Neurological soft signs in primary headache patients

L. Tremolizzo, S. Ferrario, A. Pellegrini, L. Fumagalli, C. Ferrarese, I. Appollonio

Research output: Contribution to journalArticlepeer-review


Neurological soft signs (NSS) are semeiotic anomalies not assessed by the standard neurological examination, primarily developed in psychiatric settings and recently proposed as potential markers of minor brain circuit alterations, especially the cerebellar-thalamic-prefrontal network. Primary headache patients present with normal neurological examination and frequent psychiatric comorbidity. Aim of this exploratory study consisted in assessing NSS in 20 episodic frequent migraine (MH) and in 10 tension-type headache (ETTH) outpatients compared to 30 matched healthy controls. NSS were assessed by the Heidelberg scale; clinical characteristics and brain MRI were additionally obtained in all patients. NSS were increased by ~70 and ~90% in ETTH and MH, respectively, with respect to controls (p<0.001) and the difference remained significant even after controlling for age and education. Headache type and characteristics did not influence NSS presentation, while headache patients with white matter hyperintensities (WMH) at brain MRI had higher NSS scores compared both to normal controls and patients without WMH. NSS identify a subset of primary headache patients sharing the same comorbidities or minimal brain anomalies, suggesting that tailored prophylactic options might apply.

Original languageEnglish
Pages (from-to)41-44
Number of pages4
JournalNeuroscience Letters
Publication statusPublished - May 9 2015


  • Comorbidity
  • Endophenotypes
  • Episodic frequent tension-type headache
  • Migraine
  • Neurological soft signs
  • White matter hyperintensities

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)


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