HISTOPATHOLOGICAL, CLINICAL AND EPIDEMIOLOGICAL FEATURES OF HEPATOPORTAL SCLEROSIS IN A REFERRAL CENTER FOR LIVER DISEASE IN NORTHEASTERN BRAZIL.

BACKGROUND: Hepatoportal sclerosis HPS or obliterative portal venopathy (OPV), one of the differential diagnoses for non-cirrohtic portal hypertension, is characterized by the disappearance of the portal branches, portal and septal fibrosis, perisinusoidal fibrosis and regenerative nodular hyperplasia (RNH). It is a spectral disease that may progress to severe portal hypertension. Its etiopathogenesis is still little understood, especially in Brazil, it has been probably misdiagnosed due to its histopatological similarities with the hepatosplenic form of schistosomiasis. OBJECTIVE: To analyze the profile of patients with HPS in Northeastern Brazil and to demonstrate the pathological characteristics of HPS. METHODS: We retrospectively analyzed cases of OPV in liver biopsies and explants from a referral center for liver in Bahia - Brazil. The qualitative and quantitative analysis of the portal tracts and liver parenchyma was made so that comparisons could be done among the HPS findings of our population and the findings described by other authors. RESULTS: From the 62 patients identified with HPS, 42% were male, while 58% were female. The average age at diagnosis was 48.3 years. From this group, we analyzed the liver biopsy of 10 patients whose diagnosis of schistosomiasis could be ruled out. From these 100% (10/10) presented dense portal fibrosis and portal venous obliteration. Liver parenchymal atrophy was present in 60% (6/10) of the patients, sinusoidal dilation was present in 30% (3/10), the presence of portal septa occurred in 50% (5/10) and dense portal fibrosis in all patients analyzed. Nodular regenerative hyperplasia was found in 30% (3/10) of the patients. CONCLUSION: HPS seems to be neglected and misdiagnosed in Brazil, due to its similarities with schistossomiasis. In our study dense portal fibrosis, obliteration of the portal vein branches, parenchymal atrophy, sinusoidal dilatation and parenchymal nodular hyperplasia were the main histopathological findings and were similar to that described in other countries.

Características histopatológicas, clínicas e epidemiológicas da esclerose hepatoportal em um centro de referência para doenças do fígado no Nordeste do Brasil / Histopathological, clinical and epidemiological features of hepatoportal sclerosis in a referral center for liver disease in northeastern brazil

ABSTRACT BACKGROUND: Hepatoportal sclerosis HPS or obliterative portal venopathy (OPV), one of the differential diagnoses for non-cirrohtic portal hypertension, is characterized by the disappearance of the portal branches, portal and septal fibrosis, perisinusoidal fibrosis and regenerative nodular hyperplasia (RNH). It is a spectral disease that may progress to severe portal hypertension. Its etiopathogenesis is still little understood, especially in Brazil, it has been probably misdiagnosed due to its histopatological similarities with the hepatosplenic form of schistosomiasis. OBJECTIVE: To analyze the profile of patients with HPS in Northeastern Brazil and to demonstrate the pathological characteristics of HPS. METHODS: We retrospectively analyzed cases of OPV in liver biopsies and explants from a referral center for liver in Bahia - Brazil. The qualitative and quantitative analysis of the portal tracts and liver parenchyma was made so that comparisons could be done among the HPS findings of our population and the findings described by other authors. RESULTS: From the 62 patients identified with HPS, 42% were male, while 58% were female. The average age at diagnosis was 48.3 years. From this group, we analyzed the liver biopsy of 10 patients whose diagnosis of schistosomiasis could be ruled out. From these 100% (10/10) presented dense portal fibrosis and portal venous obliteration. Liver parenchymal atrophy was present in 60% (6/10) of the patients, sinusoidal dilation was present in 30% (3/10), the presence of portal septa occurred in 50% (5/10) and dense portal fibrosis in all patients analyzed. Nodular regenerative hyperplasia was found in 30% (3/10) of the patients. CONCLUSION: HPS seems to be neglected and misdiagnosed in Brazil, due to its similarities with schistossomiasis. In our study dense portal fibrosis, obliteration of the portal vein branches, parenchymal atrophy, sinusoidal dilatation and parenchymal nodular hyperplasia were the main histopathological findings and were similar to that described in other countries.

RESUMO CONTEXTO: Esclerose hepatoportal EHP ou venopatia portal obliterativa VPO, um dos diagnósticos diferenciais para a hipertensão portal não cirrótica, é caracterizada pelo desaparecimento dos ramos portais, fibrose portal e septal, fibrose sinusoidal e hiperplasia nodular regenerativa HNR. A EHP é um doença espectral, que pode progredir para hipertensão portal severa. Sua etiopatologia é ainda pouco compreendida, especialmente no Brasil, onde ela é provavelmente subdiagnoticada devido as suas similaridades com a forma hepatoesplênica da esquistossomose. OBJETIVO: Analizar o perfil dos pacientes com EHP no Nordeste do Brasil, e demontrar as características patológicas da EHP. MÉTODOS: Analisamos restrospectivamente os casos de VPO em biópsias hepáticas e explantes de um centro de referência em fígado na Bahia, Brasil. A análise qualiquantitativa dos tratos portais e parênquima hepático foi realizada, permitindo a comparação entre os nossos paciente e os achados descritos por outros autores. RESULTADOS: Entre os 62 paciente identificados com EHP, 42% era do sexo masculino, 58% era do sexo feminino. A média de idade no diagnótico foi 48,3 anos. Desse grupo, analizamos a biópsia hepática de 10 pacientes nos quais o diagnóstico de esquistossomose pode ser excluído. Desses pacientes, 100% 10/10 se apresentou com fibrose portal densa e obliteração venosa portal. Atrofia do perênquima hepático estava presente em 60% 6/10 dos pacientes, dilatação sinusiodal em 30% 3/10 a presença de septos portais ocorreu em 50% 5/10 e fibrose portal densa foi achada em todos os pacientes. Hiperplasia nodular regenerativa foi encontrada em 30% dos pacientes. CONCLUSÃO: A EHP parece ser negligenciada e subdiagnosticada no Brasil, devido as suas similaridades com esquistossomose. Em nosso estudo, fibrose portal densa, obliteração dos ramos da veia porta, atrofia do parênquima, dilatação sinusoidal e hiperplasia nodular do parênquima foram os principais achados histopatológicos e foram semelhantes aos descritos em outros países.

Association of lewy bodies, hippocampal sclerosis and amyloid angiopathy with dementia in community-dwelling elderly: A systematic review and meta-analysis.

INTRODUCTION: We measured the proportion of Lewy body pathology (LB), hippocampal sclerosis (HS), and cerebral amyloid angiopathy (CAA) among community-dwelling people with and without dementia. METHODS: We searched for community-based cohorts with postmortem brain autopsy until 1 January 2020. We calculated the summary risk difference and 95% confidence interval (95% CI) using a random-effects model in R. RESULTS: We found 12 articles, comprising 2197 demented and 2104 non-demented participants. LB, HS, CAA were prevalent lesions among community-dwelling elderly (15%, 10%, and 24%, respectively). These significantly increased the risk of dementia (LB: risk difference 38%, 95% CI 20-56%, HS: 34%, 24-44%, CAA: 19%, 3-34%). 20% of cases with neocortical LB, 17% with bilateral HS, and 42% with moderate/severe CAA pathology remained non-demented by death. DISCUSSION: LB or HS or CAA are common neuropathologies among community-dwelling elderly. Although these lesions independently are associated with dementia, many remain non-demented, by death.

A pioneering FreeSurfer volumetric study of a series of patients with mesial temporal lobe epilepsy and hippocampal sclerosis with comorbid depression.

Depression is the most frequent psychiatric comorbidity in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS). This study aimed to confirm whether patients with comorbid depression have different volumetric patterns on magnetic resonance imaging, analysing the influence of HS sides. Psychiatrists conducted semi-structured interviews with 75 patients, who were divided into non-depression group (NDG, n = 52) and depression group (DG, n = 23), and compared with 98 controls. The FreeSurfer software was used in the volumetric analysis of the estimated total intracranial volume (eTIV), bilateral cortical and subcortical regions of interest (ROIs), and for presence of left (L-, n = 41) or right (R-, n = 34) MTLE-HS. Twenty-three (30.7%) patients had depression, of whom 14 (34.1%) had l-MTLE-HS and 9 (26.5%) had R-MTLE-HS. No difference was observed between DG and NDG vs. controls in terms of eTIV and cortical ROIs, regardless of the severity of depression. In patients with l-MTLE-HS, the eTIV in the DG was reduced in comparison with that in the NDG and control group, with a small effect size. Hippocampal reduction occurred ipsilateral to HS in the l-MTLE-HS and R-MTLE-HS subgroups when DG and NDG were compared with controls, as expected according to Enhancing Neuro Imaging Genetics through Meta-Analysis (2018).

Neuropsychological findings related to the presence of pre-surgical comorbid depression in Latin-American patients with mesial temporal lobe epilepsy and hippocampal sclerosis.

PURPOSE: To evaluate the neuropsychological findings related to the presence of pre-surgical comorbid depression in Latin-American patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS). METHOD: Patients with drug-resistant MTLE and unilateral, left (L-) or right (R-) HS were studied. To diagnose depression, psychiatrists with expertise in epilepsy applied a semi-structured interview based on DSM. The depression group (DG) included patients with a psychiatric diagnosis in addition to a Beck Depression Inventory (BDI) score >16 points, and the non-depression group (NDG) included those without this diagnosis and with a BDI score ≤16. We analysed two clusters of neuropsychological tests, which evaluated memory (Complex Rey Figure III, Logical Memory II and RAVLT VII) and attention plus executive functions (Stroop I/II/III and Trail Making A/B). Moreover, we calculated the z-scores (Zs) using a local control group. The DG was compared to the NDG, independently and according to the HS side, using non-parametrical analyses. Due to the multivariate analysis, the p-value was corrected by applyingpost hoc Bonferroni adjustment. RESULTS: We analysed 65 patients. The NDG included 51 (78.4 %) patients, and the DG included 14 (21.5 %) patients. Pre-surgical comorbid depression occurred in eight patients with L- (n = 29) and in six patients with R-MTLE-HS (n = 36). All of these groups had similar gender, age, IQs, and years of schooling. Compared to the healthy subjects, the L-MTLE-HS patients had lower Zs in verbal episodic memory tests [Logical Memory II (p < 0.001), and RAVLT VII (p < 0.001)], and the R-MTLE-HS patients had lower scores in visual episodic memory [Complex Rey Figure III (p < 0.001)]. In the analysis of the DGvs. NDG, there were no differences in the clusters of tests of memory or in those of attention and executive functions. Moreover, when we analysed the patients according to HS side, no neuropsychological difference was observed in the DG and NDG in terms of L- and R-MTLE-HS. CONCLUSIONS: The patients with MTLE and unilateral HS in this study showed no differences in memory, attention and executive functions in relation to the presence of pre-surgical comorbid depression and independently of HS side. In this series from Latin-America, this psychiatric comorbidity did not affect cognition more than epilepsy alone.

Prevalence and risk factors of aortic stenosis and aortic sclerosis: a 21-year follow-up of middle-aged men.

Introduction. There is limited knowledge about factors associated with the development of aortic stenosis. This study aimed to examine the prevalence of aortic sclerosis or stenosis in 71-years-old men and determine which risk factors at 50 years of age predict the development of aortic sclerosis or aortic stenosis. Methods. A random sample of Swedish men from the general population, born in 1943 (n = 798) were followed for 21 years. Data on clinical characteristics and laboratory values were collected in 1993. An echocardiography was performed in 2014. We used logistic regression to examine the association between baseline data and the outcome. Results. Echocardiography was performed in 535 men, and aortic sclerosis or aortic stenosis was diagnosed in 27 (5.0%). 14 persons developed aortic stenosis (2.6%). Among men with aortic sclerosis or aortic stenosis, 29.6% were obese. In multivariable stepwise regression model, body mass index (odds ratio per unit increase 1.23 (95% CI 1.10-1.38; p = .0003)) and hypercholesterolemia, combined with high sensitive C-reactive protein (odds ratio versus all other 2.66 (1.18-6.00; p = .019)) were significantly associated with increased risk of developing aortic sclerosis or aortic stenosis. Body mass index was the only factor significantly associated with a higher risk of developing aortic stenosis. Conclusion. The prevalence of either aortic sclerosis or aortic stenosis was 5% and of aortic stenosis 2.6%. Obesity and hypercholesterolemia combined with elevated high sensitive C-reactive protein at the age of 50 predicted the development of degenerative aortic sclerosis or stenosis, whilst only obesity was correlated with the occurrence of aortic stenosis.

Visual field defects after radiosurgery versus temporal lobectomy for mesial temporal lobe epilepsy: Findings of the ROSE trial.

PURPOSE: Stereotactic radiosurgery (SRS) may be an alternative to anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). Visual field defects (VFD) occur in 9-100% of patients following open surgery for MTLE. Postoperative VFD after minimally invasive versus open surgery may differ. METHODS: This prospective trial randomized patients with unilateral hippocampal sclerosis and concordant video-EEG findings to SRS versus ATL. Humphries perimetry was obtained at 24 m after surgery. VFD ratios (VFDR = proportion of missing homonymous hemifield with 0 = no VFD, 0.5 = complete superior quadrantanopsia) quantified VFD. Regressions of VFDR were evaluated against treatment arm and covariates. MRI evaluated effects of volume changes on VFDR. The relationships of VFDR with seizure remission and driving status 3 years after surgery were evaluated. RESULTS: No patients reported visual changes or had abnormal bedside examinations, but 49 of 54 (91%) of patients experienced VFD on formal perimetry. Neither incidence nor severity of VFDR differed significantly by treatment arm. VFDR severity was not associated with seizure remission or driving status. CONCLUSION: The nature of VFD was consistent with lesions of the optic radiations. Effective surgery (defined by seizure remission) of the mesial temporal lobe results in about a 90% incidence of typical VFD regardless of method.

Risk factors of hippocampal sclerosis in the oldest old: The 90+ Study.

OBJECTIVE: To examine the risk factors and comorbidities of hippocampal sclerosis (HS) in the oldest-old. METHODS: A total of 134 participants with dementia from The 90+ Study with longitudinal evaluations and autopsy were included in this investigation. Participants were divided into 2 groups, one with and one without HS pathology, and differences in clinical and pathologic characteristics were compared. RESULTS: Persons with HS tended to have a longer duration of dementia compared to participants without HS (mean 4.0 years vs 6.7 years, odds ratio [OR] 1.26; 95% confidence interval [CI] 1.11-1.42; p < 0.001). HS was more likely in participants with a history of autoimmune diseases (rheumatoid arthritis or thyroid disease, OR 3.15; 95% CI 1.30-7.62; p = 0.011), high thyroid-stimulating hormone (OR 4.94; 95% CI 1.40-17.46; p = 0.013), or high thyroid antibodies (OR 3.45; 95% CI 1.09-10.88; p = 0.035). Lewy body disease (LBD) pathology was also associated with an increased likelihood of HS (OR 5.70; 95% CI 1.22-26.4; p = 0.027). CONCLUSION: We identified autoimmune conditions (rheumatoid arthritis and thyroid disease) as potential risk factors for HS in our cohort. LBD was the only pathology that was associated with increased odds of HS and those harboring HS pathology had a longer duration of dementia. This suggests multiple pathways of HS pathology among the oldest-old.

BDNF Val66Met polymorphism is not related with temporal lobe epilepsy caused by hippocampal sclerosis in Brazilian population.

PURPOSE: Some variants of the brain derived neurotrophic factors (BDNF) gene, namely the Val66Met (rs6265), may contribute the risk for epilepsy development. We aimed to investigate if this polymorphism was associated with the risk for epilepsy development in TLE-HS and its correlation with epilepsy-related factors and the presence of psychiatric disorders. METHODS: We assessed 119 patients with unequivocal TLE-HS and 112 healthy controls. Individuals were genotyped for the polymorphisms of the gene encoding BDNF Val66Met. RESULTS: There was no difference between TLE-HS and healthy controls, for the genotypic distribution (p = 0.636) and allelic distribution (p = 0.471). There was no correlation between Val66Met and epilepsy-related factors and for psychiatric comorbidities (p = 0.888). CONCLUSIONS: Our findings demonstrated that polymorphism Val66Met is not associated with TLE-HS, epilepsy-related factors and psychiatric comorbidities in this selected group of patients.

Hippocampal Sclerosis in the Oldest Old: A Finnish Population-Based Study.

BACKGROUND: There are only few population-based studies that have systemically investigated the prevalence of hippocampal sclerosis (HS) in the very old. The frequency of unilateral versus bilateral HS has been rarely studied. OBJECTIVE: We investigated the prevalence and laterality of HS and its association with other neurodegenerative and vascular pathologies in a population-based sample of very elderly. Furthermore, the concomitant presence of immunoreactivity for TDP-43, p62, and HPtau was studied. METHODS: The population-based Vantaa 85+ study includes all inhabitants of the city of Vantaa, who were >85 years in 1991 (n = 601). Neuropathological assessment was possible in 302 subjects. Severity of neuronal loss of CA sectors and subiculum was determined bilaterally by HE- staining. Immunohistochemistry performed using antibodies for TDP-43, p62, and HPtau. RESULTS: Neuronal loss and pathological changes in the hippocampus sector CA1 and subiculum were observed in 47 of the 302 individuals (16%), and 51% of these changes were bilateral. HS without comorbid neurodegenerative pathology was found in 1/47 subjects with HS (2%). Dementia (p < 0.001) and TDP-43 immunopositivity of the granular cell layer of the dentate fascia (p < 0.001) were strongly associated with HS. The CERAD score, immunopositivity for HPtau and p62 in the granular cell layer of the fascia dentate were also associated. CONCLUSION: HS is prevalent (16%) in the oldest old population, but HS without any comorbid neurodegenerative pathology is rare. The high frequency of unilateral HS (49%) implied that bilateral sampling of hippocampi should be routine practice in neuropathological examination.

Pulmonary hypertension associated with combined fibrosing mediastinitis and bronchial anthracofibrosis: A retrospective analysis in a single Chinese hospital.

INTRODUCTION: Both fibrosing mediastinitis (FM) and bronchial anthracofibrosis (BAF) are unique diseases. The combined appearance of FM and BAF is extremely rare. OBJECTIVES: The aim of this study was to investigate the clinical features of patients with coexisting FM and BAF. METHOD: Between January 2003 and December 2015, a total of eight patients were diagnosed at the Peking Union Medical College Hospital as having combined FM and BAF. The clinical presentations, radiographic features and bronchoscopic findings of the eight patients were reviewed. RESULTS: The patients were five women and three men with a median age of 64 years (range 56-86 years). Symptoms included dyspnea (eight patients), cough (seven patients), chest pain (two patients), hemoptysis (two patients) and so on. Chest CT of all eight patients showed mediastinal soft-tissue lesions, with multiple narrowed or obliterated lobar or segmental bronchi and arteries. Bronchoscopy showed that all of the patients had multiple stenoses of lobar or segmental bronchi with anthracotic pigmentation on the mucosa. Echocardiography showed that all of the patients had elevated pulmonary arterial systolic pressure (median 81 mm Hg, range 51-107 mm Hg). Each of the eight patients had a history of exposure to, or infection with, tuberculosis, although there was no evidence of active disease. All of the eight patients had long-term exposure to indoor coal or biomass fuel smoke. CONCLUSIONS: FM can coexist with BAF, characterized by prominent pulmonary hypertension. The possible etiological factors are tuberculosis and coal or biomass fuel exposure.

Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period.

Congenital muscular dystrophies (CMDs) are clinically and genetically heterogeneous conditions; some fatal in the first few years of life and with central nervous system involvement, whereas others present a milder course. We provide a comprehensive report of the relative frequency and clinical and genetic spectrum of CMD in the UK. Genetic analysis of CMD genes in the UK is centralised in London and Newcastle. Between 2001 and 2013, a genetically confirmed diagnosis of CMD was obtained for 249 unrelated individuals referred to these services. The most common CMD subtype was laminin-α2 related CMD (also known as MDC1A, 37.4%), followed by dystroglycanopathies (26.5%), Ullrich-CMD (15.7%), SEPN1 (11.65%) and LMNA (8.8%) gene related CMDs. The most common dystroglycanopathy phenotype was muscle-eye-brain-like disease. Fifteen patients carried mutations in the recently discovered ISPD, GMPPB and B3GALNT2 genes. Pathogenic allelic mutations in one of the CMD genes were also found in 169 unrelated patients with milder phenotypes, such as limb girdle muscular dystrophy and Bethlem myopathy. In all, we identified 362 mutations, 160 of which were novel. Our results provide one of the most comprehensive reports on genetics and clinical features of CMD subtypes and should help diagnosis and counselling of families with this group of conditions.

Coexistence of meningoencephalocele and hippocampal sclerosis: a new type of dual pathology.

Both temporal lobe meningoencephalocele (TE) and hippocampal sclerosis (HS) are causes of drug-resistant temporal lobe epilepsy. Spontaneous TE constitutes a rare but well-known and increasingly recognised cause of refractory epilepsy. It is well known that HS may be associated with another neocortical lesion (dual pathology). Here we report for the first time a new type of dual pathology; namely, the coexistence of temporal pole meningoencephalocele and HS.

Anterior temporal lobectomy for older adults with mesial temporal sclerosis.

OBJECTIVE: To compare postoperative seizure-free survival between older and younger adults. METHODS: A retrospective cohort of 107 temporal lobe epilepsy patients with a diagnosis of mesial temporal sclerosis (MTS) received anterior temporal lobectomy (ATL) between 1993 and 2014. We divided the lower three quartiles (younger) and top quartile (older, all 47+ years) of patients, then reviewed patient registry and electronic medical records to determine time to first self-reported seizure after ATL, the primary outcome (mean=3.5years of follow-up, SD=3.6). We also assessed Engel classifications, intraoperative and postoperative treatment complications, and social disability. We used Cox proportional hazard models to assess the association between individual traits and time of seizure recurrence. RESULTS: During follow-up, 35/107 (32.7%) patients had post-operative seizure(s). After adjustment for potential confounders there were no significant differences in the probability of post-operative seizures between the older and younger groups, though we had limited precision (hazard ratio of 0.67 [0.28-1.59]), (p=0.36). There were more treatment complications and disability in older patients (18% vs. 1.3% for any complications, 84.62% vs. 58.23% for driving disability, and 84.6% vs. 60.7% for work disability, p<0.05). CONCLUSION: Older patients appear to have more complications after ATL, compared with younger patients. Age, however, does not appear to have a large independent association with seizure recurrence.

Age at onset in patients with medically refractory temporal lobe epilepsy and mesial temporal sclerosis: impact on clinical manifestations and postsurgical outcome.

PURPOSE: To evaluate the demographic and clinical manifestations and postsurgical outcome of childhood-onset mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) and establishing the potential differences as compared to the patients with adult-onset MTS-TLE. METHOD: In this retrospective study all patients with a clinical diagnosis of medically refractory TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson comprehensive epilepsy center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. Clinical manifestations and outcome were compared between patients with childhood-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure below 10 years) and those with adult-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure 20 years or above). RESULTS: One hundred and twelve patients had childhood-onset MTS-TLE and 76 had adult-onset MTS-TLE. Demographic, clinical, EEG and MRI characteristics of these two groups were similar. Postoperative outcome was not statistically different between these two groups of patients (P=0.9). CONCLUSION: Temporal lobe epilepsy due to mesial temporal sclerosis is a common cause of epilepsy that can start from early childhood to late adulthood. The etiology of MTS-TLE may be different in various age groups, but it seems that when mesial temporal sclerosis is the pathological substrate of TLE, clinical manifestations and response to surgical treatment of patients are very similar in patients with childhood-onset MTS-TLE compared to those with adult-onset disease.

Hippocampal sclerosis in Lewy body disease is a TDP-43 proteinopathy similar to FTLD-TDP Type A.

Hippocampal sclerosis (HpScl) is frequent in frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), but it also occurs in dementia of the elderly with or without accompanying Alzheimer type pathology. HpScl has been hypothesized to be a neurodegenerative process given its association with TDP-43 pathology, but this is still controversial. TDP-43 pathology is found in Lewy body disease (LBD), but no study has focused on the pathologic and genetic characteristics of HpScl in LBD. We found HpScl in 5.2% of 669 LBD cases (289 transitional and 380 diffuse). Older age, higher Braak neurofibrillary tangle (NFT) stage, and presence of TDP-43 pathology were associated with HpScl. There was no difference in the frequency of HpScl between transitional and diffuse LBD, suggesting that Lewy-related pathology appears to have no direct association with HpScl. All HpScl cases had TDP-43 pathology consistent with Type A pattern. HpScl cases harbored genetic variation in TMEM106B that has been previously associated with FTLD-TDP. Interestingly, the severity of TDP-43-positive fine neurites in CA1 sector, a possible pathologic precursor of HpScl, was associated with the TMEM106B variant. These results demonstrate HpScl in LBD is a TDP-43 proteinopathy and is similar to FTLD-TDP Type A. Furthermore, a subset of LBD cases without HpScl ("pre-HpScl") had similar pathologic and genetic characteristics to typical HpScl, suggesting that the spectrum of HpScl pathology may be wider than previously thought. Some cases with many extracellular NFTs also had a similar profile. We suggest that HpScl is "masked" in these cases.

Characteristics of mesial temporal lobe epilepsy associated with hippocampal sclerosis plus neurocysticercosis.

Recent observations suggest that neurocysticercosis (NCC) might act as an initial precipitating injury (IPI) causing mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). A total of 191 patients from Brazil, a country in which NCC is endemic, were surgically treated for MTLE-HS, and subsequent findings for patients with MTLE-HS were compared with those of patients with MTLE-HS plus NCC. Seventy-one patients (37,2%) presented chronic findings of NCC (cNCC). MTLE-HS plus cNCC was significantly more common in women (O.R.=2.45; 95%CI=1.30-4.60; p=0.005), in patients with no history of classical forms of IPI (O.R.=2.67; 95%CI=1.37-5.18; p=0.004), and in those with bi-temporal interictal spikes on video-EEG (O.R.=2.00; 95%CI=1.07-3.73; p=0.03). Single cNCC lesions were observed to occur significantly more often on the same side as hippocampal sclerosis, a finding suggesting an anatomical relationship between NCC and MTLE-HS. Taken together, our results suggest that NCC may be a marker, or contributes to or even causes MTLE-HS. Based on our findings, we propose two distinct, non-excluding, and potentially synergistic mechanisms involved in the development of MTLE-HS in NCC, one of them being inflammatory-mediated, while the other is electrogenic-mediated. Taken together, our observations may provide further evidence suggesting a role of NCC in the genesis or development of MTLE-HS.

Osteoarthritis of the knee: multicompartmental or compartmental disease?

OBJECTIVE: Knee OA has been conceptualized as a multicompartmental disease, as a compartmental disease or as a combination of these two disease processes. The aim of this study was to determine the associations between four radiographic features (joint space narrowing, osteophyte formation, sclerosis and cysts) across and within the three knee compartments (medial tibiofemoral, lateral tibiofemoral and patellofemoral compartment) in knee OA. METHODS: Data from the Amsterdam OA Cohort were used. In 298 patients diagnosed with knee OA, radiographic features were examined in three knee joint compartments. Radiographic features were scored according to standardized scoring methods. Factor analysis was used to examine associations between the four radiographic features across and within compartments. RESULTS: A bifactor model showed a general multicompartmental factor: 10 of 12 radiographic features across the entire joint were associated with the general factor. The bifactor model also showed three compartmental factors-one for each compartment: joint space narrowing, sclerosis and to a lesser extent osteophyte formation were associated with these compartmental factors. CONCLUSION: These findings suggest a multicompartmental disease process in the knee, characterized by associations among features across the entire joint, as well as compartmental disease processes in each knee compartment, characterized by associations among features within specific compartments. Longitudinal studies are needed to explore the possibility of the development from a compartmental disease to a multicompartmental disease and the impact of contributing factors on the development.