Headache and epilepsy are commonly comorbid conditions that share underlying pathophysiological mechanisms. About 5-10% of those with migraine have epilepsy, and 8-15% of those with epilepsy experience migraine. Both involve neuronal hyperexcitability that can trigger cortical spreading depression or seizures. Genetic channelopathies like FHM types 1-3 alter neuronal calcium and sodium channel function, lowering seizure and migraine thresholds. Antiepileptic drugs like levetiracetam and zonisamide can treat both conditions. Careful history is needed to identify pre-ictal headaches in those with epilepsy and evaluate for epilepsy in migraine patients due to medication interactions.

1. Headache & epilepsy
STEPHANIE WROBEL GOLDBERG
THOMAS JEFFERSON
HEADACHE FELLOW

2. Headache
7% of office visits
As much disability as MS, Parkinson’s disease and epilepsy
Primary headache much more
common than secondary headache,
but secondary headache more
ominous

3. Primary vs Secondary
Primary: not accounted by any other underlying diagnosis
1) Migraine
2) Tension-type headache
3) Cluster headache
Secondary:
1) SVT
2) Pituitary apoplexy
3) Stroke
4) Tumor
5) Infection

4. Don’t forget “SNOOP” red flags
Stands for… Example… Think of…
S
Systemic
symptoms
Secondary risk
factors
Fever, weight loss, fatigue,
HIV, cancer, immune suppression
Infection, inflammation,
metastatic cancer,
carcinomatous meningitis
N
Neurologic
symptoms/signs
Altered consciousness, focal deficits Encephalitis, mass lesion,
stroke
O
Onset Thunderclap, abrupt SAH, IPH, RCVS
O
Older New after age 50 Temporal arteritis
P
Positional
Prior HA
Papilledema
Change upright vs laying down
Change with neck position
Different in quality
Visual obscurations
Intracranial hypotension,
dysautonomia
cervicogenic headache,
intracranial hypertension
Posterior fossa pathology

5. How to approach …
History
Headache onset: age, what were they doing when it started, abrupt vs
gradual
Location of pain: side locked, switches sides, originates from the neck,
temporal
Duration of pain: Migraine 4+hours, Cluster < 3 hours
Frequency and timing of attacks

6. Primary Headache Disorders
based on duration
Chronic (15+ days/month) Episodic (<15 days/month)
Long (4 hours) • Chronic migraine
• Chronic tension-type
headache
• New daily persistent
headache
• Hemicrania continua
• Episodic migraine
• Episodic tension-type
headache
Short (<4 hours) • Chronic cluster headache
• Chronic paroxysmal
hemicrania
• SUNCT
• Episodic cluster headache
• Episodic paroxysmal
hemicrania
Richard B. Lipton, MD Headache 2011

7. Epilepsy and Headache
In the general population, the life time prevalence of headache is about
46 % [1] and that of migraine 10-22 % [2].
Bi-directional relationship  one disorder increases the likelihood that
the other is also present.
1 to 17% (median of 5.9%) with migraine have epilepsy
8 to 15% with epilepsy have migraine

8. Epilepsy and Migraine
Both chronic disorders characterized by recurrent neurologic attacks accompanied by
gastrointestinal, autonomic, and psychological features.
Imbalance between excitatory and inhibitory factors results in altered brain function.
Also linked by common underlying cellular/molecular mechanisms and treatment.
Heterogeneous disorders influenced by genetic and environmental background  clinical
features and treatment response profiles.

9. 1,948 adults with epilepsy and 1,411 of their parents and siblings: strong association
between migraine and epilepsy, independent of seizure type, etiology, age at onset,
or family history of epilepsy. RR 2.4

10. Epilepsy and Migraine
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke
(MELAS), basilar migraine with seizures, migraine with primary
generalized absence.
Benign epilepsy of childhood with occipital paroxysms (BOEP) – partial
seizures, may begin with migraine like visual aura and followed by
postictal headache.
Studies in adults less convincing evidence

12. Epileptic visual hallucinations vs
MA visual
Onset within seconds vs slower onset within minutes
Lasts seconds to minutes vs typically 15-20 minutes up to 1 h
Colored and circular, may progress into complex forms vs uncolored and
linear
Rising abdominal sensation, fear, deja vu illusion
The sensory auras of migraine spreads slowly

13. MA - visual

14. ICHD 3 beta
July 2013
Alignment with the International Classification of Disease edition 11
(ICD-11)

15. ICHD 3 beta – “Migralepsy”
First described by Lennox and Lennox in 1960
1.4.4 Migraine aura-triggered seizure
Diagnostic criteria:
A. A seizure fulfilling diagnostic criteria for one type of
epileptic attack
B. Occurring in a patient with migraine with aura, and during, or within 1
hour after, an attack of migraine with aura
C. Not better accounted for by another diagnosis.

16. ICHD 3 beta
7.6 Headache attributed to epileptic seizure
Description: Headache caused by an epileptic seizure
1) 7.6.1 Hemicrania epileptica
2) 7.6.2 Post-ictal headache
unavailable ictal EEG make diagnosis difficult

17. ICHD 3 beta
7.6.1 Hemicrania epileptica
Description: Headache occurring during a partial epileptic seizure, ipsilateral to the epileptic discharge,
and remitting immediately or soon after the seizure has terminated.
Diagnostic criteria:
A. Any headache fulfilling criterion C
B. The patient is having a partial epileptic seizure
C. Evidence of causation demonstrated by both of the following:
1. headache has developed simultaneously with onset of the partial seizure
2. both of the following:
a) headache has significantly improved immediately after the partial seizure has terminated
b) headache is ipsilateral to the ictal discharge
D. Not better accounted for by another ICHD-3 diagnosis.

18. ICHD 3 beta
7.6.2 Post-ictal headache
Diagnostic criteria:
A. Any headache fulfilling criterion C
B. The patient has recently had a partial or generalized epileptic seizure
C. Evidence of causation demonstrated by both of the following:
1) headache has developed within 3 hours after the epileptic seizure has
terminated
2) headache has resolved within 72 hours after the epileptic seizure has
terminated
D. Not better accounted for by another ICHD-3 diagnosis.

19. Post-ictal headache
Over 40% of patients with temporal lobe epilepsy or frontal lobe
epilepsy
60% of patients with occipital lobe epilepsy.
Conscious obscuration

20. What hurts?
The brain parenchyma is insensate.
Dura mater, dural vessels, extra and intracranial vessels, venous sinus,
cranial nerves, upper cervical roots, muscles and nasopharynx.
Trigeminal nerve, mostly its first division (ophthalmic nerve V1)
Trigeminocervical complex

22. Cortical Spreading Depression
1940 - Discovered by Aristides Leao at the department of physiology at
Harvard med school
Wave of cortical excitation followed by a wave of inhibition.
Wave marches over the cortical mantle at a rate of 3 mm/min
Elevated extracellular potassium and glutamate

23. JAMA Neurology June 09, 2008 - Common Pathophysiologic Mechanisms n Migraine and Epilepsy Michael A. Rogawski, MD, PhD

24. Role of Glutamate
Important neurotransmitter that plays the principal role in neural
activation.
Elevated extracellular glutamate plays critical role in epileptiform
activity
Also triggers CSD
Target treatment: Magnesium, Topamax

25. Migraine and Seizure - triggered by neocortical hyperexcitability
MIGRAINE - hyperexcitability thought to transition to cortical spreading depression
SEIZURE - hyperexcitability transitions to hypersynchronous activity

26. EEGs recorded during a migraine with aura are usually normal.
Most reported EEG abnormalities in migraine are nonspecific, such as focal or diffuse
slowing and abnormalities during procedures such as hyperventilation.

27. EEG role in headache

28. Genetics
Imbalance between inhibitory and excitatory cortical function seem to
have a major role in both migraine and epilepsy
Genetically channelopathies leading to alter cortical excitability.
FHM
Comorbid non-syndromic migraine and epilepsy  complex interplay of
multiple genes and environmental factors

29. FHM type 1
CACNA1A
Encodes subunit ( α1A) of neuronal P/Q calcium channels  gain of function
First familial hemiplegic migraine gene to be described (1996)
Increased intracellular calcium
Synaptic release of glutamate, no change in GABA release  lower CSD threshold
Linked to cases of generalized epilepsy and absence-like seizures.

30. FHM type 2
ATP1A2 (early 2003)
Encodes a subunit (α2) of Na+-K+ -ATPase transporter (primarily astrocytes
and pia/arachnoid cells)  loss of function
In neonates predominantly expressed in neurons  infantile convulsions
Inhibition of this transporter can induce seizures by lowering membrane
threshold.
Most frequent association with epilepsy (20% of families) - partial seizures,
benign familial infantile convulsions, febrile seizures

31. FHM type 3
SCN1A
Encodes subunit of neuronal VG Na channel  gain of function
Correlation with generalized epilepsy with febrile seizures plus (GEFS+)
and severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome)

33. Levetiracetam (Keppra ) and Zonisamide (Zonegran)

34. Take home points
Patients with epilepsy tend to under report presence of pre and peri-ictal
headaches.
The presence of one disorder increases the likelihood the other is also
present.
Headaches adds to the already significant burden of epilepsy and so it is
fundamental for physicians to be aware, diagnose and address this
comorbid condition.
In patients with migraine, a history of epilepsy should be investigated 
tricyclic antidepressants or neuroleptics may lower seizure thresholds.

35. Take home points
Although migraine and epilepsy are associated, the mechanisms of the
association are uncertain.
Unlikely unidirectional
Altered brain state (increased excitability) might increase the risk of
both disorders.
Shared pathophysiology/molecular genetic factors

36. References
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37. References
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38. Thank you
Obrigada