2. Secondary Headaches Noah Rosen MD FAHS Zucker Hofstra Northwell Health

3. Disclosures Allergan: Amgen: Promius Pharma: Supernus: Teva:
Advisory Board, Research Support, Speaker’s Panel
Amgen:
Advisory Board
Promius Pharma:
Supernus:
Teva:
Eli Lilly:
Advisory Board, Research Support
Curelator:
Consultant paid in options
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4. Learning Objectives
1. To recognize “red flags” for headaches with a discernable cause
Is it time to rename “secondary headaches”?
2. To reinforce understanding on how to diagnose, manage and treat dangerous and rapidly progressive headaches due to specific causes.
3. To review headaches that we may not encounter on a regular basis.
How much of our practice is primary headache disorders due to access reasons?
Who is actually taking care of these patients?
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5. DIAGNOSIS AND TESTING Detailed History and Examination NO Primary
Preliminary Diagnosis
Primary
Headache? NO
Secondary
Headache
Diagnostic
Testing
Atypical
Features
YES
The cause or type of most headaches can be determined by a careful history and physical examination. The clinical imperative is to recognize the warning signals, which should raise red flags and prompt further diagnostic testing.
In the absence of worrisome features in the history or examination, the task is then to diagnose the primary syndrome based upon the clinical features. If there are atypical features or a lack of response to conventional therapy, the diagnosis should be questioned and the possibility of a secondary headache disorder revisited.
Since migraine and TTH account for over 90% of the primary headache disorders in clinical practice, this discussion will focus on their clinical features, the warning signals of serious secondary headaches, and the role of diagnostic testing in the evaluation of headache.

6. The Best 2 Tools We Have History Exam PE Headache onset Duration
Location
Severity and Quality
Associated Features
Aggravating Factors
Exam
General exam!
Neurologic exam HX
The diagnosis of headache is based on a thorough history of headache, general medical history, and a detailed physical and neurological examination.1 Some primary headache syndromes such as migraine and cluster headache are usually easily recognizable based on clinical observations and history. In other headaches that do not fit specific patterns, appropriate diagnostic tests should be performed. In addition to ruling out structural or organic conditions that cause headache, these tests serve as a reassurance to an anxious patient who is worried about an impending serious illness as the cause of headache. Fear of a brain tumor, aneurysm, or other structural abnormality is common among the headache population. Patients consult a physician not only for relief of pain but for an explanation of their pain.2 Therefore, reassurance is important in the successful management of patients with chronic recurrent headache, once organic causes have been ruled out.
1Mathew NT. Diagnostic testing in headache. In: Headache: A Clinician’s Guide to Diagnosis, Pathophysiology, and Treatment Strategies. Rapoport AM, Sheftell FD, eds. PMA Publishing Group, 1993,
2Packard RC. What does the headache patient want? Headache 1979;10: PE

7. SNOOP (or some variation…)
Systemic disease or Symptoms (or Secondary risk factors)
Malignancy
Fever
Weight loss
Neurologic signs or symptoms
Onset that is sudden (acute or thunderclap)
Onset “later in life”. (Older age of onset) Use the epidemiology!!!
Previous headache history with new or different headache features
Progressive
Postural
Precipitation by Valsalva or exertion (distinguished from simply worsening with movement)
…. Pregnancy…. Papilledema….

8. Organic Causes for Headache Missed by CT Scanning
Cerebrovascular
Arterial dissection (MRA)
Cerebral venous sinus thrombosis (MRV)
CNS vasculitis
Meningoencephalitis
Tumors
Posterior fossa
Pituitary
Leptomeninges
High and low intracranial pressure syndromes
Organic Causes for Headache Missed by CT Scanning
Routine CT or MRI scanning are not recommended for routine evaluation of headache. However, specialized imaging techniques, such as contrast enhancement, can provide critical diagnostic information under appropriate circumstances. In the magnetic resonance venography image presented, a venous sinus thrombosis causes contrast material to illuminate the superior subarachnoid sinus (arrow).
Sinus thrombosis may present clinically as a thunderclap headache (a type of headache that more often is seen with subarachnoid hemorrhage).
Bousser MG, Good J, Kittner SJ, Silberstein SD. Headache associated with vascular disorders. In: Silberstein SD, Lipton RB, Dalessio DJ, eds. Wolff’s Headache and Other Head Pain. 7th ed. New York: Oxford University Press; 2001:
Practice Parameter: the electroencephalogram in the evaluation of headache. Neurology. 1994;45:
Silberstein SD. Practice Parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:
MRA = Magnetic resonance angiography
MRV = Magnetic resonance venography
Bousser MG, et al. In: Wolff’s Headache and Other Head Pain Dodick DW. Adv Stud Med. 2003;3:S550-S555.

9. Headache Diagnoses Missed by CT
Vascular
Saccular aneurysms
SAH
AVM
Carotid or vertebral dissection
Stroke
Cerebral venous sinus thrombosis
Vasculitis
RCVS
Neoplastic
Parenchymal and extra-axial neoplasms (esp in posterior fossa)
Meningeal carcinamatosis
Pituitary tumor/hemorrhage
Brain metastasis
Infectious
Meningoencephalitis
Cerebritis and brain abscess
Cervicomedullary lesions
Chiari malformation
Foramen magnum meningioma
Acoustic neuroma
Other
CSF leak/intracranial hypotension
Intracranial hypertension
Dural and leptomeningeal disease

10. What to discuss…

11. Too Many Headaches to Cover!!!
Will focus on selected disorders:
Headaches secondary to Vascular Disorders
Headaches associated with Spinal Fluid Disorders
Headaches associated with CNS Infections
Potpourri
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12. Vascular Headaches…

13. Secondary Headache: Subarhachnoid Hemorrhage
First or worst Headache
Often missed
Maximum headache in <60sec
LOC, focal findings, seizures, cardiac death
Early CT +in > 90%, LP + early in 100%

14. Subarachnoid Hemorrhage: Beware of Blood in the PITS
Parenchymal
Intraventricular
Truncal
Sulcal
Self-explanatory

15. Subarachnoid Hemorrhage
Risks: rebleed and vasospasm
Early surgery,
then increase perfusion
10% have multiple aneurysms
Best evidence: control blood pressure!

16. Intracerebral Hemorrhage
Focal deficits plus headache
Progresses quickly
Difficult to arouse
If hemosiderin staining
And young
Think cavernoma
If older
Think Amyloidosis

17. Reversible Cerebral Vasoconstriction Syndrome (RCVS)
Most commonly precipitated post-partum or with the use of vasoactive substances
Cannabis
Cocaine
SSRIs
Binge drinking
Nasal decongestants
May result in:
SAH
ICH
Stroke
PRES
Treated with IV/PO calcium channel blockers
Ducros et al. Brain 2007; 130:

18. Temporal/ Giant Cell Arteritis
Age >60 with subacute onset of headaches
High risk to involve ophthalmic artery, posterior ciliary arteries, or branch of external carotid
Less common: cerebral and coronary arteries
Could be considered subset of primary CNS vasculitis
Symptoms:
visual loss (arteritic anterior ischemic optic neuropathy)
-Also
Temporal artery tenderness, weight loss, malaise, fever, chills, and jaw claudication
Polymyalgia rheumatica common

19. Treatment: High dose steroids (sometimes other immune suppressants
Giant Cell Arteritis
Lab: ↑↑ ESR
Also, Anemia, leukocytosis and elevated liver enzymes
Diagnosis: Need temporal artery bx although increasing evidence for ultrasound
Treatment: High dose steroids (sometimes other immune suppressants
CD4 Lymphocytes and macrophages

20. From blood vessels to spinal fluid…
Pressure Disorders:

21. Pseudotumor Headache: Unremarkable daily headache
May have coocurrence with migraine
Pulsatile tinnitus, TVOs
Papilledema
Enlargement of blind spot
Loss of inferonasal field
other
6th Nerve palsy in 10 – 20%
Empty Sella
Lateral Sinus Abnormality

22. Pseudotumor Risk factors include female gender and obesity
Not all cases are idiopathic
Increased risk of thrombosis with cigarette smoking and with the use of oral contraception.
NORDIC IIHT trial demonstrated safety and efficacy of acetazolamide for pseudotumour
38/86 tolerated the 4 grams per day in study
There is mixed evidence for the use of stenting
Shunts are possible, but complications common
Optic Nerve Fenestration is option to preserve vision

23. MRI Findings in Pseudotumor
gadolinium-enhanced MR venography findings in patients with IIH. LAO and RAO segmented maximum intensity projections on (A and B) Patient 77; (C and D) Patient 36; and (E and F) Patient 8. (A) Discontinuities (scored as = 0) are seen (arrows) in the right transverse sinus in (B). Examples of extralumenal compressive stenoses are seen (open arrows) in (B–F). Examples of intralumenal obstructions are seen bilaterally (arrowheads) in Patient 69 in (G and H).

24. 7.2 Headache attributed to low cerebrospinal fluid pressure

25. 7.2.1 Post-dural puncture headache
A. Headache worsens within 15 minutes after sitting or standing and improves within 15 minutes of lying and has at least 1 of the following
Neck stiffness, tinnitus, hypacusia, photophobia, nausea
B. Dural puncture has been performed
C. Headache develops within 5 days after dural puncture
D. Headache resolves either:
Spontaneously within 1 week
Within 48 hours after effective treatment of the spinal fluid leak (usually by blood patch)
(True in 95% of cases)

26. 7.2.2 CSF Fistula Headache
A. Headache worsens within 15 minutes after sitting or standing with at least one of the following:
Neck stiffness, tinnitus, hypacusis, photophobia, nausea
B. A known procedure or trauma has caused persistent CSF leakage with at least one of the following:
Evidence of low CSF pressure on MRI
Evidence of CSF leakage on myelography, CT myelography or cisternography
CSF pressure <60mm H2O in sitting position
C. Headache develops in close temporal relation to CSF leakage
D. Headache resolves within 7 days of sealing the CSF leak

27. 7.2.3 Headache Attributed to Spontaneous (Idiopathic) CSF Leak
A. Diffuse or dull headache that worsens within 15 minutes after sitting or standing with at least one of the following:
Neck stiffness, tinnitus, hypacusia, photophobia, nausea
B. At least one of the following:
Evidence of low CSF pressure on MRI
Evidence of CSF leakage on myelography, CT myelography or cisternography
CSF pressure <60mm H2O in sitting position
C. No history of dural puncture or other causes of CSF Fistula
Headache resolves within 72 hours after epidural blood patching

28. MRI Signs of Intracranial Hypotension
Diffuse pachymeningeal (dural) enhancement
Bilateral subdural effusion/hematomas
Downward displacement of brain
Enlargement of pituitary gland
Engorgement of dural venous sinuses
Prominence of spinal epidural venous plexus
Venous sinus thrombosis & isolated cortical vein thrombosis
AJNR 2008.; 29:

29. Diffuse Pachymeningeal, (Dural) Enhancement
Diffuse, uniform thickness
Located at convexity, along falx cerebri, tentorium & posterior fossa dura
Disappears after successful treatment
JAMA 2006.;295(19):
AJNR 2008.; 29:853-56

30. Bilateral Subdural Effusion/Hematomas
Incidence: 10-50%
Tend to be thin (2-7 mm), typically occur over supratentorial convexity
Have variable MR signal, depending on protein conc. & presence of blood
Disappear after successful treatment

31. Downward Displacement of The Brain
Low lying cerebellar tonsils
Effacement of prepontine cistern, flattening of pons against clivus
Effacement of perichiasmatic cistern with bowing of optic chiasm over pituitary fossa

32. Engorgement of Dural Venous Sinuses
On T1W the middle 1/3 of dominant transverse sinus, shows convex borders
All venous sinuses become engorged
The falx & tentorium show marked enhancement
AJNR 2007 ; 28:

33. Spinal Extradural Fluid Collections
From: AJNR 2009.; 30:147-51

34. Prominent of Epidural Venous Plexus
Patients may even present with a compressive myelopathy due to a prominent venous epidural plexus.
AJNR 2009.; 30:147-51

35. Complications
Patient with known intracranial hypotension who rapidly deteriorated shows cerebellar, brainstem & cord infarctions.
AJNR 2009, doi: /ajnr.A1749

36. Intracranial hypotension due to Post op spinal CSF leak
Patient had a tumor resection from the thoracic vertebrae & developed intracranial hypotension found to be due to paraspinal thoracic pseudomeningocele.

37. CSF leak complicated by cortical vein thrombosis
Iatrogenic- post LP- intracranial hypotension with cortical vein thrombosis (arrow).

38. Hypermobile joints sometimes seen in those with SIH
Spinal Fluid Leaks
SEEPS
Subdural fluid collection
Enhancement of meninges
Engorgement of veins
Pituitary hyperemia
Sagging of brain
Self-explanatory
Hypermobile joints sometimes seen in those with SIH

39. CNS Infections

40. Meningitis
Headache, fever, stiff neck, confusion, decreased consciousness and cranial neuropathies
Bacterial: Rapidly declining… CT, LP, antibiotics ASAP
Viral/Aseptic: Slower onset, “less sick”, lesson from Mollaret
Chronic/Fungal/TB: Cranial neuropathies more common, stiff neck less common. Often requires high volume tap to obtain positive cells.

42. Meningitis

43. Bacterial Meningitis:
Acute Meningitis
Bacterial Meningitis:
LP shows elevated PMN’s, elevated protein and reduced glucose.
treat adults with Ampicillin and Ceftriaxone pending cultures.
Viral Meningitis/ Encephalitis:
LP shows mild increase of lymphocytes, increased protein and normal glucose
Can include enteroviruses, lymphocytic choriomeningitis virus, HIV, as well as many others.

44. Chronic Meningitis Tuberculosis: Neurosyphilis:
LP shows increased lymphocytes, elevated protein and low glucose. Large volume tap gives 50% yield of acid fast mycobacteria.
Treat with four drugs for 1st 2 months until sensitivity is known.
Neurosyphilis:
Primary, Secondary, Tertiary
Gummas, aortitis, chorioretinitis
Three major syndromes: tabes dorsalis, Argyll Robertson pupils, general paresis of the insane.
LP for VDRL- may consider FTA-ABS in late syphilis.
Treat with Penicillin 2.4 million units IM weekly for 3 weeks if non neurologic. Otherwise treat Penicillin G 2-4 million units IV q4 for 10 days.

45. Chronic Meningitis Lyme Disease: Fungal Meningitis
Mononuclear pleocytosis with increase protein. Can send PCR for Borrelia or detect IgG antibodies via ELISA or Western Blot.
Ceftriaxone 2 g IV qday or Penicillin G 4 million units IV q 4 for 2-4 weeks.
Fungal Meningitis
Can include Cryptococcus, Coccidioides, Candida, Histoplasma, Blastomyces
LP shows mononuclear increase, elevated protein and near normal glucose.
Treat with Amphotericin B or some with fluconazole.

46. Leptospirosis
Spirochetal disease most often Leptospira Interrogans from cats, dogs, etc.
Fever, chills, myalgia, nausea, diarrhea, meningitis, hepatitis, renal failure.
CSF shows mononuclear pleocytosis with elevated protein
Treat with doxycycline 100mg IV q12 or Penicillin G 5 million units IV q6 for 7 days.

47. Brain Abscess Bacterial Abscess Subdural Empyema
Subacute progressive headache (75%), altered mental status(70%), focal neurological signs(50%), fever (50%)
Ring enhancing lesion; pathogen by CSF 10%, by biopsy 80%
Look for extradural cause
Treat empirically with oxacillin 2g IV q4 (or penicillin G), Metronidazole and Ceftriaxone. Consider Amphotericin B
Subdural Empyema
Cranial and Spinal Epidural Abscess
High dose dexamethasone 60 to 100mg IV push followed by mg q6 (and call surgery!).
Vancomycin and Ceftriaxone
Toxoplasmosis
Sulfadiazine and pyrimethamine, Clindamycin
Cysticercosis

48. Herpes Simplex Encephalitis
Viral Encephalitis
Herpes Simplex Encephalitis
Acyclovir mg/ kg IV q8 for 2-3 weeks.
Phenytoin
Consider Steroids
Mumps, Enterovirus, Arbovirus (Equine, St. Louis, California, colorado tick virus, West Nile, Zika, Chikungunya, Dengue)
Measles virus
Rabies Virus
Epstein Barr virus
Cytomegalovirus
Whipple’s Disease
Elizabethkingia

49. Approach to the patient (The Basics)
Think- Fever, Headache, Neurologic Sign
History and Exam
Acute or Chronic
Predisposing Factors (diabetes, EtOH abuse, Malignancy, Steroids, chemotherapy, AIDS)
Systemic Infection (endocarditis, pneumonia, osteomyelitis, skull fracture, otitis media, tick bite, animal bites)
Exam should include: signs of fever, headache, change in mental status, focal weakness and back pain, as well as: papilledema, meningismus, skin rash, sinus tenderness, spine tenderness.
Lumbar Puncture

50. Fever, Headache, Change in Mental Status
Lumbar Puncture
Fever, Headache, Change in Mental Status
Consider CT imaging if: Papilledema, Focal Neurologic Deficit (especially brainstem), Known Intracranial Mass Lesion, AIDS, Lethargy, Stupor or Coma
Don’t Forget Your Opening Pressure!!

51. Cervicogenic Headache
Headache caused by disorder of cervical spine (bone, disc and soft tissue) demonstrated by clinical, laboratory and/ or imaging evidence
Need at least 2 of 4:
Headache developed in temporal relation to onset of disorder
Headache significantly improved or resolved in parallel with improvement of cervical disorder
Cervical range of motion reduced and headache worsened with manoeuvers
Headache abolished following diagnostic blockade of cervical structure or nerve supply
Not better accounted by another diagnosis!
HA attributed to cervical myofascial pain
HA attributed to upper cervical radiculopathy

52. Temporomandibular Joint Disorder
Temporomandibular joint dysfunction is an umbrella term covering pain and dysfunction of the muscles of mastication (the muscles that move the jaw) and the temporomandibular joints 
More common in young adults
Pain in jaw and ear, restricted movement, lateral motion, locking up, difficulty chewing
Treated with exercises, bite plates, injections, muscle relaxants, relaxation
Causes: Trauma, Arthritis, Disk erosion, Inflammatory conditions

53. Some Other Secondary Headaches
Subdural hematoma
Ischemic stroke
Transient ischemic attack
Cervicocephalic arterial dissection
Cerebral venous thrombosis
Unruptured arteriovenous malformation
-Postcarotid endarterectomy
Bell’s palsy – associated with retroauricular pain
Brain tumors and abscesses
Dental abscesses
Sinusitis
Trigeminal neuralgia
Low-CSF pressure headache
Acute glaucoma
Arterial hypertension

54. Thanks William Young and Stephen Silberstein
Rashmi Halker Singh and all of our speakers
My kids…