[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.

[Traumatology in the elderly : Multimodal prevention of delirium and use of augmentation techniques]. / Alterstraumatologie : Multimodale Delirprävention und Verwendung von Augmentationstechniken.

Recent data show that 20-80% of surgery patients are affected by delirium during inpatient clinical treatment. The medical consequences are often dramatic and include a 20 times higher mortality and treatment expenses of the medical unit increase considerably. At the University Hospital of Münster a multimodal and interdisciplinary concept for prevention and management of delirium was developed: all patients older than 65 years admitted for surgery are screened by a specialized team for the risk of developing delirium and treated by members of the team if there is a risk of delirium. Studies proved that by this multimodal approach the incidence of delirium was lowered and therefore the quality of medical care improved.When surgical treatment of fractures in the elderly is required, limited bone quality as well as pre-existing implants can complicate the procedure. Secondary loss of reduction after osteosynthesis and avulsion of the implant in particular must be prevented. Augmentation of the osteosynthetic implant with bone cement can increase the bone-implant interface and therefore stability can be improved. Additional intraoperative 3D imaging can be necessary depending on the localization of the fracture. In biomechanical studies we could prove greater stability in the osteosynthesis of osteoporotic fractures of the distal femur when using additional bone cement; therefore, the use of bone cement is an important tool, which helps to prevent complications in the surgical treatment of fractures in the elderly. Nevertheless, special implants and technical skills are required and some safety aspects should be considered.

Physical Exercise in Patients with Fabry Disease - a Pilot Study.

The aim of this study was to assess the extent of exercise intolerance in Fabry disease (FD) patients and to report individual effects of physical exercise. Exercise capacity and strength of 14 patients (mean age 46 years, 6 females) were determined using cycle ergometry and isokinetic measurements. Patients performed a strength/circuit exercise training protocol for 12 months. The mean relative maximum performance of the group was low at baseline and increased by 12.1% (baseline: 1.9 [0.9-3.4] W·kg-1vs. re-test: 2.1 [1.1-3.8] W·kg-1; p=0.035) during the study. Patients' mean baseline maximum performance blood lactate of 5.4 [1.3-9.9] mmol·L-1 increased to a mean of 7.2 (2.4-10.2) mmol·L-1 (p=0.038). Mean strength of the lower limbs (left/right extensors and flexors, total work of 5 sets) changed from 2269 (1017-2913) kg·m2·s - 2 to 2325 (1359-3107) kg·m2·s-2 (not significant). Patients reported increased well-being, daily activity and reduced fatigue during the study. Our results indicate that exercise intolerance in FD patients often results from physical inactivity. FD patients may perform exercise training to improve exercise capacity and muscle strength. Future studies will address the clinical benefits of exercise in FD.

[Pain therapy for Fabry's disease]. / Schmerztherapie bei Morbus Fabry.

Fabry's disease is an X-chromosome linked lysosomal storage disorder with α-galactosidase A deficiency and subsequent multiple organ involvement. An early and common symptom also in later stages of the disease is pain. This pain depends on various precipitating factors and can severely compromise the quality of life. So-called Fabry crises can lead to the necessity for intensive care treatment. The pain can be classified as predominantly neuropathic and is difficult to treat. In addition, medication has to be adjusted to concomitant cardiac and renal involvement in Fabry's disease. This review gives guidance for pain therapy in Fabry's disease based on the available evidence and on experience.

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.

An unusual case of neuralgic amyotrophy presenting with bilateral phrenic nerve and vocal cord paresis.

BACKGROUND: Neuralgic amyotrophy (brachial plexus neuropathy, brachial plexus neuritis, or Parsonage-Turner syndrome) is an uncommon inflammatory condition typically characterized by acute and severe shoulder pain followed by paresis with muscle weakness and atrophy of the upper limb or shoulder girdle. We report an unusual clinical manifestation of neuralgic amyotrophy, namely bilateral phrenic nerve palsy with concomitant laryngeal paresis. CASE REPORT: A 55-year-old male presented with orthopnea and aphonia after an episode of bilateral shoulder pain preceded by an upper respiratory tract infection. Spirometry, chest X-ray and videolaryngoscopy revealed bilateral and simultaneous paresis of the diaphragm and the vocal cords. Clinical examination at admission and at the 2-month follow-up did not show upper limb weakness or atrophy, except for a mild atrophy of the right supraspinatus muscle. An electromyography of the upper limb muscles and nerve conduction studies did not reveal signs of denervation. Analysis of the cerebrospinal fluid and an MRI of the neuraxis were unremarkable. After treatment with prednisolone, vocal cord function markedly improved within 8 weeks, whereas paresis of the diaphragm persisted. CONCLUSION: Shoulder pain followed by diaphragmatic paralysis with dyspnea and hoarseness may be a manifestation of neuralgic amyotrophy even if upper limb or shoulder girdle palsies are absent.

Physical activity and memory functions: an interventional study.

Previous studies have suggested beneficial effects of physical activity on cognition. Here, we asked in an interventional approach if physical activity performed at different intensity levels would differentially affect episodic memory function. Additionally, we tried to identify mechanisms mediating these changes. Sixty-two healthy elderly individuals were assessed for level of physical activity, aerobic fitness, episodic memory score, neurotrophin and catecholamine levels, and received a magnetic resonance image of the brain at baseline and after a six months intervention of medium or low-intensity physical activity or control. Increase in total physical activity was positively associated with increase in memory score over the entire cohort, without significant differences between intensity groups. It was also positively associated with increases in local gray matter volume in prefrontal and cingulate cortex, and BDNF levels (trend). In conclusion, we showed that physical activity conveys the beneficial effects on memory function independently of its intensity, possibly mediated by local gray matter volume and neurotrophic factors. Our findings may carry significant implications for prevention of cognitive decline in the elderly.

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.

[Acute polyneuritis and polyradiculoneuritis: uncommon causes and their pathomechanisms]. / Akute Polyneuritiden und Polyradikuloneuritiden: Ungewöhnliche Ursachen und deren Pathomechanismen.

Although the total incidence rate of acute inflammatory polyneuropathies is low, it is the most frequent cause of acute progressive, generalized paresis in developed countries (> 50 %). The most common form of the disease is the Guillain-Barré syndrome (GBS). Even though the clinical and pathologic spectrum of GBS has substantially grown over the last decade, about 15 % of cases of acute polyneuritis or polyradiculoneuritis do not fulfil the revised and extended diagnostic criteria and classification for GBS and its variants. The underlying pathogenesis still remains unclear. It is assumed that these "untypical" acute inflammatory polyneuropathies and cases fulfilling the GBS criteria are variants of the same underlying immune disorder, but that pathogenetic mechanisms produce different acute neurological syndromes. Thus, immunotherapy (which is not GBS-specific) is also effective for treating acute inflammatory polyneuropathies that do not fulfil the diagnostic criteria for GBS, and early diagnosis and treatment of these cases is essential. Since no reliable serological and electrodiagnostic markers of autoimmune neuropathies are currently available, the diagnosis is based on its clinical presentation. However, clinical symptoms are variable, and a rational diagnostic decision can be challenging. Thus, it is important to know that acute inflammatory polyneuropathies not fulfilling the diagnostic criteria of GBS are less often preceded by an infective condition but frequently associated with uncommon causes and triggers. This report presents our experiences with uncommon variants of inflammatory polyneuropathies and polyradiculoneuritides that do not fulfil the international diagnostic criteria for GBS. We provide a detailed review of the pertinent literature discussing possible pathomechanisms, its clinical associations and possible dispositions.

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.

Nerve fiber impairment of anterior thalamocortical circuitry in juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is a syndrome of idiopathic generalized epilepsy (IGE) without structural brain abnormalities detectable by MRI or CT. OBJECTIVE: In the present study, we addressed the question of whether diffusion tensor MRI (DTI) can detect disease-specific white matter (WM) abnormalities in patients with JME. METHODS: We performed whole head DTI at 3 T in 10 patients with JME, 8 age-matched patients with cryptogenic partial epilepsy (CPE), and 67 age-matched healthy volunteers. Nerve fiber integrity was compared between the groups on the basis of optimized voxel-by-voxel statistics of fractional anisotropy (FA) maps obtained by DTI (analysis of covariance, categorical factor "group," covariate "age"). RESULTS: FA was reduced in a WM region associated with the anterior thalamus and prefrontal cortex in patients with JME compared to both control subjects and patients with CPE (p < 0.001). The patients with CPE showed normal values in this particular WM region. The FA reductions in the patients with JME correlated with the frequency of generalized tonic-clonic seizures (Spearman R = 0.54, p = 0.05). No significant correlations were found in the JME sample between FA reduction and the duration of antiepileptic medication. CONCLUSIONS: The results support the hypothesis that juvenile myoclonic epilepsy is associated with abnormalities of the thalamocortical network that can be detected by diffusion tensor MRI.

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.

[Treatment strategies for tetanus]. / Behandlungsstrategien des Tetanus.

As a result of active immunisation, tetanus has become a rare but still severe neurological disease in the developed world. Despite modern intensive care management, mortality ranges between 20 and 50%. Introduction of mechanical ventilation dramatically reduced mortality; the life-threatening vegetative dysfunctions with cardiovascular instability are now the main reasons for the remaining poor prognosis. This report provides information about clinical features, diagnosis and prophylaxis of the disease and gives an overview of the therapeutic principles of generalized tetanus, focusing on the management of autonomic instability.

Dehydration confounds the assessment of brain atrophy.

Computerized brain volumetry has potential value for diagnosis and the follow-up evaluation of degenerative disorders. A potential pitfall of this method is the extent of physiologic variations in brain volume. The authors show that dehydration and rehydration can significantly change brain volume: lack of fluid intake for 16 hours decreased brain volume by 0.55% (SD, +/-0.69), and after rehydration total cerebral volume increased by 0.72% (SD, +/-0.21).