Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study.

CONTEXT: Tissue-type plasminogen activator (tPA) is the only therapy for acute ischemic stroke approved by the Food and Drug Administration. OBJECTIVE: To assess the safety profile and to document clinical outcomes and adverse events in patients treated with intravenous tPA for acute stroke in clinical practice. DESIGN AND SETTING: Prospective, multicenter study of consecutive patients enrolled between February 1997 and December 1998 at 57 medical centers in the United States (24 academic and 33 community). INTERVENTION: Intravenous tPA (recombinant alteplase). PATIENTS: Three hundred eighty-nine patients with a mean age of 69 years (range, 28-100 years); 55% were men. MAIN OUTCOME MEASURES: Time intervals between stroke symptom onset, hospital arrival, and treatment with tPA; pretreatment computed tomographic scan results, intracerebral hemorrhage, and major systemic bleeding. The modified Rankin Scale score was used to assess clinical outcomes at 30 days. RESULTS: Median time from stroke onset to treatment was 2 hours 44 minutes, and the median baseline National Institutes of Health Stroke Scale score was 13. The 30-day mortality rate was 13%. At 30 days after treatment, 35% of patients had very favorable outcomes (modified Rankin score, 0-1) and 43% were functionally independent (modified Rankin score, 0-2). Thirteen patients (3.3%) experienced symptomatic intracerebral hemorrhage, including 7 who died. Twenty-eight patients (8.2%) had asymptomatic intracerebral hemorrhage within 3 days of treatment with tPA. Protocol violations were reported for 127 patients (32.6%), and included treatment with tPA more than 3 hours after symptom onset in 13.4%, treatment with anticoagulants within 24 hours of tPA administration in 9.3%, and tPA administration despite systolic blood pressure exceeding 185 mm Hg in 6.7%. A multivariate analysis found predictors of favorable outcome to be a less severe baseline National Institutes of Health Stroke Scale score, absence of specific abnormalities (effacement or hypodensity of >33% of the middle cerebral artery territory or a hyperdense middle cerebral artery) on the baseline computed tomographic scan, an age of 85 years or younger, and a lower mean arterial pressure at baseline. CONCLUSIONS: This study, conducted at multiple institutions throughout the United States, suggests that favorable clinical outcomes and low rates of symptomatic intracerebral hemorrhage can be achieved using tPA for stroke treatment.

Intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 80 years and older : the tPA stroke survey experience.

BACKGROUND AND PURPOSE: Intravenous tissue plasminogen activator (tPA) administered within 3 hours of symptom onset is the first available effective therapy for acute ischemic stroke (AIS). Few data exist, however, on its use in very elderly patients. We examined the characteristics, complications, and short-term outcome of AIS patients aged >/=80 years treated with tPA. METHODS: Patients aged >/=80 years (n=30) were compared with counterparts aged <80 years (n=159) included in the tPA Stroke Survey, a US retrospective survey of 189 consecutive AIS patients treated with intravenous tPA at 13 hospitals. RESULTS: Risk of intracerebral hemorrhage (fatal, symptomatic, and total) was 3%, 3%, and 7% in the elderly age group and 2%, 6%, and 9%, respectively, in their younger counterparts (P=NS for all comparisons). Likelihood of favorable outcome, defined as modified Rankin score 0 to 1, National Institutes of Health Stroke Scale score /=80 years was identified.

Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke: a multicenter survey. The t-PA Stroke Survey Group.

We assessed initial clinical experience with IV tissue plasminogen activator (t-PA) treatment of acute ischemic stroke in a standardized retrospective survey of hospitals with experienced acute stroke treatment systems. The incidence of symptomatic intracerebral hemorrhage (ICH) was 6% (11 of 189 patients; 95% CI 3 to 11%), similar to that in the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Study. Deviations from the NINDS protocol guidelines were identified in 30% of patients (56 of 189). The incidence of symptomatic ICH was 11% among patients with protocol deviations as compared with 4% in patients who were treated according to the NINDS protocol guidelines, suggesting that strict adherence to protocol guidelines is prudent.

MRI in cerebral intraventricular hemorrhage: analysis of 50 consecutive cases.

MRI of intraventricular haemorrhage (IVH) has not been studied formally. We aimed to describe the degradation rate and patterns shown on 1.5 T MRI in IVH, comparing them to other coexisting brain hemorrhage. We studied 50 consecutive cases using T1-, proton-density, and T2-weighted images. IVH was seen in two forms: layered (free-flowing in ventricles) (37 cases) and/or clotted (31). Both were best shown by proton-density image. Layered IVH was seen in the dependent portions of the lateral ventricles with fluid ("blood-CSF") levels, degrading more slowly than both clotted IVH and intraparenchymal hemorrhages (IPH) (acute blood products persisting for several more days; P < 0.05). Clotted IVH degraded at a rate comparable to IPH. IVH cleared rapidly and did not form hemosiderin. Subarachnoid hemorrhage (SAH) cleared faster and was less conspicuous than IVH. Hypertensive (22), aneurysmal (11), traumatic (2), idiopathic (9), or vascular malformation-related (6) IVH were seen. IVH coexisted with IPH (30) or SAH (12), or both (12). The high rate of layering with blood-CSF levels in IVH is most likely due to different densities of blood components and CSF and the fibrinolytic capability of the latter. Delayed degradation of layered IVH probably reflects high intraventricular oxygen and glucose content. Further study is necessary to determine if MRI characteristics of IVH are helpful in excluding other intraventricular diseases such as neoplasia and pyocephalus.

MRI findings in lumbar puncture headache syndrome: abnormal dural-meningeal and dural venous sinus enhancement.

Intracranial hypotension (IH) is a treatable cause of persistent headaches. Persistent cerebrospinal fluid (CSF) leak at a lumbar puncture (LP) site may cause IH. We present postcontrast MRI of a patient with post-lumbar-puncture headache (LPHA) showing abnormal, intense, diffuse, symmetric, contiguous dural-meningeal (pachymeningeal) enhancement of the supratentorial and infratentorial intracranial dura, including convexities, interhemispheric fissure, tentorium, and falx. MRI also showed abnormal dural venous sinus enhancement, a new finding in LPHA, suggesting compensatory venous expansion. Thus, IH and venodilatation may play a role in the development of LPHA.

Aggressive giant pituitary adenoma presenting as a nasopharyngeal mass: magnetic resonance imaging and pathologic findings.

We report a giant pituitary adenoma with aggressive histologic features that prominently invaded the nasopharynx. Magnetic resonance imaging (MRI) demonstrated a large heterogeneous nodular mass that was hypointense to isointense on T1-weighted images and mixed hypointense, isointense, and hyperintense on T2-weighted images. The mass measured 7.5 x 5 x 7 cm, extending from the nasopharynx posteriorly through the clivus, and superiorly through the paranasal sinuses, and sellar-suprasellar region. After contrast administration, heterogeneous nodular enhancement was noted. A nasopharyngeal neoplasm extending into the sella was suspected because voice change and nasal speech long preceded the patient's visual symptoms. A biopsy disclosed an aggressive, infiltrating, hemorrhagic tumor, which was diagnosed as a non-secreting pituitary macroadenoma. This report indicates that pituitary adenomas may grow invasively to tremendously large sizes resulting in their initial presentation as nasopharyngeal masses.

Fluid-attenuated inversion-recovery MR imaging in acute and subacute cerebral intraventricular hemorrhage.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion-recovery (FLAIR) MR imaging may show subarachnoid hemorrhage (SAH) with high sensitivity. We hypothesized that the FLAIR technique is effective and reliable in the diagnosis of cerebral intraventricular hemorrhage (IVH). METHODS: Two observers evaluated the 1.5-T MR fast spin-echo FLAIR images, T1- and T2-weighted MR images, and CT scans of 13 patients with IVH and the FLAIR images of 40 control subjects. RESULTS: IVH appeared bright on the FLAIR images obtained during the first 48 hours and was of variable appearance at later stages. FLAIR MR imaging detected 12 of 13 cases of IVH; no control subjects were falsely thought to have IVH (92% sensitivity, 100% specificity). However, IVH could not be fully excluded in the third ventricle (20%, n = 8) or in the fourth ventricle (28%, n = 11) on some control images because of CSF pulsation artifacts. Two cases had CT-negative IVH seen on FLAIR images. One case had FLAIR-negative IVH seen by CT. Although the sensitivities of conventional MR imaging (92%) and CT (85%) were also high, FLAIR imaging showed IVH more conspicuously than did standard MR imaging and CT in 62% of the cases (n = 8). FLAIR was as good as or better than CT in showing IVH in 10 cases (77%). FLAIR images showed all coexisting SAH. CONCLUSION: FLAIR MR imaging identifies acute and subacute IVH in the lateral ventricles with high sensitivity and specificity. In cases of subacute IVH, conventional MR imaging complements FLAIR in detecting IVH. The usefulness of the FLAIR technique for detecting third and fourth ventricular IVH may be compromised by artifacts. Blood hemoglobin degradation most likely causes the variable FLAIR appearance of IVH after the first 48 hours.

Thrombotic thrombocytopenic purpura: brain CT and MRI findings in 12 patients.

Clinical-neuroimaging analysis of 12 thrombotic thrombocytopenic purpura (TTP) patients revealed a variety of brain lesions. These included reversible cerebral edema lesions with MRI features of reversible posterior leukoencephalopathy syndrome (RPLS). Most of the RPLS patients had hypertension and renal dysfunction, suggesting RPLS due to hypertensive encephalopathy. Prompt treatment usually led to neurologic recovery and disappearance of edematous lesions. Those with infarcts or hematomas had a poorer outcome. TTP should be added to the expanding spectrum of RPLS and hypertensive encephalopathy.

Cranial magnetic resonance imaging findings in bacterial endocarditis: the neuroimaging spectrum of septic brain embolization demonstrated in twelve patients.

Infective endocarditis (IE) is an elusive systemic disorder that is often associated with neurologic complications. The contribution of brain magnetic resonance imaging (MRI) to the diagnosis of IE and the spectrum of such findings has been only sparsely described previously. The authors report cranial MRI findings in 12 patients with IE. Each of the patients had MRI evidence of cerebral embolization, with multiple brain lesions noted in most patients (n = 10). Cortical branch infarction was the most common lesion (n = 8), which usually involved the distal middle cerebral artery tree. The next most common finding (n = 7) was numerous small embolic lesions which typically lodged in the supratentorial gray-white junction, some of which were clinically silent and many of which enhanced (probable microabscesses). Brain hemorrhages were noted in four patients, most commonly subarachnoid hemorrhage (n = 3). Two patients developed multiple frank parenchymal macroabscesses/cerebritis lesions. A previously unreported finding in septic embolization, a stroke that became infected with abscess formation ("septic infarction"), was noted in two patients. MRI showed orbital cellulitis in two patients. Most patients studied with gadolinium showed enhancement of lesions (n = 5/8). The authors conclude that cranial MRI may be a valuable tool in the evaluation of patients with IE. The presence of characteristic cranial MRI lesions, especially of multiple types, may prompt early diagnosis and treatment.

The cerebral intravascular enhancement sign is not specific: a contrast-enhanced MRI study.

The intravascular enhancement (IVE) sign, also known as the "arterial enhancement sign", is an abnormal finding in the brain on contrast-enhanced MRI studies. IVE has been described in arterial cerebrovascular disorders, most commonly in acute or subacute arterial ischemic infarcts. However, the specificity of this sign has not been established. We describe four patients with disorders other than arterial strokes in whom gadolinium-enhanced high-field (1.5 T) MRI suggested IVE. The conditions were herpes simplex viral encephalitis, idiopathic cerebellitis, pneumococcal meningitis, and superior sagittal sinus thrombosis with venous infarction. IVE in these cases may be due to multiple factors, including arterial, venous, perivascular, and leptomeningeal or sulcal contrast medium accumulation. Our observations suggest that arterial ischemia, previously described as the cardinal cause of IVE, probably does not explain all instances, and urge caution in interpreting this sign as a specific MRI manifestation of acute arterial infarction or ischemia.

Cerebral venous infarctions presenting as enhancing space-occupying lesions: MRI findings.

Cerebral venous thrombosis is an unusual form of cerebrovascular disease that may cause cerebral venous infarction (CVI). Magnetic resonance imaging (MRI) of the brain may improve the often elusive diagnosis of CVI. However, the sensitivity, specificity, and full spectrum of such MRI findings are poorly understood. The authors present the cases of three patients with CVI whose MRI scans showed abnormally enhancing tumor-like brain lesions. Two of the CVIs were hemorrhagic and exerted mass effect. One patient showed increasingly nodular and heterogeneous ring-like enhancement progressing from the single-dose to the triple-dose gadolinium contrast images. The CVI of a second patient also showed ring-like enhancement. Biopsy was performed on one of these patients and was strongly considered for the other two patients to exclude neoplastic disease. Careful examination of the MRI appearance of venous structures and the use of specialized MRI techniques improved the recognition of CVI for two patients and prevented biopsy. This represents the first description of abnormal triple-dose MRI contrast enhancement in CVI. Consideration of CVI in the care of patients with enhancing tumor-like masses may lead to earlier diagnosis and treatment, preventing unnecessary invasive diagnostic procedures. CVI should be added to the differential diagnosis of supratentorial ring-enhancing masses.

Neurosarcoidosis presenting as a large suprasellar mass. Magnetic resonance imaging findings.

We present unusual magnetic resonance imaging (MRI) findings in a case of neurosarcoidosis. MRI revealed a large solitary suprasellar mass which resembled a neoplasm. The lesion was isointense and hyperintense on T1-weighted images, hypointense on T2-weighted images, and intensely homogeneously enhancing. Biopsy revealed a polymorphous inflammatory lesion with giant cells, which extended from the hypothalamus, consistent with neurosarcoidosis. The diagnosis of neurosarcoidosis should be considered in patients presenting with large midline tumor-like suprasellar mass lesions.

Occipital lobe seizures as the major clinical manifestation of reversible posterior leukoencephalopathy syndrome: magnetic resonance imaging findings.

PURPOSE: Reversible posterior leukoencephalopathy syndrome (RPLS) is an increasingly recognized brain disorder most commonly associated with malignant hypertension, toxemia of pregnancy, or the use of immunosuppressive agents. When associated with acute hypertension, RPLS typically occurs concurrently with the fulminant clinical syndrome of hypertensive encephalopathy. We describe occipital lobe seizures, in the setting of only moderate elevations of blood pressure, as the major clinical manifestation of RPLS. METHODS: Two patients from the Dent Neurologic Institute are presented with clinical and magnetic resonance imaging (MRI) correlation. RESULTS: New onset secondarily generalized occipital seizures were noted, with MRI findings consistent with RPLS. Both of the patients had chronic renal failure and a moderate acute exacerbation of chronic hypertension. Other features of hypertensive encephalopathy were lacking, such as headache, nausea, papilledema, and an altered sensorium. Magnetic resonance imaging (MRI) showed edematous lesions primarily involving the posterior supratentorial white matter and corticomedullary junction, consistent with RPLS. With lowered blood pressure, the MRI lesions resolved and the patients became seizure-free without requiring chronic anticonvulsant therapy. CONCLUSIONS: Occipital seizures may represent the only major neurologic manifestation of RPLS due to acute hypertension, especially in patients with renal failure. Other evidence of hypertensive encephalopathy, such as cerebral signs and symptoms, need not be present. Blood pressure elevations may be only moderate. Early recognition of this readily treatable cause of occipital seizures may obviate the need for extensive, invasive investigations. Despite the impressive lesions on MRI, prompt treatment of this disorder carries a favorable prognosis.

Magnetic resonance imaging findings in acute cerebellitis.

Cerebellitis, also known as acute cerebellar ataxia, is an inflammatory syndrome of cerebellar dysfunction that may reflect an infectious, post-infectious, or post-vaccination disorder. We present serial magnetic resonance imaging (MRI) findings in a partially reversible, idiopathic cerebellitis. Bilateral cerebellar parenchymal abnormalities were noted, including hyperintensities on T2-weighted images and cerebellar swelling. After contrast administration, the cerebellum showed abnormal bilateral enhancement. The authors state this represents the first report of abnormal contrast enhancement in this condition. The MRI lesions most likely reflect the reversible, inflammatory nature of the syndrome.

Cerebral ventricular empyema associated with severe adult pyogenic meningitis: computed tomography findings.

Cerebral ventricular empyema (CVE), also known as pyocephalus, is a rare form of pyogenic ventriculitis. We present cranial computed tomography (CT) in an adult who developed a bilateral CVE associated with acute pyogenic meningitis. CT showed an obstructive ventriculomegaly and fluid-fluid levels layering in the lateral ventricles and the third ventricle. Frank neutrophilic pus was taken from the subarachnoid space. After antibiotic treatment, the pyocephalus resolved. CVE may be visualized on CT with pus layering in the ventricular CSF, creating a fluid level of intermediate hypodensity.

Multiple giant intracranial aneurysms associated with lymphomatoid granulomatosis. A magnetic resonance imaging and angiographic study.

Lymphomatoid granulomatosis is an uncommon lymphoproliferative disorder that frequently has central nervous system manifestations. Lymphomatoid granulomatosis has clinical features similar to both vasculitis and lymphoma. The pathological hallmarks of this disease include necrotic angiocentric and angiodestructive infiltrations of premalignant or malignant lymphoid cells. There are, to the authors' knowledge, only a few magnetic resonance imaging reports and no magnetic resonance angiographic reports of this disorder. Presented here is a case of lymphomatoid granulomatosis producing multiple giant fusiform and saccular aneurysms throughout the major intracerebral arteries, along with patterns of vascular beading typically seen with vasculitis demonstrated by magnetic resonance angiography.

Elevated TRH levels in pyriform cortex after partial and fully generalized kindled seizures.

In a previous study we reported significant elevations of TRH in neocortex, hippocampus and combined amygdala/pyriform cortex in rats 48 h after the last of a series of stage 5 kindled seizures. In the present study, to determine whether the increases in TRH were proportional to the intensity of the convulsions, and the degree of development of the kindling process, we compared the effects of partially kindled (stage 2) vs fully kindled (stage 5) seizures. As a further refinement, we examined separately the TRH responses in the pyriform, cingulate and frontal cortices. The responses were especially marked in the pyriform cortex, where TRH increased 7-fold after stage 5 kindled convulsions, compared with 2-fold increases after stage 2-3 seizures. Increases were seen in other cortical regions, as well, but only after stage 5 seizures. These findings are consistent with reports suggesting that the increases in brain TRH occurring after convulsions are aftereffects of the seizures, possibly representing homeostatic anticonvulsant responses, and that the pyriform cortex is a site that is uniquely activated by convulsions.

Combined treatment with muscarinic and nicotinic cholinergic antagonists slows development of kindled seizures.

Rats were given daily injections of atropine, mecamylamine or both drugs in combination, 1 h prior to daily electrical amygdaloid kindling stimulation. Neither drug was effective alone, but the two drugs in combination significantly increased the latency to develop stage 5 kindled seizures.