Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children.

OBJECTIVE: Open-label studies indicate that oral dichloroacetate (DCA) may be effective in treating patients with congenital lactic acidosis. We tested this hypothesis by conducting the first double-blind, randomized, control trial of DCA in this disease. METHODS: Forty-three patients who ranged in age from 0.9 to 19 years were enrolled. All patients had persistent or intermittent hyperlactatemia, and most had severe psychomotor delay. Eleven patients had pyruvate dehydrogenase deficiency, 25 patients had 1 or more defects in enzymes of the respiratory chain, and 7 patients had a mutation in mitochondrial DNA. Patients were preconditioned on placebo for 6 months and then were randomly assigned to receive an additional 6 months of placebo or DCA, at a dose of 12.5 mg/kg every 12 hours. The primary outcome results were (1) a Global Assessment of Treatment Efficacy, which incorporated tests of neuromuscular and behavioral function and quality of life; (2) linear growth; (3) blood lactate concentration in the fasted state and after a carbohydrate meal; (4) frequency and severity of intercurrent illnesses and hospitalizations; and (5) safety, including tests of liver and peripheral nerve function. OUTCOME: There were no significant differences in Global Assessment of Treatment Efficacy scores, linear growth, or the frequency or severity of intercurrent illnesses. DCA significantly decreased the rise in blood lactate caused by carbohydrate feeding. Chronic DCA administration was associated with a fall in plasma clearance of the drug and with a rise in the urinary excretion of the tyrosine catabolite maleylacetone and the heme precursor delta-aminolevulinate. CONCLUSIONS: In this highly heterogeneous population of children with congenital lactic acidosis, oral DCA for 6 months was well tolerated and blunted the postprandial increase in circulating lactate. However, it did not improve neurologic or other measures of clinical outcome.

Affect in patients with epilepsy undergoing video/EEG monitoring: retrospective versus momentary assessment and temporal relationship to seizures.

This study was designed to (1) compare retrospective and momentary assessments of mood/affect, and (2) examine the temporal relationship between affect and seizure occurrence. Patients with epilepsy undergoing long-term video/EEG monitoring (LTM) completed an affect rating of how they felt "at that moment" each time a programmed watch beeped (momentary assessment); these ratings were averaged across each patient's hospital stay. Prior to discharge, patients were asked to think back and rate how they felt "during their hospital stay" using the same rating scale (retrospective assessment). Results indicated that patients retrospectively recalled feeling significantly more positive during their LTM than they reported feeling when they were actually undergoing LTM. Among patients who had EEG-verified seizures, momentary assessments were used to compare affect during the interictal periods with affect during the prodromal and postictal periods. The latter two periods were characterized by significantly less activated positive affect than were the interictal periods.

Posttraumatic stress disorder, dissociation, and sexual abuse history in epileptic and nonepileptic seizure patients.

Rates of posttraumatic stress disorder (PTSD), dissociative symptoms, and childhood sexual abuse (CSA) are believed to be higher among patients with nonepileptic seizures (NES) than those with epileptic seizures (ES). However, women have higher rates of CSA and sexual assault than men. Comparisons of seizure type controlling for gender may produce different results. Data from an opportunity sample of 34 patients with ES and 17 with NES evaluated during or following phase 1 video-EEG monitoring demonstrated that patients with NES had statistically higher rates of PTSD and CSA and higher Dissociative Experiences Scale (DES) scores than patients with ES. No differences were found between women with NES and ES for histories of PTSD or CSA. Mean between-group DES score differences remained. Results indicated that PTSD, dissociation, and CSA may be common among women presenting to a tertiary epilepsy referral center for both ES and NES. Neither a positive history of CSA nor a history of PTSD was evidence against epilepsy.

Category-specific naming deficits for objects and actions: semantic attribute and grammatical role hypotheses.

Research on category-specific naming deficits and on noun and verb naming has raised questions about how organization of knowledge in the brain impacts word retrieval. The semantic attribute hypothesis posits that lexical access is mediated by brain systems that process the most definitive attributes of specific concepts. For example, it has been suggested that the most definitive attribute of living things is their visual form, whereas the most definitive attribute of non-living things is their function. The competing grammatical role hypothesis posits that access to a word depends on the grammatical role it plays in a sentence. Since nouns and verbs have different roles, it is assumed that the brain uses different systems to process them. These two hypotheses were tested in experimental subjects who had undergone left anterior temporal lobectomy (LATL) or right anterior temporal lobectomy (RATL) by assessing confrontation naming of living things, tools/implements, non-human actions, and human actions. The names of living things and implements are nouns and the names of actions are verbs. Within each grammatical class, items were characterized either predominantly by visual attributes (living things and non-human actions) or by attributes related to human activity (implements and human actions). Our results support the semantic attribute hypothesis. Patients with LATL were worse at naming tools/implements and human actions than RATL patients. Dysfunction in or removal of the left anterior temporal lobe disrupts fronto-temporal connections from the uncinate fasciculus. These connections may mediate activation of action-related information (i.e. movement plan and/or motor use) that facilitates the retrieval of names for tools/implements and human actions.

Progressive dementia and hypersomnolence with dream-enacting behavior: oneiric dementia.

BACKGROUND: Sleep disorders are associated with several types of degenerative dementias, including Alzheimer and prion diseases. Animal models have demonstrated abolition of rapid eye movement atonia, resulting in dream-enacting complex movements termed oneiric behavior, and patients with fatal familial insomnia may have vivid dreams that intrude on wakefulness. OBJECTIVE: To describe a new form of progressive dementia with hypersomnia and oneiric behavior. METHODS: Neuropsychological and polysomnographic studies of a middle-aged woman with a progressive dementia, excessive daytime sleepiness, and a vertical gaze palsy. RESULTS: Neuropsychological testing revealed decreased verbal fluency, impaired attention and working memory, amnesia, poor recall, and bradyphrenia with hypersomnia. Polysomnography revealed a rapid eye movement behavioral disorder with complete absence of slow wave sleep. Prion protein analysis did not reveal the mutation associated with fatal familial insomnia, and other diagnostic test findings were unrevealing. CONCLUSION: Our patient had a previously unreported syndrome of progressive dementia associated with rapid eye movement behavioral disorder and the absence of slow wave sleep.