Hypoechogenicity of brainstem raphe correlates with depression in migraine patients

DOI: https://doi.org/10.1186/s10194- 019- 1011- 2

Abstract-Summary Up to date, the association of BR alterations in TCS with depression in migraineurs has never been reported.

This study was to investigate the possible role of BR examination via TCS in

migraineurs with depression.

Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and brainstem raphe (BR) and width of the frontal horns of the lateral ventri- cles and the third ventricle were assessed with TCS.

There were no significant differences between migraineurs and controls in the width of frontal horn of the lateral ventricle (p = 0.955), width of third ventricle (p = 0.129) as well as in the echogenicity of SN (p = 0.942), CN (p = 0.053), LN (p = 0.052) and BR (p = 0.677).

2.2 Biology

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Patients with hypoechogenic BR had significantly higher HAM-D and HADS-D scores than those with normal BR signal (p = 0.000 for both HAM-D and HADS-D), and most (83.33%) migraineurs with depression exhibited hypoechogenic raphe but none (0.00%) of the migraineurs without depression exhibited hypoechogenic raphe (p = 0.000).

TCS signal alteration of BR can be a biomarker for depression in migraine but it

is not associated with migraine headache itself.

Extended: Up to date, it has never been reported about the association of BR alterations in TCS with depression in migraineurs, though BR hypoechogenicity has been shown to be correlated to higher headache attack frequency in migraineurs without depression in one study [297] but not in another one study [298].

Background The hypoechogenicity of BR has been found to be associated with depression in a number of neurological disorders such as Parkinson’s disease (PD) [299], Huntington’s disease [300], idiopathic Rapid Eye Movement (REM) sleep behav- ior disorder [301], myotonic dystrophies [302] and cerebral small vessel dis- ease [303].

Up to date, it has never been reported about the association of BR alterations in TCS with depression in migraineurs, though BR hypoechogenicity has been shown to be correlated to higher headache attack frequency in migraineurs without depres- sion in one study [297] but not in another one study [298].

In order to investigate the possible role of BR in migraine with depression, migraine without aura (MwoA) patients with or without depression will be included in this study.

Possible alterations of BR echogenicity in TCS in migraineurs will be studied in

comparison with the healthy control.

Possible difference in BR echogenicity between migraineurs with and without

depression will be studied.

Methods A total of 42 patients fulfilling the International Headache Society (IHS) classifica- tion criteria for MwoA [304] were prospectively screened from the Outpatient Clinic of the Department of Neurology, the First Affiliated Hospital of Anhui Medical University, China.

Migraine with aura (MA) patients were not included in this study in order to avoid possible statistical analysis confusion caused by fewer cases of MA as much fewer MA patients are available in clinic.

All included patients had recurrent headaches and none of them had ever accepted

regular prophylactic therapy before this study.

Magnetic resonance imaging (MRI) was performed in a headache-free period for

all patients.

All control subjects had no history of recurrent headaches. TCS examination was carried out on standardized axial imaging planes as rec-

ommended for deep brain parenchyma detection [305].

Of non-normally distributed data, the Mann-Whitney U test was used.

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2 Mechanisms

Results The width of frontal horn of the lateral ventricle was found normal (≤17 mm) in all migraineurs and controls, mean width was 4.62 ± 0.98 mm in migraineurs and 4.63 ± 1.30 mm in controls (p = 0.955).

The width of the third ventricle (> 7 mm) was found abnormal in one migraine

patients (4.8%) and normal in the rest migraineurs and controls.

Mean width of third ventricle is 4.13 ± 1.26  mm and 3.77 ± 0.81  mm in

migraineurs and controls respectively (p = 0.129).

Mean HAM-D score was 18.6 ± 4.6 (range 11–24) in patients with hypoecho-

genic BR, and 6.1 ± 4.6 (range 0–14) in patients with normal BR (p = 0.000).

Mean HADS-D score was 12.6 ± 3.8 (range 7–18) in patients with hypoecho-

genic BR, and 4.6 ± 2.7 (range 0–11) in patients with normal BR (p = 0.000).

Discussion This is the first study to correlate alterations of BR echogenicity with depression in migraine patients.

Whereas, neither the increased occurrence rate of BR hypoechogenicity in migraineurs compared with healthy control nor the association of BR hypoecho- genicity with migraine headache attack frequency was found in current study.

Migraine patients with hypoechogenic raphe had higher depression score com- pared with migraine patients without hypoechogenic raphe, and one patient with undetectable BR echogenicity had obviously depressive symptoms with high score on HAM-D and HADS-D.  This indicates a significant association of BR sono- graphic signal alterations with clinically evident depression in migraine patients.

The aim of this study was not to investigate the possible role of this deep brain parenchyma in the pathogenesis of migraine but to determine whether the alteration of BR echogenecity could be a biomarker of depression in migraine patients.

Conclusions In TCS level, there was no significant difference between migraine patients and normal controls in deep brain parenchyma including brain ventricles and brainstem nuclei, but it seems that more migraineurs were detected with increased echogenec- ity of CN and LN compared with controls.

Acknowledgement A machine generated summary based on the work of Tao, Wei-Wei; Cai, Xin-Ting; Shen, Jie; Shi, Xue-Gong; Wang, Yu. 2019 in The Journal of Headache and Pain.

High asymmetric dimethylarginine, symmetric dimethylarginine and L-arginine levels in migraine patients