Acute symptomatic extracranial internal carotid occlusion - natural course and clinical impact.

Background: To assess the vascular and clinical course of acute symptomatic extracranial internal carotid artery (ICA) occlusion. Patients and methods: Patients with an acute ischemic event in the anterior circulation and corresponding extracranial ICA occlusion at CT angiography and/or color-coded duplex sonography underwent recurrent duplex follow-up for detection of spontaneous recanalization. Stroke recurrence and functional outcome 4.5 months after the ischemic index event assessed by modified Rankin scale served as secondary outcome parameters. Results: 133 patients (91 men, mean age 62.3 years, SD 10.8) demonstrated symptomatic occlusion of the extracranial ICA with open intracranial ICA and open middle cerebral artery and were followed-up for spontaneous recanalization. Twenty-eight recanalized spontaneously, 25 to high-grade focal stenosis within 12 days, revealing an early cumulative recanalization rate of 23 %. Detection of recanalization was independently associated with de novo dual anti-platelet therapy (adjusted odds ratio [OR], 3.24; 95 % confidence interval [CI], 1.34 to 7.80). Ischemic recurrence occurred in 16 patients, of which 10 deemed to be embolic and 5 hemodynamic. Spontaneous ICA recanalization and an exhausted cerebrovascular reserve in the hemisphere distal to the occluded ICA were both independently associated with the occurrence of a recurrent ischemic event at Cox regression. An increasing NIHSS score at admission, a decreasing middle cerebral artery flow velocity and an ischemic recurrence independently predicted poor outcome (modified Rankin scale 3 to 6) in multivariate analysis. Conclusions: Acute symptomatic extracranial ICA occlusion is an unstable condition with frequent spontaneous recanalization to severe stenosis and early embolic stroke recurrence, demanding appropriate prevention especially in those patients with only mild deficit.

Interhemispheric connectivity in amyotrophic lateral sclerosis: A near-infrared spectroscopy and diffusion tensor imaging study.

PURPOSE: Aim of the present study was to investigate potential impairment of non-motor areas in amyotrophic lateral sclerosis (ALS) using near-infrared spectroscopy (NIRS) and diffusion tensor imaging (DTI). In particular, we evaluated whether homotopic resting-state functional connectivity (rs-FC) of non-motor associated cortical areas correlates with clinical parameters and disease-specific degeneration of the corpus callosum (CC) in ALS. MATERIAL AND METHODS: Interhemispheric homotopic rs-FC was assessed in 31 patients and 30 healthy controls (HCs) for 8 cortical sites, from prefrontal to occipital cortex, using NIRS. DTI was performed in a subgroup of 21 patients. All patients were evaluated for cognitive dysfunction in the executive, memory, and visuospatial domains. RESULTS: ALS patients displayed an altered spatial pattern of correlation between homotopic rs-FC values when compared to HCs (p = 0.000013). In patients without executive dysfunction a strong correlation existed between the rate of motor decline and homotopic rs-FC of the anterior temporal lobes (ATLs) (ρ = - 0.85, p = 0.0004). Furthermore, antero-temporal homotopic rs-FC correlated with fractional anisotropy in the central corpus callosum (CC), corticospinal tracts (CSTs), and forceps minor as determined by DTI (p < 0.05). CONCLUSIONS: The present study further supports involvement of non-motor areas in ALS. Our results render homotopic rs-FC as assessed by NIRS a potential clinical marker for disease progression rate in ALS patients without executive dysfunction and a potential anatomical marker for ALS-specific degeneration of the CC and CSTs.

Near-infrared spectroscopy and transcranial sonography to evaluate cerebral autoregulation in middle cerebral artery steno-occlusive disease.

The measurement of autoregulatory delay by near-infrared spectroscopy (NIRS) has been proposed as an alternative technique to assess cerebral autoregulation, which is routinely assessed via transcranial Doppler sonography (TCD) in most centers. Comparitive studies of NIRS and TCD, however, are largely missing. We investigated whether cerebrovascular reserve (CVR), as assessed via TCD, correlates with the delay of the autoregulatory response to changes in arterial blood pressure (ABP) as assessed by NIRS, i.e., if impaired upstream vasomotor reactivity is reflected by downstream cortical autoregulation. Twenty patients with unilateral high-grade steno-occlusion of the middle cerebral artery (MCA) underwent bilateral multichannel NIRS of the cortical MCA distributions over a period of 6 min while breathing at a constant rate of 6 cycles/min to induce stable oscillations in ABP. The phase shift φ between ABP and cortical blood oxygenation was calculated as a measure of autoregulatory latency. In a subgroup of 13 patients, CO2 reactivity of the MCAs was determined by TCD to assess CVR in terms of normalized autoregulatory response (NAR). Mean phase shift between ABP and blood oxygenation was significantly increased over the hemisphere ipsilateral to the steno-occlusion (n = 20, p = 0.042). The interhemispheric difference Δφ in phase shift was significantly larger in patients with markedly diminished or exhausted CVR (NAR < 10) than in patients with normal NAR values (NAR ≥ 10) (p = 0.007). Within the MCA core distribution territory, a strong correlation existed between Δφ and CO2 reactivity of the affected MCA (n = 13, r = -0.78, p = 0.011). NIRS may provide an alternative or supplementary approach to evaluate cerebral autoregulation in risk assessment of ischemic events in steno-occlusive disease of cerebral arteries, especially in patients with insufficient bone windows for TCD.

Peripheral nerve ultrasound in amyotrophic lateral sclerosis phenotypes.

INTRODUCTION: In this study we sought to determine the cross-sectional area (CSA) of peripheral nerves in patients with distinct subtypes of amyotrophic lateral sclerosis (ALS). METHODS: Ulnar and median nerve ultrasound was performed in 78 ALS patients [classic, n = 21; upper motor neuron dominant (UMND), n = 14; lower motor neuron dominant (LMND), n = 20; bulbar, n = 15; primary lateral sclerosis (PLS), n = 8] and 18 matched healthy controls. RESULTS: Compared with controls, ALS patients had significant, distally pronounced reductions of ulnar CSA (forearm/wrist level) across all disease groups, except for PLS. Median nerve CSA (forearm/wrist level) did not differ between controls and ALS. CONCLUSION: Ulnar nerve ultrasound in ALS subgroups revealed significant differences in distal CSA values, which suggests it has value as a marker of LMN involvement. Its potential was particularly evident in the UMND and PLS groups, which can be hard to separate clinically, yet their accurate separation has major prognostic implications.

[Ischemic stroke--diagnosis and treatment]. / Ischämischer Insult - Diagnostik und Therapie.

Management of ischemic stroke is targeted on four therapeutic objectives: limitation of neurological deficit, prevention of earyl stroke recurrence, protection against complications, and secondary prevention. Intravenous thrombolysis within 4.5h of stroke onset is the only proven therapy to improvefunctional outcome. Although promising, neither endovascular recanalisation nor neuroprotective strategies have demonstrated efficacy so far. Immediate administration of antiplatelet agents like acetylsalicylic acid and clopidogrel - in case of intravenous thrombolysis at the earliest after 24h - is effective to prevent early stroke recurrence, whereas anticoagulants should be ommitted in this stage because of an increased risk of cerebral hemorrhage. Subcutaneous heparin/low molecular weight heparin, mobilisation, nasogastric tube, and decompressive craniectomy may protect from venous thromboembolism, aspiration pneumonia, and malignant brain edema, respectively. Secondary prevention is guided by stroke etiology, e.g. oral anticoagulation in the presence atrial fibrillation or endarterectomy in case of sympomatic high-grade carotid stenosis.

Sonography of the median nerve in CMT1A, CMT2A, CMTX, and HNPP.

INTRODUCTION: In this study we compare the ultrasound features in the median nerve in patients with different types of Charcot-Marie-Tooth (CMT) disease and hereditary neuropathies with liability to pressure palsies (HNPP) as a typical entrapment neuropathy. METHODS: Median nerve ultrasound and conduction studies were performed in patients with CMT1A (n = 12), MFN2-associated CMT2A (n = 7), CMTX (n = 5), and HNPP (n = 5), and in controls (n = 28). RESULTS: Median nerve cross-sectional area (CSA) was significantly increased in CMT1A, whereas, in axonal CMT2A, fascicle diameter (FD) was enlarged. CSA correlated with nerve conduction slowing in CMT1A and with axonal loss, as shown by motor and sensory nerve amplitudes in both CMT1A and CMT2A. A relatively low wrist-to-forearm-ratio (WFR <0.8) or a relatively high WFR (>1.8) appeared to be unlikely in MFN2 and Cx32 mutations of CMT2A and CMTX, respectively. CONCLUSION: Differences in CSA, FD, and WFR of the median nerve can be helpful in defining subtypes of hereditary neuropathies.

Assessment of cortical hemodynamics by multichannel near-infrared spectroscopy in steno-occlusive disease of the middle cerebral artery.

BACKGROUND AND PURPOSE: In a pilot study we evaluated near-infrared spectroscopy as to its potential benefit in monitoring patients with steno-occlusive disease of a major cerebral artery for alterations in cortical hemodynamics. METHODS: Cortical maps of time-to-peak (TTP) in 10 patients unilaterally affected by severe stenosis or occlusion of the middle cerebral artery were acquired by multichannel near-infrared spectroscopy after bolus application of indocyanine green. Hemodynamic manifestations were assessed by comparison between affected and unaffected hemisphere and evaluated for common constituents by principal component analysis. In one patient, TTP values were compared with those obtained by dynamic susceptibility contrast imaging. RESULTS: TTP was increased on the affected hemisphere in 9 patients. Mean difference in TTP between hemispheres was 0.44 second (P<0.05) as compared with a mean lateral difference of 0.12 second found in a control group of 10 individuals. In group analysis a significant rise in TTP was found in the distribution of the affected middle cerebral artery, whereas principal component analysis suggests augmentation of hemodynamic effects toward the border zones as a dominant pattern. A linear correlation of 0.61 between TTP values determined by dynamic susceptibility contrast MRI and near-infrared spectroscopy was found to be statistically significant (P<0.001). CONCLUSIONS: Multichannel near-infrared spectroscopy might facilitate detection of disease-related hemodynamic changes as yet only accessible by tomographic imaging modalities. Being indicative for hypoperfusion and collateral flow increased values of TTP, as found to a varying extent in the present patient group, might be of clinical relevance.

Do basophile structures as age dependent phenomenon indicate small vessel wall damage?

Here we demonstrate basophile structures located in the arteriolar wall and being associated with a plasma-protein-leakage. We assume, that the structures indicate blood-brain-barrier-disturbances and degenerative small vessel wall alterations.

Stases are associated with blood-brain barrier damage and a restricted activation of coagulation in SHRSP.

Cerebral small vessel disease (CSVD) is a chronically proceeding pathology of small brain vessels associated with white matter lesions, lacunar infarcts, brain atrophy and microbleeds. CSVD leads to slowly increasing cognitive and functional deficits but may also cause stroke-like symptoms, if vessels in critical brain areas are affected. Spontaneously hypertensive stroke-prone rats (SHRSP) exhibit several vascular risk factors, develop infarcts and hemorrhages and therefore represent a relevant model for the study of CSVD. Using this animal model, we recently demonstrated that intravasal accumulations of erythrocytes, we interpreted as stases, stand at the beginning of a pathological vascular cascade. After stases microbleeds occur, which are followed by reactive microthromboses. Bleeds and thromboses finally cause hemorrhagic infarcts. Immunohistochemical stainings show, that plasma proteins like IgG are deposited in the walls of vessels affected by stases. Further, we found small clots and thread-shaped aggregations of thrombocytes as well as thread-shaped structures of von Willebrand-Factor within stases. Thus, we conclude that blood-brain barrier damages occur in the neighborhood of stases and stases seem to be associated with a restricted activation of blood coagulation without formation of obstructive thromboses. Finally, we demonstrate that small vessel damage rarely appears in the cerebellum. Even animals with multiple cerebral infarcts may be free of any cerebellar vascular pathology.

Risk of wound hematoma at carotid endarterectomy under dual antiplatelet therapy.

BACKGROUND AND PURPOSE: This study aims to assess perioperative incidence of wound hematoma and bleeding in patients who underwent carotid endarterectomy (CEA) under dual antiplatelet therapy. METHODS: Consecutive patients with initial CEA receiving aspirin, clopidogrel, or a combination of both were subjected to standard patch endarterectomy. Postoperative wound hematoma was assessed as moderate (subcutaneous bleeding, nonspace-occupying hematoma, and oozing suture bleeding) or severe, i.e., needing operative re-exploration. RESULTS: Six hundred eighty-four (80.9%) patients with one of the three types of antiplatelet therapy out of 844 patients registered from 1995 to 2010 were enrolled. Wound hematoma occurred in 27 of 112 (24.1%) patients under combined aspirin and clopidogrel, 33 of 162 (20.4%) under clopidogrel, and 48 of 410 (11.7 %) under aspirin. Relative risk compared to aspirin was 2.4 (95% CI, 1.4 to 4.1) for aspirin and clopidogrel and 1.9 (95% CI, 1.2 to 3.1) for clopidogrel. Severe space-occupying hematoma needing operative re-exploration occurred in four (3.6%) patients under aspirin and clopidogrel, seven (4.3%) under clopidogrel, and five (1.2%) under aspirin. Corresponding relative risks were 3.0 (95% CI, 0.8 to 11.4) for aspirin and clopidogrel and 3.7 (95% CI, 1.1 to 11.7) for clopidogrel. Relative risks remained without relevant change after adjustment for potentially confounding variables. CONCLUSIONS: Dual antiplatelet therapy with combined aspirin and clopidogrel as well as clopidogrel is associated with an increased incidence of perioperative wound hematoma compared to aspirin but on an acceptable low level of incidence. The latter may be achieved by adapting operative procedures to more intensive antiplatelet regimes.

Three-dimensional angiography of classic and occult lesion types in choroidal neovascularization.

PURPOSE: To identify characteristic features of classic and occult choroidal neovascularization (CNV) by using a novel technique of topographic angiography for three-dimensional (3D) visualization. METHODS: A confocal scanning laser ophthalmoscope (SLO, Heidelberg Retina Angiograph; Heidelberg Engineering, Dossenheim, Germany) was used to perform fluorescein (FA) and indocyanine green (ICGA) angiography in158 patients. Ninety-four eyes had predominantly classic and 64 eyes had occult lesions. With an image frequency of 20 Hz, a tomographic series of 32 images per set were taken over a depth of 4 mm. Axial analyses for each x/year position were performed, to determine the fluorescence distribution along the z-axis. After the axial location of hyperfluorescence was detected, a depth profile was generated. All results were integrated into a gray-scale-coded depth image and imaged as a 3D relief. RESULTS: Characteristic features of classic and occult lesions were distinguished. Classic CNV appeared as a well-demarcated lesion with steep, prominent borders, often craterlike, and frequently surrounded by a halo, suggesting choroidal perfusion changes. Occult CNV was documented by 3D as a convex lesion with flat, ill-defined borders and without any surrounding halo. Topographic imaging is superior to conventional angiography regarding definition of lesion type, configuration, and extension, because masking phenomena do not interfere. CONCLUSIONS: Topographic angiography allows a realistic 3D representation of CNV. Characteristic features based on the neovascular architecture and the differences in leakage behavior of different lesion types are clearly identified.