RESUMEN
Importance: In patients with space-occupying hemispheric infarction, surgical decompression reduces the risk of death and increases the chance of a favorable outcome. Uncertainties, however, still remain about the benefit of this treatment for specific patient groups. Objective: To assess whether surgical decompression for space-occupying hemispheric infarction is associated with a reduced risk of death and an increased chance of favorable outcomes, as well as whether this association is modified by patient characteristics. Data Sources: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Stroke Trials Registry were searched from database inception to October 9, 2019, for English-language articles that reported on the results of randomized clinical trials of surgical decompression vs conservative treatment in patients with space-occupying hemispheric infarction. Study Selection: Published and unpublished randomized clinical trials comparing surgical decompression with medical treatment alone were selected. Data Extraction and Synthesis: Patient-level data were extracted from the trial databases according to a predefined protocol and statistical analysis plan. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and the Cochrane Collaboration's tool for assessing risk of bias were used. One-stage, mixed-effect logistic regression modeling was used for all analyses. Main Outcomes and Measures: The primary outcome was a favorable outcome (modified Rankin Scale [mRS] score ≤3) at 1 year after stroke. Secondary outcomes included death, reasonable (mRS score ≤4) and excellent (mRS score ≤2) outcomes at 6 months and 1 year, and an ordinal shift analysis across all levels of the mRS. Variables for subgroup analyses were age, sex, presence of aphasia, stroke severity, time to randomization, and involved vascular territories. Results: Data from 488 patients from 7 trials from 6 countries were available for analysis. The risk of bias was considered low to moderate for 6 studies. Surgical decompression was associated with a decreased chance of death (adjusted odds ratio, 0.16; 95% CI, 0.10-0.24) and increased chance of a favorable outcome (adjusted odds ratio, 2.95; 95% CI, 1.55-5.60), without evidence of heterogeneity of treatment effect across any of the prespecified subgroups. Too few patients were treated later than 48 hours after stroke onset to allow reliable conclusions in this subgroup, and the reported proportions of elderly patients reaching a favorable outcome differed considerably among studies. Conclusions and Relevance: The results suggest that the benefit of surgical decompression for space-occupying hemispheric infarction is consistent across a wide range of patients. The benefit of surgery after day 2 and in elderly patients remains uncertain.
Asunto(s)
Infarto Cerebral/diagnóstico , Infarto Cerebral/cirugía , Descompresión Quirúrgica/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Infarto Cerebral/mortalidad , Humanos , Tasa de Supervivencia/tendenciasRESUMEN
Background Space-occupying middle cerebral artery brain infarcts are associated with the development of brain edema, which may lead to cerebral herniation and death despite early hemicraniectomy. Aims To evaluate the benefit of therapeutic hypothermia in patients with space-occupying cerebral infarction treated with hemicraniectomy within 48 h of stroke onset. Methods Patients aged 18-60 years with space-occupying cerebral infarction treated with hemicraniectomy within 48 h and hypothermia (33-34°C) were selected from a single university hospital between 2001 and 2010 (n = 53). Patients treated with hemicraniectomy alone served as comparison group (n = 58), originating from three randomized controlled trials evaluating the effects of early decompressive surgery (DECIMAL, DESTINY, HAMLET). Primary outcome was the score on the modified Rankin scale at 12 months dichotomized between modified Rankin scale 0-3 and modified Rankin scale 4-6. Secondary outcome measures were modified Rankin scale score 0-4 and survival. Risk ratios were adjusted with Poisson regression. Results Mean patient age was 48 years. Median time from stroke onset to hemicraniectomy was 23.5 h in both treatment groups. Treatment with hypothermia had no effect on the primary outcome (modified Rankin scale 0-3 versus 4-6 (13/53 (25%) versus 24/58 (41%)); adjusted risk ratio 0.66, 95% confidence interval 0.38-1.13). Fewer patients treated with hypothermia had a modified Rankin scale score of 0-4 (21/53 (40%) versus 42/58 (72%); adjusted risk ratio 0.53, 95% confidence interval 0.37-0.76) and fewer patients survived (26/53 (49%) versus 46/58 (79%); adjusted risk ratio 0.60, 95% confidence interval 0.44-0.82). Conclusions In patients with space-occupying cerebral infarction, treatment with hypothermia had no additional benefit on functional outcome compared with treatment with hemicraniectomy alone.
Asunto(s)
Isquemia Encefálica/terapia , Infarto Cerebral/terapia , Craneotomía , Hipotermia Inducida , Adulto , Isquemia Encefálica/epidemiología , Infarto Cerebral/epidemiología , Cuidados Críticos , Femenino , Alemania/epidemiología , Humanos , Hipotermia Inducida/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Medición de Riesgo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Adenocarcinoma/diagnóstico , Autoanticuerpos/inmunología , Enfermedad de la Neurona Motora/diagnóstico , Proteínas del Tejido Nervioso/inmunología , Degeneración Cerebelosa Paraneoplásica/diagnóstico , Neoplasias de la Próstata/diagnóstico , Adenocarcinoma/inmunología , Anciano , Humanos , Masculino , Enfermedad de la Neurona Motora/inmunología , Degeneración Cerebelosa Paraneoplásica/inmunología , Neoplasias de la Próstata/inmunologíaRESUMEN
BACKGROUND: Homocystinuria caused by cystathionine beta synthase (CBS) deficiency is most often diagnosed in childhood and has a variable expressivity. The most frequent abnormalities include intellectual disability, ectopia lentis, myopia, skeletal abnormalities or thromboembolism. OBJECTIVE: To report a case of homocystinuria unraveled by cerebral venous thrombosis (CVT). OBSERVATION: A 17 year old female was admitted in our department of neurology for subacute headache and presented seizures in the emergency room. Cerebral imaging revealed CVT. Severe hyperhomocysteinemia was found and led to the diagnosis of homocystinuria due to composite heterozygous mutations in the CBS gene. Further investigations disclosed lens subluxation in association with myopia, mild scoliosis and osteopenia. The patient was treated by heparin followed by warfarin, vitamin therapy and dietary methionine restriction. Total homocysteine and methionine levels became normal in a few weeks and the patient had a complete recovery. CONCLUSION: In patients with CVT, plasma total homocysteine measurement as part of the etiologic work up may reveal severe hyperhomocysteinemia due to CBS or remethylation defects that require specific treatment and management including perhaps protein-restricted diet and/or vitamin therapy for life.
Asunto(s)
Cistationina betasintasa/genética , Homocistinuria/diagnóstico , Homocistinuria/genética , Trombosis Intracraneal/diagnóstico , Trombosis Intracraneal/genética , Mutación/genética , Adolescente , Femenino , Homocistinuria/complicaciones , Humanos , Trombosis Intracraneal/complicacionesRESUMEN
PURPOSE OF REVIEW: This review dsecribes the clinical spectrum of a newly identified disorder related to COL4A1 gene mutations. COL4A1 encodes type IV collagen α1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. RECENT FINDINGS: The human phenotypes are extremely variable between patients and between families, with disease onset as early as in the fetal period. COL4A1 mutations are responsible for a wide range of abnormalities affecting mainly the brain and the retinal vasculature, the anterior and posterior ocular structures and the renal glomerules. In the brain, intracerebral hemorrhage is the most frequent phenotype. It affects mainly young adults, children and more typically neonates. Mutated patients develop a diffuse small vessel disease of the brain as shown by a diffuse leukoencephalopathy on MRI. In the eye, patients may have retinal arteriolar tortuosities and retinal hemorrhages or anterior segment dysgenesis. Other phenotypes include intracranial aneurysms, porencephaly, infantile hemiparesis, muscle cramps, optic nerve dysgenesis and secondary glaucoma. There is in addition a specific phenotype called HANAC with constant nephropathy, muscle cramps and frequent intracranial aneurysms. SUMMARY: COL4A1 disorder is probably largely underestimated because of its multisystem and variable phenotype. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients.
Asunto(s)
Colágeno Tipo IV/genética , Colágeno Tipo IV/fisiología , Mutación/fisiología , Enfermedades del Sistema Nervioso/genética , Adulto , Niño , Ambiente , Asesoramiento Genético , Pruebas Genéticas , Humanos , Hemorragias Intracraneales/genética , Enfermedades Renales/genética , Sistema Nervioso/diagnóstico por imagen , Fenotipo , Radiografía , Enfermedades de la Retina/genéticaRESUMEN
PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations of the NOTCH3 gene. Marked variations in disease severity have raised the hypothesis that non-genetic factors may modulate the expressivity of the phenotype. The aim of the current study was to evaluate whether atherosclerosis, assessed by carotid duplex ultrasonography, is associated with variations in the clinical and MRI phenotype of CADASIL. METHODS: Data from 144 consecutive patients enrolled in an ongoing prospective cohort study were collected. Degree of disability was assessed by the modified Rankin Scale, that of cognitive impairment by the Mattis Dementia Rating Scale (MDRS). The total volume of the brain, of lacunar lesions and of white matter hyperintensities, the number of cerebral microhemorrhages, and parameters derived from histograms of apparent diffusion coefficient were measured on cerebral MRI. Atherosclerosis was evaluated by B-mode ultrasonography of carotid arteries. Both the carotid intima-media thickness (cIMT) and the presence of carotid plaques or stenosis were recorded. RESULTS: Higher cIMT was found to be independently associated with lower MDRS scores when this score was less than the quartile limit (p = 0.02). Only a trend for a positive association was detected between cIMT and the Rankin score (p = 0.06). There was no significant association between carotid markers and the occurrence of stroke or MRI parameters except for diffusion data. The mean and peak values of MRI diffusion histograms were found positively associated with the presence of plaques (p < 0.01). CONCLUSION: The results suggest that the severity of atherosclerosis may relate to cognitive decline in CADASIL and that this effect is possibly related to the degree of microstructural cerebral tissue lesions. Longitudinal studies are needed to confirm these results.
Asunto(s)
CADASIL/diagnóstico , Enfermedades de las Arterias Carótidas/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Encéfalo/patología , CADASIL/complicaciones , CADASIL/patología , CADASIL/psicología , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/psicología , Arteria Carótida Común/diagnóstico por imagen , Cognición , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Imagen de Difusión por Resonancia Magnética , Evaluación de la Discapacidad , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Oportunidad Relativa , Paris , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Ultrasonografía Doppler Dúplex , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: In malignant cerebral venous thrombosis (CVT) patients, emergency decompressive surgery has been suggested as a life-saving procedure. We report 12 patients with malignant CVT, among whom 8 underwent operation. METHODS: Retrospective study of 12 patients from 3 stroke units who had a malignant CVT as defined: (1) supratentorial cortical lesions attributable to superficial venous system thrombosis with or without sinus involvement; (2) with clinical (decreased consciousness and dilated pupils) or radiological signs of transtentorial herniation; (3) either at onset or after worsening despite heparin therapy. Surgery or abstention was decided individually by neurosurgeons on call. RESULTS: There were 9 women and 3 men with a mean age of 45+/-15 years. The delay between heparin therapy and signs of malignancy ranged from 2 to 30 hours. At malignant worsening all but 1 patient had hemorrhagic lesions; the median deviation of septum pellucidum was 12 mm (interquartile range, 6.7-13); 5 patients (including 3 who underwent operation) had a unilateral dilated pupil; and 4 (2 who underwent operation) had bilateral dilated pupils. Eight patients underwent surgical decompression, external decompression in 4, both external and internal decompression in 3, and internal decompression in 1. The 4 patients who did not undergo operation died within 1 to 5 days after diagnosis. One patient who underwent operation died of a pulmonary embolism. The 7 others survived, with, at last follow-up (median, 23.1 months; interquartile range, 19.7-45.6), an excellent recovery of mRS 0 or 1 in 6 and mRS 3 in 1. CONCLUSION: Decompressive surgery may save lives and may even allow a good functional outcome in malignant CVT, even in patients with bilateral dilated pupils.
Asunto(s)
Descompresión Quirúrgica/métodos , Trombosis Intracraneal/cirugía , Trombosis de la Vena/cirugía , Adolescente , Adulto , Anciano , Femenino , Humanos , Trombosis Intracraneal/mortalidad , Trombosis Intracraneal/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Trombosis de la Vena/mortalidad , Trombosis de la Vena/patología , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: "Sinking skin flap" (SSF) syndrome is a rare complication after large craniectomy that may progress to "paradoxical" herniation as a consequence of atmospheric pressure exceeding intracranial pressure. The prevalence and characteristics of SSF syndrome after hemicraniectomy for malignant infarction of the middle cerebral artery are not well known. METHODS: We analyzed a prospective cohort of 27 patients who underwent hemicraniectomy for malignant middle cerebral artery infarction. All had a clinical and brain imaging follow-up at 3 months and were followed until cranioplasty. RESULTS: Three of 27 patients (11%) had, at 3 to 5 months posthemicraniectomy, SSF syndrome with severe orthostatic headache as the main symptom. In addition, 4 patients (15%) had radiological SSF syndrome but no clinical symptoms except partial seizures in one. Patients with SSF syndrome had a smaller surface of craniectomy (76.2 cm(2) versus 88.7 cm(2), P=0.05) and a tendency toward larger infarct volume, an older age, and a longer delay to cranioplasty than those without this syndrome. CONCLUSIONS: SSF syndrome either clinically symptomatic or asymptomatic affects one fourth of patients 3 to 5 months after hemicraniectomy for malignant middle cerebral artery infarction. It should be diagnosed as early as possible to avoid progression to a paradoxical herniation.
Asunto(s)
Infarto Cerebral/cirugía , Craniectomía Descompresiva/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Colgajos Quirúrgicos/efectos adversos , Adulto , Infarto Cerebral/patología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hernia , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Adulto JovenRESUMEN
Episodic ataxia is an autosomal dominant ion channel disorder characterized by paroxysmal attacks of incoordination. Episodic ataxia type 2 (EA2) is caused by mutations in CACNA1A. EA2 mutations are mostly nonsense and sometimes missense mutations. However, in some typical EA2 families, CACNA1A sequencing does not detect any point mutation. Herein, we have designed a quantitative multiplex polymerase chain reaction of short fluorescent fragment test to screen the 50 exons of CACNA1A and investigated 27 probands referred for molecular diagnosis of EA2 who did not show any point mutation in CACNA1A. We have identified four different exonic deletions in four patients with a typical EA2 phenotype. These results establish the need to complete sequencing analysis by a screening for deletions to ensure an accurate molecular diagnosis of EA2.
Asunto(s)
Canales de Calcio/genética , Eliminación de Gen , Ataxias Espinocerebelosas/genética , Adulto , Anciano , Secuencia de Bases , Salud de la Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Mutación Puntual , Homología de Secuencia de Ácido NucleicoAsunto(s)
Edema Encefálico/genética , Canales de Calcio/genética , Análisis Mutacional de ADN , Traumatismos Cerrados de la Cabeza/genética , Migraña con Aura/genética , Alelos , Secuencia de Bases/genética , Encéfalo/patología , Edema Encefálico/diagnóstico , Preescolar , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Dominancia Cerebral/fisiología , Epilepsia Postraumática/diagnóstico , Epilepsia Postraumática/genética , Exones/genética , Femenino , Pruebas Genéticas , Traumatismos Cerrados de la Cabeza/diagnóstico , Humanos , Imagen por Resonancia Magnética , Migraña con Aura/diagnóstico , Mutación Missense/genética , Examen NeurológicoRESUMEN
Malignant middle cerebral artery infarction is associated with up to 80% mortality due to ischemic edema and brain herniation. No medical therapy has proven its efficacy in efficiently and durably reducing brain edema and improving patients' outcome. Decompressive surgery by a large hemicraniectomy with durotomy has been suggested as a life-saving emergency procedure. However, because of the lack of established prognostic criteria, the fear of severe and "unacceptable" residual disability in surviving patients, and the impossibility of considering the opinion of the patient at the time of decision, there was no consensus regarding this surgery. Recently the results of a pooled analysis of three European randomized trials (DECIMAL, DESTINY, and HAMLET) of early (= 48 hours) decompressive large hemicraniectomy in patients less than 60 years of age showed that, compared with medical therapy alone, there was a 50% (95% CI, 33%-67%) absolute risk reduction (ARR) of death, with more patients surviving with a slight to moderate disability (modified Rankin score of 2 or 3) (ARR of 23% ) or with a slight to moderately severe disability (modified Rankin score of 2, 3, or 4) (ARR of 51% ). About 5% of all patients in each therapeutic group were left with a severe residual disability (Rankin 5). These data indicate that early decompressive hemicraniectomy should be considered and fully discussed with the relatives of selected patients with a malignant hemispheric infarction.
Asunto(s)
Fístula del Seno Cavernoso de la Carótida/fisiopatología , Malformaciones Vasculares del Sistema Nervioso Central/fisiopatología , Anciano , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/fisiopatología , Fístula del Seno Cavernoso de la Carótida/diagnóstico , Seno Cavernoso/diagnóstico por imagen , Seno Cavernoso/fisiopatología , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico , Femenino , Humanos , Radiografía , Flujo Sanguíneo Regional/fisiologíaRESUMEN
BACKGROUND AND PURPOSE: There is no effective medical treatment of malignant middle cerebral artery (MCA) infarction. The purpose of this clinical trial was to assess the efficacy of early decompressive craniectomy in patients with malignant MCA infarction. METHODS: We conducted in France a multicenter, randomized trial involving patients between 18 and 55 years of age with malignant MCA infarction to compare functional outcomes with or without decompressive craniectomy. A sequential, single-blind, triangular design was used to compare the rate of development of moderate disability (modified Rankin scale score < or =3) at 6 months' follow-up (primary outcome) between the 2 treatment groups. RESULTS: After randomization of 38 patients, the data safety monitoring committee recommended stopping the trial because of slow recruitment and organizing a pooled analysis of individual data from this trial and the 2 other ongoing European trials of decompressive craniectomy in malignant MCA infarction. Among the 38 patients randomized, the proportion of patients with a modified Rankin scale score < or =3 at the 6-month and 1-year follow-up was 25% and 50%, respectively, in the surgery group compared with 5.6% and 22.2%, respectively, in the no-surgery group (P=0.18 and P=0.10, respectively). There was a 52.8% absolute reduction of death after craniectomy compared with medical therapy only (P<0.0001). CONCLUSIONS: In this trial, early decompressive craniectomy increased by more than half the number of patients with moderate disability and very significantly reduced (by more than half) the mortality rate compared with that after medical therapy.
Asunto(s)
Craneotomía , Descompresión Quirúrgica/estadística & datos numéricos , Infarto de la Arteria Cerebral Media/cirugía , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Francia , Humanos , Infarto de la Arteria Cerebral Media/patología , Masculino , Persona de Mediana Edad , Calidad de Vida , Recuperación de la Función , Proyectos de Investigación , Estadística como Asunto , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Recently COL4A1, a gene encoding the type IV collagen alpha1 chain, has been found to be involved in families with autosomal-dominant porencephaly and infantile hemiparesis. In addition to neonatal stroke, some family members had experienced, during adulthood, spontaneous intracerebral hemorrhages (ICHs) and leukoencephalopathy, suggestive of underlying small-vessel disease of the brain. We now report a patient with sporadic, recurrent ICHs and a novel COL4A1 mutation. METHODS: We performed a clinical and genetic study of a 25-year-old-patient with an 8-year history of recurrent ICHs. RESULTS: This young, normotensive patient with a history of infantile hemiparesis had experienced, since the age of 17, recurrent, spontaneous, deep ICHs occurring during sports activities. He became severely disabled. Brain magnetic resonance imaging showed ventricular enlargement, diffuse white-matter abnormalities, and newly appearing, deep, silent microbleeds. Extensive investigations found no cause. There was no family history of stroke or infantile hemiparesis. A novel COL4A1 mutation (G805R) was identified. CONCLUSIONS: The clinical spectrum of COL4A1 mutations includes recurrent ICHs in association with diffuse leukoencephalopathy in young adults, even in the absence of a family history of infantile hemiparesis or ICH. In addition to birth trauma, anticoagulant use, and head trauma previously reported, sports activities may be a precipitating factor of ICHs in persons with COL4A1 mutations.
Asunto(s)
Hemorragia Cerebral/genética , Colágeno Tipo IV/genética , Adulto , Hemiplejía/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Mutación , RecurrenciaRESUMEN
BACKGROUND: Malignant infarction of the middle cerebral artery (MCA) is associated with an 80% mortality rate. Non-randomised studies have suggested that decompressive surgery reduces this mortality without increasing the number of severely disabled survivors. To obtain sufficient data as soon as possible to reliably estimate the effects of decompressive surgery, results from three European randomised controlled trials (DECIMAL, DESTINY, HAMLET) were pooled. The trials were ongoing when the pooled analysis was planned. METHODS: Individual data for patients aged between 18 years and 60 years, with space-occupying MCA infarction, included in one of the three trials, and treated within 48 h after stroke onset were pooled for analysis. The protocol was designed prospectively when the trials were still recruiting patients and outcomes were defined without knowledge of the results of the individual trials. The primary outcome measure was the score on the modified Rankin scale (mRS) at 1 year dichotomised between favourable (0-4) and unfavourable (5 and death) outcome. Secondary outcome measures included case fatality rate at 1 year and a dichotomisation of the mRS between 0-3 and 4 to death. Data analysis was done by an independent data monitoring committee. FINDINGS: 93 patients were included in the pooled analysis. More patients in the decompressive-surgery group than in the control group had an mRSAsunto(s)
Descompresión Quirúrgica
, Infarto de la Arteria Cerebral Media/cirugía
, Procedimientos Neuroquirúrgicos
, Adolescente
, Adulto
, Afasia/etiología
, Femenino
, Humanos
, Infarto de la Arteria Cerebral Media/mortalidad
, Imagen por Resonancia Magnética
, Masculino
, Persona de Mediana Edad
, Selección de Paciente
, Estudios Prospectivos
, Ensayos Clínicos Controlados Aleatorios como Asunto
, Accidente Cerebrovascular/mortalidad
, Accidente Cerebrovascular/cirugía
, Tomografía Computarizada por Rayos X
, Resultado del Tratamiento
RESUMEN
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is caused by mutations in the Notch3 receptor expressed at the surface of vascular smooth muscle cells. The functional consequences of the disease at the peripheral microcirculation level are incompletely elucidated. In this study, we aimed to assess, in vivo, the endothelium-dependent and independent vasodilation of the skin microvasculature in CADASIL patients. Twenty-three affected subjects were compared with 23 gender and age-matched controls. The brachial artery endothelium-dependent and endothelium-independent vasodilation were assessed after forearm cuff occlusion and nitroglycerin administration. Skin vasoreactivity to transcutaneous administration of acetylcholine and sodium nitroprussiate, and after postocclusive hyperemia were measured by Laser Doppler flowmetry. The maximum changes in the diameter of the brachial artery after the cuff release or after nitroglycerin administration did not differ between patients and controls. With iontopheresis, only the peak value of the dose response was found decreased in normocholesterolemic patients after nitroprussiate administration. The postocclusive test revealed a large increase of the time to peak value and whole duration of the hyperemic response in CADASIL patients. The results of this study show that the skin vasoreactivity is altered in CADASIL. Particularly, the kinetics of reactive hyperemia after cuff occlusion is dramatically changed with a lengthened and delayed response. This characteristic pattern may be related to the specific ultrastructural modifications related to Notch3 gene mutations involving smooth muscle cells in the microvasculature.
Asunto(s)
CADASIL/fisiopatología , Piel/irrigación sanguínea , Adulto , Anciano , Arteria Braquial/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hiperemia/fisiopatología , Imagen por Resonancia Magnética , Masculino , Microcirculación/fisiología , Persona de Mediana Edad , Nitroprusiato/farmacología , Flujo Sanguíneo Regional/fisiología , Vasodilatación/fisiología , Vasodilatadores/farmacologíaRESUMEN
Small-vessel diseases of the brain underlie 20 to 30 percent of ischemic strokes and a larger proportion of intracerebral hemorrhages. In this report, we show that a mutation in the mouse Col4a1 gene, encoding procollagen type IV alpha1, predisposes both newborn and adult mice to intracerebral hemorrhage. Surgical delivery of mutant mice alleviated birth-associated trauma and hemorrhage. We identified a COL4A1 mutation in a human family with small-vessel disease. We concluded that mutation of COL4A1 may cause a spectrum of cerebrovascular phenotypes and that persons with COL4A1 mutations may be predisposed to hemorrhage, especially after environmental stress.
Asunto(s)
Encéfalo/irrigación sanguínea , Hemorragia Cerebral/genética , Colágeno Tipo IV/genética , Predisposición Genética a la Enfermedad , Mutación , Animales , Encéfalo/patología , Hemorragia Cerebral/etiología , Femenino , Membrana Basal Glomerular/anomalías , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL/genética , Ratones Mutantes , Microcirculación , Linaje , Arteria Renal/anomalías , Arteria Retiniana/anomalías , Factores de Riesgo , Estrés Fisiológico/complicaciones , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/genéticaRESUMEN
BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited systemic arteriopathy caused by highly stereotyped mutations in NOTCH3. The clinical expression of CADASIL is confined to the central nervous system with characteristic recurrent subcortical infarcts and vascular dementia. However, cases have been reported with associated circulatory small vessel abnormalities in the retina or the myocardium and with myocardial infarction. Classical cardiovascular risk factors may influence such circulatory abnormalities. Thus, we conducted a case control study to determine the frequency of electrical abnormalities on a 12-lead resting ECG in CADASIL patients without classical atherosclerotic risk factors. METHODS: Twenty-three CADASIL patients (mean age+/-SD; 55.1+/-11 years) free of any classical cardiovascular risk factors except for hypercholesterolemia were recruited from 1 neurology department and compared with 23 sex- and age-matched healthy controls (mean age+/-SD; 54.7+/-9.5 years). A resting supine 12-lead ECG was recorded at inclusion and analyzed later by 2 reviewers. Signs of myocardial infarction or ischemia, conduction, and rhythm disturbances were looked for. RESULTS: We found no ECG sign evoking myocardial infarction or myocardial ischemia. CADASIL patients had, compared with healthy controls, a significantly higher heart rate and a significantly lower Sokolow index, but these values remained in the normal ranges. CONCLUSIONS: In this case-control study, we found no ECG evidence for myocardial infarction or ischemia, conduction disturbances, or arrhythmias in CADASIL patients compared with healthy controls.
Asunto(s)
CADASIL/complicaciones , Electrocardiografía , Cardiopatías/complicaciones , Cardiopatías/diagnóstico , Adulto , Animales , Arritmias Cardíacas/complicaciones , Arritmias Cardíacas/diagnóstico , Estudios de Casos y Controles , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Cardiopatías/fisiopatología , Frecuencia Cardíaca , Humanos , Hipercolesterolemia/complicaciones , Masculino , Registros Médicos , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/diagnóstico , Factores de RiesgoRESUMEN
BACKGROUND: Migraine with aura (MA) is one of the clinical hallmarks of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a small vessel disease of the brain caused by mutations in the NOTCH3 gene, but its exact mechanisms are unknown. OBJECTIVES: To describe the patterns of MA in CADASIL and to compare brain magnetic resonance signal abnormalities between CADASIL patients with and without MA. DESIGN: Comparison of brain magnetic resonance signal abnormalities between cases and controls. SETTING: Patients with CADASIL seen at Lariboisière Hospital. PATIENTS: Forty-one CADASIL patients with MA and 31 age-matched CADASIL controls without MA. RESULTS: The mean age at onset of MA was significantly younger in women compared with men and occurred a mean of 15 years prior to stroke onset. A majority of patients (56%) reported at least 1 migraine attack with atypical aura. All CADASIL patients either with or without MA had white matter signal abnormalities on T2-weighted imaging. There was no difference in the frequency and distribution of brain signal abnormalities between CADASIL patients with and without MA. CONCLUSIONS: In CADASIL, MA is characterized by an unusually high frequency of attacks of migraine with atypical aura. The distribution and extent of magnetic resonance signal abnormalities did not differ according to migraine phenotype.
Asunto(s)
Encéfalo/patología , Demencia por Múltiples Infartos/patología , Imagen por Resonancia Magnética/métodos , Migraña con Aura/patología , Adulto , Anciano , Distribución de Chi-Cuadrado , Demencia por Múltiples Infartos/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Migraña con Aura/complicaciones , Estudios ProspectivosRESUMEN
BACKGROUND: Medullary infarcts can be associated with breathing disorders that usually consist in central hypoventilation. PATIENT: We describe the case of a 54-year-old man, fully conscious, presenting with an uncontrollable high frequency and shallow tachypnea (95/min) at the onset of a unilateral medial medullary infarct. This disorder disappeared under inspiratory pressure support mechanical ventilation. MEASUREMENTS AND RESULTS: Respiratory drive (respiratory rate, occlusion pressure, and mean inspiratory flow), efferent pathway (transcranial and cervical magnetic stimulation), and afferent pathway (response to CO(2) and to lung inflation) were investigated. The respiratory drive was increased. The phrenic nerve conduction time was normal. The sensitivity of the central pattern generator to lung inflation and to CO(2) was preserved. The territory of the infarct was supplied by the spinal anterior artery. CONCLUSIONS: An extremely rapid and shallow tachypnea due to the increase in respiratory drive can be associated with unilateral medullary infarction.