The Cortical Signature of Central Poststroke Pain: Gray Matter Decreases in Somatosensory, Insular, and Prefrontal Cortices.

It has been proposed that cortical structural plasticity plays a crucial role in the emergence and maintenance of chronic pain. Various distinct pain syndromes have accordingly been linked to specific patterns of decreases in regional gray matter volume (GMV). However, it is not known whether central poststroke pain (CPSP) is also associated with cortical structural plasticity. To determine this, we employed T1-weighted magnetic resonance imaging at 3 T and voxel-based morphometry in 45 patients suffering from chronic subcortical sensory stroke with (n = 23) and without CPSP (n = 22), and healthy matched controls (n = 31). CPSP patients showed decreases in GMV in comparison to healthy controls, involving secondary somatosensory cortex (S2), anterior as well as posterior insular cortex, ventrolateral prefrontal and orbitofrontal cortex, temporal cortex, and nucleus accumbens. Comparing CPSP patients to nonpain patients revealed a similar but more restricted pattern of atrophy comprising S2, ventrolateral prefrontal and temporal cortex. Additionally, GMV in the ventromedial prefrontal cortex negatively correlated to pain intensity ratings. This shows for the first time that CPSP is accompanied by a unique pattern of widespread structural plasticity, which involves the sensory-discriminative areas of insular/somatosensory cortex, but also expands into prefrontal cortex and ventral striatum, where emotional aspects of pain are processed.

Levetiracetam in patients with central neuropathic post-stroke pain--a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: Central post-stroke pain (CPSP) is a severe chronic neuropathic pain condition defined as a spontaneous pain or allodynia corresponding to a vascular lesion. It usually evolves weeks after stroke, and can distinctively impair the quality of life. Treatment is complex and mostly unsatisfactory. We hypothesized that the anti-epileptic drug levetiracetam (LEV) improves CPSP compared with placebo. The purpose of this study was to examine the efficacy and tolerability of LEV in patients with CPSP. METHODS: In a double-blind, placebo-controlled, crossover study design patients with CPSP lasting at least 3 months and a pain score ≥ 4 on the 11-point Likert scale were treated over two 8-week periods with a maximum dose up to 3000 mg LEV or placebo. Primary endpoint was a median pain lowering ≥ 2 in the final treatment week compared with the last baseline week. Secondary outcome measures comprised additional pain ratings, depression, sleep quality, quality of life and patients' global impression of change. RESULTS: Of 42 patients, 33 [61.5 years (40-76); 38% women] completed the study. Side effects and withdrawals were more frequent in the LEV (n = 5) group than in the placebo group (n = 1). Patients treated with LEV did not show any improvement of pain or changes in secondary outcome parameters compared with placebo. CONCLUSIONS: LEV is not effective in treatment for CPSP. The mode of action of LEV does not exert an analgesic effect in chronic CPSP.

FLAIR vascular hyperintensities in acute ICA and MCA infarction: a marker for mismatch and stroke severity?.

BACKGROUND: Vascular hyperintensities of brain-supplying arteries on stroke FLAIR MRI are common and represent slow flow or stasis. FLAIR vascular hyperintensities (FVH) are discussed as an independent marker for cerebral hypoperfusion, but the impact on infarct size and clinical outcome in acute stroke patients is controversial. This study evaluates the association of FVH with infarct morphology, clinical stroke severity and infarct growth in patients with symptomatic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion. METHODS: MR images of 84 patients [median age 73 years (IQR 65-80), 56.0% male, median NIHSS 7 (IQR 3-13)] with acute stroke due to symptomatic ICA or MCA occlusion or stenosis were reviewed. Vessel occlusions were identified by MRA time of flight and graded with the TIMI score. Diffusion and perfusion deficit volumes on admission and FLAIR lesion volumes on discharge were assessed. The presence and number of FVH were evaluated according to MCA-ASPECT areas, and associations with MR volumes, morphology of infarction, recanalization status, presence of white matter disease and hemorrhagical transformation as well as with stroke severity (NIHSS), stroke etiology and thrombolysis rate were analyzed. RESULTS: FVH were detectable in 75 (89.3%) patients. The median number of FVH was 4 (IQR 2-7). Patients with FVH >4 presented with more severe strokes due to NIHSS (p = 0.021), had larger initial DWI lesions (p = 0.008), perfusion deficits (p = 0.001) and mismatch volumes/ratios (p = 0.005). The final infarct volume was larger (p = 0.005), and hemorrhagic transformation was more frequent (p = 0.029) in these patients. CONCLUSIONS: The presence of FVH indicates larger ischemic areas in brain parenchyma predominantly caused by proximal anterior circulation vessel occlusion. A high count of FVH might be a further surrogate marker for initial ischemic mismatch and stroke severity.

Thrombophilia screening in young patients with cryptogenic stroke. Prevalence of gene polymorphisms compared to healthy blood donors and impact on secondary stroke prevention.

UNLABELLED: The clinical relevance of thrombophilia screening in stroke patients is still a matter of debate, and descriptions of larger patterns of genetic variability are rare. We assessed the frequency of hereditary hypercoagulability in young patients with cryptogenic stroke (n = 44) and in healthy blood donors (n = 282) without prior cardiovascular event. Furthermore, we focused on the impact of thrombophilia screening on secondary stroke prevention. RESULTS: Compared to the control group (19-67 years; median 38.5 years; 64% women), there was a lower prevalence of the FVII-R353Q mutation (p = 0.033) in stroke patients (17-52 years; median 36 years; 59.1% women). Of note, the FVII-R353Q mutation lowers FVII plasma levels, probably reducing the risk of cardiovascular events. The prevalence of the remaining 13 gene polymorphisms did not differ significantly. However, the prevalence of FV Leiden mutation tended to be higher among stroke patients. CONCLUSION: Overall, extended screening for inherited thrombophilia had an impact on medical stroke prevention in every sixth patient with cryptogenic stroke.

Small-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury.

Limited axonal plasticity within the central nervous system (CNS) is a major restriction for functional recovery after CNS injury. The small GTPase RhoA is a key molecule of the converging downstream cascade that leads to the inhibition of axonal re-growth. The Rho-pathway integrates growth inhibitory signals derived from extracellular cues, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, oligodendrocyte-myelin glycoprotein, Ephrins and repulsive guidance molecule-A, into the damaged axon. Consequently, the activation of RhoA results in growth cone collapse and finally outgrowth failure. In turn, the inhibition of RhoA-activation blinds the injured axon to its growth inhibitory environment resulting in enhanced axonal sprouting and plasticity. This has been demonstrated in various CNS-injury models for direct RhoA-inhibition and for downstream/upstream blockade of the RhoA-associated pathway. In addition, RhoA-inhibition reduces apoptotic cell death and secondary damage and improves locomotor recovery in clinically relevant models after experimental spinal cord injury (SCI). Unexpectedly, a subset of "small molecules" from the group of non-steroid anti-inflammatory drugs, particularly the FDA-approved ibuprofen, has recently been identified as (1) inhibiting RhoA-activation, (2) enhancing axonal sprouting/regeneration, (3) protecting "tissue at risk" (neuroprotection) and (4) improving motor recovery confined to realistic therapeutical time-frames in clinically relevant SCI models. Here, we survey the effect of small-molecule-induced RhoA-inhibition on axonal plasticity and neurofunctional outcome in CNS injury paradigms. Furthermore, we discuss the body of preclinical evidence for a possible clinical translation with a focus on ibuprofen and illustrate putative risks and benefits for the treatment of acute SCI.

[Vascular syndromes of the thalamus]. / Vaskuläre Syndrome des Thalamus.

The thalamus comprises numerous nuclei that can be grouped into five major functional domains: (1) the reticular and intralaminar nuclei influence arousal and nociception, (2) sensory nuclei handle afferent pathways, (3) the effector nuclei are involved in motor function and language, (4) associative nuclei participate in higher cognitive functions and (5) limbic nuclei influence mood and motivation. The thalamic nuclei are mainly supplied by the following four cerebral arteries: paramedian artery, anterior thalamoperforating artery, thalamogeniculate artery and posterior choroidal artery (lateral branches). Occlusions of these arteries affect the thalamic nuclei to varying degrees and produce partly characteristic and partly overlapping deficits. This article describes the clinical pictures.

Vascular risk factor awareness before and pharmacological treatment before and after stroke and TIA.

BACKGROUND AND PURPOSE: Educating the public to screen for vascular risk factors and have them treated is a major public health issue. We assessed the vascular risk factor awareness and frequency of treatment in a cohort of patients with cerebral ischaemia. METHODS: Data on awareness and pharmacological treatment of vascular risk factors before hospital admission of patients with confirmed ischaemic stroke/transient ischaemic attack (TIA) were analyzed. A follow-up questionnaire assessed the frequency of treatment 1 year after discharge and assessed non-adherence to antithrombotic medication. RESULTS: At time of stroke/TIA, individual awareness regarding existing hypertension, diabetes, hyperlipidemia and atrial fibrillation (AF) was 83%, 87%, 73% and 69% respectively (n = 558). Pharmacological treatment for hypertension, diabetes, hyperlipidemia and AF was being administered in 80%, 77%, 37% and 62% of patients aware of their conditions. The follow-up was completed by 383 patients (80% recall rate): of the patients with hypertension, diabetes, hyperlipidemia and AF, 89%, 78%, 45% and 86% were receiving risk factor targeted medication. This represents a significant increase concerning AF and hyperlipidemia. Non-adherence to recommended antithrombotics (15%) was higher in patients who had had a TIA. CONCLUSIONS: All risk factors leave room for improvement in screening and treatment efforts. Adherence to treatment is higher for hypertension and diabetes than for hyperlipidemia. Education efforts should bear in mind less well recognized risk factors.

Ultrasound perfusion imaging of small stroke involving the thalamus.

PURPOSE: Ultrasound (US) perfusion imaging of ischemic stroke has mainly been applied to large middle cerebral artery infarction. We investigated whether small stroke involving the thalamus can also be detected. MATERIALS AND METHODS: Phase inversion harmonic imaging (PIHI) was applied to patients with small infarctions involving the thalamus (maximal longitudinal infarct diameter less than 3 cm). PIHI was performed from both the left and right side in axial diencephalic planes. Infarct size and location as well as perfusion properties (MTT maps) were known from MRI. US perfusion parameters were derived from the signal enhancement time course (bolus kinetics, SonoVue for peak-signal increase and time-to-peak. RESULTS: Seventeen patients (52 +/- 11 years, 24% female) with 18 strokes (16 unilateral, 1 bilateral) were included. Six US examinations (18%) were inadequate for analysis due to an insufficient transtemporal bone window. US perfusion depicted 90 % of infarcts with a longitudinal diameter of more than 2 cm. Infarcts with a longitudinal diameter of less than 2 cm were hardly identified. CONCLUSION: PIHI allows identification of a small infarction involving the thalamus subject to infarct size.

[Successful thrombolysis after an ischemic stroke in an 92-year-old woman]. / Erfolgreiche Thrombolyse nach Schlaganfall bei einer 92-jährigen Patientin.

HISTORY: A 92-year-old woman was found by her domestic help to have suddenly sustained a left-sided weakness in her limbs 30 minutes after she had seemed perfectly well. She had undergone a total hip replacement 4 weeks previously. ADMISSION FINDINGS: Her National Institutes of Health stroke scale (NIHSS) score was 18. She had a left hemiparesis with sensory deficits, left-sided neglect, dysarthria and aphasia. INVESTIGATIONS: Stroke magnetic resonance imaging (MRI) confirmed the suspected diagnosis of ischemic infarction within the territory supplied by the right middle cerebral artery, with diffusion in the periventricular region and the cortex of the right basal temporal lobe. TREATMENT AND FURTHER COURSE: Recombinant tissue plasminogen activator (rtPA) was administered intravenously. At completion of the infusion the neurological deficits had lessened. The NIHSS was reduced to 6 and ultimately was 0. CONCLUSION: Patients older than 80 years who have sustained a stroke can benefit from rtPA administration. Stroke-MRI is a valuable tool in the early diagnosis and may improve the safety of thrombolysis, especially in borderline situations such as advanced age or in the face of a closing "time window". Currently the mismatch concept (greater perfusion deficit than diffusion abnormality) does not replace the time criterion.

Prevalence of stroke and stroke symptoms: a population-based survey of 28,090 participants.

BACKGROUND: Stroke is associated with a considerable burden of disease worldwide. Data about prevalence needs regular updating to facilitate health care planning and resource allocation. The purpose of the present study was to determine stroke prevalence in a large urban population in an easy and reliable way. METHODS: In a population survey a total of 75,720 households with at least 1 person >or=50 years received information about stroke symptoms by mail. In addition, the Stroke Symptom Questionnaire assessing the prevalence of stroke and of stroke symptoms was sent. Stroke prevalence was determined by a single physician-diagnosed stroke-screening question or by the combination of the latter with reported visual impairment and/or articulation problems in the past. RESULTS: A total of 28,090 persons responded (37.5%). Mean (+/-SD) age was 64.4 +/- 9.7 years, 62.9 +/- 8.9 for men (43.3%), and 65.5 +/- 10.2 for women. Of all participants 2.7% reported impaired vision, 2.8% facial weakness, 2.8% articulation problems, 3.9% limb weakness, and 5% sensory disturbances. A total of 4.5% reported a physician-diagnosed stroke (women 4.3%; men 4.9%). Combining reported stroke history with reported impaired vision and/or articulation problems, the prevalence of stroke increased to 7.6% (men 8.4%; women 7.2%). Factors associated with higher prevalence were higher age, male gender, non-German nationality, lower education, positive family history of stroke, and living alone. CONCLUSIONS: The combination of questions concerning a prior stroke and stroke symptoms is a useful and easy approach to assess prevalence. It results in prevalence numbers which might compensate for an underestimation of stroke numbers.

Emergency department delays in acute stroke - analysis of time between ED arrival and imaging.

We determined the factors leading to emergency department (ED) delays in patients with acute stroke. Data were collected prospectively in four Berlin inner-city hospitals by ED documentation, medical records, imaging files and patient interviews. An extended Cox proportional hazards model was fitted to the data. Analyses were performed in 558 patients with confirmed diagnosis of stroke. Median time from admission at ED to beginning of computed tomography/magnetic resonance imaging (CT/MRI) was 108 min. In a subgroup of patients potentially eligible for thrombolysis with a pre-hospital delay <120 min and a National Institutes of Health Stroke Scale (NIHSS) >4 (n = 74), the median interval to imaging was 68 min. Multivariable analysis revealed that a more severe initial NIHSS, a pre-hospital delay <3 h, admission at two specific hospitals, admission at weekends, and private health insurance were significantly associated with reduced delays. In stroke patients, the time interval between ED admission and imaging depends both on factors that emerge from clinical needs and on factors independent of clinical necessities. Considering the urgency of therapeutic measures in acute stroke, there is necessity and room for both improvement of in-hospital management and of medical and non-medical factors influencing pre-hospital delays.

[Two simple questions to diagnose post-stroke depression]. / Zwei einfache Fragen zur Diagnose der Post-Schlaganfall Depression.

BACKGROUND AND PURPOSE: Many patients develop a depression after having suffered a stroke. Such a Post-Stroke Depression (PSD) impairs rehabilitation and quality of life. PSD is underdiagnosed in spite of available treatment. Several questionnaires have been created to diagnose a PSD. But questionnaires have been considered cumbersome and time-consuming. The aim of this study was to find out whether two simple, standardised questions will identify those stroke patients, who have developed a PSD. METHODS: The two case-finding questions and the Beck Depression Inventory (BDI) were sent to patients of the Berlin Acute Stroke Study (BASS) four years after their stroke. Incomplete questionnaires were complemented via mail or telephone. Severity of depression was assessed by means of BDI. RESULTS: Out of 211 patients, 199 responded to the questionnaire (94 %). 193 questionnaires were complete (97 %). Forty-two patients affirmed both case-finding questions (22 %). Compared to patients, who did not affirm both questions, these patients had a higher BDI score (19 +/- 8 vs. 7 +/- 5; p < 0.001). The sensitivity and specificity of the two questions were 89 % and 90 %, respectively. The positive and negative predictive value were 60 % and 98 % respectively. The number of confirmed questions (0, 1, 2) correlated well with the BDI score (r (2) = 0.67, p < 0.001). CONCLUSIONS: Two standardized questions can identify patients with PSD for further diagnostic evaluation and therapy. Diagnosis of PSD might be facilitated by using them as screening instrument.

Medical resource use and costs of health care after acute stroke in Germany.

The purpose of this study was to determine the 12 months medical resource use following admission to hospital with acute stroke and to calculate costs from a societal perspective. Data of consecutive patients with confirmed stroke were analysed. Acute hospital data were taken from medical records, socio-demographic variables from patients' interviews. A follow-up questionnaire about resource utilization was completed by patients or proxies 12 months after acute hospital admission. Costs were calculated by multiplying medical resource units used with cost factors per unit. Mean age of a total of 383 patients was 65 years and 41% were female. The median length of the initial stay in the acute hospital was 12 days at an average cost of 4650 per patient (49% of direct costs). Rehabilitation (16%), readmission (11%), medication (9%), and nursing costs (6%) were other contributors to the direct costs which amounted to a total of 9452 +/- 7599 per patient during 12 months. Indirect cost amounted to a total of 2014 +/- 5312. Patients' age, severity and type of stroke influenced the total stroke-associated costs. The large economic burden of stroke indicates the need for assessing and improving efficient health care for affected patients.

[Symptoms, risk factors, and etiology of transient ischemic attack and stroke]. / Symptome, Risikofaktoren und Atiologie von transitorisch ischämischer Attacke und Schlaganfall.

BACKGROUND: It is unclear whether clinical signs and symptoms differ in the presentation of transient ischemic attack (TIA) and stroke, apart from temporal dynamics. METHODS: Signs and symptoms of patients diagnosed with TIA or stroke were prospectively collected and compared by means of an age-adjusted logistic regression analysis. Risk factors, prehospital medication, and diagnostic workup were obtained from the charts. RESULTS: Four hundred five patients diagnosed with stroke (68+/-12 years old, 45% female) and 143 diagnosed with TIA (64+/-14 years old, 48% female) were included. Signs and symptoms of patients with TIA were less often "classic" such as paresis (48% vs 71%, P<0.001) or sensory loss (38% vs 48%, P=0.03). The etiology of TIA was more often classified as "undetermined" (57% vs 46%, P<0.05). CONCLUSIONS: Transient ischemic attack needs special attention and intensive diagnostic workup, because it bears a considerable risk of death and disability but presents less often with classic signs and symptoms and its etiology often remains undetermined.

Eyelid tremor in a patient with a unilateral paramedian thalamic lesion.

A patient with a circumscribed infarction of the right paramedian thalamus developed a tremor of both eyelids on voluntary eye closure. Co-registration of the magnetic resonance image to a stereotactic atlas of the human thalamus revealed that the lesion was confined to a small subgroup of paramedian nuclei, including the parvocellular part of the mediodorsal nucleus. It is concluded that this region provides inhibitory input to cortical and/or subcortical regions controlling eyelid movements. Voluntary eye closure may involve direct cortico-nuclear connections and indirect pathways through the paramedian thalamus, most probably through the mediodorsal nucleus.