Surgery for symptomatic infant-onset epileptic encephalopathy with and without infantile spasms.

Children undergoing surgery with infant-onset epilepsy were classified into those with medically refractory infantile spasms (IS), successfully treated IS, and no IS history, and the groups were compared for pre- and postsurgery clinical and Vineland Adaptive Behavior Scale (VABS) developmental quotients (DQ). Children without an IS history were older at surgery and had longer epilepsy durations than those with IS despite similar substrates, surgeries, and seizure frequencies. In all groups, better postsurgery VABS-DQ scores were associated with early surgical intervention indicating that infant-onset epilepsy patients with or without IS are at risk for seizure-induced encephalopathy.

Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes.

OBJECTIVE: To compare hemispherectomy patients with different pathologic substrates for hospital course, seizure, developmental, language, and motor outcomes. METHODS: The authors compared hemispherectomy patients (n = 115) with hemimegalencephaly (HME; n = 16), hemispheric cortical dysplasia (hemi CD; n = 39), Rasmussen encephalitis (RE; n = 21), infarct/ischemia (n = 27), and other/miscellaneous (n = 12) for differences in operative management, postsurgery seizure control, and antiepilepsy drug (AED) usage. In addition, Vineland Adaptive Behavior Scale (VABS) developmental quotients (DQ), language, and motor assessments were performed pre- or postsurgery, or both. RESULTS: Surgically, HME patients had the greatest perioperative blood loss, and the longest surgery time. Fewer HME patients were seizure free or not taking AEDs 1 to 5 years postsurgery, but the differences between pathologic groups were not significant. Postsurgery, 66% of HME patients had little or no language and worse motor scores in the paretic limbs. By contrast, 40 to 50% of hemi CD children showed near normal language and motor assessments, similar to RE and infarct/ischemia cases. VABS DQ scores showed +5 points or more improvement postsurgery in 57% of patients, and hemi CD (+12.7) and HME (+9.1) children showed the most progress compared with RE (+4.6) and infarct/ischemia (-0.6) cases. Postsurgery VABS DQ scores correlated with seizure duration, seizure control, and presurgery DQ scores. CONCLUSIONS: The pathologic substrate predicted pre- and postsurgery differences in outcomes, with hemimegalencephaly (but not hemispheric cortical dysplasia) patients doing worse in several domains. Furthermore, shorter seizure durations, seizure control, and greater presurgery developmental quotients predicted better postsurgery developmental quotients in all patients, irrespective of pathology.

Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study.

BACKGROUND: This study tested the hypothesis that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining if first-degree relatives of COS probands have an increased risk for schizophrenia and schizotypal and paranoid personality disorders. METHODS: Relatives of COS probands (n = 148) were compared with relatives of attention-deficit/hyperactivity disorder (ADHD) (n = 368) and community control (n = 206) probands. Age-appropriate structured diagnostic interviews were used to assign DSM-III-R diagnoses to probands and their relatives. Family psychiatric history was elicited from multiple informants. Diagnoses of relatives were made blind to information about probands' diagnoses. Final consensus diagnoses, which integrated family history, direct interview information, and medical records, are reported in this article. RESULTS: There was an increased lifetime morbid risk for schizophrenia (4.95% +/- 2.16%) and schizotypal personality disorder (4.20% +/- 2.06%) in the parents of COS probands compared with parents of ADHD (0.45% +/- 0.45%, 0.91% +/- 0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophrenia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder (9.41% +/- 3.17%) was increased in the parents of COS probands compared with parents of community controls (1.67% +/- 1.17%). CONCLUSIONS: The psychiatric disorders that do and do not aggregate in the parents of COS probands are remarkably similar to the disorders that do and do not aggregate in the parents of adults with schizophrenia in modern family studies. These findings provide compelling support for the hypothesis of etiological continuity between COS and AOS.

Attention in HIV-infected children: results from the Hemophilia Growth and Development Study.

Attentional functioning was examined in three groups of 7- to 19-year-old male participants with hemophilia: (1) HIV seronegative controls (HIV-, N = 66), (2) HIV seropositive participants with CD4+ lymphocyte counts greater than or equal to 200 (HIV+ CD4+ > or = 200, N = 79), and (3) severely immune suppressed HIV seropositive participants (HIV+ CD4+ < 200, N = 28). Two measures sensitive to attention deficits were used: the Continuous Performance Test (CPT) and the Span of Apprehension (Span). On the CPT, there was a decrement in attention in both HIV+ groups, as indexed by an increase in false alarm rate from Block 1 to Block 3, that was not present in the HIV- group. The longer the HIV+ children were required to sustain attention to the CPT, the more they responded to the incorrect stimulus. This effect decreased as age increased. Span percent correct and latency to correct were associated with the presence of a premorbid history of intracerebral hemorrhage, but were not sensitive to HIV status or degree of immune suppression in the HIV+ children, suggesting morbidity related to hemophilia. The remaining CPT and Span variables--hit rate, sensitivity, latency, percent correct, and latency to correct--showed the expected associations with age, but none showed conclusive associations with HIV status or immune suppression in the HIV+ participants.

Thought disorder in childhood schizophrenia: replication and update of concept.

OBJECTIVES: To examine whether measures of thought disorder differentiated schizophrenic from normal children and to examine the relationship of these measures with developmental and cognitive factors. METHOD: The speech samples of 88 schizophrenic and 190 normal children, aged 9 to 13 years, were coded with the Kiddie Formal Thought Disorder Rating Scale and Halliday and Hassan's analysis of cohesion. RESULTS: Above and beyond differences in mental age, gender, and neuroleptic status, the patients had significantly more formal thought disorder (FTD) and cohesive deficits than the normal children matched by mental age. The younger schizophrenic and normal children had significantly more thought disorder than the older children with these diagnoses. Combined FTD and cohesion scores correctly identified 76% of schizophrenic and 88% of normal children with little variability across mental age. The thought disorder measures generated 2 independent components: FTD and cohesion. CONCLUSIONS: Thought disorder measures that include both FTD and cohesion provide a quantitative diagnostic tool of childhood-onset schizophrenia.

Accelerated age-related decline in processing resources in schizophrenia: evidence from pupillary responses recorded during the span of apprehension task.

Cognitive impairment in schizophrenia may be related to reduced availability of information-processing resources (resource limitations hypothesis). An abnormally accelerated age-related decline in processing resource availability may also occur in older patients with schizophrenia (neurodegeneration hypothesis). To test these hypotheses, pupillary responses were recorded as an index of processing resource availability during performance of the span of apprehension (SOA) task in 33 middle-aged and older patients with schizophrenia and 37 age-comparable nonpsychiatric participants. Consistent with the resource-limitations hypothesis, the patients with schizophrenia showed impaired detection accuracy and abnormally small pupillary responses (reduced resource allocation) only in the higher processing load SOA conditions. This pattern of results suggests that the patients depleted their available processing resources at lower processing loads than the nonpsychiatric participants. Consistent with the neurodegeneration hypothesis, cross-sectional analyses showed abnormally accelerated rates of age-related decline in SOA performance and pupillary responses in the patients with schizophrenia relative to age-comparable normal participants.

Neuropsychological deficits in pediatric patients with childhood-onset schizophrenia and psychotic disorder not otherwise specified.

OBJECTIVE: Children with transient psychotic symptoms and serious emotional disturbances who do not meet current criteria for schizophrenia or other presently recognized diagnostic categories commonly present diagnostic and treatment problems. Clarifying the connections between children with narrowly defined schizophrenia and children with a more broadly defined phenotype (i.e., Psychotic Disorder Not Otherwise Specified, PD-NOS) has implications for understanding the pathophysiology of schizophrenia. In this study, the neuropsychological test performance of a subgroup of children with atypical psychosis was compared with that of patients with childhood-onset schizophrenia (COS). METHOD: Cognitive function was assessed with neuropsychological test battery regimens in 51 neuroleptic-nonresponsive patients within the first 270 at NIMH testing (24 PD-NOS, 27 COS) were included in this analysis. Seventeen (39%) of 44 COS subjects were unavailable for this study as their IQ tested <70. The PD-NOS patients were younger than the COS patients at the time of testing (12.0+/-2.8 vs 14.4+/-1.8years, respectively, p<0.004). The test levels of these groups were compared with each other. RESULTS: The neuropsychological test results for the PD-NOS and COS patients were 1-2standard deviations below normative data across a broad array of cognitive functions. There were no overall differences in the test levels for the six summary scales (F=2.82, df=1, 36, p=0.10) or in the profile shape (F=1.70, df=5, 180, p=0.14) between the PD-NOS and COS groups. For the COS patients, there was a significant difference between their mean full-scale WISC IQ (84.7+/-16.2) and their average standard scores for both the spelling (97.7+/-16.1, n=23, t=4.0, p=0.001) and reading decoding subtests (97.7+/-13.7, n=23, t=3.7, p=0.001) of the Kaufman Test of Educational Achievement. CONCLUSIONS: Treatment-refractory PD-NOS and COS patients share a similar pattern of generalized cognitive deficits, including deficits in attention, learning and abstraction which are commonly observed in adult patients with schizophrenia. These data support a hypothesis that at least some of the PD-NOS cases belong within the schizophrenic spectrum, which is of importance for future genetic studies planned for this cohort.

Relevance of the cerebellar hemispheres for executive functions.

The aim of the present study was to elucidate the role of the cerebellar hemispheres in executive functions. The findings are relevant because of the large number of children who survive cerebellar tumors. Neuropsychologic assessments of four patients (8-21 years of age) who had undergone neurosurgery for removal of tumors in the cerebellar hemispheres were conducted and compared with the assessments of six children who had been diagnosed with temporal lobe tumors or cysts. The executive functions were assessed using the Wisconsin Card Sorting Test. IQs were average in both groups. As expected, patients with cerebellar hemispheric lesions had impaired executive functions. In particular, they appeared to have difficulty generating and testing hypotheses regarding the matching rules on the Wisconsin Card Sorting Test. Patients with temporal lesions had a different pattern of deficits on this test. The findings are consistent with the theories that propose that the cerebellar hemispheres are involved in cognitive processes. The findings also demonstrate that subtle deficits in executive functions can be masked by a normal IQ in survivors of cerebellar tumors and highlight the need to design interventions targeted toward problem-solving skills.

Neurocognitive impairments in schizophrenia: a piece of the epigenetic puzzle.

This paper is a review of studies examining the neurobehavioral antecedents of schizophrenia which flesh out neurodevelopmental models of schizophrenia by detailing the time course of the ontogeney of neurobehavioral impairments in schizophrenia. A follow back design was used to identify precursors of psychotic symptoms in children with a schizophrenic disorder. The vast majority of children with a schizophrenic disorder had significant developmental delays beginning early in life. For example, gross deficits in early language development were found in almost 80% of the schizophrenic children. Somewhat later in development impairments in fine motor and bi-manual coordination are noted. Some of these early developmental delays are transitory. For example, basic language skills are among the best preserved neurocognitive functions in children and adults with schizophrenia. The results of our cross-sectional neurocognitive studies suggest that children with schizophrenia suffer from limitations in the ability to engage in effortful cognitive processing or impairments in working memory. The links between these elementary neurocognitive impairments and the development of formal thought disorder as well as discourse deficits in children with a schizophrenic disorder will be discussed.

Persistent Post-Concussive Syndrome: A proposed methodology and literature review to determine the effects, if any, of mild head and other bodily injury.

Following mild head injury, a subgroup of individuals exhibit a constellation of chronic symptoms, a condition Alexander (1995) labeled Persistent Post-Concussive Syndrome (PPCS). He implicated neurological factors in the initial phase of the syndrome but psychological factors in the maintenance of symptoms. However, it is unclear as to whether an initial mild head injury is necessary or sufficient to cause the symptoms of PPCS. We first outline a study design comparing a mild closed-head injury group to both a normal and an other injury control group to answer this question. Next, we review the literature since 1960 to determine the findings of any studies using this design. The results of the literature review indicate that few such studies exist. To date, those that have been done suggest that there is no strong evidence for a specific effect for mild head injury on cognitive functioning. We discuss directions for future research given these findings.

Neurobehavioral deficits at adolescence in children at risk for schizophrenia: The Jerusalem Infant Development Study.

BACKGROUND: The Jerusalem Infant Development Study is a prospective investigation comparing offspring of schizophrenic parents with offspring of parents who have no mental disorder or have nonschizophrenic mental disorders. During infancy and school age, a subgroup of offspring of schizophrenic parents showed global neurobehavioral deficits that were hypothesized to be indicators of vulnerability to schizophrenia. The purposes of the present investigation were to determine if neurobehavioral deficits were present in the offspring of schizophrenics at adolescence, to examine their stability over time, and to explore their relation to concurrent mental adjustment. METHODS: Sixty-five Israeli adolescents were assessed on a battery of neurologic and neuropsychological assessments. They were also administered psychiatric interviews from which best-estimate DSM-III-R diagnoses and scores of global adjustment were derived. RESULTS: Adolescents with poor neurobehavioral functioning were identified from composites of motor and cognitive-attentional variables. A disproportionate number of offspring of schizophrenic parents (42%; 10/24), and especially male offspring of schizophrenic parents (73%; 8/11), showed poor neurobehavioral functioning relative to offspring of nonschizophrenic parents (22%; 9/41). Adolescent offspring of schizophrenics with poor neurobehavioral functioning had been poorly functioning at earlier ages and had poor psychiatric adjustment at adolescence. All 4 offspring of schizophrenics receiving schizophrenia spectrum diagnoses by adolescence showed a pattern of poor neurobehavioral functioning across developmental periods. CONCLUSIONS: Results are consistent with the hypothesis that individuals at genetic risk for schizophrenia may display lifelong neurobehavioral signs that are indicators of vulnerability to schizophrenia and that are associated with psychiatric adjustment generally and schizophrenic spectrum disorder specifically.

Continuous-processing related ERPS in adult schizophrenia: continuity with childhood onset schizophrenia.

BACKGROUND: Previous work with schizophrenic children disclosed deficits on two continuous performance tests (CPTs) and ERP indices of reduced attentional resource allocation. METHODS: The two CPTs were administered to adult schizophrenics and matched control subjects. The simple CPT required only that the subject respond whenever the target digit was displayed. The complex version required a response whenever any digit was displayed on two successive trials. Event-related potentials (ERPs) were recorded during task performance. RESULTS: Schizophrenics had fewer hits on both CPT versions, showed a greater drop in performance from the simple to the complex CPT, and took longer to respond than controls. The processing negativity (Np) showed a greater amplitude increase from nontarget to target in normals than in schizophrenics, and the overlapping P2 component was more negative in normals. P3 latency was longer in schizophrenics, but P3 amplitude did not differ. CONCLUSIONS: Group performance and processing negativity effects replicated those from an earlier study of schizophrenic and normal children administered the same versions of the CPT, suggesting similar abnormalities in the allocation and modulation of information processing resources.

Exploratory eye movements to pictures in childhood-onset schizophrenia and attention-deficit/hyperactivity disorder (ADHD).

We investigated exploratory eye movements to thematic pictures in schizophrenic, attention-deficit/hyperactivity disorder (ADHD), and normal children. For each picture, children were asked three questions varying in amount of structure. We tested if schizophrenic children would stare or scan extensively and if their scan patterns were differentially affected by the question. Time spent viewing relevant and irrelevant regions, fixation duration (an estimate of processing rate), and distance between fixations (an estimate of breadth of attention) were measured. ADHD children showed a trend toward shorter fixations than normals on the question requiring the most detailed analysis. Schizophrenic children looked at fewer relevant, but not more irrelevant, regions than normals. They showed a tendency to stare more when asked to decide what was happening but not when asked to attend to specific regions. Thus, lower levels of visual attention (e.g., basic control of eye movements) were intact in schizophrenic children. In contrast, they had difficulty with top-down control of selective attention in the service of self-guided behavior.

Parallel and serial search in two teenagers with lesions of the mesial parietal cortex.

Visual-spatial attention was examined in two 14-year-olds who had undergone occipital-parietal craniotomies for removal of mesial parietal tumors, one in the right and one in the left hemisphere. Neither patient showed clinically significant visual neglect. They were administered two visual search tasks from Treisman and Souther [43] that make significantly different demands on visual spatial attention. In feature-present (parallel) search, they searched for the presence of a feature. In feature-absent (serial) search, they searched for its absence. Search rate was estimated from the slope of the function relating display size to response time. Both patients had flat slopes in feature-present search to target-present (TP) displays, indicating that they could conduct parallel search at the same rate as controls. Although the patient with the right-hemisphere lesion also had a flat slope to target-absent (TA) displays, the patient with the left-hemisphere lesion had a steep slope (30 ms/item) in this condition. In feature-absent search, the patients had equally slow search rates compared to controls, suggesting that the mesial parietal cortex is part of the network that mediates serial shifts of attention. Results support the distinction between detection of the target in parallel vs serial search and suggest that processes involved in TP and TA trials in parallel search are also dissociable.

Components of visual search in childhood-onset schizophrenia and attention-deficit/hyperactivity disorder.

This study tested the hypotheses that visual search impairments in schizophrenia are due to a delay in initiation of search or a slow rate of serial search. We determined the specificity of these impairments by comparing children with schizophrenia to children with attention-deficit hyperactivity disorder (ADHD) and age-matched normal children. The hypotheses were tested within the framework of feature integration theory by administering children tasks tapping parallel and serial search. Search rate was estimated from the slope of the search functions, and duration of the initial stages of search from time to make the first saccade on each trial. As expected, manual response times were elevated in both clinical groups. Contrary to expectation, ADHD, but not schizophrenic, children were delayed in initiation of serial search. Finally, both groups showed a clear dissociation between intact parallel search rates and slowed serial search rates.

Working memory in childhood-onset schizophrenia and attention-deficit/hyperactivity disorder.

We investigated verbal and spatial working memory in participants with childhood-onset schizophrenia (N=13), attention-deficit/hyperactivity disorder (ADHD; N=31) and age-matched normal children (N=27). The ages of the participants ranged from 9 to 20 years, with an average age of approx. 14 in all groups. Diagnoses were based on structured interviews (Kiddie-Schedule for Affective Disorders and Schizophrenia) with the children and their parents and made using DSM-III-R criteria. Verbal working memory was assessed by the highest number of digits recalled in forward and backward order on the Digit Span subtest of the Wechsler Intelligence Scale. Results showed that normal children recalled more digits than schizophrenic and ADHD children, who did not differ. Spatial working memory was assessed with the Dot Test of Visuospatial Working Memory: The children were presented with a dot on a page for 5 s and asked to mark its location on a blank page immediately after presentation or 30 s later. A distracter task was used during the delay to prevent verbal rehearsal. The average distance between the target dot and the child's mark in the 30-s condition was shorter for normal than for schizophrenic and ADHD children, who did not differ. Thus, both schizophrenic and ADHD children showed deficits in verbal and spatial working memory. These results suggest that in both disorders, the capacity of the sensory buffers may be diminished, and/or the availability and allocation of resources to the central executive may be limited.

Neuropsychological, psychosocial and vocational correlates of the Glasgow Outcome Scale at 6 months post-injury: a study of moderate to severe traumatic brain injury patients.

Traumatic brain injury (TBI) subjects at Glasgow Outcome Scale levels 3 (severe disability), 4 (moderate disability), 5 (good recovery), and an other-injury control group (OIC) were compared in terms of neuropsychological, psychosocial, and vocational functioning 6 months after injury. Subjects were a sample of 100 patients with a moderate to severe traumatic brain injury (TBI) and a matched sample of 30 other-injury control subjects (OIC) enrolled in the UCLA Brain Injury Research Center study of TBI outcome. Overall, the results showed a systematic decrease in mean neuropsychological test performance as a function of increasing GOS severity, as well as an increased prevalence of symptoms of depression and lower ratings on measures assessing employability and capacity for self care. TBI patients in the 'severe' and 'moderate disability' groups were distinctly inferior to the 'good recovery' and 'OIC' groups, who were quite similar to each other in terms of cognitive, psychosocial, and vocational outcomes. The results demonstrate overall support for the predictive and concurrent validity of the GOS 6 months post injury. Despite these results, which strengthen the utility and appeal of the GOS for multicentre studies, concerns still remain regarding GOS category 4 (moderate disability), which was shown to lack sufficient discriminability in this study.

Depressive symptoms in the early course of schizophrenia: relationship to familial psychiatric illness.

OBJECTIVE: This study examined the relation between the presence of depressive symptoms in schizophrenic patients with a recent first psychotic episode and affective disorders among their relatives. METHOD: Data on depressive symptoms in 70 patients with schizophrenia diagnosed according to the DSM-III-R criteria, who had had a recent first psychotic episode, and psychiatric diagnostic information on 293 of their first-degree and 674 of their second-degree relatives were collected. Depressive symptoms in the schizophrenic probands were examined at the index psychotic episode (at study entry) and systematically over a 1-year follow-through period. The majority of first-degree family members were interviewed in person with the use of semistructured diagnostic interviews. RESULTS: The linear regression findings confirmed the hypothesis that depressive symptoms in the early course of schizophrenia are associated with a family history of unipolar affective illness. CONCLUSIONS: Because depression in the patients was associated with a family history of depression, this suggests that depression in schizophrenia is not solely either a reaction to having had a psychotic episode or part of the recovery process. The findings are consistent with a model in which a familial genetic liability to affective disorder, when present, is viewed a s exerting a modifying influence on the patient's schizophrenic illness to increase expression of depressive symptoms.

Event-related potential correlates of linguistic information processing in schizophrenics.

Event-related potentials (ERPs) were recorded from adult schizophrenics and age- and education-matched normal controls during performance of an idiom recognition task involving judgments of the meaningfulness of idiomatic, literal, and nonsense phrases. Schizophrenics produced more errors and had prolonged reaction times while attempting to correctly differentiate meaningful from meaningless phrases. An ERP correlate of that deficit was a larger than normal N400 to idioms and literals, with no difference in N400 amplitude to nonsense phrases. This result was interpreted as evidence that the influence of the linguistic context provided by the first word of two-word idiomatic and literal phrases is reduced in schizophrenia. Schizophrenics also showed reduced amplitude P300.