Cognitive functioning in patients with suspected chronic toxic encephalopathy: evidence for neuropsychological disturbances after controlling for insufficient effort

OBJECTIVES: Chronic toxic encephalopathy (CTE) caused by long term occupational exposure to organic solvents is still a controversial disorder. Neuropsychological testing is the cornerstone for diagnosing the syndrome, but can be negatively influenced by motivational problems. In this nationwide study, we investigated the neuropsychological functioning and psychological symptoms of a large group of patients with suspected CTE, and ruled out alternative explanations for their complaints, including suboptimal performance due to insufficient effort. METHODS: We studied participants with suspected CTE (n = 386) who were referred for further diagnosis to the Netherlands Centre of Occupational Diseases in the period 1998-2003 and who had completed the entire diagnostic protocol. Patients were excluded if there was the slightest suspicion that test performance had been negatively influenced by insufficient effort (n = 221), or if comprehensive assessment identified an alternative diagnosis (n = 80). Insufficient effort was defined by a combination of three indices. The neuropsychological test scores of the patient group (n = 85) were compared with those of a control group of building trade workers matched for sex, age, and educational level (n = 35). RESULTS: The patient group had significantly more psychological complaints and performed significantly worse than the control group on tests of speed of information processing and memory and learning. However, only a small percentage of the patients had clearly abnormal scores for cognitive speed (9%) or memory (8%). Attention, verbal abilities, and constructional functions were not disturbed. Exposure duration and cognitive complaints were significantly correlated, whereas the correlation between exposure duration and neuropsychological domain scores was not significant. CONCLUSIONS: Insufficient effort was present in a substantial part of the patient group. After minimising the likelihood that insufficient effort negatively influenced neuropsychological scores, we still found neuropsychological deficits in speed of cognitive processing and memory; however, these scores were clearly abnormal only in a minority of patients with suspected CTE. Screening instruments should focus on these domains.     

Multidisciplinary analysis of patients with extratemporal complex partial seizures. I. Intertest agreement

In 15 patients we hypothesized the origin of epilepsies to be 'extratemporal' based on videotaped seizures and surface EEG. Neuropsychological tests and neuroimaging (CAT, MRI, and PET scans) were then compared to the hypothesized ictal sites. Neuropsychological tests were abnormal in 86.6% and FDG-PET scans were abnormal in 73%. The neuropsychological tests and PET localized or lateralized areas of dysfunction to the same sites as electroclinical characteristics did in 85% of patients (P less than 0.01, Fisher exact test). No statistically significant correlation between lesion sites on CT and MRI and the ictal origin was observed due to the high proportion of normal or non-specific scans. These observations should be verified in a larger series of extratemporal seizures.     

Chronic cognitive sequelae after traumatic brain injury are not related to growth hormone deficiency in adults

Objective: The objective of the study was to asses the possible influence of hypothalamo–pituitary deficiencies, and growth hormone (GH) deficiency in particular, on cognition in adult patients with traumatic brain injury (TBI). TBI is a recently identified risk factor for cognitive deficits and hypopituitarism. Even the patients with favorable outcome after TBI may present with persistent bodily, psychosocial, and cognitive impairments, resembling patients with untreated partial or complete pituitary insufficiency. Design: We performed retrospective and cross‐sectional study of endocrine and cognitive function in TBI in 61 patients (aged 37.7 ± 1.7 years) of both sexes (44 m,17 f), at least 1 year after TBI (3.9 ± 0.6 years). Serum insulin‐like growth factor 1 (IGF‐I), thyroxin, thyroid‐stimulating hormone (TSH), follicle‐stimulating hormone (FSH), luteinizing hormone (LH), testosterone (in men), prolactin, and cortisol were measured, and GH secretion was assessed by growth hormone releasing hormone (GHRH) + growth hormone releasing peptide‐6 (GHRP‐6) test. Cognitive function was assessed by using a standard neuropsychological battery. Results: GH deficiency (GHD) and GH insufficiency (GHI) were found in 20 patients (32.8%). After adjustment for confounders [age, body mass index (BMI), education level, time elapsed from TBI], there were no significant differences in results of neuropsychological tests between patients with TBI with GHD, GHI, and normal GH secretion. There were no correlations of neuropsychological variables with stimulated peak GH secretion or IGF‐I level. Conclusions: GHD persists long after the TBI, independently of trauma severity and age at traumatic event. GH secretion is more sensitive to TBI than other pituitary hormones. No evidence is found for an association of cognitive function impairment and somatotropic axis impairment in adult patients tested more than 1 year after the TBI.     

MR序列优化组合在创伤性脑损伤的诊断价值

目的分析MR诊断创伤性脑损伤(TBI)的价值,探讨TBI患者MR一站式诊断的可行性。方法对260例TBI病例进行MR序列组合扫描,包括小角度激发快速梯度回波序列(FLASH)、流动衰减反转恢复序列(FLAIR)、自旋回波(SE)T1WI、快速自旋回波(TSE)T2WI,比较MR序列组合和CT对各种类型TBI诊断的差异。结果脑实质内出血61例,MR显示61例,CT显示53例;硬膜下出血55例,MR显示55例,CT显示49例;硬膜外出血45例,MR显示45例,CT显示40例;脑挫(裂)伤35例,MR显示35例,CT显示25例;蛛网膜下腔出血35例,MR显示31例,CT显示33例;弥漫性轴索损伤29例,MR显示29例,CT显示5例。MR序列组合准确显示病变256例,CT为209例,两者差异有极显著统计学意义(P0.01),MR序列组合总体诊断敏感性高于CT。结论 MR序列组合(FLASH\FLAIR\T1WI\T2WI)诊断创伤性脑损伤明显优于CT,可列为TBI常规检查方法,实行TBI一站式诊断。     

Why Don’t Neurosurgery Patients Return for Neuropsychological Follow-Up? Predictors for Voluntary Appointment Keeping and Reasons for Cancellation

Neuropsychological follow-up appointments are important for patients who have had intracranial surgery because cognitive deficits are common in this population and prognosis is not always optimistic. Unfortunately some patients cancel or do not show up. The current study attempted to identify predictors of non-attendance in this population. A total of 428 patients recruited over 2 years with a scheduled neuropsychological follow-up appointment after intracranial surgery in the St. Elisabeth Hospital, Tilburg, The Netherlands were included. Demographic, clinical, and other miscellaneous variables were extracted from medical records. Of this total population, 42% were non-attenders. The predictors of non-attendance were as follows: patients who had subdural hematomas and/or malignant tumors (compared to those who had other diagnoses prior to intracranial surgery); those who had been transferred to another hospital (compared to those sent home); those who had been referred for further medical treatment before the appointment; a shorter time interval between discharge and follow-up appointment; and finally, if the patient’s home was further away from the hospital. Patients who undergo intracranial surgery are a very heterogeneous group with different needs. Neuropsychological follow-up after surgery may be important for some patients (the better-functioning and/or those with cognitive complaints) but perhaps not for others (those with more severe prognoses and/or no complaints). We provide suggestions which should increase attendance in those who could benefit from follow-up neuropsychological assessment.     

Comprehensive Clinical Picture of Patients with Complicated vs Uncomplicated Mild Traumatic Brain Injury

To compare the acute clinical profile of patients with uncomplicated vs complicated mild TBI (MTBI), socio-demographic and medical history variables were gathered for 176 patients diagnosed with MTBI and with (complicated, N = 45) or without (uncomplicated, N = 131) positive findings on cerebral imaging. Neurological examination, neuropsychological assessment and self-evaluation of post-concussive symptoms were done at 2 weeks post trauma. Patients with complicated MTBI were more likely to show auditory and vestibular system dysfunction. Surprisingly, the uncomplicated group reported more severe post-concussive symptoms than patients with positive CT scans. The groups showed no other difference in neurological, psychological, or cognitive outcome. A complete neurological examination should be done acutely in patients with MTBI to determine more specific follow-up required.     

Sequential computerized tomographic appearance of strokes

Eighteen consecutive patients satisfying predefined clinical criteria for embolic strokes were prospectively studied by sequential computerized tomography (CT). Their findings were compared to CT scans obtained from patients presumed to have suffered thrombotic strokes. Our data reveal that the CT appearance of hemorrhagic infarction is likely to occur twice as frequently (22%) in CT scans of strokes presumed embolic than in those presumed thrombotic, where hemorrhagic infarction appeared at some time in 10% of the patients. No patient deteriorated with anticoagulation regardless of the CT appearance. In patients showing hemorrhagic infarction before anticoagulants, follow-up scans obtained after the administration of anticoagulants revealed resolution of the hemorrhagic aspect.     

The clinical spectrum of hemorrhagic infarction

The hospital records and head CT scans of 44 patients with hemorrhagic infarction were retrospectively analyzed. The majority of cases (73%) were embolic or possibly embolic in etiology, and 55% were not associated with anticoagulant therapy. Adverse prognosis was most clearly related to infarct size, underlying systemic illness, and symptomatic hemorrhage. Of the nineteen patients in whom serial CT scans documented conversion from bland to hemorrhagic infarction, 12 exhibited no clinical worsening at the time that hemorrhagic infarction was observed; the remaining seven, all of whom worsened, were receiving anticoagulant therapy at the time of documented conversion. Fourteen patients in whom anticoagulant therapy was used despite the findings of hemorrhagic infarction remained stable or improved during hospitalization.     

Correlation of a neuropsychologic syndrome with computer-tomographically defined focal lesions of the left brain hemisphere

The intention was to examine critically, which new possibilities, limitations and possible faultiness are to be expected in connexion with applying computerized tomography in the field of brain localization. The examinations concern the correlation of neuropsychological symptoms with focal cerebral lesions. From july 1980 until september 1982 52 persons out of all patients examined in our CT-department during this time, were chosen if they had computertomographically defined focal lesions of one brain hemisphere. They were further examined neurologically, neuropsychologically and by psychological tests using a well-connected plan. The results of 33 cases with circumscribed lesions of the left hemisphere are presented in details. The classification of psychological syndromes followed the most important features. A simple procedure for lesion mapping of CT informations, described by MAZZOCCHI and VIGNOLO (1978) was used for documentation and proof of inclusion of the cortical speech region in the examined brain lesions. Thus it was possible to compare the different patterns of lesions and to form groups of patients with a certain localization of the lesions. The correlations of these lesions with the neuropsychological findings were examined in each group. A high degree of correlation in the sense of the classic conception of brain localization of neuropsychological syndromes was found. The ideocinetic motor aphasia was confirmed as a frequent, well-defined syndrome in cases with lesions of the left lower parietal lobulus.     

Subcortical type cognitive impairment in herpes zoster encephalitis

Nine immunocompetent patients with acute herpes zoster encephalitis (HZE) were studied with the help of neurological, neuroradiological and neuropsychological investigations. All patients were treated with acyclovir. Neuropsychological performance was compared with that of a group of 16 healthy controls. Computed tomography of the head showed infarct-like hypodense lesions in two patients, involving the internal capsule in one case and the temporoparietal cortex and white matter in another. Hypoperfusion shown by single photon emission computed tomography, mostly involving the frontal areas bilaterally, was seen in six of the seven patients examined. Hyperperfusion as seen in herpes simplex encephalitis was not encountered. One patient remained mildly demented, but all the other patients recovered relatively well. Neuropsychological examination after acyclovir treatment showed a decline in memory and speed of cognitive processes, without circumscribed neuropsychological deficits. Six of the nine patients showed behavioural disinhibition, and mood changes were also observed. Memory impairment in HZE was not as global or as severe as is described after encephalitis due to herpes simplex virus. In HZE both the brain perfusion pattern and the neuropsychological test profile showed features compatible with subcortical dysfunction. Received: 3 June 1996 Received in revised form: 7 November 1996 Accepted: 11 November 1996     

Clinical significance of subcortical vascular disease in patients with mild cognitive impairment

Patients with mild cognitive impairment (MCI) typically present with memory complaints. Some of these patients have subcortical vascular disease on computed tomography (CT) scan, namely white matter changes and lacunar infarcts, however it is not known whether these findings are associated with more pronounced cognitive deficits. In the present study we compare demographic, clinical and neuropsychological characteristics of MCI patients according to the presence or the absence of subcortical vascular disease. Forty consecutive patients with memory complaints, at least one neuropsychological memory test below 1 SD the normal for age and education, and maintained activities of daily living, were included. Patients with dementia, history of stroke or transient ischemic attack, or other brain disorders, were excluded. Twenty-five (62.5%) patients with MCI had no ischemic lesions on CT scan, and 15 (37.5%) were found to have subcortical vascular changes. MCI patients with subcortical vascular changes were older (77.1 +/- 6.8 vs. 70.8 +/- 7.5 years old), and more often males. The number of vascular risk factors, the frequency of neurological signs, the Hachinski score and the neuropsychological tests scores were not significantly different. The presence of subcortical vascular disease on CT scan is frequent in older patients with MCI, but does not appear to be associated with the severity of cognitive deficits.     

Functional outcome is tied to dynamic brain states after mild to moderate traumatic brain injury

The current study set out to investigate the dynamic functional connectome in relation to long‐term recovery after mild to moderate traumatic brain injury (TBI). Longitudinal resting‐state functional MRI data were collected (at 1 and 3 months postinjury) from a prospectively enrolled cohort consisting of 68 patients with TBI (92% mild TBI) and 20 healthy subjects. Patients underwent a neuropsychological assessment at 3 months postinjury. Outcome was measured using the Glasgow Outcome Scale Extended (GOS‐E) at 6 months postinjury. The 57 patients who completed the GOS‐E were classified as recovered completely (GOS‐E = 8; n = 37) or incompletely (GOS‐E < 8; n = 20). Neuropsychological test scores were similar for all groups. Patients with incomplete recovery spent less time in a segregated brain state compared to recovered patients during the second visit. Also, these patients moved less frequently from one meta‐state to another as compared to healthy controls and recovered patients. Furthermore, incomplete recovery was associated with disruptions in cyclic state transition patterns, called attractors, during both visits. This study demonstrates that poor long‐term functional recovery is associated with alterations in dynamics between brain networks, which becomes more marked as a function of time. These results could be related to psychological processes rather than injury‐effects, which is an interesting area for further work. Another natural progression of the current study is to examine whether these dynamic measures can be used to monitor treatment effects.     

Longitudinal study of objective and subjective cognitive performance and psychological distress in OEF/OIF Veterans with and without traumatic brain injury

Objective: To describe changes in post-deployment objective and subjective cognitive performance in combat Veterans over 18 months, relative to traumatic brain injury (TBI) status and psychological distress. Method: This prospective cohort study examined 500 Veterans from Upstate New York at four time points, six months apart. TBI status was determined by a structured clinical interview. Neuropsychological instruments focused on attention, memory, and executive functions. Subjective cognitive complaints were assessed with the Neurobehavioral Symptom Inventory (NSI). A psychological distress composite included measures of post-traumatic stress disorder (PTSD), depression, and generalized anxiety. Results: Forty-four percent of the sample was found to have sustained military-related TBI, 97% of which were classified as mild (mTBI), with a mean time since injury of 41 months. Veterans with TBI endorsed moderate cognitive symptoms on the NSI. In contrast to these subjective complaints, mean cognitive test performance was within normal limits at each time point in all domains, regardless of TBI status. Multilevel models examined effects of TBI status, time, and psychological distress. Psychological distress was a strong predictor of all cognitive domains, especially the subjective domain. Substantial proportions of both TBI+ and TBI? groups remained in the clinically significant range at the initial and final assessment for all three distress measures, but the TBI+ group had higher proportions of clinically significant cases. Conclusions: Objective cognitive performance was generally within normal limits for Veterans with mTBI across all assessments. Psychological distress was elevated and significantly related to both objective and subjective cognitive performance.     

Frequent Hemorrhagic Lesions in Cerebral Toxoplasmosis in AIDS Patients

Cerebral toxoplasmosis is a frequent complication in immunosuppressed patients such as AIDS (acquired immunodeficiency syndrome). Frequently, lesions are located deep in the brain which are inaccessible for biopsy making rapid diagnosis dependent on accurate interpretation of neuroimaging findings. The commonest cranial CT findings reported in toxoplasmosis are ring enhancing hypodense lesions in basal ganglia or cortical gray matter. Hemorrhage has only rarely been described and is usually seen following antitoxoplasma treatment. We reviewed the records of 11 AIDS patients with cerebral toxoplasmosis and found multiple hemorrhagic cerebral, cerebellar, or brain stem lesions in 7 of 11 patients. Six patients had hemorrhage at the time of initial clinical presentation and one developed hemorrhage following 2 weeks of antitoxoplasma treatment. We conclude that hemorrhagic lesions are frequently found on cranial MRI scans in cerebral toxoplasmosis. AIDS patients presenting with hemorrhagic cerebral lesions should be considered for a trial of presumptive antitoxoplasma treatment.     

Ventricle size, cortical atrophy and the relationship with neuropsychological status in closed head injury: a quantitative analysis

Forty-eight patients with a history of moderate to severe closed-head injury (CHI) were examined with neuropsychological measures and computerized tomography (CT). CT scans were assessed with computerized techniques to determine estimated ventricular volumes (VV) and the degree of cortical atrophy (ATVOL) in each patient. VV's then were used to determine volumetric ventricle-brain ratios (VBR) to correct for head size. The WAIS, Wechsler Memory Scale (WMS) and Halstead-Reitan Neuropsychological Test Battery (HRNTB) were administered to all patients. Correlational analyses were undertaken between VBR and ATVOL measures. PIQ but not VIQ was negatively correlated with VBR and ATVOL, particularly in terms of right-hemisphere measures. WMS Memory Quotient (MQ) also was negatively correlated with VBR and ATVOL with no lateralization. Several HRNTB measures similarly were correlated with ventricular and atrophy estimates. Correlational results also were analyzed in terms of the influence of higher and lower VBR and ATVOL, and the prior presence of hematoma. Results are discussed in terms of the latent effects of cerebral damage secondary to CHI on neuropsychological functioning.     

Neuropsychological test performance, brain morphological measures and CSF monoamine metabolites in schizophrenic patients

Twenty-three drug-free patients with an acute schizophrenic psychosis were studied by clinical rating scales, neuropsychological tests, computed tomography (CT) of the brain and analysis of monoamine metabolites in the cerebrospinal fluid (CSF). The psychological tests used were the Swedish version of the Wechsler-Bellevue Intelligence scale (WBI) and the Block Design test. The patients' performance in the Block Design test was negatively correlated to the width of the third and lateral ventricles. Test profiles indicative of schizophrenic cognitive impairment and left hemisphere dysfunction correlated significantly with a wide third ventricle, but not with the size of the lateral ventricles. Patients with a test profile indicative of left hemisphere dysfunction also had wider Sylvian fissures than the remaining patients. Neuropsychological test scores did not correlate with the CSF levels of the monoamine metabolites HVA, MHPG and 5-HIAA. Positive psychotic and autistic symptoms did not correlate with psychological test results, monoamine metabolites or with CT measures. The association between neuropsychological impairment and enlargement of the brain ventricles is in line with previous findings indicating that a subgroup of schizophrenic patients may be identified by neuropsychological and morphological methods.     

Apolipoprotein E epsilon 4 and short-term recovery from predominantly mild brain injury

OBJECTIVE: To determine whether APOE genotype explained variability in short-term recovery from predominantly mild traumatic brain injury (TBI). METHODS: A total of 87 adult patients presenting with mild or moderate TBI to a shock trauma center were enrolled prospectively. A battery of 13 neuropsychological tests was administered twice, at approximately 3 and 6 weeks after injury. Eighty of 87 patients were successfully genotyped for APOE using a buccal swab technique. RESULTS: Ninety percent of study patients had mild TBI (Glasgow Coma Scale score of 13 to 15); 18 (22.5%) had one APOE epsilon 4 and none had two epsilon 4 alleles. After adjusting for potential confounders, patients positive for the APOE epsilon 4 allele had lower mean scores on 12 of 13 neuropsychological outcomes at visit 1 compared with APOE epsilon 4-negative patients. Two of the differences were significant (grooved pegboard test, p = 0.005; paced auditory serial addition task 2.8-second trial, p = 0.004). At visit 2, APOE epsilon 4-positive patients had lower adjusted mean scores on 11 of the 13 neuropsychological outcomes. None of the differences was significant. CONCLUSIONS: APOE genotype may influence the severity of the acute injury. However, with no consistent pattern to the recovery curves, it is not clear if APOE genotype influences the rate of recovery.     

Awareness of behavioral limitations after traumatic brain injury: A cross-cultural study of New Zealand maoris and non-maoris

Forty-one New Zealand traumatic brain injury (TBI) patients were studied using the Patient Competency Rating Scale (PCRS) and selected neuropsychological tests. An attempt was made to replicate earlier reported findings in American TBI patients and determine if cultural factors influence self-perceptions (i.e., awareness) of impairments after brain injury. TBI patients with Maori ancestry were compared to New Zealanders with non-Maori (English) ancestry. Both groups showed no correlation between their actual neuropsychological status and self-reports of behavioral competency. In contrast, the ratings of their relatives concerning their behavioral competency were correlated with the patient's neuropsychological test performance. Maori TBI patients reported less behavioral competency than non-Maori TBI patients. Non-Maori TBI patients' performance on the PCRS replicated the findings obtained with American TBI patients. An earlier finding of slow speed of left-hand finger tapping in patients who overestimate their behavioral competency was not replicated, but a confounding of ethnicity and finger-tapping speed was observed. Brain damage may contribute to patients' misperceptions of their behavioral competency, but cultural factors also seem to play an important role.     

Neuropsychological and Behavioral Measures of Attention Assess Different Constructs in Children With Traumatic Brain Injury

Neuropsychological and behavioral measures are used to assess attention, but little convergence has been found between these two assessment methods. However, many prior studies have not considered attention as a multicomponent system, which may contribute to this lack of agreement between neuropsychological and behavioral measures. To address this the current study examined the relationship between the neuropsychological measures that comprise a four-component model of attention and parent-report behavioral ratings of attention problems and hyperactivity. A total of 65 children and adolescents who had sustained a traumatic brain injury (TBI) were included in the study. Principal components analysis identified the four attention components in this sample, which accounted for 80.9% of the variance. However, correlations between the neuropsychological measures of attention and behavioral ratings of attention and hyperactivity were low and non-significant. This minimal correspondence suggests that neuropsychological and behavioral measures assess different aspects of attentional disturbances in children with TBI.     

Long-term neurological and neuropsychological outcome in patients with severe traumatic brain injury

Background

Severe traumatic brain injury (TBI) remains a major cause of death and disability worldwide. The aim of the study was to evaluate predictors for neurological and neuropsychological long-term outcome in patients with severe TBI treated according to an intracranial pressure (ICP-) targeted therapy.

Methods

From 08/2005 to 12/2008, 46 patients with severe TBI and more than 12 h of intensive care treatment were included in this study. Neurological outcome was assessed with the Glasgow Outcome Scale (GOS). Neuropsychological performance assessing 9 different domains was evaluated at long-term follow-up (median 20.5 months; range 10–46). Logistic regression was used to identify favourable outcomes according to the GOS and Fisher's exact tests were used to identify predictors of severe neuropsychological impairments at follow-up.

Results

Twenty-nine patients were available for neuropsychological assessment at long-term follow-up. Only 2 out of 29 patients presented normal or average neuropsychological findings throughout all 9 neuropsychological domains at long-term follow-up. The percentage of a favourable outcome (GOS 4-5) increased from 13.8% at hospital discharge to 75.8% at rehabilitation discharge to 79.3% at long-term follow-up, respectively. Age ≤40 was found to be a strong predictor of favourable outcome at follow-up (OR 5.95, 95% CI 1.41 25.00, p = 0.015). The GOS at hospital discharge was not a predictor for severe impairments in any of the 9 different neuropsychological domains (all p-values were p > 0.268). In contrast, the GOS at rehabilitation discharge was found to be a predictor of severe impairments at follow-up in all but one domain assessed (all p-values less than p < 0.038).

Conclusions

The GOS at rehabilitation discharge should be regarded as a better predictor for neuropsychological impairments at long-term follow-up than the GOS at hospital discharge. Even in patients with favourable GOS after finishing a course of rehabilitation, three quarters of these patients may have at least one severe neuropsychological deficit. Therefore, it remains of paramount importance to provide long-term neuropsychological support to further improve outcome after TBI.