Labeling Dual Presynaptic Inputs using cFork Anterograde Tracing System

Understanding brain function-related neural circuit connectivity is essential for investigating how cognitive functions are decoded in neural circuits. Trans-synaptic viral vectors are useful for identifying neural synaptic connectivity because of their ability to be transferred from transduced cells to synaptically connected cells. However, concurrent labeling of multisynaptic inputs to postsynaptic neurons is impossible with currently available trans-synaptic viral vectors. Here, we report a neural circuit tracing system that can simultaneously label postsynaptic neurons with two different markers, the expression of which is defined by presynaptic input connectivity. This system, called “cFork (see fork)”, includes delivering serotype 1-packaged AAV vectors (AAV1s) containing Cre or flippase recombinase (FlpO) into two different presynaptic brain areas, and AAV5 with a dual gene expression cassette in postsynaptic neurons. Our in vitro and in vivo tests showed that selective expression of two different fluorescence proteins, EGFP and mScarlet, in postsynaptic neurons could be achieved by AAV1-mediated anterograde trans-synaptic transfer of Cre or FlpO constructs. When this tracing system was applied to the somatosensory barrel field cortex (S1BF) or striatum innervated by multiple presynaptic inputs, postsynaptic neurons defined by presynaptic inputs were simultaneously labeled with EGFP or mScarlet. Our new anterograde tracing tool may be useful for elucidating the complex multisynaptic connectivity of postsynaptic neurons regulating diverse brain functions.

Genitopatellar Syndrome Secondary to De Novo KAT6B Mutation: The First Genetically Confirmed Case in South Korea

Genitopatellar syndrome (GPS) is a rare disorder characterized by patellar hypoplasia, flexion contractures of the lower limbs, psychomotor retardation and genital and renal anomalies. We report the case of a female infant diagnosed with GPS to a KAT6B gene mutation, which was identified using whole exome sequencing.

Gait Patterns in Parkinson's Disease with or without Cognitive Impairment

BACKGROUND AND PURPOSE: Cognitive and gait disturbance are common symptoms in Parkinson's disease (PD). Although the relationship between cognitive impairment and gait dysfunction in PD has been suggested, specific gait patterns according to cognition are not fully demonstrated yet. Therefore, the aim of this study was to investigate gait patterns in PD patients with or without cognitive impairment. METHODS: We studied 86 patients at an average of 4.8 years after diagnosis of PD. Cognitive impairment was defined as scoring 1.5 standard deviation below age- and education-specific means on the Korean version of the Mini-Mental State Examination (K-MMSE). Three-dimensional gait analysis was conducted for all patients and quantified gait parameters of temporal-spatial data were used. Relationships among cognition, demographic characteristics, clinical features, and gait pattern were evaluated. RESULTS: Cognitive impairment was observed in 41 (47.7%) patients. Compared to patients without cognitive impairment, patients with cognitive impairment displayed reduced gait speed, step length, and stride length. Among K-MMSE subcategories, “registration,”“attention/calculation,” and “visuospatial function” were significantly associated with speed, step length, and stride length. However, age, disease duration, Hoehn-Yahr (HY) stage, or Unified Parkinson's Disease Rating Scale (UPDRS) motor score was not significantly related to any gait analysis parameter. CONCLUSIONS: Our present study shows that cognitive impairment is associated with slow and short-stepped gait regardless of HY stage or UPDRS motor score, suggesting that cognitive impairment may serve as a surrogate marker of gait disturbance or fall in PD patients.

Embolic Stroke of Undetermined Source Accompanied by Lipomatous Hypertrophy of Interatrial Septum

No abstract available.

Unusual FDG-PET Findings in Traumatic Brain Injury; Did Traumatic Brain Injury Provoke Rapid Progression of Alzheimer's Disease?

No abstract available.

Hypertension and Neuropsychiatric Symptoms in Patients with Drug-Naïve Alzheimer's Disease

BACKGROUND AND PURPOSE: Neuropsychiatric symptoms (NPS) such as anxiety, depression, and delusions affect up to 90% of all patients with Alzheimer's disease (AD). NPS is associated with significant caregiver burden and patient distress. Given the severe burden of NPS in AD, it is critical to know potential modifiable risk factors of NPS in AD. This study explores the association between hypertension and NPS in patients with drug-naïve AD. METHODS: We reviewed medical records of 149 patients with AD with (n=80) and without (n=69) hypertension. NPS were assessed using the Korean version of Neuropsychiatric Inventory (K-NPI). Affective, psychotic, and behavior symptom clusters were assessed separately. RESULTS: The total score of K-NPI was not significantly different between patients with AD with and without hypertension. Among K-NPI domains, scores of depression/dysphoria (p=0.045), anxiety (p=0.022), and apathy/indifference (p=0.037) were significantly higher in patients with AD with hypertension. Systolic blood pressure (BP) was associated with higher total K-NPI and affective symptom cluster scores. Diastolic BP was associated with affective symptom cluster scores. CONCLUSIONS: Results suggest that hypertension increases risk of specific NPS in patients with AD. Among NPS, hypertension was associated with affective symptom cluster.

Persistent Hiccup Treated by Levetiracetam

No abstract available.

Inhibitory Effect of Rotundarpene on Parkinsonian Neurotoxin 1-Methyl-4-Phenylpyridinium-Induced Apoptotic Cell Death

BACKGROUND: The extract and hemiterpene glycosides of Ilex Rotunda Thunb exert antioxidant and anti-inflammatory effects. The effect of rotundarpene on apoptosis in neuronal cells caused by the 1-methyl-4-phenylpyridinium (MPP⁺) has not been reported previously. METHODS: Using differentiated PC12 cells and human neuroblastoma SH-SY5Y cells, we investigated the effect of rotundarpene on MPP⁺-caused apoptosis in relation to the cell death process. RESULTS: MPP⁺-induced cell death was identified using the MTT and neutral red uptake tests. Apoptosis was induced by eliciting decreases in the cytosolic levels of Bid and Bcl-2 proteins, increases in the cytosolic levels of Bax and p53, disruption of the mitochondrial transmembrane potential, and the release of cytochrome c and the activation of caspase-8, -9, and -3 in differentiated PC12 cells and SH-SY5Y cells. Treatment with rotundarpene reduced the MPP⁺-induced changes in the levels of apoptosis-regulated proteins, formation of reactive oxygen species, depletion and oxidation of glutathione, and cell death in both PC12 and SH-SY5Y cells. CONCLUSIONS: Rotundarpene may reduce MPP⁺-induced apoptosis in neuronal cells by suppressing the activation of the mitochondria-mediated pathway and the caspase-8 and Bid pathways. Rotundarpene appears to act by inhibiting the production of reactive oxygen species and by the depletion and oxidation of glutathione.

Inhibitory Effect of Apocynin on Proteasome Inhibition-Induced Apoptosis in Differentiated PC12 Cells

BACKGROUND: The dysfunction of the proteasome system has been implicated in neuronal degeneration. Apocynin, a specific inhibitor for nicotinamide adenine dinucleotide phosphate oxidase, has anti-inflammatory and anti-oxidant effects. However, the effect of apocynin on the neuronal cell death induced by proteasome inhibition has not been studied. METHODS: Using differentiated PC12 cells, in the respect of cell death process the suppressive effect of apocynin on the proteasome inhibition-mediated apoptosis was examined. RESULTS: The proteasome inhibitors MG132 and MG115 induced a decrease in Bid and Bcl-2 protein levels, an increase in Bax and p53 levels, mitochondrial depolarization, efflux of cytochrome c into cytosol and increase in caspases (-8, -9 and -3) activities. Treatment with apocynin attenuated the proteasome inhibitor-induced changes in the apoptosis-related protein levels, formation of reactive oxygen species, glutathione (GSH) depletion and cell death. CONCLUSIONS: Apocynin may attenuate the proteasome inhibitor-mediated apoptosis in differentiated PC12 cells by inhibiting the activation of the mitochondria-mediated pathway and the caspase-8- and Bid-dependent pathways. The preventive effect of apocynin appears to be attributed to inhibition of the production of reactive oxygen species and the depletion of cellular GSH contents.

Differences in the clinical manifestations and short-term prognosis of acute cerebral infarction after exposure to Agent Orange

BACKGROUND: Agent Orange (AO) is the code name for one of the herbicides and defoliants used in the Vietnam War. Studies conducted thus far show a significant correlation between AO and the occurrence of cardiovascular diseases. But there is little data on the association between AO and stroke, and limited studies have targeted patient groups exposed to AO. METHOD: Bohun medical center Institutional Review Board (IRB) approved the study. (ID: 341) We studied patients with acute ischemic stroke within 7 days of onset in VHS medical center and 4 other general hospitals. Among them, 91 consecutive patients with previous exposure to AO were evaluated. For controlled group, 288 patients with no history of AO exposure were chosen. RESULT: There were 49 (44.0 %) DM patient with a higher frequency in the exposure group (93 (32.3 %) in control P = 0.045). There were 6 (6.6 %) hyperlipidemia in exposure group and 69 (24.0 %) in control. (P < 0.002). Small vessel occlusion was the most common subtype (36, 39.6 %) in exposure group but in control group, the large artery atherosclesosis was (120, 41.7 %) (P = 0.014). The NIHSS of the exposure group on admission showed lower scores (median values, 2 and 4, respectively; P = 0.003). The median mRS was 1 for the exposure group and 2 for the control group, at discharge and after 3 months. After 3 months of discharge, 55 (60.4 %) in the exposure group and 171 (59.4 %) in the control group showed below mRS 1 (P = 0.001). CONCLUSION: This study targeted patients who are Vietnam veteran. There is some difference in vascular risk factors and clinical manifestations suggest AO exposure has contributed to a certain extent to the stroke.

Unilateral Sudden Deafness Accompanied by Short Circumferential Pontine Artery Territorial Infarction

No abstract available.

A Recurrent Ischemic Stroke Stabilization after Using Non-Vitamin K Antagonist Oral Anticoagulant (NOAC)

Current stroke guidelines recommend the administration of non-vitamin-K-antagonist oral anticoagulant (NOAC) for the prevention of cardioembolic stroke induced by nonvalvular atrial fibrillation. We report a patient who suffered from recurrent posterior circulation strokes-occurring eight times in 4 months-even under adequate antiplatelet medication. Changing the medication from antiplatelet agents to NOAC stopped the stroke recurrence. We suggest that NOAC has a role in the prevention of recurrent stroke of undetermined etiology in the posterior circulation.

Hypertensive Encephalopathy with Atypical Imaging Findings

No abstract available.

Cervicogenic Headache due to Seronegative Rheumatoid Arthritis

No abstract available.

Hyperintense Cerebrospinal Fluid on Fluid Attenuation Inverse Recover Image Caused by Left Internal Carotid Arterty Stenosis

No abstract available.

Inhibitory Effect of 3,4,5-Tricaffeoylquinic Acid on Parkinsonian Toxin 1-Methyl-4-phenylpyridinium-induced Apoptosis

BACKGROUND: 1-Methyl-4-phenylpyridinium (MPP+) causes a neuronal cell injury that is similar to the findings observed in Parkinson's disease. Caffeoylquinic acid derivatives have demonstrated anti-oxidant and anti-inflammatory effects. Nevertheless, the effect of 3,4,5-tricaffeoylquinic acid (3,4,5-triCQA) on the neuronal cell death due to exposure of parkinsonian toxin MPP+ remains unclear. METHODS: Using differentiated PC12 cells, the preventive effect of 3,4,5-triCQA on the MPP+-induced cell death in relation to apoptotic process was examined. RESULTS: MPP+ induced a decrease in Bid, Bcl-2 and survivin protein levels, increase in Bax levels, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (-8, -9 and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. 3,4,5-Tricaffeoylquinic acid attenuated the MPP+-induced changes in the apoptosis-related protein levels, formation of reactive oxygen species, depletion of GSH, nuclear damage and cell death. 3,4,5-Tricaffeoylquinic acid attenuated another parkinsonian neurotoxin rotenone-induced cell death. CONCLUSIONS: 3,4,5-Tricaffeoylquinic acid may attenuate the MPP+-induced apoptosis in PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The preventive effect seems to be ascribed to its inhibitory effect on the formation of reactive oxygen species and depletion of GSH.

Spinocerebellar Ataxia Type 2 with Only Clinical Feature of Memory Impairment: Case Report

Spinocerebellar ataxia (SCA) is one of a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. There are more than 35 different types of spinocerebellar ataxias, each caused by a different genetic mutation. Spinocerebellar ataxia type 2 (SCA2) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I) characterized by truncal ataxia, dysarthria, slowed saccades and less commonly ophthalmoparesis and chorea. The age at onset varies from 3 to 79 years (mean 33). Usually, the first symptom of the disease is the gait ataxia, followed by the cerebellar dysarthria. Of late, other clinical manifestations of SCA2 are the cognitive dysfunctions, which include frontal executive impairment, verbal short-term memory deficits as well as reduction of attention and concentration. We report a 56-year old woman identified as spinocerebellar ataxia type 2 (SCA2) with only clinical feature of memory impairment.

Inhibitory Effect of Flavonoid Luteolin on 6-Hydroxydopamine Cytotoxicity via Suppression of Apoptosis-Related Protein Activation

BACKGROUND: Flavonoid luteolin has been shown to exhibit cell protective effect. However, it is still uncertain whether the effect of luteolin on cellular toxicity of the parkinsonian toxin 6-hydroxydopamine is mediated by apoptosis-related protein activation. METHODS: In differentiated PC12 cells exposed to 6-hydroxydopamine in combination with luteolin, we observed the apoptosis-related protein activation, nuclear damage, formation of reactive oxygen species and cell death. RESULTS: 6-Hydroxydopamine caused apoptosis by inducing a decrease in Bid, Bcl-2, Bcl-xL and survivin levels, increase in Bax levels, cytochrome c release and activation of caspases. Treatment with luteolin reduced changes in the apoptosis-related protein levels, formation of reactive oxygen species, nuclear damage and cell death. CONCLUSIONS: Luteolin may reduce the 6-hydroxydopamine-induced apoptosis in differentiated PC12 cells by suppressing the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway, leading to caspase activation. The preventive effect of luteolin may be associated with its inhibitory effect on the production of reactive oxygen species. Luteolin may attenuate the oxidative stress and mitochondrial dysfunction-induced neuronal cell death take place in Parkinson's disease.

A Case of Prosopometamorphopsia Restricted to the Nose and Mouth with Right Medial Temporooccipital Lobe Infarction that Included the Fusiform Face Area

BACKGROUND: Metamorphopsia includes a broad spectrum of visual perceptual distortions, such as alteration of perceived object size or, rarely, altered perception of faces, termed prosopometamorphopsia. CASE REPORT: This report describes a patient who complained of metamorphopsia restricted to the center of the face, particularly the lower part of the face (nose and mouth), following infarction of the right medial temporooccipital lobe that included the fusiform face area. CONCLUSIONS: The fusiform face area is commonly believed to be a face-selective cortical region dedicated to the visual analysis of face stimuli. We speculate that any injury to this brain area could bring about prosopometamorphopsia involving whole or unilateral face perception, or very rarely, as in our case, distortion restricted to the central area of the face. Furthermore, there could be topographical correspondences between facial structures and the fusiform face area.

A Case of Cushing's Disease in Pregnancy

Developing Cushing's syndrome during pregnancy is rare because menstruation is irregular and hypercortisolism causes infertility. Developing Cushing's disease during pregnancy is very rare because there is even less ovulation than those with the adrenal adenoma. The clinical manifestations of Cushing's syndrome may easily be missed during pregnancy as the features of weight gain, hypertension, and hyperglycemia overlap with those that occur during a pregnancy. Diagnosing Cushing's syndrome during a pregnancy is complex because the biochemical features are obscured by the natural changes in the hypothalamic-pituitary-adrenal axis that occur during pregnancy. Having Cushing's syndrome during a pregnancy results in increased fetal and maternal complications, so early diagnosis and treatment are critical. We report the clinical and endocrine findings of a pregnant women with Cushing's disease who underwent transsphenoidal surgery after delivery.