Huntley Hardison | Drexel University College of Medicine (original) (raw)
Papers by Huntley Hardison
Neuropediatrics, Feb 1, 2008
and strokes) syndrome, stroke-like episodes occur often and are accompanied by focal EEG abnormal... more and strokes) syndrome, stroke-like episodes occur often and are accompanied by focal EEG abnormalities [26]. EEG fi ndings of high amplitude slow waves and polyspikes have been described in a series of patients with Alpers disease [7]. Tulinius et al. [39] reported EEG changes in 25 children and adolescents with mitochondrial disease and found sequential EEG patterns in Alpers disease, MERRF and MELAS syndromes, which they thought were typical for the respective syndromes. The majority of children with ME do not fi t into one of the clearly defi ned clinical syndromes of MERRF, MELAS, Kearns Sayre syndrome (KSS) or Leigh disease. Often they present as a non-specifi c encephalopathy and diagnosis is based on morphological and biochemical mitochondrial abnormalities [30, 42]. Diagnostic criteria for pediatric mitochondrial disorders have been modifi ed from an adult classifi cation scheme known as the modifi ed Walker criteria [4] .
Pediatrics, Aug 1, 2005
Objectives. To describe our experience with acute disseminated encephalomyelitis (ADEM), focusing... more 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.
– The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, t... more – The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, topiramate and lamotrigine have also been shown to be effective. The objective of this study was to evaluate the efficacy and tolerability of zonisamide (ZNS) in the treatment of JME. We retrospectively analyzed the records of 15 patients (three M, 12 F, ages 11-20 years) diagnosed with JME at our institution during 2001-2003, and treated with ZNS. General-ized tonic-clonic (GTC), myoclonic and absence seizure response was as-sessed. The ZNS dose range was 200-500 mg/day (2.0-8.5 mg/kg/day). ZNS was started as the first drug, and as monotherapy, in 13 and was added to VPA in two patients. Follow-up range was 2-24 months (mean 12 months). Overall, 80 % of patients on ZNS monotherapy showed good control ( ≥ 50 % seizure reduction). Sixty-nine, 62 and 38 % of patients were free of GTC, myoclonic, and absence seizures, respectively. Seizure control was achieved within four to eight weeks of a...
Iron deficiency in children: the relationship between pretreatment laboratory tests and subsequent hemoglobin response to iron therapy
The American Journal of Clinical Nutrition, Oct 1, 1981
The goal of detecting iron deficiency in children is to identify those whose Hb concentration wil... more The goal of detecting iron deficiency in children is to identify those whose Hb concentration will rise in response to treatment with iron. In a controlled treatment trial conducted among Eskimo children, we examined the effectiveness of various measures of iron nutrition in predicting a response to iron therapy (greater than 1.0 g/dl rise in Hb). A response was seen in 43%, and an additional 26% had an intermediate response (0.5 to 1.0 g/dl rise). When individual Hb values were expressed as SD scores of the Hb distribution of a reference population, a marked skew toward low scores was seen before treatment. After treatment, the distribution became more Gaussian, indicating that iron deficiency had been the major cause of anemia. Serum ferritin, transferrin saturation, and free erythrocyte protoporphyrin levels moved toward normal with treatment, however, none of the tests used was very effective in distinguishing individuals who would have a response t Hb from those who would not (sensitivities: 63 to 42%, specificities: 45 to 61%). Laboratory measures of iron nutrition were far more helpful in depicting the iron status of the population than they were in distinguishing iron-responsive from nonresponsive individuals.
The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, top... more The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, topiramate and lamotrigine have also been shown to be effective. The objective of this study was to evaluate the efficacy and tolerability of zonisamide (ZNS) in the treatment of JME. We retrospectively analyzed the records of 15 patients (three M, 12 F, ages 11-20 years) diagnosed with JME at our institution during 2001-2003, and treated with ZNS. Generalized tonic-clonic (GTC), myoclonic and absence seizure response was assessed. The ZNS dose range was 200-500 mg/day (2.0-8.5 mg/kg/day). ZNS was started as the first drug, and as monotherapy, in 13 and was added to VPA in two patients. Follow-up range was 2-24 months (mean 12 months). Overall, 80% of patients on ZNS monotherapy showed good control (> or = 50% seizure reduction). Sixty-nine, 62 and 38% of patients were free of GTC, myoclonic, and absence seizures, respectively. Seizure control was achieved within four to eight weeks of a...
Epileptic seizures in the pediatric intensive care unit setting
PURPOSE The clinical features of seizures occurring in the pediatric intensive care unit (PICU) s... more 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...
Child Nerv Syst, 1987
The influence of clinical and treatment factors on the outcome of children with primary !ntramedu... more The influence of clinical and treatment factors on the outcome of children with primary !ntramedullary spinal cord tumors (PST) was evaluated by reviewing the records of 26 children diagnosed during the 15-year period 1970-1984. Five-year survival was 39%, but 5-year eventfree survival (EFS) was only 14%. Eighteen-month EFS was 53% (9/17) among children with low-grade astrocytoma, 100% (2/2) with ependymoma, and 0 of 7 with anaplastic astrocytoma or ganglioglioma. There was no significant difference in the 18-month EFS by location of tumor, duration of symptoms, or extent of surgical removal. Five of 9 children with locally recurrent PST had a second operation, and 4 were alive a median of 56 months later. PST disseminated to the leptomeninges or the III ventricle in 5 children: 2 at diagnosis, 2 as the first sign of disease relapse, and 1 after local recurrence. Given the poor outcome of our children, different methods of treatment for children with tumors in this location should be evaluated.
International Journal of Cancer, Jul 15, 1981
The records of 20 Alaskan Native patients with primary hepatocellular carcinoma (PHC) diagnosed i... more The records of 20 Alaskan Native patients with primary hepatocellular carcinoma (PHC) diagnosed in the I I-year period 1969-1979 were reviewed. The annual incidence of PHC was found to be high among Alaskan Native males and especially high among Alaskan Eskimo males (7.6 and 11.2 per 100,000, respectively) in comparison to Greenland and Canadian Eskimos and US white males. Familial and geographic clustering of PHC patients was noted in areas known to be hyperendemic for hepatitis B virus (HBV) infection. A bimodal age distribution among PHC patients occurred with peaks at 15-25 years and 40-65 years. A high prevalence of hepatitis B surface antigen (HBsAg) in serum of patients in the younger age group suggests that HBV infection might be a factor associated with the development of PHC in young Eskimos. PHC in Alaskan Natives is apparently not closely associated with alcoholic cirrhosis.
Efficacy and tolerability of ADHD medications in a clinical practice
Journal of Pediatric Neurology, 2008
Abstract. Randomized controlled trials have shown that stimulants reduce symptoms of impulsivity ... more Abstract. Randomized controlled trials have shown that stimulants reduce symptoms of impulsivity and hyperactivity in children with attention deficit/hyperactivity disorder (ADHD); however, these rigid protocols show no advantage of one medication over another. Our study examined ...
Relapse of Herpes Encephalitis after Acyclovir Therapy: Report of Two New Cases and Review of the Literature
Neuropediatrics, 2004
Relapse of herpes simplex virus (HSV) encephalitis following acyclovir therapy has been reported ... more Relapse of herpes simplex virus (HSV) encephalitis following acyclovir therapy has been reported infrequently in children beyond the neonatal period. The pathogenic mechanism of the recurrence is not fully understood. We report two new cases that support a mechanism of latent HSV infection with reactivation of the disease. Our patients were 2 years (#1) and 8 months (#2) old at initial infection. Both presented with fever, lethargy, focal seizures, and focal motor abnormalities. Serum HSV antibodies (Abs) were negative. The patients were treated with acyclovir for 14 and 21 days, respectively. They were readmitted at 1 month, and 4 days after discharge, respectively, with recurrent lethargy, seizures, and choreo-athetoid movements. Serum and CSF HSV Abs were significantly increased. CSF PCR was positive. In patient # 2 acyclovir-sensitive HSV was isolated from a brain biopsy. Both patients were re-treated with acyclovir, but progressed to a neurovegetative state. In our cases, latent HSV infection and reactivation is the most likely explanation for recurrent encephalitis. The immuno-pathogenic mechanisms of the infection recurrence are discussed. Based on the reported cases in the literature, patients younger than 2 years of age and with lower total dose of acyclovir treatments have a higher risk of recurrence.
Mitochondrial enzyme dysfunction in autism spectrum disorders; a novel biomarker revealed from buccal swab analysis
Biomarkers in Medicine, 2015
Mitochondrial function studies in autism spectrum disorders (ASD) have detected skeletal muscle m... more Mitochondrial function studies in autism spectrum disorders (ASD) have detected skeletal muscle mitochondrial enzyme deficiencies in respiratory complex (RC) activities. As a muscle biopsy is expensive and invasive, we assessed RC-I and RC-IV activities in buccal swabs. 92 children with ASD and 68 controls were studied with immunocapture for RC-I and microspectrophotometry for RC-IV. Significant RC activity deficiencies were found in 39 (42%) ASD patients (p < 0.01) and more prevalent in more severe cases. Aberrant RC overactivity was seen in 9 children. RC-I/RC-IV activity ratio was significantly increased in 64% of the entire ASD cohort including 76% of those more severely affected (p < 0.05). Buccal swab analysis revealed extensive RC abnormalities in ASD providing a noninvasive biomarker to assess mitochondrial function in ASD patients.
Epileptic seizures in the pediatric intensive care unit setting
Epileptic disorders: international epilepsy journal with videotape
The clinical features of seizures occurring in the pediatric intensive care unit (PICU) setting a... more 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. 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. 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...
Mitochondrial dysfunction in migraine
Seminars in pediatric neurology, 2013
Migraine is the most frequent type of headache in children. In the 1980s, scientists first hypoth... more Migraine is the most frequent type of headache in children. In the 1980s, scientists first hypothesized a connection between migraine and mitochondrial (mt) disorders. More recent studies have suggested that at least some subtypes of migraine may be related to a mt defect. Different types of evidence support a relationship between mitochondria (mt) and migraine: (1) Biochemical evidence: Abnormal mt function translates into high intracellular penetration of Ca(2+), excessive production of free radicals, and deficient oxidative phosphorylation, which ultimately causes energy failure in neurons and astrocytes, thus triggering migraine mechanisms, including spreading depression. The mt markers of these events are low activity of superoxide dismutase, activation of cytochrome-c oxidase and nitric oxide, high levels of lactate and pyruvate, and low ratios of phosphocreatine-inorganic phosphate and N-acetylaspartate-choline. (2) Morphologic evidence: mt abnormalities have been shown in mi...
Immunomodulatory treatments in epilepsy
Seminars in pediatric neurology, 2014
The role of immunity and inflammation appears to be an integral part of the pathogenic processes ... more 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.
Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi
Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the c... more Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the central nervous system. The experience in children is limited. We retrospectively reviewed our experience with 20 ADEM patients (10 females, 10 males) with age of onset before 18 years old in Taiwan to clarify the clinical manifestations, neuroimaging findings, and the relationship between ADEM and multiple sclerosis (MS). The age at onset ranged from 4 months to 15 years. Seventeen (85%) children had a recent infectious prodrome. Children presented most often with acute consciousness disturbance (70%) and motor deficits (55%). Seizures occurred in 10 (50%), but only one child developed epilepsy in follow-up. Brain magnetic resonance imaging (MRI) evaluations done in all patients revealed multifocal lesions, mainly in subcortical white matter (80%), brainstem (65%), basal ganglia (55%), cerebellum (45%), thalamus (40%), and periventricular white matter (35%). Spinal cord MRI was performed...
Acute disseminated encephalomyelitis in children: discordant neurologic and neuroimaging abnormalities and response to plasmapheresis
Pediatrics, 2005
To describe our experience with acute disseminated encephalomyelitis (ADEM), focusing on (1) the ... more 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. A retrospective record review was conducted of 13 children who were admitted as inpatients with the diagnosis of ADEM during the period 1998-2003. 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...
Epileptic disorders : international epilepsy journal with videotape, 2004
The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, top... more The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, topiramate and lamotrigine have also been shown to be effective. The objective of this study was to evaluate the efficacy and tolerability of zonisamide (ZNS) in the treatment of JME. We retrospectively analyzed the records of 15 patients (three M, 12 F, ages 11-20 years) diagnosed with JME at our institution during 2001-2003, and treated with ZNS. Generalized tonic-clonic (GTC), myoclonic and absence seizure response was assessed. The ZNS dose range was 200-500 mg/day (2.0-8.5 mg/kg/day). ZNS was started as the first drug, and as monotherapy, in 13 and was added to VPA in two patients. Follow-up range was 2-24 months (mean 12 months). Overall, 80% of patients on ZNS monotherapy showed good control (> or = 50% seizure reduction). Sixty-nine, 62 and 38% of patients were free of GTC, myoclonic, and absence seizures, respectively. Seizure control was achieved within four to eight weeks of a...
Hepatitis B testing in the families and villages of five young eskimos with primary hepatocellular carcinoma
American journal of epidemiology, 1981
A 15-year-old female Eskimo and a 22-year-old male Eskimo from a southwestern Alaskan village (po... more A 15-year-old female Eskimo and a 22-year-old male Eskimo from a southwestern Alaskan village (population 540) were diagnosed as having primary hepatocellular carcinoma (PHC) in December, 1977. The fathers of both patients also died of PHC. Three additional cases of PHC affecting young Alaskan Eskimos had been diagnosed since 1972, all from neighboring villages. Four of the five young patients were positive for hepatitis B surface antigen (HBsAg), and the family members of three patients were all positive for HBsAg or antibody to this antigen (anti-HBs). The other two families had no members positive for HBsAg. The prevalence of HBsAg in the villages of these patients ranged from 0--5%, and the prevalence of anti-HBs ranged from 3--25%. This part of Alaska has a high rate of infection with hepatitis B virus and an increased incidence of PHC. However, other Alaskan villages of similar ethnic background have considerably higher rates of hepatitis B infection than the four villages des...
Neuroimaging Abnormalities and Response to Plasmapheresis Acute Disseminated Encephalomyelitis in Children: Discordant Neurologic and
Epileptic disorders : international epilepsy journal with videotape, 2011
Childhood absence epilepsy (CAE) typically starts between four and seven years of age. Onset befo... more Childhood absence epilepsy (CAE) typically starts between four and seven years of age. Onset before three years is rare and has not been previously reported from North America. We retrospectively reviewed the electroencephalography laboratory database and paediatric neurology clinic records (from January 2000 to June 2009) at our institution in order to identify patients with absence seizures beginning before age three. Information was collected for age, gender, neurodevelopment, antiepileptic drugs (AEDs) used, seizure control, follow-up, and side effects. Of 12 patients identified, mean age at onset was 20.5 months (range: 11 months to two years; follow-up: six months to 11 years). Seven of 12 patients had normal neurodevelopment and five had speech delay. Four patients were seizure-free without AEDs, three were seizure-free with a single AED, and five still had seizures with multiple AEDs. Three patients had recurrences after medication withdrawal. Other previously published seri...
Neuropediatrics, Feb 1, 2008
and strokes) syndrome, stroke-like episodes occur often and are accompanied by focal EEG abnormal... more and strokes) syndrome, stroke-like episodes occur often and are accompanied by focal EEG abnormalities [26]. EEG fi ndings of high amplitude slow waves and polyspikes have been described in a series of patients with Alpers disease [7]. Tulinius et al. [39] reported EEG changes in 25 children and adolescents with mitochondrial disease and found sequential EEG patterns in Alpers disease, MERRF and MELAS syndromes, which they thought were typical for the respective syndromes. The majority of children with ME do not fi t into one of the clearly defi ned clinical syndromes of MERRF, MELAS, Kearns Sayre syndrome (KSS) or Leigh disease. Often they present as a non-specifi c encephalopathy and diagnosis is based on morphological and biochemical mitochondrial abnormalities [30, 42]. Diagnostic criteria for pediatric mitochondrial disorders have been modifi ed from an adult classifi cation scheme known as the modifi ed Walker criteria [4] .
Pediatrics, Aug 1, 2005
Objectives. To describe our experience with acute disseminated encephalomyelitis (ADEM), focusing... more 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.
– The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, t... more – The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, topiramate and lamotrigine have also been shown to be effective. The objective of this study was to evaluate the efficacy and tolerability of zonisamide (ZNS) in the treatment of JME. We retrospectively analyzed the records of 15 patients (three M, 12 F, ages 11-20 years) diagnosed with JME at our institution during 2001-2003, and treated with ZNS. General-ized tonic-clonic (GTC), myoclonic and absence seizure response was as-sessed. The ZNS dose range was 200-500 mg/day (2.0-8.5 mg/kg/day). ZNS was started as the first drug, and as monotherapy, in 13 and was added to VPA in two patients. Follow-up range was 2-24 months (mean 12 months). Overall, 80 % of patients on ZNS monotherapy showed good control ( ≥ 50 % seizure reduction). Sixty-nine, 62 and 38 % of patients were free of GTC, myoclonic, and absence seizures, respectively. Seizure control was achieved within four to eight weeks of a...
Iron deficiency in children: the relationship between pretreatment laboratory tests and subsequent hemoglobin response to iron therapy
The American Journal of Clinical Nutrition, Oct 1, 1981
The goal of detecting iron deficiency in children is to identify those whose Hb concentration wil... more The goal of detecting iron deficiency in children is to identify those whose Hb concentration will rise in response to treatment with iron. In a controlled treatment trial conducted among Eskimo children, we examined the effectiveness of various measures of iron nutrition in predicting a response to iron therapy (greater than 1.0 g/dl rise in Hb). A response was seen in 43%, and an additional 26% had an intermediate response (0.5 to 1.0 g/dl rise). When individual Hb values were expressed as SD scores of the Hb distribution of a reference population, a marked skew toward low scores was seen before treatment. After treatment, the distribution became more Gaussian, indicating that iron deficiency had been the major cause of anemia. Serum ferritin, transferrin saturation, and free erythrocyte protoporphyrin levels moved toward normal with treatment, however, none of the tests used was very effective in distinguishing individuals who would have a response t Hb from those who would not (sensitivities: 63 to 42%, specificities: 45 to 61%). Laboratory measures of iron nutrition were far more helpful in depicting the iron status of the population than they were in distinguishing iron-responsive from nonresponsive individuals.
The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, top... more The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, topiramate and lamotrigine have also been shown to be effective. The objective of this study was to evaluate the efficacy and tolerability of zonisamide (ZNS) in the treatment of JME. We retrospectively analyzed the records of 15 patients (three M, 12 F, ages 11-20 years) diagnosed with JME at our institution during 2001-2003, and treated with ZNS. Generalized tonic-clonic (GTC), myoclonic and absence seizure response was assessed. The ZNS dose range was 200-500 mg/day (2.0-8.5 mg/kg/day). ZNS was started as the first drug, and as monotherapy, in 13 and was added to VPA in two patients. Follow-up range was 2-24 months (mean 12 months). Overall, 80% of patients on ZNS monotherapy showed good control (> or = 50% seizure reduction). Sixty-nine, 62 and 38% of patients were free of GTC, myoclonic, and absence seizures, respectively. Seizure control was achieved within four to eight weeks of a...
Epileptic seizures in the pediatric intensive care unit setting
PURPOSE The clinical features of seizures occurring in the pediatric intensive care unit (PICU) s... more 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...
Child Nerv Syst, 1987
The influence of clinical and treatment factors on the outcome of children with primary !ntramedu... more The influence of clinical and treatment factors on the outcome of children with primary !ntramedullary spinal cord tumors (PST) was evaluated by reviewing the records of 26 children diagnosed during the 15-year period 1970-1984. Five-year survival was 39%, but 5-year eventfree survival (EFS) was only 14%. Eighteen-month EFS was 53% (9/17) among children with low-grade astrocytoma, 100% (2/2) with ependymoma, and 0 of 7 with anaplastic astrocytoma or ganglioglioma. There was no significant difference in the 18-month EFS by location of tumor, duration of symptoms, or extent of surgical removal. Five of 9 children with locally recurrent PST had a second operation, and 4 were alive a median of 56 months later. PST disseminated to the leptomeninges or the III ventricle in 5 children: 2 at diagnosis, 2 as the first sign of disease relapse, and 1 after local recurrence. Given the poor outcome of our children, different methods of treatment for children with tumors in this location should be evaluated.
International Journal of Cancer, Jul 15, 1981
The records of 20 Alaskan Native patients with primary hepatocellular carcinoma (PHC) diagnosed i... more The records of 20 Alaskan Native patients with primary hepatocellular carcinoma (PHC) diagnosed in the I I-year period 1969-1979 were reviewed. The annual incidence of PHC was found to be high among Alaskan Native males and especially high among Alaskan Eskimo males (7.6 and 11.2 per 100,000, respectively) in comparison to Greenland and Canadian Eskimos and US white males. Familial and geographic clustering of PHC patients was noted in areas known to be hyperendemic for hepatitis B virus (HBV) infection. A bimodal age distribution among PHC patients occurred with peaks at 15-25 years and 40-65 years. A high prevalence of hepatitis B surface antigen (HBsAg) in serum of patients in the younger age group suggests that HBV infection might be a factor associated with the development of PHC in young Eskimos. PHC in Alaskan Natives is apparently not closely associated with alcoholic cirrhosis.
Efficacy and tolerability of ADHD medications in a clinical practice
Journal of Pediatric Neurology, 2008
Abstract. Randomized controlled trials have shown that stimulants reduce symptoms of impulsivity ... more Abstract. Randomized controlled trials have shown that stimulants reduce symptoms of impulsivity and hyperactivity in children with attention deficit/hyperactivity disorder (ADHD); however, these rigid protocols show no advantage of one medication over another. Our study examined ...
Relapse of Herpes Encephalitis after Acyclovir Therapy: Report of Two New Cases and Review of the Literature
Neuropediatrics, 2004
Relapse of herpes simplex virus (HSV) encephalitis following acyclovir therapy has been reported ... more Relapse of herpes simplex virus (HSV) encephalitis following acyclovir therapy has been reported infrequently in children beyond the neonatal period. The pathogenic mechanism of the recurrence is not fully understood. We report two new cases that support a mechanism of latent HSV infection with reactivation of the disease. Our patients were 2 years (#1) and 8 months (#2) old at initial infection. Both presented with fever, lethargy, focal seizures, and focal motor abnormalities. Serum HSV antibodies (Abs) were negative. The patients were treated with acyclovir for 14 and 21 days, respectively. They were readmitted at 1 month, and 4 days after discharge, respectively, with recurrent lethargy, seizures, and choreo-athetoid movements. Serum and CSF HSV Abs were significantly increased. CSF PCR was positive. In patient # 2 acyclovir-sensitive HSV was isolated from a brain biopsy. Both patients were re-treated with acyclovir, but progressed to a neurovegetative state. In our cases, latent HSV infection and reactivation is the most likely explanation for recurrent encephalitis. The immuno-pathogenic mechanisms of the infection recurrence are discussed. Based on the reported cases in the literature, patients younger than 2 years of age and with lower total dose of acyclovir treatments have a higher risk of recurrence.
Mitochondrial enzyme dysfunction in autism spectrum disorders; a novel biomarker revealed from buccal swab analysis
Biomarkers in Medicine, 2015
Mitochondrial function studies in autism spectrum disorders (ASD) have detected skeletal muscle m... more Mitochondrial function studies in autism spectrum disorders (ASD) have detected skeletal muscle mitochondrial enzyme deficiencies in respiratory complex (RC) activities. As a muscle biopsy is expensive and invasive, we assessed RC-I and RC-IV activities in buccal swabs. 92 children with ASD and 68 controls were studied with immunocapture for RC-I and microspectrophotometry for RC-IV. Significant RC activity deficiencies were found in 39 (42%) ASD patients (p < 0.01) and more prevalent in more severe cases. Aberrant RC overactivity was seen in 9 children. RC-I/RC-IV activity ratio was significantly increased in 64% of the entire ASD cohort including 76% of those more severely affected (p < 0.05). Buccal swab analysis revealed extensive RC abnormalities in ASD providing a noninvasive biomarker to assess mitochondrial function in ASD patients.
Epileptic seizures in the pediatric intensive care unit setting
Epileptic disorders: international epilepsy journal with videotape
The clinical features of seizures occurring in the pediatric intensive care unit (PICU) setting a... more 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. 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. 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...
Mitochondrial dysfunction in migraine
Seminars in pediatric neurology, 2013
Migraine is the most frequent type of headache in children. In the 1980s, scientists first hypoth... more Migraine is the most frequent type of headache in children. In the 1980s, scientists first hypothesized a connection between migraine and mitochondrial (mt) disorders. More recent studies have suggested that at least some subtypes of migraine may be related to a mt defect. Different types of evidence support a relationship between mitochondria (mt) and migraine: (1) Biochemical evidence: Abnormal mt function translates into high intracellular penetration of Ca(2+), excessive production of free radicals, and deficient oxidative phosphorylation, which ultimately causes energy failure in neurons and astrocytes, thus triggering migraine mechanisms, including spreading depression. The mt markers of these events are low activity of superoxide dismutase, activation of cytochrome-c oxidase and nitric oxide, high levels of lactate and pyruvate, and low ratios of phosphocreatine-inorganic phosphate and N-acetylaspartate-choline. (2) Morphologic evidence: mt abnormalities have been shown in mi...
Immunomodulatory treatments in epilepsy
Seminars in pediatric neurology, 2014
The role of immunity and inflammation appears to be an integral part of the pathogenic processes ... more 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.
Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi
Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the c... more Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the central nervous system. The experience in children is limited. We retrospectively reviewed our experience with 20 ADEM patients (10 females, 10 males) with age of onset before 18 years old in Taiwan to clarify the clinical manifestations, neuroimaging findings, and the relationship between ADEM and multiple sclerosis (MS). The age at onset ranged from 4 months to 15 years. Seventeen (85%) children had a recent infectious prodrome. Children presented most often with acute consciousness disturbance (70%) and motor deficits (55%). Seizures occurred in 10 (50%), but only one child developed epilepsy in follow-up. Brain magnetic resonance imaging (MRI) evaluations done in all patients revealed multifocal lesions, mainly in subcortical white matter (80%), brainstem (65%), basal ganglia (55%), cerebellum (45%), thalamus (40%), and periventricular white matter (35%). Spinal cord MRI was performed...
Acute disseminated encephalomyelitis in children: discordant neurologic and neuroimaging abnormalities and response to plasmapheresis
Pediatrics, 2005
To describe our experience with acute disseminated encephalomyelitis (ADEM), focusing on (1) the ... more 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. A retrospective record review was conducted of 13 children who were admitted as inpatients with the diagnosis of ADEM during the period 1998-2003. 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...
Epileptic disorders : international epilepsy journal with videotape, 2004
The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, top... more The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, topiramate and lamotrigine have also been shown to be effective. The objective of this study was to evaluate the efficacy and tolerability of zonisamide (ZNS) in the treatment of JME. We retrospectively analyzed the records of 15 patients (three M, 12 F, ages 11-20 years) diagnosed with JME at our institution during 2001-2003, and treated with ZNS. Generalized tonic-clonic (GTC), myoclonic and absence seizure response was assessed. The ZNS dose range was 200-500 mg/day (2.0-8.5 mg/kg/day). ZNS was started as the first drug, and as monotherapy, in 13 and was added to VPA in two patients. Follow-up range was 2-24 months (mean 12 months). Overall, 80% of patients on ZNS monotherapy showed good control (> or = 50% seizure reduction). Sixty-nine, 62 and 38% of patients were free of GTC, myoclonic, and absence seizures, respectively. Seizure control was achieved within four to eight weeks of a...
Hepatitis B testing in the families and villages of five young eskimos with primary hepatocellular carcinoma
American journal of epidemiology, 1981
A 15-year-old female Eskimo and a 22-year-old male Eskimo from a southwestern Alaskan village (po... more A 15-year-old female Eskimo and a 22-year-old male Eskimo from a southwestern Alaskan village (population 540) were diagnosed as having primary hepatocellular carcinoma (PHC) in December, 1977. The fathers of both patients also died of PHC. Three additional cases of PHC affecting young Alaskan Eskimos had been diagnosed since 1972, all from neighboring villages. Four of the five young patients were positive for hepatitis B surface antigen (HBsAg), and the family members of three patients were all positive for HBsAg or antibody to this antigen (anti-HBs). The other two families had no members positive for HBsAg. The prevalence of HBsAg in the villages of these patients ranged from 0--5%, and the prevalence of anti-HBs ranged from 3--25%. This part of Alaska has a high rate of infection with hepatitis B virus and an increased incidence of PHC. However, other Alaskan villages of similar ethnic background have considerably higher rates of hepatitis B infection than the four villages des...
Neuroimaging Abnormalities and Response to Plasmapheresis Acute Disseminated Encephalomyelitis in Children: Discordant Neurologic and
Epileptic disorders : international epilepsy journal with videotape, 2011
Childhood absence epilepsy (CAE) typically starts between four and seven years of age. Onset befo... more Childhood absence epilepsy (CAE) typically starts between four and seven years of age. Onset before three years is rare and has not been previously reported from North America. We retrospectively reviewed the electroencephalography laboratory database and paediatric neurology clinic records (from January 2000 to June 2009) at our institution in order to identify patients with absence seizures beginning before age three. Information was collected for age, gender, neurodevelopment, antiepileptic drugs (AEDs) used, seizure control, follow-up, and side effects. Of 12 patients identified, mean age at onset was 20.5 months (range: 11 months to two years; follow-up: six months to 11 years). Seven of 12 patients had normal neurodevelopment and five had speech delay. Four patients were seizure-free without AEDs, three were seizure-free with a single AED, and five still had seizures with multiple AEDs. Three patients had recurrences after medication withdrawal. Other previously published seri...