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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.

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.

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.

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.

Background: Scalp EEG localization of epileptic foci may be obscured by electromyographic (EMG) artifact produced by ictal contraction of cranial muscles. Injection of botulinum toxin type A (BTX-A) into frontotemporal scalp muscles reduces EMG activity. Initial scalp video-EEG monitoring in three patients suggested partial seizures, but definitive lateralization or localization was precluded by EMG artifact., Methods: EMG-guided BTX-A injection to bilateral frontotemporal muscles was performed. When artifact persisted, BTX-A administration was selectively repeated. Patients subsequently underwent scalp video-EEG monitoring 1 week later., Results: All patients had reduction of EMG artifact during subsequent scalp video-EEG monitoring. No patient had adverse effects after BTX-A administration. All three patients had localization to either frontal or temporal lobes and definitive lateralization. Two of the three patients were able to proceed to invasive placement of frontotemporal subdural grid electrodes based on the BTX-A scalp video-EEG localization, and the third patient was determined to have a multifocal seizure disorder., Conclusions: Paralysis of frontotemporal scalp muscle after BTX-A administration reduces EMG artifact and may improve localization and lateralization of a seizure focus, providing a noninvasive technique for advancement toward epilepsy surgery.

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.

Objectives: Definitive localization of an epileptic focus correlates with a favorable outcome following epilepsy surgery. This study was undertaken to determine the incremental value of data yielded for surgical decision making when using subdural electrodes alone and in addition to depth electrodes for temporal lobe epilepsy., Methods: Standardized placement for intracranial electrodes included: (1) longitudinal placement of bilateral temporal lobe depth electrodes; (2) bilateral subtemporal subdural strips; and (3) bilateral orbitofrontal subdural strips. Sixty-three events were randomly reviewed for: (1) subdural electrodes alone; and (2) depth electrodes in conjunction with subdural electrodes., Results: Of the 63 seizures, 54 (85.7%) demonstrated congruent lateralization to ipsilateral subtemporal subdural strip electrodes (based on depth electrode localization) when subdural strip electrodes were utilized alone. In 3 of 22 patients, 7 seizures demonstrated 'false localization' on subdural electrode analysis alone when compared with depth recording and post-surgical outcome. For these 3 patients, retrospective review of neuroimaging demonstrated suboptimal ipsilateral placement of subtemporal subdural electrodes with the most mesial electrode lateral to the collateral sulcus. Four additional patients had suboptimal placement of subtemporal subdural electrodes. Two of these 4 patients had congruent localization with subdural electrodes to ipsilateral depth electrodes despite suboptimal placement. Subtemporal subdural electrodes accurately localized for all seizures from the mesial temporal lobe when the mesial electrodes of the subtemporal subdural strip recorded mesial to the collateral sulcus from the parahippocampal region., Conclusion: We conclude that although there are high concordance rates between subdural and depth electrodes, localization of seizure onset based on subdural strip electrodes alone may result in inaccurate focus identification with potential for possible suboptimal treatment of temporal lobe epilepsy. When subtemporal subdural electrodes provide recording from the parahippocampal region, there is accurate localization of the seizure focus. If suboptimal placement occurs lateral to the collateral sulcus, the electroencephalographer cannot make a definitive identification of the seizure focus.

Objective: Patients who misperceive that they are moving their paralysed arm (phantom movements) may not recognise its weakness. Therefore, the relation between phantom limb movements and anosognosia for hemiplegia during selective right hemispheric anaesthesia (the Wada test) was examined., Methods: Nine patients with intractable epilepsy underwent the Wada test. During the right hemispheric injection, after the onset of hemiparesis, anosognosia was assessed by asking patients if they were weak. The patient's vision was limited such that they could not see the position of their limbs. Phantom movements were tested for by asking patients to attempt to lift their left upper limb, and to demonstrate their left limb's position by placing their right limb in the same position as their left. Proprioception was tested by lifting the patient's paretic upper limb and having patients demonstrate this position by lifting their right limb to the same position., Results: Three patients experienced left phantom limb movements, and five were anosognosic for their hemiplegia. However, phantom movement occurred in only one patient with anosognosia. The other two patients with phantom movement were without anosognosia. The patient with phantom movement and anosognosia had impaired proprioception. The two patients with phantom movement but without anosognosia had intact proprioception., Conclusions: Phantom movement in the presence of a proprioceptive deficit could contribute to anosognosia. However, anosognosia and phantom movement are dissociable; therefore phantom movement cannot alone account for anosognosia. Because phantom movement occurred with and without proprioceptive deficits, proprioceptive loss is not a prerequisite for phantom movement.

Context: Anterior temporal lobectomy is an effective treatment for medically intractable temporal lobe seizures. Identification of seizure focus is essential to surgical success., Objective: To examine the usefulness of presurgical electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychological data in the lateralization of seizure focus., Design: Presurgical EEG, MRI, and neuropsychological data were entered, independently and in combination, as indicators of seizure focus lateralization in discriminant function analyses, yielding correct seizure lateralization rates for each set of indicators., Setting: Comprehensive Epilepsy Program, Shands Teaching Hospital, University of Florida, Gainesville., Patients: Forty-four right-handed adult patients who ultimately underwent successful anterior temporal lobectomy. Left-handed patients, those with less-than-optimal surgical outcome, and any patients with a history of neurological insult unrelated to seizure disorder were excluded from this study., Main Outcome Measures: For each patient presurgical EEG was represented as a seizure lateralization index reflecting the numbers of seizures originating in the left hemisphere, right hemisphere, and those unable to be lateralized. Magnetic resonance imaging data were represented as left-right difference in hippocampal volume. Neuropsychological data consisted of mean scores in each of 5 cognitive domains., Results: The EEG was a better indicator of lateralization (89% correct) than MRI (86%), although not significantly. The EEG and MRI were significantly superior to neuropsychological data (66%) (P=.02 and .04, respectively). Combining EEG and MRI yielded a significantly higher lateralization rate (93%) than EEG alone (P<.01). Adding neuropsychological data improved this slightly (95%)., Conclusions: The EEG and MRI were of high lateralization value, while neuropsychological data were of limited use in this regard. Combining EEG, MRI, and neuropsychological improved focus lateralization relative to using these data independently.

Emotions may be classified into two major divisions: experience and behavior. Because the brain is critical for mediating emotional experience and behavior, diseases of the brain may induce changes in emotional behavior and experience. Disorders of almost all portions of the cerebral hemisphere, including the cortex, limbic system, and basal ganglia, have been associated with changes of emotional experience and behavior. Dysfunction of the cerebral cortex may be associated with disorders of emotional communication. Whereas deficits of the left hemisphere appear to impair the comprehension and expression of propositional language, deficits of the right hemisphere may be associated with an impaired ability to comprehend and express emotional gestures such as facial expression and emotional prosody. Some patients have either prosodic or facial emotional deficits. Some have only expressive or receptive deficits. However, others may be globally impaired, either within or across modalities. The posterior portions of the neocortex appear to be important for comprehension and the anterior for expression of both emotional prosody and faces. Injury and dysfunction of the limbic system may also alter emotional communication and experience. For example, damage to the amygdala may be associated with an impaired ability to recognized emotional faces and a reduction of affect, especially anger, rage, and fear. In contrast, lesions of the septal region may be associated with increased ragelike behaviors. Seizures frequently emanate from the limbic system, and seizures that start in the amygdala can induce fear and perhaps even rage. Disorders of the basal ganglia may also be associated with defects of emotional communication and experience. Patients with Parkinson's disease not only may be impaired at communicating emotions with both expressive and receptive deficits but also are often depressed and anxious. Patients with Huntington's disease may have emotional comprehension deficits with an impaired ability to recognize emotional faces and prosody. Patients with Huntington's disease may have mood changes even before motor dysfunction becomes manifest. Many of the defects in emotional experience may be related to the associated changes in neurotransmitter systems. Unfortunately, how alteration of neurotransmitters induce mood changes remains unknown. In this chapter we review the feedback and central theories of emotional experience. Although we argue against the postulates that feedback is critical to the experience of emotions, we do suspect that feedback may influence emotions. Emotions may be conditioned and may use thalamic-limbic circuits, as proposed by LeDoux. However, most emotional behaviors and experiences are induced by complex stimuli that an isolated thalamus could not interpret. The cerebral cortex of humans has complex modular systems that analyze stimuli, develop percepts, and interpret meaning. We discuss the proposal that the experience of emotions is dimensional. Almost all primary emotions can be described with two or three factors, including valence, arousal, and motor activation.

Reduction of seizures associated with arteriovenous malformations (AVMs) following radiosurgery has been reported. This investigation assessed the effect of LINAC radiosurgical treatment of AVMs on the associated epilepsies correlated to AVM location, size, seizure type, and postradiosurgical thrombosis. Of 100 patients with AVMs, 33 presented with seizures (11 generalized tonic-clonic seizures, 8 simple partial seizures, and 14 complex partial seizures with or without secondary generalization). Patients with AVMs >/=25.0 mm were more likely to have seizures. Patients with frontal lobe AVMs were the most likely to have associated epilepsy (72.7%). Following radiosurgery, 59% were seizure-free and 19% had marked reduction of seizure frequency. Seizure remission was most frequent for AVMs of the centrum (83.3%). Of 14 patients with 2-year follow-up angiography, 9 had complete thrombosis and 6 became seizure-free. Four of 5 patients without thrombosis also became seizure-free. We conclude that LINAC radiosurgery is effective for epilepsies associated with AVMs. Radiosurgery was most effective for generalized tonic-clonic and complex partial seizures. There was no statistically significant correlation between reduction in epilepsy and original AVM size. Four of 5 patients without thrombosis became seizure-free, suggesting that structural or biochemical alterations of epileptogenic neurons following radiosurgery may reduce epileptogenicity.

Objective: To test the hypothesis that anosognosia for hemiparesis results from intrahemispheric disconnection., Methods: Using right carotid barbiturate injection as a model for anosognosia for hemiparesis, systematic attempts were made to modify deficit awareness by providing the left hemisphere with explicit information regarding left upper extremity function., Results: Experimental interventions failed to modify deficit awareness in 19 of 32 patients. In those patients who discovered their weakness, attempted movement of the weak limb seems more important than explicit observation of the extremity by the left hemisphere., Conclusions: The results fail to support Geschwind's disconnection hypothesis for anosognosia for hemiparesis.

Feinberg et al. proposed that right-hemisphere-damaged stroke patients with anosognosia for hemiplegia (AHP) confabulate seeing stimuli on the left side but those without AHP admit to having inadequate visual information. This study examines the relationship between AHP and confabulation using selective anesthesia of the cerebral hemispheres. Seventeen patients with intractable epilepsy were tested during intracarotid methohexital infusion. For half of the trials, subjects were stimulated on their paretic hand with a material (sandpaper, metal, or cloth), and for the remaining trials they were not stimulated. The subjects were trained to use a pointing response to indicate if they been stimulated and the type of material they had felt. Admission of uncertainty was defined as pointing to a question mark. Confabulation was defined as any material response to a no-touch trial. During anesthesia of either hemisphere, subjects with and without AHP confabulated responses. The AHP and non-AHP groups did not differ in admission of uncertainty. Our results support the postulate that confabulation and AHP are independent disorders, and therefore confabulation cannot fully account for AHP.

We describe a 27-year-old woman who developed encephalopathy and cerebral edema during treatment of refractory complex partial seizures that included acute administration of valproate (VPA) at a dosage of 35 mg/kg per day. Multiple random VPA levels were within therapeutic range, and results of liver function studies did not show evidence of hepatic failure. Cerebral computerized tomography (CT) showed evidence of massive cerebral edema with central herniation. Just prior to death, plasma levels of free and acyl carnitines were markedly decreased. Analysis of urinary organic acids showed increased excretion of lactate, but a normal distribution of VPA metabolites. Carnitine deficiency may predispose patients to the development of coma and life-threatening cerebral edema associated with acute administration of VPA, even in the absence of concomitant hepatic failure. We suggest specific guidelines for the evaluation and management of altered consciousness in patients with seizures receiving VPA.

Secondary epileptogenesis as it applies to humans remains a controversial topic despite 40 years of investigation. Part of the controversy stems from disagreement about the definition of secondary epileptogenesis, and part of the controversy stems from the imperfect fit of animal models to the human epileptic syndromes. It may be that models of secondary epileptogenesis can be useful to describe specific epileptic syndromes such as bitemporal epilepsy and secondary bilateral synchrony, but other models may be required for remitting syndromes such as the Landau-Kleffner syndrome. The concept of secondary epileptogenesis may also provide a useful construct for evaluating patients with partial epileptic syndromes, especially those under consideration for epilepsy surgery, and for the evaluation of preventive strategies in epilepsy.

Electrographic recordings from depth and subdural electrodes, performed in two patients with seizures of mesial temporal origin, were analyzed for the presence of non-linearities in the signal. The correlation integral, a measure sensitive to a wide variety of non-linearities, was used for detection. Statistical significance was determined by comparison of the original signal to surrogate datasets. Statistically significant non-linearities were present in signals generated by the epileptogenic hippocampus and interictal spike foci in the temporal neocortex. Less prominent non-linearities were found in EEG signals generated by more normal areas of the brain. These results indicate that techniques developed for the study of non-linear systems can be used to characterize the epileptogenic regions of the brain during the interictal period and can elucidate the dynamical mechanisms of the epileptic transition.

Purpose: To correlate prospective imaging findings in patients with intractable partial epilepsy with site of surgery and clinical outcome., Materials and Methods: Thirty-five patients (25 male, 10 female) underwent positron emission tomography (PET; n=25), interictal single photon emission computed tomography (SPECT; n=33), or postictal SPECT (n=23) for localization of epileptogenic foci. The standard of reference was site of surgery., Results: Sensitivity was 60%, 61%, and 52%; positive predictive value was 83%, 71%, and 55%; and localization was incorrect in 12% (three of 25 cases), 24% (eight of 33 cases), and 43% (10 of 23 cases) in PET, interictal SPECT, and postictal SPECT, respectively. There was no statistically significant difference in localization capabilities in a comparison of interictal SPECT and PET (correct localization, P=.999; incorrect localization, P=.625). There was a trend toward higher incorrect localization with interictal SPECT., Conclusion: Postictal SPECT has low sensitivity and a high incorrect localization rate and should not be performed in these patients. Interictal SPECT with 6-8-mm full-width at half-maximum is an alternative to PET. However, the trend toward higher false-localization rates must be taken into consideration.

The T1-weighted volumetric magnetic resonance images of 31 patients with intractable temporal lobe epilepsy, and 13 control subjects matched for age and sex, were subjected to semiautomated threshold analysis. The method used proved to be relatively fast and reliable. An index of temporal lobe interhemispheric asymmetry was extracted by thresholding high-signal (white matter) pixels. Patients had significantly more asymmetrical indices for white matter and hippocampal volumes that did control subjects, and the two indices were significantly correlated, providing evidence for the validity of the white matter index. Differences in both indices were consistent with decreased tissue on the side of the focus. In classification analyses a combination of these two indices correctly predicted the side of focus at a greater rate than did either used alone. Findings provide support for the hypothesis that seizure activity is associated with atrophy in both mesial and lateral temporal lobe structures.

The pars triangular is a portion of Broca's area. The convolutions that form the inferior and caudal extent of the pars triangularis include the anterior horizontal and anterior ascending rami of the sylvian fissure, respectively. To learn if there are anatomic asymmetries of the pars triangularis, these convolutions were measured on volumetric magnetic resonance imaging scans of 11 patients who had undergone selective hemispheric anesthesia (Wada testing) to determine hemispheric speech and language lateralization. Of the 10 patients with language lateralized to the left hemisphere, 9 had a leftward asymmetry of the pars triangularis. The 1 patient with language lateralized to the right hemisphere had a significant rightward asymmetry of the pars triangularis. Our data suggest that asymmetries of the pars triangularis may be related to speech-language lateralization.

Objective: To test the personal neglect hypothesis of anosognosia for hemiplegia (AHP) using selective anesthesia of the right hemisphere., Background: Although AHP most commonly follows right-hemisphere injury, the mechanism responsible for this hemispheric asymmetry has not been entirely elucidated. Because denial of ownership of parts on the contralesional side of one's body (personal neglect) also more commonly follows right-hemisphere damage, personal neglect might account for AHP., Design/methods: AHP and personal neglect were assessed in 20 patients during right intracarotid barbiturate infusion. With vision restricted to the central field, patients were randomly presented with either their own hands or those of examiners matched for size, gender, and race. Patients were asked to read numbers placed on the hands to establish that hemianopia did not confound hand recognition., Results: All subjects correctly read the numbers on all trials. Only 4 of 20 subjects misidentified their hands and denied awareness of left hemiplegia. All errors occurred for the left hand, indicating personal neglect. However, the 16 subjects without personal neglect also demonstrated AHP., Conclusion: Because AHP and personal neglect are dissociable, personal neglect cannot completely account for AHP.

Objective: To determine whether the occurrence of hippocampal formation (HF) volumetric asymmetry can reliably discriminate between complex partial seizures (CPSs) of a temporal lobe origin and CPSs of an extra-temporal lobe origin in a prospective study of patients with intractable CPSs (approximately 70% of patients have electrographic foci in the temporal lobe [HF volumetric asymmetry on magnetic resonance imaging scans has been shown to lateralize such foci reliably)]., Design: We examined HF volumetrics on magnetic resonance imaging scans that were acquired with a 1-T magnetic resonance imaging scanner (Siemens Magnetom, Siemens Medical Systems, Iselin, NJ) by using magnetization-prepared rapid gradient echo three-dimensional sequences (producing a gapless series of high-contrast 1.25-mm images). These data were compared with ictal, interictal, invasive, and noninvasive videoelectroencephalographic monitoring data, functional imaging data, and outcome data to define each patient's type of epilepsy., Setting and Patients: Forty-one patients were recruited from a tertiary university comprehensive epilepsy program, and 22 control subjects were recruited from the neurologically normal university community., Results: Among the control subjects, the difference in HF volumetrics (right-left HF volumetrics) was + 0.085 +/- 0.253 cm3. Of the 41 patients, 25 had temporal lobe epilepsy. When we set the upper limit of normal at the mean +/- 3 SDs, all patients beyond the upper limit had CPSs of a temporal lobe origin. Of the patients with temporal lobe epilepsy, only three fell within normal limits. No patient with CPSs of an extratemporal lobe origin fell beyond the upper limit., Conclusion: The presence of significant HF volumetric asymmetry makes it highly unlikely that a patient's CPSs are of an extratemporal lobe origin.

Apraxia is the loss of the ability to perform learned skilled movements correctly. In right-handers, apraxia and aphasia are most frequently associated with left-hemisphere lesions. When they are dissociated, however, aphasia is more common in the absence of apraxia than vice versa. There are two hypotheses that can account for this discrepancy: (1) in right-handers, praxis is more likely than language to be mediated by the right hemisphere, or (2) the left-hemisphere network that mediates language is either more widely distributed than the network that mediates praxis or is more likely to be in the middle cerebral artery distribution. We studied apraxia in a group of right-handers undergoing selective hemispheric anesthesia, or Wada testing. All nine subjects had language lateralized to the left hemisphere, and seven of the nine had praxis lateralized to the left hemisphere. Two of the subjects had praxis bilaterally represented. Although our data suggest that speech and praxis functions tend to be lateralized to the left hemisphere in most right-handers, praxis appears to be more distributed between the hemispheres than speech-language functions. Furthermore, an analysis of the types of errors made during praxis testing suggests differential roles of the hemispheres in praxis functions.

Disorders of neuronal migration in humans are associated with intractable epilepsy and some evidence suggests a causal relationship. This study evaluated electroencephalograms (EEG) of rats with experimentally induced disorders of neuronal migration. Fetal Sprague-Dawley rats were exposed to 196 cGy external irradiation on days 16 and 17 of gestation. This produced adult offspring with diffuse cortical dysplasias, agenesis of the corpus callosum, periventricular heterotopias, and dispersion of the pyramidal cell layer of the hippocampus. Epidural electrodes were implanted in four experimental (irradiated on gestational day 17) and four control rats. EEGs were recorded without anesthesia and in the presence of the anesthetic agents ketamine, acepromazine, and xylazine. In the presence of acepromazine, xylazine, or a combination of the two drugs, two of the four experimental rats had prolonged ictal activity on EEG. In one of the rats the ictal activity progressed to electrographic status epilepticus. Ketamine alone did not produce ictal EEG activity. None of the control rats demonstrated ictal activity under any treatment condition. This study demonstrates that disorders of neuronal migration are associated with an increased propensity for seizures in the presence of certain sedating agents.

Hashimoto's encephalopathy (HE) is a steroid-responsive relapsing disorder that frequently presents with seizures and diffuse EEG abnormalities. We report the EEG findings in seven patients with encephalopathy, seizures, or both, associated with elevated antithyroid antibodies. There were several combinations of findings within the same patient and between patients. The EEGs of five patients had generalized slowing or frontal rhythmic slowing; two also had triphasic waves and one had periodic sharp waves. Three had focal left temporal slowing. HE is heterogeneous clinically and electrographically. A high level of suspicion is necessary to establish the diagnosis.

Previous studies have demonstrated asymmetric hemispheric contributions to deficit awareness during hemisphere inactivation with intracarotid barbiturate infusion (Wada studies). These observations provide insight into the neuropsychological basis of anosognosia for hemiparesis (AHP), arguing against earlier explanations based upon psychological denial, global cognitive disturbance, or emotional indifference. Although prior Wada studies equated AHP after the procedure with AHP during the period of deficit, a selective memory failure could also account for these findings. We, therefore, assessed the occurrence of AHP during and after right-hemisphere inactivation in a group of epilepsy patients undergoing preoperative Wada testing. Because aphasia obscures assessment of deficit awareness during left carotid studies, we compared the frequency of AHP between right- and left-hemisphere inactivation only after recovery. As noted in earlier reports, AHP was present significantly more often after right- than left-hemisphere inactivation. The proportions of subjects with AHP during right-hemisphere anesthesia compared with the proportion of subjects with AHP after the procedure were statistically equivalent, suggesting that the AHP observed after right-hemisphere anesthesia results from true failure of deficit awareness rather than inability to recall the deficit.

The stroke literature indicates that the explicit denial of hemiplegia, a form of anosognosia, is associated more commonly with right- than left-hemisphere lesions. Some investigators have suggested that this asymmetry may be an artifact and that the aphasia that often accompanies left-hemisphere dysfunction may mask some instances of anosognosia. Mechanisms suggested for anosognosia have been either "global" or "modular" in nature. Mechanisms posited in global explanations include psychological denial and general mental deterioration; modular explanations include feedback and feedforward theories. Videotapes of 54 patients with medically intractable seizures who had selective barbiturate anesthesia (Wada test) as part of their evaluation for seizure surgery were assessed for anosognosia of hemiplegia and aphasia after hemispheric anesthesia had worn off. The results suggest that, although aphasia may confound the reported rate of anosognosia for hemiplegia following left-hemisphere dysfunction, the frequency of anosognosia for hemiplegia is still higher with right- than left-side dysfunction. Anosognosia for hemiplegia and aphasia were dissociable, providing support for the postulate that awareness of dysfunction is mediated by a modular system.

Meperidine neurotoxicity, characterized by recurrent convulsions, myoclonus, and asterixis, was diagnosed in an organ transplant recipient. Aside from cyclosporine toxicity, the literature regarding neurologic complications of transplantation contains limited reference to the neurotoxicity of therapy. The case reported illustrates how pharmacokinetic factors might render transplant patients particularly vulnerable to the neurotoxic side effects of certain medications, such as meperidine.

A 4-year-old boy developed Rasmussen's syndrome and was treated with alpha interferon intraventricularly. An improvement in the epileptic and neurologic syndrome was noted for several weeks following interferon. No adverse side effects were encountered. Since hemispherectomy is the only established therapy in Rasmussen's Syndrome, further studies are needed to establish if intraventricular alpha interferon may halt the clinical progression of the syndrome.

We report the chance observation of two generalized seizures in a fetal lamb that received cocaine. Cocaine was infused intravenously into a 138-day-old fetus while electrocortical (ECoG), electroocular (EOG), and neck electromyographic (EMG) activity were recorded. Fetal rapid eye movement (REM) and nonrapid eye movement (NREM) sleep were disrupted during the cocaine exposure and returned to a normal pattern after infusions were stopped. Seventy-two hours later, however, we recorded generalized seizures with ECoG spike and spike wave activity.

Anosognosia, the verbally explicit denial of hemiplegia, is more often reported after right- than left-hemisphere lesions. However, this asymmetric incidence of anosognosia may be artifactual and related to the aphasia that often accompanies left-hemisphere lesions. Anosognosia has been attributed to psychological denial and the emotional changes associated with hemispheric dysfunction. Eight consecutive patients undergoing intracarotid barbiturate (methohexital) injections as part of their presurgical evaluations for intractable epilepsy were assessed for anosognosia after their hemiplegia and aphasia had cleared. After their left-hemisphere anesthesia, all subjects recalled both their motor and language deficits. However, after right-hemisphere anesthesia, none of the eight patients recalled their hemiplegia. These results suggest that anosognosia is more often associated with right- rather than left-hemisphere dysfunction and that it cannot be attributed to either psychological denial or the emotional changes associated with hemispheric dysfunction.

Möbius syndrome is a complex neurologic disorder characterized by congenital bilateral facial paralysis associated with lateral gaze paralysis. The syndrome has variable manifestations and several variants, some with somatic stigmata. In 1990, Möbius syndrome is conceptualized as a spectrum of clinical caudal brain-stem signs. Some deficits are manifested by laryngeal paralysis and aspiration. Sleep-disordered breathing syndromes have not been previously reported in association with Möbius syndrome. We report two children with Möbius syndrome and sleep-disordered breathing. Based on known pathologic findings and clinical manifestations, we believe that sleep-disordered breathing may be a common complication of Möbius syndrome and should be sought, since potential outcomes of such complications include serious morbidity.

L-Asparaginase is commonly used for induction therapy of acute lymphocytic leukemia of childhood. Severe clinical bleeding secondary to clotting dysfunction has not been previously reported. We observed intracranial hemorrhagic infarcts with focal seizures and hemiparesis associated with clotting abnormalities, including severe hypofibrinogenemia, probably the result of L-asparaginase administered during induction therapy of acute lymphocytic leukemia.

We prospectively examined 58 patients with suspected or confirmed multiple sclerosis (MS) to evaluate the impact of paraclinical studies (evoked potentials (EPs) and magnetic resonance imaging (MRI] in the diagnostic evaluation of these patients. All patients had cranial MRI studies, brain-stem auditory (BAEP), visual (VEP), posterior tibial (PTN-SSEP) and median somatosensory (MN-SSEP) EPs. Patients were categorized according to criteria of Poser et al. initially without knowledge of paraclinical studies. On the basis of clinical history, neurological examination and CSF chemical analysis, there were 18 (31%) clinically definite (CD). 10 (17%) laboratory supported definite (LSD), 13 (22%) clinically probable (CP) MS cases; 17 (29%) cases could not be classified. By providing electrophysiological and/or anatomical evidence for a 'second lesion,' paraclinical studies permitted 25 patients to move from one diagnostic category to another, reflecting an increased certitude of the diagnosis. Twelve moved to CDMS by either MRI or one EP study. Four moved to CDMS on the basis of MRI only, and four moved to CDMS by VEP only. Five moved from an unclassified status to either LSDMS or CPMS by PTN-SSEP (2), by PTN-SSEP or MRI (1), by MRI or VEP (1) and by VEP only (1). Thus, the diagnosis of MS was refined in 28% of the patients (7/25) by incorporation of EPs alone whereas cranial MRI by itself increased the diagnostic certainty in only 16% (4/25). In the remaining 56%, the diagnosis was refined by use of either EPs or MRI. Overall, EP provided evidence for a 'second lesion' in 36% of the patients (21/58) and MRI 31% (18/58). While MRI may ultimately prove the single most useful paraclinical study in the diagnosis of MS. VEPs, and PTN-SSEPs by assessing areas currently not imaged by MRI, remain essential in patient evaluation. Changes in EPs and MRI technology will undoubtedly redefine the role of these diagnostic techniques.

Positive occipital sharp transients of sleep (POSTS) are well recognized as a normal electroencephalographic phenomenon in young to middle-aged persons, but little comment has been made concerning their occurrence in geriatric age groups. This study encompassing 365 electroencephalograms, showing POSTS among patients aged 22 to 86 years, demonstrates that the presence of POSTS is not an age limited occurrence, but extends over a wide age range into the later decades of life. Though the incidence of POSTS declined with advancing age, the diminution was not striking until after age 70. POSTS appeared only in normal and mildly abnormal EEGs. POSTS did not occur in markedly abnormal EEGs, and thus they resemble other features of normal sleep including sleep spindles and K-complexes.

We have described a 47-year-old white woman who had spontaneous E coli K1 meningitis after acquiring an E coli K1 urinary tract infection with associated sepsis. The patient's symptoms consisted only of severe headache, fever, and malaise. She had no meningeal or focal neurologic signs, and the CSF did not contain white blood cells. Evidence of meningitis included elevated opening pressure on lumbar puncture, positive CSF culture, and small ventricles on CT scan.

The purposes of this study were to demonstrate the effects of infrared laser radiation on the sensory nerve conduction of a specified peripheral nerve in man and determine temperature changes in the tissue surrounding the treated nerve. Twenty healthy adults were divided into three groups: control (n = 5); experimental (n = 10), infrared laser radiation at 20 sec/cm2; and experimental (n = 5), infrared laser radiation treatment at 120 sec/cm2. Antidromic sensory nerve conduction studies were performed on the superficial radial nerve of each subject's right forearm. The infrared laser radiation was applied at a fixed intensity for five 1-cm2 segments. Latency, amplitude, and temperature measurements were recorded pretest; posttest; and posttest intervals of 1, 3, 5, 10, and 15 minutes. An analysis of variance with repeated measures was used to examine the data. No significant change was noted in the distal sensory latency or amplitude of the evoked sensory potential in either experimental or control groups as a result of the applications of the infrared laser radiation treatment. This study demonstrates that infrared laser used at clinically applied intensities does not alter conduction of sensory nerves nor does it elevate the subcutaneous temperature.

We assessed the overnight sleep and breathing as well as daytime medical, sleep, and psychological status of a group of 34 healthy older persons. Analyses indicated that sleep-disordered breathing (SDB) was not related to any aspects of daytime functioning as measured in this study and that persons with an apnea + hypopnea index (AHI) greater than or equal to 5 (M AHI = 14.6) were not significantly impaired relative to those with lower levels of SDB (M AHI = 1.0) on any aspect of daytime performance. We conclude that SDB occurring in healthy aged persons is probably not of immediate concern and that the use of a cutting score of AHI greater than or equal to 5 for diagnosis of sleep apnea syndrome is not indicative in healthy aged persons. However, these results may not be applicable to older persons who are not in the excellent state of health that was required for participants in our study.

Somatosensory evoked potentials (SSEPs) and F-wave responses were compared after tibial (PTN) and median (MN) nerve stimulation in patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP). Nineteen patients were evaluated within 2 weeks of AIDP onset. Each had F-wave and PTN-SSEP studies; 18 had MN-SSEP studies. Ten patients had absent or prolonged MN-SSEP latencies, whereas 16 had abnormal MN F-wave studies. Seventeen patients had an abnormal PTN-SSEP while 12 had abnormal PTN F waves. Every patient with an abnormal MN-SSEP also had an abnormal PTN-SSEP. The most common PTN-SSEP findings were an absent or prolonged latency of N8 or N22. All patients had either an abnormal MN F wave or PTN-SSEP.

Neonatal herpes simplex encephalitis (HSE) can represent a difficult diagnostic problem when it occurs without concomitant mucocutaneus lesions and usually requires brain biopsy for diagnosis. Asymptomatic for the initial 2 to 4 weeks of life, the three infants we describe with localized HSE came to medical attention only because they developed persistent seizures and other nonspecific symptoms. Lumbar spinal fluid obtained from these children at clinical presentation showed an encephalitic pattern. Radionuclide brain scans revealed focal uptake of isotope in a variety of cortical areas, and electroencephalograms (EEGs) demonstrated repetitive, high amplitude, polyphasic sharp waves arising from analogous regions. Computed tomography (CT) showed nonspecific ill-defined areas of low density or contrast enhancement that did not correlate well with radionuclide, EEG, or clinical findings in two neonates. No infant had predominant temporal lobe involvement. Because these data suggested a multifocal, encephalitic process, all three infants underwent brain biopsy. A widespread infiltration of leukocytes and macrophages was observed in each specimen, and abundant intranuclear inclusions were present. Electron microscopy revealed abundant herpesvirus particles, and herpes simplex virus (HSV) was subsequently isolated from each sample. From our observations and our review of the literature, we propose the following criteria as indications for brain biopsy: Brain biopsy is warranted to rule out HSE when a neonate presents with seizures, cerebrospinal fluid mononuclear pleocytosis with a negative gram stain, and focal, cortical disease on EEG and radionuclide scan.(ABSTRACT TRUNCATED AT 250 WORDS)

We recorded brainstem auditory evoked potentials (BAEPs) in two patients with Guillain-Barré syndrome (GBS). One patient was acutely deaf with total absence of BAEP waveforms indicative of acoustic nerve conduction block. Hearing improved during early convalescence, and there were prolonged wave I latencies. Normal BAEPs were recorded on recovery. A second patient had bilaterally prolonged wave I latencies. These BAEP findings suggest that acoustic nerve conduction abnormalities from demyelination may occur in GBS.

Neonatal poliomyelitis, which was rare even when poliomyelitis was widespread, has not been reported in the United States since use of live oral poliovirus vaccine (Sabin's vaccine) became widespread. We report a child who became symptomatic with apnea at 18 days of age and who subsequently developed a permanent monoparesis. Serologic and cultural evidence indicated the virus as poliovirus vaccine type. Another infant who received live oral poliovirus vaccine was probably the source of the infecting virus. Recognition that poliovirus infection can still occur in the United States and an understanding of the serologic, cultural, and typing tests required to substantiate this diagnosis are needed so that such patients will be accurately diagnosed.

Somesthetic information from lower extremities is processed by cerebral cortex after traversing the sensory pathways of peripheral nerve, spinal cord, brain-stem and thalamus. Clinical utility of somatosensory evoked potentials (SSEPs) during human development requires systematic analysis of normative data acquired during various stages of body growth and nervous system maturation. Accordingly, SSEPs after tibial nerve stimulation were studied in 32 normal awake children (1-8 years old) and compared with values obtained in young adults (18-40 years old). Potentials were recorded from the tibial nerve (N5), first lumbar spinous process (N14), seventh cervical spinous process (N20) and from the scalp, 2 cm behind the vertex (P28). In all children studied, the N5, N14 and N20 latencies were positively correlated with age and height yielding a predictive nomogram. An extremely variable electropositive cortical SSEP was recorded from Cz' which did not show a highly predictable linear relationship in association with a relatively poor correlation coefficient for height and age. It may be concluded that between 1 and 8 years of normal postnatal development, latencies reflecting peripheral nerve and lumbar spinal cord vary directly with height and age and can be represented by a simple cable model of a lengthening myelinated pathway. In contrast, the latency of the cortical SSEP reflects asynchronous maturation of elongating polysynaptic pathways and apparently requires a more complex model for prediction in order to enhance its clinical utility.

This report details the management of status epilepticus with high-dose lorazepam in a 14-year-old patient who was receiving oral clonazepam, ethosuximide, and phenobarbital for an intractable seizure disorder. Although respiratory depression is a frequently cited potential complication of therapy, it did not occur in this patient despite an extraordinarily high total dose of lorazepam, possibly because of tolerance associated with benzodiazepine-receptor down-regulation in this patient's chronic clonazepam therapy. Aggressive dosing of a benzodiazepine may be required for patients receiving chronic benzodiazepine therapy.

Recurrent episodes of speech arrest were observed in a man as the primary manifestation of a partial seizure disorder. To determine whether speech arrest was associated with a language disorder, the Syntactic Comprehension test was administered during and after speech arrest. This test does not depend upon speech production, but evaluates ability to comprehend sentences in which meaning depends on syntactic relationships. Using this test, we were able to show that speech arrest was associated with a language disturbance.

Seizures may occur as an isolated manifestation of an acute encephalopathy or, less frequently, recur as a manifestation of epilepsy in transplant patients. Determining which of these is the case will lead to appropriate treatment. The selection of the antiepileptic drug (AED) will depend on the patient's type of seizure, general medical condition, and transplant type and also depend on the consideration of potential adverse effects of individual AEDs.