Cliniconeuropathologic correlations show astroglial albumin storage as a common factor in epileptogenic vascular lesions Academic Article uri icon

abstract

  • Focal chronic seizures are frequent in patients with vascular malformations of the brain (Kraemer & Awad, 1994), and often require epilepsy surgery as a consequence of pharmacoresistance. Cavernous angiomas (CAs, also called cavernous hemangiomas, cavernous malformations, or cavernomas) and arteriovenous malformations (AVMs) represent the most frequent vascular lesions, and approximately 40–80% of patients with intracerebral CAs have seizures (Del Curling et al., 1991; Moran et al., 1999; Moriarity et al., 1999; Awad & Jabbour, 2006; Baumann et al., 2007). From a histopathologic standpoint, CAs are characterized by dilated, endothelium-lined blood vessels without arterial features. Generally, the sinusoidal blood cavities lie back-to-back and there is no substantial brain tissue interposed between the vessels. However, a rim of gliotic parenchyma with varying amounts of hemosiderin deposits containing large amounts of iron is frequently present in the surrounding tissue due to blood–brain barrier (BBB) dysfunction. Magnetic resonance images typically show a “popcorn”-like pattern with mixed high- and low-signal intensities in the core and a dark rim of hemosiderin (Fig. 1, Aa–Bc). Ultrastructural studies revealed dysfunction of BBB components with poorly formed tight junctions and abnormalities in the basal lamina (Wong et al., 2000; Clatterbuck et al., 2001). Figure 1 Representative histopathologic and neuroradiologic findings in patients with cavernous angiomas and arteriovenous malformations. Cavernous angiomas (CAs) are composed of thin, endothelium-lined vascular channels without muscular layers (Aa–c, ... AVMs are composed of structurally altered veins, arteries, and transitory “shunt”-vessels surrounded by intervening brain tissue. Microscopically, the vascular walls show various pathologies such as collagenous replacement of muscles and interruption of the lamina elastic interna. Tightly packed flow void structures can be seen on MR imaging (MRI) (Fig. 1, Ca–Dc). Although seizures are the most frequent initial symptoms in patients with supratentorially and cortically located CAs, little is known about the basic mechanisms of epileptogenicity. Dysfunction of BBB and intracerebral deposits of iron-containing blood products may be responsible for the strong epileptogenic potential of CAs (Willmore et al., 1978; Singh & Pathak, 1990; Kraemer & Awad, 1994). This is in line with reports that neurosurgical removal of the hemosiderin deposits next to the vascular lesions achieves better seizure results than the restricted vascular lesionectomy (Baumann et al., 2006). Nevertheless, restricted lesionectomy has been shown to reduce seizures in some cases (Ferroli et al., 2006). Results regarding the association between a long history of epilepsy and clinical outcome vary (Moran et al., 1999; Baumann et al., 2007; Stavrou et al., 2008). Hammen and collaborators suggested a more extensive resection in patients with long disease duration (Hammen et al., 2007). Because an intrinsic epileptogenicity of CAs is unlikely, cellular and/or structural alterations in adjacent brain tissue probably play an important role in the epileptogenic potential of vascular lesions. Recent data emphasized a contribution of BBB opening to the progression of mesial temporal lobe epilepsy and neocortical epilepsy (Ivens et al., 2007; van Vliet et al., 2007). Particularly, albumin uptake into astrocytes has been discussed as a key pathogenic factor (Ivens et al., 2007; Ralay Ranaivo et al., 2010). Here we retrospectively analyzed a series of 80 patients with vascular malformations who underwent surgery for drug-refractory epilepsy between 1988 and 2009. We addressed correlations between iron deposits, albumin accumulation, and several clinical parameters.

publication date

  • January 1, 2012