Paroxysmal Nocturnal Hemoglobinuria (Pnh): Brain Mri Ischemic Lesions In Neurologically Asymtomatic Patients

Wilma Barcellini,Francesca Binda,Marika Grottaroli,Carlo Alfredo Altamura,Elisa Scola,Silvia Lanfranconi,Massimiliano Buoli,Fabio Triulzi,Claudia Maria Cinnante,Carla Boschetti,Bruno Fattizzo,Gloria Valcamonica,Agostino Cortelezzi,Anna Zaninoni,Alberto Zanella,Nereo Bresolin

doi:10.1038/s41598-017-18936-0

Abstract

This study investigated for the first time brain ischemic involvement in 19 consecutive neurologically asymptomatic PNH patients by non-enhanced cerebral MRI, and by intracranial arterial and venous angio-MRI. Eleven cases (58%, 7 aged <65) showed pathological findings: 9 white matter (WM) abnormalities related to chronic ischemic small vessel disease, 2 a focal abnormality >5 mm, and 5 cases a score >4 by the age-related white matter changes (ARWMC) scale. Compared with age and sex-matched controls (1:2 ratio), patients showed an increased frequency of periventricular WM vascular degeneration (32% versus 5.2%, p = 0.04) and of severe lesions (ARWMC scale score >4) (26% versus 2.6%, p = 0.05), and a higher overall ARWMC scale score (3.5 ± 1.07 versus 2.0 ± 0.8, mean ± SD, p < 0.0001). Notably, vascular abnormalities suspected for prior partial venous thrombosis, were observed in PNH cases only. MRI lesions were not related to blood counts, hemolytic markers, clone size, disease duration, and therapy with eculizumab. Neurological examination was unremarkable in all patients but one (Parkinson disease). Psychiatric assessment revealed a case of generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder. In conclusion, brain MRI may be useful at diagnosis and during the course of the disease to explore subclinical neurological involvement.

Highlights

PNH type hemolytic hemolytic hemolytic hemolytic hemolytic hemolytic hemolytic hemolytic hemolytic hemolytic hemolytic hemolytic aplastic aplastic hemolytic hemolytic hemolytic hemolytic hemolytic
Pathological magnetic resonance imaging (MRI) findings, involving the periventricular and deep WM as well as the vascular district, were observed in more than a half of patients, this overall frequency being not significantly different from that observed in age- and gender-matched controls
Vascular abnormalities suspected for prior partial venous thrombosis, were observed in PNH cases only

Summary

Introduction

The largest series reported[17] described 15 PNH cases with cerebral venous thrombosis, mostly women, and younger than a control population without PNH; 3 cases had a concomitant splancnic thrombosis and 1 patient died. In a PNH case with mild left hemiparesis, a brain computed tomography scan showed multiple lacunar infarcts, and a magnetic resonance demonstrated several acute and chronic ischemic stroke areas[19]. Cerebral occlusive lesions involving various intracranial arteries have been reported in PNH as a result of Moya-Moya phenomenon[20,21]. The aim of this study was to investigate brain involvement in asymptomatic PNH patients, either or not in eculizumab treatment, by non-enhanced cerebral magnetic resonance imaging (MRI), and by intracranial arterial and venous angio-MRI, and to compare MRI findings with an age and sex-matched control group. Neuro-radiological patients’ findings were completed with a neuro-psychiatric evaluation, and correlated with clinical/hematologic features and therapy

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