Abnormal cardiac [(123)I]-meta-iodobenzylguanidine uptake in multiple system atrophy.

[(123)I]-Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is useful for distinguishing multiple system atrophy (MSA) from Parkinson disease. In this study, longitudinal observation using MIBG myocardial scintigraphy was carried out in patients with MSA to evaluate the association of myocardial MIBG uptake with clinical features. A total of 96 MIBG examinations were performed in 52 patients with MSA. The heart/mediastinum (H/M) ratio of MIBG uptake at 240 minutes after injection was below the lower limit in 16 patients with MSA (31.3%). Overall, the H/M ratio correlated with neither disease duration nor severity. In the follow-up observations, the H/M ratio did not show any specific trends, in contrast with the continuous decrease observed in patients with Parkinson's disease. This data clearly showed that cardiac MIBG uptake cannot necessarily be preserved in patients with MSA and that approximately 30% of patients with MSA showed decreased MIBG uptake without any correlation to disease duration or severity.

Two cases of subacute combined degeneration: magnetic resonance findings.

We report two cases of subacute combined degeneration. Both patients had undergone total gastrectomy. The chief complaints were numbness in both upper extremities in case 1 and numbness in both the upper and lower extremities and gait disturbance in case 2. The pain, temperature, and vibration senses of both patients were decreased. Laboratory examinations showed macrocytic anemia and a decreased serum vitamin B12 level in both cases. In both cases T2-weighted magnetic resonance images showed an area of hyperintensity in the dorsal columns of the cervical spinal cord. The patients were treated with vitamin B12. The abnormal signals had disappeared on follow-up magnetic resonance examination 1 year later in case 1 and 3 months later in case 2. These patients showed neurological improvement, but the numbness in the upper extremities persisted even after the area of abnormal signal intensity had disappeared in case 1.

Factors influencing outcome in Guillain-Barré Syndrome: comparison of plasma adsorption against other treatments.

OBJECTIVE: This study was performed to evaluate which factors influence the outcome of Guillain-Barré Syndrome (GBS), focusing on the choice of treatments. METHODS: Sixty-three GBS patients were retrospectively studied and the following factors were evaluated: sex, age, days from onset of disease to the start of treatment, severity of symptoms, prior infection, autonomic dysfunction, bulbar palsy, anti-ganglioside antibody, and disease form, as well as the choice of treatment. Plasma adsorption (PA, n=39), plasma exchange (PE, n=14), or immunoglobulin treatment (IVIg, n=10) were performed in this study. Outcomes were evaluated using the functional grading scale (FGS) of Hughes. RESULTS: The number of days needed for one functional grade improvement was significantly longer in the elderly, the severe symptom group, and patients with acute motor axonal form, and days needed for two functional grade improvement was significantly longer in the elderly, patients with autonomic dysfunction, and acute motor axonal form. The choice of treatments (PA, PE, or IVIg) did not significantly influence the outcome as determined by both univariate and multivariate analysis. CONCLUSION: Although patient age, symptoms, and disease form influenced the outcome, treatment methods did not significantly influence the outcome. Since PA does not result in a risk of unknown infection, choosing a PA treatment may be justified, especially for patients (or doctors) who may be anxious about a possibility of unknown infection.

Efficacy of edaravone, a free radical scavenger, for the treatment of acute lacunar infarction.

The effect of edaravone as an inhibitor of ischemic brain damage in addition to routine treatment was retrospectively examined in 70 patients with lacunar infarction who were admitted within 24 hours of symptom onset. Clinical status was assessed using the National Institutes of Health Stroke Scale (NIHSS). The modified Rankin Scale (MRS) was used to assess clinical outcomes at 3 months after onset, with a good outcome defined as MRS score < or =2. Risk factors were also evaluated, including evidence of hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, and a history of smoking longer than 2 months. The probability of a good outcome and independence at 3 months was assessed by backward stepwise logistic regression analysis based on the maximum likelihood ratio. Administration of edaravone yielded an odds ratio with multivariate adjustment of 6.49 (95% confidence interval, 1.35 to 50.32; p < 0.05) for a good outcome at 3 months. Higher baseline NIHSS score and higher age also adversely affected the outcome at 3 months (p < 0.005). Administration of edaravone improves the outcome of patients with lacunar infarction.

Cerebrospinal fluid tau in dementia disorders: a large scale multicenter study by a Japanese study group.

A large scale multicenter study of cerebrospinal fluid (CSF) tau levels was conducted to determine the cut-off value, sensitivity and specificity for clinical usage as a biomarker of Alzheimer's disease (AD). Its use for early and differential diagnosis and the factors that increase CSF tau levels were also examined. CSF samples from a total of 1,031 subjects including 366 patients with AD, 168 patients with non-Alzheimer type dementia (NA), 316 patients with non-dementia neurological diseases (ND) and 181 normal controls (NC) were measured using ELISA for tau. The cut-off value of tau, 375 pg/ml, showed 59.1% sensitivity and 89.5% specificity for diagnosis of AD compared with the other groups. The tau levels were increased from the early to late stages of AD. Elevation of CSF tau in the non-tauopathy and tauopathy dementia groups, chronic and acute damage to the cerebrum, and meningeal disturbance were other factors that required attention for clinical practice. Measurement of CSF tau was useful as a biomarker for early and differential diagnosis of AD.

The effect of ascorbic acid on the pharmacokinetics of levodopa in elderly patients with Parkinson disease.

Levodopa (LD) is one of the most effective drugs for clinical symptoms in patients with Parkinson disease (PD). Most PD patients are advanced in age and may have trouble with LD absorption because aging influences drug absorption processes. Previous reports have indicated that ascorbic acid (AsA) can reduce LD dosage without losing its effectiveness. The current study sought to determine whether AsA affects LD absorption in elderly PD patients. Sixty-seven elderly PD patients took a tablet orally containing 100 mg LD and 10 mg carbidopa following an overnight fast. Plasma LD concentrations were determined at 6 points up to 3 hours, using high-performance liquid chromatography with electrochemical detection. The area under the curve (AUC), peak drug concentration (Cmax), and time to peak drug concentration (Tmax) were calculated. The pharmacokinetic evaluation was repeatedly performed 1 week later in the same way except for adding 200 mg AsA to the tablet. The changes in AUC, Cmax, and Tmax between the tests were evaluated. Significant changes in these parameters were not observed when analyzed using data from all patients. However, significant increases in AUC and Cmax, and a significant reduction in Tmax by adding AsA were observed in 25 patients with baseline AUC < or =2500 ng.hour/mL. In conclusion, AsA can improve LD absorption in elderly PD patients with poor LD bioavailability. LD therapy in combination with AsA may be one of the strategies for PD treatment.

Simple solution for preventing cerebrospinal fluid loss and brain shift during multitrack deep brain stimulation surgery in the semisupine position: polyethylene glycol hydrogel dural sealant capping: rapid communication.

This study evaluated preliminary findings on the efficacy of polyethylene glycol (PEG) hydrogel dural sealant capping for the prevention of cerebrospinal fluid (CSF) leakage and pneumocephalus during deep brain stimulation (DBS) surgery in the semisupine position. Group A consisted of 5 patients who underwent bilateral subthalamic nucleus (STN)-DBS surgery without PEG hydrogel dural sealant capping. Group B consisted of 5 patients who underwent bilateral STN-DBS surgery with PEG hydrogel dural sealant capping. The immediate postoperative intracranial air volume was measured in all patients and compared between the 2 groups using the Welch test. Adverse effects were also examined in both groups. The intracranial air volume in Group A was 32.3 ± 12.3 ml (range 19.1-42.5 ml), whereas that in Group B was 1.3 ± 1.5 ml (range 0.0-3.5 ml), showing a significant difference (p < 0.005). No hemorrhage or venous air embolisms were observed in either group. The effect of brain shift was discriminated by STN recordings in Group B. These preliminary findings indicate that PEG hydrogel dural sealant capping may reduce adverse effects related to CSF leakage and brain shift during DBS surgery.

Influence of ageing on the pharmacokinetics of levodopa in elderly patients with Parkinson's disease.

Levodopa (LD) is the most effective drug to treat the symptoms of Parkinson's disease (PD). It has been reported that the bioavailability of LD is higher in elderly patients than in young patients; however, it is not known how ageing changes the bioavailability of LD among elderly patients. In this study, we compared the pharmacokinetics of LD between two groups of elderly PD patients, early- (75 years or younger) and late-elderly (76 years or older). After oral administration of a tablet containing 100 mg LD per 10 mg carbidopa in 155 PD patients, we measured plasma LD concentrations. Peak drug concentration (C(max)), time to peak drug concentration (T(max)), halftime of drug (T1/2) and area under the curve (AUC) were determined. AUC and T1/2 were significantly higher and longer, respectively, in the late-elderly group than in the early-elderly group (p < 0.05 and <0.05, respectively). However, C(max) and T(max) were not statistically different between the groups. The present data indicate that LD absorption is consistent in PD patients, regardless of age. The difference in oral LD bioavailability between the groups may result from a difference in excretion ability. Physicians should consider LD pharmacokinetics when treating elderly PD patients.

Adenosine A(2A) receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

Adenosine A(2A) receptors (A2ARs) are thought to interact negatively with the dopamine D(2) receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test). In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.

Neuromyelitis optica preceded by brain demyelinating episode.

Neuromyelitis optica (NMO) is considered a distinct disease from multiple sclerosis (MS) because of its pathogenesis. It is well accepted that NMO selectively affects the spinal cord and optic nerve and is not associated with brain lesions at the onset of the disease, unlike MS. We present a unique case where the patient's initial lesion was in the brain, and optic neuritis and myelitis were revealed 6 years after the brain lesion. In addition, the patient's serum antiaquaporin 4 (AQP4) antibody was positive. We consider the brain lesion to precede abnormal lesion of NMO, and the AQP4 measurement is important for diagnostics, even if it occurs with brain lesions.

Cerebral blood flow index: dynamic perfusion MRI delivers a simple and good predictor for the outcome of acute-stage ischemic lesion.

OBJECTIVES: To evaluate the feasibility of utilizing cerebral blood flow (CBF) index images, calculated automatically and quickly from dynamic perfusion imaging (DPI), to identify acute cerebral ischemia. We attempted to investigate (1) whether the CBF index has a threshold for assessing tissue outcome, (2) whether CBF index images can predict the resulting infracted area, and if so, (3) whether the predictive capacity of the CBF index image is comparable to the regional CBF (rCBF) image delivered from singular value decomposition (SVD) deconvolution methods, which are regarded as most accurate in predicting the final infarct area. METHODS: Diffusion-weighted images (DWI) and DPI were obtained in 17 patients within 12 hours of stroke onset and follow-up magnetic resonance imaging (MRI). On 3 DPI-delivered images, namely relative regional cerebral blood volume (rrCBV), uncorrected mean transit time (MTTu) and CBF index images, univariate discriminant analysis was done to estimate cut-off values to discriminate between infarcted and noninfarcted areas. Subsequently, correlations between the initial lesion volume of 3 images together with rCBF images delivered with SVD methods and the final infarct volume on follow-up T2-weighted MRI taken at the 8th to 20th day were determined. RESULTS: Among the 3 images, only the CBF index image was able reveal the threshold of the ischemic region. Lesion volume of CBF index images against follow-up infarct volume had the highest correlation (r = 0.995) to a linear fit and the slope was closest to 1.0 (0.91) among the 3 and had identical accuracy to the regression coefficient of rCBF images. CONCLUSIONS: CBF index images can predict final infarct volume. Evaluating CBF index images together with DWI can guide the initial assessment in the acute stage of cerebral ischemia.