Showing papers in "Journal of Child Neurology in 2012"
TL;DR: Several forms of encephalitis that occur in children, and for which an autoimmune etiology has been demonstrated or is strongly suspected, and several disorders that may be immune mediated are reviewed.
Abstract: The causes of encephalitis are numerous, and extensive investigations for infectious agents and other etiologies are often negative The discovery that many of these encephalitis are immune mediated has changed the approach to the diagnosis and treatment of these disorders Moreover, the broad spectrum of symptoms including, psychosis, catatonia, alterations of behavior and memory, seizures, abnormal movements, and autonomic dysregulation usually requires a multidisciplinary treatment approach This review focuses in several forms of encephalitis that occur in children, and for which an autoimmune etiology has been demonstrated (eg, anti-N-methyl-d-aspartate receptor encephalitis) or is strongly suspected (eg, Rasmussen encephalitis, limbic encephalitis, opsoclonus-myoclonus) The authors also review several disorders that may be immune mediated, such as the rapid onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) syndrome and some encephalopathies with fever
172 citations
Stanford University1, University of Michigan2, University of Sydney3, University of Wisconsin-Madison4, Karolinska Institutet5, Harvard University6, Boston Children's Hospital7, National Institutes of Health8, Washington University in St. Louis9, Universidade Federal de Minas Gerais10, University of Pennsylvania11, Children's National Medical Center12, University of Western Australia13, University of New Mexico14, University of Florida15, University of São Paulo16
TL;DR: The International Standard of Care Committee for Congenital Myopathies worked through frequent e-mail correspondences, periodic conference calls, 2 rounds of online surveys, and a 3-day workshop to achieve a consensus for diagnostic and clinical care recommendations.
Abstract: Recent progress in scientific research has facilitated accurate genetic and neuropathological diagnosis of congenital myopathies. However, given their relatively low incidence, congenital myopathies remain unfamiliar to the majority of care providers, and the levels of patient care are extremely variable. This consensus statement aims to provide care guidelines for congenital myopathies. The International Standard of Care Committee for Congenital Myopathies worked through frequent e-mail correspondences, periodic conference calls, 2 rounds of online surveys, and a 3-day workshop to achieve a consensus for diagnostic and clinical care recommendations. The committee includes 59 members from 10 medical disciplines. They are organized into 5 working groups: genetics/diagnosis, neurology, pulmonology, gastroenterology/nutrition/speech/oral care, and orthopedics/rehabilitation. In each care area the authors summarize the committee's recommendations for symptom assessments and therapeutic interventions. It is the committee's goal that through these recommendations, patients with congenital myopathies will receive optimal care and improve their disease outcome.
142 citations
TL;DR: An overview of the clinical features of Friedreich ataxia is provided and differential diagnoses are discussed, including the main nonneurological sites of morbidity are the heart, resulting in cardiomyopathy, and the pancreas, resulted in diabetes mellitus.
Abstract: Friedreich ataxia, the most common hereditary ataxia, affects approximately 1 per 29,000 white individuals. In about 98% of these individuals, it is due to homozygosity for a GAA trinucleotide repeat expansion in intron 1 of FXN; in the other 2%, it is due to compound heterozygosity for a GAA expansion and point mutation or deletion. The condition affects multiple sites in the central and peripheral nervous system as well as a number of other organ systems, resulting in multiple signs and symptoms. Onset of this autosomal recessive condition is usually in the first 2 decades of life. Major clinical features include progressive ataxia, absent lower limb reflexes, upgoing plantar responses, and peripheral sensory neuropathy. The main nonneurological sites of morbidity are the heart, resulting in cardiomyopathy, and the pancreas, resulting in diabetes mellitus. In this review, we provide an overview of the clinical features of Friedreich ataxia and discuss differential diagnoses.
141 citations
132 citations
TL;DR: Except when accompanied or followed by a white matter lesion, intraventricular hemorrhage is associated with no more than a modest increase (and possibly no increase) in the risk of adverse developmental outcome during infancy.
Abstract: Whether intraventricular hemorrhage increases the risk of adverse developmental outcome among premature infants is controversial. Using brain ultrasound, we identified intraventricular hemorrhage and white matter abnormalities among 1064 infants born before 28 weeks' gestation. We identified adverse developmental outcomes at 24 months of age using a standardized neurologic examination and the Bayley Scales of Infant Development Mental and Motor Scales. In logistic regression models that adjusted for gestational age, sex, and public insurance, isolated intraventricular hemorrhage was associated with visual fixation difficulty but no other adverse outcome. Infants who had a white matter lesion unaccompanied by intraventricular hemorrhage were at increased risk of cerebral palsy, low Mental and Motor Scores, and visual and hearing impairments. Except when accompanied or followed by a white matter lesion, intraventricular hemorrhage is associated with no more than a modest increase (and possibly no increase) in the risk of adverse developmental outcome during infancy.
100 citations
TL;DR: A review of the current published literature on acute transverse myelitis, including epidemiology, diagnostic criteria, pathogenesis, clinical presentation, clinical evaluation, and differential diagnosis, suggests that the majority of children diagnosed with acuteTransverse Myelitis have a good outcome.
Abstract: Acute transverse myelitis is a clinical syndrome affecting the spinal cord, which is characterized by acute onset of motor, sensory, and autonomic dysfunction. Approximately 20% of cases of acute transverse myelitis occur in children. This review summarizes the current published literature on acute transverse myelitis, including epidemiology, diagnostic criteria, pathogenesis, clinical presentation, clinical evaluation, and differential diagnosis. The article also summarizes the neuroimaging features, acute and chronic complications, treatments, and prognosis of acute transverse myelitis in the pediatric population. The initial evaluation centers on differentiation from other causes of myelopathy, and cases are further divided into idiopathic or disease-associated acute transverse myelitis. Correct diagnosis is important for treatment and prognosis. Treatment begins with intensive surveillance for acute life-threatening respiratory or autonomic complications. Immunomodulating therapy is recommended for noninfectious causes, using high-dose intravenous corticosteroids or plasma exchange. Other therapeutic options are also discussed. Prognosis depends on a number of factors, and evidence suggests that the majority of children have a good outcome. A small percentage of children diagnosed with acute transverse myelitis later are diagnosed with other demyelinating diseases, especially neuromyelitis optica, or multiple sclerosis. The most common long-term complications of acute transverse myelitis are urinary, motor, or sensory dysfunction.
89 citations
TL;DR: Severe cases of cerebellitis represent the other end of the spectrum, presenting with acute cerebellar signs often overshadowed by alteration of consciousness, focal neurological deficits, raised intracranial pressure, hydrocephalus, and even herniation.
Abstract: Acute cerebellar ataxia and acute cerebellitis represent a process characterized by parainfectious, postinfectious, or postvaccination cerebellar inflammation. There is considerable overlap between these entities. The mildest cases of acute cerebellar ataxia represent a benign condition that is characterized by acute truncal and gait ataxia, variably with appendicular ataxia, nystagmus, dysarthria, and hypotonia. It occurs mostly in young children, presents abruptly, and recovers over weeks. Neuroimaging is normal. Severe cases of cerebellitis represent the other end of the spectrum, presenting with acute cerebellar signs often overshadowed by alteration of consciousness, focal neurological deficits, raised intracranial pressure, hydrocephalus, and even herniation. Neuroimaging is abnormal and the prognosis is less favorable than in acute cerebellar ataxia. Acute disseminated encephalomyelitis may be confused with acute cerebellitis when the clinical findings are predominantly cerebellar, but lesions on neuroimaging are usually widespread. Paraneoplastic opsoclonus-myoclonus syndrome is often initially misdiagnosed as acute cerebellar ataxia, but has very specific features, course, and etiopathogensis.
88 citations
TL;DR: The authors cover recent basic and clinical findings regarding the heart in Friedreich ataxia, offer recommendations for clinical management of the cardiomyopathy in this disease, and point out new research directions to advance the field.
Abstract: Friedreich ataxia is the most common human ataxia and results from inadequate production of the frataxin protein, most often the result of a triplet expansion in the nuclear FXN gene. The gene cannot be transcribed to generate the messenger ribonucleic acid for frataxin. Frataxin is an iron-binding protein targeted to the mitochondrial matrix. In its absence, multiple iron-sulfur-dependent proteins in mitochondria and the cytosol lack proper assembly, destroying mitochondrial and nuclear function. Mitochondrial oxidant stress may also participate in ongoing cellular injury. Although progressive and debilitative ataxia is the most prominent clinical finding, hypertrophic cardiomyopathy with heart failure is the most common cause of early death in this disease. There is no cure. In this review the authors cover recent basic and clinical findings regarding the heart in Friedreich ataxia, offer recommendations for clinical management of the cardiomyopathy in this disease, and point out new research directions to advance the field.
85 citations
TL;DR: It was found that in up to one-third of patients, the headache was not migrainous or associated with Migrainous symptoms, and Observational data suggest systemic corticosteroids may be beneficial acutely.
Abstract: Ophthalmoplegic migraine is a poorly understood neurologic syndrome characterized by recurrent bouts of head pain and ophthalmoplegia. By reviewing cases presenting to our centers in whom the phenotype has been carefully dissected, and systematically reviewing all published cases of ophthalmoplegic migraine in the magnetic resonance imaging (MRI) era, this review sets out to clearly define the syndrome and discuss possible etiologies. We found that in up to one-third of patients, the headache was not migrainous or associated with migrainous symptoms. In three-quarters of the cases involving the third nerve, there was focal nerve thickening and contrast enhancement on MRI. Observational data suggest systemic corticosteroids may be beneficial acutely. The etiology remains unclear, but may involve recurrent bouts of demyelination of the oculomotor nerve. "Ophthalmoplegic migraine" is a misnomer in that it is probably not a variant of migraine but rather a recurrent cranial neuralgia. A more appropriate name might be "ophthalmoplegic cranial neuropathy."
81 citations
TL;DR: The authors collected demographic, clinical, and neuroimaging data prospectively on 38 children with transverse myelitis, finding that 16% are wheelchair-dependent, 22% have persisting bladder dysfunction, and 13% have been diagnosed with multiple sclerosis at follow-up.
Abstract: The authors collected demographic, clinical, and neuroimaging data prospectively on 38 children with transverse myelitis. One child died during the illness. The female:male ratio was 1.2:1 for children under age 10 years and 2.6:1 over age 10 years. Twenty-eight (74%) reported a prodromal event. Twenty-two patients (58%) had longitudinally extensive transverse myelitis, 9 (24%) had focal lesions, and 5 (13%) had both. Twenty of 33 with brain imaging (61%) had brain lesions; 7 fulfilled McDonald criteria for dissemination in space. Seven of 22 (36%) tested had cerebrospinal fluid oligoclonal banding, 6 of whom had brain lesions. Serum neuromyelitis optica IgG antibodies were absent in all 20 of the children for whom this test was available. At follow-up (mean 3.2 ± 2.0 years), 16% are wheelchair-dependent, 22% have persisting bladder dysfunction, and 13% have been diagnosed with multiple sclerosis.
70 citations
TL;DR: The autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders are discussed, which is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system.
Abstract: The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system.
TL;DR: Children with attention-deficit hyperactivity disorder (ADHD) being treated with methylphenidate and standard behavior therapy for more than 6 months, whose parents reported no improvement in behavior and academic learning, were randomly assigned to receive supplementation with a combined ω3 and ω6 preparation or a placebo.
Abstract: Children (6-12 years) with attention-deficit hyperactivity disorder (ADHD) being treated with methylphenidate and standard behavior therapy for more than 6 months, whose parents reported no improvement in behavior and academic learning, were randomly assigned to receive supplementation with a combined ω3 and ω6 preparation or a placebo. Outcome was measured at 3 and 6 months after treatment using a self-assessment checklist completed by the parents. Statistically significant improvement was found in the treatment group compared with the placebo group (P < .01) in the following measures: restlessness, aggressiveness, completing work, and academic performance. Statistically significant improvement was not found at 3 months of treatment between groups but was evident at 6 months of treatment (P < .05) with inattention, impulsiveness, and cooperation with parents and teachers. Distractibility failed to show improvement. Effect sizes ranged from 0.3 to 1.1 at 3 months and 0.2 to 1.4 at 6 months for individual symptom variables.
TL;DR: Higher scores of hyperactivity/inattention are linked to different lifestyle characteristics that may in part contribute to a future development of overweight/obesity.
Abstract: We performed a cross-sectional study in 450 nonreferred preschool children aged 4 to 6 years to assess the association between hyperactivity/inattention with adiposity and lifestyle characteristics. Measurements included scores of hyperactivity/inattention, adiposity, objectively measured physical activity, television viewing, and eating habits. Higher scores of hyperactivity/inattention were associated with lower percentage body fat, higher levels of physical activity, and less time spent in sedentary activity (all P ≤ .01). However, higher scores of hyperactivity/inattention were also associated with more television viewing and less healthy eating habits (all P ≤ .04). Except for some selected eating habits (P ≥ .07), those relationships remained significant after adjustment for age, sex, and sociodemographic confounders. To conclude, higher scores of hyperactivity/inattention are linked to different lifestyle characteristics that may in part contribute to a future development of overweight/obesity. Precise mechanisms explaining these associations and possible preventive approaches should be further investigated.
TL;DR: It is concluded that melatonin could be effective and safe for decreasing daytime seizure frequency in patients with intractable epilepsy.
Abstract: Melatonin is effective for treating sleep-wake cycle disturbances and has been reported occasionally to decrease epileptic seizure frequency, with no long-term side effects. In this pilot study, the investigators examined the effect of melatonin on seizures, sleep quality, and behavior in 10 patients aged 9 to 32 years with intractable epilepsy. Patients were randomized to receive melatonin (10 mg daily at bedtime) followed by placebo or placebo followed by melatonin for 3 weeks each, with a 1-week washout period in between. Seizure frequency was monitored by daily diaries and actigraphy recordings; behavioral and sleep parameters were rated by caregivers. Diurnal seizures decreased significantly with melatonin compared with placebo (P = .034, Wilcoxon test). Maximal number of seizures, seizure duration, sleep efficiency or latency, and behavioral parameters remained unchanged. No major side effects or seizure aggravation were documented. It is concluded that melatonin could be effective and safe for decreasing daytime seizure frequency in patients with intractable epilepsy.
TL;DR: This work describes a 14-year-old boy with autistic disorder, focal epilepsy, severe and progressive macrocephaly, and multiple papular skin lesions and palmoplantar punctate keratoses, characteristic of Cowden syndrome, who has a de novo phosphatase and tensin homolog gene mutation.
Abstract: Phosphatase and tensin homolog (PTEN) gene mutations are associated with a spectrum of clinical disorders characterized by skin lesions, macrocephaly, hamartomatous overgrowth of tissues, and an increased risk of cancers. Autism has rarely been described in association with these variable clinical features. At present, 24 patients with phosphatase and tensin homolog gene mutation, autism, macrocephaly, and some clinical findings described in phosphatase and tensin homolog syndromes have been reported in the literature. We describe a 14-year-old boy with autistic disorder, focal epilepsy, severe and progressive macrocephaly, and multiple papular skin lesions and palmoplantar punctate keratoses, characteristic of Cowden syndrome. The boy has a de novo phosphatase and tensin homolog gene mutation. Our patient is the first case described to present a typical Cowden syndrome and autism associated with epilepsy.
TL;DR: The diagnosis of fetal alcohol spectrum disorders and the developmental implications of prenatal alcohol exposure and the mechanism of alcohol exposure, dosimetry, and the teratogenic pathways of damage to the fetus are reviewed.
Abstract: In part 1, we discussed the mechanism of alcohol exposure, dosimetry, and the teratogenic pathways of damage to the fetus. In part 2, we review the diagnosis of fetal alcohol spectrum disorders and the developmental implications of prenatal alcohol exposure. Fetal alcohol spectrum disorders are associated with increased rates of mental retardation, seizure disorders, brain malformations, and premature mortality. The risk of comorbid disorders is increased among this population, which enhances phenotype severity and complexity of management. Recurrence rates are high and younger siblings tend to be more severely affected. Detection of prenatal alcohol use warrants substance abuse intervention, which can avoid exposure in subsequent pregnancies. Fetal alcohol spectrum disorders are common developmental disorders with a phenotype that is influenced by both age and development and require long-term management. Child neurologists are essential in the diagnosis and management of fetal alcohol spectrum disorders.
TL;DR: Prevalence rates of prenatal alcohol exposure in the United States are reviewed and the mechanisms of prenatalalcohol exposure and placental-umbilical effects are discussed.
Abstract: In the United States, approximately 80 000 women consume ethanol through all 3 trimesters of pregnancy each year. In this article, we review prevalence rates of prenatal alcohol exposure in the United States and discuss the mechanisms of prenatal alcohol exposure and placental-umbilical effects. Cigarette smoking and delayed prenatal care are often associated with prenatal alcohol exposure. In addition, increased risk for postnatal adversity is common, including maternal depression, foster care placement, and developmental delay. In part 2, we review prevalence rates and the diagnostic criteria for fetal alcohol spectrum disorder and the implications for child neurologists. We discuss management strategies and the importance of a long-term management plan and anticipatory management to prevent the development of secondary disabilities in fetal alcohol spectrum disorders. Child neurologists play a key role in diagnosis and the development of appropriate intervention programs for affected children and their...
TL;DR: Pediatric multiple sclerosis has been increasingly recognized in the past 10 to 15 years; 3% to 5% of all multiple sclerosis patients experience their first attack in childhood, and patients with childhood-onset multiple sclerosis reach permanent disability or enter the secondary progressive disease course 10 years younger than patients with adult-onsets multiple sclerosis.
Abstract: Pediatric multiple sclerosis has been increasingly recognized in the past 10 to 15 years; 3% to 5% of all multiple sclerosis patients experience their first attack in childhood. Childhood multiple sclerosis has a relapsing-remitting disease course. The first attack, or "acquired demyelinating syndrome," consists of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and monofocal or polyfocal neurological deficits. The diagnosis of multiple sclerosis necessitates the clinical or magnetic resonance imaging confirmation of dissemination in space and time and exclusion of other disorders. The morbidity of childhood multiple sclerosis is significant; within the first 2 years from onset, 30% of children have significant cognitive impairment, 50% show signs of depression, and 75% are fatigued. The relapse rate in children with multiple sclerosis is higher than in adult-onset disease. Following acute treatment, recovery after the first attacks is usually excellent, but patients with childhood-onset multiple sclerosis reach permanent disability or enter the secondary progressive disease course 10 years younger than patients with adult-onset multiple sclerosis.
TL;DR: In children, adjunctive levetiracetam was associated with long-term stability in cognitive functioning and improvement in emotional/behavioral functioning over time.
Abstract: The objective of this study was to assess cognition and behavior in children (4-16 years; n = 103) with partial-onset seizures using the Leiter-R International Performance Scale and Achenbach Child Behavior Checklist. The study was a multicenter, open-label, noncomparative 48-week extension study (NCT00152516) of adjunctive levetiracetam (20-100 mg/kg/d, mean 50.2 mg/kg/d). Improvement from baseline in Leiter-R Memory Screen composite score at weeks 24 and 48 (mean [SD] change, +4.8 [12.6] and +4.5 [15.3]) was similar to changes observed with levetiracetam and placebo in a prior study. Child Behavior Checklist Syndrome scores improved from baseline at weeks 24 and 48 (total problems mean [SD] change, -9.3 [22.2] and -10.4 [23.4]). Adjunctive levetiracetam was well tolerated (most frequently reported central nervous system-related treatment-emergent adverse events: headache [24.3%], aggression [7.8%], irritability [7.8%]). Of the patients, 4.9% discontinued because of treatment-emergent adverse events. Levetiracetam provided good and sustained seizure control (median percentage reduction from baseline in partial-onset seizure frequency/wk during maintenance: 86.4%); 24.7% of patients had continuous seizure freedom from all seizure types for ≥40 weeks. In children, adjunctive levetiracetam was associated with long-term stability in cognitive functioning and improvement in emotional/behavioral functioning over time.
TL;DR: A detailed review of 300 patients with confirmed cerebellar atrophy on magnetic resonance imaging over a 10-year period foundMitochondrial disorders were most common, followed by neuronal ceroid lipofuscinosis, ataxia telangiectasia, and late-onset GM2 gangliosidosis.
Abstract: Hereditary ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. Selection of appropriate clinical and genetic tests for patients with cerebellar atrophy poses a diagnostic challenge. Neuroimaging is a crucial initial investigation in the diagnostic evaluation of ataxia in childhood, and the presence of cerebellar atrophy helps guide further investigations. We performed a detailed review of 300 patients with confirmed cerebellar atrophy on magnetic resonance imaging over a 10-year period. A diagnosis was established in 47% of patients: Mitochondrial disorders were most common, followed by neuronal ceroid lipofuscinosis, ataxia telangiectasia, and late-onset GM2 gangliosidosis. We review the common causes of cerebellar atrophy in childhood and propose a diagnostic approach based on correlating specific neuroimaging patterns with clinical and genetic diagnoses.
TL;DR: For the first time, a novel event-related potential paradigm shows that hemiparetic children have slower and less efficient tactile cortical perception in their affected extremities.
Abstract: The brain's response to somatosensory stimuli is essential to experience-driven learning in children. It was hypothesized that advances in event-related potential technology could quantify the response to touch in somatosensory cortices and characterize the responses of hemiparetic children. In this prospective study of 8 children (5-8 years old) with hemiparetic cerebral palsy, both event-related potential responses to sham or air puff trials and standard functional assessments were used. Event-related potential technology consistently measured signals reflecting activity in the primary and secondary somatosensory cortices as well as complex cognitive processing of touch. Participants showed typical early responses but less efficient perceptual processes. Significant differences between affected and unaffected extremities correlated with sensorimotor testing, stereognosis, and 2-point discrimination (r > 0.800 and P = .001 for all). For the first time, a novel event-related potential paradigm shows that hemiparetic children have slower and less efficient tactile cortical perception in their affected extremities.
TL;DR: It is found that the diagnostic evaluation and the use of first-line treatments varied among responders, and future clinical trials will require multicenter collaboration.
Abstract: The optimal evaluation and treatment of children with infantile spasms is unknown. To aid in the development of a standardized approach to infantile spasms, members of the Child Neurology Society were surveyed to determine common practice. The survey had 222 responders with a responder rate of 18.5%. We found that the diagnostic evaluation and the use of first-line treatments varied among responders. For example, although adrenocorticotropic hormone continues to be the most commonly used first-line treatment for infantile spasms not due to tuberous sclerosis, some clinicians use corticosteroids, vigabatrin, and topiramate as first-line treatments for this group. Seventy percent of our responders reported seeing fewer than 10 new-onset cases of infantile spasms per year. Thus, future clinical trials will require multicenter collaboration. An important first step in such collaboration is to standardize the evaluation and treatment of infantile spasms within and between participating centers.
TL;DR: Common etiologies are outlined and a comprehensive approach to the evaluation of both acquired and genetic cerebellar ataxia in children is described, which is recommended for efficient diagnosis.
Abstract: Childhood presentations of ataxia, an impairment of balance and coordination caused by damage to or dysfunction of the cerebellum, can often be challenging to diagnose. Presentations tend to be clinically heterogeneous, but key considerations may vary based on the child's age at onset, the course of illness, and subtle differences in phenotype. Systematic investigation is recommended for efficient diagnosis. In this review, we outline common etiologies and describe a comprehensive approach to the evaluation of both acquired and genetic cerebellar ataxia in children.
TL;DR: Current clinical, pathological, and pathogenetic knowledge is reviewed with a focus on clinical presentation, neuroimaging findings, serological investigations, and treatment of children with disorders within the spectrum of central nervous system aquaporin-4 autoimmunity.
Abstract: The evaluation of inflammatory central nervous system disorders in childhood with predominant involvement of the optic nerves and spinal cord has been greatly enhanced over the last decade with identification of a group of disorders unified by the detection of neuromyelitis optica (NMO)-IgG, an antibody targeting the central nervous system-predominant water channel aquaporin-4. Clinical syndromes are predominated by the relapsing form of NMO but also include encephalopathic variants that can mimic acute disseminated encephalomyelitis. Maintenance immunotherapy is used to prevent relapses in NMO-IgG-seropositive patients. In contrast, NMO-IgG-seronegative children with NMO more commonly have a monophasic course (simultaneous occurrence of optic neuritis and transverse myelitis) and do not require remission-maintaining immunotherapy, but close surveillance is advised. Current clinical, pathological, and pathogenetic knowledge is reviewed with a focus on clinical presentation, neuroimaging findings, serological investigations, and treatment of children with disorders within the spectrum of central nervous system aquaporin-4 autoimmunity.
TL;DR: The authors report the progress of a large international noninterventional cohort, tracking the natural history of disease progression using the neurologic examination-based Friedreich Ataxia Rating Scale, suggesting this measure is most useful in subjects before maximal deficit is approached.
Abstract: Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia, dysarthria, and areflexia. The authors report the progress of a large international noninterventional cohort (n = 410), tracking the natural history of disease progression using the neurologic examination-based Friedreich Ataxia Rating Scale. The authors analyzed the rate of progression with cross-sectional analysis and longitudinal analysis over a 2-year period. The Friedreich Ataxia Rating Scale captured disease progression when used at 1 and 2 years following initial evaluation, with a lower ratio of standard deviation of change to mean change over 2 years of evaluation. However, modeling of disease progression identified substantial ceiling effects in the Friedreich Ataxia Rating Scale, suggesting this measure is most useful in subjects before maximal deficit is approached.
TL;DR: A randomized study made of the outcomes of 10 children treated with standard management alone compared to 10 who received additional intravenous immunoglobulin, and all three outcome measurement tools found improved outcomes in the group that received intravenous immune globulin.
Abstract: Sydenham chorea is a post-streptococcal, autoimmune, neuropsychiatric, movement disorder. There is no effective treatment. In a randomized study, comparison was made of the outcomes of 10 children treated with standard management alone compared to 10 who received additional intravenous immunoglobulin. The outcomes were assessed using a clinical rating scale, brain single-photon emission computed tomography, and the duration of symptomatic treatment. All three outcome measurement tools found improved outcomes in the group that received intravenous immunoglobulin.
TL;DR: The findings raise the possibility that rolandic epilepsy may affect neural networks affecting cognition and mediating social cognition essential for social behavior, thus challenging the benign nature of the condition.
Abstract: The aim of the present study was to assess the emotional and cognitive aspects of social cognition among patients with rolandic epilepsy. A computerized neuropsychological battery was used for cognitive evaluation. Affective and cognitive social cognition were evaluated using two computerized Theory of Mind tasks. Cognitive abilities and social behavior of 15 children, diagnosed with rolandic epilepsy, ages 7 to 13 years were assessed and compared with 15 age- and education-matched healthy controls. Compared with controls, the epileptic patients had lower scores on verbal and visual learning rate parameters and on verbal processing and were significantly impaired on "affective Theory of Mind" tasks but not on "cognitive Theory of Mind" conditions. Our findings raise the possibility that rolandic epilepsy may affect neural networks affecting cognition and mediating social cognition essential for social behavior, thus challenging the benign nature of the condition.
TL;DR: This study demonstrates greater efficacy of corticotropic-based multimodal therapy compared with conventional therapy, greater response to corticotropin than corticosteroid-based therapy, and overall tolerability.
Abstract: To test the efficacy and safety of corticotropin-based immunotherapies in pediatric opsoclonus-myoclonus syndrome, 74 children received corticotropin alone or with intravenous immunoglobulin (groups 1 and 2, active controls); or both with rituximab (group 3) or cyclophosphamide (group 4); or with rituximab plus chemotherapy (group 5) or steroid sparers (group 6). There was 65% improvement in motor severity score across groups (P < .0001), but treatment combinations were more effective than corticotropin alone (P = .0009). Groups 3, 4, and 5 responded better than group 1; groups 3 and 5 responded better than group 2. The response frequency to corticotropin was higher than to prior corticosteroids (P < .0001). Fifty-five percent had adverse events (corticosteroid excess), more so with multiagents (P = .03); and 10% had serious adverse events. This study demonstrates greater efficacy of corticotropin-based multimodal therapy compared with conventional therapy, greater response to corticotropin than corticosteroid-based therapy, and overall tolerability.
TL;DR: The frequency of perioperative morbidity and mortality in cerebral palsy patients undergoing anesthesia was characterized by undertaking a systematic review of the Mayo Database by finding factors associated with increased risk included American Society of Anesthesiologists physical status score exceeding 2.
Abstract: The severity of preoperative cerebral palsy appears to correlate directly with postoperative complications. The primary aim of this study was to characterize the frequency of perioperative morbidity and mortality in cerebral palsy patients undergoing anesthesia. This was accomplished by undertaking a systematic review of the Mayo Database. The risk for perioperative adverse events was 63.1% (95% confidence interval 59.8%-66.5%). However, it deserves clarification that hypothermia and clinically significant yet non-life-threatening hypotension represented the majority (80%) of these complications. When these 2 events are excluded, the rate of adverse perioperative events was 13.1% (95% confidence interval 10.8%-15.5%). Risk factors associated with increased risk included American Society of Anesthesiologists physical status score exceeding 2, history of seizures, upper airway hypotonia, general surgery procedures, and adults. Our findings are useful to counsel patients with cerebral palsy, their caregivers, and their guardians regarding the risk of general anesthesia.
TL;DR: The authors reviewed 21 pediatric patients with various seizure types who were started on oral lacosamide as part of a prospective add-on study as adjunctive therapy for refractory epilepsy, finding Lacosamide was effective therapy for most seizure types but was particularly effective for partial-onset seizures.
Abstract: Lacosamide is a new antiepileptic drug that is currently approved by the US Food and Drug Administration (FDA) for adults 17 years or older for partial-onset seizures. The authors reviewed 21 pediatric patients (<17 years) with various seizure types who were started on oral lacosamide as part of a prospective add-on study as adjunctive therapy for refractory epilepsy. Five patients were excluded due to less than 3 months of meaningful follow-up. Maintenance dosages used ranged from 2.4 to 19.4 mg/kg/d. Eight of 16 (50%) patients had greater than 50% reduction in seizure frequency with adjunctive lacosamide therapy. Eight (50%) patients had generalized epilepsy including 4 with Lennox-Gastaut syndrome. Lacosamide was effective therapy for most seizure types but was particularly effective for partial-onset seizures. Lacosamide was effective in treating 5 of 8 (62.5%) localization-related epilepsies but only 2 of 8 (25%) generalized epilepsies, both Lennox-Gastaut syndrome patients with greater than 90% seizure reduction. None of these very refractory patients remained seizure free.