Headache Flashcards

Question

Benign Paroxysmal Torticollis

Answer 1

Recurrent episodes of head tilt to one side, perhaps with slight rotation, which remit spontaneously. Occurs in infants and small children, with onset in the first year.

Answer 2

Episodic attacks, stereotyped in an individual patient, of intense nausea and vomiting lasting from 1 hour to 5 days

Answer 3

Preceded by a mild head bump, first manifestation of migraine, rare (consider other mimics IE seizures)

Answer 4

Age \> 50 years History of malignancy or immunocompromised state Pregnancy Associated symptoms (fever, weight loss) Worse with postural changes or Valsava maneuvers Thunderclap onset Adult with headache (2020): HA begins after age 50 Sudden-onset HA Accelerating pattern of HA New-onset HA in a patient with cancer, immunosuppressed, HIV HA with systemic illness (fever, rash, stiff neck) Focal neurological symptoms of signs (other than typical aura) Papilledema Child with headache Aura \> 1h Persistent neurologic findings/exam between headaches Occipital headaches Loss of vision at headache peak Change in headache pattern Decline in cognitive function Changing growth velocity Headache red flags include systemic symptoms (fever, chills, and weight loss), history of prior cancer or immunodeficiency, focal neurologic signs or symptoms, new headache with onset to peak of seconds to minutes (thunderclap), “first or worst headache,” new- onset headache after age 50 years, precipitation by exertion, strain, or positional changes, increasing headache frequency and severity, and new-onset seizures.

Answer 5

Subarachnoid hemorrhage Intracerebral hemorrhage Reversible cerebral vasoconstriction syndrome Cerebral venous thrombosis Spontaneous intracranial hypotension Arterial dissection Pituitary apoplexy Third ventricular colloid cyst Pheochromocytoma

Answer 6

CSF hypovolemia Causes of CSF leak: 1. Dural weakness of nerve root sleeves 2. Dural tear from disk herniation 3. CSF-venous fistula Headache characteristics – Positional, orthostatic – Worsened with cough, valsalva Accompanying symptoms – Neck stiffness – Tinnitus – CN deficits – Limb parasthesias Dx/Tx Lumbar puncture of limited benefit Brain MRI with and without contrast CT myelography (slow leaks) vs. heavily T2-weighted spinal MRI/MR myelography • Treat with blood patch – blind versus targeted

Answer 7

Onset within 7 days of head injury Similar mechanisms and presentation as migraine although differences shown in fMRI and in reported autonomic symptoms

Answer 8

68% of migraine patients report neck pain Cervical MRI not that helpful Other causes of neck pain and headache to consider: – Cervical dystonia – Cervical carotid or vertebral artery dissection – Occipital neuralgia Treatment of cervicogenic headache • Anti-inflammatories, Neuropathic pain meds, physical therapy • Anesthetic blockade (+/- steroid) – Greater occipital nerve, lesser occipital nerve, third occipital nerve, facet joints (C2/C3), segmental nerve roots

Answer 9

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy • Autosomal dominant • Missense mutation in NOTCH3 gene, chromosome 19q13.1

Answer 10

Mitochondrial Encephalopathy with Lactic Acidosis and Stroke Mitochondrial inheritance

Answer 11

Most common headache type (prevalence up to 80%) Mild to moderate, bilateral Pressure, squeezing, band-like Rarely with associated symptoms MOA: Poorly understood Thought to be due to muscle tension and myofascial trigger point Excitation of peripheral nociceptors Chronic form may be due to central sensitization Treatment of tension type headaches: Very few studies Non-pharmacologic approaches – biofeedback, physical therapy Acute – acetaminophen, NSAIDs Preventive – amitriptyline

Answer 12

Unilateral pain (V1) and ipsilateral autonomic symptoms Restlessness often present Important to rule out secondary headache and obtain brain MRI with attention to pituitary (and posterior fossa) fMRI studies of cluster headache and other TACs have shown posterior hypothalamic activation Long-acting autonomic symptoms with hemicrania is also a long TAC, responsive to indomethacin Think of it as minutes to seconds, minutes to hour, continuous for table attached

Answer 13

Unilateral orbital/temporal severe pain with autonomic features and migrainous features Attacks recur at the same time of day (1 to 8 times per day, 15 minutes to 180 minutes) Episodic 80%, Chronic 20% (unlike PH which is chronic) Cyclical (4-8 weeks) and Remits ( 6-12 months) Risk Factors: Males (3 males\>1 female), genetic (increased risk in 1st degree relative), smoking Circannual and 24-hour periodicity Episodic vs. chronic (if \> 1 year without remission or remission \< 3 months) Acute treatment: – Oxygen: 100% O2 at 12-15 lit/min by non-rebreather mask – Sumatriptan 4-6 mg SQ or zolmitriptan 5-10 mg intranasal – Lidocaine nasal spray 4-10% – GammacoreVNS Transitional treatment: – Prednisone taper (e.g. 80 mg x 3 days, 60 mg x 3 days, 50 mg x 3 days, 40 mg x 3 days, 30 mg x 3 days, 20 mg x 3 days, 20 mg x 3 days, 10 mg x 3 days, then stop) – Ipsilateral greater occipital nerve block with steroids (lidocaine + dexamethasone) Preventive treatment (start as soon as cluster begins): – Cluster headache preventive therapy should be started immediately at the beginning of a cluster period in episodic cluster. If the cluster periods become chronic (\<1 month headache-free period per year) or are significantly increasing in duration, preventive therapy should be continued indefinitely. Preventive therapy should be thought of as “verapamil plus.” Plus includes VPA, Lithium, Melatonin. – Verapamil – 360-560 mg/d, although can reach 960 mg/d (check EKG!) – Lithium 600-900 mg/day (aiming for level of 0.6-0.8) – Gammacore VNS (FDA approved for preventive treatment of episodic and chronic cluster) Any medication taken by mouth is a poor choice for acute treatment of cluster headache because cluster attacks peak very rapidly, so a fast onset of action is needed to abort the headache quickly. Triptans can be used, but the choice would need to be a formulation with a rapid onset of action, such as sumatriptan subcutaneous injections, sumatriptan nasal spray, or zolmitriptan nasal spray. Sumatriptan subcutaneous needle-free drug delivery system may also be used. Oxygen is very effective as an abortive for cluster and is often used as a first-line treatment. All of the other choices (sumatriptan SC injection, DHE SC injection, zolmitriptan nasal spray, intranasal lidocaine) listed previously, except for frovatriptan, are used for acute treatment of cluster.

Answer 14

Often presents \> 50 years old Awakens patients ~ 2-4 am Preventives: caffeine, indomethacin at bedtime Acute: caffeine, triptans

Answer 15

``` Common in patients with migraine Variable location (as opposed to neuralgias) Indomethacin responsive, also responsive to gabapentin ```

Answer 16

Distinct onset, often preceded by infection or trauma Migraine versus tension-type phenotype Often difficult to treat Begins abruptly, patients will recall exact date it started Exam and workup up normal Continuous and unremitting Persists for more than 3 months Must rule out secondary causes of headache Doesn’t have all typical characteristics of other primary headache types. The diagnosis of NDPH requires a distinct and clearly remembered onset of a continuous and unremitting headache, and it must be present for more than 3 months. Secondary causes or other diagnoses must also be excluded. In general, the pain of NDPH lacks characteristic features and may be migraine-like or tension-type-like, or have overlapping features of both.

Answer 17

Brief, lancinating, “electric shock” pain Usually in distribution of V2 or V3 Often has cutaneous triggers Get brain MRI for underlying cause (most commonly vascular compression) Medications (carbamazepine, oxcarbazepine), other treatments include lamotrigine, topamax, and gabapentin Surgery (microvascular decompression) The diagnosis of trigeminal neuralgia requires at least three attacks of unilateral facial pain in the trigeminal nerve distribution (one or more divisions), with no radiation outside the boundaries of this territory. Characterization of the pain includes recurrent attacks lasting a fraction of a second or up to 2 minutes, severe in intensity, shooting/electric shock-like/stabbing or sharp, and that could be precipitated by stimuli to the affected area. At least three of those four features are required, and there should be no focal neurologic deficit. Secondary causes or other diagnoses must be excluded. Hypoesthesia or hypoalgesia in the affected trigeminal region suggests axonal damage and trigeminal neuropathy, warranting further diagnostic workup to exclude an etiology.

Answer 18

Must have paroxysms of pain Can elicit Tinel sign over the nerve Should be eliminated using nerve block

Answer 19

Onset older: 40-70 yo. 1.5 males to 1 female Stabbing, burning, associated with tearing and eye redness SHORTEST and MOST ATTACKS: Only last 5-240 sec, 1-100 attacks per day. Often treatment refractory: Consider carbamazepine, lamotrigine, gabapentin, topiramate, or hypothalamic stimulation. IV lidocaine may work acutely. Rule out lesions of the skull base, which have been reported with SUNCT (sellar and posterior fossa tumors)

Answer 20

20-30 year olds, women\>men Frequent attacks: 7-22/day, AT LEAST 8 episodes per day Short lasting (5 minutes to 45 minutes) Unilateral, severe, BORING, pulsatile. Around eye w/ ipsilateral autonomic sx’s (V1) Diagnosis: MRI! Ddx: aneursym, AVM, pancoast tumor, etc Treatment: IndometHacin is tx of choice Defined by response to indomethacin as ppx No abortive tx Oxygen and tripans not effective

Answer 21

ICHD-3 Criteria Unilateral, present for \>3 months, with at least one of the following: - Conjunctival injection/lacrimation, nasal congestion/rhinorrhea, eyelid edema, forehead and facial sweating, miosis/ptosis - Sense of restlessness or agitation, or aggravation of pain by movement“ - Foreign body sensation”, misdiagnosed as migraine or chronic daily headache IndometHacin responsive Diagnostics: Most get MRI brain and C-spine Indomethacin trial is diagnostic (work up to 75mg TID for 1 week)

Answer 22

Autonomic symptoms ○ Overshadow headache and precede headache and continue after headache ○ No continuous “interictal” headache Lasts several days Unilateral headache IndometHacin sensitive

Answer 23

Those with H's in the name: Paroxysmal hemicrania Hemicrania continua LASH Also, primary cough headaches, primary stabbing headaches, and for some patients, primary headaches associated with sexual activity. In order to diagnose or exclude HC and PH, indomethacin should be used in a dose of ≥150 mg daily and increased up to 225 mg daily orally for at least a week (adequate trial generally requires up to 75 mg three times a day, but sometimes a higher dose is required), but for maintenance, smaller doses are often sufficient. It is reasonable to obtain a magnetic resonance (MR) image and magnetic resonance angiogram of the brain with and without gadolinium with thin cuts through the cerebellopontine angle and Meckel’s cave in patients presenting with suspected involvement of the trigeminal nerve, as in HC, trigeminal neuralgia, or any of the trigeminal autonomic cephalalgias.

Answer 24

Transient visual obscurations, pulsatile tinnitus, VI nerve palsies, papilledema, poor visual acuity Patient population: ○ Adult overweight woman. Children likely boy with normal body weight ○ Associated with tetracycline, minocycline, vitamin A containing compounds, or steroid withdrawal in chronic steroid user Diagnostics: LP with increased ICP (OP\>30) without a mass lesion. Also therapeutic acutely! Treatment: weight loss, acetazolamide/topamax

Answer 25

“Benign” lesions typically in the 3rd ventricle near/at at the foramen of Monroe Can cause intermittent hydrocephalus due to its “ball-valve” effect Results in positional headaches Sudden death has been reported with this lesion Avoid LPing!

Answer 26

At least 2 attacks fulfilling criteria A, B, and C: A. Aura consisting of both of the following 1. Fully reversible motor weakness 2. Fully reversible visual, sensory, and/or speech/language symptoms B. At least 2 of 4 characteristics 1. At least 1 aura symptom spreads gradually ≥ 5 min and/or 2 or more symptoms occur in succession 2. Each non-motor aura symptom lasts 5-60 minutes and motor symptoms \<72 hours 3. At least one aura unilateral 4. Aura accompanied, or followed within 60 mins by a headache C. Not accounted for by another diagnosis (TIA/Stroke excluded)

Answer 27

Monocular vision loss +/-HA Unlike visual aura visual deficit in BOTH eyes 2/2 vasospasm of the retinal circulation. Avoid vasospasm inducing medications. Headache ipsilateral to visual loss At least 2 reversible attacks lasting \<60 min associated with migraine headache DDx amaurosis fugax Prevention: calcium channel blockers in addition to typical migraine ppx +/- ASA

Answer 28

AKA Recurrent Painful Ophthalmoplegic Neuropathy Repeated attacks of one or more ocular cranial nerves with ipsilateral headache CN III most often involved (ptosis, pupillary dilation, exotropia, and diplopia). Long headache duration (up to a week or more) and a long latent period (up to 14 days) before the onset of ophthalmoplegia MRI post-GAD can show enhancement of the affected cranial nerve

Answer 29

≥ 2 episodes/year of migraine associated with severe, but episodic vestibular symptoms (eg.vertigo) Work up: Neuroimaging –normal, Vestibular testing (e.g. VNG) – may be abnormal Likely on spectrum with basilar migraine DDx: Meniere disease, Vestibular neuritis, Perilymphatic fistula

Answer 30

Rhinorrhea, lacrimation, sinus pressure, nasal congestion, and conjunctival injection frequently coexist with migraine because of trigeminal nerve (cranial nerve V) cross-activation of the parasympathetics via stimulation of the superior salivatory nucleus (SSN) of the facial nerve (cranial nerve VII). Migraine is frequently misdiagnosed as sinus headache because of these “sinus-like” signs and symptoms. It is important to re-emphasize the point that rhinorrhea, lacrimation, sinus pressure, nasal congestion, and conjunctival injection frequently coexist with migraine and many other headache disorders such as the others listed due to trigeminal nerve (cranial nerve V) cross-activation of the parasympathetics via stimulation of the SSN of the facial nerve (cranial nerve VII). Migraine is frequently misdiagnosed as sinus headache because of these “sinus-like” signs and symptoms.

Answer 31

Diagnosis of episodic tension-like headache requires episodic tension-type headache requires _10 headaches_, each lasting between 30 minutes and 7 days. The diagnosis requires at least two of those four features. Neither nausea nor vomiting is present, and there can be only one of either photophobia or phonophobia (either or neither, not both). Secondary causes or other diagnoses must also be excluded. In essence, the criteria for tension-type headache are the complete opposite for that of migraine headache, and this point can be helpful in differentiating between them.

Answer 32

1) Activation of hypersensitive “central generator” (it is debated whether the initiating trigger for migraine occurs in the cortex or in the brainstem, or both). → 2) Disrupted ion homeostasis, release of neurochemicals, and transient neuronal dysfunction (cortical spreading depression). → 3) Meningeal blood vessel dilation and activation of trigeminovascular system. → Release of vasoactive neuropeptides (calcitonin gene-related peptide (CGRP), neurokinins, prostaglandins, substance P, etc.) from activated trigeminal sensory nerves leads to sterile neurogenic inflammation. → 4) Worsening vasodilation, increasing firing of trigeminal afferents and further release of vasoactive neuropeptides causing pain intensification (the vasodilation itself is no longer felt to be the source of pain). → - This is where you want triptans to intevene- 5) Trigeminal nociceptive afferents carry pain signals to trigeminal nucleus caudalis (TNC) for processing and ascent through thalamus to cortex. → 7) Continuous ascending pain signals activate more neurons, leading to associated symptoms such as photophobia, phonophobia, nausea, and vomiting. → 8) Continuous TNC firing leads to central sensitization (allodynia) if activated pathways are not stopped (triptans have minimal to no effect at this stage; thus, the importance of early triptan administration).

Answer 33

A triptan combined with a non–steroidal anti- inflammatory drug (NSAID) for early treatment aimed at decreasing neurogenic sterile inflammation. oncurrent administration of NSAIDs with the triptan decreases the neurogenic inflammation, the cause of worsening migraine symptoms. The purpose of the triptan is to reverse meningeal vasodilation, prevent release of vasogenic neuropeptides from the trigeminovascular system, and interfere with return of pain signals to the brainstem. Intravenous DHE infusion would be reasonable and safe at this point because she has not had a triptan within the last 24 hours. Other intravenous (IV) medications commonly infused with DHE for additional benefit include antiemetics, magnesium, ketorolac, valproate sodium, and steroids. Dihydroergotamine, steroids, promethazine, and ketorolac can all be administered intramuscularly in the absence of infusion capability. Inhaled DHE appears to be as effective as IV DHE with less side effects, although it is not available for clinical use at the time this edition is written.

Answer 34

Other side effects to instruct the patient to be aware of when using topiramate include paresthesias in the digits, cognitive slowing, word-finding difficulty, kidney stone formation, and, rarely, acute angle closure glaucoma.

Answer 35

Computed tomographic sensitivity for detecting SAH is highest in the first 12 hours after SAH (nearly 100%), is about 92% sensitive for SAH within 24 hours, and it falls to around 58% by the end of day 5 postbleed. Lumbar puncture is best performed at least 6 hours after symptom onset and becomes very low yield at 3 weeks. If LP is obtained, an opening pressure should be measured, and the cerebrospinal fluid (CSF) should be sent for cell counts in tubes 1 and 4, protein, glucose, xanthochromia, and gram stain.

Answer 36

The triptans work as agonists at the serotonin receptor subtypes 5HT-1B and 5HT-1D. Agonism at 5-HT1B receptors -\>constricts the pain-producing intracranial, extracerebral blood vessels in the meninges (as well as 1D effects, B for both) Agonism at 5-HT1D receptors presynaptically inhibits trigeminal peptide release and interferes with central TNC nociceptive transduction and processing, whereas those of the nucleus tractus solitarius in the brainstem are thought to inhibit nausea/vomiting.

Answer 37

Parasympathetic outflow from the SSN of cranial nerve VII leads to activation of lacrimal and nasal mucosal glands. * Parasympathetic fibers travel with the greater superficial petrosal nerve of cranial nerve VII to the sphenopalatine ganglion, synapse, and then travel with the maxillary division (second division; V2) of cranial nerve V to the lacrimal glands. → Lacrimation * Parasympathetic fibers also travel in the lesser superficial petrosal nerve of cranial nerve VII to the otic ganglia. * There is a brainstem connection between the TNC and the SSN causing the trigeminal-autonomic reflex. This reflex is activated by a noxious stimulus applied to the trigeminal distribution. → Rhinorrhea For example, getting hit in the face with a ball will cause lacrimation and rhinorrhea.

Answer 38

Secondary headache disorders have many possible etiologies and are related to an underlying pathologic process. They are associated with an abnormal neurologic examination and/or abnormal diagnostic workup. A family history of brain tumor is not considered a typical “red flag,” although certainly something to keep in mind as you evaluate the patient. A common mnemonic used for headache red flags is SNOOP: * Systemic symptoms (fever, chills, and weight loss) or secondary headache risk factors (HIV and cancer) * Neurologic symptoms or signs (confusion, impaired consciousness, and focal findings) * Older: New-onset or progressive headache, especially \>50 years of age (temporal arteritis) * Onset: Sudden, abrupt (thunderclap) * Progression of headache (change in frequency, severity, or clinical features)

Answer 39

The duration of a cluster headache is 15 to 180 minutes. The diagnosis of cluster headache requires at least 5 _attacks of severe unilateral temporal, orbital, and/or supraorbital pain lasting between 15 and 180 minutes if untreated_. To make the diagnosis, there should be the presence of either agitation or restlessness and/or at least one autonomic sign or symptom on the side of the headache including conjunctival injection, lacrimation, facial sweating or flushing, rhinorrhea, congestion, sense of ear fullness, partial Horner’s syndrome (ptosis and/or miosis), or eyelid edema. _Attacks occur at a frequency ranging from one every other day to eight per day for more than 50% of the time during a cluster cycle_. Secondary causes or other diagnoses must also be excluded. Cluster headache is much more common in men, in contrast to HC and PH which are more common in women.

Answer 40

The diagnosis of PH requires at least _20 attacks_ of severe unilateral temporal, orbital, and/or supraorbital pain lasting 2 to 30 minutes. There should be at least one autonomic sign or symptom on the side of the headache including conjunctival injection, lacrimation, facial sweating or flushing, rhinorrhea, congestion, sense of ear fullness, partial Horner’s syndrome (ptosis and/or miosis), or eyelid edema. The attacks occur more than five times a day for more than 50% of the time. To make the diagnosis, the patient must respond completely to a therapeutic dose of indomethacin. Secondary causes or other diagnoses must be excluded.

Answer 41

SUNCT; short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing SUNA: Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms The diagnosis of short-lasting unilateral neuralgiform headache attacks (which include SUNCT and SUNA) requires at _least 20_ attacks of moderate to severe unilateral head pain in the temporal, orbital, supraorbital, and/or other trigeminal distribution. The duration of the pain ranges from 1 to 600 seconds and may occur as single or series of stabs. The attacks must have a frequency of at least once daily for more than 50% of the time when the disorder is active; however, the attacks generally occur in a very high daily frequency when active. At least one autonomic sign or symptom on the side of the headache is required to make the diagnosis, including conjunctival injection, lacrimation, facial sweating or flushing, rhinorrhea, congestion, sense of ear fullness, partial Horner’s syndrome (ptosis and/or miosis), or eyelid edema. Symptoms should not be attributable to another disorder. The difference between SUNA and SUNCT is that _SUNCT requires both conjunctival injection and lacrimation,_ whereas _SUNA requires only one or neither of conjunctival injection and lacrimation_. aSUNCT and SUNA are rare enough that an MR image without and with contrast should be obtained to rule out secondary causes, especially pituitary tumors or posterior fossa structural abnormalities.

Answer 42

The headaches are usually in the occipital region and precipitated paroxysmally by cough, bending forward, and Valsalva maneuvers. When symptomatic, there are other findings of brainstem compression or cervical cord compression, such as ataxia, visual disturbances, hoarseness, dysphagia, vertigo, nystagmus, hearing loss, and cervical myelopathy. The headache must have developed in temporal relation to the CM1, and/or the headache resolves within 3 months after treatment of the CM1. The headache is precipitated by a Valsalva-like maneuver such as coughing, and/or has an occipital or suboccipital location, and/or the headache lasts for \<5 minutes. The headache is associated with symptoms and/or findings of neurologic impairment such cranial nerve, brainstem, cerebellar, and/or cervical spinal cord dysfunction. Other causes or diagnoses must be excluded.

Answer 43

Type I involves only extension of the cerebellar tonsils into the foramen magnum - MC, can be acquired Type II involves extension of both cerebellar and brainstem tissues into the foramen magnum. The cerebellar vermis may be incomplete or absent. It is usually accompanied by a myelomeningocele, most commonly in the lumbar region, and usually results in partial or complete paralysis of the area below that level. The term Arnold-Chiari malformation is specific to type II malformations. Type III involves herniation of the cerebellum and the brainstem through the foramen magnum and into the spinal cord and is _associated with severe neurologic deficits. Part of the fourth ventricle may also protrude through_. _Rarely, the herniated cerebellar tissue and meninges are present in an occipital encephalocele protruding from the back of the head or the neck_. Type IV is rare, involves an incomplete cerebellum (cerebellar hypoplasia), and portions of the skull and spinal cord may be visible. The upper limits of normal for tonsillar descent by age are as follows: 6 mm for ages 0 to 10 years, 5 mm for ages 10 to 30 years, 4 mm for ages 30 to 80 years, and 3 mm for ages older than 80 years.

Answer 44

An MR image of the brain with gadolinium will often show pachymeningeal enhancement (dura arachnoid enhancement) and downward displacement of the brain and crowding of the posterior fossa due to the sagging and traction of intracranial structures and dura, which may mimic Chiari I malformation.

Answer 45

MRI myelography with fat suppression (CSF leak protocol) has come into favor more recently since there is no invasive need to puncture the dura in order to inject a dye or tracer, which can potentially cause a CSF leak if not already present, and there is no need for contrast administration.

Answer 46

Idiopathic intracranial hypertension occurs most commonly in young, overweight women. Most patients with IIH have a headache but not all. The headache itself does not have specific characteristics and is frequently described as retro-orbital, frontal, “pressure-like,” or explosive. They may complain of transient visual obscurations (seconds), graying of vision (especially with straining), diplopia from cranial nerve VI (abducens nerve) palsy, bilateral pulsatile tinnitus, nausea, and vomiting.

Answer 47

An early finding of increased intracranial pressure preceding papilledema is loss of spontaneous venous pulsations, although this can also be a normal variant. Disc margin splinter hemorrhages may be seen early also. Eventually, the disc becomes elevated, the cup is lost, and the disc margins become indistinct. Blood vessels appear blurred as they course the disc. Engorgement of retinal veins leads to a hyperemic disc. As the edema progresses, the optic nerve head appears enlarged and may be associated with flame hemorrhages and cotton wool spots as a result of nerve fiber infarction.

Answer 48

Topiramate is used because of its carbonic anhydrase inhibitor effect; it decreases CSF production. _Acetazolamide is the classic carbonic anhydrase inhibitor used, unless the patient has a sulfa allergy, which would make topiramate a better choice._ Treatment typically begins conservatively with measures such as weight loss, cessation of vitamin A (if toxicity is suspected), weaning steroids, and minimizing other potential risks. If there is no evidence of visual loss, some feel that treatment of the headache alone is sufficient. If there is evidence of visual loss, a carbonic anhydrase inhibitor such as acetazolamide or topiramate should be started. Hydrochlorothiazide is not a typical treatment of IIH. Procedures should generally be considered when there is progressive visual field defect, visual acuity loss from papilledema, and intractable headache while on maximal pharmacotherapy. Optic nerve fenestration can be done if visual loss is progressive on pharmacotherapy. Serial high-volume LP is no longer recommended because of the short-lasting effect and unnecessary patient discomfort and inconvenience. Procedures performed as a last resort include lumboperitoneal or ventriculoperitoneal shunt.

Answer 49

This patient’s history and family history are suggestive of CADASIL. This disorder presents with migraine with aura, stroke or stroke-like episodes, progressive dementia, and other neurodegenerative findings. This is an autosomal dominant disorder most often due to a missense mutation in the NOTCH3 gene, on chromosome 19q13.1 (like APOE4 , although splice site mutations and small in-frame deletions have also been reported. The NOTCH3 gene encodes a transmembrane protein thought to be involved in cell signaling during embryonic development. It can be diagnosed by genetic testing or skin biopsy. Magnetic resonance imaging of the brain will show confluent deep white matter changes. These deep white matter changes characteristically extend to the anterior temporal lobes/poles.

Answer 50

Although there are sporadic forms, she likely falls into the category of familial hemiplegic migraine (FHM) given her mother’s history. There are three types of FHM that are all autosomal dominant with variable penetrance. FHM1 is linked to chromosome 19p13 (CACNA1A gene), resulting in a defect in P/Q calcium-channel subunit. Additional FHM1 symptoms may include cerebellar involvement, such as gaze-evoked nystagmus or ataxia, also attacks of coma, prolonged hemiplegia, or both, but full recovery is the rule. Transient cerebral edema and cerebral atrophy are less commonly seen. FHM2 is linked to 1q23 (ATP1A2 gene), resulting in a defect in the A1A2 sodium–potassium ATPase channel. Additional FHM2 symptoms may include recurrent coma, frequent and long-lasting hemiplegia, or seizures with mental retardation. Cerebellar ataxia is not associated with FHM2. FHM3 is linked to chromosome 2q24 (SCN1A gene), resulting in defects of presynaptic and postsynaptic voltage-gated sodium channels.

Answer 51

The diagnosis of hemiplegic migraine requires at least _two attacks_ with an aura characterized by fully reversible weakness and fully reversible sensory, visual and/or speech– language symptoms. Other diagnoses or causes should be excluded, especially conditions such as transient ischemic attack, seizure, and stroke. There must also be at least two of the following features: A headache that occurs with the aura or follows the aura within 60 minutes. One or more aura symptoms that spread over 5 minutes or more and/or two or more symptoms develop in succession. Each motor aura symptom lasts less than 72 hours, and nonmotor aura symptoms last between 5 and 60 minutes. At least one aura symptom has to be unilateral.

Answer 52

In this syndrome, patients experience headache as well as other neurologic symptoms such as hemiparesis, ataxia, aphasia, and confusion. Patients have prominent leptomeningeal enhancement. CSF findings are variable but may show a lymphocytic pleocytosis. Leptomeningeal biopsy may show perivascular inflammation. Most often, the etiology is not determined; however, there have been cases seen in association with rheumatoid arthritis or vasculitis. It is essentially a diagnosis of exclusion when other infectious or inflammatory conditions are ruled out.

Answer 53

Nummular headache is an uncommon primary headache disorder with pain of variable duration (reported anywhere from seconds to days), but most commonly chronic (75%), in a small well circumscribed area of the scalp without any underlying structural lesion. Patients also often complain of variable sensory disturbances and/or tenderness in the affected area. It was previously named “coin-shaped headache.” The diagnosis of nummular headache requires the presence of head pain felt exclusively in an area of the scalp in an intermittent or continuous fashion. The pain should be round or elliptical with a fixed shape and sharply contoured, measuring between 1 and 6 cm in diameter. There should be no underlying cause.

Answer 54

Medications with the highest level A (strong) evidence established as effective for migraine prevention: topiramate, divalproex sodium, sodium valproate, metoprolol, propranolol, timolol, and Petasites (butterbur). Medications with level B (moderate) evidence are established as probably effective for migraine prevention and some of them include amitriptyline, venlafaxine, atenolol, nadolol, feverfew, riboflavin. Medications with level C (weak) evidence are established as possibly effective for migraine prevention and some of them include candesartan, lisinopril, carbamazepine, nebivolol, pindolol, clonidine, guanfacine, coenzyme Q10, and cyproheptadine. Some of the medications with level U (insufficient) evidence, which is conflicting or inadequate to support or refute the use for migraine prevention, include verapamil, nicardipine, nifedipine, nimodipine, gabapentin, fluoxetine, fluvoxamine, protriptyline, bisoprolol, and acetazolamide. There is no evidence for selective serotonin reuptake inhibitors (SSRIs) in the prevention of migraine.

Answer 55

The diagnosis of chronic migraine requires that the headache is present on 1_5 or more days per month_ for _more than 3 months_. It must occur in a patient who has had at least five attacks fulfilling criteria for either migraine without aura and/or migraine with aura. Also, on _8 or more days per month_ for _more than 3 months_, the patient must have migraine with or without aura and/or believed to have migraine at the onset, relieved by a triptan or ergot derivative. Secondary causes must have been excluded. At the time this book was being written, the only FDA-approved treatment for prevention of chronic migraine was onabotulinumtoxinA (Botox®). It was approved for this diagnosis in October 2010.

Answer 56

The primary mechanism of action of onabotulinumtoxin A is by cleavage of the SNAP25 protein, which is a SNARE (Soluble N- ethylmaleimide-sensitive factor Attachment protein Receptor). The heavy chain portion of the onabotulinumtoxin A neurotoxin binds to the cell membrane of the motor nerve. After binding, it passes through the cell membrane of the motor nerve and into its cytoplasm via endocytosis, where the enzymatic light chain of the onabotulinumtoxin A is activated. Inside the motor nerve, the light chain of the onabotulinumtoxinA cleaves apart the SNAP25 protein, which normally enables vesicles storing acetylcholine to attach to the cell membrane. Cleaving the SNAP25 prevents these vesicles from fusing with the membrane and prevents the release of acetylcholine into the neuromuscular junction. Thus, nerve transmissions that normally trigger muscle contractions are blocked. This effect generally lasts for approximately 3 months. _New nerve endings sprout and connect to the muscle after the original nerve ending is blocked, renewing the ability of the nerve to cause muscle contractions._ Therefore, onabotulinumtoxin A neurotoxin does not permanently alter the neuromuscular junction. Onabotulinumtoxin A effect in chronic migraine may be related to the blockade of the release of neuropeptides involved in the transmission of pain (including substance P, glutamate, and CGRP), theoretically reducing pain sensitization of peripheral nerves.

Answer 57

Topiramate has multiple mechanisms of action, including voltage-dependent sodium channel antagonism, enhancement of GABA activity through a nonbenzodiazepine site on GABAAreceptors, and antagonism of AMPA/kainate glutamate receptors.

Answer 58

Divalproex sodium primarily increases GABA effects and may inhibit glutamate/NMDA receptor-mediated neuronal excitation. .

Answer 59

Propranolol is a nonselective beta-adrenergic antagonist, including at sites in the central nervous system

Answer 60

The patient’s headache history is most consistent with hypnic headache. “Alarm clock headache” is an old term, and it is more common in women. Her neurologic examination is normal, she denies any other neurologic symptoms, and is asymptomatic in between headache attacks, which makes a structural etiology such as brain tumor less likely, although it should still be excluded. The diagnosis of hypnic headache requires the presence of recurrent attacks of headache developing only during sleep and causing the patient to wake up. _The headache must occur on 10 or more days per month for at least 3 months, lasting between 15 minutes and 4 hours after waking. There should be absence of restlessness or cranial autonomic symptoms._ Secondary diagnoses should have been excluded. Hypnic headache typically begins after the age of 50 years and is more common in the elderly rather than the younger. The pain is usually mild to moderate, but severe pain may be seen in some patients. Pain is bilateral in the majority of the cases. _There is limited data on optimal treatment, but some of the medications that are more commonly mentioned as possibly effective include lithium, indomethacin, caffeine, and melatonin. Duloxetine has the least evidence of the medications listed._

Answer 61

This patient has retinal migraine. It can often be difficult to differentiate between migraine with aura and retinal migraine, but if the visual disturbance is truly monocular, then retinal migraine is the diagnosis. The description of the visual disturbance (positive phenomenon, although negative phenomenon can also occur), the pattern and periodicity, young age, and the association of each event with a headache easily fitting migraine criteria make amaurosis fugax (would be negative visual phenomenon; vision loss such as the classic “lowering of a lamp shade”) very unlikely. The diagnosis of retinal migraine requires the presence of at _least two attacks_ associated with fully reversible aura consisting of monocular positive and/or negative visual phenomena. These visual phenomena should be confirmed during an attack by a visual field examination and/or the patient’s drawing of a truly monocular field defect. _The attacks must also include at least two of the following features: A headache that occurs with the aura or follows the aura within 60 minutes. The aura spreads over 5 minutes or more. Each aura symptom lasts between 5 and 60 minutes. Secondary causes including other causes of amaurosis fugax must be excluded._

Answer 62

Tension-type headache is the most prevalent primary headache disorder in the general population, although migraine is the most common primary headache for which patients consult with a physician.

Answer 63

Multiple studies including the Women’s Health Initiative Study have shown an association between women who have migraine with aura and increased stroke risk. In women younger than 45 years who have migraine with aura, there is a two-fold increased risk of stroke (not true for migraine without aura). This risk increases to six- fold with the use of oral contraceptives containing estrogen and nine-fold with the combination of smoking and oral contraceptive use. In women who have migraine with aura who are smokers, estrogen- containing contraception should be considered contraindicated. In women who have migraine with aura, but are not smokers, controversy exists regarding oral contraceptive use given the small but apparent increased risk of stroke. An interesting study presented at the American Academy of Neurology’s 65th Annual Meeting in San Diego in 2013 looked at almost 28,000 women older than 45 years who were followed up for 15 years. It reported that after high blood pressure, migraine with aura was the second strongest single predictor of heart attack and strokes. It came ahead of diabetes, current smoking, obesity, and family history of early heart disease. Migraine with aura predicted heart disease in women at an adjusted incidence rate of 8% versus an incidence rate of 10% for women with systolic blood pressure spiking at more than 180 mm Hg. T_his increased risk was not seen in migraine without aura_. It is not necessarily thought that migraine with aura causes the stroke, but rather migraine with aura is a marker for young women at a greater risk for cardiovascular disease. However, the reasons for these associations are unclear and likely multifactorial. The combination of traditional vascular risk factors still shows the strongest contribution to cardiovascular disease, so risk factors such as high blood pressure, smoking, diabetes and high cholesterol should be optimized, especially in those with migraine with aura to reduce risk of heart disease or stroke.

Answer 64

The American Migraine Prevalence and Prevention Study was a population-based study that followed patients with episodic migraine for up to 6 years for the development of medication overuse headache. It showed that medication overuse can transform episodic migraine to chronic migraine with butalbital compounds (such as Fioricet®) 5 or more days per month, opiates/opioids 8 or more days per month, triptan or combination analgesics 10 or more days per month, and non– steroidal anti-inflammatories (NSAIDs) more than 10 to 15 days per month. Therefore, the medications listed are much more common and likely to be associated with chronic migraine as opposed to an organic structural abnormality such as a brain tumor. This factor must be eliminated if present and the patients must understand that their headaches will never improve until a weaning detoxification from the overused medications happens, and this can commonly take at least 3 months for significant improvement to occur following detoxification

Answer 65

Hemicrania continua, paroxysmal hemicrania, LASH

Answer 66

Temporal (giant-cell) arteritis

Answer 67

MS, sarcoidosis, Lyme's disease

Answer 68

AD, chasm 19, NOTCH3. mutation

Answer 69

AD, chsm 19p13, CACNA1A gene, defective P/Q Ca2+ channel

Answer 70

AD, chsm 1q23, ATP1A2 gene, defective A1A2 sodium-channel ATPase channel

Answer 71

AD, chromosome 2q24, SCN1A gene, defective pre and post-synaptic voltage-gated Na channels