In 1996, a 31-years-old previously healthy man presented with right hemiparesis, unsteadiness and dysarthria. After a more detailed physical examination horizontal nystagmus while looking to the right and both right arm and leg ataxia were patent. A demyelinating disease of the central nervous system was initially suspected.
Extensive laboratory tests were completed, all of them normal or negative. Erythrocyte sedimentation rate (ESR) was normal, as well as autoimmune screening including serum tests for antinuclear antibodies, antineutrophil cytoplasmic antibody, HLA-B27, HLA-DR2, anti-double stranded DNA antibodies, antithyroglobulin, and serum angiotensin-converting enzyme. Several infectious diseases were ruled out by serological and spinal cerebral fluid (CSF) tests, including Lyme disease, syphilis, HIV, herpes simplex virus, human herpes virus 6 and 8, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and Mycobacterium tuberculosis complex. On CSF analysis, the level of proteins, glucose, and cells were normal. Neither was there evidence of intrathecal immunoglobulin synthesis, as 8 identical oligoclonal bands (OCB) were found in blood and CSF.
Somatosensory-evoked potentials showed a prolongation of latencies in the right hemisphere and in brainstem auditory-evoked potentials, bilateral central conduction time prolongation was found. Visual-evoked potentials were normal.
A brain MRI showed hyperintense patchy lesions without mass effect in the brainstem, mostly affecting the pons and the cerebellar peduncles; these lesions were confluent and undefined, unlike the typical lesions described in multiple sclerosis (MS). No intravenous contrast was administered on this occasion. However, the inflammatory appearance of the lesions in the absence of proven infection or malignant cells on CSF testing prompted the decision to start treatment with intravenous methylprednisolone at high doses. After 5 of daily 1-gram doses, a significant improvement of the symptoms was observed, leaving only a minimal right arm paresis and mild gait ataxia. Due to the remaining neurological deficits, a tapering dose of 70 mg of oral prednisone after discharge was prescribed.
Unfortunately, only 2 months after stopping treatment with oral glucocorticoids, our patient presented again with symptoms similar to those in the first admission, in addition to diplopia. A second MRI with gadolinium contrast was requested then, which showed the same patchy lesions in the brainstem (Figure 1A) but with no gadolinium enhancement. However, this new imaging was obtained after initiating intravenous treatment with methylprednisolone 5 days prior, which probably altered the final results.
Over the next 4 years, despite long-term therapy with oral corticosteroids, our patient had several relapses, always involving the brainstem, with a frequency of at least 1 exacerbation per year. Each relapse was treated with intravenous glucocorticoids, but the improvement achieved was only partial and residual ataxia was more severe each time. It was clear that maintaining a low dose of oral corticosteroids was the only way to reduce the time between relapses.
On May 2000, a control MRI between relapses showed a patchy and curvilinear gadolinium enhancement on T1-weighted images, peppering the cerebellum (Figure 1B). By then, several data suggested that our patient did not have MS: he did not meet the dissemination-in-space criteria because lesions were always restricted to the cerebellum and the pons; their appearance on T2-weighted-MRI was atypical for MS; the presence of a mirror pattern on OCB testing did not fit the pattern; and the ultimate dependence on daily steroids to avoid worsening was inconsistent with the diagnosis. On the other hand, an autoimmune origin was suspected, as the infectious or tumor etiologies were safely ruled-out after 4 years of follow-up. A vasculitis of the central nervous system was considered, but the ESR and other analytical features were normal, CSF showed no pleocytosis, and there was no proof on MRI of vascular-related lesions such as microbleeds. However, after 4 years of treatment, the deleterious effects of chronic corticoid therapy caused concern and the need for a glucocorticoid-sparing therapy was evident.
After careful consideration, on July 2000, immunomodulatory treatment with subcutaneous IFNbeta-1a (Rebif 22  3 times a week) was decided on. The choice was based on the uncertainty of the diagnosis and the search for a treatment with a more secure profile than classic immunosuppressants. From that moment on, relapses occurred further apart, with a frequency of 1 exacerbation every 4-5 years, and they were no longer associated to increasing disability. The patient had a good tolerance to the treatment; he reported no significant flu-like syndrome or injection-site reactions and consecutive laboratory studies showed no alteration in leucocytes, liver, or thyroid function. However, low doses of oral Deflazacort (30 mg every 2 days, equivalent to 25 mg of Prednisone every 2 days) were sustained, in fear of further exacerbations. Suspension of corticosteroids was achieved during 11 months in 2001, but after a new relapse, we chose not to insist on total withdrawal. When Pittock et al. published their research in 2010 and the diagnosis was evident, a modification of the treatment was considered, but, taking into account both the patient s clinical stability and the excellent tolerance to immunomodulatory treatment, watchful waiting was decided on.