LAUSR

Paraneoplastic neurological syndromes (PNS) comprise a diverse group of immune-mediated neurological manifestations complicating an underlying malignancy [1]. Classical PNS are often associated with antibodies targeting intracellular antigens called onconeural antibodies which are considered nonpathogenic and constitute, therefore, essentially a diagnostic tool [2]. Treatment of onconeural antibody-associated PNS relies on tumor ablation and early aggressive immune suppression but, even so, the prognosis remains grim [3]. Acute hemorrhagic leukoencephalitis (AHLE) is a rare but devastating brain inflammatory disease first described by Weston Hurst in 1941 [4]. AHLE is often considered as a severe variant of acute disseminated encephalomyelitis but its precise pathophysiology is still unclear [5]. In this report, we present the clinical course of a patient who developed AHLE associated with onconeural antibodies. A previously healthy 21-year-old Caucasian man was admitted for major behavioral changes and severe left hemiparesis rapidly progressive over three days. Brain magnetic resonance imaging (MRI) revealed hemorrhagic supratentorial brain lesions with extensive edema and perilesional enhancement after gadolinium injection (Fig. 1a–d). Cerebrospinal fluid (CSF) analysis showed moderate increase in white blood cell count (21 cells per microliter) with predominant lymphocytic pattern and high protein level (1.5 g per liter). Polymerase chain reaction (PCR) multiplex assay for herpes simplex viruses 1 and 2, cytomegalovirus, varicella-zoster virus, human herpes virus 6, Epstein–Barr virus, enterovirus and human parechovirus were negative on two CSF samples collected 5 days apart, as well as direct examination and bacterial, mycobacterial and fungal cultures. The patient was seronegative for human immunodeficiency virus. Serum analyses revealed elevated titer of dense fine speckled antinuclear antibodies (dilution: 1/1280) further characterized as anti-dense fine speckled 70 kilodaltons (DFS70) antibodies, which were considered irrelevant. Anti-neuronal antibodies were screened in the serum and antibodies directed against Sry-like high-mobility group box (SOX) 1 and recoverin were found by immunodot assay (EUROIMMUN, Lübeck, Germany). Anti-recoverin antibodies were also found in the CSF. A whole-body [18F]-fluorodeoxyglucose positron emission tomography (18FDG-PET) was performed and did not find any lesion suspected to be malignant. Eye examination was completely normal. Despite treatment with high-dose intravenous corticosteroids (methylprednisolone 1000 mg per day for 5 days), the patient’s clinical condition rapidly worsened, leading to left hemiplegia and severely altered mental status. Brain MRI was repeated and showed lesion progression (Fig. 1e–f). A brain biopsy was performed, showing multifocal perivascular CD8 + T-cell infiltration and scattered demyelination (Fig. 2). Together, rapidly progressive clinical deterioration, inflammatory demyelinating lesions on brain pathology and presence of extensive hemorrhagic lesions on brain MRI were consistent with the diagnosis of AHLE. Intravenous immunoglobulins (0.4 g per kilogram of bodyweight per day for 5 days) and pulses of cyclophosphamide (750 mg per square meter of body surface area every month) were initiated and temporarily ceased disease progression. Nevertheless, the patient died 2 months later from a massive brain hemorrhage. AHLE’s precise pathophysiology remains unknown. A post-infectious mechanism is usually postulated based on frequent observation of flu-like symptoms or documented * Nicolas Lambert [email protected]