Cerebral lesion correlates of sympathetic cardiovascular activation in multiple sclerosis

Klemens Winder, Ralf A. Linker, Frank Seifert, Ruihao Wang, De Hyung Lee, Tobias Engelhorn, Arnd Dörfler, Kilian Fröhlich, Max Hilz

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Cardiovascular autonomic dysfunction is common in multiple sclerosis (MS) and contributes significantly to disability. We hypothesized that cerebral MS-lesions in specific areas of the central autonomic network might account for imbalance of the sympathetic and parasympathetic cardiovascular modulation. Therefore, we used voxel-based lesion symptom mapping (VLSM) to determine associations between cardiovascular autonomic dysfunction and cerebral MS-related lesion sites. In 74 MS-patients (mean age 37.0 ± 10.5 years), we recorded electrocardiographic RR-intervals and systolic and diastolic blood pressure. Using trigonometric regressive spectral analysis, we assessed low (0.04–0.15 Hz) and high (0.15–0.5 Hz) frequency RR-interval-and blood pressure-oscillations and determined parasympathetically mediated RR-interval–high-frequency modulation, mainly sympathetically mediated RR-interval–low-frequency modulation, sympathetically mediated blood pressure-low-frequency modulation, and the ratios of sympathetic and parasympathetic RR-interval-modulation as an index of sympathetic-parasympathetic balance. Cerebral MS-lesions were analyzed on imaging scans. We performed a VLSM-analysis correlating parameters of autonomic dysfunction with cerebral MS-lesion sites. The VLSM-analysis showed associations between increased RR-interval low-frequency/high-frequency ratios and lesions most prominently in the left insular, hippocampal, and right frontal inferior opercular region, and a smaller lesion cluster in the right middle cerebellar peduncle. Increased blood pressure-low-frequency powers were associated with lesions primarily in the right posterior parietal white matter and again left insular region. Our data indicate associations between a shift of cardiovascular sympathetic-parasympathetic balance toward increased sympathetic modulation and left insular and hippocampal lesions, areas of the central autonomic network. The VLSM-analysis further distinguished between right inferior fronto-opercular lesions disinhibiting cardiac sympathetic activation and right posterior parietal lesions increasing sympathetic blood pressure modulation.

Original languageEnglish
Pages (from-to)5083-5093
Number of pages11
JournalHuman Brain Mapping
Issue number17
StatePublished - 1 Dec 2019


  • autonomic dysfunction
  • insular lesion
  • multiple sclerosis
  • visceral arousal
  • voxel-based lesion symptom mapping


Dive into the research topics of 'Cerebral lesion correlates of sympathetic cardiovascular activation in multiple sclerosis'. Together they form a unique fingerprint.

Cite this