Background and Purpose— We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods— This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0–1). Results— Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68–1.41]; P =0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P >0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06–12.58]; P >0.999), respectively. Conclusions— No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02002325.
Most accepted operations for childhood moyamoya disease have attempted to increase cerebral blood flow (CBF) in the ischaemic cortical areas around the central fissure. Developed ischaemic brain damage in the prefrontal area may lead to poor intellectual outcome and restrict patients' daily lives. Thus, extensive cerebral revascularization in both the ischaemic anterior and middle cerebral artery territories is mandatory. We describe the long-term follow-up results for intellectual outcome and performance status and make an evaluation of regional cerebral haemodynamics after extensive omental transplantation spread over both frontal lobes performed as the initial management. In the past 10 years, 10 moyamoya patients less than 12 years of age consecutively underwent omental transplantation. The omental flap was spread over not only the symptomatic hemisphere but also the contralateral frontal lobe after a large craniotomy. Superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis was accomplished simultaneously. On the contralateral hemisphere, STA-MCA anastomosis combined with encephalomyosynangiosis was subsequently performed. The clinical observation period averaged 6.7 years (ranged 1.9 to 9.2 years). Apart from 2 patients in whom severe mental retardation had been disclosed pre-operatively, full-scale intelligence quotient scores have been maintained at over 90, that is, within the normal intellectual range. With respect to quality of life (QOL), these 8 patients have been leading normal daily lives since the operation. The focal decrease in CBF observed in the frontal lobe pre-operatively in 7 cases had disappeared after surgical treatment. In these patients, serial post-operative MR angiography revealed developed omental vessels and STAs. Deterioration of intellectual functions and QOL as well as cerebral ischaemic events in paediatric moyamoya patients can be prevented by extensive omental transplantation spread over both frontal lobes combined with STA-MCA anastomosis.
Sirs: Idiopathic intracranial hypertension (pseudotumour cerebri) is uncommon in Japan, but no accurate data have been reported on its incidence. To determine the incidence of idiopathic intracranial hypertension (IIH) in Hokkaido, the northernmost island of Japan, we surveyed patients by post or telephone who were diagnosed with the condition in 1993. Hokkaido is the second largest island in Japan, at a latitude of 42°-46°N. It is served by 230 hospitals with 70 neurology departments, 196 neurosurgery departments and 64 ophthalmology departments. The population of Hokkaido was 5,780,000 in 1993. Inquiries were sent to all hospitals asking for information on cases of IIH diagnosed according to the modified Dandy criteria [1]. Of the 230 hospitals 221 responded.Only two cases of IIH were diagnosed during the year 1993.Case 1 was a 25-year-old woman presented with a 3-month history of severe headache and nausea. On examination she was thin and had bilateral papilledema. Magnetic resonance imaging of the brain and angiography ruled out mass lesion and sinus occlusion. Laboratory studies were normal. She was taking no medications. CSF pressure was 260 mmH 2 O. Administration of diuretics improved her symptoms.Case 2 was a 20-year-old man with non-Hodgkin lymphoma presented with a 2-month history of headache, nausea, and diplopia. He was not obese. Neurological examination showed bilateral papilledema and abducens nerve paresis. At this time he was not receiving chemotherapy or other drugs. Mass lesion and sinus occlusion were ruled out by magnetic resonance imaging of the brain and angiography. Laboratory studies were normal. CSF pressure was 290 mmH 2 O. Glycerol (hyperosmolar agent with concentrated glycerin fructose to reduce raised intracranial pressure) improved his symptoms. After 1 year he died of pneumonia. Autopsy showed no abnormalities in the central nervous system including the meninges, which supported the clinical diagnosis of IIH by excluding a meningitic infiltrative process.During this 1-year period only two patients, one man and one woman, were diagnosed as IIH. The crude incidence of IIH in Hokkaido in 1993 was thus 0.03 per 100,000. Both patients were atypical in the sense that neither was obese or was taking any medication. The papilledema and documented CSF pressures over 250 mmH 2 O were compatible with IIH according to the modified Dandy criteria.
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