SummaryBackgroundCerebral cavernous malformations (CCMs) are prone to bleeding but the risk of intracranial haemorrhage and focal neurological deficits, and the factors that might predict their occurrence, are unclear. We aimed to quantify these risks and investigate whether they are affected by sex and CCM location.MethodsWe undertook a population-based study using multiple overlapping sources of case ascertainment (including a Scotland-wide collaboration of neurologists, neurosurgeons, stroke physicians, radiologists, and pathologists, as well as searches of registers of hospital discharges and death certificates) to identify definite CCM diagnoses first made in Scottish residents between 1999 and 2003, which study neuroradiologists independently validated. We used multiple sources of prospective follow-up both to identify outcome events (which were assessed by use of brain imaging, by investigators masked to potential predictive factors) and to assess adults' dependence. The primary outcome was a composite of intracranial haemorrhage or focal neurological deficits (not including epileptic seizure) that were definitely or possibly related to CCM.Findings139 adults had at least one definite CCM and 134 were alive at initial presentation. During 1177 person-years of follow-up (completeness 97%), for intracranial haemorrhage alone the 5-year risk of a first haemorrhage was lower than the risk of recurrent haemorrhage (2·4%, 95% CI 0·0–5·7 vs 29·5%, 4·1–55·0; p<0·0001). For the primary outcome, the 5-year risk of a first event was lower than the risk of recurrence (9·3%, 3·1–15·4 vs 42·4%, 26·8–58·0; p<0·0001). The annual risk of recurrence of the primary outcome declined from 19·8% (95% CI 6·1–33·4) in year 1 to 5·0% (0·0–14·8) in year 5 and was higher for women than men (p=0·01) but not for adults with brainstem CCMs versus CCMs in other locations (p=0·17).InterpretationThe risk of recurrent intracranial haemorrhage or focal neurological deficit from a CCM is greater than the risk of a first event, is greater for women than for men, and declines over 5 years. This information can be used in clinical practice, but further work is needed to quantify risks precisely in the long term and to understand why women are at greater risk of recurrence than men.FundingUK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.
Objective: There have been few comparative studies of microsurgical excision vs conservative management of cerebral cavernous malformations (CCM) and none of them has reliably demonstrated a statistically and clinically significant difference. Methods:We conducted a prospective, population-based study to identify and independently validate definite CCM diagnoses first made in 1999-2003 in Scottish adult residents. We used multiple sources of prospective follow-up to assess adults' dependence and to identify and independently validate outcome events. We used univariate and multivariable survival analyses to test the influence of CCM excision on outcome, adjusted for prognostic factors and baseline imbalances.Results: Of 134 adults, 25 underwent CCM excision; these adults were younger (34 vs 43 years at diagnosis, p 5 0.004) and more likely to present with symptomatic intracranial hemorrhage or focal neurologic deficit than adults managed conservatively (48% vs 26%; odds ratio 2.7, 95% confidence interval [CI] 1.1-6.5). During 5 years of follow-up, CCM excision was associated with a deterioration to an Oxford Handicap Scale score 2-6 sustained over at least 2 successive years (adjusted hazard ratio [HR] 2.2, 95% CI 1.1-4.3) and the occurrence of symptomatic intracranial hemorrhage or new focal neurologic deficit (adjusted HR 3.6, 95% CI 1.3-10.0).Conclusions: CCM excision was associated with worse outcomes over 5 years compared to conservative management. Long-term follow-up will determine whether this difference is sustained over patients' lifetimes. Meanwhile, a randomized controlled trial appears justified. Classification of evidence:This study provides Class III evidence that CCM excision worsens shortterm disability scores and increases the risk of symptomatic intracranial hemorrhage and new focal neurologic deficits.
Management of children with high flow arteriovenous shunts of the brain is among the most challenging areas in modern medicine. Intracranial arteriovenous shunts (AVS) in children differ considerably from those seen in adults, in whom brain arteriovenous malformations (AVMs) and acquired dural arteriovenous fistulae predominate. These differences are seen both in the types of lesion and in their effects. In the neonatal and infantile age groups, the most common type of AVS is the vein of Galen aneurysmal malformation (VGAM), which has a male-to-female ratio of 3:1. Progressing further into childhood, dural malformations and brain arteriovenous malformations become more common.1 The consequences of an AVS in the developing brain are different from those in an adult, principally because of the immature cerebral venous system: the arachnoid granulations by which cerebrospinal fluid will be returned to the cerebral venous sinuses are not fully matured until 16-18 months of age.2 In infancy, cerebrospinal fluid is reabsorbed across the ventricular ependyma and brain parenchyma into the medullary veins. The presence of a large AVS such as a VGAM may raise venous sinus pressure, which is transmitted in turn to the cortical and finally the medullary veins. This will result in water congestion of the brain parenchyma, and impaired oxygenation leading to subependymal atrophy and in severe cases a progressive "melting brain syndrome". 3 The most common presentation of VGAM results from the size of the shunt itself, imposing elevated preload on the right side of the heart leading to cardiac failure. This may progress to multisystem failure. Haemorrhage in children with VGAMs is rare. 4 These are rare lesions and experience in their management has been restricted generally to large paediatric centres where a close collaboration between neuroradiologists, neonatologists, paediatric cardiologists, and neurologists has been achieved. Foremost among these centres has been Bicetre Hospital in Paris where Professor Pierre Lasjaunias' group has done much to clarify the nature of the disease and its appropriate management. A typical neurosciences unit serving a population of about three million could expect approximately one new VGAM patient a year. The aetiology of VGAMs is unknown; however, an early insult, perhaps resulting in a somatic mutation in neural crest and/or adjacent cephalic mesoderm in the early embryo, could be expected to cause such vascular abnormalities. 5 c ANATOMY OF VGAMThe VGAM is a rare and dramatic form of embryonic arteriovenous shunt located in the midline in the choroidal fissure. It consists of multiple feeding arteries, principally the anterior and posterior choroidal arteries and the anterior cerebral artery (following the cingulate gyrus and representing the embryonic limbic arterial arch), draining directly into an enlarged venous pouch (fig 1). This usually grossly dilated vein was recognised by Raybaud and colleagues to be the embryonic precursor of the vein of Galen-the median vein of the prosence...
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