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PubMed1996

Prevention and treatment of aluminum toxicity including chelation therapy: status and research needs.

The prevention and treatment of aluminum (Al) accumulation and toxicity are reviewed. Recommendations to further our understanding of desferrioxamine (deferoxamine, DFO) treatment and to develop more effective chelation approaches are provided. Reduction of Al accumulation and toxicity may benefit end-stage renal disease (ESRD) patients and perhaps those suffering from specific neurodegenerative disorders as well as workers with Al-induced neurocognitive disorders. The clearance of Al may be increased by extracorporeal chelation, renal transplantation, perhaps complexation with simple ligands such as silicon (Si), and systemic chelation therapy. The abilities of extracorporeal chelation and Si to reduce Al accumulation require further evaluation. Although it may not be possible to design Al-specific chelators, chelators with greater Al selectivity are desired. Aluminum-selective chelation might be achieved by targeted chelator distribution or by the use of adjuvants with the chelator. The ability of carboxylic acids to facilitate Al elimination, under specific conditions, warrants further study. Desferrioxamine does not produce significant biliary Al excretion. A chelator with this property may be useful in ESRD patients. The necessity for an Al chelator to distribute extravascularly to be effective is unknown and should be determined to guide the selection of alternatives to DFO. The lack of oral efficacy and occasional side effects of DFO encourage identification of orally effective, safer Al chelators. The bidentate 3-hydroxypyridin-4-ones are currently the most encouraging alternatives to DFO. They have been shown to increase urinary Al excretion in rats and rabbits, but to have toxicity comparable to, or greater than, DFO. Their toxicity may relate to incomplete metal complexation. The ability of orally effective chelators to increase absorption of chelated metal from the gastrointestinal (Gl) tract needs to be evaluated. Orally effective, safe Al chelators would be of benefit to peritoneal dialysis patients and those with neurodegenerative disorders, if Al chelation therapy is indicated. The reduction of Alzheimer's disease (AD) progression and the reversal of Al-induced behavioral deficits and neurofibrillary tangles by DFO encourage further study of Al chelation therapy for selected neurodegenerative disorders.

Aluminum↗
PubMed1997

Evaluating the neurocognitive complications of SLE. Lessons from HIV disease.

In this paper, we have attempted to define some of the theoretical, methodological, and practical issues involved in the use of NP testing to detect, classify, and monitor neurocognitive impairment secondary to systemic lupus erythematosus. We have drawn on experience with other clinical entities-primarily HIV disease-to inform this discussion. We have argued that for the purposes of studying NP-SLE, NP testing remains the gold standard and is also the most practicable approach in most settings, be they clinical or research. At the same time, the selection of NP tests must be carefully considered, particularly in a disease such as SLE in which the neurocognitive complications arise from several etiological mechanisms, affect people at various points in the course of disease, and in which the anatomic distribution of pathology in the brain varies from patient to patient. In this context, it is safest to select a test procedure that assesses all major areas of cognitive functioning with tests for which adequate demographically adjusted norms exist. In this way, a more reliable diagnosis of neurocognitive impairment, mild neurocognitive disorder, or dementia may be made. A reliable and valid neurocognitive diagnosis is the first step in monitoring patients clinically, in designing research aimed at neuropathogenesis, or in the design of treatment trials geared toward neuroprotection or neuroremediation.

Cognition Disorders↗
PubMed1995

Nongalenic cerebral arteriovenous malformations in neonates and infants. Review of 26 consecutive cases (1982-1992).

We present 26 consecutive cases of nongalenic pial arteriovenous malformations (PAVMs) diagnosed in the neonatal period or in infancy. No diagnosis was made antenatally. Presenting symptoms in neonates were systemic cardiac manifestations (54%), seizures (31%), and hemorrhages (15%). In infants, hemorrhagic strokes and hydrodynamic disorders (external or internal hydrocephaly, macrocephaly, atrophy) both occurred in 38% of cases. Systemic cardiac manifestations and seizures were rare at that age (respectively 16% and 8%). Sixty-two percent of neonates and 31% of infants already had neurocognitive disorders (assessed by pediatric neurocognitive testing: Brunet-Leizine and Denver tests) when referred. The venous drainage and its anomalies (ectasias, stenoses, thromboses) were the main causes of symptoms. Atrophy and leukomalacic lesions occurred rapidly; they express local hydrovenous disorders and are specific to this population group. Untreated neonates and infants have a poor prognosis. Endovascular treatment, although partial and challenging in all instances, represents the treatment of choice in our series. Of the eight neonates treated, one improved to normal (12.5%), while four remained stable (50%): two neurologically normal, two with mild neurological deficit. Three (37%) died despite embolization (heart failure, multiorgan failure, postoperative death). Transient neurological complications occurred in two cases (25%): hemiparesis in one patient with a rolandic and in one with a thalamic AVM. Of the eight infants successfully embolized, one was significantly improved (12.5%) and is now neurologically normal, while five remained stable (62.5%): four neurologically normal, one with mild neurological deficit. One died between two sessions of embolization from intracerebral hemorrhage (12.5%). Hemianopsy occurred in one case (12.5%) after embolization of an occipital AVM. In one additional case in a normal child we failed to embolize the last small pial AVM of four after the three others had spontaneously thrombosed. With a minimal follow-up of 18 months and a maximum of 7 years, the review of our series shows 53% of the initial group of neonates and infants growing neurologically normal after therapeutic management in our institution; 23.5% died despite treatment, and the remaining 23.5% present minor neurological deficit. When targeted at the points of angioarchitectural weakness, embolization contributes to stabilizing a lesion. It should be undertaken rapidly to avoid loss of brain substance secondary to hemorrhage, atrophy, or leukomalacia, and to allow neurocognitive recovery and normal brain maturation. In our experience, these lesions are the most aggressive ones for the maturing brain, and the most difficult to approach technically. They represent a new therapeutic field and have their own specific anatomy and physiology.

Adolescent↗
PubMed2003

Off-Pump versus on-pump coronary artery bypass: can OPCAB reduce neurologic injury?

OBJECTIVE: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass is still the gold standard for surgical myocardial revascularization. Despite advances in techniques and technologies, documented evidence indicates that cardiopulmonary bypass remains the major source of intraoperative brain injury. This study was set up to test whether offpump coronary artery bypass (OPCAB) is superior to CABG regarding postoperative neurologic outcome or neurocognitive function. METHODS: Between January 1999 and June 2001, 251 patients scheduled for coronary revascularization were divided into 2 groups, CABG (control) and OPCAB. All patients underwent an extensive neurologic and neurocognitive battery of tests preoperatively and postoperatively at 48 hours, 7 days, and 3 months following surgery. RESULTS: There were no statistically significant differences between the 2 groups regarding the preoperative or intraoperative data. The means for patient age, number of grafts, and number of central anastomoses were, respectively, 65.4 years (CABG) and 64.6 years (OPCAB), 3.0 (CABG) and 2.2 (OPCAB), and 2.0 (CABG) and 1.2 (OPCAB). The occurrence of stroke was 2.3% (CABG) and 0% (OPCAB). CONCLUSION: Neurologic complications and postoperative neurocognitive dysfunction remain major concerns in coronary artery surgery. Besides the occurrence of stroke, which dramatically reduces the success of the heart operation, the importance of neurocognitive disorders for postoperative quality of life is not yet well defined. OPCAB significantly improves postoperative neurocognitive function, which may in turn improve the postoperative quality of life.

Aged↗
PubMed2004

Visual, auditory, and tactile temporal processing in children with oral clefts.

Neurocognitive disorders may compromise the outcome of surgical cleft lip palate repair and thus need to be identified. Processing of rapidly changing sequential information (temporal processing) is a fundamental neurocognitive capacity that may contribute to various communication functions and has been found impaired in several developmental disorders. The occurrence of temporal processing difficulties in the cleft population is not known, however. We investigated the relation between oral clefting and temporal estimations of simultaneity/nonsimultaneity in visual, auditory, and tactile modalities. Subjects were 10-year-old controls and children with oral clefts of various types [i.e., cleft lip (alveolar), cleft lip and palate, cleft palate, and cleft palate submucous]. The visual and tactile tasks but not so clearly the auditory task differentiated the groups. Further, paralleling previous findings, the patients with cleft lip and palate outperformed the others, whereas the cognitive temporal processing acuity of the cleft palate and cleft palate submucous children was worse.

Analysis of Variance↗
PubMed1997

Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group.

OBJECTIVE: To determine if mortality is increased in individuals with human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders less severe than frank dementia. DESIGN: A prospective cohort study; median duration of follow-up was 2.4 years. Kaplan-Meier analysis and Cox proportional hazards models were used to compare survival times according to neurocognitive classification. SETTING: University-based research unit. PARTICIPANTS: A volunteer sample of 414 individuals seropositive for HIV-1. Subjects were classified at their baseline evaluation as neuropsychologically (NP) normal or abnormal (impaired in > or = 2 NP test domains). A subgroup of NP abnormal subjects met operational criteria for HIV-associated minor cognitive motor disorder; the remaining subjects were designated NP impaired. Subjects with frank dementia were excluded. MAIN OUTCOME MEASURE: Mortality. RESULTS: At the baseline evaluation, 256 (62%) of 414 subjects were designated normal; 109 (26%). NP impaired; and 49 (12%), minor cognitive motor disorder. One hundred six participants (26%) died during follow-up. Compared with the NP normal group, the unadjusted relative risk (RR) of death for all NP abnormal subjects (minor cognitive motor disorder and NP impaired) was significantly increased (RR, 1.7; 95% confidence interval [CI], 1.2-2.6; P < .005). After adjusting for concurrently measured predictors of survival (CD4 lymphocyte counts, Centers for Disease Control and Prevention HIV disease classification, hemoglobin concentration, and serum beta 2-microglobulin) in proportional hazards models, mortality for all NP abnormal subjects remained elevated (RR, 1.8; 95% CI, 1.2-2.8; P < .01). The elevation in mortality risk for subjects with minor cognitive motor disorder was statistically significant (RR, 2.2; 95% CI, 1.2-3.8; P < .01); for NP impaired subjects it was marginally significant (RR, 1.6; 95% CI, 1.0-2.8; P = .06). CONCLUSIONS: The HIV-infected individuals with NP impairment had a higher risk of dying than those without impairment. This was particularly true for those meeting syndromic diagnostic criteria.

Adult↗
PubMed2004

Effects of HIV-1 infection and aging on neurobehavioral functioning: preliminary findings.

OBJECTIVE: The effects of aging on the presentation of HIV-associated neurocognitive disorders are largely unknown. In a cross-sectional observational study, we compared the neuropsychological profiles of 67 HIV-positive patients aged at least 50 years with those of 52 participants aged 35 years or less. METHODS: Participants received neuropsychological, psychiatric and neuromedical evaluations. Raw neuropsychological test scores were converted to demographically corrected T-scores; all were corrected for the effects of normal aging. Clinical ratings of impairment were assigned to the neuropsychological results. RESULTS: The two groups did not differ statistically with respect to demographic variables, percentage with AIDS, or CD4 cell counts. The 'younger' group had higher viral burdens in plasma and cerebrospinal fluid (CSF), and fewer were receiving antiretroviral treatment. The proportion of neuropsychologically impaired subjects in the 'older' group was slightly greater than in the younger group, and the older group tended to have higher rates of impairment across most ability domains. When group differences in CSF viral load were modeled statistically, both viral burden and age were significant predictors of neuropsychological impairment, together with a significant interaction between viral burden and age. Older individuals with detectable virus in CSF had twice the prevalence of neuropsychological impairment of those with undetectable levels. Among younger individuals, this proportion was not affected by viral load. Lifetime major depression, substance use disorder, and current depression symptoms were not associated with neuropsychological impairment. CONCLUSION: Although further studies with larger and older samples are needed, this investigation suggests that older adults may be at greater risk of HIV-related neurocognitive dysfunction.

Acquired Immunodeficiency Syndrome↗
PubMed2005

[Hyperactivity in preschoolers: a clinical description].

INTRODUCTION: Hyperactivity is a behavioural development disorder characterised by disruptive motor activity that prevents the individual from establishing adequate social ties and normal communication, which are an essential part of a child's overall development. It is an unspecific symptom of several neurocognitive disorders, the most frequent of which is attention deficit hyperactivity disorder (ADHD). PATIENTS AND METHODS: We present the results of two investigations. In the first, a case-control study, we conducted a comparative analysis of how the parents of 50 children diagnosed with ADHD remember the behaviour of their children during the first 12 months of their lives. The symptoms were separated into 3 clinical profiles (daytime irritability, eating disorders and sleep dysfunctions). Up to 33% of the families reported a history of at least one of these aspects. 41% of the children were described as being excessively restless, crying a lot or irritability, and being easily startled and very sensitive to noises, and 42.7% had difficulty in getting to sleep or displayed intermittent periods of sleep and woke up crying. For the second research project, which was to complement the previous one, we designed a survey which was answered by the parents of 78 patients diagnosed with ADHD. The questionnaire collected information about the first 5 years of life in 4 sections (28 items): behaviour up to the age of one year, psychomotor development, development of play, and the parents' general perception of their child (distracted-inattentive, impulsive, destructive, immature, negativist, oppositional, other). The Rasch mathematical model was used to obtain the clinical profile of the case mix. CONCLUSIONS: The clinical symptoms appear on a continuum throughout the early years of the child's life. The results of our experience allow us to develop a method of clinical examination focused on the evaluation of the individual's development, play, and communication and socialisation skills which can be used to approach the differential diagnosis of the hyperactive preschooler.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Specific memory impairment in a multiple disabled male with fragile X syndrome and temporal lobe epilepsy.

Evaluation of the cognitive repercussions of an epileptic disorder and its treatment are important issues in clinical follow-up. This especially holds true for temporal lobe epilepsy (TLE) where resective surgery can be a valid treatment option. However, in patients where TLE coexists with another neurocognitive disorder, questions can arise about the precise nature of the neuropsychological deficits. The aim of the present study was to evaluate memory impairments, found in a male aged 12 years who had the dual pathology of fragile X syndrome and refractory TLE. Memory functions of this child were compared with those of a male aged 11 years 7 months with fragile X syndrome matched for intellectual functioning as indicated by highly comparable verbal (5 y 5 mo vs 5 y 9 mo) and non-verbal (7 y 2 mo vs 6 y 1 mo) cognitive age equivalents. Performance on each neuropsychological measure was evaluated twice, separately with normative data based on chronological age and on verbal or non-verbal cognitive level. A specific, distinguishable profile of task performance could be found only when controlling for general level of cognitive functioning. This made it possible to accurately evaluate neuropsychological abilities before and 6 months after anterior temporal lobe resection even in this male with a complex neurological pathology.

Abnormalities, Multiple↗
PubMed2007

HIV and antiretroviral therapy in the brain: neuronal injury and repair.

Approximately 40 million people worldwide are infected with human immunodeficiency virus (HIV). Despite HIV's known propensity to infect the CNS and cause neurological disease, HIV neurocognitive disorders remain under-recognized. Although combination antiretroviral therapy has improved the health of millions of those living with HIV, the penetration into the CNS of many such therapies is limited, and patients' quality of life continues to be diminished by milder, residual neurocognitive impairment. Synaptodendritic neuronal injury is emerging as an important mediator of such deficits in HIV. By carefully selecting specific antiretrovirals and supplementing them with neuroprotective agents, physicians might be able to facilitate innate CNS repair, promoting enhanced synaptodendritic plasticity, neural function and clinical neurological status.

Animals↗
PubMedDate not supplied

Long-term follow-up of children with retinoblastoma.

Twenty-one pediatric retinoblastoma (RB) patients treated between 1976 and 1994 were evaluated for late treatment-related complications. Median age at diagnosis was 24 months; median age at follow-up was 12 years; median follow-up time was 12 years. Of the 21 patients, 14 had unilateral RB and 7 had bilateral RB. Thirteen patients had received external radiotherapy and 8 children were treated by chemotherapy. Twenty-one patients had undergone enucleation. Radiation-induced cataracts were found in 3 patients, radiation retinopathy in 1, enucleation and postradiotherapy contracted socket in 1, very low visual acuity postradiotherapy in 3, severe hypotelorism in 2, growth hormone deficiency in 2, neurocognitive disorders in 6, and orbital deformation due to radiation bone atrophy was moderate-severe in 12 patients. Azoospermia was found in 1 patient treated by cyclophosphamide and vincristine. The most frequent sequela in this group of RB-cured children were postradiotherapy orbital deformation due to bone atrophy and neurocognitive disabilities. Late radiation effects must be avoided by using modern, innovative, and more sophisticated radiotherapeutic techniques. Late treatment-related complications justify the long-term follow-up of childhood RB survivors.

Adolescent↗
PubMed2002

Acquired epileptiform aphasia: a dimensional view of Landau-Kleffner syndrome and the relation to regressive autistic spectrum disorders.

Acquired epileptiform aphasia (AEA) is characterized by deterioration in language in childhood associated with seizures or epileptiform electroencephalographic abnormalities. Despite an extensive literature, discrepancies and contradictions surround its definition and nosological boundaries. This paper reviews current conceptions of AEA and highlights variations in the aphasic disturbance, age of onset, epileptiform EEG abnormalities, temporal course, and long-term outcome. We suggest that AEA, rather than being a discrete entity, is comprised of multiple variants that have in common the features of language regression and epileptiform changes on EEG. Viewed this way, we argue that AEA can be conceptualized on a spectrum with other epileptiform neurocognitive disorders that may share pathophysiological features. The implications of this viewpoint are discussed, with emphasis on parallels between the AEA variants and regressive autistic spectrum disorders.

Adolescent↗
PubMed2002

The structure of schizotypy: relationships between neurocognitive and personality disorder features in relatives of schizophrenic patients in the UCLA Family Study.

Schizotypal personality features and certain neurocognitive deficits have been shown to aggregate in the relatives of schizophrenic patients, supporting the view that both are likely to reflect genetic contributions to liability to schizophrenia. Within the relatives of schizophrenic patients, however, the interrelationships between these potential indicators of liability to schizophrenia are not well known. Using data from the UCLA Family Study, we examine the interrelationships between personality disorder symptoms and neurocognitive functioning in nonpsychotic first-degree relatives of schizophrenic patients. Factor analyses indicate that several dimensions of schizotypy can be identified. A neurocognitive dysfunction dimension includes loadings from measures of sequential visual conceptual tracking, rapid perceptual encoding and search, and focused, sustained attention as well as the rating of odd and eccentric behavior from schizotypal personality disorder. Other aspects of schizotypal personality disorder form separate positive schizotypy and negative schizotypy dimensions. These analyses support the view that schizotypy is multidimensional in relatives of schizophrenic patients and indicate that neurocognitive deficits in perception and attention are associated with particular schizotypal personality features.

Adolescent↗
PubMed2004

Particle separation using ultrasound can radically reduce embolic load to brain after cardiac surgery.

BACKGROUND: Microembolism during cardiopulmonary bypass has been suggested as being the predominant cause of neurocognitive disorders after cardiac surgery. Shed blood, normally retransfused into the patient during cardiopulmonary bypass, is a major source of lipid microemboli in the brain capillaries. A newly developed technique based on acoustic standing-wave separation of particles in fluid in microchannels, with the capacity to remove lipid particles in blood, is presented. METHODS: A separator consisting of eight parallel, high-fidelity microfabricated channels was actuated with an ultrasound field to create a standing wave. Three different concentrations of lipid particles (diameter, 0.3 microm) were added to blood samples with increasing hematocrits and introduced into the separator channels to separate lipid particles and erythrocytes. RESULTS: The mean separation rates for lipid particles were 81.9% +/- 7.6% and for erythrocytes 79.8% +/- 9.9%, and both were related to the hematocrit level of the incoming blood sample. The procedure was atraumatic and did not cause hemolysis. CONCLUSIONS: Particle separation by means of an acoustic standing-wave technique can be used for atraumatic and effective removal of lipid particles from blood, with the possible clinical implication of reducing neurocognitive complications after cardiopulmonary bypass.

Animals↗
PubMedDate not supplied

Behavioral evaluation in children with obstructive sleep disorders.

AIM: The purpose of this study was to evaluate the behavior in children with obstructive sleep disorder. STUDY DESIGN: Prospective study. MATERIAL AND METHOD: Children's parents (4 to 18 years old) completed the CBCL4/18 (Child Behavior Checklist) in the period of January to July 2005. RESULTS: In the group, 12 (60%) were males and 8 (40%) females; the total problem score was abnormal in 5 children (25%); introversion was affected in 2 children (10%); extroversion in 5 children (25%). The scales of individual syndromes were abnormal in between 0 and 20% of patients. The individual scales most frequently affected were: total competency (20%), somatic complaints (10%), social problems (10%) and aggressive behavior (10%). DISCUSSION: This study demonstrates high prevalence (25%) of abnormal behavior. Although widely reported as a common complication of pediatric OSAS, behavioral and neurocognitive disorders have mostly been inferred in several cases and studies. There are few recent studies using standardized assessment to evaluate these alterations. Our study presents preliminary results of the behavior of children with obstructive sleep disorders.

Adolescent↗
PubMed2006

The progression of cognition, psychiatric symptoms, and functional abilities in dementia with Lewy bodies and Alzheimer disease.

BACKGROUND: Although dementia with Lewy bodies (DLB) may be one of most common forms of dementia, relatively little is known about its cognitive and functional course. OBJECTIVE: To compare change over time in general cognitive status, memory test performance, psychiatric symptoms, neurological signs, and functional abilities in patients with probable DLB and probable Alzheimer disease (AD). DESIGN: Twenty-eight patients who met diagnostic criteria for DLB were recruited into the study from 3 sites. Patients with AD (n = 55) were selected from a larger cohort and matched 2 to 1 to the patients with DLB on age and baseline global cognitive status. Patients were followed up at 6-month intervals for an average of 6.2 visits and assessed at each visit with tests of global cognitive functioning and verbal learning and memory and measures of psychiatric, neurological, and functional status. RESULTS: At the baseline evaluation, patients with DLB performed more poorly on a measure of constructional praxis and all measures of functional status. They also had more severe psychiatric symptoms and neurological signs than the AD group. Despite these initial differences, generalized estimating equations applied to regression analyses with repeated measures determined that the only difference between the 2 groups in change in cognitive test performance was on a measure of recognition memory; patients with AD declined, while patients with DLB remained relatively stable. Patients with DLB had relatively stable behavioral symptoms and visual illusions, whereas patients with AD had a significant increase in these symptoms over time. Neurological and functional changes over time were similar in the 2 groups. CONCLUSIONS: Both baseline and longitudinal differences between patients with DLB and patients with AD were noted; these have implications for clinical diagnosis and treatment.

Aged↗
PubMed1976

Serum creatine phosphokinase activity in psychiatrically hospitalized children.

Serum creatine phosphokinase (CPK) activity was determined in a series of 101 sequential admissions to the Pritzker Children's Hospital, an inpatient psychiatric facility. Black children had significantly higher serum CPK levels than whites, and males had significantly higher levels than females, as is the case with adults. There was a higher incidence of CPK elevations in children with organic brain pathology than in children with personality disorders or schizoprenia. Children with chronic symptoms of a psychotic nature did not have increased serum CPK activity, which is similar to the findings in adults. There were no children in the sample with acute psychotic symptoms, so it was not possible to determine whether acute psychosis in children is accompanied by increased serum CPK activity, as it frequently is in psychotics over the age of 17.

Adolescent↗