[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.

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.

[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.

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.

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.

Common exonic missense variants in the C2 domain of the human KIBRA protein modify lipid binding and cognitive performance.

The human KIBRA gene has been linked to human cognition through a lead intronic single-nucleotide polymorphism (SNP; rs17070145) that is associated with episodic memory performance and the risk to develop Alzheimer's disease. However, it remains unknown how this relates to the function of the KIBRA protein. Here, we identified two common missense SNPs (rs3822660G/T [M734I], rs3822659T/G [S735A]) in exon 15 of the human KIBRA gene to affect cognitive performance, and to be in almost complete linkage disequilibrium with rs17070145. The identified SNPs encode variants of the KIBRA C2 domain with distinct Ca(2+) dependent binding preferences for monophosphorylated phosphatidylinositols likely due to differences in the dynamics and folding of the lipid-binding pocket. Our results further implicate the KIBRA protein in higher brain function and provide direction to the cellular pathways involved.

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.

A brief review of Susac syndrome.

Susac syndrome was named after J.O. Susac who first described the syndrome in 1979. It is characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. It mainly occurs in young women. This underdiagnosed disease needs to be considered in the differential diagnosis of a broad variety of disorders. In Susac syndrome, autoimmune processes leading to damage and inflammation-related occlusion of the microvessels in brain, retina, and inner ear are thought to play a causal role. The diagnosis is based primarily on the clinical presentation, the documentation of branch retinal artery occlusion by fluorescence angiography, and characteristic findings on cerebral MRI, that help in distinguishing Susac syndrome from other inflammatory entities, like multiple sclerosis. Antiendothelial cell antibodies could be detected in some patients. Patients are successfully treated with immunosuppression, however, the best regimen still needs to be defined. As a result of the rarity of the disease, controlled therapeutic trials are missing so far. In this review, we want to demonstrate the clinical features, natural history, treatment, and clinical course of Susac syndrome, illustrated by a typical case history.

Impact of common KIBRA allele on human cognitive functions.

The rs17070145 polymorphism (C → T substitution, intron 9) of the KIBRA gene has recently been associated with episodic memory and cognitive flexibility. These findings were inconsistent across reports though, and largely lacked gene-gene or gene-environment interactions. The aim of the present study was to determine the impact of the rs17070145 polymorphism on clinically relevant cognitive domains and its interaction with the modifiers 'lifestyle' and 'cardiovascular risk factors'. Five-hundred forty-five elderly volunteers (mean age 64 years, ±7 years, 56% women) accomplished a comprehensive cognitive testing. Principal component analysis was used to reveal the internal structure of the data, rendering four composite scores: verbal memory, word fluency, executive function/psychomotor speed, and working memory. Lifestyle was assessed with a detailed questionnaire, age-associated risk factors by clinical interview and examination. There was no main effect of the rs17070145 genotype on any cognitive composite scores. However, we found worse performance in executive functions for T-allele carriers in the presence of arterial hypertension (ß=-0.365, p=0.0077 and 0.031 after Bonferroni correction). This association was further modified by gender, showing the strongest association in hypertensive females (ß=-0.500, p=0.0072 and 0.029 after Bonferroni correction). The effect of KIBRA on cognitive function seems to be complex and modified by gender and arterial hypertension.

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.

Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function.

OBJECTIVE: C-reactive protein is a marker of inflammation and vascular disease. It also seems to be associated with an increased risk of dementia. To better understand potential underlying mechanisms, we assessed microstructural brain integrity and cognitive performance relative to serum levels of high-sensitivity C-reactive protein (hs-CRP). METHODS: We cross-sectionally examined 447 community-dwelling and stroke-free individuals from the Systematic Evaluation and Alteration of Risk Factors for Cognitive Health (SEARCH) Health Study (mean age 63 years, 248 female). High-field MRI was performed in 321 of these subjects. Imaging measures included fluid-attenuated inversion recovery sequences for assessment of white matter hyperintensities, automated quantification of brain parenchyma volumes, and diffusion tensor imaging for calculation of global and regional white matter integrity, quantified by fractional anisotropy (FA). Psychometric analyses covered verbal memory, word fluency, and executive functions. RESULTS: Higher levels of hs-CRP were associated with worse performance in executive function after adjustment for age, gender, education, and cardiovascular risk factors in multiple regression analysis (beta = -0.095, p = 0.02). Moreover, higher hs-CRP was related to reduced global fractional anisotropy (beta = -0.237, p < 0.001), as well as regional FA scores of the frontal lobes (beta = -0.246, p < 0.001), the corona radiata (beta = -0.222, p < 0.001), and the corpus callosum (beta = -0.141, p = 0.016), in particular the genu (beta = -0.174, p = 0.004). We did not observe a significant association of hs-CRP with measures of white matter hyperintensities or brain atrophy. CONCLUSION: These data suggest that low-grade inflammation as assessed by high-sensitivity C-reactive protein is associated with cerebral microstructural disintegration that predominantly affects frontal pathways and corresponding executive function.

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.

[False aneurysm of the deep femoral artery due to pertrochanteric fracture of the hip with displaced fragment of the lesser trochanter]. / Aneurysma spurium der A. profunda femoris - Komplikation nach pertrochantärer Femurfraktur mit Dislokation des Trochanter minor.

We report the case of an 82-year-old man with a pertrochanteric fracture of the hip and an avulsion of the lesser trochanter. During the third postoperative week after unproblematic correction with a gamma nail, a swelling of the proximal thigh occurred. Angiographs showed a false aneurysm of the deep femoral artery which was treated by suture.

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.

A novel form of autosomal recessive hereditary spastic paraplegia caused by a new SPG7 mutation.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by progressive spastic paraparesis of the lower limbs. OBJECTIVE: To identify the genotype and characterize the phenotype in a family with a novel form of complicated autosomal recessive hereditary spastic paraparesis (ARHSP). METHODS: Six subjects of a Turkish family were examined by clinical evaluation, detailed neuropsychological testing, neurophysiologic studies, MRI, diffusion tensor imaging (DTI), and mutation analysis of SPG7 gene. RESULTS: Three individuals were affected by a juvenile-onset form of complicated ARHSP due to the missense mutation c.2075G>C in exon 15 of the SPG7 gene in the homozygous state, substituting serine with threonine at codon 692. As additional clinical features, cerebellar syndrome, supranuclear palsy, and cognitive impairment, particularly disturbance of attention and executive functions, were found. MRI showed cerebellar atrophy and mild frontal cerebral atrophy. DTI revealed bilateral disturbance of white matter integrity in corticospinal tracts, frontal lobes, and the midbrain. CONCLUSIONS: The new SPG7 gene mutation leads to a novel complicated autosomal recessive hereditary spastic paraparesis phenotype that widens the spectrum of different brain systems that are optionally affected in hereditary spastic paraplegia (HSP). In this novel phenotype, spastic paraparesis is related to cerebral damage of corticospinal tracts. Impairment of attention and executive functions is due to white matter loss in frontal lobes. Furthermore, supranuclear palsy is caused by white matter damage in the midbrain. This multisystem affection, which was detected by the use of diffusion tensor imaging, may reflect a mitochondrial dysfunction that contributes to the underlying pathogenesis of SPG7-HSP.

[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.