A case of the Starr-Edwards ball valve (Model 6120) in the mitral position for 45 years.

A 59-year-old male who had undergone mitral valve replacement with the Starr-Edwards ball valve Model 6120 (S-E ball valve) 45 years ago was admitted to our hospital for hemolytic anemia and heart failure. Echocardiography revealed that there was no valve dysfunction but paravalvular leakage between the annulus of P2 and the sewing ring of the Starr-Edwards ball valve. He underwent mitral valve replacement. The S-E ball valve was successfully replaced with bileaflet mechanical valve. The explanted S-E ball valve was free from signs of structural valve degeneration. This case shows one of the longest durability of the S-E ball valve in mitral position in the world.

Application of dissolving microneedles to glucose monitoring through dermal interstitial fluid.

Dissolving microneedles (DMs) were applied to glucose monitoring in the dermal interstitial fluid (ISF) of rats and their potential as an alternative blood glucose monitoring device was evaluated. Sodium chondroitin sulfate was used to prepare DM array chips, which consisted of 300 DMs/cm(2). The mean length of the DMs was 475±18 µm and the mean diameter of the basement was 278±8 µm. After DMs were inserted into the skin of the hair-removed rat abdomen, a wet unwoven cloth containing 10-30 µL of water was placed on the skin and ISF was extracted. By increasing the absorbed amount of water on the unwoven cloth from 10 to 30 µL, the extracted amount of glucose increased from 1.66±0.35 µg to 2.75±0.61 µg. Increasing the adhesion time of the wet unwoven cloth to the skin from 0.1 to 5.0 min, increased the amount of ISF glucose from 1.99±0.13 µg to 5.04±0.38 µg. The relation between the amount of glucose in ISF and blood glucose concentrations was examined. With increase in the adhesion time, the coefficient of determination, r(2), increased from 0.501 to 0.750. The number of DMs also affected the relationship and values of the coefficient of determinations, r(2) were: 0.340 (25 DMs), 0.758 (50 DMs), 0.763 (100 DMs), 0.774 (200 DMs), and 0.762 (300 DMs). These results indicate the usefulness of DMs as an alternative blood glucose monitoring device.

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 (1) H-magnetic resonance spectroscopy ((1) H-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 (1) H-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 (1) H-MRS might reflect anterior horn cell damage causing neck/arm weakness and respiratory dysfunction in ALS patients.

Different human copper-zinc superoxide dismutase mutants, SOD1G93A and SOD1H46R, exert distinct harmful effects on gross phenotype in mice.

Amyotrophic lateral sclerosis (ALS) is a heterogeneous group of fatal neurodegenerative diseases characterized by a selective loss of motor neurons in the brain and spinal cord. Creation of transgenic mice expressing mutant Cu/Zn superoxide dismutase (SOD1), as ALS models, has made an enormous impact on progress of the ALS studies. Recently, it has been recognized that genetic background and gender affect many physiological and pathological phenotypes. However, no systematic studies focusing on such effects using ALS models other than SOD1(G93A) mice have been conducted. To clarify the effects of genetic background and gender on gross phenotypes among different ALS models, we here conducted a comparative analysis of growth curves and lifespans using congenic lines of SOD1(G93A) and SOD1(H46R) mice on two different genetic backgrounds; C57BL/6N (B6) and FVB/N (FVB). Copy number of the transgene and their expression between SOD1(G93A) and SOD1(H46R) lines were comparable. B6 congenic mutant SOD1 transgenic lines irrespective of their mutation and gender differences lived longer than corresponding FVB lines. Notably, the G93A mutation caused severer disease phenotypes than did the H46R mutation, where SOD1(G93A) mice, particularly on a FVB background, showed more extensive body weight loss and earlier death. Gender effect on survival also solely emerged in FVB congenic SOD1(G93A) mice. Conversely, consistent with our previous study using B6 lines, lack of Als2, a murine homolog for the recessive juvenile ALS causative gene, in FVB congenic SOD1(H46R), but not SOD1(G93A), mice resulted in an earlier death, implying a genetic background-independent but mutation-dependent phenotypic modification. These results indicate that SOD1(G93A)- and SOD1(H46R)-mediated toxicity and their associated pathogenic pathways are not identical. Further, distinctive injurious effects resulted from different SOD1 mutations, which are associated with genetic background and/or gender, suggests the presence of several genetic modifiers of disease expression in the mouse genome.

Influenza-associated monophasic neuromyelitis optica.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder characterized by optic neuritis and acute myelitis. A parainfectious pathogenesis may play a partial role in the development of this disorder. Several viral infections are known to cause NMO. Here we report the case of a 15-year-old girl diagnosed with postinfluenza monophasic NMO. The patient developed sudden fever and chills, and the rapid diagnostic test for influenza was positive. She was diagnosed as influenza A and was treated with zanamivir hydrate (10 mg/day, inhalation). Three days later, she complained of dysuria and dysesthesia in the lower extremities. After nine days, she experienced blurred vision bilaterally. Neurological examination revealed visual disturbance, dysuria, dysesthesia and hyperreflexia in the lower extremities. Her visual acuity was counting fingers in OD and 2/100 in OS. Pupillary size was 4.0 mm and light reflexes were sluggish on both sides. Ophthalmoscopy showed marked edema of the optic discs. Serum influenza immunoglobulin M antibodies were elevated and serum anti-aquaporin 4 (AQP4) antibodies were undetectable. Spinal cord magnetic resonance imaging (MRI) displayed longitudinally extensive lesions in the thoracic cord. Brain MRI disclosed three subcortical lesions. The patient fulfilled the revised diagnostic criteria for NMO (2006). After methylprednisolone pulse therapy followed by oral administration of prednisolone, visual dysfunction, dysuria, limb dysesthesia and hyperreflexia were improved. Subsequently, she experienced no attacks for 3 years. This is the first case report of influenza A-associated NMO with such features of postinfectious NMO as a pediatric onset, monophasic course and anti-AQP4 antibody-seronegative status.

Clinicoradiological profile and serum lipid levels of intracerebral hemorrhage in prior statin users.

OBJECTIVE: We aimed to evaluate whether serum lipid levels can influence the clinicoradiological recovery of intracerebral hemorrhage (ICH) in prior statin users. PATIENTS AND METHODS: Medical records were reviewed retrospectively in 381 ICH patients (253 men and 128 women). Cardiovascular disease (CVD) risk factors, blood pressure at admission and the first in-hospital day, admission and 30-day scores of National Institute Health Stroke Scale (NIHSS) and modified Rankin scale (mRS), hematoma volume (HV), serum lipid levels were compared between prior statin users and non-users. RESULTS: Statins were pretreated in 56 patients (31 men and 25 women). Statin users were older age, and had higher frequencies of dyslipidemia, diabetes mellitus, atrial fibrillation, prior stroke history and large HV compared to non-users. Serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly decreased in the statin group compared to the non-statin group. There were no statistical differences in the other CVD risk factors, functional scores and other serum lipid levels between the two groups. HV was correlated inversely with serum levels of TC and LDL-C in both groups. Multiple logistic regression analysis showed that serum TC levels ≤150 mg/dL were associated with statin use [Odds ratio (OR)=5.5, 95% confidence interval (CI)=1.55-19.58], worsening of NIHSS score (OR=1.4, 95% CI=1.21-1.63) and HV (OR=1.1, 95% CI=1.07-1.13) in ICH patients. A significant association was found between worsening of NIHSS score (OR=2.0, 95% CI=1.32-3.12) and worsening of mRS score (OR=3.3, 95% CI=1.33-8.00), HV (OR=1.3, 95% CI=1.01-1.76), and serum TC levels ≤150 mg/dL in statin users. CONCLUSION: Prior statin users with serum TC levels ≤150 mg/dL had worsening of outcome and HV. Excessive lowering of serum TC levels due to statin pretreatment may cause unfavorable clinicoradiological recovery of ICH. Physicians should monitor serum lipid levels carefully in statin users.

Pulse wave velocity study in middle-aged migraineurs at low cardiovascular disease risk.

BACKGROUND: Migraine is associated with an increased risk for ischemic stroke and cardiovascular disease (CVD). Recent studies have suggested vascular dysfunction in the aorta, the brachial and femoral artery. Little is known about such arterial changes in Japanese midlife migraineurs. We aimed to evaluate arterial pulse wave velocity (PWV) and ankle-brachial index (ABI) in middle-aged migraineurs at low CVD risk. METHODS: Brachial-ankle PWV (baPWV) and ABI, using an oscillometric technique, were measured in 111 migraineurs (81 women and 30 men) and 110 controls. All participants had no CVD risk factors. Statistical comparison of baPWV and ABI between both groups and the relationship to clinical variables of migraineurs were analyzed. RESULTS: Twenty-two subjects had migraine with aura and 89 had migraine without aura. Mean age (SD) of migraineurs was 44.4 (8.4) years. Mean duration (SD) was 18.0 (10.8) years. Attack frequency was 60 subjects in ≥1 time/month and 51 subjects in <1 time/month. Mean score (SD) of Headache Impact Test-6 (HIT-6) was 61.4 (8.7). CVD risk profile did not differ statistically between migraineurs and controls. Mean baPWV (SD) of migraineurs was 1247 (189) cm/second in women and 1356 (126) in men. That of controls was 1138 (136) in women and 1250 (121) in men. baPWV was increased significantly in female and male migraineurs. Mean ABI (SD) was 1.05 (0.06; 1.04 [0.07] in men and 1.05 [0.06] in women) in migraineurs and 1.06 (0.07) in controls (1.05 [0.08] in men and 1.06 [0.08] in women). ABI did not differ statistically between migraineurs and controls. Migraine subtypes, duration, attack frequency, and HIT-6 score were not associated with baPWV and ABI. CONCLUSION: The present study indicated higher baPWV in midlife migraineurs without CVD risk factors. This pathogenesis could reflect distinct vascular reactivity rather than arterial stiffness due to atherosclerosis.

Neurobiology of depression and anxiety in Parkinson's disease.

Depression and anxiety are common in Parkinson's disease (PD) and have important consequences on quality of life. These have long been recognized as frequent accompanying syndromes of PD, and several reports suggest that these are the causative process or risk factors that are present many years before the appearance of motor symptoms. The neurochemical changes in PD involving dopamine, norepinephrine, and serotonin might be related to the pathophysiology of depression and anxiety, but this is still not clear. Several studies showed that anxiety in PD patients occurs earlier than depression, during premotor phase, suggesting that there may be a link between the mechanisms that cause anxiety and PD. Whereas a recent study reported that PD patients with depression and anxiety were associated with different demographic and clinical features.

Repeated non-enhancing tumefactive lesions in a patient with a neuromyelitis optica spectrum disorder.

A 51-year-old woman had developed fever and consciousness disturbance at 47 years of age. Brain magnetic resonance imaging (MRI) revealed acute disseminating encephalomyelitis (ADEM)-like lesions without gadolinium enhancement (GDE). One year later, she had an episode of bilateral optic neuritis and cerebellar ataxia. Speech deficit and right hand weakness occurred at the age of 51 years. Neurological examination showed motor aphasia, finger agnosia, right-left disorientation, and right hand paresis. Neuromyelitis optica (NMO)-IgG was seropositive. Cerebrospinal fluid examination showed negative results for myelin basic protein and oligoclonal IgG band. The IgG index was normal. Brain MRI revealed a tumefactive lesion in the left temporo-parietal region and conglomerate ovoid lesions in the pericallosal regions. No GDE was found in the brain lesions. Visual evoked potential test showed bilateral prolongation of P100 latencies. She was treated twice with methylprednisolone pulse therapy followed by oral prednisolone, but the motor aphasia did not respond to steroid treatment. She had no prior history of myelitis and was diagnosed as NMO spectrum disorder (NMOSD). Similar to previous studies of NMO-IgG seropositive extensive brain lesions, this patient with NMOSD indicated no GDE in tumefactive lesions at two episodes of encephalopathy. Compared to multiple sclerosis (MS), a high frequency of non-enhancing tumefactive lesions is reported in patients with NMO or NMOSD. The absence of GDE in tumefactive lesions could help to differentiate between NMO and MS.

Loss of glial fibrillary acidic protein marginally accelerates disease progression in a SOD1(H46R) transgenic mouse model of ALS.

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is highly expressed in reactive astrocytes. Increased production of GFAP is a hallmark of astrogliosis in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). However, the physiological and pathological roles of GFAP, particularly in chronic neurodegenerative conditions, remain unclear. To address this issue, we here investigate whether absence of GFAP affects the phenotypic expression of motor neuron disease (MND) using an H46R mutant Cu/Zn superoxide dismutase-expressing mouse model of ALS (SOD1(H46R)). GFAP deficient SOD1(H46R) mice showed a significant shorter lifespan than SOD1(H46R) littermates. Further, at the end stage of disease, loss of GFAP resulted in increased levels of Vim and Aif1 mRNAs, encoding vimentin and allograft inflammatory factor 1 (AIF1), respectively, in the spinal cord, although no discernible differences in the levels and distribution of these proteins between SOD1(H46R) and GFAP-deficient SOD1(H46R) mice were observed. These results suggest that loss of GFAP in SOD1(H46R) mice marginally accelerates the disease progression by moderately enhancing glial cell activation. Our findings in a mouse model of ALS may have implication that GFAP is not necessary for the initiation of disease, but it rather plays some modulatory roles in the progression of ALS/MND.

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 (99m)Tc-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.

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.

Unilateral Measles-Associated Retrobulbar Optic Neuritis without Encephalitis: A Case Report and Literature Review.

Optic neuritis (ON) is a rare neurological complication of measles infection. Little is known about measles-associated retrobulbar ON. Here, we report a distinct patient with unilateral retrobulbar ON due to measles infection. A 26-year-old woman developed maculopapular rash and Koplik spots. On the following 3 days, she noticed blurred vision in the left eye. A Goldmann visual field test showed inferior nasal quadrantanopsia in the left eye. Visual acuity was 20/20 in OD and 20/100 in OS. Pupillary size was 2.0 mm in the right eye and 4.0 mm in the left eye. Light reflexes were slightly sluggish in the left eye. Ophthalmoscopy showed mild pallor of the left optic disc. Central critical flicker fusion frequency (CFF) was 40.7 Hz in the right eye and 10.1 Hz in the left eye (normal =29.0). Visual evoked potentials showed that P100 latencies were delayed on the left side (133 ms). Brain and spinal cord MRI was normal. Orbital MRI displayed abnormal enhancement in the left optic nerve. Serum and cerebrospinal fluid IgG titers of anti-measles antibodies were increased. Left measles-associated ON was diagnosed. Methylprednisolone pulse therapy followed by oral administration of prednisolone ameliorated visual acuity, visual field and CFF. The neuroophthalmic profile of our patient indicated that measles infection triggered isolated retrobulbar ON, leading to unusual visual deficits. Thus, physicians should pay more attention to variable patterns of measles-associated ON.

Rheumatoid leptomeningitis: radiological alteration of cerebral hypoperfusion and subarachnoid lesions.

A 56-year-old man with rheumatoid arthritis developed emotional lability and myoclonic seizure in the left arm, followed by fever and generalized convulsion. Brain magnetic resonance imaging (MRI) revealed leptomeningeal lesions with abnormal enhancement. MRI lesions were localized predominantly in the right cerebral subarachnoid spaces. Electroencephalogram showed epileptogenic focus at the right frontal and central points. After administration of valproate sodium improved convulsion and myoclonus, single photon emission computed tomography (SPECT) using N-isopropyl-p-(123)I-iodoamphetamine was performed. Brain SPECT displayed hypoperfusion predominantly in the right cerebral hemisphere. Cerebrospinal fluid (CSF) disclosed mild pleocytosis and marked elevations of interleukin-6 levels. Repeated CSF analyses showed cytology of class I and negative results for infectious pathogens. Methylprednisolone pulse therapy (1 g for 3 days, iv) and subsequent prednisolone administration (daily 50 mg, po) ameliorated neurological symptoms dramatically. Prednisolone was tapered to 20 mg/day for 5 months. Leptomeningeal MRI lesions were attenuated gradually followed by restoration of cerebral hypoperfusion on SPECT. He was diagnosed as rheumatoid leptomeningitis (RLM). Although clinical features of RLM exhibited variable deficits of the central nervous system (CNS), MRI failed to detect the corresponding CNS lesions. We first highlighted neuroradiological changes of cerebral hypoperfusion and leptomeningeal lesions in RLM. These neuroimages of our patient supported that leptomeningeal inflammation and the adjacent cerebrocortical ischemia could cause encephalitis-like symptoms in RLM patients.

Genetic background and gender effects on gross phenotypes in congenic lines of ALS2/alsin-deficient mice.

Loss-of-function mutations in human ALS2 account for several juvenile recessive motor neuron diseases (MNDs). To understand the molecular basis underlying motor dysfunction in ALS2-linked MNDs, several lines of Als2(-/-) mice with a mixed genetic background were thus far generated, and their phenotypes were thoroughly characterized. However, several phenotypic discrepancies among different Als2-deficient lines became evident. To investigate whether genetic backgrounds are associated with such discrepancies, we here generated congenic lines of Als2(-/-) mice on two different genetic backgrounds; C57BL/6 (B6) and FVB/N (FVB), and investigated their gross phenotypes. Both B6 and FVB congenic lines were viable and fertile with no evidences for obvious abnormalities. There were no differences in growth curves between wild-type and Als2(-/-) mice on each genetic background. Remarkably, Als2(-/-) mice on a FVB, but not a B6, background exhibited a shorter life span than wild-type litters. Further, B6 female, but not male, Als2(-/-) mice showed a significantly lower spontaneous rearing activity than wild-type litters. These genetic background- and/or gender-specific findings suggest the presence of modifiers for life span and motor activities in Als2(-/-) mice. These congenic mice should provide a useful means to understand the molecular and genetic basis for variable expression of pathological phenotypes in MNDs.

Familial amyotrophic lateral sclerosis with a novel G85S mutation of superoxide dismutase 1 gene: clinical features of lower motor neuron disease.

Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by upper and lower motor neuron damage. Mutations of Cu/Zn superoxide dismutase gene (SOD1) account for 20% of familial ALS (FALS). We report a unique clinicogenotype of a Japanese family with a novel SOD 1 mutation. A 37-year-old woman (the proband) noticed muscle weakness in the left lower limb. Her mother had developed progressive lower motor neuron signs in four extremities at 38 years of age. Subsequently she was diagnosed as ALS and died of respiratory failure at 15 months after clinical onset. Neurological examination of the proband showed absent muscle stretch reflexes in the left knee and the left ankle without Babinski signs. Mild to moderate degree of muscle weakness existed in the left lower extremity. Muscle atrophy was presented in the left thigh. Initial pulmonary function revealed forced vital capacity of 91.1%. Electromyography disclosed ongoing denervation muscle potentials in the left lower extremity. SOD1 analysis demonstrated amino acid substitution of glycine by serine at codon 85 (G85S) in exon 4. Six months later, marked muscle weakness and atrophy expanded to four extremities. All muscle stretch reflexes were absent. Three months later, ventilator support with a tracheostomy was needed. The patient died at 18 months after clinical onset. Clinical hallmarks of this FALS family indicate that G85S mutation of SOD1 may cause rapidly progressive form of pure lower motor neuron signs.

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.

Atorvastatin treatment attenuates motor neuron degeneration in wobbler mice.

We aimed to study whether atorvastatin treatment can retard motor neuron degeneration in wobbler mice. Wobbler mice and their normal littermates were fed 0.01% atorvastatin-mixed food (10 mg/kg/day) or regular food from age 3-4 weeks of disease onset for four weeks (n=10/group) or more than eight weeks (n=10/group). Motor function was evaluated by pull-strength and deformity scale of the forelimbs. For those symptomatic assessment and body weight were measured weekly. Neuropathological and biochemical changes of the biceps muscle and the cervical cord were analyzed at four weeks after treatment. Compared to vehicle, atorvastatin-treated wobbler mice delayed progression of forelimb motor deficits by more than four weeks. Wobbler mice significantly increased body weight from three weeks post-treatment of atorvastatin, compared with vehicle (p<0.05). Atorvastatin administration suppressed denervation atrophy at 30% (p<0.01), maintained choline acetyl transferase activities of the biceps muscle (p<0.05), and attenuated approximately 30% loss of motor neurons in wobbler mice (p<0.01). Atorvastatin fed to normal littermates did not influence body weight gain, neuropathological and biochemical findings. These data suggest that atorvastatin has neuroprotective effects on denervating muscles and degenerating motor neurons in wobbler mice.