The 82.6% of the sample was diagnosed with migraine, episodic (with or without aura) in 48% of the cases and chronic in the remaining 52%. Since CM was complicated by medication overuse (MOH) in the 91% of cases, the CM and MOH groups were lumped together in the CM-MOH group. The remaining 17.4% of the patients suffered from TTH, including episodic (71.4%) and chronic (28.5%) forms. Thus, a 3-category study variable (EM, CM-MOH, TTH) was taken into consideration for headache diagnosis.
Table 1 displays how the categorial variables were distributed in the 3 headache diagnostic groups.
Table 1
Demographic and Clinical data
|
All patients (n=80)
|
EM
(n=32) 40
|
CM-MOH
(n=34) 42.5%
|
TTH
(n=14) 17.5
|
Chi-square ; p
|
Sex (females)
|
92.5%
|
37.5%
|
38.8%
|
16.3%
|
0.16; p=0.923
|
Work
|
|
|
|
|
|
inside
|
81.7%
|
26.8%
|
38%
|
16.9%
|
1.20; p=0.549
|
outside
|
18.3%
|
7%
|
10%
|
1.3%
|
|
Sport
|
|
|
|
|
|
None
|
67%
|
24%
|
33%
|
10.4%
|
2.478; p=0.649
|
inside
|
19.4%
|
9%
|
7.5%
|
3%
|
|
outside
|
13.4%
|
3%
|
6%
|
4.5%
|
|
BMI
|
|
|
|
|
|
<18 kg/m2
|
4.8%
|
0%
|
3.2%
|
1.6%
|
4.027; p=0.673
|
18-24.99 kg/m2
|
66.7%
|
28.6%
|
31.7%
|
6.4%
|
|
>25 kg/m2
|
28.6%
|
9.5%
|
14.3%
|
4.8%
|
|
Dairy- free diet
|
|
|
|
|
|
yes
|
14%
|
4.2%
|
8.5%
|
1.4%
|
0.774; p=0.679
|
no
|
86%
|
31%
|
39.4%
|
15.5%
|
|
Comorbilities
|
|
|
|
|
|
autoimmune diseases
|
7.6%
|
2.5%
|
5%
|
0%
|
12.098; p=0.598
|
diabetes mellitus
|
1.3%
|
0%
|
1.3%
|
0%
|
|
fibromyalgia
|
3.8%
|
2.5%
|
1.3%
|
3.8%
|
|
endometriosis and PCOS
|
7.6%
|
3.8%
|
2.5%
|
1.3%
|
|
Menopause
|
|
|
|
|
|
Yes
|
36%
|
10.7%
|
21.3%
|
4%
|
5.620; p=0.060
|
no
|
64%
|
30.7%
|
20%
|
13.3%
|
|
Extracranial pain
|
|
|
|
|
|
yes
|
45%
|
10%
|
31%
|
4%
|
10.161; p=0.006
|
no
|
55%
|
26.8%
|
16.9%
|
11.3%
|
|
Allodynia
|
|
|
|
|
|
yes
|
47%
|
10.6%
|
33.3%
|
3%
|
10.40; p=0.005
|
no
|
53%
|
25.8%
|
16.7%
|
10.6%
|
|
BMI = Body mass Index; EM= episodic migraine; TTH = tension type headache; CM-MOH = chronic migraine and medication overuse headache; POCS= polycystic ovary syndrome;
|
The mean age of the CM-MOH group (51.8 years, standard deviation 11) was slightly but significantly (F04.46, p = 0.015) larger than those of the EM (43.1, 15.4) and of the TTH (41.6, 15.3) groups.
The 45% of the cephalalgic patients also had extracranial pain and 47% suffered from allodynia, and the occurrence of extracranial pain and allodynia was significantly larger in the CM-MOH than in the other groups. On the other hand, the number of subjects with extracranial pain and allodynia was not related to the co-occurrence of vit-D deficit as shown in Table 2.
Table 2
Association between headache type, pain extension and vitamin D levels
|
All patients (n = 80)
|
ICHD-3 classification
|
VitD > 20 (n = 44)
|
VitD < 20 (n = 36)
|
Chi-square; p
|
EM
|
23 (52.3%)
|
9 (25%)
|
|
TTH
|
9 (20.5%)
|
5 (13.9%)
|
|
CM-MOH
|
12 (27.3%)
|
22 (61.1%)
|
9.504; p = 0.009
|
Extracranial pain
|
|
|
|
yes
|
15 (47%)
|
17 (53.1%)
|
2.121; p = 0.145
|
no
|
25 (64.1%)
|
14 (36%)
|
|
Allodynia
|
|
|
|
yes
|
15 (48.4%)
|
16 (51.6%)
|
0.506; p = 0.477
|
no
|
20 (57.1%)
|
15 (43%)
|
|
EM = episodic migraine; TTH = tension type headache; CM-MOH = chronic migraine and medication overuse headache; VitD = vitamin D. |
Table 3 shows the mean values and the out of normal range values (i.e. % of subjects falling outside the normal limits) of the continuous variables in the 3 headache diagnostic groups.
Table 3
Main biochemical parameters
Variables
|
All patients (n = 80)
|
EM (n = 32)
|
CM-MOH (n = 34)
|
TTH (n = 14)
|
Chi-square; p
|
|
OOR
|
mean ± SD
|
OOR
|
mean ± SD
|
OOR
|
mean ± SD
|
OOR
|
mean ± SD
|
|
VitD, ng/ml (< 20 ng/ml)
|
45%
|
20.3 ± 10.2
|
28.1%
|
19.9 ± 11.4
|
64.7%
|
20.1 ± 5.9
|
35.7%
|
21.7 ± 15.3
|
9.504; p = 0.009
|
Ca, mg/dl (vn 8.6–10.2)
|
3.8%
|
9.2 ± 1.3
|
3.1%
|
9.9 ± 0.6
|
5.9%
|
9 ± 1.9
|
0%
|
9.35 ± 0.2
|
1.008; p = 0.6
|
P, mg/dl (< 2.5)
|
1.3%
|
3.3 ± 0.3
|
3.1%
|
3.4 ± 0.4
|
0%
|
3.3 ± 0.3
|
0%
|
3.2 ± 0.3
|
1.519; p = 0.4
|
PTH, pg/ml (n 15–88)
|
9.8%
|
35 ± 26
|
8%
|
33.4 ± 19.6
|
10.7%
|
32.5 ± 25.1
|
12.5%
|
49 ± 45.4
|
0.183; p = 0.9
|
Folate, ng/ml (< 8.1)
|
27.3%
|
14.7 ± 10
|
21.4%
|
15 ± 10.8
|
33.3%
|
12.1 ± 5.3
|
27.3%
|
20.5 ± 17.1
|
3.099; p = 0.5
|
Vit B12, pg/ml (< 133)
|
11.4%
|
304 ± 142.8
|
20.7%
|
270.1 ± 145.3
|
6.9%
|
315.5 ± 141.8
|
0.0%
|
363.3 ± 125.2
|
4.594; p = 0.1
|
Homocysteine, µmol/l (> 12)
|
42%
|
12.7 ± 6.8
|
25%
|
12.8 ± 9.4
|
47.4%
|
12.1 ± 3.7
|
63.6%
|
13.4 ± 5.3
|
4.711; p = 0.095
|
Fe, µmol/dl (< 33)
|
15%
|
88.8 ± 41
|
15.4%
|
97.9 ± 43.3
|
19.2%
|
76.2 ± 41.8
|
0.0%
|
100.1 ± 19.4
|
1.780; p = 0.411
|
EM = episodic migraine; CM-MOH = chronic migraine and medication overuse headache; TTH = tension type headache; Ca = calcium; Fe = Iron; OOR = out of range; P = phosphate; VitB12 = Vitamin B12; VitD = Vitamin D; OOR = out of range. |
The analyses of variance (not shown in the Table) invariably proved that the mean values of the three groups were not statistically different. As for the occurrence of out of range values, the only significant comparison involved the vit D deficit that was larger in the CM-MOH than in the other two groups.
The season of enrollment, Table 4, did not significantly influence 25(OH)D concentrations. In detail, almost half of patients suffering from VitD deficit (45.8%) were enrolled during spring-summer season. Moreover, the mean value of vitD measured during the spring (20.09 pg/ml) and the one measured during autumn (20.7 pg/ml) were not statistically different (F = 0.69; p = 0.79).
Table 4
seasons of enrollment in the whole sample divided by vitamin D levels and headache categories.
Season
|
All
(n = 80)
|
VitD > 20 ng/ml
(n = 44)
|
VitD < 20 ng/ml (n = 36)
|
Chi-square;
p
|
EM
(n = 32)
|
CM-M0H
(n = 34)
|
TTH
(n = 14)
|
Chi-square;
p
|
Aut-Wint
n
(%)
|
32 (40%)
|
18
(56.3%)
|
14
(43.8%)
|
0.034; p = 0.854
|
13 (40.6%)
|
13
(38.2%)
|
6
(42.9%)
|
0.097; p = 0.953
|
Spring-Sum n
(%)
|
48 (60%)
|
26
(54.2%)
|
22
(45.8%)
|
19 (59.4%)
|
21
(61.8%)
|
8
(57.1%)
|
Aut-Wint = Autumn-Winter; Spring-Sum = Spring-Summer; EM = episodic migraine; CM-MOH = chronic migraine and medication overuse headache; TTH = tension type headache; VitD = vitamin D. Data are reported as number (frequency). |
Regarding the analyses of questionnaires, the mean FFS scale final score in the whole sample was 36 points. The subgroups suffering from EM and CM-MOH got higher scores at FFS (respectively 43 ± 15.1 and 41 ± 14.7 points) compared to TTH group (29.3 ± 14.4), but these differences were not statistically significant (F = 0.98; p = 0.38). According to the results of the HADS-A questionnaire, the three groups suffered from a mild state of anxiety (respectively: EM 10.5 ± 4.7, CM-MOH 8.9 ± 4.5 and TTH 10 ± 2.6 points), again not statistically significant (F = 0.44, p = 0.65).
We compared the mean values and the occurrence of an abnormal values using the occurrence of vitD deficit as the explanatory variable, but all these comparisons did not prove to be significant. Finally, both the headache diagnosis and the occurrence of vit D deficit were non influenced by the ongoing pharmacological treatment (both prophylactic and abortive).