Rare brain biopsy findings in a first ADEM-like event of pediatric MS: histopathologic, neuroradiologic and clinical features

Abstract

Pediatric MS tends to present more often with an acute onset and a polysymptomatic form of the disease, possibly with encephalopathy and large tumefactive lesions similar to those observed in some cases of acute disseminated encephalomyelitis (ADEM), which makes it more difficult to differentiate between an explosive and severe onset of MS vs. ADEM. An ADEM-like first demyelinating event can be the first attack of pediatric MS, but international consensus definitions require two or more non-ADEM demyelinating events for diagnosis of MS. In our patient KIDMUS MRI criteria for MS (Mikaeloff et al. J Pediatr 144:246–252, 2004a; Mikaeloff et al. Brain 127:1942–1947, 2004b) were negative at first attack, but Barkhof criteria for lesion dissemination in space in adults (Barkhof et al. 120:2059–2069, 1997), Callen modified MS-criteria and Callen MS-ADEM criteria for children (Callen et al. Neurology 72:961–967, 2009a; Callen et al. Neurology 72:968–973, 2009b) were positive suggesting pediatric MS. As the clinical course was devastating with non-responsiveness upon high-dose immune modulatory therapy and due to the absence of an alternative diagnosis other than demyelinating disease brain biopsy was performed. Brain biopsy studies or autopsy case reports of fulminant pediatric MS patients are extremely rare. Histopathology revealed an inflammatory demyelinating CNS process with confluent demyelination, indicating the likelihood of a relapsing disease course compatible with an acute to subacute demyelinating inflammatory disease. This pattern was corresponding to the early active multiple sclerosis subtype I of Lucchinetti et al. (Ann Neurol 47(6):707–717, 2000).

Chinese Guidelines for the Diagnosis and Management of Tumefactive Demyelinating Lesions of Central Nervous System

“…[ 18 ] Adolescent ADEM may have comorbid TDLs. [ 19 ] Poser and Brinar believed that TDL is a phenotypic variant of classic MS and so did Lolekha and Kulkantrakorn. [ 20 ] Recently, studies in China and other countries showed that most of the TDLs were monophasic, and some cases of TDLs may transform to relapsing-remitting MS (RRMS)[ 2 17 ] or take the form of recurrent TDLs.…”

Life-saving decompressive craniectomy for acute disseminated encephalomyelitis in a child: a case report

“…The pathophysiology is still unclear and probably involves a transient autoimmune response directed at myelin or other self-antigens, possibly by molecular mimicry or by nonspecific activation of autoreactive T cell clones [2,10]. Brain biopsies are performed in difficult cases [7,8]. Histologically, ADEM is characterized by perivenous demyelination and infiltration of the vessel wall and perivascular spaces by lymphocytes, plasma cells, and monocytes [4].…”

Increased multiple sclerosis disease activity in patients transitioned from fingolimod to dimethyl fumarate: a case series

“…The injury to the CNS may be mediated by the cytotoxic CD8+ T cells that remain unregulated. The injury may result in large tumefactive lesions in the brain, quite similar to the large lesions of acute disseminated encephalomyelitis (ADEM)-like event described in pediatric MS reported to be mediated by cytotoxic CD8+ T cells [ 19 ]. If the mechanism of CNS injury with the characteristic tumefactive lesions is primarily mediated by CD8+ T cells, DMF which is known to preferentially deplete the CD8+ T cell population [ 20 ] could be helpful in mitigating the fingolimod rebound phenomenon.…”