Yasuteru Inoue

Low Serum Calcium Levels Contribute to Larger Hematoma Volume in Acute Intracerebral Hemorrhage

Background and Purpose— We investigate whether admission serum calcium levels are associated with hematoma volume, stroke severity, and outcomes in patients with acute intracerebral hemorrhage. Methods— A total of 273 patients admitted within 24 hours after intracerebral hemorrhage onset was divided into quartiles based on admission serum calcium levels (Q1 [⩽9.0], Q2 [9.1–9.3], Q3 [9.4–9.7], Q4 [≥9.8] mg/dL). Results— Median hematoma volumes for each quartile (Q1 to Q4) were 18, 9, 10, and 9 mL (P=0.005), and median National Institutes of Health Stroke Scale scores were 16, 11, 11, and 9 (P=0.010), respectively. On multivariate analysis, Q1 had larger hematoma volume (P=0.025) and higher National Institutes of Health Stroke Scale score (P=0.020) than Q4. There were fewer patients with modified Rankin Scale scores 0 to 2 in Q1 than Q4 after adjustment for risk factors and comorbidities (odds ratio, 0.31; 95% confidence interval, 0.11–0.84) but not after additional adjustment for hematoma volume and National Institutes of Health Stroke Scale score. There were more patients with modified Rankin Scale scores 5 to 6 (P=0.016) and with fatal outcomes (P=0.048) in Q1 than Q4 as crude values, but not after adjustment. Conclusions— Low admission serum calcium levels were associated with larger hematoma volume and higher National Institutes of Health Stroke Scale score among patients with acute intracerebral hemorrhage.

Effective Education Materials to Advance Stroke Awareness Without Teacher Participation in Junior High School Students.

BACKGROUND Youth stroke education is promising for the spread of stroke awareness. The aim of this study was to examine whether our stroke awareness teaching materials without teachers participation can increase student awareness to act fast on suspected stroke signs. METHODS We used the face, arm, speech, and time (FAST) mnemonic derived from the Cincinnati Prehospital Stroke Scale. Seventy-three students of the second grade and 72 students of the third grade (age range, 13-15 years) in a junior high school were enrolled in the study. The students were divided into 2 groups: students who received a teachers lesson (group I) and those who did not receive a teachers lesson (group II). Students in group II watched an animated cartoon and read a Manga comic in class. All students took the educational aids home, including the Manga comic and magnetic posters printed with the FAST message. Questionnaires on stroke knowledge were examined at baseline and immediately and 3 months after receiving the intervention. RESULTS At 3 months after the intervention, a significant improvement in understanding the FAST message was confirmed in both the groups (group I, 85%; group II, 94%). Significant increases in the knowledge of risk factors were not observed in each group. CONCLUSIONS Our education materials include a Manga comic, an animated cartoon, and a magnetic poster, without an accompanying teachers lesson can increase stroke awareness, including the FAST message, in junior high school students.

Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy

Objective: To elucidate early skin denervation in hereditary transthyretin (TTR) amyloidosis and iatrogenic TTR amyloidosis. Methods: We investigated intraepidermal nerve fiber density (IENFD) and clinical findings in 32 patients with hereditary TTR amyloidosis, 11 asymptomatic mutation carriers, 6 patients with iatrogenic TTR amyloidosis, and 23 healthy volunteers. Results: IENFD values were reduced in patients with the V30M mutation (1.9 ± 2.1 per 1 mm), patients with non-V30M mutations (5.8 ± 3.2 per 1 mm), and patients with iatrogenic TTR amyloidosis (3.5 ± 1.8 per 1 mm) compared with healthy volunteers (11.8 ± 3.2 per 1 mm) (p < 0.01). Skin denervation also occurred, even in presymptomatic V30M mutation carriers (5.0 ± 2.2 per 1 mm). The IENFD was correlated with disease duration (ρ = −0.533, p = 0.002) and various peripheral neuropathy parameters such as sensory impairment in the Kumamoto clinical score (ρ = −0.575, p = 0.001), heat-pain detection threshold (ρ = −0.704, p < 0.001), and sural sensory nerve action potential (ρ = 0.481, p = 0.005). TTR amyloid deposits frequently occurred in connective tissues and vessels of the dermal reticular layer in patients with hereditary TTR amyloidosis and those with iatrogenic TTR amyloidosis. Conclusions: Patients with hereditary TTR amyloidosis and those with iatrogenic TTR amyloidosis may show early skin denervation even in the presymptomatic stage. IENFD may thus be useful for early diagnosis and may serve as a biomarker in clinical trials for hereditary and iatrogenic TTR amyloidosis.

Sushi repeat-containing protein 1: a novel disease-associated molecule in cerebral amyloid angiopathy

Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid beta (Aβ) deposits and causes cerebral hemorrhage and dementia. The exact molecules that co-accumulate with cerebrovascular Aβ deposits are still not fully known. In our study here, we performed proteomic analyses with microdissected leptomeningeal arteries and cerebral neocortical arterioles from 8 cases with severe CAA, 12 cases with mild CAA, and 10 control cases without CAA, and we determined the levels of highly expressed proteins in cerebral blood vessels in CAA. We focused on sushi repeat-containing protein 1 (SRPX1), which is specifically expressed in CAA-affected cerebral blood vessels. Because SRPX1, which is known as a tumor suppressor gene, reportedly induced apoptosis in tumor cells, we hypothesized that SRPX1 may play an important role in Aβ-induced apoptosis in CAA. Immunohistochemical studies revealed that SRPX1 co-accumulated with Aβ deposits in cerebral blood vessels of all autopsied cases with severe CAA. In contrast, no SRPX1 co-accumulated with Aβ deposits in senile plaques. Furthermore, we demonstrated that both Aβ40 and Aβ42 bound to SRPX1 in vitro and enhanced SRPX1 expression in primary cultures of cerebrovascular smooth muscle cells. SRPX1 enhanced caspase activity induced by Aβ40. Knockdown of SRPX1, in contrast, reduced the formation of Aβ40 accumulations and the activity of caspase in cultured cerebrovascular smooth muscle cells. SRPX1 may thus be a novel molecule that is up-regulated in cerebrovascular Aβ deposits and that may increase Aβ-induced cerebrovascular degeneration in CAA.

Clinicopathological and biochemical findings of thyroid amyloid in hereditary transthyretin amyloidosis with and without liver transplantation

Abstract Hereditary transthyretin (TTR) amyloidosis is a fatal disease causing systemic organ dysfunctions. Histopathological studies revealed that thyroid glands are major target tissues. However, details about thyroid functions remain to be fully elucidated in this disease. For patient treatment, liver transplantation (LT) reportedly prolongs patient survival, but thyroid gland function after LT still remains poorly understood. In this study, we investigated the thyroid functions in 101 patients with hereditary TTR amyloidosis and the effects of LT on thyroid functions in those patients. In addition, we investigated histopathological and biochemical findings of thyroid specimens obtained at autopsy. Disease duration and age at examination inversely correlated with serum levels of free triiodothyronine (fT3) in hereditary TTR amyloidosis. On the contrary, in patients who underwent transplantation, time from disease onset to transplantation and age at transplantation clearly correlated with serum fT3and thyroid stimulating hormone (TSH) levels. In autopsy studies, amounts of thyroid amyloid deposits in patients with transplantation were significantly lower than those in patients without transplantation. Mass spectrometric analyzes also revealed that proportions of wild-type (WT) TTR in thyroid amyloid deposits in patients with hereditary TTR amyloidosis who underwent transplantations were higher than those in patients without transplantation. Thyroid hormone functions may diminish according to the disease progression. LT could prevent thyroid dysfunction in hereditary TTR amyloidosis.

Educational Campaigns at Point of Purchase in Rural Supermarkets Improve Stroke Knowledge

BACKGROUND The number of elderly people is dramatically increasing, and this trend is especially pronounced in rural populations. The aim of the present study was to verify the effectiveness of stroke education in a rural area. METHODS The stroke educational flyers were distributed for 3 weeks at the point of purchase within supermarkets. Questionnaires were used to determine knowledge about stroke and appropriate emergent action on identifying stroke. RESULTS A total of 882 people responded to the questionnaires before (n = 409) and 3 months after (n = 473) the campaign. Of these, 686 (77.8%) were aged 65 years or older. The percentages of correct answers for hemiplegia and one-sided numbness (P < .05 for both) and calling emergency medical services (EMS) on identifying stroke occurrence (P < .001) were higher after the campaign compared with those before the campaign. Of the respondents aged 65 years or older, the percentages of correct answers for numbness on one side and calling for EMS on identifying stroke were higher after the campaign (P < .05 and P < .001, respectively). CONCLUSIONS A simple point-of-purchase stroke campaign using educational flyers could meaningfully affect stroke knowledge among elderly persons in a rural community.

Serum amyloid P component: A novel potential player in vessel degeneration in CADASIL

In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), granular osmiophilic material (GOM) may play some roles in inducing cerebrovascular events. To elucidate the pathogenesis of CADASIL, we used laser microdissection and liquid chromatography-tandem mass spectrometry to analyze cerebrovascular lesions of patients with CADASIL for GOM. The analyses detected serum amyloid P component (SAP), annexin A2, and periostin as the proteins with the largest increase in the samples, which also demonstrated NOTCH3. For the three proteins, anti-human SAP antibody had the strongest reaction in the lesions where the anti-human NOTCH3 antibody showed positive staining. Moreover, immunofluorescence staining with the two antibodies clearly showed co-localization of SAP and NOTCH3. mRNA analyses indicated no positive SAP expression in the brain materials, which suggested that the source of SAP found in the GOM was only the liver. A solid phase enzyme-linked immunosorbent assay confirmed the binding of SAP with NOTCH3. Serum SAP concentrations were neither up-regulated nor down-regulated in CADASIL patients, when compared with those in control subjects. SAP may play an important role in GOM formation although precise mechanisms remain to be elucidated.

Panmedullary Edema with Inferior Olivary Hypertrophy in Bilateral Medial Medullary Infarction

Bilateral medial medullary infarction (MMI) is a rare type of stroke with poor outcomes. Inferior olivary nucleus hypertrophy results from a pathologic lesion in the Guillain-Mollaret triangle. The relationship between inferior olivary nucleus hypertrophy and the medullary lesion is obscure. To the best of our knowledge, only 1 autopsy case with unilateral medial medullary infarction that was associated with ipsilateral inferior olivary nucleus hypertrophy has been reported. We describe a rare case with acute infarction in the bilateral medial medulla oblongata accompanied by subacute bilateral inferior olivary nucleus hypertrophy and panmedullary edema. The hypertrophy appeared to have been caused by local ischemic damage to the termination of the central tegmental tract at the bilateral inferior olivary nucleus.

Anterior Inferior Cerebellar Artery Territorial Infarction Caused by Vertebral Artery Dissection

Case Report A 56-year-old woman presented with posterior cervical pain, vertigo, left peripheral facial palsy, left facial sensory loss, left hearing loss, and left ataxia immediately after she bent her head back in the supine position. Diffusion-weighted MRI on admission revealed hyperintensity in the left anterior inferior cerebellar artery (AICA) territory. Digital subtraction angiography showed bilateral vertebral artery (VA) dissection, and the artery supplying the left AICA territory originated from the left VA distal to the origin of the left posterior inferior cerebellar artery. Published online: July 10, 2013

Clinical Characteristics and Outcomes of Intracerebral Hemorrhage in Very Elderly.

BACKGROUND Intracerebral hemorrhage (ICH) incidences increase with age. Patients of advanced age may have limitations during acute care and recovery. We investigated baseline characteristics, hematoma features, and outcomes of very elderly ICH patients (≥80 years old) and compared them with those of younger ICH patients (<80 years old). METHODS We studied 377 patients (122 women; 69 ± 11 years old) admitted within 24 hours of ICH onset. Outcome measures included hematoma volumes, National Institutes of Health Stroke Scale scores on admission, and vital and functional prognoses at 30 days. RESULTS After adjustments for sex, very elderly patients had a higher subcortical hematoma prevalence (odds ratio [OR], 2.62; 95% confidence interval [CI], 1.39-4.86]. On multivariate analyses, very elderly patients had larger hematoma volumes (OR, 1.33; 95% CI, 1.01-1.75, per 10-mL increase). After adjustments for risk factors and comorbidities, modified Rankin scale scores of 0-2 in very elderly patients occurred less often (OR, .34; 95% CI, .14-.82), and those with scores of 5-6 occurred more often (OR, 3.01; 95% CI, 1.09-8.54). CONCLUSIONS Hematomas were relatively large and often found in the subcortex in very elderly ICH patients. Outcomes of very elderly ICH patients were relatively poor.