Prevention of age-induced N(ε)-(carboxymethyl)lysine accumulation in the microvasculature.

OBJECTIVE: N(ε)-(carboxymethyl)lysine (CML) is one of the major advanced glycation end products in both diabetics and nondiabetics. CML depositions in the microvasculature have recently been linked to the aetiology of acute myocardial infarction and cognitive impairment in Alzheimer's disease, possibly related to local enhancement of inflammation and oxidative processes. We hypothesized that CML deposition in the microvasculature of the heart and brain is age-induced and that it could be inhibited by a diet intervention with docosahexaenoic acid (DHA), an omega-3 fatty acid known for its anti-inflammatory and antioxidative actions. MATERIALS AND METHODS: ApoE(-/-) mice (n = 50) were fed a Western diet and were sacrificed after 40, 70 and 90 weeks. Part of these mice (n = 20) were fed a Western diet enriched with DHA from 40 weeks on. CML in cardiac and cerebral microvessels was quantified using immunohistochemistry. RESULTS: Cardiac microvascular depositions of CML significantly increased with an immunohistochemical score of 11·85 [5·92-14·60] at 40 weeks, to 33·17 [17·60-47·15] at 70 weeks (P = 0·005). At the same time points, cerebral microvascular CML increased from 6·45; [4·78-7·30] to 12·99; [9·85-20·122] (P = 0·003). DHA decreased CML in the intramyocardial vasculature at both 70 and 90 weeks, significant at 70 weeks [33·17; (17·60-47·15) vs. 14·73; (4·44-28·16) P = 0·037]. No such effects were found in the brain. CONCLUSIONS: Accumulation of N(ε)-(carboxymethyl)lysine in the cerebral and cardiac microvasculature is age-induced and is prevented by DHA in the intramyocardial vessels of ApoE(-/-) mice.

Fatal B-cell lymphoma following chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.

IMPORTANCE: Recent reports on chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) suggest that patients who have a relapse respond very well and that disease progression can be avoided if timely corticosteroid therapy is started. We report on a well-documented patient who presented with clinical, radiological, and pathological characteristics of CLIPPERS and who had an unfavorable outcome. OBSERVATIONS: We present the clinical, imaging, laboratory, brain biopsy, and autopsy findings of a 57-year-old male patient with CLIPPERS who repeatedly responded well to high-dose corticosteroids. During follow-up, however, treatment failed, and he had a biopsy-confirmed diagnosis of lymphomatoid granulomatosis that evolved into fatal B-cell lymphoma of the central nervous system. CONCLUSIONS AND RELEVANCE: The clinical and imaging features of CLIPPERS include an abundance of differential diagnoses, and the follow-up periods of the described cases classified as CLIPPERS have been limited. Therefore, the question remains whether CLIPPERS is an actual new disease entity or represents a syndrome that includes different overlapping diseases and their prestages. Our case report shows that a typical presentation of CLIPPERS does not uniformly imply a favorable outcome, even when timely treatment regimens have been given.