Brain Pathology Case of the Month - November 2018
Acute Hemorrhagic Leukoencephalitis (AHL) - Weston-Hurst's disease.
Acute disseminated encephalomyelitis (ADEM) is a monophasic, immune-mediated inflammatory demyelinating disease which can progress to a fulminant, fatal and rare disorder known as acute hemorrhagic leukoencephalitis (AHL) or Weston-Hurst's disease ((1, 2). The clinical, radiographic and neuropathologic features seen in this case are typical of the latter. Though the exact etiologies are unknown, both ADEM and AHL are thought to be preceded by an immunologic trigger, in the form of a viral upper respiratory tract infection 1-4 weeks before clinical symptoms manifest (3). ADEM occurs predominantly in the pediatric age group, and is thought to be due to immature myelin, though it can present at any age (4). Neurologic symptoms develop subacutely and evolve to hospitalization within days (5, 6). Symptoms common to both adult and pediatric cases include ataxia, altered consciousness, signs of encephalopathy, decline in neurological function, and brainstem symptoms. However, adults present more frequently with motor and sensory deficits compared to pediatric patients, who present with fever and headaches (5-8). Characteristic neuroimaging findings of ADEM include hyperintense multifocal, diffuse, white matter lesions with indistinct margins on T2/FLAIR (1). Gray matter lesions most commonly include bilateral thalamus and basal ganglia involvement. Mass effect and edema are seen with larger lesions (9-11) Histological features include perivascular axon-sparing demyelination and infiltration of vessel walls by lymphocytes, plasma cells and monocytes (12). In AHL, characteristic lesions are perivascular hemorrhagic demyelinating lesions with edema, axonal injury, meningeal inflammation and neutrophilic infiltrates. Hemorrhagic lesions are most concentrated in the white matter and the pons (13). Clinical symptoms are similar to ADEM except neurological deterioration occurs within hours (14). Earlier literature usually describes the disorder as fatal in outcome, although a better prognosis has been reported. No specific treatment is available and clinical management is supportive in nature. Survival is rare in AHL, except in a small number pediatric cases where early treatment with craniotomy, IVIG and corticosteroids was implemented (15).
- Rahmlow MR, Kantarci O. Fulminant demyelinating diseases. The Neurohospitalist. 2013;3(2):81-91.
- Young NP, Weinshenker BG, Lucchinetti CF. Acute disseminated encephalomyelitis: current understanding and controversies. Seminars in neurology. 2008;28(1):84-94.
- de Seze J, Debouverie M, Zephir H, Lebrun C, Blanc F, Bourg V, et al. Acute fulminant demyelinating disease: a descriptive study of 60 patients. Archives of neurology. 2007;64(10):1426-32.
- Wender M. Acute disseminated encephalomyelitis (ADEM). Journal of neuroimmunology. 2011;231(1-2):92-9.
- Menge T, Hemmer B, Nessler S, Wiendl H, Neuhaus O, Hartung HP, et al. Acute disseminated encephalomyelitis: an update. Archives of neurology. 2005;62(11):1673-80.
- Schwarz S, Mohr A, Knauth M, Wildemann B, Storch-Hagenlocher B. Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients. Neurology. 2001;56(10):1313-8.
- Tenembaum S, Chamoles N, Fejerman N. Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurology. 2002;59(8):1224-31.
- Gupte G, Stonehouse M, Wassmer E, Coad NA, Whitehouse WP. Acute disseminated encephalomyelitis: a review of 18 cases in childhood. Journal of paediatrics and child health. 2003;39(5):336-42.
- Tillema JM, Pirko I. Neuroradiological evaluation of demyelinating disease. Therapeutic advances in neurological disorders. 2013;6(4):249-68.
- Ketelslegers IA, Neuteboom RF, Boon M, Catsman-Berrevoets CE, Hintzen RQ, Dutch Pediatric MSSG. A comparison of MRI criteria for diagnosing pediatric ADEM and MS. Neurology. 2010;74(18):1412-5.
- Callen DJ, Shroff MM, Branson HM, Li DK, Lotze T, Stephens D, et al. Role of MRI in the differentiation of ADEM from MS in children. Neurology. 2009;72(11):968-73.
- Singh S, Alexander M, Korah IP. Acute disseminated encephalomyelitis: MR imaging features. AJR American journal of roentgenology. 1999;173(4):1101-7.
- Payne ET, Rutka JT, Ho TK, Halliday WC, Banwell BL. Treatment leading to dramatic recovery in acute hemorrhagic leukoencephalitis. Journal of child neurology. 2007;22(1):109-13.
- Robinson CA, Adiele RC, Tham M, Lucchinetti CF, Popescu BF. Early and widespread injury of astrocytes in the absence of demyelination in acute haemorrhagic leukoencephalitis. Acta neuropathologica communications. 2014;2:52.
- Broderick L, Gandhi C, Mueller JL, Putnam CD, Shayan K, Giclas PC, et al. Mutations of complement factor I and potential mechanisms of neuroinflammation in acute hemorrhagic leukoencephalitis. Journal of clinical immunology. 2013;33(1):162-71.
Contributed by Zuhha Ashraf MD, Nathaniel Todnam MD, John Morgan MD, Amyn M Rojiani MD, PhD