Fulminant inflammatory demyelination presenting as stroke‐in‐evolution in an elderly subject

Abstract Background Fulminant inflammatory demyelination is a possible presentation of inflammatory demyelinating disorders, thus representing a potential stroke mimic especially in younger patients. Aims of the study To describe clinical and diagnostic pitfalls in a case of fulminant inflammatory demyelination presenting with stroke‐like symptoms in an elderly patient. Methods Case report and case‐based review of the literature. Results A 67‐year‐old woman, who accessed the emergency room as suspect stroke for hyperacute onset of rapidly worsening speech impairment and drowsiness, was later diagnosed with a huge brain inflammatory demyelination. Clinical, laboratory, and neuroimaging tests did not allow to put a more specific diagnosis. Due to the rapidly deteriorating course, she received immunosuppression with benefit. Conclusion This report is meant to highlight the diagnostic challenges connected with fulminant inflammatory demyelination, which sometime can resemble a stroke‐in evolution and appear clinically unfitting for inclusion in any specific pathological entities within the broad‐spectrum of inflammatory demyelinating disorders.

Here, we describe a case of FID in an elderly woman, where the hyperacute onset and the rapid worsening of symptoms resembled a stroke-in evolution.

| C A S E REP ORT
A 67-year-old woman, without remarkable medical and neurological history, accessed the ED for acute onset of speech impairment and drowsiness. Clinical assessment revealed moderate hypertension (165/85 mmHg) and mild leukocytosis (12.1 × 10 3 /microL; r.v. 4.8-10.8) without fever. Neurological examination, at 2 hr from onset, revealed normal alertness, nonfluent aphasia and moderate motor and sensory right-side impairment (NIHSS 9). In the suspect of a left middle cerebral artery stroke, a brain CT was performed, detecting a wide, pale hypodensity, with finger-like borders and flattened cer-

| D ISCUSS I ON
The goal of the present report is to emphasize the diagnostic challenge connected with FID, particularly when affecting elderly.
Whereas the hyperacute onset of focal neurological signs and the age of our patient initially suggested a cerebrovascular disorder, the subsequent clinical course and the neuroradiological features of the lesion oriented toward a possible IDD.
The prototypical IDD is represented by multiple sclerosis (MS), which generally affects young subjects showing F I G U R E 1 Brain CT performed at the ED, revealing in the left hemisphere an extensive, pale hypodensity with finger-like borders associated to flattened cerebral sulci* space-and time-disseminated WM lesions (Thompson et al., 2018). Besides the stroke-mimic deception we faced in the ED, the diagnostic challenge of the present case is represented by the difficulty in formulating a definite diagnosis based on clinic-radiological data in the absence of histo-pathological assessment. The clinical course during the 2-year follow-up period, coherently with the negative hematological tests performed at onset, helped to exclude cerebral lymphoma from the neuroradiological differential diagnosis (Chiavazza et al., 2018). Furthermore, no diffusion restriction was indeed evident at any time-point within the lesion described, making less likely the possibility of lymphoma and ruling out the possibility of a stroke outside of the ED setting. It is, however, important to remember that in FID there can be association of gadolinium enhancement and restricted diffusion, with the former sometime chronologically following the latter (Hyland et al., 2013) BCS was excluded by the lack of the classical "onion-like" MRI appearance, showing alternated iso-and hyperintense rings on T2-weighted imaging, likely as expression of layers with relatively preserved or lost myelin (Bevan & Cree, 2015). MVMS could as well be excluded given the absence of progressive deterioration overtime, usually leading to death within months from onset (Bevan and Cree, 2015).
TMS mostly occurs during the 2nd and 3rd decade (Lucchinetti et al., 2008), thus is atypical in the elderly. In our case, the lack of previous neurological history and pre-existing demyelinating lesions, as well as the 2-year follow-up, ruled out MS.* Acute disseminated encephalomyelitis affects mainly children and young individuals, with an incidence of 0.6 per 100,000 per F I G U R E 2 Axial FLAIR and postcontrast T1w images at different time points: additionally, for A and B, DWI trace and ADC sequences are shown. (a) 24 hr after symptoms onset: diffuse hyperintense alteration involving the left frontal lobe and deep white matter of the right frontal lobe, associated with a peripheral ring of contrast enhancement; there is no evidence of restricted diffusion on DWI trace and ADC sequences. (b) 11 days after symptoms onset (after conclusion of intravenous methylprednisolone treatment): disappearing of peripheral ring of contrast enhancement with progression of hyperintense alteration now partially involving the left parietal lobe and, more extensively, the right frontal lobe; there is no evidence of restricted diffusion on DWI trace and ADC sequences. (c) 25 days after symptoms onset (after first cyclophosphamide administration): initial reduction in size of T2 hyperintense alteration, without contrast enhancement. (d) 50 days after symptoms onset (after second cyclophosphamide administration): further reduction in size of T2 hyperintense alteration without contrast enhancement* year. This diagnosis is rare among young adults and almost exceptional beyond the age of 65, with only few cases reported in literature (Wang et al., 1996;Kaunzner et al., 2017). No criteria, indeed, have ever been established for diagnosis among adults.
ADEM usually follows infections or vaccinations (Pohl et al., 2016) and occurs within 6 days to 6 weeks from an antigenic challenge; overlapping of neurologic and infective symptoms, as here described, is unusual and may point to a parainfective, rather than postinfective process. It is well known, however, that up to 26% of ADEM lacks of clear prodromal manifestations (Tenembaum et al., 2002).
Typically, ADEM patients develop neurological deficits subacutely, conveying to peak within 2-5 days instead of the 24 hr here reported. Aggressive variants, such as Hurst's disease, present neurological deterioration within hours (Rahmlow & Kantarci, 2013) but are associated with hemorrhagic lesions, which were never detected in our patient.
Our report highlights the difficulty in defining a clear-cut diagnosis in FID presenting some clinical features of multiple pathological entities (TDL, TMS, ADEM, Hurst's disease, parainfective demyelination) but also some relevant atypia precluding a conclusive labeling. The outcome-arranged agreement to overlook pathological examination, deriving from a thoughtful riskbenefit evaluation, contributed to this diagnostic pitfall (Hardy et al., 2016).

First-line treatment with high-dose intravenous steroids may
show scarce efficacy, especially in IDD with atypical presentation (Jaskowiak, 2016). In these cases, progressive neurological and radiological deterioration can justify aggressive immunosuppression strategies (Berzero et al., 2016;Rahmlow and Kantarci, 2013). Plasma exchange is generally considered the second-line therapy for FID patients not responding to corticosteroids (Hardy and Chataway, 2013), especially children and in patients with ring-enhancing lesions and mass effect (Magaña et al., 2011), and however, given the rarity of the disease, no randomized controlled clinical studies are available and there are no evidences for effect on eventual disease reactivation. Other therapeutic options include immunosuppressors such as cyclophosphamide (Berzero et al., 2016;Rahmlow & Kantarci, 2013) that in our patient was associated with an impressive recovery. It is unclear, however, whether the recovery was associated with the treatment rather than the disease's nature itself. Clinical recovery is indeed frequent in ADEM, and follow-up imaging demonstrates, in the majority of cases, partial or complete resolution usually conveying to a monophasic course of disease (Rahmlow and Kantarci, 2013;Tenembaum et al., 2002).
Nonetheless, a recent case series described the stroke-mimic, fulminant course of pathologically proven ADEM affecting 5 subjects with age ranging from 57 to 85 (Tenembaum et al., 2002). The authors suggested that an exceptionally fulminant course in this population may be due to an age-related decrease in repair efficacy and oligodendrocyte response.

CO N FLI C T O F I NTE R E S T
None to declare.

AUTH O R CO NTR I B UTI O N
All authors participated in the study and manuscript editing and

E TH I C A L A PPROVA L
Written informed consent was obtained from the patient.

PE E R R E V I E W
The peer review history for this article is available at https://publo ns.com/publo n/10.1002/brb3.1967.

DATA AVA I L A B I L I T Y S TAT E M E N T
Complete clinical data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy restrictions. Other data sharing is not applicable to this article as no datasets were generated or analyzed during the current study (case report and case-based narrative review).