Conventional and advanced imaging throughout the cycle of care of gliomas.

Although imaging of gliomas has evolved tremendously over the last decades, published techniques and protocols are not always implemented into clinical practice. Furthermore, most of the published literature focuses on specific timepoints in glioma management. This article reviews the current literature on conventional and advanced imaging techniques and chronologically outlines their practical relevance for the clinical management of gliomas throughout the cycle of care. Relevant articles were located through the Pubmed/Medline database and included in this review. Interpretation of conventional and advanced imaging techniques is crucial along the entire process of glioma care, from diagnosis to follow-up. In addition to the described currently existing techniques, we expect deep learning or machine learning approaches to assist each step of glioma management through tumor segmentation, radiogenomics, prognostication, and characterization of pseudoprogression. Thorough knowledge of the specific performance, possibilities, and limitations of each imaging modality is key for their adequate use in glioma management.

The debate on apraxia and the supplementary motor area in the twentieth century.

Hand function and apraxia are equally relevant to neurosurgeons: as a symptom, as well as through the functional anatomy of "praxis" which underlies the dexterity needed for neurosurgical practice. The supplementary motor area is crucial for its understanding. Historically, Hugo Liepmann dominated the apraxia debate at the beginning of the twentieth century, a debate that has remained influential until today. Kurt Goldstein, a contemporary of Liepmann, is regularly mentioned as the first to have described the alien hand syndrome in 1909. Wilder Penfield was a key figure in exploring the role of the fronto-mesial cortex in human motor control and coined the term "supplementary motor area". It was Goldstein who not only contributed substantially to the apraxia debate more than 100 years ago; he also established the link between the dysfunction of the fronto-mesial cortex and abnormal higher motor control in humans.

MKP1 phosphatase is recruited by CXCL12 in glioblastoma cells and plays a role in DNA strand breaks repair.

Glioblastoma (GBM) is the most frequent and aggressive primary tumor in the central nervous system. Previously, the secretion of CXCL12 in the brain subventricular zones has been shown to attract GBM cells and protect against irradiation. However, the exact molecular mechanism behind this radioprotection is still unknown. Here, we demonstrate that CXCL12 modulates the phosphorylation of MAP kinases and their regulator, the nuclear MAP kinase phosphatase 1 (MKP1). We further show that MKP1 is able to decrease GBM cell death and promote DNA repair after irradiation by regulating major apoptotic players, such as Jun-N-terminal kinase, and by stabilizing the DNA repair protein RAD51. Increases in MKP1 levels caused by different corticoid treatments should be reexamined for GBM patients, particularly during their radiotherapy sessions, in order to prevent or to delay the relapses of this tumor.

Neurologists, neurosurgeons, and psychiatrists' personality traits: a comparison.

BACKGROUND: Clinicians in neuroscientific disciplines may present distinct personality profiles. Despite of potential relevance to clinical practice, this has not yet been studied. We therefore aimed to compare personality profiles of physicians working in the three main disciplines of clinical neuroscience, i.e., neurologists, neurosurgeons, and psychiatrists, between each other, across levels of training and to other specialties. METHODS: An online survey using the Ten-Item Personality Inventory (TIPI), an internationally validated measure of the five-factor model of personality dimensions, was distributed to board-certified physicians, residents, and medical students in several European countries and Canada. Differences in personality profiles were analyzed using multivariate analysis of variance and canonical linear discriminant analysis on age- and sex-standardized z-scores of personality traits. Single personality traits were analyzed using robust t tests. RESULTS: Of the 5148 respondents who completed the survey, 723 indicated the specialties neurology, neurosurgery, or psychiatry. Compared to all other specialties, personality profiles of training and trained physicians in these three main clinical neuroscience disciplines ("NN&P") significantly differed, with significantly higher scores in openness to experience. Within NN&P, there were significant differences in personality profiles, driven by lower neuroticism in neurosurgeons, higher conscientiousness in neurosurgeons and neurologists, and higher agreeableness in psychiatrists. Across levels of training, NN&P personality profiles did not differ significantly. CONCLUSION: The distinct clinical neuroscience personality profile is characterized by higher levels of openness to experience compared to non-neuroscience specialties. Despite high variability within each discipline, moderate, but solid differences in the personality profiles of neurologists, neurosurgeons and psychiatrists exist.

Age related metabolic modifications in the migraine brain.

PURPOSE: The aim of this study was to evaluate the possibility that migraine patients exhibit specific age-related metabolic changes in the brain, which occur regardless of disease duration or the frequency of attacks. METHODS: We analysed the relation between brain glucose (18F-fluorodeoxyglucose) uptake and age in healthy volunteers (n = 20) and episodic migraine patients (n = 19). In the latter, we additionally compared the correlation between 18F-fluorodeoxyglucose uptake and disease duration and monthly migraine days. RESULTS: In contrast to controls, in migraine patients advancing age was positively correlated to increased metabolism in the brainstem (especially the posterior pons), hippocampus, fusiform gyrus and parahippocampus. Conversely, no significant correlations between cerebral metabolism and disease duration or migraine days were observed. CONCLUSIONS: Findings of this cross-sectional study show that episodic migraine patients exhibit specific metabolic brain modifications while ageing. As such, age is correlated with metabolic changes in key regions of the brain previously associated with migraine's pathophysiology to a better extent than disease duration or the number of monthly migraine days. More than the repeated headache attacks, the continuous interaction with the environment seemingly models the brain of migraine sufferers in an adaptive manner. A positive control (e.g. chronic pain) is missing in this study and therefore findings cannot be proven to be migraine-specific.

Evidence of an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients: a study comparing 18FDG-PET and visual evoked potentials.

BACKGROUND: Migraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but this functional abnormality may not be sufficient to disrupt the physiological equilibrium of the cortex unless it is accompanied by additional pathological mechanisms, like a reduction in energetic reserves. The aim of this study was to compare resting cerebral glucose uptake (using positron emission tomography (18fluorodeoxyglucose-PET)), and visual cortex activation (using visual evoked potentials (VEP)), between episodic migraine without aura patients in the interictal period and healthy volunteers. METHODS: Twenty episodic migraine without aura patients and twenty healthy volunteers were studied. 18FDG-PET and VEP recordings were performed on separate days. The overall glucose uptake in the visual cortex-to-VEP response ratio was calculated and compared between the groups. Additionally, PET scan comparisons adding area under the VEP curve as a covariate were performed. For case-wise analysis, eigenvalues from a specific region exhibiting significantly different FDG-PET signal in the visual cortex were extracted. Standardized glucose uptake values from this region and VEP values from each subject were then coupled and compared between the groups. RESULTS: The mean area under the curve of VEP was greater in migraine patients compared to healthy controls. In the same line, patients had an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex. Statistical parametric mapping analysis revealed that cortical FDG-PET signal in relation to VEP area under the curve was significantly reduced in migraineurs in a cluster extending throughout the left visual cortex, from Brodmann's areas 19 and 18 to area 7. Within this region, case-wise analyses showed that a visual neuronal activation exceeding glucose uptake was present in 90% of migraine patients, but in only 15% of healthy volunteers. CONCLUSION: This study identifies an area of increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients between attacks. Such observation supports the concept that an activity-induced rupture of cerebral metabolic homeostasis may be a cornerstone of migraine pathophysiology. This article has been selected as the winner of the 2018 Enrico Greppi Award. The Enrico Greppi Award is made to an unpublished paper dealing with clinical, epidemiological, genetic, pathophysiological or therapeutic aspects of headache. Italian Society for the Study of Headaches (SISC) sponsors this award, and the award is supported through an educational grant from Teva Neuroscience. This article did not undergo the standard peer review process for The Journal of Headache and Pain. The members of the 2018 Enrico Greppi Award Selection Committee were: Francesco Pierelli, Paolo Martelletti, Lyn Griffiths, Simona Sacco, Andreas Straube and Cenk Ayata.

Surgical clipping or endovascular coiling for unruptured intracranial aneurysms: a pragmatic randomised trial.

BACKGROUND: Unruptured intracranial aneurysms (UIAs) are increasingly diagnosed and are commonly treated using endovascular treatment or microsurgical clipping. The safety and efficacy of treatments have not been compared in a randomised trial. How to treat patients with UIAs suitable for both options remains unknown. METHODS: We randomly allocated clipping or coiling to patients with one or more 3-25 mm UIAs judged treatable both ways. The primary outcome was treatment failure, defined as: initial failure of aneurysm treatment, intracranial haemorrhage or residual aneurysm on 1-year imaging. Secondary outcomes included neurological deficits following treatment, hospitalisation >5 days, overall morbidity and mortality and angiographic results at 1 year. RESULTS: The trial was designed to include 260 patients. An analysis was performed for slow accrual: 136 patients were enrolled from 2010 through 2016 and 134 patients were treated. The 1-year primary outcome, available for 104 patients, was reached in 5/48 (10.4% (4.5%-22.2%)) patients allocated surgical clipping, and 10/56 (17.9% (10.0%-29.8%)) patients allocated endovascular coiling (OR: 0.54 (0.13-1.90), p=0.40). Morbidity and mortality (modified Rankin Scale>2) at 1 year occurred in 2/48 (4.2% (1.2%-14.0%)) and 2/56 (3.6% (1.0%-12.1%)) patients allocated clipping and coiling, respectively. New neurological deficits (15/65 vs 6/69; OR: 3.12 (1.05-10.57), p=0.031), and hospitalisations beyond 5 days (30/65 vs 6/69; OR: 8.85 (3.22-28.59), p=0.0001) were more frequent after clipping. CONCLUSION: Surgical clipping or endovascular coiling of UIAs did not show differences in morbidity at 1 year. Trial continuation and additional randomised evidence will be necessary to establish the supposed superior efficacy of clipping.

Distribution of Psychological Instability Among Surgeons.

BACKGROUND: High emotional instability (i.e., neuroticism) is associated with poor mental health. Conversely, traumatic experiences may increase neuroticism. Stressful experiences such as complications are common in the surgical profession, with neurosurgeons being particularly affected. We compared the personality trait neuroticism between physicians in a prospective cross-sectional study. METHODS: We used an online survey using the Ten-Item Personality Inventory, an internationally validated measure of the 5-factor model of personality dimensions. It was distributed to board-certified physicians, residents, and medical students in several European countries and Canada (n = 5148). Multivariate linear regression was used to model differences between surgeons, nonsurgeons, and specialties with occasional surgical interventions with respect to neuroticism, adjusting for sex, age, age squared, and their interactions, then testing equality of parameters of adjusted predictions separately and jointly using Wald tests. RESULTS: With an expected variability within disciplines, average levels of neuroticism are lower in surgeons than nonsurgeons, especially in the first part of their career. However, the course of neuroticism across age follows a quadratic pattern, that is, an increase after the initial decrease. The acceleration of neuroticism with age is specifically significant in surgeons. Levels of neuroticism are lowest towards mid-career, but exhibit a strong secondary increase towards the end of the surgeon's career. This pattern seems driven by neurosurgeons. CONCLUSIONS: Despite initially lower levels of neuroticism, surgeons suffer a stronger increase of neuroticism together with age. Because, beyond well-being, neuroticism influences professional performance and health care systems costs, explanatory studies are mandatory to enlighten causes of this burden.

Multifocal choroid plexus papilloma: a case report.

BACKGROUND: Multiple choroid plexus papillomas (CPPs) are rare. Usually, they correspond to villous hypertrophy or metastasis occurring during cerebrospinal dissemination. Multiple CPPs have rarely been reported as synchronous tumors. CASE REPORT: Three synchronous CPPs were resected in a 59-year-old female 6 years after their first imaging description. Pathology showed mucus-producing CPP in all 3, 1 of the 3 presenting some signs of atypia. No p53 or hSNF5/INI1 mutation, or signs of polyoma viruses infection were found. CONCLUSION: Although no clear cause for the multifocality was found, the simultaneous presence of the three tumors and their benign histology suggest that they were synchronous and not metastatic. The issue of differentiating synchronous CPPs from metastatic CPP is discussed.

Post-traumatic thoracic outlet syndrome.

BACKGROUND: To evaluate the clinical presentation, diagnostic and therapeutic management and outcome of 27 cases of post-traumatic thoracic outlet syndrome (PT TOS). METHODS: Retrospective chart analysis. RESULTS: Nineteen women and eight men were included in this study. Involvement in a traffic accident was the most common scenario. Fracture of either the first rib or the clavicle was reported in eight patients at the time of injury; in others, the diagnosis was cervical or shoulder soft tissue trauma. Upon presentation at our clinic at a mean 41 months after injury, four patients had bilateral symptoms and 17 reported decreased function of either the arm or hand. Two patients presented with severe lower trunk deficits including one who had received surgical intervention at both the cervical spine and elbow before diagnosis of TOS was made. Sixteen and 15 patients were suffering from some degree of anxiety and/or depression. Upon diagnosis of neurogenic TOS, the two patients with atrophy of the hand musculature were treated surgically. Conservative treatment was applied to all other patients. Six months after presentation to our clinic, nine patients demonstrated a significant improvement. The remainder that reported incapacitating symptoms were offered surgical treatment. Three patients declined the latter. Fifteen patients received surgical treatment via an anterior supraclavicular approach with resection of the anterior scalene muscles. Eleven patients had resection of the middle scalene muscle while five had resection of an osseous structure (partial claviculectomy, C7 transverse process or a cervical rib). The two patients with atrophy of the hand only slightly improved their motor deficit but had a notable relief of symptoms of pain. Postoperative improvement occurred in 80% of surgically treated patients. CONCLUSIONS: The majority of patients suffering from a post-traumatic TOS present a neurogenic, usually subjective syndrome. Prompt therapeutic management is necessary, addressing both physical and psychological complaints. Most patients are cured or well improved by conservative and/or surgical treatment.

Solitary fibrous tumour of the vagus nerve.

We describe the complete removal of a foramen magnum solitary fibrous tumour in a 36-year-old woman. It originated on a caudal vagus nerve rootlet, classically described as the 'cranial' accessory nerve root. This ninth case of immunohistologically confirmed cranial or spinal nerve SFT is the first of the vagus nerve.

The dural vascular plexus in subdural hematoma: Illustration through a case of dural arteriovenous fistula.

Background: The initiation of chronic subdural hematoma (cSDH) is traditionally explained by rupture of bridging veins. Recent descriptions of the embryology and anatomy of the meninges and their vascularization, however, point to the dural vascular plexus (DVP) as a plausible origin of cSDH. This dural plexus is supplied by meningeal arteries. Their endovascular occlusion is efficient in cSDH treatment. Dural arteriovenous fistulae (dAVF) may also present with subdural hematoma. Case Description: A 65-year-old female patient presented with parietal parasagittal dAVF and bilateral cSDH requiring surgical disconnection followed by complete clinical and imaging resolution of dAVF and cSDH. Conclusion: In common cSDH, pressure in the DVP may be normal and subdural bleeding may occur due to mechanical traction on the DVP. In the setting of dAVF, it may be the increase in pressure due to the fistula, within the DVP, that causes subdural hematoma. The DVP, supplied by meningeal arteries, thus not only allows for convergent pathophysiological explanation of subdural bleeding in both cSDH and dAVF but may also be the actual target of the emergent endovascular treatment of cSDH trough meningeal artery embolization.

Hans Joachim Scherer: an under-recognized pioneer of glioma research in Belgium.

Hans Joachim Scherer (1906-1946) was a German pathologist who fled Germany to Belgium to work on glioma genesis, growth and progression. Despite being seldom cited, and due to the contributions discussed in this article, Hans Joachim Scherer, can be considered a founding father of contemporary neuropathology and glioma research. We discuss Scherer's achievements in glioma classification, glomerular structures of glioma, primary and secondary glioblastoma, glioma growth patterns, non-resectability of glioma, pseudopalisadic necrosis and the late occurrence of symptoms in glioma.

The expression of B7-H3 isoforms in newly diagnosed glioblastoma and recurrence and their functional role.

Short survival of glioblastoma (GBM) patients is due to systematic tumor recurrence. Our laboratory identified a GBM cell subpopulation able to leave the tumor mass (TM) and invade the subventricular zone (SVZ-GBM cells). SVZ-GBM cells escape treatment and appear to contribute to GBM recurrence. This study aims to identify proteins specifically expressed by SVZ-GBM cells and to define their role(s) in GBM aggressiveness and recurrence. The proteome was compared between GBM cells located in the initial TM and SVZ-GBM cells using mass spectrometry. Among differentially expressed proteins, we confirmed B7-H3 by western blot (WB) and quantitative RT-PCR. B7-H3 expression was compared by immunohistochemistry and WB (including expression of its isoforms) between human GBM (N = 14) and non-cancerous brain tissue (N = 8), as well as newly diagnosed GBM and patient-matched recurrences (N = 11). Finally, the expression of B7-H3 was modulated with short hairpin RNA and/or over-expression vectors to determine its functional role in GBM using in vitro assays and a xenograft mouse model of GBM. B7-H3 was a marker for SVZ-GBM cells. It was also increased in human GBM pericytes, myeloid cells and neoplastic cells. B7-H3 inhibition in GBM cells reduced their tumorigenicity. Out of the two B7-H3 isoforms, only 2IgB7-H3 was detected in non-cancerous brain tissue, whereas 4IgB7-H3 was specific for GBM. 2IgB7-H3 expression was higher in GBM recurrences and increased resistance to temozolomide-mediated apoptosis. To conclude, 4IgB7-H3 is an interesting candidate for GBM targeted therapies, while 2IgB7-H3 could be involved in recurrence through resistance to chemotherapy.

Clinical Uncertainty and Equipoise in the Management of Recurrent Glioblastoma.

BACKGROUND: A significant proportion of glioblastoma (GBM) patients are considered for repeat resection, but evidence regarding best management remains elusive. Our aim was to measure the degree of clinical uncertainty regarding reoperation for patients with recurrent GBM. METHODS: We first performed a systematic review of agreement studies examining the question of repeat resection for recurrent GBM. An electronic portfolio of 37 pathologically confirmed recurrent GBM patients including pertinent magnetic resonance images and clinical information was assembled. To measure clinical uncertainty, 26 neurosurgeons from various countries, training backgrounds, and years' experience were asked to select best management (repeat surgery, other nonsurgical management, or conservative), confidence in recommended management, and whether they would include the patient in a randomized trial comparing surgery with nonsurgical options. Agreement was evaluated using κ statistics. RESULTS: The literature review did not reveal previous agreement studies examining the question. In our study, agreement regarding best management of recurrent GBM was slight, even when management options were dichotomized (repeat surgery vs. other options; κ=0.198 [95% confidence interval: 0.133-0.276]). Country of practice, years' experience, and training background did not change results. Disagreement and clinical uncertainty were more pronounced within clinicians with (κ=0.167 [0.055-0.314]) than clinicians without neuro-oncology fellowship training (κ=0.601 [0.556-0.646]). A majority (51%) of responders were willing to include the patient in a randomized trial comparing repeat surgery with nonsurgical alternatives in 26/37 (69%) of cases. CONCLUSION: There is sufficient uncertainty and equipoise regarding the question of reoperation for patients with recurrent glioblastoma to support the need for a randomized controlled trial.

Surgical or Endovascular Management of Middle Cerebral Artery Aneurysms: A Randomized Comparison.

OBJECTIVE: There are few randomized data comparing clipping and coiling for middle cerebral artery (MCA) aneurysms. We analyzed results from patients with MCA aneurysms enrolled in the CURES (Collaborative UnRuptured Endovascular vs. Surgery) and ISAT-2 (International Subarachnoid Aneurysm Trial II) randomized trials. METHODS: Both trials are investigator-led parallel-group 1:1 randomized studies. CURES includes patients with 3-mm to 25-mm unruptured intracranial aneurysms (UIAs), and ISAT-2 includes patients with ruptured aneurysms (RA) for whom uncertainty remains after ISAT. The primary outcome measure of CURES is treatment failure: 1) failure to treat the aneurysm, 2) intracranial hemorrhage during follow-up, or 3) residual aneurysm at 1 year. The primary outcome of ISAT-2 is death or dependency (modified Rankin Scale score >2) at 1 year. One-year angiographic outcomes are systematically recorded. RESULTS: There were 100 unruptured and 71 ruptured MCA aneurysms. In CURES, 90 patients with UIA have been treated and 10 await treatment. Surgical and endovascular management of unruptured MCA aneurysms led to treatment failure in 3/42 (7%; 95% confidence interval [CI], 0.02-0.19) for clipping and 13/48 (27%; 95% CI, 0.17-0.41) for coiling (P = 0.025). All 71 patients with RA have been treated. In ISAT-2, patients with ruptured MCA aneurysms managed surgically had died or were dependent (modified Rankin Scale score >2) in 7/38 (18%; 95% CI, 0.09-0.33) cases, and 8/33 (24%; 95% CI, 0.13-0.41) for endovascular. One-year imaging results were available in 80 patients with UIA and 62 with RA. Complete aneurysm occlusion was found in 30/40 (75%; 95% CI, 0.60-0.86) patients with UIA allocated clipping, and 14/40 (35%; 95% CI, 0.22-0.50) patients with UIA allocated coiling. Complete aneurysm occlusion was found in 24/34 (71%; 95% CI, 0.54-0.83) patients with RA allocated clipping, and 15/28 (54%; 95% CI, 0.36-0.70) patients with RA allocated coiling. CONCLUSIONS: Randomized data from 2 trials show that better efficacy may be obtained with surgical management of patients with MCA aneurysms.

Multiparameter quantitative histological MRI values in high-grade gliomas: a potential biomarker of tumor progression.

BACKGROUND: Conventional MRI poorly distinguishes brain parenchyma microscopically invaded by high-grade gliomas (HGGs) from the normal brain. By contrast, quantitative histological MRI (hMRI) measures brain microstructure in terms of physical MR parameters influenced by histochemical tissue composition. We aimed to determine the relationship between hMRI parameters in the area surrounding the surgical cavity and the presence of HGG recurrence. METHODS: Patients were scanned after surgery with an hMRI multiparameter protocol that allowed for estimations of longitudinal relaxation rate (R1) = 1/T1, effective transverse relaxation rate (R2)*=1/T2*, magnetization transfer saturation (MTsat), and proton density. The initial perioperative zone (IPZ) was segmented on the postoperative MRI. Once recurrence appeared on conventional MRI, the area of relapsing disease was delineated (extension zone, EZ). Conventional MRI showing recurrence and hMRI were coregistered, allowing for the extraction of parameters R1, R2*, MTsat, and PD in 3 areas: the overlap area between the IPZ and EZ (OZ), the peritumoral brain zone, PBZ (PBZ = IPZ - OZ), and the area of recurrence (RZ = EZ - OZ). RESULTS: Thirty-one patients with HGG who underwent gross-total resection were enrolled. MTsat and R1 were the most strongly associated with tumor progression. MTsat was significantly lower in the OZ and RZ, compared to PBZ. R1 was significantly lower in RZ compared to PBZ. PD was significantly higher in OZ compared to PBZ, and R2* was higher in OZ compared to PBZ or RZ. These changes were detected 4 to 120 weeks before recurrence recognition on conventional MRI. CONCLUSIONS: HGG recurrence was associated with hMRI parameters' variation after initial surgery, weeks to months before overt recurrence.

A case of aphasia due to temporobasal edema: Contemporary models of language anatomy are clinically relevant.

BACKGROUND: Understanding the anatomy of language in the human brain is crucial for neurosurgical decision making and complication avoidance. The traditional anatomical models of human language, relying on relatively simple and rigid concepts of brain connectivity, cannot explain all clinical observations. The clinical case reported here illustrates the relevance of more recent concepts of language networks involving white matter tracts and their connections. CASE DESCRIPTION: Postoperative edema of the ventral occipitotemporal cortex, where modern network models locate a crucial language hub, resulted in transient severe aphasia after a subtemporal approach. Both verbal comprehension and expression were lost. The resolution of edema was associated with complete recovery from phonetic and semantic dysfunction. CONCLUSION: Complete aphasia due to a functional disturbance remote from the areas of Broca and Wernicke could be explained by contemporary neuroanatomical concepts of white matter connectivity. Knowledge of network-based models is relevant in brain surgery complication avoidance.

Anatomical integrity within the inferior fronto-occipital fasciculus and semantic processing deficits in schizophrenia spectrum disorders.

The core symptoms of schizophrenia spectrum disorders (SSD) include abnormal semantic processing which may rely on the ventral language stream of the human brain. Thus, structural disruption of the ventral language stream may play an important role in semantic deficits observed in SSD patients. Therefore, we compared white matter tract integrity in SSD patients and healthy controls using diffusion tensor imaging combined with probabilistic fiber tractography. For the ventral language stream, we assessed the inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus, and uncinate fasciculus. The arcuate fasciculus and corticospinal tract were used as control tracts. In SSD patients, the relationship between semantic processing impairments and tract integrity was analyzed separately. Three-dimensional tract reconstructions were performed in 45/44 SSD patients/controls ("Bern sample") and replicated in an independent sample of 24/24 SSD patients/controls ("Basel sample"). Multivariate analyses of fractional anisotropy, mean, axial, and radial diffusivity of the left IFOF showed significant differences between SSD patients and controls (p(FDR-corr) < 0.001, ηp2 = 0.23) in the Bern sample. Axial diffusivity (AD) of the left UF was inversely correlated with semantic impairments (r = -0.454, p(FDR-corr) = 0.035). In the Basel sample, significant group differences for the left IFOF were replicated (p < .01, ηp2 = 0.29), while the correlation between AD of the left IFOF and semantic processing decline (r = -0.376, p = .09) showed a statistical trend. No significant effects were found for the dorsal language stream. This is direct evidence for the importance of the integrity of the ventral language stream, in particular the left IFOF, in semantic processing deficits in SSD.