[Effect of sailuotong capsule on intervening cognitive dysfunction of multi-infarct dementia in rats].

OBJECTIVE: To study the effect of Sailuotong capsule (Sailuotong) on learning and memory functions of multi-infarct dementia (MID) rats and its mechanism. METHOD: All SD rats were divided into five groups, namely the sham operation group, the model group, the positive group, the low dosage Sailuotong-treated group and the high dosage Sailuotong-treated group. The multi-infarct dementia model was established by injecting the micro-sphere vascular occlusive agent. On the 10th day after the successful operation, the rats were administered intragastrically with distilled water, memantine hydrochloride (20 mg x kg(-1)) and Sailuotong (16.5 mg x kg(-1) and 33.0 mg x kg(-1)) once a day for 60 days respectively, in order to detect the effect of Sailuotong in different doses on the latent period and route length in Morris water maze and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissues. RESULT: Compared with the sham operation rats, it had been observed that the latent period and route length of MID rats in Morris water maze were significantly increased (P < 0.05 or P < 0.01), and the activity of ChAT in brain tissues was significantly decreased (P < 0.05). After the intervention with Sailuotong for sixty days, the latent period and route length of MID rats in Morris water maze significantly shrank (P < 0.05 or P < 0.01). Additionally, Sailuotong decreased AchE activity, while increasing ChAT activity in brain tissues of MID rats (P < 0.05 or P < 0.01). CONCLUSION: Sailuotong capsule can improve cognitive dysfunction of MID rats to some extent. Its mechanism may be related to its different regulation of activities of ChAT and AchE in brain tissues.

Metastatic versus primary oncocytic papillary adenocarcinoma of the endometrium: a report of a case and review of the literature.

We report a case of an oncocytic papillary adenocarcinoma of the endometrium in an 89-year-old female with vaginal bleeding. Imaging studies revealed lesions in the uterus, kidneys, pancreas, gluteus, and an enlarged portacaval lymph node. Diagnostic workup included an endometrial biopsy which showed malignant, oncocytic cells in a predominantly papillary pattern. These cells stained positive for epithelial markers (pan-cytokeratin, CK7, epithelial membrane antigen) and weakly for estrogen receptor. The cells were negative for cytokeratin 903, CAM 5.2, progesterone receptor, CD10, RCC Marker, CA-125, c-kit, and vimentin. Consultation with experts in Gynecologic and Genitourinary pathology returned a diagnosis of "adenocarcinoma compatible with metastatic renal cell carcinoma"--an intriguing possibility worthy of further exploration. To our knowledge, there are no reports in the literature of metastatic oncocytic papillary renal cell carcinoma to the endometrium. The clinical and pathologic features of oncocytic papillary endometrial lesions, including primary and metastatic processes, are reviewed.

Tratamiento con galantamina en la demencia asociada a CADASIL / Galantamine therapy in dementia associated with cadasil

Introducción. Se ha sugerido que en la arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL) existe un déficit colinérgico neuronal. La terapia colinomimética podría ser útil. Casos clínicos. Cuatro pacientes con CADASIL y demencia fueron tratados con el inhibidor de acetilcolinesterasa galantamina y se valoraron los aspectos cognitivos, conductuales, funcionales y de sobrecarga del cuidador. Tres pacientes mostraron una leve mejoría o una estabilización de las alteraciones conductuales y de la sobrecarga del cuidador. Conclusión. Nuestros resultados sugieren algún beneficio del tratamiento con galantamina y apoyarían la teoría del déficit colinérgico en la CADASIL

Introduction. Cholinergic neuronal impairment has been suggested in cerebral autosomal dominant arteriopathywith subcortical infarcts and leucoencefalopathy (CADASIL). Cholinomimetic therapy could be useful. Case reports. Four patients with CADASIL and dementia were treated with the acetylcholinesterase inhibitor galantamine and we assessed cognitive, behavioral, functional and the caregiver burden aspects. Three patients showed either mild improvement orstabilization in the behavior and caregiver burden. Conclusion. Our results suggest some benefit from galantamine treatment and they could support the existence of a cholinergic deficit in CADASIL

Variabilidad clínica y controversias diagnósticas en el CADASIL / Clinical variability and diagnostic controversies in CADASIL

Los factores de riesgo cardiovascular están presentes en un 85% de los pacientes con enfermedad cerebrovascular. No obstante, en un 6-15% de los pacientes el ictus se debe a causas poco frecuentes como enfermedades sistémicas, alteraciones de la coagulación, etc. y, en algunos casos, a pesar de un estudio exhaustivo, no es posible identificar la causa del ictus. Esto ocurre con más frecuencia en pacientes jóvenes. En estos casos es necesario ampliar el estudio al examen de causas genéticas de la enfermedad cerebrovascular. CADASIL, una arteriopatía autosómica dominante que afecta a la sustancia blanca cerebral, está emergiendo como una causa no infrecuente de enfermedad cerebrovascular con diversas manifestaciones clínicas. Su diagnóstico es objeto de controversia por el diferente papel que tiene el estudio de imagen cerebral, el examen mediante biopsia de los vasos de la piel u otros órganos y el estudio genético molecular (AU)

Cardiovascular risk factors are present in 85% of patients with stroke. However, up to 6%-15% of patients have a stroke secondary to unusual reasons such as systemic diseases, coagulation disorders, etc., and, in some cases, no reason can be identified even after performing an extensive study. This usually happens in young people. In this regard, the diagnostic screening must consider hereditary causes of stroke. CADASIL, an autosomal dominant brain white matter angiopathy, is emerging as a not uncommon cause of stroke with diverse clinical manifestations. Its clinical diagnosis is controversial because of the diverse role of the brain imaging study, the biopsy of the vessels of skin or other tissues and the DNA study (AU)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited autosomal dominant condition characterized by migrane, recurrent stroke, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in -33% of patients. CADASIL is commonly overlooked or misdiagnosed owing to its recent identification. The pathological hallmark of angiopathy is the presence of multiple, small, deep cerebral infarcts, leucoencephalopathy, and nonatherorosclerotic, nonamyloid angiopathy involving mainly small, deep perforating cerebral arteries. Changes also are present in vascular smooth muscle cells and consist in the presence of granular osmiophilic material (GOM). The defective gene in CADASIL is Notch 3, which encodes a large transmembrane receptor. Magnetic resonance imaging shows high intensity signal lesions, often confluent, and areas of cystic degeneration of subcortical white matter and basal ganglia. Diagnostic strategies in CADASIL are matter of discussions because the electron microscopic demonstration of GOM was reported in 100% of symptomatic patients of French authors, but only in 45% of a British study. GOMs are not present in presymptomatic patients.

Forgetting in dementia with and without subcortical lacunes.

Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD) are common causes of dementia, often co-occur, and can present quite similarly, making differential diagnosis clinically challenging. This study tested the hypothesis that patients with SIVD retain information better than AD patients. Participants were 35 dementia patients with subcortical lacunes (SIVD group), 27 dementia patients without lacunar infarction (AD group), and 56 normal controls. Results indicated that despite comparable levels of initial acquisition, AD patients showed more rapid forgetting. Further analysis indicated that memory patterns within the SIVD group were heterogeneous, with some participants exhibiting rapid forgetting and some exhibiting good retention. SIVD participants with good retention showed a trend for greater executive impairments relative to SIVD participants with rapid forgetting and AD participants. Results suggest that rapid forgetting in SIVD may imply concomitant AD, whereas the dementia in patients with good retention may be purely vascular in origin. Three SIVD patients with rapid forgetting followed to autopsy all had AD pathology, further supporting the link between memory patterns and AD.

Communicative responsibility and semantic task in the language of adults with dementia.

A probe technique requiring convergent and divergent semantic behavior and representing five levels of communicative responsibility served as the research tool. Stimuli were presented to adults identified as having Alzheimer disease or multi-infarct dementia. Within each group differences were observed on the semantic task (convergent and divergent) and on communicative responsibility. Group characteristics are compared with data previously published in 1994 on aphasic and schizophrenic adults responding to the same stimuli.

Migraine with aura and brain magnetic resonance imaging abnormalities in patients with CADASIL.

BACKGROUND: Migraine with aura (MA) is one of the clinical hallmarks of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a small vessel disease of the brain caused by mutations in the NOTCH3 gene, but its exact mechanisms are unknown. OBJECTIVES: To describe the patterns of MA in CADASIL and to compare brain magnetic resonance signal abnormalities between CADASIL patients with and without MA. DESIGN: Comparison of brain magnetic resonance signal abnormalities between cases and controls. SETTING: Patients with CADASIL seen at Lariboisière Hospital. PATIENTS: Forty-one CADASIL patients with MA and 31 age-matched CADASIL controls without MA. RESULTS: The mean age at onset of MA was significantly younger in women compared with men and occurred a mean of 15 years prior to stroke onset. A majority of patients (56%) reported at least 1 migraine attack with atypical aura. All CADASIL patients either with or without MA had white matter signal abnormalities on T2-weighted imaging. There was no difference in the frequency and distribution of brain signal abnormalities between CADASIL patients with and without MA. CONCLUSIONS: In CADASIL, MA is characterized by an unusually high frequency of attacks of migraine with atypical aura. The distribution and extent of magnetic resonance signal abnormalities did not differ according to migraine phenotype.

Retinal vascular abnormalities in CADASIL.

To assess retinal vascular alterations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the authors examined 10 affected individuals with ophthalmologic evaluation including fluorescence angiography. Findings included bilateral peripapillary arteriolar sheathing (30%), arteriolar narrowing (80%), and arteriovenous nicking (90%). No retinal infarcts, vascular occlusions, exudation, or hypoperfusion of affected vessels were found.

Perioperative management of a CADASIL type arteriopathy patient.

We report the anaesthetic management of a patient suffering from an ischaemic arteriopathy of the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) type. The anaesthetic implications of this pathology are discussed. By analogy with other cerebral arteriopathies, the aim of our management was to keep mean arterial blood pressure and end-tidal carbon dioxide so as to prevent any cerebral ischaemic or vasospastic phenomenon. We preserved the cerebral venous return by avoiding excessive head-down position. We used a balanced anaesthetic technique because it allows easier titration of the depth of anaesthesia with regard to mean arterial pressure. There is no contraindication to the use of loco-regional anaesthesia.

Myocardial infarction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an angiopathy caused by mutations in the NOTCH3 gene. Typical microvascular changes are found throughout the arterial tree, but the documented disease expression is confined to the central nervous system. In an ongoing CADASIL study, we noted a number of patients with early acute myocardial infarction (before the age of 50 years), as well as patients with electrocardiogram (ECG) abnormalities. We analyzed these data to determine whether myocardial ischemia is associated with NOTCH3 mutations. ECGs were recorded in mutated (n = 41) and nonmutated (n = 22) individuals from 15 genetically confirmed CADASIL families, and blindly classified according to the Minnesota code. Cardiologic history was assessed and cardiovascular disease risk factors were determined. Evidence for myocardial infarction was defined as a positive history for acute myocardial infarction and/or a Minnesota Code 1 (Q-waves) on ECG. We examined CADASIL myocardial tissue ultrastructurally and immunohistochemically for evidence of microangiopathy. We found that almost 25% (10/41) of mutation carriers had evidence of myocardial infarction, versus none of the 22 nonmutation carriers (p = 0.011). Five had a medical history of acute myocardial infarction, and 5 had current pathologic Q-waves on ECG. Acute myocardial infarction occurred at a mean age of 39.6 +/- 5.22 years, and predated major neurologic symptoms of CADASIL in all cases. Pathologic examination of myocardial tissue revealed typical CADASIL arteriopathic changes of the coronary microvasculature. To our knowledge, this is the first study showing that NOTCH3 mutation carriers may be at increased risk of early acute myocardial infarction, expanding CADASIL disease expression beyond the central nervous system to include the heart.

Progressive supranuclear palsy phenotype secondary to CADASIL.

BACKGROUND AND PURPOSE: To report a unique case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy manifesting as a progressive supranuclear palsy phenotype, thereby expanding its recognized presentations. METHODS: Review of the pertinent literature from MEDLINE, cross-referencing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, progressive supranuclear palsy, and parkinsonism. Description of a 60-year-old woman who presented with a several year history of step-wise, progressive parkinsonism secondary to cerebral autosomal dominant arteriopathy. RESULTS: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy may present with a progressive supranuclear phenotype. CONCLUSION: Parkinsonism, including a progressive supranuclear palsy phenotype, is one of a growing number of recognized ways that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy may present.

Early visual function impairment in CADASIL.

The authors carried out genetic analyses and visual electrophysiologic evaluations in six asymptomatic sons and daughters of patients with symptomatic cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Three subjects showed Notch3 Cys146Tyr missense mutation and a dysfunction of the outer, middle, and innermost retinal layers, with normal neural conduction in postretinal visual pathways, whereas in the remaining subjects without genetic mutations, no electrophysiologic abnormalities were found. An early vascular retinal impairment in CADASIL may precede the onset of clinical manifestations.

Coexistence of CADASIL and Alzheimer's disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is caused by point mutations in the Notch3 gene. Presenilins are proteins involved in the cleaving of both Notch and the amyloid precursor protein (APP). In cases of early onset Alzheimer's disease mutations of the presenilin genes (PSEN 1 and PSEN 2) and APP can be found. A 64 year old patient with CADASIL (R169C-mutation) is reported, who, in addition to subcortical infarcts and granular osmiophilic deposits, had numerous senile plaques and neurofibrillary tangles on pathological examination. Mutations in the APP, PSEN1, and PSEN2 genes were not identified. Neuropathological findings of Alzheimer's disease may be found in CADASIL patients.