Neurocognitive Functions After 6-Month Buprenorphine (Naloxone)-Based Opioid Agonist Maintenance Treatment: A Controlled Prospective Study.

BACKGROUND: Medications for opioid use disorder (OUD) may influence neurocognitive functions. Inadequate power, confounders, and practice effects limit the validity of the existing research. We examined the change in cognitive functions in patients with OUD at 6-month buprenorphine (naloxone) posttreatment and compared the cognitive performance of the buprenorphine-treated group with control subjects. METHODS: We recruited 498 patients with OUD within a week of initiating buprenorphine. Assessments were done twice-at baseline and 6 months. Those abstinent from illicit opioids and adherent to treatment (n = 199) underwent follow-up assessments. Ninety-eight non-substance-using control subjects were recruited from the community. The neurocognitive assessments comprised the Wisconsin Card Sorting Test, Iowa Gambling Task, Trail-Making Tests A and B (TMT-A and TMT-B), and verbal and visual N-Back Test. We controlled for potential effect modifiers. RESULTS: Twenty-five of the 32 test parameters significantly improved with 6 months of buprenorphine treatment; 20 parameters withstood corrections for multiple comparisons (P < 0.001). The improved test domains spread across cognitive tests: Wisconsin Card Sorting Test (perseverative errors and response, categories completed, conceptual responses), TMTs (time to complete), verbal and visual N-Back Tests (hits, omission, and total errors). After treatment, OUD (vs control subjects) had less perseverative response and error (P < 0.001) and higher conceptual response (P = 0.004) and took lesser time to complete TMT-A (P < 0.001) and TMT-B (P = 0.005). The baseline neurocognitive functions did not differ between those who retained and those who discontinued the treatment. CONCLUSION: Cognitive functions improve in patients with OUD on buprenorphine. This improvement is unlikely to be accounted for by the practice effect, selective attrition, and potential confounders.

Neurocognitive Dysfunctions in People with Concurrent Cannabis Use and Opioid Dependence: A Cross-Sectional, Controlled Study.

Cannabis and opioid co-dependence is independently associated with cognitive impairments. We examined neurocognitive dysfunctions in people with concurrent opioid dependence with cannabis dependence (OD+CD) or cannabis use (OD+CU) compared to those with only opioid dependence (OD) and healthy controls (HC). We selected adult participants, any sex, who met the diagnosis of OD (N = 268), OD+CU (N = 58), and OD + CD (N = 115). We recruited 68 education-matched HC. We administeredStandard progressive matrices (SPM), Wisconsin card sorting test (WCST), Iowa gambling task (IGT), Trail making tests A and B (TMT), and verbal and visual working memory 1-, 2-backtests. 496 (97.5%) were men, and 13 (2.5%) were women. In WCST, OD and OD+CD had significantly higher non-perseverative errors than HC. OD+CD group completed significantly lesser categories than HC. In verbal working memory 2-back, HC scored significantly fewer errors than OD and OD +CD. All patient groups, OD, OD+CU, and OD+CD, scored higher commission errors than HC in visual working memory 1-back. OD and OD+CD scored higher commission and total errors than the controls. OD+CU showed lesser error score than HC in TMT B. Cannabis and opioid co-dependence contribute to cognitive impairments, especially in working memory and executive functions.

Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF - An Open Label Randomized Clinical Trial.

Background: Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. We conducted a prospective, randomized controlled clinical trial to study the efficacy of intravenous branched chain amino acids (IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24 h, day 3, and day 7. The primary outcome was an improvement in encephalopathy by ≥ 1 grade at 72 h. Patients and methods: European association for study of liver (EASL) defined ACLF patients with overt HE were assessed and randomized into the experimental arm (IV-BCAA - 500 mL/day for 3 days + Lactulose; n = 39) and the comparator arm (Lactulose alone; n = 37). Six patients developed COVID-19 after randomization and were excluded (4-experimental arm and 2-comparator arm). Results: Of 222 screened patients, 70 (35 in each arm) were included in the analysis. Baseline characteristics, including HE grade (2.9 ± 0.7 vs 2.8 ± 0.7; P = 0.86) and (chronic liver failure) CLIF-C ACLF score (54.2 ± 5.6 vs 54.8 ± 5.7; P = 0.65), were similar. Overall survival was 40% at 28 days (48.5% vs 31.4%; P = 0.14). Improvement in hepatic encephalopathy scoring algorithm (HESA) by ≥ 1 grade at 24 h occurred in 14 patients (40%) in the BCAA arm and 6 patients (17.1%) in the control group (P = 0.03) which translated to a shorter intensive care unit (ICU) stay. The median change in HESA at 24 h was greater in the BCAA arm than the control arm (P = 0.006), which was not sustained at days 3 or 7. Ammonia levels did not correlate with the grade of HE (Spearman's correlation coefficient (ρ) = - 0.0843; P = 0.29). Conclusion: Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. Trial registration no: NCT04238416 (clinicaltrials.gov).

A Case Series of Scrub Meningoencephalitis from a Tertiary Care Center in North India.

Scrub typhus infection is reemerging leading cause of acute febrile illnesses in post-rainy or monsoon season in Southeast Asia. It is caused by Orientia tsutsugamushi and spread by the bite of chiggers, larval forms of trombiculid mites. The clinical picture can range from simple acute febrile illness to multiorgan dysfunction. Neurological manifestations also vary from aseptic meningitis, meningoencephalitis, cerebral infarction, acute disseminated encephalomyelitis, transverse myelitis, and psychiatric manifestations. Here, we present a case series of eight cases of scrub meningoencephalitis diagnosed based on clinical, laboratory, and radiological criteria.

Morphology of intra tumoral cystic vestibular schwannoma and their response to gammaknife radiosurgery.

BACKGROUND: Cystic vestibular schwannoma (CVS) traditionally considered as poor responder to gammaknife radiosurgery (GKRS). Their longterm radiobiological behavior is less known. Here we discuss 38 cases with intra tumoral cyst CVS primarily treated with GKRS. Tumor morphology was assessed to understand their response to GKRS. METHODS: Total 38 patients(21 male and 17 female with median age of 41.7 years) of CVS treated with GKRS were retrospectively analysed. Tumors were divided as predominantly (greater than50% of total tumor volume) cystic or solid. They were subclassified as type 1 (predominantly cystic CVS, single cyst), type 2 (predominantly solid CVS, single cysts), type 3 (multicystic CVS). The entire cyst was incorporated for radiosurgery. The results were compared with volume matched control of 58 solid tumors(SVS). RESULT: The median tumor volume of CVS was 5.8 cc. The median tumor volume reduction was 44.5 % at a median follow-up of 68.5 months (30-110 months). Median tumor volume reduction was 68.5 %, 34.0%, 11.0.%, 30.5% at a median follow up of 52.5months, 66 months, 78.6 months, 96.5 months for type 1 CVS, type 2 CVS, type 3 CVS and SVS respectively. One patient with multicystic CVS showed increased tumor volume and expired after 9 months of surgery.The tumor volume reduction in type 1CVS was statistically significant as compared to type 3 CVS and SVS. However the tumor volume reduction among other groups did not differ significantly. CONCLUSION: Intra tumoral cystic components respond better to gammaknife radiosurgery in CVS. Tumor with single cyst respond better than multicystic vestibular schwannoma.

Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India.

Importance: Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water. Objective: To identify cognitive impairments following commonly prevalent low-level arsenic exposure and characterize their underlying brain mechanisms. Design, Setting, and Participants: This multicenter population-based cohort study analyzed cross-sectional data of the Indian Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA) cohort, recruited between November 4, 2016, and May 4, 2019. Participants aged 6 to 23 years were characterized using deep phenotyping measures of behavior, neuropsychology, psychopathology, brain neuroimaging, and exposure to developmental adversities and environmental neurotoxins. All analyses were performed between June 1, 2020, and December 31, 2021. Exposure: Arsenic levels were measured in urine as an index of exposure. Main Outcomes and Measures: Executive function measured using the cVEDA neuropsychological battery, gray matter volume (GMV) from T1-weighted magnetic resonance imaging, and functional network connectivity measures from resting state functional magnetic resonance imaging. Results: A total of 1014 participants aged 6 to 23 years (589 male [58.1%]; mean [SD] age, 14.86 [4.79] years) were included from 5 geographic locations. Sparse-partial least squares analysis was used to describe a negative association of arsenic exposure with executive function (r = -0.12 [P = 5.4 × 10-4]), brain structure (r = -0.20 [P = 1.8 × 10-8]), and functional connectivity (within network, r = -0.12 [P = 7.5 × 10-4]; between network, r = -0.23 [P = 1.8 × 10-10]). Alterations in executive function were partially mediated by GMV (b = -0.004 [95% CI, -0.007 to -0.002]) and within-network functional connectivity (b = -0.004 [95% CI, -0.008 to -0.002]). Socioeconomic status and body mass index moderated the association between arsenic and GMV, such that the association was strongest in participants with lower socioeconomic status and body mass index. Conclusions and Relevance: The findings of this cross-sectional study suggest that low-level arsenic exposure was associated with alterations in executive functioning and underlying brain correlates. These results indicate potential detrimental consequences of arsenic exposure that are below the currently recommended guidelines and may extend beyond endemic risk areas. Precision medicine approaches to study global mental health vulnerabilities highlight widespread but potentially modifiable risk factors and a mechanistic understanding of the impact of low-level arsenic exposure on brain development.

Development, Validation, and Impact of Patient Information Booklet for Gamma Knife Radiosurgery.

Background: The inadequate awareness in the general population is a primary concern for the management of various neurosurgical ailments treated with gamma knife radiosurgery (GKRS). Objective: Our study aimed to assess the written patient information by focusing on readability, recall, communication, compliance, and patient satisfaction. Methodology: The senior author formulated disease-specific patient information booklets. The booklets comprised two segments: general information about GKRS and disease-specific information. The common themes for discussion were "What is your disease?", "What is gamma knife radiosurgery?", "What are the alternatives to gamma knife radiosurgery," "The benefits of gamma knife radiosurgery," "About gamma knife radiosurgery," "Recovering from gamma knife radiosurgery," "Follow up," "What are the risks," and "Contact." The booklet was emailed after the first consultation to 102 patients. Patients' socioeconomic status and comprehensibility were assessed on validated scoring. Post-GKRS, we emailed a custom-made Google feedback survey of 10 leading questions about the role of patient information booklet in educating and decision-making process. We tried to assess if the booklet helped the patient understand the disease and treatment options. Results: In total, 94% of patients read it thoroughly and understood it to their satisfaction. They also shared and discussed the information booklet with their family members and relatives (92%). Furthermore, 96% of patients found the disease-specific information informative. For 83% of patients, the information brochure cleared the doubts regarding the GKRS completely. For 66% of patients, their expectations met the reality. In addition, 94% of patients still recommended giving the booklet to the patients. All high, upper- and middle-class responders were happy and content with the patient information booklet. In contrast, 18 (90%) of the lower middle class and 2 (66.7%) of the lower class considered the information useful to the patients. Also, 90% patients found the language of the patient information booklet comprehensible and not too technical to understand. Conclusions: An essential component of disease management is to relieve the anxiety and confusion in the patient's mind and help one choose a treatment modality among the available options. A patient-centric booklet helps impart knowledge, clears doubts, and provides an opportunity to discuss options with family members.

Radiological Parameters for Gamma Knife Radiosurgery.

Accurate lesion targeting is the essence of stereotactic radiosurgery. With the currently available imaging modalities, scanning has become quick and robust providing a high degree of spatial resolution resulting in optimal contrast between normal and abnormal tissues. Magnetic resonance imaging (MRI) forms the backbone of Leksell radiosurgery. It produces images with excellent soft tissue details highlighting the target and surrounding "at-risk" structures conspicuously. However, one must be aware of the MRI distortions that may arise during treatment. Computed tomography (CT) has quick acquisition times giving excellent bony information but inferior soft tissue details. To avail benefits of both these modalities and overcome their individual fallacies and shortcomings, they are often co-registered/fused for stereotactic guidance. Vascular lesions like an arteriovenous malformation (AVM) are best planned with cerebral digital subtraction angiography (DSA) in conjunction with MRI. In specific cases, specialized imaging methods like magnetic resonance (MR) spectroscopy, positron emission tomography (PET), magneto-encephalography (MEG), etc., may be added to the treatment planning for stereotactic radiosurgery (SRS).

Hypo-fractionated Gamma Knife Radiosurgery for Intra-cranial Pathologies: A Single-Center Prospective Analysis of Feasibility, Safety, Efficacy, and Complication Profile.

Background: Single-session stereotactic radiosurgery (SRS) is a proven and effective treatment modality for various benign, malignant, and functional intra-cranial pathologies. In certain situations, single-fraction SRS is limited because of lesion size and location. Hypo-fractionated gamma knife radiosurgery (hfGKRS) is an alternative approach for such unconventional indications. Objective: To evaluate the feasibility, efficacy, safety, and complication profile of hfGKRS with evaluation of different fractionation schemes and dosing patterns. Methodology: The authors prospectively evaluated 202 patients treated with frame-based hfGKRS over a 9-year period. GKRS was administered fractionated because of either a large volume (>14 cc) or an inability to spare neighboring organs at risk from permissible radiation in single-session GKRS. The inter-fraction interval was kept at 24 hours, and the dose calculation was performed with linear quadratic equations. Patients with more than 3 years of clinical and radiological follow-up were included in prospective analysis. At pre-decided follow-up criteria, treatment effects and side effects were documented on objective scales. Results: A total of 169/202 patients met inclusion criteria. 41% patients received treatment in three fractions, whereas 59% received two-fraction GKRS. Two patients of giant cavernous sinus hemangiomas were treated with 5 Gy in the five-fraction regimen. In patients with more than 3 years of follow-up, the obliteration rate was 88% for complex arteriovenous malformations (AVMs) treated with hfGKRS because of eloquent locations, whereas it was 62% for Spetzler-Martin grade 4-5 AVMs. For non-AVM pathologies (meningiomas, schwannomas, pituitary adenomas, paragangliomas, hypothalamic hamartomas, etc.), the 5-year progression free survival was 95%. Tumor failure was noted in 0.05% patient population. Radiation necrosis developed in 8.1% patients, and radiation-induced brain edema developed in 12% patients. It was resistant to treatment in 4% patients. No patient developed radiation-induced malignancy. Hypo-fractionation did not provide any hearing improvement in giant vestibular schwannomas. Conclusion: hfGKRS is a valuable standalone treatment option for candidates unsuitable for single-session GKRS. The dosing parameters need to be tailored as per the pathology and neighboring structures. It provides comparable results to single-session GKRS with an acceptable safety and complication profile.

Impulse Control Disorders with Short-term Use of Cabergoline in Macroprolactinomas: A Prospective Study with a Brief Review of Literature.

Impulse control disorders (ICDs) are less-emphasized adverse effects of dopamine agonists. Evidence on prevalence and predictors of ICDs in patients with prolactinomas is limited and confined chiefly to cross-sectional studies. This was a prospective study performed to investigate ICDs in treatment-naïve patients with macroprolactinomas (n = 15) using cabergoline (Group I), compared to consecutive patients of nonfunctioning pituitary macroadenomas (n = 15) (Group II). Clinical, biochemical, radiological parameters and psychiatric comorbidities were evaluated at baseline. ICD was assessed by Minnesota impulsive disorder interview, modified hypersexuality and punding questionnaires, South Oaks gambling scale, kleptomania symptom assessment scale, Barratt impulsive scale (BIS), and internet addiction scores (IAS) at baseline and 12 weeks. Group I had a significantly lower mean age (28.5 vs. 42.2 years) with a female predominance (60%) compared to group II. Median tumor volume was lower in group I (4.92 vs. 14 cm3) despite significantly longer symptom duration (2.13 vs. 0.80 years) than in group II. Serum prolactin decreased by 86% (P = 0.006) and tumor volume decreased by 56% (P = 0.004) at 12 weeks in group I, with a mean weekly cabergoline dose of 0.40 ± 0.13 mg. There was no difference between both groups in hypersexuality, gambling, punding, and kleptomania symptom assessment scale scores at baseline and 12 weeks. Mean BIS showed a more remarkable change in group I (16.2% vs. 8.4%, P = 0.051), and 38.5% of patients transitioned from average to above-average IAS in group I. The current study found no increased risk of ICD with short-term use of cabergoline in patients with macroprolactinomas. The use of age-appropriate scores (such as IAS in younger individuals) may help diagnose subtle alterations in impulsivity.

Heroin use and neuropsychological impairments: comparison of intravenous and inhalational use.

BACKGROUND AND OBJECTIVES: Injection and inhalational heroin use are associated with different levels of brain exposure to heroin and its metabolites and differences in the severity of dependence, which might lead to differential impacts on neuropsychological functions. We examined the difference and the magnitude of difference in the neuropsychological functions between inhalational and injection heroin-dependent subjects and also compared them with healthy controls. METHODS: The study sample comprised three groups: 73 subjects with injection heroin dependence, 74 with inhalational heroin dependence, and 75 healthy controls (HC). We excluded patients with HIV, head injury, epilepsy, and severe mental illness. Neuropsychological assessments were done by Standard Progressive Matrices, Wisconsin Card Sorting Test (WCST), Iowa Gambling Task, Trail-Making Tests A and B (TMT), and Verbal and Visual Memory 1 and 2 Backtests (NBT). We estimated independent effects of the groups on various neuropsychological test parameters, adjusted for age and duration of dependence. RESULTS: In the WCST, the inhalational heroin-dependent group took more trials to complete the first category and had higher scores in the failure to maintain set than controls. The intravenous group had higher total errors than controls in verbal working memory tests and Visual Working Memory 2 Backtest. This group scored higher commission errors in the Verbal 2 Backtest than the controls. The two groups of heroin users differed in failure to maintain set and Verbal Working Memory 2 Backtests. The effect sizes of the group differences were modest. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Either route of heroin use is associated with cognitive impairments; inhalational and injection use involve different cognitive domains.

Infected Haller Cell Misdiagnosed as Invasive Fungal Sinusitis - A Parallax.

We report an unusual case of a 29-year-old female with a short duration of right lower eyelid swelling, painful eye movement and paraesthesia of right cheek. She was subsequently worked up with mucormycosis in mind, but intra-operative findings were suggestive of an infected Haller cell and post-operatively she was symptom free.

Complex neurocysticercosis lesions on imaging: Explained through correlative histomorphology.

OBJECTIVES: Neurocysticercosis, the commonest neuro-parasite, sometimes presents as complex ring enhancing lesion causing diagnostic dilemma. We aim to establish radio-histo-morphological equivalents of early events in degeneration of the parasite to explain such imaging phenotypes. METHODS: We compared patterns of degeneration in 23 randomly selected complex NCC on MRI with histo-morphology in 30 cysts obtained from an unrelated post mortem brain. RESULTS: The anatomy of the parasite and the degenerative patterns of the scolex (hydropic changes, calcification, evagination, and fragmentation) and the cyst wall (undulation, accessory loculi, and frank disruption) were well demonstrated on both. The intact scolex remarkably resembled head of intestinal Taenia. The complex lesions were conglomeration of multiple communicating cysts with a single parent cyst and multiple daughter cysts. The parent cysts contained a solitary variably degenerated scolex, had thicker walls and associated chronic inflammation. The remaining cysts of the lesion complex contained no scolex, had poorly organized walls, turbid contents, and florid perilesional enhancement with leakage of contrast. Three lesions assumed a multi-cystic pseudo-tumorous pattern, of which two resolved into solitary calcific remnants on follow up. CONCLUSION: Complex lesion in NCC result from degeneration of solitary parasite with perilesional gliosis, surrounded by multiple non-larval daughter cysts inciting acute intra and perilesional inflammation due to enhanced antigenic challenge. Possibly, attempted abortive asexual reproduction by the cellulose cyst as a preterminal event results in a "limited Racemose like transition." Correct interpretation has diagnostic and therapeutic implications as active lesions and their fibrocalcific residue may have greater epileptogenic potential.

Comparison of Effects of Propofol and Sevoflurane on the Cerebral Vasculature Assessed by Digital Subtraction Angiographic Parameters in Patients Treated for Ruptured Cerebral Aneurysm: A Preliminary Study.

BACKGROUND: Studies have evaluated the effects of volatile and intravenous anesthetic agents on the cerebral vasculature with inconsistent results. We used digital subtraction angiography to compare the effects of propofol and sevoflurane on the luminal diameter of cerebral vessels and on cerebral transit time in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: This prospective preliminary study included adult patients with good-grade aSAH scheduled for endovascular coil embolization; patients were randomized to receive propofol or sevoflurane anesthesia during endovascular coiling. The primary outcome was the luminal diameter of 7 cerebral vessel segments measured on the diseased and nondiseased sides of the brain at 3 time points: awake, postinduction of anesthesia, and postcoiling. Cerebral transit time was also measured as a surrogate for cerebral blood flow. RESULTS: Eighteen patients were included in the analysis (9 per group). Baseline and intraoperative parameters were similar between the groups. Propofol increased the diameter of 1 vessel segment at postinduction and postcoiling on the diseased side and in 1 segment at postcoiling on the nondiseased side of the brain ( P <0.05). Sevoflurane increased vessel diameter in 3 segments at postinduction and in 2 segments at postcoiling on the diseased side, and in 4 segments at postcoiling on the nondiseased side ( P <0.05). Cerebral transit time did not change compared with baseline awake state in either group and was not different between the groups. CONCLUSIONS: Sevoflurane has cerebral vasodilating properties compared with propofol in patients with good-grade aSAH. However, sevoflurane affects cerebral transit time comparably to propofol.

Tetraventricular hydrocephalus with aqueductal flow void: an overlooked entity having consistent improvement following endoscopic third ventriculostomy.

BACKGROUND: Tetraventricular Hydrocephalus (TetHCP) is a heterogeneous group of cerebrospinal fluid (CSF) flow disorders having varying success rates with Endoscopic third ventriculostomy (ETV). This is report on the efficacy and rationale of ETV in a specific subset of primary TetHCP with aqueductal CSF flow voids. METHODS: Patients of primary acquired TetHCP presenting with increasing head size and/or headache having aqueductal CSF flow void on sagittal Magnetic Resonance Imaging (MRI) were included in this study. All of them underwent ETV. All patients were evaluated for clinical improvement & MRI at 3 months, and need for any additional procedure, in contrast to those without CSF flow void. The pathophysiology of hyperdynamic CSF circulation and its correlation to ETV was further reviewed. RESULTS: Eleven patients had tetraventricular hydrocephalus and aqueductal flow void, with age ranging from 10 months to 59 years. Two patients who could undergo quantitative flow study confirmed the hyperdynamic flow across the aqueduct. Following ETV, all showed clinical improvement. MRI at 3 months showed CSF flow void across the third ventricular stoma in addition to across the aqueduct. None of these patients required any redo procedures for a mean follow-up of 39.2 months. In contrast, there was 30% failure rate after ETV among 10 patients of tetraventricular hydrocephalus without aqueductal flow void. CONCLUSION: Tetraventricular hydrocephalus with aqueductal CSF flow void may be a unique entity with hyperdynamic CSF circulation and relative resistance at fourth ventricular outlets. ETV is highly efficacious in these patients, resulting in consistent clinico-radiological improvement.

Surface-based brain morphometry in schizophrenia vs. cannabis-induced psychosis: A controlled comparison.

BACKGROUND & AIM: We examined group differences in cortical thickness and surface-parameters among age and handedness--matched persons with cannabis-induced psychosis (CIP), schizophrenia with heavy cannabis use (SZC), and healthy controls (HC). METHODS: We recruited 31 men with SZC, 28 with CIP, and 30 with HC. We used the Psychiatric Research Interview for Substance and Mental Disorders to differentiate between CIP and SZC. We processed and analyzed T1 MR images using the Surface-based Brain Morphometry (SBM) pipeline of the CAT-12 toolbox within the statistical parametric mapping. After pre-processing, volumes were segmented using surface and thickness estimation for the analysis of the region of interest. We used the projection-based thickness method to assess the cortical thickness and Desikan-Killiany atlas for cortical parcellation. RESULTS: We observed the lowest cortical thickness, depth, and gyrification in the SZC, followed by CIP and the control groups. The differences were predominantly seen in frontal cortices, with limited parietal and temporal regions involvement. After False Discovery Rate (FDR) corrections and post-hoc analysis, SZC had reduced cortical thickness than HC in the middle and inferior frontal, right entorhinal, and left postcentral regions. Cortical thickness of SZC was also significantly lower than CIP in bilateral postcentral and right middle frontal regions. We found negative correlations (after FDR corrections) between the duration of cannabis use and cortical thickness in loci of parietal and occipital cortices. CONCLUSION: Our study suggested cortical structural abnormalities in schizophrenia, in reference to healthy controls and cannabis-induced psychosis, indicating different pathophysiology of SZC and CIP.

Phosphorylation of ß-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours.

Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the ß-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, ß-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of ß-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs.