Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum

Background@#Cerebrospinal fluid (CSF) biomarkers are increasingly used in clinical practice for the diagnosis of Alzheimer's disease (AD). We aimed to 1) determine cutoff values of CSF biomarkers for AD, 2) investigate their clinical utility by estimating a concordance with amyloid positron emission tomography (PET), and 3) apply ATN (amyloid/taueurodegeneration) classification based on CSF results. @*Methods@#We performed CSF analysis in 51 normal controls (NC), 23 mild cognitive impairment (MCI) and 65 AD dementia (ADD) patients at the Samsung Medical Center in Korea. We attempted to develop cutoff of CSF biomarkers for differentiating ADD from NC using receiver operating characteristic analysis. We also investigated a concordance between CSF and amyloid PET results and applied ATN classification scheme based on CSF biomarker abnormalities to characterize our participants. @*Results@#CSF Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) significantly differed across the three groups. The area under curve for the differentiation between NC and ADD was highest in t-tau/Aβ42 (0.994) followed by p-tau/Aβ42 (0.963), Aβ42 (0.960), t-tau (0.918), and p-tau (0.684). The concordance rate between CSF Aβ42 and amyloid PET results was 92%. Finally, ATN classification based on CSF biomarker abnormalities led to a majority of NC categorized into A-T-N-(73%), MCI as A+T-N-(30%)/A+T+N+(26%), and ADD as A+T+N+(57%). @*Conclusion@#CSF biomarkers had high sensitivity and specificity in differentiating ADD from NC and were as accurate as amyloid PET. The ATN subtypes based on CSF biomarkers may further serve to predict the prognosis.

The Cortical Neuroanatomy Related to Specific Neuropsychological Deficits in Alzheimer's Continuum

BACKGROUND AND PURPOSE: In Alzheimer's continuum (a comprehensive of preclinical Alzheimer's disease [AD], mild cognitive impairment [MCI] due to AD, and AD dementia), cognitive dysfunctions are often related to cortical atrophy in specific brain regions. The purpose of this study was to investigate the association between anatomical pattern of cortical atrophy and specific neuropsychological deficits. METHODS: A total of 249 participants with Alzheimer's continuum (125 AD dementia, 103 MCI due to AD, and 21 preclinical AD) who were confirmed to be positive for amyloid deposits were collected from the memory disorder clinic in the department of neurology at Samsung Medical Center in Korea between September 2013 and March 2018. To analyze neuropsychological test-specific neural correlates representing the relationship between cortical atrophy measured by cortical thickness and performance in specific neuropsychological tests, a linear regression analysis was performed. Two neural correlates acquired by 2 different standardized scores in neuropsychological tests were also compared. RESULTS: Cortical atrophy in several specific brain regions was associated with most neuropsychological deficits, including digit span backward, naming, drawing-copying, verbal and visual recall, semantic fluency, phonemic fluency, and response inhibition. There were a few differences between 2 neural correlates obtained by different z-scores. CONCLUSIONS: The poor performance of most neuropsychological tests is closely related to cortical thinning in specific brain areas in Alzheimer's continuum. Therefore, the brain atrophy pattern in patients with Alzheimer's continuum can be predict by an accurate analysis of neuropsychological tests in clinical practice.

Role of High-Resolution Magnetic Resonance Imaging in the Diagnosis of Primary Angiitis of the Central Nervous System

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare disorder and is often difficult to diagnose due to the lack of a confirmatory test. PACNS can generally be diagnosed based on typical angiographic findings. We describe herein a patient diagnosed with PACNS despite the presence of normal findings on conventional angiography. CASE REPORT: A 44-year-old man with a recent history of ischemic stroke in the right posterior cerebral artery territory developed acute-onset vertigo. Diffusion-weighted imaging revealed an acute infarction within the left posterior inferior cerebellar artery. His medical history was unremarkable except for hyperlipidemia; the initial examination revealed mild gait imbalance. During the 10 days of hospital admission, the patient experienced four recurrent ischemic strokes within the posterior circulation territory (occipital lobe, pons, and cerebellum). He was diagnosed with recurrent cerebral infarctions due to PACNS. The basilar artery exhibited no demonstrable luminal stenosis, but there were direct imaging signs of central nervous system angiitis including wall thickening and contrast enhancement. High-dose intravenous steroid therapy followed by oral prednisolone was administered. There was no further stroke recurrence and follow-up imaging of the arterial walls showed normalization of their characteristics. CONCLUSIONS: The present case emphasizes the importance of wall imaging in the diagnosis and treatment of PACNS.

Primary Angiitis of the Central Nervous System Diagnosed by High-Resolution Vessel Wall MRI

Primary angiitis of the central nervous system (PACNS) is a poorly understood form of vascular inflammatory disease that is restricted to the brain and spinal cord. A 38-year-old woman presented with severe headache and transient aphasia. Her cerebrospinal fluid exhibited aseptic meningitis, and high-resolution vessel-wall MRI (HRVW-MRI) revealed narrowing of multiple intracranial vessels with concentric wall thickening and diffuse enhancement, suggestive of PACNS. High-dose steroid and azathioprine therapy resulted in a significant improvement in vessel wall thickening, and enhancement was observed on the follow-up HRVW-MRI.

Possibility of Undifferentiated Human Thigh Adipose Stem Cells Differentiating into Functional Hepatocytes

BACKGROUND: This study aimed to investigate the possibility of isolating mesenchymal stem cells (MSCs) from human thigh adipose tissue and the ability of human thigh adipose stem cells (HTASCs) to differentiate into hepatocytes. METHODS: The adipose-derived stem cells (ADSCs) were isolated from thigh adipose tissue. Growth factors, cytokines, and hormones were added to the collagen coated dishes to induce the undifferentiated HTASCs to differentiate into hepatocyte-like cells. To confirm the experimental results, the expression of hepatocyte-specific markers on undifferentiated and differentiated HTASCs was analyzed using reverse transcription polymerase chain reaction and immunocytochemical staining. Differentiation efficiency was evaluated using functional tests such as periodic acid schiff (PAS) staining and detection of the albumin secretion level using enzyme-linked immunosorbent assay (ELISA). RESULTS: The majority of the undifferentiated HTASCs were changed into a more polygonal shape showing tight interactions between the cells. The differentiated HTASCs up-regulated mRNA of hepatocyte markers. Immunocytochemical analysis showed that they were intensely stained with anti-albumin antibody compared with undifferentiated HTASCs. PAS staining showed that HTASCs submitted to the hepatocyte differentiation protocol were able to more specifically store glycogen than undifferentiated HTASCs, displaying a purple color in the cytoplasm of the differentiated HTASCs. ELISA analyses showed that differentiated HTASCs could secrete albumin, which is one of the hepatocyte markers. CONCLUSIONS: MSCs were islolated from human thigh adipose tissue differentiate to heapatocytes. The source of ADSCs is not only abundant abdominal adipose tissue, but also thigh adipose tissue for cell therapy in liver regeneration and tissue regeneration.

Effect of Epidermal Growth Factor on Full Thickness Skin Defects of the Inoperable Patients

For treatment of full thickness skin defects caused by trauma or infections, skin grafts or flaps have been the treatment of choice to date. However, in patients who are not candidates for surgery, either due to his general conditions or refusal to receive treatment, supportive methods have been the only means of care, which inherently caused psychological trauma to the patient due to uncertainties of ultimate outcome and the length of treatment. This study aimed to heal full thickness skin defects through application of topical epidermal growth factor in patients who have received 2 to 3 weeks of conservative management using medifoam B(R) without improvement. Six patients from March 2002 to July 2004 were enrolled. The mean size of defects was 5.4x4.6cm in 4 patients with carcinoma and 6.4x4.1 cm in 2 patients with osmidrosis. Commercially available 0.005% EGFR solution was used, and dressing was performed once daily. All patients benefitted from the use of EGF, with closure of skin defects taking an average of 28 days in cancer patients and 22.5 days in osmidrosis cases. EGF can be used as a supportive mean of treatment in the inoperable patients with skin defects, with resultant hastening of healing shortening duration of treatment.

Techniques of Clinical Digital Photography in Plastic Surgery

Nowadays, clinical digital photography is very prevalent, though the pitfalls, problems, and standardizing works of its techniques have not yet been discussed well enough in Korea. Digital single lens reflex cameras and macro capacity lenses are still recommended for plastic surgeons for its reproducibility and high quality of developed photographs. Since the selection of digital camera itself is as important as the choice of the film in film cameras, the selected digital equipments should not be exchanged in a center or a clinic. Eighteen percents gray card(Eastman Kodak) could be used for the strict setting of the white balance as the white balance is essential in digital imaging. Studio flash lighting is good enough in clinical digital photographing settings and, soft, even lighting effect should be achieved using flash accessories (e. g. bouncer) minimizing loss of details. Taken images could be optimized through the software working (image processing) after the monitor color balancing work. They must be always developed or printed under the uniform setup status of the whole equipments to get accurate, constant pictures.

Secure and Convenient Three-point and Multi-point Suture Technique

Skin closure is the surgeon's final operation technique. Although there have been many descriptions about the different kinds of sutures, the report on a 'three-point suture' were quite limited to the horizontal half buried suture technique up till now. The three-point suture can be met frequently in cases like irregular laceration, V-Y advancement flap, and reduction mammaplasty. Authors came up with and thereby introduce a more secure and convenient three-point suture technique, which proved to be superior to the horizontal half buried suture technique in that it gives a better skin approximation and eversion. It can also be applied to a multi- point suture such as a four-point suture or a five-point suture and a three-point mattress suture.

A Case of Giant Fronto-Ethmoidal Osteoma using rib and Calvarial Bone Graft

Osteoma is a slowly growing benign tumor which mainly grows on the mandible and in the paranasal sinuses of the craniofacial region. Embryological, inflammatory, and traumatic theories make up the etiological basis of osteoma, but is still unclear and yet to be studied. We can classify osteoma by morphology and pathology into eburnated, cancellous, and mixed type, of which eburnated type is relatively common. Most osteomas accompany no symptoms, so they are often discovered accidentally by a radiological examination. They never develop into a malignant form, so that periodic observation is sufficient enough for management, but when they grow and invade intraorbitally or intracranially and then compress clinically important structures, need a surgical management, because of possibility of diplopia, exophthalmos, epiphora, blindness due to optic atrophy, mucocele, brain abscess, meningitis. A 52-year-old man complaining of right eye pain, diplopia, and exophthalmos was diagnosed a 4.5x3.0x 2.0cm sized fronto-ethmoidal osteoma by means of a three dimensional computed tomography. We experienced a osteoma removal through bicoronal incision, and orbital reconstruction with both rib and calvarial bone graft, and received satisfying results after 1 year follow-up, thereby report this case with a short review of references.

Symptomatic Tendency of Temporomandibular Joint Disorders after Whiplash Injury

TM joint disorder resulting from whiplash injury by a traffic accident is usually diagnosed depending on patient's subjective symptom complaints. It is difficult to treat the patient without any consideration for his intentional secondary gain because of the compensation related with the traffic accident. With the prospective study of the symptom and the result of the treatment for the patients who complained TM joint disorder symptoms among 142 admitted patients diagnosed as whiplash injury in our hospital. Clinical follow up was available on 67 patients with TM joint disorder symptom complaints of total 142 patients diagnosed as acute whiplash injury in our hospital from Sep. 1, 1999 to march. 31, 2001.the follow up period was an average of 9.8 months(range from 7 months to 19 months). We treated them by means of soft diet, non-steroidal anti-inflammatory agent, muscle relaxants, and physical therapy. As the result of this study, we found that the most of TM joint disorder symptoms occurred in 2-3 days(an average of 2.73 days) after whiplash injury and the symptom continued an average of 19.3 days and disappeared completely in about 3 months. The purpose of this article is to understand the relationship between these entities of disease and the psychologic factor and to analayze the tendency of the symptoms. in our study, we reached the conclusion that it is more reasonable to regard them as disease related with not psychological factor but organic factor.

A Case Report of Verrucous Carcinoma in Lower Lip

Verrucous carcinoma as a well differentiated squamous cell carcinoma appeared in skin and mucosa, so called Ackerman's tumor, is a slow-growing tumor with local infiltration rather than the tendency of metastasis. Though this tumor has been reported by many authors since named by Ackerman, despite the relatively small number of skin cancers, the difficulty in diagnosis due to benignity and pathologic finding and the high recurrence rate has aroused the interest in the disease. In addition, the premalignant region or pathogenesis has not been discovered clearly yet, besides the assosiation with chewing tabacco, but such as the correlation with hereditary carcinogenic factor(gene) in etiology with recent molecular biological approach has been clarified steadly. In the 51-year-old male patient with 1.5 x 1.5cm verrucous carcinoma originating from lower lip, it was possible to achieve a good result in terms of both aethetics and function with the use of surgical excision. Since 1980 when one case originating from postauricular area was reported in 1980, there has been no reports on the case from oral cavity in Korea. Therefore, we report one case of verrucous carcinoma from lower lip, experienced for the first time, on this literature.

Surgical Treatment of Medial Orbital Wall Fracture According to Proper Indication

Compared with orbital floor fracture, the frequency and significance of medial orbital wall fracture has been relatively ignored because of the lack of proper diagnosis and the difficulty of surgical approach. The surgical delay results to the troublesome complications like enophthalomos, extraocular muscle movement dysfunction. For the reason, it is necessary to measure the exact fracture part and bone defect size with CT scan, the ophthalmologic evaluation and the proper treatment for the indication. We operated on 17 medial orbital wall fracture patients with transnasal endoscopic approach, open reduction through minimal medial canthus incision(6-7 mm), or both methods according to the fracture type. We classified them into three types according to the degree of periosteal injury, the size of the bone defect and the degree of comminution with CT scanning and ophthalmologic evalution. In the case of Type 1, there is no herniation of orbital contents and periosteum is intact despite fracture. The patients of Type 1 can be treated by packing with Foley catheter, Merocel(R) sponge, etc. after bone reduction with transnasal endoscope. In the case of Type 2, which has the herniation of orbital contents and bone defect of approximately 1 cm or less in diameter with periosteum injury, after the bone defect site can be confirmed with an endoscope, the medial wall can be reconstructed by Titanium Mesh, silastic sheet or autogenous bone graft through minimal medial canthus incision. In the case of Type 3, the bone defect is over 1 cm in diameter accompanying comminuted fracture. The fractured medial wall of type 3 can be reconstructed with bone graft through coronal incision or open sky incision. Minor complications occurred in 7 patients but all patients were successfully treated without patient's complaints during the follow-up period of 6-18 months. In addition, the scar by minimal medial canthus incision is imperceptible. The indicaions make the fracture reduction easy and accurate. Especially, it is proper to pediatric patients and young female patients because it corresponds to minimal invasive Technique.

Clinical Application of the HE-NE Laser

Although the medical applications of He-Ne lasers remain controversial, the clinical use of these devices for a variety of analgesic and wound healing applications is steadily increasing. Research studies of the effects of He-Ne laser irradiation on biologic function are growing in number and scope. Many investigators have described successful treatment of a wide variety of painful musculoskeletal, rheumatologic, and neurologic conditions with He-Ne lasers. Since we have recently initiated studies examing the effects of He-Ne lasers on wound healing and pain relief, we investigated the effect of He-Ne laser irradiation on the healing of skin defect, abrasion, burn and on the pain relief of temporomandibular joint dysfunction in admitted patients. The total number of patients was 96. The He-Ne laser power was 1 mW, dose was 1 J/cm2 and the wavelength was 632.8 nm. Each patient underwent 2 to 8 trials of irradiation on point around the wound area and painful joint at a frequency of 2 times a week. After every 1 trial up to 8 trials, we evaluated the efficacy of He-Ne laser irradiation by checking the wound size and by questioning the patients about degree of pain. Following the estimation by patients, excellent, good, and fair were accounted as effective, and poor as noneffective. The efficacy of the laser at the end of 2 to 8 trials was noticed on 78.1%, and the degree of pain relief was 73.9%. These results suggested that the irradiation of He-Ne laser is an effective and safe treatment for wound healing and pain relief. In this overview, we are summarizing some of our results which suggest a potential usefulness of He-Ne lasers for stimulation of wound healing and pain relief. Although its clinical use can be anticipated in the future, further research is required to clarify the basic mechanisms and the preferred optical parameters, such as treatment time and intensity, for increased wound healing and pain relief.