Daniel Hänggi

Microscope-integrated quantitative analysis of intraoperative indocyanine green fluorescence angiography for blood flow assessment: first experience in 30 patients.

BACKGROUND: Intraoperative measurements of cerebral blood flow are of interest during vascular neurosurgery. Near-infrared indocyanine green (ICG) fluorescence angiography was introduced for visualizing vessel patency intraoperatively. However, quantitative information has not been available. OBJECTIVE: To report our experience with a microscope with an integrated dynamic ICG fluorescence analysis system supplying semiquantitative information on blood flow. METHODS: We recorded ICG fluorescence curves of cortex and cerebral vessels using software integrated into the surgical microscope (Flow 800 software; Zeiss Pentero) in 30 patients undergoing surgery for different pathologies. The following hemodynamic parameters were assessed: maximum intensity, rise time, time to peak, time to half-maximal fluorescence, cerebral blood flow index, and transit times from arteries to cortex. RESULTS: For patients without obvious perfusion deficit, maximum fluorescence intensity was 177.7 arbitrary intensity units (AIs; 5-mg ICG bolus), mean rise time was 5.2 seconds (range, 2.9-8.2 seconds; SD, 1.3 seconds), mean time to peak was 9.4 seconds (range, 4.9-15.2 seconds; SD, 2.5 seconds), mean cerebral blood flow index was 38.6 AI/s (range, 13.5-180.6 AI/s; SD, 36.9 seconds), and mean transit time was 1.5 seconds (range, 360 milliseconds-3 seconds; SD, 0.73 seconds). For 3 patients with impaired cerebral perfusion, time to peak, rise time, and transit time between arteries and cortex were markedly prolonged (>20, >9 , and >5 seconds). In single patients, the degree of perfusion impairment could be quantified by the cerebral blood flow index ratios between normal and ischemic tissue. Transit times also reflected blood flow perturbations in arteriovenous fistulas. CONCLUSION: Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.

Evolution of Management of Intracranial Aneurysms in Children: A Systematic Review of the Modern Literature

Pediatric intracranial aneurysms are rare. Management of their more common adult counterparts was profoundly influenced by recent high-quality clinical studies. The aim of this review was to aggregate the modern pediatric data published in the wake of these studies and to analyze their impact on management of aneurysms in children. A systematic PubMed search identified 135 publications published between 2000 and 2015, accounting for 573 children and 656 aneurysms. Descriptive statistical analyses revealed differences between children and adults concerning demographics and aneurysm characteristics. A significant proportion of patients were treated endovascularly, suggesting endovascular treatment has been established in the therapeutic armamentarium for pediatric aneurysms. However, these data highlight the unique nature of pediatric aneurysms, and neither this review nor generalization from adult data can replace high-quality clinical research. Multicenter registries and controlled trials are required to establish the natural history and evidence-based treatment of pediatric aneurysms.

The transorbital keyhole approach: early and long-term outcome analysis of approach-related morbidity and cosmetic results. Technical note.

OBJECT In 2003 the authors introduced a minimally invasive transorbital keyhole approach. Because this approach requires removal of the orbital rim and orbital roof, there have been concerns regarding perioperative morbidity, long-term morbidity, and cosmetic results. The authors evaluated approach-related morbidity and cosmetic results in their patients to determine the rate of complications and compared this to published reports of similar approaches. MATERIAL Seventy-one patients (41 female, 30 male) underwent operations using this approach between 2004 and 2008. Immediate approach-related morbidity was recorded after the operation. Late morbidity was determined after 7 months by an independent examiner while cosmetic results were self-rated by the patient using a questionnaire. RESULTS Fifty-one (72%) of 71 patients had no postoperative complications and 12 (16.9%) had minor complications, the most common of which was subgaleal CSF collection (7.0%). Other minor complications included facial nerve palsy (2.8%), hyposphagma (2.8%), periorbital swelling due to periorbital hematoma (2.8%), and subdural hematoma (1.4%). Major complications requiring surgical revision occurred in 4 patients (5.6%); these were CSF fistulas in 2 patients, pneumocephalus in 1 patient, and a hematoma in 1 patient. Forty-nine (90.7%) of all 54 examined patients rated the cosmetic results as very good or good. Major long-term morbidity was hyposmia or anosmia (14 patients) followed by hypoesthesia around the scar (9 patients). CONCLUSIONS The transorbital keyhole approach is a feasible approach with a low-risk profile for postoperative or long-term morbidity and excellent cosmetic outcome.

Radiobiology of Radiosurgery for the Central Nervous System

According to Leksell radiosurgery is defined as “the delivery of a single, high dose of irradiation to a small and critically located intracranial volume through the intact skull.” Before its birth in the early 60s and its introduction in clinical therapeutic protocols in late the 80s dose application in radiation therapy of the brain for benign and malignant lesions was based on the administration of cumulative dose into a variable number of fractions. The rationale of dose fractionation is to lessen the risk of injury of normal tissue surrounding the target volume. Radiobiological studies of cell culture lines of malignant tumors and clinical experience with patients treated with conventional fractionated radiotherapy helped establishing this radiobiological principle. Radiosurgery provides a single high dose of radiation which translates into a specific toxic radiobiological response. Radiobiological investigations to study the effect of high dose focused radiation on the central nervous system began in late the 50s. It is well known currently that radiobiological principles applied for dose fractionation are not reproducible when single high dose of ionizing radiation is delivered. A review of the literature about radiobiology of radiosurgery for the central nervous system is presented.

Quality of life and socio-professional reintegration after mild traumatic brain injury

Abstract Background. Controversy exists about the influence of intracranial injuries in mild traumatic brain injury (mTBI) on quality of life (QoL). Some patients do not fully recover from mTBI and experience neurocognitive impairment and reduction in quality of life. We evaluated the influence of structural brain damage on QoL and employment status (ES) after mTBI. Methods. In a partially prospective design we evaluated QoL using Short-Form-36 (SF36) and current ES three years after trauma in 36 patients with mTBI in a matched pair design with two groups of 18 patients each with and without structural brain damage. Results. Both groups showed a reduction in physical (Physical Functioning, Role Physical, Bodily Pain and General Health) and emotional parameters (Vitality, Social Functioning, Role Emotional and Mental Health) without significant difference between both groups (p = 0.305, p = 0.406, p = 0.624, p = 0.720, p = 0.934, p = 0.282, p = 0.811 and p = 0.270 respectively). ES was independent of structural brain damage and an influential factor for QoL. Conclusion. MTBI specific QoL assessment including focus on ES is necessary to identify patients at risk for impaired recovery. Structural brain injury as seen on CT scan is not useful as a prognostic tool to predict QoL or ES after mTBI.

Diversity of presynaptic calcium channels displaying different synaptic properties.

Abstract Why mediate P-/Q-type and not N-type Ca2+ channels in cerebellar inhibitory interneurons? Neurotransmitter release relies most on P-/Q- and N-type Ca2+ channels in the vast majority of neurons, although all types of voltage-gated Ca2+ channels are competent in initiating exocytosis. Up to date, it remains unclear why a particular Ca2+ channel type mediates neurotransmission in certain axon terminals and another type of Ca2+ channel evokes neurotransmission in axon terminals of another region. Therefore, the present review analyzes the diversity of presynaptic Ca2+ channels displaying different synaptic properties and focuses on an analysis of distribution and function of presynaptic voltage-gated Ca2+ channels, as well as on developmental changes.

Randomized, Open-Label, Phase 1/2a Study to Determine the Maximum Tolerated Dose of Intraventricular Sustained Release Nimodipine for Subarachnoid Hemorrhage (NEWTON [Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage])

Background and Purpose— We conducted a randomized, open-label, phase 1/2a, dose-escalation study of intraventricular sustained-release nimodipine (EG-1962) to determine safety, tolerability, pharmacokinetics, and clinical effects in aneurysmal subarachnoid hemorrhage. Methods— Subjects with aneurysmal subarachnoid hemorrhage repaired by clipping or coiling were randomized to EG-1962 or enteral nimodipine. Subjects were World Federation of Neurological Surgeons grade 2 to 4 and had an external ventricular drain. Cohorts of 12 subjects received 100 to 1200 mg EG-1962 (9 per cohort) or enteral nimodipine (3 per cohort). The primary objective was to determine the maximum tolerated dose. Results— Fifty-four subjects in North America were randomized to EG-1962, and 18 subjects were randomized to enteral nimodipine. The maximum tolerated dose was 800 mg. One serious adverse event related to EG-1962 (400 mg) and 2 EG-1962 dose-limiting toxicities were without clinical sequelae. There was no EG-1962-related hypotension compared with 17% (3/18) with enteral nimodipine. Favorable outcome at 90 days on the extended Glasgow outcome scale occurred in 27/45 (60%, 95% confidence interval 46%–74%) EG-1962 subjects (5/9 with 100, 6/9 with 200, 7/9 with 400, 4/9 with 600, and 5/9 with 800 mg) and 5/18 (28%, 95% confidence interval 7%–48%, relative risk reduction of unfavorable outcome; 1.45, 95% confidence interval 1.04–2.03; P=0.027) enteral nimodipine subjects. EG-1962 reduced delayed cerebral ischemia (14/45 [31%] EG-1962 versus 11/18 [61%] enteral nimodipine) and rescue therapy (11/45 [24%] versus 10/18 [56%]). Conclusions— EG-1962 was safe and tolerable to 800 mg, and in this, aneurysmal subarachnoid hemorrhage population was associated with reduced delayed cerebral ischemia and rescue therapy. Overall, the rate of favorable clinical outcome was greater in the EG-1962-treated group. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01893190.

Calcium and potassium channels in experimental subarachnoid hemorrhage and transient global ischemia.

Healthy cerebrovascular myocytes express members of several different ion channel families which regulate resting membrane potential, vascular diameter, and vascular tone and are involved in cerebral autoregulation. In animal models, in response to subarachnoid blood, a dynamic transition of ion channel expression and function is initiated, with acute and long-term effects differing from each other. Initial hypoperfusion after exposure of cerebral vessels to oxyhemoglobin correlates with a suppression of voltage-gated potassium channel activity, whereas delayed cerebral vasospasm involves changes in other potassium channel and voltage-gated calcium channels expression and function. Furthermore, expression patterns and function of ion channels appear to differ between main and small peripheral vessels, which may be key in understanding mechanisms behind subarachnoid hemorrhage-induced vasospasm. Here, changes in calcium and potassium channel expression and function in animal models of subarachnoid hemorrhage and transient global ischemia are systematically reviewed and their clinical significance discussed.

Intraoperative neurophysiological monitoring during resection of infratentorial lesions: the surgeon's view

OBJECTIVE Methods of choice for neurophysiological intraoperative monitoring (IOM) within the infratentorial compartment mostly include early brainstem auditory evoked potentials, free-running electromyography, and direct cranial nerve (CN) stimulation. Long-tract monitoring with somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) is rarely used. This study investigated the incidence of IOM alterations during posterior fossa surgery stratified for lesion location. METHODS Standardized CN and SEP/MEP IOM was performed in 305 patients being treated for various posterior fossa pathologies. The IOM data were correlated with lesion locations and histopathological types as well as other possible confounding factors. RESULTS Alterations in IOM were observed in 158 of 305 cases (51.8%) (CN IOM alterations in 130 of 305 [42.6%], SEP/MEP IOM alterations in 43 of 305 [14.0%]). In 15 cases (4.9%), simultaneous changes in long tracts and CNs were observed. The IOM alterations were followed by neurological sequelae in 98 of 305 cases (32.1%); 62% of IOM alterations resulted in neurological deficits. Sensitivity and specificity for detection of CN deficits were 98% and 77%, respectively, and 95% and 85%, respectively, for long-tract deficits. Regarding location, brainstem and petroclival lesions were closely associated with concurrent CN IOM and SEP/MEP alterations. CONCLUSIONS The incidence of IOM alterations during surgery in the posterior fossa varied widely between different lesion locations and histopathological types. This analysis provides crucial information on the necessity of IOM in different surgical settings. Because MEP/SEP and CN IOM alterations were commonly observed during posterior fossa surgery, the authors recommend the simultaneous use of both modalities based on lesion location.

The influence of decompressive craniectomy for major stroke on early cerebral perfusion.

OBJECT Multiple trials have shown improved survival and functional outcome in patients treated with decompressive craniectomy (DC) for brain swelling following major stroke. It has been assumed that decompression induces an improvement in cerebral perfusion. This observational study directly measured cerebral perfusion before and after decompression. METHODS Sixteen patients were prospectively examined with perfusion CT within 6 hours prior to surgery and 12 hours after surgery. Preoperative and postoperative perfusion measurements were compared and correlated. RESULTS Following DC there was a significant increase in cerebral blood flow in all measured territories and additionally an increase in cerebral blood volume in the penumbra (p = 0.03). These changes spread as far as the contralateral hemisphere. No significant changes in mean transit time or Tmax (time-to-peak residue function) were observed. CONCLUSIONS The presurgical perfusion abnormalities likely reflected local pressure-induced hypoperfusion with impaired autoregulation. The improvement in perfusion after decompression implied an increase in perfusion pressure, likely linked to partial restoration of autoregulation. The increase in perfusion that was observed might partially be responsible for improved clinical outcome following decompressive surgery for major stroke. The predictive value of perfusion CT on outcome needs to be evaluated in larger trials.