Distinguishing clinical and radiological features of non-traumatic convexal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The full spectrum of causes of convexal subarachnoid hemorrhage (cSAH) requires further investigation. Therefore, our objective was to describe the spectrum of clinical and imaging features of patients with non-traumatic cSAH. METHODS: A retrospective observational study of consecutive patients with non-traumatic cSAH was performed at a tertiary referral center. The underlying cause of cSAH was characterized and clinical and imaging features that predict a specific etiology were identified. The frequency of future cSAH or intracerebral hemorrhage (ICH) was determined. RESULTS: In all, 88 patients [median age 64 years (range 25-85)] with non-traumatic cSAH were identified. The most common causes were reversible cerebral vasoconstriction syndrome (RCVS) (26, 29.5%), cerebral amyloid angiopathy (CAA) (23, 26.1%), indeterminate (14, 15.9%) and endocarditis (9, 10.2%). CAA patients commonly presented at an older age than RCVS patients (75 years versus 51 years, P < 0.0001). Thirteen patients (14.7%) had recurrent cSAH, and 12 patients (13.6%) had a subsequent ICH. However, the risk was high amongst those with CAA compared to those caused by RCVS, with recurrent cSAH in 39.1% and subsequent lobar ICH in 43.5% of CAA cases. CONCLUSIONS: Our study demonstrates the clinical diversity of cSAH. Older age, sensorimotor dysfunction and stereotyped spells suggest CAA as the underlying cause. Younger age and thunderclap headache predict RCVS. Yet, various other causes also need to be considered in the differential diagnosis.

Tobacco use increases lesion burden in familial cerebral cavernous malformation syndrome.

BACKGROUND: Familial cerebral cavernous malformation (CCM) syndrome is characterized by multiple, non-contiguous cavernous malformations. The lesion burden may affect morbidity. Our aim was to identify risk factors for high lesion burden in these patients. METHODS: Patients with radiologically confirmed CCM were screened between 2015 and 2023. Only familial or presumed familial CCM patients were included. Demographic information and medical history at the time of diagnosis were evaluated. The first diagnostic MRI was used to determine T2 total and T2 large lesion (≥5 mm) count. Chi-square was used to determine risk factors for total T2 large lesion count ≥5. RESULTS: Of 107 patients with familial or presumed familial CCM (55.1 % female, age 42.4 years), the median total T2 lesion count and large lesion count was 4 (range: 1-109) and 2 (range: 0-50) respectively. Current tobacco use was a risk factor for T2 large lesion count ≥5. CONCLUSION: Further studies combining familial cohorts and assessing length of exposure may be useful to confirm tobacco as a risk factor for T2 large lesion formation in familial CCM.

Baseline and Evolutionary Radiologic Features in Sporadic, Hemorrhagic Brain Cavernous Malformations.

BACKGROUND AND PURPOSE: Much has been written about the initial radiologic features of cavernous malformations, but less known are the radiologic natural history and evolution of the lesions, particularly when they initially present with hemorrhage. We aimed to describe the typical evolution of a sporadic, hemorrhagic brain cavernous malformation with time. MATERIALS AND METHODS: From our institutional review board-approved cavernous malformation registry, we assessed initial clinical and radiologic features and the subsequent MR imaging evolution of 51 patients with sporadic, hemorrhagic brain cavernous malformations (with follow-up brain MRIs available for review). RESULTS: The initial MR imaging demonstrated mostly Zabramski type I lesions (94.2%) with T1 hyperintensity (94.2%) and associated edema (76.5%). Eight patients (15.6%) rebled in the first year with lesions characterized by new T1 hyperintensity (100%), edema (61.5%), and growth (median, 4 mm). By 90 days, most lesions had changed from Zabramski type I to type II or III (65.2%). While 76.5% had edema associated with the acute hemorrhage, none had persistent edema beyond 90 days unless rebleeding occurred. Across time, the frequency of T1 hyperintensity decreased from 94.2% at baseline to 73.9%, 57.1%, and 50.0% at <90, 91-365, and >365 days. DWI intensity at baseline and <90, 91-365, and >365 days was hypointense at 53.1%, 56.5%, 70.1%, and 81.2%, respectively. CONCLUSIONS: Hemorrhagic cavernous malformation demonstrates a characteristic pattern of evolution on follow-up imaging. Knowing this evolution helps to analyze the timing of imaging in relation to the clinical presentation and may help distinguish true cavernous malformation hemorrhagic evolution from mimics and guide appropriate timing of interval-imaging follow-up after symptomatic bleeds in untreated patients.

Clinical and Imaging Characteristics of Diffuse Intracranial Dolichoectasia.

BACKGROUND AND PURPOSE: Among patients with vertebrobasilar dolichoectasia is a subset of patients with disease affecting the anterior circulation as well. We hypothesized that multivessel intracranial dolichoectasia may represent a distinct phenotype from single-territory vertebrobasilar dolichoectasia. The purpose of this study was to characterize clinical characteristics and angiographic features of this proposed distinct phenotype termed "diffuse intracranial dolichoectasia" and compare them with those in patients with isolated vertebrobasilar dolichoectasia. MATERIALS AND METHODS: We retrospectively reviewed a consecutive series of patients with diffuse intracranial dolichoectasia and compared their demographics, vascular risk factors, additional aneurysm prevalence, and clinical outcomes with a group of patients with vertebrobasilar dolichoectasia. "Diffuse intracranial dolichoectasia" was defined as aneurysmal dilation of entire vascular segments involving ≥2 intracranial vascular beds. Categoric and continuous variables were compared by using χ2 and Student t tests, respectively. RESULTS: Twenty-five patients had diffuse intracranial dolichoectasia, and 139 had vertebrobasilar dolichoectasia. Patients with diffuse intracranial dolichoectasia were older than those with vertebrobasilar dolichoectasia (70.9 ± 14.2 years versus 60.4 ± 12.5 years, P = .0002) and had a higher prevalence of abdominal aortic aneurysms (62.5% versus 14.3%, P = .01), other visceral aneurysms (25.0% versus 0%, P < .0001), and smoking (68.0% versus 15.9%, P < .0001). Patients with diffuse intracranial dolichoectasia were more likely to have aneurysm growth (46.2% versus 21.5%, P = .09) and rupture (20% versus 3.5%, P = .007) at follow-up. Patients with diffuse intracranial dolichoectasia were less likely to have good neurologic function at follow-up (24.0% versus 57.6%, P = .004) and were more likely to have aneurysm-related death (24.0% versus 7.2%, P = .02). CONCLUSIONS: The natural history of patients with diffuse intracranial dolichoectasia is significantly worse than that in those with isolated vertebrobasilar dolichoectasia. Many patients with diffuse intracranial dolichoectasia had additional saccular and abdominal aortic aneurysms. These findings suggest that diffuse intracranial dolichoectasia may be a distinct vascular phenotype secondary to a systemic arteriopathy affecting multiple vascular beds.

Rapidly progressive hippocampal atrophy: evidence for a seizure-induced mechanism.

Hippocampal formation atrophy (HFA) developed in an adult, who did not have epilepsy previously, after the occurrence of new-onset partial seizures from acute thrombosis of an ipsilateral parietal venous angioma. There was no evidence of hippocampal injury, and the patient had only one brief, generalized tonic-clonic seizure. Although HFA progressed rapidly over 5.5 months, the partial seizures did not become prolonged or secondarily generalized. Evidence from the patient indicates that partial seizure activity can cause rapid and progressive hippocampal atrophy.

Hyperhomocysteinemia in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

OBJECTIVE: To determine whether patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) had evidence of increased homocysteine levels compared with non-CADASIL patients with ischemic stroke or transient ischemic attack. PATIENTS AND METHODS: We compared fasting plasma homocysteine levels and levels 6 hours after oral loading with methionine, 100 mg/kg, in non-CADASIL patients with ischemic stroke or transient ischemic attack and in patients with CADASIL. Prechallenge, postchallenge, and change in homocysteine levels between the 2 groups were compared with use of the Wilcoxon rank sum test. RESULTS: CADASIL and non-CADASIL groups were similar in age (mean, 48.8 vs. 46.5 years, respectively; 2-tailed t test, P=.56) and sex (men, 86% vs 59%; Fisher exact test, P=.12). The 59 patients in the CADASIL group had higher median plasma homocysteine levels compared with the 14 patients in the non-CADASIL group, both in the fasting state (12.0 vs 9.0 micromol/L; P=.03) and after methionine challenge (51.0 vs 34.0 micromol/L; P=.007). Median difference between homocysteine levels before and after methionine challenge was greater in the CADASIL group than in the non-CADASIL group (34.5 vs. 24.0 micromol/ L; P = .02). CONCLUSION: Our findings raise the possibility that increased homocysteine levels or abnormalities of homocysteine metabolism may have a role in the pathogenesis of CADASIL.

Cerebral infarction and transient ischemic attacks. Efficient evaluation is essential to beneficial intervention.

Rapid but precise evaluation of patients presenting with cerebral infarction is essential to determine immediate intervention. Initial assessment should include history taking, physical examination, routine laboratory testing, electrocardiography, chest radiology, and noncontrast head CT. Localizing the event to the appropriate arterial circulation (anterior versus posterior) and determining topography (subcortical versus cortical) guide sequential testing to ascertain the mechanism of cerebral infarction. Diagnostic testing focuses on selectively identifying potential cardiac, large-vessel, small-vessel, or hematologic causes. Although diagnostic tools are evolving, 15% of cerebral infarctions still have an unknown cause or multiple potential sources.

Prospective hemorrhage risk of intracerebral cavernous malformations.

OBJECTIVE: Our goal was to describe the prospective risk and timing of symptomatic hemorrhage in a large cohort of followed patients with intracerebral cavernous malformations (ICMs). METHODS: All patients between 1989 and 1999 with the radiographic diagnosis of intracerebral cavernous malformation were identified retrospectively. The records and radiographic data were reviewed, and follow-up after diagnosis was obtained. An incidence rate was used to calculate annual risk of symptomatic hemorrhage. Predictive factors for outcomes used univariate and multivariable analysis with p < 0.05. RESULTS: A total of 292 patients were identified (47.3%male) with 2,035 patient years of follow-up. Seventy-four patients presented with hemorrhage, 108 with symptoms not related to hemorrhage (seizure or focal deficit), and 110 as asymptomatic. The overall annual rate of hemorrhage in those presenting initially with hemorrhage, with symptoms not related to hemorrhage, or as an incidental finding was 6.19%, 2.18%, and 0.33%, respectively. Patients who presented initially with symptomatic hemorrhage (hazard ratio 5.14; 95% confidence interval [CI] 2.54-10.4; p < 0.001) were at higher risk for future hemorrhage, and hemorrhage risk decreased with time. Male gender (hazard ratio 2.36; 95% CI 1.14-4.89; p = 0.02), and multiplicity of ICMs (hazard ratio 2.65; 95% CI 1.30-5.43; p = 0.01) also increased the risk of hemorrhage. The median time from first to second hemorrhage was 8 months. CONCLUSIONS: This study provides an estimate of prospective annual symptomatic hemorrhage risk in patients with ICMs stratified by initial presenting symptom. Prior hemorrhage, male gender, and multiplicity of ICMs may predict future hemorrhage. Hemorrhage risk decreases with time in those initially presenting with hemorrhage.

Can we predict poor outcome at presentation in patients with lobar hemorrhage?

OBJECTIVE: Supratentorial lobar hemorrhage can be devastating. Outcome prediction at presentation is important in triage and management decisions as well as appropriate resource utilization. We performed a decision tree analysis combining clinical and CT scan features to predict poor and hopeless outcome at initial presentation in patients with lobar hemorrhage. METHODS: We analyzed 81 patients with spontaneous lobar hemorrhage presenting within 48 hours of initial neurologic symptoms. In the first analysis, poor outcome was defined as Glasgow outcome score (GOS) of 1 (death), 2 (vegetative state) or 3 (dependence) at discharge. A second analysis was based on worst possible outcome (GOS 1-2). Binary recursive partitioning was fitted in a model, and odds ratios with 95% confidence intervals (CI) were calculated. RESULTS: Lobes involved were temporal (36%), parietal (33%), frontal (25%) and occipital (6%). Seventy-three percent of patients presented less than 17 h after initial ictus. The probability of poor outcome was 97% (CI 85-100%) in patients with hemorrhage greater than 40 cm(3). In the subset of patients with a volume less than 40 cm(3), time interval from ictus to presentation (< 17 h) together with a Glasgow coma score (GCS) less than or equal to 13 predicted poor outcome. Eighty-five percent (CI 42-99%) of those presenting early with GCS less than or equal to 13 had a poor outcome. In the second analysis, all patients with GCS less than or equal to 12 and septum pellucidum shift > 6 mm had GOS of 1 or 2 (CI 72-100%). CONCLUSION: Poor outcome in patients with lobar hemorrhage is associated with a hemorrhage size of more than 40 cm(3), GCS less than or equal to 13, but also dependent on time interval between ictus and presentation. This is consistent with prior studies demonstrating deterioration from enlargement may occur when patients present early on. Stupor and septum pellucidum shift greater than 6 mm on CT scan at presentation predict a hopeless outcome in conservatively treated patients. Ninety-one percent of patients were treated medically, thus these outcomes are largely a reflection of the natural history of spontaneous lobar hemorrhage. These signs may influence triage and management decisions.

Subarachnoid Hemorrhage.

All patients who present with subarachnoid hemorrhage should be admitted to the intensive care unit for close neurologic and cardiorespiratory monitoring. Neurosurgical consultation should be obtained if external ventricular drain placement, arteriography, or surgical planning are considered. Seizure prophylaxis, antihypertensive treatment for mean arterial blood pressure greater than 130 mm Hg, pain control, and bed rest are important measures for the prevention of rebleeding, which is associated with a high mortality rate. Standard deep venous thrombosis and gastrointestinal prophylaxis are recommended to prevent medical complications associated with critical illness. In patients with good-grade subarachnoid hemorrhage, early arteriography and definitive aneurysm management are recommended. The location and neck size of the aneurysm and the medical condition of the patient are factors in the decision to proceed with surgical rather than interventional aneurysm management. Postoperatively, clinical examination and transcranial Doppler ultrasonography are recommended for surveillance of vasospasm. If clinical or arteriographic evidence of vasospasm is present, hemodilution, hypertension, and hypervolemia (triple H) therapy should be instituted. If vasospasm is resistant to conservative measures, balloon angioplasty or intra-arterial papaverine therapy should also be considered.

Predicting deterioration in patients with lobar haemorrhages.

OBJECTIVE: To study the clinical course and determine predictors of deterioration in patients with lobar haemorrhages). METHODS: A comprehensive review of 61 consecutive patients with lobar haemorrhages was performed. Neurological deterioration was defined as (1) decrease in Glasgow coma sum score by 2 points, (2) new neurological deficit, or (3) clinical signs of brain herniation. A univariate logistic regression was performed and expressed in odds ratios. RESULTS: Sixteen of 61 (26%) patients with lobar haemorrhages deteriorated after admission. In a univariate analysis, only a Glasgow coma score <14 predicted deterioration (75% of deteriorators v 24% who did not deteriorate; p<0.0001). Initial CT characteristics predictive of deterioration included haemorrhage volume >60 ml (63% v 16%, p< 0.0001), shift of the septum pellucidum (75% v 36%, p<0.01), effacement of the contralateral ambient cistern (33% v 0%, p<0.0001), and widening of the contralateral temporal horn (50% v 0%, p<0.0001). Patients presenting and deteriorating within 12 hours of ictus declined due to enlargement of the haemorrhage. Those who deteriorated more than 12 hours after initial neurological symptoms, showed increased mass effect secondary to oedema. CONCLUSION-Patients with lobar haemorrhages presenting immediately after ictus are at risk for deterioration from enlargement of the haemorrhage and predictors of deterioration may be absent. Patients with large volume lobar haemorrhages presenting to the emergency department with decreased level of consciousness and shift on CT are at risk for further deterioration from worsening oedema. These patients require close observation and early aggressive management may be warranted.