Helmut Bertalanffy

Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated patients.

Abstract. 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.

Endoscopic third ventriculostomy for obstructive hydrocephalus

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.

Seizure Outcome after Resection of Supratentorial Cavernous Malformations: A Study of 168 Patients

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.

Neuroendoscopic treatment for colloid cysts of the third ventricle: The experience of a decade - Commentary

OBJECTIVEMicrosurgical resection or ventriculoperitoneal shunt placement was for a long time the only means of treatment for patients with colloid cysts. In the past few years, however, endoscopic procedures have gained increasing significance and have been used more widely. Long-term results are now available for the first time, which enabled us to evaluate this method and assess its future relevance. METHODSTwenty patients with symptomatic colloid cysts of the third ventricle have been treated endoscopically in our department during the past 10 years. Retrospective analysis and follow-up of the patients’ clinical and radiological outcomes were performed. RESULTSIn the early postoperative period, 18 patients had excellent outcomes, with clinical signs improving immediately. One patient experienced intraoperative hemorrhage followed by temporary postoperative psychosis and IIIrd cranial nerve palsy. Another patient remained shunt-dependent because of aseptic meningitis after the endoscopic procedure. In the long-term follow-up, one patient had to be reoperated to treat cyst recurrence. The operative time was strongly dependent on the cyst material as well as on the surgeon’s experience with endoscopic techniques; it varied between 60 and 300 minutes (mean operative time, 200 min). The average hospitalization time was 9 days. Long-term follow-up ranging from 1 to 10 years showed a clear benefit in each patient. In three individuals with pre- and postoperative short-term memory deficits and in one patient who complained of headaches, symptoms resolved gradually during the first few months after surgery. The patient with intraoperative hemorrhage complained of slight permanent short-time memory deficit. The analysis of postoperative computed tomographic and magnetic resonance imaging scans revealed a remaining cyst wall in the majority of patients and an inconsistent decrease in ventricular size. Postoperative cine magnetic resonance imaging studies showed normalization of cerebrospinal fluid flow in 17 patients. CONCLUSIONContinued 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.

Intrathecal baclofen alleviates autonomic dysfunction in severe brain injury.

Sympathetic storm phenomena are well known therapeutic problems in patients with severe brain injury. We have treated four patients with intrathecal baclofen (ITB) who suffered from severe hypertension, tachycardia and other sympathetic storm phenomena after different primary events. In all patients conventional therapy with sedatives and antiadrenergic medication had been taken to the upper limits before initiating ITB. Autonomic dysfunction immediately improved in three of four patients. In all patients ITB, via lumbar or ventricular route, proved safe and without complications. The anatomical and pharmacological basis of the GABA-B agonist action on such sympathetic storm phenomena are not yet fully understood. However, the positive results observed in three out of four patients are promising and require further investigation. ITB is a new therapeutic approach to control otherwise unresponsive sympathetic storm phenomena in severe brain injury.

Effects of Moderate Hypothermia on Leukocyte- Endothelium Interaction in the Rat Pial Microvasculature After Transient Middle Cerebral Artery Occlusion

Background and Purpose--It has been demonstrated that moderate hypothermia attenuates brain damage, but the mechanism whereby this is achieved has not been clearly shown. Recently, the role of leukocytes as mediators of secondary brain damage after brain ischemia has been discussed. The aim of this study is to examine the effects of moderate hypothermia on leukocyte-endothelium interaction in the rat pial microvasculature after transient middle cerebral artery occlusion (MCAO). Methods--Rhodamine 6G-labeled leukocytes in brain surface were visualized with intravital fluorescence videomicroscopy through a closed cranial window. We analyzed the number of leukocytes adhering to the venular and arteriolar endothelium before ischemic insult and up to 3 hours after reperfusion. Rats were divided into 4 experimental groups. Group I (n=6) consisted of sham-operated animals. Groups II (n=6) and III (n=6) received left MCAO for 1 hour under normothermia (36 degrees C to 37 degrees C, group II) and under moderate hypothermia (30 degrees C to 32 degrees C, group III). Group IV (n=4) received left common carotid artery occlusion for 1 hour under normothermia. Results--The number of adhering leukocytes in venules in groups II and IV increased significantly (P<0.001) after reperfusion compared with the group I, but that in group III did not increase significantly (P>0.05). The number of adhering leukocytes in arterioles in group II increased significantly (P<0.01) compared with the other groups, although the adhering leukocytes were not as numerous as those seen in venules. Conclusions--It is demonstrated that hypothermia attenuates adhering leukocytes in venules and arterioles after reperfusion of MCAO. The inhibition of the leukocyte function may be an important factor in the neuroprotective effect of hypothermia.

Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex.

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. Hum Mutat 29(5), 709–717, 2008.

Advanced image-guided skull base surgery

BACKGROUND Tumors of the skull base frequently encase or extend into normal neural and vascular structures. Preoperative planning and intraoperative identification of anatomic landmarks is especially important in complex tumors since it helps avoid or minimize surgical morbidity. METHODS By creating a surgical plan the image guidance software offers help in the establishment of a surgical approach. During surgery, the neuronavigation system displays the location of anatomic landmarks of the skull base regardless of any erosion or displacement. RESULTS A series of 10 patients with complex tumors in various skull base locations is reported. Osseous structures are easily identified using the CT-based image guidance since these landmarks do not shift due to CSF loss. Image fusion of CT and MRI data gives additional information on the displacement of soft tissue structures. Image fusion in a substraction mode is helpful when a tumor has invaded bony structures or when the encasement of major vessels has to be visualized. CONCLUSION The preoperative data preparation (planning of the approach, image fusion) plays a vital role in modern neuronavigation and contributes useful information during surgery for complex skull base tumors. Such advanced neuronavigation increases the efficacy and safety of intraoperative maneuvers. Eroded and distorted anatomic landmarks are not subject to a significant amount of intraoperative shift throughout the surgical procedure.

Treatment-induced neoangiogenesis in cerebral arteriovenous malformations.

We investigated the angiogenetic and proliferative activity of the endothelium of 30 consecutive surgical cases of AVM treated at our institution by immunohistochemical detection of the PCNA, MIB-1, Flk-1 and VEGF antibodies. Endothelial positive immunostaining was observed in 87% of the cases for PCNA, in 20% for MIB-1, and in 80% for Flk-1. Of 22 individuals treated with incomplete embolization prior to surgery, 17 showed an expression of VEGF (77%), but only two of the eight patients (25%) who were treated without prior embolization exhibited such an immunoreaction (P=0.0086). The proliferation and growth of cerebral AVMs is documented by endothelial expression of PCNA and MIB-1. The statistically significantly higher expression of VEGF in partially obliterated (embolized) AVMs is most likely caused by transient regional hypoxia within the AVM nidus that mediates neoangiogensis. It points out the clinical relevance of a complete occlusion in order to avoid neovascularization associated with subsequent morbidity and mortality.

Endoscope-assisted Microsurgery for Microvascular Compression Syndromes

OBJECTIVETo discuss the results of endoscope-assisted surgery in microvascular decompression (MVD) of Cranial Nerves (CNs) V, VII, and VIII. METHODSNeuroendoscopy was used as an adjunct to the surgical microscope in the MVD of the trigeminal (17 patients), facial (10 patients), and vestibulocochlear (1 patient) nerves in a series of 28 consecutive patients. After a standard microsurgical approach to CNs V, VII, and VIII, the endoscope was used to inspect all aspects of neural anatomy, to assess vascular compression, and to check the results of the decompression. Endoscope use was graded in four categories: Grade I, used but no definite role; Grade II, visualization assisted; Grade III, procedure assisted; and Grade IV, primary role. The usefulness of the endoscope was evaluated in each case. RESULTSThe endoscope was useful in visualizing the anatomy in all cases. It was especially useful in establishing trigeminal vein compression of CN V in Meckel’s cave; observing multiple sources of vascular compression; ensuring adequate decompression after cauterization of vein, insertion of the Teflon felt, or a pexy procedure; and permitting observation of the compression of CN VII at the root exit zone by small arteries and veins. In six patients with trigeminal neuralgia, the trigeminal vein was cauterized and divided by using endoscopic vision only because the venous compression was not completely visualized with the microscope. During a follow-up period of 6 to 52 months (mean, 29 mo; median, 40 mo), all patients were asymptomatic and receiving no medication. CONCLUSIONThe endoscope is a useful adjunct to MVD in the treatment of trigeminal neuralgia, hemifacial spasm, and disabling positional vertigo or tinnitus.