Masakazu Sugino

Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS.

The authors calculated the progression rate (ΔFS) using the total revised ALS Functional Rating Scale (ALSFRS-R) and symptom duration at diagnosis in 82 Japanese patients with ALS. Survival (death or tracheostomy) differed significantly with the ΔFS and postdiagnostic period according to log-rank testing, but Cox proportional hazards modeling revealed no strong association between total ALSFRS-R and mortality, suggesting that the ΔFS provides an additional predictive index beyond ALSFRS-R alone.

Onset and spreading patterns of lower motor neuron involvements predict survival in sporadic amyotrophic lateral sclerosis

Objective To define patterns of spread through the order of lower motor neuron involvement (first, second or third order), relationships between interval or sites of affected areas from onset to involvement of a second region, and prognosis, including 5 year survival, normal preservation of motor function at onset of respiratory symptoms and cumulative occurrence of each region and direction of spread. Method 150 patients with sporadic amyotrophic lateral sclerosis (ALS) underwent follow-up at 3 month intervals until the appearance of respiratory symptoms. Symptom appearances were determined using the revised version of the ALS Functional Rating Scale. Result Median survival with combined type onset (two regions simultaneously) was shorter (18 months) than with bulbar onset (26 months, p=0.01). The interval from onset to involvement of the second region correlated significantly with survival, independent of particular combinations. 5 year survival rate was 21% for lower limb onset, 18% for upper limb onset and 16% for bulbar onset. No patient with a rapid spread pattern (two regions within 3 months from onset) survived >5 years. Early manifestations of bulbar symptoms within 1 year were associated with worse survival (p<0.001) although no significant difference in survival was seen between groups with and without bulbar symptoms (p=0.51). In terms of cumulative occurrence, symptoms spread longitudinally to adjacent regions. Bulbar function remained preserved in 27%, lower limb function in 10% and upper limb function in 2.7%. Conclusion The interval between onset and involvement of the second region is an important predictor of survival. The data support the contiguous anatomical propagation of lower motor neuron involvement in sporadic ALS.

Expression of Th1/Th2-Related Chemokine Receptors on Peripheral T Cells and Correlation with Clinical Disease Activity in Patients with Multiple Sclerosis

Th1 cells play an important role in the pathogenesis of multiple sclerosis (MS), a disease likely linked to an autoimmune process. We measured the levels of chemokines in serum or cerebrospinal fluid (CSF) samples by ELISA, and also studied the expression of Th1-related CXCR3/CCR5 chemokine receptors and Th2-related CCR4/CCR3 chemokine receptors on blood cells from MS patients using three-color flow cytometry. The Bonferroni correction was used for the statistical analysis. The levels of CXCL10, CCL3, and CCL5 in the CSF samples for the MS groups were significantly higher than those for the control group. However, the levels of CCL2 in both the CSF and serum samples for the remission group were significantly higher than those for the active group. The percentage of CXCR3-expressing CD4+ T cells in patients with MS was significantly elevated compared with the healthy controls. Moreover, MS patients in an active phase showed a more increased CD4+CXCR3+/CD4+CCR4+ ratio than patients in a remission phase. The increased percentage of CD4+CXCR3+ cells in the blood was associated with relapses in MS. This study suggested that the CD4+CXCR3+/CD4+CCR4+ ratio could be a sensitive maker of immune dysfunction in MS.

A pilot study of dehydroepiandrosterone sulfate in myotonic dystrophy

We studied the effect of IV administration of a dehydroepiandrosterone sulfate (DHEAS) preparation (200 mg/day for 8 weeks) in 11 patients with myotonic dystrophy (MyD). After DHEAS, activities of daily living improved, muscle strength increased, and myotonia decreased. Conduction block and premature beats also improved in the four patients with cardiac involvement. This pilot study may provide a rationale for a controlled study of DHEAS in MyD.

Visual field defects of optic neuritis in neuromyelitis optica compared with multiple sclerosis

BackgroundNeuromyelitis optica (NMO) is an inflammatory demyelinating disease that predominantly affects the optic nerves and the spinal cord, and is possibly mediated by an immune mechanism distinct from that of multiple sclerosis (MS). Central scotoma is recognized as a characteristic visual field defect pattern of optic neuritis (ON), however, the differing pathogenic mechanisms of NMO and MS may result in different patterns of visual field defects for ON.MethodsMedical records of 15 patients with NMO and 20 patients with MS having ON were retrospectively analyzed. A thorough systemic and neurological examination was performed for evaluating ON. The total number of relapses of ON and visual fields was investigated. Visual fields were obtained by Goldmann perimeter with each ON relapse.ResultsAll MS patients experienced central scotoma, with 90% of them showing central scotoma with every ON relapse. However, 53% of NMO patients showed central scotoma with every ON relapse (p = 0.022), and the remaining 47% of patients experienced non-central scotoma (altitudinal, quadrant, three quadrant, hemianopia, and bitemporal hemianopia). Thirteen percent of NMO patients did not experience central scotoma during their disease course. Altitudinal hemianopia was the most frequent non-central scotoma pattern in NMO.ConclusionsNMO patients showed higher incidence of non-central scotoma than MS, and altitudinal hemianopia may be characteristic of ON occurring in NMO. As altitudinal hemianopia is highly characteristic of ischemic optic neuropathy, we suggest that an ischemic mechanism mediated by anti-aquaporin-4 antibody may play a role in ON in NMO patients.

Increased serum matrix metalloproteinase-9 in neuromyelitis optica: implication of disruption of blood-brain barrier.

Matrix metalloproteinase-9 (MMP-9) plays an important role in some neuroinflammatory diseases through the blood-brain barrier (BBB) disruption. To investigate the pathogenicity of MMP-9 in neuromyelitis optica (NMO), serum and CSF MMP-9 concentrations were measured in 13 NMO and 15 multiple sclerosis (MS) patients and 14 healthy controls, and correlated with clinical and laboratorial parameters. Serum MMP-9 concentrations were significantly higher in NMO than MS and controls, and correlated with EDSS score, CSF/serum albumin ratio, and CSF IL-8 concentrations. Our results indicate that MMP-9, promoted by elevated IL-8 activation, plays a crucial role in the pathogenesis of NMO through the BBB disruption.

Possible Regulation of Intracranial Pressure by Human Atrial Natriuretic Peptide in Cerebrospinal Fluid

To clarify the function of human atrial natriuretic peptide (hANP) in the cerebrospinal fluid (CSF), we examined hANP levels in the CSF of patients with various neurological diseases. The subjects were 16 controls without neurological disease and 45 patients with neurological disease. The 45 patients with neurological disease were divided into a group of 15 patients with intracranial hypertension (IH) and a group of 30 patients with normal pressure (NP). hANP in both CSF (1-hANP) and serum (s-hANP) was measured by RIA. Patients with IH were followed up. We analyzed correlations between 1-hANP and other parameters of CSF. Increase in concentration of 1-hANP was positively correlated with intracranial pressure (ICP; r = 0.72; p < 0.01), but not with other CSF parameters or with s-hANP. The concentration of 1-hANP appeared to be increased especially over a threshold value of ICP. In a followup study of patients with IH, changes in 1-hANP paralleled changes in ICP in every case (r = 0.79; p < 0.01). Our findings strongly suggest that 1-hANP plays an important role in the regulation of ICP in humans.

Anhedonia in Japanese patients with Parkinson's disease

Aim:  Anhedonia has been proposed as a specific mood disorder related to the dopaminergic nerve dysfunction seen in Parkinsons disease (PD). This study examined hedonic tone in patients with PD using the Snaith–Hamilton Pleasure Scale (SHAPS) and investigated the associations with depressive mood by the Self‐Rating Questionnaire for Depression (SRQ‐D).

Expression of vascular endothelial growth factor by plasma cells in the sclerotic bone lesion of a patient with POEMS syndrome

Sirs: Bone lesions are frequently present in patients with POEMS syndrome [1, 2]. Since solitary bone lesions are often plasmacytomas, they must be aggressively treated with surgery or radiotherapy. We report a case of POEMS syndrome with a solitary bone lesion. In this patient, plasma cells in the osteosclerotic lesion were the source of vascular endothelial growth factor (VEGF). A 42–year-old man developed distal dominant polyneuropathy two months after myocardial infarction. Following the onset of neurological symptoms, he exhibited edema, bristly skin, and swelling of the liver in the abdominal CT. Platelet counts were 822,000/mm, and immunoelectrophoresis demonstrated Mprotein of IgA k. Serum IL-6 and VEGF were measured using standardized ELISA (SRL, Inc., Tokyo, Japan). Although the IL-6 level was normal (2.1 pg/ml. Normal value; <4.0 pg/ml), the serum VEGF level was significantly elevated (18,500 pg/ml). He was diagnosed with POEMS syndrome. However, bone marrow aspiration from the ileum exhibited a normal appearance, and CT of the chest and the abdomen revealed no abnormal lesions, suggesting solitary or extramedullary plasmacytoma. Following steroid pulse therapy, treatment with prednisolone reduced the serum VEGF to 860 pg/ ml with marked improvement of muscle weakness and skin lesions. Although the neuropathy remained clinically stable, he again exhibited edema and bristly skin 9 months after the pulse therapy, and the serum VEGF was increased to 5,120 pg/ml. Bone scintigraphy demonstrated a spot

Cerebrovascular Disease in Type 2 Diabetic Patients Without Hypertension

To the Editor: The close relationship between diabetes mellitus and arteriosclerosis of the cerebral arteries has recently been reported. However, in these studies, the subjects included older patients with hypertension, which itself is a significant risk factor for arteriosclerosis of the cerebral arteries.1–3 Thus, previous studies on the effect of diabetes on the development of sclerosis were confounded by hypertension and aging. Therefore, we examined relatively young patients with diabetes mellitus who did not have hypertension in order to clarify the influence of diabetes mellitus itself on the development of sclerosis of the cerebral arteries. The subjects included 30 patients with type 2 diabetes mellitus (DM). The subjects with DM did not have hypertension (systolic blood pressure <140 mm Hg, diastolic blood pressure <90 mm Hg) and had no history of cerebral infarction, diabetic retinopathy, diabetic neuropathy, or diabetic nephropathy. Among the 30 diabetic patients, 4 were being treated with insulin injections, 10 with oral hypoglycemic agents, and 16 with dietary therapy alone. The control group (C) consisted of 20 healthy adults without a history of diabetes, hypertension, or cerebral infarction. There were no significant differences in age (DM: 50.1±7.0 years versus C: 49.7±6.7 years), sex (DM: 21/9 versus C: 11/9 [M/F]), systolic blood pressure (DM: 120±11 mm Hg versus C: 117±10 mm Hg) between the …