1. Randolph W. Evans, MD, FAHS Baylor College of Medicine, Houston, Texas
Epidemiology of Incidental Findings and Normal Anatomical Variants on MRI of the Brain for Primary Headaches in Adults
Randolph W. Evans, MD, FAHS
Baylor College of Medicine, Houston, Texas

2. Disclosures
Speaker’s bureau and advisory board: Alder, Allergan, Amgen/Novartis, Depomed, Lilly, TEVA. 
Royalties: Elsevier, Lippincott Williams&Wilkins, Medscape Neurology, Oxford, UpToDate
I have migraine
My wife and 3 children have migraine
One son has an incidental pineal cyst (case 1), another an incidental left anterior cranial fossa arachnoid cyst (case 2)

3. Case 1
This is a 32-year-old male with a history of increasingly frequent episodic migraine. MRI of the brain was normal except for a 7 mm pineal cyst. Another MRI of the brain 5 years later for chronic migraine showed no change in the size of the cyst.

4. Case 2
This is a 27-year-old male, the brother of case 1, with a history of headaches consistent with migraine without aura since childhood. Headaches have increased to twice a week in frequency. Past medical history is negative. Neurological examination is normal. Magnetic resonance imaging (MRI) of the brain shows a left anterior cranial fossa arachnoid cyst measuring 1.2-cm anteroposterior by 1.6-cm transverse by 1.5-cm craniocaudad without significant parenchymal compression. He is placed on a triptan with a good response.

5. Prevalence of Incidental Findings (IF) in normal volunteers
A meta-analysis of 16 studies, 19,559 people with a range of 1-97 years: IF 2.7% (excluded white matter hyperintensities, silent infarcts, microbleeds, and anatomical variants
206 people ages 9-50 yrs (mean 25.7) on a 3T scanner: IF 19%
203 volunteers ages yrs (mean 21.9) on 1.5 T scanner: variations of the normal in 30.5%, IF 9.4%
General population study of 1006 adults on 1.5 T scanner: IF 27.1%, two or more IF in 21.8%, and clinically relevant findings in 15.1%
General population study of 2000 people yrs (mean 63.3): asymptomatic infarct, 7.2% (ages y, 4%; yr, 6.8%; y, 18.3%); aneurysms, 1.8%; benign primary tumors, 1.6%; CM1, .9%;

6. Normal anatomic variants (NAV) are common
666 children (mean age 9.82) at tertiary pedi neuro practice: NAV in 17% (asymmetric ventricles, 2.1%; cavum septum pellicidum. 0.5%, cisterna magna enlargement, 0.2%; enlarged periventricular spaces, 3.8%; external hydrocephalus, 0.6%; pineal cyst, 1.8%; white matter abnormalities, 4.5%)
2536 healthy young men ages y (mean 20.5): NAV in 18.45% (cavum vergae, 4.77%; large basal cisterns, 1.74%; pineal gland cysts, 3.43%; enlarged perivascular spaces, 2.56%; asymmetry of the lateral ventricles, 2.68%; occasional white matter lesions, 2.6%; ossification of the cerebral falx, 0.32%; and empty sella, 0.35%.

7. Discuss chance of IF with patients and family before you order the MRI scan. Will decrease potential anxiety and save you time!

8. Unruptured saccular intracranial aneurysms (UIA)
Patients and their families are often concerned they have an aneurysm as the cause of their primary headache
About 3.2% of the adult population has an UIA which develops over the life course with a mean age of 50 years % have more than 1
In ages 30 yrs and older: females:males=1.61 and over 50 yrs, 2.2
Risk factors: family history, hypertension, hyperlipidemia, smoking, autosomal dominant polycystic kidney disease
Risk factors for rupture: straining for a BM, caffeine, episodes of anger, startling, sexual intercourse, nose blowing, and vigorous physical exercise.
Would need to avoid 1.3 million episodes of sexual intercourse to avoid on rupture

9. UIA (continued)
4% prevalence of UIA if you have one first degree relative with SAH
9.2% prevalence if you have 2 or more affected first degree relatives
AHA/ASA guidelines (2015): “It may be reasonable to offer noninvasive screening to patients with familial (at least 1 first-degree relative) aneurysmal SAH and/or a history of aneurysmal SAH to evaluate for de novo aneurysms or late regrowth of a treated aneurysm, but the risks and benefits of this screening require further study (Class IIb; Level of Evidence B).”

10. UIA (continued)
For those with even small UIA, consider serial MRA or CTA. Optimum interval not known. Consider yearly for 3 years and then less every 2- 5 years if stable. Some do the first reimage after 6 months.
Counsel to avoid smoking, heavy alcohol use, stimulant medications, illicit drugs, and excessive straining and Valsalva.

11. Common sites of formation of intracranial saccular aneurysms (Lancet Neurol 2014;13:393-404)

12. A) A 5×4×4 mm anterior communicating artery aneurysm in a 52-year-old man. (B) A 5×6×5 mm azygous anterior cerebral artery aneurysm in a 48-year-old woman. Lancet Neurol 2014;13:

13. Arachnoid cysts
About 1% of intracranial masses, found in 1.1% of those ages 45-97
Collections of CSF between 2 membranes of normal the arachnoid matter with the CSF secreted by arachnoid cells lining the cyst
75% of symptomatic cysts occur in children
Supratentorial 88% (middle fossa 66%, bilateral in 10%; cerebral convexity, 14%); infratentorial 14%
Population based study in Sweden comparing those with cysts to without: same frequency of headache, epilepsy, dizziness, cognitive impairment, and depression (J Neurol 2016:263:689). Surgery rare: 35 pts per year (15 children, 20 adults) out of 200,000 in Swedish population. Larger cysts might be more symptomatic.
Rare risk of post-traumatic or spontaneous rupture resulting in a subdural hemorrhage

14. Axial T2-weighted MRI image through the body of the lateral ventricles, showing superior extension of a right middle cranial fossa lesion. The lesion is homogeneous, with no perceptible wall, no internal complexity, and CSF signal intensity. There is associated remodeling of the adjacent calvarium and brain displacement. These imaging features are typical of an arachnoid cyst(from Medscape).

15. Cavum septum pellucidi (CSP) and cavum vergae (CV)
Anatomical variants
CSP: the space between the two leaflets of the septum pellucidum, which has been reported as persisting in adults in 3- 60% of cases.
CV: the continuation of the CSP posterior to a coronal plate through the columns of the fornix. The CV is a horizontal cleft that is formed between the commissura fornicis and the corpus callosum when the two commissural plates fail to fuse completely during fetal development with a prevalence of 0.4-3% often present along with CSP.

17. Single axial image through the brain demonstrates a CSF filled area in between between two septal leaves, consistent with a cavum septum pellucidum and vergae. (from Radiopaedia)

18. Cerebral vascular malformations
Developmental venous anomalies or venous angiomas in 2% of population: a radially arranged configuration of medullary veins ("caput medusae") separated by normal brain parenchyma (most commonly white matter). Headache may be unrelated. Hemorrhage is rare: 0.34% per year or less
Capillary telangiectasias in 0.7% of population: small, dilated capillaries devoid of smooth muscle or elastic fibers  n the pons, middle cerebellar peduncles, and dentate nuclei. Multiple lesions are common. Clinically silent.

19. Cavernous malformations (cavernous angiomas or hemangiomas or cavernomas)
 Dilated, thin walled capillaries with a simple endothelial lining and a thin, fibrous adventitia from 2 mm to several cms. In the cerebrum in 75% (most commonly subcortical) and posterior fossa in 25% (most in pons and cerebellar hemispheres). M=F
Can be sporadic or familial (CCM1, CCM2, and CCM3)
Supratentorial present with hemorrhage, seizures, and progressive neuro deficits. Annual bleeding rates of %
Infratentorial present with hemorrhage and progressive neuro deficits. Annual bleeding rates 2-3% per year.
In 34 month followup: hemorrhage in asymptomatic 0.6% and 4.5% in symptomatic
Asymptomatic CMs are observed regardless of location

20. Large, right frontal and left occipital cavernous angiomas on a T1-weighted axial MRI. These 2 heterogeneous masses have a reticulated core of high and low signal intensities surrounded by a hypointense rim of hemosiderin. (from Medscape)

21. Arteriovenous malformations (AVMs)
In 0.1% of the population, supratentorial in 90%, 10% posterior fossa
Sporadic congenital developmental vascular lesions with a direct arterial to venous connection without an intervening capillary network
0.2% of those with headache and a normal neuro exam have AVMs. May be incidental.
Presentations: intracranial hemorrhage, 41-79% and seizure, 11-33%
Decision to intervene based upon size, location, and vascular features

22. Arteriovenous malformation (AVM) of the brain
Arteriovenous malformation (AVM) of the brain. An axial T2-weighted MRI showing numerous flow voids corresponding to the CT findings (not shown). Note the mass effect on the lateral ventricle despite the lack of a mass or hemorrhage. (from Medscape)

23. Chiari malformations 1891: first case of CM1 reported by Hans Chiari
1% of population with tonsillar herniation extended more than 5 mm below the foramen magnum in those 15 years or older and more than 6 mm in younger than mm might be symptomatic)
Tonsillar position descends with older age into young adulthood and then ascends with older age through adult life
Syringomyelia present in 30-70% of cases of CM1. Obtain cervical MRI in cases of CM1.

24. CM (continued) Symptomatic CM1: headache in up to 73%
Cough type headache. Usually sharp or throbbing occipital or upper cervical, can be precipitated by neck flexion, and usually lasts less than 5 minutes
Does not cause primary episodic headaches with the rare exception of migraine with brainstem aura like cases

25. Hans Chiari (1851-1916) (Journal of Neurology 2010;257:1218)

26. Sagittal T1-weighted magnetic resonance image of the brain
Sagittal T1-weighted magnetic resonance image of the brain. The line joining the basion to the opisthion defines the lower limit of the posterior cranial fossa and is the reference point for measuring tonsillar ectopia (from Medscape)

27. Primary empty sella turcica (PES)
Due to intrasellar herniation of the suprasellar arachnoid and subarachnoid space CSF resulting in flattening of the pituitary
Partially empty sella when <50% of the sella is filled with CSF and pituitary gland thickness is < 2mm
Most occur due to a normal variant with an anatomical defect of the diaphragma sella (a fold of dura pierced by the infundibulum to connect the pituitary to the hypothalamus) that separates the CSF filled subarachnoid space from the pituitary present in 50% of adults
Present in %, F/M = 4/1, more common in middle aged multips and obesity
8-60% have hypopituitarism due to chronic compression of the pituitary and stalk by CSF. Hyperprolactinemia and deficient GH most common.

28. The sella is filled with CSF and the infundibulum can be seen to traverse the space, thereby excluding a cystic mass. (from Radiopaedia)

29. Grey matter heterotopia
Heterotopia.—Interruption of normal neuronal migration from near the ventricle to the cortex with normal neurons in abnormal locations.
Prevalence of 0.5% in health volunteers ages 9-50 years
The most common form is subependymal with nodules of gray matter immediately beneath, the ependyma of the lateral ventricles usually causing seizures

30. Subependymal heterotopia (from Radiopaedia)

31. Mastoiditis
Increased fluid signal in the mastoid air cells on T2-weighted MRI
In a series of 275 adults with mastoiditis on MRI, ENT evaluation had normal physical findings in 92%; 9% acute serous or chronic OM; 7% had eustachian tube dysfunction, and 2% had tympanosclerosis

32. Axial T1
Hypointensity seen involving the left mastoid air cells

33. Mega cisterna magna
A normal variant with a focal enlargement of the subarachnoid space in the inferior and posterior portions of the posterior fossa
Present in about 1% of the population.

34. T2 image showing a prominent retrocerebellar CSF appearing space with a normal vermis, normal 4th ventricle, and normal cerebellar hemisphere.

35. Meningioma
Annual incidence of 7.61/100,000 population, 20% of all primary tumors, about 26,000 new cases per year in the U.S.
F:M=2:1, increasing incidence with older age
25% are symptomatic on presentation with headache the most common presenting symptom in 36%
Tension type more than migraine-like occurring daily in 31% and less than weekly in 22%
No tumor growth over 5 years in 63%
Most ≤2 cm in diameter incidental tumors can be observed with a f/u scan in 3-6 months. If no change in size and asymptomatic, f/u scans once a year for 3-5 years and then every 2-3 years as long as a candidate for treatment

36. Harvey Cushing (1869-1939). Coined term “meningioma” in 1922
Harvey Cushing ( ). Coined term “meningioma” in First described by Felix Plater in 1614.

37. Contrast-enhanced T1- weighted axial magnetic resonance image demonstrates a typical parasagittal meningioma. A homogeneous, enhancing, globose mass is depicted.

38. Normal variants of cerebral circulation found on MRA or CTA
Duplication (2 distinct arteries with separate origins and no distal arterial convergence): aca, 18%; mca %
Fenestration: division of arterial lumen into distinctly separate channels. More common in vertebrobasilar than anterior circulation. Association with aneurysm formation due to turbulent flow
Azygos (“single) ACA prevalence of 0.2-4% with supply of the bilateral cerebral territories by a single midline A2 trunk
Persistent trigeminal artery occurs in 0.1-0/6% of population. Originates from ICA after exit from carotid canal, can follow a lateral or intrasellar course with anastomoses with mid-basilar artery. Can cause trigeminal neuralgia
Persistent hypoglossal artery occurs in % of population. Originates from ICA at C1-2 vertebral body levels, travels though hypoglossal canal, and anastomoses with BA. Can cause glossopharyngeal neuralgia

39. There is a single trunk forming the A2 segment of ACAs
There is a single trunk forming the A2 segment of ACAs. The left A1 ACA is hypoplastic and dives a hypoplastic A2 which ends below the level of genu of corpus callosum.  From Radiopaedia.

40. Paranasal sinuses
Opacifications (mucosal thickening, polyps, retention cysts, and fluid level ≥1 mm) in 66% with mucosal thickening in 49%, commonly in maxillary sinuses in those years. Also common in younger adults
Polyps and retention cysts mainly in maxillary sinuses in 32%
Migraine and TTH not associated with an increased degree of paranasal sinus opacification

41. Axial T1
Right maxillary sinus retention cyst.
Usually T1 and T2 hyperintense as opposed to polyps that tend to be of low T1 signal.

42. Pineal cysts Present in up to 6.1% of healthy young volunteers
Migraines may be more common in those with pineal cysts
In asymptomatic patients, most cysts are stable in size over times
Some experts recommend f/u with a single MRI after 12 months and no further f/u if cyst stable. Others recommend no imaging f/u wit adults with asymptomatic cysts

43. T1 image: Pineal cyst demonstrating very thin regular peripheral enhancement. (from Radiopaedia)

44. Pituitary tumors
15% of adult brain tumors, 3.47/100,000 incidence, F>M, and with increasing age
Can cause symptomatic cluster type headache and be associated with migraine. No association between pituitary tumor volume, cavernous sinus invasion, and headache.
Other than pituitary apoplexy, no significant improvement of headache after neurosurgery (Endocrine 2017;56:325).
For adenomas < 10mm, measure only serum prolactin if no clinical suspicion of hormonal hypersecretion, Lesions 5-9 mm in diameter, yearly MRI for 2 years and, if stable, decreased to every few years and then less often.
For adenomas 2-4 mm in diameter, no further imaging.
For adenomas ≥ 10 mm without neurological symptoms or hormonal hypersecretion, hormonal testing, visual testing, and MRI at 6 and 12 months during the first year. Those with visual impairment or other neurological sxs can be considered for surgery.

45. Sagittal T1.
Centered within the right aspect of the pituitary gland is a rounded hypo-enhancing lesion measuring 8 x 6 x 6.5 mm. Pituitary tissue is elevated upwards only 1mm, away from of the right side of the optic chiasm, which is not yet contacted or compressed. The infundibulum remains deviated towards the left. There is no evidence of invasion of the cavernous sinuses.

46. Radiologically isolated syndrome (RIS)
Incidental MRI findings of white matter lesions suggestive of multiple sclerosis showing dissemination in space (Barkhof’s criteria) in subjects with a normal neurological exam and without a history of typical multiple sclerosis symptoms.
MRI diagnostic criteria: ovoid, well-circumscribed, and homogeneous foci with or without cerebellar involvement; T2 hyperintensities measuring >3 mm and fulfilling at least three out of four Barkhof criteria, which are (1) nine or more lesions or one or more gadolinium-enhancing lesions, (2) three or more periventricular lesions, (3) one or more juxtacortical lesions, and (4) one or more infratentorial lesions; and the CNS white matter anomalies are not consistent with a vascular pattern.

47. RIS continued
In those having MRI for headache without a diagnosis of MS or CIS, the prevalence of white matter hyperintensities was 51.5%.63 Barkhof “touching” criteria were met in 2.4% and 7.1% met the Barkof 3 mm criteria. McDonald criteria were met in 24.4% for “touching” and 34.5% for 3 mm. The “touching” criteria include periventricular lesions in contact with the ventricles and the 3 mm criteria include periventricular lesions having an edge within 3 mm of the ventricles. The prevalence of MS in the general population is 0.085%.
Within 5 years after initial RIS detection, up to 30% will develop a symptomatic demyelinating episode and almost 2/3 will have new lesions on MRI
Disease modifying treatment is not recommended

48. From AJNR;2014:35:106

49. Rathke’s cleft cysts
Rathke’s pouch is an evagination at the roof of the developing mouth which gives rise to the anterior pituitary.
The cysts are benign sellar and suprasellar lesions (most commonly pars intermedia) arising from the epithelial remnants of Rathke’s pouch which contain mucoid or gelatinous material within a thin cyst wall.
1% of all intracranial lesions found in 13-33% at autopsy
Usually incidental and asymptomatic

50. Rathke cleft cysts (continued)
Headache is the most common manifestation in up to 40% of cases as the only symptom
Headaches are usually episodic (but can be chronic or continuous) non-pulsating frontal, bilateral, or deep retroorbital (occasional occipital, temporal, or generalized) pain with occasionally associated nausea and vomiting.
12-75% reports visual disturbances at presentation
Anterior pituitary hormone deficits in 19-81% (hyperprolactinemia and growth hormone deficiency most common)

51. Rathke cleft cysts (continued)
In a retrospective study of 75 patients with follow-up for months (median 24 months): 57% no change in size, 28% increase in size, and 15% decrease in size (J Clin Endocrinol Metab 2015:100:3943).
When no clear compressive effects on optic chiasm and the potential for adverse outcomes with surgery, follow with imaging by regular intervals. Initial MRI follow-up at 1 year and then consider increasing the interval if size is stable

52. Martin Rathke (1793-1860): described pouch in 1839

53. T1-weighted sagittal image without contrast shows Rathke cleft cyst extending into the suprasellar cistern. The mass has homogenous high signal intensity relative to the brain parenchyma (from Radiopaedia)

54. Vein of Galen aneurysm
A misnomer: is actually aneurysmal dilation of the median prosencephalic vein of Markowski which drains into the vein of Galen.
1% of all intracranial vascular lesions
Rarely present past infancy (can present with high-output cardiac failure and hydrocephalus)
Can manifest in adults rarely as cerebral hemorrhage or a seizure disorder

55. Galen of Pergamon (129-200 AD)
Galen of Pergamon ( AD). His statue in Pergamon (Bergama, Turkey)

56. 30 yo female with headaches, szs, and development delay
T1 sagittal
Vein of Galen aneurysmal malformation, compressing the Sylvian aqueduct. Lateral and 3rd ventricles are moderately dilated without transependymal edema. Deep cerebral veins, vein of Rosenthal, and superior cerebellar veins are dilated bilaterally. Convexity subarachnoid space narrowing. (from Radiopaedia)

57. Vestibular schwannomas (acoustic neuromas)
Incidence of 1/100,000 person-years with a median age of diagnosis of 50 years
90% unilateral, 10% bilateral primarily those in NF2
Disturbances of the acoustic (hearing loss in 95% and tinnitus in 63%), vestibular (61%, most often with intermittent unsteadiness while walking or uncommonly vertigo), trigeminal nerve (17%; most common facial numbness, hypesthesia, and pain), facial nerve (6%, facial paresis and less often disturbance of taste), and mass effects in large tumors (herniation, hydrocephalus).
Headaches in 29% which mostly lateralize to side of tumor. Can be due to a small tumor causing dural traction within the IAC and porus acusticus.
Follow-up scans every 6-12 months especially in small and medium sized tumors. Surgery may be indicated in those with large tumors, young age, and/or significant hearing loss

58. A large left cerebellar pontine angle mass measuring 3 cm in diameter is demonstrated with extension into the internal acoustic meatus, with central non-enhancing components. 
There is marked mass effect on the brainstem with encephalomalacia of the left cerebellar peduncle.  (from Radiopaedia)

59. Virchow-Robin Space (VRS)
Described by Virchow in 1851 and Robin in 1859
A perivascular space that surrounds small arteries and arterioles as they go from the subarachnoid space and into the brain parenchyma which are most commonly around the lenticulostriate arteries as they perforate the anterior border of the basal ganglia and are also present around the medullary arteries entering the cortex over the high convexities projecting down into the hemispheric white matter and in the mesencephalon. VRS have no direct connection with the ubarachnoid space.
Etat crible describes the multiple enlarged VRS most commonly in the basal ganglia with thickened, ectatic, and sclerotic vessel walls.

60. Virchow-Robin space (continued)
Have been reported in up to 100% of patients
Significance is not mistaking VRS for pathology especially lacunar infarcts
Dilated
VRS are smaller and more round and linear with normal adjacent white matter than the more wedgeshaped lacunar infarcts with a rim of surrounding gliosis on the fluid attenuation inversion recovery sequence. However, there is an overlap in size so it may be difficult to distinguish the two in occasional cases.

61. Rudolf Virchow ( )
Charles-Philippe Robin ( )

62. Coronal T2
Typical enlarged VR space - location inferior to the basal ganglia adjacent ot the terminal ICA with fluid having identical characteristics to CSF (it is a CSF-filled space).  In this case we can actually see the vessel (penetrating barnch of the terminal ICA) passing through the space. (from Radiopaedia)

63. White matter abnormalities (WMA)
Foci of hyperintensity on both proton density and T2-weighted images in the deep and periventricular white matter due to either interstitial edema or perivascular demyelination.
Prevalence ranges from 4-59% in migraineurs and 6-14% in controls.
Migraineurs often misunderstand the significance and have been told or think they have little strokes or MS
While the cause and clinical significance of WMA in migraineurs is uncertain, various hypotheses have been advanced including increased platelet aggregability with microemboli, abnormal cerebrovascular regulation, and repeated attacks of hypoperfusion during the aura.

64. a, b: A 26-year-old man affected by MwA
a, b: A 26-year-old man affected by MwA. 3D FLAIR scan shows punctate T2- hyperintensities in the white matter within the frontal lobes (from Neurol Sci 2017;38 (suppl1):S11-S13

65. REFERENCES
Evans RW. Incidental Findings and Normal Anatomical Variants on MRI of the Brain in Adults for Primary Headaches. Headache ;57(5):
Strauss LD, Cavanaugh BA, Yun ES, Evans RW. Incidental Findings and Normal Anatomical Variants on Brain MRI in Children for Primary Headaches. Headache Nov;57(10):