Sarah Hodges, DO Staff Neurologist sarah.d.hodges3.mil@mail.mil Approach to Headache Sarah Hodges, DO Staff Neurologist sarah.d.hodges3.mil@mail.mil My aim today is to provide you with a framework on which to build your knowledge of headache diagnosis and management. Once that is established, you will know what is within your wheelhouse to treat and what should be referred on. I have no disclosures

A 34-year-old woman came to the office complaining of severe, left-sided throbbing headaches that last about 12–24 hours. She has had these headaches once a week for several months. During an episode, she is sensitive to both bright lights and loud sounds and feels nauseous. Sleep seemed to help her headaches. Neurological examination was normal. What is the diagnosis? What are 3-4 other questions you would ask to determine if any other diagnostics are necessary and which treatment to choose? (What is she using now, is she over-using, have the headaches changed or are associated with any abnormal symptoms, does she have plans to become pregnant?) What might you prescribe for her? Is MRI necessary?

Objectives Respect the history Make a diagnosis Know when to order more Be confident when treating Know when to refer

Overview Headache attacks How it begins How to take the history The exam Define migraine Dilemmas in diagnosing migraine Treating migraine Define medication overuse headache Treating MOH Define cluster headache Issues in pregnancy/lactation Summary New patient appointments in Neurology are slotted for one hour because we take extensive history. You will not have that luxury, but in headache, history is key so you need to become efficient in your headache history taking. This entails knowing when to dig deeper and when to divert the conversation to a more pertinent line of questioning. Headache attacks How it begins Precipitating event, illness, injury Headache attack descriptions Frequency and patterns Any significant changes Location Time to peak intensity Duration Quality and intensity Warning symptoms and aura Associated symptoms and level of disability Triggers and aggravating or relieving factors: In addition to this, their concurrent medical/psychiatric conditions and medications will determine your further diagnostic plan and treatment approach. Often, by urging the patient to divulge exacerbating factors, we can help them realize the lifestyle changes that need to occur in order to gain relief i.e. “headaches happen only when I’m sleep deprived” or “I didn’t start having daily headaches until I had been taking ibuprofen 3x/day, every day, for my back pain”. You get the picture. Many patients with headaches have significant psychosocial stressors. These stressors lead to lifestyle choices that are incompatible with good headache control such as poor sleep, excessive alcohol use, and overconsumption of caffeine.

Studies Exam History Headache attacks How it begins The bedrock of the encounter is the history. As you take the history, you are first trying to determine if the patient has a primary or a secondary headache. This is largely achieved through the history-taking process. The examination helps a little, but is usually normal. Imaging is rarely useful in patients whose history indicates a primary headache disorder. New patient appointments in Neurology are slotted for one hour because we take extensive history. You will not have that luxury, but in headache, history is key so you need to become efficient in your headache history taking. This entails knowing when to dig deeper and when to divert the conversation to a more pertinent line of questioning. Headache attacks How it begins Precipitating event, illness, injury Headache attack descriptions Frequency and patterns Any significant changes Location Time to peak intensity Duration Quality and intensity Warning symptoms and aura Associated symptoms and level of disability Triggers and aggravating or relieving factors: In addition to this, their concurrent medical/psychiatric conditions and medications will determine your further diagnostic plan and treatment approach. Often, by urging the patient to divulge exacerbating factors, we can help them realize the lifestyle changes that need to occur in order to gain relief i.e. “headaches happen only when I’m sleep deprived” or “I didn’t start having daily headaches until I had been taking ibuprofen 3x/day, every day, for my back pain”. You get the picture. Many patients with headaches have significant psychosocial stressors. These stressors lead to lifestyle choices that are incompatible with good headache control such as poor sleep, excessive alcohol use, and overconsumption of caffeine.

Green Flags Stable pattern for >6 months Long-standing HA history Family history of similar HA Normal exam Consistently triggered by hormonal cycle, specific sensory input, weather HA meets criteria HA changes sides Instead of starting with the “red flags” or things that indicate a secondary headache, let’s start with the more reassuring signs. If the patient has these characteristics, chances are that you are dealing with a primary headache disorder.

Red Flags New headache, Severe headache Onset age >50 years Presence of fever or systemic symptoms Focal neurologic symptoms or signs Precipitated by positional changes, Valsalva, bending or coughing History of cancer, immunocompromise, or HIV Headache during pregnancy or postpartum Progressive headache or escalating medication requirements Neuroimaging is recommended when patients have headache and unexplained neurologic findings, atypical neurologic symptoms, findings that do not fulfill criteria for migraine, and risk factors such as immunocompromise or cancer. CT is indicated for suspected acute subarachnoid hemorrhage or trauma. MRI/A or CTA for anything else, depending on the clinical context. Now, on to ominous signs. In general, err on the side of caution. A patient with “worst headache of my life” deserves at least a head CT +/- spinal tap. Even if the headache resolves, the pain may have been a sentinel headache heralding an upcoming aneurysm rupture. Subarachnoid hemorrhage If the patient is over age 50 when they get their first headache, that’s unusual. Probe for trauma, subtle neuro/cognitive deficits, vision changes. GCA, brain tumor, SDH Think infection if there is fever. Most people might get a mild headache during the flu, but if there is significant headache, have a low threshold for LP and imaging. Chronic meningitis, sinusitis, vasculitis, GCA The presence of focal neurologic signs signifies the possibility of a focal lesion. These patients generally required expedited workup either via ER or Neurology with imaging. Reliable change in headache severity with position change can indicate either intracranial hypotension or intracranial hypertension. Concern for elevated ICP requires urgent evaluation with imaging. Patients with cancer, HIV, or immunosuppression require imaging for new headaches. Period. The postpartum period is a dangerous one for women: the risk of cerebral venous thrombosis and pituitary apoplexy increase. This can be tricky in patients who had a pre-partum history of migraines as headaches generally wane during pregnancy and then rebound after delivery. If the headache pattern is very similar to prenatal headaches and she has a normal exam, can probably wait and see. If the headaches are different or completely new, need imaging. Cortical vein/cranial sinus thrombosis, carotid dissection, pituitary apoplexy In a patient with a history of headaches who comes in with progressive worsening, take a fresh look and ensure you have the right diagnosis. Also, query the patient about medication overuse (more on this later). This is a huge reason why patients with episodic headaches become chronic and refractory.

A 26-year-old woman came to the office complaining of a 3-month history of dull, constant headaches that involved the entire cranium. These headaches were made worse by lying down and coughing. Over the last 2 weeks, she had noticed some blurred vision and diplopia on looking to the left. Neurological examination revealed bilateral papilledema and a partial left CN VI palsy.

Neurologic Exam for Headache Appearance and alertness Signs of meningeal irritation Signs of papilledema Ensuring that the cranial nerves are normal Evaluation of strength, sensory modalities, reflex and coordination. The mental status of the patient and cranial nerve exam is highest yield. You can do this in 5 minutes. How many of you are proficient using an ophthalmoscope? If not, call someone who is for some cases, ophtho is probably best….emerging data using non-mydriatic fundscopy photos in ED may be helpful

Migraine without Aura At least 5 attacks fulfilling below items Pain lasts 4-72 untreated ≥2 of the following: Unilateral Pulsating Moderate-severe pain Aggravated by or causing avoidance of physical activity ≥1 during the headache Nausea ± vomiting Photophobia ± phonophobia *Aggravation by or causing avoidance of physical activity is the most sensitive indicator of migraine as opposed to other headache types. These criteria are here for classification, but are not strict. Migraine headaches can be bilateral and non-pulsatile. Can also have neck pain. Can have lacrimation and rhinorrhea secondary to activation of cranial parasympathetic nerves. If the headache lasts more than 4 hours untreated, chances are that it is migraine. *If there are less than 5 attacks, it is called probable migraine without aura *If the pt falls asleep with the migraine and wakes up without it, the duration is until the time of awakening.

Migraine with aura At least two attacks fulfilling criterion below At least three of the following four characteristics are present:    fully reversible aura symptoms occur    develops gradually over more than 4 minutes Lasts less than 60 minutes.    Headache follows aura with a free interval of less than 60 minutes    

Symptoms before the headache You can get patient to pin down the semiology of headaches with proper history taking. If the patient can reliably observe that excessive yawning is almost always followed by a headache, you can treat sooner and get better control. Pre-headache symptoms are not limited to aura, but can include mood changes, fatigue, sensitivity to light/sounds/odors, food cravings, difficulty concentrating, irritability, muscle tension, nasal stuffiness or drainage, excessive yawning, anxiety, excessive energy

Dilemmas in Diagnosing Migraine Migraine is, far and away, the most common headache type that makes it to a provider’s office and as such, there are many variations on this theme. 15-20% have visual aura 40% have non-throbbing head pain 40% can have bilateral head pain Most have some sinus pain/pressure, stuffiness, rhinorrhea, or weather association 75% have concomitant neck pain

Let’s have a few words about sinus headaches Let’s have a few words about sinus headaches. In this study, nearly 3000 patients with “sinus” headache were evaluated by neurologists. 80% actually had migraine. A proper diagnosis leads to proper treatment. If the headache lasts more than 4 hours untreated and meets criteria for migraine, treat it like a migraine. Schreiber, et al. Arch Intern Med. 2004

Migraine prevalence Migraine wanes as folks get older

A 51-year-old woman complained of several episodes of severe, paroxysmal stabbing pains that affected her right forehead and cheek regions for 3 months. These episodes lasted about 10–30 seconds and were triggered by chewing, washing her face, or brushing her teeth. Her last episode was about 2 days ago. Neurological examination in the clinic was normal. Is this a migraine? (no) Is this a primary headache? (no) What is the diagnosis? (trigeminal neuralgia)

Migraine Treatment Prevention The patient needs to own the migraines and know how often they occur, triggers, etc. The medications that we prescribe all have side effects and they will get the most benefit by optimizing their lifestyle in addition to medications. Encourage your patients to track their headaches with use of a headache diary or phone app. Avoidance of sleep deprivation, triggers, stress, caffeine are all important. Underlying psychiatric comorbities should be addressed. TREAT EACH HEADACHE MAXIMALLY ---- HEADACHES BEGET HEADACHES Preventing or minimizing CENTRAL SENSITIZATION is crucial for achieving rapid and sustained pain-free outcomes.

Migraine Treatment Lifestyle changes Abortive No more than 2 times per week!!!! The patient needs to own the migraines and know how often they occur, triggers, etc. The medications that we prescribe all have side effects and they will get the most benefit by optimizing their lifestyle in addition to medications. Encourage your patients to track their headaches with use of a headache diary or phone app. Avoidance of sleep deprivation, triggers, stress, caffeine are all important. Underlying psychiatric comorbities should be addressed. TREAT EACH HEADACHE MAXIMALLY ---- HEADACHES BEGET HEADACHES. Preventing or minimizing CENTRAL SENSITIZATION is crucial for achieving rapid and sustained pain-free outcomes. The general rule with all abortive medications is to limit use to no more than twice per week. Any more than this will predispose to MOH and is an indication for preventative therapy. NSAIDs Can be useful if early and in large doses. Excedrin migraine contains acetominophen, aspirin, and caffeine. Triptans Work on the 5-HT1 receptors. Work well when given early. There are differences in pharmacokinetics between formulations in this class, so try a different brand if one triptan doesn’t work. Sumatriptan and zolmitriptan are available in a nasal spray. Sumatriptan is available as an injectable. PO formulations include almotriptan, eletriptan, frovatriptan, naratriptan, sumatriptan, and zolmitriptan. Avoid PO if there is nausea early. Recurrence within 24 hours is decreased if co-administration with an NSAID. Can take up to 2 doses per day. In migraine with aura, the injectable form isn’t effective until the pain starts. “Triptan sensations” are chest and neck tightness and pressure that are probably d/t esophageal, pulmonary artery constriction or a change in metabolism of the chest wall muscles. Triptans are contraindicated in cerebrovascular disease, CAD; triptan-triggered cardiac events are rare. Beware serotonin syndrome in people taking SSRIs (altered mental status, autonomic instability, neuromuscular problems, GI upset) treatment is supportive and 5-ht antagonists cyproheptadine or methysergide Ergots Works on 5-HT2 receptors. Dihydroergotamine (DHE) is a venoconstrictor that is used to tx: status, inpt tx of intractable and med overuse headache. Use IV and give an antiemetic beforehand. This class is more likely than triptans to trigger a cardiac event b/c 5-HT2 is the major serotonin receptor in the coronary arteries. Because of this, don’t use triptans and ergots within 24 hours of each other. Steroids Have been shown to decrease the duration and frequency of migraines, but don’t work acutely and there are far better agents. Isometheptene The active ingredient in Midrin. You will notice that Fioricet and opioids are not on this list. That is because they are terrible drugs for headache and should be avoided aggressively.

Migraine Treatment Lifestyle changes Abortive No more than 2 times per week!!!! The patient needs to own the migraines and know how often they occur, triggers, etc. The medications that we prescribe all have side effects and they will get the most benefit by optimizing their lifestyle in addition to medications. Encourage your patients to track their headaches with use of a headache diary or phone app. Avoidance of sleep deprivation, triggers, stress, caffeine are all important. Underlying psychiatric comorbities should be addressed. TREAT EACH HEADACHE MAXIMALLY ---- HEADACHES BEGET HEADACHES. Preventing or minimizing CENTRAL SENSITIZATION is crucial for achieving rapid and sustained pain-free outcomes. The general rule with all abortive medications is to limit use to no more than twice per week. Any more than this will predispose to MOH and is an indication for preventative therapy. NSAIDs Can be useful if early and in large doses. Excedrin migraine contains acetominophen, aspirin, and caffeine. Triptans Work on the 5-HT1 receptors. Work well when given early. There are differences in pharmacokinetics between formulations in this class, so try a different brand if one triptan doesn’t work. Sumatriptan and zolmitriptan are available in a nasal spray. Sumatriptan is available as an injectable. PO formulations include almotriptan, eletriptan, frovatriptan, naratriptan, sumatriptan, and zolmitriptan. Avoid PO if there is nausea early. Recurrence within 24 hours is decreased if co-administration with an NSAID. Can take up to 2 doses per day. In migraine with aura, the injectable form isn’t effective until the pain starts. “Triptan sensations” are chest and neck tightness and pressure that are probably d/t esophageal, pulmonary artery constriction or a change in metabolism of the chest wall muscles. Triptans are contraindicated in cerebrovascular disease, CAD; triptan-triggered cardiac events are rare. Beware serotonin syndrome in people taking SSRIs (altered mental status, autonomic instability, neuromuscular problems, GI upset) treatment is supportive and 5-ht antagonists cyproheptadine or methysergide Ergots Works on 5-HT2 receptors. Dihydroergotamine (DHE) is a venoconstrictor that is used to tx: status, inpt tx of intractable and med overuse headache. Use IV and give an antiemetic beforehand. This class is more likely than triptans to trigger a cardiac event b/c 5-HT2 is the major serotonin receptor in the coronary arteries. Because of this, don’t use triptans and ergots within 24 hours of each other. Steroids Have been shown to decrease the duration and frequency of migraines, but don’t work acutely and there are far better agents. Isometheptene The active ingredient in Midrin. You will notice that Fioricet and opioids are not on this list. That is because they are terrible drugs for headache and should be avoided aggressively.

Preventive Rx Class A Evidence Propranolol 80-240mg daily is target dose Topiramate 25-150mg daily Butterbur Class B Evidence Amitriptyline 25-150mg daily Venlafaxine 37.5-150mg daily Magnesium sulfate 400mg daily Riboflavin Feverfew A special case Onabotulinum toxin There are more within each class, but here are the ones with which you should be familiar. When to consider migraine prevention therapy: More than 3 HA/month Significant interference with daily activity Acute meds are ineffective, contraindicated, or overused Adverse effects from acute meds Patient preference for prevention Special circumstances i.e. elderly, pregnant, pediatric Patients should have a trial of 2 months, at a minimum. You can see that there are some non-standard substances on here. Ensure that your patients buy quality product and try to stick with things that come from our pharmacy i.e. mg if possible. Topiramate: Start with 25mg daily and titrate up by 25mg daily every week to a goal dose of 100mg daily Elavil: start with 10 and titrate up each week to 50.

Treat migraine early

Serotonin Syndrome May develop when triptans are used with selective serotonin or serotonin/norepinephrine reuptake inhibitors (remember tramadol also) Agitation Abnormal eye movements Fever Hyperreflexia Muscle clonus Tachycardia Alterations in blood pressure Tramadol and its active metabolite bind to mu-opiate receptors in CNS and also inhibit reuptake of NE and serotonin. If you suspect serotonin syndrome, stop the meds and get patient to emergent evaluation.

What to AVOID OPIOIDS FIORICET Too many NSAIDs

What goes wrong with prevention tx? Wrong drug Excessive initial dose Inadequate final dose Duration of treatment too short Combination treatment required Non-compliance Medication overuse headache nullifies preventative Unrealistic expectations Failure to provide acute treatment for breakthrough

Parenteral Rx for intractable H/A Dihydroergotamine (DHE) 0.25 – 1mg Diphenhydramine 25-50mg Prochlorperazine (Compazine) 5 – 10mg IV slow Metoclopramide 10-20mg IV Ketorolac 10mg IV or 30mg IM Mg SO4 1gm IV Steroids-dexamethasone 10mg IV Sumatriptan 6mg SC Opioids are not a proper treatment for migraine

Medication Overuse Headache Doesn’t take much to transform to MOH Fioricet 5 days/month Opioids 8 days/month Triptans 10 days/month NSAIDs 10-15 days/month This is the second most common headache type I see in clinic and can be very difficult to treat. MOH causes structural and functional brain changes that predispose to more headaches. These patients wake up with headaches because they are withdrawing from medication overnight. As part of the withdrawal, they can have autonomic symptoms (runny nose, eye tearing). Don’t get tricked into thinking this is cluster headache.

MOH Treatment Steps 100% wean off overused medications over 4 weeks ****Extreme caution when weaning patients off benzos, barbiturates, or opioids. May need to be done as inpatient!! This is a difficult treatment plan for most patients. They have grown accustomed to habitual use of medications and will have increased pain during the tapering process. Cold turkey generally isn’t going to work because patients will not comply. I cannot emphasize enough the importance of caution when weaning BZD, barbs, opiates, and caffeine. Make the diagnosis Educate the patient, set expectations Establish a preventative medication Place strict limits on use of abortive medication and AVOID FIORICET AND OPIOIDS Can use high-dose prednisone for 2 weeks as a bridge if wean is intolerable Medrol dose pack is insufficient

A 41-year-old man came to the ER complaining of severe, pounding right periorbital headaches associated with nasal congestion and rhinorrhea lasting about 45–60 minutes. He had experienced his third episode that night and was unable to fall asleep. He had a similar episode 6 months ago. On examination, temperature was 37.4°C, HR was 96 per minute, BP was 135/85 mmHg, and RR was 16 per minute. He was restless with normal cognition. Neurological examination revealed right conjunctival injection, miosis, and eyelid ptosis. Is this a migraine? (No) Is this a primary headache? (probably) What is the dx? (episodic cluster) What needs to be done in the ER? (treatment, referral to neurology as outpatient) What is the treatment? (high-flow O2…10-12L/min, SC sumatriptan)

Cluster Headache (trigeminal-autonomic cephalgias) Intense unilateral pain Shorter than migraine Autonomic symptoms Males more commonly than females    Peak occurrence in 20s    Tobacco and alcohol use common    Distinct facial characteristics    Cycles begin near summer and winter solstices    Individual attacks occur same time of day in given patient    Attacks commonly occur during sleep    Pain lasts 15 minutes to 2 hours    Strictly unilateral    Eye and temple region    “Hot poker” pain description    Rhinorrhea    Lacrimation    Partial Horner syndrome Paces, doesn’t want to stay still. (Cf Migraine behavior – lying in dark)

Pregnancy Issues Natural history of migraine in pregnancy Risk vs benefit Many migraines improve during pregnancy. Goal is to use the minimal number of medications to achieve satisfactory control. Don’t make mother suffer. Magnesium 400mg daily is perfectly safe. Can use APAP and some can use triptans cautiously.

Summary History, history, history Green and red flags Treatment strategies

What if WE tried all that… Refer to Neurology Call our duty cell for questions 619-886-7741 Email me sarah.d.hodges3.mil@mail.mil We are here to help!