Lack of brain involvement was originally considered characteristic of NMO. However, brainstem lesions that are typically continuous with high cervical myelitis are recognized in NMO on MR imaging and confirmed by histological examination of affected brain tissues from patients who develop bulbar dysfunction manifesting as dizziness, vertigo, ataxia, diplopia, dysphagia, intractable hiccups, facial sensory impairment or paresthesia, nystagmus, or dysautonomia, which may cause sudden cardiac arrest.3,24,30,36- 38 Patients with NMO may initially be seen with endocrinopathies and hypothalamic dysfunction, including hyperphagia with weight gain, amenorrhea, galactorrhea, diabetes insipidus, and hypothyroidism, with lesions seen in the hypophysis and hypothalamus on MR imaging.39,40 Recently, brain involvement in NMOSDs is increasingly recognized. At the Mayo Clinic, Pittock et al30 systematically studied brain involvement of patients with NMO and reported the following observations: up to 60% of patients had brain lesions on MR imaging, approximately 10% of patients had brain abnormalities on MR imaging that are typical of classic MS (usually asymptomatic), and 8% of patients, mostly children, had diencephalic, brainstem, and cerebral lesions that are atypical of classic MS. These investigators also noticed a pattern of abnormalities on MR imaging involving the hypothalamus, periaqueductal region, and periventricular region surrounding the third and fourth ventricles (periependymal regions) in 6 of 89 patients with NMO and in 2 of 31 relapsing patients with LETM, which was characteristic of NMOSDs. This is pathogenetically relevant because these sites are regions with a high level of AQP4 expression.31 Our findings that 59% (20 of 34) of patients with NMOSDs had brain involvement and that 56% (19 of 34) of patients had brain abnormalities on MR imaging, with 6% (2 of 34) of the latter fulfilling criteria by Barkhof for classic MS, were consistent with results reported by Pittock et al.30 However, 32% (11 of 34) of our patients had clinical manifestation of brain involvement, especially as BE with florid bulbar signs and symptoms of severe brainstem dysfunction in 24% (8 of 34) and as initial clinical presentation in 18% (6 of 34). This differed from the findings by Pittock et al in which most patients with brain lesions on MR imaging were asymptomatic or mildly symptomatic only.30,31 Among 88 pediatric patients with NMO who were seropositive for AQP4 autoantibodies, McKeon et al41 reported that 45% had clinical manifestation of brain involvement, including episodic encephalopathy, ophthalmoparesis, ataxia, seizures, intractable vomiting, or hiccups, and that 68% had brain abnormalities on MR imaging predominantly involving periventricular areas, including the medulla (34%), supratentorial (29%) and infratentorial (23%) white matter, midbrain (21%), cerebellum (18%), thalamus (13%), and hypothalamus (5%). Lotze et al42 reported on 9 pediatric patients with NMO; all had brain abnormalities on MR imaging, and 5 were symptomatic, including encephalopathy, seizures, hemiparesis, aphasia, vomiting, or hiccups. The abnormalities were detected in periventricular regions (88%), brainstem (77%), juxtacortical (55%) and central (55%) white matter, corpus callosum (44%), and hypothalamus (44%). The frequent clinical manifestation of brain involvement in our patients is similar to that among these pediatric patients with NMO, but none of our patients had encephalopathy or seizures.