Outcomes with Endovascular Treatment of Patients with M2 Segment MCA Occlusion in the Late Time Window.

BACKGROUND AND PURPOSE: Randomized trials in the late window have demonstrated the efficacy and safety of endovascular thrombectomy in large-vessel occlusions. Patients with M2-segment MCA occlusions were excluded from these trials. We compared outcomes with endovascular thrombectomy in patients with M2-versus-M1 occlusions presenting 6-24 hours after symptom onset. MATERIALS AND METHODS: Analyses were on pooled data from studies enrolling patients with stroke treated with endovascular thrombectomy 6-24 hours after symptom onset. We compared 90-day functional independence (mRS ≤ 2), mortality, symptomatic intracranial hemorrhage, and successful reperfusion (expanded TICI = 2b-3) between patients with M2 and M1 occlusions. The benefit of successful reperfusion was then assessed among patients with M2 occlusion. RESULTS: Of 461 patients, 367 (79.6%) had M1 occlusions and 94 (20.4%) had M2 occlusions. Patients with M2 occlusions were older and had lower median baseline NIHSS scores. Patients with M2 occlusion were more likely to achieve 90-day functional independence than those with M1 occlusion (adjusted OR = 2.13; 95% CI, 1.25-3.65). There were no significant differences in the proportion of successful reperfusion (82.9% versus 81.1%) or mortality (11.2% versus 17.2%). Symptomatic intracranial hemorrhage risk was lower in patients with M2-versus-M1 occlusions (4.3% versus 12.2%, P = .03). Successful reperfusion was independently associated with functional independence among patients with M2 occlusions (adjusted OR = 2.84; 95% CI, 1.11-7.29). CONCLUSIONS: In the late time window, patients with M2 occlusions treated with endovascular thrombectomy achieved better clinical outcomes, similar reperfusion, and lower symptomatic intracranial hemorrhage rates compared with patients with M1 occlusion. These results support the safety and benefit of endovascular thrombectomy in patients with M2 occlusions in the late window.

Imaging Triage of Patients with Late-Window (6-24 Hours) Acute Ischemic Stroke: A Comparative Study Using Multiphase CT Angiography versus CT Perfusion.

BACKGROUND AND PURPOSE: The role of collateral imaging in selecting patients for endovascular thrombectomy beyond 6 hours from onset has not been established. To assess the comparative utility of collateral imaging using multiphase CTA in selecting late window patients for EVT. MATERIALS AND METHODS: We used data from a prospective multicenter observational study in which all patients underwent imaging with multiphase CT angiography as well as CTP. Two blinded reviewers evaluated patients' eligibility for endovascular thrombectomy using published collateral imaging (multiphase CTA) criteria compared with CTP using the selection criteria of the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) and Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE-3) trials. CTP images were processed using automated commercial software. The outcomes of patients eligible for endovascular thrombectomy according to multiphase CTA, DAWN, or DEFUSE-3 criteria were compared using multivariable logistic regression modeling. Model characteristics were compared using the C-statistic for the receiver operating characteristic curve, the Akaike information criterion, and the Bayesian information criterion. RESULTS: Eighty-six patients presented beyond 6 hours from onset/last known well (median, 9.6 hours; interquartile range, 4.1 hours). Thirty-five patients (40.7%) received endovascular thrombectomy, of whom good functional outcome (90-day mRS, 0-2) was achieved in 16/35 (47%). Collateral-based imaging paradigms significantly modified the treatment effect of endovascular thrombectomy on 90-day mRS 0-2 (P interaction = .007). The multiphase CTA-based regression model best fit the data for the 90-day outcome (C-statistic, 0.86; 95% CI, 0.77-0.94) and was associated with the least information loss (Akaike information criterion, 95.7; Bayesian information criterion, 114.9) compared with CTP-based models. CONCLUSIONS: The collateral-based imaging paradigm using multiphase CTA compares well with CTP in selecting patients for endovascular thrombectomy in the late time window.

Very Early Carotid Endarterectomy After Intravenous Thrombolysis.

OBJECTIVE/BACKGROUND: The timing of carotid endarterectomy (CEA) after thrombolysis is still a matter of debate. The aim of this study was to analyse a cohort of patients undergoing urgent endarterectomy after intravenous thrombolysis for acute ischaemic stroke. METHODS: This was an observational study. Prospective databases were reviewed and matched to identify patients who underwent CEA early after intravenous thrombolysis (2009-14). The focus was carotid surgery performed within 12 hours of stroke onset in patients with a high grade (≥70%) symptomatic carotid stenosis, associated with vulnerable plaques or stroke in evolution, and evidence of a significant salvageable ischaemic penumbra on perfusion computed tomography scan. Demographic and clinical information, as well as data on relevant outcomes were extracted. RESULTS: Thirty four consecutive stroke patients who underwent CEA within 2 weeks of thrombolysis for acute ischaemic stroke and ipsilateral high grade carotid stenosis were identified. In 11 patients the surgical procedure was performed within 12 hours of the onset of symptoms. All patients showed a clinical improvement after combined treatment. The 3 month outcome was favourable (modified Rankin Scale ≤ 2) in 10 patients. No haemorrhagic complications were registered. There was neither peri-operative stroke nor stroke within 3 months of surgery. One patient died from acute myocardial infarction 3 days after intervention. CONCLUSION: This experience suggests that very early CEA after thrombolysis, aimed at removing the source of potential embolisation and restoring blood flow, may be safe and can lead to a favourable outcome.

Bimanual non-congruent actions in motor neglect syndrome: a combined behavioral/fMRI study.

In Motor Neglect (MN) syndrome, a specific impairment in non-congruent bimanual movements has been described. In the present case-control study, we investigated the neuro-functional correlates of this behavioral deficit. Two right-brain-damaged (RBD) patients, one with (MN+) and one without (MN-) MN, were evaluated by means of functional Magnetic Resonance Imaging (fMRI) in a bimanual Circles-Lines (CL) paradigm. Patients were requested to perform right-hand movements (lines-drawing) and, simultaneously, congruent (lines-drawing) or non-congruent (circles-drawing) left-hand movements. In the behavioral task, MN- patient showed a bimanual-coupling-effect, while MN+ patient did not. The fMRI study showed that in MN-, a fronto-parietal network, mainly involving the pre-supplementary motor area (pre-SMA) and the posterior parietal cortex (PPC), was significantly more active in non-congruent than in congruent conditions, as previously shown in healthy subjects. On the contrary, MN+ patient showed an opposite pattern of activation both in pre-SMA and in PPC. Within this fronto-parietal network, the pre-SMA is supposed to exert an inhibitory influence on the default coupling of homologous muscles, thus allowing the execution of non-congruent movements. In MN syndrome, the described abnormal pre-SMA activity supports the hypothesis that a failure to inhibit ipsilesional motor programs might determine a specific impairment of non-congruent movements.

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.

Intrathecal levels of vitamin D and IgG in multiple sclerosis.

BACKGROUND: Intrathecal synthesis of IgG is a hallmark of multiple sclerosis (MS). Vitamin D may modulate B-cell function and dampen the synthesis of IgG. OBJECTIVE: To investigate the relation between vitamin D levels in cerebrospinal fluid and serum and intrathecal synthesis of IgG. METHODS: 25-hydroxyvitamin D (25(OH)D) and IgG were assessed in cerebrospinal fluid and serum in 40 patients with MS. RESULTS: There was no significant correlation between the IgG index and 25(OH)D levels in cerebrospinal fluid or serum. The levels of 25(OH)D in cerebrospinal fluid and serum did not differ between patients with and without intrathecal synthesis of IgG. There was a non-significant trend towards a positive correlation between the concentrations of 25(OH)D and IgG in the cerebrospinal fluid, but not in serum. CONCLUSION: Physiological variation in vitamin D does not exert a major impact on intrathecal synthesis of IgG in MS.

Awake surgery in low-grade gliomas harboring eloquent areas: 3-year mean follow-up.

Low-grade gliomas are slow-growing tumors invading eloquent areas and white matter pathways. For many decades these tumors were considered inoperable because of their high tropism for eloquent areas. However, the young age of the patients and the inescapable anaplastic transformation have recently suggested more aggressive treatments. We analyzed the neurological and neuro-oncological outcome of 12 patients who underwent surgery fully awake for the resection of LGG, harboring eloquent areas. 10 right- and 2 left-handed patients underwent pre-operative assessment: Karnofsky Performance Status, Edinburgh Handedness Inventory Score; neuropsychological and neurophysiological evaluations, according to the tumor location. During surgery we performed: sensory-motor-evoked potentials, continuous electro-corticography and bipolar/monopolar cortico-subcortical mapping during neuropsychological tests. The resection rate was calculated with neuro-imaging elaboration software. No permanent post-operative deficits were reported; 2 patients improved after surgery. No impairment of cognitive functions was reported. The KPS improved in 8 patients and was steady in the others. The mean resection rate was 78.3%. The resection allowed the control of pre-operative seizures without increasing the drug intake. Awake surgery allowed a good resection rate despite the eloquent location of the tumors, without post-operative deficit. The neuropsychological outcome was unchanged after surgery. The resection seems to improve seizure control. All the patients came back to normal life and work. In conclusion, awake surgery is reliable and feasible in removal of LGG, even if invading the main eloquent areas and networks. All the patients experienced a normal life after surgery, without permanent deficits.

Potential relevance of cerebrospinal fluid and serum levels and intrathecal synthesis of active matrix metalloproteinase-2 (MMP-2) as markers of disease remission in patients with multiple sclerosis.

BACKGROUND: Little is known about the involvement of matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor TIMP-2 in multiple sclerosis (MS). OBJECTIVE: To elucidate the actual implication of MMP-2 and TIMP-2 in MS. METHODS: Cerebrospinal fluid (CSF) and serum levels of active MMP-2 and TIMP-2 were measured by activity assay system and ELISA, respectively, in 67 patients with relapsing-remitting MS (RRMS), categorized according clinical and magnetic resonance imaging (MRI), and in 129 controls. RESULTS: Cerebrospinal fluid and serum active MMP-2/TIMP-2 ratio mean values and an intrathecal active MMP-2 production were more increased in RRMS than in non-inflammatory conditions (P < 0.001, P < 0.05, and P < 0.0001, respectively) and in MRI inactive than in MRI active RRMS (P < 0.02, P < 0.01 and P < 0.001, respectively). An intrathecal synthesis of active MMP-2 was more frequent in RRMS than in inflammatory disorders (P < 0.01). Serum active MMP-2/TIMP-2 ratio and MS disease duration were positively correlated (P < 0.02). CONCLUSION: These findings suggest a potential role for MMP-2 activity in the termination of MS neuroinflammation related to remission of the disease and seem to indicate that serum MMP-2/TIMP-2 ratio may represent a useful biomarker for monitoring MS recovery phase.

Molecular detection of Parachlamydia-like organisms in cerebrospinal fluid of patients with multiple sclerosis.

The presence of Chlamydia-like organism DNA was investigated by polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) samples from 27 patients previously found positive for Chlamydia pneumoniae DNA: 12 with multiple sclerosis (MS), grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, 8 with other inflammatory neurological disorders and 7 with non-inflammatory neurological disorders. PCR evidence of Chlamydia-like organisms in CSF was observed only in two relapsing-remitting MS patients with clinical and MRI disease activity. These findings suggest a possible association between C. pneumoniae and Chlamydia-like organism brain infections as a cofactor in MS development.

CSF levels of soluble HLA-G and Fas molecules are inversely associated to MRI evidence of disease activity in patients with relapsing-remitting multiple sclerosis.

Cerebrospinal fluid (CSF) concentrations of soluble human leukocyte antigen class I (HLA-I) (sHLA-I), HLA-G (sHLA-G) and anti-apoptotic Fas (sFas) molecules were measured by enzyme linked immunosorbent assay technique in 65 relapsing-remitting (RR) MS patients classified according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Sixty-four patients with other inflammatory neurological disorders (OIND) and 64 subjects with noninflammatory neurological disorders (NIND) served as controls. CSF concentrations were higher in RRMS and in OIND than in NIND patients for sHLA-I (P < 0.02), greater in RRMS than in OIND and in NIND for sHLA-G (P < 0.001 and P < 0.01, respectively) and lower in RRMS than in OIND and in NIND for sFas (P < 0.001 and P < 0.02, respectively). An increase in CSF levels was identified in MRI active RRMS for sHLA-I (P < 0.01) and in MRI stable RRMS for sHLA-G (P < 0.01), whereas CSF values of sFas were decreased in RRMS without Gd-enhancing lesions (P < 0.02). In MS patients with no evidence of MRI disease activity, a trend towards an inverse correlation was found between CSF concentrations of sHLA-G and sHLA-I and between CSF levels of sHLA-G and sFas. Our results indicate that enhanced CSF levels of sHLA-I antigens most likely represent an indirect manifestation of intrathecal immune activation taking place in neuroinflammation. Conversely, reciprocal fluctuations in CSF sHLA-G and sFas levels observed when MRI disease activity resolved suggest that sHLA-G could play an immunomodulatory role in MS through Fas/FasL-mediated mechanisms.

Cerebral blood flow thresholds predicting new hypoattenuation areas due to macrovascular ischemia during the acute phase of severe and complicated aneurysmal subarachnoid hemorrhage. A preliminary study.

BACKGROUND: Focal ischemia may affect patients with aneurysmal subarachnoid hemorrhage (SAH), and the potential evolution of cerebral infarction may greatly influence the patients' outcome. The aim of the study was to assess the values of regional cortical cerebral blood flow (rCBF) thresholds predictive for ischemia during the acute phase of SAH. METHODS: In 34 patients affected by poor grade or complicated SAH, 52 pairs of Xenon-CT (Xe-CT) studies of regional CBF were analyzed, in which the follow-up Xe-CT study was obtained no later than 72 hours after the baseline study. Corresponding cortical ROIs were placed in the perimeter of the cortex on both the Xe-CT studies. A blinded, experienced neuroradiologist classified for each ROI, the development of a new hypoattenuation at the unenhanced CT images included in the follow-up Xe-CT, while another independent investigator collected rCBF levels of the ROI in the baseline Xe-CT study. FINDINGS: New hypoattenuation developed in 3.94% of the ROIs in the paired follow-up Xe-CT studies, and these evolving ROIs were associated with a lower rCBF in baseline Xe-CT. However, the positive predictive value of rCBF levels for the development of new hypoattenuation was only moderately predictive (28.3%) for very low physiological values (5 ml/100gr/min). CONCLUSIONS: The results suggest that there is no absolute rCBF threshold ofischemia in severe and complicated SAH patients and that the rCBF values are only moderately predictive at levels lower than previously described.

Multiple sclerosis in the province of Ferrara : evidence for an increasing trend.

BACKGROUND: Epidemiological studies on the distribution of multiple sclerosis (MS) conducted in the Mediterranean area in the last two decades have disclosed a significant increase in frequency of the disease, indicating caution when a latitude-related model of MS is accepted. Previous descriptive surveys in the province of Ferrara, northern Italy, carried out by our own epidemiological research group, have established that this area is at high risk for MS. OBJECTIVE: To confirm the above assumption and to update MS frequency estimates in this area. DESIGN AND SETTING: We conducted a community-based intensive prevalence and incidence study, by adopting a complete enumeration approach. RESULTS: On December 31, 2004, 423 patients (300 women and 123 men) suffering from definite or probable MS (Poser's criteria) living in the province of Ferrara, yielded a crude prevalence rate of 120.93 (95 % CI, 110.05-134.23) per 100,000, 164.26 for women and 73.59 for men. The average incidence from 1990 to 2003 was 4.35 per 100,000 (95 % CI, 3.77-4.99), 5.91 for women and 2.63 for men. The incidence rate,which was relatively stable during the previous 25 years (1965-1989) with a mean rate of 2.3 per 100,000, increased to a value of 3.39 per 100,000 in the period 1990-1994, 4.09 per 100,000 in the period 1995-1999 and 3.84 per 100,000 in the period 2000-2003. CONCLUSIONS: These results confirm that in Ferrara MS occurs more frequently than suggested by the geographic- related distribution model and, based on other recent national surveys, support the view that northern Italy is a high-risk area for the disease. The marked increase in MS prevalence rate, in comparison with previous investigations, is in part due to the increasing survival of patients as a result of improved supportive care and the accumulation of new incidence cases owing to the reduction in diagnostic latency for better quality of neurological diagnostic procedures. The incidence in the province of Ferrara was found to slowly change with an incremental trend,which cannot only be attributed to improvements in diagnostic ability. Environmental risk factors in genetically predisposed people over time could be considered.

Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis.

In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND (P < 0.05, < 0.02 and < 0.02, respectively), serum active MMP-9/TIMP-1 ratio was higher in MS (P < 0.01) and OIND (P < 0.02) than in NIND, and serum TIMP-1 concentrations were lower in MS than in NIND (P<0.05). More importantly, serum active MMP-9 mean levels, serum active MMP-9/TIMP-1 ratio and intrathecal production of active MMP-9 were increased in MS patients with clinical (P < 0.001, < 0.001 and < 0.05, respectively) and MRI (P < 0.001, < 0.001 and < 0.02, respectively) disease activity, whereas CSF mean concentrations of active MMP-9 and CSF active MMP-9/TIMP-1 ratio were enhanced only in MS patients with MRI evidence of disease activity (P < 0.02 and < 0.01, respectively). Altogether, these findings suggest that a shift in MMP-9/TIMP-1 balance towards proteolytic activity of MMP-9 could be relevant in MS immune dysregulation. In addition, our results indicate that CSF and serum levels of active MMP-9 may represent a potential surrogate biomarker for monitoring MS disease activity. In particular, serum active MMP-9/TIMP-1 ratio seems to be a very appropriate indicator of ongoing MS inflammation, since it is easily measurable.

Regional cerebral blood flow levels as measured by xenon-CT in vascular territorial low-density areas after subarachnoid hemorrhage are not always ischemic.

INTRODUCTION: The aim of this study was to assess regional cerebral blood flow (rCBV) in areas of CT hypoattenuation appearing in the postoperative period in patients treated for aneurysmal subarachnoid hemorrhage (SAH) using xenon-enhanced CT scanning (Xe-CT). METHODS: We analyzed 15 patients (5 male and 10 female; mean age 49.7+/-12.1 years) with SAH on CT performed on admission to hospital and who showed a low-density area within a well-defined vascular territory on CT scans after clipping or coiling of a saccular aneurysm. All zones of hypoattenuation were larger than 1 cm(2) and showed signs of a mass effect suggesting a subacute phase of evolution. Two aneurysms were detected in two patients. Aneurysms were located in the middle cerebral artery (n=7), in the anterior communicating artery (n=6), in the internal carotid artery (n=3), and in the posterior communicating artery (n=1). Treatments were surgical (n=8), endovascular (n=2) or both (n=1). A total of 36 Xe-CT studies were performed and rCBF values were measured in two different regions of interest (ROI): the low-density area, and an area of normal-appearing brain tissue located symmetrically in the contralateral hemisphere. RESULTS: rCBF levels were significantly lower in the low-density area than in the contralateral normal-appearing area (P<0.01). In the low-density areas, irreversible ischemia (CBF <10 ml/100 g per minute) was present in 11/36 lesions (30.6%), ischemic penumbra (CBF 10-20 ml/100 g per minute) and oligemia (CBF 20-34 ml/100 g per minute) in 8/36 lesions (22.2%), relative hyperemia (CBF 34-55 ml/100 g per minute) in 7/36 lesions (19.4%), and absolute hyperemia (CBF >55 ml/100 g per minute) in 2/36 lesions (5.6%). CONCLUSION: Our study confirmed that rCBF is reduced in new low-density lesions related to specific vascular territories. However, only about one-third of the lesions showed rCBF levels consistent with irreversible ischemia and in a relatively high proportion of lesions, rCBF levels indicated penumbral, oligemic and hyperemic areas.

Diagnostic impact of the spectrum of ischemic cerebral blood flow thresholds in sedated subarachnoid hemorrhage patients.

OBJECTIVE: Ischemia is the main cause of secondary damage in subarachnoid hemorrhage (SAH). Cerebral blood flow (CBF) measurement is useful to detect critical values. We analyzed the diagnostic impact of CBF ischemic thresholds to predict a new low attenuation area on computed tomography (CT) due to failure of large vessel perfusion. METHODS: We analyzed 48 xenon CT (Xe-CT) studies from 10 patients with SAH. CBF measurements were obtained by means of Xe-CT and cortical regions of interest (ROls). The ROIs which appeared in a hypoattenuation area were recorded. Cortical CBF was tested for specificity and sensitivity as a predictor of hypoattenuation by means of a receiver operating characteristic curve. RESULTS: Mean age was 58 (SD +/- 12.4) years. The median Fisher score and Hunt and Hess scale were 2 and 3, respectively. The area under the receiver operating characteristic curve was 0.912 (CI 0.896 to 0.926). The cut-off value for best accuracy was 6 mL/ 100 g/min, with a likelihood ratio of 37. CONCLUSION: The present study suggests a threshold of 6 mL/100 g/ min as a predictor of a new low attenuation area. However, each clinician should choose the most useful threshold according to pre-test probability and the cost/effectiveness ratio of the applied therapies.

Evaluation of acute perihematomal regional apparent diffusion coefficient abnormalities by diffusion-weighted imaging.

In this study, we investigated 40 patients (18 male, 22 female; mean age = 64.5 +/- 11.0; GCS = 9 to 14) with acute supratentorial spontaneous intracerebral hemorrhage (SICH) at admission by using a 1-tesla magnetic resonance imaging (MRI) unit equipped for single-shot echo-planar spin-echo isotropic diffusion-weighted imaging (DWI) sequences. All DWI studies were obtained within 48 hours after symptom onset. Regional apparent diffusion coefficient (rADC) values were measured in 3 different regions of interest (ROIs) drawn freehand on the T2-weighted images at b 0 s/mm2 on every section in which hematoma was visible: 1) the perihematomal hyperintense area; 2) 1 cm of normal appearing brain tissue surrounding the perilesional hyperintense rim; 3) an area mirroring the region including the clot and perihematomal hyperintense area placed in the contralateral hemisphere. rADC mean values were higher in perihematomal hyperintense and in contralateral than in normal appearing areas (p < 0.001), with increased rADC mean levels in all regions examined. Our findings show that rADC values indicative of vasogenic edema were present in the perihematomal area and in normal appearing brain tissue located both ipsilateral and contralateral to the hematoma, with lower levels in non-injured areas located in the T2 hyperintense rim around the clot.

Reperfusion of low attenuation areas complicating subarachnoid hemorrhage.

Hypoattenuation areas shown on brain CT scans after subarachnoid hemorrhage (SAH) are believed to be associated with persistent ischemia. The aim of this study was to evaluate regional cerebral blood flow (rCBF) in hypoattenuation areas and its evolution over time by means of Xenon CT (Xe-CT). We enrolled 16 patients with SAH who developed a hypoattenuation area in the middle cerebral artery territory. Patients were studied at time zero (the first Xe-CT), within 24 to 96 hours, and 96 hours after the initial Xe-CT. We analyzed 19 hypoattenuation areas caused by vascular distortion, vasospasm, or post-surgical embolization in 48 Xe-CT studies. Areas of hypoattenuation were divided in 2 groups according to initial rCBF. In the first group (n = 15), rCBF was initially above 6 mL/100 gr/min but only 2 were still ischemic (rCBF < 18 mL/ 100 gr/min) 96 hours after the first Xe-CT, while 7 (58%) were hyperemic. Conversely, in the second group with severe ischemia (rCBF < 6 mL/100 gr/min; n = 4) mean rCBF increased (p = 0.08) but still remained below the ischemic threshold. In severely ischemic lesions, rCBF reperfusion occurs but is probably marginally relevant. Conversely, in lesions not initially severely ischemic, residual CBF gradually improved and frequently became hyperemic. The functional recovery of these zones remains to be evaluated.

Intrathecal synthesis of soluble HLA-G and HLA-I molecules are reciprocally associated to clinical and MRI activity in patients with multiple sclerosis.

The aim of this study was to provide further insight into the effective contribution of classical soluble HLA-A, B and C class Ia (sHLA-I) and non-classical soluble HLA-G class Ib (sHLA-G) molecules in immune dysregulation occurring in multiple sclerosis (MS). We evaluated by enzyme-linked immunosorbent assay (ELISA) technique intrathecal synthesis and cerebrospinal fluid (CSF) and serum levels of sHLA-I and sHLA-G in 69 relapsing-remitting (RR), 21 secondary progressive (SP) and 13 primary progressive (PP) MS patients stratified according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also tested, as neurological controls, 91 patients with other inflammatory neurological disorders (OIND) and 92 with non-inflammatory neurological disorders (NIND). Eighty-two healthy volunteers served as further controls for sHLA-I and sHLA-G determinations. An intrathecal production of sHLA-I and sHLA-G detected by specific indexes was significantly more frequent in MS patients than in controls (P<0.01). An intrathecal synthesis of sHLA-I was prevalent in clinically (P<0.02) and MRI active (P<0.001) MS, whereas a CSF-restricted release of sHLA-G predominated in clinically (P<0.01) and MRI stable (P<0.001) MS. sHLA-I levels were low in the serum of clinically active (P<0.001) and high in the CSF of MRI active (P<0.01) MS. Conversely, sHLA-G concentrations were decreased in the serum of clinically stable MS (P<0.01) and increased in the CSF of MRI inactive MS (P<0.001). The trends towards a negative correlation observed between CSF and serum concentrations and intrathecal synthesis of sHLA-I and sHLA-G in patients without evidence of clinical and MRI activity confirmed that intrathecal production and fluctuations in CSF and serum concentrations of sHLA-I and sHLA-G were reciprocal in MS. Our results suggest that, in MS, a balance between classical sHLA-I and non-classical sHLA-G products modulating both MRI and clinical disease activity in opposite directions may exist.