Importance of neurophysiological investigations in the diagnosis of multiple sclerosis

Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system affecting young adults. Although adults and children share important features of the disease, they also differ in some clinical, radiological and laboratory aspects. This review focuses on the neuroimmunological findings in the cerebrospinal fluid of children with MS pointing out that there is already at earliest time of clinical manifestation a neuroimmunological pattern, which differs only in intensity of the humoral immune response but not in frequency and does not support a neuroimmunological difference between early onset from adult onset MS. The humoral immune response with intrathecal IgG and IgM class response and the polyspecific production of antibodies against a wide range of antigens (MRZ antibody response) further helps to differentiate childhood MS from ADEM as the main differential diagnostic challenge. Introduction: Adult MS patients have a relapsingremitting (80%) and less frequently a primaryprogressive course of the disease (20%) (1). Children with MS have also a predominantly relapsing– remitting course. No reports on a primary-progressive course below the age of 10 years do exist. Even between 10 and 16 years of age a primary-progressive course of the disease is exceedingly rare (2). Children with MS have a longer disease duration until they enter a phase of secondary-progression compared to adults (2,3). Children with MS reach an expanded disability status scale (EDSS) 4 after a much longer time than adults (20.2 vs. 10.7 years), but are still significantly younger (median 31.6 years) than adults (median 41.1 years) when they suffer from significant disability (2,3). When children enter the phase of secondary progression they appear to follow the same time course as adults (3). Children more often than adults present initially with more than one functional system involved (4). In a cohort of 132 patients reported by Pohl and colleagues 67% of children with MS had a polysymptomatic manifestation (5). Cerebellar and brainstem symptoms in pediatric MS are more and pyramidal symptoms less frequent than in adults with MS (2,5). Children with MS have a higher relapse rate in the first 2 years, which in general correlates with a faster disease progression, than in adults (6). Before the age of 10 years a male preponderance exists. During and after puberty (between 15 and 16 years) several studies report a rise in the female/male ratio to 2.1:1 to 2.4:1, which is slightly higher compared to adults with MS (2,5). Of particular diagnostic relevance is the observation that children with MS often do not meet the McDonald MRI criteria for dissemination in space at the time of their first exacerbation or their MS diagnosis (7). This underscores the importance of other diagnostic features such as the presence of oligoclonal bands for an accurate diagnosis also in view of the broad differential diagnosis in pediatric MS. The most frequently considered differential diagnosis is acute dissem-