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

Abstract

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