Sunday, September 30, 2018

Pediatric migraine and obesity

As in adults, headache and obesity are highly common in the pediatric population, with conservative estimates indicating a prevalence of 17.1% and 18.5%, respectively.  Both have been linked with substantial morbidity, functional impairment, and cost, and a growing body of research suggests important associations between the 2 conditions, including frequent comorbidity and potentially overlapping risk factors, pathophysiologic mechanisms, and treatment implications.

In research published in 2010 (n=5847), risk for migraine was found to be 60% greater in overweight or obese adolescents, and a 2008 study of 273 children showed a greater prevalence of episodic migraine in those with vs without obesity (8.9% vs 2.5%, respectively).  Another investigation of 124 children found a higher migraine frequency in those with obesity compared with normal-weight or overweight children.

While the mechanisms underlying the association between migraine and obesity have yet to be elucidated, it is “likely to be multifactorial, related on both central and peripheral pathways regulating feeding and adipose tissue function, that overlap with pathways implicated in migraine pathophysiology, as well as lifestyle and environmental factors,” wrote the authors of a 2017 systematic review.6 Shared factors may include “inflammatory mediators such as the calcitonin gene-related protein, neurotransmitters such as serotonin, peptides such as orexin, and adipocytokines such as adiponectin and leptin [which] play a role both in feeding and migraine physiopathology and could explain the common pathogenesis.”

Determinants of pediatric obesity include poor nutritional habits, low physical activity, urban residence, socioeconomic status, and female gender.  Key strategies to address childhood obesity include healthy eating habits such as increased consumption of produce and fiber, eating breakfast and avoiding frequent snacking, and limiting intake of nutrient-poor foods; physical activity, ideally for 60 minutes per day at a moderate to vigorous level of intensity, and less sedentary time in general; and education of parents regarding these health-promoting behaviors and the nutritional needs of their children.

In addition, depression and anxiety have been found to affect eating behavior as well as headache frequency and disability, highlighting the need for adequate screening and referral to mental health treatment if indicated.

To learn more about the connection between migraine and obesity in pediatric patients, Neurology Advisor spoke with Lauren Doyle Strauss, DO, FAHS, assistant professor of pediatric neurology at Wake Forest University Baptist Medical Center.

Neurology Advisor: What is known about the link between migraine and obesity in children, including lifestyle factors that have an impact on this risk?

Dr Strauss: This is a very important concern that warrants attention, as rates of pediatric obesity are rising in the United States. Studies in adults have shown that obesity is not only associated with an increased risk for having migraine, but is also a known risk factor for conversion to chronic migraine. There was a large meta-analysis published in 2017, which included 288,981 participants age 18 to 98 years, that showed a 27% increased risk for migraine in obese people even when adjusted by sex and age, compared with subjects with normal weight.

Overall, data in children do support an association between pediatric obesity and headache disorders in general, but more research is needed to confirm the association specifically with pediatric migraine. We know that pediatric obesity is associated with obesity in adulthood. Addressing young-onset obesity at an early age is important due to the multiple associated health concerns that can [persist or emerge] over subsequent years.

Neurology Advisor:  What are the treatment implications for clinicians, including the role of exercise?

Dr Strauss: There are multiple implications for clinical practice and whether weight reduction will reduce the number of headaches. Many of our daily preventive medications used in the management of migraine and other headaches can be associated with weight gain, and as a result, medication choices may be limited by obesity. Topiramate, the only daily medication with [US Food and Drug Administration] approval for migraine in adolescents, can be associated with decreased appetite or weight loss. However, in the recent multicenter [National Institutes of Health]-funded CHAMP study led by Andrew Hershey, MD, PhD, and Scott Powers, PhD, both of Cincinnati Children's, topiramate did not fare as well as placebo and was associated with more side effects compared with amitriptyline.10 Topiramate may be contraindicated in the obese population, as it can interact with metformin, which is often used to treat common obesity-associated health conditions such as polycystic ovary syndrome or insulin resistance.

There are various weight loss approaches that are being studied in pediatric patients, including the role for exercise, dietary recommendations, and surgical options. In 2013, there was an Italian multicenter study of obese adolescents ([body mass index] ≥97th percentile) with migraine who were 14 to 18 years old, that examined how weight loss can affect headache outcomes.11 Participants were treated in a multidisciplinary program including dietary education, physical exercise, and behavioral therapy. Weight reduction was shown over 1 year and was significantly associated with a reduction in headache frequency and intensity.

Another study by Dr Hershey showed a positive correlation between change in [body mass index] and reduction in headache frequency.  However, these studies included behavioral therapy interventions or the elimination of foods that may also trigger migraines.

Increasing physical exercise is often recommended to overweight and obese patients as a weight-loss tool and maintenance strategy, but exercise in patients with migraine has several considerations. There is some evidence that yoga and tai chi may be particularly helpful for patients with migraine.   On the other hand, exercise can also be a trigger for some patients with migraine.

Neurology Advisor: What should be the focus of future research in this area?

Dr Strauss: More research is needed to investigate whether obesity is a risk factor for conversion from episodic to chronic migraine in pediatric patients. The overall association between obesity and migraine is likely multifactorial, and more research exploring mechanisms involving obesity-related bioactive substances and the role of the hypothalamus may help us better understand migraine pathophysiology. This understanding may lead to potential new behavioral therapies, interventions, or targeted treatments for migraine.

Wanting to become a pediatric neurologist when he grows up

Garett Ozmer has a personal reason for wanting to become a Pediatric Neurologist when he grows up.

The 2017-18 Guyer High School Valedectorian– and All-District baseball player– has struggled with a condition throughout his life that has made the act of attending school more challenging.

“I had epilepsy as a child and experienced frequent seizures from fourth grade until I grew out of the condition my freshman year,” Ozmer said. “My Pediatric Neurologist was the kindest and most caring doctor that I have ever had. She showed me the correct way to care for patients and especially how to make kids feel safe. After I grew out of my seizures, it made sense for me to pursue a career in neurology, because I’ve had personal experience in the field; and, I know exactly what kids are going through.”

Ozmer, a member of the National Honor Society and National English Honor Society when he was at Guyer High School, said he struggled in a number of ways with his condition in school.

“It was embarrassing to be sitting in class and suddenly have every student looking at me as I was having a seizure,” Ozmer said. “A side effect of the seizures was speech stuttering. At times, I was made fun of in school for it and I became self-conscious whenever I would speak to someone. I got to where I wouldn’t talk as much, because I was afraid I would always be made fun of.”

Ozmer, 18, was also a member of PALS (Peer Assistance Leadership and Service), a school-sponsored organization that pairs its mentors with at-risk students at local elementary and middle schools.

The Lantana teen was selected as a two-time All-District baseball player, received Academic All-State honors and carried a 5.0 grade point average at Guyer High School.

Because of his experiences growing up with epilepsy, Ozmer said becoming a Pediatric Neurologist was a “no brainer,” and said he has been preparing for it for quite some time.

“Ever since taking my first science class in middle school, the subject has been my absolute favorite,” Ozmer said. “Along with science, I’ve always had a love for children. I enjoy playing and spending time with children of all ages. It was easy to see that a career in pediatrics was the right thing for me. However, the neurology side was a work in progress.”

Ozmer is headed to the University of Tulsa on a Presidential Scholarship– a full scholarship that is awarded to 28 incoming freshmen from roughly 450 applicants.

Thursday, September 27, 2018

Neuropsychological outcomes of children 1 year after pediatric cardiac arrest

Beth S. Slomine, Faye S. Silverstein, James R. Christensen, et al.  Neuropsychological Outcomes of Children 1 Year After Pediatric Cardiac Arrest.  JAMA Neurology.  Published online September 17, 2018. doi:10.1001/jamaneurol.2018.2628

Key Points

Question  How do caregiver-reported measures compare with performance-based measures in describing neuropsychological outcomes of children resuscitated after cardiac arrest who were initially comatose after return of circulation?

Findings  This secondary analysis of 2 clinical trials found that, of 160 survivors of pediatric cardiac arrest without significant developmental delay before cardiac arrest, 114 had favorable caregiver-rated outcomes 1 year later. However, significant performance-based neuropsychological deficits were evident across measures.

Meaning  These data provide clinicians with a greater understanding of neuropsychological outcomes in pediatric cardiac arrest survivors and of strong correlations in young children and moderate correlations in older children between caregiver-reported outcomes used in clinical trials and performance-based cognitive outcomes.


Importance  Little is known about neuropsychological outcomes of children who survived pediatric cardiac arrest (CA).

Objective  To describe the neuropsychological outcomes of CA survivors enrolled in the Therapeutic Hypothermia After Pediatric Cardiac Arrest In-Hospital (THAPCA-IH) and Out-of-Hospital (THAPCA-OH) trials and compare the results with the primary outcome measure for these trials.

Design, Setting, and Participants  Secondary analysis of 222 CA survivors aged 1 to 18 years who received chest compressions for 2 minutes or more, remained comatose and required mechanical ventilation after return of circulation, and were enrolled in targeted temperature-management trials from 41 pediatric intensive care units. Data were collected from September 3, 2009, to February 3, 2016, and analyzed from March 10, 2017, to April 20, 2018.

Main Outcomes and Measures  The Vineland Adaptive Behavior Scales, Second Edition (VABS-II), a standardized measure of neurobehavioral functioning based on caregiver report (age-corrected mean [SD] scores = 100 [15]), was used to evaluate pre-CA functioning within 24 hours after enrollment; VABS-II<70 indicated significant developmental delays; VABS-II and neuropsychological testing were completed 1 year after CA. Neuropsychological testing included the Mullen Scales of Early Learning (Mullen) for children younger than 6 years and the Wechsler Abbreviated Scale of Intelligence (WASI) and neuropsychological measures of attention, memory, processing speed, and executive functioning for older children.

Results  Of 160 participants who completed neuropsychological testing, 96 (60.0%) were male; the median (interquartile range [IQR]) age was 2.5 years (1.3-6.1 years). Ninety-six (60.0%) were white, 41 (25.6%) were black, and 23 (14.4%) were of other/unknown race; 343 (21.2%) were Hispanic or Latino; 119 (74.4%) were non-Hispanic or Latino; and 7 (4.4%) were of unknown ethnicity. One hundred fourteen participants (71.2%) were classified as having favorable outcomes (VABS-II ≥70). Impairments (>2 SD below the mean for age) across neuropsychological measures ranged from 7% to 61%. Correlations between global cognitive and VABS-II scores were strong for younger children (Mullen, r = 0.69-0.87) but moderate for older children (r = 0.21-0.54 for the WASI). Of 111 children with favorable outcomes on VABS-II, 25.2% had global cognitive impairment and 30 of 35 older children (85.7%) had selective neuropsychological deficits.

Conclusions and Relevance  In this prospectively evaluated cohort of pediatric CA survivors who were initially comatose, although 71.2% were classified as having favorable outcomes, significant neuropsychological deficits were identified in pediatric CA survivors who were classified as having favorable outcomes. The findings provide clinicians with a greater understanding of the spectrum of neuropsychological outcomes of pediatric CA survivors and the complex relationship between standardized caregiver-reported functional outcome measures incorporated in clinical trials and performance-based neuropsychological assessments.

Pediatric cardiac arrest survivors initially classified as having favorable outcomes had significant neuropsychological impairments when tested a year later, a prospective evaluation found.

While 71% of survivors in the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) and the Therapeutic Hypothermia After Pediatric Cardiac Arrest In-Hospital (THAPCA-IH) clinical trials were rated as having favorable neurobehavioral outcomes by their caregivers, a secondary analysis showed many of these children had performance-based neuropsychological deficits, reported Beth Slomine, PhD, of the Kennedy Krieger Institute, and colleagues in JAMA Neurology. 

"The data collected for the THAPCA trials provide a unique opportunity to report on the largest sample of neurobehavioral and neuropsychological outcomes of prospectively recruited pediatric cardiac arrest survivors," Slomine told MedPage Today.

"These results provide clinicians with a better understanding of the range of outcomes in pediatric cardiac arrest survivors and provide researchers with a better understanding of the relationship between distinct outcomes assessment methods used in clinical trials."

THAPCA trials compared outcomes of two targeted temperature-management strategies (hypothermia at 33°C/91.4°F versus normothermia at 36.8°C/98.24°F) in children ages 2 days to 18 years who survived cardiac arrest and received chest compressions for 2 minutes or more, remained comatose, and required mechanical ventilation after circulation returned.

In both trials, hypothermia did not significantly improve 1-year survival with a favorable neurobehavioral outcome, which was defined as a score of 70 or greater (>2 SD below the mean for age) on the Vineland Adaptive Behavior Scales, second edition (VABS-II). The VABS-II assessment was based on telephone surveys with caregivers who reported daily functioning in multiple domains 1 year after cardiac arrest.

To complement VABS-II data collected 12 months after the arrest event, Slomine and co-authors conducted on-site neuropsychological testing with 160 THAPCA survivors, excluding children with severe impairment who lacked functional means of communication. For children under age 6 (n=119), they administered the Mullen Scales of Early Learning; for older children (n=41), they used the Wechsler Abbreviated Scale of Intelligence (WASI) and tests of processing speed, attention, learning and memory, executive functioning, and visuomotor functioning. 

Impairment across neuropsychological measures ranged from 7% to 61%. Correlations between VABS-II outcomes and global cognitive scores were strong for younger children (Mullen r=0.69-0.87), but moderate for older children (WASI r=0.21-0.54).

Test results showed global cognitive impairments in younger children and domain-specific impairments in older children. Of 111 children with favorable outcomes on VABS-II, 25.2% had global cognitive impairment and 30 of 35 older children (85.7%) had selective neuropsychological deficits. Older children showed the highest impairment in measures of executive functioning, fine motor skill, visuomotor skills, and visual memory; IQ generally was spared.

This study is subject to several limitations, the authors noted. A minority of patients survived to 1 year after cardiac arrest (33.4% in THAPCA-OH and 47.4% in THAPCA-IH); brain death or withdrawal of life support due to poor neurologic prognosis was a frequent cause of death. Older children with severe hypoxic-ischemic brain injury were excluded from the study, so results underestimate impairment in this age group. Deficits may become more apparent as children mature, and neuropsychological functioning may need to be reassessed.

Sunday, September 23, 2018

Long-term follow-up of a community sample of adolescents with frequent headaches

Larsson B, Sigurdson JF, Sund AM. Long-term follow-up of a community sample of adolescents with frequent headaches. J Headache Pain. 2018 Sep 4;19(1):79.


Several outcome studies have reported on the short- and long-term effects of migraine in selected clinical samples of children and adolescents. However, current knowledge of the course, incidence, and outcome predictors of frequent headaches in early adolescents in community populations is limited, and little is known about the long-term effects. Headache remains untreated in most of these young people. Here we examined the course, incidence, and outcome predictors of frequent headaches (at least once a week) over the long term (14 years) using previously assessed data at the baseline and 1-year follow-up of early adolescents.

Out of an original sample of 2440 who participated in the first two assessments, a sample of 1266 participants (51.9% response rate) aged 26–28 years (mean = 27.2 years) completed an electronic questionnaire comprising questions about their headache frequency and duration at the long-term follow-up. These headache characteristics together with gender, age, parental divorce, number of friends, school absence, impairment of leisure-time activities and seeing friends, pain comorbidity, and emotional (in particular, depressive symptoms) and behavioral problems were analyzed.

In these young people, 8.4% reported frequent headaches (at least once a week) at the extended follow-up, while 19% of the participants having such headaches at baseline again reported such levels with a negligible gender difference. Over the follow-up period, 7.4% had developed frequent headaches, and a higher percentage of females reported such headaches (11.3% in females, 1.5% in males). In a multivariate model, frequent headaches at the baseline, gender (worse prognosis in females), impairment of leisure-time activities and seeing friends, and higher level of depressive symptoms significantly predicted headache frequency at the long-term follow-up.

Our findings suggest that gender, greater social impairment, and comorbid depressive symptoms are important indicators for both the short- and long-term prognosis of frequent headaches in early adolescents in community populations.

From the manuscript

We found that a sizable proportion of adults aged 26–28 years reported frequent headaches to the same extent as they did in early adolescence. This and other findings of short- and long-term follow-up studies of community samples of children and adolescents suggest that there is strong risk for continuation of frequent headaches commonly associated with higher levels of emotional problems and impairment in social activities. In the long-term perspective, they are likely to have developed into chronic tension-type or migraine headaches or a combination. Although the prevalence of headaches improves in a substantial proportion of adolescents as they move into adulthood, the persistence of frequent headaches, particularly among girls, along with higher levels of depressive symptoms and impairment, emphasizes the need to provide effective psychological and pharmacological treatments to reduce frequent headache complaints and their associated social burden.

In future longitudinal research, more frequent and repeated assessment over time will reveal whether changes in persistence, improvement rates, and relapses occur in adolescents with recurrent headaches. This information will improve the identification of individuals experiencing persistent frequent headaches over extended periods. More importantly, for these people, the potential influence of gender, presence of depressive symptoms, and extent of impairment should be tested in the context of controlled treatment trials to examine whether these factors also contribute to changing the outcome.

Courtesy of:

Friday, September 21, 2018

Clinical characteristics and burden of illness in pediatric patients with narcolepsy

Giuseppe Plazzi MD, PhD, Heather M. Clawges MD and Judith A. Owens MD, MPH.  Clinical Characteristics and Burden of Illness in Pediatric Patients with Narcolepsy.  Pediatric Neurology, in press.


Narcolepsy is a chronic and lifelong neurologic disorder with onset commonly occurring in childhood or adolescence, and affecting approximately 0.025% to 0.05% of the general population. The primary symptom is excessive daytime sleepiness, which is accompanied by cataplexy in 70% of patients. Other common symptoms include sleep paralysis, hallucinations upon falling asleep or waking, and disrupted nocturnal sleep. Narcolepsy is associated with a considerable burden of illness (BOI), which has been well characterized in adults, and is exacerbated by delays in symptom recognition, diagnosis, and intervention. METHODS: This review describes the specific characteristics and BOI of pediatric narcolepsy, using a wide range of published research data. RESULTS: Pediatric narcolepsy presents distinct challenges in diagnosis and management. Narcolepsy symptoms often initially manifest differently in children and adolescents versus adults, which may pose diagnostic dilemmas. Children often respond to sleepiness with irritability, hyperactivity, and poor attention, which may be misinterpreted as misbehavior or neurocognitive sequelae of other conditions. Pediatric cataplexy symptoms may include subtle and unusual facial expressions or choreic-like movements, which are not observed in adults. Insufficient sleep and circadian rhythm disorders presenting with excessive daytime sleepiness are common in adolescents, potentially confounding narcolepsy diagnosis. Pediatric narcolepsy is also associated with comorbidities including rapid weight gain, precocious puberty, and attention deficit hyperactivity disorder, and increased risk for deficits in social functioning, depression, and anxiety. School performance is also typically impaired, requiring special education services. CONCLUSIONS: Thus, the discrete BOI of pediatric narcolepsy underscores the need for prompt and accurate diagnosis, and appropriate treatment of this disorder.

Thursday, September 20, 2018

Fremanezumab for migraine

The Food and Drug Administration (FDA) has approved fremanezumab-vfrm (Ajovy; Teva Pharmaceutical Industries, Jerusalem, Israel) for prevention of migraine in adults. Fremanezumab is administered as a subcutaneous injection by the patient or a health care professional and can be prescribed as a monthly dose in which a single injection (225 mg) is given each month or as a quarterly dose (675 mg) in which 3 consecutive injections are given every 3 months.

Fremanezumab is expected to be available in approximately 2 weeks through retail and specialty pharmacies. The price is set at $575 per monthly dose and $1,725 per quarterly dose. Through a savings offer for insured patients, some may be responsible for as little as $0 per dose until the offer expires. Support services are also available for patients who have difficulty paying for the drug. More information is available at

Fremanezumab is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand to block binding to the CGRP receptor. Approval was based on data from 2 phase 3 clinical trials that showed treatment with fremanezumab significantly reduced patients’ number of migraine days/month compared to placebo (P < .001) and increased the number of patients who had a 50% or more reduction in headache days/ month compared to placebo (P < .001). Treatment with fremanzumab also significantly reduced the number of days per month patients need acute (abortive) headache treatment and reduced disability as measured by the migraine disability assessment score (MIDAS).

Stephen Silberstein, MD, Director, Jefferson Headache Center at Thomas Jefferson University Hospital, lead investigator of the phase 3 clinical trial program for fremanezumab, and a member of the Practical Neurology editorial board said, “About 40% of people living with migraine may be appropriate candidates for preventive treatment, yet the majority of them are untreated. I am pleased to have another treatment option that may allow my patients to experience fewer monthly migraine days.”

Epilepsy surgery near or in eloquent cortex in children

Jayakar P, Jayakar A, Libenson M, Arzimanoglou A, Rydenhag B, Cross JH, Bhatia S, Tassi L, Lachhwani D, Gaillard WD; Pediatric Epilepsy Surgery Task Force; International League Against Epilepsy. Epilepsy surgery near or in eloquent cortex in children-Practice patterns and recommendations for minimizing and reporting deficits. Epilepsia. 2018 Aug;59(8):1484-1491.


We aimed to investigate the current practices guiding surgical resection strategies involving epileptogenic zones (EZs) near or in eloquent cortex (EC) at pediatric epilepsy surgery centers worldwide.

A survey was conducted among 40 respondents from 33 pediatric epilepsy surgery centers worldwide on the weight assigned to diagnostic tests used to define the EZ and EC, how EC is viewed, and how surgeries are planned for foci near or in eloquent cortex.

A descriptive analysis was performed that revealed considerable variation in the use of diagnostic tests and resective strategies toward EZ and EC.

The wide variation in strategies may contribute to undesirable outcomes characterized by poor seizure control with added deficits and underscores the need to establish best practices in pediatric epilepsy surgery. The survey data were used to formulate a set of recommendations to help minimize deficits and to report them consistently.

From the article

In defining the EZ, the seizure aura was weighted heavily by participants, with 73% scoring it as a 4 or 5, whereas the early seizure semiology and postictal findings scored lower (63% and 9%, respectively) (Table 2). The type of magnetic resonance imaging (MRI) lesion played a significant role in the amount of weight given to the MRI. Although focal cortical dysplasia and vascular lesions were weighted heavily along with the MRI findings of hemimegalencephaly and Rasmussen's encephalitis, weights assigned to other types of lesions including polymicrogyria showed considerable variation across centers. With regard to nuclear medicine imaging, 35% of respondents weighted ictal single‐photon emission computed tomography (SPECT) hyperperfusion and positron emission tomography (PET) hypometabolism heavily in favor of extending the resection to EC, with 50% considering subtraction ictal and interictal SPECT co‐registered to MRI (SISCOM) and PET hypermetabolism reliable. This percentage was 75% for magnetoencephalography/electrophysiologic source imaging (MEG/ESI) clusters, a rating that was even higher than for interictal epileptiform discharges recorded on intracranial electroencephalography (EEG)…

The different types of focal background abnormalities seen on intraoperative electrocorticography (ECoG) were weighted variably; continuous epileptiform discharges were regarded as a reliable marker of the EZ by 90% of the respondents. Regarding extraoperative recordings, the ictal‐onset zone on the intracranial EEG was seen as the most reliable marker of the EZ by all respondents, but early seizure propagation and specific patterns such as high‐frequency oscillations and ictal direct current (DC) shifts were variably weighted…

Electrical stimulation mapping (ESM) was regarded as a reliable modality to define eloquent cortex by 90% of the respondents; functional MRI (fMRI) and MEG were also felt to be reliable by 75% of the respondents, whereas transcranial magnetic stimulation (TMS) was lower at 45%. Centers were asked to grade how “critical” they viewed specific functions. Broca's and Wernicke's areas were regarded as highly critical by all respondents.

Verbal memory and the dominant hand motor function were likewise regarded highly critical by more than 90% respondents. The nondominant hand (83%) came in next followed by leg motor at 66% and homonymous visual fields with 63%. Motor face, executive function, nonverbal memory, and calculation were regarded critical by less than 50% of respondents. With regard to plasticity of language cortex, 85% of the respondents considered it to be maximum below age 5 years, whereas 15% considered maximum plasticity to extend to the end of the first decade.

There was a wide range in the threshold of the chance of seizure freedom based on the preoperative assessment that would be required to accept postoperative deficits. Thirty percent of the respondents considered that the possibility of seizure freedom would have to exceed 90% to accept postoperative deficits, whereas the majority accepted a moderate chance (60%‐80%) chance of seizure freedom and 10% of respondents were comfortable accepting deficits at estimated rates of seizure freedom as low as 50%. Eighty‐five percent of respondents adopted a conservative strategy favoring an initial EC‐sparing resection, whereas the remaining generally opted for more aggressive “complete” resections at initial surgery. Involvement of EC by an MRI lesion prompted its resection by nearly 30% of respondents. In patients for whom the MRI lesion was nearby but did not involve EC, 25% would extend the resection to include EC based solely on functional abnormalities; the remaining would opt for lesionectomy alone. In nonlesional cases, 12% of respondents would consider resection of EC based on functional abnormalities.

With respect to dominant mesial temporal resections, in patients with proven unilateral temporal lobe onsets and with preserved verbal memory function, 40% would resect the hippocampus only if there was evidence of sclerosis on MRI scans, 30% would resect it in any case, and 20% would tailor using invasive EEG, whereas only 10% would refrain from pursuing surgery.

Protective strategies such as intraoperative functional mapping including motor mapping under anesthesia were employed by 90% of respondents, and awake surgery required for language mapping was used by 65% when feasible. Fifty percent of respondents also performed subcortical tract mapping; multiple subpial transections were performed by 30%. With regard to specific etiologies, respondents were more inclined to resect EC if the substrate was focal cortical dysplasia vs all other substrates (85% vs 60%)….

Current views of how critical the various functions of EC displayed some variation. Although there was near unanimous agreement that language, dominant hand motor function, and memory were critical, the perceived importance of leg motor, nondominant hand, visual fields, and other functions was much more variable, with a substantial proportion of respondents regarded these as relatively reasonable to sacrifice. Specifically, with regard to mesial temporal resections with preserved memory function, the majority would consider resection only in the presence of mesial temporal sclerosis on MRI. Resection strategies were further compounded by uncertainties surrounding plasticity and impact of deficit on quality of life across different age groups. It was generally agreed that face motor function recovers almost completely following resection. With regard to language cortex, although most respondents accept age of 5 years as the upper limit beyond which plasticity starts to decline, a minority believed that full plasticity extended to the end of the first decade; a presumption that prompts resection strategies carrying risk of incurring long‐term deficits. 

Irrespective of one's biases toward the handling of EC, wider usage of protective strategies such as awake surgery when feasible, tractography and intraoperative navigation tools, and intraoperative functional mapping is justified and strongly recommended. There is also increasing emphasis on ensuring the integrity of white matter tracts via subcortical mapping to maximize preservation of eloquent function36 and deployment of minimally invasive surgical strategies.

The respondents varied considerably in their expectation of the chances of seizure freedom that were considered acceptable thresholds to “justify” a new deficit ranging from 50% to exceeding 90%. This is of considerable concern, as lowering the acceptable threshold for expected seizure freedom increases the chance of a category IV outcome. However, there was virtually unanimous agreement that surgical decisions toward EC resection should be made in conjunction with the family. This is worthy of further dialogue. Although most parents and caregivers are aware of the seizure burden and are rightfully concerned in alleviating it, they are generally less aware of the consequences of new deficits and their potential impact on quality of life. Bias in how this information is presented to the family may thus significantly influence their willingness to accept a new deficit for their child. Better attempts to explicitly explain deficits including video clips of subjects who have undergone EC resection are used by some centers and should be considered as a standard protocol in counseling families faced with this difficult decision.

Whereas seizure freedom following surgery is reported uniformly, reporting of other outcomes including the occurrence of planned deficits is variable. Whereas some studies use specific tools to document deficits, most epilepsy surgical outcome series do not document the type or severity of new deficits incurred. Sometimes deficits are reported under the broader category of complications or unplanned deficits, and it not possible to sort out those that were a part of planned surgical strategy.39 The majority of respondents perform neuropsychological testing postoperatively, yet there is little reporting on cognitive outcomes, neurodevelopment, and the long‐term impact of surgery on quality of life. We recommend the deficit index scale proposed in Table 5 to standardize reporting of both planned and unplanned deficits. Such data reporting is the first step toward measuring impact on quality of life at various ages and the development of more objective decision analysis algorithms balancing the tradeoff between seizure freedom and acceptable deficits.

The survey responses and comments reflect different practice patterns and help to explain the biases that influence surgical strategies toward resection of EC across centers. The survey participants represent a majority of the main epilepsy surgery centers worldwide. The survey results show that among these centers, there is a considerable amount of variability in how the EZ and EC are delineated. Furthermore, there does not appear to be a set of standard circumstances that are agreed upon to justify resection of EC. These results raise grave concern that some of the deviant strategies may contribute to unacceptably high levels of category 4 outcomes. We recognize that a survey requiring entries for individual queries may not reflect the complexity of the analyses that go into surgical decision‐making. In addition to the results of clinical tests, factors such as seizure burden, patient age, or coexisting encephalopathy also play a role; family preference or palliative goals are also important factors in the complex decision‐making process in epilepsy surgery. Furthermore, there will always be exceptional cases that require deviation from preestablished practice. However, we feel that in the more normative or routine cases and given the lack of class I or II evidence to guide practice, recommendations derived from expert opinion help to standardize surgical strategies in pediatrics…

The survey demonstrates that there is variation among the major epilepsy surgery centers in the process of defining the EZ and EC, acceptable outcomes, and the use of protective strategies. Our recommendations include using the full spectrum of tools to educate families on all potential functional losses that may result from a proposed resection as what is deemed “critical” by practitioners is not consistent among centers. Multimodal mapping should be implemented to ensure that maximum EC is spared while removing the EZ. Staged surgeries with function‐sparing resections should be considered when the perceived EZ involves EC, especially in MRI‐negative cases. Finally, standardized reporting of deficits using the recommended classification will facilitate shifting the focus of surgical outcomes to overall well‐being of the patient from both a seizure and a functional perspective.

Courtesy of:

Monday, September 17, 2018

Can't sleep kid

Hensel twins

Sunday, September 16, 2018

Laser ablation surgery for temporal lobe epilepsy 2

Cara became a viral sensation months ago after the teen with a seizure disorder delivered a blunt message to her insurer. Her two words for Aetna -- "screw you" -- expressed the anger she felt at being denied a minimally invasive brain surgery that promised to end her seizures.
Her story, first told by CNN in December, triggered a massive uproar, and Aetna eventually approved the procedure.

This Saturday evening, amid the cheers of her closest friends, Cara radiates on stage beneath strings of white flashing lights. Then someone shouts, and the dance floor clears. Everyone rushes outside. It's as if Mother Nature has joined the party: A rainbow stretches from the Hudson River high into the heavens…

Each time they struck, her body would grow cold and shake. She'd zone out anywhere from 20 seconds to two minutes, typically still aware of what was going on around her. She had seizures on the soccer field, during softball games, on stage during plays, in the classroom. Most anywhere. Her doctors last year recommended Cara for laser ablation surgery, a minimally invasive procedure in which a thin laser is used to heat and destroy lesions in the brain where the seizures originate. It's cutting-edge work, performed through an eighth-inch hole in the skull. Neurosurgeons believe it to be more precise and less invasive than traditional open brain surgery, in which a two-inch hole is cut in the skull or, in some cases, the entire skull cap is removed…

Yet the nation's third-largest insurance company overruled her treating physicians. In denying her coverage, Aetna said it considered laser ablation surgery "experimental and investigational for the treatment of epilepsy because the effectiveness of this approach has not been established."
"Clinical studies have not proven that this procedures [sic] effective for treatment of the member's condition," Aetna said.

When first approached for comment by CNN late last year, the insurance giant stood by its denial.

Cara underwent the laser ablation surgery on July 25. Three weeks later, she says she's adjusting well: "It kind of feels like it's a little bit of a dream, but I also know it's real."

In response, Cara had this message: "Considering they're denying me getting surgery and stopping this thing that's wrong with my brain, I would probably just say, 'screw you.' "

From there, the story took off. The hashtags #ScrewAetna and #CaraPressman were shared across Twitter. Her grandmother made T-shirts for family members for Christmas that read "I'm on Cara's team" on the front; on the back, the message said #SYA (short for #ScrewYouAetna).

Behind the scenes, neurologists and neurosurgeons reached out to the family, offering support. But none was more powerful than Mark Solazzo, the executive vice president and chief operating officer of Northwell Health, New York's largest health care provider.

The hospital executive was so moved by Cara's story he told the family: "This is the last day you're going to fight Aetna on your own."

Solazzo is passionate on this issue: Insurance denials for what Northwell deems medically necessary procedures have swelled the past two years, with the health provider saying it lost $150 million in justifiable reimbursements at a time when insurance companies have been setting record profits. The Northwell executive set in motion a chain of events. He tapped Dr. Ashesh Dinesh Mehta, the director of Northwell's epilepsy surgery, to handle Cara's case and even offered the surgery for free if Aetna still refused to cover it.

"I was happy to do that," Mehta said.

Cara underwent a series of tests this spring with her new team at Northwell. Mehta said her case was complex because the focal point of her seizures was fairly deep in her brain behind her temple. To perform an open brain surgery, he said, he would need to dissect a portion of her brain to get to the spot.

As a result, Mehta said, her team agreed with her previous doctors that laser ablation was the route to go.

"We did our due diligence, and we did determine that this would be the best way to treat her epilepsy," he told CNN.

Along the way, Aetna had a change of heart. In April, the insurer notified the family it would cover the surgery: "Coverage for this service has been approved, subject to the requirements in this letter."…

Mehta gave all the credit to the diminutive teen with the powerful voice: "She really advocated for herself, and it worked out for her. Whatever happened, it got her the appropriate treatment. I've got to hand it to her."

Northwell's Solazzo added, "Cara has been an inspiration to all those who have had the privilege of caring for her. Her advocacy and courage will hopefully clear the way for other epilepsy patients who could benefit from this surgery."…

Cara told staff at North Shore University Hospital in Manhasset she had "never been more excited for anything in my life." Her first grand mal seizure, when she fell to the floor and shook, came at the age of 9, but she remembers having smaller aura seizures, when she would space out for brief spells, as far back as kindergarten. She can have five seizures in a day, sometimes as many as 30…

There are only about 40 to 50 centers around the nation, Mehta said, where laser ablation surgeries are performed, with the technique becoming more popular in recent years. Mehta said existing data show about a 50% seizure-free rate for those who undergo laser ablation, compared to about 70% who undergo traditional open brain surgeries.

A comprehensive study is underway to better define its efficacy. But Mehta said he has had better success than the national average: "My results are about as good as the open temporal lobectomy." The laser surgery is more appealing to patients and parents, he says, because open surgery can be so daunting. Laser surgery is less invasive, requires less time in the hospital and has a quicker recovery, Mehta said…

Cara had one grand mal seizure in the days after the surgery, but she'd forgotten to take her anti-seizure medicine the day before. Mehta also says it's not unusual for patients to have seizures in the week or two right after surgery.

Based on her recovery three weeks after surgery, he believes Cara has a 60% to 80% chance of being seizure-free. The benchmark will be a year from now. "The big question is whether she will have one or two seizures a year or whether she has no seizures," Mehta says. "We want no seizures.

"I'm keeping my fingers crossed."


Fingolimod for pediatric multiple sclerosis

Chitnis T, Arnold DL, Banwell B, Brück W, Ghezzi A, Giovannoni G, Greenberg B, Krupp L, Rostásy K, Tardieu M, Waubant E, Wolinsky JS, Bar-Or A, Stites T, Chen Y, Putzki N, Merschhemke M, Gärtner J; PARADIGMS Study Group. Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis. N Engl J Med. 2018 Sep 13;379(11):1017-1027.


Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.

In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of ≤40 kg) or intramuscular interferon beta-1a at a dose of 30 μg per week for up to 2 years. The primary end point was the annualized relapse rate.

Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included seizures (in 4 patients), infection (in 4 patients), and leukopenia (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient).

Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis. (Funded by Novartis Pharma; PARADIG MS number, NCT01892722 .).

Saturday, September 15, 2018

Seizure boy

I'll never forget the time my son was mocked as "seizure boy" in elementary school. The kids created a game called "Billy Touch": If you got tagged, you had seizures.

All these years later, it still hurts.

Adults with seizure disorders fear losing their jobs. Children with epilepsy fear losing their friends. They all fear being ridiculed.

That's what makes Netflix's depiction of seizures in its new film "The After Party" so shocking. The online streaming service's deafening silence since the movie's August 24 release has done little to quiet the controversy.

In the movie, the main character has a seizure while rapping on stage. He vomits and writhes, a moment captured on video that goes viral. He gets dubbed "Seizure Boy," and soon everyone is doing a #SEEZJAHBOY dance.

The film treats seizures like the dab. Like the Electric Slide.

The movie has outraged the epilepsy community like little else.

"The way seizures are portrayed in the film only adds to the ignorance, misunderstanding and fear that exist about seizures. This Netflix film harkens back into the Dark Ages," Phil Gattone, president of the Epilepsy Foundation, said in a written statement.

Gattone said he reached out to Netflix in hopes of working with it to produce a public service announcement about seizure disorders that could be played at the end of the movie or posted on Netflix's digital outlets. He never heard back.

The Epilepsy Foundation is now planning to seek a grant to create the PSA from a fund started by Netflix founder Reed Hastings. Gattone said it would use "the 'seizure boy' missteps as an opportunity to empower kids with epilepsy and prevent bullying."

He called the movie a "serious affront to our community when so-called entertainment mocks or jokes about having epilepsy or seizures" -- a sentiment echoed by many advocates across social media.

"Implying that seizures are an ok thing to bully someone about is unacceptable," tweeted Kelly Cervantes, whose baby daughter has a debilitating form of epilepsy and who has become a powerful advocate for those with seizure disorders.

In a lengthy thread, Cervantes went on to say, "I can't believe I'm typing this but naming someone seizure boy or girl is unacceptable." She invited the producers and the creative team of "The After Party" to come to her home to hold her daughter "while she screams during one of her daily seizures."

"Epilepsy and seizures are no joking matter," Cervantes wrote.

Dr. M. Scott Perry, a pediatric neurologist and medical director of neurology at Cook Children's Medical Center in Fort Worth, Texas, blasted Netflix for doing "nothing more than increase the stigma for those with epilepsy, erasing all we in the epilepsy community work to alleviate each day."
"It is unfortunate in this day and age, there is still so much misunderstanding, misrepresentation, and stigma for those with epilepsy," Perry wrote in a piece distributed by his hospital.

As the father of a boy with epilepsy, I watched the movie trailer and found it hard to stomach. It was made more difficult because of my son's own version of being teased as "seizure boy."

Like Cervantes tweeted, a seizure is no joke.

When I take my son to the swimming pool, I'm on edge, wondering whether Billy will seize in the water and die in my arms. On a recent beach trip, my wife decided that parasailing was worth trying, because if the worst happened, "he at least will die with a smile on his face." A fun outing at a sporting event can get upended in a second if Billy seizes amid 70,000 people.

Billy's older sister put it this way in a documentary about people with epilepsy: "Don't make fun of people for it. Just don't."

I wanted to know why Netflix thought it was OK to portray people with seizure disorders like it did, and I wanted to hear how it would respond to the controversy within the epilepsy community.

But like Gattone at the Epilepsy Foundation, I never got a response. Attempts to reach writer and director Ian Edelman also were unsuccessful.

More than 3 million Americans, including 450,000 children, have epilepsy. Many live full and productive lives, while for others, the seizure disorder is debilitating, affecting cognitive abilities and almost all aspects of their lives…

University of Minnesota football coach Jerry Kill had to give up his dream of coaching big-time football when his seizures could no longer be controlled. He had just earned Big Ten Coach of the Year honors.

He well knows the stigma people with epilepsy face. "We've got a freak coaching the Minnesota Gophers," a fan once emailed him. Another time, after he had a seizure on the field during a game, a columnist wrote that he should be fired because fans don't pay money to be "rewarded with the sight of a middle-aged man writhing on the ground."

My son and Kill have become close friends since I told their stories in a story for CNN four years ago. At a recent party for the coach that doubled as a fundraiser for the Epilepsy Foundation, Billy took the microphone from Kill.

Ever since his seizures started in May 2011, Billy has only had three months seizure-free. Lately, his seizures strike nearly every day.

He told the crowd of having seizures in the grocery store, at school, of falling down stairs and thinking he would no longer be able to walk. He spoke of riding in ambulances and staying in hospitals.

"It just kind of sucks," he said.

He paused before finishing with "yeah, it sucks."

My son is just 14, but he has helped raise more than $300,000 for people with epilepsy.

Maybe Netflix will consider helping the cause instead of ridiculing.

Courtesy of Doximity

Friday, September 14, 2018

Early outcomes in youth with psychogenic nonsyncopal collapse

Heyer GL, Pabst LM, Kaucic BN, Coley TA. Early outcomes in youth with psychogenic nonsyncopal collapse. Neurology. 2018 Aug 28;91(9):e850-e858.


To evaluate several early outcome measures following diagnosis of psychogenic nonsyncopal collapse (PNSC).

Over a 34-month period, a prospective cohort study was conducted of patients referred for tilt-table evaluation of fainting and orthostatic intolerance. Clinical histories were obtained and anxiety and depressive symptom questionnaires were completed prior to testing. Among 539 patients referred, 100 (18.6%) were diagnosed with PNSC. Outcome data were collected by telephone or during routine follow-up a median of 572 days postdiagnosis.

Eighty-four patients (84%) provided outcome data. Following communication of the diagnosis, 32 patients (38%) had immediate PNSC resolution. Attack resolution occurred in 44% by 1 month, 51% by 6 months, 52% by 12 months, 69% after 12 months, and 31% continued to have PNSC at the time of follow-up. Patients with continued PNSC had higher anxiety scores than patients with immediate resolution (p = 0.047). Following diagnosis, emergency department visits for fainting decreased from 78.6% to 20.2% (p = 0.017), and management by psychology or psychiatry increased from 26.2% to 76.2% (p < 0.001). During the follow-up period, 8 patients (9.5%) were hospitalized for suicidal ideation, a median of 253 (range 33-470) days postdiagnosis; 12 patients (14.3%) developed new (non-PNSC) conversion disorders, a median of 86 (range 9-504) days postdiagnosis. Suicidal ideation was associated with higher anxiety (p = 0.007) but not higher depression scores.

The diagnostic rate of PNSC parallels that of PNES among patients referred for tertiary care evaluations. The improvements in attack frequency following PNSC diagnosis must be tempered by the potential risks of self-harm and the development of new conversion disorders.

Thursday, September 13, 2018

Biotin-thiamine-responsive basal ganglia disease

Ali Mir, Rami Alhazmi  and Raidah Albaradie.  Biotin-Thiamine-Responsive Basal Ganglia Disease—A Treatable Metabolic Disorder .  Pediatric Neurology.  In press.

This two-year-old girl presented with a nine day history of excessive sleepiness, inability to walk, ptosis, irritability, and tonic posturing of extremities. There was no history of fever or recent illness. Magnetic resonance imaging of the brain was performed, and she received intravenous immunoglobulin and pulse corticosteroids for presumed acute disseminated encephalomyelitis (ADEM). The lactate peak on magnetic resonance spectroscopy raised the suspicion of mitochondrial disease. Repeat imaging three weeks later showed improvement, and she returned to baseline. She presented two months later with similar symptoms following gastroenteritis and fever. She was again treated with pulse steroids for suspected recurrent ADEM, but biotin-thiamine-responsive basal ganglia disease (BTBGD) was also considered. Biotin and thiamine were given. Genetic testing detected a pathogenic homozygous c.1264A>G (p.Thr422Ala) variant in SLC19A3. At her 10-month follow-up visit, she was asymptomatic with a normal examination .

BTBGD is an underdiagnosed treatable metabolic disorder. It is an autosomal recessive disorder caused by a mutation in the SLC19A3 gene. It typically presents in children aged three to ten years and is usually preceded by febrile illness.  It is characterized by recurrent subacute encephalopathy, seizures, ataxia, dystonia, supranuclear facial palsy, and external ophthalmoplegia, and if left untreated, can lead to coma and even death.  The central necrosis of both heads of the caudate and complete or partial, involvement of the putamina are consistent radiographic findings during the initial acute encephalopathy and may persist. 

Early recognition is important to avoid delay and misdiagnosis, as the clinical picture could look like ADEM or mitochondrial disease. Prompt administration of biotin and thiamine early in the disease course results in partial or complete improvement.

Heuristic principles

Akbar MOHAMED Chettali

Consultant Paediatric Neurologist/ Lead Director Aster KIND - Kids Integrated Neuro Development Unit/ Deductive Clinician with expertise for Rare Disease/ Mind Consultant, Coach, Mentor and Teacher

A clinician needs to follow certain rules to improve his skills

Diagnostic errors happen due to certain common mistakes

Some common ones are

1. Premature closure —- coming quickly to conclusion

2. Faulty triggering — due to faulty information gathering and poor history taking / poor      
    interpretation of  tests

3. Faulty estimation of probability —- Occam Razor concept

Common things are always common

4. Failure to identify a pattern of disease and failure to anticipate natural course of a disease—     
    known as Gestalt  recognition

5. Over reliance on investigations

Diagnosis can be improved if we follow fisher rules

1. At least three out of five features of a disease should be met to confidently say the diagnosis

2. Always keep an open mind and list differential diagnosis

3. Be vigilant—- symptoms can evolve

4. Be like a police dog —- take a very detailed history and perform good examination/ think you
    are a detective in crime scene

5. Most important—- maintain interest in your patients

These were some concepts I learnt and inculcated during my practice

Thanks to my Patients my Teachers from PGI and AIIMS

Happy Teachers Day



From LinkedIn

Caplan LR. Fisher's Rules. Arch Neurol. 1982 Jul;39(7):389-90.

1.   The bedside can be your laboratory.  Study the patient seriously.

2 .  Settle an issue as it arises at the bedside.

3.   Make a hypothesis and then try as hard as you can to disprove it or find the    
      exception before accepting it as valid.

4 .  Always be working on one or more projects; it will make the daily routine more meaningful.

5.   In arriving at a clinical diagnosis, think of the five most common findings   
      physical findings or laboratory) found in a given disorder.
6.   Describe quantitatively and precisely.

7.   The details of the case are important; their analysis distinguishes the expert from the

8.   Collect and categorize phenomena; their mechanism and meaning may become clearer        
      later if enough cases are gathered.

 9.   Fully accept what you have heard or read only when you have verified it yourself.

10.  Learn from your own past experience and that of others (literature and experienced

11.  Didactic talks benefit most the lecturer. We teach others best by listening, questioning           
       and demonstrating.

12.  Write often and carefully. Let others gain from your work and ideas.

13.  Pay particular attention to the specifics of the patient with a known diagnosis; it will    
       be helpful later when similar phenomena occur in an unknown case.                

14.  Be a good listener; even from the mouths of beginners may come wisdom.

15.  Resist the temptation to prematurely place a case or disorder into a diagnostic cubbyhole
       that fits poorly.

16.  The patient is always doing the best he can.

17.  Maintain a lively interest in patients as people.

Wednesday, September 12, 2018

Corporate psychopathy

Babiak P, Neumann CS, Hare RD. Corporate psychopathy: Talking the walk. Behav Sci Law. 2010 Mar-Apr;28(2):174-93.

There is a very large literature on the important role of psychopathy in the criminal justice system. We know much less about corporate psychopathy and its implications, in large part because of the difficulty in obtaining the active cooperation of business organizations. This has left us with only a few small-sample studies, anecdotes, and speculation. In this study, we had a unique opportunity to examine psychopathy and its correlates in a sample of 203 corporate professionals selected by their companies to participate in management development programs. The correlates included demographic and status variables, as well as in-house 360 degrees assessments and performance ratings. The prevalence of psychopathic traits-as measured by the Psychopathy Checklist-Revised (PCL-R) and a Psychopathy Checklist: Screening Version (PCL: SV) "equivalent"-was higher than that found in community samples. The results of confirmatory factor analysis (CFA) and structural equation modeling (SEM) indicated that the underlying latent structure of psychopathy in our corporate sample was consistent with that model found in community and offender studies. Psychopathy was positively associated with in-house ratings of charisma/presentation style (creativity, good strategic thinking and communication skills) but negatively associated with ratings of responsibility/performance (being a team player, management skills, and overall accomplishments).

From the article:

However, nine of the participants(4.4%) had a score of 25 or higher, eight (3.9%) had a score of 30 or higher (the common research threshold for psychopathy), two had a score of 33, and one had a score of 34. By way of comparison, the mean score for male offenders is approximately 22 (SD  7.9), with about 15% of the scores being 30 or higher…

Psychopathy was not associated with any of the demographic variables (age, gender, education) in this study, or with whether or not an organization considered an individual a high potential candidate (which may be a reflection of the anti-discriminatory affirmative action efforts of the corporations studied). Interestingly, some with very high psychopathy scores were high potential candidates and held senior management positions: vice-presidents, supervisors, directors. This provides support for the argument that some psychopathic individuals manage to achieve high corporate status…

Perhaps the most dramatic results of this study had to do with how the corporation viewed individuals with many psychopathic traits. That is, high psychopathy total scores were associated with perceptions of good communication skills, strategic thinking, and creative/innovative ability and, at the same time, with poor management style, failure to act as a team player, and poor performance appraisals (as rated by their immediate bosses). These latter associations were rather strong. It is noteworthy that, in general, each psychopathy factor contributed to the zero-order correlations with the360 degree assessments and performance appraisals. However, the result s of the structural equation model (which accounted for the shared variance among the factors) indicated that only the latent Interpersonal psychopathy factor strongly predicted both increased ratings on the charisma/presentation composite and decreased ratings on the responsibility/performance composite. The latent Antisocial factor moderately predicted only increased ratings on the charisma/presentation compo site (considered valuable assets in high-level executives), perhaps indicating that in the presence of charm and charisma a failure to adhere to rules can impress others…

Although executives with many psychopathic traits may be visible to various members of the organization, and identifiable with existing mechanisms, they may have the communication, persuasion, and interpersonal skills to override any negative impact on their career.  For example, our finding that some companies viewed psychopathic executives as having leadership potential, despite having negative performance reviews and low ratings on leadership and management by subordinates, is evidence of the ability of these individuals to manipulate decision makers. Their excellent communication and convincing lying skills, which together would have made them attractive hiring candidates in the first place, apparently continued to serve them well in furthering their careers…

In conclusion, results provide evidence that a high level of psychopathic traits does not necessarily impede progress and advancement in corporate organizations. Most of the participants with high psychopathy scores held high-ranking executive positions, and their companies had invited them to participate in management development programs. This was in spite of negative performance reviews and other 360 degree data that were in the hands of corporate decision makers. Overall, the patterns of correlations and plots suggest that psychopath y is more strongly associated with style than with substance. Presumably, impression management and the ability to present well can obscure or trump subpar performance and behaviors that are damaging to the organization. In this sense, the devil is in the details. Better vetting procedures and the use of instruments designed to assess psychopathic and other problematical traits may help prevent those who excel at ‘‘talking the walk’’ from sliding into the pre-management ranks. Even so, it is likely that sour cream will continue to rise to the top.

Inspired by a colleague

Conscious while being considered in an unresponsive wakefulness syndrome for 20 years

Vanhaudenhuyse A, Charland-Verville V, Thibaut A, Chatelle C, Tshibanda J-FL, Maudoux A, Faymonville M-E, Laureys S and Gosseries O (2018) Conscious While Being Considered in an Unresponsive Wakefulness Syndrome for 20 Years. Front. Neurol. 9:671. doi: 10.3389/fneur.2018.0067

Despite recent advances in our understanding of consciousness disorders, accurate diagnosis of severely brain-damaged patients is still a major clinical challenge. We here present the case of a patient who was considered in an unresponsive wakefulness syndrome/vegetative state for 20 years. Repeated standardized behavioral examinations combined to neuroimaging assessments allowed us to show that this patient was in fact fully conscious and was able to functionally communicate. We thus revised the diagnosis into an incomplete locked-in syndrome, notably because the main brain lesion was located in the brainstem. Clinical examinations of severe brain injured patients suffering from serious motor impairment should systematically include repeated standardized behavioral assessments and, when possible, neuroimaging evaluations encompassing magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography…

In 1992, the patient sustained a severe traumatic brain injury as a result of a car accident. He had no previous significant medical history. On admission to a general hospital, the Glasgow Coma Scale total score was 4/15 and both pupils were in myosis. Babinski reflex was present bilaterally. The patient was intubated and mechanically ventilated. Brain CT scan revealed left parietal, basal ganglia, and retro-pontic hemorrhages. The EEG displayed a non-reactive global slowing of basic rhythms without paroxystic activity. The patient was tracheotomized, received nasogastric feeding and left the intensive care unit 24 days later with the diagnosis of “coma vigil.” Six weeks after the insult, the treating nurse of the neuropsychiatry department reported that the patient had moved his right hand to command, but this observation did not change the clinical diagnosis and it was never reported on later occasions. Two epileptic seizures were observed 6 months post-injury. The tracheal tube was removed 8 months after the brain trauma. Neurological examination performed 9 months post-onset reported spontaneous eye opening without reproducible response to command, and concluded to a state of “irreversible coma vigil” (i.e., permanent vegetative state). One year and 5 months post-injury, he was transferred to a chronic nursing care home with the diagnosis of “comatose state.” The patient did not receive physiotherapy, speech therapy or occupational therapy. No stimulation or rehabilitation treatment was reported by the medical team in the nursing home.

Twenty years after his brain injury, the patient was transferred to our neurology department for a diagnostic evaluation as requested by the general practitioner of his nursing care home. The request was initiated by the family of the patient who was staying in the same room who had the impression that he was conscious. The diagnosis on referral was “coma vigil.” Pharmacological treatment included diphantoine (4 × 100 mg/d—antiepileptic), mirtazapine (1 × 30 mg—antidepressant) and lormetazepam (1 × 2 mg/d—sedative benzodiazepine). Medication was not modified during the week of assessment. Hetero-anamnesis was limited given that no family could be reached…

The [Coma Recovery Scale-Revised] CRS-R total score varied between 12 and 17. During every single assessment, the patient was able to repeatedly follow simple commands (e.g., close your eyes, open your mouth, lift your thumb). On two consecutive assessments, he could also functionally communicate (i.e., being able to systematically and accurately answer simple questions using a “YES/NO” codes), which means that he emerged from the minimally conscious state. The first time, the patient correctly answered the CRS-R visual questions using YES and NO cards. The second time, he responded accurately to self-related questions using a buzzer (i.e., buzz once to say yes). On three other assessments, the patient presented an intentional non-functional communication [i.e., clearly discernible communicative responses occurred on at least two out of the six questions, irrespectively of accuracy]. During all these assessments, we tried different codes of communication with the patient, such as point out YES/NO cards or rise your thumb to say YES/do not move your thumb to say NO, to finally observe that the best way to communicate was with visual fixation of YES/NO cards on the vertical axis…

When assessing his spatio-temporal orientation using YES/NO cards, the patient was able to correctly indicate his first and last name, the names of his roommate and the mother's roommate. He was, however, not able to give his age, to locate the hospital, neither the exact date (day, month, year) nor the season…

Despite recent advances in our understanding of disorders of consciousness and the redefinition of nosological distinctions between altered states of consciousness, diagnosis of severely brain-damaged patients continues to represent a major clinical challenge. If neuroimaging techniques support clinical examinations and help to improve the accuracy of the diagnosis of altered state of consciousness, behavioral assessment remains the principal method used to detect awareness in these patients . 

Nowadays, standardized scales such as the CRS-R are validated to assess the level of consciousness of these patients. In addition, series of studies have reported that specific clinical tools [e.g., using a mirror to assess visual pursuit or the own name to assess localization to sounds] can increase the chance of observing behavioral responses. In spite of these developments, clinical practice shows that disentangling reflexive from voluntary behaviors can still be very difficult.

Several misdiagnosis studies have been described in patients at an early stage after severe brain damage, as well as in the long-term care. Some studies reported cases of patients considered unconscious while they actually presented behavioral signs of consciousness when assessed more thoroughly. Other studies recount cases of patients who were considered unconscious at the bedside but who were actually found to be conscious with neuroimaging techniques, and some of these patients could even communicate with adapted communication code. Different factors can explain the high rate of diagnosis errors in patients with disorders of consciousness: the lack of knowledge about the diagnosis criteria and terminology, the absence or misuse of standardized assessment scale, the use of insensitive tools, the patients' perceptual and/or motor deficits, the presence of language impairment, the fluctuating arousal level, and the presence of pain or sedative drugs…

Our standardized-repeated behavioral assessments detected signs of consciousness and functional communication at the patient's bedside, which indicates that the patient emerged from the minimally conscious state. The neuroimaging results confirmed that the patient was conscious and that he actually was in a [locked-in syndrome] LIS due to a lesion in the brainstem. Because the patient could move more than a classical LIS, the diagnosis of incomplete LIS was finally made.

This patient had a brain injury 20 years before his admission to our center and he was misdiagnosed as being unconscious all these years when he was in fact fully conscious. The lack of knowledge about differential diagnosis of disorders of consciousness during this time period can explain that the patient received the diagnosis of “coma vigil” or “vegetative state.” The LIS was defined in 1966, while criteria of the minimally conscious state and emergence of this state were defined much later, in 2002. Moreover, 20 years ago, behavioral assessment of consciousness were limited to very few scales such as the Glasgow Coma Scale, which is not sensitive enough to detect small signs of consciousness . Our clinical practice shows that once stamped with the diagnosis of [unresponsive wakefulness syndrome ] UWS, it is often difficult to change the label, and the first signs of recovery of consciousness can be missed. The negative associations intrinsic to the term “vegetative state” can result to diagnostic errors and can also lead to potential effect on the treatment and care…

Our patient showed spontaneous eyes opening and severe motor impairment that could be related to quadriparesis. Communication, which was detected and could be possible via eye movements, was not easily reproducible: out of seven assessments, the patient was able to functionally communicate only on two consecutive assessments while a non-functional intentional communication was detected on three evaluations. Even if the patient presented an eye-movement-based communication, the diagnosis of incomplete LIS is challenging at the behavioral level because his communication responses fluctuated a lot. In addition, we should consider that the patient's deficit in spatio-temporal orientation (such as his inability to report the exact date or to locate the hospital) could be related to his 20-years-long impossibility to read a calendar or to be informed about the world outside his room rather than to a cognitive impairment. Inconsistency of behavioral responses and difficulties to correctly answer to orientation questions could also be the result of a lack of stimulation for the past 20 years.

At the neuroimaging level, structural MRI, DTI, and FDG-PET results highlighted a preservation of global cerebral metabolism and cerebral white matter combined with a lesion in the brainstem. The brain lesions observed with the neuroimaging tools, specifically in the brainstem, are typically observed in patients with LIS, with additional brain lesions.

In 33% of cases, a previous study showed that it was the relatives of the patient with LIS who were the first to detect consciousness and ability to communicate. In addition, guidelines emphasize the importance that the diagnosis should be made by involving information from family members or other persons who see the patient regularly. Other studies have also insisted on the critical role of the family or of a close relative in the assessment of patients.

The story of the patient we reported here is marked by an important social isolation. Indeed, since his accident, his family and friends were disengaged from the care and his general condition. The only people in daily contact with him were members of the medical staff. Since 1994, the patient was in a long care nursing home. Even if nurses knew him very well after all these years, they always referred to him as a “vegetative state.” The intrinsic negative connotation of the term “vegetative state” can lead to situations where the patients' relatives interpret this diagnosis as he is no longer a human being (but more a “vegetable”), and that there is no hope of recovery. The “unresponsive wakefulness syndrome” terminology was thus adopted to be more descriptive of the actual state of these patients and preventing the use of a pejorative term. In addition, even if the medical team usually strive to maintain these people's rights as human beings and treat them with respect, it is difficult to be optimistic and adopt a positive attitude during years when patients are very low responsive.