Diagnostic, prognostic and management aspects of different types of multiple sclerosis

Sammanfattning: Background: The aim in the thesis is to study diagnostic issues, clinical features, therapy, and prognosis in selected demyelinative disorders of the nervous system: optic neuritis (ON), primary progressive MS (PPMS), and tumefactive MS (a very rare acute demyelinating disorder). Methods: From an initial cohort of 110 patients with ON collected 19 to 31 years ago, a new follow-up survey was conducted in 50 patients who on a previous follow up had not developed MS. 30 out of 50 patients had a MRI examination, 22 of whom also agreed to neuropsychological testing. The clinical applicability of the revised 2005 McDonald diagnostic criteria for PPMS was assessed in 17 patients. A file search identified two patients with tumefactive MS. Results: The risk of developing MS after ON was 40% after a mean of 26 years. No patient developed MS 15 years or later after the ON. Risk factors for MS were abnormal CSF findings at baseline, winter onset, and recurrent ON. MRI at follow-up identified lesions compatible with MS in 20 out of 30 “healthy” patients with isolated ON. 15 out of 22 patients with ON demonstrated significant cognitive dysfunction, unrelated to MRI findings. 12 out of 17 patients with PPMS fulfilled the revised McDonald MRI criteria, whereas 5 patients required additional CSF analysis to establish a PPMS diagnosis. Both patients with tumefactive MS were diagnostic challenges, and developed severe brain oedema with mass effect which was successfully treated with decompressive hemicraniectomy. Conclusions: Less than half of all our patients with an ON developed MS in the long term. Two thirds of patients who did not develop MS clinically had late MRI findings compatible with demyelinating disease; surprisingly no less than two thirds displayed cognitive impairment on detailed neuropsychological testing despite no apparent disabilities. In PPMS, MRI failed to establish the diagnosis in one third of the patients: CSF analysis should therefore be an integral part in the diagnostic work-up. Finally, clinical and neuroimaging features of tumefactive MS needs to be more widely recognized. High dose corticosteroids should be first line therapy, whereas decompressive craniectomy may be used in patients who develop mass effect with increased intracranial pressure (ICP).