NEURODEGENERATIVE AND DEMYELINATING DISEASES AND OTHER CNS DISORDERS

Amy Houtrow

This chapter covers numerous conditions that pediatric rehabilitation medicine physicians may encounter during their training and career. Because data contained in other chapters of this book are particularly relevant to the conditions presented here, the reader will be guided back to other chapters from time to time. This chapter will address pediatric demyelinating diseases of the central nervous system (CNS) and acquired brain injury from encephalitis (including anti-N-methyl-D-aspartate receptor [NMDAR] encephalitis), pediatric brain tumors, and seizure focus resection.

PEDIATRIC DEMYELINATING DISEASES

In this section of this chapter, the following pediatric demyelinating diseases of the CNS will be described: multiple sclerosis (MS), transverse myelitis, neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM). Together, these conditions have incidence in children of 1.66 per 100,000 person-years (1). They are more common among Whites and Blacks and less common among Hispanics and Asians (2). Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barre syndrome), a peripheral process, is described in Chapter 18. Generally, demyelinating diseases are described as mono-phasic or polyphasic and monofocal or polyfocal. Mono-phasic disease is also often referred to as a clinically isolated syndrome (3). Some children with monophasic disease go on to develop chronic demyelinating conditions such as MS or NMO. And it is important to note that there is considerable clinical overlap between these conditions (4).

PEDIATRIC MULTIPLE SCLEROSIS

Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease characterized by demyelination and axonal degeneration. Approximately 5% of the total population of individuals with MS are children (5). In 2007, the International Pediatric Multiple Sclerosis Study Group proposed provisional definitions for CNS demyelinating disorders for children that were updated in 2012 and published in 2013 (6). The diagnosis requires the presence of CNS inflammatory disease that is disseminated in time and space. Pediatric MS can be diagnosed when any one of the following exists:

• Two or more nonencephalopathic clinically identified CNS events with presumed inflammatory cause, which are separated by more than 30 days and involve more than one area of the CNS

• One nonencephalopathic episode with associated MRI findings consistent with the revised 2010 McDonald criteria (7) (see Table 19.1), and follow-up MRI demonstrates one or more lesions consistent with the disseminated in time criteria

• One encephalopathic (ADEM) attack followed by a nonencephalopathic attack three or more months after the onset of symptoms with MRI lesions that meet the disseminated in space criteria

• For children 12 years old or older, a single nonencephalopathic event with MRI findings consistent with the criteria for dissemination in time and space

EPIDEMIOLOGY OF PEDIATRIC MS

While 1.7% to 5.6% of the total MS population is under the age of 18, diagnosis under the age of 10 is very rare. The incidence of pediatric MS worldwide is not known, but in California, the reported incidence is 0.51/100,000 person-years (1). There is greater racial/ethnic diversity among children with MS compared to adults, among whom most are non-Hispanic Whites (5). The remote

TABLE 19.1 2010 MCDONALD MRI CRITERIA FOR THE DIAGNOSIS OF MULTIPLE SCLEROSIS

Source: Adapted from Ref. (7). Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292-302.

history of Epstein-Barr virus is associated with pediatric MS and many studies have supported the gene-viral environment hypothesis (7). The exact mechanisms that lead to MS are not understood and ongoing research is being conducted to identify triggers and the pathophysiology.