**7. Clinical features**

Most of the patients with pediatric MS have a relapsing remitting course. A primary pro‐ gressive course is extremely rare in pediatric MS. The definition of an attack (relapse/exacer‐ bation) in pediatric MS is similar to that in adults. An attack is defined as "the appearance of new symptoms and neurologic signs, or worsening of old symptoms and signs due to an acute inflammatory demyelinating event in the CNS, with duration of at least 24 hours in the absence of fever or infection," and the onset of the attack should be separated from the onset of a previous attack by at least 30 days [27].

Visual, sensory, motor, brainstem, cerebellar symptoms, sphincter, and cognitive dysfunctions may also occur in pediatric MS, as they do in adults. Polysymptomatic and ADEM-like onset are more common in prepuberal patients, particularly in very young children. Visual and sensory symptoms may go unnoticed in very young children. In adolescents, the presentation of monosymptomatic and sensorimotor symptoms is frequent, and optic neuritis is the most common initial presentation. The interval between the initial demyelinating event and the second attack varies, and this interval may be longer in very young children. Relapses are more frequent and may be more severe in pediatric patients but recovery is often better than it is in adults. The accumulation of disability takes a long time in pediatric MS; however, over the long term, patients can become disabled at a younger age. The transition to secondary progressive MS occurs at a younger age in pediatric-onset MS than in adult-onset MS. The risk of transition to secondary progressive MS in pediatric patients is associated with a higher frequency of relapses and shorter intervals between attacks in the first few years of the disease [2, 29–31].

Cognitive disturbance is an important feature in pediatric MS. Cognitive impairment can occur even in the first few years of the disease and does not correlate with physical disability, number of relapses, and disease duration. The onset of multiple sclerosis in very young children increases the risk of cognitive impairment [3]. In adult MS patients, the most commonly affected cognitive functions include processing speed, visual-spatial function, memory, and executive functions. The most commonly affected cognitive areas in pediatric MS are attention span, processing speed, and visual-motor skills as adults. Receptive language, verbal fluency, and intelligence also are affected in pediatric MS, and they are affected differently than they are in adult MS. Linguistic involvement (verbal fluency, naming, and comprehension) is an important neuropsychological difference between pediatric and adult-onset MS [32, 33]. Pediatric MS patients are also at risk for a lower IQ [3]. Differences in cognitive dysfunctions between pediatric MS and adult MS may be due to the effect of inflammatory demyelination on the developing central nervous system and neuronal networks. All patients with pediatric MS should be checked for cognitive dysfunction because it occurs in the early stages of the disease and is unrelated to physical disability [29, 30, 33].

Psychiatric disorders such as depression or anxiety are common in pediatric MS, as they are in adults. Fatigue is also reported in patients with pediatric MS. Cognitive impairment, depression, and fatigue disrupt the child's academic performance and quality of life [3].
