Epidemiology and natural history of cavernous malformations

Cavernous malformations (CM) are multilobulated lesions composed of sinusoids derived from endothelium embedded in collagen matrix without histological elements found in mature vasculature [1]. CMs may be found at any location in the central nervous system and therefore can present with diverse clinical presentations like seizures (23–50%), headaches (6–52%), and focal deficits (20–45%) arising from mass effect or lesion hemorrhage; however, up to 40% of patients may be asymptomatic [2]. Most CMs are found supratentorially. They are usually characterized clinically by seizures and less commonly by inconspicuous growth or intermittent bleeding. Seizures caused by perilesional deposits of epileptogenic hemosiderin may become intractable [3]. Hemorrhages associated with CMs are of low pressure and frequently clinically asymptomatic [4]. When a lesion is present in eloquent locations like the brainstem, however, even a small bleed can cause clinically significant neurological deficits [5]. The natural history of CMs is affected by several factors like gender, lesion location, and genotype. This chapter discusses the natural history of CMs and its clinical relevance. Etiology. Cavernous malformations may be of sporadic or familial type. Familial CMs are caused by mutations of CCM1 or CCM2 or CCM3 genes [6–9]. Most reports have described familial lesions in patients of French or Hispanic descent, but familial occurrence may be more widespread than these reports suggest [9–12]. Most CMs including sporadic lesions were historically considered congenital lesions; however, several cases of their de novo appearance following brain irradiation or viral infection have been reported [13, 14]. It is believed that de novo appearance of CMs occurs in genetically predisposed individuals [15].