Short communicationIntractable hiccup caused by medulla oblongata lesions: A study of an autopsy patient with possible neuromyelitis optica
Introduction
Hiccup is a repetitive involuntary, spasmodic, and temporary contraction of the diaphragm accompanied by sudden closure of the glottis [1], which is mediated through the center located in the medulla oblongata [2]. In neuromyelitis optica (NMO), involvement of medulla oblongata has been reported [3], [4], [5], [6], [7], and clinical observations suggest a possible link with intractable hiccup. Recently, Misu et al. reported that intractable hiccup was found in eight of 47 cases of relapsing NMO but in none of 130 cases of multiple sclerosis (MS) [4].
There has been a long controversy as to whether NMO is a variant of MS or a distinct disease [8]. However, recent serological findings strongly suggest that NMO is a distinct disease that has characteristic clinical and pathological features [9]. The main target antigen is aquaporin 4 (AQP4) that is a water channel protein located in the astrocytic foot process. AQP4 is found on all surfaces of astrocytes, but occurs at the highest concentration in the perivascular and peripial end-feet, and ependymal-cell membranes. In the nervous system, AQP4 is predominantly expressed within optic nerves, spinal cord, and periventricular regions such as brainstem and hypothalamus, and this correlates with the predominant lesion sites in NMO [10]. Histopathologically, AQP4 immunoreactivity is undetectable at the lesions of NMO [6], [8], [11] in contrast to MS [8], [11], [12]. Here, we demonstrated the involvement of the nucleus tractus solitarius (NTS) in a patient with possible NMO who developed intractable hiccup.
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Case report
A 48-year-old woman noticed pain around the left triceps muscle of the calf, weakness at the distal portion of the right leg and urinary incontinence within 3 weeks prior to admission to our hospital. Neurological examination disclosed distal weakness and hyperreflexia in the bilateral lower limbs with hypesthesia below the S2 dermatome. Hyperintensities at the cervical cord were noted on T2-weighted image. Cerebrospinal fluid (CSF) examination showed pleocytosis (cell count 237/mm3,
Neuropathological findings
Brain weight was 1280 g after fixation. Samples were fixed with 10% formalin and embedded in paraffin. Ten-μm-thick sections were prepared from the bilateral optic nerves, cerebrum, midbrain, pons, medulla oblongata, cerebellum, and spinal cord (C6, C7, C8, Th3, Th6, Th10, L3, L5, and S1). These sections were stained with hematoxylin–eosin (H&E) and Klüver–Barrera (KB). For immunohistochemistry, we prepared four-μm-thick sections, and used anti-CD68 (KP1, mouse, monoclonal Dako, 1:100),
Discussion
Clinical features of this patient are characterized by recurrent myelitis, later complicated by bulbar dysfunctions, manifesting as intractable hiccup, respiratory failure, and dysphagia. Clinically, our case did not fulfill the diagnostic criteria of NMO [13] because there were no visual manifestations throughout the clinical course. Further, serum antibodies to AQP4 could not be measured. Abnormalities of the optic nerves might have been detected if visual evoked potentials were examined. On
Acknowledgements
The authors thank Yo Shoda and Kyoko Suzuki for the excellent photographic assistance.
This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology (14570957) and a research grant from the Zikei Institute of Psychiatry.
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