Added Value of Chemical Exchange-Dependent Saturation Transfer MRI for the Diagnosis of Dementia

Objective@#Chemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia. @*Materials and Methods@#Our institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTR asym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves. @*Results@#Amine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTR asym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTR asym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91. @*Conclusion@#CEST MRI potentially allows noninvasive image alterations in the Alzheimer’s disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.

Added Value of Chemical Exchange-Dependent Saturation Transfer MRI for the Diagnosis of Dementia

Objective@#Chemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia. @*Materials and Methods@#Our institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTR asym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves. @*Results@#Amine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTR asym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTR asym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91. @*Conclusion@#CEST MRI potentially allows noninvasive image alterations in the Alzheimer’s disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.

Cognition enhancing effect of panax ginseng in Korean volunteers with mild cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial

This study aimed to investigate the cognition-enhancing effect of Panax ginseng. A randomized, double-blind, placebo-controlled clinical trial was conducted to address the cognition-enhancing effects of Panax ginseng. A total of 90 Korean volunteers with mild cognitive impairment participated in this study. All subjects were allocated randomly into ‘Ginseng’ group or ‘Placebo’ group. All subjects were administered 3g of Panax ginseng powder or starch (placebo) for 6 months. The Korean version of the Mini-Mental Status Examination (K-MMSE), Korean version of Instrumental Activities of Daily Living (K-IADL), and Seoul Neuropsychological Screening Battery (SNSB) were used to assess the changes in cognitive function at the end of the 6 month study period. The subjects of the ‘Ginseng’ group improved significantly on the Rey Complex Figure Test (RCFT) immediate recall (P = 0.0405 and P = 0.0342 in per-protocol (PP) and intention-to-treat (ITT) analysis, respectively) and on the RCFT 20-min delayed recall (P = 0.0396 and P = 0.0355 in PP and ITT analysis, respectively) compared with ‘placebo’ group throughout the 6 months of Panax ginseng administration. There were no serious adverse events. These results suggest that Panax ginseng has a cognition-enhancing effect.

Clinical Characteristics of Non-Amnestic Mild Cognitive Impairment: A Single-Center Experience

BACKGROUND: To evaluate the clinical characteristics of patients with non-amnestic mild cognitive impairment (naMCI) in a memory disorder clinic at a single center. METHODS: A retrospective study was conducted involving 312 patients with naMCI from May 2011 to July 2018. Brain magnetic resonance imaging and detailed neuropsychological tests were performed in all patients. We used the proposed criteria for naMCI to classify the patients into single- and multiple-domain groups. We compared the baseline clinical characteristics, neuroimaging findings, and the rate of progression to dementia between these two groups. RESULTS: The 312 patients comprised 210 in the single-domain group (67.3%) and 102 in the multiple-domain group (32.7%). The mean age was significantly higher in the multiple-domain group than in the single-domain group. The years of education, mean Mini Mental State Examination score, and mean Clinical Dementia Rating Scale Sum of Boxes score were significantly lower in the multiple-domain group than in the single-domain group. The Z-scores of neuropsychological tests in most cognitive domains were significantly lower in the multiple-domain group than in the single-domain group. Compared to the single-domain group, the multiple-domain group showed more-severe medial temporal atrophy and contained a higher proportion of patients with moderate white-matter hyperintensities. Thirteen (8.4%) patients with naMCI progressed to dementia, most of who were diagnosed with Alzheimer's disease. CONCLUSIONS: We present a single-center experience of clinical characteristics in patients with naMCI. Close observation of the clinical profiles of patients with naMCI may help identify individuals at the greatest risk of dementia.

A Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes: Protocol of a Multicenter, Randomized Controlled Trial

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is the most common cause of vascular dementia and a major contributor to mixed dementia. CSVD is characterized by progressive cerebral white matter changes (WMC) due to chronic low perfusion and loss of autoregulation. In addition to its antiplatelet effect, cilostazol exerts a vasodilating effect and improves endothelial function. This study aims to compare the effects of cilostazol and aspirin on changes in WMC volume in CSVD.METHODS: The comparison study of Cilostazol and aspirin on cHAnges in volume of cerebral smaLL vEssel disease white matter chaNGEs (CHALLENGE) is a double blind, randomized trial involving 19 hospitals across South Korea. Patients with moderate or severe WMC and ≥ 1 lacunar infarction detected on brain magnetic resonance imaging (MRI) are eligible; the projected sample size is 254. Participants are randomly assigned to a cilostazol or aspirin group at a 1:1 ratio. Cilostazol slow release 200 mg or aspirin 100 mg are taken once daily for 2 years. The primary outcome measure is the change in WMC volume on MRI from baseline to 104 weeks. Secondary imaging outcomes include changes in the number of lacunes and cerebral microbleeds, fractional anisotropy and mean diffusivity on diffusion tensor imaging, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability.CONCLUSIONS: CHALLENGE will provide evidence to support the selection of long-term antiplatelet therapy in CSVD.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932203

A Case of Restless Legs Syndrome in Patient with Neurogenic Sciatic Nerve Tumor

Restless legs syndrome (RLS) is chronic neurological disorder, in which the primary symptoms is unpleasant and disturbing sensation accompanied by urge to move in multiple body parts especially in legs. RLS may present in distinct phenotypes often described as “primary” vs. “secondary.” Secondary RLS can arise from etiologies such as iron deficiency, pregnancy, peripheral neuropathy, and end-stage renal disease. We report a rare case of RLS associated with neurogenic tumor of the sciatic nerve. A 72-year-old man complained of recurrent and worsening RLS symptoms in his right lower extremity, despite medical treatment. Interestingly, we found a neurogenic tumor at the right greater sciatic notch region on magnetic resonance imaging of the hip.

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.

Solid Cerebellar Hemangioblastoma with Peritumoral Edema: 5-Years Follow up

Hemangioblastomas are angioblastic tumors of the central nervous system. Cerebellar hemangioblastomas are traditionally classified into two morphologic types-cystic and solid. Cystic hemangioblastomas are associated with peritumoral edema, but solid hemangioblastomas are not. We report a case of solid cerebellar hemangioblastoma with massive peritumoral edema. An 83-year-old female visited our hospital due to a sudden headache. Five years ago, she had been admitted to our hospital with similar headache and diagnosed with cerebellar hemangioblastoma. Follow-up brain MRI 5 years later showed an increased size of a homogeneous enhancing mass with aggravated peritumoral edema in the left lower cerebellar hemisphere. Cerebral angiography showed a highly vascularized mass in the cerebellum, which was compatible with a solid-type hemangioblastoma.

Fatal ischemic stroke in a case of progressive moyamoya vasculopathy associated with uncontrolled thyrotoxicosis

No abstract available.

Isolated Weakness of Radial-side Fingers Due to a Small Cortical Infarction

Predominant involvement of a particular group of fingers due to a central nervous system lesion has been described as pseudoperipheral palsy. Two patients visited our hospital with isolated weakness of a particular group of fingers due to small cortical infarctions. A 51-year-old woman suddenly developed weakness in her left index and middle fingers. The brain MRI showed a small infarct in the right frontal cortex. A 67-year-old man was sudden difficulty using his chopsticks and had weakness in his right thumb and index finger. The brain MRI showed a small infarct in the left precentral cortex.

Sleep Disturbances and Predictive Factors in Caregivers of Patients with Mild Cognitive Impairment and Dementia

BACKGROUND AND PURPOSE: We examined the characteristics of sleep disturbances and sleep patterns in the caregivers of patients with amnestic mild cognitive impairment (aMCI) and dementia. METHODS: We prospectively studied 132 patients (60 with aMCI and 72 with dementia) and their caregivers, and 52 noncaregiver controls. All caregivers and controls completed several sleep questionnaires, including the Pittsburgh Sleep Quality Index (PSQI). The patients were administered neuropsychological tests and the neuropsychiatric inventory to evaluate their behavioral and neuropsychiatric symptoms of dementia (BPSD). RESULTS: The PSQI global score was 6.25+/-3.88 (mean+/-SD) for the dementia caregivers and 5.47+/-3.53 for the aMCI caregivers. The Insomnia Severity Index (ISI) and short form of the Geriatric Depression Scale (GDS-S) predicted higher PSQI global scores in aMCI caregivers, and higher scores for the ISI, Epworth Sleepiness Scale (ESS), and GDS-S in dementia caregivers. BPSD, including not only agitation, depression, and appetite change in dementia patients, but also depression, apathy, and disinhibition in aMCI patients, was related to impaired sleep quality of caregivers, but nighttime behavior was not. Age and gender were not risk factors for disturbed sleep quality. CONCLUSIONS: Dementia and aMCI caregivers exhibit impaired quality of sleep versus non-caregivers. ISI, GDS-S, and ESS scores are strong indicators of poor sleep in dementia caregivers. In addition, some BPSD and parts of the neuropsychological tests may be predictive factors of sleep disturbance in dementia caregivers.

Superior Rectus-Levator Palpebrae Complex Myositis Presenting as Isolated Painless Ptosis

No abstract available.

Prediction of Hemorrhagic Transformation and Functional Outcome Using HAT Score in Acute Ischemic Stroke Patients Treated with Intravenous Alteplase

BACKGROUND: Intravenous thrombolysis with alteplase is the most effective therapy for acute ischemic stroke, but hemorrhagic transformation (HT) is a potentially dangerous complication of such thrombolysis. Few studies have investigated the predictors of HT after thrombolysis in Korean stroke patients. METHODS: From 2003 to 2009, acute ischemic stroke patients who received intravenous alteplase were included from the prospective stroke registry of Kyung Hee University Hospital. Patients submitted to CT or MRI scans with gradient echo sequences within 12-36 hours of thrombolysis. The Hemorrhage After Thrombolysis (HAT) score [ranging from 0 (minimum risk) to 5 (maximum risk)] was calculated retrospectively for each patient. The predictive ability of the HAT score for HT and symptomatic intracranial hemorrhage (sICH) was calculated using C statistics. RESULTS: Among 151 consecutive patients, HT was confirmed in 35 on follow-up brain imaging. Atrial fibrillation (OR=2.709, 95%CI=1.118-6.567) and low one-third CT scan (OR=3.419, 95%CI=1.281-9.121) increased the risk of HT after intravenous thrombolysis in multivariate logistic regression analysis. HT, sICH (based on the National Institute of Neurological Disorders and Stroke and the Safe Implementation of Treatment in Stroke-Monitoring Study definitions), unfavorable [modified Rankin Scale (mRS) score of 2-6] and poor (mRS score of 3-6) outcomes at 3 months, and mortality at 3 months were increased with higher HAT scores (C statistic=0.632, 0.637, 0.843, 0.670, 0.689, and 0.659, respectively; p=0.018, 0.036, 0.042, 0.002, 0.015, and <0.001). CONCLUSIONS: The HAT score can be used to predict the risk of sICH following intravenous thrombolysis and the long-term clinical outcome.

Acute Cerebral Infarction Related to Stenosis of Accessory Middle Cerebral Artery / 대한뇌졸중학회지

The accessory middle cerebral artery (MCA) is an anomalous vessel which arises from the anterior cerebral artery (ACA) and runs through the Sylvian fissure along with the normal MCA. Here we present a case of acute cerebral infarction in a patient with stenosis of the accessory MCA. The accessory MCA, which originated from the proximal A1 segment of the ACA, had severe focal stenosis in its proximal part and the ischemic lesions were in the frontal subcortical white matter. This case illustrates the anomalous vessel and its territory, the atheromatous vascular change, and the related ischemic insults.

Plaque Rupture is a Determinant of Vascular Events in Carotid Artery Atherosclerotic Disease: Involvement of Matrix Metalloproteinases 2 and 9

BACKGROUND AND PURPOSE: Unstable carotid atherosclerotic plaques are characterized by cap rupture, leading to thromboembolism and stroke. Matrix metalloproteinases (MMPs) have been implicated in the progression of atherosclerosis and plaque rupture. The aim of this study was to assess the relationship between the expressions of MMP-2 and MMP-9 and carotid plaque instability. METHODS: Eighty atherosclerotic plaques were collected from 74 patients undergoing carotid endarterectomy. Clinical information was obtained from each patient, and plaque morphology was examined at the macroscopic and microscopic levels. The immunohistochemical expressions of MMPs were graded using semiquantitative scales. RESULTS: Macroscopic ulceration (84.6% versus 63.4%, p=0.042) and microscopic cap rupture (79.5% versus 51.2%, p=0.010) were more common in symptomatic than in asymptomatic patients. Immunoreactivities of MMP-2 and MMP-9 were increased in 40 and 36 atheromatous plaques, respectively. Macroscopic ulceration was strongly correlated with the expressions of MMP-2 (p<0.001) and MMP-9 (p=0.001). There were significant correlations between increased MMP-2 expression and cap rupture (p=0.002), intraplaque hemorrhage (p=0.039), and a thin fibrous cap (p=0.002), and between increased MMP-9 expression and cap rupture (p=0.010) and a large lipid core (p=0.013). CONCLUSIONS: Plaque rupture was significantly associated with the development of vascular events in carotid atherosclerotic disease. MMP-2 and MMP-9 are strongly correlated with plaque instability.

Development of Global Deterioration Scale Staging Algorithm

BACKGROUND: The Global Deterioration Scale (GDS) is a useful tool for staging dementia; each stage is described by specific characteristics. However, one should not rely on the presence or absence of a single symptom in determining the stage. There is a need for a systematic computerized program to enable untrained doctors to easily assess dementia. This study aimed to generate an algorithm to help stage dementia. METHODS: Items were drawn from each stage and sorted out into questions adequate for the caregiver and questions adequate for the patient. Subjects recruited were 50 years or older and had visited the neurologic and/or psychiatric clinic at any of the university affiliated hospitals with symptoms of memory impairment. Structured questionnaires with 20 questions were administered to the subject-informant dyads. Psychometricians or well-trained nurses then assessed the remaining 10 items and decided the overall stage. Classification tree analysis was accomplished by using SPSS Answer Tree 3.0 software. RESULTS: 182 subject-informant dyads were included in the analysis. The mean age was 74.5 years; 112 (61.5%) were female. Among the 30 predictors, the item 'get lost when travelling' was the most important predictor of GDS score (chi2=96.6, p=0.0000). The classification tree algorithm begins with the item 'get lost when travelling' and includes 13 predicting variables. The most probable GDS predicted scores are presented in the final nodes of the algorithm. Risk estimate, probability of misclassification in the developed model, was 35.2%. CONCLUSION: A classification tree algorithm for GDS staging was developed to narrow down the range of choices when staging cognitive impairment. The algorithm is yet to undergo validity and reliability tests.

Acute Ischemic Stroke Associated with Essential Thrombocythemia and Suspected Platelet Aggregation in Intracranial Artery / 대한뇌졸중학회지

Acute ischemic stroke is often the first manifestation of essential thrombocythemia (ET). We report two cases of acute ischemic stroke in patients with ET who suffered acute thrombus formation in a large cerebral artery with related cortical infarction. We suggest that platelet aggregation and its distal embolization may occur in large intracranial arteries in patients with ET.

A Case of Herpes Zoster Ophthalmicus with Isolated Trochlear Nerve Involvement

BACKGROUND: Herpes zoster ophthalmicus (HZO) can involve the oculomotor nerve; however, isolated trochlear nerve palsy has rarely been reported. CASE REPORT: An 83-year-old man who suffered from HZO in the right frontal area and scalp subsequently developed vertical diplopia and severe pain. Cerebrospinal fluid examination and brain MRI revealed no abnormalities. Isolated right trochlear nerve palsy was diagnosed based on the findings of neuro-ophthalmological tests. CONCLUSIONS: Isolated trochlear nerve involvement associated with HZO is very rare and may be easily overlooked. Physicians should carefully examine oculomotor involvement in HZO.

Association of Serum Uric Acid With Early Prognosis Stratified by the Stroke Subtype in Patients With Moderate to Severe Ischemic Stroke

BACKGROUND: The role of uric acid in cerebrovascular disease is controversial. Uric acid may be an independent risk factor for cerebrovascular diseases but its neuroprotective role as an antioxidant has also been suggested. We studied the effects of uric acid on the early prognosis in acute ischemic stroke. METHODS: The subjects were 721 patients with moderate-to-severe acute stroke who arrived at hospital within 48 hours from the onset of symptoms. Patients were divided into quartiles based on serum uric acid levels at admission. In-hospital stroke outcome were calculated on the National Institutes of Health Stroke Scale (NIHSS) and analyzed by multivariate logistic regression. RESULTS: Differences in NIHSS scores between baseline and discharge in the patients were not significantly related to serum uric acid levels. However, in large artery atherosclerosis group, the proportion of patients with neurological improvement and differences in NIHSS score between baseline and discharge differed between the quartile uric acid groups (p<0.01 and p=0.04, respectively). A multivariate analysis adjusting for known vascular risk factors showed that a higher uric acid level was associated with a higher probability of a good in-hospital outcome (odds ratio, 1.31 per additional 1 mg/dL; 95% confidence interval, 1.07-1.60 per additional 1 mg/dL), but only in those with large-artery atherosclerosis. CONCLUSIONS: Uric acid level is independently correlated with the neurological improvement in patients with acute ischemic stroke caused by large-artery atherosclerosis.