Masaki Saitoh

Quantitative analysis of brain perfusion SPECT in Alzheimer's disease using a fully automated regional cerebral blood flow quantification software, 3DSRT

PURPOSE The clinical symptoms of Alzheimers disease (AD) show great diversity depending on the clinical stage. We investigated the correlation of regional cerebral blood flow (rCBF) changes and the clinical severity of AD patients. METHODS Thirty-nine AD patients and 16 normal subjects participated in this study. AD patients were divided into three subgroups by clinical severity. Quantitative brain perfusion SPECT analyses were performed using a rCBF quantification software, 3DSRT. RESULTS In mild AD, significant decreases of rCBF were detected in the bilateral parietal, angular gyrus, pericallosal, thalamus, right temporal and left hippocampal regions. Moderate AD patients showed significantly lower blood flow than those with mild AD only to the right hippocampus. Analysis of the severe AD group revealed a nearly diffuse decrease of rCBF throughout the cerebral cortex except for part of the frontal lobe compared with moderate patients. CONCLUSIONS These results were consistent with previous findings demonstrated by qualitative analysis of CBF. The decreased thalamic blood flow was noteworthy as this finding has rarely been reported. In consideration of the structure and function of the Papez circuit, which connects the medial temporal lobe and thalamus, a remote metabolic effect might be the cause of lower rCBF in the thalamus.

A correlation study between serum adenosine deaminase activities and peripheral lymphocyte subsets in Parkinson's disease

Adenosine deaminase (ADA) and its isozyme activities in serum were measured together with peripheral lymphocyte subsets in 42 patients with idiopathic Parkinsons disease. The total and ADA 2 activities were significantly higher than normal controls (p < 0.01). As regards the peripheral lymphocyte subsets, the proportion of OKT 10+ cells (activated T lymphocytes) and the proportions of interleukin-2 receptor+ and HLA-DR+ cells (mainly activated T lymphocytes) were significantly higher than normal controls (p < 0.05, 0.01, 0.01, respectively). On the other hand, OKT 10+ cells demonstrated a significant correlation not only with total ADA but also with ADA 2 activity. These results suggest that high serum ADA activity may be involved in the pathogenesis of Parkinsons disease through peripheral T lymphocyte activation.

A novel type of binding specificity to phospholipids for rat mannose-binding proteins isolated from serum and liver.

Mannose‐binding protein (MBP) belongs to the collectin subgroup of C‐type lectins with specificity for mannose and N‐acetylglucosamine sugars. We investigated whether rat MBPs isolated from serum (S‐MBP) and liver (L‐MBP) interact with phospholipids using antibody against each MBP. Both S‐ and L‐MBPs bound to phosphatidylinositol coated onto microtiter wells in a concentration‐ and a Ca2+‐dependent manner. L‐MBP also bound to phosphatidylglycerol and weakly to phosphatidylserine. MBPs interacted with liposomes composed of these lipids. S‐ and L‐MBPs bound to phosphatidylinositol 4‐monophosphate. L‐MBP also bound to cardiolipin. These results provide evidence for a novel type of ligand binding specificity for MBPs, and raise the possibility that phospholipids are ligands for collectins.

Cervical dural arteriovenous malformation presenting with right-sided occipitalgia: Before and after successful treatment by embolization

SYNOPSIS

Correlation of bite force with excitation–contraction coupling time of the masseter in myasthenia gravis

OBJECTIVE The aim of this study was to elucidate the relationship between the impairment of excitation-contraction (E-C) coupling of masseter and the bite force in patients with myasthenia gravis (MG). METHODS In 20 patients with MG, masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRP) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The E-C coupling time (ECCT) was calculated by the latency difference between CMAP and MRP. Bite force was measured using a pressure-sensitive sheet. Serial assessments of % decrement in masseteric repetitive nerve stimulation (RNS), ECCT, and bite force were performed before and after corticosteroid therapy alone or in various combinations with FK506, cyclosporin A, intravenous immunoglobulin and immunoabsorption. RESULTS Percent amplitude decrement in RNS and ECCT decreased significantly accompanying an increase in bite force after treatment. Simple regression analysis demonstrated a linear correlation among % decrement, ECCT and bite force. However, ECCT shortening accompanying bite force recovery without reduction in % decrement was observed in 4 patients. CONCLUSIONS Masseteric E-C coupling is impaired in some MG patients, and functional recovery of E-C coupling contributes at least in part to the increase in bite force after treatment. SIGNIFICANCE Impaired E-C coupling contributes to muscle weakness in patients with MG.

Eosinophilic fasciitis: MRI evaluation

We conducted repeat muscle MR imaging (figure) on a 46-year-old man with relapsing eosinophilic fasciitis that can be classified in a continuum around the so-called Shulman syndrome.1 The …

Contribution of anti-ryanodine receptor antibody to impairment of excitation-contraction coupling in myasthenia gravis.

OBJECTIVE The aim of this study was to elucidate the relationship between the impairment of excitation-contraction (E-C) coupling and anti-ryanodine receptor (RyR) antibody in patients with myasthenia gravis (MG). METHODS Masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRPs) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The E-C coupling time (ECCT) was calculated as the latency difference between CMAP and MRP. For each patient, we selected a representative data set when there was no abnormal decrement in response to repetitive nerve stimulation. The 26 data sets were divided into an anti-RyR-positive group (n=12) and an anti-RyR-negative group (n=14). RESULTS Masseteric ECCT was significantly longer (p=0.017) in anti-RyR-positive group (median, mean, range; 3.6, 3.8, 3.0-5.9 ms) than in anti-RyR-negative group (3.1, 3.1, 2.7-4.0) although there were no significant differences in masseteric CMAP amplitude and % decrement between the two groups. The bite force was significantly lower in anti-RyR-positive group than in normal controls. CONCLUSIONS Presence of anti-RyR antibodies is associated with significantly prolonged masseteric ECCT compared to absence of the antibodies in MG. SIGNIFICANCE Anti-RyR antibody contributes to E-C coupling impairment in the masseter muscle in patients with MG.

Early effect of tacrolimus in improving excitation–contraction coupling in myasthenia gravis

OBJECTIVES Tacrolimus (FK506) is a macrolide T-cell immunomodulator used to treat myasthenia gravis (MG). Besides immunosuppression, tacrolimus has been reported to have the potential to increase muscle strength by enhancing ryanodine receptor (RyR) function. However, few attempts have been made to demonstrate the early effect of tacrolimus as an RyR enhancer in clinical investigation. METHODS In 20 MG patients, masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRPs) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The excitation-contraction (E-C) coupling time (ECCT) was calculated by the latency difference between CMAP and MRP. Bite force was measured using a pressure-sensitive sheet. Serial assessments of % decrement in masseteric repetitive nerve stimulation (RNS), ECCT and bite force were performed before and within 4 weeks of tacrolimus (3 mg day(-1)) treatment. The median (mean, range) interval of assessment was 2 (2.4, 1-4) weeks. We also measured serum antibodies against RyR, acetylcholine receptor and muscle-specific receptor tyrosine kinase. RESULTS Bite force increased after tacrolimus treatment accompanying clinical improvement assessed by Myasthenia Gravis Foundation of America classification, but the bite force difference did not reach statistical significance. Wilcoxon matched-pairs signed-ranks test detected a significant ECCT shortening in 12 patients assessed after 1-2 weeks of tacrolimus treatment as well as in eight patients assessed after 3-4 weeks. In contrast, masseteric CMAP and % decrement showed no significant changes after short-term tacrolimus treatment. CONCLUSIONS Tacrolimus induces ECCT shortening accompanying clinical improvement despite no improvement in % decrement within 2 weeks. SIGNIFICANCE This early effect of tacrolimus may imply a pharmacological enhancement of RyR function to improve E-C coupling in MG.

Progressive multifocal leukoencephalopathy after autologous peripheral blood stem cell transplantation in a patient with multiple myeloma treated with combination therapy

A 62-year-old Japanese man presented with gait disturbance, difficulty of speech, and spilling of food from the left corner of his mouth, andwas admitted for investigation. His relevantmedical history included hypertension, diabetes, and carrier of hepatitis B virus. At the age of 54, he was diagnosed with IgG-κ type multiple myeloma (MM), stage IIA according to the Durie and Salmon classification and stage I according to the International Staging System.With bisphosphonate, stringent complete remission (sCR) wasmaintained for seven years. At age of 61, bortezomib-dexamethazone therapywas started because of significantly elevated IgG levels. One year later, hewas treatedwith a combination of cyclophosphamide and bortezomib, and peripheral blood stem cells were collected (CD34 cells: 1.104 × 10 cells/kg). In July, auto peripheral blood stem cell transplantation (auto-PBSCT) was performed after conditioning with high-dose melphalan. In December, he began to walk clumsily, tended to fall sideways, and was unable to talk fluently. He was examined by a neurosurgeon and admitted to our department. On admission, neurologic examinations showed mild clouding of consciousness, left-sided facial droop, and bilateral extensor plantar responses. The total and differential leukocyte counts as well as CD4 T lymphocytes were normal. He was seronegative for HIV. Cerebrospinal fluid (CSF) analysis showed slightly elevated proteins at 49 mg/dl, but normal cell counts and cytology. On brain MRI, fluid-attenuated inversion recovery (FLAIR) images showed abnormal increased signal in the white matter of right frontal lobe and diffusion-weighted images (DWI) showed hyperintensity in the periphery and hypointensity in the core of the lesion (Fig. 1a–d). The CSF testing for JC virus (JCV) DNA was supported by the National Institute of Infectious Diseases