Cerebrospinal Fluid Levels of β-Amyloid 40 and β-Amyloid 42 are Proportionately Decreased in Amyloid Positron-Emission Tomography Negative Idiopathic Normal-Pressure Hydrocephalus Patients

BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) could be misleading in idiopathic normal-pressure hydrocephalus (iNPH). We therefore investigated the CSF biomarkers in 18F-florbetaben amyloid-negative positron-emission tomography (PET) [amyloid PET(−)] iNPH, amyloid-positive PET [amyloid PET(+)] AD, and cognitively normal (CN) subjects. METHODS: Ten amyloid PET(+) AD patients (56.7±5.6 years old, mean±standard deviation), 10 amyloid PET(−) iNPH patients (72.8±4.5 years old), and 8 CN subjects (61.2±6.5 years old) were included. We measured the levels of β-amyloid (Aβ)40, Aβ42, total tau (t-tau) protein, and phosphorylated tau (p-tau) protein in the CSF using enzyme-linked immunosorbent assays. RESULTS: The level of Aβ42 and the Aβ42/Aβ40 ratio in the CSF were significantly lower in AD than in iNPH or CN subjects. The Aβ40 level did not differ significantly between AD and iNPH (p=1.000), but it did between AD and CN subjects (p=0.032). The levels of both t-tau and p-tau were higher in AD than in iNPH or CN subjects. The levels of Aβ42, Aβ40, t-tau, and p-tau were lower in iNPH than in CN subjects, but there was no significant difference after controlling for age. CONCLUSIONS: Our results suggest that the mechanism underlying low CSF Aβ levels differs between amyloid PET(−) iNPH and amyloid PET(+) AD subjects. The lower levels of all CSF biomarkers in iNPH patients might be due to reduced clearances from extracellular fluid and decreased brain metabolism of the periventricular zone in iNPH resulting from glymphatic dysfunction.

Clinical and Demographic Predictors of Adverse Outcomes in Caregivers of Patients with Dementia

BACKGROUND AND PURPOSE: We aimed to elucidate independent predictors of adverse outcomes in caregivers of patients with dementia using readily available clinical and demographic data of patients with dementia and their caregivers. METHODS: We reviewed patient-caregiver data from the Clinical Research Center for Dementia of South Korea and Caregivers of Alzheimer Disease Research study. The clinical factors of the patients and the demographics of both patients and caregivers were used to predict adverse outcomes for caregivers. Correlation and linear regression analyses were performed. RESULTS: We enrolled 454 patients and their caregivers for the present study. The general burden for the caregiver was higher amongst female caregivers, patients with further decreased the level of activities of daily living (ADL), patients with more abnormal behavior, or younger patients. The time spent by the caregivers was more in cases of patients with higher Caregiver Administered Neuropsychiatric Inventory scores, younger patients and for patients with decreased level of ADL. Depression amongst caregivers was more prominent in patients with higher Clinical Dementia Rating Sum of Boxes scores. Physical health-related quality of life (HRQoL) was lower in female caregivers, more physically affected patients, and older caregivers. Lastly, mental HRQoL was lower in younger, more physically affected, and in patients with abnormal behaviors. CONCLUSIONS: Clinical and demographic characteristics of patients and caregivers predict adverse outcomes for caregivers. Therefore, these factors should be considered to provide support to both patients and their caregivers.

Predictors of Institutionalization in Patients with Alzheimer's Disease in South Korea

BACKGROUND AND PURPOSE: We investigated predictors of institutionalization in patients with Alzheimer's disease (AD) in South Korea. METHODS: In total, 2,470 patients with AD aged 74.5±7.8 years (mean±standard deviation, 68.1% females) were enrolled from November 2005 to December 2013. The dates of institutionalization were identified from the public Long-Term-Care Insurance program in January 2014. We used a Cox proportional-hazards model to identify predictors for future institutionalization among characteristics at the time of diagnosis in 2,470 AD patients. A similar Cox proportional-hazards model was also used to investigate predictors among variables that reflected longitudinal changes in clinical variables before institutionalization in 816 patients who underwent follow-up testing. RESULTS: A lower Mini Mental State Examination score [hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92–0.97] and higher scores for the Clinical Dementia Rating and Neuro-Psychiatric Inventory (HR=1.01, 95% CI=1.00–1.01) at baseline were independent predictors of institutionalization. The relationship of patients with their main caregivers, presence of the apolipoprotein E e4 allele, and medication at baseline were not significantly associated with the rate of institutionalization. In models with variables that exhibited longitudinal changes, larger annual change in Clinical Dementia Rating Sum of Boxes score (HR=1.15, 95% CI=1.06–1.23) and higher medication possession ratio of antipsychotics (HR=1.89, 95% CI=1.20–2.97) predicted earlier institutionalization. CONCLUSIONS: This study shows that among Korean patients with AD, lower cognitive ability, higher dementia severity, more-severe behavioral symptoms at baseline, more-rapid decline in dementia severity, and more-frequent use of antipsychotics are independent predictors of earlier institutionalization.

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.

Vitamin B12 Deficiency with Extreme Hyperhomocysteinemia Presenting with a Brain Ischemic Lesion

No abstract available.

Sustained downgaze as the only remained sign after regaining consciousness in hepatic encephalopathy

Sustained downgaze mostly occurs in association with lesions affecting the dorsal midbrain. We report sustained downgaze in a patient with hepatic encephalopathy. The sustained downgaze existed for seven more days after she regained her consciousness. The persistent downgaze even after regaining full consciousness indicates localized pretectal dysfunction rather than diffuse encephalopathy as the mechanism of sustained downgaze in our patient. The ocular motor dysfunction in hepatic encephalopathy may be due to localized dysfunction of the brainstem

Neuro-Behcet's Disease Presented with Progressive Disinhibition

We report a man who presented with progressive disinhibition and through clinicoradiologic correlation using magnetic resonance imaging (MRI), aim to investigate the pathomechanism of disinhibition in neuro-Behcet's disease (NBD). A 46-year-old man presented with progressive disinhibition and apathy for 4 months. One month after his visit, additionally, he developed left partial third nerve palsy. His brain MRI showed lesions in the ventral caudate nucleus as well as left midbrain and thalamus. Taking his recurrent oral ulcers, uveitis, and erythema nodosum into consideration, he was diagnosed with NBD. We found that progressive disinhibition could be one of presenting symptoms in BD and might be associated with the caudate nucleus. This finding suggests that involvement of the basal ganglia in BD prior to the involvement of the brainstem could result in unique clinical features such as behavioral changes without extrapyramidal signs.

Neuro-Behcet's Disease Presented with Progressive Disinhibition

We report a man who presented with progressive disinhibition and through clinicoradiologic correlation using magnetic resonance imaging (MRI), aim to investigate the pathomechanism of disinhibition in neuro-Behcet's disease (NBD). A 46-year-old man presented with progressive disinhibition and apathy for 4 months. One month after his visit, additionally, he developed left partial third nerve palsy. His brain MRI showed lesions in the ventral caudate nucleus as well as left midbrain and thalamus. Taking his recurrent oral ulcers, uveitis, and erythema nodosum into consideration, he was diagnosed with NBD. We found that progressive disinhibition could be one of presenting symptoms in BD and might be associated with the caudate nucleus. This finding suggests that involvement of the basal ganglia in BD prior to the involvement of the brainstem could result in unique clinical features such as behavioral changes without extrapyramidal signs.

Sequential Changes of the Brain Over 10 Years Following Radiation Treatment

No abstract available.

Erratum: Topographical Disorientation in Mild Cognitive Impairment: A Voxel-Based Morphometry Study

No abstract available.

Sulfasalazine-induced Reversible Leukoencephalopathy

A 50-year-old woman presented with a 4-day history of apathy, perseveration, and confusion. These symptoms appeared 16 days after she had started taking sulfasalazine for rheumatoid arthritis. Brain MRI showed bilateral symmetrical discoid lesions involving the corona radiata. She fully recovered 7 days after stopping the medications. Follow-up brain MRI revealed remarkable improvement of the lesions. The pathomechanisms related to sulfasalazine-induced leukoencephalopathy may be demyelinating processes due to impaired T-cell-mediated immunity.

Topographical Disorientation in Mild Cognitive Impairment: A Voxel-Based Morphometry Study

BACKGROUND AND PURPOSE: To assess the neural substrates underlying topographical disorientation (TD) in patients affected by mild cognitive impairment (MCI), forty-one patients diagnosed with MCI and 24 healthy control individuals were recruited. METHODS: TD was assessed clinically in all participants. Neurological and neuropsychological evaluations and a volumetric-head magnetic resonance imaging scan were performed in each participant. Voxel-based morphometry was used to compare patterns of gray-matter atrophy between patients with and without TD, and a group of normal controls. RESULTS: We found TD in 17 out of the 41 MCI patients (41.4%). The functional abilities were significantly impaired in MCI patients with TD compared to in MCI patients without TD. Voxel-based morphometry analyses showed that the presence of TD in MCI patients is associated with loss of gray matter in the medial temporal regions, including the hippocampus and parahippocampal cortex, the fusiform gyrus, the inferior occipital gyrus, the amygdala, and the cerebellum. CONCLUSIONS: The findings found in this study represent the first evidence that the presence of TD in patients with MCI is associated with loss of gray matter in those brain regions that have been documented to be responsible for orientation in both neuropsychological and neuroimaging studies.

Middle Cerebral Artery Infarction Caused by Cerebral Vasospasm After Brain Tumor Surgery by Pterional Approach

No abstract available.

Significance of Increased Signal Intensity on T2 Weighted MRI in Patients with Cervical Spondylosis

The cases of 33 patients with cervical spondylosis, who had preoperative magnetic resonance imaging(MRI) and surgical intervention, were reviewed. There were areas of increased signal intensity on T2 weighted image in 13 patients out of 33 patients, whereas there were none in the other 20. The pre- and postoperative clinical condition, severity of cord compression and preoperative value of somatosensory evoked potentials(SSEP) of patients whose preoperative MRI showed areas of increased signal intensity in the spinal cord on T2 weighted image were worse than that of the patients who did not have areas of increased signal intensity. The areas of increased signal intensity on T2 weighted image in spinal cord might be edema, cord gliosis, demyelination, or microcavities.