Unrecognized neuromyelitis optica spectrum disorder with pontine and corpus callosum microhemorrhage

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) represents an
 immune-mediated neuroinflammatory syndrome, classified as separate entity
 after discovery of aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). The
 neuroimaging spectrum of NMOSD classically consisted of bilateral optic
 neuritis and longitudinally extensive transverse myelitis (LETM), recently
 broadened with lesions in area postrema, diencephalon, brainstem and
 cerebellum, and extensive cord atrophy. Case report: Here we present a case
 of an AntiAQP4-positive 65-year old female patient who initially presented
 with underappreciated LETM and developed multiple cerebral and cerebellar lytic demyelinating lesions associated with acute long segment optic nerve
 involvement two years later. Two new imaging findings are described in this
 case: the involvement of complete cross-sectional area of pons and
 microhemorrhage in the pons and corpus callosum. Conclusion: Raising
 suspicion of NMOSD is of a crucial importance in cases with isolated LETM in
 order to prevent relapses in Anti-AQP4 positive cases, improve patient
 outcome and recovery.

. The patient was initially treated with pulse doses of 1g methylprednisolone for 7 days, which resulted in minimal neurological improvement. Due to unsatisfactory response to treatment, plasma exchange was performed, followed by the introduction of immunosuppressive therapy with prednisone and azathioprine. The outcome was lethal.

Discussion
The diagnosis of NMOSD is based on both clinical and radiologic findings, according to the international consensus diagnostic criteria for NMOSD (1). In this case the patient was a 63-year-old female, and disease followed relapsing course, in concordance with typical NMOSD epidemiologic findings (3). Mortality rates are high in NMOSD, varying from 25-50%, highly associated with neurogenic respiratory failure and extensive brainstem lesions (4).
The initial imaging finding in our patient was an isolated acute LETM, misinterpreted as a syrinx, with no concurrent brain lesions. LETM is typically considered as one of the cardinal clinical findings in NMOSD, in conjunction with optic neuritis (5). At the initial presentation, no signs of optic neuritis were evident, although it developed later during the disease. However, isolated myelitis as the only clinical manifestation has been shown to be more common in male patients (67% vs 28%) (6). Follow-up MRI scans revealed the progression of LETM leading to severe and rapid atrophy of the affected spinal cord.
Relapsing course was observed two years later with newly detected lesions in the brain, all classical NMOSD locations (1).
Spinal cord atrophy is considered a chronic manifestation of NMOSD. However, it usually develops over a longer period of time, up to 12 years (5). It is suggested that spinal cord atrophy can potentially help differentiate between Anti-AQP4 and Anti-MOG positive patients, with anti-AQP4 patients having significantly more severe atrophy, which was true for our patient (5). It must be noted that our patient was under no specific treatment for lesions in the spinal cord due to misinterpretation. Although modern therapy in concordance with the current guidelines was given (high-dosage methylprednisolone therapy for 3-5 days continuously, followed with plasma exchange as a rescue therapy option) (7), the outcome was lethal.
Previously reported brainstem lesions only accounted for focal lesions in the pons (8), while our patient presented with diffuse pontine lesions. This is the finding not so commonly observed in NMOSD patients, given that proposed patterns for brainstem lesions are focal and more dorsally located (9). One previously unreported finding was observed in our patient, a discrete linear hemorrhage in the right aspect of the pons and in the splenium of corpus callosum, visible on SWI. Kamo et al. previously reported a case of major pontine hemorrhage, which was secondary to corticosteroid treatment and hypertension (202/127 mmHg) (10). In our patient, the form of hemorrhage resembled that of microbleeds (Figure 3, D and E) and no elevation of blood pressure was detected. This finding could be associated to the corticosteroid therapy but might also represent the endstage changes in demyelinating lesions (11).

Conclusion
To conclude, raising suspicion of NMOSD is of crucial importance in cases with isolated LETM, especially in cases of Anti-AQP4 seropositivity, even when no lesions in the brain and optic nerves are present, in order to prevent delay in diagnosis and improve patient outcome and recovery.