Tuesday, May 30, 2017

Characteristics associated with quality of life among people with drug-resistant epilepsy.

Ridsdale L, Wojewodka G, Robinson E, Landau S, Noble A, Taylor S, Richardson M, Baker G, Goldstein LH; SMILE Team.. Characteristics associated with quality of life among people with drug-resistant epilepsy. J Neurol. 2017 May 26. doi:10.1007/s00415-017-8512-1. [Epub ahead of print]

Quality of Life (QoL) is the preferred outcome in non-pharmacological trials, but there is little UK population evidence of QoL in epilepsy. In advance of evaluating an epilepsy self-management course we aimed to describe, among UK participants, what clinical and psycho-social characteristics are associated with QoL. We recruited 404 adults attending specialist clinics, with at least two seizures in the prior year and measured their self-reported seizure frequency, co-morbidity, psychological distress, social characteristics, including self-mastery and stigma, and epilepsy-specific QoL (QOLIE-31-P). Mean age was 42 years, 54% were female, and 75% white. Median time since diagnosis was 18 years, and 69% experienced ≥10 seizures in the prior year. Nearly half (46%) reported additional medical or psychiatric conditions, 54% reported current anxiety and 28% reported current depression symptoms at borderline or case level, with 63% reporting felt stigma. While a maximum QOLIE-31-P score is 100, participants' mean score was 66, with a wide range (25-99). In order of large to small magnitude: depression, low self-mastery, anxiety, felt stigma, a history of medical and psychiatric comorbidity, low self-reported medication adherence, and greater seizure frequency were associated with low QOLIE-31-P scores. Despite specialist care, UK people with epilepsy and persistent seizures experience low QoL. If QoL is the main outcome in epilepsy trials, developing and evaluating ways to reduce psychological and social disadvantage are likely to be of primary importance. Educational courses may not change QoL, but be one component supporting self-management for people with long-term conditions, like epilepsy.

The clinicians performed this work to describe what clinical and psycho–social characteristics are associated with quality of Life (QoL) among UK participants in advance of evaluating an epilepsy self–management course. Developing and evaluating ways to reduce psychological and social disadvantage are likely to be of primary importance if QoL is the main outcome in epilepsy trials. Educational courses may not change QoL, but be one component supporting self–management for people with long–term conditions, such as epilepsy.


The clinicians enrolled 404 adults attending specialist clinics, with at least two seizures in the prior year and measured their self-reported seizure frequency, co-morbidity, psychological distress, social characteristics, including self-mastery and stigma, and epilepsy-specific QoL (QOLIE-31-P).


In this study, mean age was 42 years, 54% were female, and 75% white.
Since diagnosis, median time was 18 years, and 69% experienced ≥10 seizures in the prior year.
About half (46%) reported additional medical or psychiatric conditions, 54% reported current anxiety and 28% reported current depression symptoms at borderline or case level, with 63% reporting felt stigma.
Participants’ mean score was 66, with a wide range (25–99) while a maximum QOLIE-31-P score is 100.
In order of large to small magnitude: depression, low self-mastery, anxiety, felt stigma, a history of medical and psychiatric comorbidity, low self-reported medication adherence, and greater seizure frequency were correlated with low QOLIE-31-P scores.
UK people with epilepsy and persistent seizures experience low QoL despite specialist care.


Cerebrospinal fluid procalcitonin as a biomarker of bacterial meningitis in neonates

Reshi Z, Nazir M, Wani W, Malik M, Iqbal J, Wajid S. Cerebrospinal fluid procalcitonin as a biomarker of bacterial meningitis in neonates. J Perinatol. 2017 May 25. doi: 10.1038/jp.2017.73. [Epub ahead of print]

The objective of the study was to study the performance of cerebrospinal fluid (CSF) procalcitonin as a marker for bacterial meningitis in neonates, and to determine its optimal 'cutoff' in CSF that can be called significant for the diagnosis.
Neonates qualifying for lumbar puncture were prospectively studied. Procalcitonin and established CSF parameters were recorded.
At a cut-off value of 0.33 ng ml-1, CSF procalcitonin had a sensitivity of 0.92, specificity of 0.87, with positive and negative likelihood ratios of 7.13 and 0.092, respectively. The area under the curve for different CSF parameters was: 0.926 (0.887 to 0.964) (P<0.001) for procalcitonin, 0.965 (0.956 to 0.974) for total leukocyte count, 0.961 (0.94 to 0.983) for neutrophil count, 0.874 (0.825 to 0.923) for protein, 0.946 (0.914 to 0.978) for sugar and 0.92 (0.955 to 0.992) for CSF:serum sugar ratio. The lumbar puncture was traumatic in 36 (21.4%) patients; out of these 15 (41.7%) had bacterial meningitis and 21 (58.3%) had no meningitis. In traumatic lumbar tap group, the median (IQR) CSF procalcitonin in patients with and without meningitis was 1.41 (0.32-3.42) ng/ml and 0.21(0.20-0.31) ng/ml respectively (p<0.05).
Procalcitonin measurement has diagnostic efficiency similar to the established CSF markers. Routine assessment of procalcitonin in clean non-contaminated CSF may not yield additional information, but it may have clinical utility in situations where diagnosis of meningitis is in dilemma, as in the case of blood contamination of CSF in traumatic lumbar punctures.

Courtesy of:  https://www.mdlinx.com/neurology/medical-news-article/2017/05/30/bacterial-meningitis-neonates-procalcitonin/7190689/?category=latest&page_id=2

Friday, May 26, 2017

When disease names honor the infamous

By Dr. Robert Marion

The field of medicine is littered with eponyms that celebrate physicians who first described syndromes, signs, surgical procedures and anatomic structures. Though we use these eponyms every day, we rarely take the time to consider the lives of the people behind the names. Recently, while evaluating a five-year-old named Ben, I was forced to stop and think about the contributions to the world made by the people behind one of these eponyms. It’s a story worth telling.

Ben, who had been referred to me by an ophthalmologist, had been in excellent health until two months before, when he began bumping into walls, a problem that was worse at night. The ophthalmologist diagnosed bilateral optic atrophy and noted early signs of retinitis pigmentosa. Because of these findings, he’d sent the boy to me, asking if I could find a genetic basis for his problems.

In the three weeks between his eye exam and his visit to my office, Ben’s parents noticed another problem. “He’s become unsteady,” his father told me. “He keeps falling. It seems to be getting worse.”

Though on physical exam Ben seemed otherwise fine, he clearly had ataxia, a wide-based gait, difficulty walking and a movement disorder. In trying to put the pieces of his puzzle together, I thought of a condition I’d learned about during my residency from Dr. Isabelle Rapin, one of my mentors. At that time, the condition was known as Hallervorden-Spatz disease.

I remembered that Hallervorden-Spatz was a neurodegenerative disease in which the accumulation of iron in the basal ganglia and other parts of the brain caused a steady downhill course leading to dysarthria, rigidity of the limbs, dementia and ultimately death, usually by age 25. It was a horrible disorder, and although I prayed that I was wrong, I knew in my heart that Ben probably had this or some other terrible progressive condition.

After finishing my exam, I excused myself and went into the consultation room. It had been years since I’d seen a patient with this condition, and I needed to check how to confirm the diagnosis. I navigated to the website for OMIM (Online Mendelian Inheritance in Man) and typed in the name. It was then that I came to consider the men who had originally described this condition.

In OMIM, rather than Hallervorden-Spatz disease, the condition was called pantothenate kinase-related neurodegeneration, a term that does not exactly roll off the tongue (not that “Hallervorden-Spatz disease” does either). In reading further, I came across this paragraph:

“Julius Hallervorden (1882-1965)...made important contributions to neurologic science.... However...his active involvement in a euthanasia program in Germany during World War II raises serious questions about the moral obligations of medical science.... Hallervorden’s enthusiastic encouragement of the killings and the other aspects that led to dehumanization of...the victims...was detailed by [M.] Shevell.... In responding...several authors...suggested that Hallervorden’s name should be removed from this disorder.”

Hallervorden was a Nazi. In reading further, I found that he admitted that the nearly 700 brains he studied following 1940, essentially the entirety of the work that formed the basis of his “important contributions to neurologic science,” all came from victims of euthanasia performed on Nazi prisoners; he had personally presided over the killing of more than 60 children at the Brandenburg Psychiatric Institution on October 28, 1940.

And Hallervorden wasn’t the only physician whose work for the Third Reich resulted in a discovery that earned him an eponym. Hugo Spatz, Hallervorden’s research partner, was the director of the brain research institute that “collaborated with the killing institute at Brandenburg-Gorden” to provide “hundreds of brains from the mentally ill of all ages.” Friedrich Wegener (of Wegener’s granulomatosis) was, “at least at some point of his career, a follower of the Nazi regime...was wanted by Polish authorities and...worked in close proximity to the genocide machinery in Lodz.” Hans Reiter (of Reiter’s syndrome), “a physician leader of the Nazi party, authorized medical experiments on concentration camp prisoners.” And Hans Asperger “was an ambitious opportunist who uncritically spouted Nazi ideology in his first public lecture on autism in 1938, and enthusiastically signed letters ‘Heil Hitler!’ Most devastatingly, he signed a letter...condemning a little girl with encephalitis...to death in a Vienna rehab facility that had been converted into a killing center.”

Unfortunately, genetic testing revealed that Ben had mutations in both copies of PANK2, the gene known to be associated with pantothenate kinase-related neurodegeneration, confirming his diagnosis. A month after our initial visit, with these results in hand, I sat and explained the condition to Ben’s parents. The discussion was difficult; by the end of the session, all of us were in tears. However, at no time during that visit were the names Julius Hallervorden and Hugo Spatz mentioned. Having read about them, I’ve erased the eponym bearing their names from my database.


Cannabidiol in Dravet syndrome

Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S; Cannabidiol in Dravet Syndrome Study Group.. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25;376(21):2011-2020.

The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome.
In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period.
The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, -22.8 percentage points; 95% confidence interval [CI], -41.1 to -5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient's overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group.

Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375 .).

Courtesy of a colleague

Pain in children and adolescents with cerebral palsy

Westbom L, Rimstedt A, Nordmark E. Assessments of pain in children and adolescents with cerebral palsy: a retrospective population-based registry study. Dev Med Child Neurol. 2017 May 16. doi: 10.1111/dmcn.13459. [Epub ahead of print]

To explore pain screening in CPUP, a follow-up surveillance programme for people with cerebral palsy (CP), specifically to describe reported pain prevalence, localizations, patterns of distribution; to compare with studies using psychometrically sound assessment instruments; and to assess agreement between pain documented in CPUP and medical records.
Registry study of a population with CP, born 1993 to 2008, living in Skåne, Sweden in 2013. Descriptive data, cross-tabulations, and chi-square tests to characterize and compare the study groups. Kappa analysis to test the concordance between register and medical record reports on pain.
Pain was reported by 185 out of 497 children (37%; females 40%, males 35%). Level V in both Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) was associated with highest prevalence of pain (50% and 54%), and level I with lowest prevalence of pain (30% and 32%). Pain was most frequent in dyskinetic CP (46%) and least frequent in unilateral spastic CP (33%). Feet and knees were the dominant localizations. Fair-moderate agreement (kappa 0.37, prevalence-adjusted bias-adjusted kappa [PABAK] 0.44) was found between documented pain in CPUP and medical records, although more seldom recognized in medical records.

The distribution of pain between CP subtypes, functional levels, sex, and age in CPUP is concordant with previous population-based studies, indicating the validity of the CPUP pain screening. Despite this, further clinical evaluation with extended pain assessments and pain management were largely neglected in children reporting chronic pain.

Courtesy of:  https://www.mdlinx.com/neurology/medical-news-article/2017/05/26/pain-cerebral-palsy-children-and-adolescents/7172299/?category=latest&page_id=2

Perampanel in the general population and in people with intellectual disability

Rohit Shankar,  Rohit Shankar, Rohit Shankar, William Henley, Tim Wehner, Carys Wiggans, Brendan McLean, Adrian Pace, Monica Mohan, Martin Sadler, Zoe Doran, Sharon Hudson, Jon Allard, Josemir W. Sander.   Perampanel in the general population and in people with intellectual disability: Differing responses.  Seizure.  In press.

•No large scale comparative study has yet been conducted for any AED in people with ID.
•The UK Ep-ID Register looks at outcomes of different AEDs beginning with PER.
•People with severe ID had better retention & efficacy than mild ID/general population.
•There is no evidence of any obvious concerns to prescribe PER in people with ID.
•Titration and past mental or behavioural issues can influence retention.

There is a shortfall of suitably powered studies to provide evidence for safe prescribing of AEDs to people with Intellectual Disability (ID). We report clinically useful information on differences in response to Perampanel (PER) adjunctive treatment for refractory epilepsy between ID sub-groups and general population from the UK Ep-ID Research Register.

Pooled retrospective case notes data of consented people with epilepsy (PWE) prescribed PER from 6 UK centres was classified as per WHO guidance into groups of moderate -profound ID, mild ID and General population. Demographics, concomitant AEDs, starting and maximum dosage, exposure length, adverse effects, dropout rates, seizure type and frequency were collected. Group differences were reported as odds ratios estimated from univariable logistic regression models.

Of the 144 PWE (General population 71, Mild ID 48, Moderate to profound ID 48) examined the association between withdrawal and ID type was marginally statistically significant (p = 0.07). Moderate to profound ID PWE were less likely to come off PER compared to mild ID (OR = 0.19, CI = 0.04–0.92, p = 0.04). Differences in mental health side effects by groups was marginally statistically significant (p = 0.06). Over 50% seizure improvement was seen in 11% of General population, 24% mild ID and 26% Moderate to profound ID.


PER seems safe in PWE with ID. It is better tolerated by PWE with Moderate to profound ID than PWE with higher functioning. Caution is advised when history of mental health problems is present. The standardised approach of the Ep-ID register UK used confirms that responses to AEDs by different ID groups vary between themselves and General population.

Courtesy of  https://www.mdlinx.com/neurology/medical-news-article/2017/05/26/epilepsy-intellectual-disability-uk-ep-id/7171347/?category=latest&page_id=1

Thursday, May 25, 2017

This isn't the life I ordered

“This Isn’t the Life I Ordered” was the title of a class my daughter attended the other night. Just hearing the title jolted me back to reality.

Life is not a Disney story and God is not our fairy godmother making all of our wishes come true. As soon as we let go of that fantasy, we can come to terms with what we have been given.

I don’t mean this in a begrudging sense; I mean that we can truly recognize all the good the Almighty has given us and stop longing for something else.

How often do we say that this isn’t how we imagined our lives would turn out? Rarely is that stated with awe and wonder. It’s said too frequently with regret and disappointment.

Life is so much better in our fantasies, our imaginings, our dreams than it is in our very real here and now (or so we tell ourselves).

But that’s actually impossible. Because it violates so many basis tenets of Jewish understanding, beginning with the fact that the Almighty loves us and wants to give us good. And on to the idea that He could give us anything He (or we) wants, and if He thought it was to our benefit, we would have it.

It must be – wait for it, drum roll please – that my dream of how my life would be improved is just flat-out wrong. Wow.

Many of us know that. We understand that God is all kindness and all good. We recognize that the Almighty doesn’t have a finite pie to be split among all his many supplicants. He could give us anything. If we don’t have it, not only do we not need it, it may in fact be damaging to us.

We are able to tone down the voice but it’s still whispering, “This isn’t the life I ordered.” It sneaks in and catches us unawares and drags us down.

We need to fight fire with fire. “You’re right,” we must respond. “It isn’t the life I ordered. But it’s the one I’ve got. And my job is to make the best of it.”

In fact, if I’m really attuned to the workings of my Creator, I’d acknowledge that not only is it the one I’ve got but because of the Source, it must actually be better than the life of my dreams.

It’s hard to get there. It’s even harder to stay there! It’s hard to accept this. It’s hard to let go – of long-held imaginings, of the belief that we know best.

But the recognition that the life we have is superior to the one we ordered is freeing and empowering – and can lead to joy, born of the confidence that the Almighty who loves me and runs the show has given me the perfect tools to lead the best life possible. Wasn’t that what I was ordering anyway?


Wednesday, May 24, 2017

When your child is a psychopath

Samantha’s parents, Jen and Danny, adopted Samantha when she was 2. They already had three biological children, but they felt called to add Samantha (not her real name) and her half sister, who is two years older, to their family. They later had two more kids.

From the start, Samantha seemed a willful child, in tyrannical need of attention. But what toddler isn’t? Her biological mother had been forced to give her up because she’d lost her job and home and couldn’t provide for her four children, but there was no evidence of abuse. According to documentation from the state of Texas, Samantha met all her cognitive, emotional, and physical milestones. She had no learning disabilities, no emotional scars, no signs of ADHD or autism. 

But even at a very young age, Samantha had a mean streak. When she was about 20 months old, living with foster parents in Texas, she clashed with a boy in day care. The caretaker soothed them both; problem solved. Later that day Samantha, who was already potty trained, walked over to where the boy was playing, pulled down her pants, and peed on him. “She knew exactly what she was doing,” Jen says. “There was an ability to wait until an opportune moment to exact her revenge on someone.”

When Samantha got a little older, she would pinch, trip, or push her siblings and smile if they cried. She would break into her sister’s piggy bank and rip up all the bills. Once, when Samantha was 5, Jen scolded her for being mean to one of her siblings. Samantha walked upstairs to her parents’ bathroom and washed her mother’s contact lenses down the drain. “Her behavior wasn’t impulsive,” Jen says. “It was very thoughtful, premeditated.”

Jen, a former elementary-school teacher, and Danny, a physician, realized they were out of their depth. They consulted doctors, psychiatrists, and therapists. But Samantha only grew more dangerous. They had her admitted to a psychiatric hospital three times before sending her to a residential treatment program in Montana at age 6. Samantha would grow out of it, one psychologist assured her parents; the problem was merely delayed empathy. Samantha was impulsive, another said, something that medication would fix. Yet another suggested that she had reactive attachment disorder, which could be ameliorated with intensive therapy. More darkly—and typically, in these sorts of cases—another psychologist blamed Jen and Danny, implying that Samantha was reacting to harsh and unloving parenting.

One bitter December day in 2011, Jen was driving the children along a winding road near their home. Samantha had just turned 6. Suddenly Jen heard screaming from the back seat, and when she looked in the mirror, she saw Samantha with her hands around the throat of her 2-year-old sister, who was trapped in her car seat. Jen separated them, and once they were home, she pulled Samantha aside.

“What were you doing?,” Jen asked.

“I was trying to choke her,” Samantha said.

“You realize that would have killed her? She would not have been able to breathe. She would have died.”

“I know.”

“What about the rest of us?”

“I want to kill all of you.”

Samantha later showed Jen her sketches, and Jen watched in horror as her daughter demonstrated how to strangle or suffocate her stuffed animals. “I was so terrified,” Jen says. “I felt like I had lost control.”

Four months later, Samantha tried to strangle her baby brother, who was just two months old.

Jen and Danny had to admit that nothing seemed to make a difference—not affection, not discipline, not therapy. “I was reading and reading and reading, trying to figure out what diagnosis made sense,” Jen tells me. “What fits with the behaviors I’m seeing?” Eventually she found one condition that did seem to fit—but it was a diagnosis that all the mental-health professionals had dismissed, because it’s considered both rare and untreatable. In July 2013, Jen took Samantha to see a psychiatrist in New York City, who confirmed her suspicion.

“In the children’s mental-health world, it’s pretty much a terminal diagnosis, except your child’s not going to die,” Jen says. “It’s just that there’s no help.” She recalls walking out of the psychiatrist’s office on that warm afternoon and standing on a street corner in Manhattan as pedestrians pushed past her in a blur. A feeling flooded over her, singular, unexpected. Hope. Someone had finally acknowledged her family’s plight. Perhaps she and Danny could, against the odds, find a way to help their daughter. 

Samantha was diagnosed with conduct disorder with callous and unemotional traits. She had all the characteristics of a budding psychopath.

Pssychopaths have always been with us. Indeed, certain psychopathic traits have survived because they’re useful in small doses: the cool dispassion of a surgeon, the tunnel vision of an Olympic athlete, the ambitious narcissism of many a politician. But when these attributes exist in the wrong combination or in extreme forms, they can produce a dangerously antisocial individual, or even a cold-blooded killer. Only in the past quarter century have researchers zeroed in on the early signs that indicate a child could be the next Ted Bundy.

Researchers shy away from calling children psychopaths; the term carries too much stigma, and too much determinism. They prefer to describe children like Samantha as having “callous and unemotional traits,” shorthand for a cluster of characteristics and behaviors, including a lack of empathy, remorse, or guilt; shallow emotions; aggression and even cruelty; and a seeming indifference to punishment. Callous and unemotional children have no trouble hurting others to get what they want. If they do seem caring or empathetic, they’re probably trying to manipulate you.

Researchers believe that nearly 1 percent of children exhibit these traits, about as many as have autism or bipolar disorder. Until recently, the condition was seldom mentioned. Only in 2013 did the American Psychiatric Association include callous and unemotional traits in its diagnostic manual, DSM-5. The condition can go unnoticed because many children with these traits—who can be charming and smart enough to mimic social cues—are able to mask them.


See: http://childnervoussystem.blogspot.com/2016/03/child-of-rage.html

Tuesday, May 23, 2017

Grandma knows best

Sicherman N, Loewenstein G, Tavassoli T, Buxbaum JD. Grandma knows best: Family structure and age of diagnosis of autism spectrum disorder. Autism. 2016 Dec 1:1362361316679632. doi: 10.1177/1362361316679632. [Epub ahead of print]

This pilot study estimates the effects of family structure on age of diagnosis, with the goal of identifying factors that may accelerate or delay diagnosis. We conducted an online survey with 477 parents of children with autism. In addition, we carried out novel, follow-up surveys of 196 "friends and family," who were referred by parents. Family structure and frequency of interactions with family members have significant effects on age of diagnosis (p < 0.05). In all, 25% of parents report that other individuals indicated that their child might have a serious condition before they themselves suspected it. Moreover, around 50% of friends and family report that they suspected that the child had a serious condition before they were aware that either parent was concerned, suggesting that the clues were there to see, especially for experienced viewers. While half of those individuals shared their concerns with the parents, the other half either did not raise any concern (23%) or just "hinted" at their concern (27%). Among children with siblings, children with an older sibling are diagnosed approximately 10 months earlier (p < 0.01) than those without, and children with no siblings were diagnosed 6-8 months earlier than children with siblings (p < 0.01). Interestingly, frequent interactions with grandparents, especially grandmothers, significantly lowered the age of diagnosis by as much as 5 months (p < 0.05). While this pilot study requires replication, the results identify potential causes for accelerated or delayed diagnosis, which if better understood, could ultimately improve age of diagnosis and treatment, and hence outcomes.

Kids with autism who spend a lot of time with their grandmothers may get diagnosed with the disorder at a younger age, a small study suggests.

“This finding is incredibly important, as these individuals have the potential to lower the age of diagnosis,” senior study author Joseph Buxbaum of the Icahn School of Medicine at Mount Sinai in New York said by email. “Early diagnosis means early intervention, which is critical for improving treatment outcomes.”

Even though autism spectrum disorder (ASD) may be identified starting when kids are around 2 years old, many children are not formally diagnosed until they are closer to 4, the researchers note in the journal Autism, online February 8. The earlier autism is caught and treated, the better, because younger kids have more adaptable brains that may respond more to therapy than older children.
In the current study, an online survey of parents of children with autism as well as some friends and family members, parents reported about 25 percent of the time that another person close to the child noticed signs of autism first.

Kids in the study were diagnosed with autism when they were about 40 months old on average. When they regularly spent time with their grandmothers, however, they typically were diagnosed about 5 months sooner.

“Around 50 percent of friends and family noticed something was wrong with the child before they were aware that the parents themselves suspected something,” lead study author Nachum Sicherman of Columbia University in New York said by email…

Children without siblings were diagnosed with autism about six to eight months earlier on average than kids with brothers or sisters living in the household at the time of their diagnosis, the study found.

Birth order also matters. Kids with older siblings get diagnosed about nine to 10 months sooner than children who only have younger brothers and sisters.

When parents said another adult close to the child first identified the possibility of autism, that person was a maternal grandmother 27 percent of the time and a teacher in 24 percent of cases…

“Parents need to be open to concerns from their family members, including their parents, regarding their children,” Frazier, who wasn’t involved in the study, said by email. “The more eyes the better, and this is especially true in situations where the child with possible difficulties is the older child with younger siblings.”


Lacosamide and status epilepticus

Strzelczyk A, Zöllner JP, Willems LM, Jost J, Paule E, Schubert-Bast S, Rosenow F, Bauer S. Lacosamide in status epilepticus: Systematic review of current evidence. Epilepsia. 2017 Mar 11. doi: 10.1111/epi.13716. [Epub ahead of print]

The intravenous formulation of lacosamide (LCM) and its good overall tolerability and safety favor the use in status epilepticus (SE). The aim of this systematic review was to identify and evaluate studies reporting on the use of LCM in SE.
We performed a systematic literature search of electronic databases using a combined search strategy from 2008 until October 2016. Using a standardized assessment form, information on the study design, methodologic framework, data sources, efficacy, and adverse events attributed to LCM were extracted from each publication and systematically reported.
In total, 522 SE episodes (51.7% female) in 486 adults and 36 children and adolescents were evaluated with an overall LCM efficacy of 57%. Efficacy was comparable between use in nonconvulsive (57%; 82/145) and generalized-convulsive (61%; 30/49; p = 0.68) SE, whereas overall success rate was better in focal motor SE (92%; 34/39, p = 0.013; p < 0.001). The efficacy with later positioning of LCM decreased from 100% to 20%. The main adverse events during treatment of SE are dizziness, abnormal vision, diplopia, and ataxia. Overall, lacosamide is well tolerated and has no clinically relevant drug-drug interactions.
The available data regarding the use of LCM in SE are promising, with a success rate of 57%. The strength of LCM is the lack of interaction potential and the option for intravenous use in emergency situations requiring rapid uptitration.

Misra UK, Dubey D, Kalita J. A randomized controlled trial of lacosamide versus sodium valproate in status epilepticus. Epilepsia. 2017 Feb 18. doi:10.1111/epi.13706. [Epub ahead of print]

To compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)-resistant status epilepticus (SE).
Patients with LOR-resistant SE were randomized to intravenous LCM 400 mg at a rate of 60 mg/kg/min or SVA 30 mg/kg at a rate of 100 mg/min. The SE severity score (STESS), duration of SE and its etiology, and magnetic resonance imaging (MRI) findings were noted. Primary outcome was seizure cessation for 1 h, and secondary outcomes were 24 h seizure remission, in hospital death and severe adverse events (SAEs).
Sixty-six patients were included, and their median age was 40 (range 18-90) years. Thirty-three patients each received LCM and SVA. Their demographic, clinical, STESS, etiology, and MRI findings were not significantly different. One hour seizure remission was not significantly different between LCM and SVA groups (66.7% vs. 69.7%; p = 0.79). Twenty-four hour seizure freedom was higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%), but this difference was not statistically significant. Death (10 vs. 12) and composite side effects (4 vs. 6) were also not significantly different in LCM and SVA groups. LCM was associated with hypotension and bradycardia (one patient), and SVA with liver dysfunction (six patients).
In LOR-resistant SE patients, both LCM and SVA have comparable efficacy and safety. SVA resulted in slightly better 24 h seizure remission.

Verrotti A, Ambrosi M, Pavone P, Striano P. Pediatric status epilepticus: improved management with new drug therapies? Expert Opin Pharmacother. 2017 May 19:1-10. doi:10.1080/14656566.2017.1323873. [Epub ahead of print]

Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications. Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed. Expert opinion: In early SE in children, in the prehospital setting, rectal diazepam or buccal midazolam are efficacious drugs; whereas in the hospital setting, intravenous lorazepam or diazepam are indicated. As regard estabilished stage of SE, in addition to the 'classic' compounds, such as phenytoin and phenobarbital, other drugs such as valproic acid, levetiracetam and lacosamide have been demonstrated efficacious. Treatment recommendations of refractory SE depend on retrospective case series and uncontrolled studies. We reported experiences about the use of midazolam, propofol, ketamine and lidocaine. They could be a valid option, but further prospective studies are necessary. Over the last few decades, important advances in basic mechanisms underlying refractory SE have been achieved, but few data are available regarding management of these stages.

Bauer S, Willems LM, Paule E, Petschow C, Zöllner JP, Rosenow F, Strzelczyk A.The efficacy of lacosamide as monotherapy and adjunctive therapy in focal epilepsy and its use in status epilepticus: clinical trial evidence and experience. Ther Adv Neurol Disord. 2017 Feb;10(2):103-126.

Lacosamide (LCM) is approved for anticonvulsive treatment in focal epilepsy and exhibits its function through the slow inactivation of voltage-gated sodium channels (VGSCs). LCM shows comparable efficacy with other antiepileptic drugs (AEDs) licensed in the last decade: in three randomized placebo-controlled trials, significant median seizure reduction rates of 35.2% for 200 mg/day, 36.4-39% for 400 mg/day and 37.8-40% for 600 mg/day were reported. Likewise, 50% responder rates were 38.3-41.1% for 400 mg/day and 38.1-41.2% for 600 mg/day. Similar rates were reported in post-marketing studies. The main adverse events (AEs) are dizziness, abnormal vision, diplopia and ataxia. Overall, LCM is well tolerated and has no clinically-relevant drug-drug interactions. Due to the drug's intravenous availability, its use in status epilepticus (SE) is increasing, and the available data are promising.

Matthieu Perrenoud, Pascal André, Vincent Alvarez, Christine Stähli, Laurent A. Decosterd, Andrea O. Rossetti, Jan Novy.  Intravenous lacosamide in status epilepticus: Correlation between loading dose, serum levels, and clinical response.  Epilepsy research. [Epub ahead of print]

Intravenous lacosamide (LCM) is increasingly used in the treatment of status epilepticus (SE), but optimal loading dose and target serum levels are unclear. We analysed the correlation between LCM serum levels after intravenous loading dose and clinical response.

Materials and methods
Retrospective study in two centres from December 2014 to May 2016 including consecutive SE patients treated with LCM, in which trough serum levels after intravenous loading dose were available. Trough levels were correlated with the loading dose and the clinical response, defined as LCM introduction terminating SE without the need of further treatment. Correlations were adjusted for other SE characteristics.

Among 40 patients, 16 (40%) responded to LCM. LCM serum concentrations within the reference interval (10–20 mg/l) were associated with loading doses of >9 mg/kg (p = 0.003; χ2). However, we observed no difference between LCM serum levels in responders (median 10.4 mg/l) versus non-responders (median 9.5 mg/l; p = 0.36; U-test), even after adjusting for other predictors of clinical outcome (SE severity, aetiology, and number of previous treatment).


High intravenous LCM loading doses ( > 9 mg/kg) were associated with serum levels within the reference interval, there was however no correlation with the clinical response. Prospective studies are needed to evaluate the benefit of increasing the LCM loading dose in SE.

Monday, May 22, 2017

Circadian rhythms in severely brain-injured patients: A clue to consciousness?

Blume C, Lechinger J, Santhi N, Giudice RD, Gnjezda MT, Pichler G, Scarpatetti M, Donis J, Michitsch G, Schabus M. Significance of circadian rhythms in severely brain-injured patients: A clue to consciousness? Neurology. 2017 May 16;88(20):1933-1941.

To investigate the relationship between the presence of a circadian body temperature rhythm and behaviorally assessed consciousness levels in patients with disorders of consciousness (DOC; i.e., vegetative state/unresponsive wakefulness syndrome or minimally conscious state).
In a cross-sectional study, we investigated the presence of circadian temperature rhythms across 6 to 7 days using external skin temperature sensors in 18 patients with DOC. Beyond this, we examined the relationship between behaviorally assessed consciousness levels and circadian rhythmicity.
Analyses with Lomb-Scargle periodograms revealed significant circadian rhythmicity in all patients (range 23.5-26.3 hours). We found that especially scores on the arousal subscale of the Coma Recovery Scale-Revised were closely linked to the integrity of circadian variations in body temperature. Finally, we piloted whether bright light stimulation could boost circadian rhythmicity and found positive evidence in 2 out of 8 patients.

The study provides evidence for an association between circadian body temperature rhythms and arousal as a necessary precondition for consciousness. Our findings also make a case for circadian rhythms as a target for treatment as well as the application of diagnostic and therapeutic means at times when cognitive performance is expected to peak.

Sunday, May 21, 2017

ECT for kids

Seventeen-year-old Jonah Lutz is severely autistic. He's also prone to outbursts of violent behaviour, in which he sometimes hits himself repeatedly.

His mother, Amy, is convinced that if it wasn't for electroconvulsive therapy - ECT - he would now have to be permanently institutionalised for his own safety, and the safety of those around him…

"ECT has been transformative for Jonah's life and for our life," she says. "We went for a period of time - for years and years - where Jonah was raging, often multiple times a day, ferociously. The only reason he's able to be at home with us, is because of ECT."

It's estimated that one in 10 severely autistic children like Jonah violently attack themselves, often causing serious injuries ranging from broken noses to detached retinas. No-one really knows why. Some theories link self-injuring behaviour to anxiety caused by an overload of sensory signals, others to frustration as the autistic child struggles to communicate.

Amy and husband Andy tried countless traditional treatments using medication or behavioural therapy before finally turning to ECT - a treatment that first began to be used on children like Jonah a decade ago, in parts of the US. Each session alleviates his symptoms for up to 10 days at a time - but it's not a cure.

Jonah's doctor, Charles Kellner, ECT director at Mount Sinai Hospital in New York, is so convinced it's effective and safe that he allows Amy to witness the procedure and the BBC to film it.

Prof Kellner says the best way to overcome the negative image of ECT portrayed in popular culture is "to show people what modern ECT is really like, and show them the results with patients like Jonah". Jonah is one of a few hundred children in the US to receive the controversial treatment. He has had about 260 ECT sessions since the age of 11.

"There's a lot of interesting new neural imaging research showing that ECT actually reverses some of the brain problems in the major psychiatric illnesses," Kellner explains, as he makes final checks on the wiring around Jonah's temples.

"We don't know exactly why it works in people with autism and superimposed mood disorders, but we think it probably reregulates the circuits in the brain that are deregulated because of autism."

The modern treatment is carried out under general anaesthetic, with muscle relaxants to prevent violent convulsions. At the flick of a switch, Kellner administers just under an amp of electric current in a series of very short pulses.

Jonah's body begins to shake as the current induces a seizure - ECT specialists think this may "reset" the malfunctioning brain. The convulsions last for about 30 seconds.

Amy is unperturbed by what she sees.

"If a doctor says they need to cut open your child's chest to conduct life-saving surgery, you would allow it. That is more barbaric yet we accept it," she says.

Within an hour Jonah is fully alert. He and his mother head out of the hospital and on to the New York street to find an ice cream parlour…

Because the long-term effects of ECT on children exhibiting self-injuring behaviour are unknown, in some countries - and in a handful of US states - the treatment is not allowed. The UK's National Institute for Health and Care Excellence doesn't recommend ECT for use on under 18s.

But ECT is a well-established treatment in adults for severe, often life-threatening depression. Its use is controversial, though, with memory loss the main acknowledged side-effect. What's disputed is the scale of the memory loss. Studies carried out by ECT doctors suggest lapses are mostly short-term and that memory function soon returns to normal. But opponents of ECT cite surveys claiming to show that more than half of patients suffer serious long-term memory loss.

"It's a traumatic brain injury," says Dr Peter Breggin, a psychiatrist who has long fought the psychiatric establishment, and campaigns for a total ban on ECT. "The electricity not only travels through the frontal lobes - that's the seat of intelligence, and thoughtfulness and creativity and judgment - it also goes through the temporal lobes - the seat of memory. You are damaging the very expression of the personality, the character, the individuality, and even, if you believe in it, the expression of the soul."…

Sofija spent much of her early life suffering neglect and abuse in a Serbian orphanage, before Chad and Kaci adopted her in 2009. They were determined to give her a better life in America, but in 2016 they suffered the heartbreak of institutionalising her again - this time for her own safety.

"She beat herself so bad her nose was busted and bleeding, her lips were busted open and bleeding," Chad explains. "She gave herself a black eye. I was scared of my own daughter."

For six months Sofija received medication and therapy as an in-patient at the renowned Kennedy Krieger Institute in Baltimore, but there was little improvement. During her frequent violent episodes it often took three highly trained care staff - all wearing protective clothing and shielding Sofija with padded mats - to prevent her injuring herself or others.

After exhausting all other options, Sofija's doctors finally agreed to Chad and Kaci's request to give her ECT. Just a month later her behaviour had improved enough for her to return home.

We caught up with the family after six months and more than 30 treatments, and the transformation was remarkable. Sofija was swimming in the family pool and playing with her siblings, and while her violent episodes hadn't disappeared completely, her parents felt they were less intense and more manageable. Sofija was also receiving home schooling in maths and English. "She's sharp as a tack," says Kaci. "The only memory loss that Sofija has had from ECT is she forgets the procedure has actually happened."

ECT for severely self-injuring autistic children like Sofija is still in very limited use, and without a long-term scientific study it remains highly controversial. But even though Sofija is likely to need ECT every week for the foreseeable future, her parents have no regrets - they have their daughter back home…

"It's overwhelming if I think about it," says Kaci, "but what future did she have without it? My hope is she doesn't need it for the rest of her life but at this point I see it like a diabetic needing insulin. It keeps her alive. Literally it keeps her alive and it makes it possible for us to be able to have her in our home living life with our family and enjoying Sofija."


Courtesy of a colleague

HELLP syndrome

The U.S. has the worst rate of maternal deaths in the developed world, and 60 percent are preventable. The death of Lauren Bloomstein, a neonatal nurse, in the hospital where she worked illustrates a profound disparity: The health care system focuses on babies but often ignores their mothers…

Inductions often go slowly, and Lauren’s labor stretched well into the next day. Ennis talked to her on the phone several times: “She said she was feeling okay, she was just really uncomfortable.” At one point, Lauren was overcome by a sudden, sharp pain in her back near her kidneys or liver, but the nurses bumped up her epidural and the stabbing stopped.

Inductions have been associated with higher cesarean-section rates, but Lauren progressed well enough to deliver vaginally. On Saturday, Oct. 1, at 6:49 p.m., 23 hours after she checked into the hospital, Hailey Anne Bloomstein was born, weighing 5 pounds, 12 ounces. Larry and Lauren’s family had been camped out in the waiting room; now they swarmed into the delivery area to ooh and aah, marveling at how Lauren seemed to glow.

Larry floated around on his own cloud of euphoria, phone camera in hand. In one 35-second video, Lauren holds their daughter on her chest, stroking her cheek with a practiced touch. Hailey is bundled in hospital-issued pastels and flannel, unusually alert for a newborn; she studies her mother’s face as if trying to make sense of a mystery that will never be solved. The delivery room staff bustles in the background in the low-key way of people who believe everything has gone exactly as it’s supposed to.

Then Lauren looks directly at the camera, her eyes brimming.

Twenty hours later, she was dead…

Larry Bloomstein’s  first inkling that something was seriously wrong with Lauren came about 90 minutes after she gave birth. He had accompanied Hailey up to the nursery to be weighed and measured and given the usual barrage of tests for newborns. Lauren hadn’t eaten since breakfast, but he returned to find her dinner tray untouched. “I don’t feel good,” she told him. She pointed to a spot above her abdomen and just below her sternum, close to where she’d felt the stabbing sensation during labor. “I’ve got pain that’s coming back.”…

An hour after Hailey’s birth, the reading was 160/95; an hour after that, 169/108. At her final prenatal appointment, her reading had been just 118/69. Obstetrics wasn’t Larry’s specialty[orthopedics], but he knew enough to ask the nurse: Could this be preeclampsia?...

As Larry suspected, Lauren’s blood pressure readings were well past the danger point. What he didn’t know was that they’d been abnormally high since she entered the hospital— 147/99, according to her admissions paperwork. During labor, she had 21 systolic readings at or above 140 and 13 diastolic readings at or above 90, her records indicated; for a stretch of almost eight hours, her blood pressure wasn’t monitored at all, the New Jersey Department of Health later found…

According to Lauren’s records, Vaclavik did order a preeclampsia lab test around 8:40 p.m., but a nurse noted a half-hour later: “No abnormal labs present.” (According to Larry, the results were borderline.) Larry began pushing to call in a specialist. Vaclavik attributed Lauren’s pain to esophagitis, or inflammation of the esophagus, which had afflicted her before, he said in his deposition. Around 10 p.m., according to Lauren’s medical records, he phoned the on-call gastroenterologist, who ordered an X-ray and additional tests, more Dilaudid and different antacids — Maalox and Protonix. Nothing helped.

Meanwhile, Larry decided to reach out to his own colleagues in the trauma unit at Cooper University Hospital in Camden. In his training, perhaps the most important lesson he’d learned was to ask for help: “If there’s a problem, I will immediately get another physician involved.” By chance, the doctor on call happened to be a fairly new mother. As Larry described Lauren’s symptoms, she interrupted him. “You can stop talking. I know what this is.” She said Lauren had HELLP syndrome, an acronym for the most severe variation of preeclampsia, characterized by hemolysis, or the breakdown of red blood cells; elevated liver enzymes; and low platelet count, a clotting deficiency that can lead to excessive bleeding and hemorrhagic stroke.

Larry’s colleague urged him to stop wasting time, he recalled. Lauren’s very high blood pressure, the vomiting, and the terrible pain radiating from her kidneys and liver were symptoms of rapid deterioration. “Your wife’s in a lot of danger,” the trauma doctor said….

The last 16 hours of Lauren’s life were consistent with that grim pattern. Distressed by what the trauma doctor had told him, Larry immediately went to Lauren’s caregivers. But they insisted the tests didn’t show preeclampsia, he said. Not long after, Larry’s colleague called back to check on Lauren’s condition. “I don’t believe those labs,” he recalls her telling him. “They can’t be right. I’m positive of my diagnosis. Do them again.’”…

Just after midnight, her blood pressure about to peak at 197/117, Lauren began complaining of a headache. As Larry studied his wife’s face, he realized something had changed. “She suddenly looks really calm and comfortable, like she’s trying to go to sleep.” She gave Larry a little smile, but only the right side of her mouth moved.

In an instant, Larry’s alarm turned to panic. He ordered Lauren, “Lift your hands for me.” Only her right arm fluttered. He peeled off her blankets and scraped the soles of her feet with his fingernail, testing her so-called Babinski reflex; in an adult whose brain is working normally, the big toe automatically jerks downward. Lauren’s right toe curled as it was supposed to. But her left toe stuck straight out, unmoving. As Larry was examining her, Lauren suddenly seemed to realize what was happening to her. “She looked at me and said, ‘I’m afraid,’ and, ‘I love you.’ And I’m pretty sure in that moment she put the pieces together. That she had a conscious awareness of … that she was not going to make it.”

A CT scan soon confirmed the worst: The escalating blood pressure had triggered bleeding in her brain. So-called hemorrhagic strokes tend to be deadlier than those caused by blood clots. Surgery can sometimes save the patient’s life, but only if it is performed quickly…

“The obstetrician just said, ‘She’s going to be all right,’” Linda Bloomstein said. “And Larry was standing behind him, and I saw the tears coming down, and he was shaking his head, ‘No.’”

Around 2 a.m., the neurosurgeon finally confirmed what the trauma doctor had said four hours before: Lauren had HELLP syndrome. Then he delivered more bad news: Her blood platelets — essential to stopping the hemorrhage — were dangerously low. But, according to Larry, the hospital didn’t have sufficient platelets on site, so her surgery would have to be delayed. Larry was dumbfounded…

The neuro team did another CT scan around 6 a.m. Larry couldn’t bring himself to look at it, “but from what they’ve told me, it was horrifically worse.” While Lauren was in surgery, friends began dropping by, hoping to see her and the baby, not realizing what had happened since her cheerful texts the night before. Around 12:30 p.m., the neurosurgeon emerged and confirmed that brain activity had stopped. Lauren was on life support, with no chance of recovery.

Video at link

Courtesy of:  http://www.foxnews.com/health/2017/05/21/nurses-childbirth-death-brings-questions-about-whether-new-moms-being-ignored.html

See:  http://childnervoussystem.blogspot.com/2015/04/why-preganant-women-in-mississippi-keep.html

Phineas Gage revisited

It took an explosion and 13 pounds of iron to usher in the modern era of neuroscience.

In 1848, a 25-year-old railroad worker named Phineas Gage was blowing up rocks to clear the way for a new rail line in Cavendish, Vt. He would drill a hole, place an explosive charge, then pack in sand using a 13-pound metal bar known as a tamping iron.

But in this instance, the metal bar created a spark that touched off the charge. That, in turn, "drove this tamping iron up and out of the hole, through his left cheek, behind his eye socket, and out of the top of his head," says Jack Van Horn, an associate professor of neurology at the Keck School of Medicine at the University of Southern California.

Gage didn't die. But the tamping iron destroyed much of his brain's left frontal lobe, and Gage's once even-tempered personality changed dramatically.

"He is fitful, irreverent, indulging at times in the grossest profanity, which was not previously his custom," wrote John Martyn Harlow, the physician who treated Gage after the accident.

This sudden personality transformation is why Gage shows up in so many medical textbooks, says Malcolm Macmillan, an honorary professor at the Melbourne School of Psychological Sciences and the author of An Odd Kind of Fame: Stories of Phineas Gage.

"He was the first case where you could say fairly definitely that injury to the brain produced some kind of change in personality," Macmillan says.

And that was a big deal in the mid-1800s, when the brain's purpose and inner workings were largely a mystery. At the time, phrenologists were still assessing people's personalities by measuring bumps on their skull.

Gage's famous case would help establish brain science as a field, says Allan Ropper, a neurologist at Harvard Medical School and Brigham and Women's Hospital.

"If you talk about hard core neurology and the relationship between structural damage to the brain and particular changes in behavior, this is ground zero," Ropper says. It was an ideal case because "it's one region [of the brain], it's really obvious, and the changes in personality were stunning."

So, perhaps it's not surprising that every generation of brain scientists seems compelled to revisit Gage's case.

For example:

In the 1940s, a famous neurologist named Stanley Cobb diagrammed the skull in an effort to determine the exact path of the tamping iron.

In the 1980s, scientists repeated the exercise using CT scans.

In the 1990s, researchers applied 3-D computer modeling to the problem.

And, in 2012, Van Horn led a team that combined CT scans of Gage's skull with MRI scans of typical brains to show how the wiring of Gage's brain could have been affected.

Two renderings of Gage's skull show the likely path of the iron rod and the nerve fibers that were probably damaged as it passed through. Van Horn JD, Irimia A, Torgerson CM, Chambers MC, Kikinis R, et al./Wikimedia

"Neuroscientists like to always go back and say, 'we're relating our work in the present day to these older famous cases which really defined the field,' " Van Horn says….

There is something about Gage that most people don't know, Macmillan says. "That personality change, which undoubtedly occurred, did not last much longer than about two to three years."

Gage went on to work as a long-distance stagecoach driver in Chile, a job that required considerable planning skills and focus, Macmillan says.

This chapter of Gage's life offers a powerful message for present day patients, he says. "Even in cases of massive brain damage and massive incapacity, rehabilitation is always possible."

Gage lived for a dozen years after his accident. But ultimately, the brain damage he'd sustained probably led to his death.

He died on May 21, 1860, of an epileptic seizure that was almost certainly related to his brain injury.


Courtesy of a colleague

Friday, May 19, 2017

MRI findings in neonatal nonketotic hyperglycinemia

Christopher J. Butler, Marcus Likeman and Andrew A. Mallick. Distinctive Magnetic Resonance Imaging Findings in Neonatal Nonketotic Hyperglycinemia.  Pediatric Neurology.  In press.

This term neonate was born by normal vaginal delivery following an uneventful pregnancy. No resuscitation was required. A few hours after birth, he required invasive ventilation because of a decreasing conscious level, generalized hypotonia, and a reduced respiratory drive. There were no dysmorphic features except bilateral talipes equinovarus. After extubation, he had antigravity movements in all limbs and preservation of deep tendon reflexes. He appeared jittery and demonstrated an exaggerated startle reflex to external stimuli.

Cranial magnetic resonance imaging performed on day ten of life showed symmetrical high intensity of the corticospinal tracts, central tegmental tracts, and internal capsule. The posterior fossa cerebrospinal fluid space was enlarged in keeping with a mega cisterna magna. A comprehensive metabolic screen later identified increased plasma and cerebrospinal fluid glycine levels. GLDC gene analysis showed that the child was compound heterozygous with a GLDC exon 1-4 deletion and a missense mutation consistent with a diagnosis of nonketotic hyperglycinaemia (NKH).

T2-weighted axial magnetic resonance (A) and diffusion-weighted (B) images show high intensity of central tegmental and corticospinal tracts.


NKH is a rare autosomal recessive neurometabolic disorder resulting in excessive accumulation of glycine.  This child had a classical presentation of neonatal NKH; however, diagnosis can be problematic with nonspecific presentations. Widespread spongiosis of the myelinating ascending and descending white matter tracts is the main histopathological feature of neonatal NKH.  This child exhibited increased white matter signal intensity on T2-weighted and diffusion-weighted images in the classical anatomical locations of spongiosis. Neuroimaging may be available before the results of many biochemical investigations in a sick neonate, and this pattern of white matter change should alert readers to a possible diagnosis of NKH.

Thursday, May 18, 2017

Death by caffeine

Too much caffeine caused the death of a 16-year-old high school student from South Carolina who collapsed during class last month, according to the county coroner.

Davis Allen Cripe died from a caffeine-induced cardiac event causing a probable arrhythmia, Richland County Coroner Gary Watts announced in a news conference Monday. During an arrhythmia, or abnormal heart rhythm, the heart may not be able to pump enough blood to the body, and lack of blood flow affects the brain, heart and other organs.

The teen consumed three caffeine-laced drinks -- a cafe latte, a large Diet Mountain Dew and an energy drink -- in a two-hour period before collapsing in his classroom at Spring Hill High School on April 26, Watts said.

Among those at the news conference Monday was the teen's father, Sean Cripe.

"Like all parents, we worry about our kids as they grow up. We worry about their safety, their health, especially once they start driving. But it wasn't a car crash that took his life. Instead, it was an energy drink," Sean Cripe said of his son's death.

Watts said Davis had purchased the latte at McDonald's around 12:30 p.m. After that he consumed the Diet Mountain Dew and the energy drink.

Davis collapsed at the school in Chapin, near Columbia, just before 2:30 p.m. and according to Watts was pronounced dead at 3:40 p.m.

Davis' autopsy showed no undiagnosed heart conditions and that Davis was healthy and had no conditions that could have triggered by the caffeine intake. Also, no other drugs or alcohol were found in the teen's system, according to Watts.

"This was not an overdose. We lost Davis from a totally legal substance," Watts said. "Our purpose here today is to let people know, especially our young kids in school, that these drinks can be dangerous, and be very careful with how you use them, and how many you drink on a daily basis."

Sean Cripe said he hopes that if nothing else comes out of this, parents and kids will realize the dangers of caffeinated beverages.

"Parents, please talk to your kids about the dangers of these energy drinks," he said.

The American Academy of Pediatrics recommends that adolescents, age 12 to 18, should not consume more than 100 milligrams of caffeine per day. An intake of caffeine greater than that has been associated with elevated blood pressure in adolescents, Sheri Zidenberg-Cherr, nutrition specialist and vice chairwoman in the department of nutrition at the University of California, Davis, previously told CNN.

When it comes to energy drinks specifically, "children and adolescents are advised to avoid energy drinks. They can contain a significant amount of caffeine as well as other stimulants," she said. A 2014 study found an estimated 73% of children consume some kind of caffeine each day. While there is no designated standard for children, according to the US Food and Drug Administration adults can consume 400 milligrams of caffeine per day -- equivalent to four or five cups of coffee -- without experiencing side effects.

Caffeine is a stimulant that can improve alertness and mood. It can also be habit forming. Too much caffeine can cause mild symptoms such as shaky hands and an upset stomach. Severe symptoms can include high blood pressure, seizures and coma, according to the National Capital Poison Center.


See comment immediately following.

An article you may hear of

Mawson AR, Ray BD, Bhuiyan AR, Jacob B (2017) Pilot comparative study on the health of vaccinated and unvaccinated 6- to 12-year-old U.S. children. J Transl Sci 3: DOI:10.15761/JTS.1000186

Vaccinations have prevented millions of infectious illnesses, hospitalizations and deaths among U.S. children, yet the long-term health outcomes of the vaccination schedule remain uncertain. Studies have been recommended by the U.S. Institute of Medicine to address this question. This study aimed 1) to compare vaccinated and unvaccinated children on a broad range of health outcomes, and 2) to determine whether an association found between vaccination and neurodevelopmental disorders (NDD), if any, remained significant after adjustment for other measured factors. A cross-sectional study of mothers of children educated at home was carried out in collaboration with homeschool organizations in four U.S. states: Florida, Louisiana, Mississippi and Oregon. Mothers were asked to complete an anonymous online questionnaire on their 6- to 12-year-old biological children with respect to pregnancy-related factors, birth history, vaccinations, physician-diagnosed illnesses, medications used, and health services. NDD, a derived diagnostic measure, was defined as having one or more of the following three closely-related diagnoses: a learning disability, Attention Deficient Hyperactivity Disorder, and Autism Spectrum Disorder. A convenience sample of 666 children was obtained, of which 261 (39%) were unvaccinated. The vaccinated were less likely than the unvaccinated to have been diagnosed with chickenpox and pertussis, but more likely to have been diagnosed with pneumonia, otitis media, allergies and NDD. After adjustment, vaccination, male gender, and preterm birth remained significantly associated with NDD. However, in a final adjusted model with interaction, vaccination but not preterm birth remained associated with NDD, while the interaction of preterm birth and vaccination was associated with a 6.6-fold increased odds of NDD (95% CI: 2.8, 15.5). In conclusion, vaccinated homeschool children were found to have a higher rate of allergies and NDD than unvaccinated homeschool children. While vaccination remained significantly associated with NDD after controlling for other factors, preterm birth coupled with vaccination was associated with an apparent synergistic increase in the odds of NDD. Further research involving larger, independent samples and stronger research designs is needed to verify and understand these unexpected findings in order to optimize the impact of vaccines on children’s health.


From the article:

What credence can be given to the findings? This study was not intended to be based on a representative sample of homeschool children but on a convenience sample of sufficient size to test for significant differences in outcomes. Homeschoolers were targeted for the study because their vaccination completion rates are lower than those of children in the general population. In this respect our pilot survey was successful, since data were available on 261 unvaccinated children.

To eliminate opportunities for subjectivity or opinion in the data, only factual information was requested and the questions involved memorable events such as physician-diagnosed diseases in a child. With regard to minimizing potential bias in the information provided by mothers, all communications with the latter emphasized neutrality regarding vaccination and vaccine safety. To minimize recall bias, respondents were asked to use their child’s vaccination records. To enhance reliability, closed-ended questions were used and each set of questions had to be completed before proceeding to the next. To enhance validity, parents were asked to report only physician-diagnosed illnesses.

Mothers’ reports could not be validated by clinical records because the survey was designed to be anonymous. However, self-reports about significant events provide a valid proxy for official records when medical records and administrative data are unavailable. Had mothers been asked to provide copies of their children’s medical records it would no longer have been an anonymous study and would have resulted in few completed questionnaires. We were advised by homeschool leaders that recruitment efforts would have been unsuccessful had we insisted on obtaining the children’s medical records as a requirement for participating in the study.

A further potential limitation is under-ascertainment of disease in unvaccinated children. Could the unvaccinated have artificially reduced rates of illness because they are seen less often by physicians and would therefore have been less likely to be diagnosed with a disease? The vaccinated were indeed more likely to have seen a doctor for a routine checkup in the past 12 months (57.5% vs. 37.1%, p < 0.001; OR 2.3, 95% CI: 1.7, 3.1). Such visits usually involve vaccinations, which non-vaccinating families would be expected to refuse. However, fewer visits to physicians would not necessarily mean that unvaccinated children are less likely to be seen by a physician if their condition warranted it. In fact, since unvaccinated children were more likely to be diagnosed with chickenpox and whooping cough, which would have involved a visit to the pediatrician, differences in health outcomes are unlikely to be due to under-ascertainment.

Strengths of the study include the unique design of the study, involving homeschool mothers as respondents, and the relatively large sample of unvaccinated children, which made it possible to compare health outcomes across the spectrum of vaccination coverage. Recruitment of biological mothers as respondents also allowed us to test hypotheses about the role of pregnancy-related factors and birth history as well as vaccination in NDD and other specific conditions. In addition, this was a within-group study of a demographically homogeneous population of mainly white, higher-income and college-educated homeschooling families in which the children were all 6-12 years of age. Information was provided anonymously by biological mothers, obviously well-informed about their own children’s vaccination status and health, which likely increased the validity of the reports.

See comments immediately following.

Peripheral nerve ultrasonography in differential diagnosis

Jingwen Niu,  Liying Cui and Mingsheng Liu.  Multiple Sites Ultrasonography of Peripheral Nerves in Differentiating Charcot–Marie–Tooth Type 1A from Chronic Inflammatory Demyelinating Polyradiculoneuropathy.  Front. Neurol., 04 May 2017 | https://doi.org/10.3389/fneur.2017.00181

Introduction: Multiple sites measurement of cross-sectional areas (CSA) by ultrasound was performed to differentiate Charcot–Marie–Tooth type 1A (CMT1A) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Methods: Nine patients with CMT1A, 28 patients with CIDP, and 14 healthy controls (HC) were recruited prospectively. Consecutive ultrasonography scanning was performed from wrist to axilla on median and ulnar nerves. CSAs were measured at 10 predetermined sites of each nerve.

Results: CMT1A had significantly larger CSAs at all sites of median and ulnar nerves (p < 0.01). In CMT1A, CSAs increased gradually and homogeneously from distal to proximal along the nerve, except potential entrapment sites. CIDP displayed three different morphological patterns, including mild enlargement in 15 patients, prominent segmental enlargement in 12, and slight enlargement in 1, among which different treatment responses were observed. All patients with mild nerve enlargement treated with intravenous immunoglobulin were responsive (7/7), while less than half of those with prominent segmental enlargement (3/7) were responsive (p < 0.01).

Discussion: Consecutive scan along the nerve and multiple sites measurement by ultrasound could supply more detailed morphological feature of the nerve and help to differentiate CMT1A from CIDP.


See: http://childnervoussystem.blogspot.com/2017/05/nerve-ultrasound-in-neurofibromatosis.html 

Doctor in disguise

He wasn’t one of my most favorite people in the world, but since my son had a medical condition that required regular checkups, I had steady interactions with Dr. D. He could be gruff and often low on patience, but his redeeming grace was his quirky sense of humor which parents loved. His field of expertise was highly specialized, so I didn’t have many other options even had I wanted to go elsewhere. 

I learned the hard way that Dr. D wouldn’t give me a minute more than my allotted 15. “Can I ask one more question?” I asked innocently at the end of a visit. “You already did. Your time is up. If you don’t leave now, my other patients will lynch you.” From that time on, I came prepared with an index card of questions and concerns, practiced my “speech” in advance, and walked out with the necessary paperwork I would need until our next visit, with time to spare.

I still found myself on the receiving end of his unpleasant barbs. I once had an appointment scheduled for after-school hours and I had my other kids with me. My crew was being their usual kvetchy selves, although I was trying my best to keep it under control. As our visit came to a close, Dr. D said, “I can’t stand all the whining for one more minute. Please get out of here before my head explodes!” without a trace of embarrassment at his impoliteness.

On my next visit, when I asked if my son could fly, obviously referring to going on a plane with his condition, the doctor replied in all seriousness, “Well, I wouldn’t recommend throwing him off a cliff like superman, if I were you.” I couldn’t tell if he was being nasty or funny. It was probably a mixture of both.

On one visit as I was called into his office, he gestured me to sit down as he picked up his phone. “I’m sorry I just need to make a quick call before we start,” he said. I nodded, hoping that my allotted 15 minutes wouldn’t start until after his phone call ended. “I need to call my wife,” he said in way of explanation.

Wife? I had never thought about Dr. D as a family man and wondered if he was as gruff with his wife as he was with his patients. “My first priority in life is to be a good husband,” he said to me as he waited for her to pick up. “My second priority is to be a good father. And my third is to be a good doctor.” I smiled at his uncharacteristic revelation.

I had a hard time fathoming how one person could have two such very different personas. Which one was the real him?

When she picked up Dr. D’s voice dropped several notches. “Hi sweetheart! How are you feeling today?” he said with such warmth that I felt that I was intruding on a private conversation. Perhaps I should step outside? But no, Dr. D was gesturing me to sit still. “I feel so bad. I saw we had no bread in the house. Are you going to manage? Maybe it’s too cold to get out with the baby?” he asked with affectionate concern.

It was 8:30 in the morning and the doctor travelled from far, probably leaving the house before her morning started. This conversation about nothing in particular went on for a few more minutes until he wished her a good day in such a tender voice, it was almost a whisper.

What a lucky wife, I thought to myself. I had a hard time fathoming how one person could have two such very different personas. Which one was the real him? And then it struck me how I was judging him based on one sliver of his makeup that I am privy to see, without realizing the complexity of his personality.

I still don’t look forward to my visits with Dr. D but I’ve learned to look at him in a more nuanced way. While he’s a bit rough around the edges and it wouldn’t hurt if he’d be a bit more patient, I know that behind that white coat is a wonderful husband and loving father who has his priorities straight.


Epilepsy surgery in tuberous sclerosis

Liang, S., Zhang, J., Yang, Z. et al.  Long-term outcomes of epilepsy surgery in tuberous sclerosis complex J Neurol (2017) In press.


Approximately 50% of patients with tuberous sclerosis complex (TSC) present intractable epilepsy, and surgery is an option for those patients. Hereby, we analyze long-term seizure control and neuropsychological outcomes of epilepsy surgery in patients with TSC. Clinical data were retrospectively collected from 66 patients with TSC and epilepsy followed up over 5 years, 51 of whom underwent epilepsy surgery between 2001 and 2011. Reductions in the number of seizures were analyzed at 1-year (1FU), 5-year (5FU), and 10-year (10FU) follow-ups visits after the operation. Influential factors on postoperative seizure free and intelligence quotient (IQ) and quality-of-life (QOL) outcomes were evaluated at 5FU. Resective procedures included 26 tuber resections, 15 lobectomies, and 10 tuber resections and lobectomies. Corpus callosotomies were performed as the adjunctive approach in 11 cases with low IQ. The percentages of seizure-free cases were 74.5% at 1FU, 58.8% at 5FU, and 47.8% at 10FU, and the predictive factor for long-term postoperative seizure freedom was the history of preoperative seizures and preoperative full-scale IQ. Significant improvements were found in performance IQ, full-scale IQ, and QOL in patients from the surgery group, particularly those who were seizure free after the operation. Our study showed that epilepsy surgery in TSC with epilepsy rendered improvements in seizure control, full-scale IQ, and QOL. Satisfactory long-term seizure control was often achieved with an early operation and without mental retardation, and improvements in QOL and IQ were frequently observed in postoperative patients who remained seizure free.