Hypothalamus Syndrome in Opticospinal Multiple Sclerosis

Discussion

MS is a demyelinating inflammatory condition of the CNS thought to be caused by autoimmune attacks targeting CNS myelin. In Asians, MS is rare. Reported prevalence rates of MS from population surveys in China are rather low (1–2 per 100,000) and higher in women than in men; these rates are comparable with the results from other populations in Asia.¹ In 1996, Kira et al² first reported that MS in Asians can be divided into 2 subtypes, including OSMS (Asian-type MS) and CMS (Western-type MS) and proposed clinical classification criteria for OSMS: selective involvement of the optic nerves and spinal cord by clinical symptoms with or without minor brain stem signs. Our patient satisfied several characteristic features of OSMS compared with CMS³: absence of oligoclonal bands in the CSF and fewer brain lesions and LESCLs detected by MR imaging.

Optic nerve and spinal cord involvement in our patient made us consider NMO as a differential diagnosis. In 2004, an NMO-specific antibody (NMO-IgG) was found in the sera of patients with NMO, and its target antigen was identified as AQP4 water channel protein.⁴ The serum anti-AQP4 antibody is thus recognized as a specific biomarker for NMO. Although anti-AQP4 antibodies are present in about 60% of Japanese patients with OSMS over a wide range of disease durations, there are also cases of anti-AQP4 antibody–negative OSMS with LESCLs and few brain lesions.⁵ Our final diagnosis of this patient was anti-AQP4 antibody–negative OSMS.

Recent data from MR imaging studies suggest that pathologic changes in the deep gray matter, particularly in the caudate nucleus and thalamus, are frequent in patients with MS.⁶ However, involvement of the hypothalamus is uncommon. In very recent histochemistry, immunohistochemistry, and morphometry research performed on whole coronal sections of 14 MS brains, deep gray matter demyelinating lesions were detected most often in the thalamus (11/14) and caudate (9/14), while hypothalamus involvement was only 4/14, and a preponderance of activated microglia were found in these lesions in the postmortem series of cases.⁷ Because ferritin can be used as an activation marker of microglia and reflects the extent of inflammation in brain,⁸ we presumed that microglia activation may exist in the hypothalamus and that elevated serum ferritin might be found in our patient. In agreement with our hypothesis, an increased serum ferritin level was found, which represented active inflammation with ongoing oxidative damage.⁹ IL-6, which is crucial for the induction of EAE, an animal model for MS, was also found increased in this patient, indicating that she had active CNS inflammation.

Although periodic hypothermia or hyperthermia has been occasionally reported in MS, hyperthemia and disturbances in the sleep-wake cycle and amenorrhea as a result of hypothalamic disease have not been previously reported among subjects with MS. In our patient, systemic causes of hyperthermia were not found. A probable relation of the periodic hyperthermia with a hypothalamic dysfunction is suggested due to the hypothalamic involvement observed in the radiologic study and the abnormal temperature rhythm. Bilateral lesions in the hypothalamus might have provoked the hyperthermia by central rhythm disruption due to excessive heat production or defective heat loss.¹⁰ Animal studies have emphasized the importance of the preoptic area of the anterior hypothalamus in the regulation of body temperature and the sleep-wake cycle.¹¹ The patient had no gynecologic disease previously, and her elevated prolactin level and amenorrhea may be explained by impaired hypothalamus-pituitary-adrenal axis activity, which has been described in patients with MS and EAE.¹²