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Background Biallelic variants in POLR3A encoding the largest subunit of RNA polymerase III cause POLR3-related (or 4H) leukodystrophy characterized by neurologic dysfunction, abnormal dentition, endocrine abnormalities and ocular abnormality. Recently, whole-exome sequencing enabled the discovery of POLR3A variants in cases lacking diffuse hypomyelination, the principal MRI phenotype of POLR3-related leukodystrophy. Homozygous c.1771-6C > G variants in POLR3A were recently suggested to cause striatal and red nucleus involvement without white matter involvement. Case report: Here, we report three cases in two families with biallelic POLR3A variants. We identified two sets of compound heterozygous variants in POLR3A, c.1771-6C > G and c.791C > T, p.(Pro264Leu) for family 1 and c.1771-6C > G and c.2671C > T, p.(Arg891*) for family 2. Both families had the c.1771-6C > G variant, which led to aberrant mRNA splicing. Neuropsychiatric regression and severe intellectual disability were identified in three patients. Two cases showed dystonia and oligodontia. Notably, characteristic bilateral symmetric atrophy and abnormal signal of the striatum without diffuse white matter signal change were observed in brain MRI of all three individuals. Conclusions Striatum abnormalities may be another distinctive MRI finding associated with POLR3A variants, especially in cases including c.1771-6C > G variants and our cases can expand the phenotypic spectrum of POLR3A-related disorders.

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

Controlling the oral microbial flora is putatively thought to prevent not only oral diseases, but also systemic diseases caused by oral diseases. This study establishes the antibacterial effect of the novel bioactive substance “S-PRG filler” on oral bacteria. We examined the state of oxidative stress caused by the six types of ions released in eluate from the S-PRG filler in oral bacterial cells. Moreover, we investigated the effects of these ions on the growth and pathogenicity of Gram-positive and Gram-negative bacteria. We found that the released ions affected SOD amount and hydrogen peroxide in bacterial cells insinuating oxidative stress occurrence. In bacterial culture, growth inhibition was observed depending on the ion concentration in the medium. Additionally, released ions suppressed Streptococcus mutans adhesion to hydroxyapatite, S. oralis neuraminidase activity, and Porphyromonas gingivalis hemagglutination and gingipain activity in a concentration-dependent manner. From these results, it was suggested that the ions released from the S-PRG filler may suppress the growth and pathogenicity of the oral bacterial flora. This bioactive material is potentially useful to prevent the onset of diseases inside and outside of the oral cavity, which in turn may have possible applications for oral care and QOL improvement.

Background and Purpose: The characteristics of patients with stroke prior receiving direct oral anticoagulant (DOAC) have not been fully clarified. We planned to recruit patients prospectively and to investigate the characteristics and outcomes in stroke patients taking DOAC and warfarin treatment prior to the event. Methods: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke patients receiving OAC. Patient enrollment started in April 2016 at 25 tertiary centers across Japan. We compared clinical characteristics and discharge modified Rankin Scale (mRS) between DOAC-and warfarin-treatment in patients with atrial fibrillation (AF). Results: A total of 580 patients (231 women; median age 80 [quartiles 73-84] years) were analyzed (Fig. A). Of these, 365 patients (63%) received prior DOAC treatment and the remaining 215 (37%) received prior warfarin treatment (Fig. B and C). There were significant differences in clinical characteristics and outcome between DOAC-and warfarin-treatment prior to the event regarding initial NIHSS score (median [quartiles]: DOAC, 4 [2-16] vs. warfarin, 9 [3-21]; P =0.0001), rate of medium-large size of infarct (DOAC, 202/340 [59%] versus warfarin, 152/203 [75%]; P =0.0003) and the proportion of patients with favorable outcome (mRS, 0-3: DOAC 218/354 [62%] vs. warfarin 108/212 [49%]; P =0.0036). Subclassification according to DOAC dosing revealed patients with low-dose (259/365; 71%) to be older and to have a higher NIHSS score compared with regular dose (low-dose, 5 [2-17] vs. regular-dose, 3 [1-11]; P =0.0023) (Fig. D). Type of DOAC agent did not result in relevant differences in clinical characteristics or outcome (Fig. E). Conclusions: Our results showed that patients with DOAC treatment before the event showed smaller infarct size, milder initial stroke severity, and favorable outcome compared to patients with warfarin.

Background and Purpose: The characteristics of direct oral anticoagulant (DOAC)-related intracerebral hemorrhage (ICH) have not been fully clarified. We planned to recruit patients prospectively and to investigate the characteristics and outcomes in patients with ICH receiving direct oral anticoagulant (DOAC) and warfarin treatment. Methods: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke patients receiving OAC. Patient enrollment started in April 2016 at 25 tertiary centers across Japan. We compared imaging, clinical characteristics, and discharge modified Rankin Scale (mRS) between DOAC- and warfarin-related ICH patients with atrial fibrillation (AF). Results: A total of 154 patients (51 women; median age 77 [quartiles 69-87] years) were analyzed. Of these, 111 patients (72%) received prior DOAC treatment and the remaining 43 (28%) received prior warfarin treatment (Fig. A, B and C). There were no relevant differences in clinical and hematoma characteristics between DOAC- and warfarin-related ICH regarding baseline hematoma volume (median [quartiles]: DOAC, 11 [5-23] mL vs. warfarin, 12 [5-30] mL; P =0.95), rate of hematoma expansion (DOAC, 12/111 [11%] vs. warfarin, 4/43 [9%]; P =0.80), rate of subcortical hemorrhage (DOAC, 15/111 [11%] vs. warfarin, 10/43 [9%]; P =0.80) and the proportion of patients with unfavorable outcome (mRS, 4-6: DOAC 76/108 [70%] vs. warfarin 23/38 [61%]; P =0.26). Cerebral microbleeds (CMBs) were detected more frequently in DOAC group than in warfarin (47/76 [62%] vs. 11/32 [34%]; P Conclusions: Our results showed that there were no significant differences in hematoma characteristics and functional outcome among AF patients with DOAC- or warfarin-related ICH.

This is an extension from a selected paper from JSAI2019. Social learning is crucial in acquisition of the intelligent behaviors of humans and many kinds of animals, as it makes behavior learning far more efficient than pure trial-and-error. In imitation learning, a representative form of social learning, the agent observes specific action-state pair sequences produced by another agent (expert) and reflect them into its own action. One of its implementations in reinforcement learning is the inverse reinforcement learning. We propose another form of social learning, emulation learning, which requires much less information from another agent (pioneer). In emulation learning, the agent is given only a certain level of achievement by another agent, or a record. In this study, we implement emulation learning in the reinforcement learning setting by applying a model of satisficing action policy. We show that the emulation learning algorithm works well both in stationary and non-stationary reinforcement learning tasks, breaking the often observed trade-off like relationship between efficiency and flexibility.

Mutations in small heat shock protein beta-1 (HspB1) have been linked to Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole-exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1-related disorders.

Foix-Chavany-Marie syndrome (FCMS) is a rare cortical type of pseudobulbar palsy characterized by the loss of voluntary control of the facial, pharyngeal, lingual, and masticatory muscles with preserved reflexive and autonomic functions. FCMS is generally associated with cerebrovascular diseases affecting the bilateral opercular regions. We herein report the clinical features of an 84-year-old right-handed Japanese man with FCMS due to a unilateral brain abscess. The patient's symptoms were resolved after treating the brain abscess. The present clinical results suggest that a unilateral brain abscess in the temporal operculum with a persistent old lesion in the contralateral insular cortex can induce FCMS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the brainstem and spinal cord. Clinical studies have indicated that there is a distinct region-dependent difference in the vulnerability of motor neurons. For example, the motor neurons in the facial and hypoglossal nuclei are more susceptible to neuronal death than those in the oculomotor nucleus. To understand the mechanism underlying the differential susceptibility to cell death of the neurons in different motor nuclei, we compared the effects of chemical anoxia on the membrane currents and postsynaptic currents in different motor nuclei. The membrane currents were recorded from neurons in the oculomotor, facial and hypoglossal nuclei in brain slices of juvenile Wistar rats by using whole-cell recording in the presence of tetrodotoxin that prevents action potential-dependent synaptic transmission. NaCN consistently induced an inward current and a significant increase in the frequency of spontaneous synaptic inputs in neurons from these three nuclei. However, this increase in the synaptic input frequency was abolished by strychnine, a glycine receptor antagonist, but not by picrotoxin in neurons from the hypoglossal and facial nuclei, whereas that in neurons from the oculomotor nucleus was abolished by picrotoxin, but not by strychnine. Blocking ionotropic glutamate receptors did not significantly affect the NaCN-induced release facilitation in any of the three motor nuclei. These results suggest that anoxia selectively facilitates glycine release in the hypoglossal and facial nuclei and GABA release in the oculomotor nucleus. The region-dependent differences in the neurotransmitters involved in the anoxia-triggered release facilitation might provide a basis for the selective vulnerability of motor neurons in the neurodegeneration associated with ALS.

A 77-year-old man with a right kidney stone was admitted to our hospital. A ureteroscope was introduced into the ureter without dilation under direct vision. We then performed flexible transurethral lithotripsy (f-TUL) using a ureteral access sheath and successfully fragmented the stone and extracted almost all the stone fragments without any complications. Just 3 hours after the operation, he suddenly developed right abdominal pain with a decrease in hemoglobin. A CT scan showed a retroperitoneal hemorrhage around the lower ureter. We herein describe a rare complication associated with flexible transurethral lithotripsy.

Purpose Vertebral artery hypoplasia (VAH) is a common congenital anatomical variation. In previous reports, it was unclear whether VAH was an independent risk factor for posterior circulation ischemia. The purpose of this study was to evaluate the impact of VAH on posterior circulation ischemia. Methods Subjects were patients with acute ischemic stroke who underwent brain magnetic resonance imaging (MRI) and carotid ultrasonography. Diagnostic criteria for VAH were as follows: (1) Vertebral artery (VA) diameter less than 2.5 mm; (2) VA diameter less than 3.0 mm and a difference in length equal to or greater than 1:1.7; (3) VA diameter less than 3.0 mm, peak systolic velocity less than 40 cm/second, and resistance index value greater than .75. The patients were categorized by the location of the ischemic stroke on MRI as follows: lesion in posterior circulation (P group), lesion in anterior circulation (A group), and multiple lesions in both the anterior and posterior circulations (AP group). Results We evaluated 129 consecutive patients. VAH was seen in 39, and VA occlusion was found in 15. The prevalence of VAH in the P group (44.4%) was significantly higher than that in the A + AP group (24.7%, P = .034). Multivariate regression analysis showed that large-artery atherosclerosis (odds ratio, 6.3; 95% confidence interval [CI], 1.3-30.1), posterior circulation ischemia (odds ratio, 12.0; 95% CI, 2.8-51.2), and VAH (odds ratio, 4.2; 95% CI, 1.2-15.0) were independent factors related to VA occlusion. Conclusion VAH was an independent factor related to VA occlusion. Therefore, VAH likely plays a role in posterior circulation ischemia.

Objectives The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. Design The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. Conclusions The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

The term cerebral small vessel disease (SVD) refers to a group of pathological processes with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. SVD occurs in approximately 5% of patients. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL),a recessive form of heritable SVD, is caused by a mutation in the high temperature requirement A serine peptidase (HTRA1) gene. Recently, heterozygous mutations in HTRA1 were identified in patients with symptomatic SVD. We identified two families harboring HTRA1 (p.S284 N and p.V216 M) heterozygous mutations with symptoms that mimicked common symptoms of CARASIL.

Mutations in small heat shock protein beta‐1 (HspB1) have been linked to Charcot‐Marie‐Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole‐exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1‐related disorders.

Background Precise associations between clinical characteristics of transient ischemic attack (TIA) patients and diffusion-weighted imaging (DWI) positivity are still controversial. Thus, the purposes of this were to investigate the clinical characteristics associated with DWI positivity in patients with TIA and to develop a risk score for the prediction of DWI positivity in TIA. Methods Between April 2008 and June 2011, we retrospectively enrolled consecutive patients, who were admitted to our hospital with TIA and underwent DWI within 24 hours of admission. Patients were divided into a DWI-positive or DWI-negative group. The clinical characteristics of the 2 groups were compared, and a DWI positivity score was determined for each patient. We calculated the DWI positivity score by assigning a point value of 1 to the following factors: blood urea nitrogen to serum creatinine (BUN/Cr) ratio greater than 17.5, glucose greater than 161 mg/dL, and brain natriuretic peptide (BNP) greater than 55.4 pg/dL. Values below these cutoffs were given a value of 0, and the 3 point values were summed to obtain the final DWI positivity score (from 0 to 3). Results A total of 41 patients (median age = 62 years; 8 women) were enrolled in this study. There were 14 (35%) patients with DWI positivity. The median of the BUN/Cr ratio, blood glucose, and BNP were significantly higher in the DWI-positive than that in the DWI-negative group. As the DWI positivity score increased, there was an increased rate of DWI positivity. Conclusions Our data indicate that seminal scores that included BUN/Cr ratio, glucose, and BNP contributed to DWI positivity in TIA patients.

We recently showed using prepro-orexin knockout (ORX-KO) mice and orexin neuron-ablated (ORX-AB) mice that orexin neurons in the hypothalamus, but not orexin peptides per se, are indispensable for stress-induced thermogenesis. To examine whether orexin neurons are more generally involved in central thermoregulatory mechanisms, we applied other forms of thermogenic perturbations, including brain prostaglandin E2 (PGE2) injections which mimic inflammatory fever and environmental cold exposure, to ORX-KO mice, ORX-AB mice and their wild-type (WT) litter mates. ORX-AB mice, but not ORX-KO mice, exhibited a blunted PGE2-induced fever and intolerance to cold (5°C) exposure, and these findings were similar to the results previously obtained with stress-induced thermogenesis. PGE2-induced shivering was also attenuated in ORX-AB mice. Both mutants responded similarly to environmental heating (39°C). In WT and ORX-KO mice, the administration of PGE2 and cold exposure activated orexin neurons, as revealed by increased levels of expression of c-fos. Injection of retrograde tracer into the medullary raphe nucleus revealed direct and indirect projection from the orexin neurons, of which the latter seemed to be preserved in the ORX-AB mice. In addition, we found that glutamate receptor antagonists (D-(-)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione) but not orexin receptor antagonists (SB334867 and OX2 29) successfully inhibited PGE2-induced fever in WT mice. These results suggest that orexin neurons are important in general thermogenic processes, and their importance is not restricted to stress-induced thermogenesis. In addition, these results indicate the possible involvement of glutamate in orexin neurons implicated in PGE2-induced fever.

A 54-year-old-woman with sarcoidosis presented with progressive symmetric, predominantly distal weakness and sensory dysfunction with areflexia in all four limbs. Nerve conduction studies showed multifocal conduction blocks in several nerves. Oral steroids were ineffective; however, intravenous immunoglobulin (IVIG) therapy rapidly and repeatedly improved the patient's neurologic symptoms with a resolution of the conduction blocks. Multifocal conduction blocks are not frequently reported in patients with sarcoid neuropathy, but they may respond to early treatment with IVIG.

Deficiency in energy supply, such as occurs during hypoxia, anoxia, metabolic stress and mitochondrial failure, strongly affects the excitability of central neurons. Such lowered energy supply evokes various changes in spontaneous synaptic input to the hippocampal and cortical neurons. However, how this energy deprivation affects synaptic input to motor neurons, which are also vulnerable to energy deprivation, has never been addressed. Here we report for the first time the effect of metabolic stress on synaptic input to motor neurons by recording postsynaptic currents in the hypoglossal nucleus. Chemical anoxia with NaCN (1 mM) and anoxia with 95% N 2 induced a persistent inward current and a marked and robust increase in action potential-independent synaptic input. This increase was abolished by strychnine, but not by picrotoxin, CNQX or MK-801, indicating glycine release facilitation. Blockade of voltage-dependent Ca 2+ channels and extracellular Ca 2+ deprivation strongly attenuated this facilitation. The amplitude of inward currents evoked by local application of NMDA to the motor neurons in the presence of strychnine was significantly increased during NaCN application. A saturating concentration of D-serine occluded this potentiation, suggesting that released glycine activated the glycine-binding sites of NMDA receptors. By contrast, neurons in the dorsal motor nucleus of the vagus showed no detectable change in synaptic input in response to NaCN. These data suggest that increase in synaptically released glycine in response to metabolic stress may play an exacerbating role in NMDA receptor-mediated excitotoxicity in motor neurons.

Introduction: Cortical vessel signs (CVSs) on susceptibility-weighted MR imaging (SWI) are frequently observed in acute ischemic stroke patients. However, the clinical implications of this sign have not yet been clearly defined. We assumed the hypothesis that grade of CVSs on SWI predicts outcomes in acute stroke patients. Methods: We retrospectively enrolled stroke patients who presented with anterior circulation cerebral infarction within 24 hours after onset. We excluded patients with no SWI. CVSs was defined as more veins or lager veins with a greater signal loss on SWI than those in the opposite normal hemisphere. CVSs was graded as 1) absent, 2) subtle as presence of CVSs less than 1/3 of the anterior circulation perfusion lesion, or 3) prominent as presence of CVSs more than 1/3 of the perfusion lesion. Unfavorable outcome was defined as discharge modified Rankin scale score 4-6. Results: We included 114 patients from October 2012 to June 2014, 71% of patients were men, median age was 71 years, and the average initial NIHSS score was 7 (range 0-32). CVSs was seen in 53 (47%) of patients. There were 14 patients (13%) with subtle CVSs, and 39 patients (35%) with prominent CVSs. Unfavorable outcome was as follows: 15% of patients with none CVSs, 43% with subtle CVSs, and 59% with prominent CVSs (figure 1). As with grade of CVSs, proportional rate of unfavorable patients gradually increased (P < 0.01). Conclusions: Grade of CVSs on SWI can predict outcomes in acute stroke patients.

Objective This study aimed to examine whether the volume of the olfactory bulbs and tracts (OB & T) on magnetic resonance imaging (MRI) is useful for differentiating Parkinson's disease (PD) from PD-related disorders. Methods The study group comprised 13 patients with PD, 11 with multiple system atrophy (MSA), five with progressive supranuclear palsy, and five with corticobasal degeneration (PSP/CBD). All patients were evaluated using the odor stick identification test for Japanese (OSIT-J), 123I-meta-iodobenzylguanidine (MIBG) scintigraphy, and brain MRI. OB & T areas on 1-mm-thick coronal images were measured and summed for volumes. We examined relationships between olfactory function and volume, and cardiovascular dysautonomia. We defined the cut-off values for OSIT-J score or MIBG uptake and OB & T volume to discriminate PD from PD-related disorders and calculated the proportional rate of PD in four categorized groups. Results OB & T volume was smaller in PD than in MSA or PSP/CBD (p

Background Carotid duplex ultrasonography (CUS) has been used to identify reversed vertebral artery flow (RVAF) at the extracranial cervical artery in some patients with subclavian steal syndrome. However, the characteristics of intracranial RVAF as evaluated by transcranial color flow imaging (TC-CFI), which can examine intracranial hemodynamics in a real-time and noninvasive fashion, remain unclear. The goal of this study was to analyze the prevalence of intracranial RVAF and its associated clinical characteristics. Methods Subjects were consecutive patients who underwent TC-CFI and CUS. We evaluated blood flow in both intracranial vertebral arteries (VAs) from the suboccipital echo window using TC-CFI. RVAF was defined as a flow signal directed toward the probe. We calculated the prevalence of intracranial RVAF in our subjects. Then, we investigated vascular condition (ie, site of lesion, stenosis, occlusion, and dissection) using magnetic resonance angiography, computed tomography angiography , and CUS in patients with intracranial RVAF. Results Seven hundred twenty patients (508 men; median age, 73 years) were included in this study from September 2007 to March 2013. Intracranial RVAF was seen in 12 patients (1.7%; 11 men; median age, 61 years). Among the 12 patients with intracranial RVAF, 8 patients (67%) had ischemia of the vertebrobasilar territory with distal VA occlusion, according to CUS. Of those patients, 6 (75%) had dissection of the VA. Conclusions TC-CFI detected intracranial RVAF in 1.7% of consecutive examinations in our facility. In vertebrobasilar territory stroke patients with intracranial RVAF, VA dissection may contribute to the development of stroke.

A 30-year-old man presented with headache, left hemiparesis, and uncal herniation. Magnetic resonance imaging showed acute infarction in the right middle cerebral artery (MCA). Lifesaving craniotomy proceeded because of the uncal herniation. Assessment of brain tissue led to a diagnosis of MCA dissection. His skin biopsy showed ultrastructural abnormalities of dermal connective tissue. This is the unique case that dissection was diagnosed from both a biopsy specimen of the MCA and the dermal connective tissue.

Background The goal of this study was to investigate the relationship between white matter lesions on magnetic resonance imaging and flow parameters in the middle cerebral artery (MCA) measured by transcranial color flow imaging. Methods Patients with acute ischemic stroke or transient ischemic attack were included. The relationship between severities of periventricular hyperintensity (PVH) and ultrasonographic parameters in the MCA was investigated. The frequency of PVH was calculated for different categories according to the presence or absence of 2 considerable parameters according to the value of area under the receiver operating characteristic curve. Results MCA flow was successfully measured in 203 temporal windows among 124 patients. After determining the cutoff value of end-diastolic velocity (EDV) and pulsatility index (PI) for the presence of PVH, 4 different categories were established: Category A, EDV more than 40 cm/second and PI less than .7; Category B, EDV more than 40 cm/second and PI more than .7; Category C, EDV less than 40 cm/second and PI less than .7; and Category D, EDV less than 40 cm/second and PI more than .7. The prevalence of PVH gradually increased along with category ( P Conclusions The evaluation of MCA parameters using the combination of PI and EDV may be useful for the prediction of PVH.

Objective The usefulness of conventional magnetic resonance imaging (C-MRI) for diagnosing amyotrophic lateral sclerosis (ALS) remains controversial. The aim of this study was to investigate the utility of C-MRI in identifying ALS, specifically the association between corticospinal tract (CST) hyperintensity on C-MRI and clinical characteristics in patients with ALS. Methods Between June 2008 and April 2012, we retrospectively enrolled consecutive patients diagnosed with sporadic ALS who underwent C-MRI. Patients with ALS were classified as definite-phase ALS (D-ALS) and indefinite-phase ALS (ID-ALS). We focused on the hyperintensity of T2-weighted images in the CST in patients with ALS. Based on the MRI results, we divided patients into two groups: a positive CST group showing CST hyperintensity; and a negative CST group with no such findings. Clinical characteristics of the two groups were compared. Results Seventeen patients (median age, 62 years; 8 women, 9 men) were enrolled in this study, with D-ALS in eight (47%) and ID-ALS in nine (53%). Eight patients (47%) showed CST positivity. The rate of CST positivity was higher in patients with D-ALS (75%) than in patients with ID-ALS (22%, p = 0.03). Conclusions CST positivity appears significantly increased in D-ALS patients. C-MRI can play an important role in diagnosing ALS.

Purpose: Vertebral artery hypoplasia (VAH) is congenital anatomical variation, which is frequently observed in clinical situation. In previous reports, it was not unclear whether VAH was the independent risk factor for posterior circulation ischemia. The purpose of this study is to evaluate an impact of VAH on posterior circulation ischemia. Methods: Subjects were patients with acute ischemic stroke who underwent brain MRI and carotid ultrasonography. The diameter of vessel and flow velocities of extracranial vertebral artery (VA) was measured by carotid ultrasonography. Diagnostic criteria of VAH was as follows: 1) diameter of VA 0.75. We divided all patients into three groups by the location of the acute ischemic stroke evaluated by MRI: ischemic lesion on posterior circulation (P group), on anterior circulation (A group), and multiple lesions on both anterior and posterior circulation (AP group). Then, the prevalence rate of VAH was compared between P group and A+AP group. In order to evaluate independent factors of VA occlusion, we conducted multivariate regression analyses. Results: We evaluated a total of 129 consecutive patients (87 male, median age; 71 years). P group was 36 patients, and A+AP group was 93 patients. VAH was seen in 39 patients (31.5%), and VA occlusion was found in 15 patients. The prevalence rate of VAH in P group (44.4%) was significantly higher than in A+AP group (24.7%, p=0.034). In univariate analysis, the patients with VA occlusion were higher rates of hypertension (p=0.066), large artery atherosclerosis (p=0.095), posterior circulation ischemia (p=0.001), and the presence of VAH (p=0.038). Multivariate regression analysis demonstrated that large artery atherosclerosis (odds ratio, 6.3; 95% confidence interval, 1.3-30.1), posterior circulation ischemia (odds ratio, 12.0; 95% confidence interval, 2.8-51.2) and VAH (odds ratio, 4.2; 95% confidence interval, 1.2-15.0) were independently associated with the presence of VA occlusion. Conclusion: VAH was independent factor of VA occlusion, and should be associated with posterior circulation ischemia.

Encephalopathy related to idiopathic hypereosinophilic syndrome (HES encephalopathy) is a rare (but well-documented) syndrome. Magnetic resonance imaging (MRI) findings of HES encephalopathy, particularly diffusion-weighted images (DWI) findings, have not been reported. We report a case of HES encephalopathy in a 79-year-old male presenting with a focal neurological deficit and cognitive function disorders. Eosinophil number was >20,000/mm 3 . Initial DWI revealed multiple high-signal lesions that were clearer than on T2-weighted images. After corticosteroid therapy, symptoms improved and MRI-identified lesions decreased. This is the first report demonstrating DWI findings of HES encephalopathy. We suggest that lesions identified on MRI may be related to a combination of demyelination, inflammation and/or even small-vessel infarction due to local intimal lesions and clotting, secondary to eosinophilic toxicity. Investigation using DWI should therefore be done in patients with HES encephalopathy even if T2-weighted images are normal.

We report a case of generalized myasthenia gravis with obstructive sleep apnea in which myasthenia gravis symptoms improved dramatically after initiation of continuous positive airway pressure therapy. A 42-year-old man was admitted with generalized myasthenia gravis. He was found to snore loudly during sleep and was diagnosed with obstructive sleep apnea by polysomnography. Continuous positive airway pressure therapy contributed to immediate improvements in not only the apnea–hypopnea index (70.6–20.9), but also the myasthenia gravis-specific activities of daily living scale (10–1) and quantitative myasthenia gravis scale (21–8). We suggest that when a myasthenia gravis patient is obese and suspected to have sleep problems, examinations to detect obstructive sleep apnea should be carried out. If obstructive sleep apnea is diagnosed, continuous positive airway pressure therapy might also improve the patient's myasthenia gravis.

A decrease in myocardial uptake of iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) has been reported in idiopathic Parkinson's disease (PD) using 123I-MIBG myocardial scintigraphy. However, the patient with autosomal recessive juvenile parkinsonism (AR-JP), caused by the parkin gene, presented here showed normal 123I-MIBG myocardial uptake, suggesting that AR-JP is a distinct disease entity from PD. Although the clinical features of AR-JP are sometimes quite similar to those of late-onset idiopathic PD, 123I-MIBG myocardial scintigraphy may be a powerful tool to differentiate PD from other parkinsonian syndromes, including AR-JP.

Background We estimated the stiffness parameter β (β value), which is useful in the assessment of premature atherosclerosis, among patients with different subtypes of cerebral infarction (CI; eg, small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined and undetermined etiologies) to determine the clinical utility of the β value in classification of stroke patients into CI subtypes. Methods Carotid ultrasonography (ALOKA ProSound SSD-alpha10) was performed in 31 CI patients and 38 control subjects, and the β value of the bilateral common carotid artery at 2.0 cm proximal to the bifurcation was measured using the echo-tracking method. The relationship between β value and age was examined, and the β value was compared among the different CI subtypes. Results Positive β value correlated with age in control subjects ( R = .69, P R = −.01, P = .996). There was no significant difference in the β value when comparing control patients and patients with cardioembolic stroke ( P = .106), but the β value were lower in patients with cardioembolic stroke than in patients with noncardioembolic stroke (eg, small-vessel occlusion, large-artery atherosclerosis, and others, P = .009). Conclusions The β value was lower in patients with cardioembolic stroke than in patients with noncardioembolic stroke. The β value may be useful for estimating the risk of different stroke subtypes.

We recently showed using prepro-orexin knockout (ORX-KO) mice and orexin neuron-ablated (ORX-AB) mice that orexin neurons in the hypothalamus, but not orexin peptides per se, are indispensable for stress-induced thermogenesis. To examine whether orexin neurons are more generally involved in central thermoregulatory mechanisms, we applied other forms of thermogenic perturbations, including brain prostaglandin E2 (PGE2) injections which mimic inflammatory fever and environmental cold exposure, to ORX-KO mice, ORX-AB mice and their wild-type (WT) litter mates. ORX-AB mice, but not ORX-KO mice, exhibited a blunted PGE2-induced fever and intolerance to cold (5°C) exposure, and these findings were similar to the results previously obtained with stress-induced thermogenesis. PGE2-induced shivering was also attenuated in ORX-AB mice. Both mutants responded similarly to environmental heating (39°C). In WT and ORX-KO mice, the administration of PGE2 and cold exposure activated orexin neurons, as revealed by increased levels of expression of c-fos. Injection of retrograde tracer into the medullary raphe nucleus revealed direct and indirect projection from the orexin neurons, of which the latter seemed to be preserved in the ORX-AB mice. In addition, we found that glutamate receptor antagonists (d-(–)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione) but not orexin receptor antagonists (SB334867 and OX2 29) successfully inhibited PGE2-induced fever in WT mice. These results suggest that orexin neurons are important in general thermogenic processes, and their importance is not restricted to stress-induced thermogenesis. In addition, these results indicate the possible involvement of glutamate in orexin neurons implicated in PGE2-induced fever.

Cerebral microbleeds (CMBs) are recognized as a manifestation of arteriolosclerosis in cerebral small vessels. However, little is known regarding whether stroke patients with CMBs often have systemic atherosclerosis. The aim of the present study was to elucidate this issue using the cardio-ankle vascular index (CAVI), a new index of systemic atherosclerosis, in acute ischemic stroke patients. We prospectively studied 105 patients (71 males, median age=70.0 years) with acute ischemic stroke. All of the patients were examined using T2*-weighted gradient echo magnetic resonance imaging (MRI) to look for and assess the CMBs and using fluid-attenuated inversion recovery to evaluate white matter hyperintensity (WMH). We assigned the patients into CMB and non-CMB groups and compared the clinical characteristics of these groups. The factors associated with CMBs were investigated using multivariate logistic regression analysis. T2*-weighted gradient echo MRI revealed CMBs in 47 patients (44.8%) and no CMBs in 58 patients (55.2%). The CAVI was significantly higher in the CMBs group (10.5 vs. 8.6, P

We report here in a 61-year-old woman in whom sensory disturbance predominantly affecting the distal portion of the limbs progressed over the course of 1 year. Blood tests showed IgM monoclonal gammopathy as well as the presence of anti-myelin-associated glycoprotein (MAG) antibody. Nerve conduction studies revealed significant prolongation of distal latency, and sural nerve biopsy showed IgM deposition on the myelin sheath. She was diagnosed as suffering anti-MAG neuropathy. High-dose intravenous immunoglobulin therapy proved to be ineffective and her symptoms progressed. Therefore, rituximab was administered and the sensory disturbance improved. Although no detailed studies on rituximab therapy for anti-MAG neuropathy have been reported in Japan, the present findings suggest that rituximab may be more effective than immunoglobulin therapy and other conventional therapies that have been used for autoimmune neuropathies.

Keywords: corticospinal tract; dying-back; magnetic resonance imaging; Waller degeneration; X-linked adrenoleukodystrophy

Deficiency in energy supply, such as occurs during hypoxia, anoxia, metabolic stress and mitochondrial failure, strongly affects the excitability of central neurons. Such lowered energy supply evokes various changes in spontaneous synaptic input to the hippocampal and cortical neurons. However, how this energy deprivation affects synaptic input to motor neurons, which are also vulnerable to energy deprivation, has never been addressed. Here we report for the first time the effect of metabolic stress on synaptic input to motor neurons by recording postsynaptic currents in the hypoglossal nucleus. Chemical anoxia with NaCN (1 mm) and anoxia with 95% N(2) induced a persistent inward current and a marked and robust increase in action potential-independent synaptic input. This increase was abolished by strychnine, but not by picrotoxin, CNQX or MK-801, indicating glycine release facilitation. Blockade of voltage-dependent Ca(2+) channels and extracellular Ca(2+) deprivation strongly attenuated this facilitation. The amplitude of inward currents evoked by local application of NMDA to the motor neurons in the presence of strychnine was significantly increased during NaCN application. A saturating concentration of d-serine occluded this potentiation, suggesting that released glycine activated the glycine-binding sites of NMDA receptors. By contrast, neurons in the dorsal motor nucleus of the vagus showed no detectable change in synaptic input in response to NaCN. These data suggest that increase in synaptically released glycine in response to metabolic stress may play an exacerbating role in NMDA receptor-mediated excitotoxicity in motor neurons.

A 26-year-old woman was admitted to our hospital for the treatment of hyperbaric oxygen therapy to acute carbon monoxide intoxication. The consciousness disturbance improved and she was discharged after 23 times of the hyperbaric oxygen therapy. However, she was readmitted because of dementia and urinary incontinence after 22 days. Diffusion-weighted images showed bright high signal intensities in the periventicular white matter and corpus callosum. The condition was considered to be an interval form of carbon monoxide intoxication. She was treated by 38 times of the hyperbaric oxygen therapy with cytochrome C and fully recovered. MRI images and cerebrospinal fluid abnormality (high protein content and IgG index) became normalized somewhat later than the improvement of the symptoms. By an investigation utilizing diffusion-weighted images, we thought that not only the demyelination which mentioned formerly, but the vasogenic edema was involving in the mechanism of these high signal intensities in the periventicular white matter of the interval form. And in the range which we searched, this is the first report which mentioned the abnormal findings of cerebrospinal fluid in an interval form of carbon monoxide intoxication. So we believe this case is very important for telling us suspected the mechanism and some indications about the treatment of an interval form.

We report on a 31-year-old gravid woman with reversible posterior leukoencephalopathy syndrome (RPLS) associated with HELLP syndrome. The patient was hospitalized and underwent an emergency cesarean section at the 34th week of pregnancy due to severe toxemia. After labor her blood pressure acutely increased to 180/100 mmHg and a generalized convulsion occurred. Laboratory data revealed hemolysis, elevated liver enzymes, and low platelets, consistent with HELLP syndrome. FLAIR and Apparent Diffusion Coefficient images on MRI showed hyperintense lesions bilaterally in the posterior white matter, however Diffusion-Weighted images revealed slightly hyperintense changes in the same locations. With the use of diltiazem for blood pressure control, and anticonvulsants, convulsions disappeared and consciousness level improved. Moreover the MRI abnormalities also improved after therapy. This case was diagnosed as RPLS associated with HELLP syndrome and is the first case of an investigation utilizing Diffusion-Weighted and Apparent Diffusion Coefficient images to establish this diagnosis. Based on these results, possible mechanisms of RPLS may be vasogenic edema mediated by a cerebrovascular endothelial disturbance of cerebral vessels and a rapid blood-pressure increase due to HELLP syndrome.

A decrease in myocardial uptake of iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) has been reported in idiopathic Parkinson's disease (PD) using 123I-MIBG myocardial scintigraphy. However, the patient with autosomal recessive juvenile parkinsonism (AR-JP), caused by the parkin gene, presented here showed normal 123I-MIBG myocardial uptake, suggesting that AR-JP is a distinct disease entity from PD. Although the clinical features of AR-JP are sometimes quite similar to those of late-onset idiopathic PD, 123I-MIBG myocardial scintigraphy may be a powerful tool to differentiate PD from other parkinsonian syndromes, including AR-JP.

Visual hallucinations (VHs) are common psychiatric symptoms in patients with long-standing Parkinson's disease (PD). Treatment with neuroleptics or withdrawal of anti-PD drugs may improve VHs but will worsen motor dysfunctions. The authors report on 3 patients with long-standing PD who were treated with the cholinesterase inhibitor donepezil for the treatment of VHs. Each received a daily dose of 5 mg of donepezil, after reducing or discontinuing anti-PD medications had failed to relieve the VHs. In 2 patients (patient 1, 2), donepezil decreased VHs without worsening motor dysfunctions. In addition, the cognitive status of patient 2 improved. In patient 3, donepezil also resolved VHs, but delusions developed during treatment. After discontinuing donepezil, delusions disappeared and VHs reappeared. Donepezil may ameliorate visual hallucinations in PD patients, but controlled, double-blind trials are necessary to further clarify the effect of this drug on VHs in PD. ( J Geriatr Psychiatry Neurol 2003; 16:184-188).