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Biomedical subjects

W E Dodson

Publications and source records attributed to W E Dodson.

At least 19 recordsLinked to original sources
PubMed1994

Course and outcome of acute cerebellar ataxia.

We report a study of 73 consecutive children with acute cerebellar ataxia, representing all of the children evaluated at St. Louis Children's Hospital during a 23-year-period to whom this diagnosis could appropriately be assigned. Twenty-six percent had chickenpox, 52% had other illnesses that were presumed to be viral, and in 3% the ataxia was related to immunization. Nineteen percent had no definite prodrome. Sixty children were followed for 4 months or longer after onset of their ataxia (mean, 7.4 +/- 6.0 years). Ninety-one percent (55/60) of these, including all children with chickenpox, recovered completely from ataxia. Eighty-nine percent (39/44) of the children with non-varicella-related ataxia recovered completely from the ataxia, a much better rate of recovery than what was found in prior large studies. One fifth of the children followed for more than 4 months experienced transient behavioral or intellectual difficulties, but only 5 of the 60 children demonstrated sustained learning problems. This study represents the largest reported series of acute cerebellar ataxia and the most complete characterization of the clinical features and outcome of this illness.

Acute Disease↗
PubMed1994

Pharmacology and therapeutic aspects of antiepileptic drugs in pediatrics.

In the past year, several new antiepileptic drugs have emerged that have potential benefits for children with epilepsy. The spectrum of adverse effects is the principal feature that differentiates among the older drugs used to treat partial and related seizures, including simple partial, complex partial, and partial secondarily generalized seizures. Based on studies in adults with refractory seizures, the new or investigational compounds felbamate, gabapentin, lamotrigine, and vigabatrin should be active against these types of seizures in children, but none of them have been subjected to pediatric randomized controlled trials, and no studies have been done that compare new and old drugs in this category. Thus, the new drugs hold promise in children with these types of seizures, but their role relative to old drugs has not been elucidated. Several of the new drugs are active against myoclonic and generalized tonic-clonic seizures, but thus far, none have been proven to possess antiabsence activity in children. Open-label investigations suggest that lamotrigine may be helpful in Lennox-Gastaut syndrome, and vigabatrin in infantile spasms. Only felbamate has been evaluated in a randomized controlled study in children, in which it has proven beneficial against astatic and generalized tonic-clonic seizures in children with Lennox-Gastaut syndrome. Whereas investigations of these and other novel drugs are ongoing, this is an active and exciting period in pediatric antiepileptic drug development.

Adult↗
PubMed1993

Felbamate in the treatment of Lennox-Gastaut syndrome: results of a 12-month open-label study following a randomized clinical trial.

Felbamate (FBM) is a new antiepileptic drug (AED) that has been evaluated in partial seizures and in the Lennox-Gastaut syndrome (LGS). When tested against placebo in an add-on, randomized, double-blind trial in 73 children with LGS, FBM significantly reduced the frequencies of astatic (atonic) seizures and generalized tonic-clonic seizures plus total seizure counts. In addition, FBM-treated subjects improved significantly on a parent-rated global evaluation and had fewer injuries. Overall, approximately 50% of subjects experienced a 50% or greater reduction in total seizure frequency and a dose-response relationship was apparent. The improvement that occurred in the double-blind study has been sustained for at least 12 months in subsequent open-label follow-up studies. In the first month of FBM treatment, 62% of the subjects who had previously received placebo had a reduction in total seizure frequency of > 50%. By the 12-month follow-up point, approximately half of the patients had a 50% reduction in total seizure count. Astatic seizures responded even better, with two-thirds of patients having a reduction of > 50% in astatic seizure frequency after 12 months of treatment. Based on adverse experience reports thus far, FBM appears to be well tolerated. FBM is the first drug to be shown effective in the LGS in randomized controlled trials. Although few subjects with LGS became seizure free, the frequency of the most severe seizure types decreased and the patients' global functioning improved.

Anticonvulsants↗
PubMed1992

Early childhood hepatocerebral degeneration misdiagnosed as valproate hepatotoxicity.

Four unrelated children were thought to have valproate-associated hepatotoxicity. They presented with recurrent partial secondarily generalized status epilepticus and epilepsia partialis continua followed by mental and motor regression. Despite treatment with multiple antiepileptic medications, they continued to have seizures. After initiation of valproic acid (VPA), all 4 manifested liver failure within 3 months. Two of these children each had 1 sibling who was not exposed to VPA, but who developed the same clinical picture including liver failure. At the time of autopsy, all 6 children had similar neuropathological findings with focal areas of spongiosis and neuronal loss, diffuse gliosis, and Alzheimer type II cells. One VPA-treated patient underwent a successful liver transplantation only to die from relentlessly progressive neurological deterioration. We propose that many of the reported patients with VPA-associated hepatotoxicity represent undiagnosed patients with early childhood hepatocerebral degeneration, the Huttenlocher variant of Alpers' syndrome. This disease manifests by obstinate partial seizures, recurrent partial secondarily generalized status epilepticus, epilepsia partialis continua, psychomotor deterioration, and hepatic dysfunction that is exacerbated by VPA administration. The accelerated demise from liver failure in the nontransplanted patients before the central nervous system pathology fully evolves makes the diagnosis of this rare condition difficult. The occurrence of disease in the unexposed siblings suggests recessive inheritance.

Brain↗
PubMed1991

Cytochrome c oxidase-associated Leigh syndrome: phenotypic features and pathogenetic speculations.

Fourteen new cases of cytochrome oxidase (COX)-associated Leigh syndrome (LS) are combined with 20 reported cases to describe the clinical, laboratory, and radiological features of this devastating metabolic condition. Three clinical stages are identified. Most patients have normal neurological development during the first 8-12 months (stage I). Somatic complaints are common, including chronic diarrhea, recurrent vomiting, anorexia, and decelerating body and head growth. The second stage evolves during late infancy and early childhood when motor regression becomes evident. Eye signs, altered breathing patterns, pyramidal, extrapyramidal, and cerebellar signs emerge and sudden clinical deterioration occurs during intercurrent infectious or metabolic stress. The last stage may extend from 2 to 10 years and is manifested by extreme hypotonia, swallowing difficulties and undernutrition. Feeding assistance is necessary and seizures may occur. The CSF lactate concentration is consistently elevated and MRI abnormalities are seen in the subcortical structures. COX deficiency affects most tissues, but is not always generalized. For example, 3 patients with a cardiomyopathy had normal COX activity in cultured skin fibroblasts. Nearly normal amounts of cross-reacting material are present by ELISA and immunoblot analyses. Parental consanguinity has been found in several families, the hereditary pattern is recessive and males are affected more commonly (2:1). The biomolecular abnormality causing COX deficiency in LS is unknown, but the available evidence implicates a nuclear-encoded protein that affects the structure or the stability of the holoenzyme complex.

Adolescent↗
PubMed1990

Combined deficiency of beta-galactosidase and neuraminidase: natural history of the disease in the first 18 years of an American patient with late infantile onset form.

We describe the clinical findings over the first 18 years of a patient with a novel phenotype for galactosialidosis, the storage disease produced by the combined deficiency of beta-galactosidase and neuraminidase. Clinical findings in the first few months included somewhat unusual appearance and hepatosplenomegaly. Dysostosis multiplex was evident by age 2 1/2 years. Mitral and aortic valvular disease appeared over the next few years and cardiac disease has become the most important clinical problem. Foam cells were present in the bone marrow, and vacuolated lymphocytes were present in the peripheral blood smear. The patient had no neurological symptoms, cherry red spots, or intellectual deterioration during the first 18 years. Evidence presented elsewhere indicates that the basic defect in this late infantile form of galactosialidosis (as is thought to be true for the other forms of galactosialidosis) is a reduced amount of the 32 kDa phosphoglycoprotein which associates with beta-galactosidase and alpha-neuraminidase in lysosomes.

Aortic Valve Insufficiency↗
PubMed1989

Medical treatment and pharmacology of antiepileptic drugs.

Antiepileptic drugs are effective even when metabolic, infectious, or structural lesions are present. Therefore, the underlying cause should be sought, and not just the seizure treated. After this is done, the drug therapy can be directed to controlling the seizure.

Anticonvulsants↗
PubMed1989

Level off.

Explore the source record for details and available documents.

Animals↗
PubMed1989

Immunochromatographic measurement of phenobarbital in whole blood with a non-instrumented assay.

We tested the precision and accuracy of the AccuLevel Phenobarbital Test, which reports whole-blood (fingerstick) results in plasma equivalent values, and compared these values with plasma results obtained using established methods. We conclude that the assay is precise, reliable, accurate for single tests, and is appropriate for use in offices, outpatient settings, and emergency rooms.

Chromatography↗
PubMed1989

Deleterious effects of drugs on the developing nervous system.

In the past two decades, several categories of drugs have emerged as serious neuroteratogens. These include vitamin A congeners, isotretinoin and etretinate, certain antiepileptic drugs, especially trimethadione, and valproic acid. Other antiepileptic drugs have low teratogenic potential and variably affect the developing CNS. When multiple antiepileptics are administered during pregnancy, however, the risk to the fetus increases considerably.

Abnormalities, Drug-Induced↗
PubMed1988

Cerebrospinal fluid IgG in childhood: the establishment of reference values.

A retrospective analysis of quantitative and qualitative immunoglobulin G (IgG) results from 253 children who were either medically and neurologically normal or highly unlikely to have abnormalities of CSF IgG is reported. Normal values in this reference population vary with age for CSF/albumin IgG ratio and CSF/serum IgG index and are significantly different from the adult reference values. The rate of false positivity is lower for quantitative values than for qualitative IgG determinations (oligoclonal bands).

Adolescent↗
PubMed1988

Aspects of antiepileptic treatment in children.

About 75% of patients with epilepsy have seizures during childhood, often requiring antiepileptic therapy. Children possess all the drug-specific pharmacokinetic features of adults (e.g., nonlinearity of phenytoin elimination and autoinduction of carbamazepine metabolism), plus other factors (e.g., age, intercurrent illness, comedication) that influence dosage. Kinetic differences are maximal in newborns and infants, with limited drug elimination in premature and full-term babies, soon followed by accelerated elimination during infancy and childhood, before lower adult elimination rates develop during late childhood or early adolescence. Most children with epilepsy require two- to fourfold larger doses relative to bodyweight than adults, to achieve comparable drug levels and therapeutic effects. Although rapid growth may require increased dosage, the need is limited as relative clearance declines with age. Children of any age, but particularly premature and newborn babies, show greater individual variability in drug handling and therefore in dose requirements than adults. Clinical response and antiepileptic drug concentrations should both be monitored carefully in children.

Child↗
PubMed1987

Special pharmacokinetic considerations in children.

Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.

Administration, Rectal↗
PubMed1987

Carbamazepine efficacy and utilization in children.

Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmaco-kinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.

Carbamazepine↗
PubMed1987

Phenytoin and carbamazepine, alone and in combination: anticonvulsant and neurotoxic effects.

Comedication with phenytoin and carbamazepine is frequently used in patients with refractory seizures, although the benefit of this strategy has not been established. To assess whether the combination is a rational anticonvulsant treatment, we determined the therapeutic index (toxicity:efficacy ratio) for the drugs, alone and together, in mice, The individual agents were virtually identical in anticonvulsant and neurotoxic activity, and combined use had no additional therapeutic advantage. Analysis of drug concentrations in brain showed an additive pharmacodynamic interaction for phenytoin and carbamazepine, indicating that the combination is unlikely to be superior to either drug alone. Thus, we find no experimental justification for the simultaneous use of phenytoin and carbamazepine in the treatment of epilepsy.

Animals↗
PubMed1984

Clinical investigation in Duchenne muscular dystrophy: IV. Double-blind controlled trial of leucine.

Ninety-six patients with Duchenne muscular dystrophy (DMD) were randomized and placed either on placebo or oral leucine at a dose of 0.2 g per kg per day. Patients were evaluated using a protocol that measured muscle strength, joint contracture, functional grade and activity, and pulmonary function tests. After 1 month there was a transient but significant difference in the strength of the two groups, the treated group being stronger than the placebo group. At 6 months there was also a transient difference in joint contracture measurements. Analysis of the data showed that the difference between the groups for both these measurements could not be ascribed to a therapeutic effect of leucine but rather to an unexpected drop in the placebo group. This was recognized only because the slope of deterioration for these functions had been well documented during the natural history phase of the study. These results indicate that oral leucine failed to produce a therapeutic response over a 1-year double-blind, controlled trial.

Child↗
PubMed1984

The steroid treatment of hereditary motor and sensory neuropathy.

A placebo or methylprednisolone (45-60 mg/M2) was administered in a crossover study as a single morning dose on alternate days to fourteen patients who had a familial progressive polyneuropathy that either began or was maximum in the distribution of the peroneal nerves. Neither the patients nor the examining physician were told whether the patient was taking a placebo or steroid but the steroid side-effects made a double-blind trial impossible. Patients were evaluated at the initiation of the study, the time of crossover, and at the conclusion of the study. Five patients with proven HMSN-I completed the study; eight patients with HMSN-I were placed on a placebo or on steroids for a six-month-period. In neither group was there any evidence of a significant increase in nerve conduction times, a decrease in terminal latencies, an increase in strength or a decrease in sensory loss when evaluated by quantitative methods. These patients were subject to a high incidence of complications from steroids possibly because of root hypertrophy, relative inactivity, and high CSF proteins. These included excessive weight gain, a compression fracture of T-12; cord compression from enlarged nerve roots; myopathy; pseudotumor; and psychiatric disturbances. Considering the lack of benefit of steroids and the high incidence of complications due to the medication further trials of adrenal-corticosteroids in patients who definitely have familial HMSN-I do not seem to be justified.

Adolescent↗