Structural interhemispheric connectivity defects in mouse models of BBSOAS: Insights from high spatial resolution 3D white matter tractography.

White matter (WM) tract formation and axonal pathfinding are major processes in brain development allowing to establish precise connections between targeted structures. Disruptions in axon pathfinding and connectivity impairments will lead to neural circuitry abnormalities, often associated with various neurodevelopmental disorders (NDDs). Among several neuroimaging methodologies, Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) technique that has the advantage of visualizing in 3D the WM tractography of the whole brain non-invasively. DTI is particularly valuable in unpinning structural tract connectivity defects of neural networks in NDDs. In this study, we used 3D DTI to unveil brain-specific tract defects in two mouse models lacking the Nr2f1 gene, which mutations in patients have been proven to cause an emerging NDD, called Bosch-Boonstra-Schaaf Optic Atrophy (BBSOAS). We aimed to investigate the impact of the lack of cortical Nr2f1 function on WM morphometry and tract microstructure quantifications. We found in both mutant mice partial loss of fibers and severe misrouting of the two major cortical commissural tracts, the corpus callosum, and the anterior commissure, as well as the two major hippocampal efferent tracts, the post-commissural fornix, and the ventral hippocampal commissure. DTI tract malformations were supported by 2D histology, 3D fluorescent imaging, and behavioral analyses. We propose that these interhemispheric connectivity impairments are consistent in explaining some cognitive defects described in BBSOAS patients, particularly altered information processing between the two brain hemispheres. Finally, our results highlight 3DDTI as a relevant neuroimaging modality that can provide appropriate morphometric biomarkers for further diagnosis of BBSOAS patients.

Microglial phagolysosome dysfunction and altered neural communication amplify phenotypic severity in Prader-Willi Syndrome with larger deletion.

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of cases. Two distinct genetic subtypes of PWS deletions are characterized, where type I (PWS T1) carries four extra haploinsufficient genes compared to type II (PWS T2). PWS T1 individuals display more pronounced physiological and cognitive abnormalities than PWS T2, yet the exact neuropathological mechanisms behind these differences remain unclear. Our study employed postmortem hypothalamic tissues from PWS T1 and T2 individuals, conducting transcriptomic analyses and cell-specific protein profiling in white matter, neurons, and glial cells to unravel the cellular and molecular basis of phenotypic severity in PWS sub-genotypes. In PWS T1, key pathways for cell structure, integrity, and neuronal communication are notably diminished, while glymphatic system activity is heightened compared to PWS T2. The microglial defect in PWS T1 appears to stem from gene haploinsufficiency, as global and myeloid-specific Cyfip1 haploinsufficiency in murine models demonstrated. Our findings emphasize microglial phagolysosome dysfunction and altered neural communication as crucial contributors to the severity of PWS T1's phenotype.

Ultrasonographic imaging of the fetal hippocampus.

OBJECTIVES: The objective was to identify the fetal hippocampus and fornix using 2D and to measure the C-shaped length of fornix and hippocampus. METHODS: This study was designed in cross-section. Healthy singleton and between 18 and 24 weeks of gestation pregnant women who applied to the perinatology outpatient clinic for second-level ultrasound scanning between December 2022 and February 2023 were included in the study. Patients were screened consecutively. Demographic information of the participants was obtained and an ultrasound scan was performed. The fetal fornix-hippocampus' length and hippocampal height were measured in the sagittal section. Data were presented as mean ± standard deviation, median (min, max), or number (percent). RESULTS: A total of 92 patients were included in the study. Fetal fornix and hippocampus measurements were taken in % 97.8 (90/92) patients. The mean of the fetal fornix-hippocampus length and fetal hippocampus height of 90 patients were measured as 35.6 ± 3.0 and 4.7 ± 3.9, respectively. CONCLUSION: Fetal fornix and hippocampus can be visualized in easily with two-dimensional ultrasound during anomaly scanning in the second trimester.

Altered fornix integrity is associated with sleep apnea-related hypoxemia in mild cognitive impairment.

INTRODUCTION: The limbic system is critical for memory function and degenerates early in the Alzheimer's disease continuum. Whether obstructive sleep apnea (OSA) is associated with alterations in the limbic white matter tracts remains understudied. METHODS: Polysomnography, neurocognitive assessment, and brain magnetic resonance imaging (MRI) were performed in 126 individuals aged 55-86 years, including 70 cognitively unimpaired participants and 56 participants with mild cognitive impairment (MCI). OSA measures of interest were the apnea-hypopnea index and composite variables of sleep fragmentation and hypoxemia. Microstructural properties of the cingulum, fornix, and uncinate fasciculus were estimated using free water-corrected diffusion tensor imaging. RESULTS: Higher levels of OSA-related hypoxemia were associated with higher left fornix diffusivities only in participants with MCI. Microstructure of the other white matter tracts was not associated with OSA measures. Higher left fornix diffusivities correlated with poorer episodic verbal memory. DISCUSSION: OSA may contribute to fornix damage and memory dysfunction in MCI. HIGHLIGHTS: Sleep apnea-related hypoxemia was associated with altered fornix integrity in MCI. Altered fornix integrity correlated with poorer memory function. Sleep apnea may contribute to fornix damage and memory dysfunction in MCI.

Associations between cortical ß-amyloid burden, fornix microstructure and cognitive processing of faces, places, bodies and other visual objects in early Alzheimer's disease.

Using two imaging modalities, that is, Pittsburgh compound B (PiB) positron emission tomography (PET) and diffusion tensor imaging (DTI) the present study tested associations between cortical amyloid-beta (Aß) burden and fornix microstructural changes with cognitive deficits in early Alzheimer's disease (AD), namely deficits in working memory (1-back) processing of visual object categories (faces, places, objects, bodies and verbal material). Second, we examined cortical Aß associations with fornix microstructure. Seventeen early AD patients and 17 healthy-matched controls were included. Constrained spherical deconvolution-based tractography was used to segment the fornix and a control tract the central branch of the superior longitudinal fasciculus (CB-SLF) previously implicated in working memory processes. Standard uptake value ratios (SUVR) of Aß were extracted from 45 cortical/subcortical regions from the AAL atlas and subject to principal component analysis for data reduction. Patients exhibited (i) impairments in cognitive performance (ii) reductions in fornix fractional anisotropy (FA) and (iii) increases in a component that loaded highly on cortical Aß. There were no group differences in CB-SLF FA and in a component loading highly on subcortical Aß. Partial correlation analysis in the patient group showed (i) positive associations between fornix FA and performance for all the visual object categories and (ii) a negative association between the cortical Aß component and performance for the object categories but not for the remaining classes of visual stimuli. A subsequent analysis showed a positive association between overall cognition (performance across distinct 1-back task conditions) with fornix FA but no association with cortical Aß burden, in keeping with influential accounts on early onset AD. This indicates that the fornix degenerates early in AD and contributes to deficits in working memory processing of visual object categories; though it is also important to acknowledge the importance of prospective longitudinal studies with larger samples. Overall, the effect sizes of fornical degeneration on visual working memory appeared stronger than the ones related to amyloid burden.

A role for the fornix in temporal sequence memory.

Converging evidence from studies of human and nonhuman animals suggests that the hippocampus contributes to sequence learning by using temporal context to bind sequentially occurring items. The fornix is a white matter pathway containing the major input and output pathways of the hippocampus, including projections from medial septum and to diencephalon, striatum, lateral septum and prefrontal cortex. If the fornix meaningfully contributes to hippocampal function, then individual differences in fornix microstructure might predict sequence memory. Here, we tested this prediction by performing tractography in 51 healthy adults who had undertaken a sequence memory task. Microstructure properties of the fornix were compared with those of tracts connecting medial temporal lobe regions but not predominantly the hippocampus: the Parahippocampal Cingulum bundle (PHC) (conveying retrosplenial projections to parahippocampal cortex) and the Inferior Longitudinal Fasciculus (ILF) (conveying occipital projections to perirhinal cortex). Using principal components analysis, we combined Free-Water Elimination Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging measures obtained from multi-shell diffusion MRI into two informative indices: the first (PC1) capturing axonal packing/myelin and the second (PC2) capturing microstructural complexity. We found a significant correlation between fornix PC2 and implicit reaction-time indices of sequence memory, indicating that greater fornix microstructural complexity is associated with better sequence memory. No such relationship was found with measures from the PHC and ILF. This study highlights the importance of the fornix in aiding memory for objects within a temporal context, potentially reflecting a role in mediating inter-regional communication within an extended hippocampal system.

Brain-wide associations between white matter and age highlight the role of fornix microstructure in brain ageing.

Unveiling the details of white matter (WM) maturation throughout ageing is a fundamental question for understanding the ageing brain. In an extensive comparison of brain age predictions and age-associations of WM features from different diffusion approaches, we analyzed UK Biobank diffusion magnetic resonance imaging (dMRI) data across midlife and older age (N = 35,749, 44.6-82.8 years of age). Conventional and advanced dMRI approaches were consistent in predicting brain age. WM-age associations indicate a steady microstructure degeneration with increasing age from midlife to older ages. Brain age was estimated best when combining diffusion approaches, showing different aspects of WM contributing to brain age. Fornix was found as the central region for brain age predictions across diffusion approaches in complement to forceps minor as another important region. These regions exhibited a general pattern of positive associations with age for intra axonal water fractions, axial, radial diffusivities, and negative relationships with age for mean diffusivities, fractional anisotropy, kurtosis. We encourage the application of multiple dMRI approaches for detailed insights into WM, and the further investigation of fornix and forceps as potential biomarkers of brain age and ageing.

Deep brain stimulation of fornix in Alzheimer's disease: From basic research to clinical practice.

Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases associated with the degradation of memory and cognitive ability. Current pharmacotherapies show little therapeutic effect in AD treatment and still cannot prevent the pathological progression of AD. Deep brain stimulation (DBS) has shown to enhance memory in morbid obese, epilepsy and traumatic brain injury patients, and cognition in Parkinson's disease (PD) patients deteriorates during DBS off. Some relevant animal studies and clinical trials have been carried out to discuss the DBS treatment for AD. Reviewing the fornix trials, no unified conclusion has been reached about the clinical benefits of DBS in AD, and the dementia ratings scale has not been effectively improved in the long term. However, some patients have presented promising results, such as improved glucose metabolism, increased connectivity in cognition-related brain regions and even elevated cognitive function rating scale scores. The fornix plays an important regulatory role in memory, attention, and emotion through its complex fibre projection to cognition-related structures, making it a promising target for DBS for AD treatment. Moreover, the current stereotaxic technique and various evaluation methods have provided references for the operator to select accurate stimulation points. Related adverse events and relatively higher costs in DBS have been emphasized. In this article, we summarize and update the research progression on fornix DBS in AD and seek to provide a reliable reference for subsequent experimental studies on DBS treatment of AD.

Isolated bilateral fornix anterior columns infarction with acute amnesia and fiber tracts damage, a case report.

Isolated fornix anterior column infarction has rarely been described and is difficult to assess accurately using conventional magnetic resonance imaging (MRI). We report the case of a 75-year-old female who experienced acute anterograde amnesia. MRI performed within 24 h after amnesia onset showed an isolated infarction of the bilateral anterior columns of the fornix on diffusion-weighted imaging (DWI). Her symptoms persisted for up to 50 days, and diffusion tensor imaging (DTI) showed disruption of the fiber tracts of the fornix. when acute amnesia syndrome onset, fornix anterior column infarction should be considered, and optimized DWI and DTI methods are needed to study the fornix in vivo in future research.

The fornix supports episodic memory during childhood.

Episodic memory relies on the coordination of widespread brain regions that reconstruct spatiotemporal details of an episode. These topologically dispersed brain regions can rapidly communicate through structural pathways. Research in animal and human lesion studies implicate the fornix-the major output pathway of the hippocampus-in supporting various aspects of episodic memory. Because episodic memory undergoes marked changes in early childhood, we tested the link between the fornix and episodic memory in an age window of robust memory development (ages 4-8 years). Children were tested on the stories subtest from the Children's Memory Scale, a temporal order memory task, and a source memory task. Fornix streamlines were reconstructed using probabilistic tractography to estimate fornix microstructure. In addition, we measured fornix macrostructure and computed free water. To assess selectivity of our findings, we also reconstructed the uncinate fasciculus. Findings show that children's memory increases from ages 4 to 8 and that fornix micro- and macrostructure increases between ages 4 and 8. Children's memory performance across nearly every memory task correlated with individual differences in fornix, but not uncinate fasciculus, white matter. These findings suggest that the fornix plays an important role in supporting the development of episodic memory, and potentially semantic memory, in early childhood.

Structural Connectivity Changes After Fornix Transection in Macaques Using Probabilistic Diffusion Tractography.

The fornix, the limbic system's white matter tract connecting the extended hippocampal system to subcortical structures of the medial diencephalon, is strongly associated with learning and memory in humans and nonhuman primates (NHPs). Here, we sought to investigate alterations in structural connectivity across key cortical and subcortical regions after fornix transection in NHPs. We collected diffusion-weighted MRI (dMRI) data from three macaque monkeys that underwent bilateral fornix transection during neurosurgery and from four age- and cohort-matched control macaques that underwent surgery to implant a head-post but remained neurologically intact. dMRI data were collected from both groups at two time points, before and after the surgeries, and scans took place at around the same time for the two groups. We used probabilistic tractography and employed the number of tracking streamlines to quantify connectivity across our regions of interest (ROIs), in all dMRI sessions. In the neurologically intact monkeys, we observed high connectivity across certain ROIs, including the CA3 hippocampal subfield with the retrosplenial cortex (RSC), the anterior thalamus with the RSC, and the RSC with the anterior cingulate cortex (ACC). However, we found that, compared to the control group, the fornix-transected monkeys showed marked, significant, connectivity changes including increases between the anterior thalamus and the ACC and between the CA3 and the ACC, as well as decreases between the CA3 and the RSC. Our results highlight cortical and subcortical network changes after fornix transection and identify candidate indirect connectivity routes that may support memory functions after damage and/or neurodegeneration.

Long-term outcomes of adjustable strabismus surgery at a Pakistani university hospital.

PURPOSE: Strabismus, whether congenital or acquired, is a common visual and cosmetic problem, especially for the young. Adjustable suture strabismus surgery is not in vogue in our country. This technique gives the surgeon a second attempt to provide a better outcome for the patients. Our objective was to assess the long-term success of adjustable strabismus surgery in terms of postoperative alignment. METHODS: We carried out a prospective study utilizing the fornix approach for adjustable strabismus surgery, in mainly horizontal, but also vertical strabismus in adults and cooperative children, to enhance the postoperative outcomes. The patient characteristics, preoperative deviation, type and pattern of strabismus, were evaluated and analyzed. The postoperative alignment was evaluated at 1 year and beyond, to assess the success of this adjustable surgery. RESULTS: This study recruited 50 adults and children with a female predominance of 39 (78%); and with the mean age being 18.34 ± 9.88 years. Exotropia was the primary diagnosis in the majority with 21 (42%) cases; with purely horizontal strabismus in 23 (46%) cases. The mean preoperative horizontal deviation was 48.76 ± 20.35 prism diopters (PD) and the mean postoperative horizontal deviation was 2.73 ± 3.63 PD. The mean preoperative vertical deviation was 4.8 ± 8.54 PD whereas the mean postoperative vertical deviation was 0.86 ± 1.73 PD. The Wilcoxon Signed Ranks test analyzed the difference between the two which was statistically significant (p = 0.000). Surgical success, defined as postoperative horizontal alignment within ≤ 10 PD of orthotropia at the end of one year or more of follow-up after surgery, was achieved in 49 (98%) cases. The average follow-up was 21.47 ± 8.7 months. CONCLUSION: Adjustable strabismus surgery has very good long-term outcomes in terms of postoperative alignment and patient satisfaction.

Free water diffusion MRI and executive function with a speed component in healthy aging.

Extracellular free water (FW) increases are suggested to better provide pathophysiological information in brain aging than conventional biomarkers such as fractional anisotropy. The aim of the present study was to determine the relationship between conventional biomarkers, FW in white matter hyperintensities (WMH), FW in normal appearing white matter (NAWM) and in white matter tracts and executive functions (EF) with a speed component in elderly persons. We examined 226 healthy elderly participants (median age 69.83 years, IQR: 56.99-74.42) who underwent brain MRI and neuropsychological examination. FW in WMH and in NAWM as well as FW corrected diffusion metrics and measures derived from conventional MRI (white matter hyperintensities, brain volume, lacunes) were used in partial correlation (adjusted for age) to assess their correlation with EF with a speed component. Random forest analysis was used to assess the relative importance of these variables as determinants. Lastly, linear regression analyses of FW in white matter tracts corrected for risk factors of cognitive and white matter deterioration, were used to examine the role of specific tracts on EF with a speed component, which were then ranked with random forest regression. Partial correlation analyses revealed that almost all imaging metrics showed a significant association with EF with a speed component (r = -0.213 - 0.266). Random forest regression highlighted FW in WMH and in NAWM as most important among all diffusion and structural MRI metrics. The fornix (R2=0.421, p = 0.018) and the corpus callosum (genu (R2 = 0.418, p = 0.021), prefrontal (R2 = 0.416, p = 0.026), premotor (R2 = 0.418, p = 0.021)) were associated with EF with a speed component in tract based regression analyses and had highest variables importance. In a normal aging population FW in WMH and NAWM is more closely related to EF with a speed component than standard DTI and brain structural measures. Higher amounts of FW in the fornix and the frontal part of the corpus callosum leads to deteriorating EF with a speed component.

Diffusion imaging of fornix and interconnected limbic deep grey matter is linked to cognitive impairment in multiple sclerosis.

Diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) have shown white matter (WM) and deep grey matter (GM) abnormalities in the limbic system of multiple sclerosis (MS) participants. Structures like the fornix have been associated with cognitive impairment (CI) in MS, but the diffusion metrics are often biased by partial volume effects from cerebrospinal fluid (CSF) due to its small bundle size and intraventricular location. These errors in DTI parameter estimation worsen with atrophy in MS. The goal here was to evaluate DTI parameters and volumes of the fornix, as well as associated deep GM structures like the thalamus and hippocampus, with high-resolution fluid-attenuated inversion recovery (FLAIR)-DTI at 3T in 43 MS patients, with and without CI, versus 43 controls. The fornix, thalamus and hippocampus displayed atrophy and/or abnormal diffusion metrics, with the fornix showing the most extensive changes within the structures studied here, mainly in CI MS. The affected fornix volumes and diffusion metrics were associated with thalamic atrophy and atypical diffusion metrics in interconnected limbic GM, larger total lesion volume and global brain atrophy. Lower fractional anisotropy (FA) and higher mean and radial diffusivity in the fornix, lower hippocampus FA and lower thalamus volume were strongly correlated with CI in MS. Hippocampus FA and thalamus atrophy were negatively correlated with fatigue and longer time since MS symptoms onset, respectively. FLAIR-DTI and volumetric analyses provided methodologically superior evidence for microstructural abnormalities and extensive atrophy of the fornix and interconnected deep GM in MS that were associated with cognitive deficits.

Quantitative magnetic resonance imaging for segmentation and white matter extraction of the hypothalamus.

Since the hypothalamus is involved in many neuroendocrine, metabolic, and affective disorders, detailed hypothalamic imaging has become of major interest to better characterize disease-induced tissue damages and abnormalities. Still, image contrast of conventional anatomical magnetic resonance imaging lacks morphological detail, thus complicating complete and precise segmentation of the hypothalamus. The hypothalamus' position lateral to the third ventricle and close proximity to white matter tracts including the optic tract, fornix, and mammillothalamic tract display one of the remaining shortcomings of hypothalamic segmentation, as reliable exclusion of white matter is not yet possible. Recent studies found that quantitative magnetic resonance imaging (qMRI), a method to create maps of different standardized tissue contents, improved segmentation of cortical and subcortical brain regions. So far, this has not been tested for the hypothalamus. Therefore, in this study, we investigated the usability of qMRI and diffusion MRI for the purpose of detailed and reproducible manual segmentation of the hypothalamus and data-driven white matter extraction and compared our results to recent state-of-the-art segmentations. Our results show that qMRI presents good contrast for delineation of the hypothalamus and white matter, and that the properties of these images differ between subunits, such that they can be used to reliably exclude white matter from hypothalamic tissue. We propose that qMRI poses a useful addition to detailed hypothalamic segmentation and volumetry.

Feasibility of contrast-enhanced ultrasound and flank position during percutaneous nephrolithotomy in patients with no apparent hydronephrosis: a randomized controlled trial.

PURPOSE: To investigate the puncture accuracy and feasibility of contrast-enhanced ultrasound (CEUS) guided percutaneous nephrolithotomy (PCNL) in flank position for patients with no apparent hydronephrosis. METHODS: Between May 2018 and June 2020, 72 kidney stone patients with no or mild hydronephrosis were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided group. Patients' demographics and perioperative outcomes were compared, including the success rate of puncture via calyceal fornix, the success rate of a single-needle puncture, puncture time, operative time, postoperative hemoglobin loss, stone-free rate, incidence of complications and postoperative stay. RESULTS: The success rate of puncture via calyceal fornix for CEUS-guided group was significantly higher than that for conventional US-guided group (86.1 vs. 47.2%, p = 0.002). Patients performed with CEUS-guided PCNL required shorter renal puncture time than those guided with conventional US (36.5 s vs. 61.0 s, p < 0.001). The median postoperative hemoglobin loss in the CEUS-guided group was significantly lower than that in conventional US-guided group (2.5 vs. 14.5 g/L, p < 0.01). There was no statistically significant difference in the success rate of a single-needle puncture, operative time, stone-free rate, incidence of complications and postoperative stay between the two groups. CONCLUSION: CEUS guidance facilitates identification of the renal calyx fornix, and benefits more precise renal puncture and less hemoglobin loss in PCNL. CEUS-guided PCNL in flank position is a feasible approach to the treatment of kidney stone patients with no apparent hydronephrosis. TRIAL REGISTRATION NUMBER: ChiCTR1800015417.

Late-occurring pain/other dysfunctions in midurethral sling class actions are likely caused by uterosacral ligament weakness, not implant or surgeon.

BACKGROUND: Large sums of money have been awarded against manufacturers of midurethral slings (MUS) because of complaints of pain and other complications, even though pelvic pain is rarely seen at the 6-12 weeks review. HYPOTHESIS AND AIMS: Pain/other posterior fornix symptoms (urge, frequency, nocturia, and abnormal emptying) may appear weeks or months after MUS surgery due to dislocation of already weakened uterosacral ligaments (USL), a consequence of diversion of pelvic forces from pubourethral ligaments strengthened by the sling. METHODS: Review for prevalence, pathogenic pathway from damaged USLs to pain, OAB, emptying, and other late complications by reference to data from functional anatomy imaging, mechanical support of USLs (speculum test), and post-USL surgical repair. RESULTS: Pelvic pain and other pelvic symptoms frequently co-exist pre-operatively with SUI, but are not volunteered because patients complain of one main pelvic symptom, others being "under the surface" (Pescatori Iceberg). Late de novo occurrence of symptom complications beyond perioperative MUS surgery may occur: pain (5.7%), retention (5.4%), UTI (9.3%), and OAB (10.2%). Xray/ultrasound evidence of pelvic forces acting on USLs support the hypothesis of diversion of forces. Improvement of pain and urgency by the "speculum test" indicates USL causation, as do cure of pain and other pelvic symptoms by USL slings. CONCLUSIONS: Late-occurring PFS symptoms are the fault of neither implant, nor surgeon, but more likely consequences of pelvic forces acting on USLs already weakened by childbirth/age. Bladder/bowel/pain symptoms need to be sought out preoperatively and discussed before MUS surgery. BRIEF SUMMARY: Late MUS complications, OAB, pain, retention subject to class actions, may be caused by uterosacral dislocation from pre-existing structural weakness, not surgeon or device.

Bilateral fornix infarction presented with acute amnesia: case report.

Acute episodes of amnestic syndrome can be a challenging diagnostic problem. Except for nonvascular etiology, thalamic strokes or infarction involving several temporal lobe structures has been reported in earlier cases. The authors report a patient who suddenly developed memory loss without any other focal neurologic deficits. Brain magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) performed 1 day after onset revealed acute infarction involving the bilateral fornix column and the genu of corpus callosum. Because simple fornix infarcts often have no obvious positive neurological signs, most of the related manifestations were provided by family members, are easy to be diagnosed falsely, and missed in clinical areas, we suggest that bilateral fornix infarction should be considered in the diagnosis of an acute onset amnestic syndrome.

Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy.

OBJECTIVE: Pharmacoresistant bilateral mesial temporal lobe epilepsy often implies poor resective surgical candidacy. Low-frequency stimulation of a fiber tract connected to bilateral hippocampi, the fornicodorsocommissural tract, has been shown to be safe and efficacious in reducing seizures in a previous short-term study. Here, we report a single-blinded, within-subject control, long-term deep-brain stimulation trial of low-frequency stimulation of the fornicodorsocommissural tract in bilateral mesial temporal lobe epilepsy. Outcomes of interest included safety with respect to verbal memory scores and reduction of seizure frequency. METHODS: Our enrollment goal was 16 adult subjects to be randomized to 2-Hz or 5-Hz low-frequency stimulation of the fornicodorsocommissural tract starting at 2 mA. The study design consisted of four two-month blocks of stimulation with a 50%-duty cycle, alternating with two-month blocks of no stimulation. RESULTS: We terminated the study after enrollment of five subjects due to slow accrual. Fornicodorsocommissural tract stimulation elicited bilateral hippocampal evoked responses in all subjects. Three subjects underwent implantation of pulse generators and long-term low-frequency stimulation with mean monthly seizures of 3.14 ±â€¯2.67 (median 3.0 [IQR 1-4.0]) during stimulation-off blocks, compared with 0.96 ±â€¯1.23 (median 1.0 [IQR 0-1.0]) during stimulation-on blocks (p = 0.0005) during the blinded phase. Generalized Estimating Equations showed that low-frequency stimulation reduced monthly seizure-frequency by 0.71 per mA (p < 0.001). Verbal memory scores were stable with no psychiatric complications or other adverse events. SIGNIFICANCE: The results demonstrate feasibility of stimulating both hippocampi using a single deep-brain stimulation electrode in the fornicodorsocommissural tract, efficacy of low-frequency stimulation in reducing seizures, and safety as regards verbal memory.

The historical evolution of the fornix and its terminology: a review.

The historical evolution of the fornix has not been sufficiently reviewed in the literature. In this article, we follow this evolution from the first mention of the fornix in animal dissections of the second century AD, to the legalization of cadaver dissection in the 1300 s, to the introduction of neural staining techniques and the microscope in the seventeenth century, to today. We summarize the focus of fornix studies on memory to reveal its relationship with the hippocampus. We then cover the detection of the fornix and its neural connections noninvasively with the advancement of radiological imaging techniques. Finally, we discuss the prominence of the fornix as a target for deep brain stimulation in Alzheimer's disease and post-traumatic brain injury memory disorders.