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1.
Encephalitis ; 4(2): 35-39, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38589019

ABSTRACT

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune disorder with diverse clinical manifestations including myelitis, meningitis, encephalitis, and optic neuritis. MOGAD rarely presents with unilateral cerebral cortical encephalitis (CCE), rendering the diagnosis difficult in these cases. Furthermore, MOGAD is frequently accompanied by other autoimmune diseases such as thyroid disease or inflammatory bowel disease. Herein, we report a case of unilateral CCE with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. In addition, our patient presented with systemic symptoms as well as neurologic symptoms and was finally diagnosed with ulcerative colitis (UC). A 60-year-old female was admitted to the hospital with an acute onset of headache and fever. Neurological examination revealed left-sided homonymous hemianopsia with intermittent visual hallucinations as flickering red-circular spots in the left visual field. Brain magnetic resonance imaging showed focal hyperintensities and enhancement in the right temporo-parieto-occipital cortex. Electroencephalography indicated a focal seizure in the right occipital cortex. After the administration of an antiepileptic drug, the patient showed clinical and radiological improvements. She tested positive for serum anti-MOG antibodies and was diagnosed with anti-MOG-associated unilateral CCE. However, the gastrointestinal symptoms persisted, thus, a sigmoidoscopy was performed. The patient was diagnosed with comorbid UC. Steroids were administered to treat the UC and the gastrointestinal symptoms improved. To the best of our knowledge, this is the first case of MOGAD presenting as a unilateral CCE in Korea. This case highlights the clinical phenotypes of MOGAD and the need to assess comorbid autoimmune diseases in patients with MOGAD.

2.
Sci Rep ; 14(1): 7228, 2024 03 27.
Article in English | MEDLINE | ID: mdl-38538679

ABSTRACT

Loss of myelin in the brain may lead to cognitive decline in Alzheimer's disease (AD). The ratio of T1 weighted/T2 weighted (T1w/T2w) on magnetic resonance imaging has been used as a proxy for myelin content in the brain. Using this approach, we investigated the correlation between the white matter (WM) T1w/T2w ratio and both cognitive scores and disease progression in AD. A total of 93 participants who were cognitively unimpaired or diagnosed with mild cognitive impairment or AD dementia were recruited between March 2021 and November 2022. All participants were assessed using neuropsychological tests, and a subset of the participants was assessed every 1 year to monitor disease progression. We observed significant positive associations between the WM T1w/T2w ratio and executive function within the fornix, sagittal stratum, anterior internal capsule, and body of the corpus callosum (False discovery rate [FDR]-corrected P-value < 0.05). There was a marginal interaction between the WM T1w/T2w ratio of the left anterior internal capsule and the longitudinal change in sum of boxes of the Clinical Dementia Rating Scale (FDR-corrected P-value = 0.05). The present study demonstrated that the WM T1w/T2w ratio was associated with executive function and disease progression, suggesting that it may be a novel neuroimaging marker for AD.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , White Matter , Humans , White Matter/diagnostic imaging , Alzheimer Disease/diagnostic imaging , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Cognition , Cognitive Dysfunction/diagnostic imaging , Myelin Sheath , Disease Progression
3.
J Ethnopharmacol ; 319(Pt 3): 117359, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-37924999

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Woohwangchungsimwon (WCW) is a traditional medicine used in East Asian countries to treat central nervous system disorders. Reported pharmacological properties include antioxidant effects, enhanced learning and memory, and protection against ischemic neuronal cell death, supporting its use in treating neurodegenerative diseases like Alzheimer's disease (AD). AIM OF THE STUDY: The study aims to assess the effects of co-treatment with WCW and donepezil on cognitive functions and serum metabolic profiles in a scopolamine-induced AD model. MATERIALS AND METHODS: Cell viability and reactive oxygen species (ROS) levels were measured in amyloid ß-peptide25-35 (Aß25-35)-induced SH-SY5Y cells. An AD model was established in ICR mice by intraperitoneal scopolamine administration. Animals underwent the step-through passive avoidance test (PAT) and Morris water maze (MWM) test. Hippocampal tissues were collected to examine specific protein expression. Serum metabolic profiles were analyzed using nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Co-treatment with WCW and donepezil increased cell viability and reduced ROS production in Aß25-35-induced SH-SY5Y cells compared to that with donepezil treatment alone. Co-treatment improved cognitive functions and was comparable to donepezil treatment alone in the PAT and MWM tests. Pathways related to tyrosine, phenylalanine, and tryptophan biosynthesis, phenylalanine metabolism, and cysteine and methionine metabolism were altered by co-treatment. Levels of tyrosine and methionine, major serum metabolites in these pathways, were significantly reduced after co-treatment. CONCLUSIONS: Co-treatment with WCW and donepezil shows promise as a therapeutic strategy for AD and is comparable to donepezil alone in improving cognitive function. Reduced tyrosine and methionine levels after co-treatment may enhance cognitive function by mitigating hypertyrosinemia and hyperhomocysteinemia, known risk factors for AD. The serum metabolic profiles obtained in this study can serve as a foundation for developing other bioactive compounds using a scopolamine-induced mouse model.


Subject(s)
Alzheimer Disease , Neuroblastoma , Humans , Mice , Animals , Mice, Inbred ICR , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Donepezil , Amyloid beta-Peptides , Reactive Oxygen Species , Cognition , Metabolome , Methionine , Phenylalanine , Tyrosine , Scopolamine Derivatives
4.
Dement Neurocogn Disord ; 22(4): 148-157, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38025407

ABSTRACT

Background and Purpose: Episodic memory is a system that receives and stores information about temporally dated episodes and their interrelations. Our study aimed to investigate the relevance of episodic memory to time perception, with a specific focus on simultaneity/order judgment. Methods: Experiment 1 employed the simultaneity judgment task to discern differences in time perception between patients with mild cognitive impairment or dementia, and age-matched normals. A mathematical analysis capable of estimating subjects' time processing was utilized to identify the sensory and decisional components of temporal order and simultaneity judgment. Experiment 2 examined how differences in temporal perception relate to performance in temporal order memory, in which time delays play a critical role. Results: The temporal decision windows for both temporal order and simultaneity judgments exhibited marginal differences between patients with episodic memory impairment, and their healthy counterparts (p = 0.15, t(22) = 1.34). These temporal decision windows may be linked to the temporal separation of events in episodic memory (Pearson's ρ = -0.53, p = 0.05). Conclusions: Based on our findings, the frequency of visual events accumulated and encoded in the working memory system in the patients' and normal group appears to be approximately (5.7 and 11.2) Hz, respectively. According to the internal clock model, a lower frequency of event pulses tends to result in underestimation of event duration, which phenomenon might be linked to the observed time distortions in patients with dementia.

5.
Encephalitis ; 3(4): 109-113, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37621190

ABSTRACT

The global severe acute respiratory syndrome coronavirus 2 pandemic contributed to the development of a large variety of vaccines, of which postvaccinal hyperacute encephalopathy is a very rare complication. Despite its rarity, if diagnosed properly, appropriate treatment can be rapidly applied. A healthy 53-year-old woman was admitted for a seizure on the day she received the second dose of the BNT 162b2 nCoV-19 vaccine. She subsequently developed irritability, which gradually worsened over several days. Cerebrospinal fluid analysis revealed mild pleocytosis and normal protein levels. Brain magnetic resonance imaging (MRI) revealed diffuse sulcal hyperintensity on the entire brain surface on fluid-attenuated inversion recovery images with meningeal enhancement. The patient was diagnosed with hyperacute postvaccinal encephalopathy and received immunosuppressive therapy with corticosteroids and therapeutic plasmapheresis. Fortunately, the patient responded to therapy, achieving almost complete recovery from the neurological symptoms, with only mild memory impairment remaining after 3 weeks. Based on the clinical presentation, electroencephalogram findings, and MRI, our patient developed hyperacute encephalopathy within 24 hours of vaccine administration, which we surmised from the temporal course of symptoms and brain imaging findings. Further studies are required to elucidate the pathogenesis of coronavirus disease 2019 vaccination-related encephalopathy.

6.
Healthcare (Basel) ; 11(14)2023 Jul 16.
Article in English | MEDLINE | ID: mdl-37510478

ABSTRACT

Behavioral and psychological symptoms of dementia are a major factor in the burden of care and medical expenses. Conventional pharmacological treatments do not exert a distinct effect on the benefits versus the risks. The herbal medicine woohwangchungsimwon is frequently prescribed for neuropsychiatric disorders. An effect of woohwangchungsimwon on behavioral and psychological symptoms of dementia has been previously reported; however, no clinical studies have been conducted. We aim to evaluate the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating these symptoms in probable Alzheimer's disease. In this randomized, assessor-blinded, parallel-group clinical trial, 74 participants with probable Alzheimer's disease will be divided via block randomization into a woohwangchungsimwon + donepezil combination group (n = 37) or a donepezil single group (n = 37). Participants will include patients under donepezil treatment for at least a month. We will perform the study for 24 weeks. The Neuro-Psychiatric Inventory subscale scores will be the primary outcome. Secondary outcomes will include cognitive function, dementia severity, physical function, quality of life, depression, anxiety, and insomnia. For safety evaluation, we will assess adverse reactions, measure vital signs, and conduct laboratory tests. This is the first trial aiming to confirm the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating behavioral and psychological symptoms of dementia. Its findings could provide a basis for their co-administration to control these symptoms in probable Alzheimer's disease.

7.
Epilepsy Behav ; 145: 109291, 2023 08.
Article in English | MEDLINE | ID: mdl-37336136

ABSTRACT

OBJECTIVE: To assess the effectiveness and tolerability of perampanel monotherapy following conversion from adjunctive therapy. METHODS: This was a multicenter, retrospective, non-interventional study of Korean patients aged ≥12 years with focal-onset seizures (FOS) with or without focal to bilateral tonic-clonic seizures. Data were extracted from electronic medical records of perampanel-treated patients from 1 February 2016 to 31 October 2020. Kaplan-Meier estimated retention rates, effectiveness, and safety were recorded. RESULTS: Subjects (n = 66, mean age 46.2 years) were mostly male (68.2%) with focal to bilateral tonic-clonic seizure (71.2%). Mean duration of illness was 86.3 months. Retention rates after conversion to perampanel monotherapy at 3, 6, and 12 months (primary outcome) were 96.0%, 96.0%, and 75.6%, respectively. Overall retention rates in patients receiving perampanel as adjunctive or monotherapy at 3, 6, 12, 18, and 24 months after perampanel add-on were 100%, 98.3%, 95.9%, 92.6%, and 92.6%, respectively. Mean retention duration was 41.2 months (overall perampanel administration) and 21.4 months (monotherapy). Mean seizure frequency/28 days in the Full Analysis Set (n = 61) was comparable for adjunctive and monotherapy (0.2 ± 0.79 vs 0.2 ± 0.64; change between adjunctive and monotherapy periods: 0.0 ± 0.59; p = 0.498). Perampanel was well tolerated and no new safety signals were identified. Dizziness (4.6%), only reported during adjunctive therapy, was the most common treatment-emergent adverse event. CONCLUSIONS: Conversion to perampanel monotherapy from adjunctive therapy showed promising results in subjects with FOS with/without focal to bilateral tonic-clonic seizures; further studies in a larger population are needed to confirm these encouraging data.


Subject(s)
Anticonvulsants , Seizures , Humans , Male , Middle Aged , Female , Retrospective Studies , Anticonvulsants/adverse effects , Treatment Outcome , Seizures/epidemiology , Pyridones/adverse effects , Drug Therapy, Combination , Republic of Korea
8.
Medicine (Baltimore) ; 101(38): e30301, 2022 Sep 23.
Article in English | MEDLINE | ID: mdl-36197176

ABSTRACT

Despite the urgent need to control dementia, an effective treatment has yet to be developed. Along with the Korean government's policy of cooperation between conventional medicine (CM) and Korean medicine (KM), integrative medical services for dementia patients are being provided. This study aimed to compare the integrative medical clinic (IMC) for dementia used by Dongguk University Hospitals (DUH) with other service models and to review the characteristics and treatment outcomes of patients who had visited DUH over the past 5 years. Patients' electronic medical records from May 2015 to June 2020 were searched and their data were analyzed to evaluate the IMC's service model. Patient demographic and clinical characteristics, diagnostic tests, and treatment patterns for CM and KM were collected. The proportion of patients who did not show worsening cognitive function was described in detail. A strength of the DUH integrative medicine clinic is its ability to manage both KM and CM patients in the same space at the same time. Among the 82 patients who visited the clinic during our study period, 56 remained for data analysis after we excluded patients who met the exclusion criteria; nineteen patients had diagnoses of mild cognitive impairment. Among collaboration patterns, the first visit to the IMC had the highest proportion (55.4%). Among diagnosed tests in CM, laboratory tests and neuropsychological tests were used the most. In KM, a heart rate variability test was frequently used. The most common CM treatment prescribed was anticonvulsants, with 22 patients (39.2%) receiving donepezil, whereas the most frequent KM treatments were acupuncture (82.1%) and herbal medicine (78.6%). Twelve patients were followed up with the Mini-Mental State Examination, and 8 demonstrated either no worsening or improved cognition (baseline Mini-Mental State Examination range: 21-26). All 8 patients had mild cognitive impairment including 6 with amnestic, multidomain impairment. This study searched for a way to improve cognitive dysfunction and dementia using an integrative approach, and it shows promising results for mild cognitive impairment. However, more precisely designed follow-up studies are needed to address the present work's limitations of a retrospective study design and a small sample size.


Subject(s)
Cognitive Dysfunction , Dementia , Integrative Medicine , Anticonvulsants , Cognition , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/therapy , Dementia/complications , Dementia/diagnosis , Dementia/therapy , Donepezil/therapeutic use , Humans , Neuropsychological Tests , Retrospective Studies
9.
J Korean Soc Radiol ; 83(4): 945-950, 2022 Jul.
Article in English | MEDLINE | ID: mdl-36238909

ABSTRACT

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a common autoimmune encephalitis that is noted to be a severe but treatable disease entity. Patients with anti-NMDAR encephalitis often develop psychotic symptoms, including delusions, hallucinations, and paranoia, as well as memory impairment and persistent loss of attention. However, MRI findings in such patients show no abnormalities in most cases. Although typical brain abnormality features, known as T2 hyperintensities, involve the brain parenchyma and contrast enhancement at the cerebral cortex or overlying meninges, isolated leptomeningeal enhancement has been rarely reported in anti-NMDAR encephalitis. Herein, we report a patient with anti-NMDAR encephalitis who presented with isolated leptomeningeal enhancement, additionally showing the diagnostic value of contrast-enhanced fluid-attenuated inversion recovery imaging.

10.
Curr Alzheimer Res ; 19(3): 246-263, 2022.
Article in English | MEDLINE | ID: mdl-35422218

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is a lethal, progressive neurodegenerative disorder that has been linked to a deficiency of the neurotransmitter acetylcholine. Currently, many acetylcholinesterase inhibitors, such as donepezil, are widely used for the treatment of AD. On the other hand, the efficacy of long-term donepezil use is limited. SIP3, a mixture of three herbal extracts from Santalum album, Illicium verum, and Polygala tenuifolia, is a new formula derived from traditional Korean herbal medicine. OBJECTIVE: We assessed the synergistic effect of SIP3 and donepezil co-treatment on symptoms of AD using APP/PS1 transgenic mice. METHODS: In this study, a Drosophila AD model and SH-SY5Y clles were used to assess the toxicity of SIP3, and APPswe/PS1dE9 (APP/PS1) transgenic mice were used to evaluate the cognitive-behavioral and depression-like behavior effect of SIP3 and donepezil co-treatment on symptoms of AD. The cerebral cortex or hippocampus transcriptomes were analyzed by RNA sequencing and miRNA to investigate the molecular and cellular mechanisms underlying the positive effects of SIP3 on AD. RESULTS: In the passive avoidance test (PAT) and Morris water maze (MWM) test, the combination of SIP3 and donepezil improved the learning capabilities and memory of APP/PS1 mice in the mid-stage of AD compared to the group treated with donepezil only. In addition, co-administration of SIP3 and donepezil effectively reduced the depression-like behavior in the forced swimming and tail suspension tests. Furthermore, RNA sequencing of the cerebral cortex transcriptome and miRNA of the hippocampus showed that the gene expression profiles after a low dose SIP3 co-treatment were more similar to those of the normal phenotype mice than those obtained after the donepezil treatment alone. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, showed that differentially expressed genes were involved in the locomotor behavior and neuroactive ligand-receptor interactions. These results suggest that a co-treatment of low dose SIP3 and donepezil improves impaired learning, memory, and depression in the mid-stage of AD in mice. CONCLUSION: Co-treatment of low dose SIP3 and donepezil improves impaired learning, memory, and depression in the mid-stage of AD in mice.


Subject(s)
Alzheimer Disease , MicroRNAs , Neuroblastoma , Acetylcholinesterase/metabolism , Alzheimer Disease/complications , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Depression , Disease Models, Animal , Donepezil/pharmacology , Herbal Medicine , Hippocampus/metabolism , Humans , Maze Learning , Mice , Mice, Inbred C57BL , Mice, Transgenic
11.
Epilepsy Behav ; 112: 107446, 2020 11.
Article in English | MEDLINE | ID: mdl-32919205

ABSTRACT

PURPOSE: There have been little researches examining the role of family functioning on psychological outcomes in the field of adult epilepsy. We determined whether family functioning is correlated with felt stigma in adults with epilepsy. METHODS: In this cross-sectional study, adults with epilepsy and their caregivers were recruited. Data were collected using the Family Adaptability and Cohesion Evaluation Scale (FACES) III, the Family adaptation, partnership, growth, affection, and resolve (APGAR) questionnaire, the Stigma Scale for Epilepsy (SS-E), the modified questionnaire for episodes of discrimination, and the Beck Depression Inventory. Family functioning was measured by the caregivers. RESULTS: A total of 273 adult patients and their primary caregivers were included. Multivariate logistic analyses showed that family cohesion and excellent family functioning were negatively correlated with felt stigma after controlling for confounding variables. Enacted stigma, depressive symptoms, and university education were also significant. Interaction between enacted stigma and family cohesion on felt stigma was significant (p = 0.049). Family cohesion was negatively correlated with felt stigma only in the patients with enacted stigma (p = 0.011). CONCLUSIONS: Family functioning especially family cohesion may have protective effects against development of felt stigma in adults with epilepsy. Such protecting effects against felt stigma may be different according to enacted stigma. This understanding is helpful for developing effective psychosocial interventions to reduce felt stigma in patients with epilepsy.


Subject(s)
Epilepsy , Social Stigma , Adult , Cross-Sectional Studies , Emotions , Family Relations , Humans
12.
J Korean Med Sci ; 35(24): e207, 2020 Jun 22.
Article in English | MEDLINE | ID: mdl-32567259

ABSTRACT

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a potentially life-threatening but reversible autoimmune disorder characterized by psychiatric symptoms, cognitive dysfunction, speech dysfunction, seizures, movement disorder, decreased level of consciousness, and autonomic dysfunction or central hypoventilation. It occurs predominantly in young women and approximately half of them have underlying tumors, mainly ovarian teratoma. A 24-year old woman was admitted because of fever, headache, abnormal movement and decreased mental status. Five cycles of plasmapheresis improved her neurological and mental status. Anti-NMDAR antibodies in her CSF and serum were positive, and computed tomography revealed a 1-cm sized mass suggestive of mature cystic teratoma arising from the right ovary. We promptly performed laparoscopic right ovarian cystectomy. She was discharged after 2 weeks with mild memory deficit. Prompt removal of ovarian teratoma and multidisciplinary care are particularly important for good outcome.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnosis , Ovarian Neoplasms/diagnosis , Teratoma/diagnosis , Abdomen/diagnostic imaging , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/complications , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/pathology , Female , Humans , Ovarian Neoplasms/complications , Ovarian Neoplasms/pathology , Pelvis/diagnostic imaging , Plasmapheresis , Teratoma/complications , Teratoma/pathology , Thorax/diagnostic imaging , Tomography, X-Ray Computed , Young Adult
13.
Technol Health Care ; 28(4): 439-446, 2020.
Article in English | MEDLINE | ID: mdl-32444584

ABSTRACT

BACKGROUND: Sleep monitoring is essential to maintain a healthy life, especially for the elderly who want to age well. Among various forms of sleep devices, the non-wearable and home-adapted device might be preferred because it can be easily used. OBJECTIVE: In this study, we evaluated the performance of a non-contact home-adapted device compared to polysomnography (PSG), a gold standard method. METHODS: As a preliminary study, eight subjects were recorded over fourteen nights through PSG. The non-contact home-adapted device comprised a microwave sensor, passive infrared sensor, and smartphone application. Through the device, heart rate, respiratory rate, and body movement were collected and used to estimate sleep stages. Sleep structure was labeled in four classes: wake, REM, light, and deep sleep, and were classified using a weighted k-nearest neighbor algorithm. RESULTS: The device correctly estimated sleep structures with an overall epoch-by-epoch accuracy of 98.65% ± 0.05% based on leave-one-out cross-validation. The device showed significantly positive correlations with PSG in sleep indices including total sleep time, sleep efficiency, and wake after sleep onset. CONCLUSIONS: Our findings demonstrate a good performance of this non-contact and home-adapted device and suggest its suitability for sleep monitoring.


Subject(s)
Sleep Stages , Heart Rate , Humans , Male , Middle Aged , Movement , Polysomnography
14.
Neuroreport ; 30(18): 1289-1293, 2019 12 18.
Article in English | MEDLINE | ID: mdl-31688423

ABSTRACT

Torrance Test of Creative Thinking is the most widely used form of creativity test. Although creativity assessed using the figural form of Torrance Test of Creative Thinking has been considered non-unidimensional, the structural correlates for each separable dimension have yet to be explored. The present study investigated the underlying cortical structure of separable dimensions for creativity using the figural Torrance Test of Creative Thinking. To this end, we recruited healthy young adults and conducted a regression analysis of the figural Torrance Test of Creative Thinking scores of gray matter volume after factorizing the five subscales using exploratory factor analysis. As a result, two factors of the figural Torrance Test of Creative Thinking were identified: (1) 'FO' factor consisting of fluency and originality and (2) 'RAS' factor consisting resistance to premature closure, abstractness of titles, and sophistication/elaboration. Subsequently, the FO factor showed a positive association with cerebral volumes in the parieto-temporal regions of the left angular gyrus and the right inferior parietal lobule, inferior and middle temporal, and parahippocampal gyri, which overlapped the default network. The RAS factor showed a positive correlation with the fronto-temporal regions including the bilateral temporal area, the left inferior parietal, and the right dorsolateral prefrontal regions representing the semantic control network. Our findings revealed the morphological substrates for the figural Torrance Test of Creative Thinking depending on two creative dimensions. The implications of the results are discussed.


Subject(s)
Brain/diagnostic imaging , Creativity , Gray Matter/diagnostic imaging , Thinking/physiology , Adolescent , Female , Humans , Image Processing, Computer-Assisted , Male , Neuropsychological Tests , Young Adult
15.
Int Clin Psychopharmacol ; 34(3): 131-137, 2019 05.
Article in English | MEDLINE | ID: mdl-30855515

ABSTRACT

This retrospective observational study was performed to investigate electroencephalogram abnormalities in clozapine-treated patients with refractory schizophrenia or bipolar disorder. The electroencephalogram and plasma clozapine and norclozapine levels in 71 patients were measured on the same day. Fifty-nine patients (85.9%) had a diagnosis of schizophrenia, and 12 patients (14.1%) had a diagnosis of bipolar disorder. The mean daily clozapine dose was 242.9 ± 105.5 mg (range 25-500 mg), and the mean plasma clozapine and norclozapine levels were 429.4 ± 264.1 and 197.8 ± 132.6 ng/ml, respectively. Twenty-five patients (35.2%) were taking valproate in combination with clozapine. electroencephalogram abnormalities were found in 51 (71.8%) patients. No patient reported clinical seizures. Plasma clozapine level was significantly associated with electroencephalogram abnormalities and was identified as a significant predictor of electroencephalogram abnormalities in a logistic regression analysis. The plasma norclozapine levels of patients taking both clozapine and valproic acid were significantly lower than those of patients treated with clozapine alone. These results demonstrate that electroencephalogram abnormalities are closely correlated with plasma clozapine levels. Valproate reduced plasma norclozapine levels. Simultaneous monitoring of electroencephalogram and plasma clozapine levels was useful for adjusting clozapine doses, improving clinical efficacy, and preventing the side effects of clozapine treatment.


Subject(s)
Clozapine/adverse effects , Clozapine/blood , Electroencephalography/drug effects , Adult , Antipsychotic Agents/adverse effects , Bipolar Disorder/drug therapy , Drug Monitoring , Female , Humans , Male , Middle Aged , Retrospective Studies , Schizophrenia/drug therapy , Treatment Outcome , Valproic Acid/therapeutic use
16.
J Epilepsy Res ; 8(1): 33-40, 2018 Jun.
Article in English | MEDLINE | ID: mdl-30090760

ABSTRACT

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) leads to cognitive dysfunction and neuronal loss, both of which can be exacerbated by seizures. For the treatment and diagnosis of AD, it is imperative to identify the cortical characteristics of comorbidities of AD such as seizures. The present study investigated the alterations in cortical volumes in patients with comorbid AD and seizures. METHODS: In this retrospective study, magnetic resonance T1-weighted brain images were collected from six patients with early AD or amnestic mild cognitive impairment without seizures (AD-No Seizure, age: 66.17 ± 4.92 years) and six individuals with seizures (AD-Seizure, age: 80.33 ± 4.63 years). The gray matter volumes estimated from the T1 images were compared between the groups using nuisance variables (e.g., age). Subsequently, a correlation analysis was performed to investigate the relationship between cortical structure and global cognitive function. RESULTS: AD-Seizure group showed volumetric alterations compared with AD-No Seizure group. In the volumetrically altered regions, correlation analysis revealed that the AD-Seizure group showed a positive correlation between the mini-mental state examination (MMSE) score and cortical volume, with smaller volumes than the AD-No Seizure group in the right parahippocampal gyrus, left angular gyrus, and middle temporal gyrus. The AD-No Seizure group showed negative correlations with MMSE score in the volume of right inferior frontal gyrus and cerebellar culmen and a positive correlation with the volume of the left middle frontal gyrus. CONCLUSIONS: Our findings revealed that smaller temporal region volumes are predictive of cognitive dysfunction in AD patients with seizures. Given that these temporal areas overlap with regions showing abnormal brain activities in AD patients with seizures, these results suggest synergistic effects of AD and seizures on cortical volume and cognitive function.

17.
J Neuroimmunol ; 315: 1-8, 2018 02 15.
Article in English | MEDLINE | ID: mdl-29306399

ABSTRACT

Autoimmune and unknown/cryptogenic encephalitis have been increasingly noted in the inflammatory etiology of new-onset status epilepticus (SE). We aimed to investigate clinical characteristics and the potential role of immunotherapy in encephalitis-related adult SE through our multicenter prospective SE registry. Among the 274 patients with SE, 35 (12.8%) patients demonstrated an inflammatory etiology and 19 out of 35 (54.3%) patients demonstrated unknown/cryptogenic cause. Patients with autoimmune and unknown/cryptogenic encephalitis shared similar clinical features. In unknown/cryptogenic encephalitis, the proportion of favorable outcomes (mRS 0-3) showed a different propensity at 3-6months after discharge between patients receiving active immunotherapy and not receiving any immunotherapy, although it was not statistically significant (at admission 28.6% vs 20%, p=0.603; at discharge 57.1% vs 60%, p=0.570; at 3-6months after discharge 90% vs 60%, p=0.214 in patients treated with active immunotherapy or without immunotherapy, respectively). Extensive autoantibody screening should be carried out and empirical immunotherapy may be potentially helpful even in patients without antibodies, although longer term and multi-national studies may be necessary to make a stronger recommendation.


Subject(s)
Encephalitis/complications , Encephalitis/immunology , Encephalitis/therapy , Immunotherapy/methods , Status Epilepticus/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Young Adult
18.
Neural Netw ; 98: 251-262, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29287188

ABSTRACT

An overview is provided of dynamic artificial neural network models (DANNs) for nonlinear dynamical system identification and control problems, and convex stability conditions are proposed that are less conservative than past results. The three most popular classes of dynamic artificial neural network models are described, with their mathematical representations and architectures followed by transformations based on their block diagrams that are convenient for stability and performance analyses. Classes of nonlinear dynamical systems that are universally approximated by such models are characterized, which include rigorous upper bounds on the approximation errors. A unified framework and linear matrix inequality-based stability conditions are described for different classes of dynamic artificial neural network models that take additional information into account such as local slope restrictions and whether the nonlinearities within the DANNs are odd. A theoretical example shows reduced conservatism obtained by the conditions.


Subject(s)
Algorithms , Neural Networks, Computer , Nonlinear Dynamics , Computer Simulation/statistics & numerical data
19.
J Epilepsy Res ; 7(1): 57-59, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28775958

ABSTRACT

Palinacousis is an auditory illusion rarely reported in cases of temporal lobe dysfunction. After reviewing the literature and comparing our clinical experience, we believe that palinacousis can occur as an aura, a simple partial seizure, a complex partial seizure, and/or a postictal event. Palinacousis maybe more common than recognized in patients with receptive aphasias or diffuse cerebral dysfunction, whose language deficits preclude adequate description. We report the case of a 71 years old man with the previously diagnosis of an infarction of left middle cerebral artery and valvular heart disease who presented with the symptoms of palinacousis. He was not diagnosed psychotic diseases. An electroencephalography showed normal wave. He was diagnosed as temporal lobe epilepsy with palinacousis due to post-stroke. Palinacousis was completely reversed after treatment with antiepileptic drug. We report that palinacousis as an epileptic phenomenon can help localized potential lesions and can improve patient care.

20.
Dement Neurocogn Disord ; 16(2): 48-53, 2017 Jun.
Article in English | MEDLINE | ID: mdl-30906370

ABSTRACT

BACKGROUND AND PURPOSE: Torrance Tests of Creative Thinking (TTCT) is a well-known and commonly used measure of creativity. However, the TTCT-induced creative hemodynamic brain activity is rarely revealed. The purpose of this study is to elucidate the neural correlates of creative thinking in the setting of a modified version of the figural TTCT adapted for an functional magnetic resonance imaging (fMRI) experiment. METHODS: We designed a blocked fMRI experiment. Twenty-five participants (11 males, 14 females, mean age 19.9±1.8) were asked to complete the partially presented line drawing of the figural TTCT (creative drawing imagery; creative). As a control condition, subjects were asked to keep tracking the line on the screen (line tracking; control). RESULTS: Compared to the control condition, creative condition revealed greater activation in the distributed and bilateral brain regions including the left anterior cingulate, bilateral frontal, parietal, temporal and occipital regions as shown in the previous creativity studies. CONCLUSIONS: The present revealed the neural basis underlying the figural TTCT using fMRI, providing an evidence of brain areas encompassing the figural TTCT. Considering the significance of a creativity test for dementia patients, the neural correlates of TTCT elucidated by this study may be valuable to evaluate the brain function of patients in the clinical field.

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