Multidetector computed tomography angiography to detect the cause of multiple brain infarctions.

BACKGROUND: Multidetector computed tomography angiography (MDCTA) is useful to inspect cardiovascular pathologic changes with minimal invasiveness. Here we evaluated the usefulness of MDCTA to determine the cause of acute multiple brain infarction (AMBI). METHODS: AMBI was defined as multiple recent infarcts demonstrated on diffusion-weighted imaging. A new infarction within 2 weeks from the last was also considered an AMBI. RESULTS: Between January 2012 and December 2013, 967 patients were diagnosed with acute brain infarction and 138 (14.3%) with AMBI. Among them, 57 (39 men and 18 women; age, 38-93 years) were examined by MDCTA using the dual-phase method. All images were diagnostic, even if patients found it difficult to hold their breath. Fifteen patients (26.3%) were diagnosed with patent foramen ovale (PFO). Two had complications of atrial fibrillation (AF), necessitating anticoagulant therapy (ACT). Four had both PFO and severe aortic atherosclerotic plaque formation, necessitating single antiplatelet therapy (APT) and/or ACT. Fifteen patients (26.3%) developed complicated arterial plaques around the aortic arch and were administered single or dual APT and/or ACT, except 1 patient with a history of multiple cerebral bleeding. Nine patients had pre-existing AF. Furthermore, ACT was initiated for 2 other patients with thrombus or circulatory stasis in the left atrial appendage despite normal electrocardiographic findings. Two other patients were diagnosed with advanced cancer, which was considered Trousseau syndrome. The cause of AMBI was determined in 36 (63.2%) patients. CONCLUSIONS: MDCTA is a useful and less invasive method to identify the cause of embolic infarction.

Amantadine may reverse punding in Parkinson's disease--observation in a patient.

Punding, complex stereotyped behavior, sometimes occurs in patients with Parkinson's disease under dopaminergic replacement therapy. Reduction of dopaminergic drugs may reduce the problem but risks enhancing motor impairment. We report a patient with Parkinson's disease presenting disabling punding, which was reversed by amantadine without aggravating motor function. Amantadine may reduce punding by blocking NMDA receptors, in the same manner as in levodopa-induced dyskinesias.

A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia.

Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia.

Prevalence of subclinical coronary artery disease in ischemic stroke patients.

BACKGROUND: Recently, ischemic stroke has emerged as a new coronary artery disease (CAD) risk equivalent. Our purpose is to study the prevalence of CAD in ischemic stroke patients compared with that in non-stroke patients. METHODS AND RESULTS: We measured coronary calcium score (CCS) in 151 ischemic stroke patients without known CAD (stroke group) and compared it with 151 age- and sex-matched non-stroke patients (control group). CCS was significantly higher in the stroke group than in the control group (stroke group, median: 64, interquartile range: 3-382 vs. control group, median: 3, interquartile range: 0-65, p<0.0001). High-risk CAD, defined as a CCS≥400, was detected in 24.5% of the stroke group compared with 9.3% of the control group (p<0.0001). Agreement between the Framingham risk score and CCS was found in only 62 patients (41.1%). In a multiple logistic regression analysis, age [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.03-1.14], diabetes (HR 2.97, 95%CI 1.52-5.78), stroke (HR 3.85, 95%CI 1.89-7.81), and male sex (HR 4.41, 95%CI 1.82-0.75) were significantly associated with high-risk CAD (p<0.001). CONCLUSIONS: Our results show that the prevalence of subclinical CAD in ischemic stroke patients was high, and that a quarter of them had high-risk CAD. Age, diabetes, stroke, and male sex were independent predictors of high-risk CAD.

The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia.

BACKGROUND: The dihydropyrimidinase-related protein (DRP) family, also called the collapsin response mediator protein, is implicated in the developmental process of the nervous system. Dysfunction of DRPs may result in neurodevelopmental abnormalities, which may be a factor in the pathogenesis of schizophrenia. The expression of one member of DRP-2 in humans has been reported to be decreased in the brains of people with schizophrenia. In addition, the DRP-2 gene (Dihydropyrimidinase-like 2; DPYSL2) is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. METHODS: We investigated a genetic association between five polymorphisms of the DRP-2 gene and schizophrenia in the Japanese population. RESULTS: The *2236T>C polymorphism in the 3' untranslated region (3'UTR) exhibited significant differences with respect to the distribution of the genotype and allele in patients compared with control subjects. The frequency of the *2236C allele was significantly higher in control subjects than patients with schizophrenia (p =.0097) and paranoid-type schizophrenia (p =.0083). CONCLUSIONS: Our results suggest that the *2236C allele in the 3'UTR of the DRP-2 gene, or an unknown mutation in linkage disequilibrium with this allele, may reduce the susceptibility to schizophrenia, especially the paranoid subtype.

No association between the dihydropyrimidinase-related protein 2 (DRP-2) gene and bipolar disorder in humans.

Several susceptibility loci for both of schizophrenia and bipolar disorder (BPD) have been found to overlap on several chromosomes including 8p21. Expression of dihydropyrimidinase-related protein 2 (DRP-2), which gene is located on 8p21, was found to be reduced in the brains of individuals with schizophrenia and BPD. Recently, we demonstrated a significant association between the DRP-2 gene and schizophrenia. Based on the rationale, we investigated the genetic association of the DRP-2 gene with BPD using a case-control study in the Japanese population. However, no significant associations were found between five polymorphisms of the DRP-2 gene (-975C>G, 352G>A, 426C>T, 1506T>C, and *2236T>C), and BPD, nor were associations detected between either of the polymorphisms and any subtype of BPD, bipolars I and II. The present study did not provide any evidence for a contribution of the DRP-2 gene to susceptibility to BPD.

Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder.

Brain-derived neurotrophic factor (BDNF) belongs to a family of neurotrophic factors and has been demonstrated to promote the survival, differentiation, and maintenance of a broad variety of central nervous system neurons. Several reports have suggested that the BDNF gene is a plausible functional candidate gene underlying the predisposition for developing bipolar disorder (BPD). In the present study, we investigated the possible role of the BDNF gene in the etiology of BPD using a matched case-control association design in a Japanese population. There was no evidence for an allelic or genotypic association of two polymorphisms (-1360C>T and 196G>A) of the BDNF gene with BPD. Furthermore, no significant association was observed between these polymorphisms and either of two diagnostic subtypes (bipolars I and II disorder). The results suggest that the BDNF gene is unlikely to confer susceptibility to BPD.

The human frizzled-3 (FZD3) gene on chromosome 8p21, a receptor gene for Wnt ligands, is associated with the susceptibility to schizophrenia.

Neurodevelopmental abnormalities have been reported in studies on the pathogenesis of schizophrenia. The Wnt-signaling pathway has been implicated in a variety of processes in neurodevelopment, and the frizzled proteins have been identified as receptors for Wnt ligands. Of the frizzled proteins, frizzled-3 (FZD3) is required for formation of the neural crest and for development of major fiber tracts in the CNS. The human FZD3 gene is located on chromosome 8p21, a positive linkage locus for schizophrenia. We analyzed polymorphisms of the FZD3 gene in patients with schizophrenia and control subjects in the Japanese population. We found a significant association between schizophrenia and the FZD3 gene in single nucleotide polymorphisms and haplotype analyses. Our data suggest that dysregulation of the Wnt-signaling pathway may be involved in the susceptibility to schizophrenia.

No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studies.

BACKGROUND: Several lines of evidence have supported possible roles of the sigma receptors in the etiology of schizophrenia and mechanisms of antipsychotic efficacy. An association study provided genetic evidence that the sigma receptor type 1 gene (SIGMAR1) was a possible susceptibility factor for schizophrenia, however, it was not replicated by a subsequent study. It is necessary to evaluate further the possibility that the SIGMAR1 gene is associated with susceptibility to schizophrenia. METHODS: A case-control association study between two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Gln2Pro, and schizophrenia in Japanese population, and meta-analysis including present and previous studies. RESULTS: There was no significant association of any allele or genotype of the polymorphisms with schizophrenia. Neither significant association was observed with hebephrenic or paranoid subtype of schizophrenia. Furthermore, a meta-analysis including the present and previous studies comprising 779 controls and 636 schizophrenics also revealed no significant association between the SIGMAR1 gene and schizophrenia. CONCLUSION: In view of this evidence, it is likely that the SIGMAR1 gene does not confer susceptibility to schizophrenia.

[Progress of introduction of artificial respirator at home--the knowledge I have gained from a 19 year-old patient requiring a home respiratory management care and through the friendship with his family members].

The patient developed right cerebellar hemorrhage at the age of 15 and spent four years at hospital. The patient and the family members had a strong wish to bring the patient back home and the patient was admitted to the hospital to undergo guidance about home medical care. The patient had paralysis of right upper and lower extremities and generalized strong ataxic motion and was under gastric feeding and had underwent tracheotomy to cope with hypoventilation, which required use of an artificial respirator at night hours. Since the patient was still as young as 19, we want to have the patient "go home" as they wanted. Fortunately, the mother who had to play key roles was still young and the parents worked at home. It didn't take long for them to master the techniques though they had various anxieties. It is considered important in the guidance on home medical care to what degrees the caregivers accept the condition of the patient and can imagine the long lasting care at home. We provided assistance while repeatedly interviewing with the patient and family members considering the significance to confirm their willingness and psychological condition. As a result, the patient was discharged from the hospital in two months. Now, two years have passed, and the patient is still cared at home and the possibility of the patient is sought for. The progress is reported here in this article.

Frequency and clinical correlates of retrocollis in Parkinson's disease.

PURPOSE: To investigate the incidence of retrocollis and to determine its clinical correlates in patients with idiopathic Parkinson's disease (PD). METHODS: Seventy-four patients with PD at Hoehn and Yahr stage 5 were examined for abnormal neck postures and were classified according to neck posture. Differences in age, age at PD onset, disease duration, years from PD onset to Hoehn and Yahr stage 5, cognitive state, the levodopa equivalent dose (LED) for dopaminergic drugs, and rigidity of the neck and upper and lower extremities were examined to determine the clinical correlates of abnormal neck posture. We also evaluated retrocollis in 356 patients with PD at Hoehn and Yahr stage 1, 2, 3, and 4 and 65 age matched normal controls. RESULTS: Of the 74 patients with PD at Hoehn and Yahr stage 5 examined, 21 (28.4%) had retrocollis, 3 (4.1%) had antecollis, and 1 (1.4%) had antecollis and torticollis. Whereas, only one patient had retrocollis in PD patients at Hoehn and Yahr stage 4 and under. Patients with antecollis were significantly younger than those with normal neck posture and retrocollis. There were no differences in age at PD onset, disease duration, sex, years from PD motor symptom onset to Hoehn and Yahr stage 5, cognitive state, or LED between patients with and without abnormal neck postures. Neck rigidity scores were significantly higher in patients with retrocollis and antecollis than in those with normal neck posture. CONCLUSIONS: Retrocollis is not rare in patients with PD at Hoehn and Yahr stage 5, and the incidence appeared to increase as axial rigidity increased.

High-dose intravenous methylprednisolone for the prophylactic treatment of cluster headache.

BACKGROUND: Triptans are effective for immediate relief of episodic cluster headache (CH) but do not reduce the frequency of attacks. Intravenous bolus injection of corticosteroids like methylprednisolone (MP) has been reported to decrease the frequency of CH attacks. We validated the prophylactic efficacy of MP pulse therapy by monitoring CH recurrence over several years following treatment of six consecutive male patients (mean age: 38.8 years, range: 26-54 years) afflicted by frequent (often daily) CH attacks. FINDINGS: Total MP dose per infusion was 250-500 mg for five patients and 125 mg for the sixth (a diabetic). High-dose MP was administered for 2 or 3 consecutive days in hospital for the first two patients treated. The next four patients received a single bolus injection at presentation, and in some cases a second injection days later at an outpatient clinic. The first two cases treated were also prescribed daily oral prednisolone for at most 6 months while the latter four cases were not. The frequency of CH attacks was markedly reduced in all patients, with intervals between attacks ranging from 4 to 23 months. We noted no apparent adverse events following MP administration. CONCLUSIONS: High-dose MP therapy reduced CH attack frequency and improved patient quality of life.

Clinical correlates of anterior and lateral flexion of the thoracolumbar spine and dropped head in patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is often accompanied by postural disorders such as anterior and lateral flexion of the thoracolumbar spine and dropped head. We examined frequencies and clinical correlates of postural disorders in patients with PD. METHODS: We interviewed 365 consecutive PD patients between 40 and 80 years of age, at Hoehn and Yahr stages 1, 2, 3 and 4, and evaluated postural deformities, including anterior and lateral flexion of the trunk and dropped head as well as other clinical characteristics. Control subjects were 65 age-matched patient spouses without neurological or spinal disorders. RESULTS: There were no differences in age or sex between PD patients and controls. The frequencies of anterior and lateral flexion of the trunk were significantly higher in PD patients than in controls. The frequency and severity of anterior and lateral flexion and the incidence of dropped head increased as the disease progressed. Other factors related to anterior and lateral flexion included age, disease duration, lower MMSE score, lumbago and levodopa equivalent daily dose of dopaminergic drugs. Women tended to develop more severe anterior flexion than men. Anterior flexion severity also correlated with that of lateral flexion and the emergence of dropped head. CONCLUSIONS: Postural disorders are frequent complications in PD patients and their severity increases with disease progression. Advancing age and disease severity may be the major risks for developing postural disorders.

Frequency and characteristics of taste impairment in patients with Parkinson's disease: results of a clinical interview.

OBJECTIVE: Patients with Parkinson's disease (PD) frequently complain of a diminished sense of smell. Less frequently, they may complain of taste impairment. In the present study, we investigated the symptoms, frequency, and severity of taste impairment as well as smell impairment in PD patients and compared the results with those of age- and sex-matched healthy controls. PATIENTS AND METHODS: We interviewed 285 PD patients (120 men, 165 women) without dementia or nasal problems. Control subjects comprised 61 (20 men, 41 women) healthy spouses of the PD patients. Alteration of smell and taste sense lasting more than 3 months was defined as abnormal. RESULTS: One hundred and sixteen patients with PD complained of smell impairment and 26 complained of taste impairment. Only 5 controls complained of smell impairment, and no control subjects reported taste impairment. Taste impairment was more marked in patients with smell impairment. Impaired taste included diminished taste perception in 21 patients, altered sense of taste in 4 patients and burning mouth in 1 patient. CONCLUSION: Taste as well as smell perception is impaired in patients with PD. The frequency of smell and taste impairments tended to increase with disease progression.

Cardiac 123I-MIBG uptake is reduced more markedly in patients with REM sleep behavior disorder than in those with early stage Parkinson's disease.

We investigated cardiac uptake of (123)I-metaiodobenzylguanidine (MIBG) in patients with REM sleep behavior disorder (RBD) and compared the findings with those of idiopathic Parkinson's disease (IPD). Thirteen RBD, 222 IPD and 50 controls underwent cardiac (123)I-MIBG scintigraphy. Resulting heart-to-mediastinum (H/M) ratios were significantly lower in patients with RBD and IPD as compared to the control ratios. H/M ratios were lower for delayed than for early images in patients with RBD and IPD; whereas, the controls had higher ratios for delayed images. H/M ratios were significantly lower for patients with RBD than for those with IPD at Hoehn and Yahr stages 1 and 2. Disease duration did not differ between the two groups. Our study revealed that cardiac (123)I-MIBG uptake was more markedly reduced in patients with RBD than in those with early stage IPD. RBD may not necessarily be a prodromal condition of IPD with respect to cardiac (123)I-MIBG uptake results.

Association study between the fibronectin gene and schizophrenia.

Fibronectin is one of the cell adhesion proteins. Adhesion molecules play an important role in neural and synaptic genesis, and their dysfunction may result in neurodevelopmental abnormalities, which have been assumed to be a factor in the pathogenesis of schizophrenia. To examine the possible involvement of fibronectin in the etiology of schizophrenia, we analyzed six polymorphisms, located in introns 2, 21, 24, and 26, and exons 20 and 28, in the human fibronectin gene (FN1) of schizophrenic patients in the Japanese population (n = 104) and age-and gender-matched controls (n = 104). No significant positive association was observed between either of the polymorphisms and schizophrenia, nor was an association found between either of the polymorphisms and any subtypes of schizophrenia. These data did not provide evidence for a contribution of the FN1 gene to susceptibility to schizophrenia.

Association of the Neprilysin gene with susceptibility to late-onset Alzheimer's disease.

Neprilysin (NEP), also known as neutral endopeptidase, enkephalinase, CD 10, and common acute lymphoblastic leukemia antigen, is a 97-kD protein. NEP can degrade amyloid beta peptides, and its mRNA and protein levels are known to be reduced in the brains of patients with Alzheimer's disease (AD), making the NEP gene a substantial candidate for an AD risk factor. We examined the genetic association of three NEP polymorphisms, a GT-repeat polymorphism and two single nucleotide polymorphisms (SNPs, -1075A>G and -1284G>C) in its promoter region, with AD in a Japanese case-control sample (240 patients and 163 controls). The GT-repeat polymorphism, but not the SNPs, was significantly associated with late-onset AD (p = 0.0007). Our findings suggest that the GT-repeat polymorphism in the promoter region of the NEP gene or some other unknown polymorphisms, which are in a linkage disequilibrium, confer a susceptibility to late-onset AD.

No association between the insulin degrading enzyme gene and Alzheimer's disease in a Japanese population.

Susceptibility to Alzheimer's disease (AD) is thought to be regulated by multiple genetic factors. Recently, three independent studies have reported that loci on chromosome 10q are linked with AD, and the insulin degrading enzyme (IDE; MIM 146680) gene located on chromosome 10q23-q25; IDE is located close to the maker D10S583, which exhibits a maximum LOD score for late-onset AD. We examined seven polymorphisms in the IDE gene, the marker D10S583 in the 5' flanking region, and SNPs in introns 1, 3, 11, 20, 21, and 22 (rs#1999764, 1855915, 1970244, 538469, 551266, and 489517, respectively). Four SNPs in introns 3, 11, 20, and 22 did not exhibit any polymorphisms in the Japanese population that was studied. D10S583 and two SNPs in introns 1 and 21 did not exhibit a significant association with early- or late-onset AD. In addition, no associations were observed for subgroups of AD grouped according to APOE status. The present study indicates that the IDE gene polymorphisms do not confer susceptibility to early- or late-onset AD at least in a Japanese population.