Effective Tools to Predict Depression in Acute and Subacute Phase of Ischemic Stroke.

OBJECTIVE: Despite the high frequency of depression in the first year following stroke, few studies have predicted risk of depression after the acute and subacute stroke periods. The aim of this study was to identify, in the acute and subacute periods, measures that would predict major depression during the first year after stroke. METHODS: Study subjects were inpatients with ischemic stroke aged 20-85 years within 6 weeks of onset. Patients were evaluated at baseline and at 3, 6, 9, and 12 months. Patients were diagnosed with major depression using the Structured Clinical Interview for DSM-IV. The severity of depressive symptoms was measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Of the 152 potential patients who met inclusion criteria, 49 had follow-up evaluations; one patient with major depression in the acute and subacute periods was excluded from the analysis. Among the remaining 48 patients, the number of those with major depression during the first year of stroke onset was five (10.4%). Patients who developed major depression had significantly more depressive symptoms in the acute and subacute stroke phase as assessed by both the PHQ-9 and MADRS. Patients with PHQ-9 scores ≥9 in the acute and subacute stroke phases were significantly more likely to develop major depression in a chronic phase of stroke. CONCLUSIONS: The self-administered PHQ-9 can identify patients in the acute and subacute stroke periods who are at increased risk for developing major depression during the first year after stroke.

Optimal Heating Temperature and Time for Echelon 10 and Excelsior SL-10 Shaping Using a Heat Gun.

Objective: The optimal heating temperature and time for the Echelon10 and Excelsior SL-10 microcatheters using a heat gun was investigated. The durability of the microcatheters after heat gun shaping for the second and third times was also examined. Methods: HAKKO FV-310 was used as the heat gun in this study. This heat gun can be set to 115°C, 125°C, and others. We measured the temperature at 2.5 cm from the nozzle of the heat gun. The Echelon10 and SL-10 microcatheters were shaped under two temperature conditions (115°C and 125°C) and three heating times (30 sec, 60 sec, and 90 sec). The microcatheter shape before heating had twice the curvature of the targeted shape. Results: The temperatures at 2.5 cm from the nozzle were 120.6°C and 127.8°C with the heat gun set at 115°C and 125°C, respectively. There was no macroscopic difference in the results of heat gun shaping of the Echelon10 among temperature settings (115°C and 125°C) or heating times (30 sec, 60 sec, and 90 sec). As degeneration of the heated tip of the SL-10 at 125°C occurred in four of five trials, heat gun shaping was performed using the 115°C setting. There was no macroscopic difference in the results of heat gun shaping of the SL-10 among heating times. Shaping for the second and third times was successful at 115°C and 30-sec heating time. Conclusions: The Echelon10 and SL-10 can be successfully shaped from twice the curvature of the targeted shape using a heat gun at 120°C for 30 sec. Shaping for the second and third times was successful using the same settings. Degeneration of the SL-10 was noted at temperatures above 130°C.

Stent Migration during Coil Embolization with an Open Cell Stent: A Report of Three Cases.

Objective: Among 36 cerebral aneurysm cases of stent-assisted coil embolization with the Neuroform Atlas since April 2017, there were three cases of stent migration during the operation. The status of stent deployment, cause of trouble, results of coil embolization, and complications were assessed. Case Presentations: There were two cases with trouble during stent deployment, a case of internal carotid artery aneurysm, and a case of middle cerebral artery (MCA) aneurysm. The proximal marker of the stent was advanced during stent deployment with the simple pull maneuver, then a part of the stent migrated to the aneurysm sac in both cases. Stent migration to the aneurysm sac during microcatheter navigation by the trans-cell technique occurred in another MCA aneurysm case. No postoperative complications were observed, and a volume embolization ratio (VER) of 24.1%-33% was achieved in these three cases. Conclusions: The Neuroform Atlas is a safe and convenient stent system. However, stent advancement during deployment and migration during trans-cell microcatheter navigation can occur.

A Young Patient with Emery-Dreifuss Muscular Dystrophy Treated with Endovascular Therapy for Cardioembolic Stroke: A Case Report.

We had a case of Emery-Dreifuss muscular dystrophy (EDMD) in an 18-year-old woman who underwent endovascular therapy for a cardioembolic stroke. At 5 years old, she showed a high creatine kinase level and atrial fibrillation on electrocardiography in our hospital. Finally, she was diagnosed as having EDMD by genetic screening that revealed mutations in the LMNA gene (c.810+1G>T). Before this event, she received no medications. At 18 years old, she was admitted to our hospital>8 hours after the onset of sudden consciousness disturbance. Neurological examination on admission revealed consciousness disturbance and right hemiplegia. Magnetic resonance imaging revealed a cerebral infarction in the left insular cortex and putamen with left internal carotid artery occlusion. We performed endovascular therapy and completely recanalized her left internal carotid artery. Thereafter, her neurological symptoms improved. She was subsequently transferred to a rehabilitation hospital. EDMD is a rare genetic muscular disease that mainly presents with contractures, weakness, and cardiac conduction abnormalities. Although patients with EDMD are young with low CHADS2 score, they have a disease-specific cardiovascular pathogenesis caused by a fatal risk factor. Therefore, we consider anticoagulant therapy necessary to prevent thrombotic events, even if the CHADS2 score is low, in patients with EDMD.

Symptomatic Lacunar Infarct Accompanied with Posterior Reversible Encephalopathy Syndrome: A Case Report.

We present a 48-year-old man with a history of hypertension, who suddenly noticed dysarthria and right hemiparesis. Diffusion-weighted MRI at 1 day after the onset showed a small high-intensity region in the left corona radiata, indicating the acute phase of lacunar infarction. Fluid attenuation inversion recovery images showed extensive hyperintense lesions predominantly in the white matter of the fronto-temporoparietal lobes and pons, indicating posterior reversible encephalopathy syndrome (PRES). In addition, T2*-weighted gradient-echo images showed multiple small round hypointense lesions in white matter and basal ganglia, indicating cerebral microbleeds. This is a rare case of symptomatic lacunar infarction accompanied with both PRES and microbleeds, which may suggest that the pathophysiology of PRES is related to hypertension.

A case of recurrent Mikulicz's disease with mononeuritis multiplex.

We report an 82-year-old man with recurrence of Mikulicz's disease accompanied with mononeuritis multiplex. On admission, both upper eyelids, the salivary gland, the dorsum of the left hand and both legs were swollen. Neurological examination showed motor weakness of distal limbs (manual muscle testing 3/5) and decreased touch, pain and vibration sensation of the dorsum of the left hand and both legs. Deep tendon reflex in both legs was also decreased. We diagnosed Mikulicz's disease based on high serum immunoglobulin (Ig)G4 (630 mg/dl, 26.1% of total IgG) and lacrimal gland biopsy findings. Clinical symptoms and motor conduction study findings improved after steroid therapy. However, tapering of the steroid dose resulted in recurrence two years later. Steroid therapy is usually effective for IgG4-related neuropathy, and we found that an increase of steroid dose was effective to treat the recurrence. But, in general, a suitable maintenance dose of steroid in combination with an immunosuppressant may be necessary to prevent relapse.

Trigeminal Neuropathy Accompanied by a Pontine Lesion on MRI.

A 63-year-old man presented with the loss of the sensations of pain and temperature sensation in the right facial region innervated by the trigeminal nerve (V1 to 3). He showed abnormal lesions in the pons and the trigeminal nerve on magnetic resonance imaging (MRI). He had recurrent herpes in the nasal cavity, and a history of left facial palsy. We herein present the unique MRI findings and suggest that herpes simplex infection may cause trigeminal neuropathy. This is the first reported case of dissociated trigeminal neuropathy with herpes simplex infection which was accompanied by a pontine lesion on MRI.

Clinical Utility of Platelet Function Testing Following Non-Cardioembolic Stroke.

OBJECTIVE: To verify the usefulness in selection of antiplatelet agent based on the platelet functional assays on the secondary prevention of ischemic stroke. METHODS: Platelet functional assays were performed twice for acute ischemic stroke patients at hospitalization and 1 month after. An antiplatelet agent was administered based on the results of initial assay. The alterations of platelet aggregation by antiplatelet agent were evaluated in the second assay, and the patients were subsequently divided into inhibited and invariance groups. The relationship between incidence of recurrent ischemic or hemorrhagic stroke and the alterations of platelet aggregation by each selected antiplatelet agent was assessed. RESULTS: Of the 585 consecutive patients, 124 were enrolled in the present study. Recurrent ischemic stroke was seen in 6 (5.3%) and 2 (18.2%) patients in the inhibited and invariance groups during the study period, respectively. In patients who were observed for more than 12 months, recurrent ischemic stroke was seen in 4 (5.0%) and 2 (33.3%) patients in the inhibited and invariance groups, respectively (p = 0.009). CONCLUSIONS: We indicated that selection of the optimum antiplatelet agent based on the platelet functional assays for each individual patient may contribute to a reduction in the incidence of recurrence of ischemic stroke.

[Hemichorea improved by carotid artery stenting in a 73-year-old man with hypoperfusion of the basal ganglia].

A 73-year-old man presented with continuous hemichoreic movement of right arm and leg and with dyskinesia in his tongue. Magnetic resonance image (MRI) showed no ischemic lesion within the basal ganglia, but magnetic resonance angiography (MRA) and carotid duplex ultrasonography showed the left internal carotid occlusion and 80% stenosis in the right common carotid artery. Tc-99m-ECD-SPECT showed hypoperfusion of the frontal lobe, temporal lobe, parietal lobe, basal ganglia and thalamus. A trial of haloperidol had no effect; therefore, the right carotid artery stenting was performed. Hypoperfusion in the left internal carotid artery area was improved by cross flow from the right side, and his hemichorea gradually improved. This result supports the notion that hypoperfusion-related hemichorea may occur, even in the absence of cerebral ischemia.

A novel prolyl hydroxylase inhibitor protects against cell death after hypoxia.

Hypoxia-inducible factor 1 (HIF-1) is regulated by the oxygen-dependent hydroxylation of proline residues by prolyl hydroxylases (PHDs). We recently developed a novel PHD inhibitor, TM6008, that suppresses the activity of PHDs, inducing continuous HIF-1α activation. In this study, we investigated how TM6008 affects cell survival after hypoxic conditions capable of inducing HIF-1α expression and how TM6008 regulates PHDs and genes downstream of HIF-1α. After SHSY-5Y cells had been subjected to hypoxia, TM6008 was added to the cell culture medium under normoxic conditions. Apoptotic cell death was significantly augmented just after the hypoxic conditions, compared with cell death under normoxic conditions. Notably, when TM6008 was added to the media after the cells had been subjected to hypoxia, the expression level of HIF-1α increased and the number of cell deaths decreased, compared with the results for cells cultured in media without TM6008 after hypoxia, during the 7-day incubation period under normoxic conditions. Moreover, the protein expression levels of heme oxygenase 1, erythropoietin, and glucose transporter-3, which were genes downstream of HIF-1α, were elevated in media to which TM6008 had been added, compared with media without TM6008, during the 7-day incubation period under normoxic conditions. However, the protein expression levels of PHD2 and p53 which suppressed cell proliferation were suppressed in the media to which TM6008 had been added. Thus, TM6008, which suppresses the protein expressions of PHD2 and p53, might play an important role in cell survival after hypoxic conditions, with possible applications as a new compound for treatment after ischemic stroke.

Cerebral microbleeds on T2*-weighted images and hemorrhagic transformation after antithrombotic therapies for ischemic stroke.

To assess the predictive value of cerebral microbleeds (CMBs) on gradient-echo T2*-weighted magnetic resonance imaging for hemorrhagic transformation (HT) after antithrombotic therapy for an acute ischemic stroke, we prospectively examined the relationship between CMBs on T2*-weighted images before the start of therapy and the appearance of HT in a series of patients treated with antithrombotic therapies. The subjects were consecutive acute ischemic stroke patients admitted to Tokai University Hospital (187 subjects, mean age±SD: 74±11 years). The prevalence of CMBs was not significantly different between the subjects with and without HT on computed tomography (CT) (19% versus 36%, P=.081). In both the subgroup of patients treated with anticoagulants and the subgroup treated with antiplatelets, the prevalence of HT was not significantly different between the subjects with and without CMBs (anticoagulants, 9% versus 21%, P=.161; antiplatelets, 0% versus 9%, P=.542). The odds ratios (ORs) of increasing the National Institutes of Health Stroke Scale score (1.14, 95% confidence interval [CI]: 1.04-1.26, P=.005) and decreasing the Alberta Stroke Program Early CT Score on diffusion-weighted images (ASPECTS-DWI) (1.32, 95% CI: 1.10-1.59, P=.003) were significantly increased for the appearance of HT, but the OR of CMBs (.35, 95% CI: .09-1.41, P=.140) was not significantly increased for the appearance of HT. In conclusion, the severity of neurological deficits and the ASPECTS-DWI are closely correlated to the development of HT related to anticoagulants/antiplatelets but not to CMBs on T2*-weighted images.

Predictors for hemorrhagic transformation with intravenous tissue plasminogen activator in acute ischemic stroke.

We examined the predictive value of clinical and radiological findings, including cerebral microbleeds (CMBs) seen in gradient-echo T2*-weighted magnetic resonance images, for hemorrhagic transformation (HT) following ischemic stroke, in ischemic stroke patients treated with recombinant tissue plasminogen activator (rt-PA). The subjects were 71 patients with acute ischemic stroke treated with rt-PA (50 males, 21 females; mean age±standard deviation 73±10 years; 53 cardiogenic stroke, 18 atherothrombotic). HT on computed tomography (CT)(mean: 24 hours after onset) was seen in 26 (37%) subjects. The mean Alberta stroke programme early CT score on diffusion-weighted images (ASPECTS-DWI) score was significantly lower in the group with HT than that in the group without HT (6.5±2.3 vs 8.4±1.6, P<0.001). Prevalence of CMBs was not significantly different between the groups with and without HT. Relative risk of various factors for appearance of HT was evaluated by logistic regression analysis. Increased ASPECTS-DWI score showed a significantly reduced relative risk for HT (odds ratio: 0.54, 95% confidence interval: 0.33-0.87), while the influence of CMBs (1.22, 0.23-6.53) was not significant. In conclusion, ASPECTS-DWI score (a measure of the volume of ischemic tissue) is a useful marker for predicting HT. On the other hand, CMBs on T2*-weighted images may not be predictive for HT in patients treated with intravenous rt-PA.

Phase I study of intravenous low-dose granulocyte colony-stimulating factor in acute and subacute ischemic stroke.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF; filgrastim) may be useful for the treatment of acute ischemic stroke because of its neuroprotective and neurogenesis-promoting properties, but an excessive increase of neutrophils may lead to brain injury. We examined the safety and tolerability of low-dose G-CSF and investigated the effectiveness of G-CSF given intravenously in the acute phase (at 24 hours) or subacute phase (at 7 days) of ischemic stroke. METHODS: Three intravenous dose regimens (150, 300, or 450 µg/body/day, divided into 2 doses for 5 days) of G-CSF were examined in 18 patients with magnetic resonance imaging (MRI)-confirmed infarct in the territory of the middle cerebral artery. Nine patients received the first dose at 24 hours poststroke (acute group) and 9 patients received the first dose on day 7 poststroke (subacute group; n = 3 at each dose in each group). A scheduled administration of G-CSF was skipped if the patient's leukocyte count exceeded 40,000/µL. Patients received neurologic and MRI examinations. RESULTS: We found neither serious adverse event, drug-related platelet reduction nor splenomegaly. Leukocyte levels remained below 40,000/µL at 150 and 300 µg G-CSF/body/day, but rose above 40,000/µL at 450 µg G-CSF/body/day. Neurologic function improvement between baseline and day 90 was more marked after treatment in the acute phase versus the subacute phase (Barthel index 49.4 ± 28.1 v 15.0 ± 22.0; P < .01). CONCLUSIONS: Low-dose G-CSF (150 and 300 µg/body/day) was safe and well tolerated in ischemic stroke patients, and leukocyte levels remained below 40,000/µL.

A sartan derivative with a very low angiotensin II receptor affinity ameliorates ischemic cerebral damage.

Angiotensin II receptor blockers (ARBs) have a potent ability to inhibit oxidative stress and advanced glycation, in addition to their protective effects originated from blood pressure lowering and angiotensin II type 1 receptor (AT(1))-blockade. To obtain a pharmacological tool to dissect the mechanisms of ARBs' protective benefits in experimental stroke, we synthesized a novel ARB-derivative, R-147176, which is 6,700 times less potent than olmesartan in AT(1)-binding inhibition and therefore has a minimal antihypertensive effect, but retains marked inhibitory effects on oxidative stress and advanced glycation. We evaluated the effect of R-147176 (10-30 mg/kg per day), administered orally or intravenously, on brain infarct volume in transient thread occlusion and photothrombotic models in rats. The antioxidative and antiinflammatory properties were also investigated. R-147176 significantly reduced infarct volume, without influence on blood pressure, in both models. R-147176 significantly reduced the numbers of ED-1-positive cells and of TUNEL-positive cells, and protein carbonyl formation in the damaged brain. This ARB derivative, despite its significantly lower AT1 affinity and virtually no antihypertensive effect, ameliorated ischemic cerebral damage through antioxidative and antiinflammatory properties. These findings suggest potential usefulness of R-147176 as a pharmacological tool to investigate the ARBs' protective effect in experimental stroke and open new therapeutic avenues.

Administration of hematopoietic cytokines increases the expression of anti-inflammatory cytokine (IL-10) mRNA in the subacute phase after stroke.

We investigated the effect of the subcutaneous administration of hematopoietic cytokines, granulocyte colony-stimulating factor (G-CSF)+stem cell factor (SCF), on mRNA expression of tissue cytokines in the acute or subacute phase after focal ischemia in male C57 BL/6J mice. The expression of IL-10 mRNA was elevated at 4-14 days after occlusion when cytokines were given in the acute phase (days 1-10). The expression of IL-10 mRNA was markedly elevated at 14 days after occlusion, then remained high until 28 days when cytokines were given in the subacute phase (days 11-20). However, there were no significant changes in IL-6, TGF-beta1, TNF, G-CSF, SCF and iNOS expression following either acute- or subacute-phase treatment. Further, hematopoietic cytokine treatment in the subacute phase, but not in the acute phase, reduced ED1-positive microglia/macrophages in the infarcted brain. Our recent study showed that the subacute-phase treatment is effective for functional recovery, enhancing generation of neuronal cells from both bone-marrow-derived and neural stem/progenitor cells. Taken together, these results suggest that cytokine treatment in the subacute phase may provide a favorable microenvironment for neurogenesis after ischemic stroke through the up-regulation of IL-10.

Three-dimensional CT and histopathological findings of airway malacia in Hunter syndrome.

A 19-year-old man with known Hunter syndrome presented with dyspnea, and was admitted to our hospital. Bronchoscopy revealed tracheal narrowing with excessive granulation tissue formation in the trachea. Three-dimensional CT clearly demonstrated severe stenosis in the trachea and both main bronchi. Autopsy showed granulomatous tissue proliferation and deposition of mucopolysaccharide in the tracheal wall. We demonstrated the clinico-radiological-pathological correlation of bronchial lesions in Hunter syndrome, and emphasized that three-dimensional CT is helpful in deciding upon therapeutic strategy to treat stenosis in the large airway.