ABSTRACT: Interleukin-1β Biosynthesis Inhibition Reduces Acute Seizures and Drug Resistant Chronic Epileptic Activity in Mice.

Maroso M, Balosso S, Ravizza T, Iori V, Wright CI, French J, Vezzani A. Neurotherapeutics. 2011 Mar 24. [Epub ahead of print]

Experimental evidence and clinical observations indicate that brain inflammation is an important factor in epilepsy. In particular, induction of interleukin-converting enzyme (ICE)/caspase-1 and activation of interleukin (IL)-1β/IL-1 receptor type 1 axis both occur in human epilepsy, and contribute to experimentally induced acute seizures. In this study, the anticonvulsant activity of VX-765 (a selective ICE/caspase-1 inhibitor) was examined in a mouse model of chronic epilepsy with spontaneous recurrent epileptic activity refractory to some common anticonvulsant drugs. Moreover, the effects of this drug were studied in one acute model of seizures in mice, previously shown to involve activation of ICE/caspase-1. Quantitative analysis of electroencephalogram activity was done in mice exposed to acute seizures or those developing chronic epileptic activity after status epilepticus to assess the anticonvulsant effects of systemic administration of VX-765. Histological and immunohistochemical analysis of brain tissue was carried out at the end of pharmacological experiments in epileptic mice to evaluate neuropathology, glia activation and IL-1β expression, and the effect of treatment. Repeated systemic administration of VX-765 significantly reduced chronic epileptic activity in mice in a dose-dependent fashion (12.5-200 mg/kg). This effect was observed at doses ≥ 50 mg/kg, and was reversible with discontinuation of the drug. Maximal drug effect was associated with inhibition of IL-1β synthesis in activated astrocytes. The same dose regimen of VX-765 also reduced acute seizures in mice and delayed their onset time. These results support a new target system for anticonvulsant pharmacological intervention to control epileptic activity that does not respond to some common anticonvulsant drugs. Source.

ABSTRACT: Efficacy of Aripiprazole in Sulpiride-induced Tardive Oromandibular Dystonia.
Imai N, Ikawa M.
Intern Med. 2011;50(6):635-7. Epub 2011 Mar 15.
Department of Neurology, Shizuoka Red Cross Hospital, Japan.

Tardive dystonia is a side effect of dopamine receptor-blocking agents, which are mainly used as antipsychotic drugs. The treatment of tardive dystonia is difficult and often unsuccessful. An 82-year-old woman experienced mandibular deviation to the left due to spasm of the masticatory muscles with involuntary chewing movement and Parkinsonism. She had been treated with sulpiride for motility disorder for 5 years. Parkinsonism almost disappeared after the withdrawal of sulpiride, but tardive oromandibular dystonia showed no improvement. Aripiprazole treatment at 3 mg/day improved tardive oromandibular dystonia without worsening Parkinsonism. Low-dosage aripiprazole may be effective for tardive oromandibular dystonia in patients with no other psychiatric disorder.

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ABSTRACT: Enhanced Cortisol Response to Stress in Children in Autism.
Spratt EG, Nicholas JS, Brady KT, Carpenter LA, Hatcher CR, Meekins KA, Furlanetto RW, Charles JM.
J Autism Dev Disord. 2011 Mar 22. [Epub ahead of print]

Children with Autism often show difficulties in adapting to change. Previous studies of cortisol, a neurobiologic stress hormone reflecting hypothalamic-pituitary-adrenal (HPA) axis activity, in children with autism have demonstrated variable results. This study measured cortisol levels in children with and without Autism: (1) at rest; (2) in a novel environment; and (3) in response to a blood draw stressor. A significantly higher serum cortisol response was found in the group of children with autism. Analysis showed significantly higher peak cortisol levels and prolonged duration and recovery of cortisol elevation following the blood-stick stressor in children with autism. This study suggests increased reactivity of the HPA axis to stress and novel stimuli in children with autism.

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ABSTRACT: Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine.
Cummings C, Stewart M, Stevenson M, Morrow J, Nelson J.
Arch Dis Child. 2011 Mar 17. [Epub ahead of print]
Department of Child Health, Queen's University, Belfast, UK.

Objective To establish the relative risks of in utero exposure to lamotrigine (LTG), sodium valproate (NaV) and carbamazepine (CBZ) monotherapy for neurodevelopment. Design Observational cohort study. Patients and methods The study group consisted of children in Northern Ireland aged 9-60 months born to mothers who had enrolled with the UK Epilepsy and Pregnancy Register. The control group consisted of children identified from the Child Health System database across Northern Ireland. Data were gathered on covariates recognised as influencing child development. Main outcome measures Neurodevelopment assessed using either the Bayley Scales of Infant Development or the Griffiths Mental Development Scales. Results 210 children underwent assessment by a single researcher blinded to antiepileptic drug exposure. 23 (39.6%) children exposed in utero to NaV, 10 (20.4%) exposed to CBZ and one (2.9%) exposed to LTG had evidence of mild or significant developmental delay, compared to two (4.5%) children in the control group. Multivariable analysis demonstrated that in utero exposure to NaV (OR 26.1, 95% CI 4.9 to 139; p Conclusion In utero exposure to LTG did not have the detrimental effect on child development that was seen with NaV and with CBZ.

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ABSTRACT: Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and risk of autism.
Price CS, Thompson WW, Goodson B, Weintraub ES, Croen LA, Hinrichsen VL, Marcy M, Robertson A, Eriksen E, Lewis E, Bernal P, Shay D, Davis RL, DeStefano F.
Pediatrics. 2010 Oct;126(4):656-64. Epub 2010 Sep 13.

OBJECTIVE: Exposure to thimerosal, a mercury-containing preservative that is used in vaccines and immunoglobulin preparations, has been hypothesized to be associated with increased risk of autism spectrum disorder (ASD). This study was designed to examine relationships between prenatal and infant ethylmercury exposure from thimerosal-containing vaccines and/or immunoglobulin preparations and ASD and 2 ASD subcategories: autistic disorder (AD) and ASD with regression.

METHODS: A case-control study was conducted in 3 managed care organizations (MCOs) of 256 children with ASD and 752 controls matched by birth year, gender, and MCO. ASD diagnoses were validated through standardized in-person evaluations. Exposure to thimerosal in vaccines and immunoglobulin preparations was determined from electronic immunization registries, medical charts, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We used conditional logistic regression to assess associations between ASD, AD, and ASD with regression and exposure to ethylmercury during prenatal, birth-to-1 month, birth-to-7-month, and birth-to-20-month periods.

RESULTS: There were no findings of increased risk for any of the 3 ASD outcomes. The adjusted odds ratios (95% confidence intervals) for ASD associated with a 2-SD increase in ethylmercury exposure were 1.12 (0.83-1.51) for prenatal exposure, 0.88 (0.62-1.26) for exposure from birth to 1 month, 0.60 (0.36-0.99) for exposure from birth to 7 months, and 0.60 (0.32-0.97) for exposure from birth to 20 months.

CONCLUSIONS: In our study of MCO members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to increased risk of ASDs.

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ABSTRACT: Shank3 mutant mice display autistic-like behaviours and striatal dysfunction
João Peça,1, 2, 8 Cátia Feliciano,1, 3, 8 Jonathan T. Ting,1 Wenting Wang,1 Michael F. Wells,1 Talaignair N. Venkatraman,4 Christopher D. Lascola,1, 4 Zhanyan Fu1, 5, 6 & Guoping Feng1, 6, 7

Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan–McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice.

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ABSTRACT: Clinical features of childhood narcolepsy. Can cataplexy be foretold?
Nevsimalova S, Jara C, Prihodova I, Kemlink D, Sonka K, Skibova J.
Eur J Paediatr Neurol. 2011 Feb 21. [Epub ahead of print]

BACKGROUND: Narcolepsy is a life-long disease characterized by abnormal regulation of the sleep-wake cycle and increased penetration of rapid eye movement (REM) sleep. In children, narcolepsy without cataplexy is more frequently seen than in adults. The aim of our study was to evaluate clinical and polysomnographic parameters to verify if cataplexy appearing later in life can be foretold.

CONCLUSION: Narcolepsy in childhood leaves very little scope for the prediction of cataplexy later in life.

Read the full abstract here.

ABSTRACT: Transverse-plane Pelvic Asymmetry in Patients With Cerebral Palsy and Scoliosis.
Ko PS, Jameson PG 2nd, Chang TL, Sponseller PD.

BACKGROUND: Pelvic obliquity and loss of sitting balance develop from progressive scoliosis in cerebral palsy (CP) and are indications for surgery. Our goal was to quantify pelvic asymmetry to help understand skeletal deformity in CP and its surgical correction.

CONCLUSIONS: Transverse pelvic asymmetry, a little-recognized deformity in patients with severe CP, is most pronounced above the acetabulum and is more common in patients with windswept hips. Spine surgeons should be aware of such asymmetry because it may make iliac fixation challenging and account for some persistent postoperative deformity.

Read the full article here.

Defective calcium channels as a possible cause of epilepsy

Hereditary diseases such as epilepsy or various coordination disorders may be caused by changes in nerve cells of the cerebellum, which do not set in until after birth. This is reported by Bochum’s neuroscientists in the Journal of Neuroscience.

The team of Prof. Dr. Stefan Herlitze, the Chair of the Department of Zoology and Neurobiology at RUB, showed that the diseases broke out in mice if, a week after birth, they eliminated a particular protein in the cerebellum which regulates the influx of ions into nerve cells. “It's the first time that we have gained an insight into the origin of these diseases” said Prof. Herlitze. “We can now start conducting research to develop new therapeutic approaches.”

Various forms of epilepsy, coordination disturbances (ataxias) and migraines are caused by mutations in the so-called P/Q-type calcium channel that controls the influx of calcium ions into the nerve cells of the brain. Dr. Melanie Mark from Prof. Herlitze’s team developed an animal model in which this calcium channel could be deactivated at any time in a brain region of choice. The researchers focused on specific cells in the cerebellum (Purkinje cells) that coordinate the movements of the body. “The calcium channel is actually present throughout the entire brain”, explains Dr. Mark. “It is the first time that we have been able to show that the diseases can be triggered by dysfunctional signal processing originating in the cerebellum.”

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Original abstract.

ABSTRACT: Body weight supported treadmill training improves the regularity of the stepping kinematics in children with Cerebral Palsy.
Kurz MJ, Stuberg W, Dejong SL.
Dev Neurorehabil. 2011;14(2):87-93.

Objective: To examine if body weight supported treadmill training (BWSTT) improves the regularity of stepping kinematics in children with cerebral palsy (CP). Methods: Twelve children with CP who had Gross Motor Function Classification Scores that ranged from II-IV participated in 12 weeks of body weight supported treadmill training that was performed 2 days a week. The primary outcome measure was the regularity of the stepping kinematics, which was assessed with Fourier analysis methods. The secondary measures were the preferred walking speed, step length, lower extremity strength and section E of the GMFM. Results: BWSTT improved the rhythmical control of the stepping kinematics, preferred walking speed, step length and GMFM score. The improvements in the regularity of the stepping kinematics were strongly correlated with changes in the preferred walking speed, step length and GMFM score. Conclusion: BWSTT can improve the motor control of the walk performance of children with CP.

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Vitamin b6 deficiency: a potential cause of refractory seizures in adults.
Gerlach AT, Thomas S, Stawicki SP, Whitmill ML, Steinberg SM, Cook CH.
ABSTRACT: JPEN J Parenter Enteral Nutr. 2011 Mar-Apr;35(2):272-5.

OBJECTIVE: In children, vitamin B(6) (pyridoxine) deficiency has been described as a cause of seizures that are refractory to conventional antiepileptic medications. We describe the clinical presentation of 3 adults with refractory seizures (later diagnosed with vitamin B(6) deficiency) that resolved after pyridoxine treatment. Design: Case series. Setting: Tertiary care surgical intensive care unit. Patients: In the first case, a 54-year-old male with history of alcoholic cirrhosis developed new-onset seizures refractory to phenytoin and levetiracetam 8 days after liver transplantation. In the second case, a 59-year-old male with hepatitis C infection developed intracranial hemorrhage and new-onset seizures refractory to phenytoin, levetiracetam, and pentobarbital. The third patient is a 78-year-old male with a history of alcohol dependence who was admitted for an intraventricular bleed and developed new onset of refractory seizures. Interventions: Intravenous pyridoxine followed by oral pyridoxine. Measurement and Main

RESULTS: In all 3 cases, seizures persisted despite escalation of conventional antiepileptic medications but resolved within 2 days of pyridoxine supplementation. In each case, low serum pyridoxal 5'-phosphate concentrations normalized with pyroxidine administration.

CONCLUSIONS: Although refractory seizures caused by vitamin B(6) deficiency are rare in adults, it should be considered in critically ill adult patients with refractory seizures.

Source.

ABSTRACT: Nonadherence to antiepileptic drugs and increased mortality: findings from the RANSOM Study.
Faught E, Duh MS, Weiner JR, Guérin A, Cunnington MC.
Neurology. 2008 Nov 11;71(20):1572-8. Epub 2008 Jun 18.

OBJECTIVES: The primary objective was to investigate whether nonadherence to antiepileptic drugs (AEDs) is associated with increased mortality and the secondary objective to examine whether nonadherence increases the risk of serious clinical events, including emergency department (ED) visits, hospitalizations, motor vehicle accident (MVA) injuries, fractures, and head injuries.

CONCLUSION: These findings suggest that nonadherence to antiepileptic drugs can have serious or fatal consequences for patients with epilepsy.

Read the full abstract here.

ABSTRACT: Language skills of school-aged children prenatally exposed to antiepileptic drugs.
Nadebaum C, Anderson VA, Vajda F, Reutens DC, Barton S, Wood AG.
School of Psychology, University of Birmingham, Edgbaston, B15 2TT, UK a.g.wood@bham.ac.uk.
Neurology. 2011 Feb 22;76(8):719-26.

Abstract
OBJECTIVES: Fetal exposure to some antiepileptic drugs (AEDs) carries increased risk of major birth defects, and may be associated with reduced intellectual abilities. The impact on language remains unclear. This study aimed to investigate the impact of fetal AED exposure on language skills.

CONCLUSIONS: Fetal exposure to sodium valproate increases the risk of language impairment. This should be taken into account when making treatment decisions for women with epilepsy of childbearing age.

Read more at the link.

ABSTRACT: Childhood and adolescent migraine: A neuropsychiatric disorder?
Balottin U, Chiappedi M, Rossi M, Termine C, Nappi G.
Med Hypotheses. 2011 Feb 26.

Migraine is a neurological disorder characterized by unilateral head pain, nausea and/or vomiting and altered sensory perception (particularly phono- and/or photophobia). It is a common and disabling condition in children and adolescents, just as it is in adults; its origins, pathophysiology and long-term course are still not fully understood. Biological factors are currently held to be crucial in the aetiopathogenesis of primary headaches, such as migraine. In children and adolescents, we hypothesize that for migraine to develop, life events and their psychological processing are fundamental and can act in two different ways: either as a predisposing factor, inducing a chronic state of anxiety or depression (even subclinical), or as a trigger factor, activating a cascade of psychological events which, in turn, activate the biological mechanisms that produce the migraine attack. According to our hypothesis, psychological processing of life events (i.e. how the child perceives and mentally processes them) is the main factor in migraine aetiopathogenesis. This hypothesis has important implications in terms of diagnostic and therapeutic choices for children and adolescents with migraine.

Source.

ABSTRACT: Relationships of muscle strength and bone mineral density in ambulatory children with cerebral palsy.
Chen CL, Lin KC, Wu CY, Ke JY, Wang CJ, Chen CY.
Osteoporos Int. 2011 Mar 3.

This work explores the relationships of muscle strength and areal bone mineral density (aBMD) in ambulatory children with cerebral palsy (CP). The knee extensor strength, but not motor function, was related to aBMD. Thus, muscle strength, especially antigravity muscle strength, was more associated with aBMD in these children than motor function.

INTRODUCTION: Muscle strength is related to bone density in normal children. However, no studies have examined these relationships in ambulatory children with CP. This work explores the relationships of muscle strength and aBMD in ambulatory children with CP.

CONCLUSIONS: These results suggest the muscle strength, especially antigravity muscle strength, were more associated with the bone density of ambulatory children with CP than motor function. The data may allow clinicians for early identifying the ambulatory CP children of potential low bone density.

Read the full abstract here.

ABSTRACT: Influence of Continuous Positive Airway Pressure on Outcomes of Rehabilitation in Stroke Patients With Obstructive Sleep Apnea.
Stroke. 2011 Mar 3.
Ryan CM, Bayley M, Green R, Murray BJ, Bradley TD.


BACKGROUND AND PURPOSE: In stroke patients, obstructive sleep apnea (OSA) is associated with poorer functional outcomes than in those without OSA. We hypothesized that treatment of OSA by continuous positive airway pressure (CPAP) in stroke patients would enhance motor, functional, and neurocognitive recovery.

CONCLUSIONS: Treatment of OSA by CPAP in stroke patients undergoing rehabilitation
improved functional and motor, but not neurocognitive outcomes.

Read the full abstract here.

The utility of omega-3 fatty acids in epilepsy: more than just a farmed tilapia!

The utility of omega-3 fatty acids in epilepsy: more than just a farmed tilapia!

Terra VC, Arida RM, Rabello GM, Cavalheiro EA, Scorza FA.
Arq Neuropsiquiatr. 2011 Feb;69(1):118-21.


The epilepsies are one of the most common serious brain disorders and 20 to 30% of people developing epilepsy continue to have seizures and are refractory to treatment with the currently available therapies. Approximately one in a 1000 patients with chronic epilepsy will die suddenly, unexpectedly, and without explanation, even with post-mortem examination and this phenomenon is called sudden unexplained death in epilepsy (SUDEP). Understanding the mechanisms underlying SUDEP may lead to the identification of previously unrecognized risk factors that are more amenable to correction. We discuss here the possible implications of omega-3 fatty acids consumption on SUDEP prevention.

Read the full article here.

ABSTRACT: Identifying Autism Loci and Genes by Tracing Recent Shared Ancestry
Eric M. Morrow1,2,3,4,5,*, Seung-Yun Yoo1,2,4,5,*, Steven W. Flavell5,6, Tae-Kyung Kim5,6, Yingxi Lin5,6, Robert Sean Hill1,2,4,5, Nahit M. Mukaddes7, Soher Balkhy8, Generoso Gascon8,9, Asif Hashmi10, Samira Al-Saad11, Janice Ware5,12, Robert M. Joseph5,13, Rachel Greenblatt1,2, Danielle Gleason1,2, Julia A. Ertelt1,2, Kira A. Apse1,2,5, Adria Bodell1,2, Jennifer N. Partlow1,2, Brenda Barry1,2, Hui Yao1, Kyriacos Markianos1, Russell J. Ferland14, Michael E. Greenberg5,6 and Christopher A. Walsh1,2,4,5,†

To find inherited causes of autism-spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning. A subset of genes, including NHE9 (Na+/H+ exchanger 9), showed additional potential mutations in patients with unrelated parents. Our findings highlight the utility of “homozygosity mapping” in heterogeneous disorders like autism but also suggest that defective regulation of gene expression after neural activity may be a mechanism common to seemingly diverse autism mutations.

Source.

ABSTRACT: Protective equipment and the prevention of concussion - what is the evidence?
Navarro RR.
Curr Sports Med Rep. 2011 Jan-Feb;10(1):27-31.

The complex nature of the evaluation and management of concussion lends to controversy, and the immediate and long-term implications still are being investigated. Various types of protective equipment have been used as a means to prevent concussions, and protective equipment is being used more frequently in different sports. Recent investigations have suggested that a protective, but not preventive, effect may be afforded by mouthguard use in rugby players, headgear use in soccer players, and customized mandibular orthotic use in football players. The use of faceshields has not shown a proven benefit in preventing the incidence of sport-related concussion in ice hockey or field hockey participants. Further studies are needed to clarify the role of protective equipment in the prevention of sport-related concussion.

http://journals.lww.com/acsm-csmr/Fulltext/2011/01000/Protective_Equipment_and_the_Prevention_of.10.aspx#

ABSTACT: Prevalence of Migraine Headache in the United StatesRelation to Age, Income, Race, and Other Sociodemographic Factors
Walter F. Stewart, PhD, MPH; Richard B. Lipton, MD; David D. Celentano, ScD; Michael L. Reed, PhD

Objective —To describe the magnitude and distribution of the public health problem posed by migraine in the United States by examining migraine prevalence, attack frequency, and attack-related disability by gender, age, race, household income, geographic region, and urban vs rural residence.

Conclusions —A projection to the US population suggests that 8.7 million females and 2.6 million males suffer from migraine headache with moderate to severe disability. Of these, 3.4 million females and 1.1 million males experience one or more attacks per month. Females between ages 30 to 49 years from lower-income households are at especially high risk of having migraines and are more likely than other groups to use emergency care services for their acute condition

Read the full abstract here.