Cranial Lesions Research Articles

Using a multimethod life history approach to navigate the osteological paradox: A case study from Prehispanic Nasca, Peru.

We leverage recent bioarchaeological approaches and life history theory to address the implications of the osteological paradox in a study population. The goal of this article is to evaluate morbidity and mortality patterns as well as variability in the risk of disease and death during the Late Intermediate period (LIP; 950-1450 C.E.) in the Nasca highlands of Peru. We demonstrate how the concurrent use of multiple analytical techniques and life history theory can engage the osteological paradox and provide salient insights into the study of stress, frailty, and resilience in past populations. Crania from LIP burial contexts in the Nasca highlands were examined for cribra orbitalia (n=325) and porotic hyperostosis (n=270). All age groups and both sexes are represented in the sample. Survivor/nonsurvivor analysis assessed demographic differences in lesion frequency and severity. Hazard models were generated to assess differences in survivorship. The relationship between dietary diversity and heterogeneity in morbidity was assessed using stable δ15 N and δ13 C isotope values for bone collagen and carbonate. One hundred and twenty-four crania were directly AMS radiocarbon dated, allowing for a diachronic analysis of morbidity and mortality. The frequency and expression of both orbital and vault lesions increases significantly during the LIP. Survivor/nonsurvivor analysis indicates cranial lesions co-vary with frailty rather than robusticity or longevity. Hazard models show (1) decreasing survivorship with the transition into the LIP, (2) significantly lower adult life expectancy for females compared to males, and (3) individuals with cranial lesions have lower survivorship across the life course. Stable isotope results show very little dietary diversity. Mortality risk and frequency of pathological skeletal lesions were highest during Phase III (1300-1450 C.E.) of the LIP. Results provide compelling evidence of increasing physiological stress and mortality in the Nasca highlands during the LIP, but also reveal substantial heterogeneity in frailty and the risk of death. Certain members of society experienced a heavier disease burden and higher mortality compared to their contemporaries. Elevated levels of disease and lethal trauma among females account for some of the sex differences in survivorship but cannot explain the large degree of female-biased mortality. We hypothesize that parental investment in males or increased female fertility rates may explain these differences.

P76.13 Osimertinib Delays but Not Prevents Central Nervous System Metastasis in EGFR-Mutant Advanced Non-Small Cell Lung Cancer

Central nervous system (CNS) is a common site of EGFR Tyrosine kinase inhibitor (TKI) treatment failure in advanced non-small cell lung cancer (NSCLC). Various EGFR TKIs with distinct potencies against CNS metastasis are approved. This study aims to compare the incidence of symptomatic CNS metastasis in advanced EGFR-mutant NSCLC without baseline CNS lesions and receiving first- or third-generation EGFR TKIs. Patients with EGFR-mutant advanced NSCLC without baseline CNS metastasis and receiving standard of care EGFR-TKIs were included. Cumulative incidences of symptomatic CNS metastasis upon EGFR-TKI treatment failure were calculated using the Kaplan-Meier method and significant risk factors of CNS metastasis were identified using the Cox proportional hazards models. Furthermore, radiographic features and clinical outcomes of patients who developed CNS metastasis were analyzed. Among 935 patients enrolled, 633, 143 and 35 received first-line gefitinib, erlotinib and osimertinib, respectively, and the remaining 124 received second-line Osimertinib. At a median follow-up of 10 months (range, 1-93 months), 517 patients developed EGFR-TKI treatment failure, of whom 45 had symptomatic CNS metastasis. The 1-, 2- and 3-year cumulative incidences of symptomatic CNS metastasis were 4.2%, 7.9% and 14.4%, respectively. There was no difference of developing symptomatic CNS metastasis among patients receiving gefitinib or erlotinib (p=0.857), while patients receiving osimertinib (Group B) had a significant lower risk than those receiving first-generation EGFR-TKIs (Group A) (HR 0.45; 95%CI 0.20-0.99, p=0.049). Of note, the survival curves tended to reach a plateau after three years, and the cumulative incidence of symptomatic CNS metastasis beyond that time, as well as the percentage of patients who developed symptomatic CNS metastasis among those who had EGFR-TKI treatment failure, was similar in Group A and Group B. Patients harboring L858R mutation had a higher risk developing symptomatic CNS metastasis than patients harboring other types of sensitizing EGFR mutations (p=0.003). Among 45 patients who developed symptomatic CNS metastasis, 20 had single cranial lesion, 39 had a largest tumor lesion smaller than 3cm and 39 had metastatic lesion outside the hippocampus region. Moreover, among the 45 patients, median overall survival (OS) calculated from the diagnosis of advanced disease was 33.3 (95%CI 24.8-41.8) months, and patients with single cranial lesion had a significantly longer OS (p=0.011). Compared with first-generation EGFR-TKIs, osimertinib significantly delays the development of symptomatic CNS metastasis in EGFR-mutant advanced NSCLC and L858R mutation is an independent risk factor of CNS metastasis.

Mucormycosis originated total maxillary and cranial base osteonecrosis: a possible misdiagnosis to malignancy

BackgroundThis is a case of mucormycosis originated osteonecrosis of the maxilla extended to the cranial base, initially suspected of malignancy. The patient was first suspected with osteolytic sarcomatous lesion but was later diagnosed with total maxillary necrosis and cranial base through biopsy-proven invasive mucormycosis.Case presentationA 71-year-old male was presented with unknown total maxillary osteonecrosis. CT and MRI results showed extensive osteolytic change with bone destruction of the cranial base, and PET-CT showed irregular hypermetabolic lesion in the area suspected of malignancy. The first biopsy results only presented tissue inflammation. Thus, several further endoscopic biopsy were performed through posterior pharyngeal wall. The patient was eventually diagnosed with mucormycosis and associated osteomyelitis with subsequent bone necrosis. With confirmed diagnosis, partial maxillectomy of the necrosed bone was performed under general anesthesia. At the 4 week follow-up, the patient showed full mucosal healing and no recurrence or aggravation of the maxilla and cranial base lesion was observed.ConclusionsAccurate diagnosis of atypical symptoms, timely diagnosis, and proper combination therapy of surgical intervention, antifungal agent, and antibiotic use for skull base osteomyelitis are all critical for proper treatment planning. In addition, biopsy and CT scans are essential in differentiating osteonecrosis from malignancy.

IgG4 Licks base of skull, wastes tongue: An unusual presentation

IgG4 Related disease (IgG4 RD) is a rapidly evolving clinical entity, involving multiple organs, manifesting clinically as tumefactive lesions, histopathologically characterized by an IgG4 predominant, dense lymphoplasmacytic tissue infiltrate. It might mimic malignancy, infection as well as various other inflammatory disorders. First described in literature in 2003, in the pancreas, it has been subsequently seen to involve a wide range of organs like salivary glands, paranasal sinuses, thyroid gland, retroperitoneum, lung and kidney. Rarely, it may present as a skull base osteomyelitis (SBO). Diagnosing IgG4 RD in such patients is a herculean challenge in view of absence of systemic symptoms, difficulty in obtaining adequate tissue specimens in view of densely fibrotic cranial base lesions, as well as the close proximity of the lesions to critical neurovascular structures. The standard of care, in such cases is medical, and comprises of steroids and rituximab. Herein, we discuss one such case of IgG4 RD, who presented as multiple lower cranial nerve palsies and headache, with imaging evidence of SBO, which was diagnosed as a case of IgG4RD on histopathology, and who despite receiving the standard of care, had a poor outcome. The purpose of presenting this case is to stress upon a high index of suspicion and an aggressive management approach while treating such cases.

Teriflunomide treatment is associated with optic nerve recovery in early multiple sclerosis.

Background and aims:Various attempts have been made to support recovery following optic neuritis (ON), but the respective trials have mostly been negative. The aim of this study was to determine whether disease-modifying treatment (DMT) following ON as first manifestation of relapsing-remitting multiple sclerosis influences long-term outcomes.Methods:A total of 79 patients with ON were identified and evaluated at relapse, DMT induction, and 12 months following treatment induction with either glatiramer acetate (GLAT), interferon-beta (IFN), or teriflunomide (TRF). Low-contrast letter acuity (LCLA) and full-field visual-evoked potentials (FF-VEP) were compared between treatment groups using multivariable regression models. The impact of TRF treatment induction compared with IFN or GLAT following relapses outside the optic nerves was evaluated in an independent cohort of 122 patients. Magnetic resonance imaging (MRI) outcomes and rates of confirmed improvement of relapse-related disability were evaluated.Results:TRF-treated patients exhibited higher LCLA and lower relative P100 latencies normalized to the fellow-eye. Findings were significant following covariate-adjustment by multivariable analyses. Cranial MRI lesion load as well as disability progression rates were not significantly different between groups. The cohort of patients following relapses other than ON showed no differences in confirmed improvement of disability.Conclusion:TRF treatment is associated with favorable outcomes regarding functional optic nerve recovery following ON in early multiple sclerosis.

NEUROLOGICAL COMPLICATIONS OF COVID-19

After the first cases of the new disease COVID-19 (caused by the SARS-CoV-2 coronavirus) were registered in Wuhan, China in December 2019, its spread rapidly became a pandemic and within a few months it covered almost 200 countries [6]. The global COVID-19 pandemic has infected more than 79 million people around the world and claimed more than 1.7 million lives as of December 24, 2020 (according to the Center for Systems Science and Engineering at Johns Hopkins University). Thus, the mortality rate is 2.2%, which significantly exceeds the mortality rate for influenza. It is believed that the peak of the COVID-19 pandemic will continue in the next few months, after which the pandemic will decline. Although the predominant manifestations of COVID-19 are respiratory symptoms, more and more attention is paid to neurological complications. Some neurological complications are potentially life-threatening and can lead to death. The most common neurological complications of acute phase of COVID-19 are impairments of olfaction and taste, which are observed in 33-88% of patients [3]. These symptoms are important for differential diagnosis with influenza and ARVI viruses. Headaches, dizziness, fatigue, and myalgia according to different studies can be observed in 6.5-16.8% of patients. Other neurological complications of COVID-19 often develop in severe and very severe disease (although there are exceptions). Apparently, such neurological complications as ischemic stroke, transient ischemic attack, encephalopathy, delirium can be observed in approximately 0.5-3% of patients. Even less common are hemorrhagic stroke, venous sinus thrombosis, meningitis, encephalitis, encephalomyelitis, cerebral vasculitis, III, V, VI, VII, VIII, IX cranial nerves lesions, Guillain-Barre syndrome, Miller-Fisher syndrome, polyneuropathy, acute dysautonomia, myopathy, myoclonus, epileptic seizures and status epilepticus [2, 4-8]. Awareness of the neurological complications of COVID-19 can influence treatment strategies and simultaneously improve the prognosis for critically ill patients [5]. Keywords: COVID-19, SARS-CoV-2, coronavirus, neurological complications

GJA1 Gene Polymorphisms and Topographic Distribution of Cranial MRI Lesions in Cerebral Small Vessel Disease.

Vascular endothelial cell (EC) and blood–brain barrier (BBB) dysfunction is the core pathogenesis of cerebral small vessel disease (CSVD). Moreover, animal experiments have shown the importance of connexin (Cx)-43 in EC and BBB function. In this study, we recruited 200 patients diagnosed with sporadic CSVD. Initially, we examined imaging scores of white matter hyperintensities (WMH), lacunar infarction (LI), and cerebral microbleeds (CMB). Additionally, we performed next-generation sequencing of the GJA1 gene (Cx43 coding gene) to examine correlation between these single-nucleotide polymorphisms and the burden and distribution of CSVD. Fourteen target loci were chosen. Of these, 13 loci (92.9%) contributed toward risk for cerebellar LI, one locus (7.1%) was shown to be a protective factor for lobar CMB after FDR adjustment. In conclusion, single-nucleotide polymorphisms in the GJA1 gene appear to affect the distribution but not severity of CSVD.

Managing respiratory disease in finisher pigs: Combining quantitative assessments of clinical signs and the prevalence of lung lesions at slaughter

This study aimed to assess the relationship between quantitative assessments of clinical signs of respiratory disease (recorded manually and automatically) and the prevalence of lung lesions at slaughter to validate the use of both in the management of respiratory disease on farm. This was an observational study where pigs (n = 1573) were monitored from 25 ± 5.3 kg (week 12) to slaughter at 114 ± 15.4 kg (week 24). Pigs were housed in eight rooms divided into six pens on a wean-to-finish farm. A manual pen-based coughing (CF) and sneezing (SF) frequency was recorded weekly, for ten consecutive weeks, and a SOMO box (SoundTalks®) was installed in each room, issuing a daily respiratory distress index (RDI) for 13 weeks. Lungs were individually scored for pneumonia, scarring and dorsocaudal (DC) and cranial (CP) pleurisy lesions at slaughter. Relationship between prevalence of lung lesions and weekly RDI and CF and SF was assessed using Spearman’s rank correlations and multivariable linear and logit-normal models.Both coughing and lung lesions were largely pen-specific, which fit the disease presentation of Mycoplasma hyopneumoniae. Results showed agreement between RDI and CF (rs = 0.5, P < 0.001), measuring higher levels of coughing at the beginning (weeks 13–14) and end (weeks 21–24, and weeks 21–22, respectively) of the finisher period. Positive associations were found between the prevalence of pneumonia and CF on week 21 and 22 (P < 0.001 and P = 0.011, respectively) and RDI on week 21–24 (rs > 0.70; P < 0.050); the prevalence of DC and CP, and CF on week 22 (P < 0.001); and prevalence of scar lesions and CF on week 17 and 21 (P = 0.013 and P = 0.004, respectively), and RDI on week 21–24 (rs > 0.70; P < 0.050).In the earlier weeks of the finisher stage, coughing was recorded but was not reflected in a higher prevalence of lung lesions at slaughter. These findings highlight the benefit of including measurements of coughing frequency to complement post mortem findings, to improve the management of respiratory disease on farm.

Restless legs syndrome/Willis-Ekbom disease in multiple sclerosis: a contributing factor for anxiety, disability, sleep disorder, and quality of life.

Restless legs syndrome (RLS) is one of the most common and burdensome sleep disorders in the course of multiple sclerosis (MS). To evaluate common MS-related symptoms and consequences between groups with and without RLS and further assess the association of quality of life determinants with RLS symptom severity. According to their RLS status, 46 relapsing-remitting MS patients were divided into MS-RLS+ (n=19) and MS-RLS- groups (n=27). Specific questionnaires were administered to assess the patients' health-related quality of life (HRQoL), fatigue levels, sleep quality, daily sleepiness, anxiety, and depression symptoms. Functional capacity was examined using the Expanded Disability Status Scale (EDSS). The prevalence of RLS was 41.3%. Compared to the MS-RLS- group, those with RLS had higher EDSS scores, more cranial and spinal lesions, longer disease duration, and were older. In the MS-RLS+ group, symptom severity scores were positively correlated with higher anxiety and poorer sleep quality. The symptom severity score was negatively correlated with mental HRQoL and pain scores. In conclusion, the findings of the current study indicate the negative impact of RLS on functional capacity, anxiety, sleep quality, and mental HRQoL of MS patients. Further studies using more accurate diagnostic strategies for identifying RLS and other sleep disorders are necessary to clarify the association of MS with RLS and explore relevant clinical implications.

Prevalence of Oligometastatic Disease of Solid Tumors and Stereotactic Ablative Body Radiotherapy Adverse Events

There is a growing evidence of better outcome of oligometastatic disease (OMD) of solid tumors compared to those with diffuse metastases when treated with stereotactic Ablative body radiotherapy (SABR) and or Stereotactic Radiosurgery (SRS). We reviewed our institution database about the prevalence of OMD in solid tumors, patients’ characteristics and the adverse events due to SABR/SRS. A retrospective review was performed for all solid tumor patients who treated with SABR and/or SRS at our institution from January 2017 to August 2019. Patients were defined to have OMD if ≤ 5 sites of disease were identified at time of diagnosis or first time of development of metastases. univariate analysis was performed to determine the association between treatment toxicity and patient characteristics, treated lesion volume and dose. The chi-square test or Fisher exact test were used as appropriate depending on sample being tested for comparing proportions in categorical variables and the t-test or ANOVA for continuous variables. Late toxicity was graded using the “Common Terminology Criteria for Adverse Events” (CTCAE V.5.0). Of 986 patients with solid tumors reviewed, 109 (11.05%) found to have OMD and treated with SABR and /or SRS for 225 metastatic lesions. The mean age of our OMD population was 57 years. Majority of them had Performance Status (PS) of one (53%) and two (30%) with Charlson Comorbidity index (CCI) of six (67%). Among OMD patients, 47 (43%) had primary colorectal cancer (CRC) followed by non-small cell lung cancer (NSCLC) 21(19%) and breast cancer 17(16%). Of 225 treated sites, 64 (28%) were brain metastatic sites followed by liver and lung (23%) and (21%), respectively. Median SABR dose was 48 Gy (range: 30-54 Gy) in 3 to 5 fractions and the median SRS dose was 21 Gy. Median volume of extracranial lesions was 22cc and 1.8cc for cranial lesions. SABR was well tolerated with infrequent late adverse events. No Grade 4 or 5 toxicity was encountered. Four treated sites (1.8%) in four patients (3.7%) had grade 3 toxicities; 16 treated sites (7%) in 12 treated patients (11%) had grade 2 toxicities. Toxicity correlation with PS, dose or volume was not statistically significant. OMD patients constitute a significant portion of oncology patients. SABR is a safe local treatment modality in OMD patient population. A prospective study with larger sample size is required to confirm these finding and evaluate any correlation between toxicity to SABR/SRS dose and treated lesion volume.

Preventing Symptomatic Central Nervous System Metastasis in EGFR-Mutant Advanced Non-Small Cell Lung Cancer: Comparison of First- and Third-Generation EGFR Tyrosine Kinase Inhibitors

Epidermal growth factor receptor (EGFR)-Tyrosine kinase inhibitors (TKIs) are standard treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). Central nervous system (CNS) metastases, including brain parenchymal metastasis (BM) and leptomeningeal metastasis (LM), are common in the EGFR-TKI treatment failure. The different generation EGFR-TKIs have variant potencies of penetrating into the blood-brain-barrier. This study aims to compare the efficacy of first- and third-generation EGFR-TKIs in preventing symptomatic CNS metastases and to identify their risk factors. Patients with EGFR-mutant advanced NSCLC without baseline CNS metastasis and receiving EGFR-TKI treatment were selected. The cumulative incidence of symptomatic CNS metastasis upon treatment failure, and overall survival (OS) of patients who developed CNS metastasis, were measured from the initiation of EGFR-TKIs, using the Kaplan-Meier method. The risk factors for CNS metastasis, and predictors of OS were identified using Cox proportional hazard regression. 935 patients from two academic medical centers were enrolled, with 633, 143 and 35 receiving first-line gefitinib, erlotinib and osimertinib, respectively, the remain 124 patients received osimertinib for acquired T790M mutation. On baseline, 19del, L858R and uncommon mutations were detected in 427, 386 and 122 patients, respectively. At the median follow-up of 10 months, treatment failure was observed in 517 patients, of whom 45 developed symptomatic CNS metastasis, with 37 developing BM, 4 LM, and 4 with both BM and LM. The 1-year, 2-year and 3-year cumulative rate of symptomatic CNS metastasis, were 4.2%, 7.9% and 14.4%, respectively. There was no significant difference in symptomatic CNS metastasis among patients receiving gefitinib or erlotinib, while osimertinib treatment was found to have a lower rate compared to first-generation TKIs (HR 0.45; 95%CI 0.20-0.99, p = 0.049). However, cumulative rate of symptomatic CNS metastasis at 3-year in osimertinib group reached the similar level as the first-generation TKIs. Of interest, the curves of CNS metastasis tend to reached a plateau after three years no matter which generation was used. Patients harboring L858R mutation were at a higher risk of developing CNS metastasis, than other mutations (p = 0.003). Among the 45 patients with CNS metastasis, median OS was 22 months, and patients with single cranial lesion had a significant longer OS (p = 0.011). Compared with first-generation EGFR TKIs, osimertinib significantly delays the development of symptomatic CNS metastasis in the EGFR-mutant advanced NSCLC without baseline CNS metastasis. L858R mutation is a risk factor for CNS failure during EGFR-TKIs treatment.

A new case of prehistoric trepanation and scalping in the Iberian Peninsula: The tomb of La Saga (Cáseda, Navarre)

AbstractTrepanation is considered one of the oldest surgical procedures in the world, of which the earliest evidence goes back to the Mesolithic. Over 130 cases of trepanated crania have been documented in the recent prehistory of the Iberian Peninsula, one of the areas with the highest number of cases. This paper analyses and discusses a new case from northern Spain. The cranium was found in the site of La Saga, Cáseda, Navarre, a small tomb where nine individuals were simultaneously placed at the end of the Bronze Age. It belongs to an adult female and displays a pentagonal hole in the central area of the cranial vault over the sagittal suture. The pentagonal shape of the injury, its regular outline, and the presence of 10 fusiform and two rounded grooves suggest that the bone was intentionally removed by means of cutting and leverage, a technique documented in another example from the Iberian Peninsula. Neither cranial lesions nor pathological evidence have been identified to justify the surgical procedure. Furthermore, the case is exceptional due to the presence of superficial and parallel cut marks in longitudinal and transversal directions across the parietal and temporal bones, unequivocally associated with scalping practice, and which would be performed prior to the trepanation in order to facilitate it. The absence of any kind of healing or bone regeneration points towards the death of the individual during the procedure. Together with the presence of marks of violence and manipulation of the skeletal remains of some individuals buried in the same grave, this leads us to propose that the trepanation was possibly performed to heal a previous trauma resulting from a violent conflict that caused the death of this and eight other individuals from the community.

Role of diffusion tensor imaging and diffusion metrics in primary, secondary brain tumours and tumour mimics

Background and Aim: Diffusion Tensor Imaging studies provide a valuable information regarding the status of white matter tracts adjacent to the intracranial brain lesions. The quantitative nature of Diffusion Tensor Imaging will play a role in assessing the outcome of clinical trials, as an additional surrogate marker in monitoring the therapeutic response. The aim of our study were to determine the Mean Diffusivity and Fractional Anisotropy coefficients in the affected white matter tracts and thereby to compare the Fractional Anisotropy and Mean Diffusivity of the affected white matter tracts in primary, secondary brain tumours and tumour like lesions.Materials and Methods: From December 2018 to September 2019, 49 patients were included in the study who were referred to the department for conventional Magnetic Resonance Imaging. The histopathological diagnosis was obtained and confirmed in patients who have undergone surgical resection.Results: Diffusion Tensor Imaging studies provide a valuable information regarding the status of white matter tracts adjacent to the intra cranial brain lesions. Fractional Anisotropy depends on the orientation and density of white matter fibres and Mean Diffusivity depends on the degree of perilesional edema. Gliomas present with white matter fibre destruction and less vasogenic edema when compared to tumour like lesions, and a higher perilesional Apparent Diffusion Coefficient favours a non-neoplastic etiology. Thus, the Diffusion Tensor Imaging sequences may help in differentiating the brain lesions of different aetiologies.Conclusion: The quantitative nature of Diffusion Tensor Imaging will play a role in assessing the outcome of clinical trials, as an additional surrogate marker in monitoring the therapeutic response. Careful studies to validate Diffusion Tensor Imaging and its metrics will allow it to become more applicable clinically and can affect therapeutic decision-making, choosing appropriate treatment and eventually patient outcome.

Nörofibromatozis Tip 1: Çocuk hastalarda Klinik ve Beyin MRG bulguları

Objective: Neurofibromatosis type 1 is a most common neurocutaneous syndrome characterized by multi-system involvement and an increased incidence of both benign and malignant tumors. Its diagnosis and follow-up is important because of increased cancer susceptibility in children. The aim of this study is to review the cranial MRI findings, neoplastic and non-neoplastic lesions of the brain in neurofibromatosis type I in pediatric patients. Material and Methods: 183 patients which diagnosed with neurofibromatosis type 1 and had at least 1 MRI between July 2010 and March 2019 were evaluated. Twelve patients were siblings. Contrasted cranial MRI obtained from 82 female and 101 male patients, between ages 1-18 years (averageage 10) retrospectively scanned thereafter type and locations of lesions evaluated by a 9 years experienced radiologist. Results: Out of 183 patients; 37 had no hamartomatous cranial lesions, 24 had optic gliomas or optic nerve thickening (9 bilaterally, 10 rightside, 5 leftside), 8 had plexiform neurofibromas (head or neck location), 9 had subcutaneous neurofibromas. Additionally 9 had intracranial arachnoid cysts, 6 low grade glial tumor, 1 medulloblastoma, 1 glioblastoma, 1 nodular heterotopia. Two patients had suspected low grade glial tumor and their size and view are stableat follow-up. The most common localization of hamartomatous lesions are the globus pallidus, dentate nucleus, mesencephalon, thalamus and pons respectively. The least common area is putamen. In addition, 3 patients are followed with Noonan Syndrome. In two of these patients, intracranial arachnoid cysts were observed in addition to hamartomatous lesions. Conclusion: Neurofibromatosis type 1 is one of the tumor predisposition syndrome that leads to an increased incidence of malign and benign tumors, which are major cause of mortality and morbidity. Gliomas are the most common intracranial tumors and the second most common tumor type after neurofibromas. Regular follow up is important for early diagnosis and treatment of malignancy. Brain MRI is adequate and necessary imaging modality for the diagnosis and follow up of brain involment in Neurofibromatosis type 1 patients.

Evaluation of Six-Dimensional Cranial Target Positioning Accuracy in Two Different Immobilization Methods Using Exactrac System

Introduction: The aim of this study was to determine the accuracy of two different immobilization methods in patient positioning in cranial radiotherapy. The six-dimensional (6D) target localization accuracy of using a dedicated stereotactic mask was compared with that of a conventional head mask by the ExacTrac system. Material and Methods: A total of 56 patients with cranial lesions were included in this study (26 patients with a dedicated stereotactic mask and 30 subjects with a conventional head mask). The ExacTrac image-guided positioning system was utilized to obtain daily translational and rotational patient positioning displacement from the intended position. The 6D setup data was analyzed to obtain population mean, systematic and random errors, and three-dimensional (3D) vector shifts in all the patients. Results: The population mean values of setup errors were comparable with both immobilization systems; however, the spread as indicated by population systematic and population random errors was more in the use of a conventional head mask. The mean values of the 3D vector shifts were 2.09±1.00 and 4.51±3.38 mm with the use of a dedicated stereotactic mask and conventional head mask, respectively. The frequency distribution of maximum rotational deviation and statistical analysis demonstrated a significant difference in immobilization accuracy between stereotactic immobilization and 3-clamp immobilization (p <0.05). Conclusion: The results revealed that there was a significant reduction in target positioning errors with a dedicated stereotactic mask, compared to that with a conventional cranial mask. Furthermore, a dedicated stereotactic mask is required to keep rotational deviations within system correctable limits.

3‐T MRI of protothecosis encephalic lesions in a Scottish shepherd dog

A four‐year‐old Scottish Shepherd dog was referred for acute onset of disorientation, blindness and chronic diarrhoea. The neurological examination was consistent with a multifocal neurolocalisation involving the prosencephalon and the brainstem. The ophthalmological exam showed bilateral chorioretinitis with retinal detachment. The brain MRI showed periventricular and left caudate nucleus lesions, increased thickness of the left III, IV, VI and opthalmic branch of V cranial nerves and bilateral multifocal lesions in the temporal and masseter muscles. Cerebrospinal fluid examination showed mild mixed pleocytosis. Faecal and urine cultures were positive for Prototheca zopfii genotype 2. Despite starting itraconazole therapy, the dog's conditions deteriorated and the owner elected euthanasia. Protothecosis should be suspected in young dogs with multifocal neurological signs, blindness and chronic diarrhoea.MRI study of the central nervous system (CNS), together with blood exam, cytology and cultures, is a useful tool to evaluate the CNS in disseminated form of Prototheca infection.

Cribra orbitalia and porotic hyperostosis are associated with respiratory infections in a contemporary mortality sample from New Mexico

Cribra orbitalia (CO) and porotic hyperostosis (PH) are porous cranial lesions (PCLs) classically associated with iron-deficiency anemia in bioarchaeological contexts. However, recent studies indicate a need to reassess the interpretation of PCLs. This study addresses the potential health correlates of PCLs in a contemporary sample by examining relationships between the known cause of death (COD) and PCL presence/absence. This study includes a sample of 461 juvenile individuals (6 months to 15 years of age) who underwent examination at the University of New Mexico's Office of the Medical Investigator between 2011 and 2019. The information available for each individual includes their sex, age at death, and their COD and manner of death. Odds ratio of having CO (OR = 3.92, p < .01) or PH (OR = 2.86, p = .02) lesions are increased in individuals with respiratory infections. Individuals with heart conditions have increased odds of having CO (OR = 3.52, p = .03) lesions, but not PH. Individuals with respiratory infection are more likely to have CO and/or PH. CO appears to have a greater range of health correlates than PH does, as indicated by the heart condition results. However, individuals with congenital heart defects are at higher risk for respiratory infections, so bony alterations in cases of heart conditions may be due to respiratory illness. Since respiratory infection remains a leading cause of mortality today, CO and PH in bioarchaeological contexts should be considered as potential indicators of respiratory infections in the past.

Treatment and Outcomes of Iatrogenic Cerebrospinal Fluid Leak Caused by Different Surgical Procedures

Iatrogenic cerebrospinal fluid (CSF) leaks are associated with serious sequelae. We analyzed the causes, complications, treatments, and outcomes of iatrogenic CSF leaks. Furthermore, the comorbidities and outcomes between timely and delayed repairs of iatrogenic CSF leaks were also compared. Medical records of patients with iatrogenic CSF leaks from January 2010 to January 2020 were reviewed. Iatrogenic CSF leaks can be attributed to endoscopic sinus surgery (ESS), transsphenoidal pituitary surgery, open craniotomy, or postradiation necrosis. Twenty-nine patients diagnosed with iatrogenic CSF leak were recruited. The primary diagnoses included 12 (41.4%) nasal lesions, 7 (24.2%) pituitary tumors, 3 (10.3%) anterior cranial fossa lesions, 4 (13.8%) cerebellopontine angle lesions, and 3 (10.3%) clival lesions. The longest interval from symptom onset to presentation at our hospital was observed after craniotomy, followed by transsphenoidal surgery and ESS, increasing the risks of meningitis in these patients. The most common leakage sites after ESS and transsphenoidal surgery were the cribriform plate/ethmoid roof and sella turcica, respectively, whereas the defect sites related to open craniotomy varied. The grafts used for repair varied according to the defect location and prior surgical history. Additionally, patients in whom repair was delayed had a higher incidence of meningitis (P= 0.003), than those with timely repair. Delayed intervention of CSF leak after transsphenoidal surgery and craniotomy was observed, increasing the risks of meningitis. Timely intervention with grafts based on the defect sites and patient prior surgical history is crucial for avoiding life-threatening comorbidities.

Frameless Stereotactic Biopsy with DTI-Based Tractography Integration: How to Adjust the Trajectory—A Case Series

Frameless stereotactic biopsy represents a minimally invasive procedure used for the histopathological diagnosis of brain tumors or to safely approach deep-seated lesions near eloquent areas not amenable for classical neurosurgical procedures. Traditionally, biopsy is performed relying on anatomical landmarks, but it can lead itself to intra- and postoperative complications, such as hemorrhage and fiber disruption. Diffusion tensor imaging (DTI) tractography represents a useful tool that can analyze the individual fiber tract conformation in cases of brain tumor and consequently identify the best biopsy trajectory, preserving white matter pathways. In our study, we present a novel technique that is based on the use of preoperative DTI for biopsy. Between January 2018 and January 2020, data about patients who underwent frameless biopsy using DTI tractography were retrospectively reviewed. The inclusion criterion was adult patients eligible for elective surgery for a single or multiple deep-seated lesions with contraindications to complete surgical resection. We included 12 patients (mean age of 67.9 [±9.6] years). A single cranial lesion was detected in 7 cases, and multiple lesions in 5 cases. The use of DTI enabled the identification of white matter pathways in all cases and adjustment of the biopsy trajectory based on anatomical landmarks in 7 cases. Postoperative hematoma was reported in 1 case, and histological diagnosis was obtained in 11 cases. According to our results, tractography is a useful tool that can enhance the safety of cerebral lesions biopsy sparing any fiber tract damages.

Cranial trepanation and healing process in modern patients-Bioarchaeological and anthropological implications.

The diagnosis of cranial trepanation in the archaeological record has always been a big challenge for archaeologists. The identification is first and foremost based on the shape and edges of the opening, and in cases where the individual survived, the shape and edges resulted from both the surgical procedure and the healing process. Because of the lack of reliable data on the osseous remodelling process of the skull, it is difficult to distinguish true trepanations from some pathological or physiological defects called pseudotrepanations. Furthermore, it is challenging to investigate the post-operative survival time. The purpose of this paper was to summarize observations made on a total of 90 archaeological samples of cranial lesions interpreted as 'partially' or 'completely' healed trepanations, and compare them with 14 modern case studies. Observations made on monitoring post-operative scans of modern patients, at varying times after craniotomy, provided a preliminary timetable for the successive post-surgery bony changes in the skull, and confirmed that the process of osseous remodelling does lead to smooth and rounded edges of the profile of the opening. However, contrary to what has been observed in several archaeological case studies, none of the cases shows a complete closure of the cranial vault. The sharp vertical edges of the opening become bevelled at late stages of healing, which has to be taken into consideration when interpreting the procedures and methods in past population. By bridging bioarchaeology and medical sciences, this study adds to previous discussions on the diagnosis of healed trepanation in the archaeological record, by providing detailed descriptions of morphological changes at various healing stages, that may help archaeologists to identify ancient trepanations more accurately.