Description
Brain (head) MRI is the procedure of choice for most brain disorders. It provides clear images of the brainstem and posterior brain, which are difficult to view on a CT scan. It is also useful for the diagnosis of demyelinating disorders (such as multiple sclerosis (MS) that cause destruction of the myelin sheath of the nerve). The evaluation of blood flow and the flow of cerebrospinal fluid (CSF) is possible with this non-invasive procedure

Headache and Migraine
MRI for Headache — Generally, magnetic resonance imaging is the preferred imaging technique for evaluating the brain parenchyma, and CT is preferable for evaluating subarachnoid hemorrhage. CT is faster and more readily available than MRI and is often used in urgent clinical situations. Neurologic imaging is warranted in patients with headache disorders along with abnormal neurologic examination results or predisposing factors for brain pathology. Contrast-enhanced MRI is performed for evaluation of inflammatory, infectious, neoplastic, and demyelinating conditions.

Headache time frames and other characteristics — Headaches can be classified as acute, subacute or chronic. Acute headaches are present from hours to days, subacute from days to weeks and chronic headaches for more than 3 months. Acute severe headaches are more likely to be pathological (e.g., SAH, cerebral venous thrombosis) than non-acute (e.g., migraine, tension-type). Headaches can also be categorized as new onset or chronic/recurrent. Non-acute new onset headaches do not require imaging unless there is a red flag as delineated above. Incidental findings lead to additional medical procedures and expense that do not improve patient well-being. Primary headache syndromes, such as migraine and tension headaches, are often episodic with persistent or progressive headache not responding to treatment requiring further investigation (e.g., new daily persistent headache). Imaging is indicated in chronic headaches if there is a change in the headache frequency (number of headaches episodes/month), duration of each episode, severity of the headaches or new characteristics, such as changing aura or associated symptoms.^{1,2,3,4,220,221,222,223,224}

Migraine with aura^4,5,225 — The headache phase of a migraine is preceded and/or accompanied by transient neurological symptoms referred to as aura in at least a third of migraine attacks. Migraine with typical aura consists of visual and/or sensory and/or speech/language symptoms, but no motor, brainstem or retinal symptoms and is characterized by gradual development, duration of each symptom no longer than one hour, a mix of positive and negative features and complete reversibility. Atypical or complex aura includes motor, brainstem, monocular visual disturbances, or ocular cranial nerve involvement (hemiplegic migraine, basilar migraine/brainstem aura, retinal migraine, ophthalmoplegic migraine) and secondary causes need to be excluded. Additional features of an aura that raise concern for an underlying vascular etiology include late age of onset, short duration, evolution of the focal symptoms, negative rather than positive visual phenomenon, and history of vascular risk factors.

Individuals presenting with a new migraine with aura (especially an atypical or complex aura) can mimic a transient ischemic attack or an acute stroke. If there is a new neurologic deficit, imaging should be guided by concern for cerebrovascular disease, not that the individual has a headache.^9,226

Drop Metastases
Drop Metastases — Drop metastases are intradural extramedullary spinal metastases that arise from intracranial lesions. Common examples of intracranial neoplasms that result in drop metastases include pineal tumors, ependymomas, medulloblastomas, germinomas, primitive neuroectodermal tumors (PNET), glioblastomas multiform, anaplastic astrocytomas, oligodendrogliomas and less commonly choroid plexus neoplasms and teratomas.²⁰⁹

Pulsatile Tinnitus
Pulsatile tinnitus has many etiologies, and the choice of study should be based on accompanying signs and symptoms. For general screening MRI brain with IAC/MRA brain and neck is approvable. If IIIH is suspected (typically with headache and vision changes in a younger woman with a high BMI), MRI/MRV brain is indicated. If there is concern for vascular etiology, CTA or MRA brain/neck is indicated. If there is associated hearing loss and neurological signs/symptoms, MRI brain with IAC is indicated. If the temporal bone is suspected to be involved and/or retrotympanic lesion seen on otoscopy, CT temporal bone/IAC is indicated. If there is concurrent concern for boney and a vascular issue, CTA of the head and neck can be used to evaluate both.

Leptomeningeal Carcinomatosis
Leptomeningeal Carcinomatosis^{210,227,228,229} — Leptomeningeal metastasis is an uncommon and typically late complication of cancer with poor prognosis and limited treatment options. Diagnosis is often challenging with nonspecific presenting symptoms ranging from headache and confusion to focal neurologic deficits such as cranial nerve palsies. Standard diagnostic evaluation involves a neurologic examination, MRI of the brain and spine with gadolinium, and cytologic evaluation of the cerebral spinal fluid (CSF).
Hematologic malignancies (leukemia and lymphoma), primary brain tumors as well as solid malignancies can spread to the leptomeninges. The most common solid tumors giving rise to LM are breast cancer (12% – 35%), small and non-small cell lung cancer (10% – 26%), melanoma (5% – 25 %), gastrointestinal malignancies (4% – 14%), and cancers of unknown primary (1 – 7%).

Brain MRI/MRA
Combination MRI/MRA of the Brain — This is one of the most misused combination studies and other than what is indicated above these examinations should be ordered in sequence, not together. Vascular abnormalities can be visualized on the brain MRI.

Vertigo
MRI and Vertigo — The most common causes of vertigo seen are benign paroxysmal positional vertigo (BPPV), vestibular neuronitis (VN) and Meniere’s disease. These peripheral causes of vertigo are benign, and treatment involves reassurance and management of symptoms. Central causes of vertigo, such as cerebrovascular accidents (CVAs), tumors and multiple sclerosis (MS), need to be considered if the individual presents with associated neurological symptoms, such as weakness, diplopia, sensory changes, ataxia, or confusion. Magnetic resonance imaging is appropriate in the evaluation of individuals with vertigo who have neurologic signs and symptoms, progressive unilateral hearing loss or risk factors for cerebrovascular disease. MRI is more appropriate than CT for diagnosing vertigo due to its superiority in visualizing the posterior portion of the brain, where most central nervous system disease that causes vertigo is found. A full neurologic and otologic evaluation including provocative maneuvers, vestibular function testing and audiogram can help evaluate vertigo of unclear etiology and differentiate between central and peripheral vertigo.

Macrocephaly
MRI for Macrocephaly — Consider ultrasound in infants with macrocephaly and a normal neurological examination, no evidence of increased ICP and an open anterior fontanelle. If head US is normal, the infant should be monitored closely.²³⁰ The anterior fontanelle generally closes between 10 and 24 months of age, with 3% closing between 5 – 9 months and 11% after 24 months. (231)

Anosmia
Anosmia — Nonstructural causes of anosmia include post-viral symptoms, medications (Amitriptyline, Enalapril, Nifedipine, Propranolol, Penicillamine, Sumatriptan, Cisplatin, Trifluoperazine, Propylthiouracil). These should be considered prior to advanced imaging to look for a structural cause.

Anosmia and dysgeusia have been reported as common early symptoms in individuals with COVID-19, occurring in greater than 80 percent of individuals. For isolated anosmia, imaging is typically not needed once the diagnosis of COVID has been made given the high association. As such, COVID testing should be done prior to imaging.^232,233,234
MRI Orbits, Face, and Neck MRI rather than MRI Brain is the mainstay for directly imaging the olfactory apparatus and sinonasal or anterior cranial fossa tumors that may impair or directly involve the olfactory apparatus.

Temporal Arteritis
Giant cell arteritis (GCA) is an inflammatory disorder that should be considered in individuals over the age of 50 with the following signs or symptoms: new headaches, acute onset of visual disturbances (especially transient monocular visual loss), jaw claudication, constitutional symptoms, tenderness over the temporal artery, and elevated ESR and/or CRP. A diagnosis of polymyalgia rheumatica (PMR) is highly associated. Extra- and intracranial cerebral vasculitis can also be seen but is rarer, and strokes are related to vasculitis of extracranial cerebral arteries causing vertebral or internal carotid arteries stenosis. Gold standard for diagnosis of GCA is temporal artery biopsy. Color Doppler ultrasound (CDUS) can be used as a surrogate for temporal artery biopsy in some cases.

High-resolution magnetic resonance imaging (MRI) can visualize the temporal arteries when used with contrast.

Galactorrhea and Hyperprolactinemia
Galactorrhea and MRI — Isolated galactorrhea without elevated prolactin (normoprolactinemic) is usually due to breast pathology, i.e., breast feeding, trauma, ill-fitting undergarments. Consider mammogram, breast ultrasound, and serial dilution of the individual’s prolactin sample to correct for possible hook effect.^235,236

Chart 1: Causes of Hyperprolactinemia⁴⁸

Central Venous Thrombosis
A MR venogram is indicated for the definite evaluation of a central venous thrombosis/dural sinus thrombosis. The most frequent presentations are isolated headache, intracranial hypertension syndrome (headache, nausea/vomiting, transient visual obscurations, pulsatile tinnitus, CN VI palsy, papilledema),²³⁷ seizures, focal neurological deficits, and encephalopathy. Risk factors are hypercoagulable states inducing genetic prothrombotic conditions, antiphospholipid syndrome and other acquired prothrombotic diseases (such as cancer), oral contraceptives, pregnancy, puerperium (6-weeks postpartum), infections, and trauma. COVID-19 infection is associated with hypercoagulability, a thromboinflammatory response, and an increased incidence of venous thromboembolic events (VTE).^238,239 Since venous thrombosis can cause SAH, infarctions, and hemorrhage, parenchymal imaging with MRI/CT is also appropriate.^30,240,241

Non-aneurysmal Vascular Malformations
Non-aneurysmal vascular malformations can be divided in low flow vascular malformations and high flow vascular malformations. Low flow vascular malformations include dural venous anomalies (DVA), cavernomas, and capillary telangiectasias. High flow vascular malformations include AVM and dural arteriovenous fistulas (dAVF). For low flow malformations, MRI is the study of choice. Limited medical literature is available to support vascular imagining (CTA or MRA). CTA plays a limited role in the assessment of cavernoma but may be used to demonstrate a DVA. MRA is not usually helpful in the assessment of cavernoma, capillary telangiectasia, and DVA. Vascular imaging is indicated in high flow vascular malformations.²⁴²

There is no evidence to support screening of first-degree relatives for AVMs.²⁴³ The risk of having an AVM may be higher than in the general population, but absolute risk is low.

Stroke/TIA
MRI and recent stroke or transient ischemic attack — When revascularization therapy is not indicated or available in patients with an ischemic stroke or TIA, the focus of the work-up is on secondary prevention. Both stroke and TIA should have an evaluation for high-risk modifiable factors such as carotid stenosis atrial fibrillation as the cause of ischemic symptoms.²⁴⁴ Diagnostic recommendations include neuroimaging evaluation as soon as possible, preferably with magnetic resonance imaging, including DWI; noninvasive imaging of the extracranial vessels should be performed, and noninvasive imaging of intracranial vessels is reasonable.²⁴⁵

Patients with a history of stroke and recent work-up with new signs or symptoms indicating progression or complications of the initial CVA should have repeat brain imaging as an initial study. Patients with remote or silent strokes discovered on imaging should be evaluated for high-risk modifiable risk factors based on the location and type of the presumed etiology of the brain injury.

Table 1: Gait and Brain Imaging
Table 1: Gait and Brain Imaging^{246,247,248,249,250,251}

Non-neurological causes of gait dysfunction include pain (antalgic), side effects of drugs (analgesic, antihistamines, benzos, psych meds, antihypertensives), visual loss, hearing impairment, orthopedic disorders, rheumatologic disorders, psychogenic, and cardiorespiratory problems (orthostasis).^{247,249,250,251}

Neurological Deficits
Examples of abnormal reflexes related to upper motor neuron lesion/central pathology include hyperreflexia, clonus, Hoffman sign and Babinski, snout, palmar grasp, and rooting reflexes.

Visual loss has many possible etiologies, and MRI is only indicated in suspected neurological causes of visual loss based on history and exam. Visual field defects, such as bitemporal hemianopsia, homonymous hemianopsia, or quadranopsia, require imaging as well as does suspected optic nerve pathology. Subjective symptoms such as blurred vision or double vision with no clear correlate on neurological examination requires a comprehensive eye evaluation to exclude more common causes, such as cataracts, refractive errors, retinopathy, glaucoma, or macular degeneration. Transient visual loss with history consistent with TIA but normal exam at time of examination also should be imaged. Positive visual phenomena, such as photopsias or scintillations that march across the visual field, suggest migraine whereas negative phenomenon, such as shaded or blurred, is more characteristic of ischemia.

Definitions
MMSE — The Mini Mental State Examination (MMSE) is a tool that can be used to assess mental status systematically and thoroughly. It is an 11-question measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. The MMSE has been the most commonly used measure of cognitive function in dementia research, but researchers have recognized that it is relatively insensitive and variable in mildly impaired individuals. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The MMSE takes only 5 – 10 minutes to administer and is, therefore, practical to use repeatedly and routinely.

MoCA — The Montreal Cognitive Assessment (MoCA) was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. MoCA differs from the MMSE mainly by including tests of executive function and abstraction, and by putting less weight on orientation to time and place. Ten of the MMSE's 30 points are scored solely on the time- place orientation test, whereas the MoCA assigns it a maximum of six points. The MoCA also puts more weight on recall and attention-calculation performance, while de-emphasizing language skill. Time to administer the MoCA is approximately 10 minutes. The total possible score is 30 points; a score of 26 or above is considered normal.

MRI and developmental delay — Significant developmental delay is defined as significant delay (more than two standard deviations below the mean) in one or more developmental domains: gross/fine motor, speech/language, cognition, social/personal, and activities of daily living. Isolated delay in social/language development is characteristic of autism spectrum disorders or hearing loss. Isolated delay in motor development is characteristic of cerebral palsy (a static encephalopathy) or myopathy. Global developmental delay (GDD) is a subset of developmental delay defined as significant delay (by at least 2 SD’s) in two or more developmental categories. Note that the term “GDD” is usually reserved for children <5 years old, whereas in older children >5 years, disability is quantifiable with IQ testing.

Trigeminal Neuralgia (TN) — According to the International Headache Society, TN is defined as “a disorder characterized by recurrent unilateral brief electric shock-like pain, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve and triggered by innocuous stimuli.”⁴ Atypical features include bilateral, hearing loss, dizziness/vertigo, visual changes, sensory loss, numbness, pain > 2 min, pain outside trigeminal nerve distribution and progression.¹²¹

Occipital Neuralgia — According to the International Headache Society, occipital neuralgia is defined as “Unilateral or bilateral paroxysmal, shooting or stabbing pain in the posterior part of the scalp, in the distribution(s) of the greater, lesser and/or third occipital nerves, sometimes accompanied by diminished sensation or dysesthesia in the affected area and commonly associated with tenderness over the involved nerve(s). Pain is eased temporarily by local anesthetic block of the affected nerve(s). Occipital neuralgia must be distinguished from occipital referral of pain arising from the atlantoaxial or upper zygapophyseal joints or from tender trigger points in neck muscles or their insertions.”¹²¹

Low risk brief resolved unexplained event (BRUE) formerly apparent life-threatening event (ALTE) requires all the following:

• Age > 60 days
• Gestational age ≥ 32 weeks or older and corrected gestational age ≥ 45 weeks
• First brief event
• Event lasting < 1 minute
• No CPR required by the trained medical provider
• No concerning historical features or physical examination findings.

Policy 
INDICATIONS

Headache^1,2
Evaluation of Headache

• Cluster headaches or other trigeminal-autonomic cephalgias, i.e., paroxysmal hemicrania, hemicrania continua, short-lasting unilateral neuralgiform headache attacks (SUNCT/SUNA) imaging is indicated once to eliminate secondary causes^3,4
• Acute headache, sudden onset:
  • With a personal or family history (brother, sister, parent, or child) of brain aneurysm or AVM (arteriovenous malformation) OR
  • < 48 hours of “worst headache in my life” or “thunderclap” headache (Sudden onset new headache reaching maximum intensity within 2-3 minutes, lasting more than 5 minutes).
  • Prior history of stroke or intracranial bleed
  • Known coagulopathy or anticoagulation.
• New onset of headache with any of the following:^3,5,6
  • Acute, new, or fluctuating neurologic deficits, such as sensory deficits, limb weakness, abnormal reflexes (pathological, asymmetric, hyperreflexia), speech difficulties, visual loss, lack of coordination, or mental status changes or with signs of increased intracranial pressure (papilledema). (See background)
  • History of cancer or significantly immunocompromised
  • Fever
  • Subacute head trauma
  • Pregnancy or puerperium^7,8
  • Age ≥ 50^3,5,9,10
  • Severe unilateral headache with radiation to or from the neck, associated with suspicion of carotid or vertebral artery dissection
  • Related to activity or event (sexual activity, exertion, Valsalva, position), new or progressively worsening^3,10,11,12
  • Persistent or progressively worsening during a course of physician-directed treatment^3,13

Note: Neuroimaging warranted for atypical/complex migraine aura, but not for a typical migraine aura³ (see background)

Special Considerations in the Pediatric Population With Persistent Headache^14,15,16

• Documented absence of family history of headache
• Severe headache in a child with an underlying disease that predisposes to intracranial pathology (e.g., immune deficiency, sickle cell disease, neurofibromatosis, history of neoplasm, coagulopathy, hypertension, congenital heart disease)

Neurological Symptoms or Deficits^{17,18,19,20,21,22}
Acute, new, or fluctuating neurologic symptoms or deficits such as, sensory deficits, limb weakness, abnormal reflexes (pathological, asymmetric, hyperreflexia), speech difficulties, visual loss, lack of coordination, or mental status changes (see background)

Stroke and Vascular Disease

• Known or suspected stroke with any acute, new, or fluctuating symptoms or deficits such as sensory deficits, limb weakness, speech difficulties, visual loss, lack of coordination, or mental status changes (see background)
• Suspected stroke with a personal or first-degree family history (brother, sister, parent, or child) of aneurysm or known coagulopathy or on anticoagulation.
• Symptoms of transient ischemic attack (TIA) (episodic neurologic symptoms such as sensory deficits, limb weakness, speech difficulties, visual loss, lack of coordination, or mental status changes)
• Screening for silent cerebral infarcts in early school age children and adults with

HbSS sickle cell disease or HbSβ0 thalassemia²⁶

• Evaluation of neurological signs or symptoms in sickle cell disease^26,27
• High stroke risk in sickle cell patients (2 – 16 years of age) with a transcranial doppler velocity > 200^26,28

Evaluation of Known or Suspected Vascular Disease

• Evaluation of suspected acute subarachnoid hemorrhage (SAH)
• Suspected central venous thrombosis — see background^29,30
• Known Moyamoya disease or reversible cerebral vasoconstriction with any new or changing neurological signs or symptoms.
• Follow-up for known hemorrhage, hematoma, or vascular abnormalities

Note: MRI is the study of choice for detecting cavernous malformations (CCM) and other low flow vascular malformations (see background). Follow-up imaging of known CCM should be done only to guide treatment decisions or to investigate new symptoms. First-degree relatives of patients with more than one family member with a CCM should have a screening MRI as well as genetic counseling^31,32,33

Head Trauma
Evaluation of Known or Suspected Trauma^34,35,36
For evaluation of known or suspected trauma

• Known or suspected trauma or injury to the head with documentation of one or more of the following acute, new, or fluctuating:
  • Focal neurologic findings
  • Motor changes
  • Mental status changes
  • Amnesia
  • Vomiting
  • Seizures
  • Headache
  • Signs of increased intracranial pressure
• Known coagulopathy or on anticoagulation.
• Known or suspected skull fracture by physical exam and/or prior imaging
• Post concussive syndrome if persistent or disabling symptoms and MRI has not been performed.
• Subacute or chronic traumatic brain injury with new cognitive and/or neurologic deficit

Brain Tumor, Mass, or Metastasis
Evaluation of Suspected Tumor/Mass/Cyst (3,37)

• • • Hypopituitarism
    • Growth hormone deficiency
    • Hypogonadotropic hypogonadism [low sex hormones and gonadotropins (FSH/LH)]⁴⁴
      • Total testosterone persistently < 150 with low or normal LH/FSH i.e., severe secondary hypogonadism OR
      • Total testosterone levels persistently borderline around the lower limits of normal range (200 – 400 ng/dL) with low or normal LH/FSH; AND
        • Neurological signs or symptoms; OR
        • Other pituitary hormonal abnormalities; OR
        • Low free testosterone and consideration and addressment of reversible functional causes of gonadotropin suppression (e.g., obesity, opioid use, diabetes, steroid use, or comorbid illness)
  • Suspected hyperfunctioning pituitary gland based on hormonal testing.
    • Central hyperthyroidism (high TSH)
    • Cushing syndrome suspected (high ACTH (> 5) with cortisol suppression on low or high dose dexamethasone suppression test)^45,46,47
    • Acromegaly/gigantism (high GH/IGF-1)
    • Elevated prolactin^48,49
      • ≥ 250 ng/mL OR
      • After evaluation for another cause (e.g., pregnancy, hypothyroidism, renal insufficiency, medication- see background)
        • ≥ 100 ng/mL OR
        • Persistently elevated OR
        • Neuroendocrine signs or symptoms (i.e., headache, galactorrhea, abnormal menses, infertility, or bitemporal hemianopsia) OR
        • Abnormal pituitary hormones (low testosterone/estrogen/ progesterone AND low or normal LH/FSH)
  • Central Diabetes Insipidus (low ADH)
  • Precocious puberty in a child (male < 9; female < 8), with hormonal studies suggesting a central cause⁵⁰
  • Pituitary apoplexy with sudden onset of neurological and hormonal symptoms
• Histiocytic Neoplasms for screening and/or with neurological signs or symptoms^51,52
  • Erdheim-Chester Disease
  • Langerhans Cell Histiocytosis
  • Rosai-Dorfman Disease

Evaluation of Known Brain Lesion/Cyst

• Follow-up of known pituitary adenoma
  • New neuroendocrine signs or symptoms
  • Functioning adenoma to assess response to treatment and 1-year follow-up after drug holiday^38,39,40,53
  • Asymptomatic Macroadenoma (≥ 10 mm) follow-up every 6 – 18 months, post-surgical follow-up every 1 – 2 years after surgery⁵⁴
  • Asymptomatic, non-functioning Microadenoma < 10 mm repeat in one year; if stable, repeat every 2 – 3 years⁵⁴
• Follow-up of known pineal cyst (≥ 5 mm) if there are atypical features or symptoms (e.g., headaches, gaze paresis, ataxia, papilledema, nausea/vomiting)⁵⁵
• Follow up of known Rathke cleft cyst⁵⁶
  • If no symptoms, MRI at 1/3/5 years to stability
  • With new neurological symptoms or atypical imaging features
  • Post treatment, yearly for 5 years.
• Follow-up of known arachnoid cyst^57,58
  • In patients < 4 years old, serial imaging is warranted.
  • In patients > 4 years old, repeat imaging only if newly symptomatic, i.e., headaches, increased intracranial pressure, hydrocephalus, local mass effect, seizures, visual/endocrine dysfunction.
• Midline dermoid cysts/sinuses with concern for intracranial extension^59,60,61
• Histiocytic neoplasms to assess treatment response and surveillance of known brain lesions^51,52
  • Erdheim-Chester Disease
  • Langerhans Cell Histiocytosis
  • Rosai-Dorfman Disease

Brain MRI for Known Cancer
Brain MRI is appropriate for any malignancy when there are signs or symptoms of brain metastases (e.g., headache, sensory deficits, memory problems). There does not need to be a neuro deficit on exam or other workup done first for a patient with cancer.

Initial Staging
Brain MRI is appropriate during the initial diagnostic workup for the following cancer types:

• Kidney cancer⁶²
• Lung cancer (NSCLC and SCLC)^63,64
• Melanoma
  • Primary mucosal tumor of the head and neck — any stage⁶⁵
  • Stage III or IV for any primary site⁶⁶
• Poorly differentiated neuroendocrine cancer⁶⁷
• Gestational trophoblastic neoplasia with pulmonary metastases⁶⁸
• Leukemia with suspicion of CNS involvement^69,70,71
• Breast cancer stage IV⁷²

Restaging
Brain MRI is appropriate every 2 – 3 cycles of chemotherapy during active treatment for the following diseases:

• B Cell lymphomas (if CNS lymphoma present or concern for CNS lymphoma)⁷³
• Breast cancer, stage IV or any stage if suspected development of brain metastases⁷²
• Cutaneous melanoma, stage III or IV or any stage if suspected development of brain metastases⁶⁶
• Non-small cell lung cancer⁶³
  • All stages — initial staging and end of treatment
  • Stage IV — every 2 – 3 cycles of treatment
• Small cell lung cancer⁶⁴
• Neuroendocrine carcinoma of the cervix⁷⁴
  • All stages — initial staging
  • Stage IV — every 2 – 3 cycles of treatment
• Adult and pediatric CNS tumors⁷⁵

Surveillance
Brain MRI is appropriate during surveillance in the following diseases:

• Cutaneous melanoma⁶⁶
  • Stage III, IV every 3 months for 2 years, then every 6 – 12 months indefinitely
  • All other stages if suspected development of brain metastases
  • Non-small cell lung cancer⁶³
  • Stage IV every 3 months
  • All other stages if suspected development of brain metastases
• Small cell lung cancer⁶⁴
  • Limited stage every 2 – 6 months for 1 – 2 years then every 6 – 12 months indefinitely
  • Extensive stage every 2 months for 1 year, every 3 – 4 months for years 2 and 3, every 6 months during years 4 and 5, then annually
• Neuroendocrine carcinoma of the cervix⁷⁴
  • If suspected development of brain metastases
• Adult and pediatric CNS tumors⁷⁵
  • For histologies not specifically detailed below, every 3 – 6 months for 3 – 5 years then at least annually.
    • High-grade glioma/Glioblastoma — 2 – 8 weeks after radiation therapy, then every 2 – 4 months for 3 years, then every 3 – 6 months indefinitely
    • Ependymoma — every 3 – 4 months for 1 year, every 4 – 6 months for 1 year, every 6 – 12 months for 5 – 10 years, then as clinically indicated
    • Medulloblastoma — every 3 months for 1 year, every 6 – 12 months for 5 – 10 years, then as clinically indicated.
    • Meningioma — every 2 – 4 months for 3 years then every 3 – 6 months indefinitely

Combination Studies for Initial Staging, Active Monitoring, or Evaluation of Suspected Metastases³⁷
< 5 concurrent studies to include CT or MRI of any of the following areas as appropriate depending on the cancer: Neck, Abdomen, Pelvis, Chest, Brain, Cervical Spine, Thoracic Spine or Lumbar Spine
 

Seizure Disorders
Evaluation of Known or Suspected Seizure Disorder^{76,77,78,79,80,81,82}

• New onset of an unprovoked seizure
• Newly identified change in seizure activity/pattern
• Known seizure disorder without previous imaging.
• Medically refractory epilepsy

Special considerations in the pediatric population^76,82,83,84
Imaging is indicated in complex febrile seizures accompanied by any of the following:

• Abnormal neurologic exam.
• Autism, cerebral palsy or developmental delay
• Focal onset
• Post-ictal Todd's paralysis (when a seizure is followed by a brief period of temporary paralysis)
• Recurrent in 24 hours
• Duration > 15 minutes
• Abnormal EEG

Note imaging is not indicated for:

• Simple febrile seizures that have none of the above characteristics.
• Benign epilepsy syndromes/idiopathic focal or generalized epilepsy with typical features such as: Childhood absence epilepsy (JAE),(BECTS) Benign epilepsy with centrotemporal spikes also known as Benign Rolandic Epilepsy (BRE), Juvenile absence epilepsy (JAE), Juvenile myoclonic epilepsy (JME), benign epilepsy childhood with centrotemporal spikes (BECCT)

Multiple Sclerosis
Evaluation of Suspected Multiple Sclerosis^85,86

• To demonstrate dissemination in time for diagnosis (every 6 – 12 months)

Evaluation of Known Multiple Sclerosis^86,87

• To establish a new baseline (no recent imaging, postpartum, or 3 – 6 months after switching disease modifying therapy)
• Prior to starting or switching disease-modifying therapy
• 6-month repeat scan in patients with MRI disease activity that is not associated with new clinical symptoms on a routine follow-up scan (i.e., Radiographically isolated syndrome)⁸⁸
• Every 1 – 2 years while on disease-modifying therapy to assess for subclinical disease activity, less frequently when stable for 2 – 3 years.
• New signs or symptoms suggested of an exacerbation or unexpected clinical worsening.
• Progressive Multifocal Leukoencephalopathy (PML) surveillance for patients on natalizumab (Tysabri)⁸⁹
  • 12 months after the start of treatment in all patients
  • Further surveillance MRI scanning timing is based on risk.
    • Annually, if anti-JCV antibody negative,
    • Every 3 – 4 months, if high risk of PML occurrence:
      • seropositive for JC virus and have been treated with natalizumab for ≥ 18 months OR
• • • • high anti-JC virus antibody index values (> 0.9) OR
      • previously treated with immunosuppressive therapies
  • Brain MRI every 3 – 4 months for up to 12 months, in high-risk patients who switch from natalizumab to other therapeutics.

Note: In the pediatric population, use a similar scan frequency for disease and therapeutic monitoring. Increase frequency of imaging (e.g., every 6 months) in children with highly active disease or in situations where imaging will change management.

Infectious or Inflammatory Disease
Evaluation of Known or Suspected Infection or Inflammatory Disease

• Meningitis with positive signs and symptoms (such as fever, headache, mental status changes, stiff neck) OR with positive lab findings (such as elevated white blood cells or abnormal lumbar puncture fluid exam)^90,91
• Suspected encephalitis with headache and altered mental status or follow-up as clinically warranted.
• Endocarditis with suspected septic emboli
• Suspected Giant Cell (temporal arteritis) in a patient ≥ 50 with temporal headache, abrupt visual changes, jaw claudication, temporal artery tenderness, constitutional symptoms or elevated ESR;^92,93,94,95 AND
  • Negative initial work-up (color Doppler ultrasonography or biopsy); OR
  • Atypical features, failure to response to treatment or concern for intracranial involvement

Note: Protocol should include high-resolution contrast-enhanced imaging the temporal artery

• Vasculitis
  • Central Nervous System (CNS) involvement in patients with known or suspected vasculitis or autoimmune disease with abnormal inflammatory markers or autoimmune antibodies
  • Suspected primary CNS vasculitis based on neurological signs and symptoms with completed infectious/inflammatory lab work-up^29,96,97

Note: Vessel wall MRI (ordered as Brain MRI) can also be performed in the evaluation of vasculitides⁹⁸

• Immunocompromised patient (e.g., transplant recipients, HIV with CD4 < 200, primary immunodeficiency syndromes, hematologic malignancies) with focal neurologic symptoms, headaches, behavioral, cognitive or personality changes
• Progressive Multifocal Leukoencephalopathy (PML)^99,100,101)
  • Suspected based on clinical symptoms and/or JC virus status in an immunocompromised patient.
  • Follow-up of known PML as clinically indicated.
• Neurosarcoidosis^102,103
  • Initial Evaluation:
    • Suspected based on neurological sign/symptoms and lab work (ACE, CSF analysis) OR
    • Known history of sarcoidosis with neurological signs or symptoms
  • Follow-up of known neurosarcoidosis:
    • To assess treatment response
    • Worsening signs or symptoms

Cognitive Impairment
Evaluation of Cognitive Impairment^{104,105,106,107}

• Mental status score of either MMSE or MoCA of less than 26 or other similar mental status instruments*/formal neuropsychological testing showing at least mild cognitive impairment AND a completed basic metabolic workup (such as thyroid function testing, liver function testing, complete blood count, electrolytes, and B12)
• *Other examples include Mini-Cog, Memory Impairment Screen, Saint Louis University Mental Status Examination (SLUMS), Brief Alzheimer's Screen (BAS), Blessed Dementia Scale (BDS), Clinical Dementia Rating (CDR)^108,109

Treatment of Alzheimer's disease With Anti-Amyloid-β Monoclonal Antibodies^110,111
Baseline and surveillance imaging as per FDA labeling

Movement Disorders^{21,112,113,114,115}
Evaluation of Movement Disorders

• For evaluation of acute onset of a movement disorder with concern for stroke or hemorrhage
• For evaluation of suspected Parkinson’s with atypical feature or unresponsive to levodopa
• Note: Atypical parkinsonian syndromes include progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and dementia with Lewy bodies.
• For evaluation of new non-Parkinson neurological symptoms in known Parkinson’s disease complicating the evaluation of the current condition
• For the evaluation of other movement disorder to exclude a structural lesion (i.e., suspected Huntington disease, chorea, hemiballismus, atypical dystonia)

Note: MRI not indicated in essential tremor, Tourette’ syndrome, or isolated focal dystonia (e.g., blepharospasm, cervical dystonia, laryngeal dystonia, oromandibular dystonia, writer’s dystonia)^114,116

Cranial Nerve and Vision Abnormalities
Vision Abnormalities
For evaluation of cranial nerve and visual abnormalities

• Optic neuritis
• Abnormal eye findings on physical or neurologic examination (papilledema, pathologic nystagmus, optic atrophy, ocular nerve palsies, new onset anisocoria, visual field deficit, etc.) Note: See background
• Binocular diplopia with concern for intracranial pathology after comprehensive eye evaluation^117,118
• Childhood strabismus with development delay or abnormal fundoscopic exam to rule out intracranial abnormalities¹¹⁹
• Horner’s syndrome with symptoms localizing the lesion to the central nervous system¹²⁰

Other Cranial Neuropathies

• Trigeminal neuralgia or neuropathy^{3,121,122,123}
• Occipital Neuralgia to exclude a structural lesion, notably in atypical cases¹²⁴
• Bell’s Palsy — if atypical signs, slow resolution beyond three weeks, no improvement at four months, or facial twitching/spasms prior to onset^125,126
• Hemifacial spasm^121,127
• Other objective cranial nerve palsy (CN IX – XII)^121,128
• Bulbar symptoms, i.e., difficulty in chewing, weakness of the facial muscles, dysarthria, palatal weakness, dysphagia, and dysphonia and/or signs, i.e., atrophy and fasciculations of the tongue and absent gag reflex¹²¹
• Pseudobulbar symptoms, i.e., dysphagia, dysarthria, facial weakness, sudden, stereotyped emotional outbursts that are not reflective of mood and/or signs, i.e., spastic tongue and exaggerated gag/jaw jerk¹²⁹

Congenital Abnormalities
Evaluation of Known or Suspected Congenital Abnormalities

• Evaluation of the corticomedullary junction in Achondroplasia¹³⁴
• Cerebral palsy if etiology has not been established in the neonatal period, there is change in the expected clinical or developmental profile or concern for progressive neurological disorder¹³⁵
• Prior treatment OR treatment planned for congenital abnormality.

Note: For evaluation of known or suspected hydrocephalus please see section on CSF abnormalities.

Cerebrospinal Fluid (CSF) Abnormalities
Evaluation of Known or Suspected CSF Abnormalities

• Evaluation of suspected hydrocephalus with any acute, new, or fluctuating neurologic, motor, or mental status changes
• Known hydrocephalus^†
• For initial evaluation of a suspected Arnold Chiari malformation^136,†
• Follow-up imaging of a known type II or type III Arnold Chiari malformation. For Arnold Chiari type I, follow-up imaging only if new or changing signs/symptoms¹³⁷
• Initial evaluation for a known syrinx or syringomyelia^†
• Known or suspected normal pressure hydrocephalus (NPH)¹³⁸
  • With symptoms of gait difficulty, cognitive disturbance, and urinary incontinence
• Follow-up shunt evaluation¹³⁹
  • Post operativity if indicated based on underlying disease or pre-operative radiographic findings and/or
  • 6 – 12 months after placement and/or
  • With neurologic symptoms that suggest shunt malfunction
• Evaluation of known or suspected cerebrospinal fluid (CSF) leakage¹⁴⁰
• Cisternography for intermittent and complex CSF rhinorrhea/otorrhea. CSF fluid should always be confirmed with laboratory testing (Beta-2 transferrin assay)^140,141
• Suspected spontaneous intra-cranial hypotension with distinct postural headache (other symptoms include nausea, vomiting, dizziness, tinnitus, diplopia neck pain or imbalance)^3,142
• CSF flow study for evaluation and management of CSF flow disorders^143,144

^†Often congenital, but can present later in life; or less commonly acquired secondary to tumor, stroke, trauma, infection, etc.

Procedural Evaluations
Preoperative/Procedural Evaluation

• Pre-operative evaluation for a planned surgery or procedure

Postoperative/Procedural Evaluation

• A follow-up study may be needed to help evaluate a patient’s progress after treatment, procedure, intervention, or surgery. Documentation requires a medical reason that clearly indicates why additional imaging is needed for the type and area(s) requested.

Prior Imaging
Further Evaluation of Indeterminate Findings on Prior Imaging
Unless follow up is otherwise specified within the guideline:

• For initial evaluation of an inconclusive finding on a prior imaging report that requires further clarification.
• One follow-up exam of a prior indeterminate MR/CT finding to ensure no suspicious interval change has occurred. (No further surveillance unless specified as highly suspicious or change was found on last follow-up exam)

Other Indications

• Syncope with clinical concern for seizure or associated neurological signs or symptoms^149,150
• Cyclical vomiting syndrome or abdominal migraine with any localizing neurological symptoms^151,152,153
• Soft tissue mass of the head with nondiagnostic initial evaluation (ultrasound and/or radiograph)^154,155,156
• Psychological changes with neurological deficits on exam or after completion of a full neurological assessment that suggests a possible neurologic cause¹⁵⁷
• Child < 18 years with global developmental delay OR a developmental delay with abnormal neurological examination^158,159,160
  • Note: MRI is not recommended as a part of routine evaluation in children with autism spectrum disorder and no other neurologic findings.²⁵²
• Unexplained event (BRUE) formerly apparent life-threatening event (ALTE) in infants

< 1 year with concern for neurological cause based on history and exam¹⁶¹

• • Note: Imaging is not indicated in low-risk patients
• Bone Marrow Transplant (BMT)¹⁶²
  • For initial workup of BMT (along with CT Chest, CT Sinus and CT Abdomen and Pelvis)

MR Perfusion Imaging^{163,164,165,166,167}

• Neurovascular disease
  • Assessment of ischemic penumbra in acute stroke
  • Assessment of cerebrovascular reserve
  • Further evaluation of known vascular abnormality (stenosis, malformation, vasospasm, vasculitis, Moya-Moya)
• Mass lesions
  • Differentiating tumor from tumor mimic
  • Differentiating glioblastoma from brain metastasis
  • Discriminating low- from high-grade gliomas
  • Differentiating recurrent brain tumors from radiation/chemo necrosis
  • Surgical planning

MRI Brain With IAC
(If only images of the IACs is needed w/o Brain imaging see Evolent Clinical Guideline 014 for Sinus, Face, Orbit, Neck and Internal Auditory Canal MRI)

• Unilateral non-pulsatile tinnitus
• Pulsatile tinnitus
• Suspected acoustic neuroma (Schwannoma) or cerebellar pontine angle tumor with any of the following signs and symptoms: unilateral hearing loss by audiometry, headache, disturbed balance or gait, unilateral tinnitus, facial weakness, or altered sense of taste.
• Suspected cholesteatoma
• Suspected glomus tumor
• Asymmetric sensorineural hearing loss on audiogram
• Congenital/childhood sensorineural hearing loss suspected to be due to a structural abnormality (CNVIII, the brain parenchyma, or the membranous labyrinth).^17,168,169 CT is the preferred imaging modality for the osseous anatomy and malformations of the inner ear.
• CSF otorrhea (MRI/Nuclear Cisternography for intermittent leaks, CT for active leaks);¹⁴¹ there should be a high suspicion or confirmatory CSF fluid laboratory testing (Beta-2 transferrin assay)
• Clinical suspicion of acute mastoiditis as a complication of acute otitis media with intracranial complications (i.e., meningeal signs, cranial nerve deficits, focal neurological findings, altered mental status)¹⁷⁰
• Bell’s Palsy for evaluation of the extracranial nerve course -if atypical signs, slow resolution beyond three weeks, no improvement at four months, or facial twitching/spasms prior to onset¹²¹

Genetics and Rare Diseases

• Note: diagnosis is met with both genetic testing AND clinical features due to incomplete penetrance
• Sturge Weber Syndrome — once after age 1 to rule out intracranial involvement; in patients < 1 year, only if symptomatic¹⁷⁷ 
• Turcot Syndrome — low threshold for MRI for any neurological sign or symptoms of medulloblastoma¹⁷⁸
• Tuberous Sclerosis — every 1 – 3 years, until the age of 25 years¹⁷⁹
  • Those with asymptomatic subependymal giant cell astrocytoma (SEGA) in childhood should continue to be imaged periodically in adulthood.
  • With large or growing SEGA or SEGA causing ventricular enlargement, more frequent brain MRIs as deemed clinically appropriate.
• Rhabdoid Tumor Predisposition Syndrome — brain MRI at diagnosis and monthly age 0 – 6 months if whole body MRI not done; Q2 – 3 months age 7 – 18 months, Q3months age 19 months – 5 years¹⁸⁰
• Constitutional mismatch repair deficiency syndrome (CMMRD) — brain MRI every 6 months after diagnosis
• Fabrys disease — annual neurologic assessment with brain MRI/MRA every two to three years beginning at age 18 years¹⁸¹
• X-linked Adrenoleukodystrophy¹⁸²
  • Baseline MRI between 12 and 18 months old
  • Second MRI 1 year after baseline
  • MRI every 6 months between 3 and 12 years old
  • Annual MRI after 12 years old
• Heritable retinoblastoma (Pineoblastoma surveillance)
  • Brain MRI at the time of retinoblastoma diagnosis; some centers recommend a brain MRI every 6 months until 5 years old^183,184
• For other syndromes and rare diseases not otherwise addressed in the guideline, coverage is based on a case-by-case basis using societal guidance.

Combination Studies
These body regions might be evaluated separately or in combination as documented in the clinical notes by physical examination findings (e.g., localization to a particular segment of the neuroaxis), patient history, and other available information, including prior imaging.

Note: MRA and CTA are generally comparable noninvasive imaging alternatives each with their own advantages and disadvantages. Brain MRI can alternatively be combined with Brain CTA/Neck CTA.
 

Exception: For approved indications as noted above and being performed in a child under 8 years of age who will need anesthesia for the procedure and there is a suspicion of concurrent intracranial pathology¹⁸⁵

Brain MRI/Brain MRA

• Recent ischemic stroke or transient ischemic attack (TIA)^186,187
• Thunderclap headache with continued concern for underlying vascular abnormality (i.e., aneurysm or reversible cerebral vasoconstriction syndrome) after initial negative brain imaging^{188,189,190,191}
  • Note: Negative brain CT < 6 hours after headache onset excludes subarachnoid hemorrhage in neurologically intact patients.¹⁹⁰ MRI lacks sensitivity in excluding subarachnoid hemorrhage less than 24 hours after headache onset.^188,192

• Acute, sudden onset of headache with personal history of a vascular abnormality or first-degree family history of aneurysm^191,193
• Headache associated with exercise, exertion, Valsalva or sexual activity^4,11,12
• Suspected venous thrombosis (dural sinus thrombosis)¹⁸⁷ — Brain MRV — see background
• Neurological signs or symptoms in sickle cell patients¹⁹⁴
• High stroke risk in sickle cell patients (2 – 16 years of age) with a transcranial doppler velocity > 200²⁶
• Known Moyamoya disease^195,196 or reversible cerebral vasoconstriction with any new or changing neurological signs or symptoms^191,197
• Suspected secondary CNS vasculitis based on neurological signs or symptoms in the setting of an underlying systemic disease with abnormal inflammatory markers or autoimmune antibodies ¹⁹³
• Suspected primary CNS vasculitis based on neurological signs and symptoms with completed infectious/inflammatory lab work-up^193,198,199
• Giant cell arteritis with suspected intracranial involvement⁹³
• Fabrys disease annual neurologic assessment with brain MRI/MRA every two to three years beginning at age 18 years¹⁸¹

Brain MRI/Brain MRA/Neck MRA

• Pulsatile tinnitus with concern for a suspected arterial vascular and/or intracranial etiology^200,201 (Brain MRI should include IAC.)
• Giant cell arteritis with suspected intracranial and extracranial involvement
• Approved indications as noted above and being performed in a child under 8 years of age who will need anesthesia for the procedure and there is a suspicion of concurrent intracranial pathology¹⁸⁵

Note: CTA and MRA are generally comparable noninvasive imaging alternatives each with their own advantages and disadvantages. Brain MRI can be combined with Brain CTA/Neck CTA.

Brain MRI/Cervical Spine MRI

• Horner’s syndrome with symptoms localizing the lesion to the central nervous system²⁰²

Brain MRI/Cervical Spine MRI/Thoracic Spine MRI (any combination)

• Combination studies for MS: These body regions might be evaluated separately or in combination as guided by physical examination findings (e.g., localization to a particular segment of the spinal cord), patient history (e.g., symptom(s), time course, and where in the CNS the likely localization(s) is/are), and other available information, including prior imaging.
  • For evaluation of neuromyelitis optica spectrum disorders (recurrent or bilateral optic neuritis; recurrent transverse myelitis)²⁰³
  • For known MS, prior to the initiation or change of disease modification treatments and assess disease burden (to establish a new baseline)^204,205
  • Follow-up scans, including brain and spine imaging, if patients have known spine disease:
    • 6 – 12 months after starting/changing treatment.
    • Every 1 – 2 years while on disease-modifying therapy to assess for subclinical disease activity, less frequently when stable for 2 – 3 years.

Brain MRI/Cervical Spine MRI/ Thoracic Spine MRI/Lumbar Spine MRI (any combination)

• Oncological Applications (e.g., primary nervous system, metastatic)²⁰⁸
  • Drop metastasis from brain or spine²⁰⁹
  • Suspected leptomeningeal carcinomatosis²¹⁰
• CSF leak highly suspected and supported by patient history and/or physical exam findings (known or suspected spontaneous (idiopathic) intracranial hypotension (SIH), post lumbar puncture headache, post spinal surgery headache, orthostatic headache, rhinorrhea or otorrhea, or cerebrospinal-venous fistula)
• For evaluation of known Arnold-Chiari Malformation
• Tumor evaluation and monitoring in cancer predisposition syndromes
  • Von Hippel Lindau (VHL) — imaging of the brain and spinal cord for hemangioblastomas every 2 years starting at age 14^40,62,172
  • Rhabdoid Tumor Predisposition Syndrome — Brain and Spine MRI at diagnosis and monthly age 0 – 6 months if whole body MRI not done; Q2 – 3 months age 7 – 18 months, Q3 months age 19 months – 5 years.
  • NF-2 — Brain IAC — annually starting at the age of 10 years and spinal imaging at baseline and every 2 to 3 years with more frequent imaging, if warranted, based on sites of tumor involvement¹⁷⁶
  • Schwannomatosis - Brain and spine MRI every two to three years beginning at age 12 years²¹¹

Note: diagnosis is met with both genetic testing AND clinical features due to incomplete penetrance.

Brain/Cervical/Thoracic/Lumbar/Abdomen MRI

• Von Hippel Lindau (VHL) every 2 years starting at age 15

Brain MRI and Face/Sinus MRI

• Granulomatosis with polyangiitis (Wegener’s granulomatosis) disease²¹²
• Trigeminal neuralgia or neuropathy with an atypical presentation (for evaluation of the extracranial nerve course)¹²¹ (See background.)
• For approved indications as noted above and being performed in a child under 8 years of age who will need anesthesia for the procedure and there is a suspicion of concurrent intracranial pathology¹⁸⁵

Brain MRI and Orbit MRI

• Bilateral optic disk swelling (papilledema) with visual loss^{19,214,215,216}
• Optic Neuritis^214,215,217
  • If atypical presentation (bilateral, absence of pain, optic nerve hemorrhages, severe visual impairment, lack of response to steroids, poor recovery or recurrence)
  • If needed to confirm optic neuritis and rule out compressive lesions
• Known or suspected neuromyelitis optica spectrum disorder with severe, recurrent, or bilateral optic neuritis²⁰³
• Suspected retinoblastoma^218,219

Chest CT (or MRI) and Brain/Abdomen/Pelvis MRI

• Multiple Endocrine Neoplasia Syndrome Type 1 (MEN-1)
  • Chest/Abdomen/Pelvis annually
  • Brain/Chest/Abdomen/Pelvis every 3 years

Sinus/Chest/Abdomen and Pelvis CT and Brain MRI

• Prior to Bone Marrow Transplantation

Combination Studies for Malignancy for Initial Staging or Restaging
Unless otherwise specified in this guideline, indication for combination studies for malignancy for initial staging or restaging:

• Concurrent studies to include CT or MRI of any of the following areas as appropriate depending on the cancer: Abdomen, Brain, Chest, Neck, Pelvis, Cervical Spine, Thoracic Spine or Lumbar Spine.

References