M.K. Kim

Serotonergic and BDNF genes and risk of depression after stroke

BACKGROUND Polymorphisms of serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) have been investigated as candidate genes for post-stroke depression (PSD). Serotonin 2a receptor (5-HTR2a) genes have not been yet investigated in PSD. This study aimed to investigate whether the 5-HTT, 5-HTR2a, and BDNF genes are associated with PSD independently and/or interactively in a Korean sample with high prevalence of risk alleles. METHODS In 276 stroke cases, depression was diagnosed using DSM-IV at 2 weeks after stroke, further classified to major PSD (N=29), all (major plus minor) PSD (N=77), and control (N=199) groups. Associations between PSD and 5-HTTLPR, STin2 VNTR, 5-HTR2a 1438A/G, 5-HTR2a 102T/C, and BDNF val66met genotypes were estimated using logistic regression models, and gene-gene interactions were investigated using the generalized multifactor dimensionality reduction method. RESULTS 5-HTR2a 1438 A/A genotype was associated with major PSD, while 5-HTTLPR s/s and BDNF met/met genotypes were associated with all PSD. There was a significant interaction between 5-HTR2a 1438A/G and BDNF val66met polymorphisms for major PSD and a borderline significant interaction between 5-HTTLPR and BDNF val66met polymorphisms for all PSD. CONCLUSIONS In a large cohort, we found evidence for serotonin and BDNF polymorphisms as susceptibility factors and gene-gene interactions between these systems for depression at 2 weeks post-stroke.

The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea

Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73-19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61-27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95-284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia.

Clinical features and epileptogenesis of dysembryoplastic neuroepithelial tumor

IntroductionDysembryoplastic neuroepithelial tumor (DNT) frequently causes medically intractable epilepsy.ObjectiveThe aim of this study was to investigate the basic mechanism of epileptogenecity of the tumor.Materials and methodsClinicopathological data in 13 cases of DNT and immunohistochemical changes of ionotropic glutamate receptor subunits in the tumor and peritumoral epileptogenic cortex were studied.ConclusionsMagnetic resonance imaging combined with electroencephalography (EEG), electrocorticography, and depth-electrode EEG was valuable to localize complicated epileptogenic zones of the patients with DNT. Neuropathological examinations of the peritumoral cerebral cortex presenting abnormal spikes showed different histopathological grades of neuronal migration disorder (NMD). The tumor cells in DNT disclosed increased immunopositivities of N-methyl-d-aspartate receptor 1 (NR1) and NR2A/B, and peritumoral epileptogenic NMD revealed increased immunopositivities of GluR2 and GluR3. The amplification of ionotropic glutamate receptor subunits in the tumor and peritumoral NMD may be the underlying cause of epileptic seizures in DNT patients.

The serum ferritin level is an important predictor of hemorrhagic transformation in acute ischaemic stroke.

Background and purpose:  Because hemorrhagic transformation (HT) is associated with morbidity and mortality, we need a better understanding of the factors that predict HT after ischaemic stroke. HT is a well‐known factor that limits the use of thrombolytics and it negates the effect of treatment. This study investigated whether a high serum ferritin level is associated with HT in acute ischaemic stroke.

Thrombolysis as a factor associated with favorable outcomes in patients with unclear-onset stroke.

Background and purpose:  Clinical and radiological features of patients with unclear‐onset stroke do not differ significantly from those with known‐onset stroke. There is a lack of evidence for the safety and efficacy of thrombolysis in patients with unclear‐onset stroke. We sought to provide supportive data on the safety and efficiency of thrombolysis in patients with unclear‐onset stroke.

Spontaneous Vertebral Artery Dissection Mimicking Cluster Headache

Trigeminal autonomic cephalalgias (TACs) are characterized by severe, strictly unilateral pain in the territory of the distribution of the trigeminal nerve in association with autonomic manifestations (1). The International Headache Society (IHS) classification divides strictly unilateral headaches into three groups: cluster headache (CH), episodic and chronic paroxysmal hemicrania (PH), and shortlasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (1). Symptomatic TACs are not common. However, they have been reported in association with the lesions of the sellar or parasellar structures, internal carotid artery dissection and vertebro-basilar artery diseases (1, 2). As for the disorders involving the vertebral artery, a case of a vertebral artery aneurysm and some cases of vertebral artery dissections (VADs) with lateral medullary infarctions have been reported (3–6). To the best of our knowledge, there has not been any case report of VAD without infarction that was manifested by cluster-like headache. We describe here a case of a spontaneous VAD that presented with cluster-like headache without other neurological manifestations.

Granuloma pyogenicum arising in an arteriovenous haemangioma associated with a port‐wine stain

Sir, Epidermal grafting with suction blisters is used in treatment of stable vitiligo. Previous reports have shown various complications including postinflammatory hyperpigmentation, peripheral hypopigmentation and hypertrophic scarring. However, the risk of infection has not been reported to date. We report an unusual case of verruca vulgaris that appeared after epidermal grafting. It seems likely that virus particles might have been transferred from the operator, who had verruca vulgaris on his hand, to the patient during the surgical procedure. A 12-year-old girl with localized stable vitiligo was treated by epidermal grafting. Blisters on the recipient site formed within 24 h after three freeze±thaw cycles with liquid nitrogen. Blisters on the donor site were made by suction on the inner portion of the thigh. After approximately 3 h of suction at 200 mmHg, large unilocular bullae appeared. After removal of the blisters at the recipient site, the epidermal sheets were grafted to the denuded recipient site and held in place. Two weeks after grafting, once weekly systemic psoralen-ultraviolet A treatment was started. Almost complete repigmentation was observed 3 months after grafting. Four months after grafting, the patient noticed two verrucous plaques in the grafted site (Fig. 1). She denied warts on any other body sites. There was no history of similar lesions in her family or close friends. The operator, who wore gloves, had a verrucous papule on his hand during the surgery. Skin biopsy of two different lesions, on the patients back and the operators hand, demonstrated histological features of verruca vulgaris. Human papillomavirus (HPV) typing was not performed. Although epidermal grafting appears to be an effective and safe method for the treatment of vitiligo, various complications have been reported, of which some are associated with the application of liquid nitrogen, such as postinflammatory hyperpigmentation, hypertrophic scarring, peripheral hypopigmentation and uneven pigmentation. Koebner phenomenon and recurrence have also been considered complications of epidermal grafting. The possibility of transmission of virus from patient to patient or from patient to doctor has been reported. One study showed that virus may survive on a cotton swab dipped into liquid nitrogen and suggested that virus transmission from patient to patient may occur via this route. Charles and Sire reported the possibility of transmission of papovavirus indirectly by cotton-tipped applicators which had been used earlier to treat verruca in other patients. In our case, the same liquid nitrogen and cotton-tipped applicators were not used for multiple patients. Bergbrant et al. reported that there is a risk of contamination of the operator by HPV DNA, during both carbon dioxide laser and electrocoagulation treatment. Once an individual has been infected, new warts may develop in sites of inoculation over a period of weeks to months. After experimental HPV inoculation, it requires from 2 to 9 months for a verruca to become clinically apparent. This observation implies a relatively long period of subclinical infection. In our patient, the verruca appeared 4 months after grafting. It is unclear whether the verruca vulgaris resulted from direct contact with the operators hand during the surgical procedure, or with another person after grafting. However, there are several possible mechanisms of viral transmission from the operator to the patient: the operator may have palpated the lesion with his bare hand immediately after cryosurgery to evaluate the effectiveness of the freezing, or transmission may have occurred during application of a dressing after surgery. We suggest that the risk of transmission of infection from doctor to patient should be considered as a new complication of epidermal grafting.

Valproate associated diffuse alveolar hemorrhage.

Sir, Valproic acid (VPA) is a widely used antiepileptic drug for the prevention and treatment of generalized and focal epilepsy. Although clinical bleeding with this drug seems relatively uncommon, VPA possesses a well-described association with a tendency toward increased bleeding [1]. A variety of laboratory hematological abnormalities in the coagulation system that are associated with VPA have been reported. Studies have described VPA as affecting platelet function, and it also may affect coagulation factors, such as fibrinogen and factor VIII [2]. Affected individuals have usually been children undergoing chronic VPA treatment. In addition, there have been reports of coagulation disorders, with fatal manifestations, in valproate therapy [3]. However, no previous study has reported reversible diffuse alveolar hemorrhage (DAH) without thrombocytopenia in a patient receiving VPA monotherapy. A 15-year-old boy with epilepsy was admitted to our hospital because of a 3-minute, generalized seizure. He had been receiving chronic VPA treatment since age 10 for well-controlled, juvenile myoclonic epilepsy. He had tolerated the VPA well throughout the treatment, without obvious adverse effects and, notably, without any evidence of coagulopathy. He had no history of bleeding events. And he had not been treated with other medications. His VPA monotherapy (20mg/kg body weight/day) continued after this incident. Four months later, he presented with hemoptysis and dyspnea. On physical examination, we heard crackles over both his lungs. The neurologic examination was normal. Chest radiographs revealed diffuse lung infiltrations in both lungs, suggestive of DAH, and extensive hemorrhagic aspirations (Figures A, D, and E). Laboratory tests showed his hemoglobin was 14.6 mg/dL and his platelet count was 215,000/mm. Bleeding time, clotting time, prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen were entirely normal. The patient s plasma VPA level was 69.75 lg/mL (reference range, 50 to 100 lg/mL). WBC count was 15100/mL, and CRP was 0.5 mg/dL. We administered broad-spectrum antibiotics but withdrew them immediately because of the patient s severe skin rash. To determine the etiology of the pulmonary process, we performed a diagnostic bronchoscopy, with bronchoalveolar lavage (BAL), and a transbronchial biopsy. The bronchoscopy revealed scattered blood aspirates in both bronchial trees, which, upon cytologic examinations of the BAL fluid and transbronchial biopsy specimen, were consistent with alveolar hemorrhage. Cultures for bacteria, fungi, and mycobacteria, as well as viral cultures, from the patient s blood, urine, and BAL specimens were negative. Autoimmune antibody tests, including for ANA, ANCA, anticardiolipin Ab, and anti-GBM Ab, for Goodpasture s syndrome or vasculitis were also entirely negative. On day 2 after the VPA treatment termination, the patient s chest radiographs showed marked improvement (Figure B). After 1 week, he had recovered

Usefulness of direct sequencing of pooled DNA for SNP identification and allele-frequency determination compatible with a common disease/common variant hypothesis

We examined the efficiency of direct sequencing of pooled DNA for developing common single nucleotide polymorphisms (SNPs) and its accuracy for estimating allele frequencies. A pool of 200 control DNAs was established and was used for developing SNPs and estimating minor allele frequencies (MAF). The sensitivity of the pooled DNA method for successfully detecting an SNP with an MAF >0.01 listed in the database was approximately 0.7; it was particularly efficient for detecting SNPs with MAF >0.1, which is compatible with the common disease/common variant hypothesis. The mean difference between the estimated and the observed MAFs was 0.03 +/- 0.023. The pooled DNA method identified four additional SNPs, for which the allele frequency information was not available in the database. The pooled DNA method is a cost- and time-effective tool for both qualifying and quantifying SNPs with considerable accuracy, and it can be particularly useful for dissecting the common disease/common variant hypothesis; this represents a best-case scenario for large-scale association mapping.

The association of infarct pattern on coronal diffusion-weighted MR image and early neurologic deterioration in deep subcortical infarction

WCN 2013 No: 289 Topic: 3 — Stroke Clinico-epidemiological features of cerebral venous thrombosis in Algarve H. Nzwalo, F. Rodrigues, P. Carneiro, L. Arez, F. Ferreira, C. Basilio. Neurology, Faro Hospital, Faro, Portugal; Internal Medicine, Centro Hospitalar do Barlavento Algarvio E.P.E., Portimao, Faro, Portugal; Universidade do Algarve, Faro, Portugal Background: Cerebral vein thrombosis (CVT) is a very uncommon disorder with a wide variety of clinical manifestations. Little information exists about CVT, particularly from peripheral regions. Objective: To describe the epidemiology and clinical characteristics of CVT in a relatively small region. Material and methods: Hospital based retrospective study of CVT occurred between January 2001 and December 2012, in the public hospitals serving a population of 395,218–451,005 habitants. Results: Thirty-five cases of CVT were identified. Children (4) and non-residents (3) were excluded from the analysis. Gross incidence was approximately 0.56–0.64/100,000 cases/year. The mean and median ages were 40.4 and 35 years respectively [18–71 years]. The majority (21/75%) were woman. The mean interval between the onset of symptoms and the diagnosis was 8 days [8–41 days]. Patients presented with isolated intracranial hypertension (17/61%), focal syndrome (4/14%), and encephalopathy (7/25%). Brain TC was diagnostic in 10 (42%) cases. Brain MRI and MR venography was performed in all. Use of oral contraceptives was found in 14/66 % of females, with/without other risk factors. In 6 (21%), no risk factor was found. All cases received heparin or LMWH followed by warfarin. Complete recovery occurred in 24 (85 %); death in 1 (3.6%); important sequels in 3 (11%): epilepsy, severe visual loss and motor deficit. Conclusion: Our findings are comparable to those described in similar case series. However, in comparison to what has been found in our country (0.22/100,000 cases/year), our incidence is high. Diagnosis improvement, availability of MRI, and use of oral contraceptives may explain this. doi:10.1016/j.jns.2013.07.670 Abstract — WCN 2013 No: 325 Topic: 3 — Stroke The value of apparent diffusion coefficient maps in subcortical infarct lesion D.S. Oh, M.H. Park, D.E. Kim, K.H. Choi, Y.J. Choi, T.S. Nam, J.T. Kim, S.H. Lee. Department of Neurology, ChonnamNational University Hospital, Gwang-Ju, Republic of Korea Background: Prediction of the early neurologic deterioration (END) in patients with acute ischemic stroke is one of great clinical interests. Objective: This study was designed to analyze whether apparent diffusion coefficient (ADC) values provide reliable quantitative information for the prediction of the neurologic deficits in stroke patients. Patient and methods: We reviewed 36 patients not treated by thrombolytics who had a diffusion restricted lesion in deep subcortical area within 24 h after stroke onset. Serial National Institutes of Health Stroke Scale (NIHSS) scores were checked from admission. We compared the ADC values in the initial diffusion weighted image (DWI). We tested the value of the ADC to predict tissue outcome and development of END. All images were processed on an independent workstation by using custom software (MIDAS 1.11). Results: Among 36 patients, 14 patients developed END and 22 patients did not develop END. Univariate analysis showed that the ADC values in diffusion restricted lesion were significantly decreased in patient that developed to END compared with those that remained without END. (p value = 0.037). Conclusions: Initial ADC values can predict the development of END in patient with deep subcortical infarct. doi:10.1016/j.jns.2013.07.671 Abstract — WCN 2013 No: 266 Topic: 3 — Stroke The association of infarct pattern on coronal diffusion-weighted MR image and early neurologic deterioration in deep subcortical infarction WCN 2013 No: 266 Topic: 3 — Stroke The association of infarct pattern on coronal diffusion-weighted MR image and early neurologic deterioration in deep subcortical infarction D.S. Oh, D.E. Kim, K.H. Choi, Y.J. Choi, T.S. Nam, J.T. Kim, S.H. Lee, B.C. Kim, M.K. Kim. Department of Neurology, Chonnam National University Hospital, Gwang-Ju, Republic of Korea Background: Early neurological deterioration (END) is frequently observed in patients with small deep infarction of subcortical area. Objective: In this study, we investigated the association between the END and the patterns of small deep infarction in coronal diffusionweighted imaging (DWI). Patients and methods: Consecutive 95 patients diagnosed with acute ischemic stroke in subcortical area, whowere admitted to stroke center betweenMarch 2008 and June 2009, were included. Brain coronal DWI and MR angiography (MRA) were carried out. The patterns of infarct lesions are divided into 3 categories: (1) lacunar pattern; isolated lesion in the subcortical area, (2) skipped pattern: lesions that presented with disconnected shape, separated by unaffected white matter of internal capsule, on coronal DWI, (3) linear pattern; linear lesion extending to the basal surface on coronal DWI. ENDwas defined as an increase of 2 or more points of the National Institutes of Health Stroke Scale (NIHSS) within 7 days of stroke onset. Results: 23 patients were presented with lacunar pattern, 20 with skipped patterns, and 52 patients with linear pattern. END was observed in 36 (45.8%). Patients with skipped and lacunar patterns on coronal DWI experienced END less frequently than those with linear patterns (25% vs. 55.8% and 8.7% vs. 55.8%, p = 0.034 and 0.000, respectively). Abstracts / Journal of the Neurological Sciences 333 (2013) e152–e214 e160