Unusual progression of herpes simplex encephalitis with basal ganglia and extensive white matter involvement

We report a 51-year old male with herpes simplex encephalitis (HSE) showing unusual progression and magnetic resonance (MR) findings. The initial neurological manifestation of intractable focal seizure with low-grade fever persisted for three days, and rapidly coma, myoclonic status, and respiratory failure with high-grade fever emerged thereafter. The polymerase chain reaction (PCR) result of cerebrospinal fluid (CSF) was positive for HSV-1 DNA. In the early stage, MR images (MRI) were normal. On subsequent MR diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) images, high-intensity areas first appeared in the left frontal cortex, which was purely extra-temporal involvement, and extended into the basal ganglia, then the white matter, which are relatively spared in HSE. Antiviral therapy and immunosuppressive therapy did not suppress the progression of HSE, and finally severe cerebral edema developed into cerebral herniation, which required emergency decompressive craniectomy. Histological examination of a biopsy specimen of the white matter detected perivascular infiltration and destruction of basic structure, which confirmed non specific inflammatory change without obvious edema or demyelination. The present case shows both MR and pathological findings in the white matter in the acute stage of HSE

Reducing Hemorrhagic Complication by Dabigatran Via Neurovascular Protection After Recanalization With Tissue Plasminogen Activator in Ischemic Stroke of Rat

This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study

Thrombolysis with Low-Dose Tissue Plasminogen Activator 3–4.5 h After Acute Ischemic Stroke in Five Hospital Groups in Japan

Clinical data from Japan on the safety and real-world outcomes of alteplase (tPA) thrombolysis in the extended therapeutic window are lacking. The aim of this study was to assess the safety and real-world outcomes of tPA administered within 3-4.5 h of stroke onset. The study comprised consecutive acute ischemic stroke patients (n = 177) admitted across five hospitals between September 2012 and August 2014. Patients received intravenous tPA within <3 or 3-4.5 h of stroke onset. Endovascular therapy was used for tPA-refractory patients. In the 3-4.5 h subgroup (31.6 % of patients), tPA was started 85 min later than the <3 h group (220 vs. 135 min, respectively). However, outcome measures were not significantly different between the <3 and 3-4.5 h subgroups for recanalization rate (67.8 vs. 57.1 %), symptomatic intracerebral hemorrhage (2.5 vs. 3.6 %), modified Rankin Scale score of 0-1 at 3 months (36.0 vs. 23.4 %), and mortality (6.9 vs. 8.3 %). We present data from 2005 to 2012 using a therapeutic window <3 h showing comparable results. tPA following endovascular therapy with recanalization might be superior to tPA only with recanalization (81.0 vs. 59.1 %). Compared with administration within 3 h of ischemic stroke onset, tPA administration within 3-4.5 h of ischemic stroke onset in real-world stroke emergency settings at multiple sites in Japan is as safe and has the same outcomes

Tomotaka Tanaka, Hisashi Narai,

High blood pressure in acute ischemic stroke and clinical outcom

High Blood Pressure in Acute Ischemic Stroke And Clinical Outcome

This study aimed to evaluate the prognostic value of acute phase blood pressure in patients with acute ischemic stroke by determining whether or not it contributes to clinical outcome. We studied 515 consecutive patients admitted within the first 48 hours after the onset of ischemic strokes, employing systolic and diastolic blood pressure measurements recorded within 36 hours after admission. High blood pressure was defined when the mean of at least 2 blood pressure measurements was ≥200 mmHg systolic and/or ≥110 mmHg diastolic at 6 to 24 hours after admission or ≥180 mmHg systolic and/or ≥105 mmHg diastolic at 24 to 36 hours after admission. The high blood pressure group was found to include 16% of the patients. Age, sex, diabetes mellitus, hypercholesterolemia, atrial fibrillation, ischemic heart disease, stroke history, carotid artery stenosis, leukoaraiosis, NIH Stroke Scale (NIHSS) on admission and mortality were not significantly correlated with either the high blood pressure or non-high blood pressure group. High blood pressure on admission was significantly associated with a past history of hypertension, kidney disease, the modified Rankin Scale (mRS) on discharge and the length of stay. On logistic regression analysis, with no previous history of hypertension, diabetes mellitus, atrial fibrillation, and kidney disease were independent risk factors associated with the presence of high blood pressure [odds ratio (OR), 1.85 (95% confidence interval (CI): 1.06-3.22), 1.89 (95% CI: 1.11-3.22), and 3.31 (95% CI: 1.36-8.04), respectively]. Multi-organ injury may be presented in acute stroke patients with high blood pressure. Patients with high blood pressure had a poor functional outcome after acute ischemic stroke

Parkinsonism in Association with Dihydropteridine Reductase Deficiency

We report a 16-year-old man with disorders of tetrahydrobiopterin metabolism due to dihydropteridine reductase (DHPR) deficiency. He revealed moderate mental retardation, parkinsonism, and spastic paralysis with levodopa and 5-hydroxytryptophan (5-HTP) supplementation from the age of 2 months. Brain MRI showed high intensity areas in bilateral frontal and posterior deep white matter on fluid-attenuated inversion recovery (FLAIR). Coronal FLAIR image showed a high signal in bilateral pyramidal tracts. Single photon computed tomography (SPECT) imaging of the dopamine transporter was normal. This imaging indicates no dopaminergic cell loss. Our patient had no motor fluctuations or dyskinesias. Early diagnosis and replacement treatment might lead to a favorable outcome

Successful Delayed Aortic Surgery for a Patient with Ischemic Stroke Secondary to Aortic Dissection

The diagnosis of aortic dissection (AD) is sometimes difficult within the limited time window of recombinant tissue plasminogen activator (tPA) for ischemic stroke (IS). A 60-year-old man developed sudden left hemiparesis due to IS. During tPA infusion, his blood pressure dropped and consciousness declined. After transfer to our hospital, carotid duplex ultrasonography led to a diagnosis of AD. Emergency surgery was postponed because of the risk of hemorrhagic transformation. The patient successfully underwent aortic surgery on day 5 and was discharged with a remarkable improvement in his symptoms. Delayed surgery may avoid hemorrhagic transformation in patients with AD-induced IS who have received tPA