Magnetic resonance imaging spectrum of acute hemorrhagic leukoencephalitis: Four case reports

Table 1 Blood investigation, cerebrospinal fluid analysis and magnetic resonance imaging findings of patients

Investigation	Patient 1	Patient 2	Patient 3	Patient 4
Complete blood count	Hb-9.0 gm, Leukocytosis with neutrophilia	Hb-12 gm, Leukocytosis	Hb-13.2 gm, Leukocytosis with neutrophilia	Hb-12 gm, Leukocytosis with neutrophilia
C-reactive protein	Elevated (14.43 mg/L)	Elevated (19.67 mg/L)	Elevated (15.24 mg/L)	Elevated (13.73 mg/L)
Erythrocyte sedimentation rate	Elevated (47 mm/hour)	Elevated (56 mm/hour)	Elevated (52 mm/hour)	Elevated (45 mm/hour)
Liver function test	Raised AST, ALT. Normal ALP and bilirubin	Raised AST, ALT. Normal ALP and bilirubin	Raised AST, ALT, ALP and bilirubin (1.1 mg/dL)	Normal AST, ALT and bilirubin level
Renal function test	Normal	Normal	Normal	Normal
Viral markers	Negative	Negative	Negative	Negative
Cerebrospinal fluid analysis	Elevated protein levels, neutrophilic pleocytosis, elevated glucose, no organism detected, normal ADA levels (8.2 U/L)	Decreased glucose level, increased. Proteins and neutrophilic pleocytosis. Normal ADA levels (9.7 U/L). No organism detected on Gram stain	Elevated protein, normal glucose. Neutrophilic pleocytosis. Normal ADA level (7.6 U/L)	Elevated protein, normal glucose. Neutrophilic pleocytosis. Normal ADA level (5.6 U/L)
Autoimmune markers	Negative	NA	Negative	Negative
Blood culture	Negative	Negative	NA	Negative
MRI brain	Multiple flocculent predominant white matter hyperintensties on T2/FLAIR weighted images with internal micro and macrohemorrhages. Corpus callosum, brainstem, capsular region, hypothalamus also involved	Multiple hyperintense areas were seen on T2/FLAIR images involving subcortical/deep white matter of the bilateral cerebral hemisphere with internal hemorrhagic changes with involvement of hypothalamus, brainstem, cerebellum and scanned spinal cord	Multiple white matter hyperintensties on T2/FLAIR weighted images with involvement of corpus callosum, capsular region and brainstem. Internal hemorrhagic foci were detected in few lesions	Multifocal white matter hyperintensities both in subcortical/deep white matter on T2/FLAIR weighted images with internal hemorrhagic areas

Hb: Hemoglobin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; ADA: Adenosine deaminase; FLAIR: Fluid attenuated inversion recovery.

Table 2 Summary of previous studies on acute hemorrhagic leukoencephalitis

Ref.	Study type	Patient profile	Clinical features	Neuroimaging/pathology findings	Treatment	Final outcome
Hurst[1], 1941	Case report (1st ever reported case)	Young male	Post infectious fever, seizures, rapid coma	Not available, hemorrhagic demyelination was seen on autopsy	Not described	Death
Meilof et al[9], 2001	Case report	Adult male	Fever, headache, altered consciousness, and motor deficits	MRI findings-extensive white matter lesions with haemorrhages	High-dose IV methylprednisolone	Full recovery with early steroids
Tenembaum et al[5], 2002	Prospective cohort study	84 pediatric patients (age range: 5 months to 14 years) diagnosed with ADEM	ADEM cases; some with hemorrhagic features suggestive of AHLE	MRI findings: Widespread T2 hyperintense lesions in white matter; some with basal ganglia/thalami involvement	High-dose intravenous methylprednisolone followed by oral tapering. IVIG or plasmapheresis in some refractory cases	Good recovery in most patients. Poorer outcomes were seen in cases with brainstem or hemorrhagic involvement
An et al[7], 2002	Retrospective case series and molecular pathology study	6 Post-mortem confirmed AHLE adult patients	Fever, headache after viral prodrome with rapid and fulminant neurological decline leading to death in all patients	Diffuse white matter changes with haemorrhages detected on imaging. Detected HSV, CMV, EBV and other viruses in AHLE brain sample which suggested infection triggered immune pathology hypothesis	IV corticosteroids, Supportive ICU care	All patient died despite aggressive interventions
Kuperan et al[6], 2003	Comparative case study	1 patient with ADEM and 1 with AHLE	Clinical presentation was similar with rapid onset of symptoms in AHLE while subacute onset in ADEM	MRI findings- Extensive white matter lesions with central necrosis, peripheral edema, and hemorrhagic foci in AHLE patient while ADEM patient showed multifocal, non-hemorrhagic, symmetric lesions without necrosis	High dose intravenous corticosteroids were given in both patients	AHLE patient showed rapid neurological deterioration ultimately leading to coma and death. Favorable outcome seen in ADEM patient
Ryan et al[10], 2007	Case report with review of literature	Young female	Headache, confusion and rapid progression to coma	Diffuse bilateral white matter hyperintensities with hemorrhagic foci on MRI	High-dose IV methylprednisolone with supportive care followed by therapeutic plasma exchange 5 times	Survived with good functional recovery
Pinto et al[2], 2011	Case report	Adult male	Fever, headache, progressive altered consciousness	On MRI: Diffuse white matter hyperintensities on T2/FLAIR weightedimages with hemorrhage. Brainstem and spinal cord also involved. Diagnosis confirmed on pathology with findings of perivascular demyelination with fibrinoid and hemorrhagic necrosis of small vessels associated with neutrophilic infiltration	High-dose IV methylprednisolone	Death
Grzonka et al[3], 2020	Case report and systematic review	Adult male	Rapid progression of neurological decline	T2-weighted FLAIR images showed increasing bilateral confluent widespread hyperintensities of the supratentorial white matter predominantly on the left side. SWI images demonstrated microbleeds in corpus callosum and pedunculus cerebelli	Intensive immunosuppressive therapy including intravenously administered immunoglobulins, high dose IV methylprednisolone for 3 days, cyclophosphamide with supportive care	Death

ADEM: Acute disseminated encephalomyelitis; AHLE: Acute-hemorrhagic leukoencephalitis; MRI: Magnetic resonance imaging; IVIG: Intravenous Immunoglobulin; HSV: Herpes simplex virus; CMV: Cytomegalovirus; EBV: Epstein-Barr virus; FLAIR: Fluid attenuated inversion recovery; SWI: Susceptibility weighted imaging; IV: Intravenous; ICU: Intensive care unit.