Diagnostic Criteria for Multiple Sclerosis Research Involving Multiply Affected Families

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Abstract
• Existing diagnostic criteria for multiple sclerosis present significant limitations when assessing multiplex families for three reasons: (1) restricting age of onset to 10 to 50 years is likely to exclude 10% of patients known to have a later onset, (2) diagnoses based on subjective information can potentially result in a falsepositive diagnosis, and (3) including progressive myelopathies occurring within families, particularly when highly symmetrical, may result in the improper inclusion of genetically determined neurological diseases such as familial spastic paraparesis. The validity of any molecular genetic approach for determining disease susceptibility critically depends on diagnostic accuracy. We present adapted diagnostic criteria that address each of these diagnostic pitfalls unique to multiplex multiple sclerosis family research.