Exploring the Link Between Ankylosing Spondylitis and Inflammatory Bowel Disease: A Retrospective Cohort Study.

BACKGROUND: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link. OBJECTIVES: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship. METHODS: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors. RESULTS: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls. CONCLUSIONS: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

Cannabis oil extracts for chronic pain: what else can be learned from another structured prospective cohort?

Introduction: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials. Objectives: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain. Methods: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 months thereafter. Generalized linear mixed model was used to analyze changes over time. In addition, "responders" (≥30% reduction in weekly pain at any time point) were identified. Results: The study included 218 patients at baseline, and 188, 154, and 131 at 1, 3, and 6 months, respectively. At 6 months, the mean daily doses of cannabidiol and Δ9-tetrahydrocannabinol were 22.4 ± 24.0 mg and 20.8 ± 30.1 mg, respectively. Pain decreased from 7.9 ± 1.7 at baseline to 6.6 ± 2.2 at 6 months (F(3,450) = 26.22, P < 0.0001). Most secondary parameters also significantly improved. Of the 218 participants, 24% were "responders" but could not be identified by baseline parameters. "Responders" exhibited higher improvement in secondary outcomes. Adverse events were common but mostly nonserious. Conclusion: This prospective cohort demonstrated a modest overall long-term improvement in chronic pain and related symptoms and a reasonable safety profile with the use of relatively low doses of individually titrated Δ9-tetrahydrocannabinol and cannabidiol.

Two cases of dermatomyositis associated with neuroendocrine tumors.

Dermatomyositis is an idiopathic inflammatory myopathy with cutaneous manifestations, which is associated with several types of malignancies, yet it has been rarely linked to neuroendocrine tumors (NETs). Here we report two cases of dermatomyositis associated with NETs of differing primary sites. Case 1: A 46-year-old female presented with a facial rash and proximal muscle weakness of both extremities. Investigations revealed elevated creatine kinase (CK) and positive anti-transcriptional intermediary factor 1-γ antibody (TIF1γ). The patient had been diagnosed with dermatomyositis and underwent a total body CT scan, which revealed prominent mediastinal lymphadenopathy, which a subsequent biopsy determined to be neuroendocrine carcinoma of small cell type. Treatment with high-dose corticosteroids was initiated, in addition to chemotherapy-based oncological management. Case 2: A 54-year-old female presented with a facial rash, progressive dyspnea, and general malaise. Laboratory investigations revealed positive anti-melanoma differentiation-associated gene-5 (MDA5) and positive anti-Ro antibody, with a normal level of creatine kinase (CK). A chest CT scan revealed multiple ground-glass opacities. Despite treatment with high-dose intravenous methylprednisolone, IVIG and an infusion of the anti-IL-6 sarilumab [Kevzara], the patient rapidly deteriorated and was intubated. Within days, the patient developed bowel ischemia and underwent a laparotomy which was then complicated by an invasive infection. This resulted in patient's death. Pathology results from colonic tissue demonstrated an appendiceal neuroendocrine tumor. These cases demonstrate the heterogeneity and complexity of dermatomyositis in association with neuroendocrine tumors.

The existence of a bidirectional link between ischemic heart disease and fibromyalgia.

STUDY OBJECTIVES: Fibromyalgia (FM) is one of the most common causes of chronic widespread musculoskeletal pain, but also sleep disturbances, cognitive and psychological disorders. It has been suggested that FM may have a correlation with cardiovascular events. In this study, we aimed to assess the association between FM and ischemic heart disease (IHD). METHODS: A population-based cross-sectional study was conducted utilizing data retrieved from the largest medical records database in Israel, Clalit Health Services. Patients were defined as having FM or IHD when there were at least two such documented diagnoses in their medical records. The occurrence of IHD was compared between FM and age- and sex-frequency-matched healthy controls. A logistic regression model was used to estimate this association following an adjustment for conventional cardiovascular risk factors and depression. RESULTS: An overall population of 18 598 FM patients and 36 985 age- and gender-matched controls were included in the study. The proportion of IHD amongst FM patients was increased in comparison to controls (9.2% and 6.2%, respectively; P  < 0.001). Furthermore, FM demonstrated an independent association with IHD on multivariate analysis (odds ratio [OR], 1.43; 95% confidence intervals [CI], 1.33-1.54; P  < 0.0001). Finally, IHD was also found to be independently associated with the diagnosis of FM (OR, 1.40; CI, 1.31-1.51; P  < 0.0001). CONCLUSION: Our data suggest a bidirectional link between FM and IHD even after the adjustment for conventional cardiovascular risk factors. These findings should be considered when treating patients with either FM or IHD, and their routine interactional screening may be of clinical importance.

TMS in combination with a pain directed intervention for the treatment of fibromyalgia - A randomized, double-blind, sham-controlled trial.

BACKGROUND: Fibromyalgia Syndrome (FMS) is a highly prevalent condition, that causes chronic pain and severe reduction in quality of life and productivity, as well as social isolation. Despite the significant morbidity and economic burden of FMS, current treatments are scarce. OBJECTIVE: To investigate whether stimulation of ACC -mPFC activity by dTMS enhances a pain-directed psychotherapeutic intervention. METHODS: 19 FMS patients were randomised to receive either 20 sessions of dTMS or sham stimulation, each followed by a pain-directed psychotherapeutic intervention. With the H7 HAC coil or sham stimulation, we targeted the ACC -mPFC; specific brain areas that play a central role in pain processing. Clinical response to treatment was assessed with the McGill Pain Questionnaire Short Form (SF-MPQ), the Visual Analogue Fibromyalgia Impact Questionnaire, the Brief Pain Inventory questionnaire, and the Hamilton Depression Rating Scale. RESULTS: DTMS treatment was safe and well tolerated by FMS patients. A significant decrease in the combined sensory and affective pain dimensions was specifically demonstrated in the dTMS cohort, as measured by the SF-MPQ (Significant group × time interaction [F(2, 32) = 3.51, p < .05,ηp2 = 0.18]; No significant changes were found in depressive symptoms in both the dTMS and sham groups. CONCLUSION: Our results suggest that a course of dTMS combined with a pain-directed psychotherapeutic intervention can alleviate pain symptoms in FMS patients. Beyond clinical possibilities, future studies are needed to substantiate the innovative hypothesis that it is not dTMS alone, but rather dTMS-induced plasticity of pain-related networks, that enables the efficacy of pain-directed psychotherapeutic interventions.

The Risk and Predictors of Malignancies in Ankylosing Spondylitis Patients in Israel-A Retrospective Electronic Data-Based Study.

BACKGROUND: Previous studies demonstrated unclear and vast variability in the association between Ankylosing Spondylitis (AS) and the risk of cancer. OBJECTIVES: To assess the risk of overall and site-specific malignancies for AS patients in Israel, while examining the role of comorbidities and immunomodulatory therapy. METHODS: We conducted a retrospective electronic data-based study including all AS patients diagnosed between 2002 and 2018, with no history of cancer prior to enrollment, with 5:1 ratio matched-control by age, gender, and place of residence. The odds Ratios (OR) for site-specific malignancies, comparing AS patients and controls, were calculated using logistic regression. Risk factors for malignancies within the AS cohort were evaluated in the same manner. RESULTS: This study comprised 5825 AS patients and 28,356 matched controls. There was a higher overall risk of cancer in AS patients compared to controls (OR = 1.4, 95% CI 1.24-1.6), specifically for solid malignancies (OR = 1.5, 95% CI 1.3-1.7), CNS (OR = 3.72, 95% CI 1.29-10.7), kidney (OR = 2.06, 95% CI 1.12-3.8), and malignancy of unknown primary (OR = 3.06, 95% CI 2.35-3.98). Regarding predictors for malignancy within AS patients, older age at diagnosis (OR = 1.31, 95%,CI 1.25-2.36), diabetes (OR = 1.52, 95% CI 1.18-1.97), IBD (OR = 2.61, 95% CI 1.75-3.89), and treatment with DMARDs (OR = 2.17, 95% CI 1.65-2.83) were associated with a higher risk of solid malignancies, while NSAIDs treatment alone had a protective effect for solid malignancies (OR = 0.78, 95% CI 0.61-0.99). No significant association was found between anti-TNF therapy and the risk of solid or hematologic malignancies within the AS group. CONCLUSION: AS is associated with an increased risk of overall and site-specific malignancies, with independently higher risk for older age, comorbidity of DM, IBD, and treatment with DMARDs.

The Prognostic Value of Anti-PLA2R Antibodies Levels in Primary Membranous Nephropathy.

Anti-PLA2R antibodies (Ab) are a diagnostic and prognostic biomarker in primary membranous nephropathy (PMN). We assessed the relationship between the levels of anti-PLA2R Ab at diagnosis and different variables related to disease activity and prognosis in a western population of PMN patients. Forty-one patients with positive anti-PLA2R Ab from three nephrology departments in Israel were enrolled. Clinical and laboratory data were collected at diagnosis and after one year of follow-up, including serum anti-PLA2R Ab levels (ELISA) and glomerular PLA2R deposits on biopsy. Univariable statistical analysis and permutation-based ANOVA and ANCOVA tests were performed. The median [(interquartile range (IQR)) age of the patients was 63 [50-71], with 28 (68%) males. At the time of diagnosis, 38 (93%) of the patients had nephrotic range proteinuria, and 19 (46%) had heavy proteinuria (≥8 gr/24 h). The median [IQR] level of anti-PLA2R at diagnosis was 78 [35-183] RU/mL. Anti-PLA2R levels at diagnosis were correlated with 24 h proteinuria, hypoalbuminemia and remission after one year (p = 0.017, p = 0.003 and p = 0.034, respectively). The correlations for 24 h proteinuria and hypoalbuminemia remained significant after adjustment for immunosuppressive treatment (p = 0.003 and p = 0.034, respectively). Higher levels of anti-PLA2R Ab at diagnosis in patients with active PMN from a western population are associated with higher proteinuria, lower serum albumin and remission one year after the diagnosis. This finding supports the prognostic value of anti-PLA2R Ab levels and their possible use in stratifying PMN patients.

Anti-TPO-mediated specific features of the placenta immunohistochemical profile and possible mechanisms for fetal loss.

Passive transfer of antithyroid antibodies in mice leads to reproductive disorders. The purpose was to assess the placental tissue of experimental animals under the influence of the circulating thyroperoxidase antibodies. We performed an immunohistochemical examination of murine placentae after a passive transfer of thyroperoxidase antibodies. Placentae of mice that passively transferred IgG from healthy donors were used as control samples. For histological examination, 30 placental samples were selected from mice from the anti-TPO group and 40 placental samples were taken from mice from the IgG group. Immunostaining for VEGFR1, THBS 1, Laminin, CD31, CD34, FGF-ß, CD56, CD14, TNF-α, kisspeptin, MCL 1, and Annexin V was performed. There is a significant decrease in the relative area of the expression of VEGFR1 (23.42 ± 0.85 vs. 33.44 ± 0.35, P < 0.01), thrombospondin 1 (31.29 ± 0.83 vs. 34.51 ± 0.75, P < 0.01), CD14 (25.80 ± 0.57 vs. 32.07 ± 0.36, P < .01), CD56 (30.08 ± 0.90 vs. 34.92 ± 0.15, P < 0.01), kisspeptin (25.94 ± 0.47 vs. 31.27 ± 0.57, P < 0.01), MCL 1 (29.24 ± 1.06 vs. 38.57 ± 0.79, P < 0.01) in the labyrinth zone of the placentae of mice from the anti-TPO group compared with control group. A significant increase in the relative expression of laminin and FGF-ß was noted in the group of mice to which antibodies to thyroperoxidase were transferred, compared with the control group (36.73 ± 1.38 vs. 29.83 ± 0.94, P < 0.01 and 23.26 ± 0.61 vs. 16.38 ± 1.01, P < 0.01respectively). Our study exposed an imbalance of pro- and anti-angiogenic factors, decreased representation of placental macrophages and NK cells, abnormal trophoblast invasion processes, and insufficient expression of antiapoptotic factors in the placentae of mice in which anti-TPO antibodies were passively transferred.

Association of fibromyalgia with cancerous and non-cancerous gastrointestinal comorbidities: a cross-sectional study.

OBJECTIVES: Several studies have shown a higher prevalence of irritable bowel syndrome (IBS) among patients with fibromyalgia yet, data regarding association between fibromyalgia and other gastrointestinal disorders have been relatively overlooked. Our aim was to investigate the association between fibromyalgia and gastrointestinal disorders including both benign and malignant conditions. METHODS: We conducted a retrospective cross-sectional study based on the comprehensive electronic database of the largest health maintenance organisation in Israel. All subjects with a diagnosis of fibromyalgia in their medical records and age- and sex-matched controls were included in the study. We investigated the association of fibromyalgia with benign gastrointestinal disorders including IBS, gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), celiac disease, Crohn's disease, ulcerative colitis, and with gastrointestinal malignancies including colorectal, pancreatic, stomach, liver, and bile duct cancers. RESULTS: The study enrolled 18,598 patients with fibromyalgia and 36,985 controls. The mean age was 56.5 years (standard deviation=14) with a female predominance (91%). Fibromyalgia was significantly associated with IBS (OR 4.61, 95% CI 4.09-5.2, p<0.001), GERD (OR 2.62, 95% CI 2.5-2.75, p<0.001), PUD (OR 2.13, 95% CI 1.98-2.3, p<0.001), celiac disease (OR 2.08, 95% CI 1.63-2.65, p<0.001), Crohn's disease (OR 1.85, 95% CI 1.408-2.32, p<0.001) and ulcerative colitis (OR 1.81, 95%CI 1.4-2.33, p<0.001). Nonetheless, no significant differences were found regarding the prevalence of gastrointestinal malignancies between the fibromyalgia patients and controls. CONCLUSIONS: Our findings suggest that FM is positively associated with various benign but not malignant GI disorders.

Increased risk for stroke in patients with familial Mediterranean fever: results from a large population-based study.

OBJECTIVE: The association between chronic inflammatory conditions and cardiovascular disease is well established. Considering FMF, few studies exist investigating the risk of ischaemic heart disease, and none address the risk of stroke. We aimed to evaluate the incidence and risk for stroke in FMF patients compared with the general population. METHODS: A retrospective cohort study using the electronic database of Clalit Health Services (CHS), the largest health organization in Israel. All FMF patients diagnosed between 2000 and 2016 were included and matched with control according to age, gender and place of residence. Follow-up continued until the first diagnosis of stroke or death. The incidence of stroke was compared between the groups using univariate and multivariate models adjusting for cardiovascular risk-factors. RESULTS: A total of 9769 FMF patients and a similar number of controls were followed up for a median period of 12.5 years. The mean age at the beginning of the follow-up was 25.7 years. In total, 208 FMF patients were diagnosed with stroke compared with 148 controls, resulting in an incidence rate (per 10 000 persons-years) of 19.8 (95% CI 17.2, 22.7) and 13.9 (95% CI 11.8, 16.4), respectively, and a crude HR of 1.42 (95% CI 1.15-1.76; P < 0.001). In a multivariate analysis, FMF patients who developed amyloidosis with related or non-related renal failure demonstrated significant stroke risk (HR = 2.16; 95% CI 1.38, 3.38; P < 0.001), as well as for those who did not develop these complications (HR = 1.32; 95% CI 1.04, 1.67; P < 0.05). CONCLUSION: FMF patients are at increased risk for stroke regardless of known complications.

Susac syndrome following COVID-19 vaccination: a case-based review.

COVID-19 vaccine circulation approval was a turning point for the coronavirus pandemic. The current approved COVID-19 vaccines, including messenger ribonucleic acid (mRNA)-based and adenovirus vector-based vaccines, were shown to significantly reduce the disease mortality and severity, and its adverse reactions are mainly mild ones. However, few cases of autoimmune conditions, both flare-ups and new-onset, were described in association with these vaccines. Susac vasculitis (SaS) is a rare autoimmune disease characterized by the clinical triad of encephalopathy, visual disturbances, and sensorineural hearing loss. Its pathogenesis is still not fully understood but is believed to be related to autoimmune processes, including autoantibodies to anti-endothelial cells and cellular immune processes that lead to microvascular damage and, consequently, micro-occlusions of the cerebral, inner ear, and retinal vessels. It has been previously described following vaccination and, most recently, few cases following coronavirus vaccines. We here describe a case of a previously healthy 49-year-old man diagnosed with SaS 5 days following the first dose of the BNT162b2 COVID-19 vaccine.

Possible Association Between Anti-Trisulfated-Heparin-Disaccharide (TS-HDS) Immunoglobulin M Autoantibody and Fibromyalgia Syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is estimated to affect 2-4% of the general population. While FMS has some known environmental and genetic risk factors, the disorder has no clear etiology. A common coexisting disorder with FMS is small fiber neuropathy (SFN). High levels of serum immunoglobulin M (IgM) binding to trisulfated-heparin-disaccharide (TS-HDS) were recently found to be associated with SFN. OBJECTIVES: To evaluate potential differences in anti-TS-HDS antibody titers in women with FMS compared to healthy controls. METHODS: In this cross-sectional study, we evaluated 51 female participants: 30 with a diagnosis of FMS and 21 healthy controls who had been recruited at the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel. All of the participants were older than 18 years of age. Anti-TS-HDS IgM levels were measured in their sera using the enzyme immunoassay technique. RESULTS: The mean anti-TS-HDS IgM levels were significantly lower in the FMS group, compared with the control group (7.7 ± 5 vs. 13.2 ± 8.6 U/ml, respectively; P = 0.013). CONCLUSIONS: There is a possible association between FMS and anti-TS-HDS IgM. This association might be the missing link for the coexistence of SFN and FMS, but further study should be performed to assess this association and this auto-antibody characteristic.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) in 2023.

In 2011, a syndrome entitled ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants; Shoenfeld's syndrome) was first described. ASIA aimed to organize under a single umbrella, the existing evidence regarding certain environmental factors which possess immune stimulatory properties, in order to shed light on a common pathway of autoimmune pathogenesis. Such environmental immune stimulators, or adjuvants, include among others: aluminum salts as in vaccines, various medical implants, as well as various infectious agents. After the launch of the ASIA syndrome, the expansion and recognition of this syndrome by different researchers from different countries began. During the past decades, evidence had been accumulating that (auto)immune symptoms can be triggered by exposure to environmental immune stimulatory factors that act as an adjuvant in genetically susceptible individuals. A panoply of unexplained subjective and autonomic-related symptoms has been reported in patients with ASIA syndrome. The current review summarizes and updates accumulated knowledge from the past decades, describing new adjuvants- (e.g. polypropylene meshes) and vaccine- (e.g. HPV and COVID vaccines) induced ASIA. Furthermore, a direct association between inflammatory/autoimmune diseases with ASIA syndrome, will be discussed. Recent cases will strengthen some of the criteria depicted in ASIA syndrome such as clear improvement of symptoms by the removal of adjuvants (e.g. silicone breast implants) from the body of patients. Finally, we will introduce additional factors to be included in the criteria for ASIA syndrome such as: (1) dysregulated non-classical autoantibodies directed against G-protein coupled receptors (GPCRs) of the autonomic nervous system and (2)) small fiber neuropathy (SFN), both of which might explain, at least in part, the development of 'dysautonomia' reported in many ASIA patients.

The possible onset of fibromyalgia following acute COVID-19 infection.

INTRODUCTION: The exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, various infectious have been implicated with the development of FM after their acute phase. We aimed to investigate the incidence of FM syndrome among convalesced individuals following hospitalization for Acute Coronavirus Disease-2019 (COVID-19). METHODS: We performed a cross-sectional study on patients who were discharged after COVID-19 hospitalization from the Sheba Medical Center, Israel, between July 2020 to November 2020. A phone interview was performed consisting of the following questionnaires: the Fibromyalgia Survey Diagnostic Criteria Questionnaire, Sense of Coherence Questionnaire to evaluate resilience, and the Subjective Traumatic Outlook Questionnaire to assess the associated psychological aspects of the trauma. The incidence of post-COVID FM was calculated and regression models were performed to identify predictors. RESULTS: The study population consisted of 198 eligible patients who completed the phone interview. The median age was 64 (52-72) and 37% were women. The median follow-up was 5.2 months (IQR 4.4-5.8). The incidence of FM was 15% (30 patients) and 87% (172 patients) had at least one FM-related symptom. Female gender was significantly associated with post-COVID FM (OR 3.65, p = 0.002). In addition, high median Subjective Traumatic Outlook scores and low median Sense of Coherence scores were both significantly associated with post-COVID FM (OR 1.19, p<0.001 and OR 0.92, p<0.001, respectively). CONCLUSIONS: FM is highly prevalent among COVID-19 convalescent patients. Our finding suggests that a significant subjective traumatic experience and a low resilience are highly associated with post-COVID FM.

The association between ankylosing spondylitis and psychiatric disorders: Insights from a population based cross-sectional database.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease involving the axial skeleton ultimately resulting in physical disability and psychological sequalae. The current study aims to evaluate the link between AS and psychiatric disorders, and to investigate the impact of different disease modifying drugs on such link. METHODS: A large retrospective, population-based, cross-sectional study utilizing the Clalit-Health-Service (CHS) database was conducted on 5825 AS patients and 25,984 age- and sex-matched control individuals. The prevalence of psychiatric morbidity was compared between AS patients and age- and gender-matched controls. Predictors for psychiatric disorders in AS patients were also investigated. RESULTS: The prevalence of psychiatric morbidity was higher in AS patients compared to controls (13.8 % vs. 9.8 %, p < 0.001). Similarly, major depression was positively associated with AS (OR 1.60, 95 % CI 1.43-1.79, p < 0.001), however, schizophrenia was negatively associated with AS (OR 0.60, 95 % CI 0.42-0.89, p < 0.011). Conventional DMARDs (cDMARDs) and anti-TNF used for management of AS were not shown to be predictors for psychiatric illnesses in AS patients. CONCLUSIONS: Patients with AS are at a higher risk of developing psychiatric disorders, with increased risk of depression and lower risk of schizophrenia. cDMARDs and TNF-inhibitors are not predictors of psychiatric disorders in AS patients.

Artificial neural networks can be effectively used to model changes of intracranial pressure (ICP) during spinal surgery using different noninvasive ICP surrogate estimators.

BACKGROUND: Artificial intelligence (AI) techniques play a major role in anesthesiology, even though their importance is often overlooked. In the extant literature, AI approaches, such as artificial neural networks (ANNs), have been underutilized, being used mainly to model patient's consciousness state, to predict the precise number of anesthetic gases, the level of analgesia, or the need of anesthesiological blocks, among others. In the field of neurosurgery, ANNs have been effectively applied to the diagnosis and prognosis of cerebral tumors, seizures, low back pain, and also to the monitoring of intracranial pressure (ICP). METHODS: A multilayer perceptron (MLP), which is a feedforward ANN, with hyperbolic tangent as activation function in the input/hidden layers, softmax as activation function in the output layer, and cross-entropy as error function, was used to model the impact of prone versus supine position and the use of positive end expiratory pressure (PEEP) on ICP in a sample of 30 patients undergoing spinal surgery. Different noninvasive surrogate estimations of ICP have been used and compared: namely, mean optic nerve sheath diameter (ONSD), noninvasive estimated cerebral perfusion pressure (NCPP), Pulsatility Index (PI), ICP derived from PI (ICP-PI), and flow velocity diastolic formula (FVDICP). RESULTS: ONSD proved to be a more robust surrogate estimation of ICP, with a predictive power of 75%, whilst the power of NCPP, ICP-PI, PI, and FVDICP were 60.5%, 54.8%, 53.1%, and 47.7%, respectively. CONCLUSIONS: Our MLP analysis confirmed our findings previously obtained with regression, correlation, multivariate receiving operator curve (multi-ROC) analyses. ANNs can be successfully used to predict the effects of prone versus supine position and PEEP on ICP in patients undergoing spinal surgery using different noninvasive surrogate estimators of ICP.