Mirko Pham
Research interests
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InterestsMRI, Stroke, Interventional Neuroradiology, Diagnostic Radiology, Imaging, Neuroimaging, Peripheral Nerves
Other
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Scientific MembershipsDGNR, DRG, ESNR
Publications
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5.00Impact points
Blood coagulation factor XII--a neglected player in stroke pathophysiology.
Journal of molecular medicine (Berlin, Germany). 09/2011; 90(2):119-26.
Ischemic stroke is a devastating disease which, in most cases, is caused by thrombotic occlusion of brain arteries. The molecular mechanisms involved in microvascular thrombus formation during focal cerebral ischemia are not well understood. As a consequence, the current antithrombotic drugs used to... [more] Ischemic stroke is a devastating disease which, in most cases, is caused by thrombotic occlusion of brain arteries. The molecular mechanisms involved in microvascular thrombus formation during focal cerebral ischemia are not well understood. As a consequence, the current antithrombotic drugs used to treat acute stroke or prevent stroke recurrence either show limited efficacy or put patients at risk for serious bleeding complications. The serine protease blood coagulation factor XII (FXII) initiates the intrinsic pathway of coagulation which, together with the extrinsic pathway, culminates in the formation of fibrin. A physiological function of FXII in clot formation and hemostasis in vivo has been questioned for more than 50 years. This was mainly due to the fact that hereditary FXII deficiency does not induce any bleeding phenotype in humans. However, recent studies in transgenic mice challenged this concept by demonstrating that FXII deficiency prevents pathological thrombus formation, but does not affect regular hemostasis. These findings entailed investigations in relevant disease models of thromboembolism including ischemic stroke. The present review summarizes the pathophysiological role of FXII in experimental cerebral ischemia and highlights novel therapeutic strategies based on FXII inhibition.
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7.04Impact points
Mechanical thrombectomy in acute embolic stroke: preliminary results with the revive device.
Stroke; a journal of cerebral circulation. 08/2011; 42(10):2954-6.
The purpose of this study was to evaluate the safety and technical feasibility of a new thrombectomy device (Revive; Micrus Endovascular) in the endovascular treatment of acute ischemic stroke. Ten patients with acute large vessel occlusions were treated with the Revive device between October 2010 a... [more] The purpose of this study was to evaluate the safety and technical feasibility of a new thrombectomy device (Revive; Micrus Endovascular) in the endovascular treatment of acute ischemic stroke. Ten patients with acute large vessel occlusions were treated with the Revive device between October 2010 and December 2010. Mean National Institutes of Health Stroke Scale on admission was 19.0; mean duration of symptoms was 172 minutes. Recanalization was assessed using the Thrombolysis In Cerebral Infarction score. Clinical outcome (National Institutes of Health Stroke Scale) after thrombectomy was determined on Day 1, at discharge, and at Day 30. Vessel recanalization (Thrombolysis In Cerebral Infarction 2b or 3) was successful in all patients without device-related complications. Mean National Institutes of Health Stroke Scale 24 hours after the intervention, at discharge, and at Day 30 was 14.0, 11.5, and 5.1, respectively. At Day 30, 6 patients had a clinical improvement of >8 points or an National Institutes of Health Stroke Scale of 0 to 1, 1 patient showed minor improvement, and 3 patients had died. Symptomatic intracranial hemorrhage occurred in 2 patients, of which 1 was fatal. Thrombectomy with the Revive device in patients with stroke with acute large vessel occlusions demonstrated to be technically safe and highly effective. Clinical safety and efficacy have to be established in larger clinical trials.
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3.59Impact points
MR-Imaging of teeth and periodontal apparatus: an experimental study comparing high-resolution MRI with MDCT and CBCT.
European radiology. 07/2011; 21(12):2575-83.
The aim of this study was (1) to assess the ability of magnetic resonance imaging (MRI) to visualize dental and periodontal structures and (2) to compare findings with multidetector computed tomography (MDCT) and cone beam CT (CBCT). Four porcine mandibles were examined with (1) 3T-MRI, (2) MDCT and... [more] The aim of this study was (1) to assess the ability of magnetic resonance imaging (MRI) to visualize dental and periodontal structures and (2) to compare findings with multidetector computed tomography (MDCT) and cone beam CT (CBCT). Four porcine mandibles were examined with (1) 3T-MRI, (2) MDCT and (3) CBCT. Two observers independently reviewed MR, MDCT and CBCT images and assessed image quality of different dental and periodontal structures. To assess quantitatively the accuracy of the different imaging technique, both observers measured burr holes, previously drilled in the mandibles. Dental structures, e.g. teeth roots, pulpa chamber and dentin, were imaged accurately with all imaging sources. Periodontal space and cortical/trabecular bone were better visualized by MRI (p < 0.001). MRI could excellently display the lamina dura, not detectable with MDCT and only inconstant visible with CBCT (p < 0.001). Burr hole measurements were highly precise with all imaging techniques. This experimental study shows the diagnostic feasibility of MRI in visualization of teeth and periodontal anatomy. Detection of periodontal structures was significantly better with MRI than with MDCT or CBCT. Prospective trials have to evaluate further the potential benefit of MRI in a clinical setting.
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6.34Impact points
Ulnar neuropathy at the elbow: MR neurography--nerve T2 signal increase and caliber.
Radiology. 07/2011; 260(1):199-206.
To assess nerve T2 signal and caliber as diagnostic signs at magnetic resonance (MR) neurography in ulnar neuropathy at the elbow (UNE). This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. Twenty patients with UNE we... [more] To assess nerve T2 signal and caliber as diagnostic signs at magnetic resonance (MR) neurography in ulnar neuropathy at the elbow (UNE). This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. Twenty patients with UNE were graded by using clinical criteria and nerve conduction studies as mild (n = 12) and severe (n = 8) and were compared with 20 healthy control subjects. All subjects underwent ulnar nerve MR neurography (in-plane resolution of 0.4 × 0.4 mm) covering the elbow region, including T2-weighted imaging with fat suppression (turbo inversion-recovery magnitude sequence: repetition time msec/echo time msec/inversion time msec, 6, 120/66/180) and T1-weighted turbo spin-echo imaging (843/16). Nerve T2 signal increase, measured by using T2-weighted contrast-to-noise ratios across the cubital tunnel, and nerve caliber, determined by using T1-weighted pixelwise measurement of cross-sectional nerve area, were evaluated as diagnostic signs. Qualitative assessment by using visual grading was performed additionally. Diagnostic performance, as determined with area under the receiver operating characteristic curve (AUC), was excellent for nerve T2 signal to discriminate UNE from a normal finding (AUC = 0.94; 95% confidence interval [CI]: 0.87, 1.00) and was excellent for nerve caliber to discriminate severe from mild UNE (AUC = 0.95; 95% CI: 0.85, 1.00). Qualitative assessment demonstrated sensitivity of 83% and specificity of 85% for MR neurography of UNE. Nerve T2 signal increase seems to be an accurate sign to determine the presence of UNE. Nerve caliber enlargement discriminates severe from mild UNE. UNE may be diagnosed with high accuracy by means of quantitative or qualitative evaluation of these signs.
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1.17Impact points
Inflammatory autoimmune neuropathy, presumably induced by bortezomib, in a patient suffering from multiple myeloma.
International journal of hematology. 06/2011; 93(6):791-4.
Bortezomib is a proteasome inhibitor demonstrating substantial activity in multiple myeloma. One of its key toxicities is peripheral neuropathy, which is reversible in most patients. The possibility that bortezomib might in rare cases induce severe neuropathies by auto-inflammatory mechanisms remain... [more] Bortezomib is a proteasome inhibitor demonstrating substantial activity in multiple myeloma. One of its key toxicities is peripheral neuropathy, which is reversible in most patients. The possibility that bortezomib might in rare cases induce severe neuropathies by auto-inflammatory mechanisms remains controversial. We report here the case of a 65-year-old female myeloma patient who was initially treated with bortezomib, doxorubicin, and dexamethasone (PAD). At the end of the second cycle of PAD, the patient presented with a rapid and severe onset of paresis of the left arm, accompanied by progressive sensory neuropathy and increasing neuropathic pain. After an extensive neurological work-up, including electrophysiological and laboratory evaluations as well as magnet resonance tomography imaging, we diagnosed an inflammatory autoimmune neuropathy, presumably induced by bortezomib, with accentuation of the left arm nerve plexus. We subsequently initiated regular treatment with polyvalent immunoglobulins, which gradually improved the neurological symptoms. In conclusion, the identification of an inflammatory autoimmune neuropathy, presumably associated with bortezomib, is a rare but important complication. An extensive neurological examination should be performed in patients who develop severe or unusual sensory or motor deficits under therapy with bortezomib, so as to differentiate autoimmune from toxic neuropathies, as therapeutic strategies differ for each.
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3.30Impact points
Magic angle effect: a relevant artifact in MR neurography at 3T?
AJNR. American journal of neuroradiology. 05/2011; 32(5):821-7.
MRN is an emerging diagnostic method for disorders of peripheral nerves. However, it is unclear whether the influence of the MA on intraneural T2 signal is severe enough to provoke false-positive findings. Twenty-five healthy subjects underwent MRN of the sciatic nerve of the proximal thigh at 3T. T... [more] MRN is an emerging diagnostic method for disorders of peripheral nerves. However, it is unclear whether the influence of the MA on intraneural T2 signal is severe enough to provoke false-positive findings. Twenty-five healthy subjects underwent MRN of the sciatic nerve of the proximal thigh at 3T. The T2(app) was calculated from a DE-TSE sequence (TR = 3000 ms, TE1 = 12 ms, TE2 = 69 ms) at 7 angles of the sciatic nerve relative to B0 = 0°, 30°, 35°, 40°, 45°, 50°, and 55°. Precise angle adjustments were performed with a dedicated in-bore positioning aid. Qualitative evaluation of intraneural T2-weighted contrast between this group of healthy subjects and 14 patients with neuropathic lesions was performed by comparing CNRs of a TIRM sequence (TR = 5000 ms, TE = 76 ms, TI = 180 ms). In healthy subjects, the prolongation of T2(app) from 0° to 55° was from 74.5 ± 13.4 to 104.0 ± 16.9 ms (P < .001). The increase in T2(app) relative to baseline (0°) was 9.6% (30°), 18.4% (35°), 25% (40°), 27.6% (45°), and 37% (55°). Intraneural CNR increased by 1.98 ± 0.69 at 40° and 2.93 ± 0.46 at 55°. Nevertheless, the mean CNR of healthy subjects was substantially lower than that in patients at 40° (P < .0001) and even at the position of maximum MA (55°: 20.6 ± 5.11 versus 52.6 ± 7.12, P < .0001). Neuropathic lesions are clearly distinguishable from an artificial increase of intraneural T2 by the MA. Even at a maximum MA (55°), the false-positive determination of a neuropathic lesion is unlikely.
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2.90Impact points
MR neurography of sciatic nerve injection injury.
Journal of neurology. 01/2011; 258(6):1120-5.
We report on magnetic resonance neurography (MRN) as a supplementary diagnostic tool in sciatic nerve injection injury. The object of the study was to test if T2-weighted (w) contrast within the sciatic nerve serves as an objective criterion for sciatic injection injury. Three patients presented wit... [more] We report on magnetic resonance neurography (MRN) as a supplementary diagnostic tool in sciatic nerve injection injury. The object of the study was to test if T2-weighted (w) contrast within the sciatic nerve serves as an objective criterion for sciatic injection injury. Three patients presented with acute sensory and/or motor complaints in the distribution of the sciatic nerve after dorsogluteal injection and underwent MRN covering gluteal, thigh and knee levels. Native and contrast-enhanced T1-w images were employed to identify the tibial and peroneal division of the sciatic nerve while T2-w images with fat suppression allowed visualization of the site and extent of the nerve lesion. MRN in the two patients with clinically severe sensory and motor impairment correctly depicted sciatic injury: continuity of the T2-w lesion within the nerve at the lesion site and distal to it corresponded well to severe injury confirmed by NCS/EMG as axonotmetic or neurotmetic. Topography of the T2-w lesion on cross-section corresponded to predominant peroneal involvement; moreover, associated denervation patterns of distal target muscles were revealed. One of these patients completely recovered with concomitant complete regression of MRN abnormalities on follow-up. The third patient experienced transient sensory and mild motor impairment with complete recovery after 2 weeks. In this patient, T2-w signal within the nerve and distal target muscles remained normal indicating only mild, non-axonal nerve affliction. Our case series shows that MRN can be very useful in precisely determining the site of sciatic injection injury and may provide diagnostic criteria for the assessment of lesion severity and recovery.
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6.72Impact points
Proximal neuropathic lesions in distal symmetric diabetic polyneuropathy: findings of high-resolution magnetic resonance neurography.
Diabetes care. 01/2011; 34(3):721-3.
This study investigated high-resolution magnetic resonance neurography (MRN) in distal symmetric diabetic polyneuropathy (dPNP). MRN comprised high-resolution transaxial imaging of peripheral nerves of the lower limbs in 20 patients with type 2 diabetes (10 with dPNP, type 2/dPNP[+], and 10 without ... [more] This study investigated high-resolution magnetic resonance neurography (MRN) in distal symmetric diabetic polyneuropathy (dPNP). MRN comprised high-resolution transaxial imaging of peripheral nerves of the lower limbs in 20 patients with type 2 diabetes (10 with dPNP, type 2/dPNP[+], and 10 without dPNP, type 2/dPNP[-]), seven patients with type 1 diabetes (two with dPNP, type 1/dPNP[+], five without dPNP, type 1/dPNP[-]), and 10 nondiabetic control subjects. Intraneural T2 lesions, as the main diagnostic criterion of MRN, were detected visually by two independent observers and quantitatively by analysis of T2 contrast ratios. Multifocal fascicular, symmetric intraneural T2 lesions occurred in the proximal trunks of sciatic nerves in four patients (three with type 2/dPNP[+] and one with type 1/dPNP[+]) but not in control subjects (type 2/dPNP[-], type 1/dPNP[-], nondiabetic control subjects), which was confirmed by quantitative analysis. Clinical severity was higher in patients with T2 lesions (neuropathy deficit score: 10 vs. 7.8; P = 0.05). For the first time, proximal neuropathic lesions of dPNP are reported in vivo. This supports that accumulation of proximal, multifocal fascicular injury may be important in disease progression.
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4.41Impact points
Sustained reperfusion after blockade of glycoprotein-receptor-Ib in focal cerebral ischemia: an MRI study at 17.6 Tesla.
PloS one. 01/2011; 6(4):e18386.
Inhibition of early platelet adhesion by blockade of glycoprotein-IB (GPIb) protects mice from ischemic stroke. To elucidate underlying mechanisms in-vivo, infarct development was followed by ultra-high field MRI at 17.6 Tesla. Cerebral infarction was induced by transient-middle-cerebral-artery-occl... [more] Inhibition of early platelet adhesion by blockade of glycoprotein-IB (GPIb) protects mice from ischemic stroke. To elucidate underlying mechanisms in-vivo, infarct development was followed by ultra-high field MRI at 17.6 Tesla. Cerebral infarction was induced by transient-middle-cerebral-artery-occlusion (tMCAO) for 1 hour in C57/BL6 control mice (N = 10) and mice treated with 100 µg Fab-fragments of the GPIb blocking antibody p0p/B 1 h after tMCAO (N = 10). To control for the effect of reperfusion, additional mice underwent permanent occlusion and received anti-GPIb treatment (N = 6; pMCAO) or remained without treatment (N = 3; pMCAO). MRI 2 h and 24 h after MCAO measured cerebral-blood-flow (CBF) by continuous arterial-spin labelling, the apparent-diffusion-coefficient (ADC), quantitative-T2 and T2-weighted imaging. All images were registered to a standard mouse brain MRI atlas and statistically analysed voxel-wise, and by cortico-subcortical ROI analysis. Anti-GPIb treatment led to a relative increase of postischemic CBF vs. controls in the cortical territory of the MCA (2 h: 44.2±6.9 ml/100 g/min versus 24 h: 60.5±8.4; p = 0.0012, F((1,18)) = 14.63) after tMCAO. Subcortical CBF 2 h after tMCAO was higher in anti-GPIb treated animals (45.3±5.9 vs. controls: 33.6±4.3; p = 0.04). In both regions, CBF findings were clearly related to a lower probability of infarction (Cortex/Subcortex of treated group: 35%/65% vs. controls: 95%/100%) and improved quantitative-T2 and ADC. After pMCAO, anti-GPIb treated mice developed similar infarcts preceded by severe irreversible hypoperfusion as controls after tMCAO indicating dependency of stroke protection on reperfusion. Blockade of platelet adhesion by anti-GPIb-Fab-fragments results in substantially improved CBF early during reperfusion. This finding was in exact spatial correspondence with the prevention of cerebral infarction and indicates in-vivo an increased patency of the microcirculation. Thus, progression of infarction during early ischemia and reperfusion can be mitigated by anti-platelet treatment.
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6.37Impact points
Prophylactic intravenous magnesium sulfate for treatment of aneurysmal subarachnoid hemorrhage: a randomized, placebo-controlled, clinical study.
Critical care medicine. 03/2010; 38(5):1284-90.
To examine whether the maintenance of elevated magnesium serum concentrations by intravenous administration of magnesium sulfate can reduce the occurrence of cerebral ischemic events after aneurysmal subarachnoid hemorrhage. Prospective, randomized, placebo-controlled study. Neurosurgical intensive ... [more] To examine whether the maintenance of elevated magnesium serum concentrations by intravenous administration of magnesium sulfate can reduce the occurrence of cerebral ischemic events after aneurysmal subarachnoid hemorrhage. Prospective, randomized, placebo-controlled study. Neurosurgical intensive care unit of a University hospital. One hundred ten patients were randomized to receive intravenous magnesium sulfate or to serve as controls. Magnesium treatment was started with a bolus of 16 mmol, followed by continuous infusion of 8 mmol/hr. Serum concentrations were measured every 8 hrs, and infusion rates were adjusted to maintain target levels of 2.0-2.5 mmol/L. Intravenous administration was continued for 10 days or until signs of vasospasm had resolved. Thereafter, magnesium was administered orally and tapered over 12 days. Delayed ischemic infarction (primary end point) was assessed by analyzing serial computed tomography scans. Transcranial Doppler sonography and digital subtraction angiography were used to detect vasospasm. Delayed ischemic neurologic deficit was determined by continuous detailed neurologic examinations; clinical outcome after 6 months was assessed using the Glasgow outcome scale. Good outcome was defined as Glasgow outcome scale score 4 and 5.The incidence of delayed ischemic infarction was significantly lower in magnesium-treated patients (22% vs. 51%; p = .002); 34 of 54 magnesium patients and 27 of 53 control patients reached good outcome (p = .209). Delayed ischemic neurologic deficit was nonsignificantly reduced (9 of 54 vs. 15 of 53 patients; p = .149) and transcranial Doppler-detected/angiographic vasospasm was significantly reduced in the magnesium group (36 of 54 vs. 45 of 53 patients; p = .028). Fewer patients with signs of vasospasm had delayed cerebral infarction. These data indicate that high-dose intravenous magnesium can reduce cerebral ischemic events after aneurysmal subarachnoid hemorrhage by attenuating vasospasm and increasing the ischemic tolerance during critical hypoperfusion.
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Outcome of experimental stroke in C57Bl/6 and Sv/129 mice assessed by multimodal ultra-high field MRI.
Experimental & translational stroke medicine. 03/2010; 2:6.
Transgenic mice bred on C57Bl/6 or Sv/129 genetic background are frequently used in stroke research. It is well established that variations in cerebrovascular anatomy and hemodynamics can influence stroke outcome in different inbred mouse lines. We compared stroke development in C57Bl/6 and Sv/129 m... [more] Transgenic mice bred on C57Bl/6 or Sv/129 genetic background are frequently used in stroke research. It is well established that variations in cerebrovascular anatomy and hemodynamics can influence stroke outcome in different inbred mouse lines. We compared stroke development in C57Bl/6 and Sv/129 mice in the widely used model of transient middle cerebral artery occlusion (tMCAO) by multimodal ultra-high field magnetic resonance imaging (MRI).C57Bl/6 and Sv/129 mice underwent 60 min of tMCAO and were analyzed by MRI 2 h and 24 h afterwards. Structural and functional images were registered to a standard anatomical template. Probability maps of infarction were rendered by automated segmentation from quantitative T2-relaxometric images. Whole-brain segmentation of infarction was accomplished manually on high-resolution T2-weighted (T2-w) RARE images. Cerebral perfusion (cerebral blood flow, CBF) was measured quantitatively by modified continuous arterial-spin-labeling (CASL) and apparent diffusion coefficients (ADC) by spin-echo diffusion-weighted imaging (DWI).Probabilities of cortical (95.1% +/- 3.1 vs. 92.1% +/- 2.5; p > 0.05) and subcortical (100% vs. 100%; p > 0.05) infarctions at 24 h were similar in both groups as was the whole-brain volumetric extent of cerebral infarction. In addition, CBF and ADC values did not differ between C57Bl/6 and Sv/129 mice at any time point or region of interest.The C57Bl/6 and Sv/129 genetic background is no major confounding factor of infarct size and cerebral perfusion in the tMCAO model.
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3.97Impact points
Magnetic resonance neurography for the diagnosis of extrapelvic sciatic endometriosis.
Fertility and sterility. 02/2010; 94(1):351.e11-4.
To illustrate magnetic resonance neurography findings of severe sciatic injury and muscle denervation related to deep gluteal endometriosis at the sciatic notch. Case report. Academic teaching hospital. A 39-year-old woman with a 4-year history of sciatica related to the menstrual cycle. Surgical ex... [more] To illustrate magnetic resonance neurography findings of severe sciatic injury and muscle denervation related to deep gluteal endometriosis at the sciatic notch. Case report. Academic teaching hospital. A 39-year-old woman with a 4-year history of sciatica related to the menstrual cycle. Surgical exploration of the sciatic notch for diagnostic confirmation, external neurolysis of the sciatic nerve, and eventual pharmacologic treatment. Magnetic resonance neurography imaging revealed severe neuropathic injury and muscle denervation related to a deep infiltrative endometriotic focus at the sciatic notch, which was confirmed histologically on surgical exploration. Detailed electrodiagnostic and clinical neurologic examinations at initial presentation and during follow-up were obtained for further assessment of nerve degeneration, muscle denervation, and clinical recovery. Initial gynecologic and eventual laparoscopic evaluation on persisting complaints were without pathological findings. When a progressive weakness of the leg was noted, magnetic resonance neurography revealed a severe axonal damage to the sciatic nerve and denervation of distal target muscles related to a diffuse infiltrative lesion at the sciatic notch. On surgical exploration, extragenital endometriosis was confirmed histologically. Considerable improvement in pain and strength occurred after pharmacologic therapy with a GnRH analogue. This is the first report to describe imaging findings of magnetic resonance neurography in severe neuropathic injury of the sciatic nerve and subsequent muscle denervation related to a deep infiltrative gluteal endometriotic focus.
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5.74Impact points
Enhanced cortical reperfusion protects coagulation factor XII-deficient mice from ischemic stroke as revealed by high-field MRI.
NeuroImage. 12/2009;
Intrinsic coagulation factor XII deficient (FXII(-/-)) mice are protected from ischemic stroke. To elucidate underlying mechanisms we investigated the early ischemic period in vivo by multimodal magnetic resonance imaging (MRI) at 17.6 Tesla. Cerebral ischemia was induced by either transient (60 min... [more] Intrinsic coagulation factor XII deficient (FXII(-/-)) mice are protected from ischemic stroke. To elucidate underlying mechanisms we investigated the early ischemic period in vivo by multimodal magnetic resonance imaging (MRI) at 17.6 Tesla. Cerebral ischemia was induced by either transient (60 min) or permanent occlusion of the middle cerebral artery (t/pMCAO). 10 FXII(-/-) mice underwent t- , 10 FXII(-/-) mice p- and 10 Wildtype (Wt) mice tMCAO. Cerebral blood flow (CBF), diffusion-weighted-imaging (DWI) and T2-relaxometry were measured at 2 h and 24 h after MCAO. Outcome measures were evaluated after motion correction and normalization to atlas space. 2 h after tMCAO CBF reduction was similar in FXII(-/-) and Wt mice extending over cortical (CBF (ml/100 g/min) 33.6+/-6.9 vs. 35.3+/-4.6, p=0.42) and subcortical regions (25.7+/-4.5 vs. 31.6+/-4.0, p=0.17). At 24 h, recovery of cortical CBF by +36% was observed only in tMCAO FXII(-/-) mice contrasting a further decrease of -48% in Wt mice after tMCAO (p=0.02, F((1,18))=6.24). In FXII(-/-) mice in which patency of the MCA was not restored (pMCAO) a further decrease of -75% was observed. Cortical reperfusion in tMCAO FXII(-/-) mice was related to a lower risk of infarction of 59% vs. 93% in Wt mice (p=0.04). Subcortical CBF was similarly decreased in both tMCAO groups (Wt and FXII(-/-)) relating to a similar risk of infarction of 89% (Wt) vs. 99% (FXII(-/-), p=0.17). Deficiency of FXII allows neocortical reperfusion after tMCAO and rescues brain tissue by this mechanism. This study supports the concept of FXII as a promising new target for stroke prevention and therapy.
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2.90Impact points
Magnetic resonance imaging of the peripheral nervous system.
Journal of neurology. 04/2009;
The diagnostic work up of patients with peripheral neuropathy largely depends on clinical and electrophysiological investigations. In contrast to disorders of the CNS, magnetic resonance imaging (MRI) has not been widely used as a diagnostic tool in the PNS except for detection of nerve compressing ... [more] The diagnostic work up of patients with peripheral neuropathy largely depends on clinical and electrophysiological investigations. In contrast to disorders of the CNS, magnetic resonance imaging (MRI) has not been widely used as a diagnostic tool in the PNS except for detection of nerve compressing mass lesions. Normal nerves appear isointense to the surrounding tissue on T1- and T2-weighted (w) MRIs, but upon injury the nerves become hyperintense and thus visible on T2-w MRI. These signal alterations can be exploited to diagnose nerve damage in vivo and to follow regeneration. In patients with peripheral nerve disorders, MRI has been especially useful in detecting focal intrinsic and extrinsic nerve lesions and may reveal treatable conditions even in the absence of gross electrophysiological alterations. This clinical review provides practical guidelines on the performance of nerve imaging by MRI and will focus on focal lesions exemplified by case presentations.
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0.65Impact points
[MRI as an additional diagnostic tool for the cubital tunnel syndrome]
Handchirurgie, Mikrochirurgie, plastische Chirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft für Handchirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft für Mikrochirurgie der Peripheren Nerven und Gefässe : Organ der Vereinigung der Deutschen Plastischen Chirurgen. 03/2009; 41(1):18-22.
The T(2)-weighted contrast of peripheral nerve lesions and denervated muscles is the most important diagnostic criterion in neuromuscular MRI. By exactly determining the anatomic denervation pattern of muscles and with a particularly high spatial resolution for peripheral nerves by visualising singl... [more] The T(2)-weighted contrast of peripheral nerve lesions and denervated muscles is the most important diagnostic criterion in neuromuscular MRI. By exactly determining the anatomic denervation pattern of muscles and with a particularly high spatial resolution for peripheral nerves by visualising single fascicles, MRI enables the exact localisation of ulnar nerve lesions in the cubital tunnel or at other sites. Furthermore, the extent of the lesion and the degree of its severity can be evaluated already during the early course of disease. Obviously, MRI is the method of choice for the direct visualisation of causative mass lesions such as ganglion cysts or lipoma, for example, before surgical exploration. Thus, it is a valuable diagnostic tool and supplement to conventional clinical and electrodiagnostic studies of the cubital tunnel syndrome (CuTS). The contribution of MRI to the preoperative selection of patients for either short- or long-segment decompression has to be clarified by further studies.
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2.86Impact points
THE IMPACT OF BALLOON ANGIOPLASTY ON THE EVOLUTION OF VASOSPASM-RELATED INFARCTION AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE.
Neurosurgery. 10/2008;
OBJECTIVE: Vasospasm of the cerebral vessels remains a major source for morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to evaluate the frequency of infarction after transluminal balloon angioplasty (TBA) in patients with severe subarachnoid hemo... [more] OBJECTIVE: Vasospasm of the cerebral vessels remains a major source for morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to evaluate the frequency of infarction after transluminal balloon angioplasty (TBA) in patients with severe subarachnoid hemorrhage-related vasospasm. METHODS: We studied 38 patients (median Hunt and Hess Grade II and median Fisher Grade IV) with angiographically confirmed severe vasospasm (>70% vessel narrowing). A total of 118 vessels with severe vasospasm in the anterior circulation were analyzed. Only the middle cerebral artery, including the terminal internal carotid artery, was treated with TBA (n = 57 vessel segments), whereas the anterior cerebral artery was not treated (n = 61 vessel segments). For both the treated and the untreated vessel territories, infarction on unenhanced computed tomographic scan was assessed as a marker for adverse outcome. RESULTS: Infarction after TBA occurred in four middle cerebral artery territories (four of 57 [7%]), whereas the infarction rate was 23 of 61 (38%) in the anterior cerebral artery territories not subjected to TBA (P < 0.001, Fisher exact test). Three procedure-related complications occurred during TBA (dissection n = 1, temporary vessel occlusions n = 2). One of these remained asymptomatic, whereas in two cases, this may have contributed to the development of infarction on follow-up computed tomographic scan. CONCLUSION: In a population of patients with a high risk of infarction resulting from vasospasm after subarachnoid hemorrhage, the frequency of infarction in the distribution of vessels undergoing TBA amounts to 7% and is significantly lower than in vessels not undergoing TBA despite some risk inherent to the procedure.
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14.51Impact points
The calcium sensor STIM1 is an essential mediator of arterial thrombosis and ischemic brain infarction.
The Journal of experimental medicine. 08/2008; 205(7):1583-91.
Platelet activation and aggregation are essential to limit posttraumatic blood loss at sites of vascular injury but also contributes to arterial thrombosis, leading to myocardial infarction and stroke. Agonist-induced elevation of [Ca(2+)](i) is a central step in platelet activation, but the underly... [more] Platelet activation and aggregation are essential to limit posttraumatic blood loss at sites of vascular injury but also contributes to arterial thrombosis, leading to myocardial infarction and stroke. Agonist-induced elevation of [Ca(2+)](i) is a central step in platelet activation, but the underlying mechanisms are not fully understood. A major pathway for Ca(2+) entry in nonexcitable cells involves receptor-mediated release of intracellular Ca(2+) stores, followed by activation of store-operated calcium (SOC) channels in the plasma membrane. Stromal interaction molecule 1 (STIM1) has been identified as the Ca(2+) sensor in the endoplasmic reticulum (ER) that activates Ca(2+) release-activated channels in T cells, but its role in mammalian physiology is unknown. Platelets express high levels of STIM1, but its exact function has been elusive, because these cells lack a normal ER and Ca(2+) is stored in a tubular system referred to as the sarcoplasmatic reticulum. We report that mice lacking STIM1 display early postnatal lethality and growth retardation. STIM1-deficient platelets have a marked defect in agonist-induced Ca(2+) responses, and impaired activation and thrombus formation under flow in vitro. Importantly, mice with STIM1-deficient platelets are significantly protected from arterial thrombosis and ischemic brain infarction but have only a mild bleeding time prolongation. These results establish STIM1 as an important mediator in the pathogenesis of ischemic cardio- and cerebrovascular events.
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7.04Impact points
Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis.
Stroke; a journal of cerebral circulation. 05/2008; 39(4):1262-8.
BACKGROUND AND PURPOSE: Models of photochemically-induced thrombosis are widely used in cerebrovascular research. Photothrombotic brain infarctions can be induced by systemic application of photosensitizing dyes followed by focal illumination of the cerebral cortex. Although the ensuing activation o... [more] BACKGROUND AND PURPOSE: Models of photochemically-induced thrombosis are widely used in cerebrovascular research. Photothrombotic brain infarctions can be induced by systemic application of photosensitizing dyes followed by focal illumination of the cerebral cortex. Although the ensuing activation of platelets is well established, their contribution for thrombosis and tissue damage has not formally been proved. METHODS: Infarction to the cerebral cortex was induced in mice by Rose Bengal and a cold light source. To assess the functional role of platelets, animals were platelet-depleted by anti-GPIbalpha antibodies or treated with GPIIb/IIIa-blocking F(ab)(2) fragments. The significance of the plasmatic coagulation cascade was determined by using blood coagulation factor XII (FXII)-deficient mice or heparin. Infarct development and infarct volumes were determined by serial MRI and conventional and electron microscopy. RESULTS: There was no difference in development and final size of photothrombotic infarctions in mice with impaired platelet function. Moreover, deficiency of FXII, which initiates the intrinsic pathway of coagulation and is essential for thrombus formation, or blockade of FXa, the key protease during the waterfall cascade of plasmatic coagulation, by heparin likewise did not affect lesion development. CONCLUSIONS: Our data demonstrate that platelet activation, factor XII-driven thrombus formation, and plasmatic coagulation pathways downstream of FX are not a prerequisite for ensuing tissue damage in models of photothrombotic vessel injury indicating that other pathomechanisms are involved. We suggest that this widely used model does not depend on platelet- or plasmatic coagulation-derived thrombosis.
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2.86Impact points
The impact of balloon angioplasty on the evolution of vasospasm-related infarction after aneurysmal subarachnoid hemorrhage.
Neurosurgery. 04/2008; 62(3):610-7; discussion 610-7.
OBJECTIVE: Vasospasm of the cerebral vessels remains a major source for morbidity and mortality after aneurysmal subarachnoid hemorrhage. The purpose of this study was to evaluate the frequency of infarction after transluminal balloon angioplasty (TBA) in patients with severe subarachnoid hemorrhage... [more] OBJECTIVE: Vasospasm of the cerebral vessels remains a major source for morbidity and mortality after aneurysmal subarachnoid hemorrhage. The purpose of this study was to evaluate the frequency of infarction after transluminal balloon angioplasty (TBA) in patients with severe subarachnoid hemorrhage-related vasospasm. METHODS: We studied 38 patients (median Hunt and Hess Grade II and median Fisher Grade 4) with angiographically confirmed severe vasospasm (>70% vessel narrowing). A total of 118 vessels with severe vasospasm in the anterior circulation were analyzed. Only the middle cerebral artery, including the terminal internal carotid artery, was treated with TBA (n = 57 vessel segments), whereas the anterior cerebral artery was not treated (n = 61 vessel segments). For both the treated and the untreated vessel territories, infarction on unenhanced computed tomographic scan was assessed as a marker for adverse outcome. RESULTS: Infarction after TBA occurred in four middle cerebral artery territories (four out of 57 [7%]), whereas the infarction rate was 23 out of 61 (38%) in the anterior cerebral artery territories not subjected to TBA (P < 0.001, Fisher exact test). Three procedure-related complications occurred during TBA (dissection, n = 1; temporary vessel occlusions, n = 2). One of these remained asymptomatic, whereas this may have contributed to the development of infarction on follow-up computed tomographic scans in two cases. CONCLUSION: In a population of patients with a high risk of infarction resulting from vasospasm after subarachnoid hemorrhage, the frequency of infarction in the distribution of vessels undergoing TBA amounts to 7% and is significantly lower than in vessels not undergoing TBA despite some risk inherent to the procedure.
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3.76Impact points
Experimental nerve imaging at 1.5-T.
Methods (San Diego, Calif.). 10/2007; 43(1):21-8.
Experimental lesions of the peripheral nerve system can be visualized in vivo by magnetic resonance imaging (MRI). Many studies of the rat peripheral nervous systems were performed on dedicated animal MR scanners with a high magnetic field strength for good spatial resolution. Here, we present an MR... [more] Experimental lesions of the peripheral nerve system can be visualized in vivo by magnetic resonance imaging (MRI). Many studies of the rat peripheral nervous systems were performed on dedicated animal MR scanners with a high magnetic field strength for good spatial resolution. Here, we present an MR protocol to study experimental lesions of the rat nervous system with clinical 1.5-T MR scanners and commercially available coils. Using a three-sequence approach (T1-weighted imaging, fat-saturated T2-weighted imaging and fat-saturated T1-weighted imaging with Gd-DTPA in the same plane), the relevant signal changes of the lesioned nerve can be visualized and separated from other structures, e.g., blood vessels. Furthermore, we give an overview on different types of contrast agents used for peripheral nerve MR imaging and MR findings in selected experimental models of rat peripheral nerve injury.
Following (4)
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Sabine Heiland
University Hospital Heidelberg -
Christoph Kleinschnitz
Universität Würzburg -
Andrea Kübler
Universität Würzburg -
Soenke Bartling
German Cancer Research Center / UMC Mannheim -
Carsten Wessig
Universität Würzburg
