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.

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.

Case report: Corneal endothelial degeneration and optic atrophy in dentatorubral-pallidoluysian atrophy quantified by specular micrography and optical coherence tomography.

Introduction: Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease with various neurological manifestations. Corneal endothelial degeneration and optic atrophy have been reported separately; however, there are no reports of corneal endothelial degeneration with optic atrophy. Cases: Herein, we present four related patients with DRPLA: two patients (69-year-old woman and 80-year-old man) who exhibited both corneal endothelial degeneration and optic atrophy and another two (49- and 51-year-old women, respectively) who exhibited only corneal endothelial degeneration. We quantified the reduction in corneal endothelial cell density (ECD) and hexagonality using specular microscopy and thinning of the circumpapillary retinal nerve fiber layer (RNFL) using optical coherence tomography (OCT). Conclusion: This is the first report of DRPLA accompanied by corneal endothelial degeneration and/or optic atrophy, which were both quantified based on the corneal ECD and the circumpapillary RNFL thickness using specular micrography and OCT, respectively. The pathophysiological mechanism is unclear; however, the involvement of the nuclear receptor TLX interacting with atrophin-1 may be implicated in ophthalmic manifestations of DRPLA. Therefore, we recommend performing specular micrography and/or OCT when patients with DRPLA experience visual disturbances.

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.

Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome) Complicated by Perforation of the Small Intestine and Cholecystitis.

We report a case of eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) complicated by perforation of the small intestine and necrotizing cholecystitis. A 69-year-old man with a history of bronchial asthma was admitted with mononeuritis multiplex. The laboratory findings included remarkable eosinophilia. He was treated with corticosteroids and his laboratory indices showed improvement; however, his functional deficits remained. His neuropathy gradually improved after the addition of intravenous immunoglobulin (IVIG). He was subsequently treated with oral prednisolone (40 mg/day) as maintenance therapy. Within a month after finishing IVIG, he developed perforation of the small intestine and necrotizing cholecystitis. Intestinal perforation has often been reported as a gastrointestinal complication of EGPA. In contrast, cholecystitis is a rare complication. We report this case because the manifestation of more than one complication is extremely rare. Gastrointestinal symptoms may be a complication of EGPA itself and/or immunosuppressive treatment.

Dual Therapy with Aspirin and Cilostazol May Improve Platelet Aggregation in Noncardioembolic Stroke Patients: A Pilot Study.

Objective Some previous studies have found clinical benefit of dual antiplatelet therapy with aspirin and cilostazol for prevention of secondary stroke, but the physiological mechanism involved remains unknown. We aimed to clarify the effects of aspirin/cilostazol therapy on the platelet and endothelial functions of patients with acute noncardioembolic ischemic stroke, in comparison to patients who were treated with aspirin alone. Methods The present randomized prospective pilot study enrolled 24 patients within a week after the onset of noncardioembolic ischemic stroke. The patients were randomly allocated to receive aspirin (100 mg/day) (A group; 11 patients) or cilostazol (200 mg/day) plus aspirin (100 mg/day) (CA group; 13 patients). We measured platelet aggregation, platelet activation, and the thrombomodulin (TM), highly sensitive C-reactive protein (hs-CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand (vWF) antigen levels and vWF activity over a 4-week period after enrollment. Results There was no significant difference in the platelet functions of the A and CA groups. However, the platelet aggregation induced by adenosine diphosphate (ADP) was decreased at 2 and 4 weeks (p<0.05) after treatment in comparison to the pre-treatment values in the CA group, but not in the A group. Platelet activation, and the hs-CRP, TM, ICAM-1, VCAM-1 and vWF values did not significantly decrease after treatment in either group. Conclusion Although there were no significant differences in platelet aggregation, platelet activation or the endothelial biomarker levels of the A and CA groups, dual therapy with aspirin and cilostazol inhibited platelet aggregation in comparison to the pre-treatment values, similarly to patients who received aspirin alone. This may suggest the clinical usefulness of dual therapy with aspirin and cilostazol in the treatment of patients with noncardioembolic ischemic stroke.

Acute Cerebellar Ataxia Induced by Nivolumab.

A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment.

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.

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.

A case of scrub typhus with acalculous cholecystitis, aseptic meningitis and mononeuritis multiplex.

We present an unusual case of a patient with scrub typhus who developed acalculous cholecystitis, aseptic meningitis and mononeuritis multiplex. The patient was successfully treated with oral minocycline. To our knowledge, this is the first report of mononeuritis multiplex caused by scrub typhus.