Presenting Psychiatric and Neurological Symptoms and Signs of Brain Tumors before Diagnosis: A Systematic Review.

Brain tumors can present with various psychiatric symptoms, with or without neurological symptoms, an aspect that complicates the clinical picture. However, no systematic description of symptoms that should prompt a neurological investigation has been provided. This review aims to summarize available case reports describing patients with brain tumors showing psychiatric symptoms before brain tumor diagnosis, in order to provide a comprehensive description of these symptoms as well as their potential relationship with delay in the diagnosis. A systematic literature review on case reports of brain tumors and psychiatric symptoms from 1970 to 2020 was conducted on PubMed, Ovid, Psych Info, and MEDLINE. Exclusion criteria comprised tumors not included in the World Health Organization (WHO) Classification 4th edition and cases in which psychiatric symptoms were absent or followed the diagnosis. A total of 165 case reports were analyzed. In a subset of patients with brain tumors, psychiatric symptoms can be the only manifestation or precede focal neurological signs by months or even years. The appearance of focal or generalized neurological symptoms after, rather than along with, psychiatric symptoms was associated with a significant delay in the diagnosis in adults. A timely assessment of psychiatric symptoms might help to improve early diagnosis of brain tumors.

DOCK8 Deficiency Presenting as an IPEX-Like Disorder.

PURPOSE: The dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder. METHODS: Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry. T regulatory (Treg) cells were isolated by cell sorting, and their suppressive activity was analyzed by flow cytometry. Gene mutational analysis was performed by whole-exome and Sanger sequencing. RESULTS: Patient 1 (P1) presented at 10 months of age with chronic severe diarrhea and active colitis in the absence of an infectious trigger, severe eczema with elevated serum IgE, and autoimmune hemolytic anemia, suggestive of an IPEX-related disorder. Whole-exome sequencing revealed a homozygous nonsense mutation in DOCK8 at the DOCK-homology region (DHR)-1 (c.1498C>T; p. R500X). Patient P2, a cousin of P1 who carries the same DOCK8 nonsense mutation, presented with eczema and recurrent ear infections in early infancy, and she developed persistent diarrhea by 3 years of age. Patient P3 presented with lymphoproliferation, severe eczema with allergic dysregulation, and chronic diarrhea with colitis. She harbored a homozygous loss of function DOCK8 mutation (c.2402 -1G→A). Treg cell function was severely compromised by both DOCK8 mutations. CONCLUSION: DOCK8 deficiency may present severe immune dysregulation with features that may overlap with those of IPEX and other IPEX-like disorders.

Results from a retrospective analysis of colonoscopies for Inflammatory bowel disease and colorectal cancer in a Lebanese tertiary care centre.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) and colorectal cancer have an increased impact on the Lebanese population's morbidity and mortality. This study evaluated the situation of IBD and colorectal cancer at a tertiary hospital centre in Lebanon. METHODS: 1007 patients underwent colonoscopy over a period of 12 months by qualified physicians. 91 patients were excluded from the study. Biopsy results were divided into normal versus abnormal colonic tissue. The abnormal section was further subdivided into number of polyps, IBD, dysplasia and cancer. RESULTS: Out of 916 individuals included, 61 cases of Crohn's colitis (CC) (6.7%) and 24 cases of ulcerative colitis (UC) (2.7%) were identified. A total of 92 cases of colorectal cancer (10.04%) were also identified. There was a slight male predominance in both groups of IBD without any statistical significance. One statistical significance was reported in favour to age<50 years in both IBD groups with a mean age of 37.9±9.7 years and 34.4±6.4 years for CC and UC, respectively. The incidence of granuloma in the CC group was 8.9% without any correlation compared with age or gender. No correlation was made between colorectal cancer and the existence of any IBD type. The data showed that age >50 years and male gender significantly correlate with an increased incidence of precancerous and cancerous polyps in the colon. They significantly correlate with adenocarcinoma. The estimated incidence of colorectal cancer, CC and UC was 54.1, 35.8 and 14.1 per 100 000, respectively, with a denominator of 169 959 patients per year. CONCLUSION: Within the limitations of this study, the incidence of colorectal cancer and IBD falls in the high range compared with similar European and American studies. Our data are biased because of the tertiary centre setting but they can be considered as base for further investigations.

Association of CYP3A4/5 genotypes and expression with the survival of patients with neuroblastoma.

Neuroblastoma (NB) is a rare pediatric disease in Lebanon for which poor prognosis remains a major challenge. Genetic polymorphism of genes coding for drug­metabolizing enzymes may influence the response of a patient to chemotherapy. This study investigates a possible association between CYP3A4/5 polymorphism and expression levels and survival in NB patients. All patients with stage III and IV NB diagnosed between 1993 and 2012 in three major hospitals in Beirut were included (n=27). Demographic information and survival time were obtained from medical records. CYP3A4 and CYP3A5 genotypes and expression levels were determined in archival tumors by polymerase chain reaction (PCR) and restriction fragment length polymorphism and quantitative PCR, respectively. Additionally, MYCN amplification was assessed. A Cox proportional hazards model was used to evaluate potential associations, adjusting for MYCN amplification. A statistically significant increase in the risk of mortality was observed in patients with MYCN amplification [hazard ratio (HR) 4.11, 95% confidence interval (CI) 1.14­14.80]. Patients with CYP3A5 expression levels above the median had a lower risk of mortality (HR 0.61, 95% CI 0.21­1.74) and patients with CYP3A4 expression levels above the median had a higher risk of mortality (HR 2.00, 95% CI 0.67­5.90). CYP3A5*3/*3 homozygote mutants had a 4.3­fold increase in the risk of mortality compared with that of homozygote wild­type or heterozygote mutants (HR 4.30, 95% CI 0.56­33.30). Carriers of the CYP3A4*1B mutant allele had a 52% lower risk of mortality compared with that of non­carriers (HR 0.48, 95% CI 0.06­3.76). Although the results of the present study did not achieve statistical significance, associations were observed, which indicates that CYP3A4 and CYP3A5 may modulate the clinical outcome of NB. Further studies with larger sample sizes are required to characterize the effects of the polymorphism and expression levels of CYP3A4/5 on the survival of patients with NB.