Primary Age-Related Tauopathy: An Elderly Brain Pathology Frequently Encountered during Autopsy

Due to the progressive aging of Korean society and the introduction of brain banks to the Korean medical system, the possibility that pathologists will have access to healthy elderly brains has increased. The histopathological analysis of an elderly brain from a subject with relatively well-preserved cognition is quite different from that of a brain from a demented subject. Additionally, the histology of elderly brains differs from that of young brains. This brief review discusses primary age-related tauopathy; this term was coined to describe elderly brains with Alzheimer’s diseasetype neurofibrillary tangles mainly confined to medial temporal structures, and no β-amyloid pathology.

Intensity-modulated radiotherapy for stage I glottic cancer: a short-term outcomes compared with three-dimensional conformal radiotherapy

PURPOSE: To investigate the differences in treatment outcomes between two radiation techniques, intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT).MATERIALS AND METHODS: We retrospectively analyzed 160 (IMRT = 23, 3DCRT = 137) patients with stage I glottic cancer treated from January 2005 through December 2016. The IMRT was performed with TomoTherapy (16 patients), volumetric-modulated arc therapy (6 patients), and step-and-shoot technique (1 patient), respectively. The 3DCRT was performed with bilateral parallel opposing fields. The median follow-up duration was 30 months (range, 31 to 42 months) in the IMRT group and 65 months (range, 20 to 143 months) in the 3DCRT group.RESULTS: The 5-year overall survival and 3-year local control rates of the 160 patients were 95.7% and 91.4%, respectively. There was no significant difference in 3-year local control rates between the IMRT and 3DCRT groups (94.4% vs. 91.0%; p = 0.587). Thirteen of 137 patients in the 3DCRT group had recurrences. In the IMRT group, one patient had a recurrence at the true vocal cord. Patients treated with IMRT had less grade 2 skin reaction than the 3DCRT group, but this had no statistical significance (4.3% vs. 21.2%; p = 0.080).CONCLUSION: IMRT had comparable outcomes with 3DCRT, and a trend of less acute skin reaction in stage I glottic cancer patients

Successful replantation of an amputated helical rim with microvascular anastomosis

Replantation using microvascular anastomosis is considered to be the optimal method in treating the amputated ear in terms of resulting color, texture, and shape. Only a few cases of ear replantation have been reported because it is anatomically difficult to identify suitable vessels for anastomosis. We successfully replanted the amputated helical rim of the ear using single arterial anastomosis. A 37-year-old man had his helical rim amputated by a human bite. The amputee was about 4 × 1 cm in dimension, composed of skin and soft tissue including auricular cartilage. Replantation was performed anastomosing a small artery of the amputee with a terminal branch of the posterior auricular artery. After replantation, intravenous heparinization was performed and prostaglandin E1 and aspirin were administered. Venous congestion was decompressed by stab incisions applied with heparin solution soaked gauze. Venous congestion of the amputee slowly began to resolve at 4 days after the operation. The amputated segment of the helical rim survived completely with good aesthetic shape and color. The authors propose that performing microvascular anastomosis should be attempted especially if it is possible to detect vessels on cut surfaces of ear amputee and stump. Proper postoperative care for venous congestion, arterial insufficiency, and infection should be followed for amputee survival.

The Brain Donation Program in South Korea

PURPOSE: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof. MATERIALS AND METHODS: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET. RESULTS: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD. CONCLUSION: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.

Proposal Guidelines for Standardized Operating Procedures of Brain Autopsy: Brain Bank in South Korea

To obtain an in-depth understanding of brain diseases, including neurodegenerative diseases, psychiatric illnesses, and neoplasms, scientific approach and verification using postmortem human brain tissue with or without disease are essential. Compared to other countries that have run brain banks for decades, South Korea has limited experience with brain banking; nationwide brain banks started only recently. The goal of this study is to provide provisional guidelines for brain autopsy for hospitals and institutes that have not accumulated sufficient expertise. We hope that these provisional guidelines will serve as a useful reference for pathologists and clinicians who are involved and interested in the brain bank system. Also, we anticipate updating the provisional guidelines in the future based on collected data and further experience with the practice of brain autopsy in South Korea.

An Experimental Infarct Targeting the Internal Capsule: Histopathological and Ultrastructural Changes

BACKGROUND: Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes. METHODS: Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury. RESULTS: Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume. CONCLUSIONS: Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.

Upper Arm Contouring with Brachioplasty after Massive Weight Loss

BACKGROUND: As the obese population increases in Korea, the number of patients who are trying to lose weight has been increasing steadily. In these patients, skin laxity and deformation of the body contour occurs, which could possibly be corrected by various body contouring surgeries. Here, we introduce the brachioplasty method and our experience of various body contouring surgeries performed in our center. METHODS: From November 2009 to August 2011, five cases of brachioplasty were performed. When the patient presented with sagging of the lateral inframammary crease and bat wing deformity in the axilla, extended brachioplasty was performed; in this case, the deformation of the axilla and lateral chest was corrected at the same time. A traditional brachioplasty was performed when contouring was needed only for skin laxity in the upper arm. RESULTS: Complications, such as hematomas or nerve injuries, were not evident. Some patients experienced partial wound dehiscence due to tension or hypertrophic scars found during the follow-up. In general, all of the patients were satisfied with the improvement in their upper arm contour. CONCLUSIONS: Given the demands for body contouring surgery, the number of brachioplasty surgical procedures is expected to increase significantly, with abdominoplasty comprising a large portion of these surgeries. For the brachioplasty procedure, preparation and preoperative consultation regarding design of the surgery by experienced surgeons was important to prevent complications such as nerve damage or hematoma formation.

Mondor's Disease after Operation for Axillary Osmidrosis: A Case Report

Mondor's disease is a benign, self-limited process with spontaneous resolution, which is frequently caused by breast surgery, such as axillary lymph node dissection. We present a case of Mondor's disease that occurred after an axillary osmidrosis operation, which is a less invasive procedure; Mondor's disease may be considered as a possible postoperative complication following an axillary osmidrosis surgery.

Growing Teratoma Syndrome of the Pineal Gland Recognized Very Early during Chemotherapy in a Child with a Non-Germinomatous Germ-Cell Tumor / 임상소아혈액종양

The growing teratoma syndrome (GTS) is defined as the development of mature low-grade elements in the absence of a recurrent non-germinomatous germ-cell tumor (NGGCT) after partial response to multimodal treatment. It is uncommon and may occur in intracranial NGGCTs. Here, we report that a 7-year-old boy with intracranial NGGCT presented with precocious puberty and developed growing teratoma syndrome only 2 weeks after the first cycle of chemotherapy.

Growing Teratoma Syndrome of the Pineal Gland Recognized Very Early during Chemotherapy in a Child with a Non-Germinomatous Germ-Cell Tumor / 임상소아혈액종양

The growing teratoma syndrome (GTS) is defined as the development of mature low-grade elements in the absence of a recurrent non-germinomatous germ-cell tumor (NGGCT) after partial response to multimodal treatment. It is uncommon and may occur in intracranial NGGCTs. Here, we report that a 7-year-old boy with intracranial NGGCT presented with precocious puberty and developed growing teratoma syndrome only 2 weeks after the first cycle of chemotherapy.

Fragmentectomy versus Conventional Microdiscectomy in Single-Level Lumbar Disc Herniations : Comparison of Clinical Results and Recurrence Rates

OBJECTIVE: This retrospective study aimed to compare clinical outcomes in terms of pain relief and recurrence rate between fragmentectomies and conventional microdiscectomies in patients with lumbar disc herniation (LDH). METHODS: Between January 2008 and May 2011, a total of 175 patients met the inclusion criteria of this study. The visual analogue scale (VAS) scores of back and radicular pains were recorded before surgery, 2 and 6 weeks after surgery. Recurrence was defined when a patient had the same pattern of preoperative symptoms and was confirmed with magnetic resonance imaging. RESULTS: Seventy-four patients (42.3%) were suitable for fragmentectomy, and 101 patients underwent conventional microdiscectomy. There were no significant differences in VAS scores between the fragmentectomy and conventional microdiscectomy groups 2 and 6 weeks after surgery. During the follow-up period, 3 patients (4.05%) in the fragmentectomy group and 7 patients (6.93%) in the conventional microdiscectomy group relapsed. CONCLUSION: If patients are selected according to well-defined criteria, fragmentectomy can be a good surgical option for LDH, in the physiological aspect of preserving healthy intervertebral disc materials.

Outcome Evaluation of Intravenous Infusion of Urokinase for Acute Ischemic Stroke / 전남의대학술지

The aim of this study was to evaluate the clinical effect of a continuous infusion of urokinase in cerebral stoke patients who were late admitted over 6 hours after onset. From January to December in 2008, acute cerebral stroke patients (n=143) treated with intravenous urokinase infusion (Group I, n=93) or not (Group II, n=50) after 6 hours and within 72 hours of stroke onset were reviewed. Continuous intravenous infusion of urokinase was done for 5 days. The clinical outcome for each patient was evaluated by using the modified National Institutes of Health Stroke Scale (NIHSS) on admission and on the day of discharge. The NIHSS score was decreased at discharge compared with admission in the urokinase treatment group (Group I; from 4.8+/-2.2 to 3.8+/-1.9; p=0.002). There was an improvement in the patients who initiated urokinase treatment within 24 hours from stroke onset in Group I (from 5.1+/-1.9 to 3.9+/-1.5; p=0.04). In patients with initiated urokinase treatment within 24 hours from stroke onset, intravenous urokinase infusion could be an effective modality in acute ischemic stroke patients admitted later than 6 hours after onset.

Astrocytoma in the Third Ventricle and Hypothalamus Presenting with Parkinsonism

Parkinsonism secondary to intracranial mass lesions usually results from compression or distortion of the basal ganglia. Secondary parkinsonism due to midbrain infiltration or compression is rare and generally associated with other neurologic signs caused by pyramidal tract and/or cranial nerve involvement. We report a case of 30-year-old woman in whom mild parkinsonism was the major clinical manifestation of an astrocytoma in the anterior third ventricle and hypothalamus. She underwent surgical resection, ventriculoperitoneal shunt and radiation therapy. All symptoms of parkinsonism were completely recovered 3 months after the treatment. Brain tumors can be manifested only by the symptoms of parkinsonism. This case emphasizes the significance of neuroimaging in the evaluation of parkinsonism.

Outcome Evaluation of Intravenous Infusion of Urokinase for Acute Ischemic Stroke / 전남의대학술지

The aim of this study was to evaluate the clinical effect of a continuous infusion of urokinase in cerebral stoke patients who were late admitted over 6 hours after onset. From January to December in 2008, acute cerebral stroke patients (n=143) treated with intravenous urokinase infusion (Group I, n=93) or not (Group II, n=50) after 6 hours and within 72 hours of stroke onset were reviewed. Continuous intravenous infusion of urokinase was done for 5 days. The clinical outcome for each patient was evaluated by using the modified National Institutes of Health Stroke Scale (NIHSS) on admission and on the day of discharge. The NIHSS score was decreased at discharge compared with admission in the urokinase treatment group (Group I; from 4.8+/-2.2 to 3.8+/-1.9; p=0.002). There was an improvement in the patients who initiated urokinase treatment within 24 hours from stroke onset in Group I (from 5.1+/-1.9 to 3.9+/-1.5; p=0.04). In patients with initiated urokinase treatment within 24 hours from stroke onset, intravenous urokinase infusion could be an effective modality in acute ischemic stroke patients admitted later than 6 hours after onset.

Time Point Expression of Apoptosis Regulatory Proteins in a Photochemically-Induced Focal Cerebral Ischemic Rat Brain / 전남의대학술지

Apoptosis after global or focal cerebral ischemia plays a crucial role in mediating cell death. In this study, we observed the time point expression of physiologic events involving apoptosis regulatory proteins after photochemically-induced focal cerebral ischemia in Sprague-Dawley rats. Protein expression was evaluated at days 1, 3, and 7 by Western blot. Bcl-2, Bax, caspase-3, and phosphorylated Akt (pAkt) activity markedly increased in the ischemic hemisphere in a time-dependent manner, not affected. The expression of Bcl-2, Bax, and caspase-3 was dramatically changed around day 3, whereas changes in pAkt expression occurred at day 1. Differential elevation of these apoptosis regulatory proteins at various time points indicates that different modes of cell death occur in photochemically-induced focal cerebral ischemia in a rat brain.

Stem Cell Dynamics in an Experimental Model of Stroke / 전남의대학술지

We investigated the migration of endogenous neural stem cells (NSCs) toward an infarct lesion in a photo-thrombotic stroke model. The lesions produced by using rose bengal dye (20 mg/kg) with cold light in the motor cortex of Sprague-Dawley rats were also evaluated with sequential magnetic resonance imaging (MRI) from 30 minutes through 8 weeks. Migration of NSCs was identified by immunohistochemistry for nestin monoclonal antibody in the lesion cortex, subventricular zone (SVZ), and corpus callosum (CC). The contrast to noncontrast ratio (CNR) on MRI was greatest at 12 hours in DWI and decreased over time. By contrast, T1-weighted and T2-weighted images showed a constant CNR from the beginning through 8 weeks. MRI of the lesional cortex correlated with histopathologic findings, which could be divided into three stages: acute (edema and necrosis) within 24 hours, subacute (acute and chronic inflammatory cell infiltration) at 2 to 7 days, and chronic (gliofibrosis) at 2 to 4 weeks. The volume of the infarct was significantly reduced by reparative gliofibrosis. The number of nestin+ NSCs in the contralateral SVZ was similar to that of the ipsilateral SVZ in each group. However, the number of nestin+ NSCs in the ipsilateral cortex and CC increased at 12 hours to 3 days compared with the contralateral side (p<0.01) and was reduced significantly by 7 days (p<0.01). Active emigration of internal NSCs from the SVZ toward the infarct lesion may also contribute to decreased volume of the infarct lesion, but the self-repair mechanism by endogenous NSCs is insufficient to treat stroke causing extensive neuronal death. Further studies should be focused on amplification technologies of NSCs to enhance the collection of endogenous or transplanted NSCs for the treatment of stroke.

Time Point Expression of Apoptosis Regulatory Proteins in a Photochemically-Induced Focal Cerebral Ischemic Rat Brain / 전남의대학술지

Apoptosis after global or focal cerebral ischemia plays a crucial role in mediating cell death. In this study, we observed the time point expression of physiologic events involving apoptosis regulatory proteins after photochemically-induced focal cerebral ischemia in Sprague-Dawley rats. Protein expression was evaluated at days 1, 3, and 7 by Western blot. Bcl-2, Bax, caspase-3, and phosphorylated Akt (pAkt) activity markedly increased in the ischemic hemisphere in a time-dependent manner, not affected. The expression of Bcl-2, Bax, and caspase-3 was dramatically changed around day 3, whereas changes in pAkt expression occurred at day 1. Differential elevation of these apoptosis regulatory proteins at various time points indicates that different modes of cell death occur in photochemically-induced focal cerebral ischemia in a rat brain.

Stem Cell Dynamics in an Experimental Model of Stroke / 전남의대학술지

We investigated the migration of endogenous neural stem cells (NSCs) toward an infarct lesion in a photo-thrombotic stroke model. The lesions produced by using rose bengal dye (20 mg/kg) with cold light in the motor cortex of Sprague-Dawley rats were also evaluated with sequential magnetic resonance imaging (MRI) from 30 minutes through 8 weeks. Migration of NSCs was identified by immunohistochemistry for nestin monoclonal antibody in the lesion cortex, subventricular zone (SVZ), and corpus callosum (CC). The contrast to noncontrast ratio (CNR) on MRI was greatest at 12 hours in DWI and decreased over time. By contrast, T1-weighted and T2-weighted images showed a constant CNR from the beginning through 8 weeks. MRI of the lesional cortex correlated with histopathologic findings, which could be divided into three stages: acute (edema and necrosis) within 24 hours, subacute (acute and chronic inflammatory cell infiltration) at 2 to 7 days, and chronic (gliofibrosis) at 2 to 4 weeks. The volume of the infarct was significantly reduced by reparative gliofibrosis. The number of nestin+ NSCs in the contralateral SVZ was similar to that of the ipsilateral SVZ in each group. However, the number of nestin+ NSCs in the ipsilateral cortex and CC increased at 12 hours to 3 days compared with the contralateral side (p<0.01) and was reduced significantly by 7 days (p<0.01). Active emigration of internal NSCs from the SVZ toward the infarct lesion may also contribute to decreased volume of the infarct lesion, but the self-repair mechanism by endogenous NSCs is insufficient to treat stroke causing extensive neuronal death. Further studies should be focused on amplification technologies of NSCs to enhance the collection of endogenous or transplanted NSCs for the treatment of stroke.

Neurotoxicity Screening in a Multipotent Neural Stem Cell Line Established from the Mouse Brain

Neural stem cells (NSCs) have mainly been applied to neurodegeneration in some medically intractable neurologic diseases. In this study, we established a novel NSC line and investigated the cytotoxic responses of NSCs to exogenous neurotoxicants, glutamates and reactive oxygen species (ROS). A multipotent NSC line, B2A1 cells, was established from long-term primary cultures of oligodendrocyte-enriched cells from an adult BALB/c mouse brain. B2A1 cells could be differentiated into neuronal, astrocytic and oligodendroglial lineages. The cells also expressed genotypic mRNA messages for both neural progenitor cells and differentiated neuronoglial cells. B2A1 cells treated with hydrogen peroxide and L-buthionine-(S,R)-sulfoximine underwent 30-40% cell death, while B2A1 cells treated with glutamate and kainate showed 25-35% cell death. Cytopathologic changes consisting of swollen cell bodies, loss of cytoplasmic processes, and nuclear chromatin disintegration, developed after exposure to both ROS and excitotoxic chemicals. These results suggest that B2A1 cells may be useful in the study of NSC biology and may constitute an effective neurotoxicity screening system for ROS and excitotoxic chemicals.

The Retrial of Percutaneous Vertebroplasty for the Treatment of Vertebral Compression Fracture

OBJECTIVE: For the treatment of osteoporotic vertebral compression fracture, percutaneous vertebroplasty (PVP) is currently widely used as an effective and relatively safe procedure. However, some patients do not experience pain relief after PVP. We performed several additional PVP procedures in those patients who did not have any improvement of pain after their initial PVP and we obtained good results. Our purpose is to demonstrate the effective results of an additional PVP procedure at the same previously treated level. METHODS: We reviewed the medical records and the radiologic data of the PVP procedures that were performed at our hospital from November 2005 to May 2008 to determine the patients who had undergone additional PVP. We identified ten patients and we measured the clinical outcomes according to the visual analogue scale (VAS) score and the radiologic parameters, including the anterior body height and the kyphotic angulation. RESULTS: The mean volume of polymethylmethacrylate injected into each vertebrae was 4.3 mL (range: 2-8 mL). The mean VAS score was reduced from 8 to 2.32. The anterior body height was increased from 1.7 cm to 2.32 cm. The kyphotic angulation was restored from 10.14 degrees to 2.32 degrees. There were no complications noted. CONCLUSION: The clinical and radiologic outcomes suggest that additional PVP is effective for relieving pain and restoring the vertebral body in patients who have unrelieved pain after their initial PVP. Our study demonstrates that additional PVP performed at the previously-treated vertebral levels could provide therapeutic benefit.