Key words: autonomic nervous system, cardiovascular disease risk, diabetes mellitus, heart rate variability, vagus nerve. IntroductionAutonomic diabetic neuropathy (ADN) is a frequent and serious complication of diabetes mellitus. A clinical and subclinical disease, it can affect all organ systems, including the gastrointestinal tract, the urogenital tract and the cardiovascular system. 1 ADN with multiple organ involvement occurs only rarely, however. The clinical presentation is most often a heterogeneous pattern of symptoms in different organ systems, which can lead to misdiagnosis.2,3 Since they coincide in approximately 50% of cases, in a patient with ADN evidence of sensorimotor diabetic neuropathy should be sought. 4 There are also connections to other long-term diabetic complications, such as nephropathy and retinopathy. 5Cardiac autonomic diabetic neuropathy (CADN) Cardiac autonomic diabetic neuropathy (CADN) is the primary disease of ADN and is one of the most frequently researched complications of diabetes. 6 The earliest sign of CADN is a reduction in heart rate variability (HRV), which is detectable at the subclinical stage 5,7,8 and can, for instance, be clearly verified during deep respiration (figure 1).Further symptoms become apparent at advanced stages. Primarily the vagus (pneumogastric) nerve is damaged: this results in a resting tachycardia since sympathetic influences become predominant. After about five years of latency, regression of tachycardia occurs due to damage to the sympathetic nerve fibres; 9 however, the heart rate remains higher than in healthy patients.10 Additional symptoms such as exercise intolerance, orthostatic hypotension and an increasing limitation in heart rate variability are the manifestations of progressive damage to the autonomic balance.5 Often cardiac pain perception is impaired due to the additional damage to sensory nerve fibres, so that warning signs of myocardial ischaemia are not recognised in time to be adequately treated. A meta-analysis of 12 studies by Vinik et al. 2 found that patients with CADN had DIABETES AND VASCULAR DISEASE RESEARCH PERSPECTIVES Cardiac autonomic diabetic neuropathy MARTIN SCHÖNAUER, ANDREAS THOMAS, STEPHAN MORBACH, JOSEF NIEBAUER, ULRIKE SCHÖNAUER, HOLGER THIELE

Automated analysis of HMPAO-SPECT data from MCI patients showed significant perfusion deficits in regions also involved in DAT patients, but ROC analysis demonstrated only moderate sensitivity and specificity for differentiating DAT patients from controls and DCI patients. Frontal hypoperfusion seems to correspond with conversion from MCI to DAT. Finally, the results in DCI patients again raise the question of depression as an early symptom of neurodegeneration.

Due to the increasing importance of early recognition and differential diagnosis of dementias, cerebral perfusion scans using "single photon emission computed tomography" (SPECT) are increasingly integrated into the examination routine. The goal of this study was to check the diagnostic validity of SPECT scans of MCI- and DAT-patients, two subgroups out of 369 persons with etiologically unclear cognitive dysfunction, which underwent an assessment program for probable dementia including cognitive testing, cranial computed tomography, ultrasound, routine laboratory testing including vascular risk factors. After exclusion of patients with no or other forms of dementia we analyzed SPECT data of patients with mild cognitive impairment (MCI; n = 85) and dementia of the Alzheimer type (DAT; n = 78) in comparison with a healthy control group (n = 34).Visual assessment as well as a manual "regions of interest" (ROI) regionalization of the cortex were performed, whereby a ROI/cerebellum ratio was calculated as a semi-quantitative value. Association cortex areas were assessed regarding frontal, temporal, and parietal lobes of both hemispheres. When comparing the ratios of patients with DAT and controls, we found a statistically significant reduction of the cerebral perfusion in all measured cortex areas (p < 0.001). The comparison of patients with MCI with the selected control group also established a statistically significant difference in the cerebral perfusion for the evaluated cortex areas with the exception of the left hemispheric frontal and parietal cortex.A considerable number of the MCI patients showed an MMSE-score within the normal range, but with regard to the perfusion in the right hemispheric association cortex these patients also could be distinguished unambiguously from controls. Sensitivity levels found by visual assessment were at least as high as those found by the ROI method (pathological assessment: visual 49.4% vs. ROI 47.1% for MCI; visual 75.6% vs. ROI 73.1% for DAT). High experienced visual assessment of cerebral perfusion scans using SPECT provides an useful additional tool in diagnosis of cognitive impairment. The used semiquantitative ROI-method is nearly equivalent and does not depend on the experience of the investigator.

Our case shows that flow cytometry of the CSF in addition to conventional CSF cytology has the potential to accelerate diagnosis of lymphomeningeal infiltration of B-cell lymphoma.