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. 2022 Oct;43(10):6039-6045.
doi: 10.1007/s10072-022-06143-3. Epub 2022 May 18.

Neurological soft signs are increased in migraine without aura: relationship with the affective status

Lucio Tremolizzo  1   2   3 , Daniele Selvatico  4 , Federico Emanuele Pozzi  5   4 , Diletta Cereda  5 , Jacopo Cosimo DiFrancesco  5   6 , Lorenzo Fumagalli  5 , Carlo Ferrarese  5   4   6 , Ildebrando Appollonio  5   4   6
Affiliations

Neurological soft signs are increased in migraine without aura: relationship with the affective status

Lucio Tremolizzo et al. Neurol Sci. 2022 Oct.

Abstract

Introduction: Neurological soft signs (NSS) are subtle non-localizing sensorimotor abnormalities initially reported as increased in primary headache patients. The aims of this study were confirming with full power NSS increased expression in migraine and, collaterally, determining if psychiatric traits or white matter lesions at brain imaging could influence this result.

Methods: Forty drug-free episodic migraine outpatients (MH) were recruited with 40 matched controls. NSS were determined by the 16-item Heidelberg scale; depression, anxiety and QoL by the HAM-D; the STAI-X1/X2; and the SF36, respectively. The Fazekas scale on brain MR studies was applied in n = 32 MH, unravelling deep white matter signal alterations (DWM). MH characteristics, including the headache disability inventory (HDI), were recorded.

Results: NSS were 46% increased in MH vs. controls (p = 0.0001). HAM-D and STAI-X1/X2 were increased in MH, while SF36 was unchanged, but they all failed to influence NSS, just as MH characteristics. NSS scores were increased in MH-DWM + (n = 11, + 85%) vs. MH-DWM - (n = 21, + 27%) vs. controls (p < 0.0001). NSS increased expression in MH was influenced by DWM, while psychiatric traits and headache characteristics failed to do so.

Discussion/conclusions: NSS are increased in MH and probably not influenced by the affective status, possibly marking a dysfunction within the cerebellar-thalamic-prefrontal circuit that may deserve further attention from the prognostic point of view.

Keywords: Anxiety; Brain imaging; Depression; Headache; Migraine; Neurological soft signs.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Distribution plot of neurological soft signs (NSS) scores in migraine patients (MH) versus controls (CTRL). *Two-tailed Student’s t-test (t = 3.959, df = 78)
Fig. 2
Fig. 2
Distribution plot of (a) Hamilton Rating Scale for Depression (HAM-D), (b) State-Trait Anxiety Inventory form X for state anxiety (STAI-X1), and (c) State-Trait Anxiety Inventory form X for trait anxiety (STAI-X2) scores in migraine patients (MH) with respect to controls (CTRL). Two-tailed Student’s t-test: *t = 4.661, df = 78; °t = 2.951, df = 78; #t = 4.953, df = 78
Fig. 3
Fig. 3
Neurological soft signs (NSS) are increased in migraine patients with deep white matter signal alterations (MH-DWM > 0) vs. migraine patients without such alterations (MH-DWM = 0) vs. controls (CTRL). p < 0.0001 at ANOVA, followed by Newman-Keuls multiple comparison test (p value reported). The white square indicates one MH-DWM > 0 patient with DWM score = 2 (all the other patients had a DWM score = 1)
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