1. Migraine with brainstem aura: defining the core syndrome
I would like to extend my sincerest welcome to professor Jes olesen, he is the founder of DHC and the chair of international headache classification committee. He is the author and co-author of more than 600 papers and published more than 20 books in the headache field, if you seach his name in google scholar h-index is 130. he is known as father of hedache all over the world. I had the pleasure to do my fellowship under his supervision in Denmark and learned a lot of him of the headache clinic and research. He was an excellent mentor and a great inspiration for me. today I am going to present one of my research papers in collaboration with Mona ameri and prof Olesen. This paper is accepted to be published in Brain journal and will come out in December. And the title is
Nooshin Yamani, Mona Ameri Chalmer, Jes Olesen
 BRAIN R1

2. Diagnostic criteria for migraine with brainstem aura in ICHD-3
Background:
Diagnostic criteria for migraine with brainstem aura in ICHD-3
A. Attacks fulfilling criteria for 1.2 Migraine with aura and criterion B below
B. Aura with both of the following:
1. at least two of the following fully reversible brainstem symptoms:
a. dysarthria
b. vertigo
c. tinnitus
d. hypacusis
e. diplopia
f. ataxia not attributable to sensory deficit
g. decreased level of consciousness (GCS ≤13)
2. no motor or retinal symptoms.
C. Not better accounted for by another ICHD diagnosis.
first described as basilar artery migraine by Bickerstaff in 1961
Although known for many years, its diagnosis and even its existence are still a matter of debate.
Migraine with brainstem aura (MBA) is a rare sub-type of migraine with aura. Although known for many years, its diagnosis and even its existence are still a matter of debate. according to ICHD-3, To fulfill the diagnostic criteria for migraine with brainstem aura , an individual must have attacks fulfilling criteria for migraine with aura and at least two brainstem aura symptoms consisting of dysarthria, vertigo, tinnitus, hypacusis, diplopia, ataxia and decreased level of consciousness but not motor or retinal symptoms
Bickerstaff, Lancet 1961
ICHD-3, Cephalalgia 2018

3. Background: According to previous studies:
The prevalence of MBA was estimated to be 10% among migraine with aura patients (much higher than expected from clinical experience)
Current diagnostic criteria for migraine with brainstem aura (MBA) are too open.
Brainstem symptoms may originate within the cortex and not in the brainstem.
two previous telephone interview study showed that this disorder occurs particularly among patients with migraine with typical aura and the prevalence of MBA was estimated to be 10% in these patients which is much higher than expected from clinical experience.
Another recent study has argued that brainstem aura symptoms may originate within the cortex and not in the brainstem
Kirchmann et al. Neurology 2006
Li et al. Cephalalgia 2015
Demarquay et al. Cephalalgia 2018

4. Aims: The aims of the present study were:
To analyze whether convincing cases of aura from the brainstem exist.
How prevalent such cases are?
Whether current diagnostic criteria define convincing cases.
If necessary, to develop new stricter criteria that define only the core syndrome.

5. Methods: Our material consisted of:
All cases with MBA described in detail in the literature
Clinical cases from the Danish Headache Center (DHC) in past 2 years
A very large sample of telephone interviewed cases with migraine with aura (1582 cases)
including 1582 MA patients from cohort study affliated with DHC.

6. We proposed stricter diagnostic criteria for MBA
Methods:
We selected the 20 most convincing cases from the literature and DHC and reported their most important clinical characteristics, EEG and imaging findings.
We proposed stricter diagnostic criteria for MBA
We made modifications to arrive at a set of criteria in accordance with the clinical concept that this is a very rare disorder originating from the brainstem.
After collecting data from cases reported in the literature and cases from DHC, -
We tested the proposed criteria in our convincing cases and in a group of patients reported in the literature that were not so convincing and made modifications to arrive at a set of criteria which was more in accordance with the clinical concept that this is a very rare disorder originating from the brainstem.

7. Results Literature cases:
Out of 79 MBA cases described in detail in the literature, 44 fulfilled the diagnostic criteria for MBA of the ICHD-3
Our analysis of literature cases, provided convincing cases with brainstem symptoms and signs which could only be explained by dysfunction in the brainstem.
MBA does exist.
From the literature cases

8. Evidence from literature to support MBA does exist
Aura symptoms too widespread to be explained by contiguous CSD in the cortex or of a type not encountered from the cortex.
E.g. No 1: vertigo, diplopia, dysarthria, ataxia and bilateral visual and sensory symptoms.
No 2: diplopia, tinnitus, decreased level of consciousness, pupil dilatation and bilateral sensory symptoms.
Vertebro-basilar system infarctions as complication of MBA.
Reversible transient synchronous bilateral slow EEG activity with occipital predominance.
Decrease in regional blood flow in the basilar artery territory during HMPAO-SPECT.
Spreading depression in the brainstem in rats has been shown.
1-we noticed cases with several brainstem signs that made it difficult to see how symptoms could possibly originate in the cortex. I have brought two cases as example case 1 had aura symptoms of…Another one experienced….
-that are well recognized and suggest involvement of the brainstem.
-is the most characteristic though not specific or sensitive laboratory finding in the literature consistent with brainstem involvement.
-During a typical MBA attack, there has been a
Caplan, 1991; Kreling et al., 2017; Solomon and Spaccavento, 1982; Sturzenegger and Meienberg, 1985; Wolf et al., 2011, Lapkin et al., 1977; Seto et al.; 1994, Aiba and Noebels, 2015; Richter et al., 2003, 2008

9. Results
DHC clinical cases: In the DHC after face-to-face interview, neurological examination and imaging, 4 MBA out of 293 (1.37%) with migraine with aura (MA)were found ~ 0.04% in the general population.
Cohort material: According to the telephone interview the prevalence of MBA was 258/1582 (16.3% )of cases with MA, but reviewing their charts the actual prevalence of MBA according to face-to-face expert interview, examination and laboratory tests in DHC was only 2.2% of patients with MA.
MBA is rare (1-2 % among MA patients and 0.04% in the general population).
Thus we concluded that The real prevalence of MBA is more likely to be 1-2% of cases with MA

10. Current diagnostic criteria are too unspecific.
current criteria lack specificity because they allow telephone interview and do not request that a face-to-face interview and examination must be done by a neurologist
they do not request MR and other examinations to rule out other diagnoses
Furthermore,
The problem is in the interpretation of symptoms in the absence of a neurological face-to-face interview and neurological examination. Many migraine patients have bilateral visual symptoms .Many complain of dizziness that is not always easy to distinguish from vertigo. Many feel unconcentrated, removed from reality and this can be interpreted as decreased level of consciousness. Others become anxious during attack and hyperventilate, which may cause bilateral paresthesia. Dysarthria can be drug induced and difficult to distinguish from aphasia. Thus, many symptoms especially during telephone interview sound as if they have brainstem origin, but don’t. Therefore, when a patient develops signs and symptoms referable to the brainstem, only good clinical judgement according to a neurologist conducted face-to-face interview and neurological examination can provide the appropriate diagnosis.

11. Proposed diagnostic criteria for migraine with brainstem aura
A. Attacks fulfilling criteria for 1.2 Migraine with aura and criterion B and C below.
B. Aura with both of the following by face-to-face interview by a neurologist:
1. at least three of the following fully reversible brainstem symptoms:
dysarthria
vertigo
tinnitus
hypacusis
diplopia
ataxia not attributable to sensory deficit or weakness
decreased level of consciousness (GCS ≤13)
simultaneously bilateral visual symptoms and/or simultaneously bilateral paresthesias
2. no motor or retinal symptoms
C. Other etiologies ruled out by examination by a neurologist, MRI and other laboratory tests. Attack related EEG abnormalities are fully reversible.
D. Not better accounted for by another ICHD diagnosis.
In consequence of the above, we developed more strict criteria. We required that a neurologist do a face-to-face interview and examination as well as MRI and other laboratory investigations. We also required aura to have at least three out of eight fully reversible brainstem symptoms instead of two out of seven in the current ICHD-3 version. We considered bilateral visual and/or sensory symptoms as one sub-criterion for brainstem symptoms. We applied the proposed criteria to a group of patients reported in the literature that we are not sure are convincing and to the 20 most convincing cases selected from literature or from DHC. 35 out of 44 cases reported in the literature as MBA and all 20 convincing cases fulfilled the proposed criteria. Thus, despite considerable tightening of criteria, they seemed to preserve sufficient sensitivity.   

12. Conclusion MBA does exist. MBA is rare.
Existing diagnostic criteria are too unspecific.
Proposed tighter diagnostic criteria better define the core syndrome caused by brainstem dysfunction.
Future studies of patients fulfilling these criteria are warranted before including the proposed criteria in a future version of ICHD.