Takehisa Hirayama

Cardiovascular Risk and Neuroradiological Profiles in Asymptomatic Vertebrobasilar Dolichoectasia

Background: Clinicoradiological variability of vertebrobasilar dolichoectasia (VBD) is known. Little is known about cardiovascular disease (CVD) risk and neuroradiological profiles of asymptomatic VBD. Methods: A total of 7,345 adults (5,534 men and 1,811 women) underwent physical checkup (PC) and brain magnetic resonance (MR) studies between 2004 and 2007. Asymptomatic VBD was diagnosed by neurological examination and MR angiography. Neuroradiological features were analyzed in VBD subjects. CVD risk factors were compared between VBD subjects and 5,000 controls matched by sex and age. Results: Ninety-six subjects (85 men and 11 women) had asymptomatic VBD. The detection rate was 1.3% and the male/female ratio 2.5. The mean age ± SD was 60.4 ± 10.6 years (60.0 ± 10.2 in men and 64.0 ± 13.1 in women). As compared to controls, the frequency of hypertension, obesity, smoking, dyslipidemia, diabetes mellitus and a family history of stroke or CVD was increased significantly in VBD subjects. The mean diameter ± SD of the basilar artery (BA) was 4.7 ± 0.2 mm. Only 4 subjects (4%) had a severe degree of elongation and lateral displacement of the BA. Contact of the vertebral artery with the rostral ventrolateral medulla (AMC) was found in 81 subjects: right AMC in 22 subjects and left AMC in 59 subjects. Frequency of hypertension was significantly higher in the left-AMC subjects (57%) than in subjects with right AMC (9%) and no AMC (5%). Other neuroradiological findings revealed small infarcts in 42 subjects, brainstem compression in 4, hydrocephalus in 4 and brain saccular aneurysm in 3. Conclusions: Asymptomatic VBD was detected in 1.3% of the Japanese PC group. Our data indicated male predominance, multiple CVD risk factors, neurovascular hypertension and small infarcts in asymptomatic VBD.

Serological Profiles of Urate, Paraoxonase-1, Ferritin and Lipid in Parkinson’s Disease: Changes Linked to Disease Progression

Background: Oxidative stress plays a role in the pathogenesis of neuronal death. Serum levels of urate or lipid were associated with the incidence of Parkinson’s disease (PD). Objective: We compared urate, paraoxonase-1 (PON1), iron, ferritin and lipid in sera of 119 PD patients and 120 healthy controls matched by age, sex and body mass index. We aimed to elucidate whether those serological data are correlated with disease progression. Results: Mean age (SD) of PD patients was 73.4 (8.7) years. Mean Yahr stage (SD) was 3.2 (0.9). Mean disease duration (SD) was 6.9 (5.1) years. Mean dose of L-DOPA (SD) was 355 (157) mg/day. As compared to controls, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), urate and PON1 activity were significantly reduced, and serum ferritin levels were significantly increased in male and female PD patients. Serum urate levels and PON1 activities were inversely related, and serum ferritin levels were correlated with Yahr stage and PD duration in men and women. Serum levels of TC and LDL-C were inversely related to Yahr stage or PD duration in female patients. Conclusions: Our studies indicated serological profiles of urate, PON1, ferritin, TC and LDL-C in PD patients. These serological changes were linked to PD progression. Metabolism of lipid, oxidant- and antioxidant-related substances may contribute to the pathogenesis and the progression of PD.

Pulse Wave Velocity Study in Middle-Aged Migraineurs at Low Cardiovascular Disease Risk

(Headache 2011;51:1239‐1244)

Incidental cerebral aneurysms in acute stroke patients: comparison of asymptomatic healthy controls.

Cerebral aneurysms (CA) are incidentally detected by magnetic resonance angiography (MRA) in acute stroke patients or asymptomatic volunteers. We investigated whether incidental CA influences stroke subtypes and clinical outcome of patients with acute brain infarction (BI) and hemorrhage (BH). Moreover, frequency and neuroradiological profile of incidental CA were compared between acute stroke patients and asymptomatic healthy controls. We included consecutive BI and BH patients who underwent magnetic resonance imaging and MRA within 7 days from clinical onset. CA diagnosis was performed by 3-dimensional time-of-flight MRA. Demographics, risk factors, stroke subtypes, and modified Rankin scale (mRS) at 3 months after stroke were assessed. Incidental CA was detected in 18 (3.7%) of 481 stroke patients, 13 (3.5%) of 374 BI patients, 5 (4.7%) of 107 BH patients, and 146 (2.0%) of 7345 controls. Multivariate analysis showed no significant differences in CA frequency between BI, BH, and control groups. Female sex was associated independently with incidental CA in the stroke (P<0.01), BI (P<0.05), BH (P<0.05), and healthy control groups (P<0.01). No statistical differences in CA size and location between the 4 groups were found. BI subtypes and BH sites were not correlated with incidental CA. CA rupture or subarachnoid hemorrhage did not occur until 3 months after stroke. The 3-month mRS score did not differ between stroke patients with and without CA. Prevalence of incidental CA did not differ statistically among stroke, BI, BH patients and healthy asymptomatic subjects. The 3-month mRS score was not affected by incidental CA. Female sex was only an independent factor for incidental CA. Thus, we should pay more attention to incidental CA in female BI patients treated with tissue plasminogen activator.

Clinically meaningful treatment responses after switching to galantamine and with addition of memantine in patients with Alzheimer’s disease receiving donepezil

Clinical trials have shown the benefits of acetylcholinesterase inhibitors, such as donepezil and galantamine, and an N-methyl-D-aspartate receptor antagonist, memantine, in patients with Alzheimer’s disease (AD). However, little is known regarding the effects of switching from donepezil 5 mg/day to galantamine 16 or 24 mg/day, or regarding the effects of adding memantine to established therapy compared with increasing the dose of donepezil. This report discusses two studies conducted to evaluate treatment with galantamine and memantine with respect to cognitive benefits and caregiver evaluations in patients with AD receiving donepezil 5 mg/day for more than 6 months. Patients with mild or moderate AD (scores 10–22 on the Mini-Mental State Examination) were enrolled in the Galantamine Switch study and switched to galantamine (maximum doses 16 mg versus 24 mg). Patients with moderate to severe AD (Mini-Mental State Examination scores 3–14) were enrolled in the Donepezil Increase versus Additional Memantine study and either had their donepezil dose increased to 10 mg/day or memantine 20 mg/day added to their existing donepezil dose. Patients received the study treatment for 28 weeks and their Disability Assessment for Dementia, Mental Function Impairment Scale, Cohen-Mansfield Agitation Inventory, and Neuropsychiatric Inventory scores were assessed with assistance from their caregivers. For the Galantamine Switch study after 8 weeks, agitation evaluated by the Cohen-Mansfield Agitation Inventory improved in both the 16 mg and 24 mg groups compared with baseline. However, there were no significant differences between the two galantamine groups. Agitation was also less in patients in the additional memantine group than in the donepezil increase group. In summary, switching to galantamine from donepezil and addition of memantine in patients with AD receiving donepezil were both safe and meaningful treatment options, and particularly efficacious for suppression of agitation.

Clinicoradiologic features of vertebrobasilar dolichoectasia in stroke patients.

The prevalence and implications of vertebrobasilar dolichoectasia (VBD), a causative arteriopathy of stroke are unclear in Asian stroke patients. Through a comparative study of VBD and non-VBD stroke patients, we aimed to elucidate the clinicoradiologic features of VBD patients in Japan. A total of 481 consecutive patients (302 men and 179 women) with acute stroke were admitted to our department between 2007 and 2008. Of these 481 inpatients, 374 (231 men and 143 women) had brain infarct (BI), and 107 (71 men and 36 women) had brain hemorrhage (BH). We reviewed medical records, and VBD was diagnosed by magnetic resonance angiography. Cardiovascular disease (CVD) risk profile, modified Rankin scale score at 30 days poststroke, and stroke lesions were compared among 4 groups: the VBD BI group, the VBD BH group, the non-VBD BI group, and the non-VBD BH group. The diameter, height, and lateral displacement of the basilar artery (BA) were analyzed in the VBD patients. Statistical analyses used multivariate logistic regression analysis. VBD was found in 37 patients (34 men and 3 women). Mean age (± SD) was 64.4 ± 14.7 years (63.4 ± 14.6 years in men and 65.3 ± 6.1 years in women). Twenty-four patients (21 men and 3 women) had BI, and 13 men had BH. There were significant male preferences in VBD BI (P < .01) and VBD BH patients (P < .01). Mean age (± SD) was 67.7 ± 14.3 years in BI patients and 56.7 ± 12.7 years in BH patients. The VBD BH men were significantly younger than the non-VBD BH men (P < .05) and VBD BI men (P < .01). Frequency of current smoking was significantly greater in VBD BI patients compared with non-VBD BI patients (P < .05). Other CVD risk factors did not differ among the 4 groups. Mean modified Rankin Scale score was significantly higher in VBD BH men compared with non-VBD BH men and VBD BI men (P < .01). The height and lateral displacement of the BA were scored more severely in BH patients than in BI patients (P < .01), but BA diameter did not differ between BH and BI patients. The frequency of pontine infarct and hemorrhage was 3-fold greater in VBD BI (P < .05) and VBD BH patients (P < .005) compared with non-VBD BI and BH patients. Our findings indicate a VBD prevalence of 7.7% in stroke patients, 6.4% in BI patients, and 12.1% in BH patients. Our clinicoradiologic analyses suggest male predominance, younger onset of BH, and higher frequency of pontine lesions in VBD patients. Significant BA changes and poor outcome of stroke were found in patients with hemorrhagic VBD rather than ischemic VBD. Thus, more attention should be paid to risk and care of BH in VBD patients, in addition to those of BI.

Relationship between cervical cord 1H-magnetic resonance spectroscopy and clinoco-electromyographic profile in amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons, leading to limb paralysis and respiratory failure. Methods: C1–C3 cord 1H‐magnetic resonance spectroscopy (1H‐MRS) was performed in 19 patients with ALS and 20 controls. N‐acetylaspartate (NAA), choline‐containing compounds, creatine plus phosphocreatine (Cr), and myo‐Inositol (m‐Ins) were measured. ALS Functional Rating Scale‐Revised (ALSFRS) and forced vital capacity (FVC) were assessed. The rates of decline were calculated at 6 months before and after 1H‐MRS. Results: NAA/Cr and NAA/m‐Ins were decreased significantly, and m‐Ins/Cr was increased significantly in ALS patients compared with controls. NAA/Cr and NAA/m‐Ins were correlated with ALSFRS and FVC and inversely linked to the decline rates. NAA/Cr, NAA/m‐Ins, and m‐Ins/Cr were altered markedly in 9 patients with denervation and neurogenic changes in both C2 paraspinal and upper limb muscles. Conclusions: These metabolite ratios were associated with disease progression and ongoing denervation in neck and hand muscles. C1–C3 cord 1H‐MRS might reflect anterior horn cell damage causing neck/arm weakness and respiratory dysfunction in ALS patients. Muscle Nerve, 2013

Wegener Granulomatosis-associated Optic Perineuritis

Abstract Introdunction: We report two patients with optic perineuritis (OPN) and hypertrophic pachymeningitis in Wegener granulomatosis (WG). Case report: Patient 1: a 74-year-old man developed blurred vision in each eye, sequentially, over a year. In the first episode, visual acuity in the right eye was reduced to no light perception, and in the second episode, the vision in the left eye fell to 20/100. Brain and orbital magnetic resonance imaging (MRI) revealed abnormal enhancement in the meninges and the ipsilateral optic nerve sheath. T2-hyperintense lesions were found along the outer rim of the ipsilateral optic nerve. Seropositive proteinase-3-antineutrophil cytoplasmic antibody (PR3-ANCA), microhematuria and multiple pulmonary nodules suggested the diagnosis of WG. Steroid therapy was initiated 3 months after the first onset, but with no clinical response. At the 2nd episode, rapid administration of steroid ameliorated visual disturbance and MRI lesions markedly. Patient 2: a 72-year-old man developed blurred vision in each eye. Visual acuity measured no light perception in OD and 6/12 in OS. Gadolinium-enhanced MRI disclosed enhancement in the meninges and both optic nerve sheaths. T2-weighted imaging displayed hyperintense lesions along the outer rims of optic nerves. Otolaryngologic examination, seropositive PR3-ANCA and pulmonary nodules supported the diagnosis of WG. Steroid and cyclophosphamide treatment improved visual dysfunction and MRI lesions in the meninges and the optic nerve sheaths. Comment: The morphological similarity and the anatomical continuity between the meningeal and the perioptic tissues suggest that extension of granulomatous inflammation along such tissue planes accounted for visual loss in these two patients with WG.

Alleviation of Brain Hypoperfusion after Preventative Treatment with Lomerizine in an Elderly Migraineur with Aura

Previous studies of brain single-photon emission tomography (SPECT) showed changes of regional cerebral blood flow (rCBF) in migraineurs during prodromes or headache attacks. Little is known about how successful medication of migraine prevention can reflect rCBF in migraineurs. We highlighted alternation of brain SPECT findings in a migraineur with aura before and after prophylactic treatment with lomerizine, a calcium channel blocker. A 70-year-old man with migraine developed visual disturbance frequently at walking exercise for the recent 3 months. After this visual attack, a mild-degree of throbbing headache occured occasionally. Brain SPECT using 99mTc-ethyl cysteinate dimer was performed at interictal time of migraine. Brain SPECT before lomerizine treatment revealed hypoperfusion in the frontal, parietal, and occipital regions. He was diagnosed with recurrence of migraine with aura (MA). Lomerizine (10 mg/day, po) was administered for 3 months. MA and visual aura without headache were dramatically improved. Migraine attacks and visual disturbance were not induced at exercise. At 3 months after lomerizine medication, brain SPECT showed remarkable increase of rCBF. These SPECT changes of our patient indicated that antimigraine mechanism of lomerizine could contribute to restoration of cerebral hypoperfusion.

Clinicoradiological features of recurrent ischemic stroke: healthcare for poststroke patients

Objective: Little is known about recurrent risk profile of brain infarct (BI) in Japan. The study aimed to clarify clinicoradiological features of recurrent BI patients. Methods: 374 consecutive BI patients (231 men and 143 women) were admitted to our department between 2007 and 2008. Recurrent BI was defined as a prior history of BI. Cardiovascular disease (CVD) risk profile, stroke mechanism subtypes and Bamford subtypes were compared between the first BI and the recurrent BI group. CVD risk factors, stroke subtypes of the first BI and preventative medication were analyzed in recurrent BI patients. Results: Recurrent BI existed in 72 patients (40 men and 32 women). Age of the recurrent BI group was significantly older than the first BI group (P < 0.01). In comparison to the first BI group, the recurrent BI group had a high frequency of hypertension (P < 0.01) and CVD comorbidity (P < 0.05). Recurrent rates were increased significantly in cardioembolic patients as compared to the first BI patients (P < 0.05). Bamford BI subtypes did not differ between both groups. Mean recurrent interval (SD) was 3.1 (2.3) years. Approximately half the patients experienced recurrent BI less than 2 years after the first BI. Antiplatelet agents were used in 33 patients and warfarin was used in 12 patients as preventative medication. The remaining 27 patients had no prevention therapy by self-cessation. Nine warfarin users were controlled poorly. There were no significant correlations between the first and recurrent Bamford subtypes in recurrent BI patients. Conclusions: The present study indicated that the recurrent frequency of BI was 19.3%. Causative profile of recurrent BI suggested elderly age (≥65 years), hypertension, prior history of CVD, cardioembolism, 2 years poststroke, insufficient treatment of warfarin and self-cessation of preventative medication. Thus, physicians should pay more attention to these aspects for prophylaxis of recurrent BI in poststroke patients.