Ventral Brainstem Research Articles

Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep

Sleep and wakefulness are regulated primarily by inhibitory interactions between the hypothalamus and brainstem. The expression of the states of rapid eye movement (REM) sleep and non-REM (NREM) sleep also are correlated with the activity of groups of REM-off and REM-on neurons in the dorsal brainstem. However, the contribution of ventral brainstem nuclei to sleep regulation has been little characterized to date. Here we examined sleep and wakefulness in mice deficient in a homeobox transcription factor, Goosecoid-like (Gscl), which is one of the genes deleted in DiGeorge syndrome or 22q11 deletion syndrome. The expression of Gscl is restricted to the interpeduncular nucleus (IP) in the ventral region of the midbrain-hindbrain transition. The IP has reciprocal connections with several cell groups implicated in sleep/wakefulness regulation. Although Gscl(-/-) mice have apparently normal anatomy and connections of the IP, they exhibited a reduced total time spent in REM sleep and fewer REM sleep episodes. In addition, Gscl(-/-) mice showed reduced theta power during REM sleep and increased arousability during REM sleep. Gscl(-/-) mice also lacked the expression of DiGeorge syndrome critical region 14 (Dgcr14) in the IP. These results indicate that the absence of Gscl and Dgcr14 in the IP results in altered regulation of REM sleep.

Resting state eyes-closed cortical rhythms in patients with locked-in-syndrome: An eeg study

Objective Locked-in syndrome (LIS) is a state of complete paralysis, except for ocular movements, which results from ventral brainstem lesions. Patients typically are fully conscious. Here we tested the hypothesis that electroencephalographic (EEG) rhythms are abnormal in LIS patients, possibly due to an impaired neural synchronization between brainstem and cerebral cortex. Methods Resting state eyes-closed EEG data were recorded in 13 LIS subjects and 15 cognitively normal control subjects. With reference to the individual alpha frequency (IAF), the bands of interest were delta (IAF-8 to IAF-6 Hz), theta (IAF-6 to IAF-4 Hz), alpha 1 (IAF-4 to IAF-2 Hz), alpha 2 (IAF-2 to IAF Hz), and alpha 3 (IAF to IAF + 2 Hz). Furthermore, beta 1 (13–20 Hz) and beta 2 (20–30 Hz) bands were also considered. Cortical EEG sources were estimated by low-resolution electromagnetic tomography (LORETA). Results The power of alpha 2 and alpha 3 sources in all regions was lower in patients with LIS compared to controls. The power of delta sources in central, parietal, occipital and temporal regions was higher in patients with LIS compared to controls. Conclusions These results suggest that cortical sources of resting state eyes-closed alpha and delta rhythms are abnormal in LIS patients. Significance LIS is accompanied by a functional impairment of cortical neuronal synchronization mechanisms in the resting state condition.

Clonidine, an α 2-receptor agonist, diminishes GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

In hypertension, there is an autonomic imbalance in which sympathetic activity dominates over parasympathetic control. Parasympathetic activity to the heart originates from cardiac vagal neurons located in the nucleus ambiguus. Presympathetic neurons that project to sympathetic neurons in the spinal cord are located in the ventral brainstem in close proximity to cardiac vagal neurons, and many of these presympathetic neurons are catecholaminergic. In addition to their projection to the spinal cord, many of these presympathetic neurons have axon collaterals that arborize into neighboring cardiorespiratory locations and likely release norepinephrine onto nearby neurons. Activation of α 2-adrenergic receptors in the central nervous system evokes a diverse range of physiological effects, including reducing blood pressure. This study tests whether clonidine, an α 2-adrenergic receptor agonist, alters excitatory glutamatergic, and/or inhibitory GABAergic or glycinergic synaptic neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Cardiac vagal neurons were identified in an in vitro brainstem slice preparation, and synaptic events were recording using whole cell voltage clamp methodologies. Clonidine significantly inhibited GABAergic neurotransmission but had no effect on glycinergic or glutamatergic pathways to cardiac vagal neurons. This diminished inhibitory GABAergic neurotransmission to cardiac vagal neurons would increase parasympathetic activity to the heart, decreasing heart rate and blood pressure. The results presented here provide a cellular substrate for the clinical use of clonidine as a treatment for hypertension as well as a role in alleviating posttraumatic stress disorder by evoking an increase in parasympathetic cardiac vagal activity, and a decrease in heart rate and blood pressure.

Transnasal odontoid resection followed by posterior decompression and occipitocervical fusion in children with Chiari malformation Type I and ventral brainstem compression

In rare cases, children with a Chiari malformation Type I (CM-I) suffer from concomitant, irreducible, ventral brainstem compression that may result in cranial neuropathies or brainstem dysfunction. In these circumstances, a 360 degrees decompression supplemented by posterior stabilization and fusion is required. In this report, the authors present the first experience with using an endoscopic transnasal corridor to accomplish ventral decompression in children with CM-I that is complicated by ventral brainstem compression. Two children presented with a combination of occipital headaches, swallowing dysfunction, myelopathy, and/or progressive scoliosis. Imaging studies demonstrated CM-I with severely retroflexed odontoid processes and ventral brainstem compression. Both patients underwent an endoscopic transnasal approach for ventral decompression, followed by posterior decompression, expansive duraplasty, and occipital-cervical fusion. In both patients the endoscopic transnasal approach provided excellent ventral access to decompress the brainstem. When compared with the transoral approach, endoscopic transnasal access presents 4 potential advantages: 1) excellent prevertebral exposure in patients with small oral cavities; 2) a surgical corridor located above the hard palate to decompress rostral pathological entities more easily; 3) avoidance of the oral trauma and edema that follows oral retractor placement; and 4) avoidance of splitting the soft or hard palate in patients with oral-palatal dysfunction from ventral brainstem compression. The endoscopic transnasal approach is atraumatic to the oral cavity, and offers a more superior region of exposure when compared with the standard transoral approach. Depending on their comfort level with endoscopic surgical techniques, pediatric neurosurgeons should consider this approach in children with pathological entities requiring ventral brainstem decompression.

Unexpected sudden death due to intracranial chordoma: An autopsy case

Intracranial chordoma is a locally invasive, relatively rare tumour at the base of the skull. The tumour usually grows slowly but there have been several case reports of sudden death, all of which were due to tumour-associated haemorrhages. We report an autopsy case of a sudden unexpected death due to clinically undiagnosed intracranial chordoma in the brainstem without haemorrhage. A 44-year-old man was found dead at home. The autopsy revealed two small gelatinous and semi-translucent greyish tumours on the ventral surface of the brainstem between the midbrain and pons. The tumours were not attached to the dura or bone. The brain was markedly swollen, with enlarged lateral and third ventricles, but the aqueduct was compressed and narrowed. Microscopically, the tumour invaded the cerebral peduncles, and was classified as a chordoma. The cause of death was diagnosed as acute obstructive hydrocephalus due to a ventral brainstem tumour. Even a minor intracranial tumour that is not primarily life-threatening may cause sudden death due to subsequent obstructive hydrocephalus. The brainstem is one of the most vulnerable regions in the brain, and careful examination of this region is important for forensic pathologists.

Sinoaortic Denervation (SAD) Prevents Training‐Induced Plasticity in Preautonomic Oxytocinergic and Vasopressinergic Pathways

Baroreceptor signaling plays a crucial role in driving training‐induced beneficial adjustments mediated by central autonomic pathways (Exp Physiol 2009;94:630–640; 947–960). We sought now to identify these pathways in WKY and SHR. Rats submitted to SAD or SHAM surgery were trained (55% VO2 max, for 3 month) or kept sedentary (S). After hemodynamic measurements at rest, rats were anesthetized for transcardiac perfusion (PBS). Brains were removed, frozen and sliced to isolate dorsal and ventral brain stem (comprising the solitary‐vagal complex and RVLM) and hypothalamic paraventricular nucleus (PVN); tissue samples were processed for oxytocin (OT), vasopressin (VP) and their receptors’ expression (Real Time PCR, GAPDH as the reporter gene). T‐induced pressure fall (−8% in the SHR) and resting bradycardia (−9% in both groups) were absent after SAD. There were no changes on receptors’ expression in target areas but SAD completely blocked T‐induced OT mRNA (4.3‐fold and 20% increases in SHAM WKYT and SHRT, respectively) and VP mRNA expression (+2.4‐fold in SHAM SHRT vs. S controls) within the PVN. OT and VP immunoreactivities within the PVN confirmed these responses. Baroreceptor inputs are decisive to drive plastic changes in preautonomic neurons. T‐induced PVN OTergic expression is present in both normotensive and hypertensive, while T‐induced VPergic expression is only observed in hypertensive individuals

Modified Kawase approach for microsurgical removal of petroclival tumors

Objective To discuss the outcome and surgical techniques in patients with petroclival tumors resected microsurgically via modified Kawase approach. Method 20 consecutive petroclival tumors had been resected microsurgically via modified Kawase approach. The clinical data and follow-up results were retrospectively summarized. Results In our series, there were 12 meningiomas, 5 schwannomas, 1 chordoma, 1 pontine gtioma, 1 petrosal cholesteatoma. Tumor was removed totally in 14 patients, removed subtotally in 6. There was no mortality and the main postoperative new neurological deficit was cranial nerve dysfunction. Conclusions The modified Kawase approach can provide sufficient exposure for tumors in upper petroclival region anterior to internal auditary canal. It has the advantage of early devascularization of petroclival meningioma, better visualization of the contralateral side and the ventral brainstem, less risk of venous complications, all of which facilitates safe and radical removal of the tumor. Key words: Petroclival tumor; Skull base; Microsurgery; Kawase approach

Precise pattern of recombination in serotonergic and hypothalamic neurons in a Pdx1-cre transgenic mouse line

BackgroundMulticellular organisms are characterized by a remarkable diversity of morphologically distinct and functionally specialized cell types. Transgenic techniques for the manipulation of gene expression in specific cellular populations are highly useful for elucidating the development and function of these cellular populations. Given notable similarities in developmental gene expression between pancreatic β-cells and serotonergic neurons, we examined the pattern of Cre-mediated recombination in the nervous system of a widely used mouse line, Pdx1-cre (formal designation, Tg(Ipf1-cre)89.1Dam), in which the expression of Cre recombinase is driven by regulatory elements upstream of the pdx1 (pancreatic-duodenal homeobox 1) gene.MethodsSingle (hemizygous) transgenic mice of the pdx1-creCre/0 genotype were bred to single (hemizygous) transgenic reporter mice (Z/EG and rosa26R lines). Recombination pattern was examined in offspring using whole-mount and sectioned histological preparations at e9.5, e10.5, e11.5, e16.5 and adult developmental stages.ResultsIn addition to the previously reported pancreatic recombination, recombination in the developing nervous system and inner ear formation was observed. In the central nervous system, we observed a highly specific pattern of recombination in neuronal progenitors in the ventral brainstem and diencephalon. In the rostral brainstem (r1-r2), recombination occurred in newborn serotonergic neurons. In the caudal brainstem, recombination occurred in non-serotonergic cells. In the adult, this resulted in reporter expression in the vast majority of forebrain-projecting serotonergic neurons (located in the dorsal and median raphe nuclei) but in none of the spinal cord-projecting serotonergic neurons of the caudal raphe nuclei. In the adult caudal brainstem, reporter expression was widespread in the inferior olive nucleus. In the adult hypothalamus, recombination was observed in the arcuate nucleus and dorsomedial hypothalamus. Recombination was not observed in any other region of the central nervous system. Neuronal expression of endogenous pdx1 was not observed.ConclusionsThe Pdx1-cre mouse line, and the regulatory elements contained in the corresponding transgene, could be a valuable tool for targeted genetic manipulation of developing forebrain-projecting serotonergic neurons and several other unique neuronal sub-populations. These results suggest that investigators employing this mouse line for studies of pancreatic function should consider the possible contributions of central nervous system effects towards resulting phenotypes.

Deformative stress associated with an abnormal clivo-axial angle: A finite element analysis

Background:Chiari malformation, functional cranial settling and subtle forms of basilar invagination result in biomechanical neuraxial stress, manifested by bulbar symptoms, myelopathy and headache or neck pain. Finite element analysis is a means of predicting stress due to load, deformity and strain. The authors postulate linkage between finite element analysis (FEA)-predicted biomechanical neuraxial stress and metrics of neurological function.Methods:A prospective, Internal Review Board (IRB)-approved study examined a cohort of 5 children with Chiari I malformation or basilar invagination. Standardized outcome metrics were used. Patients underwent suboccipital decompression where indicated, open reduction of the abnormal clivo-axial angle or basilar invagination to correct ventral brainstem deformity, and stabilization/ fusion. FEA predictions of neuraxial preoperative and postoperative stress were correlated with clinical metrics.Results:Mean follow-up was 32 months (range, 7-64). There were no operative complications. Paired t tests/ Wilcoxon signed-rank tests comparing preoperative and postoperative status were statistically significant for pain, bulbar symptoms, quality of life, function but not sensorimotor status. Clinical improvement paralleled reduction in predicted biomechanical neuraxial stress within the corticospinal tract, dorsal columns and nucleus solitarius.Conclusion:The results are concurrent with others, that normalization of the clivo-axial angle, fusion-stabilization is associated with clinical improvement. FEA computations are consistent with the notion that reduction of deformative stress results in clinical improvement. This pilot study supports further investigation in the relationship between biomechanical stress and central nervous system (CNS) function.

Zic1 levels regulate mossy fiber neuron position and axon laterality choice in the ventral brain stem

Pontine gray neurons of the brain stem are a major source of mossy fiber (MF) afferents to granule cells of the cerebellum. Achieving this connectivity involves an early regionalization of pontine gray neuron cell bodies within the brainstem pontine nuclei, as well as establishing the proper ratio of crossed versus uncrossed MF projections to contralateral versus ipsilateral cerebellar territories. Here, we report expression of the transcription factor Zic1 in newly postmitotic pontine gray neurons and present functional experiments in embryonic and postnatal mice that implicate Zic1 levels as a key determinant of pontine neuron cell body position within the pons and axon laterality. Reducing Zic1 levels embryonically via in utero electroporation of short hairpin RNA interference (shRNAi) vectors shifted the postnatal distribution of pontine neurons from caudolateral to rostromedial territories; by contrast, increasing Zic1 levels resulted in the reciprocal shift, with electroporated cells redistributing caudolaterally. Associated with the latter was a change in axon laterality, with a greater proportion of marked projections now targeting the ipsilateral instead of contralateral cerebellum. Zic1 levels in pontine gray neurons, therefore, play an important role in the development of pontocerebellar circuitry.

QUANTITATIVE COMPARISON OF KAWASE'S APPROACH VERSUS THE RETROSIGMOID APPROACH

Few quantitative data are available to describe Kawase's exposure of the posterior fossa. We used a cadaveric model to compare Kawase's and the retrosigmoid approach to the petroclival region. Eighteen cadaveric specimens were dissected and analyzed (6 retrosigmoid, 6 Kawase's, and 6 retrosigmoid intradural suprameatal approaches). Clival and brainstem working areas and surgical freedom were measured. The retrosigmoid approach provided a significantly larger clival and brainstem working area than Kawase's approach. Surgical freedom at the trigeminal root entry zone, origin of the anterior inferior cerebellar artery, and Dorello's canal was equivalent across approaches. Kawase's approach provided the most surgical freedom at the trigeminal porus. However, the addition of a suprameatal extension significantly improved the surgical freedom provided by the retrosigmoid approach. The retrosigmoid approach is a powerful approach to lesions of the cerebellopontine angle and ventral brainstem. Lesions involving the trigeminal porus and Meckel's cave can be approached through Kawase's approach or a suprameatal extension of the retrosigmoid approach. Kawase's approach is best suited for accessing middle fossa lesions with smaller petroclival components located above the internal auditory canal.

The microsurgical anatomy of the hypoglossal canal

The hypoglossal canal (HC) is a region of the skull base whose involvement in many pathological entities is often ignored. Adequate knowledge of the anatomy of the HC and its related bony, neural, and vascular structures is essential for surgery of lesions involving this area. Ten adult human cadaver heads from a US source fixed by formalin (20 sides) and 20 dry human skulls from Indian sources (40 sides) were used in this study. Various aspects of the anatomy of this region including the size, course and variation of the hypoglossal nerve and its relationship to the adjacent and canalicular course were recorded. The left HC was located at 10 o'clock and the right HC at the 2 o'clock position with respect to the foramen magnum. The canal was surrounded superiorly by the jugular tubercle, superolaterally by the jugular foramen, laterally by the sigmoid sinus and inferiorly by the occipital condyle. All dry skulls were drilled in the horizontal plane at an axis of about 45 degrees and directed slightly upwards. Detailed knowledge of the microsurgical anatomy of the region of the HC is crucial when performing surgery for lesions of the condylar region, the lower clivus, and ventral brain stem. This study provides the knowledge required to achieve accurate orientation and effective maneuvers during surgical procedures for treatment of the patient without injuring the vital neural and bony structures.

Transzygomatic extended middle fossa approach for upper petroclival skull base lesions

Central skull base lesions in the upper retroclival and petroclival regions can be challenging to access because of their location anterior to the brainstem. Several transpetrosal approaches have been developed to access the petroclival junction, including anterior petrosal (anterior petrosectomy), posterior petrosal (retrolabyrinthine, translabyrinthine, transcochlear), and combined petrosal approaches. The anterior petrosal approach is best suited for upper petroclival lesions located anterior and superior to the internal auditory canal and superior to the inferior petrosal sinus. This approach provides direct access to the anteromedial cerebellopontine angle, petrous apex, Meckel cave, and ventrolateral brainstem between the trigeminal root and the facial nerve. The authors describe their modification of an anterior petrosal approach, the so-called transzygomatic extended middle fossa approach, which incorporates a zygomatic osteotomy, anterior mobilization of the V3, and extensive middle fossa drilling. This exposure provides a wider surgical corridor for direct view of the clivus and ventral brainstem.

Neuroendoscopic Trans-third Ventricle Approach for Lesions of the Ventral Brainstem Surface

Due to the establishment in recent years of neuroendoscopic third ventriculostomy (ETV), it has become possible during ETV to observe the ventral brainstem surface--particularly the prepontine cistern--in a minimally invasive manner via the third ventricular base with a neuroendoscope. As an adaptation of that technique in this study, we investigated a neuroendoscopic trans-third ventricle approach (ETTVA), which accesses lesions of the ventral brainstem surface with a neuroendoscope inserted via the stoma of the third ventricular floor. Our study included 6 cases, including one case each of neurenteric cyst, chordoma, pontine glioma (astrocytoma), ecchordosis physaliphora, endodermal cyst, and cystic schwannoma. Surgical operations performed by ETTVA included 3 cases of tumor resection, 2 cases of tumor biopsy, and 1 case of cyst puncture and aspiration. There were no complications accompanying ETTVA. Out of the 6 cases, only 1 required additional surgical treatment following ETTVA surgery. In the other 5 cases, no additional surgical procedures were performed. This study showed that ETTVA allowed access to the prepontine cistern quickly and in a minimally invasive manner. In selected cases, ETTVA can offer a new approach to these lesions.

Approaches to the Foramen Magnum

Introduction: Several surgical limitations must be noted in designing an approach to the lesions placed around the clivus. Anterior approaches include transoral and transbasal. These approaches are limited by vasa, nerves, and the risk of CSF leak. The lateral transcondylar approach provides an avenue to the lower clivus, ventral brainstem, and the structures below the internal auditory canal.

QUANTITATIVE ANALYSIS OF EXPOSURE OF STAGED ORBITOZYGOMATIC AND RETROSIGMOID CRANIOTOMIES FOR LESIONS OF THE CLIVUS WITH SUPRATENTORIAL EXTENSION

A two-stage approach using orbitozygomatic (OZ) and retrosigmoid (RS) craniotomies is one option for the management of petroclival lesions with supratentorial extension. The goal of this study was to investigate the supratentorial and infratentorial exposures of the clivus obtained through this staged approach. Formalin-fixed, silicon-injected specimens underwent stereotactic imaging. Six paired OZ and RS craniotomies were performed. Neuronavigation was used to determine the areas and limits of exposure and to plot these areas on three-dimensional reconstructions of the skull base. The mean area of exposure of the parasellar region and clivus through the OZ craniotomy was 640 +/- 75 mm. Visualization of the parasellar region, cavernous sinus, and upper cranial nerves was achieved. The ventral brainstem corresponding to the cranial quarter of the clivus was visualized. The mean area of exposure of the clivus and petrous bone through the RS was 1930 +/- 250 mm. In the cranial quarter of the clivus, there was a small region of overlap in exposure between the two craniotomies. The limits of exposure are described. OZ and RS craniotomies provide complementary exposure with limited redundancy. Significant visualization of the parasellar region, clivus, and surrounding bony landmarks is obtained. The primary limitation is exposure of the contralateral half of Zones II and III of the clivus. This strategy represents a reasonable option for accessing paracentral petroclival lesions with a supratentorial extension.

Dynamic development of the calyx of Held synapse

The calyx of Held is probably the largest synaptic terminal in the brain, forming a unique one-to-one connection in the auditory ventral brainstem. During early development, calyces have many collaterals, whose function is unknown. Using electrophysiological recordings and fast-calcium imaging in brain slices, we demonstrate that these collaterals are involved in synaptic transmission. We show evidence that the collaterals are pruned and that the pruning already begins 1 week before the onset of hearing. Using two-photon microscopy to image the calyx of Held in neonate rats, we report evidence that both axons and nascent calyces are structurally dynamic, showing the formation, elimination, extension, or retraction of up to 65% of their collaterals within 1 hour. The observed dynamic behavior of axons may add flexibility in the choice of postsynaptic partners and thereby contribute to ensuring that each principal cell eventually is contacted by a single calyx of Held.

Endoscopic transcervical odontoidectomy for pediatric basilar invagination and cranial settling

Pediatric basilar invagination and cranial settling have traditionally been approached through a transoral-transpharyngeal route with or without extended maxillotomy or mandibulotomy for resection of the anterior portion of C-1 and the odontoid. The authors hypothesize that application of a recently described endoscopic transcervical odontoidectomy (ETO) technique would allow an alternative approach for the treatment of ventral pathological entities at the craniocervical junction in pediatric patients. The authors performed ETO in a consecutive series of pediatric patients presenting with myelopathy or bulbar dysfunction resulting from basilar invagination or cranial settling. All clinical, radiographic, surgical, and follow-up data were prospectively collected. The initial experience with ETO in the pediatric population is analyzed and outcomes are reported. Three patients required ETO for basilar invagination and 1 required ETO with anterior C-1 arch and distal clivus resection for cranial settling. All patients presented with myelopathy. One patient was wheelchair bound with severe quadriparesis. The mean age was 14 +/- 3 years (mean +/- standard deviation [SD]) in the 2 male and 2 female patients. The ETO and posterior fusion were performed as a 2-stage procedure in 2 (50%) and as a single-stage procedure in 2 (50%) cases. Prolonged intubation or postoperative placement of a gastrostomy tube was not needed in any case. The postoperative hospitalization lasted 9 +/- 4 days (mean +/- SD). At last follow-up (mean 5 months), head and neck pain had resolved and motor strength had improved or stabilized in all cases. All 4 children were independently functioning and ambulatory at the last follow-up. In the authors' initial experience, ETO has allowed ventral brainstem decompression without the need for prolonged intubation, worsening dysphagia requiring enteral tube feeding, or prolonged hospitalization, and has resulted in cosmetically appealing results. The ETO technique allows an alternative approach for the treatment of ventral pathological entities at the craniocervical junction in pediatric patients.

Patterns of the Cranial Venous System from the Comparative Anatomy in Vertebrates. Part II.The Lateral-Ventral Venous System.

Comparing the adult submammalian brain with the human embryonic brain, some patterns of venous drainage are quite similar. The veins lying on the lateral surface of the brain in submammals resemble those of the human embryo. In addition, the new longitudinal venous anastomosis ventral to the brain vesicles occurring late in human embryonic development seems to be similar to the late appearance of the basal vein and the ventral brain stem venous plexus found in adult mammals including man. The evolution of the new structures of the brain vesicles throughout the vertebrate series may have an induction role on the appearance of the cranial venous system. This part of the article series focuses on the evolution of the lateral-ventral venous system of the five brain vesicles. Nevertheless, the limitation of this article is due in part to the paucity of circumstantial papers and different names used for the veins.

La pétrectomie combinée: Bases anatomiques, technique chirurgicale et indications

Management of large petroclival tumors requires the use of extensive surgical approaches that usually jeopardize the intrapetrous neuro-otologic structures. To confirm the interest of the combined petrosal approach in this indication, we describe the relevant anatomy and the surgical steps of this procedure. After making a periauricular skin incision and muscle elevation, an occipitotemporal bone flap is shaped. Then a retrolabyrinthine exposure is undertaken, with optimal skeletonization of the semicircular canals. Around the internal auditory canal, the retromeatal area and the petrous apex are resected. The retrosigmoid dura is opened followed by the incision of the subtemporal and posterior fossa dura along the superior petrosal sinus. The sinus is coagulated and divided. The tentorium is sectioned transversally toward its free edge behind the porus of the trochlear nerve. The combined petrosal approach is able to provide a wide multidirectional corridor toward the ventral surface of the pons, the basilary trunk and the ipislateral cranial nerves from the oculomotor to the lower cranial nerves. This study confirms that despite a significant extra time needed for proper achievement, the combined petrosal approach is a valuable conservative approach when the petroclival area, ventral brain stem and basilary trunk are targeted. This approach should be included in the panel of the transpetrous routes available by expert skull base teams.