Sunday, May 30, 2021

Alternating hemiplegia of childhood and medical child abuse

A Renton, Washington mother under investigation for allegations of "medical child abuse" has been charged with second-degree assault of a child and second-degree attempted assault of a child.

Charging documents from the King County Prosecuting Attorney's office allege 31-year-old Sophie Hartman subjected her Black, adopted 6-year-old daughter to "medically unnecessary surgical interventions and restraints" for treatment of a rare neurological disease known as Alternating Hemiplegia of Childhood.

The documents note that the child has undergone nearly 500 medical appointments since she was around 2 years old and was given a surgically implanted feeding tube and a cecostomy tube to help flush the intestines. In addition, the documents state the child also used leg braces and a wheelchair despite doctors telling Hartman that they were unnecessary.

Four medical professionals on the child’s care team issued a report to the Washington State Department of Children Youth and Families in February, reviewed and signed by the medical director for Seattle Children’s Hospital, in which they call the risk to her child "profound."

"This situation is a case of medical child abuse," the report reads. "It is not necessary to know the possible motivation of a caregiver, only the outcome of the behavior. It is my concern that this pattern has resulted in unnecessary medical testing, medication, procedures, surgeries and debility of this child." Following the report, DCYF contacted the Renton Police Department, who began their own investigation.

Hartman told Make-A-Wish Foundation in 2018 that AHC would make her daughter "go paralyzed" at any given time. 

"She can lose the ability to talk and go into all different types of seizures and have extreme pain," Hartman said. "It's really tough." 

She added that doctors and "even the best pediatric specialists, do not know what to do and do not have treatment options." 

"She needs access to oxygen because her breathing shallows and slows," Hartman continued. "She depends on her feeding tube when she's unable to eat."

In 2019, after her daughter received her wish, Hartman said her daughter's supposed disorder "has been likened to a time bomb, that is a human time bomb for which there is no cure."

"For us, this is what life looks like," Hartman added. "It's navigating constant traumatic chaos, making plans that will inevitably fall through and battling resentment and bitterness for all that is outside of our control." 

According search warrants, while Hartman's daughter was diagnosed with AHC, doctors told investigators the diagnosis was based on information directly from Hartman, and that none of the symptoms, including severe seizures, had been observed firsthand. The girl was removed from Hartman's care in March and admitted to Seattle Children's Hospital for a 16 day admission. 

"At no point during her admission were there any findings or reported symptoms to support any of her prior diagnoses," the court documents state. "All the available evidence obtained during the course of her admission suggests (redacted) is a healthy young 6-year-old." 

Court documents also reveal that investigators found a series of diary entries in which Hartman allegedly mentioned various instances in which she lied about having different illnesses when she was younger, including meningitis and mono. 

In one entry, Hartman allegedly said "when it comes to suffering, I am a compulsive liar/exaggerator."

Hartman's attorneys told Q13 Fox that Hartman is innocent of the "wholly unjustified" charges from King County prosecutors, adding that they are "based on false statements and misrepresentations of the medical record by a doctor at Seattle Children’s Hospital who has never seen the child or spoken with Ms. Hartman," despite "overwhelming objective evidence" supporting the diagnosis. 

"Ms. Hartman’s child was diagnosed with a rare neurological disease, Alternating Hemiplegia of Childhood, by one of the few expert pediatric neurologists in the world from Duke University and by a neurologist at Mary Bridge Hospital in Tacoma," the lawyers continued. "Contrary to the allegations of the King County Prosecuting Attorney, the child’s diagnosis was made by more than one doctor, is legitimate, and is based on a substantial record beyond the reports and information provided by Ms. Hartman. That record includes independent medical examinations by multiple doctors, direct observation of the child by doctors and nurses at Duke and at Seattle Children’s Hospital, standardized testing results, videotapes of the child’s symptoms, MRI, EEG and other diagnostic tests." 

The lawyers added that the King County Prosecuting Attorney has the medical records from Duke as well as records from Seattle Children’s Hospital "amply supporting the diagnosis" as well as "the consistent reports of Ms. Hartman." 

Make-A-Wish told Q13 Fox that it was "deeply saddened and dismayed to learn about the alleged child abuse case involving one of our former wish families" and that the health and well-being of its wish children are "always of paramount concern to us.

Incidence and prevalence of drug-resistant epilepsy

Sultana B, Panzini MA, Veilleux Carpentier A, Comtois J, Rioux B, Gore G, Bauer PR, Kwon CS, Jetté N, Josephson CB, Keezer MR. Incidence and Prevalence of Drug-Resistant Epilepsy: A Systematic Review and Meta-analysis. Neurology. 2021 Apr 27;96(17):805-817. doi: 10.1212/WNL.0000000000011839. Epub 2021 Mar 15. PMID: 33722992.


Objective: To evaluate the incidence and prevalence of drug-resistant epilepsy (DRE) as well as its predictors and correlates, we conducted a systematic review and meta-analysis of observational studies. 

Methods: Our protocol was registered with PROSPERO, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology reporting standards were followed. We searched MEDLINE, Embase, and Web of Science. We used a double arcsine transformation and random-effects models to perform our meta-analyses. We performed random-effects meta-regressions using study-level data. 

Results: Our search strategy identified 10,794 abstracts. Of these, 103 articles met our eligibility criteria. There was high interstudy heterogeneity and risk of bias. The cumulative incidence of DRE was 25.0% (95% confidence interval [CI]: 16.8-34.3) in child studies but 14.6% (95% CI: 8.8-21.6) in adult/mixed age studies. The prevalence of DRE was 13.7% (95% CI: 9.2-19.0) in population/community-based populations but 36.3% (95% CI: 30.4-42.4) in clinic-based cohorts. Meta-regression confirmed that the prevalence of DRE was higher in clinic-based populations and in focal epilepsy. Multiple predictors and correlates of DRE were identified. The most reported of these were having a neurologic deficit, an abnormal EEG, and symptomatic epilepsy. The most reported genetic predictors of DRE were polymorphisms of the ABCB1 gene. 

Conclusions: Our observations provide a basis for estimating the incidence and prevalence of DRE, which vary between populations. We identified numerous putative DRE predictors and correlates. These findings are important to plan epilepsy services, including epilepsy surgery, a crucial treatment option for people with disabling seizures and DRE.

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Thursday, May 27, 2021

Short-term outcomes in infants with mild neonatal encephalopathy

Aoki Y, Kono T, Enokizono M, Okazaki K. Short-term outcomes in infants with mild neonatal encephalopathy: a retrospective, observational study. BMC Pediatr. 2021 May 7;21(1):224. doi: 10.1186/s12887-021-02688-y. PMID: 33962618; PMCID: PMC8103637.


Background: Neonatal encephalopathy due to acute perinatal asphyxia is a major cause of perinatal brain damage. Moderate to severe neonatal encephalopathy is associated with high mortality and morbidity rates. However, the neurodevelopmental outcomes in neonates with mild neonatal encephalopathy are unclear. The primary aim of this single-center observational study was to assess the short-term outcomes in term neonates with mild neonatal encephalopathy due to perinatal asphyxia. A secondary aim was to identify predictors of poor prognosis by identifying the characteristics of these infants according to their short-term outcomes. 

Methods: We retrospectively investigated all infants with perinatal asphyxia at Tokyo Metropolitan Children's Medical Center from January 2014 to December 2019. An abnormal short-term outcome was defined as any one of the following: seizures or abnormal electroencephalography, abnormal brain magnetic resonance imaging obtained within the first 4 weeks of life, and abnormal neurological examination findings at discharge. 

Results: In total, 110 term infants with perinatal asphyxia during the study period were screened and 61 were diagnosed with mild neonatal encephalopathy. Eleven (18 %) of these infants had an abnormal short-term outcome. The median Thompson score at admission was significantly higher in infants with abnormal short-term outcomes than in those with normal short-term outcomes (5 [interquartile range, 4-5.5] vs. 2 [interquartile range, 1-3], p < 0.01). Receiver operating characteristic curve analysis showed that a cutoff value of 4 had high sensitivity and specificity (90.9 and 83.0 %, respectively) for prediction of an abnormal short-term outcome. 

Conclusions: 18 % of infants with mild encephalopathy had an abnormal short-term outcome, such as abnormal brain magnetic resonance imaging findings. The Thompson score at admission may be a useful predictor of an abnormal short-term outcome in infants with mild neonatal encephalopathy.

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Eyelid myoclonia (Jeavons Syndrome): A comprehensive update

Zawar I, Knight EP. Epilepsy with Eyelid Myoclonia (Jeavons Syndrome): A comprehensive update, Pediatric Neurology (2020), doi:


Purpose of Review

The purpose of this review is to provide a comprehensive update and highlight the distinct electro-clinical features and discuss recent advances in etiology, pathophysiology and management strategies of epilepsy with eyelid myoclonias. 

Recent Findings

Recent studies indicate that certain gene mutations including CHD2 (chromo-domain helicase DNA binding protein 2), KCNB1, KIAA2022, and NAA10 may be found in these patients. In the past, it has been postulated that occipital cortex may play a role in the disease pathophysiology. Recent studies of functional MRI and connectivity of neuronal electrical activity have found additional evidence to support this hypothesis. Frontal cortex has additionally been implicated and it has been suggested that the epileptic cortex may extend beyond the occipital cortex to involve the posterior temporal cortex as well. An update on management strategies is discussed and recently described tools that maybe indicative of seizure persistence are discussed in this paper. 


Epilepsy with eyelid myoclonias or Jeavons Syndrome is an idiopathic generalized epilepsy characterized by the triad of eyelid myoclonia with or without absences, eyelid closure elicited electroencephalographic paroxysms (epileptiform discharges and/or seizures) and photosensitivity. This epilepsy may accounts for up to 12.9% of generalized epilepsies. However, it is frequently under-reported and under-recognized. A large number of patients become medically refractory and it has tendency to persist throughout life. Therefore, it is an important epilepsy for all neurologists to recognize as it is likely to be managed by both pediatric and adult neurologists.

Rates of incidental findings in brain magnetic resonance imaging in children

Li Y, Thompson WK, Reuter C, Nillo R, Jernigan T, Dale A, Sugrue LP; ABCD Consortium, Brown J, Dougherty RF, Rauschecker A, Rudie J, Barch DM, Calhoun V, Hagler D, Hatton S, Tanabe J, Marshall A, Sher KJ, Heeringa S, Hermosillo R, Banich MT, Squeglia L, Bjork J, Zucker R, Neale M, Herting M, Sheth C, Huber R, Reeves G, Hettema JM, Howlett KD, Cloak C, Baskin-Sommers A, Rapuano K, Gonzalez R, Karcher N, Laird A, Baker F, James R, Sowell E, Dick A, Hawes S, Sutherland M, Bagot K, Bodurka J, Breslin F, Morris A, Paulus M, Gray K, Hoffman E, Weiss S, Rajapakse N, Glantz M, Nagel B, Ewing SF, Goldstone A, Pfefferbaum A, Prouty D, Rosenberg M, Bookheimer S, Tapert S, Infante M, Jacobus J, Giedd J, Shilling P, Wade N, Uban K, Haist F, Heyser C, Palmer C, Kuperman J, Hewitt J, Cottler L, Isaiah A, Chang L, Edwards S, Ernst T, Heitzeg M, Puttler L, Sripada C, Iacono W, Luciana M, Clark D, Luna B, Schirda C, Foxe J, Freedman E, Mason M, McGlade E, Renshaw P, Yurgelun-Todd D, Albaugh M, Allgaier N, Chaarani B, Potter A, Ivanova M, Lisdahl K, Do E, Maes H, Bogdan R, Anokhin A, Dosenbach N, Glaser P, Heath A, Casey BJ, Gee D, Garavan HP, Dowling G, Brown S. Rates of Incidental Findings in Brain Magnetic Resonance Imaging in Children. JAMA Neurol. 2021 May 1;78(5):578-587. doi: 10.1001/jamaneurol.2021.0306. PMID: 33749724; PMCID: PMC7985817.


Importance: Incidental findings (IFs) are unexpected abnormalities discovered during imaging and can range from normal anatomic variants to findings requiring urgent medical intervention. In the case of brain magnetic resonance imaging (MRI), reliable data about the prevalence and significance of IFs in the general population are limited, making it difficult to anticipate, communicate, and manage these findings. 

Objectives: To determine the overall prevalence of IFs in brain MRI in the nonclinical pediatric population as well as the rates of specific findings and findings for which clinical referral is recommended. 

Design, setting, and participants: This cohort study was based on the April 2019 release of baseline data from 11 810 children aged 9 to 10 years who were enrolled and completed baseline neuroimaging in the Adolescent Brain Cognitive Development (ABCD) study, the largest US population-based longitudinal observational study of brain development and child health, between September 1, 2016, and November 15, 2018. Participants were enrolled at 21 sites across the US designed to mirror the demographic characteristics of the US population. Baseline structural MRIs were centrally reviewed for IFs by board-certified neuroradiologists and findings were described and categorized (category 1, no abnormal findings; 2, no referral recommended; 3; consider referral; and 4, consider immediate referral). Children were enrolled through a broad school-based recruitment process in which all children of eligible age at selected schools were invited to participate. Exclusion criteria were severe sensory, intellectual, medical, or neurologic disorders that would preclude or interfere with study participation. During the enrollment process, demographic data were monitored to ensure that the study met targets for sex, socioeconomic, ethnic, and racial diversity. Data were analyzed from March 15, 2018, to November 20, 2020. 

Main outcomes and measures: Percentage of children with IFs in each category and prevalence of specific IFs. 

Results: A total of 11 679 children (52.1% boys, mean [SD] age, 9.9 [0.62] years) had interpretable baseline structural MRI results. Of these, 2464 participants (21.1%) had IFs, including 2013 children (17.2%) assigned to category 2, 431 (3.7%) assigned to category 3, and 20 (0.2%) assigned to category 4. Overall rates of IFs did not differ significantly between singleton and twin gestations or between monozygotic and dizygotic twins, but heritability analysis showed heritability for the presence or absence of IFs (h2 = 0.260; 95% CI, 0.135-0.387). 

Conclusions and relevance: Incidental findings in brain MRI and findings with potential clinical significance are both common in the general pediatric population. By assessing IFs and concurrent developmental and health measures and following these findings over the longitudinal study course, the ABCD study has the potential to determine the significance of many common IFs.

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Safety of early discontinuation of antiseizure medication after acute symptomatic neonatal seizures

Glass HC, Soul JS, Chang T, Wusthoff CJ, Chu CJ, Massey SL, Abend NS, Lemmon M, Thomas C, Numis AL, Guillet R, Sturza J, McNamara NA, Rogers EE, Franck LS, McCulloch CE, Shellhaas RA. Safety of Early Discontinuation of Antiseizure Medication After Acute Symptomatic Neonatal Seizures. JAMA Neurol. 2021 May 24. doi: 10.1001/jamaneurol.2021.1437. Epub ahead of print. PMID: 34028496.


Importance: Antiseizure medication (ASM) treatment duration for acute symptomatic neonatal seizures is variable. A randomized clinical trial of phenobarbital compared with placebo after resolution of acute symptomatic seizures closed early owing to low enrollment. 

Objective: To assess whether ASM discontinuation after resolution of acute symptomatic neonatal seizures and before hospital discharge is associated with functional neurodevelopment or risk of epilepsy at age 24 months. 

Design, setting, and participants: This comparative effectiveness study included 303 neonates with acute symptomatic seizures (282 with follow-up data and 270 with the primary outcome measure) from 9 US Neonatal Seizure Registry centers, born from July 2015 to March 2018. The centers all had level IV neonatal intensive care units and comprehensive pediatric epilepsy programs. Data were analyzed from June 2020 to February 2021. 

Exposures: The primary exposure was duration of ASM treatment dichotomized as ASM discontinued vs ASM maintained at the time of discharge from the neonatal seizure admission. To enhance causal association, each outcome risk was adjusted for propensity to receive ASM at discharge. Propensity for ASM maintenance was defined by a logistic regression model including seizure cause, gestational age, therapeutic hypothermia, worst electroencephalogram background, days of electroencephalogram seizures, and discharge examination (all P ≤ .10 in a joint model except cause, which was included for face validity). 

Main outcomes and measures: Functional neurodevelopment was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) at 24 months powered for propensity-adjusted noninferiority of early ASM discontinuation. Postneonatal epilepsy, a prespecified secondary outcome, was defined per International League Against Epilepsy criteria, determined by parent interview, and corroborated by medical records. 

Results: Most neonates (194 of 303 [64%]) had ASM maintained at the time of hospital discharge. Among 270 children evaluated at 24 months (mean [SD], 23.8 [0.7] months; 147 [54%] were male), the WIDEA-FS score was similar for the infants whose ASMs were discontinued (101 of 270 [37%]) compared with the infants with ASMs maintained (169 of 270 [63%]) at discharge (median score, 165 [interquartile range, 150-175] vs 161 [interquartile range, 129-174]; P = .09). The propensity-adjusted average difference was 4 points (90% CI, -3 to 11 points), which met the a priori noninferiority limit of -12 points. The epilepsy risk was similar (11% vs 14%; P = .49), with a propensity-adjusted odds ratio of 1.5 (95% CI, 0.7-3.4; P = .32). 

Conclusions and relevance: In this comparative effectiveness study, no difference was found in functional neurodevelopment or epilepsy at age 24 months among children whose ASM was discontinued vs maintained at hospital discharge after resolution of acute symptomatic neonatal seizures. These results support discontinuation of ASM prior to hospital discharge for most infants with acute symptomatic neonatal seizures.

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Tuesday, May 11, 2021

Development of central precocious puberty following cannabinoid use for pediatric epilepsy

Krishnan A, Agwu JC, Kallappa C, et al. Development of central precocious puberty following cannabinoid use for paediatric epilepsy: causal or coincidence? BMJ Case Reports CP 2021;14:e239678.


Research suggests a role for cannabidiol oil in managing certain forms of paediatric onset epilepsy. However, studies on the impact of cannabis on the hypothalamo-pituitary-gonadal (HPG) axis have conflicting results. Delta-9-tetrahydrocannabinol (Δ9-THC) acutely inhibits gonadotropin-releasing hormone in the hypothalamus, reducing testosterone levels by 65% in rhesus monkeys. Additionally, there have been reports of pubertal arrest and delayed puberty in male cannabis users. In contrast, other studies have reported higher testosterone levels following long-term cannabis use. 

A 2-year-old boy presented with testicular enlargement, increased penile length and growth of coarse pubic hair developing over 6 months. His mother procured cannabidiol oil online, which he started taking 7 months earlier for severe epilepsy refractory to medical management. Subsequent investigations confirmed central precocious puberty. While it is unclear whether the precocious puberty is a direct consequence of HPG axis activation by Δ9-THC, this case demonstrates a temporal association between cannabis use and development of precocious puberty.

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Wednesday, May 5, 2021

Association of breastfeeding and child IQ score at age 5 years

Plunkett, Beth A. MD, MPH; Mele, Lisa ScM; Casey, Brian M. MD; Varner, Michael W. MD; Sorokin, Yoram MD; Reddy, Uma M. MD MPH; Wapner, Ronald J. MD; Thorp, John M. Jr MD; Saade, George R. MD; Tita, Alan T.N. MD, PhD; Rouse, Dwight J. MD; Sibai, Baha MD; Mercer, Brian M. MD; Tolosa, Jorge E. MD, MSCE; Caritis, Steve N. MD; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network Association of Breastfeeding and Child IQ Score at Age 5 Years, Obstetrics & Gynecology: April 2021 - Volume 137 - Issue 4 - p 561-570. doi: 10.1097/AOG.0000000000004314



To evaluate whether breastfeeding and its duration are associated with a reduced risk of low IQ scores or other neurodevelopmental problems.


We conducted a secondary analysis of two parallel multicenter, double-blinded randomized controlled trials in which participants with a singleton pregnancy and either subclinical hypothyroidism or hypothyroxinemia were treated with thyroxine or placebo. Our primary outcome was a low IQ score (less than 85 on the WPPSI-III [Wechsler Preschool and Primary Scale of Intelligence III] at age 5 years). Secondary outcomes included performance measures on other validated neurodevelopmental tests. Univariable and multivariable analyses were performed to evaluate the association between breastfeeding and neurodevelopmental outcomes. Stepwise backward proceeding linear and logistic regression models were used to develop the final adjusted models.


Of the 772 participants studied, 614 (80%) reported breastfeeding. Of these, 31% reported breastfeeding for less than 4 months, 19% for 4–6 months, 11% for 7–9 months, 15% for 10–12 months and 23% for more than 12 months. IQ scores were available for 756 children; mean age-5 scores were higher with any breastfeeding (96.7±15.1) than without (91.2±15.0, mean difference 5.5, 95% CI 2.8–8.2), and low IQ scores were less frequent with any breastfeeding (21.5%) than with no breastfeeding (36.2%, odds ratio 0.48, 95% CI 0.33–0.71). In adjusted analyses, breastfeeding remained associated with reduced odds of low IQ score (adjusted odds ratio [aOR] 0.62, 95% CI 0.41–0.93), and each additional month of breastfeeding was associated with lower odds of a low IQ scores (aOR 0.97, 95% CI 0.939–0.996). No significant associations between breastfeeding and other neurodevelopmental outcomes were identified in adjusted analyses.


Breastfeeding and its duration are associated with lower odds of low IQ score at age 5 years.

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Subconcussive head impacts and neurocognitive function over 3 seasons of youth football

Rose SC, Yeates KO, Nguyen JT, Ercole PM, Pizzimenti NM, McCarthy MT. Subconcussive Head Impacts and Neurocognitive Function Over 3 Seasons of Youth Football. Journal of Child Neurology. April 2021. doi:10.1177/08830738211004490



To determine the association between repetitive subconcussive head impacts and neurobehavioral outcomes in youth tackle football players.\ 


Using helmet-based sensors, we measured head impacts for 3 consecutive seasons of play in 29 male players age 9-11. Cumulative impact g’s were calculated. Players completed a battery of outcome measures before and after each season, including neuropsychological testing, vestibular-ocular sensitivity, and self- and parent-reported measures of symptoms and attention-deficit hyperactivity disorder (ADHD). 


Average cumulative impact over 3 seasons was 13 900g. High-intensity hits predicted worse change for self-reported social adjustment (P = .001). Cumulative impact did not predict change in any of the outcome measures. History of ADHD, anxiety, and depression predicted worse change for self-reported symptoms and social adjustment, independent of head impacts. When players were stratified into 3 groups based on cumulative impact across all 3 seasons, differences in outcome measures existed prior to the start of the first season. These differences did not further increase over the course of the 3 seasons. 


Over 3 consecutive seasons of youth tackle football, we found no association between cumulative head impacts and neurobehavioral outcomes. Larger sample sizes and longer follow-up times would further assist in characterizing this relationship.

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Tuesday, May 4, 2021

Valproic acid for treating cyanotic breath holding spells

Hamed SA, Elhadad AF, Farghaly HS. Evaluation of the effectiveness of valproic acid for treating cyanotic breath holding spells: A Pilot prospective study. Expert Rev Clin Pharmacol. 2020 Nov;13(11):1263-1270. doi: 10.1080/17512433.2020.1828059. Epub 2020 Nov 1. PMID: 32969724.


Background: Cyanotic breath-holding spells (CBHS) are self-limited conditions among younger children. Frequent spells cause parents' fear and anxiety. Seizures, brain damage and sudden death have been rarely reported with BHS. Some reported spells' frequency reduction with iron or piracetam. We evaluated the effectiveness of valproic acid (VPA) to treat CBHS and predictors of improvement. 

Methods: Participants were 90 children with CBHS (≥4/week) (age: 1.6±0.4yrs). They were treated with VPA (5 mg/kg/d). Follow-ups occurred after 3-≥6 months. Autonomic nervous system functions were evaluated. 

Results: The majority (74.4%) had daily spells and 19% had ≥2 spells/d. Crying or anger provoked spells. Postural hypotension was found in 46.7%. They had normal electroencephalography and QT, QTc interval or QTd or QTcd and heart rate. Compared to controls, postural fall in systolic (>20mmHg) and diastolic (>10mmHg) blood pressures and mean arterial pressure (>10mmHg) were observed in 46.7%, 74.4% and 72.2% and miosis observed with 0.125% pilocarpine in 28.9% (P=0.001). Spells' frequency reduction (P=0.001) occurred within 3 months with VPA. The independent prdictors for spell' frequency reduction were reduction of anger and crying [OR=4.52(95%CI=2.35-6.04), P =0.01]. 

Conclusion: VPA therapy reduces CBHS' frequency. Mood improvement is a suggestive effective mechanism.