Rare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer's disease.

The risk of developing Alzheimer's disease (AD) significantly increases in individuals carrying the APOEε4 allele. Elderly cognitively healthy individuals with APOEε4 also exist, suggesting the presence of cellular mechanisms that counteract the pathological effects of APOEε4; however, these mechanisms are unknown. We hypothesized that APOEε4 carriers without dementia might carry genetic variations that could protect them from developing APOEε4-mediated AD pathology. To test this, we leveraged whole-genome sequencing (WGS) data in the National Institute on Aging Alzheimer's Disease Family Based Study (NIA-AD FBS), Washington Heights/Inwood Columbia Aging Project (WHICAP), and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) cohorts and identified potentially protective variants segregating exclusively among unaffected APOEε4 carriers. In homozygous unaffected carriers above 70 years old, we identified 510 rare coding variants. Pathway analysis of the genes harboring these variants showed significant enrichment in extracellular matrix (ECM)-related processes, suggesting protective effects of functional modifications in ECM proteins. We prioritized two genes that were highly represented in the ECM-related gene ontology terms, (FN1) and collagen type VI alpha 2 chain (COL6A2) and are known to be expressed at the blood-brain barrier (BBB), for postmortem validation and in vivo functional studies. An independent analysis in a large cohort of 7185 APOEε4 homozygous carriers found that rs140926439 variant in FN1 was protective of AD (OR = 0.29; 95% CI [0.11, 0.78], P = 0.014) and delayed age at onset of disease by 3.37 years (95% CI [0.42, 6.32], P = 0.025). The FN1 and COL6A2 protein levels were increased at the BBB in APOEε4 carriers with AD. Brain expression of cognitively unaffected homozygous APOEε4 carriers had significantly lower FN1 deposition and less reactive gliosis compared to homozygous APOEε4 carriers with AD, suggesting that FN1 might be a downstream driver of APOEε4-mediated AD-related pathology and cognitive decline. To validate our findings, we used zebrafish models with loss-of-function (LOF) mutations in fn1b-the ortholog for human FN1. We found that fibronectin LOF reduced gliosis, enhanced gliovascular remodeling, and potentiated the microglial response, suggesting that pathological accumulation of FN1 could impair toxic protein clearance, which is ameliorated with FN1 LOF. Our study suggests that vascular deposition of FN1 is related to the pathogenicity of APOEε4, and LOF variants in FN1 may reduce APOEε4-related AD risk, providing novel clues to potential therapeutic interventions targeting the ECM to mitigate AD risk.

Diagnóstico de neurocisticercosis en pacientes con epilepsia residentes en el suroeste de la República Dominicana / Diagnosis of neurocysticercosis in patients with epilepsy living in the south-western Dominican Republic

Introducción La neurocisticercosis (NCC), una posible causa de epilepsia con datos epidemiológicos limitados en la República Dominicana, es endémica en cuatro provincias de la región suroeste. El objetivo de este estudio fue determinar la asociación entre la NCC y la epilepsia en personas que viven en estas regiones endémicas, así como obtener datos preliminares sobre la prevalencia de NCC en estas provincias. Sujetos y métodos Se utilizó un diseño de casos y controles compuesto por 111 pacientes con epilepsia de causa desconocida y 60 controles sin epilepsia ni NCC. El diagnóstico de NCC se basó en la tomografía computarizada y la resonancia magnética del cráneo, así como en el inmunotransferencia de Western para anticuerpos séricos contra Taenia solium, siguiendo los criterios de Del Brutto et al. Resultados Se encontró NCC en el 27% de los pacientes con epilepsia (n = 30/111) y en el 5% de los controles (n = 3/60); los casos de epilepsia tenían siete veces más probabilidades de tener NCC que los controles (odds ratio = 7,04, intervalo de confianza al 95%: 2,04-24,18; p < 0,001). Las características sociodemográficas de los participantes, como la edad, el sexo, el nivel de escolaridad, la ocupación y la provincia de residencia no mostraron significación estadística en cuanto a la asociación con NCC. Conclusiones Este estudio sugiere que la NCC está fuertemente asociada con la epilepsia en la región suroeste de la República Dominicana, y destaca la necesidad de medidas de salud pública para mejorar la prevención, el diagnóstico y el tratamiento de ambas enfermedades. (AU)

INTRODUCTION Neurocysticercosis (NCC), a possible cause of epilepsy with limited epidemiological data in the Dominican Republic, is endemic in four provinces in the country’s south-western region. This study aimed to determine the association between NCC and epilepsy among people living in these endemic regions, and to obtain preliminary data on the prevalence of NCC in these provinces. PATIENTS AND METHODS A case-control design was used, consisting of 111 patients with epilepsy with unknown causes, and 60 controls without epilepsy or NCC. The diagnosis of NCC was based on computed tomography and magnetic resonance imaging of the skull, as well as Western immunoblotting for serum antibodies using Taenia solium, following the criteria of Del Brutto et al. RESULTS NCC was found in 27% of the epileptic patients (n = 30/111) and in 5% of the controls (n = 3/60); the probability of the epileptic patients having NCC was seven times higher than the controls (odds ratio = 7.04, 95% confidence interval: 2.04-24.18; p < 0.001). The participants’ sociodemographic characteristics, including their age, sex, level of education, occupation, and province of residence presented no statistical significance in terms of their association with NCC. CONCLUSIONS This study suggests that NCC is strongly associated with epilepsy in the south-western region of the Dominican Republic, and highlights the need for public health measures to improve the prevention, diagnosis and treatment of both diseases. (AU)

Rare genetic variation in Fibronectin 1 ( FN1 ) protects against APOEe4 in Alzheimer's disease.

The risk of developing Alzheimer's disease (AD) significantly increases in individuals carrying the APOEε4 allele. Elderly cognitively healthy individuals with APOEε4 also exist, suggesting the presence of cellular mechanisms that counteract the pathological effects of APOEε4 ; however, these mechanisms are unknown. We hypothesized that APOEε4 carriers without dementia might carry genetic variations that could protect them from developing APOEε4- mediated AD pathology. To test this, we leveraged whole genome sequencing (WGS) data in National Institute on Aging Alzheimer's Disease Family Based Study (NIA-AD FBS), Washington Heights/Inwood Columbia Aging Project (WHICAP), and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) cohorts and identified potentially protective variants segregating exclusively among unaffected APOEε4 carriers. In homozygous unaffected carriers above 70 years old, we identified 510 rare coding variants. Pathway analysis of the genes harboring these variants showed significant enrichment in extracellular matrix (ECM)-related processes, suggesting protective effects of functional modifications in ECM proteins. We prioritized two genes that were highly represented in the ECM-related gene ontology terms, (FN1) and collagen type VI alpha 2 chain ( COL6A2 ) and are known to be expressed at the blood-brain barrier (BBB), for postmortem validation and in vivo functional studies. The FN1 and COL6A2 protein levels were increased at the BBB in APOEε4 carriers with AD. Brain expression of cognitively unaffected homozygous APOEε4 carriers had significantly lower FN1 deposition and less reactive gliosis compared to homozygous APOEε4 carriers with AD, suggesting that FN1 might be a downstream driver of APOEε4 -mediated AD-related pathology and cognitive decline. To validate our findings, we used zebrafish models with loss-of-function (LOF) mutations in fn1b - the ortholog for human FN1 . We found that fibronectin LOF reduced gliosis, enhanced gliovascular remodeling and potentiated the microglial response, suggesting that pathological accumulation of FN1 could impair toxic protein clearance, which is ameliorated with FN1 LOF. Our study suggests vascular deposition of FN1 is related to the pathogenicity of APOEε4 , LOF variants in FN1 may reduce APOEε4 -related AD risk, providing novel clues to potential therapeutic interventions targeting the ECM to mitigate AD risk.

Lysophosphatidylcholines are associated with P-tau181 levels in early stages of Alzheimer's Disease.

Background: We profiled circulating plasma metabolites to identify systemic biochemical changes in clinical and biomarker-assisted diagnosis of Alzheimer's disease (AD). Methods: We used an untargeted approach with liquid chromatography coupled to high-resolution mass spectrometry to measure small molecule plasma metabolites from 150 clinically diagnosed AD patients and 567 age-matched healthy elderly of Caribbean Hispanic ancestry. Plasma biomarkers of AD were measured including P-tau181, Aß40, Aß42, total-tau, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). Association of individual and co-abundant modules of metabolites were tested with clinical diagnosis of AD, as well as biologically-defined AD pathological process based on P-tau181 and other biomarker levels. Results: Over 6000 metabolomic features were measured with high accuracy. First principal component (PC) of lysophosphatidylcholines (lysoPC) that bind to or interact with docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (AHA) was associated with decreased risk of AD (OR = 0.91 [0.89-0.96], p = 2e-04). Association was restricted to individuals without an APOE ε4 allele (OR = 0.89 [0.84-0.94], p = 8.7e-05). Among individuals carrying at least one APOE ε4 allele, PC4 of lysoPCs moderately increased risk of AD (OR = 1.37 [1.16-1.6], p = 1e-04). Essential amino acids including tyrosine metabolism pathways were enriched among metabolites associated with P-tau181 levels and heparan and keratan sulfate degradation pathways were associated with Aß42/Aß40 ratio. Conclusions: Unbiased metabolic profiling can identify critical metabolites and pathways associated with ß-amyloid and phosphotau pathology. We also observed an APOE-ε4 dependent association of lysoPCs with AD and biologically based diagnostic criteria may aid in the identification of unique pathogenic mechanisms.

Lysophosphatidylcholines are associated with P-tau181 levels in early stages of Alzheimer's Disease.

Background: We investigated systemic biochemical changes in Alzheimer's disease (AD) by investigating the relationship between circulating plasma metabolites and both clinical and biomarker-assisted diagnosis of AD. Methods: We used an untargeted approach with liquid chromatography coupled to high-resolution mass spectrometry to measure exogenous and endogenous small molecule metabolites in plasma from 150 individuals clinically diagnosed with AD and 567 age-matched elderly without dementia of Caribbean Hispanic ancestry. Plasma biomarkers of AD were also measured including P-tau181, Aß40, Aß42, total tau, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). Association of individual and co-expressed modules of metabolites were tested with the clinical diagnosis of AD, as well as biologically-defined AD pathological process based on P-tau181 and other biomarker levels. Results: Over 4000 metabolomic features were measured with high accuracy. First principal component (PC) of lysophosphatidylcholines (lysoPC) that bind to or interact with docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (AHA) was associated with decreased risk of AD (OR=0.91 [0.89-0.96], p=2e-04). Restricted to individuals without an APOE ε4 allele (OR=0.89 [0.84-0.94], p= 8.7e-05), the association remained. Among individuals carrying at least one APOE ε4 allele, PC4 of lysoPCs moderately increased risk of AD (OR=1.37 [1.16-1.6], p=1e-04). Essential amino acids including tyrosine metabolism pathways were enriched among metabolites associated with P-tau181 levels and heparan and keratan sulfate degradation pathways were associated with Aß42/Aß40 ratio reflecting different pathways enriched in early and middle stages of disease. Conclusions: Our findings indicate that unbiased metabolic profiling can identify critical metabolites and pathways associated with ß-amyloid and phosphotau pathology. We also observed an APOE ε4 dependent association of lysoPCs with AD and that biologically-based diagnostic criteria may aid in the identification of unique pathogenic mechanisms.

Can Apparent Diffusion Coefficient (ADC) maps replace Diffusion Tensor Imaging (DTI) maps to predict the volumetric response of meningiomas to Gamma Knife Radiosurgery?

PURPOSE: Noninvasive methods are desired to predict the treatment response to Stereotactic Radiosurgery (SRS) to improve individual tumor management. In a previous study, we demonstrated that Diffusion Tensor Imaging (DTI)-derived parameter maps significantly correlate to SRS response. This study aimed to analyze and compare the predictive value of intratumoral ADC and DTI parameters in patients with meningiomas undergoing radiosurgery. METHODS: MR images of 70 patients treated with Gamma Knife SRS for WHO grade I meningiomas were retrospectively reviewed. MR acquisition included pre- and post-treatment DWI and DTI sequences, and subtractions were calculated to assess for radiation-induced changes in the parameter values. RESULTS: After a mean follow-up period (FUP) of 52.7 months, 69 of 70 meningiomas were controlled, with a mean volume reduction of 34.9%. Whereas fractional anisotropy (FA) values of the initial exam showed the highest correlation to tumor volume change at the last FU (CC = - 0.607), followed by the differences between first and second FU values of FA (CC = - 0.404) and the first longitudinal diffusivity (LD) value (CC = - 0.375), the correlation coefficients of all ADC values were comparably low. Nevertheless, all these correlations, except for ADC measured at the first follow-up, reached significance. CONCLUSION: For the first time, the prognostic value of ADC maps measured in meningiomas before and at first follow-up after Gamma Knife SRS, was compared to simultaneously acquired DTI parameter maps. Quantities assessed from ADC maps present significant correlations to the volumetric meningioma response but are less effective than correlations with DTI parameters.

MRI radiomics in the prediction of the volumetric response in meningiomas after gamma knife radiosurgery.

PURPOSE: This report presents the first investigation of the radiomics value in predicting the meningioma volumetric response to gamma knife radiosurgery (GKRS). METHODS: The retrospective study included 93 meningioma patients imaged by three Tesla MRI. Tumor morphology was quantified by calculating 337 shape, first- and second-order radiomic features from MRI obtained before GKRS. Analysis was performed on original 3D MR images and after their laplacian of gaussian (LoG), logarithm and exponential filtering. The prediction performance was evaluated by Pearson correlation, linear regression and ROC analysis, with meningioma volume change per month as the outcome. RESULTS: Sixty calculated features significantly correlated with the outcome. The feature selection based on LASSO and multivariate regression started from all available 337 radiomic and 12 non-radiomic features. It selected LoG-sigma-1-0-mm-3D_firstorder_InterquartileRange and logarithm_ngtdm_Busyness as the predictively most robust and non-redundant features. The radiomic score based on these two features produced an AUC = 0.81. Adding the non-radiomic karnofsky performance status (KPS) to the score has increased the AUC to 0.88. Low values of the radiomic score defined a homogeneous subgroup of 50 patients with consistent absence (0%) of tumor progression. CONCLUSION: This is the first report of a strong association between MRI radiomic features and volumetric meningioma response to radiosurgery. The clinical importance of the early and reliable prediction of meningioma responsiveness to radiosurgery is based on its potential to aid individualized therapy decision making.

FMNL2 regulates gliovascular interactions and is associated with vascular risk factors and cerebrovascular pathology in Alzheimer's disease.

Alzheimer's disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age and later and is frequently accompanied by cerebrovascular pathology at death. An interaction between CVRFs and genetic variants might explain the pathogenesis. Genome-wide, gene by CVRF interaction analyses for AD, in 6568 patients and 8101 controls identified FMNL2 (p = 6.6 × 10-7). A significant increase in FMNL2 expression was observed in the brains of patients with brain infarcts and AD pathology and was associated with amyloid and phosphorylated tau deposition. FMNL2 was also prominent in astroglia in AD among those with cerebrovascular pathology. Amyloid toxicity in zebrafish increased fmnl2a expression in astroglia with detachment of astroglial end feet from blood vessels. Knockdown of fmnl2a prevented gliovascular remodeling, reduced microglial activity and enhanced amyloidosis. APP/PS1dE9 AD mice also displayed increased Fmnl2 expression and reduced the gliovascular contacts independent of the gliotic response. Based on this work, we propose that FMNL2 regulates pathology-dependent plasticity of the blood-brain-barrier by controlling gliovascular interactions and stimulating the clearance of extracellular aggregates. Therefore, in AD cerebrovascular risk factors promote cerebrovascular pathology which in turn, interacts with FMNL2 altering the normal astroglial-vascular mechanisms underlying the clearance of amyloid and tau increasing their deposition in brain.

Cerebral and cerebellar white matter tract alterations in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN).

BACKGROUND: To examine structural connectivity of white matter tracts in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN) dystonia and identify those ones which correlate negatively to severity of symptoms. METHODS: In a group of 41 patients suffering from PKAN dystonia and an age- and gender-matched control group, white matter tractography was carried out, based on diffusion tensor imaging magnetic resonance data. Postprocessing included assessment of Quantitative Anisotropy (QA) using q-space diffeomorphic reconstruction in order to reduce influence of iron accumulation in globus pallidus of patients. RESULTS: Whole brain tractography presented significantly reduced QA values in patients (0.282 ± 0.056, as compared to controls (0.325 ± 0.046, p < 0.001). 9 fiber clusters of tracts correlated negatively to the dystonia score of patients: the middle cerebellar peduncle and the tracts of both cerebellar hemispheres as well as corpus callosum, forceps minor, the superior cortico-striate tracts and the superior thalamic radiations of both cerebral hemispheres (False Discovery Rate FDR = 0.041). CONCLUSION: The finding of a reduced global structural connectivity within the white matter and of negative correlation of motor system-related tracts, mainly those between the basal ganglia, cortical areas and the cerebellum, fits well to the concept of a general functional disturbance of the motor system in PKAN.

Progranulin mutations in clinical and neuropathological Alzheimer's disease.

INTRODUCTION: Progranulin (GRN) mutations occur in frontotemporal lobar degeneration (FTLD) and in Alzheimer's disease (AD), often with TDP-43 pathology. METHODS: We determined the frequency of rs5848 and rare, pathogenic GRN mutations in two autopsy and one family cohort. We compared Braak stage, ß-amyloid load, hyperphosphorylated tau (PHFtau) tangle density and TDP-43 pathology in GRN carriers and non-carriers. RESULTS: Pathogenic GRN mutations were more frequent in all cohorts compared to the Genome Aggregation Database (gnomAD), but there was no evidence for association with AD. Pathogenic GRN carriers had significantly higher PHFtau tangle density adjusting for age, sex and APOE ε4 genotype. AD patients with rs5848 had higher frequencies of hippocampal sclerosis and TDP-43 deposits. Twenty-two rare, pathogenic GRN variants were observed in the family cohort. DISCUSSION: GRN mutations in clinical and neuropathological AD increase the burden of tau-related brain pathology but show no specific association with ß-amyloid load or AD.

Texture Analysis of Standard Magnetic Resonance Images to Predict Response to Gamma Knife Radiosurgery in Vestibular Schwannomas.

PURPOSE: To search for texture features of routine magnetic resonance imaging to predict tumor volume reduction and transient versus permanent tumor progression of vestibular schwannomas treated by Gamma Knife stereotactic radiosurgery. MATERIALS AND METHODS: Included were 23 patients with vestibular schwannomas treated in our center and followed over a period of 23.7-80.3 months (mean 42.7). Magnetic resonance imaging was performed on a 3-Tesla scanner and included T1-weighted images with and without contrast enhancement, T2-weighted, and fluid-attenuated inversion recovery images. Volumetric results were followed longitudinally over time and correlated to texture features as mean, minimum, maximum, standard deviation, skewness, and kurtosis of normalized signals taken from regions of interest covering the total tumor volume. RESULTS: In total, 14 tumors showed early progression during the first 5-18 months (2 cases permanent, 12 cases transient), whereas 9 tumors regressed immediately after SRS. Kurtosis of T2-weighted image intensity values turned out to predict progression best with a sensitivity and specificity of 71% and 78%. From all texture feature parameters, only the minimum of the normalized T2-weighted image intensity values correlated significantly to the final reduction of tumor volume per month (correlation coefficient = -0.634, P < 0.05, corrected for false discovery rate). CONCLUSIONS: Texture feature analysis helps to predict permanent versus transient enlargement and final volume reduction of schwannomas after SRS. Thus, alternative treatment strategies might be considered, mainly in large tumors, where further clinical deterioration cannot be excluded. To confirm these results, a prospective study including more cases and a longer follow-up period is necessary.

Compression of the middle cerebellar tract by posterior fossa tumors before and after Gamma Knife radiosurgery studied with diffusion tensor imaging.

PURPOSE: To investigate if clinically asymptomatic compression of the middle cerebellar tract by extracerebral posterior fossa tumors can produce changes in diffusion tensor imaging (DTI) parameters and if these changes return to normal after Gamma Knife radiosurgery (GKRS). MATERIAL AND METHODS: In 22 patients (12 female, mean age 53.8 years) with posterior fossa tumors (14 schwannomas and 8 meningiomas), the middle cerebellar tract was tracked using DTI data. DTI parameters, such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) within these tracts were determined separately on the tumor side and on the contra-lateral side. As a surrogate parameter of tract compression, we used the distance between a tangential line extending between the anterior, not affected part of the pons and the cerebellum, and the furthest extension of the tumor into the lateral rim of the pons. In a subgroup of 15 patients, DTI parameters were recorded after a follow-up of more than 2 years (mean follow-up time 37.5 months) after GKRS and compared to initial findings. RESULTS: Before GKRS, all DTI parameters within the compressed tract had increased. The increase in MD correlated significantly with the degree of tract compression (c = 0.443, p < 0.05). Follow-up examinations after GKRS showed reduction in FA and AD, whereas MD and RD increased. After correction for time elapsed after treatment and tumor type, the changes of MD and AD following treatment correlated significantly with the reduction of tract compression, but not with radiation dose. CONCLUSION: Although without obvious clinical symptoms, disorders of the middle cerebellar tract, as in the case of posterior fossa tumors, persist after reduction of tumor size. Because of the significant correlation between the change of parameters and the reduction of tract compression, initial compression and consequent relief are regarded as the main factors responsible for persistent disorders of the middle cerebellar tract. Radiosurgery dose did not contribute significantly to changes in DTI parameters.

Adaptation of visual cortex to damage of visual pathways in suprasellar tumors before and after gamma knife radiosurgery.

PURPOSE: To demonstrate that lesions of the visual pathways due to suprasellar tumors are accompanied by alterations of the visual cortex and to see if these alterations are reversible after treatment of tumors by gamma knife radiosurgery. MATERIALS AND METHODS: In 36 patients with peri-optic tumors and defects of their visual fields and in an age-matched control group, magnetic resonance imaging was performed before and after treatment. T1 weighted images were evaluated by voxel-based morphometry and correlated to the degree of visual field defects. RESULTS: In patients, grey matter density and cortical thickness were reduced in all parts of the occipital cortex, reaching significance (p < 0.05) in the left superior and middle occipital gyri, with correlation to visual field defects. Follow-up scans showed further reduction in all occipital areas. CONCLUSION: As in other peripheral lesions of the optic system, damage of the optic pathways affects the visual cortex. A prospective follow-up study is needed to determine if these alterations are reversible after successful tumor treatment.

Pretreatment texture analysis of routine MR images and shape analysis of the diffusion tensor for prediction of volumetric response after radiosurgery for meningioma.

OBJECTIVEThe goal of this study was to identify parameters from routine T1- and T2-weighted MR sequences and diffusion tensor imaging (DTI) that best predict the volumetric changes in a meningioma after treatment with Gamma Knife radiosurgery (GKRS).METHODSIn 32 patients with meningioma, routine MRI and DTI data were measured before GKRS. A total of 78 parameters derived from first-level texture analysis of the pretreatment MR images, including calculation of the mean, SD, 2.5th and 97.5th percentiles, and kurtosis and skewness of data in histograms on a voxel-wise basis, were correlated with lesion volume change after a mean follow-up period of 3 years (range 19.5-63.3 months).RESULTSSeveral DTI-derived parameters correlated significantly with a meningioma volume change. The parameter that best predicted the results of GKRS was the 2.5th percentile value of the smallest eigenvalue (L3) of the diffusion tensor (correlation coefficient 0.739, p ≤ 0.001), whereas among the non-DTI parameters, only the SD of T2-weighted images correlated significantly with a tumor volume change (correlation coefficient 0.505, p ≤ 0.05, after correction for family-wise errors using false-detection-rate correction).CONCLUSIONSDTI-derived data had a higher correlation to shrinkage of meningioma volume after GKRS than data from T1- and T2-weighted image sequences. However, if only routine MR images are available, the SD of T2-weighted images can be used to predict control or possible progression of a meningioma after GKRS.

Inversion recovery sequences improve delineation of optic pathways in the proximity of suprasellar lesions.

INTRODUCTION: In Gamma Knife Radiosurgery (GKRS) of suprasellar lesions, the exact localization of the visual pathways is important to avoid radiation induced optic neuropathy (RION). Reliable identification of the optic nerve, chiasm and tracts can be challenging using routine magnetic resonance imaging, especially in patients with lesions compressing the optic structures or in patients who had prior operation of suprasellar tumors. This study investigates the application of inversion recovery sequences (Fast gray and white matter acquisition T1 inversion recovery, FGATIR) to improve identification of the optic pathway. METHODS: Inversion recovery sequences were performed on 5 healthy volunteers, varying their inversion times between 400 and 500 ms, and between 800 and 1100 ms. Inversion times were optimized to either suppress or to preserve the signal of the optic structures, while increasing or suppressing the signal of processes within the surrounding cisterns. Inversion recovery sequences were performed before radiosurgery on 10 patients with suprasellar tumors that were compressing or displacing the optic structures. Signal intensities of gray and white matter, of CSF and tumors were measured and subtraction images were calculated. RESULTS: Compared to a standard T1-weighted sequence, delineation of the visual pathways was superior on inversion recovery images, both on images with suppression of the optic structures as well on images with suppression of its surrounding tissues, and was rated best on subtraction images. CONCLUSION: For radiosurgery of suprasellar tumors, inversion recovery sequences can be of valuable benefit for accurate delineation of optic pathway and radiosurgical dose planning in order to avoid radiation-induced normal tissue effects.

"Spontaneous" CSF Fistula due to Transtegmental Brain Herniation in Combination with Signs of Increased Intracranial Pressure and Petrous Bone Hyperpneumatization: An Illustrative Case Report.

Background and Importance Transtegmental brain herniation into the petrous bone is a rare cause of rhinoliquorrhea. Our case presents a combination of several typical clinical and imaging findings illustrating the ongoing etiologic discussion of such cerebrospinal fluid (CSF) fistulas. Clinical Presentation A 53-year-old man presented with nasal discharge after a strong effort to suppress coughing. Imaging revealed a transtegmental herniation of parts of the inferior temporal gyrus into the petrous bone and in addition a combination of signs of chronically increased intracranial pressure and a hyperpneumatization of the petrous bone. The fistula was closed by a middle cranial fossa approach. Conclusion The case illustrates the two main predisposing factors for development of petrous bone CSF fistulas: increased intracranial pressure and thinning of the tegmental roof due to extensive development of air cells. Because the CSF leakage repair does not change the underlying cause, patients have to be informed about the possibility of developing increased intracranial pressure and recurrences of brain herniations at other sites.

Long-term follow-up in two cases of intracranial Rosai-Dorfman Disease complicated by incomplete resection and recurrence.

BACKGROUND: Although intracranial Rosai-Dorfman disease is a principally benign lymphohistiocytosis, some patients run a relapsing or progressive course. However, reports about long-term follow-up are extremely rare. CASE DESCRIPTION: In two patients, initial tumor resection was incomplete or followed by recurrences over 3 years, which finally subsided after application of chemotherapy, and patients remained tumor-free for more than 7 years thereafter. CONCLUSION: Up to now there is no agreement on how to treat complicated cases of intracranial Rosai-Dorfman disease; our good experience with adjuvant chemotherapy and long-term follow-up will contribute to treatment planning in complicated cases.