Subtle Neurological Abnormalities Research Articles

Subtle Neurological Abnormalities and Functional Cognition in Older Adults

Subtle Neurological Abnormalities and Functional Cognition in Older Adults

P2.019 Subtle neurological abnormalities as risk factors for geriatric syndromes: a longitudinal population-based study

P2.019 Subtle neurological abnormalities as risk factors for geriatric syndromes: a longitudinal population-based study

Associations between schizotypal features and indicators of neurological and morphological abnormalities

Objective Limited research suggests that subtle neurological and morphological abnormalities that have been documented in patients with schizophrenia also may be associated with schizotypal traits in non-psychiatric samples. Based on the notion that neurological soft signs (NSS) may mark a genetic diathesis, this study hypothesized that NSS scores would be related to the level of schizotypy in relatives of schizophrenia patients and in controls. Additionally, associations between MPA scores and schizotypy were explored in these two groups. Method Twenty-six first-degree relatives of schizophrenia patients and 38 controls with no personal or family history of psychosis were assessed for schizotypy using the Structured Clinical Interview for DSM-IV Axis II Disorders schizotypal personality disorder module, as well as the self-administered Schizotypal Personality Questionnaire. The Neurological Evaluation Scale and a structured examination for MPAs also were administered. Results Mean schizotypy scores did not differ between relatives and controls. Both NSS and MPAs were associated with the level of interviewer-assessed schizotypal features in controls but not in relatives of patients with schizophrenia. NSS and MPAs were not associated with self-reported schizotypy in either group. Conclusions These findings demonstrate that both NSS and MPAs are associated with interview-based schizotypal traits, at least in non-psychiatric participants. Future research should seek to replicate these results in other samples of relatives and controls.

Neurobiology of Schizophrenia

With its hallucinations, delusions, thought disorder, and cognitive deficits, schizophrenia affects the most basic human processes of perception, emotion, and judgment. Evidence increasingly suggests that schizophrenia is a subtle disorder of brain development and plasticity. Genetic studies are beginning to identify proteins of candidate genetic risk factors for schizophrenia, including dysbindin, neuregulin 1, DAOA, COMT, and DISC1, and neurobiological studies of the normal and variant forms of these genes are now well justified. We suggest that DISC1 may offer especially valuable insights. Mechanistic studies of the properties of these candidate genes and their protein products should clarify the molecular, cellular, and systems-level pathogenesis of schizophrenia. This can help redefine the schizophrenia phenotype and shed light on the relationship between schizophrenia and other major psychiatric disorders. Understanding these basic pathologic processes may yield novel targets for the development of more effective treatments.

Neurological Soft Signs as Predictors of Treatment Response to Selective Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder

Neurological soft-sign abnormalities have been implicated in obsessive-compulsive disorder (OCD). This first comprehensive data analysis evaluated the association between baseline neurological soft signs and treatment response in 117 OCD patients treated with controlled-release fluvoxamine in a double-blind placebo-controlled trial. Total and right-sided soft signs for the responders and the nonresponders did not differ significantly. Left-sided visuospatial soft signs were significantly increased in treatment nonresponders compared to responders. These subtle neurological abnormalities may implicate a potential subgroup of OCD patients with poorer treatment response. This may have treatment implications and therefore serve as a screening tool in OCD.

Deficit of Executive Functions in Schizophrenia: Relationship to Neurological Soft Signs and Psychopathology

Cognitive deficits and neurological soft signs (NSS) have frequently been reported in schizophrenic patients and they both appear related to prominent negative symptoms. The aim of the present study was to examine the relationship between deficit of executive functioning, assessed by the Wisconsin Card Sorting Test (WCST), NSS and psychopathological dimensions of schizophrenia in order to address the issue of whether a typology of schizophrenic patients may be identifiable by clinical, neurological and neuropsychological features. A sample of 26 male schizophrenic patients was divided, on the basis of the performance on the WCST, into two subgroups (‘good performers’ and ‘poor performers’) that were compared for the prevalence and severity of NSS, assessed by the Neurological Evaluation Scale (NES), and for the psychopathological features, assessed using the Positive and Negative Syndrome Scale (PANSS). To test for between-group differences, ANOVA was conducted. The ‘poor performers’ group showed greater severity of NSS: significant differences emerged for the NES total score and for the ‘sequencing of complex motor acts’ score. However, no significant differences between the groups emerged for any PANSS score. These findings seem to indicate that a common neurobiological abnormality could underlie cognitive deficits, especially concerning executive functioning, and subtle neurological abnormalities often present in schizophrenia, but they appear to deny that such dysfunctional correlates of schizophrenia are related to a prominent negative symptomatology.

An assessment of thimerosal use in childhood vaccines.

On July 7, 1999, the American Academy of Pediatrics and the US Public Health Service issued a joint statement calling for removal of thimerosal, a mercury-containing preservative, from vaccines. This action was prompted in part by a risk assessment from the Food and Drug Administration that is presented here. The risk assessment consisted of hazard identification, dose-response assessment, exposure assessment, and risk characterization. The literature was reviewed to identify known toxicity of thimerosal, ethylmercury (a metabolite of thimerosal) and methylmercury (a similar organic mercury compound) and to determine the doses at which toxicity occurs. Maximal potential exposure to mercury from vaccines was calculated for children at 6 months old and 2 years, under the US childhood immunization schedule, and compared with the limits for mercury exposure developed by the Environmental Protection Agency (EPA), the Agency for Toxic Substance and Disease Registry, the Food and Drug Administration, and the World Health Organization. Delayed-type hypersensitivity reactions from thimerosal exposure are well-recognized. Identified acute toxicity from inadvertent high-dose exposure to thimerosal includes neurotoxicity and nephrotoxicity. Limited data on toxicity from low-dose exposures to ethylmercury are available, but toxicity may be similar to that of methylmercury. Chronic, low-dose methylmercury exposure may cause subtle neurologic abnormalities. Depending on the immunization schedule, vaccine formulation, and infant weight, cumulative exposure of infants to mercury from thimerosal during the first 6 months of life may exceed EPA guidelines. Our review revealed no evidence of harm caused by doses of thimerosal in vaccines, except for local hypersensitivity reactions. However, some infants may be exposed to cumulative levels of mercury during the first 6 months of life that exceed EPA recommendations. Exposure of infants to mercury in vaccines can be reduced or eliminated by using products formulated without thimerosal as a preservative.

Neurological and cognitive abnormalities associated with chronic petrol sniffing.

Substance abuse through the deliberate inhalation of petrol (petrol sniffing or gasoline sniffing) is prevalent in inner-urban and remote rural communities. Although acute toxic encephalopathy is a well-documented consequence of petrol sniffing, the neurological and cognitive effects of chronic petrol sniffing are unknown. A structured neurological examination and the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess neurological and cognitive function in 33 current-sniffers (individuals who had sniffed petrol for >6 months), 30 ex-sniffers (individuals who had sniffed petrol in the past but had abstained for 6 months) and 34 matched non-sniffers (individuals who had never sniffed petrol). No subject was, or had been, encephalopathic from petrol sniffing and all were residing in their community. Blood lead and hydrocarbon levels and information about petrol sniffing behaviour were obtained from each subject. When compared with non-sniffers, current-sniffers showed higher rates of abnormal tandem gait, rapid alternating hand movements, finger to nose movements, postural tremor, bilateral palmomental reflexes and brisk deep reflexes. Cognitive deficits occurred in the areas of visual attention, visual recognition memory and visual paired associate learning. Ex-petrol sniffers showed higher rates of abnormal tandem gait and bilateral palmomental reflexes and cognitive deficits in the areas of visual recognition memory and pattern-location paired associate learning. Blood lead levels and length of time of petrol sniffing correlated significantly with the magnitude of neurological and cognitive deficits. Blood hydrocarbon levels were not related to neurocognitive deficits, although this may have been due to methodological difficulties in obtaining hydrocarbon levels. These results suggest that subtle neurological and cognitive abnormalities do occur in individuals who abuse petrol but who do not have acute toxic encephalopathy and that the severity of these abnormalities is reduced with abstinence.

Neurologic findings in coronary artery bypass patients: Perioperative or preexisting?

Objectives/Design: This prospective study compares the incidence of preexisting neurologic findings in elective cardiac surgery patients presenting with and without coronary atherosclerosis. Setting: This single-center study was conducted at a tertiary care hospital. Participants/Interventions: After Review Board approval and obtaining written informed consent, 11 patients undergoing valvular heart surgery, 9 patients undergoing similar valvular procedures with concomitant coronary artery bypass surgery, and 4 patients undergoing coronary artery bypass surgery alone were enrolled. Preoperatively, all patients underwent a structured neurologic assessment, and the latter four additionally had preoperative magnetic resonance imaging. Measurements and Main Results: The patients, 9 of 24 of whom were female, were aged 46 to 78 years and, other than ischemic heart disease, had medical histories that were similar between groups, with the exception of one patient having scleroderma. None of the patients had a clinical history of neurologic or cerebrovascular disease. Nine percent (1 of 11) of the valve-only patients showed subtle preoperative neurologic abnormalities, compared with 89% (eight of nine) of the valve patients having concomitant coronary surgery and 100% (four of four) of coronary artery bypass-only patients. Additionally, brain imaging scans of all four coronary bypass patients showed nonspecific changes reported as scattered punctate areas of high signal less than 3 to 4 mm in diameter. Conclusion: This survey shows that both subtle neurological abnormalities and magnetic resonance imaging lesions can be found in a high percentage of patients with coronary atherosclerosis. Furthermore, this study indicates that without a standardized preoperative neurological examination, postoperative neurologic dysfunction cannot necessarily be ascribed to perioperative events.

Neurological signs in relation to cancer in patients with asbestosis.

OBJECTIVE: To chart the subtle neurological abnormalities in patients with asbestosis relative to possible development of cancer. METHODS: In 1979-81 a standardised neurological examination was made of 115 patients with...

Visual recognition memory in drug-exposed infants.

Visual recognition memory testing in high-risk infants has been shown to have significant predictive ability for later cognitive deficits. This study evaluated cognition in infants exposed prenatally to illicit stimulant drugs compared with nonexposed controls with a standardized test of visual recognition, the Fagan Test of Infant Intelligence (FTII). Thirty-six healthy, full-term infants with prenatal exposure to cocaine and/or amphetamines and 26 infants with no drug exposures, matched for race and socioeconomic status, were tested. Average FTII scores were significantly lower and the percentage testing at risk significantly higher in the drug-exposed group (p less than .01). Differences between groups were also noted in behaviors dealing with attention, distractibility, and activity level. These data support recent evidence from longitudinal studies showing that infants exposed to drugs prenatally may be at risk for later subtle neurological abnormalities and suggest these difficulties may be identifiable long before the children reach school age.

THE NEUROLOGY OF OBSESSIONAL SLOWNESS

Seventeen of 59 patients admitted to hospital for treatment of Obsessive-Compulsive Disorder (OCD) were found to have significant slowness, mainly due to difficulty in initiating goal-directed action and suppressing intrusive and perseverative behaviour. In this subgroup subtle neurological abnormalities were found more frequently than in healthy controls and included loss of motor fluency, hesitancy of initiation of limb movements, speech and gait abnormalities, cogwheel rigidity, complex repetitive movements and tics. Difficulties in cognitive set-shifting and complex spatial-and-shifting abilities were found on neuropsychological testing, but no correlation was found between these disturbances and either the degree of obsessionality or the severity of motor dysfunction. These results suggest that patients with obsessional slowness may have a dysfunction in the frontal-basal-ganglia loop system.

Cocaine alters behavioral states in fetal sheep

Intrauterine cocaine exposure causes subtle neurologic abnormalities in human newborn infants; however, the mechanism for these abnormalities is not known. To investigate whether cocaine alters fetal behavioral state, the electrocortical, electro-ocular and neck muscle electrical activity was monitored in 7 chronically instrumented fetal sheep before and during both saline and cocaine HCl infusions directly to the fetus. Saline infusion to the fetus had no effect on the percentage of time spent in rapid eye movement sleep compared to no infusion (37.5 ± 11.6% vs 46.3 ± 4.6%, mean ± SD, P > 0.1). Cocaine infusion directly to the fetus had no effect on fetal arterial pO 2, but did increase mean arterial pressure from 53.6 ± 15 mmHg to 61.0 ± 21 mmHg ( P < 0.01). In addition, during cocaine infusion, the percentage of time spent in rapid eye movement sleep dropped to 3.9 ± 5.1% ( P < 0.0001) and the average duration of rapid eye movement epochs decreased from 10.1 ± 3.0 min precocaine infusion to 1.9 ± 2.6 min during cocaine infusion ( P < 0.02). The influence of cocaine was noted in a frequency analysis of the electrocorticogram. The amplitude of the energy centered at 1 Hz during cocaine infusion (73.8 ± 4.0 dB) was greater than the amplitude during rapid eye movement sleep (65.5 ± 4.7 dB) and less than the amplitude during non-rapid eye movement periods (79.9 ± 4.5 dB) ( P = 0.01). Cocaine appears to alter fetal behavioral state directly and this may play a role in the abnormal behavior in newborn infants exposed to cocaine in utero.

Neurofibromatosis Type 1 (Recklinghausen's Disease)

Neurologic and cognitive function in neurofibromatosis type 1 (NF1) were assessed in a controlled pilot study of 13 pairs of siblings aged 6 to 27 years. One subject in each pair was affected with NF1, and the other, the control subject, was unaffected. Subjects with evidence of focal central nervous system disease were excluded. The 13 subjects with NF1 had no excess of mental retardation, attention-deficit disorder, or specific learning disorders (using Wilcoxon's Signed Rank Test and McNemar's Test for Symmetry). These subjects, however, had significantly higher scores for subtle neurologic abnormalities (21 vs 6) and significantly lower full-scale IQ scores (94 vs 105) than their unaffected siblings. The IQ scores of the affected subjects were not clustered at the lower end of the scale but showed a slight downward shift in distribution compared with those of their siblings. In addition, a visual-spatial orientation deficit was present in eight of nine affected subjects so evaluated. The findings suggest that subjects with NF1 have a widespread alteration of the brain during development that manifests as one or more specific types of neuropsychologic deficits.

Management and outcome of children with congenital hypothyroidism detected on neonatal screening in South Australia

Thirty-eight congenitally hypothyroid children who were detected in a neonatal screening programme have been treated for a mean period of 3.8 years (range, 0.5-8.5 years) by the maintenance of the free thyroxine index in the upper normal range as the main determinant of the dose of thyroxine. Only excessive elevation of, or serial rises in, thyroid stimulating hormone (TSH) level influenced the dose of thyroxine. This treatment strategy, which aims to avoid the potentially adverse effects of thyroxine overdosage, has often resulted in delayed return of TSH levels to normal, especially in athyrotic children (mean TSH +/- SD at one year of age in athyrotic children, 72 +/- 90 mU/L; in children with ectopic thyroid glands, 24 +/- 16 mU/L; normal range, 0-7 mU/L). The mean thyroxine dose of about 100 micrograms/m2 did not change significantly with age, and is lower than the doses that are sometimes quoted in the literature; athyrotic children require significantly more thyroxine (P less than 0.05) than those with ectopic thyroid glands. Symptoms and signs of congenital hypothyroidism, although subtle, were significantly more common (P less than 0.05 for symptoms and P less than 0.001 for signs) in athyrotic children compared with those with ectopic glands. No physical or developmental abnormality related to congenital hypothyroidism has been demonstrated on follow-up; mean height and weight percentiles approximate the 50th percentile at ages one to six years and mean developmental scores +/- SD at about two years of age by the Griffiths Mental Development Scale and at 4.5-6.5 years by the Wechsler Preschool and Primary Scale are 102.4 +/- 10.4 and 111.2 +/- 12.2, respectively. Long-term follow-up studies are necessary to exclude more subtle developmental and neurological abnormalities.

Infant Apnea: Polygraphic Studies and Follow-up Monitoring

Twenty-six infants with unexplained and apparently life-threatening apnea were evaluated clinically, underwent eight- or 12-hour polygraphic recordings during sleep, and were then observed on home monitors. The one exception was an infant who was treated with theophylline and not monitored at home. Clinical evaluation revealed a history of vomiting in 19 infants, gastroesophageal reflux (GER) on esophagram in 19, and subtle neurologic abnormalities in ten. Polygraphic studies revealed questionable EEG abnormalities in nine infants, abnormal rapid eye movement (REM) time in four, prolonged apnea in one, and increased frequency of brief mixed (central and obstructive) and obstructive apneas in five. Of the 11 infants who underwent pH monitoring during their polygraphic sleep studies, seven had at least one recorded episode of GER, but the episodes were not accompanied by apnea or bradycardia. Thirteen infants had a subsequent episode of apnea that required stimulation, and in eight infants, cardiopulmonary resuscitation was given. There was two deaths. Two infants subsequently developed seizure disorders. Three of the five infants who underwent surgical fundoplication had recurrent apneic episodes. GER commonly occurred in these infant apnea patients but did not correlate with the clinical outcome. Although subtle abnormalities may be detected by sophisticated polygraphic monitoring studies, they are not predictive of recurrent apnea or death. Home monitoring may be useful in detecting the infant at risk for recurrent life-threatening apnea and in providing some safeguard for that infant.

Is low-level lead pollution dangerous?

Present-day Americans are said to have about 500 times more lead in their skeletons than Peruvians of 1800 years ago.1 Lead pollution has become widespread in developed countries, especially from the use of lead in industry and in petrol and from its contamination of canned foods and some water. Never theless, lead poisoning, which was first described by the Greek physician poet Nikander in the second century BC,2 is very rare, being associated with high blood concentrations over 3-9 pimol/1 (80 (xg/100 ml), or occasionally over 2-9 (xmol/1 (60 (xg/100 ml.). The current debate centres on whether concentrations usually considered safe?under 1-9 pimol/1 (40 (xg/100 ml)?may in fact cause subtle neurological and behavioural abnormalities.