A Patient With Atypical Multiple Sulfatase Deficiency.

BACKGROUND: Multiple sulfatase deficiency is an autosomal recessive lysosomal storage disorder characterized by the absence of several sulfatases and resulting from mutations in the gene encoding the human C (alpha)-formylglycine-generating enzyme. There have been a variety of biochemical and clinical presentations reported in this disorder. PATIENT DESCRIPTION: We present a 4-year-old girl with clinical findings of microcephaly, spondylolisthesis and neurological regression without ichthyosis, coarse facies, and organomegaly. RESULTS: The child's magnetic resonance imaging demonstrated confluent white matter abnormalities involving the periventricular and deep cerebral white matter with the U-fibers relatively spared. Biochemical testing showing low arylsulfatase A levels were initially thought to be consistent with a diagnosis of metachromatic leukodystrophy. The diagnosis of multiple sulfatase deficiency was pursued when genetic testing for metachromatic leukodystrophy was negative. CONCLUSION: This child illustrates the clinical heterogeneity of multiple sulfatase deficiency and that this disorder can occur without the classic clinical features.

Immunomodulatory treatments in epilepsy.

The role of immunity and inflammation appears to be an integral part of the pathogenic processes associated with some seizures, particularly with refractory epilepsy. Prompt treatment with immunotherapy may lead to better outcomes. Immune treatment options for treatment of epilepsy include therapies such as corticosteroids, immunoglobulins, plasmapheresis, or steroid-sparing drugs such as azathioprine. Recent alternatives have included even more aggressive treatment with cyclophosphamide, anti-pre-B-lymphocyte monoclonal antibody rituximab, and monoclonal antibodies such as efalizumab or natalizumab, which are presently used for other inflammatory disorders. Randomized controlled trials of immunotherapy in presumed autoimmune epilepsy are needed to provide further support for the rapid use of immunotherapy in patients with immune mediated epilepsy.

Mitochondrial dysfunction in neuromuscular disorders.

This review deciphers aspects of mitochondrial (mt) dysfunction among nosologically, pathologically, and genetically diverse diseases of the skeletal muscle, lower motor neuron, and peripheral nerve, which fall outside the traditional realm of mt cytopathies. Special emphasis is given to well-characterized mt abnormalities in collagen VI myopathies (Ullrich congenital muscular dystrophy and Bethlem myopathy), megaconial congenital muscular dystrophy, limb-girdle muscular dystrophy type 2 (calpainopathy), centronuclear myopathies, core myopathies, inflammatory myopathies, spinal muscular atrophy, Charcot-Marie-Tooth neuropathy type 2, and drug-induced peripheral neuropathies. Among inflammatory myopathies, mt abnormalities are more prominent in inclusion body myositis and a subset of polymyositis with mt pathology, both of which are refractory to corticosteroid treatment. Awareness is raised about instances of phenotypic mimicry between cases harboring primary mtDNA depletion, in the context of mtDNA depletion syndrome, and established neuromuscular disorders such as spinal muscular atrophy. A substantial body of experimental work, derived from animal models, attests to a major role of mitochondria (mt) in the early process of muscle degeneration. Common mechanisms of mt-related cell injury include dysregulation of the mt permeability transition pore opening and defective autophagy. The therapeutic use of mt permeability transition pore modifiers holds promise in various neuromuscular disorders, including muscular dystrophies.

Persistence of hypsarrhythmia in children beyond the age of three years.

Occurrence of hypsarrhythmia after the age of 3 years is rare. The objective of this study is to describe a group of patients who have persistence of hypsarrhythmia after the age of 3 years. The authors retrospectively reviewed the EEGs of 24 patients with hypsarrhythmia. Electroencephalographies (EEGs) were scored using a hypsarrhythmia scale. The clinical data of 7 patients with EEG scores greater than 9 at ages ≥ 3 years were analyzed. The mean age was 5.7 years (range, 3-8.7 years). EEG background amplitudes ranged from 200 to 500 µV in 5 patients and it was greater than 500 µV in the other 2. Six patients had electrodecremental responses. The etiology was developmental in 3 patients, mitochondrial disease in 2, and hypoxic ischemic encephalopathy in 2. Our study suggests that a subgroup of patients with hypsarrhythmia may not transition to a Lennox-Gastaut pattern or normalization after the age of 3 years.

Persistent focal seizures after cat scratch encephalopathy.

This report describes a 9-year-old child with status epilepticus and cat scratch disease. This patient's focal seizures and electroencephalographic changes persisted for 18 months after status epilepticus. This patient represents the third reported case of persistent focal seizures or electroencephalographic changes after status epilepticus secondary to cat scratch disease. This finding suggests that cat scratch encephalopathy may be a cause of localization-related epilepsy, and should be investigated when evaluating a patient with new-onset partial seizures.

Assessment of the QT interval in the electroencephalography (EEG) of children with syncope, epilepsy, and attention-deficit hyperactivity disorder (ADHD).

The interpretation of QT interval is often neglected during electroencephalography (EEG) reading. We compared the incidence of prolonged QT interval, as seen in the electrocardiography (ECG) recording lead of the EEG, in children presenting with seizure, syncope, or attention-deficit hyperactivity disorder (ADHD). Abnormal QT was defined as >460 ms. The incidence of prolonged QT in the seizure, syncope, and ADHD groups was 1/50 (2%), 7/50 (14%), and 2/50 (4%), respectively (P = .036, chi-square). The mean +/- SD of QT were 405 +/- 34, 424 +/- 39, and 414 +/- 36, respectively (P = .035, analysis of variance [ANOVA], syncope group, compared with seizure group). The incidence of prolonged QT as measured in the EEG was unexpectedly high in children presenting with seizure, syncope, or ADHD. These data support the concept that QT evaluation should be emphasized during routine EEG reading, as it may aid in identifying cases of undiagnosed cardiac conduction abnormalities. Prospective studies comparing EEG-ECG tracings with 12-lead ECG are warranted.

Efficacy and tolerability of topiramate in pediatric migraine.

About 5-10% of school-age children manifest migraine headaches. Treatment options for pediatric migraine are limited. Topiramate is approved for migraine prophylaxis in adults, but its use in children is limited. We retrospectively reviewed the records of 37 patients, i.e., 22 (60%) girls and 15 (40%) boys (mean age, 14 years; range, 7.3-20.5 years), diagnosed with migraine without aura in 30 (81%), with aura in four (11%), and abdominal, ophthalmoplegic, and catamenial in one each. The mean follow-up was 12 +/- 5 months standard deviation (S.D.). Clinical response was qualified as excellent, good, no change, or worse. Numbers of headaches per month were 15 +/- 7 S.D. prior to treatment and 3 +/- 3.4 S.D. (P < 0.001) after treatment. An excellent or good response (>50% migraine reduction) was attained in 28 patients (76%). Ten (27%) patients exhibited adverse effects. Patients taking >2 mg/kg/day were more likely to demonstrate side effects. The mean dose for patients without adverse effects was 1.27 +/- 0.7 mg/kg/day S.D. Those who reported adverse effects were taking a mean dose of 2.8 +/- 1.5 mg/kg/day S.D. This study demonstrated that topiramate is an effective, safe alternative for the prophylaxis of pediatric migraine. An acceptable risk/benefit maintenance dose was < or =2 mg/kg/day.

Efficacy and safety of lamotrigine monotherapy in children and adolescents with epilepsy.

Lamotrigine (LTG) has shown to confer broad-spectrum, well-tolerated control of epilepsy. Monotherapy is preferable over polytherapy because of better compliance, fewer adverse events, less interactions, lower teratogenicity and lower cost. The aim of this study is to evaluate the efficacy and safety of LTG monotherapy on seizure control in a cohort of children and adolescents with epilepsy. We retrospectively reviewed the records of children and adolescents treated with LTG monotherapy at our institution between 2001 and 2006. Data collected included demographics, seizure type, etiology of seizures, age at onset of seizures and at initiation of LTG treatment, number of antiepileptic drugs (AEDs) prior to LTG, dose of LTG, length of follow-up, treatment response, and adverse events. Seventy-two children and adolescents were identified (mean age 12.1 years); 37.5% had mental retardation. Age at onset of epilepsy was 5.7 years (0-16). Twenty three percent had symptomatic focal epilepsy, 15.5% idiopathic focal epilepsy, 19.4% symptomatic generalized epilepsy and 41.6% idiopathic generalized epilepsy. LTG was used as first-line monotherapy in 26.4% of patients and as a second-line monotherapy in 73.6%. Age at initiation of LTG therapy was 10 years (2.8-19). Mean number of AEDs tried prior to LTG was 1.3 (0-6). Mean dose of LTG was 5.5mg/kg/day (1.1-13.7). Mean follow-up period was 33 months (3 weeks to 11.5 years). The degree of seizure reduction was as follows: seizure free in 42%, 75-90% reduction in 17.4%, 50-74% in 11.6%, 25-49% in 10%. Sixteen percent had no change in seizure control and 3% became worse. The most common adverse event was rash (6.9%). Six (8.3%) patients discontinued LTG because of the adverse events. No patient had Stevens-Johnson syndrome. In conclusion, LTG was effective and well-tolerated as monotherapy in children and adolescents for both focal and generalized epilepsies.

Ocular compression pressure during EEG for the study of increased vagal reactivity.

Ocular compression (OC) is a maneuver performed during EEG to demonstrate increased vagal reactivity in children with suspected syncope including breath-holding spells. We examined the relationship between the simulated OC pressure exerted by different physicians and the cardiac slowing responses that they had historically obtained as per EEG records. Simulated OC was performed by each physician using a sphygmomanometer. EEGs were reviewed for the rate of positive cardiac slowing per physician. Among three physicians who performed a total of 73 OC, the mean +/- SD of applied pressure were 29.0 +/- 2.4, 60.7 +/- 3.5 and 42.4 +/- 2.5 mmHg, respectively. There was good intra-physician consistency for the OC pressures exerted. The mean pressure exerted was significantly different between physicians (p < 0.001, ANOVA). The positive response rate for cardiac slowing among these physicians was 11/37 (29.7%), 10/21 (47.6%) and 8/15 (53.3%) respectively. The difference in positive OC responses between physicians was not significant (p = 0.127, chi-square). Higher OC pressures did not translate into more positive responses. A pressure of 30 mmHg is as good as 60 mmHg in demonstrating cardiac slowing during OC.

Intravenous levetiracetam in children with epilepsy.

Intravenous levetiracetam recently became available for use in patients aged >16 years. There are few data about its safety and efficacy in children. We retrospectively analyzed data from children treated with intravenous levetiracetam. Ten patients (6 female, 4 male), aged 3 weeks to 19 years, were treated with intravenous levetiracetam at a mean dose of 50.5 mg/kg/day for a mean duration of 4.9 days. Four patients received intravenous levetiracetam for acute repetitive seizures/status epilepticus, and three as replacement for oral levetiracetam because administration of oral levetiracetam was temporarily infeasible. One patient each received intravenous levetiracetam for seizure prophylaxis during brain biopsy, as maintenance treatment after acute seizures, and as substitute for sodium valproate. Three of four patients with acute repetitive seizures/status epilepticus became seizure-free; the fourth patient had a partial reduction in seizure frequency. All three patients who received intravenous levetiracetam as substitute for oral levetiracetam tolerated the switch well. The other three patients were seizure-free on intravenous levetiracetam. No serious adverse effects were observed, and all patients completed treatment with intravenous levetiracetam for the intended period. Intravenous levetiracetam may be effective in various clinical situations requiring intravenous administration of an antiepileptic drug.

Levetiracetam monotherapy in children with epilepsy.

Although levetiracetam has shown efficacy in children with epilepsy, when used as adjunctive therapy, limited data are available regarding its use as monotherapy. The objective of this study is to evaluate the efficacy and tolerability of levetiracetam monotherapy in a cohort of pediatric patients with epilepsy. A retrospective analysis of pediatric epilepsy patients receiving levetiracetam at a single institution was performed over a 3-year period. Eighty-one patients were identified, 18 of whom received levetiracetam as monotherapy (mean age, 9.6 years). Epilepsy types were partial in 14 and generalized in 4. Conversion to levetiracetam monotherapy occurred in 16 patients due to lack of efficacy or adverse events, and 2 patients were initially started on monotherapy. Dose range of levetiracetam was 14-60 mg/kg, and duration of therapy ranged from 2-24 months. Eleven patients became seizure free on levetiracetam, one had at least 50% reduction in seizures, and six others had no change in seizure frequency. Adverse events included worsening of behavior, irritability, and possible cognitive changes, seen in 4 patients. Levetiracetam was discontinued in seven patients overall. Levetiracetam monotherapy appeared to be effective and well tolerated in this group of children with epilepsy and warrants further investigation in a well-controlled, prospective study.

Epileptic seizures in the pediatric intensive care unit setting.

PURPOSE: The clinical features of seizures occurring in the pediatric intensive care unit (PICU) setting are not well characterized. Adult ICU studies reveal an incidence of seizures ranging from 0.8% to 3.3%, with vascular, metabolic abnormalities, and drug withdrawal being the most common etiologies. The objective of this study is to investigate the clinical characteristics of seizures in children admitted to the PICU at our institution. METHODS: We performed a retrospective review of all patients with diagnoses of seizures or epilepsy, admitted to our PICU from 2002 to 2004. Of 6,820 admissions, 32 patients, aged one month to 19 years had seizures in the PICU. RESULTS: The incidence of seizures was 0.5%. Developmental delay or mental retardation was present in 37% of patients. Seizures were generalized in 26 (81%), and focal in 6 (19%); 34% had status epilepticus. The etiology of seizures was epilepsy in 11 (34%). Seizures that do not meet the diagnosis of epilepsy were diagnosed in 21 (66%) including post-craniotomy in five (23%), febrile seizures in three (14%), encephalitis in three (14%), and hydrocephalus in three (14%). Thirty-one patients (97%) were initially treated with either lorazepam or fosphenytoin. CONCLUSIONS: Seizures in PICU have different clinical characteristics from those in adults. Recognizing the common seizure etiologies in PICU is likely to lead to a more prompt and effective treatment. Antiepileptic drug prophylaxis may be useful in post-craniotomy patients. A neurological consultation and EEG evaluation are of the utmost importance to help rule in or out epileptic disorders in the PICU.

Anterior encephalocele associated with subependymal nodular heterotopia, cortical dysplasia and epilepsy: case report and review of the literature.

The presence of subependymal nodular heterotopia and cortical dysgenesis has been infrequently reported in patients with encephalocele. The majority of these patients were found to have posterior encephaloceles. We report a case of a Hispanic female with a frontoethmoidal encephalocele who developed epilepsy at 15 years of age. Magnetic resonance imaging of the brain demonstrated left subependymal nodular heterotopia, partial agenesis of the corpus callosum and left fronto-temporal cortical dysplasia with polymicrogyria. This case illustrates the association of anterior encephalocele with subependymal nodular heterotopia, cortical dysplasia and epilepsy. It underscores the importance of screening for intracranial abnormalities in patients with anterior encephalocele.

Usefulness of ocular compression during electroencephalography in distinguishing breath-holding spells and syncope from epileptic seizures.

Episodes of syncope or breath-holding spells are often misdiagnosed as epileptic events. The purpose of this study was to assess the usefulness of an electroencephalogram (EEG) with ocular compression to distinguish breath-holding spells and syncope from epileptic seizures. A retrospective analysis was performed on the EEG records of all children on whom ocular compression was performed from 2000 to 2003. Data from 116 patients with a clinical diagnosis consistent with either syncope or breath-holding spells were compared with a group of 46 patients with epilepsy. The RR interval during ocular compression was significantly higher in syncope patients compared with patients with epilepsy (P < .005). Using 2 seconds of asystole as the cutoff, the sensitivity of ocular compression was 26%, with 100% specificity. The change in RR interval from baseline to ocular compression also distinguished patients with breath-holding spells and syncope from patients with epilepsy. Even a small increase of 0.5 seconds in the RR interval demonstrated a sensitivity of 46%, with a specificity of 98%. Ocular compression performed during an EEG is useful in distinguishing patients with breath-holding spells and syncope from those with epileptic seizures. A requirement of a 2-second period of asystole with ocular compression excludes many patients. Our data indicate that an RR interval increase of 0.5 seconds over baseline identifies additional patients with increased vagal tone. Prompt and accurate diagnosis of the etiology of loss of consciousness might preclude the need for further extensive and expensive evaluation and reduce patient and parental distress.

Oxcarbazepine monotherapy in children and adolescents: a single-center clinical experience.

This single-center analysis evaluated the efficacy of oxcarbazepine monotherapy in children and adolescents. A retrospective chart review identified 60 patients (male=33, female=27) aged 6 months to 17.8 years (mean age 8.2+/-4.7 years) with partial onset epilepsy receiving oxcarbazepine monotherapy. The range of oxcarbazepine dose was 6-71 mg/kg/day (mean 26.3+/-11.4 mg/kg/day). The duration of therapy ranged from 3 months to 8 years (mean duration 16.7+/-14.3 months). Fifty-one patients (85%) achieved>or=50% reduction in seizure frequency, and 25 of 60 patients (42%) achieved seizure freedom. Ten patients (16.67%) reported adverse events including drowsiness, aggressive behavior, ataxia, dizziness, diplopia, and leg cramps. No hyponatremia or skin rash was observed. Twenty-four patients were switched from carbamazepine to oxcarbazepine monotherapy. In these patients carbamazepine was discontinued because of incidence of adverse events, poor seizure control, or both. Seventy-nine percent of patients switched from carbamazepine to oxcarbazepine monotherapy had >or=50% reduction in seizure frequency, and 37.5% became seizure-free. These findings suggest that oxcarbazepine monotherapy is effective and well tolerated in children and adolescents with partial epilepsy.

Oxcarbazepine therapy in very young children: a single-center clinical experience.

Oxcarbazepine is indicated for use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children >or=4 years of age. The purpose of this retrospective chart review was to assess efficacy and tolerability of oxcarbazepine in children

Efficacy and safety of zonisamide monotherapy in a cohort of children with epilepsy.

The aim of this study was to evaluate the efficacy and safety of zonisamide monotherapy in a cohort of children and adolescents with various types of epilepsy. Retrospective review of charts of our institution from 2001 through 2004 identified 69 children (19 males and 50 females, mean age 13.2 years) with epilepsy on zonisamide monotherapy. Seizure count and side effect profile were maintained during therapy. Sixty-one percent had idiopathic generalized epilepsy, 4% symptomatic generalized epilepsy, and 35% partial-onset epilepsy. Zonisamide was the first-line and second-line monotherapy for 32% and 68% of patients, respectively. The mean duration of follow-up on treatment was 22 months (range 3-48 months). The overall efficacy of zonisamide was 75.4% (> or = 50% seizure frequency reduction: good responders). Sixty-seven percent of good responders became seizure-free. Seventy-nine percent of patients with partial epilepsy and 71% with generalized epilepsy were good responders, of whom 79% and 63% were free of seizure, respectively. Eighteen (26%) patients developed side effects: weight loss (9), cognitive impairment (3), sleepiness (3), dizziness (2), and decreased appetite (1). In seven patients (10%), zonisamide had to be discontinued: four due to side effects and three because of poor seizure control. Zonisamide was demonstrated to be effective as monotherapy in children with epilepsy.

Intrathecal baclofen overdose followed by withdrawal: clinical and EEG features.

Intrathecal baclofen therapy is increasingly used to alleviate medically intractable spasticity in children with cerebral palsy, spinal cord injuries, and generalized dystonia. Complications like overdose or withdrawal can occur and could be the result of pump malfunction (device-related) or refilling and programming mistakes (human errors). This report describes a case, with emphasis on electroencephalographic changes, of a 12-year old male on long-term intrathecal baclofen therapy who had sequential occurrence of both acute inadvertent baclofen overdose followed by withdrawal symptoms. During baclofen intoxication, electroencephalography documented periodic generalized epileptiform discharges, occasionally followed by intermittent electro-decremental responses on a background of diffuse delta slowing (1-2 Hz). During withdrawal, mild generalized slowing during wakefulness was observed along with the appearance of high-amplitude, sharply contoured delta activity resembling frontal intermittent rhythmic delta activity in sleep. To our knowledge, this temporal profile of electroencephalographic features during baclofen intoxication followed by withdrawal has not been described before in pediatric patients. It is important for treating physicians to recognize the evolution of this electroencephalographic pattern in order to avoid misinterpretation of diagnosis and prognosis.

Acute disseminated encephalomyelitis in children: discordant neurologic and neuroimaging abnormalities and response to plasmapheresis.

OBJECTIVES: To describe our experience with acute disseminated encephalomyelitis (ADEM), focusing on (1) the relationship between clinical course and MRI findings and (2) the response to plasmapheresis in a subgroup of patients. METHODS: A retrospective record review was conducted of 13 children who were admitted as inpatients with the diagnosis of ADEM during the period 1998-2003. RESULTS: Diagnosis was established by clinical signs and symptoms, cerebrospinal fluid changes and multifocal involvement of deep gray and white matter based on MRI. Initial therapy was high-dose methylprednisolone and intravenous immunoglobulin in 12 patients. One child improved spontaneously. Six of 12 children did not improve with corticosteroid treatment. All 6 had an acute progressive course neurologically, and 5 of them also showed a delay in the onset of neuroimaging changes, eventually developing lesions in the deep gray matter and brainstem. This latter group received 5 sessions of plasmapheresis and recovered over the course of several months with varying degrees of residual neurologic deficits. CONCLUSIONS: Presentation of ADEM with delayed development of MRI lesions in deep gray matter and brainstem may herald a prolonged clinical course and lack of response to glucocorticoid therapy. Plasmapheresis might be an effective therapeutic intervention in these patients. The role of plasmapheresis versus corticosteroids and intravenous immunoglobulin as a primary treatment of ADEM needs to be investigated further.

Use and value of ordering emergency electroencephalograms and videoelectroencephalographic monitoring after business hours in a children's hospital: 1-year experience.

Policies of administration, availability, and utility of ordering emergency electroencephalograms (EEGs) during nonbusiness hours vary widely among different EEG laboratories. In an attempt to explore further the importance of performing such emergency procedures in children, we analyzed the utility of not only emergency EEGs but also emergency longterm bedside EEGs and emergency video-EEGs at our institution in 1 year. The number of EEG studies performed in 1 year at our neurophysiology laboratory was 1821: 1212 routine EEGs, 387 24-hour ambulatory EEGs, 81 video-EEGs, and 141 long-term bedside EEGs. The number of emergency studies during the same period of time was 32 (1.8% of the total studies): 18 emergency EEGs, 8 emergency long-term bedside EEGs, and 6 emergency video-EEGs. The reasons for ordering the 18 emergency EEGs included the evaluation of (1) altered mental status (n=10), (2) paroxysmal movement (including cluster of seizures) (n=6), and (3) prolonged febrile or afebrile seizures prior to being discharged on a weekend (n=2). The eight emergency long-term bedside EEGs were done to evaluate (1) altered mental status (n=6) and (2) frequently occurring paroxysmal events (n=2). Four of the eight emergency long-term bedside EEGs were done after an abnormal emergency EEG. The six emergency video-EEGs were done to evaluate frequently occurring paroxysmal events (n=5) and altered mental status (n=1). Overall, emergency EEGs and emergency video-EEGs were useful in decision making in 30 of 32 (94%) studies. This might be related to the fact that a neurologist approved all of the studies. Appropriate strategies need to be developed to make this essential service available for patient care.