The authors review the pertinent literature dealing with all aspects of cerebral cavernous malformations in the adult. Clinical, neuroradiological, pathological, and epidemiological aspects are presented. The clinical significance of bleeding from cavernous malformations and various hemorrhage patterns are discussed in relation to the factors that influence hemorrhage rates. Recent reports describing the genetic mechanisms of inheritance, de novo formation, and angiogenesis of cavernomas are reviewed as well. Brainstem cavernomas have received special attention, since their clinical management is controversial in the literature. Presently, microsurgical removal is favored by the majority of authors and stereotactic radiosurgery appears to be inappropriate for prevention of bleeding from a cavernoma. Our own case material consists of data of 72 patients operated upon during the past 5 years. Twenty-four patients harbored the lesion within the brainstem, 18 within the deep white matter of the hemispheres, 12 in the basal ganglia or thalamus, 11 in superficial areas of the hemisphere, and seven within the cerebellum. The perioperative morbidity rate was 29.2% (21/72) while the rate of long-term morbidity was 5.5% (4/72), with no mortality in this series. It is concluded that cerebral cavernous malformations, including lesions in critical regions of the brain, can be treated microsurgically with excellent results and an acceptable morbidity.

The complications of anterior discectomy without fusion were analyzed on the basis of 450 consecutive cases treated surgically for degenerative disc disease. There was no death related to the procedure. The most common complication was a worsening of the pre-existing myelopathy. This occurred in 3.3%, including one case with severe medullary contusion. Wound infection developed in 1.6%. Additional radicular symptoms and wound haematoma, respectively, occurred in 1.3%; recurrent nerve palsy, Horner's syndrome, and respiratory insufficiency, respectively, in 1.1% of the cases. Epidural haematoma and instability of the cervical spine, respectively, occurred in 0.9%, nerve root lesion and aseptic spondylodiscitis, respectively, in 0.4%. There was one case each (0.2%) with a pharyngeal lesion, meningitis due to dural perforation, transient additional myelopathy, and epidural abscess. The results and the management of complications are discussed in relation to numerous previously published reports, including posterior procedures and anterior fusion techniques. Precise knowledge of all potential accidents and pitfalls related to the surgical procedure and of their aetiology may contribute to preventing failures. The rate of complications in this series has been reduced in the past years by better patient selection, by paying more attention to correct positioning of the patient during the operation, and by meticulous removal of all offending structures. Discectomy without interbody fusion is now considered to be a reasonably safe procedure with an acceptable operative morbidity and lack of mortality.

The indications for neuroendoscopy are not only constantly increasing, but even the currently accepted indications are constantly being adjusted and tailored. This is also true for one of the most frequently used neuroendoscopic procedures, the endoscopic 3rd ventriculostomy (ETV) for obstructive hydrocephalus. ETV has gained popularity and widespread acceptance during the past few years, but little attention has been paid to the techniques of the procedure. After a short introduction describing the history of ETV, an overview is given of all the different techniques that have been and still are employed to open the floor of the 3rd ventricle. The spectrum of indications for ETV has been widely enlarged over the last years. Initially, the use of this procedure was restricted to patients older than 2 years, to patients with an obvious triventricular hydrocephalus, and to those with a bulging, translucent floor of the 3rd ventricle. Nowadays, indications include all kinds of obstructive hydrocephalus but also communicating forms of hydrocephalus. The results of endoscopic procedures in treating these pathologies are given under special consideration of shunt technologies. In summary, from the review of the publications since the first ETV performed by Mixter in 1923, this technique is the treatment of choice for obstructive hydrocephalus caused by different etiologies and is an alternative to cerebrospinal fluid shunt application.

Summary: Purpose:The optimal management of cerebral cavernous malformations (CCMs) with epileptic seizures is still a matter of debate. The aim of our study was to examine seizure outcome in the largest published series of surgically treated patients with epilepsy due to a supratentorial CCM, and to define predictors for good surgical outcome.Methods: We retrospectively studied 168 consecutive patients with a single supratentorial CCM and symptomatic epilepsy in a multicenter study. Pre-and postoperative clinical examinations, age at epilepsy onset, age at operation, type of symptoms due to the CCM (seizures, headache, hemorrhage, focal deficits), type and frequency of epileptic seizures, and the localization and size of the CCM were assessed. Seizure outcome was determined in the first, second, and third postoperative years. Results:The CCM was completely resected in all patients. More than two thirds of the patients were classified as seizure free in the first 3 postoperative years. Predictors for good seizure outcome were age older than 30 years at the time of surgery, mesiotemporal CCM localization, CCM size <1.5 cm, and the absence of secondarily generalized seizures. No mortality occurred in our series, but only mild postoperative neurologic deficits in 12 (7%) patients.Conclusions: Considering the natural history of CCMs, the favorable neurologic and seizure outcome, surgical resection of CCMs should be considered in all patients with supratentorial CCMs and concomitant epilepsy, irrespective of the presence or absence of predictors for a favorable seizure outcome.

Continued improvement of endoscopic techniques and instruments, together with good long-term results in endoscopically treated patients, have established this method as an alternative to microsurgical techniques and might even set a new standard for treatment.

Cerebral cavernous malformations (CCM) are prevalent cerebrovascular lesions predisposing to chronic headaches, epilepsy, and hemorrhagic stroke. Using a combination of direct sequencing and MLPA analyses, we identified 15 novel and eight previously published CCM1 (KRIT1), CCM2, and CCM3 (PDCD10) mutations. The mutation detection rate was >90% for familial cases and >60% for isolated cases with multiple malformations. Splice site mutations constituted almost 20% of all CCM mutations identified. One of these proved to be a de novo mutation of the most 3' acceptor splice site of the CCM1 gene resulting in retention of intron 19. A further mutation affected the 3' splice site of CCM2 intron 2 leading to cryptic splice site utilization in both CCM2 and its transcript variant lacking exon 2. With the exception of one in-frame deletion of CCM2 exon 2, which corresponds to the naturally occurring splice variant of CCM2 on the RNA level and is predicted to result in the omission of 58 amino acids (CCM2:p.P11_K68del), all mutations lead to the introduction of premature stop codons. To gain insight into the likely mechanisms underlying the only known CCM2 in-frame deletion, we analyzed the functional consequences of loss of CCM2 exon 2. The CCM2:p.P11_K68del protein could be expressed in cell culture and complexed with CCM3. However, its ability to interact with CCM1 and to form a CCM1/CCM2/CCM3 complex was lost. These data are in agreement with a loss-of-function mechanism for CCM mutations, uncover an N-terminal CCM2 domain required for CCM1 binding, and demonstrate full-length CCM2 as the essential core protein in the CCM1/CCM2/CCM3 complex.

These results indicate that there is endothelial proliferation as well as neoangiogenesis in cerebral cavernomas and AVMs. The increased level of angiogenesis in only partially obliterated AVMs underscores the need for radical and complete occlusion of cerebral AVMs to avoid recurrences and further risks of morbidity.

The authors review 26 patients with deep-seated cavernous angiomas which were removed by microsurgery. Ten of the angiomas were located in the insula and basal ganglia, 2 in the thalamus, 5 in the midbrain, 8 in the pons, and 1 in the brachium pontis. The patients were among 73 consecutive cases operated on between August 1983 and December 1989 for symptomatic cavernous angiomas in various locations. In 11 cases total excision of the cavernoma was achieved without producing additional neurological deficits. Postoperative neurological recovery was delayed in 7 patients. In the remaining 8, the complicated postoperative course was caused by bleeding from residual parts of the malformation or damage to long-tract pathways in two cases, respectively, vascular injury during dissection in three cases, and paradoxical air embolism in one case. In order to achieve a satisfactory surgical result, it is stressed that particular attention has to be paid to the operative approach, to careful dissection and complete removal of the malformation, to perforating arteries, and to anomalous venous drainage.