Hypothalamic Lesion and Nmo-IgG Positivity Restricted to CSF

Background: Neuromyelitis optica (NMO) is a severe demyelinating disorder of the central nervous system that predominantly affects the optic nerves and the spinal cord. NMO spectrum disorders (NMOSD) include other clinical syndromes associated with white matter lesions restricted to areas of high aquaporin-4 (AQP4) expression. Anti-AQP4 antibodies are 73% sensitive and 91% specific for the diagnosis of NMO. A review of the literature identifies only 3 out of 26 NMO patients with NMO-IgG positivity restricted to CSF.

Objectives: We present a case of NMOSD in a patient who presented with somnolence and autonomic dysfunction consistent with disturbance of the hypothalamic-pituitary axis and MRI lesions restricted to the hypothalamic pathways. Serum NMO-IgG was negative but CSF NMO-IgG was positive.

Methods: Case report.

Results: We report a case of a 22-year-old, previously healthy woman with a three-week history of progressive somnolence, hypothermia, bradycardia, hypotension and hypernatremia. Neurological exam was only significant for inability to maintain wakefulness. Patient did not have clinical signs of optic neuritis (ON) or myelitis. Patient’s wakefulness, hypothermia and hypernatremia improved after a five-day course of intravenous methylprednisolone 1-gram daily. Hypotension and bradycardia persisted for several weeks. She was able to return to work and school, however required Modafinil to maintain wakefulness as outpatient. She did not have exacerbation on three-month follow-up.

MRI of the brain revealed T2 hyper intensities involving the hypothalamus, thalami and anterior head of caudate with patchy contrast enhancement in the hypothalamus.  MRI of the spine and orbits were normal. Antinuclear antibody was weakly positive at ANA 1:40, serum NMO-IgG was negative, however cerebral spinal fluid (CSF) NMO-IgG was positive. Other CSF studies revealed 14 WBC, no RBC, normal glucose and protein, mildly elevated IgG index at 0.8, 3 OCBs and MBP 28.1.

Conclusions: Hypothalamic-pituitary axis dysfunctions can be the presenting features of NMO in the absence of signs of ON or myelitis. Negative serum NMO-IgG does not exclude the diagnosis of NMO. If clinical suspicion persists, CSF NMO-IgG should be pursued.