Startle reflex hyporeactivity in Parkinson's disease: an emotion-specific or arousal-modulated deficit?

We previously reported that patients with Parkinson's disease (PD) demonstrate reduced psychophysiologic reactivity to unpleasant pictures as indexed by diminished startle eyeblink magnitude [Bowers, D., Miller, K., Bosch, W., Gokcay, D., Pedraza, O., Springer, U., et al. (2006). Faces of emotion in Parkinsons disease: Micro-expressivity and bradykinesia during voluntary facial expressions. Journal of the International Neuropsychological Society, 12(6), 765-773; Bowers, D., Miller, K., Mikos, A., Kirsch-Darrow, L., Springer, U., Fernandez, H., et al. (2006). Startling facts about emotion in Parkinson's disease: Blunted reactivity to aversive stimuli. Brain, 129(Pt 12), 3356-3365]. In the present study, we tested the hypothesis that this hyporeactivity was primarily driven by diminished reactivity to fear-eliciting stimuli as opposed to other types of aversive pictures. This hypothesis was based on previous evidence suggesting amygdalar abnormalities in PD patients, coupled with the known role of the amygdala in fear processing. To test this hypothesis, 24 patients with Parkinson's disease and 24 controls viewed standardized sets of emotional pictures that depicted fear, disgust (mutilations, contaminations), pleasant, and neutral contents. Startle eyeblinks were elicited while subjects viewed these emotional pictures. Results did not support the hypothesis of a specific emotional reactivity deficit to fear pictures. Instead, the PD patients showed reduced reactivity to mutilation pictures relative to other types of negative pictures in the context of normal subjective ratings. Further analyses revealed that controls displayed a pattern of increased startle eyeblink magnitude for "high arousal" versus "low arousal" negative pictures, regardless of picture category, whereas startle eyeblink magnitude in the PD group did not vary by arousal level. These results suggest that previous findings of decreased aversion-modulated startle is driven by reduced reactivity to highly arousing negative stimuli rather than to a specific category (i.e., fear or disgust) of emotion stimuli.

MMPI-2 profiles of patients with intractable epilepsy.

MMPI-2 profiles of 93 presurgical intractable epilepsy patients were examined using Ward's method of cluster analysis. Three clusters were identified. The means of each cluster suggest that 45% of the sample had minimal psychological complaints, 30% presented with generalized clinical elevations, and 25% of the patients had profiles of intermediate elevations with a tendency to emphasize somatic complaints and/or depression. Gender, age of seizure onset, and seizure laterality were not found to be uniquely associated with the cluster profiles. Further examination of correlates of group membership is warranted to provide information for treatment planning.

Basal ganglia dysfunction, working memory, and sentence comprehension in patients with Parkinson's disease.

To investigate the role of the basal ganglia in working memory and sentence comprehension, 14 patients with Parkinson's disease (PD) were administered experimental measures of semantic and phonological working memory, and a measure of sentence comprehension, while receiving dopaminergic medications and after a period of withdrawal from these medications. An age- and education- matched control group (N=14) received the same measures. Comparison with control subjects revealed deficits in patients with PD in sentence processing regardless of medication status, but no deficits in working memory. In contrast to previous studies, withdrawal of dopaminergic medications had no significant impact on task- related working memory functions or on sentence comprehension. Results suggest that basal ganglia dysfunction does not solely account for sentence comprehension deficits seen in PD.

Cognitive and neuropsychological functioning in children with cerebral palsy.

This article reviews the extant literature on intellectual functioning in different subtypes of cerebral palsy. Following a definition of the characteristics of each of three major cerebral palsy groups, typical neurologic and magnetic resonance imaging findings are reported. More recent studies that examine the intellectual and neuropsychological functioning of children within these classification groups are also reviewed. This review concludes that there remains a significant lack of precise information about the impact of cerebral palsy on the intellectual, motor, and neuropsychological functioning of children and that neuropsychological assessment can provide the necessary tools for such studies.

The Test of Everyday Attention for Children (TEA-Ch): patterns of performance in children with ADHD and clinical controls.

The present study explores the utility of the Test of Everyday Attention for Children (TEA-Ch) as a measure of the attentional impairments displayed by children with Attention Deficit Hyperactivity Disorder (ADHD). Sixty-three children with ADHD and 23 non-ADHD Clinical Control children were compared on subtests of the TEA-Ch reflecting three attentional domains: sustained, selective, and attentional control. Results show that children with ADHD performed significantly worse than clinical controls on subtests of sustained attention and attentional control. The groups did not differ, however, on subtests of selective attention. These findings suggest that the TEA-Ch is sensitive to attentional deficits unique to ADHD and holds promise as a useful tool in the assessment of ADHD. Performance patterns and future directions are discussed.

A neuropsychological outcome study of a child's left pericallosal arteriovenous malformation with occult fornix lesion.

Pericallosal arteriovenous malformations are rarely reported, particularly in children. Moreover, few arteriovenous malformation studies report thorough neuropsychological outcome data for assessing post-surgical functioning. This case report provides a longitudinal study of a boy who initially presented for neuropsychological testing at the age of 8 years and 1 month, following polyvinyl alcohol embolization, two craniotomies and resections and stereotactic radiosurgery for a pericallosal arteriovenous malformation involving nearly all of the corpus callosum. Follow-up magnetic resonance imaging also indicated absence of the left fornix. Functioning has been assessed over 7 years. Neuropsychological measures identified a consistent pattern of verbally mediated cognitive and memory deficits, with relatively spared visual perceptual and visual motor functioning. No evidence of a split-brain syndrome was found. The findings are consistent with insult to dominant hemisphere language and memory systems, provide an interesting example of neurodevelopmental compensation for significant early brain insult, and may provide insight into functions subserved by the fornix.

Review: cognitive and psychological outcomes in pediatric heart transplantation.

OBJECTIVE: To review empirical literature investigating the cognitive and psychological effects of pediatric heart transplantation. METHODS: Electronic and library searches were used to identify empirical studies examining the cognitive and psychological effects of pediatric heart transplantation. Only studies investigating cognitive or psychological outcomes, either prospectively or cross-sectionally, were reviewed. RESULTS: Preliminary findings suggest that children and adolescents generally functioned within the normal range on most measures of cognitive functioning post-transplant. However, a complicated transplant course caused by infections or rejections may place these recipients at increased risk for cognitive difficulties post-transplant. Studies also suggested that approximately 20%-24% of pediatric heart transplant recipients experienced significant symptoms of psychological distress (e.g., anxiety, depression, behavior problems) during the first year post-transplant. CONCLUSIONS: Research suggests that some recipients are at risk for cognitive and psychological difficulties post-transplant and may require additional academic remediation and/or psychological intervention to address these challenges. Given the limited number of empirical studies available at this time, continued research investigating cognitive and psychological outcomes following pediatric heart transplantation is needed.

Dissociation of anosognosia and phantom movement during the Wada test.

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.

Electroencephalographic, volumetric, and neuropsychological indicators of seizure focus lateralization in temporal lobe epilepsy.

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.

Cognition, behavior, and development in Joubert syndrome.

This article reports on a series of studies of children with Joubert syndrome who were examined in three investigations from 1994 through 1998. Neuropsychologic screening of 10 of 40 children showed a variety of deficits in cognition, verbal memory, visuomotor, motor, and language-related tasks. Parent report of developmental attainments revealed only 3 of 40 children functioning in the borderline range, with the rest scoring in the severely impaired range. Parent reports of behaviors revealed problems in temperament, hyperactivity, aggressiveness, and dependency, as well as problems in physical development and care that were felt to be related to their neurologic handicaps. Future directions of research with this rare disorder are suggested.

"Joubert syndrome" revisited: key ocular motor signs with magnetic resonance imaging correlation.

Joubert syndrome is characterized by episodic hyperpnea and apnea, developmental delay, hypotonia, truncal ataxia, ophthalmologic abnormalities, and vermian dysgenesis. We studied 15 patients with the diagnosis of Joubert syndrome to (1) more fully define the syndrome's clinical features, and (2) correlate the clinical features with magnetic resonance imaging (MRI) findings. Eight of 15 patients had a history of episodic hyperpnea and apnea. All patients had developmental delay and hypotonia. Of the 13 patients receiving detailed neuro-ophthalmologic evaluations, three had optic nerve dysplasia, pendular nystagmus, and gaze-holding nystagmus. All 13 patients had a normal vestibulo-ocular reflex based on head thrust, but had absent to poor ability to cancel the vestibulo-ocular reflex horizontally and vertically. Twelve of 13 patients had impaired smooth pursuit. Twelve of 13 patients had defects in initiation of saccades and quick phases. Two of the most consistent radiologic features were absent or hypoplastic posterior cerebellar vermis, and deformed midbrain and pontomesencephalic junction, which based on ocular motor physiology correlate with the vestibulo-ocular reflex cancellation/ pursuit defect and saccade initiation defect, respectively. As a result of midbrain, vermian, and superior cerebellar peduncle abnormalities, axial neuroimaging showed a unique "molar tooth" appearance of these structures. These results indicate that Joubert syndrome results from maldevelopment of the midbrain and cerebellar vermis, producing a pathognomonic sign on MRI.

Altered cognitive functioning in children with idiopathic epilepsy receiving valproate monotherapy.

Once a child is diagnosed with epilepsy, a primary concern is whether or not the child's behavior and cognitive abilities will be affected by the disease, by the drug prescribed for seizure control, or both. Direct cognitive effects by the epileptic condition have been described. On the other hand, cognitive effects in epilepsy have been attributed to antiepileptic drug therapy. Valproate is an antiepileptic drug of choice in managing the commonest childhood epilepsy syndromes. Although frequently prescribed in pediatric neurology practice, there have been relatively few studies investigating the cognitive effects of valproate therapy in children. Cognitive effects of valproate reported in normal adult volunteers and in adults with epilepsy cannot be generalized to the pediatric population. The results of investigations on children are less conclusive. Guidelines for antiepileptic drug trials in children have recently been formulated. Carefully designed studies are required in determining the cognitive effects of valproate in the pediatric population. Neuropsychological measures that are likely to assess subtle changes in higher brain functions crucial to learning in children should be employed. We propose a test battery to assess for cognitive changes associated with anticonvulsant therapy in children.

Pars triangularis asymmetry and language dominance.

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.

Apraxia during Wada testing.

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.

Anosognosia during intracarotid barbiturate anesthesia: unawareness or amnesia for weakness.

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.

Dissociation of anosognosia for hemiplegia and aphasia during left-hemisphere anesthesia.

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.

Assessing neurobehavioral changes in HIV+ infants and children. A methodological approach.

The rationale and development of a developmental approach to assessing neurobehavioral changes in infants and children exposed to or infected with the HIV-1 virus is presented. Methodological problems in earlier approaches to assessment are reviewed. Among these are measures employed, impact of different treatments on measures of outcome, multicultural differences between samples, and analytic approaches to developmental data. The assessment protocol developed by the Pediatric Neurobehavioral Study Group of NIMH/NICHD/NIAID is described.

Brainstem glioma: I. Pathology, clinical features, and therapy.

Gliomas that arise in the brain stem have been associated with a poor prognosis. Diagnostic neuroimaging readily identifies the tumor as it extends between normal brainstem structures. Histologic sampling of tumor with stereotactic methods is notoriously unreliable in establishing a definitive prognosis. Clinical trials that incorporate high-dose chemotherapy, autologous bone marrow rescue, and irradiation hold promise of better tumor control by overcoming the inaccessibility of the central nervous system to standard doses of chemotherapy. We review the pathology, clinical features, neuroimaging features, and current therapeutic concepts relative to brainstem glioma. The pediatric neurologist has a pivotal role in identifying and monitoring children with this malignancy.

Treating a case of surface dyslexia after closed head injury.

We describe an original treatment program for surface dyslexia in a patient with a closed head injury. Addressing the question of whether the deficient lexical reading routes could be improved in this type of case. we designed three tasks and administered them over ten consecutive treatment sessions. Results indicate improved accuracy of responses as a function of presentation times or response times, or both, on all treatment tasks. Comparisons of standardized reading comprehension and oral reading tests before and after therapy disclosed increases in reading rate, with the patient's originally high level of accuracy remaining constant. This suggests that the patient incorporated the more rapid lexical reading strategy without compromising her level of accuracy.