**8. Diagnostic evaluation**

#### **8.1. Magnetic resonance imaging features**

MRI is the most important paraclinical tool for the diagnosis of MS, and it also provides information for differential diagnosis.

Demyelinating plaques are demonstrated as an increased signal on T2 and FLAIR sequences and are typically located in deep white matter, corpus callosum, periventricular zone, juxtacortical, and posterior fossa. Hypointense lesions occur on T1 sequences. These hypoin‐ tense lesions are named "black holes." Black holes are a result of tissue loss due to previous inflammatory events. Acute MS plaques may appear to be T1 hypointense as a result of transient edema, but these are not true T1-black holes. T1 hypointensity may remain for months after an acute event with such lesions evolving to isointensity (loss of edema or repair) or persisting as chronic, permanent hypointensity [34]. Active demyelinating plaques may show gadolinium enhancement due to a blood-brain barrier breakdown and enhancement is often incomplete around the periphery (open ring sign) (**Figures 1** and **2**).

**Figure 1.** Large, hyperintense lesions on T2-weighted sequences.

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

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

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].

MRI is the most important paraclinical tool for the diagnosis of MS, and it also provides

Demyelinating plaques are demonstrated as an increased signal on T2 and FLAIR sequences and are typically located in deep white matter, corpus callosum, periventricular zone, juxtacortical, and posterior fossa. Hypointense lesions occur on T1 sequences. These hypoin‐ tense lesions are named "black holes." Black holes are a result of tissue loss due to previous inflammatory events. Acute MS plaques may appear to be T1 hypointense as a result of transient edema, but these are not true T1-black holes. T1 hypointensity may remain for months after an acute event with such lesions evolving to isointensity (loss of edema or repair) or persisting as chronic, permanent hypointensity [34]. Active demyelinating plaques may show gadolinium enhancement due to a blood-brain barrier breakdown and enhancement is often

incomplete around the periphery (open ring sign) (**Figures 1** and **2**).

disease and is unrelated to physical disability [29, 30, 33].

**8. Diagnostic evaluation**

**8.1. Magnetic resonance imaging features**

information for differential diagnosis.

[2, 29–31].

174 Trending Topics in Multiple Sclerosis

**Figure 2.** Gadolonium enhanced demyelinating plaques and black holes on T1-weighted sequences.

MRI findings in McDonald's diagnostic criteria are important and provide a diagnosis of MS at the first demyelinating event. According to McDonald's diagnostic criteria, dissemination in space (DIS) can be demonstrated by one or more T2 lesions in at least two of four areas of the CNS (periventricular, juxtacortical, infratentorial, spinal cord) and dissemination in time (DIT) can be demonstrated by a new T2 and/or gadolinium-enhancing lesion(s) on a followup MRI, with reference to a baseline scan, irrespective of the timing of the baseline MRI or the simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions at any time [10]. These criteria have been found to be highly sensitive (100%) and highly specific (86%) for children older than 12 years with non-ADEM presentation, but they may not be appropriate for young children [35].

There are some differences in MRI findings between children and adults, particularly in prepuberal cases: T2-hyperintense lesion volume and lesion load in the infratentorial area are higher in children than they are in adults; first presentation may be as ADEM; there is an increased incidence of larger, tumefactive lesions in young children; spinal cord lesions may be longer than three vertebral segments in children with MS as in neuromyelitis optica [29, 36].

#### **8.2. Cerebrospinal fluid (CSF) features**

Analysis of CSF provides information about both the inflammatory process and differential diagnosis such as infection and malignancy. Cell count, presence of oligoclonal bands, and IgG index are examined in CSF analysis. A mild lymphocytic pleocystosis may be seen in children, but it has been shown that children younger than 11 years have more neutrophils in the CSF than older children. Oligoclonal band positivity has been found in 92% of patients with pediatric MS [37, 38]. An increased IgG index is more common in adolescents than in young children.

#### **8.3. Evoked potentials**

Evoked potentials help to demonstrate subclinical demyelination and to evaluate prior demyelination [39]. Visual evoked potentials are more informative than brainstem auditory and somatosensory evoked potentials.
