Q. 42-year-old woman presents with ataxia. Gadolinium-enhanced MRI reveals 
multiple subcortical white matter lesions as well as enhancing lesions 
in the cerrebellum and spinal cord. She is diagnosed with MS. Two months
 later she develops optic neuritis. What feature is associated with a 
milder disease course?
A. Her age of 42
B. Her initial presentation of ataxia
C. Her female gender
D. The interval between the two episodes of two months
E. Her MRI scan appearance
Ans: C
A. Her age of 42
B. Her initial presentation of ataxia
C. Her female gender
D. The interval between the two episodes of two months
E. Her MRI scan appearance
Ans: C
Most patients with clinically evident MS ultimately 
experience progressive neurologic disability. For unclear reasons, the 
long-term prognosis for untreated MS appears to have improved in recent years. In addition, the development of disease-modifying therapies for MS also appears 
to have favorably improved the long-term outlook. Although the prognosis in an 
individual is difficult to establish, certain clinical features suggest a more 
favorable prognosis. These include ON or sensory symptoms at onset, fewer than 
two relapses in the first year of illness, and minimal impairment after 5 years. 
By contrast, patients with truncal ataxia, action tremor, pyramidal symptoms, or 
a progressive disease course are more likely to become disabled. Patients with a 
long-term favorable course are likely to have developed fewer MRI lesions during 
the early years of disease, and vice versa. Importantly, some MS patients have a 
benign variant of MS and never develop neurologic disability. The likelihood of 
having benign MS is thought to be <20%. Patients with benign MS 15 years 
after onset who have entirely normal neurologic examinations are likely to 
maintain their benign course.
In patients with their first demyelinating event (i.e., a 
clinically isolated syndrome), the brain MRI provides prognostic information. 
With three or more typical T2-weighted lesions, the risk of developing MS after 
20 years is  80%. 
Conversely, with a normal brain MRI, the likelihood of developing MS is <20%. 
Similarly, two or more Gd-enhancing lesions at baseline is highly predictive of 
future MS, as is the appearance of either new T2-weighted lesions or new Gd 
enhancement 3 
months after the initial episode.
Mortality as a direct consequence of MS is uncommon, 
although it has been estimated that the 25-year survival is only 85% of 
expected. Death can occur during an acute MS attack, although this is distinctly 
rare. More commonly, death occurs as a complication of MS (e.g., pneumonia in a 
debilitated individual). Death can also result from suicide.
In this woman’s case, all of the features except her gender (C) point to a more aggressive disease course. Although it is close to impossible to predict an individual patient's outcome, features of a better prognosis include onset under 25 years (A), optic neuritis or sensory, rather than cerebellar symptoms on initial presentation (B), a long interval (>1 year) between relapses (D) and few lesions on MRI (E). Full recovery from relapses is also a positive feature. Progressive MS carries a poorer prognosis compared to relapsing–remitting MS.
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