Expanding the Clinical Spectrum of DRP2-Associated Charcot-Marie-Tooth Disease.

BACKGROUND AND OBJECTIVES: Germline truncating variants in the DRP2 gene (encoding dystrophin-related protein 2) cause the disruption of the periaxin-DRP2-dystroglycan complex and have been linked to Charcot-Marie-Tooth disease. However, the causality and the underlying phenotype of the genetic alterations are not clearly defined. METHODS: This cross-sectional retrospective observational study includes 9 patients with Charcot-Marie-Tooth disease (CMT) with DRP2 germline variants evaluated at 6 centers throughout Spain. RESULTS: We identified 7 Spanish families with 4 different DRP2 likely pathogenic germline variants. In agreement with an X-linked inheritance, men harboring hemizygous DRP2 variants presented with an intermediate form of CMT, whereas heterozygous women were asymptomatic. Symptom onset was variable (36.6 ± 16 years), with lower limb weakness and multimodal sensory loss producing a mild-to-moderate functional impairment. Nerve echography revealed an increase in the cross-sectional area of nerve roots and proximal nerves. Lower limb muscle magnetic resonance imaging confirmed the presence of a length-dependent fatty infiltration. Immunostaining in intradermal nerve fibers demonstrated the absence of DRP2 and electron microscopy revealed abnormal myelin thickness that was also detectable in the sural nerve sections. DISCUSSION: Our findings support the causality of DRP2 pathogenic germline variants in CMT and further define the phenotype as a late-onset sensory and motor length-dependent neuropathy, with intermediate velocities and thickening of proximal nerve segments.

Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment: A Phase 1/2 Randomized Clinical Trial.

Importance: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers. Objective: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. Design, Setting, and Participants: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT. Interventions: In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated. Main Outcomes and Measures: The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score). Results: In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:√2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 patients (36%) receiving ApTOLL, 0.05 mg/kg (11 deaths [26.2%], 3 sICH [7.2%], 2 malignant strokes [4.8%], and 2 recurrent strokes [4.8%]); and in 6 of 42 patients (14%) receiving ApTOLL, 0.2 mg/kg (2 deaths [4.8%], 2 sICH [4.8%], and 3 recurrent strokes [7.1%]). ApTOLL, 0.2 mg/kg, was associated with lower NIHSS score at 72 hours (mean difference log-transformed vs placebo, -45%; 95% CI, -67% to -10%), smaller final infarct volume (mean difference log-transformed vs placebo, -42%; 95% CI, -66% to 1%), and lower degrees of disability at 90 days (common odds ratio for a better outcome vs placebo, 2.44; 95% CI, 1.76 to 5.00). Conclusions and Relevance: In acute ischemic stroke, 0.2 mg/kg of ApTOLL administered within 6 hours of onset in combination with EVT was safe and associated with a potential meaningful clinical effect, reducing mortality and disability at 90 days compared with placebo. These preliminary findings await confirmation from larger pivotal trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04734548.

Circulating MicroRNAs as Novel Biomarkers of Stenosis Progression in Asymptomatic Carotid Stenosis.

BACKGROUND AND PURPOSE: Progression of asymptomatic carotid artery stenosis (ACAS) in patients with >50% luminal narrowing is considered a potential risk factor for ischemic stroke; however, subclinical molecular biomarkers of ACAS progression are lacking. Recent studies suggest a regulatory function for several microRNAs (miRNAs) on the evolution of carotid plaque, but its role in ACAS progression is mostly unknown. The aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS to associate circulating miRNA expression profiles with stenosis progression. METHODS: The study included 60 patients with ACAS carrying >50% luminal narrowing. First, miRNA expression profiles of circulating exosomes were determined by Affymetrix microarrays from plasma samples of 16 patients from the cohort. Second, those miRNAs among the most differentially expressed in patients with ACAS progression were quantified by real-time polymerase chain reaction in a separate replication cohort of 39 subjects within the patient sample. RESULTS: Our results showed that ACAS progression was associated with development of stroke. MiR-199b-3p, miR-27b-3p, miR-130a-3p, miR-221-3p, and miR-24-3p presented significant higher expression in those patients with ACAS progression. CONCLUSIONS: In conclusion, our study supports that specific circulating miRNA expression profiles could provide a new tool that complements the monitoring of ACAS progression, improving therapeutic approaches to prevent ischemic stroke.

Downstream Migration and Fragmentation of a Spontaneous Calcific Embolus after Thrombolysis in a Patient with Ischemic Stroke.

We report a successful treatment experience with systemic thrombolysis in a patient with acute ischemic stroked caused by spontaneous calcific embolus, which resulted in clinical improvement and embolus fragmentation.

Short- and long-term outcomes in non-aneurysmal non-perimesencephalic subarachnoid hemorrhage.

OBJECTIVE: Our aim was to assess the short- and long-term prognosis in patients suffering from non-aneurysmal non-perimesencephalic SAH (Na-NPM-SAH). METHODS: Based on admission CT-scan, SAH was categorized as perimesencephalic (PM) or non-perimesencephalic (NPM). Based on digital subtraction angiography (DSA) results, patients were classified as normal DSA (Na-SAH) or aneurysmal SAH (aSAH). Between 1997 and 2010, 67 of 571 patients with non-traumatic SAH (11.7%) suffered from non-aneurysmal non-perimesencephalic SAH. Retrospective analyses of the 67 patients were undertaken, and compared with the aneurysmal SAH group. Long-term follow-up was assessed. RESULTS: The cohort consisted of 67 Na-NPM-SAH patients, mean age 54.8 years (range: 21-84), 56.7% male. Acute phase: 10.4% mortality and 3% rebleeding (two patients) during the acute phase. Long-term: extensive follow-up was possible in all except one of the survivors at discharge. Mortality was 6.6% during the 510 patient-years follow-up period (median follow-up time per patient, 8.95 years); rebleeding rate was 0-1.6%. An aneurysmal source was found in 13% of patients who underwent a second angiography. Aneurysmal SAH: 312 patients, with confirmed aneurysm by angiography. The mortality rate for Na-NPM-SAH during the acute phase was 10.4%, vs. 20% for aneurysmal SAH in the general database, p = 0.049. DISCUSSION: Na-NPM-SAH patients without an identifiable bleeding source on initial angiography might have a more benign short- and long-term prognosis than aneurysmal SAH patients. Our study confirms an important diagnostic advantage of a second arteriography. Still, despite the major concern of an undetected aneurysm, the long-term rebleeding rate was low in this subgroup of patients.

Characterisation of DWI-MRI confirmed cerebral infarcts in patients with subarachnoid haemorrhage and their association with MMP-9 levels.

OBJECTIVES: It has been suggested that metalloproteinase-9 (MMP-9) could predict the onset of cerebral vasospasm after subarachnoidal haemorrhage (SAH). The aim of this study was to analyse, in patients with SAH, the difference between patients with MRI ischaemic infarcts and patients without, and to investigate the role of metalloproteases as a prognostic factor for ischaemic infarcts. METHODS: Sixty eight consecutive patients with SAH and diffusion-weighted magnetic resonance imaging (DWI-MRI) done 3 weeks after SAH. We define two groups, with and without DWI-MRI infarcts. Blood samples were taken at entry, 3 days and 1 week MMP-9 was determined through ELISA method. RESULTS: Forty per cent were male, with a mean age of 54 ± 14 years. Twenty five patients, 36.8%, had DWI-MRI infarcts; in patients with MRI infarcts, SAH was more severe (Fisher = 4 52 vs 25.6%, P = 0.037), with more morbi-mortality (Rankin>3 48 vs 18.6%, P = 0.014), and more symptomatic vasospasm (28 vs 7%, P = 0.031). Levels of MMP-9 were higher than controls, but there were no significant differences between patients with and without infarcts (first determination no infarcts 39.40 ng/ml ± 35.40 vs infarcts 49.75 ng/ml ± 34.54, P > 0.005, 3 days no infarcts 72.10 ng/ml ± 70.95 vs infarcts 62.28 ± 33.84, P > 0.005, 1 week no infarcts 148.48 ng/ml ± 142.73 vs infarcts 91.5 ng/ml ± 1.20, P > 0.005). CONCLUSION: Thirty eight percent in a well-studied series of patients with SAH have DWI-MRI infarcts; the infarcts were associated to SAH severity, SAH outcome and symptomatic vasospasm. Metalloproteinase-9 was higher in SAH patients than in controls, but it could not discriminate the infarct patients.

Assessment of platelet function in acute ischemic stroke patients previously treated with aspirin.

BACKGROUND: Platelet inhibition measured by platelet function tests could be critical to understand the reasons for early recurrence and to guide therapeutic recommendations. We assess the platelet function during the acute phase of ischemic stroke in patients pretreated with aspirin who continue their treatment with aspirin only, are started on clopidogrel only, or add clopidogrel to aspirin. METHODS: Sixty-four patients were taking aspirin before the stroke. Depending on the administered antiplatelet, 3 groups were defined: ASA: patients who continued on aspirin orally or intravenous acetylsalicylate of lysine, n = 30; CLO: patients who discontinued aspirin and were started on clopidogrel, n = 16; and ASA + CLO: patients who were prescribed both aspirin and clopidogrel, n = 10. Collagen-induced thromboxane A2 (TXA2) synthesis, ADP (adenosine diphosphate)-induced aggregation, and occlusion time (PF-100) were measured. RESULTS: CLO group only had a marked elevation of TXA2 (17.44 ± 15.62 ng/mL, P = .000) and a shortening of the platelet function analyzer (PFA)-100 closure time (157.13 ± 88 seconds, P = .047) compared with the other 2 groups (ASA: TXA2, .62 ± 1.59 ng/mL; ASA + CLO: TXA2 1.79 ± 4.59 ng/mL). They achieved a small (13%) but significant reduction of ADP-induced aggregation (87.00 ± 23.06 mm, P = .008) compared with the ASA group (102.82 ± 22.38 seconds). CONCLUSIONS: Stopping aspirin intake within the first 72 hours of the acute stroke drastically increases TXA2 synthesis. During the same time window, the freshly prescribed clopidogrel manages to reduce the ADP-induced aggregation only slightly (13%). This study offers analytic proof that the common practice of replacing aspirin with clopidogrel does not leave stroke patients fully protected during the first days after an ischemic stroke. Possible solutions could be to preserve aspirin during a few days or to use loading doses of clopidogrel at hospital admission.

De la teoría a la práctica: la RM spin labeling / From theory to practice: spin labeling MRI

No disponible

Mesencephalic area measured by transcranial sonography in the differential diagnosis of parkinsonism.

BACKGROUND: Transcranial B-mode sonography (TCS) has become an important tool in the differential diagnosis of parkinsonism given that current technology enables an adequate assessment of brain structures. In this study we aimed at evaluating the usefulness of midbrain area measured by TCS in the differential diagnosis between Parkinson's Disease (PD) and Progressive Supranuclear Palsy (PSP). METHODS: Patients with a diagnosis of PD or PSP according to current clinical criteria were recruited. PSP patients were classified as Richardson's syndrome and PSP-parkinsonism. TCS was performed and the mesencephalic area and third ventricle width were measured offline by an examiner blinded to clinical diagnosis. RESULTS: TCS was performed in 60 patients (75% PD, 25% PSP). Eight patients (13,3%) had inadequate acoustic window. Patients with PSP had a smaller mesencephalic area (3.58 cm(2) vs 5.28 cm(2), p < 0.001). A mesencephalic area ≥4.27 cm(2) discriminates PD from PSP with a positive predictive value 100%. Patients with PSP also had a higher third ventricle diameter (8.84 mm vs 5.11 mm, p < 0.001). Within the PSP group patients with Richardson's syndrome had a wider third ventricle than patients with PSP-Parkinsonism phenotype (9.57 mm vs 7 mm, p = 0.01), but no differences were found in the mesencephalic area between both phenotypes. CONCLUSIONS: Measurement of the mesencephalic area and the third ventricle width by TCS is a non-invasive, easily accessible technique that is useful in the differential diagnosis between PD and PSP, at least in the late stages of the disease.

Evaluación de la sustancia negra mediante ultrasonografía transcraneal / Evaluation of the substantia nigra by means of transcranial ultrasound imaging

Objetivo. Describir la prevalencia de la hiperecogenicidad de la sustancia negra en dos muestras de pacientes, unos con diagnóstico de enfermedad de Parkinson (EP) según los criterios de la United Kingdom Parkinson’s Disease Society, y una población control, con el fin de establecer los propios valores de referencia para nuestro laboratorio de neurosonología. Sujetos y métodos. Se seleccionaron dos muestras de pacientes compuestos por controles sanos sin enfermedad neurodegenerativa y pacientes con EP. Se realizaron mediciones planimétricas del área de ecogenicidad de la sustancia negra en ambos grupos. Se consideró la mayor área de ecogenicidad medida en cada lado en cada paciente. Se realizaron estadísticos descriptivos de la muestra. Se construyó la curva ROC para mostrar la precisión global, la sensibilidad y la especificidad del Doppler transcraneal en comparación con el diagnóstico clínico de EP. Resultados. Se analizaron en total 45 pacientes con EP y 91 controles. Empleando nuestro propio punto de co e (percentil 90 de los controles = 0,22 cm2), presentaban hiperecogenicidad de la sustancia negra un 73,33% de los pacientes con EP y un 8,79% de los controles (p = 0). Se pudo apreciar un área bajo la curva del 93%, lo que expresa una buena precisión global del Doppler transcraneal en el diagnóstico de EP. Conclusiones. La evaluación ultrasonográfica de la sustancia negra consigue detectar en nuestro laboratorio diferencias significativas entre los sujetos con EP y los sujetos normales. Los valores obtenidos en nuestro laboratorio están ligeramente por debajo de los establecidos como referencia internacional, y ofrecen unos excelentes valores de especificad y una aceptable sensibilidad en nuestro medio (AU)

Aim. To describe the prevalence of hyperechogenicity of the substantia nigra in two samples of patients: one group who had been diagnosed with Parkinson’s disease (PD) in accordance with United Kingdom Parkinson’s Disease Society criteria and a control population, so as to be able to establish the reference values for our neurosonology laboratory Subjects and methods. Two samples of patients consisting of healthy controls with no neurodegenerative disease and patients with PD were selected. Planimetric measurements of the area of echogenicity in the substantia nigra were performed in both groups. The greatest area of echogenicity measured on each side of each patient was considered. Descriptive statistics of the sample were carried out. The ROC curve was constructed in order to show the overall precision, sensitivity and specificity of transcranial Doppler ultrasonography in comparison to the clinical diagnosis of PD. Results. Altogether 45 patients with PD and 91 controls were analysed. Using our own cut-off point (percentile 90 of the controls = 0.22 cm2), hyperechogenicity of the substantia nigra was observed in 73.33% of patients with PD and 8.79% of the controls (p = 0). An area below the curve of 93% was seen, which represents good overall precision for transcranial Doppler ultrasonography in the diagnosis of PD. Conclusions. The evaluation of the substantia nigra conducted in our laboratory using ultrasound imaging reveals significant differences between subjects with PD and normal subjects. The values obtained in our laboratory are slightly below those established as an international reference and offer excellent values for specificity and an acceptable level of sensitivity in our locale (AU)

Diabetes does not affect outcome of symptomatic carotid stenosis treated with endovascular techniques.

BACKGROUND: The influence of diabetes on carotid revascularization techniques is controversial, with few data regarding angioplasty and stenting (CAS). Our purpose was to analyze whether its presence constitutes a risk factor for poor outcome of patients with carotid stenosis treated with CAS. METHODS: We compared 30-day and long term morbidity and mortality, as well as restenosis rates, of non diabetic and diabetic patients with symptomatic carotid stenosis treated with endovascular techniques. RESULTS: 318 consecutive patients, 116 (36.5%) of them diabetics, were followed for a median of 56 months. Cumulative 30-day stroke, ischemic cardiopathy and death rate was 4% for non diabetics and 5.2% for diabetics (non significant). Long term stroke and mortality rate was 26.4% for the first group and 34.3% for the second (non significant). The most frequent causes of death were myocardial infarction (17.5% non diabetics, 44% diabetics, p = 0.04), ischemic stroke (12.5% non diabetics, 4% diabetics, non significant) and cancer (30% non diabetics, 16% diabetics, non significant). Twelve patients (6.4%) had restenosis ≥ 50%, 5.9% non diabetic, 7.4% diabetic, also without statistical significance. CONCLUSIONS: In our series, endovascular treatment is both efficient and safe in diabetic patients with symptomatic carotid stenosis; therefore, the presence of diabetes mellitus did not increase the risks linked to CAS procedure.

[Evaluation of the substantia nigra by means of transcranial ultrasound imaging]. / Evaluacion de la sustancia negra mediante ultrasonografia transcraneal.

AIM. To describe the prevalence of hyperechogenicity of the substantia nigra in two samples of patients: one group who had been diagnosed with Parkinson's disease (PD) in accordance with United Kingdom Parkinson's Disease Society criteria and a control population, so as to be able to establish the reference values for our neurosonology laboratory. SUBJECTS AND METHODS. Two samples of patients consisting of healthy controls with no neurodegenerative disease and patients with PD were selected. Planimetric measurements of the area of echogenicity in the substantia nigra were performed in both groups. The greatest area of echogenicity measured on each side of each patient was considered. Descriptive statistics of the sample were carried out. The ROC curve was constructed in order to show the overall precision, sensitivity and specificity of transcranial Doppler ultrasonography in comparison to the clinical diagnosis of PD. RESULTS. Altogether 45 patients with PD and 91 controls were analysed. Using our own cut-off point (percentile 90 of the controls = 0.22 cm2), hyperechogenicity of the substantia nigra was observed in 73.33% of patients with PD and 8.79% of the controls (p = 0). An area below the curve of 93% was seen, which represents good overall precision for transcranial Doppler ultrasonography in the diagnosis of PD. CONCLUSIONS. The evaluation of the substantia nigra conducted in our laboratory using ultrasound imaging reveals significant differences between subjects with PD and normal subjects. The values obtained in our laboratory are slightly below those established as an international reference and offer excellent values for specificity and an acceptable level of sensitivity in our locale.

Angioplastia carotídea en estenosis tras radioterapia: revisión de 12 casos / Carotid angioplasty in stenosis following radiotherapy: a review of 12 cases

Introducción. La estenosis carotídea es una complicación de la radioterapia cervical. En estos casos, la angioplastia carotídea se ha planteado como el tratamiento de revascularización electivo. Sin embargo, la indicación de tratar es discutida, debido a la alta tasa de reestenosis y a los pocos estudios de evolución a largo plazo existentes. Objetivo. Presentar una serie de pacientes con estenosis carotídeas tras radioterapia tratadas mediante angioplastia con el fin de analizar su evolución a corto y largo plazo. Pacientes y métodos. De una serie de 426 pacientes con estenosis carotídeas tratadas endovascularmente, 12 pacientes (2,8%) habían recibido radioterapia previa en el cuello. Se realizó un seguimiento clínico y mediante imagen de todos ellos. Se recogió la tasa de complicaciones durante las primeras cuatro semanas y a largo plazo, y la tasa de reestenosis en el seguimiento. Resultados. El intervalo medio entre la radioterapia y la detección de estenosis fue de 14,7 años. Diez pacientes (83,3%) fueron sintomáticos. Durante las primeras cuatro semanas tras la angioplastia no se produjo ninguna complicación. El seguimiento medio fue de 45,09 meses: un 16,7% de pacientes presentó ictus, un 8,3% sufrió un infarto agudo de miocardio y un 33,3% falleció (16,6% a causa de cáncer). Al menos seis pacientes (50%) fueron diagnosticados de reestenosis; todas ellas fueron mayores o iguales al 50% y ninguna fue sintomática. Conclusiones. La angioplastia carotídea es una técnica segura y eficaz en la estenosis tras radioterapia, con escasas complicaciones a corto plazo. La tasa de restenosis carotídea es alta. La principal causa de fallecimiento es el cáncer(AU)

Introduction. Carotid stenosis is a complication of cervical radiotherapy. In these cases carotid angioplasty has been considered as the elective revascularisation treatment. Yet, the indication to treat is under discussion due to the high rate of restenosis and the scarcity of studies conducted on the long-term development. Aims. To report on a series of patients with carotid stenosis following radiotherapy who were treated by means of angioplasty, the aim being to analyse their long- and short-term development. Patients and methods. Of a series of 426 patients with carotid stenosis treated by endovascular means, 12 of them (2.8%) had previously received radiotherapy in the neck. All of them were submitted to a clinical and imaging follow-up. Data were collected concerning the rate of complications during the first four weeks and in the long term, as well as the rate of restenosis in the follow-up. Results. The mean interval between radiotherapy and the detection of stenosis was 14.7 years. Ten patients (83.3%) were symptomatic. No complications occurred during the first four weeks following the angioplasty. The mean follow-up time was 45.09 months: 16.7% of patients presented a stroke, 8.3% suffered acute myocardial infarction and 33.3% died (16.6% due to cancer). At least six patients (50%) were diagnosed with restenosis, all equal to or greater than 50% and none of them were symptomatic. Conclusions. Carotid angioplasty is a safe, effective technique in stenosis following radiotherapy, with few short-term complications. The rate of carotid restenosis is high. The main cause of death is cancer(AU)

Embolism and impaired washout: a possible explanation of border zone strokes in hypereosinophilic syndrome.

We describe 4 patients with stroke caused by hypereosinophilic syndrome, all of whom presented with border zone infarcts, and discuss the possible underlying mechanism. Cardioembolism (endomiocardial fibrosis) would coexist with impaired washout (perfusion disturbance due to high eosinophil count and/or eosinophil-derived substances), explaining the watershed characteristics of the infarcts.

Late clinical and radiological complications of stereotactical radiosurgery of arteriovenous malformations of the brain.

INTRODUCTION: Post-radiation injury of patients with brain arteriovenous malformations (AVM) include blood-brain barrier breakdown (BBBB), edema, and necrosis. Prevalence, clinical relevance, and response to treatment are poorly known. We present a series of consecutive brain AVM treated with stereotactic radiosurgery describing the appearance of radiation injury and clinical complications. METHODS: Consecutive patients with annual clinical and radiological follow-up (median length 63 months). Edema and BBBB were classified in four groups (minimal, perilesional, moderate, or severe), and noted together with necrosis. Clinical symptoms of interest were intracranial hypertension, new neurological deficits, new seizures, and brain hemorrhages. RESULTS: One hundred two cases, median age 34 years, 52% male. Median irradiated volume 3.8 cc, dose to the margin of the nidus 18.5 Gy. Nineteen patients underwent a second radiosurgery. Only 42.2% patients remained free from radiation injury. Edema was found in 43.1%, blood-brain barrier breakdown in 20.6%, necrosis in 6.9%. Major injury (moderate or severe edema, moderate or severe BBBB, or necrosis) was found in 20 of 102 patients (19.6%). AVM diameter >3 cm and second radiosurgery were independent predictors. Time to the worst imaging was 60 months. Patients with major radiation injury had a hazard ratio for appearance of focal deficits of 7.042 (p = 0.04), of intracranial hypertension 2.857 (p = 0.025), hemorrhage into occluded nidus 9.009 (p = 0.079), appearance of new seizures not significant. CONCLUSIONS: Major radiation injury is frequent and increases the risk of neurological complications. Its late appearance implies that current follow-up protocols need to be extended in time.

The study of deep brain structures by transcranial duplex sonography and imaging resonance correlation.

Transcranial duplex sonography (TCS) currently provides us with images of deep brain structures with sufficient resolution. We chose 2 sonographic quantitative parameters: the diameter of the third ventricle and a measurement not used by TCS to date, the midbrain area. Their reliability and reproducibility were assessed using magnetic resonance imaging (MRI) as the reference. A total of 99 patients free from neurodegenerative disorders were examined using TCS, and both parameters were measured by 2 independent explorers. Measurements of third-ventricle diameter by TCS showed very good correlation (r = 0.80) and agreement (ICC = 0.89) with measurements obtained by MRI. Measurements of the midbrain area by TCS also provided acceptable values with moderate correlation (r = 0.36) and agreement (ICC = 0.53). Interexplorer correlation values were good (ICC = 0.98 and 0.79 for the third ventricle and midbrain areas, respectively). Further studies will be required to determine the potential diagnostic usefulness of these parameters.

Postradiosurgery hemorrhage rates of arteriovenous malformations of the brain: influencing factors and evolution with time.

BACKGROUND AND PURPOSE: The long-term benefit of radiosurgery of brain arteriovenous malformations (AVM), especially nonhemorrhagic cases, is controversial. We calculated hemorrhage rates pre- and posttreatment and analyzed the risk factors for bleeding based on cases followed at our site. METHODS: One hundred eight patients, age 36 ± 17 years, 56 men. The mean follow-up was 65 ± 44 months (median, 54; interquartile range, 33-94). Most AVMs were small (74.1% <3 cm in diameter); 48.1% were located in an eloquent area, 27.8% had deep drainage, and 39.8% presented with hemorrhage. RESULTS: The annual hemorrhage rate for any undiagnosed AVM was 1.2%, and 3.3% for AVMs with hemorrhagic presentation. Older patients, cortical or subcortical AVMs, and cases with multiple draining veins were less likely to present with bleeding. During the first 36 months postradiosurgery, hemorrhagic AVMs had a rebleeding rate of 2.1%, and a rate of 1.1% from 3 years onwards. Nonhemorrhagic AVMs had a hemorrhage rate of 1.4% during the first 3 years and 0.3% afterward. Arterial hypertension and nidus volume were independent predictors of bleeding after treatment. Mean nidus obliteration time was 37 ± 18 months (median, 32; interquartile range, 25-40), with hemorrhage rate of 1.3% before and 0.6% after obliteration, and 1.9% for AVMs that were not closed at the end of follow-up. CONCLUSIONS: Both hemorrhagic and nonhemorrhagic AVMs benefit from radiosurgical therapy, with gradual decrease in their bleeding rates over the years. Albeit small, the risk of hemorrhage persists during the entirety of follow-up, being higher for cases with hemorrhagic presentation and nonobliterated AVM.

Long-term outcome in patients with carotid artery stenting and contralateral carotid occlusion: a single neurovascular center prospective analysis.

INTRODUCTION: The aim of this study was to analyze the clinical features and early and late outcome of patients treated with carotid artery stenting for carotid stenosis with occlusion of the contralateral vessel (CAS-CCO), and compare them to patients without occlusion (CAS-NO). METHODS: From 1999 through 2010, 426 patients with 479 procedures were prospectively recorded, 61 patients (14.3%) CAS-CCO, and 365 patients CAS-NO. Immediate CAS complications, complications within the first 30 days and long-term complications were documented through annual clinical and ultrasonological follow-up visits. Stenosis rate was recorded. RESULTS: Patients with mean age of 68.4 years, 80% men had: (1) periprocedural stroke in three cases (0.7%), (2) cumulative 30-day stroke, ischemic cardiopathy, and death in 4.2%, without differences between groups (CAS-CCO 3.3%, CAS-NO 4.4%). Mean follow-up period was 55 ± 32.78 months, median 56 months. (3) Stroke during the follow-up in 8%, without differences between CAS-CCO and CAS-NO groups (3.7% and 8.8%). (4) Myocardial infarction in 11.2% and (5) global mortality in 24.3%, without statistical differences between groups. Of the 254 cases enrolled in the restenosis analysis, 44 patients (17.3%) had restenosis of any grade during a mean follow-up period of 52 months, without statistical differences between CAS-CCO and CAS-NO groups. Only 7.5% presented restenosis ≥ 50%. Its occurrence was statistically associated with previous neck radiation. CONCLUSIONS: Periprocedural risks and long-term outcomes of patients treated with CAS and presenting a contralateral carotid occlusion does not differ from regular patients treated with CAS. Based on the low stenosis rate of our study, our results do not give credit to extra surveillance measures in patients with contralateral carotid occlusion.

Influence of COX-inhibiting analgesics on the platelet function of patients with subarachnoid hemorrhage.

BACKGROUND: Platelet function of patients with subarachnoid hemorrhage (SAH) may play an important part in both rebleeding and delayed cerebral ischemia, but little is known about aggregation pathways during the acute phase of stroke. Analgesics are used regularly in the first days after bleeding, and some can potentially inhibit the cyclooxygenase (COX) enzyme. We examined the platelet function of patients with SAH in order to describe their basal situation and determine whether the administration of intravenous nonsteroidal antiinflammatory drugs (NSAIDs) affected platelet aggregation. METHODS: Arachidonic acid (AA)-induced aggregation and the platelet function analyzer (PFA)-100 test with collagen/epinephrine cartridges were used to study a group of SAH patients that was treated with dexketoprofen and dipyrone and to compare them to patients that had received no analgesia. RESULTS: Ninety-six consecutive SAH patients prospectively enrolled in platelet studies. Twenty-seven patients were taking NSAIDs (10 on dexketoprofen and 17 on dipyrone), and there were 15 cases in the control group. AA-induced aggregation was 10% ± 3.2% for NSAIDs (mean ± standard error), specifically 17.2% ± 7% for dexketoprofen and 5.7% ± 1% for dipyrone. Aggregation in the control group was 72.4% ± 6% (P = .001). Both analgesics slowed the platelet plug formation during the PFA-100 test, with closure times of 237.2 ± 25 seconds for dexketoprofen and 198.4 ± 22 seconds for dipyrone and 138.1 ± 21 seconds in controls (P = .02). CONCLUSIONS: The administration of COX-inhibiting analgesics leads to an hypoaggregability state in the first days of SAH. Further insight into their impact on complications such as rebleeding and delayed cerebral ischemia is needed in order to optimize the headache treatment of SAH.