Temporal changes in blood-brain barrier permeability and cerebral perfusion in lacunar/subcortical ischemic stroke.

BACKGROUND: Cerebral microvascular abnormality is frequently associated with lacunar and subcortical ischemic lesions. We performed acute and follow-up CT perfusion scans over the first 3 months after ischemic stroke to investigate disturbances of the blood-brain barrier (BBB) and cerebral perfusion in patients with lacunar/subcortical lesions compared to those with cortical lesions alone. METHODS: Thirty-one patients with lacunar/subcortical infarct (n = 14) or with cortical large vessel infarct (n = 17) were recruited and underwent a CT perfusion study at admission, 24 h, 7 days and 3 months after stroke using a two-phase imaging protocol. Functional maps of BBB permeability surface area product (BBB-PS), cerebral blood flow (CBF) and blood volume (CBV) at follow-up were co-registered with those at admission, and the measurements in non-infarcted ipsilateral basal ganglia and thalamus were compared within each group and between the two groups. RESULTS: For the lacunar/subcortical group, BBB-PS within non-infarcted ipsilateral basal ganglia and thalamus peaked at day 7 compared to all other time points, and was significantly higher than the cortical group at day 7 and month 3. The CBF and CBV in the same region were significantly lower at admission and transient hyperemia was seen at day 7 in the lacunar/subcortical group. CONCLUSION: Disturbed BBB-PS and compromised cerebral perfusion over the first 3 months post stroke were shown in the non-infarcted basal ganglia and thalamus of lacunar/subcortical stroke using CT perfusion. Future studies are required to elucidate the relationship of post-stroke BBB disturbances to chronic cognitive impairment.

CT perfusion cerebral blood volume does not always predict infarct core in acute ischemic stroke.

We investigated the practical clinical utility of the CT perfusion (CTP) cerebral blood volume (CBV) parameter for differentiating salvageable from non-salvageable tissue in acute ischemic stroke (AIS). Fifty-five patients with AIS were imaged within 6 h from onset using CTP. Admission CBV defect (CBVD) volume was outlined using previously established gray and white matter CBV thresholds for infarct core. Admission cerebral blood flow (CBF) hypoperfusion and CBF/CBV mismatch were visually evaluated. Truncation of the ischemic time-density curve (ITDC) and hypervolemia status at admission, recanalization at 24-h CT angiography, hemorrhagic transformation (HT) at 24 h and/or 7-day non-contrast CT (NCCT), final infarct volume as indicated by 3-month NCCT defect (NCCTD) and 3-month modified Rankin Score were determined. Patients with recanalization and no truncation had the highest correlation (R = 0.81) and regression slope (0.80) between CBVD and NCCTD. Regression slopes were close to zero for patients with admission hypervolemia with/without recanalization. Hypervolemia underestimated (p = 0.02), while recanalization and ITDC truncation overestimated (p = 0.03) the NCCTD. Among patients with confirmed recanalization at 24 h, 38 % patients had an admission CBF/CBV mismatch within normal appearing areas on respective NCCT. 83 % of these patients developed infarction in admission hypervolemic CBF/CBV mismatch tissue. A reduction in CBV is a valuable predictor of infarct core when the acquisition of ITDC data is complete and hypervolemia is absent within the tissue destined to infarct. Raised or normal CBV is not always indicative of salvageable tissue, contrary to the current definition of penumbra.

Temporal changes in CT perfusion values before and after cranioplasty in patients without symptoms related to external decompression: a pilot study.

INTRODUCTION: Little is known about hemodynamic disturbances affecting cerebral hemispheres in traumatic brain injury (TBI) after cranioplasty. METHODS: We prospectively investigated six stable TBI patients who underwent cranioplasty more than 90 days after effective decompressive craniectomy. Computerized tomography perfusion (CTP) studies and evaluation of clinical outcome were performed for each patient before cranioplasty and at 7 days and 3 months after surgery. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in multiple cortical circular regions positioned in cranioplasty-treated and contralateral hemispheres. RESULTS: Neither complications associated with cranioplasty nor changes in outcome were observed. On the treated side, CBF and CBV values were higher before and 7 days after cranioplasty than at 3 months after surgery, whereas MTT values were lower at 7 days than at 3 months after surgical treatment. CONCLUSIONS: Our results indicate that cortical perfusion progressively declines in the cranioplasty treated hemisphere but remains stable in the contralateral hemisphere after surgery and suggest that CTP can represent a promising tool for a longitudinal analysis of hemodynamic abnormalities occurring in TBI patients after cranioplasty. In addition, these data imply a possible role of cranioplasty in restoring flow to meet the prevailing metabolic demand.

Temporal changes in perihematomal apparent diffusion coefficient values during the transition from acute to subacute phases in patients with spontaneous intracerebral hemorrhage.

INTRODUCTION: Diffusion-weighted imaging (DWI) studies focusing on apparent diffusion coefficient (ADC) abnormalities have provided conflicting results about the nature and fate of perihematomal edema. METHODS: We investigated 35 patients with supratentorial spontaneous intracerebral hemorrhage (SICH) by using DWI scanning obtained at 48 h and 7 days after symptom onset. Regional ADC (rADC) values were measured in three manually outlined regions of interest: (1) the perihematomal hyperintense area, (2) 1 cm of normal appearing brain tissue surrounding the perilesional hyperintense rim, and (3) a mirror area, including the clot and the perihematomal region, located in the contralateral hemisphere. RESULTS: rADC mean levels were lower at 7 days than at 48 h in each ROI (p < 0.00001), showing a progressive normalization of initial vasogenic values. Perihematomal vasogenic rADC values were more frequent (p < 0.00001) at 48 h than at 7 days, whereas perihematomal cytotoxic and normal rADC levels were more represented (p < 0.02 and p < 0.001, respectively) at 7 days than at 48 h. A neurological worsening was more frequent (p < 0.02) in patients with than in those without perihematomal cytotoxic rADC values at 7 days. CONCLUSION: Our findings suggest that the transition from acute to subacute phases after SICH is characterized by a progressive resolution of perihematomal vasogenic edema associated with an increase in cytotoxic ADC values. In the subset of patients with perihematomal cytotoxic rADC levels in subacute stage after bleeding, irreversible damage development seems to be related to poor clinical outcome.

LAMM syndrome with middle ear dysplasia associated with compound heterozygosity for FGF3 mutations.

We report on the first cases of FGF3 compound heterozygotes in two European families from non-consanguineous marriages, affected with labyrinthine aplasia, microtia, and microdontia (LAMM) Syndrome. Three not previously described mutations (p.W153VfsX51, p.Y106C, and p.Y49C) and a recurrent one (p.R104X) were found. Analysis of 50 unrelated control subjects (100 chromosomes) of the same European background did not show any of the two newly reported missense variations. We confirm the absence of otodental syndrome in heterozygous carriers, but report unilateral microtia in one of them. We also report on the involvement of the middle ear structures in LAMM Syndrome.

Potential role of CT perfusion parameters in the identification of solitary intra-axial brain tumor grading.

In this study, neoplastic perfusion abnormalities were investigated by computed tomography perfusion (CTP) scanning in 38 patients with solitary intra-axial brain tumors (19 with high grade gliomas, 7 with low grade gliomas and 12 with brain metastasis). Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), mean transit time (rMTT) and permeability surface flow (rPSF) levels were measured in two different regions of interest: (1) enhancing or non-enhancing tumor tissue and (2) a mirror area of apparently normal brain tissue located in the contralateral hemisphere. rCBF mean levels were greater in tumoral tissue than in the contralateral area for high-grade gliomas (p < 0.02). rCBV and rPSF mean values were higher in tumoral tissue than in the contralateral area for high-grade gliomas (p < 0.01 and p < 0.05, respectively) and metastasis (p < 0.05 and p < 0.001, respectively). rCBV mean values of tumoral tissue were greater in high-grade than in low-grade gliomas (p < 0.05). rPSF mean levels of tumoral tissue were higher in metastasis than in low-grade gliomas (p < 0.02). These findings indicate that multi-parametric CTP mapping may contribute to differential diagnosis of solitary intra-axial brain tumors.

White matter lesions and sudden sensorineural hearing loss.

Aim of this paper is to investigate the presence of White Matter Lesions (WMLs) in subjects affected by Sudden Sensorineural Hearing Loss (SSNHL) and possibly to evaluate the significance of WMLs in SSNHL patients. A total of 64 patients (cases) affected by SSNHL were included in this case-control study. Hearing tests were performed at SSNHL onset, after 7 days and after 30 days. Cerebral MRI sequences were performed to rule out retrocochlear pathology, and WMLs were evaluated if present. MRI control group included 32 subjects, without hearing loss, affected by pituitary adenoma, who underwent cerebral MRI of follow-up. WML presence in those affected by SSNHL resulted having a similar distribution to that of the control group; however, we observed complete hearing recovery in 42,9% of patients without WML and in 11,6% of patients with WML >1 (p = 0,017*). The incidence of WML in patients with SSNHL was not different compared to that of the control group; however, MRI could have a prognostic role for SSNHL patients, as the presence of WMLs can been linked to a poorer hearing recovery rate.

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment.

INTRODUCTION: The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. METHODS: 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. RESULTS: Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS ≤ 2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. CONCLUSIONS: Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.

Clinical and MRI disease activity in multiple sclerosis are associated with reciprocal fluctuations in serum and cerebrospinal fluid levels of soluble HLA class I molecules.

The goal of our study was to clarify the contribution of soluble human leukocyte antigens class I (sHLA-I) in multiple sclerosis (MS) immune dysregulation. We retrospectively evaluated by ELISA cerebrospinal fluid (CSF) and serum sHLA-I levels in 79 relapsing-remitting (RR), 26 secondary progressive (SP) and 15 primary progressive (PP) MS patients stratified according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. One hundred and nine patients with other inflammatory neurological disorders (OIND), 88 with noninflammatory neurological disorders (NIND) and 82 healthy donors were used as controls. An intrathecal synthesis of sHLA-I detected by a specific index was significantly more consistent in MS than in controls, with more pronounced values in MS patients with relapses and MRI enhancing brain lesions. A decrease in serum sHLA-I concentrations was observed in MS patients with demyelinating attacks, while an increase in CSF levels of sHLA-I was found in MS patients with lesional activity on MRI scans. This association between intrathecal synthesis and reciprocal fluctuations of CSF and serum levels of sHLA-I in clinically and MRI active MS seems to suggest a potential role for CSF and serum levels of sHLA-I as a sensitive marker of immune activation taking place both intrathecally and systemically in MS.

Predictors of pituitary dysfunction in patients surviving ischemic stroke.

BACKGROUND: Stroke is a leading cause of death in industrialized countries, representing the main cause of long-term disability. Recent studies indicate that hypopituitarism may be observed after an acute stroke. OBJECTIVE: The aim was to prospectively investigate incidence and pattern of pituitary dysfunction in patients suffering ischemic stroke and to assess the predictive value of different clinical and radiological parameters for hypopituitarism. PATIENTS AND METHODS: We assessed endocrine, clinical, radiological, and functional parameters in 56 patients (34 males; mean age, 64.8 ± 1.3 yr; mean body mass index, 25.8 ± 0.45 kg/m(2)) at 1-3 months (visit 1) and 12-15 months (visit 2) after an ischemic stroke. RESULTS: At visit 1, hypopituitarism was detected in 20 (35.7%) of 56 stroke patients, with multiple deficits in three and isolated deficits in 17. At visit 2, hypopituitarism was detected in 18 (37.5%) of 48 stroke patients, with multiple deficits in two. Four patients with previously diagnosed isolated GH or LH/FSH deficit exhibited normal pituitary function, whereas GH deficiency was newly diagnosed in three cases. Hypopituitarism was associated with worse outcome. We identified both clinical (preexisting diabetes mellitus, medical complications during hospitalization) and radiological (Alberta Stroke Programme Early CT Score ≤ 7) parameters as major risk factors for developing hypopituitarism after ischemic stroke. CONCLUSIONS: Hypopituitarism may associate with ischemic stroke in one third of cases and persist in a long-term period, aggravating the functional outcome. We identified specific risk factors for hypopituitarism after stroke, which may help to select patients needing an accurate endocrine evaluation to improve stroke outcome.

CT perfusion mapping of hemodynamic disturbances associated to acute spontaneous intracerebral hemorrhage.

INTRODUCTION: We sought to quantify perfusion changes associated to acute spontaneous intracerebral hemorrhage (SICH) by means of computed tomography perfusion (CTP) imaging. MATERIALS AND METHODS: We studied 89 patients with supratentorial SICH at admission CT by using CTP scanning obtained within 24 h after symptom onset. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV) and mean transit time (rMTT) levels were measured in four different regions of interest manually outlined on CT scan: (1) hemorrhagic core; (2) perihematomal low-density area; (3) 1 cm rim of normal-appearing brain tissue surrounding the perilesional area; and (4) a mirrored area, including the clot and the perihematomal region, located in the non-lesioned contralateral hemisphere. RESULTS: rCBF, rCBV, and rMTT mean levels showed a centrifugal distribution with a gradual increase from the core to the periphery (p < 0.0001). Perfusion absolute values were indicative of ischemia in hemorrhagic core, oligemia in perihematomal area, and hyperemia in normal-appearing and contralateral areas. Perihematomal rCBF and rCBV mean levels were higher in small (< or = 20 ml) than in large (>20 ml) hematomas (p < 0.01 and p < 0.02, respectively). CONCLUSION: Multi-parametric CTP mapping of acute SICH indicates that perfusion values show a progressive improvement from the core to the periphery. In the first 24 h, perihemorrhagic region was hypoperfused with CTP values which were not suggestive of ischemic penumbra destined to survive but more likely indicative of edema formation. These findings also argue for a potential influence of early amounts of bleeding on perihematomal hemodynamic abnormalities.

Symmetric sensorineural progressive hearing loss from chronic idiopathic pachymeningitis.

We present the case of a 68 year-old man with a diffused hypertrophic pachymeningitis (HP) involving both internal auditory canals. The clinical symptoms were headache, decreased vision in one eye, progressive bilateral and symmetrical sensory-neural hearing loss (PSNHL) responsive to steroid treatment. Although hearing loss is a frequent manifestation of HP, only few studies reported an adequate audiological assessment and follow-up. Mechanisms related to the auditory involvement are discussed on the basis of audiological data. Gadolinium enhanced MRI is the most adequate technique for HP detection and for the differential diagnosis. A delay in the diagnosis of HP seems to be quite common and the consequences may be severe, especially in cases of optic nerve involvement. For these reasons, a cerebral MRI should probably be included in the assessment of PSNHL, especially when neurological signs coexist or are reported in the medical history.