Clinical Relevance of Enlarged Perivascular Spaces in Neurodegenerative Disease

Background@#Enlarged perivascular space (ePVS) is recently reported to be associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD). The topographical location of ePVS may relate to the underlying pathology; basal ganglia (BG)-ePVS has been associated with cerebral vascular diseases and centrum semi-ovale (CSO)-ePVS associated with cerebral amyloid angiopathy (CAA). However, the effects of ePVS on various neurological conditions remain still controversial. To investigate the clinical relevance of ePVS in neurodegenerative diseases, we tested relationships between ePVS and cognition, markers of SVD, vascular risk factors, or amyloid pathology. @*Methods@#We retrospectively reviewed 292 patients (133 AD dementia, 106 mild cognitive impairment, 39 other neurodegenerative diseases, 14 subjective cognitive decline) who underwent both amyloid positron emission tomography and brain magnetic resonance imaging. Vascular risk factors and cognitive tests results were collected. The ePVS in the BG and CSO, SVD markers and the volume of white matter hyperintensities were measured. @*Results@#There were no significant differences in the severity and distribution of ePVS among clinical syndromes. Both BG- and CSO-ePVS were not related to cognitive function. Patients with lacunes were more likely to have high-degree BG-ePVS. High degree CSO-ePVS had an odds ratio (OR) for amyloid positive of 2.351, while BG-ePVS was a negative predictor for amyloid pathology (OR, 0.336). @*Conclusions@#Our findings support that ePVS has different underlying pathologies according to the cerebral topography. BG-ePVS would be attributed to hypertensive angiopathy considering the relation with SVD markers, whereas and CSO-ePVS would be attributed to CAA considering the association with amyloid pathology.

An Autopsy Confirmed Case of Amyotrophic Lateral Sclerosis with TDP Pathology

The phosphorylated 43-kDa transactive response DNA-binding protein (TDP-43) was identified as a major disease protein in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. We present a case with progressive muscle weakness who was diagnosed with sporadic ALS. On postmortem examination, TDP-43 immunoreactive neuronal cytoplasmic inclusions were noted in motor cortex, hippocampus and anterior horns of spinal cord, which was compatible with ALS-TDP, stage 4. This is the first documented autopsy-confirmed ALS case with ALS-TDP pathology in Korea.

Comparison of Neuropathological Characteristics between Multiple System Atrophy Cerebellar Type and Parkinsonian Type

Background@#Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by various combinations of parkinsonism, cerebellar ataxia, autonomic dysfunction and pyramidal signs. Two clinical subtypes are recognized: MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA-P). The aim of this study was to compare pathological features between MSA-C and MSA-P. @*Methods@#Two autopsy confirmed cases with MSA were included from the Pusan National University Hospital Brain Bank. Case 1 had been clinically diagnosed as MSA-C and case 2 as MSA-P. The severity of neuronal loss and gliosis as well as the glial and neuronal cytoplasmic inclusions were semiquantitatively assessed in both striatonigral and olivopontocerebellar regions. Based on the grading system, pathological phenotypes of MSA were classified as striatonigral degeneration (SND) predominant (SND type), olivopontocerebellar degeneration (OPC) predominant (OPC type), or equivalent SND and OPC pathology (SND=OPC type). @*Results@#Both cases showed widespread and abundant α-synuclein positive glial cytoplasmic inclusions in association with neurodegenerative changes in striatonigral or olivopontocerebellar structures, leading to the primary pathological diagnosis of MSA. Primary age-related tauopathy was incidentally found but Lewy bodies were not in both cases. The pathological phenotypes of MSA were MSA-OPC type in case 1 and MSA-SND=OPC type in case 2. @*Conclusions@#Our data suggest that clinical phenotypes of MSA reflect the pathological characteristics.

Bilateral Cataract after Taking Oxcarbazepine

PURPOSE: To report a case of bilateral posterior subcapsular cataract after taking oxcarbazepine (Trileptal®, Novartis, Basel, Swiss). CASE SUMMARY: A 19-year-old female visited our clinic with decreased vision in both eyes. Her best-corrected visual acuity was 0.3 in the right eye and 0.5 in the left eye, and slit-lamp examination revealed a bilateral cortical opacity and subcapsular cataract. She had been taking oxcarbazepine for epilepsy for 10 years, which was discontinued 3 years ago. Her mother had undergone cataract surgeries when she was approximately 46 years of age. No other risk factors for cataract were present. CONCLUSIONS: In the present case, bilateral cortical opacity and subcapsular cataract were assumed to be associated with the use of oxcarbazepine. We suggest that oxcarbazepine could induce a cataract and recommend a regular follow-up by a qualified ophthalmologist.

Prosopometamorphopsia and Visual Field Defect Improved by Valproic acid in a CADASIL Patient

Persistent aura without infarction is defined as an aura persisting for 1 week or more without evidence of infarction on neuroimaging. It is difficult to differentiate persistent visual aura without infarction from occipital lobe epilepsy. We report a Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy patient with prosopometamorphopsia and visual field defect improved by valproic acid. We also review ambiguity between visual aura in migraine and occipital lobe epilepsy.

Gerstmann-Sträussler-Scheinker Disease (Pro102Leu) Presenting as Rapidly Progressive Dementia

Genetic prion diseases account for about 10-15% of all cases of human prion disease and are caused by mutations in the prion protein gene. Gerstmann-Sträussler-Scheinker (GSS) disease is a rare genetic prion disease, which is characterized by slowly progressive cerebellar ataxia and the occurrence of cognitive decline in the later stage. P102L is the most common mutation in GSS. We report a patient with a P102L mutation that initially manifested as rapidly progressive dementia without cerebellar symptoms.

Association of Nutritional Status with Cognitive Stage in the Elderly Korean Population: The Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease

BACKGROUND AND PURPOSE: Epidemiological studies have suggested the presence of strong correlations among diet, lifestyle, and dementia onset. However, these studies have unfortunately had major limitations due to their inability to fully control the various potential confounders affecting the nutritional status. The purpose of the current study was to determine the nutritional status of participants in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) and to identify clinical risk factors for being at risk of malnutrition or being malnourished. METHODS: Baseline data from 212 participants [119 cognitively unimpaired (CU), 56 with mild cognitive impairment (MCI), and 37 with dementia] included in the KBASE database were analyzed. All participants underwent a comprehensive cognitive test and MRI at baseline. The presence of malnutrition at baseline was measured by the Mini Nutritional Assessment score. We examined the cross-sectional relationships of clinical findings with nutritional status using multiple logistic regression applied to variables for which p<0.2 in the univariate analysis. Differences in cortical thickness according to the nutritional status were also investigated. RESULTS: After adjustment for demographic, nutritional, and neuropsychological factors, participants with dementia had a significantly higher odds ratio (OR) for being at risk of malnutrition or being malnourished than CU participants [OR=5.98, 95% CI=1.20–32.97] whereas participants with MCI did not (OR=0.62, 95% CI=0.20–1.83). Cortical thinning in the at-risk/malnutrition group was observed in the left temporal area. CONCLUSIONS: Dementia was found to be an independent predictor for the risk of malnutrition compared with CU participants. Our findings further suggest that cortical thinning in left temporal regions is related to the nutritional status.

An Autopsy Confirmed Case of Semantic Variant Primary Progressive Aphasia with Frontotemporal Lobar Degeneration-TDP type C

A 62-year-old man presented with a one-year history of word finding difficulty, impaired single word comprehension and personality changes including aggression, apathy and eating change. Brain MRIs showed severe atrophy in the left anterior temporal lobe. The clinical syndromic diagnosis was semantic variant primary progressive aphasia. He died at age 70 of pneumonia. At autopsy, transactive response DNA-binding protein (TDP) immunoreactive long dystrophic neurites were predominantly found in the cerebral cortices, which were compatible with frontotemporal lobar degeneration-TDP type C pathology.

Cogan Syndrome Accompanied with Meningitis / 대한평형의학회지

Cogan syndrome is a rare inflammatory disease characterized by intraocular inflammation and vestibulo-auditory dysfunction. The exact etiology of Cogan syndrome is still unknown, but is currently thought to be an autoimmune disease. Cogan syndrome can be accompanied with various conditions including fever, arthritis, skin rash, aortitis, central or peripheral nerve system involvement, lymphadenopathy, splenomegaly and diarrhea. We report a case of Cogan syndrome accompanied with meningitis.

Erratum to: Prognosis of Patients with Behavioral Variant Frontotemporal Dementia Who have Focal Versus Diffuse Frontal Atrophy

The original version of this article contained wrong information of an author which should be changed.

Prognosis of Patients with Behavioral Variant Frontotemporal Dementia Who have Focal Versus Diffuse Frontal Atrophy

BACKGROUND AND PURPOSE: Only a few studies have investigated the relationship between different subtypes and disease progression or prognosis in patients with behavioral variant frontotemporal dementia (bvFTD). Since a localized injury often produces more focal signs than a diffuse injury, we hypothesized that the clinical characteristics differ between patients with bvFTD who show diffuse frontal lobe atrophy (D-type) on axial magnetic resonance imaging (MRI) scans versus those with focal or circumscribed frontal lobe atrophy (F-type). METHODS: In total, 94 MRI scans (74 scans from bvFTD and 20 scans from age-matched normal controls) were classified into 35 D- and 39 F-type bvFTD cases based on an axial MRI visual rating scale. We compared baseline clinical characteristics, progression in motor and cognitive symptoms, and survival times between D- and F-types. Survival analyses were performed for 62 of the 74 patients. RESULTS: While D-type performed better on neuropsychological tests than F-type at baseline, D-type had higher baseline scores on the Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Evaluations of motor progression showed that the disease duration with motor symptoms was shorter in D-type than F-type. Moreover, the survival time was shorter in D-type (6.9 years) than F-type (9.4 years). Cox regression analyses revealed that a high UPDRS Part III score at baseline contributed to an increased risk of mortality, regardless of the pattern of atrophy. CONCLUSIONS: The prognosis is worse for D-type than for those with F-type. Shorter survival in D-type may be associated with the earlier appearance of motor symptoms.

Thyroid Autoantibody Positive Anti-N-Methyl-D-Aspartate Receptor Encephalitis

BACKGROUND: Hashimoto's encephalopathy (HE) and anti N-methyl-D-aspartate receptor (NMDAR) encephalitis have clinical overlaps. CASE REPORT: A 70-year-old woman presented with acutely developed confusion, disorientations and psychosis. HE was suspected based on goiter, markedly elevated anti-thyroglobulin and anti-thyroid peroxidase antibody. She was placed on high dose steroid and intravenous immunoglobulins administration, which did not ameliorate her symptoms. After the antibodies to the NMDAR were identified, weekly 500 mg of rituximab with 4 cycles were started. The current followed up indicated a complete recovery. CONCLUSIONS: The possible associations between NMDAR antibody and autoimmune thyroid antibodies in anti-NMDAR encephalitis with positive thyroid autoantibodies remain unclear. However, a trend toward a higher incidence of NMDAR antibody in patients with autoimmune thyroid antibodies than without has been observed. Cases of encephalitis with only NMDAR antibody (pure anti-NMDAR encephalitis) also occur. Therefore, it is important for clinicians to know the clinical and pathogenic differences between anti-NMDAR encephalitis with positive thyroid autoantibody and pure anti-NMDAR encephalitis for relevant treatment, predicting prognosis, and future follow-up.

Mild Clinical Features and Histopathologically Atypical Cores in Two Korean Families with Central Core Disease Harboring RYR1 Mutations at the C-Terminal Region

BACKGROUND: Central core disease (CCD) is a congenital myopathy characterized by distinctive cores in muscle fibers. Mutations in the gene encoding ryanodine receptor 1 (RYR1) have been identified in most CCD patients. CASE REPORT: Two unrelated patients presented with slowly progressive or nonprogressive proximal muscle weakness since childhood. Their family history revealed some members with the same clinical problem. Histological analysis of muscle biopsy samples revealed numerous peripheral cores in the muscle fibers. RYR1 sequence analysis disclosed a novel mutation in exon 101 (c.14590T>C) and confirmed a previously reported mutation in exon 102 (c.14678G>A). CONCLUSIONS: We report herein two families with CCD in whom missense mutations at the C-terminal of RYR1 were identified. Although it has been accepted that such mutations are usually associated with a severe clinical phenotype and clearly demarcated central cores, our patients exhibited a mild clinical phenotype without facial muscle involvement and skeletal deformities, and atypical cores in their muscle biopsy specimens.

Tear Meniscus Evaluation Using Optical Coherence Tomography in Dry Eye Patients

PURPOSE: To evaluate the tear meniscus in aqueous tear-deficient dry eye patients using Fourier-domain optical coherence tomography (FD-OCT) and to investigate the clinical usefulness of tear meniscus values. METHODS: The present study included 79 aqueous tear-deficient dry eyes and 50 normal eyes. Tear meniscus height (TMH), tear meniscus depth (TMD), and tear meniscus area (TMA) were imaged using FD-OCT and measured with computer calipers. Schirmer's test, tear break-up time, and corneal fluorescein staining were also performed and the correlations between the tests were analyzed. Additionally, the diagnostic power of tear meniscus values was compared using area under the receiver operating characteristic curve (AUROC). RESULTS: Tear meniscus values were significantly decreased in the aqueous tear-deficient dry eye group (p < 0.05). TMH, TMD, and TMA were positively correlated with Schirmer's test and tear break-up time (p < 0.05), and TMH and TMD were negatively correlated with corneal fluorescein staining in the aqueous tear-deficient dry eye group (p < 0.05). The AUROCs of TMH, TMD, and TMA were 0.978, 0.788, and 0.957, respectively. CONCLUSIONS: Tear meniscus values measured using FD-OCT were significantly lower in aqueous tear-deficient dry eyes and were correlated with Schirmer's test, tear break-up time, and corneal fluorescein staining. Tear meniscus measurements obtained using FD-OCT can be useful clinical parameters for the diagnosis and treatment of aqueous tear-deficient dry eye.

Short-Term Clinical Results and Safety of Ultra Q Laser Treatment for Vitreous Floaters

PURPOSE: To evaluate the short-term clinical results and safety of Ultra Q neodymium-doped yttrium aluminium garnet (Nd:YAG) laser treatment for vitreous floaters. METHODS: The present study included 31 eyes of 31 patients with symptomatic floaters lasting more than 3 months. The vitreous floaters were photodisrupted using Ultra Q Nd:YAG laser. Preoperative and postoperative best corrected visual activity (BCVA) and intraocular pressure, change of the floater, patient satisfaction and postoperative complications were analyzed prospectively. RESULTS: There was no significant difference between preoperative and postoperative BCVA and intraocular pressure (p > 0.05). Vitreous floaters were not found in 9 eyes (29.03%), decreased floaters were observed in 19 eyes (61.29%) and definite change of floaters was not observed in 3 eyes (9.68%). Patient satisfaction after the laser treatment was very satisfied in 11 eyes (35.48%) and satisfied in 20 eyes (64.58%). Satisfaction in Weiss ring type of the floater was the highest, very satisfied in 6 of the 8 eyes (75%) and vitreous floaters were not observed in 7 of the 8 eyes (87.50%). Postoperative complications were not observed during a follow-up period of at least 3 months. CONCLUSIONS: Ultra Q Nd:YAG laser was an effective and safe treatment for the vitreous floaters in this short-term study.

Late-Onset Narcolepsy with Cataplexy Unresponsive to Intravenous High-Dose Immunoglobulin Treatment

Narcolepsy with cataplexy (NC) is associated with hypocretin deficiency, and is thought to be an autoimmunity condition. The mean age at onset is estimated to be in the early 20s. Recent papers have addressed the response to immunotherapies in NC, with challenging results. We report a case of late-onset NC in a patient who did not benefit from early intravenous high-dose immunoglobulin (IVIg) therapy. This is the first reported attempt at using IVIg to treat an NC patient in Korea.

Cerebral Syphilitic Gummata Mimicking Metastatic Brain Tumors

No abstract available.

Unilateral Sensorineural Hearing Loss in Cerebral Venous Thrombosis

A 24-year-old woman presented with headache and left-sided tinnitus. Evaluations demonstrated left sensorineural hearing loss and cerebral venous thrombosis (CVT) with normal intracranial pressure. Unilateral hearing loss has rarely been reported in patients with CVT. It is thought that the unilateral hearing loss in this case was caused by impaired drainage of the cochlear veins into the lateral sinus.