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PURPOSE OF THE REPORT In vivo tau PET imaging could help clarify the spatial distribution of tau deposition in Alzheimer disease (AD) and aid in the differential diagnosis of tauopathies. To date, there have been no in vivo F-APN1607 tau PET studies in patients with AD. METHODS We applied tau tracer in 12 normal controls (NCs) and 10 patients in the mild to moderate stage of probable AD. Detailed clinical information, cognitive measurements, and disease severity were documented. Regional SUV ratios (SUVRs) from F-AV-45 (florbetapir), F-APN1607 PET images, and regional gray matter (GM) atrophic ratios were calculated for further analysis. RESULTS Quantitative analyses showed significantly elevated SUVRs in the frontal, temporal, parietal, occipital lobes, anterior and posterior cingulate gyri, precuneus, and parahippocampal region (all P's < 0.01) with medium to large effect sizes (0.44-0.75). The SUVRs from F-APN1607 PET imaging showed significant correlations with the Alzheimer's Disease Assessment Scale (ADAS-cog) scores (all P's < 0.01) and strong correlation coefficients (R ranged from 0.54 to 0.68), even adjusted for age and sex effects. Finally, the SUVRs from F-APN1607 PET imaging of the parahippocampal region showed rapid saturation as the ADAS-cog scores increased, and the SUVRs of the posterior cingulate gyrus and the temporal, frontal, parietal, and occipital regions slowly increased. The combined SUVRs from amyloid, tau PET, and regional GM atrophic ratio showed regional specific patterns as the ADAS-cog scores increased. CONCLUSIONS Our findings suggest that the F-APN1607 tau tracer correlated well with cognitive changes and demonstrated the spatial pattern of amyloid, tau deposition, and GM atrophy in the progression of AD.

Background Angiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)–modulating effects, has additional benefits compared to other ARBs remains unclear. Methods and findings Between 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set at p < 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19% versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97; p = 0.030). They also had lower risk of dementia diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95; p = 0.022) and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97; p = 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%; HR, 0.79; 95% CI, 0.67 to 0.94; p = 0.008) during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data. Conclusions The current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population., Chi-Hung Liu and co-workers study associations between antihypertensive medication prescriptions and dementia risk in people with type 2 diabetes., Author summary Why was this study done? The drug of choice for antihypertensive treatment, and its association with dementia in patients with both type 2 diabetes mellitus (T2DM) and hypertension, is a valid question worthy of further investigations. Angiotensin receptor blockers (ARBs) modulate the renin–angiotensin–aldosterone system and potentially associate with cognitive preservation, but internal comparisons of the cognitive protective effects of different ARBs have not previously been performed. Telmisartan is the only ARB that, at a clinical dose, has agonistic effects on peroxisome proliferator-activated receptor γ (PPAR-γ), which maintains insulin sensitivity, reduces insulin resistance, and potentially has a protective impact on dementia. What did the researchers do and find? Using the electronic health records of the National Health Insurance Research Database of Taiwan between 1997 and 2013, we studied whether telmisartan was associated with a lower incidence of dementia compared to other ARBs in patients with T2DM and hypertension. Using telmisartan was associated with a lower risk of dementia diagnosis compared to using non-telmisartan ARBs (2.19% versus 3.20%). What do these findings mean? Telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any ischemic stroke events in an East-Asian population. Further work will be needed to investigate the observed association, owing to the limitations inherent in this observational study.

Background: Visual association memory test (VAMT) is a brief 6-point cognition test that has been shown to be effective in differentiating Alzheimer's disease (AD) from other types of dementia. This study aimed to investigate the correlation of the VAMT performance with amyloid plaque burden and hippocampal atrophy. Methods: Fourteen patients with AD, 29 with amnestic mild cognitive impairment (aMCI), and 11 normal cognition (NC) subjects were recruited. Brain magnetic resonance imaging (MRI) and [18F]AV-45 positron emission tomography (PET) were performed to evaluate hippocampal atrophy and amyloid plaque burden. Results: The VAMT median score and interquartile range of the NC, aMCI and AD groups were 6 (6-6), 2 (0–4), and 0 (0–1), respectively (p

Background This study aims to investigate the etiology and prognosis of spinal cord infarction (SCI). Methods Over a period of 16 years, we retrospectively analyzed 31 patients with SCI. Demographic features and symptom presentations were carefully documented. Etiology‐specific MRI features, such as the length and distribution of the lesions and owl’s eyes sign, were recorded and analyzed to determine their associations with the clinical signs/symptoms. Results In total, seven patients had aortic or vertebral artery dissections. We divided the patients with SCI into two groups: those with or without vessel dissection. Among SCI patients, the onset age was younger, and the proportion of patients with long‐segment lesions and posterior pattern involvement on axial view was higher in the group with dissection than in the group without dissection (all P

Background: Acute necrotizing encephalopathy (ANE), a fulminant encephalopathy, is often found in childhood. It is still uncertain whether adult patients with ANE display clinical features different from patients with typical pediatric onset. Furthermore, alterations in neuroinflammatory factors in patients with ANE have not been well-characterized. Here, we present an adult patient with ANE, and review all reported adult ANE cases in the literature. Methods: Serum levels of five cytokines were checked in an adult patient with ANE and compared with gender/age-matched controls. Literature search was performed with PubMed, using the term as “acute necrotizing encephalopathy” with the filter of adult 19 + years. Results: A total of 13 adult patients were reviewed. Compared with pediatric patients, adult ANE patients had similar clinical symptoms, biochemical data, and neuroimage findings, whereas adult ANE were more female-biased (female:male, 9:4) with a worse prognosis. Elevated cytokine levels in the serum and/or CSF is found in both adult-onset and pediatric-onset ANE. We found significantly elevated serum levels of IL-6 (17.17 pg/mL; healthy control: 1.43 ± 1.22 pg/mL) and VCAM-1 (3033.92 ng/mL; healthy control: 589.71 ± 133.13 ng/mL), and decreased serum TGF-β1 level (14.78 ng/mL, healthy controls: 25.81 ± 6.97 ng/mL) in our patient. Conclusions: Our findings clearly delineate the clinical features and further indicate the potential change in cytokine levels in adult patients with ANE, advancing our understanding of this rare disease. Keywords: Acute necrotizing encephalopathy, Adult, Cytokine, VCAM-1

Objective This study aims to identify metabolites with altered levels of expression in patients with early and progressive stages of Alzheimer's disease (AD). Methods All participants of the study underwent genetic screening and were diagnosed using both neuropsychological assessment and amyloid imaging before metabolome analysis. According to these assessments, the patients were classified as normal (n = 15), with mild cognitive impairment (n = 10), and with AD (n = 15). Results Using a targeted metabolomic approach, we found that plasma levels of C3, C5, and C5‐DC acylcarnitines, arginine, phenylalanine, creatinine, symmetric dimethylarginine (SDMA) and phosphatidylcholine ae C38:2 were significantly altered in patients with early and progressive stages of AD. We created a predictive model based on the decision tree that included three main parameters: age, arginine and C5 plasma concentrations. The model distinguished AD patients from other participants with 60% sensitivity and 86.7% specificity. For healthy controls, the sensitivity was 85.7% and specificity was 61.5%. Multivariate ROC analysis to develop a decision tree showed that our model reached moderate diagnostic power in differentiating between older adults who are cognitively normal (AUC = 0.77) and those with AD (AUC = 0.72). Interpretation The plasma levels of arginine and valeryl carnitine, together with subject age, are promising as biomarkers for the diagnosis of AD in older adults.

Background: The behavioral and psychological symptoms of dementia (BPSD) seriously affect the quality of life of patients with Alzheimer’s disease (AD) and their caregivers. Objective: We aimed to identify associations between demographic/genetic factors and clinical presentations of BPSD. Methods: In a cohort of 463 AD patients with BPSD, we retrospectively analyzed sex, education level, AD severity (assessed using the Clinical Dementia Rating and Mini-Mental Status Examination), and BPSD severity (assessed using the Neuropsychiatry Inventory, NPI). Severe BPSD was defined as NPI ≥10 for 3 consecutive years. Results: Among patients with severe BPSD (NPI ≥10), we observed more female patients (62.96%) and a lower level of education (6.03±4.77 years) as compared to those with mild BPSD (NPI

Background Mutations in the GRN (granulin precursor) are a frequent cause of frontotemporal dementia (FTD) and other atypical parkinsonian disorders. However, the frequency of GRN mutations in Asian patients with atypical parkinsonian disorders is still uncertain. Methods We screened GRN mutations by sequencing cDNA from 98 patients with FTD or atypical parkinsonian disorders. The functional properties of the identified mutation were evaluated by overexpression in human embryonic kidney (HEK)-293 cells. Results We identified a new missense (GRN p.T487I) mutation in a female patient with undefined atypical parkinsonism. The overexpression experiment further demonstrated that p.T487I mutation reduced the progranulin protein level and stability in HEK-293 cells. Conclusion GRN p.T487I mutation, which decreases the stability of progranulin protein, could be a new causative mutation in patients with atypical parkinsonian disorders.

Introduction Due to the high cost and high failure rate of ascertaining amyloid positron emission tomography positivity (PET+) in patients with earlier stage Alzheimer’s disease (AD), an effective pre-screening tool for amyloid PET scans is needed. Methods Patients with mild cognitive impairment (n = 33, 24.2% PET+, 42% females, age 74.4 ± 7.5, MMSE 26.8 ± 1.9) and mild dementia (n = 19, 63.6% PET+, 36.3% females, age 73.0 ± 9.3, MMSE 22.6 ± 2.0) were recruited. Amyloid PET imaging, Apolipoprotein E (APOE) genotyping, and plasma amyloid β (Aβ)1–40, Aβ1–42, and total tau protein quantification by immunomagnetic reduction (IMR) method were performed. Receiver operating characteristics (ROC) analysis and Youden’s index were performed to identify possible cut-off points, clinical sensitivities/specificities, and areas under the curve (AUCs). Results Amyloid PET+ participants had lower plasma Aβ1–42 levels than amyloid PET-negative (PET−) subjects. APOE ε4 carriers had higher plasma Aβ1–42 than non-carriers. We developed an algorithm involving the combination of plasma Aβ1–42 and APOE genotyping. The success rate for detecting amyloid PET+ patients effectively increased from 42.3 to 70.4% among clinically suspected MCI and mild dementia patients. Conclusions Our results demonstrate the possibility of utilizing APOE genotypes in combination with plasma Aβ1–42 levels as a pre-screening tool for predicting the positivity of amyloid PET findings in early stage dementia patients.

This study aims to investigate the clinical features and magnetic resonance imaging (MRI) findings in patients with spinal cord infarction (SCI) and neuromyelitis optica spectrum disorders (NMOSDs). Over a period of 16 years, we retrospectively analyzed 39 patients with SCI and 21 patients with NMOSD. The demographic features and clinical presentations of both diseases were carefully documented. Etiology-specific MRI features, such as the length and distribution of the lesions, the owl’s eyes sign and bright spotty lesions, were recorded and analyzed regarding their association with the clinical signs/symptoms. Patients with SCI were older than patients with NMOSD and had sudden onset of clinical symptoms with focal pain adjacent to the lesions. Concomitant spinal cord and vertebral body infarctions were frequently associated with aortic pathology (p = 0.04). In addition, artery dissection was highly associated with combined ASA and unilateral PSA infarctions and long segments of SCI (all p

We investigated dual-phase (18)F-florbetapir (AV-45/Amyvid) PET imaging for the concomitant detection of brain perfusion deficits and beta-amyloid deposition in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), and in cognitively healthy controls (HCs).A total of 82 subjects (24 AD patients, 44 MCI patients and 14 HCs) underwent both dual-phase (18)F-AV-45 PET and MRI imaging. Dual-phase dynamic PET imaging consisted of (1) five 1-min scans obtained 1 - 6 min after tracer injection (perfusion (18)F-AV-45 imaging, pAV-45), and (2) ten 1-min scans obtained 50 - 60 min after tracer injection (amyloid (18)F-AV-45 imaging). Amyloid-negative MCI/AD patients were excluded. Volume of interest analysis and statistical parametric mapping of pAV-45 and (18)F-AV-45 images were performed to investigate the perfusion deficits and the beta-amyloid burden in the three study groups. The associations between Mini-Mental State Examination (MMSE) scores and global perfusion deficits and amyloid deposition were investigated with linear and segmental linear correlation analyses.HCs generally had normal pAV-45 findings, whereas perfusion deficits were evident in the hippocampus, and temporal, parietal and middle frontal cortices in both MCI and AD patients. The motor-sensory cortex was relatively preserved. MMSE scores in the entire study cohort were significantly associated with the degree of perfusion impairment as assessed by pAV-45 imaging (r = 0.5156, P 0.0001). (18)F-AV-45 uptake was significantly higher in AD patients than in the two other study groups. However, the correlation between MMSE scores and (18)F-AV-45 uptake in MCI patients was more of a binary phenomenon and began in MCI patients with MMSE score 23.14 when (18)F-AV-45 uptake was higher and MMSE score lower than in patients with early MCI. Amyloid deposition started in the precuneus and the frontal and temporal regions in early MCI, ultimately reaching the maximum burden in advanced MCI.Our results indicate that brain perfusion deficits and beta-amyloid deposition in AD follow different trajectories that can be successfully traced using dual-phase (18)F-AV-45 PET imaging.

BACKGROUND The amyloid AV-45 (florbetapir) positron emission tomography (PET) has been used in the study of the familial Alzheimer's disease (FAD) with the D678H amyloid precursor protein (APP) mutation. In addition, the progress of the disease remains unknown. OBJECTIVE We aim to investigate the progression rate of amyloid accumulation in FAD patients with this mutation by neuroimages analysis. METHODS The clinical course, changes in cognitive function, brain magnetic resonance imaging (MRI) and 18F-AV-45 PET scan were investigated in FAD patients and sporadic AD (sAD) patients. We compared the amyloid deposition pattern in serial brain 18F-AV-45 PET scan among the FAD, familial mild cognitive impairment (FMCI), and sMCI and sAD patients. RESULTS Seven familial patients received a follow-up survey. The follow up duration for brain AV-45 PET was from 1.54 to 3.61 years. In 4 FMCI patients, an increased regional SUVR was noted, and the annual change rates were increased from 1.03% to 18.82%. However, a decreased regional SUVR was noted in 3 FAD patients and the annual change rates were from -2.62% to -16.03%. As compared with the sAD and sMCI patients, the annual change rate is statistically significant in FAD and FMCI patients respectively. CONCLUSIONS The data indicate a biphasic course with an initial increase and then a decrease of SUVR in brain amyloid PET scan in familial APP mutation patients. The data also reveal that the novel Taiwan APP (D678H) mutation has a more amyloid burden than the sAD patients, particularly in an MCI stage.

Introduction The novel D678H amyloid precursor protein (APP) gene mutation has been called the “Taiwan mutation”. The study aims to identify amyloid deposition patterns and clinical features associated with this mutation. Methods we analyzed the clinical manifestations, brain neuroimages and 18F-AV-45 positron emission tomography (PET) findings in symptomatic patients and asymptomatic subjects with the autosomal-dominant Alzheimer's disease (AD). We compared the amyloid deposition pattern among 10 patients with genetically-positive familial cognitive decline (CD), 18 patients with sporadic CD, and 19 healthy controls. Results The clinical features were the early onset of memory impairment in all 10 patients and cerebral amyloid angiopathy in 3 patients. The characteristic results of brain 18F-AV-45 PET included the highest standard uptake value ratio (SUVR) in the occipital and cerebellar cortical areas in the genetically-positive CD patients. In subgroup analysis, the familial AD patients had a decreased amyloid SUVR trend in most areas except for cerebellar cortex compared to those with familial mild cognitive impairment. Conclusion Our data indicate that the familial D678H gene mutation have resulted in a more potent amyloid burden than in the patients with sporadic AD patients. The high amyloid uptake in the occipital area is characteristic of the specific Taiwan APP gene.

Objective To investigate clinical and radiological features of Tolosa–Hunt syndrome (THS) and examine their diagnostic value, and to propose clinical and radiological features that indicate other symptomatic painful ophthalmoplegias (SPOs) in order to distinguish them from THS. Background Clinical presentations of THS are nonspecific and may overlap with many etiologies. Therefore, excluding other SPOs is essential for correct diagnosis. At the present time, the predictive value of the current International Classification of Headache Disorders (ICHD) criteria is not well established, and specific imaging markers that can discriminate SPOs from THS are lacking. Methods Patients referred with painful ophthalmoplegia over 12 years were recruited retrospectively and allocated into THS or SPO groups. Typical symptoms (episodic unilateral orbital pain preceding or developing with diplopia) and imaging of THS (inflammatory lesions in the cavernous sinus/orbit by magnetic resonance imaging) were proposed based on ICHD-3 beta criteria and previous literature. Atypical clinical and radiological features suggesting alternative diagnoses were also proposed to predict SPO. Initial presentations and imaging findings were registered and correlated with diagnostic outcomes. The predictive value of clinical and imaging findings was then evaluated. Results Of the 61 referred cases, 25 were classified as THS and 36 as SPO. Of the SPO cases, 52.8% manifested typical THS symptoms at onset. Patients with SPOs were prone to have atypical symptoms (47.2%) and radiographical findings (82.1%) in comparison to those with THS (4.0% and 4.2%, respectively; both P

Objective To investigate the clinical characteristics of patients with uncommon distal symmetric painful small-fiber neuropathy (DSPSFN). Methods From September 2012 to September 2014, participants between 18–70 years of age that had DSPSFN defined by clinical signs/symptoms and ID pain > 2 or DN4 > 4 on questionnaires for more than 1 month were included. Participants who had previous historical or laboratory evidence of common etiologies of DSPSFN were excluded. Enzyme activity and genetic studies for Fabry diseaseand familial amyloid polyneuropathy were performed after participants fulfilled the inclusion and exclusion criteria. The cryoglobulin test, autoantibodies studies and electrophysiological studies were performed in these participants. Results In total, 100 cases were enrolled in the current study. Three cases of subclinical diabetes mellitus and two cases of fibromyalgia were found. Fabry disease (1%) and familial amyloid polyneuropathy (3%) with Ala97Ser transthyretin (TTR) mutations were also detected. The cryoglobulin test was positive in 30% of participants, and these participants had higher DN4 scores than the negative group. In the autoantibodies studies, 59% of the participants had abnormal anti-Ro/SSA and/or anti-La/SSB antibodies. Conclusions Cryoglobulinemia is not a rare etiology of uncommon DSPSFN. The long-term prognosis is quite good in these participants. From our structuralized protocol, Fabry disease and familial amyloid polyneuropathy could be easily detected in these cases of uncommon DSPSFN.

In addition to testing blood, cerebrospinal fluid (CSF) has been analyzed in the search for biomarkers. The aim of this study was to identify biomarkers in CSF for neuropsychological symptoms in early-stage late-onset Alzheimer's disease (LOAD).CSF levels of beta-amyloid 1-42 (Aβ42), F2-isoprostanes (F2-IsoPs) and F4-neuroprostanes (F4-NPs) were assayed in nine patients with mild Alzheimer's disease (AD), nine patients with amnestic mild cognitive impairment (a-MCI) and nine individuals with normal mental function. The three groups underwent neuropsychological testing.CSF levels of F2-IsoPs and F4-NPs did not significantly differ among the three groups. Aβ42 in CSF was significantly higher in the control group compared with the mild AD group (p0.001) and a-MCI group (p = 0.03). There was a significant positive correlation between the level of F2-IsoPs and Aβ42 in the a-MCI group and between the level of F2-IsoPs and F4-NPs in the mild AD group. In comparisons between the mild AD group and a-MCI group combined, the cognitive impairment (CI) group, with the control group, the median levels of F2-IsoPs and F4-NPs were significantly higher in the CI group and median level of Aβ42 was significantly lower in the CI group. Both the levels of F2-IsoPs and Aβ42 were significantly negatively correlated with paranoid and delusional ideation and total score for the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD).The findings suggest CSF levels of Aβ42 and F2-IsoPs are associated with the severity of neuropsychological symptoms.

Amyloid positron emission tomography (PET) is an important noninvasive method for detecting amyloid burden in Alzheimer's disease (AD) patients. As amyloid PET images have limited anatomical information, magnetic resonance (MR) imaging is usually acquired to perform reliable spatial normalization needed for large-scale analysis. This work proposed and evaluated the performance of new MR-free spatial normalization methods using a perfusion-like template for amyloid PET imaging.Amyloid PET and MR images were collected in 35 subjects (cohort 1: 8 AD patients and 6 controls; cohort 2: 15 AD patients and 6 controls). Three ligand-related templates (AD, control, mixed group) and a perfusion-like template (pAV-45) from early time frames of amyloid PET images were constructed from cohort 1. The variations of (18)F-AV-45 standardized uptake value ratios (SUVRs) among AD patients, controls, and all subjects were tested with repeated two-way (template × brain region) analysis of variance (ANOVA) in cohort 2. (18)F-AV-45 SUVRs by region of interest analysis and voxelwise analysis between MR-based and MR-free approaches were compared and correlated to clinical and image parameters. Effect size (group mean SUVR difference between AD and control/standard deviation) was also evaluated for each template method.Significantly different (18)F-AV-45 SUVRs between MR-free spatial normalization and MR-based reference images were found among AD patients, controls, and all subjects by the effect of template and brain regions. The highest correlation (r=0.991) of (18)F-AV-45 SUVR to MR-based reference was found in the pAV-45 group. The SUVR percentage difference to MR-based reference showed the least variation and bias (control: -1.31±3.47 %; AD: -0.36±2.50 %) in the pAV-45 group as well. The voxelwise analysis showed the smallest t statistic value in pAV-45 followed by mixed, control, and AD groups when compared to MR-based reference images. Moreover, an overall larger effect size but compatible to that of MR-based reference result was observed in the pAV-45 group as compared to those of the other MR-free template.The novel MR-free template based on the early-phase perfusion images pAV-45 approach for amyloid imaging showed significantly better performance in quantitation accuracy, effect size, and stability when compared with other MR-free PET templates and thus has potential for large-scale clinical applications.

To determine whether dual-phasePatients diagnosed with PPA, including four semantic dementia (SD) and two progressive nonfluent aphasia (PNFA), as well as one logopenic variant (LV) of PPA, were studied. All PPA patients, and age-/sex-matched patients with probable AD (n=8) and HCs (n=8) were subjected to dual-phaseEarly phaseDual-phase

Background/Purpose The clinical analyses and prognoses of mitochondrial diseases with A3243G mutation are rarely documented in Taiwan. Our study investigated the clinical phenotypes and the outcomes of patients with mitochondrial disease and the A3243G mutation of mtDNA in a Taiwanese population, and compared these with previous reports. Methods We retrospectively studied 22 consecutive patients with mitochondrial disease and the A3243G mutation of mtDNA in Chang Gung Memorial Hospital between 1988 and 2009. All patients underwent a detailed demographic registration, neurological examinations, a muscle biopsy, and mitochondrial DNA analysis. Modified Rankin scale, the presence of recurrent strokes or seizures, critical medical complications, and death were monitored during the follow-up period. Results Of the 22 patients, seizures and stroke-like episodes were found in 12 (55%). Visceral involvement, including cardiomyopathy, nephropathy, and pulmonary hypertension, were noted in five patients (23%). Patients with seizures had a high frequency of status epilepticus (92%) and a younger age of onset (21.3 ± 7.2 years). Both the Kaplan–Meier survival analysis and the Cox-regression model showed a marked deterioration in patients with seizures after 7 years of follow-up. Conclusion Our study found that seizures and status epilepticus are the most important predictive values for a poor outcome in patients with the mtA3243G mutation of mtDNA. Age of onset and visceral organ involvement had no prominent influence on the prognosis. Some medical complications could be well controlled or even reversed after management.

Objectives To investigate the long-term neurotoxic effects in a patient with acute dimethylamine borane (DMAB) intoxication. Patients A 38-year-old man, working in a semiconductor factory, with acute DMAB intoxication presented with confusion, and drowsiness, followed by cognitive impairments and motor-predominant axonal polyneuropathy. Investigations We performed serial neurobehavioral assessments and functional neuroimaging studies, including brain 99m Tc-TRODAT single photon emission computed tomography (SPECT) and brain positron emission tomography (PET) scan to monitor the long-term central nervous system (CNS) effects of DMAB intoxication. Results Neurobehavioral tests revealed a persistent impairment in episodic memory of visual retention semantic category retrieval and working memory of digit span (backward). Brain 99m Tc-TRODAT SPECT scan showed a lower radioactivity uptake in the left striatum and F-18 FDG PET scan revealed a relatively decreased cerebral metabolism at the anterior cingulate gyrus and both frontal regions. Follow-up neurobehavioral tests showed that the cognitive improvements were mainly documented in intelligence, attention function, conceptual shift, perceptual motor speed, verbal learning and working memory but were limited in visual memory and executive functions. Conclusion Patients with acute DMAB intoxication may have a long-lasting CNS toxicity on the cognitive dysfunction, parkinsonism, and an impaired metabolic activity of the brain. Clinical improvements may sustain during the long-term follow-up period.

Myelitis is a rare complication of varicella zoster virus (VZV) infection and is more prevalent in immunocompromised individuals. Clinical features, outcomes, and presentations vary. The aim of the current study was to compare the clinical presentations of our patients with those reported in the literature, and to evaluate the differences in clinical features between immunocompromised and immunocompetent patients.A review of the literature on VZV myelitis was carried out by searching PUBMED from 1980 to 2012. Clinical features of our cases and those in the literature were compared.There were 5 cases at our hospital and 26 were reported in the literature. Seventeen patients were immunocompromised (54.8%), and most had acquired immune deficiency syndrome (AIDS). Typical presentations (skin lesions followed by myelopathy at the corresponding level) were observed in 14 patients (45.2%). The immunocompromised patients were prone to atypical presentations (p0.05). Outcomes were good in immunocompetent patients and relatively poor in immunocompromised patients (p0.05). Anti-herpetic agents had no statistically significant effect on outcomes in immunocompromised patients (p=0.280), but could reduce mortality rate in AIDS patients (p0.05).Immunocompromised individuals are susceptible to this disease, and prone to atypical presentations and poorer outcomes. Timely recognition and anti-herpes therapy may be beneficial to the outcomes. In the AIDS patients, anti-herpes therapy can reduce mortality effectively.

Background Overexposure to carbon disulfide (CS2) has been associated with an increase in coronary heart disease, but the mechanisms mediating this effect remain unclear. We aimed to examine the relationship between CS2 exposure and oxidative stress markers, in order to clarify the oxidative mechanisms involved in CS2-induced atherosclerosis. Methods A total of 89 workers from a viscose rayon plant were recruited for this study, and 111 workers not exposed to CS2 served as controls. Cholesterol, triglyceride, malondialdehyde (MDA), superoxide dismutase (SOD), catalase, GSH peroxidase, as well as total antioxidants were analyzed. Results The workers exposed to CS2 had significantly higher MDA levels and lower SOD levels than the controls. The average MDA levels were 776 ± 268.2 (240–1,220) in the high exposure (≥10 ppm; n = 38), 751.6 ± 274 (170–1,320) in the low exposure (

Background: Acute intermittent porphyria (AIP) is an inherited disorder of heme biosynthesis, the clinical manifestations of which are incompletely understood. In this report, we describe 12 cases of AIP, focusing on the neurological manifestations. Methods: Twelve patients were diagnosed with AIP on the basis of characteristic clinical findings, erythrocyte porphobilinogen deaminase (PBGD) activity, and molecular genetics. Central and peripheral nervous system manifestations were noted, and electrophysiological and radiological studies performed. Potential precipitating factors were recorded. Results: Eleven PBGD gene mutations were identified in 12 patients. Nine patients experienced neurological symptoms involving the central nervous system (consciousness disturbance, n = 8; convulsion/seizure, n = 4; behavior change, n = 1), while 7 patients experienced peripheral neuropathies (motor paresis, n = 7; impairment of bulbar or respiratory function, n = 4). The electrophysiological and electroencephalographic findings were consistent with the neurological symptoms of AIP. Urinary PBG and δ-aminolevulinic acid levels were elevated in all patients. PBGD enzyme activity levels were below normal in all patients. Eight patients had documented exposure to porphyrogenic agents. Conclusions: Our detailed description of a relatively large number of cases of AIP may help clinicians to recognize this often difficult-to-diagnose disorder.

Lipid storage myopathies (LSMs) are characterized pathologically by the accumulation of lipid droplets in muscle fibers due to impaired cellular lipid metabolism. The purpose of this study was to determine etiologies and genetic mutations associated with LSMs in ethnic Han Taiwanese. The usefulness of the blood acylcarnitine (AC) profile for diagnosing LSMs in adult patients was also investigated. Nine patients were diagnosed with late-onset LSMs following a review of muscle biopsies and medical records and were recruited retrospectively. Genetic studies were performed to detect mutations in the SLC22A5 for primary carnitine deficiency, PNPLA2 for neutral lipid storage disease with myopathy, ABHD5 for neutral lipid storage disease with ichthyosis, ETFDH for multiple acyl-CoA dehydrogenation deficiency (MADD), and CPT2 for carnitine palmitoyltransferase II deficiency. Blood AC levels were measured by tandem mass spectrometry. The mutation c.250G>A in ETFDH was detected in seven (78%) patients, six of whom were homozygous for the variant. Patients with ETFDH mutations had elevated blood levels of ACs ranging from C8 to C16 species, a pattern consistent with MADD. ETFDH c.250G>A mutation is common in Taiwanese patients with late-onset LSMs. The blood AC profile is a sensitive biochemical marker for diagnosing MADD arising from ETFDH mutations in adults.

Objective: To ascertain the characteristics of patients with sporadic Creutzfeldt-Jakob disease (CJD) and to determine the findings of electroencephalography (EEG) and brain magnetic resonance imaging (MRI). Methods: We pooled patients at a hospital from 2000 to 2008, and classified them according to WHO diagnostic criteria as having probable or possible CJD. We retrospectively analyzed their clinical manifestations, brain MRI, and EEG findings to evaluate correlations among them. Results: In this study, 12 probable and 4 possible CJD patients were identified. Ten patients with probable CJD had asymmetric manifestations with hemiparesis, focal myoclonus, dystonia or apraxia; 9 had clinical manifestations mimicking the corticobasal syndrome. In contrast, neurological examinations did not show asymmetric signs in 4 patients with possible CJD. EEG showed a typical periodic sharp wave complex (PSWC) in 12 patients with probable CJD; most of them had bright signal intensity on diffusion-weighted imaging of the cortex and/or basal ganglia. There was a high tendency for asymmetric clinical manifestations that correlated with the presentation of PSWC and cortical lesions observed on the brain MRI scan. Conclusions: Our study indicates that asymmetric extrapyramidal symptoms/signs, in clinical features with characteristic abnormalities on MRI and EEG findings, might contribute to early diagnosis of sporadic CJD.

Prostaglandin D(2) synthase (PGDS) is the most abundant brain protein in cerebrospinal fluid (CSF) and is tied closely with inflammatory processes. This study investigated whether CSF PGDS levels in patients with acute inflammatory demyelinating polyneuropathy (AIDP) are altered. The results suggest that PGDS concentration is significantly increased in the CSF of AIDP patients compared with the control patients (p

To understand cerebral blood circulation after long-term exposure to carbon disulfide (CS2), four patients with encephalopathy and polyneuropathy, who had worked in a viscose rayon plant, were studied. Clinical and laboratory examinations, including brain magnetic resonance images (MRI), computed tomography (CT), CT perfusion, and CT angiography, were carried out. Brain CT and MRI disclosed mild cortical atrophy in all four patients, and multiple lesions in the subcortical white matter, and basal ganglia in three patients. Brain CT angiography and perfusion revealed a statistically significant decrease of cerebral blood flow (CBF) in the total brain parenchyma and basal ganglia, and a decrease of the cerebral blood volume (CBV) in the basal ganglia and a prolonged mean transit time (MTT) in the total brain parenchyma, and the territories of the internal carotid artery (ICA), basal ganglia and occipital lobe. In conclusion, the decrease of CBV and CBF, and the prolonged MTT in the total brain parenchyma, ICA, basal ganglia and occipital lobes, indicated a microangiopathy in patients with CS2 encephalopathy.

Recent experimental studies revealed that dopamine neuron dysfunction in chronic manganism may be due to a reduced capacity of dopamine release in the striatum. The findings imposed further difficulty in the differential diagnosis between manganism and IPD. We conducted a long-term clinical follow-up study of 4 manganism patients, applying a new tracer 18 F-9-fluoropropyl-(+)-dihydrotetrabenazine ( 18 F-AV-133) with positron emission tomography (PET). Twenty age-matched subjects including 4 manganism patients, 8 idiopathic Parkinson's disease (IPD) patients, and 8 healthy controls were enrolled for comparison. Volumes of interest of the bilateral putamen, caudate nuclei and occipital cortex as the reference region were delineated from individual magnetic resonance images. The clinical features of the manganism patients still progressed, with increased scores on the Unified Parkinson Disease Rating Scale. The 18 F-AV-133 uptake in the IPD patients decreased at the bilateral striatum, compared with the healthy controls. In the manganism patients, there was no decreased uptake of radioactivity involving the bilateral striatum, except Patient 4, who had a stroke with decreased uptake in the right posterior putamen. The 18 F-AV-133 PET finding reveals that nigrostriatum neurons are not degenerated in chronic manganism and can provide a useful neuroimage biomarker in the differential diagnosis.

We present the clinical manifestations, brain magnetic resonance images (MRI), and genetic analysis of a family with 2 siblings with congenital myotonic dystrophy type 1 (DM1) and 4 patients with classic DM1. These 2 patients with congenital DM1 had severe mental retardation and a characteristic feature of hyperintensity of white matter at the posterior-superior trigone (HWMPST), in addition to ventricular dilatation in T2-weighted images (T2WI) of brain MRI. In 2 of the 4 classic DM1 patients, brain T2WI MRI showed hyperintensity lesions in the bilateral frontal and/or temporal regions, which were absent in congenital DM1. In conclusion, we suggest that the HWMPST in brain MRI is a characteristic finding in congenital DM1, and that the severe cognitive impairments are not only attributable to the subcortical white matter lesions. In congenital DM1, the cognitive function is a diffuse impairment, which is different from that in classic DM1.

Long-term exposure to carbon disulfide (CS(2)) may induce parkinsonian features. There may be confusion in distinguishing between CS(2) parkinsonism and idiopathic parkinsonism, especially for workers who developed parkinsonian features in viscose rayon plants. We performed clinical examinations, and laboratory studies including magnetic resonance imaging (MRI) and dopamine transporter (DAT) studies with (99m)Tc-TRODAT-1 brain single photon emission computed tomography (SPECT) in three workers who had long-term exposure to CS(2). Patient 1 had polyneuropathy, and encephalopathy with tremor; patient 2 had polyneuropathy, and encephalopathy with parkinsonian features; and patient 3 had pure parkinsonian features without polyneuropathy or cerebellar signs. The treatment with l-dopa was effective in patient 3, but non-effective in patient 2. Brain MRI revealed multiple high signal intensities over the subcortical white matter, basal ganglia, and/or even the brainstem in patients 1 and 2, but normal in patient 3. In DAT studies, the bindings were normal in patients 1 and 2 and was decreased in patient 3. We conclude that CS(2) exposure may induce polyneuropathy, and cerebellar dysfunction in addition to parkinsonian features and that brain MRI may show multiple lesions in the cerebral white matter and basal ganglia. In addition, DAT with (99m)Tc-TRODAT-1 brain SPECT may provide a useful information in differential diagnosis between CS(2) parkinsonism and idiopathic parkinsonism.

Chronic exposure to manganese may induce parkinsonism similar to idiopathic Parkinson's disease (PD). However, clinical manifestations of manganism also have some features different from PD. The mechanisms of manganese-induced parkinsonism remain not fully understood. (99m)Tc-TRODAT-1 is a cocaine analogue that can bind to the dopamine transporter (DAT) site reflecting the function of presynaptic dopaminergic terminals. The purpose of this study was to evaluate DAT function using (99m)Tc-TRODAT-1 to investigate the integrity of the presynaptic dopaminergic terminals in manganese-induced parkinsonism. Brain (99m)Tc-TRODAT-1 single photon emission computed tomography was performed in 4 patients with chronic manganese intoxication in a ferromanganese smelting plant in Taiwan. Twelve PD patients and 12 healthy volunteers served as abnormal and normal controls, respectively. Clinically, all manganism patients had a bradykinetic-rigid syndrome. The scores of the Unified Parkinson's Disease Rating Scale ranged between 19 and 64. The uptake values of the (99m)Tc-TRODAT-1 were 0.868+/-0.136 in the right corpus striatum and 0.865+/-0.118 in the left, as compared with 0.951+/-0.059 and 0.956+/-0.058, respectively for the normal controls. The data were significantly higher than 0.250+/-0.070 and 0.317+/-0.066 respectively for the PD patients. Interestingly, there was a mild decrease in the uptake of (99m)Tc-TRODAT-1 in the putamen and the ratio of putamen and caudate when compared with the normal controls. Although the DAT shows a slight decrease in the putamen of manganism patients as compared with that of the normal controls, the data indicate that the presynaptic dopaminergic terminals are not the main target of chronic manganese intoxication. In addition (99m)Tc-TRODAT-1 SPECT can provide a useful, convenient and inexpensive tool for differentiation between chronic manganism and PD.

Long-term exposure to carbon disulfide (CS2) may induce diffuse encephalopathy with parkinsonism, pyramidal signs, cerebellar ataxia, and cognitive impairments, as well as axonal polyneuropathy. The pathogenic mechanisms of diffuse encephalopathy are unclear, although vasculopathy and toxic demyelination have been proposed. Recently, we have encountered a patient who developed headache, limb tremors, gait disturbance, dysarthria, memory impairment, and emotional lability after long-term exposure to CS2. The brain magnetic resonance images (MRI) showed diffuse hyperintensity lesions in T2-weighted images in the subcortical white matter, basal ganglia, and brain stem. The brain computed tomography perfusion study revealed a diffusely decreased regional cerebral blood flow and prolonged regional mean transit time in the subcortical white matter and basal ganglion. To our knowledge, there have been few reports demonstrating diffuse white matter lesions in chronic CS2 encephalopathy using brain MRI. In addition, the 99mTc-TRODAT-1 single photon emission computed tomography showed a normal uptake of the dopamine transporter, indicating a normal presynaptic dopaminergic pathway. We conclude that diffuse white matter lesions may develop after chronic exposure to CS2, possibly through microangiopathy. In addition, CS2 poisoning can be considered as one of the causes of chronic leukoencephalopathy.

The occurrence of persistent hemiballism after subthalamotomy for Parkinson's disease (PD) has not been described as frequently as mild or transient dyskinesia. We report on 2 patients with advanced PD who developed hemiballism and/or dyskinesia after subthalamotomy. One patient with a small lesion confined to the subthalamic nucleus (STN) developed persistent hemiballism; the other with a larger lesion involving the STN and also the zona incerta presented with a transient dyskinesia in a single limb. We conclude that a precise STN lesion might bear a potential risk of persistent hemiballism.

We studied 42 individuals, including 8 patients with either complete or partial syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), 8 patients with either complete or partial syndrome of myoclonic epilepsy with ragged-red fibers (MERRF) and 26 maternal family members who carried either the A3243G or A8344G mutation of mitochondrial DNA (mtDNA). Clinical manifestations and prognosis were followed up in the patients harboring the A3243G or A8344G mutation. The relationship between clinical features and proportions of mutant mtDNAs in muscle biopsies, blood cells and/or hair follicles was studied. In the 8 regularly followed patients with the A3243G mutation, 4 died within 1 month to 7 years due to status epilepticus and/or recurrent stroke-like episodes. Two patients developed marked mental deterioration and 2 remained stationary. All of the patients harboring the A8344G mutation were stable or deteriorated slightly, except for 1 patient who died due to brain herniation after putaminal hemorrhage. The A3243G and A8344G mtDNA mutations were heteroplasmic in the muscle biopsies, blood cells and hair follicles of both the probands and their maternal family members. The mean proportion of A3243G mutant mtDNA in the muscle biopsies of the patients with MELAS syndrome (68.5 +/- 21.3%, range 33-92%) was significantly higher than that of the asymptomatic family members (37.1 +/- 12.6%, range 0-51%). The average proportions of A8344G mutant mtDNA in the muscle biopsies (90.1 +/- 3.9%, range 89-95%) and hair follicles (93.9 +/- 6.4%, range 84-99%) of the patients with MERRF syndrome were also significantly higher than those of the asymptomatic family members (muscle: 40.3 +/- 39.5%, range 1-80%; hair follicles: 51.0 +/- 44.5%, range 0.1-82%). We concluded that measurement of the proportion of mutant mtDNA in muscle biopsies may provide useful information in the identification of symptomatic patients with mitochondrial encephalomyopathies. For patients with the A3243G mutation, the prognosis was related to status epilepticus and the number of recurrent stroke-like episodes and was much worse than for patients with the A8344G mutation of mtDNA, who had stable or slowly deteriorating clinical courses.

Background:Factors affecting quality of life (QOL) ratings for people with dementia (PWD) have been well studied, but few studies have examined the effect of residence on PWD- and caregiver-rated QOL for PWDs. We designed this study to determine the factors related to PWD- and caregiver-rated QOL in dementia as well as factors related to the discrepancy in these ratings.Methods:For this cross-sectional study, we analyzed data from a convenience sample of 106 PWD-family caregiver dyads (58 community-dwelling dyads and 48 nursing-home dyads). PWDs’ data included socio-demographic variables, QOL (assessed by the Quality of Life-Alzheimer's Disease [QOL-AD] scale), cognition, dementia severity, depression, comorbidities, and quality of the dyadic relationship. Caregivers’ data included socio-demographic variables, depressive symptoms, and mutuality of the dyadic relationship.Results:QOL-AD scores were lower when rated by caregivers than by PWDs. The key factors positively related to both PWD- and caregiver-rated QOL for PWDs were fewer PWD depressive symptoms and higher quality of the PWD-caregiver relationship. The key factors related to the discrepancy in PWD- and caregiver-rated QOL in dementia were PWD residence in a nursing home and lower dementia severity, as well as higher caregiver depression, being an adult child caregiver, and lower caregiver-PWD mutuality.Conclusion:Caregiver-rated QOL for PWDs and the discrepancy in rated QOL were significantly associated with PWD residence. If caregiver-rated QOL is needed, the effect of residence of PWD should be taken into consideration. Caregivers’ depressive status and mutuality with PWD must be also carefully assessed.

BACKGROUND: Motor and somatosensory evoked potentials (MEPs and SSEPs) are sensitive tools for detecting subclinical lesions, assessing disease severity, and determining the prognosis for outcomes of patients with inflammatory neurological diseases such as multiple sclerosis. However, their roles in neuromyelitis optica (NMO), a severe inflammatory neurological disease that predominantly involves optic nerves and spinal cord, have not yet been clarified. METHODS AND FINDINGS: Clinical symptoms and examination findings at relapses of 30 NMO patients were retrospectively reviewed. Abnormal MEPs were observed in 69.2% of patients. Patients with abnormal motor central conduction time (CCT) of the lower limbs had higher Kurtzke Expanded Disability Status Scale (EDSS) scores than those with normal responses (P = 0.027). Abnormal SSEPs were found in 69.0% of patients. Patients with abnormal lower limb sensory CCT had higher EDSS scores than those with normal responses (P = 0.019). In 28 patients followed up more than 6 months, only one of 11 patients (9.1%) with normal SSEPs of the lower limbs had new relapses within 6 months, whereas 8 of 17 patients (47.1%, P = 0.049) with abnormal SSEPs of the lower limbs had new relapses. CONCLUSIONS: These results indicate MEPs and SSEPs of the lower limbs are good indicators for the disability status at relapses of NMO. Lower limb SSEPs may be a good tool for reflecting the frequency of relapses of NMO.

We present the clinical manifestations of 4 male patients with acute stroke-like symptoms and polyneuropathy after long-term exposure to carbon disulfide (CS2) in a viscose rayon plant. The ages of onset of polyneuropathy ranged from 42 to 45 years with a duration of CS2 exposure between 6 and 21 years. The ages of onset of stroke were from 42 to 48 years. The risk factors for stroke including heart disease and diabetes were denied, except for smoking in 4, hyperlipidemia in 2 and hypertension in 1. At the initial visit in 1992, only 2 patients developed sudden onset of hemiparesis suggesting a lacunar stroke before the diagnosis of CS2 intoxication. Brain computed tomography (CT) scans showed low-density lesions in the basal ganglia in 2 patients, cortical atrophy in 1 and normal in 1. Brain magnetic resonance image (MRI) study disclosed multiple lesions in the corona radiata and basal ganglia on T2-weighted images in 3 patients and cortical atrophy in 1. After the diagnosis, they left their jobs for a CS2-free environment, and improvement of the working conditions was noted. During 5 years follow-up period, another 2 patients also developed an acute episode of stroke with hemiparesis. Brain CT and/or MRI follow-up studies in these 2 patients revealed new lesions in the basal ganglia and corona radiata. Intriguingly, a patient with previous stroke also developed new lesions in the bilateral thalami and brainstem. Carotid Doppler scan, transcranial Doppler scan and/or cerebral angiography did not show any prominent stenosis or occlusion in the major intracranial large arteries. We conclude that encephalopathy may occur in patients after long-term CS2 exposure, probably due to impaired cerebral perfusion. The lesions tend to occur in the basal ganglia, corona radiata and even brainstem, particularly involving the small-sized vessels. In addition, the cerebral lesions may progress even after cessation of CS2 exposure. Therefore, we suggest that CS2 exposure may be a risk factor for stroke.

Dystonia is a common manifestation in Wilson’s disease (WD). The striatum, especially the putamen, has been considered to be responsible for dystonia. We reported 3 patients who developed acute generalized dystonia and akinetic rigid syndrome following an initial therapy with d-penicillamine 125–500 mg daily. Brain MRI revealed lesions in the thalamus and the brainstem, particularly the tegmentum, and the basis pontis in addition to the basal ganglion lesions. After the episode, 1 patient continued to receive d-penicillamine therapy and 2 changed to zinc sulfate treatment. The generalized dystonia improved in the following 3 months and 3 years respectively in 2 patients. Follow-up brain MRI of these 2 patients revealed that the lesions in the thalamus and brainstem disappeared or resolved almost completely. From these data, acute generalized dystonia with brainstem and thalamic lesions may occur in WD patients after an initial d-penicillamine therapy. Furthermore, the dystonia may resolve following the disappearance of the brainstem and thalamic lesions.

Autonomic nervous system involvement in Wilson's disease (WD) was studied in 25 patients by sympathetic skin response (SSR) and RR interval variation (RRIV). The control group consisted of age-matched healthy subjects. Palmar SSRs were obtained by central activation from median nerve stimulation and by activation of sympathetic trunk from magnetic stimulation of the neck. Electric SSRs were prolonged in 11 patients and absent in 2; magnetic SSRs were delayed in 4 and absent in 1; and the sympathetic central conduction time was prolonged in 3. The mean latencies and mean central conduction of the SSRs were all significantly prolonged in WD when compared to the control group. On the other hand, parasympathetic function was abnormal in 3 patients only during forced deep breathing, and as a group only mean D% was significantly reduced. The present findings suggest that autonomic dysfunction may occur in WD, and that sympathetic function is predominantly affected, mainly due to central involvement.

Dysesthesia, allodynia, distal muscle weakness, and sensory impairment were noted in two patients with acute thallium intoxication. Two months later, nerve conduction studies showed an axonal degeneration. Sural nerve biopsy disclosed a decreased fiber density in the large myelinated fibers. Quantitative sensory testing also revealed an impairment of pinprick, temperature, and touch sensations. Cutaneous nerve biopsy confirmed a loss of epidermal nerves indicating an involvement of the small sensory nerves.

Background Tolosa-Hunt syndrome (THS) manifests as a benign or an inflammatory type disease. The nosography differences between these types remain to be elucidated. We aimed to analyze and compare the clinical presentations of benign and inflammatory THS. Methods The ward patients who presented with THS from January 1990 to May 2011 were retrospectively reviewed. THS was diagnosed according to the recommendations of the International Headache Society. Results Of the 53 THS cases (49 patients), 30 (56.6%) were classified as benign and 23 (43.4%) as inflammatory THS. There were strong similarities between the groups in terms of clinical manifestations, laboratory findings, responses to glucocorticoid treatment, and outcomes. However, patients with inflammatory THS tended to be younger (mean age, 43.4 years; p 0.5 mg/kg/day) and low-dose (≤0.5 mg/kg/day) prednisolone were equally effective in relieving symptoms in both groups ( p > 0.05). Conclusion Benign and inflammatory THS were highly similar in terms of nosography. The responses to glucocorticoid treatment were generally good except in patients with orbital pseudotumors.

In this study we sought to differentiate participants with amnestic mild cognitive impairment (a-MCI) from those with mild dementia of Alzheimer’s type (m-DAT) and normal controls by modifying an existing test of spatial context memory (SCMT) designed so as to evaluate the function of brain regions affected in early m-DAT. We found that participants with a-MCI had better total scores on our modified SCMT than those with m-DAT. Furthermore, the locational memory subtest was able to discriminate between those with a-MCI and m-DAT. Additionally, compared with other screening tests, our spatial context memory test showed high sensitivity and specificity in discerning those with a-MCI from the normal population but, was relatively ineffective in discriminating a-MCI patients from those with m-DAT. We conclude that our modified test of SCMT is an effective tool for discriminating a-MCI from m-DAT and does so by detecting differences in locational memory.

OBJECTIVES--To understand the prevalence of polyneuropathy and correlations among the clinical manifestations, electrophysiological findings, and degree of exposure to carbon disulphide (CS2) in workers who were exposed to variable concentrations of CS2 in a viscose rayon factory. METHODS--All the 163 workers received a detailed physical and neurological evaluation. Fixed point air samples were analysed for CS2. Nerve conduction velocity was studied in 26 workers with symptoms similar to neuropathy. RESULTS--Nine workers (53%) with overt polyneuropathy from the fibre cutting department and 19 workers (13%) with oligosymptoms similar to polyneuropathy from various jobs were noted. The fixed point air concentrations of CS2 were 150-300 ppm in the cutting areas and 15 to 100 ppm in the spinning areas. The estimated eight hour time weighted averages in the fibre cutting areas were 40-67 ppm. The occurrence of polyneuropathy was generally correlated with the degree of exposure to CS2. Nerve conduction velocities (NCVs) were significantly different in the overt polyneuropathy and subclinical polyneuropathy groups from the normal controls. The sensitive indicators for CS2 polyneuropathy were distal latency, motor NCV, and amplitude of sensory nerve action potentials in sensory NCVs. CONCLUSION--The outbreak of polyneuropathy was attributed to higher concentrations of CS2 in fibre cutting areas. Even in other jobs with relatively lower concentrations of CS2, the hazard of subclinical polyneuropathy cannot be overlooked.

To understand endocrine function and to determine which endocrine systems are likely to be affected, 6 patients with mitochondrial encephalomyopathies were studied. Three patients had myoclonus epilepsy and ragged-red fibers, and the other 3 patients had mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. Clinically, short stature (5/6), amenorrhea (2/3), impotency (3/3), and poor development of secondary sexual characteristics (4/6) were noted. The endocrinological studies including triiodothyronine, tetraiodothyronine, thyrotropin, adrenocorticotropin, cortisol, parathyroid hormone and blood sugar were normal. However, there were low serum concentrations of estradiol (2), and progesterone (2) in 3 female patients. Two patients (1 man and 1 woman) had growth hormone deficiency and 1 had low testosterone level. Hypothalamopituitary dysfunction was confirmed after a series of stimulation tests. We conclude that patients with mitochondrial encephalomyopathies are common to have gonadal dysfunction. Although target organ may play a role, hypothalamopituitary lesion may be responsible for this abnormality.

Background To compare the neocortical amyloid loads among cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer's disease (AD) subjects with [18F]AV-45 positron emission tomography (PET). Materials and Methods [18F]AV-45 PET was performed in 11 CN, 13 aMCI, and 12 AD subjects to compare the cerebral cortex-to-whole cerebellum standard uptake value ratios (SUVRs) of global and individual volumes of interest (VOIs) cerebral cortex. The correlation between global cortical [18F]AV-45 SUVRs and Mini-Mental State Examination (MMSE) scores was analyzed. Results The global cortical [18F]AV-45 SUVRs were significantly different among the CN (1.08±0.08), aMCI (1.27±0.06), and AD groups (1.34±0.13) (p = 0.0003) with amyloidosis positivity rates of 9%, 62%, and 92% in the three groups respectively. Compared to CN subjects, AD subjects had higher SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, and posterior cingulate areas; while aMCI subjects had higher values in the global cortical, precuneus, frontal, occipital and posterior cingulate areas. There were negative correlations of MMSE scores with SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, posterior cingulate and anterior cingulate areas on a combined subject pool of the three groups after age and education attainment adjustment. Conclusions Amyloid deposition occurs relatively early in precuneus, frontal and posterior cingulate in aMCI subjects. Higher [18F]AV-45 accumulation is present in parietal, occipital and temporal gyri in AD subjects compared to the aMCI group. Significant correlation between MMSE scores and [18F]AV-45 SUVRs can be observed among CN, aMCI and AD subjects.

Neuromyelitis optica (NMO), which was previously considered a variant of multiple sclerosis (MS), is characterized by recurrent optic neuritis and longitudinally extensive spinal cord lesions. It has been shown that the level of haptoglobin in cerebrospinal fluid (CSF) is elevated in NMO. However, it is uncertain whether this change is specific to NMO, or is also seen in MS and other neurological diseases.We used an enzyme-linked immunosorbent assay (ELISA) to measure the haptoglobin levels in the CSF and serum in 25 NMO, 16 MS, and 15 Alzheimer's disease (AD) patients and 22 controls.The CSF haptoglobin concentration of the NMO patients (0.309±0.074mg/dl, P0.001) was significantly higher than that of MS patients (0.081±0.016mg/dl) and AD patients (0.058±0.011mg/dl), and the controls (0.060±0.009mg/dl), whereas the serum haptoglobin and albumin concentrations in the serum and CSF did not differ significantly across groups. NMO patients (0.59±0.15, P=0.001) demonstrated a higher haptoglobin index than MS patients (0.13±0.01), AD patients (0.12±0.03), and the controls (0.17±0.04). Furthermore, the haptoglobin concentration and haptoglobin index in the CSF correlated significantly with the expanded disability scale score (EDSS) in NMO patients.The high CSF haptoglobin concentration in NMO may be explained by increased intrathecal haptoglobin synthesis. The correlation between CSF haptoglobin concentration/haptoglobin index and EDSS highlights the potential of haptoglobin as a biomarker of NMO.

Four workers chronically exposed to elemental mental mercury in a lampsocket manufacturing factory were studied. The clinical manifestations were severe in one, mild in another, and suspicious in the remaining two. Correlation between severity of clinical features and increased urinary mercury concentrations was found. The time weighted average mercury concentrations were 0.945 mg/m3 and 0.709 mg/m3 for two workers in one room and 0.225 mg/m3 in the other. After stopping exposure, the workers recovered spontaneously or with D-penicillamine treatment within six months. It is concluded that recovery from chronic elemental mercury intoxication may be complete when patients are removed early from the exposure environment. The hazard of mercury intoxication in recycling of waste substances is emphasised.

We report myoclonic epilepsy with ragged-red fibers (MERRF) syndrome in a Chinese family with confirmed mitochondrial DNA point mutation. Six members of the family including the grandmother, two siblings, and three grandchildren were affected. Among them, action myoclonus was seen in five; short stature, muscle weakness, and mental retardation in four; lactic acidosis, hearing impairment, and ataxia in two; and seizures in one. Muscle biopsy from two affected siblings revealed ragged-red fibers and abundant subsarcolemmal mitochondria with paracrystalline inclusions. Pedigree analysis suggests a maternal transmission. Analysis of mitochondrial DNA showed a point mutation from A to G at the 8344th nucleotide position located in the tRNA(Lys) gene. To our knowledge, this is the first report of MERRF syndrome with such genetic defect from a Chinese family. The present and previous reports support the notion that mitochondrial DNA point mutation at the 8344th nucleotide position is the most common cause of MERRF syndrome.

(18)F-Florbetapir (AV-45/Amyvid) is a novel positron emission tomography (PET) tracer for imaging plaque pathology in Alzheimer's disease (AD), while PET images of fluorodeoxyglucose (FDG) for cerebral glucose metabolism can provide complementary information to amyloid plaque images for diagnosis of AD. The goal of this preliminary study was to investigate the perfusion-like property of relative cerebral blood flow estimates (R(1)) and summed early-phase AV-45 images [perfusion AV-45 (pAV-45)] and optimize the early time frame for pAV-45.Dynamic AV-45 PET scans (0-180 min) were performed in seven subjects. pAV-45, late-phase AV-45, and FDG images were spatially normalized to the Montreal Neurological Institute template aided by individual MRI images, and the corresponding standardized uptake value ratio (SUVR) was computed. The R(1) images were derived from a simplified reference tissue model. Correlations between regional and voxelwise R(1) and the corresponding FDG images were calculated. An optimization of time frames of pAV-45 was conducted in terms of correlation to FDG images. The optimal early time frame was validated in a separate cohort.The regional distribution in the R(1) images correlated well (R = 0.91) to that of the FDG within subjects. Consistently high correlation was noted across a long range of time frames. The maximal correlation of pAV-45 to FDG SUVR of R = 0.95 was observed at the time frame of 1-6 min, while the peak correlation of R = 0.99 happened at 0-2 min between pAV-45 and R(1). A similar result was achieved in the validation cohort.Preliminary results showed that the distribution patterns of R(1) and pAV-45 images are highly correlated with normalized FDG images, and the initial 5-min early time frame of 1-6 min is potentially useful in providing complementary FDG-like information to the amyloid plaque density by late-phase AV-45 images.