Neurological findings in early treated phenylketonuria

Twenty early treated, normal intelligent patients (IQ: mean 101.4, SD 10.0; age: mean 10.11, SD 1.3 years) with classical phenylketonuria and 20 age-, sex- and IQ-matched healthy controls were investigated for neurological outcome, especially with regard to fine motor ability using the motor performance task ("Motorische Leistungsserie"). No pathological findings were seen on clinical neurological examination. The patient group had significantly poorer results in a concentration task (Test-d-2) as well as in some subtests of the motor performance task. Patients had difficulties in tasks which needed speed and precision of arm-hand-finger movements. High serum phenylalanine concentrations were significantly correlated with these deficiencies in fine motor ability. Our data demonstrated mild neurological impairment even in early and relatively strictly treated patients with phenylketonuria.     

Intellectual, neurologic, and neuropsychologic outcome in untreated subjects with nonphenylketonuria hyperphenylalaninemia. German Collaborative Study on Phenylketonuria

Based on the serum phenylalanine levels under free diet patients with hyperphenylalaninemia are classified as "classical" (>1200 micromol/L), "mild" (600-1200 micromol/L), or "non-phenylketonuria (PKU)-hyperphenylalaninemia" (<600 micromol/L). Recent studies revealed intellectual, neurologic, and neuropsychologic deficits as well as abnormalities of cerebral white matter (magnetic resonance imaging, MRI) in patients with early and adequately treated PKU. In addition deficits in IQ were reported for a group of 4-y-old patients with untreated mild PKU and non-PKU hyperphenylalaninemia (serum phenylalanine levels below 900 micromol/L). As a consequence, a lifelong diet with serum phenylalanine levels below 400 micromol/L was recommended even for those patients with serum phenylalanine levels remaining consistently between 400 and 600 micromol/L. Generally patients with non-PKU hyperphenylalaninemia were not treated, as a normal outcome was suspected, but the clinical development of patients with non-PKU hyperphenylalaninemia was not so far studied systematically. We assessed 28 untreated patients with non-PKU hyperphenylalaninemia (age: mean = 21.8, SD = 4.2 y) for IQ, school and job career, clinical-neurologic development, fine motor performances, selective and sustained attention, as well as for frontal lobe-dependent "executive functions." In addition, cranial MRI was obtained in 10 of these patients. Compared with healthy control subjects, matched for age, sex, and socioeconomic status, the patients reached normal results in all clinical and psychometric tests. Cranial MRI revealed no abnormalities. Additionally, no significant correlations between serum phenylalanine levels and test results were obtained. In the absence of any demonstrative effect, treatment is unlikely to be of significant effect in patients with non-PKU hyperphenylalaninemia.     

Neuropsychological, intellectual, and behavioral findings in patients with centrotemporal spikes with and without seizures

Forty children (23 boys, 17 girls) with centrotemporal spikes (rolandic focus) with and without seizures (mean age 8.4 years +/- 4.8 SD), and 40 healthy controls matched for age, sex, and socioeconomic status were assessed for their neuropsychological, intellectual, and behavioral outcome. Compared with the controls, patients were significantly impaired in their IQ, visual perception, short-term memory, in their psychiatric status and in some subtests in a fine motor performance task. No significant differences could be computed for a simple finger-motor speed exercise or a linguistic performance test. In patients, deficits in IQ were significantly correlated with frequency of spikes in the EEG, but not with frequency of seizures, lateralization of the rolandic focus, or time since rolandic focus was diagnosed. It was concluded that a rolandic focus is not as benign as once thought.     

Neurobehaviour of school age children born to diabetic mothers

AIM: To study the neurobehavioural effects that diabetes during pregnancy might have on children by school age. METHODS: The neurobehavioural function of 57 school age children born to 48, well controlled diabetic mothers was compared with 57 control children matched for age, birth order, and parental socioeconomic status, using several cognitive, behavioural, sensory and motor neurological tests. RESULTS: The IQ scores of the index group children were similar to those of control children (117.7 +/- 13.4 vs 118.5 +/- 10.1). There were no differences between the groups in various sensory motor functions. However, the index group children performed less well than the controls on indices of fine and gross motor functions, as observed on the Bruininks-Oseretzky test of motor proficiency. The scores of children born to diabetic mothers were higher than controls on the Touwen and Prechtl neurological examination. They also performed worse in the Pollack tapper test which is designed to detect minor neurological deficits, inattention, and hyperactivity. The index children had higher scores on the Conners abbreviated parent-teacher questionnaire which measures hyperactivity and inattention. There was a negative correlation between the performance of the index group children on various neurodevelopmental and behavioural tests and the severity of hyperglycaemia, as assessed by blood glycosylated haemoglobin and acetonuria. CONCLUSIONS: Diabetes during pregnancy adversely affects some fine neurological functions in children at school age, but not their cognitive scores. These effects are not correlated with the degree of glycaemic control.     

Speech and language in high-functioning autistic individuals.

Verbal individuals with autism provide an important opportunity for investigating the qualitative nature of speech and language impairments in autism. In this study, a psychometric analysis of the language performance of 62 high-functioning autistic (HFA; Full Scale IQ and Verbal IQ?>?70) participants was compared with that of 50 control participants matched for age, IQ, gender, race, education, and family socioeconomic distribution. Tests were included to compare basic procedural linguistic skills with complex, interpretive linguistic skills. The HFA participants did as well as controls on basic procedural language tests, but significantly less well on tests of complex interpretive language abilities. This profile is consistent with neuropsychological reports of generalized deficits in complex information-processing abilities with preservation of basic skills in the same functional areas. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in neuropsychological functioning of first-episode and chronically ill schizophrenic patients

OBJECTIVE: The purpose of this study was to determine whether men and women with schizophrenia demonstrate differences in cognitive abilities. METHOD: Two cohorts of patients with schizophrenia, an acute first-episode and a chronically hospitalized group, were evaluated with a neuropsychological battery and compared with a normal group of subjects. RESULTS: After adjustment for age, age at onset, and premorbid IQ, male chronic patients performed worse than female chronic patients on measures of visual memory. These differences were eliminated after control for symptom severity. No other differences were found in cognitive function between men and women in either cohort. CONCLUSIONS: Sex differences in cognitive function in schizophrenic patients are not robust findings.     

Management of phenylketonuria: South Australian experience of 13 cases

The management and present status of 13 children with phenylketonuria detected on the fifth day of life, who have been treated by diet thereafter for five to eight years, are discussed. In all 10 cases in which there has been continuous adequate dietary control of blood phenylalanine levels, the physical, social and mental development of the children has been normal. In some of these cases there is an unexplained discrepancy between the verbal and performance IQ scores. The present policy is to continue restricting the diet indefinitely, relaxation being permitted conditionally only after the age of seven years.     

Mental prognosis of Apert syndrome

BACKGROUND: Mental retardation, considered as common in Apert syndrome could be in part due to associated brain abnormalities. POPULATION AND METHODS: Sixty patients (32 males, 28 females) were included in the study. Patient age at the last examination was over 3 years (mean 10 years, range 3-28 years) in 38 patients. IQ was assessed from psychometric tests adapted for age. Brain anatomy was studied by MRI. Age at operation and quality of familial environment were also evaluated. RESULTS: The IQ was over 70 in 12 patients (32%), over 90 in five (13%) and the mean IQ was 62 (10-114). Thirty percent of patients had abnormalities of the corpus callosum, 43% of the cerebral ventricles and 55% of the septum pellucidum. There was no anomaly in 28% of the patients. One or more operations were performed in 53 patients, before one year of age in 37. Ten children were institutionalized or in deleterious family situation. The main factor influencing the mental prognosis was the age at operation: the final IQ was over 70 in 50% of the children operated on before one year of age versus 8% in those operated on later (P = 0.01). Only the anomalies of the septum pellucidum seemed to play a role: 50% of the patients with normal septum had an IQ > 70 compared to 18% in those with septum anomalies (P < 0.04). The quality of the familial environment also influenced the mental development: 12.5% of the patients who were institutionalized or in difficult familial situation had an IQ > 70 compared to 39% of those who live in a normal family. CONCLUSIONS: Careful investigation including MRI is necessary for detecting associated brain abnormalities. The patients must be operated on early, if possible before the age of nine months. Attention has also to be paid to quality of the sociofamilial environment.     

Toward a model of neuropsychological activity

The main purpose of this research was to establish the intercorrelations existing among different psychological and neuropsychological test scores in a normal and homogeneous population. A second purpose was to attempt further step in the component analysis of cognitive activity measured by means of neuropsychological tests. A comprehensive neuropsychological test battery was assembled and individually administered to a 300-subject sample, aged 17-25 year-old. All of them were right-handed male university students. The battery included some basic neuropsychological tests directed to assess language, calculation abilities, spatial cognition, praxic abilities, memory, perceptual abilities, and executive functions. In addition, the Wechsler Adult Intelligence Scale was administered. Forty-one different scores were calculated. Correlations among the different test scores were analyzed. It was found that some of the tests presented a quite complex intecorrelation system, whereas other tests presented few or no significant correlations. Mathematical ability tests and orthography knowledge represented the best predictors of Full Scale IQ. A factor analysis with varimax rotation disclosed five factors (verbal, visuoperceptual, executive function, fine movements, and memory) accounting for 63.6% of the total variance. Implications of these results for a neuropsychological model about brain organization of cognition were analyzed.     

Motor function under lower and higher controlled processing demands in early and continuously treated phenylketonuria.

This study examined motor control in 61 early and continuously treated patients with phenylketonuria (PKU) and 69 control participants, aged 7 to 14 years. The pursuit task demanded concurrent planning and execution of unpredictable movements, whereas the tracking task required a highly automated circular movement that could be planned in advance. PKU patients showed significantly poorer motor control in both tasks compared with control participants. Deficits were particularly observed for younger patients (age     

Neurological and neuroradiological findings in long-term survivors of allogeneic bone marrow transplantation

The aim of this study was to assess neurological, neuropsychological, and neuroradiological findings in long-term survivors of allogeneic bone marrow transplantation (BMT) who were recruited from a hematological outpatient clinic. In addition, risk factors for the development of late neurological complications were identified. In contrast to previous studies on autopsied patients, our study design provoked a bias away from increased neurological sequelae, because patients with early complications after BMT were excluded. Fifty-nine allogeneic patients and 7 autologous BMT patients underwent clinical examination, short neuropsychological testing, and cranial magnetic resonance imaging (MRI) 34 +/- 26 months after BMT. The pathological results of the neurological examination (abnormal 64%) and the MRI examination (white matter lesions, 54%; atrophy, 11%) were associated with the occurrence of chronic graft-versus-host disease (GvHD) evolving from acute GvHD, with corticosteroid therapy and with cyclosporine medication. Neuropsychological impairment (cognitive deficits, 37%) was associated with long-term cyclosporine medication and age. No influence of pre-BMT disease, BMT donor status, or the conditioning regimen was found. These results suggest that the frequent neurological abnormalities in long-term survivors of allogeneic BMT are associated with chronic GvHD and with the resulting immunosuppression as major risk factors.     

Intellectual and cognitive functions in Parkinson's disease.

Compared the performance of 25 parkinson's disease patients and 25 normals matched for age, race, sex, and education on 32 behavioral variables including the wechsler-bellevue intelligence scale (form i), halstead neuropsychological battery, and R. Reitan's trail making test. Ss with parkinson's disease had lower mean scores than controls on all 32 measures. Statistical comparisons indicated these differences were significant beyond the .001 level for 25 tests, and on only 1 measure was the probability level greater than .05. Results indicate that parkinson's disease patients have suffered marked deterioration not only in motor abilities but also in problem-solving, sensory, memory, general cognitive, and abstracting and organizing abilities. (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improved peripheral nerve conduction, EEG and verbal IQ after bone marrow transplantation for adult metachromatic leukodystrophy

A 28-year-old woman with a 4 year history of slowly progressing 'frontal dementia' was diagnosed as having adult metachromatic leukodystrophy and was followed for 4 years after bone marrow transplantation (BMT). MRI, neurophysiological tests (EEG, ENeG, VEP, SEP and BAEP) and neuropsychological assessment were performed before, and repeatedly after BMT. MRI showed symmetrical white matter lesions in the frontal and parieto-occipital lobes and in the corpus callosum. EEG showed frontal and temporal slow wave abnormalities and nerve conduction was slow. Neuropsychological tests showed cognitive impairment in executive functions, decline in visuospatial-constructive and spatial memory tasks and disorganized thinking. IQ was low (52), with slightly better values for verbal IQ than for performance IQ. After BMT, the patient was followed for 4 years. Clear improvements were seen in EEG, in peripheral nerve conduction and in neuropsychological tests (especially in verbal IQ). MRI findings were unchanged. We believe that the improvement in our patient resulted from the bone marrow transplantation.     

Rasmussen syndrome

INTRODUCTION: Rasmussen's encephalitis is a neurological disorder probably of immunological origin, characterized by intractable epilepsy, neurological deterioration and the presence of antibodies against R3 glutamate receptors. OBJECTIVE: To present the experience of an Argentinian Paediatric Neurology Service during the past 7 years. MATERIAL AND METHODS: We analyzed the clinical histories of 12 patients with RS as defined by the diagnostic criteria proposed by Hart et al. We evaluated the following parameters: neurological examination, neuropsychological assessment, types of crises, age of onset, frequency, distribution, electroencephalogram, video EEG, evoked potentials, neuro-radiological studies; CT and cerebral MR using gadolinium, SPECT, lumbar puncture and cerebral biopsy. RESULTS: The crises were of simple partial motor type in 12 cases, secondarily generalized partial crises in 7 cases, complex partial crises in 4 cases and partial and generalized motor states in 8 cases. RESULTS. The ictal EEGs during the continuous partial crises showed contralateral focal slow activity of the affected side of the body in 30% of cases. The neuro-radiological studies (CT and MR) showed signs of cerebral hemiatrophy in all 12 cases, hyper-intense images in the T2 sequences of the fronto-temporo-parietal regions in 5 cases, an asymmetric megacisterna magna in 1 case and hypoplasia of the cerebellar vermis in another case. CONCLUSIONS: The continuous partial crises showed little correlation with the electro-encephalography. Following administration of i.v. gammaglobulin there was a transient halt in progression of the neurological deterioration and control of the crises in 55% of the cases. Surgery continued to be the treatment recommended for control of the epileptic crises.     

Neuropsychological findings in relapsing-remitting and chronic-progressive multiple sclerosis.

Administered the WAIS and an expanded Halstead-Reitan Neuropsychological Test Battery (HRB) to 100 (mean age 37.38 yrs) patients with relapsing-remitting (n?=?57) or chronic-progressive (n?=?43) courses of multiple sclerosis (MS) and to 100 normal controls to assess neuropsychological functioning in MS Ss. Both MS groups were clinically stable at the times of testing. Results indicate that both MS groups showed significant neuropsychological impairment, relative to controls, but chronic-progressive MS was associated with greater impairment in each major ability domain (cognitive, sensory, and motor) than was relapsing-remitting MS. In particular, only minimal cognitive impairment was noted in relapsing-remitting MS Ss, whereas chronic-progressive Ss showed impairment on the majority of cognitive test measures from the expanded HRB. Degree of neuropsychological impairment was significantly correlated with MS duration but was unrelated to medication status. MS subgroup differences on the test battery could not be attributed to duration of illness, indicating that disease course is an important independent determinant of neuropsychological impairment in MS. Disability ratings from clinical neurological examinations were highly correlated with motor and sensory performances on neuropsychologial testing, but clinical exams were inadequate in predicting Ss' cognitive status. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pilot neuropsychological findings from a treatment regimen consisting of intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors

Ten children (6 girls and 4 boys) who completed a protocol in which their localized brain tumors were successfully treated without cranial irradiation were referred for neuropsychological assessment. At the time of testing, they were disease free without any neuroaxis dissemination or leptomeningeal disease. Tumor types included pineoblastoma, glioblastoma, ependymoma, PNET and medulloblastoma. They had a mean age of 5 years and 8 months (SD = 1.86; range = 2.1-8.9 years) and were an average of 37.8 months post bone marrow transplant (SD = 16.42; range = 14-58 months). Neuropsychological data from this study reveal that the mean scores for this nonradiated group of children were within the average range for the following domains: academic achievement tests of reading, spelling and mathematics, verbal and visual memory, visual-motor integration, social-emotional and behavioral functioning. Furthermore, this group of children were performing within the low average range of overall Intelligence, as well as both verbal IQ/verbal reasoning and performance IQ/abstract visual reasoning. On tasks of fine motor dexterity, this group was within the low average range when using their dominant hand; however, they performed within the borderline range when using their non-dominant hand. Of note, this group of children demonstrated significant deficits within the borderline to impaired ranges on language tasks of expressive picture naming and receptive picture vocabulary.     

Digital subtraction arthrography in preoperative evaluation of painful total hip arthroplasty

The results of a neurological, neuropsychological and MRI study of the brain in 21 patients (aged 18-59 years) with Sneddon's syndrome are reported. The predominant findings were marked neuropsychological deficits in two-thirds of the patients. While sensorimotor deficits after stroke in these patients had a good prognosis, neuropsychological deficits persisted. Of the 21 patients, 14 were incapable of gainful employment, 10 because of severe cognitive dysfunction.     

Verbal IQ–performance IQ discrepancies on the Wechsler Adult Intelligence Scale-Revised in patients with unilateral or bilateral cerebral dysfunction.

Administered the WAIS-R to 89 patients (mean age 42 yrs) with neurodiagnostically confirmed unilateral or bilateral cerebral disease. Similar to findings with previous editions of these tests, Ss with left-hemisphere disease obtained significantly lower Verbal IQ (VIQ) than Performance IQ (PIQ), and Ss with right or bilateral disease obtained lower PIQ than VIQ. It is cautioned that these VIQ–PIQ discrepancies in isolation are ineffective indexes of cerebral dysfunction and that patterns of performance must be viewed in the context of a complete neuropsychological examination and relevant medical and educational historical data. (5 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial Working Memory Deficits in Children at Ages 3-4 Who Were Low Birth Weight, Preterm Infants.

The aim of this study was to investigate attention and perceptual and spatial working memory abilities in preterm, low birth weight preschool children without evident brain disorders as determined by normal cerebral ultrasound findings and normal motor development. The authors evaluated 19 preterm and 19 typically developing children who were matched for IQ and chronological age. Results indicated that children born prematurely without major neurological deficits and with a normal cognitive level may have specific difficulty in sustained attention, visuospatial processing, and spatial working memory when evaluated at ages 3-4. This finding is relevant for understanding the qualitative aspects of cognitive development in preterm children and the neurobiological substrate underlying this development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Severity of brain injury following neonatal extracorporeal membrane oxygenation and outcome at age 5 years

Neurodevelopmental evaluation in childhood provides an opportunity to study complex neurological compensation following documented neonatal brain injury, and furnishes important clinical information which may have an impact on patient care. We studied 152 term children treated with extracorporeal membrane oxygenation (ECMO) as neonates and who received routine neonatal neuroimaging and comprehensive neurodevelopmental evaluation at age 5 years. The cohort was divided into four groups based on an independent neuroimaging score: No lesion, N=88; Mild lesion, N=38; Moderate lesion, N=12; and Severe lesion, N=14. Standardized testing at age 5 included complete neuropsychological assessment, neurological evaluation, and assessment of motor function. All testing was conducted without knowledge of the neuroimaging score. The occurrence of disability by severity of neuroimaging was: No lesion=10%; Mild=13%; Moderate=33%; Severe=57%. The relative risk within the ECMO population for disability at age 5 after moderate or severe neonatal lesion was 4.3 (CI=1.0 to 17.5) and 11.7 (CI=3.3 to 41.3), respectively. The remaining non-disabled children who had moderate to severe lesions functioned within normal limits. Severity of neonatal neuroimaging was inversely associated with IQ scores, pre-academic skills, and neuromotor function. The effect size was small but the rank order was predictable. Our data identify in 5-year-old children an impact of brain lesion severity demonstrated on routine neonatal neuroimaging. The results indicate potential compensation following moderate and severe lesions, and suggest a subtle but consistent influence of even mild neonatal brain injury.