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Introduction: Acute hemorrhagic leukoencephalitis (AHLE), a rare form of acute disseminated encephalomyelitis (ADEM), has a generally poor prognosis. However, significant variation is observed, and even complete recovery has been reported. The recent increase in the frequency of AHLE case reports is possibly contributed by the advent of COVID-19 and may have added to the heterogeneity of cases. Methods: We report a fatal case of AHLE with a preceding unspecified respiratory infection, then perform a systematic review of AHLE, in an effort to delineate factors that may be associated with an ultimate outcome of severe disability (defined as modified Rankin scale score of 4 or 5) or death. Results: Descriptions of 31 cases of AHLE were found in 21 identified articles, with our case being the 32nd case. The most common antecedent event was an infection (20 patients, 62.5%), with nearly half of these being COVID-19 (9 patients). The majority of patients had a subacute progression (1 to 10 days) from onset to clinical nadir. We found that an altered mental status (AMS) and a Glasgow Coma Scale (GCS) score of less than 12 were associated with a final outcome of severe disability or death. An abnormal upgoing plantar response was associated with a final outcome of death. COVID-19 and its vaccines were not associated with either outcome. Conclusion: AMS, depressed GCS, and an upgoing plantar response at presentation may be associated with a poor outcome in AHLE. Our findings may serve as a springboard to much-needed research into the stratification of AHLE. [ABSTRACT FROM AUTHOR]

Background: The neurological complications of coronavirus disease 2019 (COVID-19) infection and the side effects of vaccination include immune-mediated diseases of the central nervous system (CNS) such as acute disseminated encephalomyelitis (ADEM). It is an acute-onset demyelinating disease that involves a rapid evolution and multifocal neurological deficits that develops following a viral or bacterial infection or, less frequently, following vaccination. Acute hemorrhagic leukoencephalitis (AHLE) is the hemorrhagic variant of ADEM that presents a more severe evolution which can be followed by coma and death. The objectives of this study consist in evaluating the diagnosis, clinical characteristics, imaging and laboratory features, evolution, and treatment of ADEM and AHLE following COVID-19 infection or vaccination. Methods: We performed a systematic review of the medical literature according to PRISMA guidelines that included ADEM cases published between 1 January 2020 and 30 November 2022 following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination and also included our own clinical experience regarding this pathology. Results: A total number of 74 patients were diagnosed with ADEM, 45 following COVID-19 infection and 29 after a SARS-CoV-2 vaccine. A total of 13 patients (17.33%) presented AHLE. The moderate form of COVID-19 presented a positive correlation with AHLE (r = 0.691, p < 0.001). The existence of coma and AHLE was correlated with poor outcomes. The following more aggressive immunomodulatory therapies applied in severe cases were correlated with poor outcomes (major sequelae and death): therapeutic plasma exchange (TPE) treatment (r = 382, p = 0.01) and combined therapy with corticosteroids and TPE (r = 0.337, p = 0.03). Conclusions: Vaccinations are essential to reduce the spread of the COVID-19 pandemic, and the monitoring of adverse events is an important part of the strategic fight against SARS-CoV-2. The general benefits and the overall good evolution outweigh the risks, and prompt diagnosis is associated with a better prognosis in these patients. [ABSTRACT FROM AUTHOR]

We present a pediatric case of acute hemorrhagic leukoencephalitis associated with SARS-CoV-2 Omicron BA 2.0 infection. A previously healthy girl presented with ataxia and diplopia three weeks after the COVID-19 confirmation from a nasopharyngeal swab. Acute and symmetrical motor weakness and drowsiness ensued within the following 3 days. She then became spastic tetraplegic. MRI revealed multifocal lesions in the cerebral white matter, basal ganglia, and brainstem, with hemorrhagic changes confirmed with T1-hyperintensity and hypointensity on susceptibility-weighted images. Peripheral areas of decreased diffusion, increased blood flow, and rim contrast enhancement were noted in the majority of lesions. She was treated with a combination of intravenous immunoglobulin and methylprednisolone pulse therapy. Neurological deterioration ensued with coma, ataxic respiratory pattern and decerebrate posture. Repeated MRI performed on day 31 revealed progression of abnormalities, hemorrhages and brain herniation. Despite the administration of plasma exchange, she died two months after admission. [ABSTRACT FROM AUTHOR]

Background: Weston Hurst syndrome (WHS), also known as acute hemorrhagic leukoencephalitis (AHLE), has not been previously associated with mixed connective tissue disease (MCTD), a rare rheumatologic disorder. Case presentation: We report a case of a 35‐year‐old female who presented with deep coma with features of previously undiagnosed MCTD and responded favorably to intravenous immunoglobulin (IVIG) therapy. On detailed historical enquiry, clinical examination, and investigation, AHLE was diagnosed. Furthermore, our patient showed significant improvement with IVIG administration, even though initial steroid therapy was unsuccessful. Conclusion: AHLE, an associated novel neurological manifestation of MCTD, can be responsive to IVIG, which makes this case reportable from the diagnostic as well as the therapeutic point of view. [ABSTRACT FROM AUTHOR]

We present three cases fulfilling diagnostic criteria of hemorrhagic variants of acute disseminated encephalomyelitis (acute hemorrhagic encephalomyelitis, AHEM) occurring within 9 days after the first shot of ChAdOx1 nCoV-19. AHEM was diagnosed using magnetic resonance imaging, cerebrospinal fluid analysis and brain biopsy in one case. The close temporal association with the vaccination, the immune-related nature of the disease as well as the lack of other canonical precipitating factors suggested that AHEM was a vaccine-related adverse effect. We believe that AHEM might reflect a novel COVID-19 vaccine-related adverse event for which physicians should be vigilant and sensitized. [ABSTRACT FROM AUTHOR]

Objectives: We describe two new cases of acute hemorrhagic leucoencephalitis (AHLE), who survived with minimal sequelae due to early measures against increased intracranial pressure, particularly craniotomy. The recently published literature review on treatment and outcome of AHLE was further examined for the effect of craniotomy. Methods: We present two cases from our institution. The outcome of 44 cases from the literature was defined either as good (no deficit, minimal deficit/no daily help) or poor outcome (severe deficit/disabled, death). Patients with purely infratentorial lesions (n = 9) were excluded. Fisher's exact test was applied. Results: Two cases are presented: A 43-year-old woman with rapidly progressive aphasia and right hemiparesis due to a huge left frontal white matter lesion with rim contrast enhancement. Pathology was consistent with AHLE. The second case was a 56-year-old woman with rapidly progressive aphasia and right hemiparesis. Cranial MRI showed a huge left temporo-occipital white matter lesion with typical morphology for AHLE. Both patients received craniotomy within the first 24 h and consequent immunosuppressive-immunomodulatory treatment and survived with minimal deficits. Out of 35 supratentorial reported AHLE cases, seven patients received decompressive craniotomy. Comparing all supratentorial cases, patients who received craniotomy were more likely to have a good outcome (71 vs. 29%). Conclusion: Due to early control of the intracranial pressure, particularly due to early craniotomy; diagnosis per biopsy; and immediate start of immunosuppressive-immunomodulatory therapies (cortisone pulse, plasma exchanges), both patients survived with minimal sequelae. Craniotomy plays an important role and should be considered early on in patients with probable AHLE. [ABSTRACT FROM AUTHOR]

Acute Hemorrhagic Leukoencephalitis (AHLE) is a rare but devastating and fatal form of Acute Disseminated Encephalomyelitis. Very rarely, this can be a complication of vaccination. There is currently no consensus on the optimal treatment strategy of AHLE. We present a rare case of AHLE after seasonal influenza vaccine promptly diagnosed with magnetic resonance imaging (MRI) brain, which showed significant areas of hemorrhage with vasogenic edema including involvement of the pons. The patient was aggressively treated with plasma exchange and corticosteroids and had a favorable outcome. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Intravenous immunoglobulin therapy should be considered in pediatric acute hemorrhagic leukoencephalitis that is refractory to steroid and plasmapheresis. Intravenous immunoglobulin therapy should be considered in pediatric acute hemorrhagic leukoencephalitis that is refractory to steroid and plasmapheresis. [ABSTRACT FROM AUTHOR]

Acute hemorrhagic leukoencephalitis (AHLE) is an acute, rapidly progressing, fulminant demyelinating disease. It is a rare disease of the central nervous system with high mortality; survivors commonly present with significant neurological deficit. We report the case of a 16-month-old girl who survived AHLE and presented with the associated neurologic deficit. The patient came into the emergency department with febrile seizure. She showed bilateral pinpoint-sized pupils and hyperactive deep tendon reflexes. Her mental status was initially drowsy and rapidly progressed to stupor. Extensive demyelination and microbleeds were found in the cerebral white matter, thalamus and left cerebellum on Magnetic resonance imaging (MRI) scans. Her mental status was improved by intravenous administration of immunoglobulin and methylprednisolone. Five months after being discharged, increased white matter connectivity was found on color-coded follow-up MR diffusion tensor imaging (DTI) as compared to previous MRI. We therefore suggest adding the DTI technique when a follow-up MRI is performed in patients with AHLE. It could be useful to visualize the status of axonal injury and to encourage patients and their parents to continue the rehabilitation program. [ABSTRACT FROM AUTHOR]

Acute hemorrhagic leukoencephalitis is a fulminant demyelinating disease and commonly considered as a rare and severe variant of acute disseminated encephalomyelitis. Here, we report the clinical, magnetic resonance imaging, and brain biopsy findings of a 35-year-old female with relapsing-remitting multiple sclerosis, who developed acute hemorrhagic leukoencephalitis. Magnetic resonance imaging revealed symmetrical hemorrhagic lesions in the basal ganglia including the thalami. Disease progression was consistent with acute hemorrhagic leukoencephalitis with rapid deterioration of consciousness and seizures. Besides hemorrhage, infiltration of neutrophils was detected in brain biopsy.Acute hemorrhagic leukoencephalitis, also known as Weston-Hurst syndrome, is an excessive immunological response of unknown etiology. So far, an association with multiple sclerosis has not been reported. The present case raises the question, whether acute hemorrhagic leukoencephalitis is a specific hyperacute form of acute disseminated encephalomyelitis, a severe and unspecific form of an immune response in the central nervous system, or belongs to the spectrum of tumefactive multiple sclerosis. [ABSTRACT FROM AUTHOR]

Purpose: Acute Hemorrhagic Leukoencephalitis (AHLE) is a rare demyelinating disorder of acute onset, rapid deterioration and significant morbidity and mortality. Most often described as a post-infectious complication of an upper respiratory illness, its precise pathophysiology remains unclear. We describe two pediatric patients with AHLE with partial complement factor I (FI) deficiency whose successful treatment included the interleukin-1 (IL-1) receptor antagonist, anakinra, implicating a role for FI and IL-1 in this disorder. Methods: Extensive clinical workup of two patients presenting with AHLE revealed complement abnormalities, specifically related to the alternative pathway and its regulator, FI. Aggressive management with steroids, immunoglobulin, and anakinra ultimately led to improvement of clinical status and near return to neurologic baseline in both patients. Genetic sequencing of the FI coding regions of the patients and their families was performed. In vitro protein expression studies and immunohistochemistry of fixed brain tissue was used to investigate pathogenic mechanisms. Results: Two novel mutations in FI were identified in our patients, which result in failure to secrete FI. Immunohistochemical evaluation of brain tissue demonstrated positive staining for C3, membrane attack complex (MAC) and IL-1. Conclusions: We propose AHLE is an unreported, rare phenotype for partial FI deficiency. The upregulation of C3, MAC and IL-1 with subsequent demyelination support a pathologic role for complement activation in AHLE, and suggest anakinra as an important adjunctive therapy in this disease. [ABSTRACT FROM AUTHOR]

The clinical course, neuroimaging, neuropathological features, and management of a 7-year-old girl with acute hemorrhagic leukoencephalitis are reported. Treatment with subtotal bifrontal craniectomies for symptoms of imminent uncal herniation followed by high-dose corticosteroid therapy was associated with dramatic clinical recovery. This report highlights the utility of aggressive intervention in acute hemorrhagic leukoencephalitis, an otherwise fatal disorder. [ABSTRACT FROM AUTHOR]

A 16-year-old girl presented signs of a common cold in combination with a hemolytic crisis. Within 3 days, she developed reduced consciousness and hemiparesis subsequently followed by coma. CT and MRI scans revealed evidence for raised intracranial pressure and an extensive inflammatory process extending from the brain stem up to the thalamus. The patient died within 3 weeks after onset of first symptoms of intracranial pressure despite maximum intensive care. Neuropathological examination revealed disseminated necrotic lesions and perivascular hemorrhages characteristic for acute hemorrhagic leukoencephalitis (Hurst’s disease), mainly of the brain stem, diencephalon and cerebellum. Serological results, in situ hybridization and PCR analysis demonstrated an acute Epstein-Barr virus (EBV) infection of the central nervous system. To our knowledge, this is the first reported case of Hurst’s disease linked to EBV. [ABSTRACT FROM AUTHOR]

Acute hemorrhagic leukoencephalitis (AHL) is a rare and usually fatal disorder characterized clinically by an acute onset of neurologic abnormalities. It may occur in association with a viral illness or vaccination. Radiology and brain biopsy are essential for the diagnosis. The etiology of AHL is unclear. We postulated that viral/bacterial infection might be responsible, directly or through an immune-mediated mechanism, for this acute inflammatory myelinopathy. Fifteen cases of AHL were studied. Infectious agents, including varicella zoster virus (VZV), herpes simplex virus (HSV), human herpes virus-6 (HHV-6), cytomegalovirus, Epstein-Barr virus, and Mycoplasma , were investigated in brain specimens using the polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, and immunohistochemistry. Using PCR, HSV DNA was found in four cases, VZV DNA in two, and HHV-6 DNA in one. Among the control cases, two were HSV DNA positive. Further investigation to detect HSV RNA and antigens in HSV DNA-positive cases revealed that two cases with AHL were both HSV RNA and antigen positive. AHL is a hyperacute disease, which is considered the most acute form of acute disseminated encephalomyelitis (ADEM). Our findings suggests that a viral infection may be implicated in its pathogenesis, most likely through an indirect mechanism; however, as only a few cases of this rare disease were examined, statistical significance was not achieved. As a number of patients with disorders of the ADEM group may progress to develop multiple sclerosis (MS), we argue that an organism that has produced the former may remain in the brain tissue and be subsequently involved in the production of a self-sustained disorder such as MS. [ABSTRACT FROM AUTHOR]

We describe the case of a 3-year-old boy diagnosed with the fulminant form of acute disseminated encephalomyelitis ( ADEM). He developed general fatigue, fever, drowsiness and difficulty in walking. He had extensive multiple high-intensity lesions in the white matter of the cerebrum and cerebellum, which are typical findings of ADEM. He became comatose and developed decerebrate rigidity with severe brain edema despite high-dose methylprednisolone therapy, and then was subjected to mild hypothermia therapy, and given i.v. immunoglobulin. The patient recovered remarkably with the sequela of only mild action tremor. The patient was considered to have acute hemorrhagic leukoencephalitis ( AHLE), an extremely severe form of ADEM, in terms of the rapidly deteriorating clinical course and neuroimaging features. It was speculated that AHLE and ADEM might be a continuous disease spectrum. It is considered that the severe brain edema associated with ADEM or AHLE is a suitable indication for mild hypothermia therapy. [ABSTRACT FROM AUTHOR]

The author presents an analysis of acute hemorrhagic leukoencephalitis (AHLE) in a patient with pluriannual relapse-remitting multiple sclerosis (MS) after a month of high-dose interferon beta-1a treatment.

A letter to the editor on the importance of EEG in acute hemorrhagic leukoencephalitis is presented.