Neuropsychological Follow-up Research Articles

Pyrethroid insecticide exposure and cognitive developmental disabilities in children: The PELAGIE mother–child cohort

Pyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children's neurodevelopment.The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders.Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children's cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend=0.04 and P-trend<0.01, respectively) and with working memory scores (P-trend=0.05 and P-trend<0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA).Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importance.

Cognitive outcome of pallidal deep brain stimulation for primary cervical dystonia: One year follow up results of a prospective multicenter trial.

Pallidal deep brain stimulation (DBS) is effective in alleviating motor symptoms of medication refractory cervical dystonia, but little is known about effects on cognitive functions. As part of the first randomized, sham-controlled multicenter trial on DBS in medication-refractory primary cervical dystonia (ClinicalTrials.gov, number NCT00148889), a subgroup of 13 patients aged 39 to 69 underwent prospective neuropsychological long-term follow-up assessments. Various cognitive domains (memory, executive functions, attention, visual perception, mental arithmetic and verbal intelligence) were examined before and after 12 months of continuous DBS. Only the number of produced words in a verbal fluency task which included alternating categories decreased after stimulation (p = 0.020). All other cognitive domains remained unchanged. These findings indicate that long-term pallidal DBS for the treatment of primary cervical dystonia seems to be safe regarding global cognitive functioning.

Morphological derivation overflow as a result of disruption of the left frontal aslant white matter tract

The frontal aslant tract (FAT) is a recently described major connection between the preSMA and Broca’s area, whose functional role remains undefined. In this study we examined a patient presenting a morphological overregularization strategy in a verb generation task during awake surgery. This specific language deficit coincided with brain tumor resection at the level of the left FAT. During the task execution the patient formed the non-existent verbs by applying a morphological derivation rule to the given nouns, instead of retrieving the appropriate verbs. DTI results confirmed left FAT damage. Neuropsychological follow-up showed that this morphological derivation impairment partially persisted after surgery, whereas the results on a wide spectrum of other language-related tasks remained satisfactory. Additionally, we compared the pre- and the post-operational fMRI activation maps for the same verb generation task. We discuss the potential role of the left FAT in the morphological derivation process and in lexical retrieval.

Long-term neuropsychological follow-up in a patient with α-mannosidase

Long-term neuropsychological follow-up in a patient with α-mannosidase

Clinical news: report from the European Society For Medical Oncology

British Journal of Hospital MedicineVol. 75, No. 11 Clinical NewsClinical news: report from the European Society For Medical OncologySusan MayorSusan MayorSearch for more papers by this authorSusan MayorPublished Online:10 Nov 2014https://doi.org/10.12968/hmed.2014.75.11.610AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Symonds P, Grouley C, Davidson S et al. (2014) CIRCCa: A randomised double blind phase II trial of carboplatin-paclitaxel plus cediranib versus carboplatin-paclitaxel plus placebo in metastatic/recurrent cervical cancer. (CRUK Grant Ref: C1256/A11416). Abstract LBA25_PR Google ScholarRyan CJ, Smith MR, Fizazi K et al. (2014) Final overall survival (OS) analysis of COU-AA-302, a randomized phase 3 study of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) without prior chemotherapy. Abstract 753O. www.webges.com/cslide/library/esmo/browse/search/pBC#9f9k02Lm (accessed 31 October 2014) Google ScholarAmant F, Vandenbroucke T, Verheecke M et al. (2014a) 268PD_PR Cancer during pregnancy: A case-control analysis of mental development and cardiac functioning of 38 children prenatally exposed to chemotherapy. www.webges.com/cslide/library/esmo/browse/itinerary/478/2014-09-27#9fad (accessed 29 October 2014) Google ScholarAmant F, Vandenbroucke T, Verheecke M et al. (2014b) LBA49_PR - Long-term neuropsychological and cardiac follow-up of children and adults who were antenatal exposed to radiotherapy. www.webges.com/cslide/library/esmo/browse/itinerary/478/2014-09-27#9fad (accessed 29 October 2014) Google ScholarSwain S, Kim S, Cortes J et al. (2014) Final overall survival (OS) analysis from the CLEOPATRA study of first-line (1L) pertuzumab (Ptz), trastuzumab (T), and docetaxel (D) in patients (pts) with HER2-positive metastatic breast cancer (MBC). Abstract 350O_PR Google Scholar FiguresReferencesRelatedDetails 2 November 2014Volume 75Issue 11ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 10 November 2014 Published in print 2 November 2014 Information© MA Healthcare LimitedPDF download

Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type

Increased peripheral and central nervous system cortisol levels have been reported in Alzheimer's disease (AD) and may reflect dysfunction of cerebral components of the hypothalamic-pituitary-adrenal (HPA) axis. However, brain exposure to high cortisol concentrations may also accelerate disease progression and cognitive decline. The objectives of this study were to investigate whether HPA-axis dysregulation occurs at early clinical stages of AD and whether plasma and CSF cortisol levels are associated with clinical disease progression. Morning plasma and CSF cortisol concentrations were obtained from the subjects with AD dementia, mild cognitive impairment of AD type (MCI-AD), MCI of other type (MCI-O), and controls with normal cognition included in a multicenter study from the German Dementia Competence Network. A clinical and neuropsychological follow-up was performed in a subgroup of participants with MCI-AD, MCI-O, and AD dementia. CSF cortisol concentrations were increased in the subjects with AD dementia or MCI-AD compared with subjects with MCI-O or normal cognition. After controlling for possible confounders including CSF measures of amyloid beta1–42 and total tau, higher baseline CSF cortisol levels were associated with faster clinical worsening and cognitive decline in MCI-AD. The findings suggest that HPA-axis dysregulation occurs at the MCI stage of AD and may accelerate disease progression and cognitive decline.

Neurocognitive and Seizure Outcomes of Selective Amygdalohippocampectomy versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy.

Objective. To report our institutional seizure and neuropsychological outcomes for a series of patients with mesial temporal lobe epilepsy (mTLE) undergoing anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SelAH) between 2004 and 2011. Methods. A retrospective study of patients with mTLE was conducted. Seizure outcome was reported using time-to-event analysis. Cognitive outcome was reported using the change principal in component factor scores, one each, for intellectual abilities, visuospatial memory, and verbal memory. The Boston Naming Test was used for naming assessment. Language dominant and nondominant resections were compared separately. Student's t-test was used to assess statistical significance. Results. Ninety-six patients (75 ATL, 21 SelAH) were included; fifty-four had complete neuropsychological follow-up. Median follow-up was 40.5 months. There was no statistically significant difference in seizure freedom or any of the neuropsychological outcomes, although there was a trend toward greater postoperative decline in naming in the dominant hemisphere group following ATL. Conclusion. Seizure and neuropsychological outcomes did not differ for the two surgical approaches which is similar to most prior studies. Given the theoretical possibility of SelAH sparing language function in patients with epilepsy secondary to mesial temporal sclerosis and the limited high-quality evidence creating equipoise, a multicenter randomized clinical trial is warranted.

Long-Term Neuropsychological and Cardiac Follow-Up of Children and Adults Who Were Antenatal Exposed to Radiotherapy

ABSTRACT Aim: The use of radiation in medical diagnostics and treatment is standard of care. Apart from deductions from atom bomb and nuclear plant disaster survivors, there are scarce data on the long-term outcome after antenatal exposure to medical radiation. We aimed to assess the general health, cardiac and neuropsychological outcome of children in utero exposed to radiotherapy. Methods: Women treated with radiotherapy during pregnancy were retro- and prospectively registered by the International Network on Cancer, Infertility and Pregnancy (INCIP). Children were assessed at 1.5, 3.0, 6.0 or 9.0 years of age, by echocardiography, a clinical neurological examination, cognitive tests and questionnaires regarding health and behavior. Adults were examined by echocardiography and questionnaires regarding health and behavior. Echocardiographic data were compared to an age- and gender-matched control group and neurocognitive data to test specific age-appropriate norms. Results: Sixteen children (median age: 6.0 years, range 1.5–9.6) and ten adults (median age: 33.0 years, range 22.0–49.0) antenatal exposed to radiotherapy from Belgium, The Netherlands and Italy were enrolled. Median maternal and estimated fetal irradiation were 48 Gy (range, 12–70) and 91 mGy (range, 0–1690), respectively. Conventional and advanced cardiac function measurements were normal. Overall neuropsychological, behavioral and general health outcomes were within normal ranges. No linear relationship was found between fetal dose of radiation and cognitive outcome. One child revealed a severe cognitive delay, however this child was exposed to a relatively low dose of radiotherapy (34 mGy) in addition to other confounding pregnancy complications. The mother suffered from an aggressive non-hodgkin tumor of the brain with impact on her general state (maternal somnolence, hemiplegia and intravenous nutrition) followed by preterm delivery. Conclusions: The overall long-term cardiac, neuropsychological, behavioral and general health outcomes after prenatal exposure to radiotherapy appear to be within normal ranges. Larger series are needed to strengthen these findings. Disclosure: All authors have declared no conflicts of interest.

Neuropsychological follow-up at school age of children with asymmetric ventricles or unilateral ventriculomegaly identified in utero.

To examine the long-term neuropsychological outcome of children with a prenatal diagnosis of asymmetric ventricles or unilateral ventriculomegaly. A clinic-based neuropsychological study. Paediatric neurology clinic. Thirty-three of 41 children, previously assessed at kindergarten age, with asymmetric ventricles or unilateral ventriculomegaly identified in utero, were recruited at school age for a neuropsychological follow-up. All children, 9-11 years of age, underwent a battery of neuropsychological tests and the parents completed behavioural rating questionnaires. Results of the neuropsychological assessment and parents' questionnaires. There were no significant differences between children diagnosed with either asymmetric ventricles or unilateral ventriculomegaly in most parameters relative to the general population; the full-scale IQ scores were 103.13 ± 12.43 and 103.56 ± 10.5, respectively. A significantly lower performance was found only on one measure of attention among the unilateral ventriculomegaly group and on writing speed tasks among the asymmetric ventricles group. Both study groups showed significantly higher scores than expected in the normal population on a verbal fluency test. Comparison of both groups combined with the normative population yielded significantly lower scores only in attention tests. Yet, the clinical population showed significantly higher scores on writing accuracy, processing speed and verbal fluency and lower rates of executive dysfunction. Asymmetric ventricles or unilateral ventriculomegaly identified in utero does not appear to affect long-term mental development and school achievements. Further prospective research on a larger sample is needed in order to confirm our findings.

Neurocognitive changes in tertiary neurosyphilis: a retrospective chart review.

Since the beginning of the new millennium, prevalence of syphilis has re-increased and is once again, a major public health problem. Neurosyphilis is the extension of syphilitic infection to the nervous system. It is considered by many as a cause of reversible dementia, when treated early. However, scarce data exist on the evolution of cognitive and behavioral impairments in patients affected by tertiary neurosyphilis. The aim of this study was to explore the cognitive and behavioral changes in a cohort of patients diagnosed with neurosyphilis. A retrospective study based on systematized chart review between 2000 and 2012 in a large neurological tertiary care facility. Clinical evaluations by treating physicians. Eighteen patients were identified with tertiary neurosyphilis. Out of this group, only two had systematic neuropsychological follow-up despite physician reports of significant and persistent cognitive and psychiatric changes. For these two cases, only slight improvements were noted in memory and executive skills while improvements in attention were marked. None of our patients had previous psychiatric history yet a large proportion developed symptoms after the infection. Although neurosyphilis is traditionally considered a reversible form of dementia, we found limited support for this claim in our two patients with close follow-up. Quality data on the cognitive and psychiatric changes in the rest of our cohort was dramatically lacking, and this could not be explained by absence of symptoms at presentation. Given the recrudescence of syphilis, we propose a systematic approach to the evaluation and follow-up of this disorder.

Bihemispheric gunshot wounds: survival and long-term neuropsychological follow-up of three siblings.

Penetrating gunshot wounds to the head (GSWH) have notoriously poor outcomes with extremely high mortality. Long-term follow-up data of affected children is scant in the medical literature. This report summarizes clinical presentation, management, and long-term outcomes from three children who survived "execution style" frontal, bihemispheric gunshot wounds with no or minimal surgical intervention. A retrospective chart review of available medical records and outcomes from standardized, validated psychological instruments was undertaken, summarized, and evaluated. Despite bihemispheric injuries in each patient, no patient required operative intervention. Each child survived without readily evident neurologic impairment; however, the extent of impaired executive function varied widely, and severe disinhibition remains profoundly disabling in one survivor. Bihemispheric penetrating gunshot injuries are not uniformly fatal and can occasionally be associated with long-term favorable survival; however, impaired executive function has significant potential to be profoundly disabling in these injuries.

Neurocognitive long term follow-up study on drowned children

Aim of the studyReport cognitive and neurological outcome later in life of surviving drowned children who had received CPR either from bystanders or from emergency medical services (EMS) units. MethodsForty children who had drowned and admitted to pediatric intensive care unit after successful CPR between 1985 and 2007, were eligible for the study. Of those 21 gave a consent for neurological and neuropsychological examinations. All data are expressed as median (interquartile range). Mann-Whitley U, Wilcoxon signed ranks and Chi square tests were used. ResultsThe median age of the 21 patients at drowning was 2.4 (1.8, 5.5) years and 12.5 (8.6, 19.4) years at the time of neurological and neuropsychological examination. The median interval between the drowning accident and examinations was 8.1 (5.4, 14.4) years. Twelve patients (57.1%) had either signs of minor (6/21) or major neurological dysfunction (6/21). Eight subjects (40.0%) had full-scale intelligence quotient (FIQ) of less than 80 (range 20–78). The median estimated submersion time of the subjects with normal FIQ was 3.5 (2.0, 7.5)min, which was significantly shorter than for those with FIQ<80, 12.5 (5.0, 22.5)min (p=0.0013). Cognitive or neurologic deficits were detected in 17 of the 21 subjects, although 11 of them were reported to have a full recovery at the hospital discharge. ConclusionsThis study showed that 57% of the drowned and resuscitated children had neurological dysfunction and 40% a low FIQ. Neurological and neuropsychological long term follow-up in drowned children is highly recommended.

Neurocognitive Impairment in Whipple Disease with Central Nervous System Involvement

Young-onset dementias pose a major challenge to both clinicians and researchers. Cognitive decline may be accompanied by systemic features, leading to a diagnosis of "dementia plus" syndromes. Whipple disease is a rare systemic illness characterized by arthralgias, chronic diarrhea, weight loss, fever, and abdominal pain. Central nervous system involvement, including severe cognitive deterioration, may precede systemic manifestations, appear during the course of the disease, or even be the only symptom. We report a previously highly functional 48-year-old man whom we first suspected of having early-onset neurodegenerative dementia but then diagnosed with Whipple disease based on a detailed clinical and laboratory evaluation. Initial neuropsychological evaluation revealed marked impairment in the patient's fluid intelligence and severe cognitive deficits in his information processing speed, complex attention, memory, visuomotor and construction dexterities, problem solving, and executive functions. At neuropsychological follow-up 21 months later, his information processing speed had improved only slightly and deficits persisted in his other cognitive functions. Repeat brain magnetic resonance imaging at that time showed that he had responded to antibiotic treatment. Because Whipple disease can cause young-onset "dementia plus" syndromes that may leave patients with neurocognitive deficits even after apparently successful treatment, we recommend comprehensive neuropsychological assessment for early detection of residual and reversible cognitive processes and evaluation of treatment response.

Can high central nervous system penetrating antiretroviral regimens protect against the onset of HIV-associated neurocognitive disorders?

To assess changes over time in neuropsychological test results (NPr) and risk factors among a regularly followed HIV-infected patient population. Prospective cohort of HIV-infected patients randomly selected to undergo neuropsychological follow-up. Test score was adjusted for age, sex and education. Patients were divided into five groups: normal tests, neuropsychological deficit (one impaired cognitive domain), asymptomatic neurocognitive disorders (ANIs), mild neurocognitive disorders (MNDs) and HIV-associated dementia (HAD). Demographic and background parameters including CSF drug concentration penetration effectiveness (CPE) score 2010 were recorded. Changes in NPr and associated risk factors were analyzed. Two hundred and fifty-six patients underwent neuropsychological tests and 96 accepted follow-up approximately 2 years later. The groups were comparable. Upon neuropsychological retesting, six patients improved, 31 worsened and 59 were stable. The proportion of patients with HIV-associated neurocognitive disorders (HANDs) rose from 26 to 45%, with ANIs and MNDs still mostly represented. Most patients initially diagnosed with HANDs remained stable, five of 25 showed clinical improvement and three of 25 deteriorated. Of 33 patients with normal tests, four deteriorated, whereas 24 of 38 with initial neuropsychological deficit had poorer NPr, and contributed most of the new HAND cases. Patients with clinical deterioration had a lower CPE score both at inclusion (6.9 vs. 8.1; P = 0.005) and at the end of follow-up (7.2 vs. 7.8; P = 0.08) than those with improved or stable performance. This was confirmed by multivariate analysis. Patients with higher CPE scores upon inclusion and at the end of follow-up were at lower risk of clinical worsening, suggesting that combination antiretroviral therapy with better CSF penetration could protect against cognitive deterioration.

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.

Access to Neuropsychologic Services After Pediatric Brain Tumor

BackgroundIncreasing survival rates for children with brain tumors creates a greater need for neuropsychologic follow-up and intervention. The aim of this study was to evaluate rates of referral by medical doctors to neuropsychologic services and patient and treatment factors that differentiated referred and nonreferred patients. MethodsData were retrieved from medical records of all pediatric brain tumor patients in southern Sweden diagnosed between 1993 and 2004 who survived more than 1 year (n = 132). Characteristics of the patients, the cancer, and treatment received were then compared for patients who were and were not referred for neuropsychologic examination during that period. ResultsSixty-four (48%) of the pediatric brain tumor patients were referred for neuropsychologic evaluation. These patients had significantly larger tumors, more recurrences of cancer, and increased intracranial pressure at diagnosis when compared with the nonreferred group (n = 68). However, most of the patients in the nonreferred group either had significant risk factors for cognitive impairment or were reporting impairments that would suggest a referral was warranted. ConclusionsGiven the high rates of cognitive impairment in children with brain tumors, referral to neuropsychologic services should be considered in all survivors. In addition to improving long-term adjustment, systematic referral can provide data on cognitive impairments, making it possible to evaluate different cancer treatment protocols not only in terms of survival but also in terms of quality of survival. Greater efforts are needed to disseminate and raise awareness about published guidelines on the long-term care of pediatric brain tumor patients.

Cognitive Performances and Mild Cognitive Impairment in Idiopathic Rapid Eye Movement Sleep Behavior Disorder: Results of a Longitudinal Follow-Up Study

To investigate the capacity of neuropsychological deficits in idiopathic rapid eye movement sleep behavior disorder (iRBD) to predict the development of dementia and/or parkinsonism. Prospective longitudinal follow-up study. Tertiary sleep center. Twenty patients with initial iRBD (19 males, mean age 66.1 ± 7.1) underwent a clinical and neuropsychological follow-up within a mean of 43 ± 19 months. Neuropsychological performances at baseline were compared with those of healthy controls matched for sex, age, and education. Discontinuation of clonazepam at least 7 days before the follow-up evaluation. At follow-up, the Wilcoxon test showed a significant worsening of scores on Raven Colored Matrices 47 (P = 0.01), Attentive matrices (P = 0.002), phonemic (P = 0.04) and sematic (P = 0.04) fluency. Thirteen patients (65%) showed cognitive deterioration involving multiple domains. Of these, four patients (20%) maintained a stable cognitive dysfunction and nine (45%) showed a progression of cognitive dysfunction: six (30%) in constructional abilities (P = 0.03), four (20%) in short-term memory (P = NS), three (15%) in executive functions and non-verbal logic (P = NS), one (5%) in verbal fluency (P = NS), and one (5%) in long-term memory (P = NS) (McNemar test). Seven patients (35%) retained a normal cognitive profile. Mild cognitive impairment (MCI) was diagnosed at baseline in seven patients (35%). At follow-up, three of these patients showed overt dementia that was accompanied by parkinsonism in all cases; one had worsened from non-amnesic single-domain to nonamnesic multiple-domain MCI, two were stable, and one patient no longer met the criteria for MCI. Four patients (20%) without MCI at baseline had MCI at follow-up. Patients who developed MCI/dementia had an older age at disease onset (65.8 ± 5.4 versus 56.8 ± 9.3; P = 0.01) compared with those who did not. Our findings corroborate evidence that visuospatial abilities constitute the area most affected in idiopathic rapid eye movement sleep behavior disorder (learning as a stable deficit and copying as an evolving deficit). Cognitive deterioration, involving mainly nonverbal logic, attention, and executive functions, can be observed in rapid eye movement sleep behavior disorder follow-up, suggesting an underlying evolving degenerative process. Our data confirm that mild cognitive impairment is frequent in idiopathic rapid eye movement sleep behavior disorder. The presence of mild cognitive impairment predicts the eventual risk of developing dementia, which seemed to be associated with parkinsonism.

Longitudinal associations between mismatch negativity and disability in early schizophrenia- and affective-spectrum disorders

Impaired mismatch negativity (MMN) is a robust finding in schizophrenia and, more recently, similar impairments have been reported in other psychotic- and affective-disorders (including at early stages of illness). Although cross-sectional studies have been numerous, there are few longitudinal studies that have explored the predictive value of this event-related potential in relation to clinical/functional outcomes. This study assessed changes in MMN (and the concomitant P3a) amplitude over time and aimed to determine the longitudinal relationship between MMN/P3a and functional outcomes in patients recruited during the early stage of a schizophrenia- or affective-spectrum disorder. Sixty young patients with schizophrenia- and affective-spectrum disorders and 30 healthy controls underwent clinical, neuropsychological and neurophysiological assessment at baseline. Thirty-one patients returned for clinical and neuropsychological follow-up 12-30months later, with 28 of these patients also repeating neurophysiological assessment. On both occasions, MMN/P3a was elicited using a two-tone passive auditory paradigm with duration deviants. Compared with controls, patients showed significantly impaired temporal MMN amplitudes and trend-level deficits in central MMN/P3a amplitudes at baseline. There were no significant differences for MMN measures between the diagnostic groups, whilst the schizophrenia-spectrum group showed reduced P3a amplitudes compared to those with affective-spectrum disorders. For those patients who returned for follow-up, reduced temporal MMN amplitude at baseline was significantly associated with greater levels of occupational disability, and showed trend-level associations with general and social disability at follow-up. Paired t-tests revealed that MMN amplitudes recorded at the central-midline site were significantly reduced in patients over time. Interestingly, those patients who did not return for follow-up showed reduced frontal MMN and fronto-central P3a amplitudes compared to their peers who did return for repeat assessment. This study provides some evidence of the predictive utility of MMN at the early stages of schizophrenia- and affective-spectrum disorders and demonstrated that MMN impairments in such patients may worsen over time. Specifically, we found that young patients with the most impaired MMN amplitudes at baseline showed the most severe levels of disability at follow-up. Furthermore, in the subset of patients with repeat neurophysiological testing, central MMN was further impaired suggestive of neurodegenerative effects. MMN may serve as a neurophysiological biomarker to more accurately predict functional outcomes and prognosis, particularly at the early stages of illness.

Cognitive effects of deep brain stimulation for essential tremor: evaluation at 1 and 6 years

Only a few studies have explored cognitive changes with deep brain stimulation (DBS) in patients with essential tremor (ET). Furthermore, the cognitive effects after years of electrical stimulation are unknown. Assessing the impact of stereotactic electrode implantation and the actual electrical stimulation on cognition in patients with ET in the short and long term is of interest, because DBS is increasingly applied and can offer deeper insight into human brain functions. We examined nine ET patients before surgery (PRE-SURGERY), and 1 and 6 years thereafter with DBS switched on (DBS-ON) and off (DBS-OFF). Standardized neuropsychological tests and reaction time tests were applied. There were no differences in tasks of verbal fluency, memory, and executive and intellectual functions comparing PRE-SURGERY, DBS-ON, and DBS-OFF at 1 and 6 years post-surgery. Imaging data revealed that the dorsolateral prefrontal cortex and mamillo-thalamic tracts crucial for cognitive functioning were spared by electrode implantation. Additionally, with electrodes targeting the thalamus and adjacent subthalamic area, the actual electrical stimulation did not affect neuropsychological functioning. However, lesions caused by electrode implantation led to an increase in simple reaction time, while the actual electrical stimulation restored impaired reaction time. This is the second largest study of neuropsychological functioning in patients with ET treated with DBS, and the first covering a neuropsychological long-term follow-up over 6 years. Neither stereotactic surgery nor electrical stimulation affected higher cognitive processes. This study proposes that cerebello-thalamo-cortical pathways in humans are involved in tasks of simple reaction time.

Kurz und einfach ist nicht immer besser: Grenzen kognitiver Demenzscreenings

The increasing prevalence of Alzheimer's dementia (AD) and limited resources in outpatient care have encouraged the distribution of cognitive screening tests, in spite of their frequently unsatisfying accuracy regarding the differentiation between incipient AD, depression and age-associated memory impairment. 8 patients with probable AD and 17 controls completed a neuropsychological follow-up two years after initial examination. Beside four screening tests a memory based testing-the-limits (TtL) paradigm as well as the German version of the California Verbal Learning Test were administered. Based on hierarchical cluster analysis we could demonstrate that only well elaborated tests, such as a plasticity based TtL paradigm, did classify AD-patients correctly. The findings confirm reservations against cognitive screening procedures in detecting dementia and suggest that dynamic test strategies offer a powerful diagnostic alternative to traditional status-oriented tests.