K Santosh Mohan Rao, Chidambaram Balasubramaniam, K Subramaniam
Journal of Pediatric Neurosciences 2015 10(3):240-243
Syringohydromyelia is a frequent finding in cases of tethered cord syndrome. The classical teaching is that the development and progression of a syrinx is a chronic process. We present a case report of an acute onset syringomyelia in an infant, who underwent an excision of a lumbosacral transitional lipoma and detethering of the cord. Immediately after recovery, the infant was found to have flaccid paraplegia. An emergency magnetic resonance imaging revealed a large acute onset syringomyelia for which he underwent an emergency midline myelotomy and release of fluid from the syrinx. Though the eventual recovery was good, this made us re-visit our understanding of the concept of syringohydromyelia. The case details and a plausible hypothesis for the rapid development of the syrinx are presented.
Linear undisplaced fracture of temporoparietal bone acting as spontaneous early decompressive craniotomy in a neonate
Siddharth Vankipuram, Srikant Balasubramanium, Devendra K Tyagi, HV Savant
Journal of Pediatric Neurosciences 2015 10(3):261-263
Decompressive craniotomy (DC) is used to treat intracranial hypertension associated with traumatic brain injury. Early DC is associated with better outcomes. We present a neonate with a history of fall with computed tomography scan showing a large frontoparietal contusion and associated parietal and temporal bone fracture. This acted as a spontaneous DC causing bony segment to separate due to which the edematous brain could be accommodated. Despite the presence of a large contusion, the child was neurologically intact and medically managed. The neonate presented with a posttraumatic leptomeningeal cyst 2 months later, which had to be repaired surgically. We discuss how a linear undisplaced fracture acts as spontaneous DC and the role of early DC in improving outcomes.
Diastematomyelia with hemimyelomeningocele: An exceptional and complex spinal dysraphism
Neha Singh, Deepak Kumar Singh, Rakesh Kumar
Journal of Pediatric Neurosciences 2015 10(3):237-239
Variations in split cord malformation (SCM) have been described earlier. However, a true hemimyelomeningocele (HMM) as only congenital malformation is extremely rare and is reported infrequently in published literature. We are reporting the case of a 3-month-old girl child who presented with a swelling on the lower back since birth. Magnetic resonance imaging revealed a type 1 SCM with right hemicord forming a HMM. Precise diagnosis and thorough anatomical detail of dysraphism is essential for optimal, individualized neurosurgical management.
Journal of Pediatric Neurosciences 2015 10(3):282-284
Brain abscesses occur as an uncommon complication of bacterial meningitis in the neonatal period. A 34 weeks preterm at-risk neonate presented with abnormal breathing pattern and inability to maintain the oxygen saturation in room air. Magnetic resonance imaging (MRI) study revealed intra-parenchymal brain abscesses in the left basal ganglion and bilateral fronto-parietal regions. Intravenous piperacillin - tazobactam was commenced and continued for 6 weeks in Neonatal Intensive Care Unit. No surgical intervention was required. The patient responded to the medical management and was discharged after the documentation of radiological clearance in repeat MRI study. No complications were recorded. An appropriate neuro-developmental outcome was observed on follow-up. Brain abscesses may not be preceded by meningitis in all neonates. A strong clinical suspicion is required for the diagnosis especially in cases with atypical presentation.
Journal of Pediatric Neurosciences 2015 10(3):294-296
Acquired Dyke-Davidoff-Masson syndrome, also known as hemispheric atrophy, is characterized by loss of volume of one cerebral hemisphere from an insult in early life. Crossed cerebellar diaschisis refers to dysfunction/atrophy of cerebellar hemisphere which is secondary to contralateral supratentorial insult. We describe magnetic resonance imaging findings in two cases of acquired Dyke-Davidoff-Masson syndrome with crossed cerebro-cerebellar diaschisis.
Journal of Pediatric Neurosciences 2015 10(3):270-272
Extradural hematoma (EDH) occurs in approximately 2% of all patients with head injuries. Bilateral EDHs account for 2-10% of all acute EDHs in adults but are exceedingly rare in children. Posterior fossa EDHs occurs in 5% of all cases of EDHs. EDHs in children are more frequently venous (from tears of a dural sinus or diploic veins) and consequently have a better prognosis than EDHs in adults. Once the diagnosis of BEH is confirmed, urgent surgical treatment should be considered. We are reporting such rare form of injury as bilateral occipital EDH with supratentorial extension in 12 years child following road traffic accident.
Lennox–Gastaut Syndrome: A State of the Art Review
Lennox–Gastaut syndrome (LGS) is a severe age-dependent epileptic encephalopathy usually with onset between 1 and 8 years of age. Functional neuroimaging studies recently introduced the concept of Lennox–Gastaut as “secondary network epilepsy” resulting from dysfunctions of a complex system involving both cortical and subcortical structures (default-mode network, corticoreticular connections, and thalamus). These dysfunctions are produced by different disorders including hypoxic–ischemic encephalopathies, meningoencephalitis, cortical malformations, neurocutaneous disorders, or tumors. The list of etiologies was expanded to pathogenic copy number variants at whole-genome array comparative genomic hybridization associated with late-onset cases or pathogenic mutations involving genes, such as GABRB3, ALG13, SCN8A, STXBP1, DNM1, FOXG1, or CHD2. Various clinical trials demonstrated the usefulness of different drugs (including rufinamide, clobazam, lamotrigine, topiramate, or felbamate), ketogenic diet, resective surgery, corpus callosotomy, and vagus nerve stimulation in the treatment of epileptic manifestations. The outcome of LGS often remains disappointing regarding seizure control or cognitive functioning. The realization of animal models, which are still lacking, and the full comprehension of molecular mechanisms involved in epileptogenesis and cognitive impairment would give a relevant support to further improvements in therapeutic strategies for LGS patients.
Acute Sensory Neuronopathy following Enterovirus Infection in a 3-Year-Old Girl
Acute sensory neuronopathy (SNN) is a rapidly developing peripheral nervous system disease that primarily affects sensory neurons in the dorsal root ganglion or trigeminal ganglion, leading to the impairment of sensory axons. SNN is notably uncommon in childhood; only three cases of childhood or adolescent SNN have been reported to date. Moreover, SSN has never been reported in association with enterovirus infection. Here, we report the case of a 3-year-old girl who was initially diagnosed with enterovirus infection based on the presentation of fevers, rashes on all extremities, and ulceration over the posterior pharynx. Nine days later, she presented with ataxic and wide-based gait and dysmetria affecting the extremities, with an absence of sensory nerve action potentials in the upper and lower limbs. The patient was diagnosed with acute SNN based on the criteria developed by Camdessanché et al in 2009. To our knowledge, this is the youngest case of SNN reported to date. In addition, this case reveals that enterovirus infection can be associated with acute SNN in children in rare cases. Accurate diagnosis relies on clinical suspicion, comprehensive knowledge of the patient's history, and careful characterization of abnormal findings in electrodiagnostic studies.
The Cerebellum and Its Wrapping Meninge: Developmental Interplay between Two Major Structures
Meninges have long been considered as a protective and supportive tissue for the central nervous system. Nevertheless, new developmental roles are now attributed to them. The meninges that surround the cerebellum come from the cephalic mesoderm. They are essential for the cerebellum to develop normally. They induce and maintain the basal lamina and glia limitans. In the absence of these structures, the external granular cells of the cerebellum migrate aberrantly and penetrate the subarachnoid space. The molecules involved in the recognition between the cerebellar primordium and the basal lamina belong to two groups in humans: dystroglycan and laminin on the one hand, and GPR56 and collagen III on the other. Finally, molecules secreted by the meninges and acting on the cerebellum begin to be demonstrated; such is the case of SDF1 secreted under the action of FOXC1.
Lacosamide Lowers Valproate and Levetiracetam Levels
Lacosamide (LCM) due to no known drug interaction and the absence of metabolic enzyme induction is a good candidate for an add-on medication, especially in combination with lamotrigine, levetiracetam (LEV), oxcarbazepine, topiramate, and valproic acid (VPA). Here we report for the first time, to our knowledge, that LCM can lower VPA and LEV serum levels. At present, there are no known explicable mechanisms of action of LCM, which lowers VPA and LEV. Here observed drug interaction of LCM is of clinical significance, which might be useful for other colleagues in the field.
Infantile Hemangioma of the Posterior Fossa in a Newborn: Early Management and Long-Term Follow-up
A 21-day-old male infant was admitted with signs of intracranial hypertension. Brain magnetic resonance imaging (MRI) revealed a voluminous mass in the posterior fossa with an intense peripheral enhancement on T1 images with gadolinium. The child was treated secondarily by surgical decompression of the posterior fossa and the lesion was biopsied. The pathological findings indicated infantile hemangioma. Treatment with oral prednisolone was initiated at 3 months, given the lack of tumor involution. Six months after corticotherapy was stopped, repeated MRIs indicated a significant reduction in tumor size and then complete disappearance. Psychometric evaluation was performed at the age of 15 years, showing heterogeneous cognitive disabilities, with verbal abilities superior to nonverbal abilities and delayed motor development. Neurological examination was normal with no focal deficit. To our knowledge, this is the first published case reporting the long-term evolution of a patient with neonatal intracerebral hemangioma. We conclude that psychometric evaluations should be part of the long-term follow-up of children who have had an intracranial capillary hemangioma.
Neurological Complications of Respiratory Diseases⁎⁎Disclosure of interests: The authors have no commercial, proprietary, or financial interest in any products or companies described in this article.
Publication date: Available online 5 January 2017 Source:Seminars in Pediatric Neurology Author(s): Puja Mehta, Ana Melikishvili, Karen S. Carvalho The respiratory and central nervous systems are intimately connected. Ventilatory control is strictly regulated by central mechanisms in a complex process that involves central and peripheral chemoreceptors, baroreceptors, the cardiovascular system and specific areas of the brain responsible for autonomic control. Disorders of the lung and respiratory system can interfere with these mechanisms and temporarily or permanently disrupt this complex network resulting in mild to severe neurological sequelae. This article explores the wide variety of neurological problems resulting from respiratory dysfunction, with emphasis on its pathophysiology, clinical features, prognosis and long term outcome.
The Neurological Manifestations of Gastrointestinal Disease
Publication date: Available online 4 February 2017 Source:Seminars in Pediatric Neurology Author(s): Melissa Shapiro, David A. Blanco There is a growing interest in the extra-intestinal manifestations of common pediatric gastrointestinal diseases such as IBD and celiac disease. This chapter specifically focuses on the neurological symptoms that manifest as a result of these disorders and their treatments. Many neurologic symptoms have been reported in association with these diseases, including neuropathy, myopathy, ataxia, headache and seizure, among others. It is currently believed that these neurologic symptoms are largely overlooked by practitioners and could be of potential use for earlier diagnosis of disease. However, additional research, especially in the pediatric population, is warranted to further elaborate on the causality and pathophysiology of these neurologic symptoms.
Publication date: Available online 23 December 2016 Source:Seminars in Pediatric Neurology Author(s): H. Jorge Baluarte Neurological manifestations related to electrolyte disorders, drug toxicity, and uremia are common in chronic kidney disease (CKD). Seizures and coma were frequent complications of acute uremia, whereas peripheral neuropathy and encephalopathy, observed in progressive uremia, were terminal events. Failure to excrete metabolic products causes an accumulation of these products and can lead to severe intoxication. Clinically, the signs and symptoms of uremia can vary widely, depending on the biological characteristics of the patient, the specific type of renal disease, and the time of the uremic intoxication. CKD is an increasing problem worldwide and is now being recognized as a global health burden particularly for cardiovascular and cerebrovascular events. Despite improvements in the medical management of advanced CKD, including dialysis and transplantation, patients manifest a number of symptoms neurologists are often confronted with. Appropriate drug dosing, awareness of potential side effects of medications, prompt diagnosis, and treatment are essential in preventing long-term morbidity and mortality.
A small pons as a characteristic finding in Down syndrome: A quantitative MRI study
Publication date: April 2017 Source:Brain and Development, Volume 39, Issue 4 Author(s): Yuta Fujii, Noriko Aida, Tetsu Niwa, Mikako Enokizono, Kumiko Nozawa, Tomio Inoue BackgroundDown syndrome (DS) is the most common chromosomal aberration, but the characteristics of the brainstem component in this condition during childhood (from newborn to preteen stages) have not been clarified.ObjectiveTo evaluate the morphological features of the brainstem in DS on magnetic resonance imaging (MRI).Materials and methodsMRIs for 32 children with DS (16 boys and girls each; age range, 0–11years) without major brain insults, and 32 age-matched controls (16 boys and girls each) were retrospectively analyzed. Height, width, and area of the midbrain, pons, and medulla oblongata were measured on sagittal T1-weighted images; these were compared in children with DS and age-matched controls. The ratios of the brainstem to the size of the posterior fossa (BS/PF index) were calculated; these were also compared in the children with DS and the control group.ResultsThe width and area of the midbrain; height, width, area of the pons; and area of the medulla oblongata were significantly smaller in children with DS than in control children (P<0.05); the area of the pons, particularly for the ventral part, showed the largest differences in the mean relative differences. The BS/PF indices of the height, width, and area of the pons were significantly smaller in children with DS than in the control group (P<0.01). However, the BS/PF indices for the midbrain and the medulla oblongata did not differ between these two groups.ConclusionsChildren with DS may have small brainstems, particularly in the pons; this may be a characteristic morphological feature of the brainstem on MRI in childhood including neonates.
Clinically mild encephalitis/encephalopathy with a reversible splenial lesion of corpus callosum in Chinese children
Publication date: April 2017 Source:Brain and Development, Volume 39, Issue 4 Author(s): Qiong Fang, Lang Chen, Qiaobin Chen, Zhi Lin, Fang Yang ObjectiveTo investigate the characteristics and etiology of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in Chinese children.MethodsWe collected ten pediatric MERS patients from local hospital and enrolled another nineteen patients by reviewing the available literatures. The information of enrolled patients about clinical features, laboratory data, treatment strategies and prognoses were collected for further analysis.ResultsA total of 29 children, the median age of twenty-nine patients was (4.09±3.64) years old. The male-to-female ratio was 1.42:1.0. The major cause of MERS was viral infection. 18 patients had consciousness disturbance which was the most prominent syndrome. 18 patients had transient seizures and only one needed anticonvulsant treatment for long. 9 patients were observed serum sodium levels <135mEq/L. The cells and protein of cerebral spinal fluid (CSF) were increased in 3 patients. In all patients, brain MRI evaluation revealed typical lesion in splenium of the corpus callosum (SCC). 5 patients had additional lesions involving the periventricular white matter or bilateral centrum semiovale diagnosed. 3 patients were treated with antivirus treatment because of virus infection. 7 patients received corticosteroid. 2 patients received intravenous IVIG. As a result, all patients had fully recovered without neurological residual.ConclusionsThe result of present study suggests that Chinese children with MERS might have favorable prognosis, although there is still no guideline for treatment.
A ten-year follow-up cohort study of childhood epilepsy: Changes in epilepsy diagnosis with age
Publication date: April 2017 Source:Brain and Development, Volume 39, Issue 4 Author(s): Yoshiyuki Hanaoka, Harumi Yoshinaga, Katsuhiro Kobayashi ObjectiveTo elucidate all of the characteristics of childhood epilepsy, we performed a long-term follow-up study on the patients who visited Okayama University Hospital.Subjects and methodsWe retrospectively investigated the patients who were involved in the previous epidemiological study and visited Okayama University Hospital for a period of 10years after December 31, 1999.ResultsOverall, there were 350 patients’ medical records that were evaluated, and 258 patients with complete clinical information available for a 10-year period were enrolled. Ten patients died and the remaining 82 were lost to follow-up. Of 258 patients with complete information, 153 (59.3%) were seizure-free for at least 5years. One hundred thirty (50.4%) had intellectual disabilities and 77 (29.8%) had motor disabilities, including 75 (29.1%) with both disabilities on December 31, 2009. Thirty-four patients of 350 (9.7%) changed the epilepsy classification during follow-up. With regard to ten patients who died, nine of them had symptomatic epilepsy, particularly those with severe underlying disorders with an onset during the first year of life.ConclusionClinical status considerably changed during the decade-long follow-up period in childhood epilepsy. Changes in the epilepsy diagnosis are especially important and should be taken into account in the long-term care of children with epilepsy.
Postnatal irradiation-induced hippocampal neuropathology, cognitive impairment and aging
Publication date: April 2017 Source:Brain and Development, Volume 39, Issue 4 Author(s): Feng Ru Tang, Weng Keong Loke, Boo Cheong Khoo Irradiation of the brain in early human life may set abnormal developmental events into motion that last a lifetime, leading to a poor quality of life for affected individuals. While the effect of irradiation at different early developmental stages on the late human life has not been investigated systematically, animal experimental studies suggest that acute postnatal irradiation with ⩾0.1Gy may significantly reduce neurogenesis in the dentate gyrus and endotheliogenesis in cerebral vessels and induce cognitive impairment and aging. Fractionated irradiation also reduces neurogenesis. Furthermore, irradiation induces hippocampal neuronal loss in CA1 and CA3 areas, neuroinflammation and reduces gliogenesis. The hippocampal neurovascular niche and the total number of microvessels are also changed after radiation exposures. Each or combination of these pathological changes may cause cognitive impairment and aging. Interestingly, acute irradiation of aged brain with a certain amount of radiation has also been reported to induce brain hormesis or neurogenesis. At molecular levels, inflammatory cytokines, chemokines, neural growth factors, neurotransmitters, their receptors and signal transduction systems, reactive oxygen species are involved in radiation-induced adverse effect on brain development and functions. Further study at different omics levels after low dose/dose rate irradiation may not only unravel the mechanisms of radiation-induced adverse brain effect or hormesis, but also provide clues for detection or diagnosis of radiation exposure and for therapeutic approaches to effectively prevent radiation-induced cognitive impairment and aging. Investigation focusing on radiation-induced changes of critical brain development events may reveal many previously unknown adverse effects.
Anatomical, animal, and cellular evidence for Zika-induced pathogenesis of fetal microcephaly
Publication date: April 2017 Source:Brain and Development, Volume 39, Issue 4 Author(s): Jing-Zhang Wang, Xin-Hua Guo, Dian-Guo Xu Several recent articles published by Brain and Development in 2016 demonstrated some rare, but innovative, genetic mechanisms for microcephaly. This concise mini-review presented another novel pathogenic mechanism for microcephaly, which has actually been a worldwide medical challenge since the World Health Organization (WHO) defined the outbreak of the Zika virus (ZIKV) as an International Public Health Emergency on 1 Feb, 2016. As a recent noteworthy clinical phenomenon, the ZIKV outbreak was accompanied by a dramatically increased number of microcephalus fetuses. However, no direct evidence supporting the suspected pathogenic effects of ZIKV on fetal microcephaly was shown previously before 2016. Herein, we evaluated the most important human pathological, animal developmental, and neuro-cytotoxic findings released in 2016, and highlighted the original experimental evidence that strengthens the potential link between ZIKV and the high incidence of microcephaly in new-born babies. Because killing mosquitoes via insecticides is currently the only effective way to suppress ZIKV-induced disorders, the animal and cellular models described in this mini-review are very beneficial to anti-ZIKV drug development and vaccine assessment.
A novel PLP1 mutation associated with optic nerve enlargement in two siblings with Pelizaeus–Merzbacher disease: A new MRI finding
Publication date: March 2017 Source:Brain and Development, Volume 39, Issue 3 Author(s): Efterpi Pavlidou, Vijaya Ramachandran, Veronica Govender, Clare Wilson, Rini Das, Victoria Vlachou, Evangelos Pavlou, Anand Saggar, Kshitij Mankad, Maria Kinali Pelizaeus–Merzbacher disease (PMD) is a rare, X-linked disorder characterized by hypomyelination of the Central Nervous System due to mutations in the PLP1 gene. Certain mutations of the PLP1 gene correlate with specific clinical phenotypes and neuroimaging findings. We herein report a novel mutation of the PLP1 gene in two siblings with PMD associated with a rare and protean neuroimaging finding of optic nerve enlargement. To the best of our knowledge this is the first time that this novel mutation H133P of PLP1 gene is identified and clinically associated with optic nerve enlargement in PMD patients.
Raised intracranial pressure and retinal haemorrhages in childhood encephalopathies
To explore the relationship between raised intracranial pressure (RICP) and retinal haemorrhages in traumatic and non-traumatic childhood encephalopathies.
A prospective study of 112 children (35 females and 77 males, age range 0.01mo–17y 8.3mo; mean 5y 8.6mo, median 4y 5.6mo) included 57 accidental traumatic brain injuries (ATBIs), 21 inflicted traumatic brain injuries (ITBIs), and 34 non-traumatic encephalopathy cases. Measurements included intracranial pressure (ICP), cerebral perfusion pressure, pressure-time index of ICP, and number, zone, and layer of retinal haemorrhages on retinal imaging.
Group I had measured elevated ICP (n=42), Group II had clinical and/or radiological signs of RICP (n=21), and Group III had normal ICP (n=49). In the combined Groups I and II, 38% had retinal haemorrhages. Multiple logistic regression confirmed that the presence of retinal haemorrhages was significantly related to the presence of RICP independent of age and aetiology; however, the occurrence and overall numbers were not significantly related to the specific ICP level. The numbers of intraretinal (nerve-fibre layer and dot blot) retinal haemorrhages were significantly greater in those with RICP. The ITBI population was significantly different from the other combined aetiological categories.
The study results indicate a complex RICP/retinal haemorrhage relationship. There was no evidence of existing retinal haemorrhages being exacerbated or new retinal haemorrhages developing during periods of confirmed RICP.
Anti-N-methyl-d-aspartate receptor encephalitis in Māori and Pacific Island children in New Zealand
To investigate the incidence and severity of anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis in children from New Zealand.
A retrospective case series was undertaken of all children (≤18y) diagnosed with anti-NMDA receptor encephalitis from January 2008 to October 2015.
Sixteen patients were identified with anti-NMDA receptor antibodies in the cerebrospinal fluid, three of whom had an associated teratoma. Fifteen children had Māori and/or Pacific Island ancestry. The incidence of anti-NMDA receptor encephalitis in Māori children was 3.4 per million children per year (95% confidence interval [CI] 1.4–7.0) and the incidence in Pacific children was 10.0 per million children per year (95% CI 4.3–19.8) compared with 0.2 per million children per year (95% CI 0.0–1.0) in children without Māori or Pacific Island ancestry. Sixty-seven per cent of children had a good outcome (modified Rankin Score ≤2) at 2 years’ follow-up. This compares unfavourably with other cohorts despite a shorter median time to first-line immunotherapy (13d; range 4–89) and a higher proportion of children being treated with second-line therapy (50%).
Māori and Pacific Island children have a higher incidence of anti-NMDA receptor encephalitis and possibly a more severe phenotype. These data suggest a genetic predisposition to anti-NMDA receptor encephalitis in these populations.
The efficacy of interventions to increase physical activity participation of children with cerebral palsy: a systematic review and meta-analysis
To determine efficacy of therapy and behaviour change interventions to increase the level of participation in leisure-time physical activities (LTPAs) and habitual physical activity in children and young people with cerebral palsy.
Five databases were systematically searched. Included studies were randomized or comparison designs. Methodological quality was assessed with a modified Downs and Black Scale. Quantitative analysis was performed using RevMan 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Intervention components and behaviour change constructs were mapped against (1) the International Classification of Functioning, Disability and Health (ICF) and (2) the Theoretical Domains Framework.
Searches yielded 2487 unique articles. Eight studies (nine articles) were included. Interventions included physical training, activity level training, combined physical training and behaviour change therapy, online behaviour change modules, and context-focused therapy. Study quality varied from moderate to high. There was a small, significant effect of physical activity intervention compared with passive usual care on level of habitual physical activity, of approximately 1000 additional steps per day (standardized mean difference 0.34, 95% confidence interval 0.03–0.66, p=0.030). There was no significant effect on LTPA participation (standardized mean difference 0.40, 95% confidence interval −0.40 to 1.19, p=0.330).
Therapy and behaviour change interventions have the potential to increase LTPA participation of children and young people with cerebral palsy, although there is a need to depart from impairment-focused approaches. Inappropriate selection of outcomes and inadequate reporting of complex interventions are barriers to progress in this field.
Ataxia-telangiectasia: recommendations for multidisciplinary treatment
Ataxia-telangiectasia is a rare, neurodegenerative, and multisystem disease, characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient's needs. Besides the classic ataxia-telangiectasia phenotype, a variant phenotype exists with partly overlapping but some distinctive disease characteristics. This guideline summarizes frequently encountered medical problems in the disease course of patients with classic and variant ataxia-telangiectasia, in the domains of neurology, immunology and infectious diseases, pulmonology, anaesthetic and perioperative risk, oncology, endocrinology, and nutrition. Furthermore, it provides a practical guide with evidence- and expert-based recommendations for the follow-up and treatment of all these different clinical topics.
Course of employment in adults with cerebral palsy over a 14-year period
To explore the course of employment in adults with cerebral palsy (CP) over 14 years, and to identify subgroups at risk for unemployment.
Sixty-five adults with CP (33 males, 32 females; baseline age 25y 8mo, standard deviation [SD] 3y 2mo; intellectual impairment 25%; bilateral CP 65%) participated in a prospective cohort study. Self-reports of employment and work hours per week in 1996, 2000, and 2010 were documented. The course of employment (including sheltered work) and work hours per week were analysed, using generalized estimating equations (GEE).
Overall, employment rate was stable over time (38–45%, p=0.413), but lower than in the general population (75-86%, p<0.001). Employment rates were specifically low in adults with intellectual impairment, bilateral CP, and in adults with Gross Motor Function Classification System (GMFCS) levels IV and V. Work hours per week declined (35.0 [SD 7.9] to 31.2 [SD 10.3], p=0.033), especially among females (32.3 [SD 6.4] to 23.4 [SD 7.4], p<0.001). Similar to the general population, females often worked part-time.
Employment was low compared with the general population, but remained stable in the long term; however, work hours per week decreased. Adults with intellectual impairment, bilateral CP, and GMFCS levels IV and V are subgroups at risk for unemployment.
The impact of seizures on epilepsy outcomes: A national, community-based survey
The aim of this study was to examine the impact of seizures on persons living with epilepsy in a national, community-based setting.
The data source was the Survey of Living with Neurological Conditions in Canada (SLNCC), a cohort derived from a national population-based survey of noninstitutionalized persons aged 15 or more years. Participants had to be on a seizure drug or to have had a seizure in the past 5 years to meet the definition of active epilepsy. The respondents were further stratified by seizure status: the seizure group experienced ≥1 seizure in the past 5 years versus the no seizure group who were seizure-free in the past ≥5 years regardless of medication status. Weighted overall and stratified prevalence estimates and odds ratios were used to estimate associations.
The SLNCC included 713 persons with epilepsy with a mean age of 45.4 (standard deviation 18.0) years. Fewer people in the seizure group (42.7%) reported being much better than a year ago versus those in the no seizure group (70.1%). Of those with seizures, 32.1% (95% confidence interval [95% CI] 18.8–45.3) had symptoms suggestive of major depression (as per the Patient Health Questionnaire-9) compared to 7.7% (95% CI 3.4–11.9) of those without seizures. Driving, educational, and work opportunities were also significantly limited, whereas stigma was significantly greater in those with seizures.
This community-based study emphasizes the need for seizure freedom to improve clinical and psychosocial outcomes in persons with epilepsy. Seizure freedom has an important influence on overall health, as those with at least one seizure over the prior 5 years had an increased risk of mood disorders, worse quality of life, and faced significantly more stigma.
Long-term white matter tract reorganization following prolonged febrile seizures
Diffusion magnetic resonance imaging (MRI) studies have demonstrated acute white matter changes following prolonged febrile seizures (PFS), but their longer-term evolution is unknown. We investigated a population-based cohort to determine white matter diffusion properties 8 years after PFS.
We used diffusion tensor imaging (DTI) and applied Tract-Based Spatial Statistics for voxel-wise comparison of white matter microstructure between 26 children with PFS and 27 age-matched healthy controls. Age, gender, handedness, and hippocampal volumes were entered as covariates for voxel-wise analysis.
Mean duration between the episode of PFS and follow-up was 8.2 years (range 6.7–9.6). All children were neurologically normal, and had normal conventional neuroimaging. On voxel-wise analysis, compared to controls, the PFS group had (1) increased fractional anisotropy in early maturing central white matter tracts, (2) increased mean and axial diffusivity in several peripheral white matter tracts and late-maturing central white matter tracts, and (3) increased radial diffusivity in peripheral white matter tracts. None of the tracts had reduced fractional anisotropy or diffusivity indices in the PFS group.
In this homogeneous, population-based sample, we found increased fractional anisotropy in early maturing central white matter tracts and increased mean and axial diffusivity with/without increased radial diffusivity in several late-maturing peripheral white matter tracts 8 years post-PFS. We propose disruption in white matter maturation secondary to seizure-induced axonal injury, with subsequent neuroplasticity and microstructural reorganization as a plausible explanation.
Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study
To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients.
Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1 year after ATL in 77 consecutive patients with unilateral MTLE-HS.
The overall QOLIE-31 score and all its subscale scores increased significantly (p < 0.0001) 1 year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1–16.1, p = 0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2–14.5, p = 0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity.
These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients.
The hemodynamic response to interictal epileptic discharges localizes the seizure-onset zone
Intracranial electroencephalography (EEG), performed presurgically in patients with drug-resistant and difficult-to-localize focal epilepsy, samples only a small fraction of brain tissue and thus requires strong hypotheses regarding the possible localization of the epileptogenic zone. EEG/fMRI (functional magnetic resonance imaging), a noninvasive tool resulting in hemodynamic responses, could contribute to the generation of these hypotheses. This study assessed how these responses, despite their interictal origin, predict the seizure-onset zone (SOZ).
We retrospectively studied 37 consecutive patients who underwent stereo-EEG (SEEG) and EEG/fMRI that resulted in significant hemodynamic responses. Hemodynamic response maps were co-registered to postimplantation anatomic imaging, allowing inspection of these responses in relation to SEEG electrode's location. The area containing the most significant t-value (primary cluster) explored with an electrode was assessed for concordance with SEEG-defined SOZ. Discriminant analysis was performed to distinguish the primary clusters having a high probability of localizing the SOZ.
Thirty-one patients had at least one study with primary cluster explored with an electrode, and 24 (77%) had at least one study with primary cluster concordant with the SOZ. Each patient could have multiple types of interictal discharge and therefore multiple studies. Among 59 studies from the 37 patients, 44 had a primary cluster explored with an electrode and 30 (68%) were concordant with the SOZ. Discriminant analysis showed that the SOZ is predictable with high confidence (>90%) if the primary cluster is highly significant and if the next significant cluster is much less significant or absent.
The most significant hemodynamic response to interictal discharges delineates the subset of the irritative zone that generates seizures in a high proportion of patients with difficult-to-localize focal epilepsy. EEG/fMRI generates responses that are valuable targets for electrode implantation and may reduce the need for implantation in patients in whom the most significant response satisfies the condition of our discriminant analysis.
Lacosamide in status epilepticus: Systematic review of current evidence
The intravenous formulation of lacosamide (LCM) and its good overall tolerability and safety favor the use in status epilepticus (SE). The aim of this systematic review was to identify and evaluate studies reporting on the use of LCM in SE.
We performed a systematic literature search of electronic databases using a combined search strategy from 2008 until October 2016. Using a standardized assessment form, information on the study design, methodologic framework, data sources, efficacy, and adverse events attributed to LCM were extracted from each publication and systematically reported.
In total, 522 SE episodes (51.7% female) in 486 adults and 36 children and adolescents were evaluated with an overall LCM efficacy of 57%. Efficacy was comparable between use in nonconvulsive (57%; 82/145) and generalized-convulsive (61%; 30/49; p = 0.68) SE, whereas overall success rate was better in focal motor SE (92%; 34/39, p = 0.013; p < 0.001). The efficacy with later positioning of LCM decreased from 100% to 20%. The main adverse events during treatment of SE are dizziness, abnormal vision, diplopia, and ataxia. Overall, lacosamide is well tolerated and has no clinically relevant drug–drug interactions.
The available data regarding the use of LCM in SE are promising, with a success rate of 57%. The strength of LCM is the lack of interaction potential and the option for intravenous use in emergency situations requiring rapid uptitration.
Cav1.3 channels play a crucial role in the formation of paroxysmal depolarization shifts in cultured hippocampal neurons
An increase of neuronal Cav1.3 L-type calcium channels (LTCCs) has been observed in various animal models of epilepsy. However, LTCC inhibitors failed in clinical trials of epileptic treatment. There is compelling evidence that paroxysmal depolarization shifts (PDSs) involve Ca2+ influx through LTCCs. PDSs represent a hallmark of epileptiform activity. In recent years, a probable epileptogenic role for PDSs has been proposed. However, the implication of the two neuronal LTCC isoforms, Cav1.2 and Cav1.3, in PDSs remained unknown. Moreover, Ca2+-dependent nonspecific cation (CAN) channels have also been suspected to contribute to PDSs. Nevertheless, direct experimental support of an important role of CAN channel activation in PDS formation is still lacking.
Primary neuronal networks derived from dissociated hippocampal neurons were generated from mice expressing a dihydropyridine-insensitive Cav1.2 mutant (Cav1.2DHP−/− mice) or from Cav1.3−/− knockout mice. To investigate the role of Cav1.2 and Cav1.3, perforated patch-clamp recordings were made of epileptiform activity, which was elicited using either bicuculline or caffeine. LTCC activity was modulated using the dihydropyridines Bay K 8644 (agonist) and isradipine (antagonist).
Distinct PDS could be elicited upon LTCC potentiation in Cav1.2DHP−/− neurons but not in Cav1.3−/− neurons. In contrast, when bicuculline led to long-lasting, seizure-like discharge events rather than PDS, these were prolonged in Cav1.3−/− neurons but not in Cav1.2DHP−/− neurons. Because only the Cav1.2 isoform is functionally coupled to CAN channels in primary hippocampal networks, PDS formation does not require CAN channel activity.
Our data suggest that the LTCC requirement of PDS relates primarily to Cav1.3 channels rather than to Cav1.2 channels and CAN channels in hippocampal neurons. Hence, Cav1.3 may represent a new therapeutic target for suppression of PDS development. The proposed epileptogenic role of PDSs may allow for a prophylactic rather than the unsuccessful seizure suppressing application of LTCC inhibitors.
Cognitive network reorganization following surgical control of seizures in Lennox-Gastaut syndrome
We previously observed that adults with Lennox-Gastaut syndrome (LGS) show abnormal functional connectivity among cognitive networks, suggesting that this may contribute to impaired cognition. Herein we report network reorganization following seizure remission in a child with LGS who underwent functional magnetic resonance imaging (fMRI) before and after resection of a cortical dysplasia. Concurrent electroencephalography (EEG) was acquired during presurgical fMRI. Presurgical and postsurgical functional connectivity were compared using (1) graph theoretical analyses of small-world network organization and node-wise strength; and (2) seed-based analyses of connectivity within and between five functional networks. To explore the specificity of these postsurgical network changes, connectivity was further compared to nine children with LGS who did not undergo surgery. The presurgical EEG-fMRI revealed diffuse activation of association cortex during interictal discharges. Following surgery and seizure control, functional connectivity showed increased small-world organization, stronger connectivity in subcortical structures, and greater within-network integration/between-network segregation. These changes suggest network improvement, and diverged sharply from the comparison group of nonoperated children. Following surgery, this child with LGS achieved seizure control and showed extensive reorganization of networks that underpin cognition. This case illustrates that the epileptic process of LGS can directly contribute to abnormal network organization, and that this network disruption may be reversible.
How Does Altered Metabolism Lead to Seizure Control? Partially Filling the Knowledge Gap
Metabolic Autocrine Regulation of Neurons Involves Cooperation Among Pannexin Hemichannels, Adenosine Receptors, and KATP Channels. Kawamura M, Jr., Ruskin DN, Masino SA. J Neurosci 2010;30(11):3886–3895. Metabolic perturbations that decrease or limit blood glucose—such as fasting or adhering to a ketogenic diet—reduce epileptic seizures significantly. To date, the critical links between altered metabolism and decreased neuronal activity remain unknown. More generally, metabolic changes accompany numerous CNS disorders, and the purines ATP and its core molecule adenosine are poised to translate cell energy into altered neuronal activity. Here we show that nonpathological changes in metabolism induce a purinergic autoregulation of hippocampal CA3 pyramidal neuron excitability. During conditions of sufficient intracellular ATP, reducing extracellular glucose induces pannexin-1 hemichannel-mediated ATP release directly from CA3 neurons. This extracellular ATP is dephosphorylated to adenosine, activates neuronal adenosine A1 receptors, and, unexpectedly, hyperpolarizes neuronal membrane potential via ATP-sensitive K+ channels. Together, these data delineate an autocrine regulation of neuronal excitability via ATP and adenosine in a seizure-prone subregion of the hippocampus and offer new mechanistic insight into the relationship between decreased glucose and increased seizure threshold. By establishing neuronal ATP release via pannexin hemichannels, and hippocampal adenosine A1 receptors coupled to ATP-sensitive K+ channels, we reveal detailed information regarding the relationship between metabolism and neuronal activity and new strategies for adenosine-based therapies in the CNS.
“For Whom the Bell Tolls”: Blockade of Toll-Like Receptors May Regulate Seizure Occurrence
Toll-Like Receptor 4 and High-Mobility Group Box-1 Are Involved in Ictogenesis and Can Be Targeted to Reduce Seizures. Maroso M, Balosso S, Ravizza T, Liu J, Aronica E, Iyer AM, Rossetti C, Molteni M, Casalgrandi M, Manfredi AA, Bianchi ME, Vezzani A. Nat Med 2010;16(4):413–419. Brain inflammation is a major factor in epilepsy, but the impact of specific inflammatory mediators on neuronal excitability is incompletely understood. Using models of acute and chronic seizures in C57BL/6 mice, we discovered a proconvulsant pathway involving high-mobility group box-1 (HMGB1) release from neurons and glia and its interaction with Toll-like receptor 4 (TLR4), a key receptor of innate immunity. Antagonists of HMGB1 and TLR4 retard seizure precipitation and decrease acute and chronic seizure recurrence. TLR4-defective C3H/HeJ mice are resistant to kainate-induced seizures. The proconvulsant effects of HMGB1, like those of interleukin-1β (IL-1β), are partly mediated by ifenprodil-sensitive N-methyl-D-aspartate (NMDA) receptors. Increased expression of HMGB1 and TLR4 in human epileptogenic tissue, like that observed in the mouse model of chronic seizures, suggests a role for the HMGB1-TLR4 axis in human epilepsy. Thus, HMGB1-TLR4 signaling may contribute to generating and perpetuating seizures in humans and might be targeted to attain anticonvulsant effects in epilepsies that are currently resistant to drugs.
Predicting the Unpredictable: Stereotactic Radiosurgery and Temporal Lobe Epilepsy
Predictors of Efficacy After Stereotactic Radiosurgery for Medial Temporal Lobe Epilepsy. Chang EF, Quigg M, Oh MC, Dillon WP, Ward MM, Laxer KD, Broshek DK, Barbaro NM; Epilepsy Radiosurgery Study Group. Neurology 2010;74(2):165–172. BACKGROUND: Stereotactic radiosurgery (RS) is a promising treatment for intractable medial temporal lobe epilepsy (MTLE). However, the basis of its efficacy is not well understood. METHODS: Thirty patients with MTLE were prospectively randomized to receive 20 or 24 Gy 50% isodose RS centered at the amygdala, 2 cm of the anterior hippocampus, and the parahippocampal gyrus. Posttreatment MRI was evaluated quantitatively for abnormal T2 hyperintensity and contrast enhancement, mass effect, and qualitatively for spectroscopic and diffusion changes. MRI findings were analyzed for potential association with radiation dose and seizure remission (Engel Ib or better outcome). RESULTS: Despite highly standardized dose targeting, RS produced variable MRI alterations. In patients with multiple serial imaging, the appearance of vasogenic edema occurred approximately 9–12 months after RS and correlated with onset of seizure remission. Diffusion and spectroscopy-detected alterations were consistent with a mechanism of temporal lobe radiation injury mediated by local vascular insult and neuronal loss. The degree of these early alterations at the peak of radiographic response was dose-dependent and predicted long-term seizure remission in the third year of follow-up. Radiographic changes were not associated with neurocognitive impairments. CONCLUSIONS: Temporal lobe stereotactic radiosurgery resulted in significant seizure reduction in a delayed fashion which appeared to be well-correlated with structural and biochemical alterations observed on neuroimaging. Early detected changes may offer prognostic information for guiding management.
Epilepsy Treatment Stimulus Package? Deep Brain Stimulation in Treatment-Resistant Focal Epilepsy
Electrical Stimulation of the Anterior Nucleus of Thalamus for Treatment of Refractory Epilepsy. Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, Oommen K, Osorio I, Nazzaro J, Labar D, Kaplitt M, Sperling M, Sandok E, Neal J, Handforth A, Stern J, DeSalles A, Chung S, Shetter A, Bergen D, Bakay R, Henderson J, French J, Baltuch G, Rosenfeld W, Youkilis A, Marks W, Garcia P, Barbaro N, Fountain N, Bazil C, Goodman R, McKhann G, Babu Krishnamurthy K, Papavassiliou S, Epstein C, Pollard J, Tonder L, Grebin J, Coffey R, Graves N; SANTE Study Group. Epilepsia 2010;51(5):899–908. PURPOSE: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. METHODS: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. RESULTS: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model ( p= 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and “most severe” seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. DISCUSSION: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.
An Update on Antiepileptic Drugs and Suicide: Are There Definitive Answers Yet?
In 2008, the Food and Drug Administration (FDA) issued a warning that any and all antiepileptic drugs (AEDs) might increase the risk of suicidal ideation, suicide attempt, and completed suicide. Considerable confusion and concern followed regarding the use of these drugs, in general, and specifically for people with epilepsy. Recently, four publications examined suicidality and AED use among several databases and illustrated how biases affect the findings. None of the studies was able to control completely for the indication for which the AEDs were prescribed or to account for the varying intensities with which different specialists monitoring patients for suicidality. Though multiple analyses were conducted for many AEDs, no study controlled for the numerous comparisons made. The result is a multitude of contradictions in the findings across studies and even within studies, with no study providing clear or convincing support for the FDA conclusions. This review attempts to clarify the methodological issues in assessing potential associations between AED use and suicidality.
Intractable Epilepsy: Relapsing, Remitting, or Progressive?
Seizure Remission and Relapse in Adults with Intractable Epilepsy: A Cohort Study. Choi H, Heiman G, Pandis D, Cantero J, Resor SR, Gilliam FG, Hauser WA. Epilepsia 2008;49(8):1440–1445. PURPOSE: To investigate the cumulative probabilities of ≥12 month seizure remission and seizure relapse following remission, and to test the associations of clinical characteristics with these two study end points in a prevalence cohort of intractable adult epilepsy patients during medical management. METHODS: A retrospective cohort study of intractable epilepsy patients seen in 2001 at a single center was conducted. Kaplan–Meier analysis was used to estimate the cumulative probabilities of seizure remission and subsequent seizure relapse. Cox proportional hazards models were used to estimate the association (1) between clinical factors and ≥12 month seizure remission and (2) between clinical factors and seizure relapse following remission. RESULTS: One hundred eighty-seven subjects met the eligibility criteria for intractable epilepsy. The estimate of probability of remission was about 4% per year. Seizure remission was temporary for some individuals, as 5 out of 20 subjects with remission ultimately relapsed. No clinical factors predicted the likelihood of achieving ≥12 month seizure remission or subsequent seizure relapse. DISCUSSION: Some people with intractable epilepsy achieve ≥12 month seizure remission during medical treatment. Remission, however, is only temporary for some individuals. We were unable to identify clear predictors for remission.Quantifying the Response to Antiepileptic Drugs: Effect of Past Treatment History. Schiller Y, Najjar Y. Neurology 2008;70(1):54–65. OBJECTIVE: To quantify the response to treatment with antiepileptic drugs (AEDs) as a function of the past treatment history and identify additional prognostic factors for predicting the response to newly administered AED treatments. METHODS: A cohort of 478 consecutive patients who received newly administered AED treatments between January 1999 and December 2004 and were followed prospectively for 1.5 to 7.5 years in a single epilepsy clinic. RESULTS: The response to newly administered AED treatments was highly dependent on the past treatment history. The seizure-free rates decreased from 61.8% for the first AED to 41.7%, 16.6%, and 0% after one, two to five, and six to seven past AEDs proved inefficient. This response curve corresponded to a mono-exponential function with a maximal response of 61.8% and half-decay constant of 1.5 AEDs. Likewise the response curve describing a greater than 50% reduction in seizure frequency corresponded to a mono-exponential function with a maximal response of 85.3% and half-decay constant of two AEDs. Three additional independent prognostic factors for predicting the response to AEDs were identified: type of epilepsy, duration of epilepsy, and number of seizures in the 3 months prior to AED initiation. CONCLUSION: Drug resistance is a graded process that follows a mono-exponential course with a half-decay constant of 1.5 to two antiepileptic drugs (AEDs). Although relative drug-resistant epilepsy can be diagnosed after failure of two past AEDs, absolute drug resistance requires failure of six AEDs, as a significant minority of patients (16.6%) is rendered seizure-free by addition of newly administered AEDs even after failure of two to five past antiepileptic drugs.
Neurosteroids on the Epilepsy Chessboard—Keeping Seizures in Check
Endogenous Neurosteroid Synthesis Modulates Seizure Frequency. Lawrence C, Martin BS, Sun C, Williamson J, Kapur J. Ann Neurol 2010;67(5):689–693. Inhibitory neurosteroids, molecules generated in glia from circulating steroid hormones and de novo from cholesterol, keep seizures in check in epileptic animals. They can enhance inhibitory transmission mediated by γ-aminobutyric acid receptors and have anticonvulsant action.
Paraneoplastic limbic encephalitis with SOX1 and PCA2 antibodies and relapsing neurological symptoms in an adolescent with Hodgkin lymphoma
Immune cross-reactivity between malignant and normal tissues causes the rare, so called paraneoplastic syndrome (PS). In approximately 60% of the patients, various onconeural antibodies are detectable in the cerebrospinal fluid (CSF) and are associated with typical tumor entities.We report an unusual case of paraneoplastic limbic encephalitis (PLE) in a 17-year-old adolescent with classical Hodgkin lymphoma. He presented with a variety of neurologic and neuropsychiatric symptoms, profound B-symptoms and typical MRI findings including hyperintense lesions with contrast enhancement in the medial temporal lobe and limbic system.
Assessing Mental Health in Boys with Duchenne Muscular Dystrophy: Emotional, Behavioural and Neurodevelopmental profile in an Italian clinical sample
To evaluate through a comprehensive protocol, the psychopathological profile of DMD boys. The primary aim of this observational study was to describe the emotional and behavioural profile and the neurodevelopmental problems of Italian boys with Duchenne Muscular Dystrophy (DMD); the secondary aim was to explore the relation between psychopathological profile and DMD genotype.
We present a revised diagnosis in a report ‘Neonatal seizures and limb malformations associated with liver-specific complex IV respiratory chain deficiency’ published 12 years ago.1 The report described an eight-week old infant (consanguineous Irish traveller parents) with intractable epilepsy, dysmorphic features (absent nail and terminal phalanges of fingers and toes), hepatomegaly, pigmentary retinopathy and hypotonia. Investigations revealed markers (retinopathy, UOA pattern and reduced liver complex IV activity) suggestive of mitochondrial disease but a specific gene mutation was not identified.
Cardiac injury after convulsive status epilepticus in children
Convulsive status epilepticus (CSE) is a medical emergency with high mortality that usually occurs within 30 days following the seizure activity. One of the potential mechanisms contributing to mortality in this period following CSE is cardiac injury. The aim of the present study was to evaluate cardiac injury after CSE in children.
Cardiac injury after convulsive status epilepticus in children
Objective: convulsive status epilepticus (CSE) is a medical emergency with high mortality that usually occurs within 30 days following the seizure activity. One of the potential mechanisms contributing to mortality in this period following CSE is cardiac injury. The aim of the present study was to evaluate cardiac injury after CSE.Patients and methods: sixty children presented with CSE were enrolled in this study. Thirty healthy children with matched age and sex were taken as a control. Electrocardiogram (ECG), echocardiographic examinations, plasma concentration of cardiac troponin I (cTnI) and brain-type natriuretic peptide (BNP) were done 6 hours after control of seizure for patients and control group.
[Correspondence] Diagnosis and treatment of carpal tunnel syndrome – Authors' response
We thank J Grant Thomson for highlighting the differing clinical perspectives in patient care. Our Review1 aimed to provide a comprehensive overview of the scientific literature that met our criteria for inclusion, which were described in our article. The conclusions of our narrative Review can therefore conflict with some opinions.
[Editorial] Investing in autism: better evidence for better care
People with autism are often poorly served, not only in terms of access to treatment and support but also by the extent to which interventions are based on robust evidence. The Autism Dividend: Reaping the Rewards of Better Investment, a report published on Jan 17, 2017, by the National Autism Project, highlights how far autistic people in the UK are from receiving care that meets their needs and is known to be cost-effective, or even effective. More funding and more evidence are needed to ensure that people affected by autism receive the care and support they need to lead fulfilling and rewarding lives.
With the growing availability of dogs ostensibly trained to alert their owners to an impending epileptic seizure, it's a question neurologists are increasingly likely to hear. But how do you decide whether to prescribe a dog? Adrian Burton investigates.
[In Context] Samuel Wiebe: new President of the International League Against Epilepsy
Say Treasure of the Sierra Madre and most people will think of John Huston's 1948 film classic starring Humphrey Bogart. Neurologists, however, might think these words a fitting accolade for Samuel Wiebe. Born in 1958 into a Hispanic–German–Dutch community in Nuevo Ideal among the foothills of Mexico's Western Sierra Madre mountains, Wiebe is now Professor of Clinical Neurosciences and Associate Dean of Clinical Research at the University of Calgary (Calgary, AB, Canada), and was recently elected President of the International League Against Epilepsy (ILAE)—positions for which he has all the right badges.
[In Context] Richard Morris' Christmas lecture double-bill
Scientists are often asked to give public lectures in the run-up to Christmas, but Richard Morris (Professor of Neuroscience at the University of Edinburgh, UK) was recently invited to deliver not one but two high-profile talks in Edinburgh during the festive season. The first, on Dec 7, 2016, was hosted by Edinburgh Neuroscience, a collection of research groups, and was entitled “Memory: why it matters and how it works”. The second was called “The making, keeping and losing of memory”, and took place on Dec 14, 2016, under the auspices of charity and membership organisation Alzheimer Scotland.
[Correspondence] Cognitive decline before diagnosis of Parkinson's disease – Authors' reply
We thank Sirwan KL Darweesh and colleagues for their interesting comments. We fully agree that cognitive decline can occur early in Parkinson's disease, including the prediagnostic phase, as demonstrated in the Article by Darweesh and colleagues,1 as well as our own,2 and other groups.3,4 As Darweesh and colleagues point out, investigation of the early clinical features and biomarkers associated with such early cognitive decline can provide not only information for clinical stratification and prognostication, but also help understand the underlying neurobiology of cognitive impairment in Parkinson's disease.
[Comment] The cause of stroke matters for secondary prevention
Cardiologists do not have to obsess about the cause of acute coronary syndromes. In more than 75% of cases, the cause of the myocardial infarction is plaque rupture with local thrombus formation.1 An understanding of this mechanism drives secondary prevention—ie, antiplatelet therapy. After acute coronary syndromes, patients are initially treated with aspirin to prevent further vascular events. Findings from studies have shown the superiority of the combination of aspirin with clopidogrel to aspirin alone2 and of more potent antiplatelet drugs, such as ticagrelor3 or prasugrel.
[Comment] Can lifestyle changes prevent cognitive impairment?
Prevention has been identified as a priority for combating the high burden of dementia.1,2 Observational cohort studies have shown several potentially modifiable risk and protective factors,3 but can changing these factors reduce the risk of cognitive impairment and dementia? Evidence from clinical trials is beginning to emerge.
[Articles] Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial
The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings.
[Review] The prognosis of dementia with Lewy bodies
Dementia with Lewy bodies is the second most common form of neurodegenerative dementia, yet scarce evidence is available about its prognosis and natural history, which are crucial to inform clinical practice and research. Patients with dementia with Lewy bodies might have a less favourable prognosis, with accelerated cognitive decline, shorter lifespan, and increased admission to residential care than patients with Alzheimer's disease. Health-care costs and, importantly, caregiver burden, are also reported to be higher in dementia with Lewy bodies than in Alzheimer's disease.
[Articles] Serotonin and dopamine transporter PET changes in the premotor phase of parkinsonism: cross-sectional studies
Dopaminergic and serotonergic changes progress in a similar fashion in LRRK2 mutation carriers with manifest Parkinson's disease and individuals with sporadic Parkinson's disease, but LRRK2 mutation carriers without manifest Parkinson's disease show increased serotonin transporter binding in the striatum, brainstem, and hypothalamus, possibly reflecting compensatory changes in serotonergic innervation preceding the motor onset of Parkinson's disease. Increased serotonergic innervation might contribute to clinical differences in LRRK2 Parkinson's disease, including the emergence of non-motor symptoms and, potentially, differences in the long-term response to levodopa.
[Articles] Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial
Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke. Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned.
[Comment] Can allogeneic stem cells improve outcomes after stroke?
Stroke is the second leading cause of death1 and the third leading cause of disability2 worldwide. Acute reperfusion therapies can improve outcomes but are only accessed by about one in 20 patients with ischaemic stroke in the USA. The need exists for additional therapies that are accessible and effective for most patients.3 One strategy in this regard is to develop new therapies that have a longer time window than the 3–6 h window of reperfusion therapies.
[Articles] Safety and efficacy of thrombectomy in acute ischaemic stroke (REVASCAT): 1-year follow-up of a randomised open-label trial
At 12 months follow-up, neurovascular thrombectomy reduced post-stroke disability and improved health-related quality of life, indicating sustained benefit. These findings have important clinical and public health implications for evaluating the cost-effectiveness of the intervention in the long term.
Gait Characteristics in Adolescents With Multiple Sclerosis
Publication date: March 2017 Source:Pediatric Neurology, Volume 68 Author(s): Alon Kalron, Lior Frid, Shay Menascu BackgroundMultiple sclerosis is a progressive autoimmune disease of the central nervous system. A presentation of multiple sclerosis before age18 years has traditionally been thought to be rare. However, during the past decade, more cases have been reported.Patient DescriptionWe examined gait characteristics in 24 adolescents with multiple sclerosis (12 girls, 12 boys). Mean disease duration was 20.4 (S.D. = 24.9) months and mean age was 15.5 (S.D. = 1.1) years. The mean expanded disability status scale score was 1.7 (S.D. = 0.7) indicating minimal disability. Outcomes were compared with gait and the gait variability index value of healthy age-matched adolescents.ResultsAdolescents with multiple sclerosis walked slower with a wider base of support compared with age-matched healthy control subjects. Moreover, the gait variability index was lower in the multiple sclerosis group compared with the values in the healthy adolescents: 85.4 (S.D. = 8.1) versus 96.5 (S.D. = 7.4).ConclusionsWe present gait parameters of adolescents with multiple sclerosis. From a clinical standpoint, our data could improve management of walking dysfunction in this relatively young population.
Harnessing Neuroimaging Capability in Pediatric Stroke: Proceedings of the Stroke Imaging Laboratory for Children Workshop
Publication date: April 2017 Source:Pediatric Neurology, Volume 69 Author(s): Nomazulu Dlamini, Max Wintermark, Heather Fullerton, Stephen Strother, Wayne Lee, Bruce Bjornson, Kristin P. Guilliams, Steven Miller, Adam Kirton, Christopher G. Filippi, Alexandra Linds, Rand Askalan, Gabrielle deVeber On June 5, 2015 the International Pediatric Stroke Study and the Stroke Imaging Laboratory for Children cohosted a unique workshop focused on developing neuroimaging research in pediatric stroke. Pediatric neurologists, neuroradiologists, interventional neuroradiologists, physicists, nurse practitioners, neuropsychologists, and imaging research scientists from around the world attended this one-day meeting. Our objectives were to (1) establish a group of experts to collaborate in advancing pediatric neuroimaging for stroke, (2) develop consensus clinical and research magnetic resonance imaging protocols for pediatric stroke patients, and (3) develop imaging-based research strategies in pediatric ischemic stroke. This article provides a summary of the meeting proceedings focusing on identified challenges and solutions and outcomes from the meeting. Further details on the workshop contents and outcomes are provided in three additional articles in the current issue of Pediatric Neurology.
Large-Vessel Vasculopathy in Children With Sickle Cell Disease: A Magnetic Resonance Imaging Study of Infarct Topography and Focal Atrophy
Publication date: April 2017 Source:Pediatric Neurology, Volume 69 Author(s): Kristin P. Guilliams, Melanie E. Fields, Dustin K. Ragan, Yasheng Chen, Cihat Eldeniz, Monica L. Hulbert, Michael M. Binkley, James N. Rhodes, Joshua S. Shimony, Robert C. McKinstry, Katie D. Vo, Hongyu An, Jin-Moo Lee, Andria L. Ford BackgroundLarge-vessel vasculopathy (LVV) increases stroke risk in pediatric sickle cell disease beyond the baseline elevated stroke risk in this vulnerable population. The mechanisms underlying this added risk and its unique impact on the developing brain are not established.MethodsWe analyzed magnetic resonance imaging and angiography scans of 66 children with sickle cell disease and infarcts by infarct density heatmaps and Jacobian determinants, a metric utilized to delineate focal volume change, to investigate if infarct location, volume, frequency, and cerebral atrophy differed among hemispheres with and without LVV.ResultsInfarct density heatmaps demonstrated infarct “hot spots” within the deep white matter internal border zone region in both LVV and non–LVV hemispheres, but with greater infarct density and larger infarct volumes in LVV hemispheres (2.2 mL versus 0.25 mL, P < 0.001). Additional scattered cortical infarcts in the internal carotid artery territory occurred in LVV hemispheres, but were rare in non–LVV hemispheres. Jacobian determinants revealed greater atrophy in gray and white matter of the parietal lobes of LVV compared with non–LVV hemispheres.ConclusionLarge-vessel vasculopathy in sickle cell disease appears to increase ischemic vulnerability in the borderzone region, as demonstrated by the increased frequency and extent of infarction within deep white matter, and increased risk of focal atrophy. Scattered infarctions across the LVV–affected hemispheres suggest additional stroke etiologies of vasculopathy (i.e., thromboembolism) in addition to chronic hypoxia-ischemia.
Design of a Multisite Study Assessing the Impact of Tic Disorders on Individuals, Families, and Communities
Publication date: March 2017 Source:Pediatric Neurology, Volume 68 Author(s): E.F. Augustine, H.R. Adams, R.H. Bitsko, E. van Wijngaarden, A.H. Claussen, A. Thatcher, C.E. Hanks, A.B. Lewin, T.G. O'Connor, A. Vierhile, M.L. Danielson, R. Kurlan, T.K. Murphy, J.W. Mink BackgroundTic disorders, including Tourette syndrome, are complex, multisymptom diseases, yet the impact of these disorders on affected children, families, and communities is not well understood.MethodsTo improve the understanding of the impacts of Tourette syndrome, two research groups conducted independent cross-sectional studies using qualitative and quantitative measures. They focused on similar themes, but distinct scientific objectives, and the sites collaborated to align methods of independent research proposals with the aim of increasing the analyzable sample size.ResultsSite 1 (University of Rochester) was a Pediatric Neurology referral center. Site 2 (University of South Florida) was a Child Psychiatry referral center. A total of 205 children with tic disorders were enrolled from both studies. The University of Rochester also enrolled 100 control children in order to clearly isolate impacts of Tourette syndrome distinct from those occurring in the general population. The majority of children with tic disorders (n = 191, 93.1%) had Tourette syndrome, the primary population targeted for these studies. Children with Tourette syndrome were similar across sites in terms of tic severity and the occurrence of comorbid conditions. The occurrence of psychiatric comorbidities in the control group was comparable with that in the general pediatric population of the United States, making this a well-justified comparison group.ConclusionsThrough collaboration, two sites conducting independent research developed convergent research methods to enable pooling of data, and by extension increased power, for future analyses. This method of collaboration is a novel model for future epidemiological research of tic disorders.