Headache Medicine, v.10, n.1, p.16-23, 2019
16
ABSTRACT
RESUMO
Descritores: Enxaqueca; Espectroscopia de Ressonância Magnética de Fósforo;
31
P-MRS; Metabolismo da Energia Cerebral; Disfunção Mitocondrial.
VIEWS AND REVIEWS
Cerebral energetic metabolism of individuals with migraine
through
31
P-MRS: A systematic review
Metabolismo energético cerebral de indivíduos com migrânea através
da
31
P-MRS: Uma revisão sistemática
Mírian Celly Medeiros Miranda David
1
*
Letycia dos Santos Neves
2
Carlúcia Ithamar Fernandes Franco
3
Rhowena Jane Barbosa de Matos
4
1
Master student in Neuropsychiatry and
Behavioral Sciences of the Universidade
Federal de Pernambuco (UFPE).
2
Nutrition Student at Academic Center of
Vitoria, Federal University of Pernambuco
(UFPE).
3
Ph.D. Professor at Physiotherapy Department
of the State University of Paraíba (UEPB).
4
Ph.D. Professor of the Physical Education
Nucleus of the Academic Center of Vitoria,
Federal University of Pernambuco (UFPE).
*Correspondence
Mírian Celly Medeiros Miranda David
E-mail: miriancelly@hotmail.com
Received: February 20, 2019.
Accepted: February 26, 2019.
Introduction: Migraine has a neurological origin and is characterized by failure
of central modulation leading to neuronal hyperexcitability. Among the factors
related to such excitability is the mitochondrial dysfunction that has been
considered since the 1980s. Objective: To investigate changes in the cerebral
energetic metabolism of individuals with migraine through phosphorus
magnetic resonance spectroscopy (
31
P-MRS). Methods: It was searched articles
on Pubmed, Web of Science and Science Direct betweenof June, 2018 and
February, 2019. There was no restriction regarding the year of publication and
language. The combination of the descriptors used for this systematic review
was: Migraine AND Magnetic resonance spectroscopy [MESH]. The inclusion
criteria chosen were: original articles using
31
P-MRS in individuals diagnosed
with migraine (with and/or without aura); studies with adults between 18 and
60 years of age diagnosed with episodic or chronic migraine; with control
group of individuals without migraine and without pathologies or conditions
that would interfere in the results. Excluded were articles: incomplete or
unpublished; animal studies; and research protocol articles. Results: Of the
319 articles found, nine were selected. The sample totaled 216 individuals with
migraine (53.7% without aura) and 233 healthy individuals in the control group.
It was veried a reduction of phosphocreatine, phosphorylation potential,
Mg
2+
and ATP, whereas it was observed increase of inorganic phosphate and
ADP. Conclusion: There are alterations in cerebral energetic metabolism in
individuals with migraine, revealing mitochondrial dysfunction. However, it is
needed more studies with higher quality and analysis of the relationships with
the socio-demographic and clinical variables.
Keywords: Migraine; Phosphorus Magnetic Resonance Spectroscopy;
31
P-MRS;
Brain Energy Metabolism; Mitochondrial Dysfunction.
Introdução: A migrânea tem origem neurológica e é caracterizada por falha
na modulação central, levando à hiperexcitabilidade neuronal. Entre os fatores
relacionados a essa excitabilidade está a disfunção mitocondrial considerada
desde os anos 80. Objetivo: Investigar alterações no metabolismo energético
cerebral de indivíduos com enxaqueca por espectroscopia de ressonância
magnética com fósforo (
31
P-MRS). Métodos: Foram pesquisados artigos no
Pubmed, Web of Science e Science Direct entre junho de 2018 e fevereiro de
2019. Não houve restrição quanto ao ano de publicação e idioma. A combinação
dos descritores utilizados para esta revisão sistemática foi: Migraine AND
Magnetic resonance spectroscopy [MESH]. Os critérios de inclusão escolhidos
foram: artigos originais utilizando
31
P-MRS em indivíduos com diagnóstico
de migrânea (com e/ou sem aura); estudos com adultos entre 18 e 60 anos
diagnosticados com enxaqueca episódica ou crônica; com grupo controle de
indivíduos sem migrânea e sem patologias ou condições que interferissem
nos resultados. Foram excluídos os artigos: incompletos ou inéditos; estudos
em animais; e artigos de protocolo de pesquisa. Resultados: Dos 319 artigos
encontrados, nove foram selecionados. A amostra totalizou 216 indivíduos
com migrânea (cerca de 53,7% sem aura) e 233 indivíduos saudáveis no grupo
controle. Vericou-se uma redução de fosfocreatina, potencial de fosforilação,
Mg
2+
e ATP, enquanto se observou um aumento de fosfato inorgânico e
ADP. Conclusão: Existem alterações no metabolismo energético cerebral
em indivíduos com migrânea, revelando disfunção mitocondrial. Porém, são
necessários mais estudos com maior qualidade e análise das relações com as
variáveis sociodemográcas e clínicas.
10(1).indb 16 21/10/2019 19:33:59
Cerebral energetic metabolism in migraine
David MCMM, et al.
17
Headache Medicine, v.10, n.1, p.16-23, 2019
INTRODUCTION
According to the World Health Organization (WHO),
1
50 to 75% of individuals between 18 and 65 years old
presented at least one headache crisis per year in the
world, 30% of them with reports of migraine attacks. Still
according to the WHO, 1.7% to 4% of adults in the world
population present chronic headache (≥ 15 days/month).
1
Migraine has a neurological origin and is
characterized by a failure in central modulation that
leads to neuronal hyperexcitability,
2
it has moderate to
severe pain intensity, usually with pulsatile character,
presenting predominantly in hemicranial form, with a
duration of 4 to 72 hours.
3
The relationship between migraine and mitochondrial
dysfunction has been considered since the 1980s
.
4
Changes in mitochondrial functionality would lead to
high intracellular Ca
2+
penetration, phosphorylation
deciency, and excessive free radical production causing
energy failure in neurons and astrocytes, triggering,
among other factors, the Cortical Spreading Depression
involved with migraine.
5
In addition, mitochondrial impairments are
presented in muscle biopsy of individuals with
migraine, as well as, therapeutic strategies focused
on the improvement of mitochondrial metabolism are
effective in the treatment of migraine, such as riboavin,
coenzyme Q10, magnesium, etc.
5
In this context, phosphorus magnetic resonance
spectroscopy (
31
P-MRS) is a non invasive technique
used to investigate cerebral energetic metabolism in
vivo6 Mitochondrial functionality is veried through
the intracellular levels of adenosine diphosphate (ADP),
phosphocreatine (PCr), inorganic phosphate (Pi),
phosphorylation potential (PP), pH and Mg
2+
factors that
are indispensable for creatine kinase balance.
7,8
Despite this context, there is still no consensus
of the possible mechanisms related to changes in the
energy metabolism of individuals with migraine, such as
whether this relationship actually exists at the brain level,
whether mitochondrial dysfunction would be related to
the onset of migraine or it would be the consequence.
Thus, this systematic review aimed to investigate
changes in cerebral energetic metabolism of
individuals with migraine through
31
P-MRS, with the
hypothesis that individuals with migraine would have
altered rates of ADP, PCr, Pi and Mg
2+
when compared
with a control group, suggesting dysfunction in
mitochondrial activity.
METHODS
The study is a Systematic Review developed between
June, 2018 and February, 2019, registered in PROSPERO
as CRD42018112763. The review was carried out to answer
the reasearch guiding question: Are there changes in
cerebral energy metabolism in individuals with migraine?
In order to answer this question, the acronym PICOS was
used to guide the review (P: Individuals with Migraine, I:
31
P-MRS, C: individuals without migraine, O: Alterations in
cerebral energy metabolism, S: Transversal studies).
Searches were performed on Pubmed and
ScienceDirect by combining the descriptors: Migraine
AND Magnetic Resonance Spectroscopy [MESH]. It
was selected articles without restriction of year of
publication and language. The search and selection of
articles according to the eligibility criteria was described
in the owchart based on the Preferred Reporting Items
for Systematic Reviews and Meta-Analyzes (PRISMA)9
model (Figure 1).
Figure 1. Flowchart of articles selection. Source: Research Data.
The inclusion criteria chosen were: original articles
using phosphorus magnetic resonance spectroscopy
(
31
P-MRS) in individuals diagnosed with migraine (with and/
or without aura); studies with adults between 18 and 60
years of age diagnosed with episodic or chronic migraine;
with control group of individuals without migraine and
without pathologies or conditions that would interfere
in the results. Excluded were articles: incomplete or
unpublished; animal studies; and research protocol articles.
The search and selection of the articles according
to the eligibility criteria was done independently by
two evaluators (MD and LN), in case of disagreement,
they discussed and entered into a consensus. When
the disagreement between the two initial evaluators
remained, the third evaluator (RM) decided whether or
not to include the article in question. At the end of the
selection, the eligibility of the studies included in the
reference list of the selected articles was veried. The
owchart used, which presents in detail the selection
process, follows the model PRISMA
34
(Figure 1).
The selected articles were evaluated according to the
Strengthening the Reporting of Observational Studies
in Epidemiology Statement - STROBE Statement
10
by
the evaluators (MD and LN) independently. There was
agreement of 43.6% among the evaluators in the title and
abstract reading stage. In the article reading phase, there
10(1).indb 17 21/10/2019 19:33:59
Cerebral energetic metabolism in migraine
David MCMM, et al.
Headache Medicine, v.10, n.1, p.16-23, 2019
18
was an initial agreement of 61.5% and, after discussion,
the decision resulted in 9 articles.
The selected studies presented different methods
and variables, making it impossible to carry out
quantitative analyzes of the studies. Therefore, results
such as age, gender, diagnosis, medication, pain
intensity, frequency of attacks, imaging techniques and
main results were extracted and expressed in tables for
qualitative data analysis.
RESULTS
The search culminated in 319 articles, among which
nine studies were selected according to the eligibility
criteria of the review. The selected studies presented
moderate quality in the writing of the article according
to STROBE reaching the average score of 14.6 (66.4%),
with a mean of 64,1% of agreement (Table 1).
Regarding the characterization of the subjects,
the sample totaled 216 individuals with migraine
and 233 healthy individuals in the control group.
Among the individuals with migraine, it was observed
predominance of female (about 78.2%), adults in middle
age, diagnosis of migraine without aura (about 53.7%)
and no medication at the time of the imaging (Table 2).
The studies used devices with varied magnetic
eld strength, between 1.5 and 3T (Table 3). There were
prevalence of individuals in the interictal period (88.5%),
and the occipital area was chosen in the majority of
studies for
31
P-MRS analysis,
8,10-15
although it was not the
only region.
Regarding the results obtained through
31
P-MRS,
there was a reduction of PCr,
10,11,16
Phosphorylation
potential,
8,16
Mg
2+
,
8,11-13
and ATP,
8,12
whereas there was
an increase in Fi
8,16
and ADP
8,16
. In addition, there was a
reduction in Pcr/Pi and Pcr/TP (TP: total phosphorus)
in the ictal phase; on the other hand, in the ictal and
interictal phase there was an increase in Pi/TP
14
and ↑pMg
at ictal stage,
17
suggesting mitochondrial dysfunction.
Other studies did not nd statistical diferences in terms
of PCr/Pi, PCr/ATP, Pi/ATP and pH.
18,15
DISCUSSION
The ndings of the review support the initial
hypothesis that suggests the existence of a dysfunction
in cerebral energetic metabolism of individuals with
migraine. The reduced energy potential observed in
individuals with migraine was assumed to result from
reduced mitochondrial reserve, which is a biochemical
substrate for susceptibility to migraine attacks.
11
At rest, ATP is the result of the balance between its
use and synthesis. ATP is almost exclusively the product
of mitochondrial oxidative phosphorylation, requiring
glucose and oxygen as a supply. Changes in PCr leads
to an imbalance between the synthesis and delivery of
ATP, since ADP is refosphorylated by the creatine kinase
reaction, converting PCr to creatine.
16
On the other hand,
Mg
2+
is important because it binds to ATP so that the ATP
can be active, necessitating ideal levels of Mg
2+
,
16
which
has not been seen in individuals with migraine.
Mitochondrial dysfunctions and disturbances in
magnesium metabolism at the cerebral and systemic
level would lead to a neuronal hyperexcitability already
observed in individuals with migraine.
11
Magnesium is
an important component in the human metabolism, it
is an essential cofactor for more than 300 biochemical
reactions.
19
These reactions include cellular energy
production and storage stabilization of mitochondrial
membranes
20-22
The Mg
2+
has membrane stabilizing properties and is
fundamental in the function of several ATPases, especially
in the Na
+
/K
+
ATPase that controls the Na
+
pump. Neuronal
hyperexcitability would be a result of the reduction of
Mg
2+
levels that would justify the appearance of Cortical
Spreading Depression and the increased sensitivity to the
factors that trigger migraine. In addition, Mg
2+
regulates
brain excitation and/or inhibition by potentiating the
gamma-aminobutyric acid (GABA) receptors, thus the
reduction of Mg
2+
would lead to hyperexcitability by
reducing the inhibitory function of GABA.
23,24
The reduction of free Mg
2+
induces the increase of
ADP, essential in the regulation of mitochondrial ATP
production. High levels of ADP, in turn, induce high rates
of oxidation in an attempt to return to homeostasis.
12
Despite the repercussion of Mg
2+
, Lodi et al.,
12
based
on their ndings, argue that therapies that increase the
efciency of the production of Mitochondrial ATP would
be more advantageous than treatments based on the
administration of magnesium.
Because of the importance of Mg
2+
for energy
production, it may have a special role in the pathogenesis
of migraine. Nevertheless, it is seen that Mg
2+
medication
is useful in some cases of migraine
25-29
The predominance of the adoption of the occipital
region for analysis through
31
P-MRS would be in the
fact that it has regional cerebral metabolic oxygen rate
higher when compared to other cortical areas. Likewise,
the regional cerebral metabolic glucose rate is higher in
the occipital white matter and visual cortex than in other
areas, and the latter one remains without metabolic
changes with age.
30,31
The reason to some studies not verify alterations
on cerebral energetic metabolism could be the brain
region choosen to investigate. Changes in energy
metabolism in migraineurs have been shown in muscle
and platelets
6,32-34
defending a generalized character
of energetic metabolism alteration in individuals with
migraine that would unlikely exclude the brain.
Some studies found relations between energy
metabolism in complicated types of migraine, such
as prolonged aura, stroke migraine or hemiplegic
migraine
6,11,12,18,34,35
Therefore, rather than inuencing the
susceptibility to developing a migraine attack, changes
in energy metabolism would determine the clinical
characteristics of an attack.
18
Probably because of that,
some treatments with magnesium do not show good
results in the relieving migraine attacks.
36-38
Another assumption is that the energetic metabolism
alterations veried in some individuals diagnosed with
typical or classical migraine could be signals to a possible
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Cerebral energetic metabolism in migraine
David MCMM, et al.
19
Headache Medicine, v.10, n.1, p.16-23, 2019
Authors
(year)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Total
Percentage
of
Agreement
(%)
Montagna et
al. (1994)
10
N/Y N/N N/Y Y/N N/Y N/Y Y/Y Y/N Y/N N/N N/N N/N Y/Y Y/Y Y/N Y/Y N/N Y/Y N/N Y/Y N/Y N/N 10/11 59.1
Reyngoudt et
al. (2011)
7
Y/Y Y/Y Y/Y Y/Y N/Y N/Y Y/Y Y/N N/N N/N Y/Y Y/Y Y/Y Y/Y Y/Y N/Y N/N Y/Y N/N Y/Y Y/Y Y/Y 15/17 81.8
Boska et al.
(2002)
11
Y/Y Y/Y Y/Y Y/Y Y/Y N/Y N/Y Y/N N/Y N/N Y/Y Y/Y Y/N Y/Y Y/Y Y/Y Y/Y Y/Y N/N Y/Y Y/N N/N 16/16 72.7
Lodi et al.
(2000)
12
Y/Y Y/Y Y/Y Y/Y N/Y N/Y Y/Y Y/N Y/Y N/N Y/Y Y/Y Y/Y Y/Y Y/Y Y/Y Y/Y Y/Y N/N Y/Y Y/N Y/Y 18/18 81.8
Ramadan et
al. (1989)
13
N/Y Y/Y Y/Y Y/Y N/Y N/Y Y/Y Y/N N/N N/N Y/N Y/N Y/Y Y/Y Y/Y N/Y Y/N Y/Y N/Y Y/Y Y/Y Y/N 15/15 54.5
Welch et al.
(1989)
14
N/Y Y/Y N/Y Y/Y N/Y N/N N/Y Y/Y N/N N/N Y/Y Y/N Y/Y Y/Y Y/N N/Y Y/N Y/Y Y/N Y/N Y/N Y/N 14/13 45.4
Halvorson et
al., (1992)
Y/Y Y/Y N/Y Y/Y N/N N/N Y/Y Y/N Y/N N/N N/Y Y/Y N/N N/N Y/Y Y/Y N/N Y/Y N/N Y/Y Y/N N/N 12/11 77.3
Schulz et al.,
2007
Y/Y Y/Y Y/Y Y/N N/Y Y/Y Y/N Y/N Y/N N/Y Y/Y Y/Y N/Y Y/Y Y/Y Y/Y Y/N Y/Y Y/N Y/N Y/N Y/Y 19/15 50.0
Welch et al.
(1988)
Y/Y Y/Y N/Y Y/N N/N N/N Y/ Y Y/ N Y/N N/N Y/N Y/N N/Y Y/Y Y/N Y/Y Y/N Y/Y N/Y Y/Y Y/Y Y/Y 16/12 54.5
Table 1. Evaluation of the selected articles in accordance with the STROBE Statement.
Source: Research Data. 1: Title and abstract; 2: Background/rationale; 3: Objectives; 4: Study design; 5: Setting; 6: Participants; 7: Variables; 8: Data sources/ measurement; 9: Bias; 10:
Study size; 11: Quantitative variables; 12: Statistical methods; 13: Participants; 14: Descriptive data; 15: Outcome data; 16: Main results; 17: Other analyses; 18: Key results; 19: Limitations;
20: Interpretation; 21: Generalisability. 22: Funding; Y= Yes; N= No
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Cerebral energetic metabolism in migraine
David MCMM, et al.
Headache Medicine, v.10, n.1, p.16-23, 2019
20
Table 2. Characteristics of the individuals in the selected studies.
Source: Research Data. 1: Title and abstract; 2: Background/rationale; 3: Objectives; 4: Study design; 5: Setting; 6: Participants; 7:
Variables; 8: Data sources/ measurement; 9: Bias; 10: Study size; 11: Quantitative variables; 12: Statistical methods; 13: Participants;
14: Descriptive data; 15: Outcome data; 16: Main results; 17: Other analyses; 18: Key results; 19: Limitations; 20: Interpretation; 21:
Generalisability. 22: Funding; Y= Yes; N= No
Authors
(year)
Subjects Sex Age
Migraine
Type
Migraine
Duration
Pain
Intensity
Attacks
Frequency
Medication
Montagna
et al. (1994)
9
40
(E:22;
C:18)w
E: 19F;
C: 19F.
E: 34.0 ±
10.0;
C: 34.0 ±
18.0
MwoA (22)
19.0 ± 10.0
anos
X
3.6 ± 1.8
attacks/
month
Without medication
Reyngoudt
et al. (2011)
7
45
(E: 19;
C:26)
E: 18F;
C: 15F
E:32.3 ± 12.1;
C: 27.6 ±
10.9
MwoA (19) X X X
Without
prophylactic
medication
Boska et al.
(2002)*
11
78
(E: 38;
C: 40)
E: 32F;
C: 27F
E: MWA
(40.9 ± 8.4),
MwoA (35.7
± 9.5); C:
37.5 ± 11.3.
MWA (19),
MwoA (19)
X X X Without medication
Lodi et al.
(2000)*
12
94
(E:58;
C: 36)
E: 40F;
C: ?
E: MWA
(23.0 ± 2.0),
MwoA (32.0
± 2.0); C:
36.0 ± 3.0.
MWA (37),
MwoA (21)
MWA: 11.0
± 2.0 anos;
MwoA: 18.0
± 2.0 anos.
X X Without medication
Ramadan et
al. (1989)
13
44
(E: 19;
C: 25)
E: 17F;
C: 15F
E: MWA
(37.1 ± 13.2)
MwoA (34.3
± 9.7); C:
43.4 ± 18.2
MWA (8),
MwoA (11)
X X X
Individuals did not
use analgesics 4
hours before the
imaging. Some
used prophylactic
medication.
Welch et al.
(1989)
14
47
(E: 20;
C: 27)
E: 18F;
C: 17F
E: MWA
(37.1 ± 13.2)
MwoA (37.2
± 12.0); C:
45.1 ± 17.6.
MWA (8),
MwoA (12)
X X X
Individuals did not
use analgesics 4
hours before the
imaging. Some
used prophylactic
medication.
Halvorson
et al.,
(1992)*
28
(E: 10;
C: 18)
X X X X X X X
Schulz et al.,
(2007)*
26
(E: 10;
C: 16)
E: 7F;
C: 8F
E: 42.7 ±
13.7;
C: 39.0 ±
15.0
MWA (10)
≤1h (6);
>1h≤24h
(2);
>24h
≤7days(1);
>7h (1)**
X
≥1 attacks/
month (3);
<1 attacks/
month (7)
X
Welch et al.
(1988)
47
(E: 20;
C: 27)
E: 18F;
C: 17F
E: MWA
(37.1 ± 13.2)
MwoA (37.2
± 12.0); C:
45.1 ± 17.6.
MWA (8),
MwoA (12)
X X X
Individuals did not
use analgesics 4
hours before the
imaging. Some
used prophylactic
medication.
progression to a complicated migraine. Knowing the
suscetibility to future migraine stroke episode or a
progression to a prolonged aura crisis or another type
of complicated migraine would help to plan a more
specic treatment for each situation. In this way, with
more studies at the eld, the
31
-RMS could became a
search tool to determine individuals at risk to develop a
complicated migraine.
This review presented some limitations, such as
the necessity to consider subgroups of interest in
the articles with various subgroups of complicated
migraine. In some articles, it was not possible to nd
all the information that was intended (age, gender,
medication, duration, frequency neither intensity
of pain). Furthermore, it was not possible to apply
a specic tool of assessment risk of bias neither to
develop a meta-analysis due to the variability of the
results.
Despite the similarities of the conclusions obtained
with the selected articles, it is necessary to carry out more
10(1).indb 20 21/10/2019 19:34:00
Cerebral energetic metabolism in migraine
David MCMM, et al.
21
Headache Medicine, v.10, n.1, p.16-23, 2019
Authors (year)
Ictal/interictal
condition
31
P-MRS
Instrument
Region Results Conclusions
Montagna et al.
(1994)
9
Interictal 1.5T, Signa Occipital lobes
↓PCr; ↑Pi; ↑ADP; ↑V/
Vmáx; ↓PP
Presence of unstable metabolic
status in brain cells, indicating a
defect in the energy metabolism
of individuals with migraine
without aura.
Reyngoudt et al.
(2011)
7
Interictal 3T, Siemes
Medial occipital
lobe
↓PCr; ↑Pi; ↓ATP;
↑ADP; ↓PP; ↓Mg
2+
Disturb in the energetic
metabolism of individuals with
migraine. The reduction of ATP
indicates a possible participation
of mitochondria in the
pathophysiology of migraine.
Boska et al.
(2002)*
11
Interictal
3T, Magnex-
SMIS
Calcarine cortex,
temporal gyri,
occipital gyri, frontal
gyri, frontal forceps,
genu of corpus
callosum, occipital
cortex
MwoA: ↑PDE in most
brain regions, ↑Mg
2+
in posterior brain
regions.
No substantial alteration of
energy metabolism, but the
disturbances in Mg
2+
homeostasis
may contribute to brain
hyperexcitability
MWA: ↓PCr in
anterior brain
regions, ↓ Mg
2+
in posterior brain
regions, but no
consistent changes
in PME,
PDE, Pi, or pH.
Lodi et al.
(2000)*
12
Interictal 1.5T, Signa Occipital lobes
↓Cytosolic free
Mg
2+
, ↓free energy
released by the
reaction of ATP
hydrolysis.
There is mitochondrial
dysfunction in individuals
with migraine secondary to
bioenergetics décit.
Ramadan et al.
(1989)
13
Ictal (10);
Interictal (9)
1.89T, Bruker
Frontal,
frontotemporal,
parieto-occipital,
occipital cortex
↓Mg
2+
, especially
between controls
and migraineurs
measured during an
attack. No changes
in pH.
Low brain Mg
2+
is important in
migraine pathofhysiology.
Welch et al.
(1989)
14
Ictal (11);
Interictal (9)
1.89T, Bruker
Frontal,
frontotemporal,
parieto-occipital,
occipital cortex
Ictal: ↓PCr/Pi; ↓PCr/
TP; ↑Pi/TP
Energy phosphate metabolism is
altered during a migraine attack.
Interictal: ↑Pi/TP
Halvorson et al.,
(1992)
Ictal (10);
Interictal (10)
1.89T, Bruker/
Oxford
Research
X
Increased variability
of pMg among
migraineurs. ↑pMg
at ictal stage.
Increased variability of pMg
concrntration. The difference
between the means of ictal and
interictal period was statistically
signicant.
Schulz et al.,
(2007)*
Interictal 2T, Bruker
Level of the basal
ganglia (white and
grey matter)
Non-signicant
differences
between control
and migraine with
non-motor aura
in terms of PCr/Pi
, PCr/ATP, Pi/ATP
and pH
Energy metabolism alterations
may not initiate a migraine attack
but may be involved you the
clinical manifestation of aura.
Welch et al.
(1988)
Ictal (11);
Interictal (9)
1.89T, Bruker
Frontal,
frontotemporal,
parieto-occipital,
occipital cortex
Non-signicant
pH differences
between control
and migraine at ictal
neither interictal
phases.
The pain of migraine is unlikely
to be caused by cerebral
vasodilatation induced by
prodromal ischemic brain
acidosis neither other pH
alterations.
Table 3. Characteristics of selected studies.
Source: Research Data. PCr: Phosphocreatine; Fi: Inorganic phosphate; ADP: Adenosine diphosphate; V/Vmáx: Rate of ATP
synthesis; PP: Phosphorylation potential; ATP: Adenosine triphosphate; MwoA: Migraine without aura; MWA: Migraine with aura; PDE:
phosphodiester concentration, PME: phosphomonoester concentration; TP: total phosphorus. *Only the group with migraine (with
and/or without aura) and the control group was considered
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David MCMM, et al.
Headache Medicine, v.10, n.1, p.16-23, 2019
22
studies in the area with higher quality and control of the
intervening variables like the medication, not only during
the imaging, but also in the routine of the individuals.
Likewise, it is important to carry out analyzes regarding
the relations of
31
P-MRS results with sociodemographic
and clinical variables such as differences between sexes
and age; duration of migraine history, pain intensity,
frequency of attacks and medication.
In addition, there has been a dearth of recent studies,
which are important, given socioeconomic and cultural
differences throughout the years, so that nowadays
greater knowledge of the disease, modication of the
eating and physical habits prole and greater exposure
to medicines may change the results.
From the results veried in the selected studies,
there are alterations in cerebral energetic metabolism
in individuals with migraine, revealing the importance of
considering mitochondrial dysfunction as a component
in the pathophysiology of this disease. More studies
in the area with higher quality, control of intervening
variables and analysis of the relationships with the
socio-demographic and clinical variables of the affected
individuals are necessary.
CONFLICT OF INTEREST AND FINANCIAL
SUPPORT
There was no conict of interest or funding for this
review.
FUNDING
This research received no specic grant from any
funding agency in the public, commercial, or not-for-
prot sectors.
ARTICLE HIGHLIGHTS
• There are alterations in cerebral energetic
metabolism in individuals with migraine;
• A mitochondrial dysfunction should be considered
as a component in the pathophysiology of
migraine;
• Energetic metabolism alterations veried
in some individuals diagnosed with typical
or classical migraine could be signals to
a possible progression to a complicated
migraine in the future.
• Treatments acting on energetic metabolism, such
as magnesium, coenzyme Q10 or riboavine
might be benecial in the migraine prophylaxis.
• More studies in the area with higher quality,
control of intervening variables and analysis of
the relationships with the socio-demographic
and clinical variables of the affected individuals
are necessary.
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