Database Review of 514 Patients with Os Odontoideum. Detailed Analysis of 258 Surgically Treated (1978-2019).

OBJECTIVE: Database review (1978-2019) is to identify the cause of os odontoideum, its presentation, associated abnormalities, and management recommendations. METHODS AND MATERIALS: Review of referral database of 514 patients and 258 surgically treated patients ages 4-64 years. Detailed history of early childhood trauma and initial encounter record retrieval were made. Patients had dynamic motion radiographs, dynamic motion MRI and also CT to identify pathology and reducibility of craniocervical instability. Preoperative crown halo traction was made before the year 2000 except in children. Intraoperative traction with O-arm/CT documentation was made since 2001. Reducible and partially reducible cases underwent halo traction under general anesthesia distraction, dorsal stabilization, and rib graft augmentation for fusion. Later semi-rigid instrumentation and subsequently rigid instrumentation was made. Irreducible compression of cervicomedullary junction was treated with ventral decompression. The follow up was 3-20 years. RESULTS: Database; acute worsening after trauma 262, insidious neurological deficit 252. Minimal/normal motion with neurological deficit was present in 18, previous C1-C2 fusion with worsening in 18. 28 patients of 64 without treatment worsened in 4 years. An intact odontoid process was seen in 52 children of 156 who had early craniovertebral junction trauma and later developed os odontoideum. SURGICAL EXPERIENCE: There were 174 patients with reducible lesions and partially reducible were 22. Irreducible lesions were 62. Of the reducible, 50 underwent transarticular C1-C2 fusion, 26 C1 lateral mass, and C2 pars screw fixation. 182 had occipitocervical fusion (19 had extension of previous C1-C2 fusion and 43 after transoral decompression). 62 with irreducible ventral compression of the cervicomedullary junction underwent transoral decompression; 43 had a trapped transverse ligament between the os and C2 body and 19 previous C1-C2 fusions. Compression was by the axis body, os odontoideum, and the posterior C2 arch. Syndromic and skeletal/connective tissue abnormalities were found in 86 (36%). COMPLICATIONS: 2 patients worsened, age 10 and 62, due to failure of semi-rigid construct. CONCLUSIONS: The etiology of os odontoideum is multifactorial considering the associated abnormalities, reports of congenital-familiar occurrence, and early childhood craniovertebral trauma which also plays a role in the etiology. Patients with reducible lesions require stabilization. Asymptomatic patients are at risk for later instability. Patients who underwent childhood C1-C2 fusion must be followed for later problems. The irreducibility was seen due to trapped transverse ligament, pannus, or previous dorsal C1-C2 fusion.

Neuromodulation with Ultrasound: Hypotheses on the Directionality of Effects and a Community Resource.

Low-intensity Transcranial Ultrasound Stimulation (TUS) is a promising non-invasive technique for deep-brain stimulation and focal neuromodulation. Research with animal models and computational modelling has raised the possibility that TUS can be biased towards enhancing or suppressing neural function. Here, we first conduct a systematic review of human TUS studies for perturbing neural function and alleviating brain disorders. We then collate a set of hypotheses on the directionality of TUS effects and conduct an initial meta-analysis on the human TUS study reported outcomes to date (n = 32 studies, 37 experiments). We find that parameters such as the duty cycle show some predictability regarding whether the targeted area's function is likely to be enhanced or suppressed. Given that human TUS sample sizes are exponentially increasing, we recognize that results can stabilize or change as further studies are reported. Therefore, we conclude by establishing an Iowa-Newcastle (inTUS) resource for the systematic reporting of TUS parameters and outcomes to support further hypothesis testing for greater precision in brain stimulation and neuromodulation with TUS.

Modern Radiation Treatment Planning Parameters and Outcomes in Pediatric Tectal Gliomas.

Purpose: Pediatric low-grade tectal gliomas are rare, indolent tumors of the brain stem. We reviewed outcomes of pediatric patients who received a diagnosis of low-grade tectal gliomas and report dosimetric parameters for those receiving radiation therapy (RT). Methods and Materials: We retrospectively reviewed all pediatric patients (age <18 years) at our institution diagnosed with a low-grade glioma between 1993 and 2020 (n = 288). Twenty-three patients with tectal gliomas were identified. Patients who received RT (n = 8) had detailed dosimetric analyses performed. Doses to critical structures and any resulting toxicities were reviewed. Minimum follow-up was 2 years and complete follow-up was available for all patients. Results: Twenty-three patients, with a median age of 8.9 years, were included (range, 0.5-16.2 years). At a median follow-up of 7.4 years (range, 2-24 years), all were alive at the end of the study period. Three patients (13%) were treated with upfront RT; none of these patients developed local failure (LF) after a median follow-up of 10.6 years. One patient was treated with upfront chemotherapy with no evidence of progression afterward. Nineteen patients were initially observed after diagnosis and 26% of them (n = 5) experienced local progression. All 5 were treated with salvage RT, with 1 patient requiring further treatment with chemotherapy. Fractionation schedules for patients undergoing upfront or salvage RT included 50.4 Gy in 28 fractions (n = 4), 54 Gy in 30 fractions (n = 2), and 51 Gy in 30 fractions (n = 2). For patients treated after 2007, the gross tumor volume was delineated on a T2 magnetic resonance imaging with an average gross tumor volume-to-planning target volume expansion of 4.5 mm (range, 3-5 mm). Detailed dosimetric parameters were available for all patients treated with RT. Conclusions: Our review supports the indolent behavior for most tectal gliomas. For the subset of tumors with evidence of progression, modern photon RT results in excellent oncologic outcomes with minimal late effects.

The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF). METHODS: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio. RESULTS: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95). CONCLUSIONS: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

Rare variant of large pediatric glioneuronal tumor with novel MYO5A::NTRK3 fusion: illustrative case.

BACKGROUND: Glioneuronal tumors (GNTs) comprise a rare class of central nervous system (CNS) neoplasms with varying degrees of neuronal and glial differentiation that predominately affect children and young adults. Within the current 2021 World Health Organization (WHO) classification of CNS tumors, GNTs encompass 14 distinct tumor types. Recently, the use of whole-genome DNA methylation profiling has allowed more precise classification of this tumor group. OBSERVATIONS: A 3-year-old male presented with a 3-month history of increasing head circumference, regression of developmental milestones, and speech delay. Magnetic resonance imaging of the brain was notable for a large left hemispheric multiseptated mass with significant mass effect and midline shift that was treated with near-total resection. Histological and molecular assessment demonstrated a glioneuronal tumor harboring an MYO5A::NTRK3 fusion. By DNA methylation profiling, this tumor matched to a provisional methylation class known as "glioneuronal tumor kinase-fused" (GNT kinase-fused). The patient was later started on targeted therapy with larotrectinib. LESSONS: This is the first report of an MYO5A::NTRK3 fusion in a pediatric GNT. GNT kinase-fused is a provisional methylation class not currently included in the WHO classification of CNS tumors. This case highlights the impact of thorough molecular characterization of CNS tumors, especially with the increasing availability of novel gene targeting therapies.

Coronavirus disease 2019-associated persistent cough and Chiari malformation type I resulting in acute respiratory failure: illustrative case.

BACKGROUND: Chiari malformation type I (CM-I) is the herniation of cerebellar tonsils through the foramen magnum, potentially resulting in the obstruction of cerebrospinal fluid flow and brainstem compression. Sleep-disordered breathing (SDB) is common in patients with CM-I, and symptomatic exacerbations have been described after Valsalva-inducing stressors. Acute decompensation in the setting of coronavirus disease 2019 (COVID-19) has not been described. OBSERVATIONS: After violent coughing episodes associated with COVID-19 infection, a 44-year-old female developed several months of Valsalva-induced occipital headaches, episodic bulbar symptoms, and worsening SDB, which led to acute respiratory failure requiring mechanical ventilation. Imaging demonstrated 12 mm of cerebellar tonsillar descent below the foramen magnum, dorsal brainstem compression, and syringobulbia within the dorsal medulla. She underwent posterior fossa and intradural decompression with near-complete resolution of her symptoms 6 months postoperatively. LESSONS: Although CM-I can remain asymptomatic, Valsalva-inducing stressors, including COVID-19 infection, can initiate or acutely exacerbate symptoms, placing patients at risk for CM-I-associated brainstem dysfunction and, in rare cases, acute respiratory failure. Worsening Valsalva maneuvers can contribute to further cerebellar tonsil impaction, brainstem compression, syringomyelia/syringobulbia, and worsening CM-I intradural pathology. Ventilator support and timely decompressive surgery are paramount, as brainstem compression can reduce central respiratory drive, placing patients at risk for coma, neurological deficits, and/or death.

Failure to breathe persists without air hunger or alarm following amygdala seizures.

Postictal apnea is thought to be a major cause of sudden unexpected death in epilepsy (SUDEP). However, the mechanisms underlying postictal apnea are unknown. To understand causes of postictal apnea, we used a multimodal approach to study brain mechanisms of breathing control in 20 patients (ranging from pediatric to adult) undergoing intracranial electroencephalography for intractable epilepsy. Our results indicate that amygdala seizures can cause postictal apnea. Moreover, we identified a distinct region within the amygdala where electrical stimulation was sufficient to reproduce prolonged breathing loss persisting well beyond the end of stimulation. The persistent apnea was resistant to rising CO2 levels, and air hunger failed to occur, suggesting impaired CO2 chemosensitivity. Using es-fMRI, a potentially novel approach combining electrical stimulation with functional MRI, we found that amygdala stimulation altered blood oxygen level-dependent (BOLD) activity in the pons/medulla and ventral insula. Together, these findings suggest that seizure activity in a focal subregion of the amygdala is sufficient to suppress breathing and air hunger for prolonged periods of time in the postictal period, likely via brainstem and insula sites involved in chemosensation and interoception. They further provide insights into SUDEP, may help identify those at greatest risk, and may lead to treatments to prevent SUDEP.

Pediatric brainstem abscess successfully treated with stereotactic aspiration: illustrative case.

BACKGROUND: Pediatric brainstem abscesses are rare entities that account for 1% of all brain abscesses and, when diagnosed, constitute a neurosurgical emergency. OBSERVATIONS: A previously healthy 11-year-old male presented with several days of worsening headache, confusion, and ataxia. Brain magnetic resonance imaging (MRI) revealed a midbrain and pons lesion. The patient subsequently had a rapid neurological decline with loss of consciousness and brainstem function. Follow-up MRI revealed significant enlargement of the brainstem lesion with extension into the pons, midbrain, and thalamus, with greater concerns for an abscess rather than a tumor or an inflammatory process. He was taken for an emergent stereotactic aspiration of the abscess, and broad-spectrum antibiotics were initiated. He had neurological improvement, which subsequently declined 5 days later with brain MRI revealing an increase in the brainstem abscess, which required a second stereotactic aspiration. After rehabilitation, he made a significant neurological recovery. LESSONS: Pediatric brainstem abscesses are rare pathologies, and a high index of suspicion is needed in patients presenting with a brainstem lesion mimicking tumor but with rapid neurological decline despite no other evidence of infection or infectious/inflammatory markers. Stereotactic aspiration is required for large lesions to target the antibiotic treatment and as an adjunct to broad-spectrum antibiotics.

Ventriculus terminalis cyst in an infant: a case report.

BACKGROUND: Filar cysts are frequently found on neonatal ultrasound and are physiologically involuting structures with natural resolution. Hence, there has been no previous histologic correlation. Ventriculus terminalis is a focal central canal dilation in the conus medullaris and usually not clinically significant. Extra-axial cyst at the conus-filum junction connected to ventriculus terminalis is extremely rare, especially when associated with tethered lipomatous filum terminale and with progressive cyst enlargement. CASE PRESENTATION: A Caucasian female neonate with abnormal gluteal cleft had ventriculus terminalis cyst with an extra-axial cyst at the conus-filar junction and taut lipomatous filum on ultrasound examination and magnetic resonance imaging. This persisted at 6-month follow up imaging. In light of the nonresolving extra-axial mass and thick taut lipomatous filum, the child underwent L1-L3 osteoplastic laminectomies. The extra-axial cyst expanded after bony decompression and furthermore on dural opening; visualized on ultrasound. It communicated with the central canal and was documented with intraoperative photomicrographs. It was excised and filum sectioned. Histological immunostaining of the cyst wall showed neuroglial and axonal elements. The child did well without deficits at 4-year follow up with normal urodynamics. CONCLUSION: Progression dilation of ventriculus terminalis and extra-axial conofilar cyst with tethered lipomatous filum will likely progress to clinical significance and require surgical intervention. The embryologic basis for this pathology is discussed, with literature review.

Extended External Rhinoplasty Approach For Nasal Dermoids With Intracranial Extension.

We present an extended external rhinoplasty approach with bilateral marginal and alar base incisions for removal of a nasal dermoid cyst with intracranial extension in a 3-year-old patient. This approach provides adequate exposure, enables nasal bone osteotomies, and allows access to the skull base while achieving a cosmetically acceptable scar. Laryngoscope, 133:2798-2802, 2023.

Intoxicating effects of alcohol depend on acid-sensing ion channels.

Persons at risk for developing alcohol use disorder (AUD) differ in their sensitivity to acute alcohol intoxication. Alcohol effects are complex and thought to depend on multiple mechanisms. Here, we explored whether acid-sensing ion channels (ASICs) might play a role. We tested ASIC function in transfected CHO cells and amygdala principal neurons, and found alcohol potentiated currents mediated by ASIC1A homomeric channels, but not ASIC1A/2 A heteromeric channels. Supporting a role for ASIC1A in the intoxicating effects of alcohol in vivo, we observed marked alcohol-induced changes on local field potentials in basolateral amygdala, which differed significantly in Asic1a-/- mice, particularly in the gamma, delta, and theta frequency ranges. Altered electrophysiological responses to alcohol in mice lacking ASIC1A, were accompanied by changes in multiple behavioral measures. Alcohol administration during amygdala-dependent fear conditioning dramatically diminished context and cue-evoked memory on subsequent days after the alcohol had cleared. There was a significant alcohol by genotype interaction. Context- and cue-evoked memory were notably worse in Asic1a-/- mice. We further examined acute stimulating and sedating effects of alcohol on locomotor activity, loss of righting reflex, and in an acute intoxication severity scale. We found loss of ASIC1A increased the stimulating effects of alcohol and reduced the sedating effects compared to wild-type mice, despite similar blood alcohol levels. Together these observations suggest a novel role for ASIC1A in the acute intoxicating effects of alcohol in mice. They further suggest that ASICs might contribute to intoxicating effects of alcohol and AUD in humans.

Management of Ventral Brainstem Compression in Chiari Malformation Type I.

Craniovertebral junction (CVJ) abnormalities are associated with the Chiari malformation type I. These abnormalities may lead to ventral brainstem compression which can be reduced with traction and posterior reduction using instrumentation. In other cases, the irreducible CVJ pathology with persistent ventral brainstem compression requires ventral decompression. In all cases, a posterior extradural or extra-intradural decompression is required along with an occipitocervical fusion to maintain the reduced and realigned CVJ or stabilize the CVJ after a ventral decompression.

Human Brainstem and Cerebellum Atlas: Chemoarchitecture and Cytoarchitecture Paired to MRI.

Lesion localization is the basis for understanding neurologic disease, which is predicated on neuroanatomical knowledge carefully cataloged from histology and imaging atlases. However, it is often difficult to correlate clinical images of brainstem injury obtained by MRI scans with the details of human brainstem neuroanatomy represented in atlases, which are mostly based on cytoarchitecture using Nissl stain or a single histochemical stain, and usually do not include the cerebellum. Here, we report a high-resolution (200 µm) 7T MRI of a cadaveric male human brainstem and cerebellum paired with detailed, coregistered histology (at 2 µm single-cell resolution) of the immunohistochemically stained cholinergic, serotonergic, and catecholaminergic (dopaminergic, noradrenergic, and adrenergic) neurons, in relationship to each other and to the cerebellum. These immunohistochemical findings provide novel insights into the spatial relationships of brainstem cell types and nuclei, including subpopulations of melanin and TH+ neurons, and allows for more informed structural annotation of cell groups. Moreover, the coregistered MRI-paired histology helps validate imaging findings. This is useful for interpreting both scans and histology, and to understand the cell types affected by lesions. Our detailed chemoarchitecture and cytoarchitecture with corresponding high-resolution MRI builds on previous atlases of the human brainstem and cerebellum, and makes precise identification of brainstem and cerebellar cell groups involved in clinical lesions accessible for both laboratory scientists and clinicians alike.SIGNIFICANCE STATEMENT Clinicians and neuroscientists frequently use cross-sectional anatomy of the human brainstem from MRI scans for both clinical and laboratory investigations, but they must rely on brain atlases to neuroanatomical structures. Such atlases generally lack both detail of brainstem chemical cell types, and the cerebellum, which provides an important spatial reference. Our current atlas maps the distribution of key brainstem cell types (cholinergic, serotonergic, and catecholaminergic neurons) in relationship to each other and the cerebellum, and pairs this histology with 7T MR images from the identical brain. This atlas allows correlation of the chemoarchitecture with corresponding MRI, and makes the identification of cell groups that are often discussed, but rarely identifiable on MRI scan, accessible to clinicians and clinical researchers.

Mapping effective connectivity of human amygdala subdivisions with intracranial stimulation.

The primate amygdala is a complex consisting of over a dozen nuclei that have been implicated in a host of cognitive functions, individual differences, and psychiatric illnesses. These functions are implemented through distinct connectivity profiles, which have been documented in animals but remain largely unknown in humans. Here we present results from 25 neurosurgical patients who had concurrent electrical stimulation of the amygdala with intracranial electroencephalography (electrical stimulation tract-tracing; es-TT), or fMRI (electrical stimulation fMRI; es-fMRI), methods providing strong inferences about effective connectivity of amygdala subdivisions with the rest of the brain. We quantified functional connectivity with medial and lateral amygdala, the temporal order of these connections on the timescale of milliseconds, and also detail second-order effective connectivity among the key nodes. These findings provide a uniquely detailed characterization of human amygdala functional connectivity that will inform functional neuroimaging studies in healthy and clinical populations.

Complications and outcomes of posterior fossa decompression with duraplasty versus without duraplasty for pediatric patients with Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

Endoscopic-assisted surgical approach for butterfly glioma surgery.

PURPOSE: Gliomas that spread along the white matter tracts of the corpus callosum to both hemispheres have traditionally been considered surgically challenging largely due to the relative complexity of safely achieving complete resections. We present a series of endoscopic-assisted resections of butterfly gliomas with post-operative radiological assessment of EOR and clinical outcome data. METHODS: Retrospective review of patients who underwent surgical resection of a butterfly glioma from 2007 to 2020. Butterfly gliomas were defined as gliomas, which appeared to arise from the corpus callosum with significant bilateral extension. All records were retrospectively reviewed with operative/clinical outcomes and complications recorded. RESULTS: 70 patients who underwent an endoscopic-assisted transcortical or interhemispheric approach for butterfly glioma resection met inclusion criteria. A unilateral transcortical approach was used in 86% of cases and an interhemispheric approach in 14%. The endoscope enhanced the visualization of the contralateral hemisphere and allowed for resection of tumor, not reached by standard microscopic visualization, in 100% of cases. 90% of resections resulted in greater than a 95% resection rate. Neurological deficits mostly consisted of motor (10%) and memory (6%) deficits and were most common with posterior tumors of the splenium. CONCLUSION: The endoscopic-assisted transcortical or interhemispheric approach for butterfly glioma resection is effective in achieving a greater than 95% resection with minimal complications. An angled approach allows careful maneuvering around complex anatomic structures and difficult corners, and should be examined further for its clinical benefits in a prospective manner.

Post-acquisition CO2 Inhalation Enhances Fear Memory and Depends on ASIC1A.

A growing body of evidence suggests that memories of fearful events may be altered after initial acquisition or learning. Although much of this work has been done in rodents using Pavlovian fear conditioning, it may have important implications for fear memories in humans such as in post-traumatic stress disorder (PTSD). A recent study suggested that cued fear memories, made labile by memory retrieval, were made additionally labile and thus more vulnerable to subsequent modification when mice inhaled 10% carbon dioxide (CO2) during retrieval. In light of this finding, we hypothesized that 10% CO2 inhalation soon after fear acquisition might affect memory recall 24 h later. We found that both cue and context fear memory were increased by CO2 exposure after fear acquisition. The effect of CO2 was time-dependent, as CO2 inhalation administered 1 or 4 h after cued fear acquisition increased fear memory, whereas CO2 inhalation 4 h before or 24 h after cued fear acquisition did not increase fear memory. The ability of CO2 exposure following acquisition to enhance fear memory was not a general consequence of stress, as restraining mice after acquisition did not alter cued fear memory. The memory-enhancing action of CO2 may be relatively specific to fear conditioning as novel object recognition was impaired by post-training CO2 inhalation. To explore the molecular underpinnings of these effects, we tested if they depended on the acid-sensing ion channel-1a (ASIC1A), a proton-gated cation channel that mediates other effects of CO2, likely via its ability to sense acidosis induced during CO2 inhalation. We found that CO2 inhalation did not alter cued or context fear memory in Asic1a-/- mice, suggesting that this phenomenon critically depends on ASIC1A. These results suggest that brain acidosis around the time of a traumatic event may enhance memory of the trauma, and may thus constitute an important risk factor for developing PTSD. Moreover, preventing peritraumatic acidosis might reduce risk of PTSD.

Cognitive and Psychological Functioning in Chiari Malformation Type I Before and After Surgical Decompression - A Prospective Cohort Study.

BACKGROUND: Chiari Malformation Type I (CM-I) is defined as cerebellar tonsil displacement more than 5 mm below the foramen magnum. This displacement can alter cerebrospinal fluid flow at the cervicomedullary junction resulting in Valsalva-induced headaches and syringomyelia and compress the brainstem resulting in bulbar symptoms. However, little is known about cognitive and psychological changes in CM-I. OBJECTIVE: To prospectively assess cognitive and psychological performance in CM-I and determine whether changes occur after surgical decompression. METHODS: Blinded evaluators assessed symptomatic CM-I patients ages ≥18 with a battery of neuropsychological and psychological tests. Testing was conducted preoperatively and 6 to 18 mo postoperatively. Data were converted to Z-scores based on normative data, and t-tests were used to analyze pre-post changes. RESULTS: A total of 26 patients were included, with 19 completing both pre- and post-op cognitive assessments. All patients had resolution of Valsalva-induced headaches and there was improvement in swallowing dysfunction (P < .0001), ataxia (P = .008), and sleep apnea (P = .021). Baseline performances in visual perception and construction (z = -1.11, P = .001) and visuospatial memory (z = -0.93, P = .002) were below average. Pre-post comparisons showed that CM-I patients had stable cognitive and psychological functioning after surgery, without significant changes from preoperative levels. CONCLUSION: CM-I patients had below average performance in visuospatial and visuoconstructional abilities preoperatively. Prospective longitudinal data following surgery demonstrated improved neurologic status without any decline in cognition or psychological functioning. Routine pre- and postoperative formal neuropsychological assessment in CM-I patients help quantify cognitive and behavioral changes associated with surgical decompression.