[Frequency and risk factors associated with post-stroke dementia-an observational study on stroke patients without premorbid cognitive impairment]. / Häufigkeit und Risikofaktoren der Post-Stroke-Demenz ­ eine Beobachtungsstudie zu Schlaganfallpatienten ohne vorbestehende kognitive Defizite.

BACKGROUND: Longitudinal studies on cognitive outcomes after stroke revealed heterogeneous results and the underlying pathology and risk factors for so-called post-stroke dementia are unclear. OBJECTIVE: To assess long-term cognitive performance changes in patients after the first ischemic stroke and to evaluate possible risk factors for post-stroke dementia. MATERIAL AND METHODS: In this study 66 clinically mildly affected patients aged 54-87 years without a history of dementia underwent extensive neuropsychological assessment after first ever ischemic stroke and again 6 months after the event (follow-up assessment). Demographic, clinical and paraclinical parameters were assessed as potential predictors for long-term cognitive outcome. RESULTS: At the group level significant performance improvements were found for most of the neurocognitive domains at the follow-up assessment. The greatest cognitive improvement was found in visuospatial processing. Immediately after stroke 54.5% of patients were considered cognitively impaired (z-scores < -2 in at least 2 neurocognitive domains). At follow-up only 16.7% were considered cognitively impaired according to this criterion and among these only 2 patients (3%) had developed a new, clinically relevant cognitive impairment (i.e. post-stroke dementia). Patients with inferior cognitive performance improvements at follow-up had on average larger brain lesions caused by the stroke as well as a prediabetic metabolic status. DISCUSSION: The probability of developing a post-stroke dementia syndrome is lower than previously assumed in patients with first ever stroke, with only mild clinical disability and without premorbid cognitive impairment. Long-term cognitive impairment could primarily be determined by the size of the lesioned brain area as well as the premorbid (pre)diabetic status.

[Implementation of the German S3 guidelines on dementia in clinical practice: wish or reality?] / Umsetzung der S3-Leitlinie "Demenzen" im klinischen Alltag: Wunsch oder Wirklichkeit?

BACKGROUND: Published in 2009, the German S3 guidelines on dementia define a milestone in quality improvement of the diagnostics and treatment of dementia. In clinical practice patients suffering from dementia are primarily treated by physicians in private practice; therefore, this study examined how the guidelines are implemented in outpatient clinical settings. Furthermore, it aimed at the identification of behavioral determinants that govern the actual diagnostic and therapeutic approach in clinical practice. METHODS: Physicians involved in the primary care of dementia patients were asked to participate in a nationwide internet survey. The questionnaire covered aspects on the diagnostic and therapeutic care of dementia patients as recommended by the S3 guidelines. Behavioral determinants of the implementation of the guidelines (e. g. treatment decisions) were derived from an established psychological prediction model. RESULTS: Out of a total of 2755 physicians contacted, the data of 225 participants could be used in this study. The diagnostic recommendations of the S3 guidelines were implemented in satisfactory measures (e.g. combined cognitive screening in at least 68%, cerebral neuroimaging in at least 93% and specific laboratory diagnostics in at least 27% of cases); however, only two thirds of the patients with indications for a guideline-conform therapy were treated in accordance with the S3 guidelines. There was a substantial prescription of non-recommended drugs and a notable long-term use of antipsychotic drugs (prescription by at least 14% of non-neurological medical specialists and by 8% of neurologists and psychiatrists). When considering the behavioral determinants in the implementation of the guidelines, normative assumptions ("my colleagues and patients expect me to comply with the guidelines") surprisingly had the highest impact, which was then followed by attitudes towards the behavior ("utilization of the guidelines improves diagnostics and therapy"). CONCLUSION: The German S3 guidelines on dementia were satisfactorily implemented in outpatient clinical practice; however, deficits existed in the frequency of the pharmaceutical treatment of patients with indications for therapy, the prescription of non-recommended drugs and the relatively common use of permanent neuroleptic medications. Interestingly, the motivation for implementation of the guidelines was not primarily influenced by the physicians' personal convictions but mainly stimulated by the expectations of others.

Cognitive impairment in HIV infection is associated with MRI and CSF pattern of neurodegeneration.

BACKGROUND AND PURPOSE: Biomarkers as indicators for the progression of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain still elusive. We performed a cross-sectional study to analyze the correlation between cognitive impairment, abnormalities in magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) markers of neurodegeneration in HIV-infected patients. METHODS: We enrolled 94 patients (82 men and 12 women; mean age 45 ± 10 years) with HIV infection, but without opportunistic infections of the CNS. All patients underwent MRI and CSF analysis. The global pattern of white matter signal intensity abnormalities, the index of atrophy, the severity of periventricular white matter abnormalities, and the severity of basal ganglia signal changes were analyzed. We measured CSF markers of neurodegeneration (total tau, phospho-tau, beta-amyloid). The findings of this evaluation were correlated with demographic and infection parameters of the patients in blood and CSF. RESULTS: We found a highly significant correlation between the severity of global brain atrophy, basal ganglia signal changes, and cognitive impairment in HIV-infected patients. Furthermore, cognitive impairment was significantly correlated with total tau, but not with phospho-tau or A-beta-amyloid in CSF analysis. CONCLUSIONS: Our results confirm the significant correlation between MRI changes and cognitive impairment in HIV infection. Furthermore, we could show that global brain atrophy and signal changes in basal ganglia are the typical MRI pattern in HAND. The correlation between cognitive impairment and total tau, but not phospho-tau, supports the hypothesis that HAND are not a subtype of Alzheimer's dementia.

Long-term cognitive and emotional consequences of mild traumatic brain injury.

BACKGROUND: The objective of this study was to investigate long-term cognitive and emotional sequelae of mild traumatic brain injury (mTBI), as previous research has remained inconclusive with respect to their prevalence and extent. METHOD: Thirty-three individuals who had sustained mTBI on average 6 years prior to the study and 33 healthy control subjects were matched according to age, gender and education. Structural brain damage at time of testing was excluded by magnetic resonance imaging (MRI). A comprehensive neuropsychological test battery was conducted to assess learning, recall, working memory, attention and executive function. Psychiatric symptoms were assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the Beck Depression Inventory (BDI). Possible negative response bias was ruled out by implementing the Word Memory Test (WMT). RESULTS: The mTBI individuals had significant impairments in all cognitive domains compared to the healthy control subjects. Effect sizes of cognitive deficits were medium to large, and could not be accounted for by self-perceived deficits, depression, compensation claims or negative response bias. BDI scores were significantly higher in the patient group, and three patients fulfilled DSM-IV criteria for a mild episode of major depression. CONCLUSIONS: Primarily, well-recovered individuals who had sustained a minor trauma more than half a decade ago continue to have long-term cognitive and emotional sequelae relevant for everyday social and professional life. mTBI may lead to a lasting disruption of neurofunctional circuits not detectable by standard structural MRI and needs to be taken seriously in clinical and forensic evaluations.

Physical activity and memory functions: are neurotrophins and cerebral gray matter volume the missing link?

Epidemiological studies reveal better cognitive function in physically active individuals. Possible mediators for this effect are neurotrophins, which are up-regulated through physical exercise and induce neuronal growth and synaptogenesis in the animal model. Here we cross-sectionally assessed 75 healthy older individuals for levels of physical activity, aerobic fitness, and memory encoding, as well as neurotrophin levels and cerebral gray matter volume. We found that physical activity, but not cardiovascular fitness, was associated with better memory encoding after controlling for age, sex, education, depression, alcohol consumption, and smoking. Higher levels of physical activity were associated with higher levels of the neurotrophin granulocyte colony stimulating factor (G-CSF) and increased cerebral gray matter volume in prefrontal and cingulate cortex as assessed by magnetic resonance voxel-based morphometry. While mediating factors will need to be further elucidated, these findings indicate that even low-level physical activity exerts beneficial effects on memory functions in older individuals.

Pattern and progression of white-matter changes in a case of posterior cortical atrophy using diffusion tensor imaging.

BACKGROUND: The progression of white-matter changes in a case of posterior cortical atrophy (PCA) was examined over a period of 15 months using diffusion tensor imaging (DTI) and the association with neuropsychological variables was studied. PATIENT AND METHODS: A PCA patient was observed over a period of 15 months. DTI and volumetric magnetic resonance imaging were obtained at visit 1 and 15 months later. Fractional anisotropy (FA) and volumetric changes were compared with findings in a typical case of Alzheimer disease (AD) and in 65 healthy volunteers, and the association of neuropsychological deficits with these changes was studied. RESULTS: Reduction in FA was focused on the occipital lobe in the early stages of PCA. During the 15-month period, the FA values of the PCA patient tended to align with the FA ratios of the AD patient, with a more pronounced FA reduction in the parietal lobes, as opposed to a stable FA level in the occipital lobe. In addition to the DTI changes, clinical and neuropsychological symptoms deteriorated further. Brain volumes (grey matter, white matter and total normalised brain volume) of the PCA patient were substantially decreased compared with the control group, but loss of tissue volumes showed only marginal progression between visit 1 and 2. CONCLUSIONS: The findings suggest that PCA starts as distinct clinical syndrome but in its later course might turn into a final pathway shared with AD. DTI might be helpful in detecting changes in cerebral white matter during disease progression in PCA patients.

[Cognitive dysfunction as a hidden multiple sclerosis related symptom relevant for an expert appraisal]. / Kognitives Defizit als gutachterlich relevantes, nicht erkanntes Syndrom infolge von Multipler Sklerose.

We report on a patient with multiple sclerosis (MS), who had severe cognitive dysfunction despite only mild changes in cerebral magnetic resonance imaging (cMRI). The severe MS-related cognitive deficits were disclosed only in a comprehensive neuropsychological evaluation. A previous appraiser was not able to detect these neuropsychological deficits as he did not conduct an appropriate neuropsychological assessment. The expert appraisal had been performed to decide whether the MS-related deficits would make the patient eligible to receive pension payments from a private pension insurance. Only after a subsequent neuropsychological expert appraisal the insurance company had to pay several ten thousands of Euro as decided by judicial decree. The presented case impressingly demonstrates that the so called hidden symptoms of MS such as fatigue or cognitive dysfunction are often not identified by treating physicians and in medico-legal evaluations. We therefore postulate that comprehensive neuropsychological evaluation is mandatory to perform expert appraisals to assess occupational disability in MS patients.

Early effective treatment may protect from cognitive decline in paediatric multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) is a critical feature for patients with childhood or juvenile multiple sclerosis (MS). OBJECTIVE: To promote the understanding of CI and to address the impact of different pharmacological treatment strategies on cognitive performance in this patient group. METHODS: A cohort of 19 patients with therapy-naïve or ß-Interferon-treated juvenile MS completed a comprehensive neuropsychological assessment at initial presentation (baseline) and on average 2.5 years later (follow-up). The assessments were complemented with a neuropaediatric examination and conventional cerebral magnetic resonance imaging (MRI). RESULTS: 9 patients (47%) were impaired in at least one test at baseline (z-score <-1.645 compared with age-adjusted normative data), with the highest impairment frequency in the domains processing speed and attention & executive functions. At follow-up a higher impairment frequency was prominent in those patients whose therapy had not been escalated (N = 13, 69% impaired in at least one test), while cognition was preserved or ameliorated in patients whose treatment had been escalated to highly effective drugs (N = 6, 0% impaired) during the observational period. These group differences at follow-up were not attributable to differences regarding demographics, MRI metrics or cognitive performance at baseline. CONCLUSION: Our findings confirm that paediatric MS is associated with considerable CI already in early disease stages. Early administration of highly effective treatment may protect from cognitive decline or alleviate CI in juvenile MS, but larger controlled trials are warranted to confirm these preliminary results.

[Primary care of fractures of the extremities]. / Erstversorgung von Extremitätenfrakturen durch den Hausarzt. Reponieren, ruhig stellen und den Schmerz behandeln.

The initial care of a fractured bone provided by the general physician includes reduction followed by immobilization and the treatment of pain. Open fractures must be covered by a sterile dressing, prior to the transportation of the patient to a hospital. Depending upon the severity of the injury, further treatment is provided by an orthopedic surgeon or in an appropriate hospital.

[Fractures of the extremities--surgical or conservative treatment?]. / Gipsen oder schrauben?

When a fracture of an extremity has been established, the question immediately arises: should it be treated conservatively or surgically? For each of these options the three "R's" of fracture treatment apply "reduction, retention, rehabilitation". In humans, the most common fracture is that of the distal radius, which is usually amenable to conservative treatment. A fracture of the ankle is treated conservatively only when it is stable with no syndesmotic injury, and the fragments are in good alignment. Should surgical treatment be necessary, stabilization is accomplished with a plate and screws. The advantages and disadvantages of each of the options must be weighed up on an individual basis.

[After care of fractures of the extremities]. / Nachsorge von Extremitätenfrakturen beim Hausarzt. Wie Sie die Patienten wieder in Gang bringen.

Today, early mobilization is recommended, irrespective of whether a patient with a fracture of the extremities has been treated conservatively or surgically. In this way, morbidity and mortality risks can be considerably reduced, in particular in the elderly patient. As a result of the continuing trend towards an ever shorter hospital stay, the general physician is faced with the task of providing aftercare to such patients at an early stage in the healing process of the fracture. This includes wound care, prevention of thromboembolism, the timely initiation of physiotherapeutic measures, and the requesting of x-ray follow-up.

Determination of volatile organic compounds from biowaste and co-fermentation biogas plants by single-sorbent adsorption.

Characterisation of biogases is normally dedicated to the online monitoring of the major components methane and carbon dioxide and, to a lesser extent, to the determination of ammonia and hydrogen sulphide. For the case of Volatile Organic Compounds (VOCs), much less attention is usually paid, since such compounds are normally removed during gas conditioning and with exception of sulphur compounds and siloxanes represent a rather low risk to conventional downstream devices but could be a hindrance for fuel cells. However, there is very little information in the literature about the type of substances found in biogases generated from biowaste or co-fermentation plants and their concentration fluctuations. The main aim of this study was to provide information about the time dependencies of the VOCs in three biogas plants spread out through Germany from autumn until summer, which have different process control, in order to assess their potential as biofuels. Additionally, this study was an attempt to establish a correlation between the nature of the substrates used in the biogas plants and the composition of the VOCs present in the gas phase. Significant time-dependent variations in concentration were observed for most VOCs but only small changes in composition were observed. In general, terpenes and ketones appeared as the predominant VOCs in biogas. Although for substances such as esters, sulphur-organic compounds and siloxanes the average concentrations observed were rather low, they exhibited significant concentration peaks. The second biogas plant which operates with dry fermentation was found to contain the highest levels of VOCs. The amount of total volatile organic compounds (TVOCs) for the first, second and third biogas plants ranged from 35 to 259 mg Nm(-3), 291-1731 mg Nm(-3) and 84-528 mg Nm(-3), respectively.

Hemispheric lateralization of spatial attention in right- and left-hemispheric language dominance.

Hemispheric lateralization of the neural systems supporting language and spatial attention most commonly dissociate in healthy individuals. However, the reverse pattern with association of language and attention within the right hemispheres has also been observed. We investigated in 75 healthy volunteers (37 right-handed, 38 left-handed) if language and spatial attention may associate not only in individuals with an atypical pattern of language lateralization, but also in subjects showing the standard, i.e. left-hemispheric dominance for language. Hemispheric lateralization of cerebral perfusion was determined with functional transcranial Doppler ultrasonography during a visuospatial attention, and a word generation task. We found that language and visuospatial attention associated within the left hemisphere in five subjects and within the right hemisphere in eight subjects. We conclude that all combinations of cerebral lateralization for language and attention may exist in the healthy brain.

Neuropsychological impact of cerebral microemboli in ablation of atrial fibrillation.

BACKGROUND: Clinically silent lesions on cerebral magnet resonance imaging have been found in larger numbers after pulmonary vein isolation (PVI) especially with phased radio frequency (pRF) using all ten electrodes. However, the neuropsychological effects of cerebral microembolism during the procedure remain unclear and data regarding this issue so far are inconsistent. METHODS: Between August 2011 and June 2012, 76 patients undergoing their first PVI were randomized to ablation with either phased (40) or irrigated (36) radio frequency (iRF). A comprehensive neuropsychological test battery was performed the day before and after PVI as well as 6 months after ablation. The occurrence of cerebral microemboli during the procedure was performed via a transcranial Doppler ultrasound device. RESULTS: PVI using pRF was associated with increased number of microembolic signals (MES) compared to iRF (1530.0 ± 979.8 vs. 645.7 ± 448.7; p < 0.001). Neuropsychological assessment did not reveal any changes in correlation with the used ablation technique. Besides an age-related effect there was a diffuse, sub-clinical impairment of neurologic function depending on age and the number of MES. CONCLUSIONS: There was no clinical overt cognitive deficit and no significant difference in cognitive function correlating with the used ablation technique. The number of MES correlated with a subtle, diffuse post-procedural impairment of neuropsychological function highlighting the need to reduce microemboli during ablation.

Assessment of hemispheric language lateralization: a comparison between fMRI and fTCD.

The cerebral blood flow velocity (CBFV) in the basal arteries during a word-generation task was assessed by functional transcranial Doppler ultrasonography (fTCD) and by functional magnetic resonance imaging (fMRI). The study investigates how event-related CBFV modulations in the middle cerebral artery (MCA) relate to regional cerebral blood flow (rCBF) changes. Both fMRI and fTCD were used in 13 subjects (7 men, 6 women, aged 21 to 44 years). The maximum difference of relative CBFV changes between the left and right MCA during the word-generation task was used as the language laterality index (LIfTCD). For the fMRI examination during the nearly identical language task, the corresponding index was defined by LIfMRI = 100(N(L) - N(R))/(N(L) + N(R)), where N(L) and N(R) refer to the numbers of voxels activated in the left and right hemisphere, respectively. The evoked CBFV changes expressed by LIfTCD and the corresponding laterality index, LIfMRI, estimated by fMRI showed a close linear relation (regression analysis: r = 0.95, p < 0.0001). The results of this study demonstrate that language-related velocity changes in the MCAs relate to rCBF increases in a linear fashion. Since the laterality indices assessed by fMRI and fTCD are in such close agreement both techniques can therefore be used in a complementary way.

Long-range horizontal connections between supragranular pyramidal cells in the extrastriate visual cortex of the rat.

In this study, we examined the morphological structure and synaptic physiology of long-range axon projections among supragranular pyramidal cells in the extrastriate visual cortex of the rat. Intra- and extracellular recordings from layer II/III pyramidal cells were performed in brain slices of area 18a following extracellular stimulation of either the underlying white matter or within layer II/III. Neurons were injected with biocytin for two-dimensional reconstruction of their axon arborizations. The conduction velocity of afferent fibers (0.58 m/s) was twice as high as that of intracortical tangential fibers (0.28 m/s). Layer II/III cells were mainly di- or polysynaptically driven by afferent activation, but predominantly monosynaptically driven from intracortical stimulation sites. The afferent as well as intracortically evoked postsynaptic potentials showed a very similar time course and shape. From both stimulation sites, suprathreshold action potentials could be elicited. The current threshold for a postsynaptic response and the slope and width of excitatory postsynaptic potentials (EPSPs) increased with the distance of lateral stimulation. The morphological properties of layer II/III pyramidal cell axon collaterals closely corresponded to the electrophysiological results. Long-range intraareal axon collaterals could be followed up to 1 mm within the supragranular layers. Their length-distance distribution showed an inverse relationship to the threshold currents of EPSPs. Pyramidal cells exhibited regularly spaced patches of horizontal axon collaterals with an interpatch distance of about 250 microns. We concluded that the supragranular horizontal network in the extrastriate visual cortex of the rat is qualitatively very similar to that of cats and monkeys. However, quantitative differences exist in its spatial extent and physiological characteristics.

Language and spatial attention can lateralize to the same hemisphere in healthy humans.

BACKGROUND: Disorders of language classically occur after left brain lesions, and disorders of spatial attention after right brain lesions. It is unclear whether the hemispheric dissociation of functions is a fixed pattern of brain organization. OBJECTIVE: The authors determined whether lateralization of language and lateralization of spatial attention also dissociate in people with atypical (i.e., right hemispheric) language dominance. METHODS: The authors selected 10 subjects with typical, i.e., left hemispheric, and 10 with atypical, i.e., right hemispheric, language representation on a random basis from a sample of 326 healthy volunteers examined with functional transcranial Doppler sonography (fTCD) for language dominance. In these subjects, hemispheric lateralization of cerebral perfusion during a line bisection task was determined with fTCD. RESULTS: The authors found a dissociation between dominance for language and spatial attention in all but four subjects. In the latter subjects, there was a significant lateralization to the right hemisphere for both tasks. The four subjects showed normal intellectual, linguistic, and spatial performance, with normal EEG and MRI scans of the brain. CONCLUSION: Even in the absence of brain pathology, the same hemisphere can be dominant in control of both language and spatial attention.

Cortical tuning: a function of anticipated stimulus intensity.

We investigated the activation of the brain during anticipation of tactile stimuli by continuous cerebral blood flow velocity (CBFV) monitoring with bilateral transcranial Doppler sonography. A forced choice paradigm was performed where a first group of subjects (n=16) was expecting suprathreshold and a second group (n=19) was anticipating threshold tactile stimuli to the index finger after a cueing tone. During the anticipation of suprathreshold stimuli the CBFV always exhibited a significantly stronger increase in the right hemisphere than in the left, even when stimuli were anticipated at the right index finger. Conversely when stimuli at perception threshold were expected, the respective contralateral hemisphere showed a significantly stronger perfusion increase. These data show that preparatory activation of the brain during stimulus anticipation is dependant on the expected stimulus intensity.

Visual receptive fields of local intracortical potentials.

We have developed a method to define a spatial-temporal receptive field (RF) for local, intracortically recorded field potentials in the visual cortex. In analogy to the classic RF concept, a relation between stimulus position and a single recording location is evaluated. Our receptive field cinematogram (RF-Cine) approach, additionally, includes the temporal dynamics between stimulus and response: A sequence ('movie') of successive 'frames' is calculated, which shows the field potential amplitudes plotted with reference to the position in visual space of a randomly moving stimulus. The exploration of the receptive fields via a randomly jumping disk stimulus is especially suitable for multi-electrode cortex mapping, because the RF-Cines of all electrodes can be evaluated simultaneously within a single stimulation period of 100 s duration. Field potential RF-Cines showed concentrical or ellipsoidal antagonistic center-surround structures with biphasic or triphasic time courses. The size of these structures increases with retinal eccentricity. The cortical surface coverage of the RF-Cine centers was calculated to be 0.8 mm2 for area 17 and 1.3 mm2 for area 18, being nearly constant within the 0-10 degrees cortical representation of the lower visual field. These values approximately correspond to the extent of one hypercolumn. The absolute positions of the RF-Cine structures can be determined with an accuracy of 0.1-0.2 mm in cortical coordinates.

Spatio-temporal summation of synaptic activity in visual cortical pyramidal cells in vitro.

We investigated the spatio-temporal summation of excitatory postsynaptic potentials (EPSPs) in supragranular pyramidal cells of the rat extrastriate visual cortex. EPSPs were evoked orthodromically from different locations within the white matter (WM) via an 8-fold multi-electrode array. Stimuli were applied either sequentially from electrodes 1 to 8 or vice versa at defined interstimulus intervals (ISIs) or separately from each electrode. Maximum EPSP amplitudes were evoked from the WM just below the intracellularly recorded neuron. Even 800 microns lateral to this location, small EPSPs could be elicited. A sequential stimulation resulted in a large compound EPSP. In 79% (n = 34) of the cells tested, the compound response was non-directional and could be predicted from responses evoked by single stimulation electrodes. However, 21% (n = 9) of the neurons showed a non-linear spatial summation and a clear preference for the direction of the stimulation sequence. ISI-tuning curves revealed either a sharply tuned, a bandpass, a highpass or a lowpass characteristic for the non-directional as well as directional cells. This feature, together with the clear directional responses observed in some neurons, may be a correlate of the response preference to moving stimuli of cortical cells found in vivo.