Double-endoscope assisted endoscopic submucosal dissection for treating tumors in rectum and distal colon by expert endoscopists: a feasibility study.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is an effective but challenging procedure. To facilitate ESD, several methods that apply traction are available; however, the optimal one remains to be established. The aim of this study was to evaluate the feasibility and safety of the double-endoscope assisted ESD (DEA-ESD) by improving traction to treat complex colorectal lesions. METHODS: Naïve or previously treated lesions in the rectum and sigmoid colon were included. A grasping forceps advanced through a small-caliber endoscope (GIF-XP190N, Olympus Medical Systems, Tokyo, Japan, 5.4 mm outer diameter) was used to apply traction to the mucosal flap. Lesions were deemed complex when they exceeded a total of nine points on the SMSA scoring system (size, morphology, site, and access) and recurrent when they were previously treated with endoscopic mucosal resection (EMR). Outcome measures included procedural success, total procedure time, complications, and recurrence rate at 3-month follow-up. RESULTS: Nine patients (mean age 62.3 ± 14.5 years) were included; five had rectal and four had tumors in the sigmoid colon. The median SMSA score was 14 (SMSA Level IV-complex polyp), while three patients were pre-treated with EMR. DEA-ESD was technically feasible in all cases. En bloc resection and R0 resection rates were 100%, respectively, with a mean procedure time of 128.4 ± 54.1 min. No immediate or delayed complications occurred. CONCLUSIONS: DEA-ESD is a feasible and safe method for treating complex or recurrent tumors in the rectum and distal colon.

[Mesothelial proliferation of the tunica vaginalis testis]. / Mesotheliale Proliferate der Tunica vaginalis testis.

Proliferative changes seen in reactive mesothelial hyperplasia of a hydrocele sac may mimic malignant mesothelioma. There is no immunohistochemical staining that reliably separates benign from malignant mesothelial proliferations. However, the combined analysis of BAP1 by immunohistochemistry and CDKN2A by FISH has been reported to yield both a high specificity and sensitivity in this differential diagnosis. In addition, the evaluation of risk factors such as asbestos exposure or prior traumata may be helpful for the correct diagnosis. Exclusion of stromal invasion, which is diagnostic for malign mesothelioma, is of utmost importance. Therefore, extended histological workup is essential.

Co-expression of truncated and full-length tau induces severe neurotoxicity.

Abundant tau inclusions are a defining hallmark of several human neurodegenerative diseases, including Alzheimer's disease. Protein fragmentation is a widely observed event in neurodegenerative proteinopathies. The relevance of tau fragmentation for the neurodegenerative process in tauopathies has yet remained unclear. Here we found that co-expression of truncated and full-length human tau in mice provoked the formation of soluble high-molecular-weight tau, the failure of axonal transport, clumping of mitochondria, disruption of the Golgi apparatus and missorting of synaptic proteins. This was associated with extensive nerve cell dysfunction and severe paralysis by the age of 3 weeks. When the expression of truncated tau was halted, most mice recovered behaviorally and functionally. In contrast, co-expression of full-length tau isoforms did not result in paralysis. Truncated tau thus induces extensive but reversible neurotoxicity in the presence of full-length tau through the formation of nonfilamentous high-molecular-weight tau aggregates, in the absence of tau filaments. Targeting tau fragmentation may provide a novel approach for the treatment of human tauopathies.

[Simultaneous bilateral humeral head disclocation and acetabular fracture. A rare manifestation after hypoglycemia-induced seizures]. / Simultane beidseitige Humeruskopfluxations- und Acetabulumfraktur. Eine seltene Folge eines hypoglykämieinduzierten Krampfanfalls.

Seizures can cause severe musculoskeletal injuries and posterior shoulder dislocation is a typical result of a seizure. Bilateral posterior shoulder dislocation is rare and acetabular fractures caused by a seizure are also a rarity. We present the case of a 48-year-old man with simultaneous bilateral posterior shoulder fracture dislocations and bilateral acetabular fractures as a result of hypoglycemia-induced seizures.

Long-term behaviour of Cs-137, Cs-133 and K in beech trees of French forests.

In the long-term after atmospheric deposit onto a forest ecosystem, Cs-137 becomes incorporated into the biogeochemical cycle of stable elements and progressively reaches a quasi-equilibrium state. This study aimed at determining to what extent Cs-137 activity distribution in tree vegetation could be predicted from that of stable caesium (Cs-133) and potassium (K), which are known to be stable chemical analogues and competitors for Cs-137 intake in tree organs. Field campaigns that focused on beech trees (Fagus sylvatica L.) were conducted in 2021 in three French forest stands with contrasted characteristics regarding either the contribution of global vs. Chornobyl fallouts, soil or climatic conditions. Decades after Cs-137 fallouts, it was found that more than 80% of the total radioactive inventory in the system remained confined in the top 20 cm mineral layers, while organic layers and beech vegetation (including roots) contributed each to less than 1.5%. The enhanced downward migration of Cs-137 in cambisol than podzol forest sites was presumably due to migration of clay particles and bioturbation. The distribution of Cs-137 and Cs-133 inventories in beech trees was very similar among sites but differed from that of K due a higher accumulation of Cs isotopes in roots (40-50% vs. < 25% for K). The aggregated transfer factor (Tag) of Cs-137 calculated for aerial beech organs were all lower than those reported in literature more than 20 years ago, this suggesting a decrease of bioavailability in soil due to ageing processes. Regarding their variability, Tags were generally lower by a factor 5 at the cambisol site, which was fairly well explained by a much higher value of RIP (radiocesium immobilisation potential). Cs-137 concentrations in trees organs normalized by the soil exchangeable fractions were linearly correlated to those of Cs-133 and the best fit was found for the linear regression model without intercept indicating that no more contribution of the foliar uptake could be observed on long term. Provided that the vertical distribution of caesium concentrations and fine root density are properly measured or estimated, Cs-133 was shown to be a much better proxy than K to estimate the root transfer of Cs-137.

Prognostic significance of histologically detected lymph node micrometastases of sizes between 0.2 and 2 mm in colorectal cancer.

PURPOSE: Minimal lymph node involvement is a potential prognostic factor in colorectal cancer. The International Union Against Cancer defined tumour deposits between 0.2 and 2 mm as micrometastases and clusters and single-cell infiltrations below this cutoff as isolated tumour cells. Nevertheless, only a minority of studies discriminated metastatic involvements according to this definition. METHODS: In order to investigate the prognostic significance of micrometastases (0.2-2 mm), we performed a retrospective study enrolling 44 routinely diagnosed micrometastatic cases within 15 years which represent about 1% of our cases. These cases have been re-evaluated. RESULTS: Seven of the micrometastatic cases turned out to be macrometastases after step sectioning. Complete follow-up was available in 33 remaining cases. Collections of node-negative and macrometastatic cases served as control groups. The Kaplan-Meier curves of macro- and micrometastatic cases showed a similar adverse course (p = 0.830) especially during the first 40 months. The 5-year-survival rates were 51, 60 and 64 months for macro-, micrometastatic and node-negative cases, respectively. The difference in overall survival, however, reached only a statistical trend and was not significant (p = 0.137). After re-evaluation with step sections and cytokeratin immunohistochemistry out of an initial 91 node-negative cases, 11 (12%) cases were identified with isolated tumour cells and one (1%) case with a micrometastasis. CONCLUSIONS: Our data show that micro- and macrometastatic colorectal cancers show very similar survival rates. Therefore, efforts to improve the detection of lymph node micrometastases seem to be justified.

[Patients with periprosthetic femur fractures and consecutive stem replacement. Analysis of survival, complications, and quality of life]. / Geriatrische Patienten mit proximalen periprothetischen Femurfrakturen nach Prothesenschaftwechsel. Letalität, Komplikationsrate und weiterer Lebensweg.

BACKGROUND: The goal of treating proximal periprosthetic femur fractures in geriatric patients is a timely postoperative mobilization. The purpose of this study is to analyze the results after treating our patients by femoral stem exchange irrespective of fixation status. The study included 32 patients (2001-2009; mean age 82 years; Vancouver classification: 12 type B1, 16 type B2, and 4 type C). METHOD: Ambulatory status and activities of daily living pre- and postoperatively were compared. Retrospective data collection was performed by reviewing patients' charts. By interviewing patients, family members, and family physicians missing information was collected. RESULTS: A total of 22 patients (69%) achieved their pre-traumatic mobilization level; 22 of 26 patients (85%) were reintegrated into their pre-traumatic environment. A 16% (n=5) complication rate and an 87% 12-month survival rate were calculated. CONCLUSION: The concept of primary stable periprosthetic fracture care by using a revision prosthetic device potentially reduces complications related to postoperative non-weight-bearing without increasing the complication rate related to a more complex surgical procedure.

[Acute abdomen-Rare cause in an 80-year-old female patient under immunosuppressive treatment]. / Akutes Abdomen ­ seltene Ursache bei einer 80-jährigen Patientin unter immunsuppressiver Therapie.

An 80-year-old woman presented to the emergency department due to abdominal pain. She had a history of opportunistic pneumonia under the effects of immunosuppression after the diagnosis of autoimmune hepatitis. The imaging showed an omental cake formation and the suspicion of peritoneal carcinomatosis. The patient developed an acute abdomen during the hospital stay, followed by exploratory laparotomy. In the presence of extensive intra-abdominal abscess formation both surgically acquired material and blood culture revealed disseminated nocardiosis. The course was fatal due to fulminant septic shock.

Endoscopic submucosal dissection in large sessile lesions of the rectosigmoid: learning curve in a European center.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) in the colorectum is not currently a standard procedure. Few data are available from the Western world. The aim of the present study was to report on the first experiences and the learning curve of colorectal ESD in a European center. PATIENTS AND METHODS: A total of 82 rectosigmoid lesions were referred for ESD. Lesion characteristics, resection rates, procedure times, complications, and recurrences were recorded prospectively. Results were compared between three consecutive study periods in order to determine the learning curve. RESULTS: Lesions were located in the rectum (86.6 %) and the sigmoid colon (13.4 %). Median diameter was 45.5 mm. Lesions were of Paris type 0-Is with pit pattern type V (n = 8), 0-IIa (n = 33), 0-IIa + Is (n = 36), and 0-IIa + IIc (n = 5). The malignancy rate in these groups was 100 %, 0 %, 14 %, and 20 %, respectively. ESD was possible in 76 lesions (92.7 %). En bloc resection rate and R0 resection rate were 81.6 % and 69.7 %, respectively. Median procedure time was 176 minutes. Between the three consecutive study periods, en bloc resection rate increased (60.0 %, 88.0 %, 96.2 %), R0 resection rate increased (48.0 %, 76.0 %, 84.5 %; P < 0.001), and procedure time decreased (200, 193, 136 minutes; P = 0.027). The perforation and bleeding rates were 1.3 % and 7.9 %, respectively. Recurrence risk was 0 % after R0 en bloc resection and 41.7 % after piecemeal resection (P < 0.05). Median follow-up was 23.6 months. CONCLUSIONS: In the European setting, ESD in the distal colon is feasible with acceptable complication risks. Resection rates were not as high as those from Japanese studies; however, a clear learning curve could be shown. Colorectal ESD needs to be further evaluated, particularly in Europe where ESD experience is low.

Clinical significance of lymph vessel density in T3 colorectal carcinoma.

PURPOSE: The purpose of the present study is to characterise the lymphatic vessel density (LVD) in the T3 colorectal carcinoma and to correlate it with N status, grading and presence of tumour budding. METHODS: A total of 56 cases of T3 colorectal carcinoma were retrieved from the pathology's archive of Klinikum Augsburg. All slides were stained immunohistochemically with D2-40 (lymphatic endothelium) and with pancytokeratin to assess the tumour budding. Tumour budding and lymph vessel density were investigated independently by BM and CC. The highest density of lymphatic vessels was counted both in tumour centre (ILVD) and at the periphery of the tumour (PLVD) within an area of 0.24 mm(2). RESULTS: Due to the strong intra-observer (BM and CC) difference in ILVD and PLVD, all cases were re-evaluated establishing a consensus that has been used for the further analyses. There was a significant difference between PLVD and ILVD (12 ± 4 versus 6 ± 3; P < 0.001). Moreover, we found a non-significant trend towards high PLVD in the cases with nodal metastasis versus the negative one, 13 ± 5/hpf versus 11 ± 4 (P = 0.072). There was no association between tumour budding and ILVD and PLVD (P = 0.249 and 0.38). CONCLUSION: Colorectal carcinoma induces lymphangiogenesis. A higher PLVD could increase the capability of cancer cell to invade the lymphatic system. However, the obvious difficulties in immunohistochemical evaluation and the rather small differences between nodal positive and negative cases in T3 colorectal cancer seem to limit the clinical value of LVD evaluation.

[Results after Judet radial head prosthesis for non-reconstructable radial head fractures]. / Ergebnisse der Radiusköpfchenprothese von Judet bei nicht rekonstruierbaren Radiusköpfchenfrakturen.

BACKGROUND: With regard to the treatment of non-reconstructable radial head fractures, both the resection and the implantation of a prosthesis are considered. Various studies have shown poor results concerning the resection of the radial head with accompanying osteoligamentous injuries. Due to these experiences, different types of prosthesis have been developed. However, the majority of them were not convincing. Judet developed a type of a bipolar prosthesis which had been modeled on the anatomy of the radial head. The aim of our retrospective study consists in examining the results of the Judet prosthesis. PATIENTS AND METHODS: Between 1995 and 2007, 50 patients were treated with an arthroplasty. These were, corresponding to the classification by McKee and Jupiter, 19 type III and 31 type IV fractures. Thirty patients were available for a follow-up after 2.5 years on average. RESULTS: According to the Morrey Score, 16 very good, 7 good, 3 fair and 4 bad results could be obtained. Following the criteria of Radin and Riseborough, 17 patients achieved a good, 9 a fair and 4 a bad result. The complications which appeared were: one patient with aseptic loosening, one patient with luxation of a prosthesis, one persistent radial joint instability, three patients with heterotopic ossification and four patients with protrusion relative to the capitulum humeri.

Role of hepatitis C virus genotype 3 in liver fibrosis progression--a systematic review and meta-analysis.

The progression of liver fibrosis in chronic hepatitis C has long been considered to be independent from viral genotypes. However, recent studies suggest an association between Hepatitis C virus (HCV) genotype 3 and accelerated liver disease progression. We completed a systematic review and meta-analysis of studies evaluating the association between HCV genotypes and fibrosis progression. PubMed, Embase and ISI Web of Knowledge databases were searched for cohort, cross-sectional and case-control studies on treatment-naïve HCV-infected adults in which liver fibrosis progression rate (FPR) was assessed by the ratio of fibrosis stage in one single biopsy to the duration of infection (single-biopsy studies) or from the change in fibrosis stage between two biopsies (paired biopsies studies). A random effect model was used to derive FPR among different HCV genotypes. Eight single-biopsy studies (3182 patients, mean/median duration of infection ranging from 9 to 21 years) and eight paired biopsies studies (mean interval between biopsies 2-12 years) met the selection criteria. The odds ratio for the association of genotype 3 with accelerated fibrosis progression was 1.52 (95% CI 1.12-2.07, P = 0.007) in single-biopsy studies and 1.37 (95% CI 0.87-2.17, P = 0.17) in paired biopsy studies. In conclusion, viral genotype 3 was associated with faster fibrosis progression in single-biopsy studies. This observation may have important consequences on the clinical management of genotype 3-infected patients. The association was not significant in paired biopsies studies, although the latter may be limited by important indication bias, short observation time and small sample size.

Stable carbon isotope evidence for nitrogenous fertilizer impact on carbonate weathering in a small agricultural watershed.

The isotopic signature of Dissolved Inorganic Carbon (DIC), δ(13)C(DIC), has been investigated in the surface waters of a small agricultural catchment on calcareous substratum, Montoussé, located at Auradé (south-west France). The Montoussé catchment is subjected to intense farming (wheat/sunflower rotation) and a moderated application of nitrogenous fertilizers. During the nitrification of the NH(4)(+), supplied by fertilization, nitrate and H(+) ions are produced in the soil. This anthropogenic acidity is combined with the natural acidity due to carbonic acid in weathering processes. From an isotopic point of view, with 'natural weathering', using carbonic acid, δ(13)C(DIC) is intermediate between the δ(13)C of soil CO(2) produced by organic matter oxidation and that of the carbonate rocks, while it has the same value as the carbonates when carbonic acid is substituted by another acid like nitric acid derived from nitrogen fertilizer. The δ(13)C(DIC) values range from -17.1‰ to -10.7‰ in Montoussé stream waters. We also measured the δ(13)C of calcareous molassic deposits (average -7.9‰) and of soil organic carbon (between -24.1‰ and -26‰) to identify the different sources of DIC and to estimate their contribution. The δ(13) C(DIC) value indicates that weathering largely follows the carbonic acid pathway at the springs (sources of the stream). At the outlet of the basin, H(+) ions, produced during the nitrification of N-fertilizer, also contribute to weathering, especially during flood events. This result is illustrated by the relationship between δ(13)C(DIC) and the molar ratio NO(3)(-)/(Ca(2+) + Mg(2+)). Consequently, when the contribution of nitrate increases, the δ(13)C(DIC) increases towards the calcareous end-member. This new isotopic result provides evidence for the direct influence of nitrogen fertilizer inputs on weathering, CO(2) consumption and base cation leaching and confirms previous results obtained using the chemistry of the major ions present in the field, and in soil column experiments.

Influence of ponds on hazardous metal distribution in sediments at a catchment scale (agricultural critical zone, S-W France).

Eight potentially toxic trace elements were investigated together with the physicochemical characteristics of sediments collected upstream, downstream, and from various ponds from three adjacent carbonated agricultural catchments in southwestern France. Geochemical indices with local references and multivariate data analysis revealed a significant enrichment of Cd, followed by Ni and Cu in sediments, originating from agricultural practices, especially in the upper catchments sensitive to erosion processes. Five other PTEs (As, Pb, Co, Cr, and Zn) mostly originated from the weathering process of the molasse. Clay minerals and/or iron oxides were the main controlling factors for most PTEs. In ponds, Cd was regulated by Ca co-precipitation favoured by the long hydraulic retention time and increased pH, whereas it was mostly controlled by silicates in stream sediments. Copper, Pb, and Cd were the highly extractable metals, suggesting the risk of a hazardous environment. Multivariate analysis revealed that several environmental factors affected the spatial variation of PTE concentrations in sediments as well as the trapping role of ponds (texture, slope, soil erosion, pond size and position, discharge, hydraulic retention time) in this area of intensive agricultural practices. Our conclusions are useful for pond management in a context of increasing water demand and climate warming.

Endoscopic submucosal dissection in gastric neoplasia - experience from a European center.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a promising technique for the resection of early gastric neoplasia. There are only a few data from the Western world to date. METHODS: Over a 7-year-period, 104 gastric lesions were treated with ESD in a European referral center, of which 91 were included in this study. A total of 66 lesions were early gastric cancer (EGC) and 25 were adenomas. Of the EGCs, 11 lesions (16.7 %) fulfilled the guideline criteria (EGC-GC) and 55 lesions (83.3 %) fulfilled the expanded resection criteria (EGC-EC) of the Japanese guidelines for the treatment of gastric cancer. RESULTS: ESD was technically possible in 85 lesions (93.4 %). In six lesions ESD was not possible due to non-lifting. En bloc resection rates for all lesions, ECGs-GC, ECGs-EC, and adenomas were 87.1 %, 100 %, 88.2 %, and 79.2 %, respectively. R0 en bloc resection rates were 74.1 %, 90 %, 68.6 %, and 79.2 %, respectively. Complications were: one perforation during piecemeal endoscopic mucosal resection of a lesion in which ESD was judged to be impossible (1.2 %); three clinically relevant bleedings (3.5 %); one gastric ischemia (1.2 %); and four strictures (4.7 %). No mortality was observed. There were five recurrences after piecemeal resection (50 %) compared with only one after en bloc resection (1.5 %; P < 0.05). The rate of recurrence for EGCs was 5.6 %, and this were seen exclusively after piecemeal resection. CONCLUSIONS: Our data show that ESD is a feasible technique in Europe even in patients with EGC according to the extended criteria. Resection rates are promising and complication rates are acceptable. Results are worse compared with large studies from Japan but still excellent regarding the learning curve of the method. ESD should be offered as the treatment of choice for early gastric neoplasia especially when en bloc resection cannot be performed with other resection techniques.

Determining cadmium critical concentrations in natural soils by assessing Collembola mortality, reproduction and growth.

The toxicity of cadmium for the Collembola Folsomia candida was studied by determining the effects of increasing Cd concentrations on growth, survival and reproduction in three cultivated and forested soils with different pH (4.5-8.2) and organic matter content (1.6-16.5%). The Cd concentration in soil CaCl(2) exchangeable fraction, in soil solution and in Collembola body was determined. At similar total soil concentrations, the Cd concentration in soil solutions strongly decreased with increasing pH. Reproduction was the most sensitive parameter. Low organic matter content was a limiting factor for reproduction. Effect of Cd on reproduction was better described by soil or body concentrations than by soil solution concentration. Values of EC(50-Repro) expressed on the basis of nominal soil concentration were 182, 111 and 107 microg g(-1), respectively, for a carbonated cultivated soil (AU), an acid forested soil with high organic matter (EPC) and a circumneutral cultivated soil with low organic content (SV). Sensitivity to Cd was enhanced for low OM content and acidic pH. The effect of Cd on reproduction is not directly related to Cd concentration in soil solution for carbonated soil: a very low value is found for EC(50-Repro) (0.17) based on soil solution for the soil with the highest pH (AU; pH=8.2). Chronic toxicity cannot be predicted on the basis of soluble fractions. Critical concentrations were 8 x 10(-5), 1.1, 0.3 microg mL(-1), respectively, for AU, EPC and SV soils.

Fulminant metastatic spread in a patient with an early gastric cancer.

A patient with an early gastric cancer was treated initially by endoscopic submucosal dissection (ESD) at our hospital. The resected specimen showed a depth of submucosal infiltration of more than 500 microm. Therefore, in accordance with the extended criteria with regard to EMR, the patient underwent gastrectomy. The TNM stage was pT1 (sm3), pN0 (0 / 58), cM0, L0, V0, G2 after surgery (UICC stage Ia). At 3 months later ultrasound revealed a new mass in the liver, and biopsy showed a rapidly growing metastasis of the gastric adenocarcinoma. Finally, immunohistochemical analysis of all the lymph nodes of the resected stomach revealed a micrometastasis (3mm) directly under the ESD site. The patient died 6 months later. This clinical case highlights the risk of affected lymph nodes in early gastric cancer and the consequent risk of metastasis which increases with greater depth of infiltration to the submucosa.

Trace elements in stream bed sediments from agricultural catchments (Gascogne region, S-W France): where do they come from?

The Gascogne region (SW of France) is cultivated for more than 75% of the area. 83 samples of stream bed sediments were collected in three main Gascogne river basins (Gers, Save and Touch, left tributaries of the Garonne river) to evaluate the impact of agricultural practices on trace elements behavior. Eight potential harmful elements (PHE) (Cr, Co, Ni, Cu, Zn, As, Cd and Pb), four reference elements for normalization (Sc, Cs, Al and Fe) and four major elements (Mn, Ca, Mg and P) were considered. The average trace element concentrations in the fine fractions (<63 microm) are in the decreasing order: Zn>Cr>Ni>Pb>Cu>Co>As>Sc>Cs>Cd. Geochemical investigations and an original approach combining regression analysis and chemical sequential extraction allowed to select the most adequate reference material (regional molasse) and reference element (Cs) for normalization procedure. The enrichment factor (EF) is generally lower than 2.5, particularly for Cr, Ni, Cu, As, Zn; however, 23% of the sampling stations are more contaminated (2.5

Hereditary systemic angiopathy (HSA) with cerebral calcifications, retinopathy, progressive nephropathy, and hepatopathy.

Several hereditary conditions affecting cerebral, retinal and systemic microvessels have recently been described. They include CADASIL, CRV, and HERNS. We here report on a variant form of a hereditary systemic angiopathy (HSA) affecting two generations of a Caucasian family. Clinical symptoms of HSA appear in the mid-forties and are characterized by visual impairment, migraine-like headache, skin rash, epileptic seizures, progressive motor paresis and cognitive decline. Late symptoms include hepatic and renal failure. Retinal capillary microaneurysms and arteriolar tortuosity are associated with marked optic disc atrophy. Radiological hallmarks consist of multiple cerebral calcifications and tumor-like subcortical white matter lesions. Brain, peripheral nerve, muscle, kidney and colon biopsies have revealed a multi organ small vessel involvement with partly altered endothelium, perivascular inflammation and thrombotic microangiopathy. No curative therapeutic options are known for hereditary cerebral vasculopathies. The use of cyclophosphamide, azathioprine and methotrexate was of no benefit in our cases of HSA. Early diagnosis of hereditary systemic angiopathies is important in order to prevent patients from repetitive invasive diagnostic measures and to avoid the use of inappropriate and potentially harmful drugs.

New insights into the pathology of Parkinson's disease: does the peripheral autonomic system become central?

Recent studies in aged, neurologically unimpaired subjects have pointed to a specific induction site of the pathological process of Parkinson's disease (PD) in the region of the dorsal glossopharyngeus-vagus complex as well as in the anterior olfactory nucleus. From the lower brainstem, the disease process would then pursue an ascending course and involve more rostral brainstem areas, limbic structures, and eventually the cerebral cortex. One barrier to the acceptance of the caudal medullary structures as the induction site of PD pathology is that not all parts of the nervous system have been investigated for the presence of PD-associated lesions in cases of early asymptomatic PD. Using alpha-synuclein immunostaining, we investigated the brain, the sacral, and thoracic autonomic nuclei of the spinal cord as well as several components of the peripheral autonomic nervous system in a autopsy cohort of 98 neurologically unimpaired subjects aged 64 or more. Our data indicate that the autonomic nuclei of the spinal cord and the peripheral autonomic nervous system belong to the most constantly and earliest affected regions next to medullary structures and the olfactory nerves in neurologically unimpaired older individuals, thus providing a pathological basis for early premotor autonomic dysfunctions at a prodromal stage of PD.