Shohei Watanabe

Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG

This study investigates the relation between the serological status of NMO (neuromyelitis optica)-IgG and the clinical and MRI features in Japanese patients with multiple sclerosis. Serum NMO-IgG was tested in 35 Japanese patients diagnosed with multiple sclerosis, including 19 with the optic–spinal form of multiple sclerosis (OSMS), three with the spinal form of multiple sclerosis (SMS), and 13 with the conventional form of multiple sclerosis (CMS), which affects the brain. NMO-IgG was detected in 14 patients, 12 with OSMS and 2 with CMS. In these patients, longitudinally extensive (>3 vertebral segments) spinal cord lesions (93% v 57%) and permanent, complete blindness (no perception of light) in at least one eye (50% v 0%) were the noticeable features as compared with NMO-IgG-negative OSMS. The two patients having CMS with NMO-IgG had unusual brain lesions, but in other respects had features suggesting OSMS. NMO-IgG was detected in more than half the number of patients with OSMS and in some patients with CMS. This newly discovered serum autoantibody was markedly associated with longitudinally extensive spinal cord lesions and with complete blindness, suggesting severe optic–spinal disease.

Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS) with a poor prognosis in terms of the optic-spinal function. Recently, a serum autoantibody (NMO-IgG) binding to the blood–brain barrier region was detected exclusively in patients with NMO and its high risk group. We treated six NMO-IgG-positive patients (all female; age 21–67 years old, median 41; three with optic neuritis and three with myelitis) who were unresponsive to high-dose intravenous methylprednisolone (HIMP), with plasma exchange (PE) (three to five exchanges, 2–3 L each). Three of the patients(one with optic neuritis and two with myelitis) showed definite functional improvement following PE. The clinical improvement started to appear after one or two exchanges, while there was little or no improvement in the other three patients. Such quick clinical responses to PE suggest a pathogenetic role of humoral immune factors in NMO, although delayed responses to the corticosteroid therapy might have contributed to the therapeutic efficacy, in part. Further clinical and in vitro studies are needed to determine whether the removal of NMO-IgG is directly relevant to the therapeutic efficacy. PE may hasten the functional recovery from corticosteroid-resistant relapses in some NMO-IgG-positive patients with NMO.

Preferential spinal central gray matter involvement in neuromyelitis optica : An MRI study

To delineate the MRI features that distinguish neuromyelitis optica (NMO) from multiple sclerosis (MS). We compared the distribution of the spinal cord lesions by analyzing 1) lesion area, 2) lesion density (by superimposing the lesions onto the standard sections of the cervical and thoracic cord with appropriate transparencies using computer software), and 3) T1-hypointensity in axial sections of MRI in NMO and MS. In NMO, 60–70% of the cervical and thoracic cord MRI lesions occupied more than half of the cord area and mainly involved the central gray matter in the acute stage. In the chronic stage, half or more of the lesions were localized at the central gray matter region. The lesion superimposition analysis also revealed much higher densities in the central gray matter region than in the peripheral white matter regions. Two patients with NMO had T1-hypointense lesions in the central region. In contrast, over 80% of the lesions in MS were localized in the lateral and posterior white matter regions of the cord in the chronic as well as acute stage. Lesion densities were much higher in the lateral and posterior white matter regions than in the central gray matter region. None of the lesions in MS were T1-hypointense. These MRI findings strongly suggest a preferential involvement in the spinal central gray matter in NMO which is distinct from MS.ObjectiveTo delineate the MRI features that distinguish neuromyelitis optica (NMO) from multiple sclerosis (MS).MethodsWe compared the distribution of the spinal cord lesions by analyzing 1) lesion area, 2) lesion density (by superimposing the lesions onto the standard sections of the cervical and thoracic cord with appropriate transparencies using computer software), and 3) T1-hypointensity in axial sections of MRI in NMO and MS.ResultsIn NMO, 60–70% of the cervical and thoracic cord MRI lesions occupied more than half of the cord area and mainly involved the central gray matter in the acute stage. In the chronic stage, half or more of the lesions were localized at the central gray matter region. The lesion superimposition analysis also revealed much higher densities in the central gray matter region than in the peripheral white matter regions. Two patients with NMO had T1-hypointense lesions in the central region. In contrast, over 80% of the lesions in MS were localized in the lateral and posterior white matter regions of the cord in the chronic as well as acute stage. Lesion densities were much higher in the lateral and posterior white matter regions than in the central gray matter region. None of the lesions in MS were T1-hypointense.ConclusionsThese MRI findings strongly suggest a preferential involvement in the spinal central gray matter in NMO which is distinct from MS.

Occurrence of acute large and edematous callosal lesions in neuromyelitis optica

Background The corpus callosum is commonly involved in multiple sclerosis (MS), but the characteristics of callosal lesions in neuromyelitis optica (NMO) are unknown. Objective To reveal the features of callosal lesions in NMO in comparison to MS. Methods We retrospectively reviewed the medical records and the brain magnetic resonance imaging films of 56 patients with MS and 22 patients with NMO. Results In MS, 36 (64.3%) of 56 patients had callosal lesions, but only four patients had acute lesions. All such acute lesions were small, isolated and non-edematous, and the intensity was homotonic. Chronic lesions were observed in 34 patients with MS, and 32 (94%) of them presented small lesions located at the callosal lower margin (“hemi-oval pattern”). Meanwhile, four (18.2%) patients with NMO had callosal lesions, and three of them had acute lesions. Those acute lesions were multiple, large edematous ones with heterogeneous intensity (“marbled pattern”). In the chronic stage, the lesions shrank or disappeared. Conclusions Acute large, edematous callosal lesions occasionally occur in NMO. Similar to longitudinally extensive transverse myelitis, such callosal lesions may reflect severe edematous inflammation in NMO, and may provide additional evidence that the pathogenesis in NMO is different from that in MS.

Successful treatment of a hypothalamic lesion in neuromyelitis optica by plasma exchange

Sirs: Neuromyelitis optica (NMO) is characterized by severe attacks of optic neuritis and myelitis. More than half of patients with NMO are positive for NMO-IgG, a serum autoantibody specific to NMO [3]. In NMO, hypothalamic lesions occasionally develop, and cases with endocrinopathy (hyperprolactinemia/galactorrhea or amenorrhea) have been reported [7, 8]. Recently, therapeutic efficacy of plasma exchange (PE) in some corticosteroid-unresponsive cases of idiopathic demyelinating diseases including NMO has been reported [2, 6, 9]. We report a therapeutic efficacy of PE for a hypothalamic lesion in an NMO-IgG-positive NMO patient totally unresponsive to high-dose intravenous methylprednisolone (HIMP). The patient was a 21-year-old woman who had had total blindness in the left eye and upper-half visual field defect in the right eye (Figure 1, A-1) as sequellae of previous attacks of NMO (a total of ten relapses of optic neuritis and myelitis and normal brain MRI). On 5 April 2004 (Day 1), she complained of deterioration of visual field defect in the right eye and was admitted to our hospital. Neurological examination revealed complete blindness in the left eye and blurred vision with visual defect in the right eye except the nasal lower quadrant, abnormal pupillary light reflex (absent on left and sluggish on right), generalized hyperreflexia, left Babinski sign and painful numbness in her left breast. Galactorrhea was not seen. Brain MRI showed T2-hyperintense lesions in the hypothalamus, medulla oblongata, and cervical cord (C2-8). The hypothalamic lesion partly involved the optic chiasma and pituitary stem (Figure 1, B-1). The hypothalamic and cervical cord (C6-7) lesions were enhanced with gadolinium (Gd). Serum NMO-IgG and antinuclear antibody were positive, and serum prolactine (PRL) level was elevated (49.51 ng/mL). Oligoclonal band were not seen. Although she was first treated with two courses of HIMP therapy (1 g/day, for 3 days) on Day 1-3 and Day 9–11, her visual symptom in the right eye became worse (Figure 1, A-2, A-3) and the hypothalamic lesion remained Gdenhanced (Figure 1, C-1). Serum PRL level became even higher (68.35 ng/ml). We then treated her with PE (2 liters of plasma was exchanged with 5% albumin solution each time.) on Days16, 18, 22, and 26. After two sessions of PE, the visual field in the right eye began to improve and later neared the prerelapse level (Figure 1, A-4). In accordance with the clinical improvement, Gd-enhancement of the hypothalamic lesion disappeared (Figure 1, C-2). Serum PRL level also decreased to 41.57 ng/ml. In our patient, the visual impairment and hyperprolactinemia clearly resolved following PE, although a spontaneous resolution or delayed effect of corticosteroid is not ruled out. Keegan et al. reported six out of ten NMO patients showed improvement following PE [2], but a therapeutic effect of PE on hypothalamic lesions in NMO has not been described. The neuropathological finding of hypothalamic lesions in NMO was demyelination with necrotic changes [7] which was similar to the lesions in the optic nerves and spinal cord of NMO. Hypothalamic involvement could be a under-recognized feature of NMO [5]. The hypothalamic lesion could involve the optic tract as seen in our case. Perivascular deposition of immunoglobulins and activated complements is a characteristic finding of NMO as compared with multiple sclerosis [4]. Moreover, rituximab, anti-CD20 monoclonal antibody targeting pre-B cells and mature B cells, may be effective in NMO [1]. PE’s efficacy in our case, the pathological findings and the rituximab trial strongly suggest that humoral immunity plays a role in the pathogenesis of the hypothalamic lesion in NMO. PE should be considered in treating NMO patients with lesions S. Watanabe AE I. Nakashima I. Miyazawa AE T. Misu AE Y. Shiga K. Fujihara (&) AE Y. Itoyama Dept. of Neurology Tohoku University School of Medicine 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan Tel.: +81-22-717-7189 Fax: +81-22-717-7192 E-Mail: fujikazu@em.neurol.med.tohoku. ac.jp

Familial Creutzfeldt-Jakob disease with a point mutation (Met to Arg) at codon 232: two different phenotypes

A 5 5-year-old woman who had no family history of dementia developed insomnia followed by somnolence, intellectual deterioration, unsteady gait, psychiatric symptoms and myoclonus. Two months after the onset, she was admitted to our hospital because of severe dementia. EEG showed periodic sharp and wave complexes (PSWC) and diffusion-weighted MRI (DWI) demonstrated a high intensity lesion in the bilateral striatum. 14-3-3 protein immunoassay in CSF was positive. Prion protein gene (PRNP) analysis revealed M232R and methionine homozygosity at codon 129 (MM 129). Three months after the onset she became akinetic and mute.