Sporadic Lesions Research Articles

Clinicopathologic features associated with recurrence of the odontogenic keratocyst: a cohort retrospective analysis

The aim of this study was to evaluate the influence of clinical, radiographic, surgical and histopathologic parameters in the recurrence of disease in a series of odontogenic keratocysts (OKCs). The sample comprised 24 sporadic OKC lesions from 24 patients. All patients had no previous treatment history and were treated by the same surgeon using a uniform treatment protocol (enucleation with peripheral ostectomy preceded or not preceded by decompression). Fourteen lesions (58.4%) were first submitted to decompression procedure. Eight patients (33%) developed recurrent lesions, with a mean follow-up time of 60.5 months (standard deviation [SD]= 31.3) and a mean disease-free interval for recurrent lesions of 19 months (SD= 4.9). Recurrence was significantly associated with poor clinical response to decompression (P= .027), remaining tooth with radiographic evidence of insinuation of the lesion between the dental roots (P= .009), and the presence of budding of the basal cells layer together with epithelial islands in the fibrous capsule (P=.019). Clinical, radiographic and histopathologic parameters may affect the relapse rate of OKCs and should individually guide treatment choice.

Cathaemasia hians infection in Black stork in Slovakia: morphological and histopathological study

Summary Cathaemasia hians is an obligate trematode parasite of Black storks that are on the List of protected birds in Europe. In the present study, adult trematodes were isolated from the Black stork post mortem and morphological study revealed C. hians species. In total, 10 worms were found in the oesophagus and the ventriculus of the bird. Histopathological examination of the tissue samples of oesophagus, proventriculus and ventriculus was performed on paraffin sections using a set of staining procedures. The sporadic lesions were seen in the tela submucosa of oesophagus containing connective tissue mast cells, eosinophils and heterophils and some foci were surrounded by the fibrous tissue. In addition, a few inflammatory nodules had larval-like material inside, probably being of the same species. There were no visible morphological alterations in the epithelial layer of lamina propria mucosae of proventriculus, rich in goblet cells as well as in the tela submucosa. Majority of trematodes were localized in the ventriculus, where the lamina propria mucosae was damaged or disrupted sporadically. In these sites, in the tela submucosa, a various food-originated inorganic/organic material and eggs of C. hians were deposited, stimulating a weak inflammatory response. Nodules containing larvae were not observed in any of ventriculus tissue layers. This study demonstrated, for the first time, infection with adults of C. hians trematode in the Black stork nesting in Slovakia. The presence of larvae and eggs in the tissues of the upper gastrointestinal tract of bird was associated with mild inflammatory response but feeding behaviour of adult worms in the ventriculus probably contributed to the enhanced susceptibility of the lamina propria mucosae to mechanical damage by inorganic material. Although larval stages have not yet been documented in the intermediate hosts in Slovakia, our report indicates that the life cycle of C. hians might occur in Central Europe.

Impact of parotid gland dose and patient-related factors on radiation damage to dental hard tissues

Background/purposeTo evaluate whether radiation damage to dental hard tissues depends on patient-related factors in addition to irradiation dose on the spared parotid gland. Materials and methodsSeventy curatively irradiated patients with head and neck cancer underwent dental treatment prior to, during, and after radiotherapy. During a follow-up period of 24 months, damages to dental hard tissues were classified. Mean doses (Dmean) during spared parotid gland radiotherapy, patients' oral hygiene practice, and socioeconomic status were determined. ResultsNo carious lesions were observed in 30 patients (Group A), while sporadic and general carious lesions were noticed in 18 patients (Group B) and 22 patients (Group C), respectively. The Dmean of Group A (21.2 ± 11.00 Gy) was significantly lower than that of Group C (33.9 ± 9.9 Gy; P < 0.001). Patients with an intermediate level of schooling qualification showed a higher risk for radiation caries than patients with higher education entrance qualification (P = 0.018). ConclusionRadiation damage to dental hard tissues correlates with increased mean irradiation doses and a lower educational level.

Adrenal insufficiency in a child following unilateral excision of a dual-hormone secreting phaeochromocytoma.

SummaryPhaeochromocytomas are a rare clinical entity, with dual hormone-secreting lesions particularly uncommon, seen in <1%. ACTH is the most common hormone co-produced, and is potentially lethal if not diagnosed. We present the case of a previously well 10-year-old boy, who presented acutely with a hypertensive crisis and was found to have a unilateral, non-syndromic phaeochromocytoma. Medical stabilization of his hypertension was challenging, and took 3 weeks to achieve, before proceeding to unilateral adrenalectomy. Post-operatively the child experienced severe fatigue and was subsequently confirmed to have adrenal insufficiency. He improved markedly with hydrocortisone replacement therapy, which is ongoing 6 months post-operatively. In retrospect this likely represents unrecognized, sub-clinical ACTH-dependent Cushing's syndrome secondary to an ACTH/or precursor dual-hormone secreting phaeochromocytoma. At follow-up, his hypertension had resolved, there was no biochemical evidence of recurrence of the phaeochromocytoma, and genetic analysis was indicative of a sporadic lesion.Learning points Dual hormone secreting phaeochromocytomas with ACTH/or a precursor may cause secondary adrenal insufficiency following surgical removal.The concurrent features of Cushing's syndrome can be mild and easily overlooked presenting diagnostic and management pitfalls.As concomitant syndromes of hormone excess are rare in phaeochromocytomas; the diagnosis requires a high index of suspicion.Serial/diurnal cortisol levels, ACTH measurement +/− low dose dexamethasone suppression (when clinically stable, appropriate adrenergic blockade in place, and well supervised), can all be considered as needed.

Next-generation sequencing is highly sensitive for the detection of beta-catenin mutations in desmoid-type fibromatoses.

Desmoid-type fibromatoses are locally aggressive and frequently recurrent tumours, and an accurate diagnosis is essential for patient management. The majority of sporadic lesions harbour beta-catenin (CTNNB1) mutations. We used next-generation sequencing to detect CTNNB1 mutations and to compare the sensitivity and specificity of next-generation sequencing with currently employed mutation detection techniques: mutation-specific restriction enzyme digestion and polymerase chain reaction amplification. DNA was extracted from formalin-fixed paraffin-embedded needle biopsy or resection tissue sections from 144 patients with sporadic desmoid-type fibromatoses, four patients with syndrome-related desmoid-type fibromatoses and 11 morphological mimics. Two primer pairs were designed for CTNNB1 mutation hotspots. Using ≥10 ng of DNA, libraries were generated by Fluidigm and sequenced on the Ion Torrent Personal Genome Machine. Next-generation sequencing had a sensitivity of 92.36 % (133/144, 95 % CIs: 86.74 to 96.12 %) and a specificity of 100 % for the detection of CTNNB1 mutations in desmoid-type fibromatoses-like spindle cell lesions. All mutations detected by mutation-specific restriction enzyme digestion were identified by next-generation sequencing. Next-generation sequencing identified additional mutations in 11 tumours that were not detected by mutation-specific restriction enzyme digestion, two of which have not been previously described. Next-generation sequencing is highly sensitive for the detection of CTNNB1 mutations. This multiplex assay has the advantage of detecting additional mutations compared to those detected by mutation-specific restriction enzyme digestion (sensitivity 82.41 %). The technology requires minimal DNA and is time- and cost-efficient.

Radiation-Associated Undifferentiated Pleomorphic Sarcoma is Associated with Worse Clinical Outcomes than Sporadic Lesions.

Radiation therapy is used increasingly as a component of multidisciplinary treatment for many solid tumors. One complication of such treatment is the development of radiation-associated sarcoma (RAS). Undifferentiated pleomorphic sarcoma (UPS), previously termed "malignant fibrous histiocytoma" (MFH) is the most common histologic subtype of RAS. This study investigated the clinical outcomes for patients with radiation-associated UPS (RA-UPS/MFH). The study identified 1068 patients with UPS/MFH treated at the authors' institution. Patient and tumor factors were collected and compared. Regression analysis was performed to identify independent predictors of survival. A matched-cohort survival and recurrence analysis was performed for radiation-associated and sporadic UPS/MFH. The findings showed that RA-UPS/MFH comprised 5.1 % of the UPS population. The median latency to the development of RA-UPS/MFH was 9.3 years. The 5-year disease-specific survival (DSS) was 52.2 % for patients identified with RA-UPS/MFH (n = 55) compared with 76.4 % for patients with unmatched sporadic UPS/MFH (n = 1,013; p < 0.001). A matched-cohort analysis also demonstrated that the 5-year DSS was significantly worse for RA-UPS/MFH (52.2 vs 73.4 %; p = 0.002). Furthermore, higher local recurrence rates were observed for patients with RA-UPS/MFH than for patients with sporadic lesions (54.5 vs 23.5 %; p < 0.001). Radiation-associated status and incomplete resection were identified as independent predictors of local recurrence. This study demonstrated worse clinical outcomes for patients with RA-UPS/MFH than for patients with sporadic UPS/MFH. Local recurrence was significantly higher for patients with RA-UPS/MFH, suggesting a unique tumor biology for this challenging disease.

Bisphosphonate-Related Osteonecrosis of The Jaw (BRONJ) in Neoplastic and Osteoporotic Patients: Statistical Analysis of the Influence of Primary Disease on the Multifocality

SYNDROMIC (NBCCS) AND SPORADIC KERATOCYSTIC ODONTOGENIC TUMOUR: DIFFERENT RECURRENCE RATE AFTER CONSERVATIVE SURGERY OF 213 LESIONS Simona Miccoli, Simonetta Franco, Matteo Favia, Maria Grazia Lacaita, Silvio Tafuri, Nicola Laforgia, Gianfranco Favia, Department of Odontostomatology and Surgery, Aldo Moro University, Bari, Italy; Department of Emergency and Organ Transplantation, Aldo Moro University, Bari, Italy; Department of Biomedical Sciences and Human Oncology, Aldo Moro University, Bari, Italy Objective: The purpose of this study is to evaluate the different recurrence rate after conservative surgery in 113 patients with 120 syndromic and 93 sporadic Keratocystic Odontogenic Tumours (KOT) treated between 1979 and 2012 at the University of Bari. Study Design: Conservative surgery consisted of KOT enucleation followed by peripheral ostectomy with rotary or piezoelectric instruments. Chi-Squared-Test (c) was used to find association between recurrence rate and syndromic or sporadic KOT using a 95% significance level (P<0.05). Results: 31 patients were affected by NBCCS (group1) and 82 patients presented sporadic lesions (group2). Out of group1, 12 patients had 26 recurrences (38.71%; n1⁄412/31), whereas out of group2, 8 patients presented 11 recurrences (9.76%; n1⁄48/82); (c1⁄412.95; P1⁄40.0003). Conclusions: Since syndromic patients usually present larger KOT and are more prone to continuous formation of new lesions, recurrence rate is significantly higher in group1; nevertheless recurrence rate in group2 is lower than data reported in literature for the same treatment modality.

Defective DNA mismatch repair activity is common in sebaceous neoplasms, and may be an ineffective approach to screen for Lynch syndrome.

A subset of individuals with Lynch syndrome (LS) has a variant called Muir-Torre syndrome (MTS) where patients develop multiple sebaceous neoplasms. Absence of gene expression and microsatellite instability (MSI) have been welldocumented in LS neoplasms. It is unclear whether the presence of these abnormalities in isolated sebaceous neoplasms would indicate the likely presence of otherwise unsuspected LS or MTS. 164 specimens of sporadic cutaneous sebaceous neoplasms were obtained. IHC was performed for expression of the DNA mismatch repair (MMR) genes MSH2 and MLH1. A 5-marker mononucleotide repeat microsatellite panel was analyzed to detect MSI, and two or more mutated markers were required for MSI. 164 sebaceous neoplasms were obtained from 162 patients. IHC data was successfully obtained from 162 samples and MSI data was obtained from 138 samples. 50/162 (31%) had abnormal IHC with loss of staining for either MSH2 (37/162, 23%), MLH1 (9/162, 5%) or both (4/162, 2%). 37% (52/138) of the tumors had MSI. 82% (111/136) of those with both IHC and MSI results correlated as expected. 18% (25/136) showed discordance between IHC and MSI. 69/163 (42%) had either abnormal IHC or MSI, indicating deficient DNA MMR activity. Given the substantial proportion of DNA MMR deficiency in these sebaceous neoplasms, screening for DNA MMR defects in sebaceous neoplasms would not appear to be an effective way to distinguish patients with LS or MTS from those with sporadic skin lesions and an ordinary risk of cancer.

Insight into the pathogenesis and nature of Central Giant Cell Lesions of the Jaws.

Central giant cell lesions of the jaws are not uncommon. While the majority of these represent single, sporadic lesions, histologically identical lesions are seen in association with a number of other bone lesions, as well as in certain syndromes. This manuscript offers a brief update on recent developments in this area that provide new insight into the pathogenesis and nature of Central Giant Cell Lesions of the Jaws. Key words:Central giant cell lesion, RASopathy

Current issues in inflammatory bowel disease neoplasia.

Recent histological criteria and developments in the field of endoscopic imaging have led to higher detection rates of neoplasms in ulcerative colitis. Once a lesion is detected, endoscopic resection is recommended to guide subsequent surveillance or therapy and to gain adequate material for histological diagnosis. Further management is based on the grade of neoplasia and on whether the neoplasia is categorized as sporadic or colitis-associated. Nevertheless it may sometimes be difficult to distinguish colitis-associated neoplasms from sporadic neoplasms. A better way to report this may be ultimately classified. Here, we review endoscopic and histological parameters to help to differentiate colitis-associated neoplasia from sporadic lesions and discuss pathogenesis and therapeutic options.

Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche.

Hereditary mixed polyposis syndrome (HMPS) is characterised by the development of mixed morphology colorectal tumours and is caused by a 40 kb duplication that results in aberrant epithelial expression of the mesenchymal Bone Morphogenetic Protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell-fate, that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem-cell properties in Lgr5 negative (non-expressing) progenitor cells that have exited the stem-cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem-cell is not the sole cell-of-origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic pre-malignant lesions with a hitherto unknown pathogenesis and these lesions can be considered the sporadic equivalents of HMPS polyps.

BAP1 and BRAFV600E expression in benign and malignant melanocytic proliferations.

BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma, and other tumors. Screening for BAP1 mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and nondesmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy) and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP1 germline mutation. Most sporadic melanocytic lesions exhibited positive BAP1 nuclear staining, except for 1 proliferative nodule arising in congenital nevus, 1 desmoplastic, 1 nevoid, and 2 metastatic melanomas. BRAFV600E positivity was demonstrated in 80% of dermal, 5% of congenital, 6% of Spitz, and 5.5% of atypical Spitz nevi; 29% of proliferative nodules arising in congenital nevi; and 24% of primary and nondesmoplastic and 35% of metastatic melanomas. Combined BAP1 loss and BRAFV600E staining was seen in 67% of BAP1 tumor syndrome-associated lesions and in none of the sporadic melanocytic proliferations including Spitz and atypical Spitz nevi and atypical Spitz tumors, with the exception of 1 primary melanoma. The combined BAP1-BRAFV600E+ immunoprofile appears to be a constant feature of BAP1 tumor syndrome-associated melanocytic lesions, and the designation of Spitz nevi or variants thereof appears to be inaccurate for this group of lesions.

Endoscopic Surveillance Patterns of Polypoid Dysplasia Among Patients With Inflammatory Bowel Disease

Introduction: The current strategy of close endoscopic surveillance following resection of polypoid dysplasia (sporadic adenoma-like lesions) in patients with ulcerative colitis is accepted; however, the follow-up interval is not well defined. The purpose of this study is to describe the community based surveillance colonoscopy recommendations following the resection of polypoid dysplasia in inflammatory bowel disease (IBD) patients. Methods: We performed a single-center case series of patients with IBD who received surveillance colonoscopies from 1998 to 2011. Patients with IBD were identified by ICD-9 code and a manual chart review was performed to confirm the diagnosis of IBD. Review of the colonoscopy and pathology reports was performed to identify cases of polypectomy with pathologic confirmation of dysplasia or indeterminate for dysplasia. Among these patients, recommendations and intervals for subsequent colonoscopies as well as the presence of subsequent dysplasia were reviewed. Results: Forty patients with a total of 134 colonoscopies were included in this study. The patients had a mean age of 45 years at the time of IBD diagnosis, 97% were men and 77% were white. A total of 81 sporadic appearing polyps were identified and resected, including 78 with low-grade dysplasia (LGD) and 3 with high-grade dysplasia (HGD). Among those patients with LGD, recommendations were made for repeat colonoscopy in less than 1 year for 5 cases, 1-2 years for 15 cases and more than 2 years for 9 cases. There was no documentation in the medical records regarding surveillance interval among 12 cases with LGD. Of the 27 patients with LGD, 67% underwent at least one subsequent surveillance colonoscopy, among which 13 additional sporadic adenomas were identified. None of the patients had subsequent HGD or colorectal cancer in a mean follow up of 10.4 years. Among the 3 patients with HGD, surgical resection was recommended for 2 patients. One patient underwent total proctocolectomy with no additional dysplasia identified on surgical pathology. One patient declined surgery and had no further follow-up. The third patient had 2 subsequent colonoscopies in the following 5.5 years prior to his death unrelated to IBD: the first did not identify dysplasia and the second had lesions that were indeterminate for dysplasia in the setting of active colitis. Conclusion: We observed a wide variation in surveillance recommendations after polypectomy in patients with IBD, from less than 1 year to greater than 2 years. We observed no colorectal cancer or advanced adenomas among IBD patients after polypectomy for sporadic- appearing polyps. Further studies defining optimal surveillance intervals after polypectomy for polypoid dysplasia are required.

The highly prevalent H3F3A mutation in giant cell tumours of bone is not shared by sporadic central giant cell lesion of the jaws.

Central giant cell lesion (CGCL) and giant cell tumour (GCT) are bone lesions that share similar microscopic features. Recently, it was reported that 90% of bone GCT exhibit either p.Gly34 Trp or p.Gly34 Leu in H3F3A, one of two genes for histone H3.3 located on chromosome 1. We aimed to test whether sporadic CGCL of the jaws share the H3F3A mutations reported in GCT of other bones. Nine samples of CGCL of the jaws were included in the study, and mutations were assessed by direct sequencing. None of the CGCL samples presented the recurrent p.Gly34 Trp or p.Gly34 Leu mutations in the H3F3A gene. On the basis of our findings, H3F3A p.Gly34 Trp or p.Gly34 Leu mutations are not a frequent event in CGCL. If these alterations are confirmed to be exclusive of GCT, the assessment of H3F3A mutations may help in the differential diagnosis of GCT and CGCL of the jaws.

OC-010 Endoscopic Resection Of Duodenal Adenomas – Comparison Of Safety And Efficacy Between Sporadic Adenomas And Adenomas In Fap

IntroductionAlthough there is a low risk of malignant conversion of duodenal polyps in FAP, EMR is often considered. However, few studies have looked at the safety and efficacy of EMR....

Lesions from patients with sporadic cerebral cavernous malformations harbor somatic mutations in the CCM genes: evidence for a common biochemical pathway for CCM pathogenesis

Cerebral cavernous malformations (CCMs) are vascular lesions affecting the central nervous system. CCM occurs either sporadically or in an inherited, autosomal dominant manner. Constitutional (germline) mutations in any of three genes, KRIT1, CCM2 and PDCD10, can cause the inherited form. Analysis of CCM lesions from inherited cases revealed biallelic somatic mutations, indicating that CCM follows a Knudsonian two-hit mutation mechanism. It is still unknown, however, if the sporadic cases of CCM also follow this genetic mechanism. We extracted DNA from 11 surgically excised lesions from sporadic CCM patients, and sequenced the three CCM genes in each specimen using a next-generation sequencing approach. Four sporadic CCM lesion samples (36%) were found to contain novel somatic mutations. Three of the lesions contained a single somatic mutation, and one lesion contained two biallelic somatic mutations. Herein, we also describe evidence of somatic mosaicism in a patient presenting with over 130 CCM lesions localized to one hemisphere of the brain. Finally, in a lesion regrowth sample, we found that the regrown CCM lesion contained the same somatic mutation as the original lesion. Together, these data bolster the idea that all forms of CCM have a genetic underpinning of the two-hit mutation mechanism in the known CCM genes. Recent studies have found aberrant Rho kinase activation in inherited CCM pathogenesis, and we present evidence that this pathway is activated in sporadic CCM patients. These results suggest that all CCM patients, including those with the more common sporadic form, are potentially amenable to the same therapy.

Central nervous system hemangioblastomas: Epidemiology, pathology and clinical spectrum in a tertiary care centre

Background: Hemangioblastomas are rare, benign, vascular neoplasm. According to the World Health Organization classification of tumors of the nervous system, hemangioblastomas are classified as meningeal tumors of uncertain origin and are Grade I neoplasm. Hemangioblastomas arise either in the setting of von Hippel-Lindau (vHL) disease or more often as solitary sporadic lesions. They account for 1-3% of primary central nervous system (CNS) tumors. The most common location is the cerebellum followed by spinal cord. Supratentorial lesions are rare. Aims: The aim was to study the prevalence of hemangioblastoma. Materials and Methods: A retrospective observational study of 7 years duration was carried out in the department of pathology of a tertiary referral center. The sample received was processed by standard formalin fixing, paraffin embedding method. Serial sections and special stains were studied as and when required. Results: During the period of 7 years, we reported total 679 cases of primary CNS tumors, of which 11 (1.62%) cases were of hemangioblastoma. Ten of them were intracranial, and one was spinal. There were seven male and four female patients that clearly indicate male preponderance. Conclusions: In our study, prevalence of hemangioblastoma was 1.62% (11 cases) out of 679 primary CNS tumors, which is low as per literature. There was a male predominance with male:female ratio 2:1. Cerebellum was the most frequent site (81.8%). No association with vHL disease was noted.

The long-term outcomes of radiosurgery for intracranial hemangioblastomas

Optimal timing in the treatment of intracranial hemangioblastoma (HB) remains controversial, particularly for patients of von Hippel-Lindau disease (VHL) with multiple small lesions. We evaluated efficacy of stereotactic radiosurgery (SRS) for intracranial HB based on the longer follow-up data with a larger number of patients and lesions. Twenty-one patients (11 men, 10 women) initially underwent SRS for 57 intracranial HBs. Seven patients had sporadic lesions and 14 had VHL-related lesions. During the follow-up, 40 lesions were additionally treated in VHL patients in 10 SRS treatments. Thus, a total of 97 lesions were included in this study. Median tumor volume was 0.13 cm(3) (range, 0.004-9.5 cm(3)), and median margin dose was 18 Gy (range, 14-20 Gy). Median duration of follow-up was 96 months (range, 3-235 mo) after initial SRS treatment. Ten tumors in 7 patients showed progression after SRS. Actuarial tumor control rates after SRS at 5 and 10 years were 94% and 80%, respectively. Factors associated with longer control were solid lesion (P = .03), smaller volume (P = .01), and lesions associated with VHL (P = .0005) in univariate analysis. Five- and 10-year tumor control rates were 67% and 44% for sporadic patients and 97% and 83% for VHL patients. SRS could be offered as an effective treatment for small, solid, and VHL-associated HBs. If the tumors show apparent enlargement in size or can possibly become symptomatic along with a slight increase in size, SRS should be recommended before they present with the clinical symptoms.

Crohn's disease: Is there a place for neurological screening?

Objective. Neurological complications of inflammatory bowel diseases (IBDs) are not rare but are under-diagnosed; some are probably immune-mediated. Several previous studies have suggested a higher incidence of demyelinating diseases such as multiple sclerosis in IBD patients. In this single-center, prospective, observational study, the authors focus on T2 focal white-matter lesions of the central nervous system on magnetic resonance imaging (MRI) in IBD patients that may be due to demyelination. Material and methods. A total of 70 patients with Crohn's disease were examined before beginning anti-TNF-α therapy. These patients were treated with azathioprine, mesalazine or both. Patients were examined by a neurologist to detect possible signs of demyelinating disease, and patients underwent brain MRI (native T1, T2, and FLAIR sequences). Results. Thirty-seven patients (53%) exhibited abnormalities on neurological examination, and 26 patients (37%) displayed abnormalities on MRI. In seven cases, these MRI abnormalities (periventricular lesions) were suspected to be due to demyelination. Cerebral spinal fluid investigation (including polyclonal bands) was completely negative in five cases and was borderline in one case, and multiple sclerosis was confirmed in one case. Pathological MRI findings in 19 other patients were clinically nonsignificant; most were nonspecific sporadic lesions in white matter or mild atrophy. Conclusions. The results support previous data that the frequency of neurological findings in IBD patients is generally underestimated. With the extension of biological anti-TNF-α treatment for IBD, the possibility of a higher risk of developing multiple sclerosis should be considered.

Presence of severe neuroinflammation does not intensify neurofibrillary degeneration in human brain

This study investigated the allegedly causal relationship between microglial activation and neurofibrillary degeneration (NFD) typical of Alzheimer's disease (AD) by determining if presence of extreme microglial activation coincides with intensified NFD. We performed comparative histopathological analyses of NFD and microglial reactivity in 18 primary subjects ranging from 4 to 51 years of age. Ten of these subjects (median age 34) died from infectious disease (HIV, sepsis) and CNS trauma, while eight subjects (median age 32.5) died from non-infectious conditions (controls). Second, we also examined two 52-year-old subjects with Down syndrome where one had comorbid sepsis and the other one did not. We found that all 10 subjects with infectious/traumatic diagnoses showed severe neuroinflammation, while the 8 control subjects completely lacked neuroinflammatory changes. However, all 18 primary subjects were found to show the same early-stage, pretangle neuropathology of Braak stage 1a and 1b, that is, they exhibited primarily subcortical NFD in the locus coeruleus and sporadic lesions in the transentorhinal cortex. Similarly, the two subjects with Down syndrome showed the same high levels of NFD (Braak stage VI) irrespective of the comorbid sepsis-related neuroinflammation present in one of these individuals. Collectively, our findings show that despite rampant microglial activation in all subjects with neuroinflammatory conditions the extent of NFD is at the same level as seen in non-inflamed controls. These findings demonstrate that microglial activation does not initiate or exacerbate NFD, and we conclude that CNS inflammation is unlikely to be causally involved in the development of NFD characteristic of AD dementia.