to her parents. But within two weeks of an onset of symptoms, Kathryn, then 9, went into the hospital for dehydration. She stayed there for three weeks. She had a feeding tube for nearly two months. Things only got worse…

But the parents of children believed to have PANDAS say their question is: what do they do if their child does not get better and how long are they supposed to wait?

As Kathryn progressed, the Barnes family continued searching for answers. Natalie and Brian Barnes had every intention of putting Parker through the intensive treatment that Latimer had suggested -- plasmapheresis, a process to remove the antibodies attacking his immune system -- even though it would mean Parker would have to spend a week at a hospital in the intensive care unit…

He and Natalie Barnes began yet another search for another doctor. They were finally able to get an appointment for later this month with a specialist who, they say, is open to the idea of giving Parker plasmapheresis in Minnesota. They estimated that the cost would be as much as $100,000 for treatment and follow-ups.

It was just a few years ago that Alexia was put into a psychiatric ward and prescribed medication for bipolar disorder and schizophrenia. Now at 8 years old, she is thriving. She was chosen out of her entire school as the "Student of the Month" for positive behavior.

Her family said Alexia had responded well to a different antibiotic than the one she'd been given when she first had strep, along with a few other medications. Her parents also are trying everything they can to keep her compromised immune system away from bacteria and infection…

Vanessa Baier said Alexia still has "flare-ups" and they expect to still have struggles with Alexia's health going forward. She has had 15 doses of antibiotics in the last three years.