鵜沢 顕之

To diagnose neuromyelitis optica (NMO), the 2006 NMO diagnostic criteria is commonly used. However, adequate studies about the time course of NMO according to the criteria have been lacking. The aim of the study was to identify the interval between disease onset and diagnosis of NMO, as well as the clinical characteristics and time course, according to the 2006 NMO diagnostic criteria in Japanese patients with NMO. Clinical progression and time course of 43 Japanese patients with NMO who fulfilled the 2006 NMO diagnostic criteria with mean disease duration of 14.2 years were investigated retrospectively. The initial inflammatory event was myelitis in 44.2% (long extensive transverse myelitis [LETM] in 14.3%), optic neuritis in 41.9%, and concurrent myelitis and optic neuritis in 9.3% of the patients. The presence of LETM and anti-aquaporin-4 antibody seropositivity by the end of the observation period was found in 85.7 and 93.0% of the patients, respectively. Among the patients whose medical information were sufficiently available, the median intervals between NMO onset and the time until development of both optic neuritis and myelitis, LETM, or fulfillment of the 2006 NMO criteria were 16.5, 35.1, and 27.8 months, respectively. The development of diagnostic method at an early stage of NMO may be needed in order to initiate early treatment.

Neuromyelitis optica (NMO) is an acute inflammatory disease that preferentially involves the optic nerves and spinal cord. Although many infectious agents, including mumps virus, are postulated to have a role in the pathogenesis of multiple sclerosis (MS), the relationship between NMO and infectious agents remains uncertain. To investigate the relationship between NMO and viruses that have special affinity for the central nervous system, we performed a nested polymerase chain reaction (PCR) to detect mumps virus or enterovirus RNA in cerebrospinal fluid samples from 13 patients with MS, 8 with NMO and 20 with other neurological diseases (ONDs). Nested PCR was positive for mumps virus in 2 (25%) of NMO patients, but in none of those with MS and ONDs. Moreover, nested PCR results became negative in the remission phase in the two PCR-positive NMO patients. Mumps virus may have some role in the pathogenesis of NMO.

Objective: To evaluate the degree of blood-brain barrier disruption in patients with neuromyelitis optica (NMO) and to clarify whether the levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) in patients with NMO can be useful biomarkers for blood-brain barrier breakdown. Design: Descriptive historical cohort. Setting: Department of Neurology, Graduate School of Medicine, Chiba University. Patients: The levels of sICAM-1 and sVCAM-1 in 25 patients with NMO, 21 patients with multiple sclerosis, and 20 patients with other noninflammatory neurologic disorders in the serum and cerebrospinal fluid (CSF) were measured using a multiplexed fluorescent magnetic bead-based immunoassay. Main Outcome Measures: Levels of the soluble adhesion molecules in serum and CSF and their associations with blood-brain barrier disruption. Results: The CSF levels of sICAM-1 and sVCAM-1 increased in patients with NMO compared with patients with multiple sclerosis and other noninflammatory neurologic disorders (P < .001), and serum levels of sICAM-1 increased in patients with NMO compared with healthy control individuals (P = .003). The CSF sICAM-1 levels from patients with NMO were correlated with the albumin quotient (P = .02) and the presence of lesions detected via gadolinium-enhanced magnetic resonance imaging. Conclusions: Severe blood-brain barrier breakdown occurs in patients with NMO. Measuring adhesion molecules is useful to evaluate this barrier disruption.

Lidocaine unmasks silent symptoms and eases neuropathic pain in multiple sclerosis patients however, the effects of lidocaine in neuromyelitis optica have never been reported. We describe the case of a 59-year-old Japanese woman with neuromyelitis optica spectrum disorder who developed optic neuritis 1 day after intravenous lidocaine injection for treating allodynia. Her symptom seemed to result from a relapse of neuromyelitis optica induced by lidocaine administration, and not because of the transient effects of intravenous lidocaine administration. The possibility that lidocaine administration results in relapse of neuromyelitis optica due to its immunomodulating effects cannot be ruled out. Copyright © 2011 Akiyuki Uzawa et al.

Background: Neuromyelitis optica (NMO) is assumed to be immunologically distinct from multiple sclerosis (MS). Adequate studies about cytokines and chemokines in NMO have been lacking. Objective: To investigate the contribution of cytokines/chemokines in the pathogenesis of NMO. Methods: We measured 27 cytokines/chemokines and Th17 cell-associated cytokines in the cerebrospinal fluid (CSF) of 31 NMO, 29 MS and 18 other non-inflammatory neurological disorders patients. The serum levels of some cytokines/chemokines were also measured. The correlations between clinical characteristics/laboratory findings and levels of cytokines/chemokines in NMO were examined. Results: The CSF levels of interleukin (IL)-1 receptor antagonist, IL-6, IL-8, IL-13 and granulocyte colony-stimulating factor were significantly increased in NMO, while IL-9, fibroblast growth factor-basic, granulocyte macrophage colony-stimulating factor, macrophage inflammatory protein-1-beta and tumor necrosis factor-alpha were increased in MS. IL-10 and interferon-gamma-inducible protein-10 were elevated in NMO and MS. In serum analyses, only the IL-6 level showed significant elevation in NMO. The CSF IL-6 level had a significant correlation with the CSF glial fibrillary acidic protein level and CSF cells, and a weak correlation with anti-aquaporin-4 antibody titers. Conclusions: Different immunological status and pathophysiologies exist between NMO and MS, and IL-6 may play important roles in the pathogenesis of NMO.

Background: The role of different chemokine receptors in the pathogenesis of multiple sclerosis (MS) has been extensively investigated; however, little is known about the difference in the role of chemokine receptors between the pathogenesis of neuromyelitis optica (NMO) and MS. Therefore, we examined the expression of chemokine receptors on peripheral blood lymphocytes (PBL) in MS and NMO. Methods: We used flow cytometry to analyse lymphocyte subsets in 12 patients with relapsing NMO, 24 with relapsing-remitting MS during relapse, 3 with NMO and 5 with MS during remission. Results: Compared with healthy controls (HC), the percentage of lymphocytes in white blood cells was significantly lower in NMO and MS patients. The percentage of T cells expressing CD4(+)CD25(+) and CD4(+)CD45RO(+) was higher, while that of CD4(+)CC chemokine receptor (CCR)3(+) (T helper 2, Th2) was significantly lower in MS patients than in HC. The ratios of CD4(+)CXC chemokine receptors (CXCR)3(+)/CD4(+)CCR3(+) (Th1/Th2) and CD8(+)CXCR3(+)/CD8(+)CCR4(+) (T cytotoxic 1, Tc1/Tc2) were higher in MS patients than in HC. The percentage of CD8(+)CXCR3(+) T cell (Tc1) and CD4(+)CXCR3(+) T cell (Th1) decreased significantly during remission in MS patients (P <0.05). No significant differences were identified in the expression of the chemokine receptors on PBL in NMO patients compared with MS patients and HC. Conclusions: Th1 dominance of chemokine receptors on blood T cells and the correlation between CXCR3(+) T cell (Th1 and Tc1) and disease activity in MS patients were confirmed by analysing chemokines receptors on PBL. In contrast, deviation in the Th1/Th2 balance was not observed in NMO patients.

Background: Although the benefit of treatment for relapsing-remitting multiple sclerosis (MS) is firmly established, whether interferon beta-1b (IFNB-1b) therapy is efficacious for neuromyelitis optica (NMO) has been debated. Methods: We reviewed the responses to IFNB-1b treatment in 18 patients with relapsing NMO and compared the results with those from 38 patients with relapsing-remitting MS. We compared clinical characteristics, the annualized relapse rate (ARR) and the probability of being relapse free before and after IFNB-1b treatment in patients with NMO and MS. Results: The proportion of patients with more than 50% increase in the ARR after IFNB-1b treatment was much higher in NMO than in MS (P = 0.046). ARR was significantly lower in patients with MS after IFNB-1b administration than before (P = 0.015), but not in NMO. Kaplan-Meier and log-rank statistical analyses revealed that relapse-free rates were lower in NMO than MS after IFNB-1b treatment (P = 0.032). The analyses also showed lower relapse-free rates during the pre-IFNB-1b treatment period than the post-IFNB-1b treatment period in MS (P < 0.001), but not in NMO. Conclusion: IFNB-1b treatment does not appear to be effective for preventing relapse in NMO likely because of differences between the immune-pathogenesis of NMO and MS.

To investigate differences in helper T cell immune responses in cerebrospinal fluid (CSF) between neuromyelitis optica (NMO) and multiple sclerosis (MS), we measured CSF levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha and interferon-gamma at the time of relapse in 17 NMO patients and 21 MS patients using fluorescence-activated cell sorting. CSF IL-6 levels were significantly higher in NMO patients than in patients with MS (P = 0.001) and other neurological diseases (P = 0.001). The other cytokines tested were undetectable. Elevated CSF levels of IL-6 in only NMO supports the view of different pathophysiologies of NMO and MS. CSF IL-6 levels may be useful in the differential diagnosis of the two disorders.

We describe 2 patients who developed anti-aquaporin-4 antibody-positive neuromyelitis optica (NMO) following the development of anti-acetylcholine receptor antibody-positive myasthenia gravis (MG). A literature review of 13 similar cases in addition to the present 2 cases of NMO with MG showed predominance among Asian women and frequent development of NMO following thymectomy for MG. Moreover, in one of our patients, serial assays of anti-aquaporin-4 antibody and anti-acetylcholine receptor antibody were performed. Accumulating evidence for the coexistence of NMO and MG suggests that a common immunopathogenesis of NMO and MG may exist, and the association of NMO with MG may be more frequent than hitherto believed. (C) 2009 Elsevier B.V. All rights reserved.

Few cases of dopamine agonist-induced antecollis in Parkinson's disease (PD) have been reported. Literature review of 16 PD patients including our 3 cases with dopamine agonist-induced antecollis showed predominance of (1) Japanese, (2) women, and (3) Hoehn-Yahr stage of >= 3. We experienced three Japanese PD patients who subacutely exhibited antecollis following increased dopamine agonist dose that improved just after withdrawal of the agonist. One patient developed antecollis during increasing pramipexole dose in combination with cabergoline. Antecollis in another patient appeared during increasing pramipexole dose; it worsened after substituting pergolide for pramipexole, but improved after withdrawal of pergolide. Our cases indicate that there is no specific dopamine agonist causing antecollis, and it is possibly caused by a number of single dopamine agonists or a combination of them. Dopamine agonist-induced antecollis should be considered when encountering antecollis in PD patients being treated with dopamine agonists and withdrawal of the agonist can improve symptoms. (C) 2009 Movement Disorder Society

Pure monoparesis of the leg due to cerebral infarction is rare compared to that of the hand. The anterior cerebral artery (ACA) territory is the most common lesion site in leg monoparesis, but diffusion-weighted (DW) MRI has not commonly been used for lesion detection. The purpose of this study was to use DW MRI to evaluate the radiological correlation with lesion location in patients presenting with pure leg monoparesis. We retrospectively studied six cerebral infarct patients with pure leg monoparesis who had undergone DW MRI. Patients were scanned within 3 days of symptom onset. DW MRI identified lesions in the posterior limb of the internal capsule (PLIC) in two patients, in the corona radiata (two patients), in the subcortical white matter of the posterior frontal lobe (one patient), and in the frontal and parietal cortex, including the paracentral lobule and precuneus (one patient). The two patients with PLIC infarctions had characteristic linear infarction abnormalities along the long axis of the internal capsule. Corona radiata infarction were located posteriorly, and the two subcortical and cortical infarction were thought to be in the territory of the ACA. We thus concluded that in leg monoparesis due to infarctions, lesions may be located in the PLIC, corona radiata, or in the ACA territory. Recently, magnetic resonance tractography has shown that foot fibres of the corticospinal tract in the PLIC somatotopically may be posteromedial to hand fibres along the short axis of the internal capsule, rather than posterolateral along the long axis as has been thought. Thus, damage along the long axis of the PLIC by linear infarctions can cause pure monoparesis of the leg. (C) 2009 Elsevier Ltd. All rights reserved.

We report the case of a 43-year-old woman who developed multiple cranial nerve palsy, the symptoms of which included hyposmia, visual loss, facial hypoesthesia, facial weakness, dysphagia, gustatory disturbance, and sensory disturbance of the trunk and ulnar side of the bilateral arms. The clinical features included swelling of the bilateral hilar lymph nodes, uveitis, an elevated serum angiotensin-converting enzyme level, and negative tuberculin reactions, which led to a diagnosis of neurosarcoidosis. Her symptoms improved after administration of steroids. An elevated cerebrospinal fluid cell count and protein level, a low-frequency F-wave and slightly decreased sensory nerve action potentials in bilateral ulnar nerves by nerve conduction studies, and normal findings in the spine by magnetic resonance imaging suggested that truncal hypoesthesia was Caused by polyradiculopathy. Although rare, in patients with neurosarcoiclosis, truncal polyradiculopathy is noteworthy findings in addition to cranial nerve palsy. (C) 2009 Elsevier B.V. All rights reserved.

A 55-year-old woman was admitted to our hospital because of sudden onset onset of dizziness and gait ataxia. A brain CT scan revealed a small cerebellar haemorrhage located in the right vermis. Brain MR angiography revealed left persistent primitive trigeminal artery (PPTA) and basilar artery (BA) dysplasia proximal to the shunting PPTA without arteriovenous malformation (AVM) or aneurysm. We speculate that BA dysplasia due to the PPTA, along with poorly controlled hypertension resulted in overload of the superior cerebellar artery blood vessels through the PPTA. leading to a haemorrhage in the right vermis, BA dysplasia and a PPTA without an obvious AVM or aneurysm possibly leading to cerebellar haemorrhage is rare. PPTA is a relatively common vascular anomaly; hence, we must consider it in the differential diagnosis for brain haemorrhages that may be caused by the specific haemodynamic consequences of PPTA. (C) 2008 Elsevier Ltd. All rights reserved.

Pure dysarthria caused by a small cortical infarction is rare. Recent reports have revealed that a small cortical lesion can lead to pure dysarthria, furthermore some reports have revealed that a middle frontal gyrus lesion might cause pure dysarthria. We report a 64-year-old woman who presented only dysarthria and had a small limited cortical infarction located at the left middle frontal gyrus. This case indicated that an isolated middle frontal gyrus lesion can cause pure dysarthria by secondary compromising of the cortical areas related or connected to the corticobulbar tract.

Aspergillosis of the central nervous system (CNS) is an uncommon infection, mainly occurring in immunocompromised patients. We report a case of nasocerebral aspergillosis in an immunocompetent patient successfully treated with voriconazole and a corticosteroid. Magnetic resonance imaging (MRI) showed contrast enhancement surrounding the brainstem and cerebellum with intramedullary pontine and cerebellar T2-hyperintense lesions. The patient's symptoms and MRI abnormalities improved after voriconazole and corticosteroid treatment; however, discontinuation of the corticosteroid caused a worsening of the T2-hyperintense lesions, whereas resuming it resulted in its improvement. This suggested that these T2-hyperintense lesions may be due to secondary inflammation caused by aspergillosis and not the aspergillosis itself. We conclude that treatment with a combination of voriconazole and a corticosteroid appears to be effective for the treatment of some patients with CNS aspergillosis.

Objective: Ataxic hemiparesis (AH) is a well recognised lacunar syndrome involving homolateral ataxia with accompanying corticospinal tract impairment. Most previous studies of lesion location in AH did not use diffusion weighted MRI (DW MRI). The purpose of this study was to use DW MRI to evaluate the radiological correlation in patients presenting with AH. Methods: Retrospectively, we studied 29 patients with AH using DW MRI. Results: All patients were scanned within 4 days of onset. Acute infarction was identified in 28 of 29 (97%) patients. A single lesion was identified in 26 patients: pons (n = 8), internal capsule (n = 6), corona radiata (n = 2), distended internal capsule from corona radiate (n = 7), frontal subcortical area (n = 1) and precentral with or without postcentral gyrus (n = 2). Two lesions were found in two patients: in the pons and corpus callosum of one patient, and in the corona radiata and subcortical white matter of the other. Conclusions: AH is mainly caused by pontine or internal capsule/corona radiata lesions. It also occurs in the precentral gyrus, including the precentral knob, with or without postcentral gyrus lesions. Fibres of the fronto-ponto-cerebellar system may originate from the frontal cortex, including the precentral gyrus, probably near the pyramidal tract. Damage at this location may cause AH.

Background A combination of acute urinary retention and aseptic meningitis has not been well known. This combination can be referred to as meningitis-retention syndrome (MRS), when accompanied by no other abnormalities. Objective To describe the results of a uro-neurological assessment in our patients with MRS. Methods In three patients (two men, one woman; age, 34-68 years), we performed urodynamic studies and relevant imaging and neurophysiological tests, in addition to cerebrospinal fluid (CSF) examination. Results All three patients developed acute urinary retention along with headache, fever and stiff neck. None had obvious neurological abnormalities, other than a slightly brisk reflex in the lower extremities. One had previously experienced generalized erythematous eruptions, but none had pain, hypalgesia or skin eruptions in the sacral dermatomes suggestive of Elsberg syndrome (infectious sacral polyradiculitis; mostly genital herpes). Brain/spinal/lumbar plexus MRI scans and nerve conduction studies were normal. CSF examination showed mild mononuclear pleocytosis, increased protein content, and normal to mildly decreased glucose content in all patients; increased myelin basic protein suggestive of central nervous system demyelination in one; and increased viral titers in none. Urodynamic study revealed, during the voiding phase, an underactive detrusor in all patients and an unrelaxing sphincter in one. These clinical manifestations were ameliorated within 3 weeks. Conclusions We reported three cases of MRS, a peculiar syndrome that could be regarded as a mild variant of acute disseminated encephalomyelitis (ADEM). Urinary retention might reflect acute shock phase of this disorder. Although MRS has a benign and self-remitting course, management of the acute urinary retention is necessary.