Ventral Brainstem Research Articles

The embryonic development of hindbrain respiratory networks is unaffected by mutation of the planar polarity protein Scribble

The central command for breathing arises mainly from two interconnected rhythmogenic hindbrain networks, the parafacial respiratory group (pFRG or epF at embryonic stages) and the preBötzinger complex (preBötC), which are comprised of a limited number of neurons located in confined regions of the ventral medulla. In rodents, both networks become active toward the end of gestation but little is known about the signaling pathways involved in their anatomical and functional establishment during embryogenesis. During embryonic development, epF and preBötC neurons migrate from their territories of origin to their final positions in ventral brainstem areas. Planar Cell Polarity (PCP) signaling, including the molecule Scrib, is known to control the developmental migration of several hindbrain neuronal groups. Accordingly, a homozygous mutation of Scrib leads to severe disruption of hindbrain anatomy and function. Here, we aimed to determine whether Scrib is also involved in the prenatal development of the hindbrain nuclei controlling breathing. We combined immunostaining, calcium imaging and electrophysiological recordings of neuronal activity in isolated in vitro preparations. In the Scrib mutant, despite severe neural tube defects, epF and preBötC neurons settled at their expected hindbrain positions. Furthermore, both networks remained capable of generating rhythmically organized, respiratory-related activities and exhibited normal sensitivity to pharmacological agents known to modify respiratory circuit function. Thus Scrib is not required for the proper migration of epF and preBötC neurons during mouse embryogenesis. Our findings thus further illustrate the robustness and specificity of the developmental processes involved in the establishment of hindbrain respiratory circuits.

Analysis and interrater reliability of pB-C2 using MRI and CT: data from the Park-Reeves Syringomyelia Research Consortium on behalf of the Pediatric Craniocervical Society.

OBJECTIVE The distance to the ventral dura, perpendicular to the basion to C2 line (pB-C2), is commonly employed as a measure describing the anatomy of the craniovertebral junction. However, both the reliability among observers and the clinical utility of this measurement in the context of Chiari malformation Type I (CM-I) have been incompletely determined. METHODS Data were reviewed from the first 600 patients enrolled in the Park-Reeves Syringomyelia Research Consortium with CM-I and syringomyelia. Thirty-one cases were identified in which both CT and MRI studies were available for review. Three pediatric neurosurgeons independently determined pB-C2 values using common imaging sequences: MRI (T1-weighted and T2-weighted with and without the inclusion of retro-odontoid soft tissue) and CT. Values were compared and intraclass correlations were calculated among imaging modalities and observers. RESULTS Intraclass correlation of pB-C2 demonstrated strong agreement between observers (intraclass correlation coefficient [ICC] range 0.72-0.76). Measurement using T2-weighted MRI with the inclusion of retro-odontoid soft tissue showed no significant difference with measurement using T1-weighted MRI. Measurements using CT or T2-weighted MRI without retro-odontoid soft tissue differed by 1.6 mm (4.69 and 3.09 mm, respectively, p < 0.05) and were significantly shorter than those using the other 2 sequences. Conclusions pB-C2 can be measured reliably by multiple observers in the context of pediatric CM-I with syringomeyelia. Measurement using T2-weighted MRI excluding retro-odontoid soft tissue closely approximates the value obtained using CT, which may allow for the less frequent use of CT in this patient population. Measurement using T2-weighted MRI including retro-odontoid soft tissue or using T1-weighted MRI yields a more complete assessment of the extent of ventral brainstem compression, but its association with clinical outcomes requires further study.

Revisiting Grade 3 Diffuse Axonal Injury: Not All Brainstem Microbleeds are Prognostically Equal.

Recovery of functional independence is possible in patients with brainstem traumatic axonal injury (TAI), also referred to as "grade 3 diffuse axonal injury," but acute prognostic biomarkers are lacking. We hypothesized that the extent of dorsal brainstem TAI measured by burden of traumatic microbleeds (TMBs) correlates with 1-year functional outcome more strongly than does ventral brainstem, corpus callosal, or global brain TMB burden. Further, we hypothesized that TMBs within brainstem nuclei of the ascending arousal network (AAN) correlate with 1-year outcome. Using a prospective outcome database of patients treated for moderate-to-severe traumatic brain injury at an inpatient rehabilitation hospital, we retrospectively identified 39 patients who underwent acute gradient-recalled echo (GRE) magnetic resonance imaging (MRI). TMBs were counted on the acute GRE scans globally and in the dorsal brainstem, ventral brainstem, and corpus callosum. TMBs were also mapped onto an atlas of AAN nuclei. The primary outcome was the disability rating scale (DRS) score at 1year post-injury. Associations between regional TMBs, AAN TMB volume, and 1-year DRS score were assessed by calculating Spearman rank correlation coefficients. Mean±SD number of TMBs was: dorsal brainstem=0.7±1.4, ventral brainstem=0.2±0.6, corpus callosum=1.8±2.8, and global=14.4±12.5. The mean±SD TMB volume within AAN nuclei was 6.1±18.7mm3. Increased dorsal brainstem TMBs and larger AAN TMB volume correlated with worse 1-year outcomes (R=0.37, p=0.02, and R=0.36, p=0.02, respectively). Global, callosal, and ventral brainstem TMBs did not correlate with outcomes. These findings suggest that dorsal brainstem TAI, especially involving AAN nuclei, may have greater prognostic utility than the total number of lesions in the brain or brainstem.

Utility of the clivo-axial angle in assessing brainstem deformity: pilot study and literature review

There is growing recognition of the kyphotic clivo-axial angle (CXA) as an index of risk of brainstem deformity and craniocervical instability. This review of literature and prospective pilot study is the first to address the potential correlation between correction of the pathological CXA and postoperative clinical outcome. The CXA is a useful sentinel to alert the radiologist and surgeon to the possibility of brainstem deformity or instability. Ten adult subjects with ventral brainstem compression, radiographically manifest as a kyphotic CXA, underwent correction of deformity (normalization of the CXA) prior to fusion and occipito-cervical stabilization. The subjects were assessed preoperatively and at one, three, six, and twelve months after surgery, using established clinical metrics: the visual analog pain scale (VAS), American Spinal InjuryAssociation Impairment Scale (ASIA), Oswestry Neck Disability Index, SF 36, and Karnofsky Index. Parametric and non-parametric statistical tests were performed to correlate clinical outcome with CXA. No major complications were observed. Two patients showed pedicle screws adjacent to but not deforming the vertebral artery on post-operative CT scan. All clinical metrics showed statistically significant improvement. Mean CXA was normalized from 135.8° to 163.7°. Correction of abnormal CXA correlated with statistically significant clinical improvement in this cohort of patients. The study supports the thesis that the CXA maybe an important metric for predicting the risk of brainstem and upper spinal cord deformation. Further study is feasible and warranted.

Endoscopic endonasal approach to the ventral brainstem: anatomical feasibility and surgical limitations.

OBJECTIVE Sporadic cases of endonasal intraaxial brainstem surgery have been reported in the recent literature. The authors endeavored to assess the feasibility and limitations of endonasal endoscopic surgery for approaching lesions in the ventral portion of the brainstem. METHODS Five human cadaveric heads were used to assess the anatomy and to record various measurements. Extended transsphenoidal and transclival approaches were performed. After exposing the brainstem, white matter dissection was attempted through this endoscopic window, and additional key measurements were taken. RESULTS The rostral exposure of the brainstem was limited by the sella. The lateral limits of the exposure were the intracavernous carotid arteries at the level of the sellar floor, the intrapetrous carotid arteries at the level of the petrous apex, and the inferior petrosal sinuses toward the basion. Caudal extension necessitated partial resection of the anterior C-1 arch and the odontoid process. The midline pons and medulla were exposed in all specimens. Trigeminal nerves were barely visible without the use of angled endoscopes. Access to the peritrigeminal safe zone for gaining entry into the brainstem is medially limited by the pyramidal tract, with a mean lateral pyramidal distance (LPD) of 4.8 ± 0.8 mm. The mean interpyramidal distance was 3.6 ± 0.5 mm, and it progressively decreased toward the pontomedullary junction. The corticospinal tracts (CSTs) coursed from deep to superficial in a craniocaudal direction. The small caliber of the medulla with very superficial CSTs left no room for a safe ventral dissection. The mean pontobasilar midline index averaged at 0.44 ± 0.1. CONCLUSIONS Endoscopic endonasal approaches are best suited for pontine intraaxial tumors when they are close to the midline and strictly anterior to the CST, or for exophytic lesions. Approaching the medulla is anatomically feasible, but the superficiality of the eloquent tracts and interposed nerves limit the safe entry zones. Pituitary transposition after sellar opening is necessary to access the mesencephalon.

Image-guided transoral approach in severe craniovertebral junction malformations at the golden age of endoscopy: Regarding 2 cases

IntroductionThe image-guided transoral approach (IGTOA) provides a safe exposure to skull base midline lesions and the ventral aspect of the craniovertebral junction (CVJ). The IGTOA has several advantages: the head being placed in the extended position, it decreases the brainstem angulation during surgery; the approach being done through the avascular median pharyngeal raphe, not only lowers the bleeding risk but also provides a direct access to the bony pathology and granulation tissue accessible only via the ventral route. Wide field exposure and maneuverability are necessary to deal with the entire ventral brainstem compression in case of severe CVJ malformation to safely perform partial clivectomy and odontoidectomy. Presentation of two casesWe illustrate the cases of two patients, 52-year-old and 42-year-old males, who presented with an impressive craniovertebral junction malformation, confirmed on CT and MRI images. They first underwent surgery by IGTOA, later completed by occipitocervical fixation. For the two patients, outcomes were assessed respectively at 4 and 5 years and showed satisfactory results both clinically and radiologically. ConclusionIn patients with marked ventral compression, the IGTOA provides direct and guided access to the anterior aspect of the CVJ and effective means for odontoidectomy and clivectomy. This approach is more easily maneuverable compared to the endonasal endoscopic approach. The IGTOA approach is quite a complex technique, requiring multidisciplinary skills, but it should primarily be used in difficult situations. We suggest that endonasal endoscopy is over-utilized. We consider that endoscopy should not be routinely performed and kept only for well-selected cases.

Progress and Achievements of Endoscopic Endonasal Transsphenoidal Surgery

For the past 11 years we gained a great experience in treating over 5,000 patients by endoscopic endonasal transsphenoidal approach. The majority of patients had pituitary adenomas (p.a.) (85%). The other tumors were represented by different pathologies: craniopharyngiomas (more 500 pts), chordomas, meningiomas, gliomas, cancers, arachnoid cysts etc. Use of endoscopic technique permitted us to considerably broaden indications for transsphenoidal surgery. In particular, this approach allowed removal of p.a. with a small-size sella, adenomas with different secondary nodes, p.a. with a narrow neck between their superior and basal parts, and giant pituitary tumors (over 60 mm). Introduction of endoscopic technologies into daily practice permitted to evacuate tumors via anterior extended transsphenoidal approach which earlier could be hardly accessed by a transcranial approach: suprasellar and intraventricular craniopharyngiomas, anterior scull base meningiomas, chiasmal and III ventricular gliomas and other suprasellar tumors. Lateral extended transsphenoidal approach allows safety removal tumors invading cavernous sinus (especially when medial displacement internal carotid artery)—p.a., chordomas, trigeminal and oculomotors nerves schwannomas. Via posterior extended transsphenoidal approach is available the removal clivus chordomas invading in posterior fossae, clivus meningiomas, some ventral brainstem tumors, clipping aneurism of Basilar artery. A modified method was used for a multilayer hermetic closure using auto- and allotransplant of major postoperative skull base defects and prevention of postoperative CSF leakage.

Disembodied Mind: Cortical Changes Following Brainstem Injury in Patients with Locked-in Syndrome.

Locked-in syndrome (LIS) following ventral brainstem damage is the most severe form of motor disability. Patients are completely entrapped in an unresponsive body despite consciousness is preserved. Although the main feature of LIS is this extreme motor impairment, minor non-motor dysfunctions such as motor imagery defects and impaired emotional recognition have been reported suggesting an alteration of embodied cognition, defined as the effects that the body and its performances may have on cognitive domains. We investigated the presence of structural cortical changes in LIS, which may account for the reported cognitive dysfunctions. For this aim, magnetic resonance imaging scans were acquired in 11 patients with LIS (6 males and 5 females; mean age: 52.3±5.2SD years; mean time interval from injury to evaluation: 9±1.2SD months) and 44 healthy control subjects matching patients for age, sex and education. Freesurfer software was used to process data and to estimate cortical volumes in LIS patients as compared to healthy subjects. Results showed a selective cortical volume loss in patients involving the superior frontal gyrus, the pars opercularis and the insular cortex in the left hemisphere, and the superior and medium frontal gyrus, the pars opercularis, the insular cortex, and the superior parietal lobule in the right hemisphere. As these structures are typically associated with the mirror neuron system, which represents the neural substrate for embodied simulation processes, our results provide neuroanatomical support for potential disembodiment in LIS.

Reelin Signaling in the Migration of Ventral Brain Stem and Spinal Cord Neurons.

The extracellular matrix protein Reelin is an important orchestrator of neuronal migration during the development of the central nervous system. While its role and mechanism of action have been extensively studied and reviewed in the formation of dorsal laminar brain structures like the cerebral cortex, hippocampus, and cerebellum, its functions during the neuronal migration events that result in the nuclear organization of the ventral central nervous system are less well understood. In an attempt to delineate an underlying pattern of Reelin action in the formation of neuronal cell clusters, this review highlights the role of Reelin signaling in the migration of neuronal populations that originate in the ventral brain stem and the spinal cord.

How I do it: the combined petrosectomy.

Petroclival and ventral brain stem tumors require a complex approach. The combined petrosectomy is an epidural transtentorial-transpetrosal otoneurosurgical approach to achieve a retrolabyrinthine presigmoidal approach and an anterior petrosectomy in one single procedure. The different steps of this approach are described and illustrated by figures and a video. The indications and limitations of the technique are presented. The combined petrosectomy offers multiple corridors to the petroclival region and ventral brainstem while preserving the intrapetrous neurotological structures. Meticulous stepwise bony resection optimizing the dural opening and preservation of veins contributes to reducing the risk inherent to this technique.

AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea.

Modulation of breathing by hypoxia accommodates variations in oxygen demand and supply during, for example, sleep and ascent to altitude, but the precise molecular mechanisms of this phenomenon remain controversial. Among the genes influenced by natural selection in high-altitude populations is one for the adenosine monophosphate-activated protein kinase (AMPK) α1-catalytic subunit, which governs cell-autonomous adaptations during metabolic stress. We investigated whether AMPK-α1 and/or AMPK-α2 are required for the hypoxic ventilatory response and the mechanism of ventilatory dysfunctions arising from AMPK deficiency. We used plethysmography, electrophysiology, functional magnetic resonance imaging, and immediate early gene (c-fos) expression to assess the hypoxic ventilatory response of mice with conditional deletion of the AMPK-α1 and/or AMPK-α2 genes in catecholaminergic cells, which compose the hypoxia-responsive respiratory network from carotid body to brainstem. AMPK-α1 and AMPK-α2 deletion virtually abolished the hypoxic ventilatory response, and ventilatory depression during hypoxia was exacerbated under anesthesia. Rather than hyperventilating, mice lacking AMPK-α1 and AMPK-α2 exhibited hypoventilation and apnea during hypoxia, with the primary precipitant being loss of AMPK-α1 expression. However, the carotid bodies of AMPK-knockout mice remained exquisitely sensitive to hypoxia, contrary to the view that the hypoxic ventilatory response is determined solely by increased carotid body afferent input to the brainstem. Regardless, functional magnetic resonance imaging and c-fos expression revealed reduced activation by hypoxia of well-defined dorsal and ventral brainstem nuclei. AMPK is required to coordinate the activation by hypoxia of brainstem respiratory networks, and deficiencies in AMPK expression precipitate hypoventilation and apnea, even when carotid body afferent input is normal.

Clinical significance of changes in pB-C2 distance in patients with Chiari Type I malformations following posterior fossa decompression: a single-institution experience.

OBJECT The coexistence of Chiari malformation Type I (CM-I) and ventral brainstem compression (VBSC) has been well documented, but the change in VBSC after posterior fossa decompression (PFD) has undergone little investigation. In this study the authors evaluated VBSC in patients with CM-I and determined the change in VBSC after PFD, correlating changes in VBSC with clinical status and the need for further intervention. METHODS Patients who underwent PFD for CM-I by the senior author from November 2005 to January 2013 with complete radiological records were included in the analysis. The following data were obtained: objective measure of VBSC (pB-C2 distance); relationship of odontoid to Chamberlain's, McGregor's, McRae's, and Wackenheim's lines; clival length; foramen magnum diameter; and basal angle. Statistical analyses were performed using paired t-tests and a mixed-effects ANOVA model. RESULTS Thirty-one patients were included in the analysis. The mean age of the cohort was 10.0 years. There was a small but statistically significant increase in pB-C2 postoperatively (0.5 mm, p < 0.0001, mixed-effects ANOVA). Eleven patients had postoperative pB-C2 values greater than 9 mm. The mean distance from the odontoid tip to Wackenheim's line did not change after PFD, signifying postoperative occipitocervical stability. No patients underwent transoral odontoidectomy or occipitocervical fusion. No patients experienced clinical deterioration after PFD. CONCLUSIONS The increase in pB-C2 in patients undergoing PFD may occur as a result of releasing the posterior vector on the ventral dura, allowing it to relax posteriorly. This increase appears to be well-tolerated, and a postoperative pB-C2 measurement of more than 9 mm in light of stable craniocervical metrics and a nonworsened clinical examination does not warrant further intervention.

The importance of atlantoaxial fixation after odontoidectomy.

OBJECT Although anterior odontoidectomy has been widely accepted as a procedure for decompression of the craniovertebral junction (CVJ), postoperative biomechanical instability has not been well addressed. There is a paucity of data on the necessity for and choice of fixation. METHODS The authors conducted a retrospective review of consecutively treated patients with basilar invagination who underwent anterior odontoidectomy and various types of posterior fixation. Posterior fixation included 1 of 3 kinds of constructs: occipitocervical (OC) fusion with atlantoaxial (AA) fixation, OC fusion without AA fixation, or AA-only (without OC) fixation. On the basis of the use or nonuse of AA fixation, these patients were assigned to either the AA group, in which the posterior fixation surgery involved both the atlas and axis simultaneously, regardless of whether the patient underwent OC fusion, or the non-AA group, in which the OC fusion construct spared the atlas, axis, or both. Clinical outcomes and neurological function were compared. Radiological results at each time point (i.e., before and after odontoidectomy and after fixation) were assessed by calculating the triangular area causing ventral indentation of the brainstem in the CVJ. RESULTS Data obtained in 14 consecutively treated patients with basilar invagination were analyzed in this series; the mean follow-up time was 5.75 years. The mean age was 53.58 years; there were 7 males and 7 females. The AA and non-AA groups consisted of 7 patients each. The demographic data of both groups were similar. Overall, there was significant improvement in neurological function after the operation (p = 0.03), and there were no differences in the postoperative Nurick grades between the 2 groups (p = 1.00). According to radiological measurements, significant decompression of the ventral brainstem was achieved stepwise in both groups by anterior odontoidectomy and posterior fixation; the mean ventral triangular area improved from 3.00 ± 0.86 cm2 to 2.08 ± 0.51 cm2 to 1.68 ± 0.59 cm2 (before and after odontoidectomy and after fixation, respectively; p < 0.05). The decompression gained by odontoidectomy (i.e., reduction of the ventral triangular area) was similar in the AA and non-AA groups (0.66 ± 0.42 cm2 vs 1.17 ± 1.42 cm2, respectively; p = 0.38). However, the decompression achieved by posterior fixation was significantly greater in the AA group than in the non-AA group (0.64 ± 0.39 cm2 vs 0.17 ± 0.16 cm2, respectively; p = 0.01). CONCLUSIONS Anterior odontoidectomy alone provides significant decompression at the CVJ. Adjuvant posterior fixation further enhances the extent of decompression after the odontoidectomy. Moreover, posterior fixation that involves AA fixation yields significantly more decompression of the ventral brainstem than OC fusion that spares AA fixation.

Who is who after spinal cord injury and repair? Can the brain stem descending motor pathways take control of skilled hand motor function?

Over the last years, anatomical, electrophysiological and genetic studies have carefully dissected the pathways connecting the brain and the spinal cord. Lawrence and Kuypers (1968) described the organization of the descending motor pathways in the non-human primate spinal cord. Although there are some differences between species regarding the precise anatomical location of each spinal pathway and the selective connectivity onto spinal interneurons and motoneurons, the pattern of organization described is conserved among the mammalian spinal cord (Courtine et al., 2007). Based on their description, the major descending motor pathways are grouped depending on their anatomical origin and their terminal distribution pattern in the spinal grey matter. The motor cortex projects corticospinal axons to the spinal cord, which mostly run in the contralateral cord and innervate the mid and dorsal grey matter neurons. On the other hand, the spinal pathways originating in the brain stem are subdivided in the lateral and ventromedial systems. The ventromedial system fibers originate in the reticular formation and the vestibular complex, and terminate in the ventral and medial parts of the ventral horn grey matter. In contrast, the lateral system fibers originate in the red nucleus and preferentially terminate in the dorsal and lateral parts of the dorsal and medial grey matter (Figure 1). Together with the corticospinal fibers, the lateral brain-stem system contacts interneurons related to motorneurons of distal muscles, whereas on the other hand, the ventromedial system pathways contact interneurons related to motoneurons of proximal muscles. Functionally, the corticospinal and lateral brain stem pathways are involved in the control of distal arm and hand muscles involved in skilled forelimb movements. The ventral brainstem pathways are mostly involved in the control of the proximal musculature of the trunk and limbs involved in posture and locomotion. Behavioral and electrophysiological studies mostly performed in cats and non-human primates corroborate these anatomical findings (Lemon, 2012). Furthermore, rodents with injuries in discrete areas of the spinal cord selectively impair specific motor functions, evidencing the functional specificity of each spinal pathway and the spinal networks that they innervate (Schucht et al., 2002; Anderson et al., 2007)

Lateral transzygomatic middle fossa approach and its extensions: Surgical technique and 3D anatomy

BackgroundVarious approaches to lesions involving the middle fossa and cavernous sinus (CS), with and without posterior fossa extension have been described. In the present study, we describe the surgical technique for the extradural lateral tranzygomatic middle fossa approach and its extensions, highlight relevant 3D anatomy. MethodsSimulations of the lateral transzygomatic middle fossa approach and its extensions were performed in four silicon-injected formalin fixed cadaveric heads. The step-by-step description and relevant anatomy was documented with 3D photographs. ResultThe lateral transzygomatic middle fossa approach is particularly useful for lesions involving the middle fossa with and without CS invasion, extending to the posterior fossa and involving the clinoidal region. This approach incorporates direct lateral positioning of patient, frontotemporal craniotomy with zygomatic arch osteotomy, extradural elevation of the temporal lobe, and delamination of the outer layer of the lateral CS wall. Extradural drilling of the sphenoid wing and anterior clinoid process allows entry into the CS through the superior wall and exposure of the clinoidal segment of the ICA. Posteriorly, drilling the petrous apex allows exposure of the ventral brainstem from trigeminal to facial nerve and can be extended to the interpeduncular fossa by division of the superior petrosal sinus. ConclusionThe present study illustrates 3D anatomical relationships of the lateral transzygomatic middle fossa approach with its extensions. This approach allows wide access to different topographic areas (clinoidal region and clinoidal ICA, the entire CS, and the posterior fossa from the interpeduncular fossa to the facial nerve) via a lateral trajectory. Precise knowledge of technique and anatomy is necessary to properly execute this approach.

Transcondylar Fossa Approach for Cerebellopontine Angle and Ventral Brainstem Lesions: Microsurgical Experiences and Avoidance of Complications

To treat the large tumors located in cerebellopontine angle (CPA) and vascular pathologies including aneurysms and dissection located around the ventral brainstem, transcondylar fossa approach (TCFA) has been regarded as less invasive one. Overall 10 patients had large tumors (D> 3 cm) including schwannomas (n = 8) and meningiomas (n = 2) located in the CPA and 17 patients had vascular pathologies including vertebra-basilar artery aneurysms (n = 14) and dissection (n = 3). Anatomical aspects of the condylar fossa, occipital condyle, and adjacent neurovascular structures were evaluated preoperatively and postoperatively using a three-dimensional computed tomography and magnetic resonance imaging. Gross-total removals in tumor patients achieved without resection of the occipital condyle. In 10 patients with saccular aneurysms, the aneurysms were clipped without resection of the occipital condyle and in 4 patients, partial resection of the condyle and jugular tubercle was necessary to obtain proximal control of the vertebral artery. We met two cases with vertebral artery injury and one case with postoperative cerebrospinal fluid. Transcondylar fossa approach was less invasive technique with minimal or no resection of the occipital condyle comparing with other approaches to ventral brainstem. To avoid complications, anatomical knowledge on the joint and the condylar veins should be reviewed.

Pure Endoscopic Endonasal Odontoidectomy for Basilar Impression

Introduction: Odontoidectomy is often required to treat basilar impression with compression of the brainstem or cervical spinal cord. The transoral resection is the approach most often used. However, it is related with significant morbidity. Recently, there is a growing interest in the expanded endoscopic endonasal corridor to approach the craniocervical junction. Study Design: We present our four initial cases of pure endoscopic endonasal odontoidectomy for the treatment of basilar impression. Results: Three women and one man were treated between 47 and 70 years old. All patients presented with long-lasting history of severe gait ataxia and less frequently, neck pain, tinnitus, dysphagia, and tongue fibrillation. The procedure was divided in two operative settings (same operative time). First, it was performed the endoscopic endonasal approach, grafting of nasoseptal flap (Hadad-Bassagasteguy type), dissection of the clival region, removal of the anterior arch of C1 and the dens of C2. Afterward the patient was turned and an occipital-cervical fixation (occiput to lateral masses of C2-C3-C4) was performed. In all patients there was a substantial improvement in gait ataxia (3-year follow-up). No major morbidity or mortality was reported. Conclusion: The endoscopic approach is safe and effective to treat ventral brainstem compression due to basilar impression in comparison with the classic transoral approach.

A method to make a craniotomy on the ventral skull of neonate rodents.

The use of a craniotomy for in vivo experiments provides an opportunity to investigate the dynamics of diverse cellular processes in the mammalian brain in adulthood and during development. Although most in vivo approaches use a craniotomy to study brain regions located on the dorsal side, brainstem regions such as the pons, located on the ventral side remain relatively understudied. The main goal of this protocol is to facilitate access to ventral brainstem structures so that they can be studied in vivo using electrophysiological and imaging methods. This approach allows study of structural changes in long-range axons, patterns of electrical activity in single and ensembles of cells, and changes in blood brain barrier permeability in neonate animals. Although this protocol has been used mostly to study the auditory brainstem in neonate rats, it can easily be adapted for studies in other rodent species such as neonate mice, adult rodents and other brainstem regions.

A Method to Make a Craniotomy on the Ventral Skull of Neonate Rodents

The use of a craniotomy for in vivo experiments provides an opportunity to investigate the dynamics of diverse cellular processes in the mammalian brain in adulthood and during development. Although most in vivo approaches use a craniotomy to study brain regions located on the dorsal side, brainstem regions such as the pons, located on the ventral side remain relatively understudied. The main goal of this protocol is to facilitate access to ventral brainstem structures so that they can be studied in vivo using electrophysiological and imaging methods. This approach allows study of structural changes in long-range axons, patterns of electrical activity in single and ensembles of cells, and changes in blood brain barrier permeability in neonate animals. Although this protocol has been used mostly to study the auditory brainstem in neonate rats, it can easily be adapted for studies in other rodent species such as neonate mice, adult rodents and other brainstem regions.

Transformation of the cerebellum into more ventral brainstem fates causes cerebellar agenesis in the absence of Ptf1a function.

Model organism studies have demonstrated that cell fate specification decisions play an important role in normal brain development. Their role in human neurodevelopmental disorders, however, is poorly understood, with very few examples described. The cerebellum is an excellent system to study mechanisms of cell fate specification. Although signals from the isthmic organizer are known to specify cerebellar territory along the anterior-posterior axis of the neural tube, the mechanisms establishing the cerebellar anlage along the dorsal-ventral axis are unknown. Here we show that the gene encoding pancreatic transcription factor PTF1A, which is inactivated in human patients with cerebellar agenesis, is required to segregate the cerebellum from more ventral extracerebellar fates. Using genetic fate mapping in mice, we show that in the absence of Ptf1a, cells originating in the cerebellar ventricular zone initiate a more ventral brainstem expression program, including LIM homeobox transcription factor 1 beta and T-cell leukemia homeobox 3. Misspecified cells exit the cerebellar anlage and contribute to the adjacent brainstem or die, leading to cerebellar agenesis in Ptf1a mutants. Our data identify Ptf1a as the first gene involved in the segregation of the cerebellum from the more ventral brainstem. Further, we propose that cerebellar agenesis represents a new, dorsal-to-ventral, cell fate misspecification phenotype in humans.