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Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell (HSC) disorder characterized by complement-mediated hemolysis, thrombosis, and bone marrow failure (1, 2). Affected cells harbor a somatic mutation [...], Patients with paroxysmal nocturnal hemoglobinuria (PNH) have a clonal population of blood cells deficient in glycosylphosphatidylinositol-anchored (GPI-anchored) proteins, resulting from a mutation in the X-linked gene PICA. Here we report on a set of patients in whom PNH results instead from biallelic mutation of PICT on chromosome 20. These PIGTPNH patients have clinically typical PNH, but they have in addition prominent autoinflammatory features, including recurrent attacks of aseptic meningitis. In all these patients we find a germ-line point mutation in one PICT allele, whereas the other PICT allele is removed by somatic deletion of a 20q region comprising maternally imprinted genes implicated in myeloproliferative syndromes. Unlike in PIGA-PNH cells, GPI is synthesized in PIGT-PNH cells and, since its attachment to proteins is blocked, free GPI is expressed on the cell surface. From studies of patients' leukocytes and of PICT-KO THP-1 cells we show that, through increased IL-1[beta] secretion, activation of the lectin pathway of complement and generation of C5b-9 complexes, free GPI is the agent of autoinflammation. Eculizumab treatment abrogates not only intravascular hemolysis, but also autoinflammation. Thus, PIGT-PNH differs from PIGA-PNH both in the mechanism of clonal expansion and in clinical manifestations.

Background The temporal and anatomical features of vasoconstriction in patients with reversible cerebral vasoconstriction syndrome within hours after symptom onset, in the hyperacute phase, are unclear. Case result Herein we report the cases of two patients with acute severe headache who were diagnosed with reversible cerebral vasoconstriction syndrome. Magnetic resonance imaging within hours after symptom onset revealed multiple areas of isolated cortical vasogenic edema and hyperintense vessel signs of the distal cerebral arteries. Follow-up imaging performed four days later in both cases showed diffuse segmental arterial vasoconstriction in the proximal regions of the cerebral arteries. Both patients received antivasoconstrictive therapy shortly after admission, and neither had neurological sequelae at discharge. The magnetic resonance imaging findings improved gradually within three months after symptom onset. Conclusion Isolated cortical vasogenic edema and hyperintense vessel signs, when observed within hours from sudden severe headache onset, may be useful early markers of reversible cerebral vasoconstriction syndrome. [ABSTRACT FROM AUTHOR]

After treatment of unilateral vertebral artery dissecting aneurysm (VADA), de novo VADA rarely occurs on the contralateral side. In this article, we report a case of subarachnoid hemorrhage (SAH) due to de novo VADA in the contralateral vertebral artery (VA) 3 years after parent artery occlusion of unilateral VADA, with a review of the literature. A 47-year-old woman was admitted to our hospital complaining of headache and impaired consciousness. Head computed tomography showed SAH, and three-dimensional computed tomography angiography showed a fusiform aneurysm in the left VA. We performed an emergency parent artery occlusion. Three years and 3 months after the initial treatment, the patient presented to our hospital with complaints of headache and neck pain. Magnetic resonance imaging revealed SAH, and magnetic resonance angiography revealed de novo VADA in the right VA. We performed a stent-assisted coil embolization. The patient had a good postoperative course and was discharged with a modified Rankin scale score of 0. Long-term follow-up is necessary in patients with VADA because contralateral de novo VADA can develop even several years after the initial treatment.