Evaluation of acute motor deficit

May not delineate the area of ischemic tissue in the first 6 hours.[49]Fazekas F, Niederkorn K, Ebner F, et al. Relevance of neuroimaging in the evaluation of cerebral ischemia. Cerebrovasc Dis. 2009 Apr;27(suppl 1):S1-8. http://www.ncbi.nlm.nih.gov/pubmed/19342828?tool=bestpractice.com CT scan has poor ability to rule in ischemia in TIA or early stroke, but has nearly 100% sensitivity in ruling out hemorrhage. Hemorrhage is an uncommon but life-threatening contraindication to antiplatelet or anticoagulant therapy.

If MRI can be completed within 3 hours of presentation, then MRI is a first-line test. However, it may not be available in all locations and requires expertise in imaging protocols and interpretation.[50]Marks MP. CT in ischemic stroke. Neuroimaging Clin N Am. 1998 Aug;8(3):515-23. http://www.ncbi.nlm.nih.gov/pubmed/9673310?tool=bestpractice.com

If positive, MRI can localize infarcts, suggest etiology, and distinguish TIA from stroke. The presence of abnormalities confirms ischemia.

Abnormal diffusion images are reversible in some but not all patients who have resolution of clinical deficits.

MRI can also evaluate for alternative etiologies such as plaques of multiple sclerosis or mass lesions.

Hypoglycemic events can give global symptoms such as confusion or syncope, but can also lead to focal symptoms and need to be ruled out as a mimic of TIA.

Severe hyponatremia can trigger seizures; extremely low potassium or high calcium can cause generalized weakness. These abnormalities are usually suggested by other elements of the history.

Used primarily to evaluate for nonischemic cause of symptoms. High WBC count can suggest infection as cause of symptoms. Profound anemia can cause weakness, but usually this would be generalized.

Atrial fibrillation increases the risk for embolic cerebral ischemia.

Other abnormalities such as bundle branch blocks or ventricular hypertrophy are more nonspecific findings of underlying cardiac disease that may reflect CHF or common risk factors for atherosclerotic disease.

Ultrasound is the usual choice of screening test.[8]American College of Radiology​. ACR appropriateness criteria: cerebrovascular disease. 2016 [internet publication]. https://www.acr.org/Clinical-Resources/ACR-Appropriateness-Criteria

Presence of ipsilateral carotid stenosis suggests artery-to-artery embolic event as etiology and is a target for surgical or interventional treatment. CT angiography or MR angiography may be used as follow-up tests to expand on abnormal carotid Doppler ultrasound results.

This test adds to the diagnostic accuracy and directs therapeutic interventions.[51]Schramm P, Schellinger PD, Klotz E, et al. Comparison of perfusion computed tomography and computed tomography angiography source images with perfusion-weighted imaging and diffusion-weighted imaging in patients with acute stroke of less than 6 hours' duration. Stroke. 2004 Jul;35(7):1652-8. https://www.ahajournals.org/doi/10.1161/01.STR.0000131271.54098.22 http://www.ncbi.nlm.nih.gov/pubmed/15155964?tool=bestpractice.com

Not typically performed as a stand-alone screening test but may be included in acute stroke imaging protocols or used to follow-up on abnormal carotid Doppler ultrasound results.

Not typically performed as a stand-alone screening test but may be included in acute stroke imaging protocols or used to follow-up on abnormal carotid Doppler ultrasound results. Less commonly used to evaluate carotid stenosis compared with carotid ultrasound and CT angiography.

Ordered in patients with a high pretest probability of hypercoagulability.

The thrombophilic states most associated with arterial thrombus are antiphospholipid antibodies or hyperhomocysteinemia.

Evaluates intracardiac abnormalities such as valvular disease, shunts, or intraventricular thrombus.

Transesophageal echocardiogram has higher sensitivity than transthoracic echocardiogram but carries greater risk and is reserved for patients with high clinical suspicion or young patients with cryptogenic stroke.

Most important test: needed to differentiate hemorrhagic from ischemic stroke. This test is used mainly to rule out hemorrhage, rather than to diagnose stroke, as an essential step in acute stroke therapy.[6]Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-418. https://www.ahajournals.org/doi/full/10.1161/STR.0000000000000211 http://www.ncbi.nlm.nih.gov/pubmed/31662037?tool=bestpractice.com [7]Scottish Intercollegiate Guidelines Network, Royal College of Physicians. National clinical guideline for stroke for the United Kingdom and Ireland. Apr 2023 [internet publication]. https://www.strokeguideline.org/app/uploads/2023/04/National-Clinical-Guideline-for-Stroke-2023.pdf

May not delineate the area of ischemic tissue in the first 6 hours.[49]Fazekas F, Niederkorn K, Ebner F, et al. Relevance of neuroimaging in the evaluation of cerebral ischemia. Cerebrovasc Dis. 2009 Apr;27(suppl 1):S1-8. http://www.ncbi.nlm.nih.gov/pubmed/19342828?tool=bestpractice.com

Can precisely localize the ischemic territory.[53]Schaefer PW, Romero JM, Grant PE, et al. Diffusion magnetic resonance imaging of acute ischemic stroke. Semin Roentgenol. 2002 Jul;37(3):219-29. http://www.ncbi.nlm.nih.gov/pubmed/12226901?tool=bestpractice.com

Has higher sensitivity for infarction and equivalent sensitivity for hemorrhage compared with CT.

Contraindicated in patients with certain metallic implants such as pacemakers.

Some specialized stroke centers are using MRI as the initial imaging modality of choice, replacing CT.

May be implemented in the subacute phase after CT in some centers

Hypoglycemic events can give global symptoms such as confusion or syncope, but can also lead to focal symptoms and need to be ruled out as a mimic of stroke.

Severe hyponatremia can trigger seizures; extremely low potassium or high calcium can cause generalized weakness. These abnormalities are usually suggested by other elements of the history.

Used primarily to evaluate for nonischemic cause of symptoms. High WBC count can suggest infection as cause of symptoms. Profound anemia can cause weakness, but usually this would be generalized.

May detect conditions that may be potential contraindications for some acute stroke treatments and interventions. Excludes anemia or thrombocytopenia before possible initiation of thrombolytics, anticoagulants, or antithrombotics.

Atrial fibrillation increases the risk for embolic cerebral ischemia.

Other abnormalities such as bundle branch blocks or ventricular hypertrophy are more nonspecific findings of underlying cardiac disease that may reflect CHF or common risk factors for atherosclerotic disease.

In some centers, noncontrast CT/MRI is immediately followed by CT angiography to identify intracranial and extracranial vessel pathology.

Indicated to reveal acute arterial occlusion or atherosclerotic stenosis of the intracranial or cervical arteries.

May suggest the presence of less common arteriopathies, including arterial dissection, reversible cerebral vasoconstriction syndrome, Moya-Moya (vascular occlusion affecting circle of Willis), or fibromuscular dysplasia.

Has higher spatial resolution than MR angiography.

In some centers, noncontrast CT/MRI is immediately followed by MR angiography to identify intracranial and extracranial vessel pathology.

Can reveal acute arterial occlusion or atherosclerotic stenosis of the intracranial or cervical arteries.

May suggest the presence of less common arteriopathies, including arterial dissection, reversible cerebral vasoconstriction syndrome, Moya-Moya (vascular occlusion affecting circle of Willis), or fibromuscular dysplasia.

If routine imaging studies do not show arterial occlusion, and if the infarct imaging and clinical presentation show characteristics of venous stroke (e.g., ischemic tissue not conforming to a vascular territory, severe hemorrhagic transformation and/or edema, intractable seizures at presentation, signs of increased intracranial pressure), then patency of cerebral venous sinuses can be assessed by CT or MR venography.[8]American College of Radiology​. ACR appropriateness criteria: cerebrovascular disease. 2016 [internet publication]. https://www.acr.org/Clinical-Resources/ACR-Appropriateness-Criteria

Ultrasound is the usual choice of screening test.[8]American College of Radiology​. ACR appropriateness criteria: cerebrovascular disease. 2016 [internet publication]. https://www.acr.org/Clinical-Resources/ACR-Appropriateness-Criteria

Presence of ipsilateral carotid stenosis suggests artery-to-artery embolic event as etiology and is a target for surgical or interventional treatment. CT angiography or MR angiography may be used as follow-up tests to expand on abnormal carotid Doppler ultrasound results.

Ordered in patients with a high pretest probability of hypercoagulability.

The thrombophilic states most associated with arterial thrombus are antiphospholipid antibodies or hyperhomocysteinemia.

Evaluates intracardiac abnormalities such as valvular disease, shunts, or intraventricular thrombus.

Transesophageal echocardiogram has higher sensitivity than transthoracic echocardiogram but carries greater risk and is reserved for patients with high clinical suspicion or young patients with cryptogenic stroke.

Most important test because differentiates hemorrhagic from ischemic stroke. May be combined with CT angiography where it adds to diagnostic accuracy and directs therapeutic accuracy.[51]Schramm P, Schellinger PD, Klotz E, et al. Comparison of perfusion computed tomography and computed tomography angiography source images with perfusion-weighted imaging and diffusion-weighted imaging in patients with acute stroke of less than 6 hours' duration. Stroke. 2004 Jul;35(7):1652-8. https://www.ahajournals.org/doi/10.1161/01.STR.0000131271.54098.22 http://www.ncbi.nlm.nih.gov/pubmed/15155964?tool=bestpractice.com

No blood test is available to diagnose stroke. Chemical analyses rule out conditions mimicking stroke (e.g., hypoglycemia, intoxication, electrolyte disturbances). Abnormal results suggest an alternative cause of symptoms.

Elevated serum glucose is likely a response to the stress and severity of intracranial hemorrhage and is a marker for death.

Necessary to exclude thrombocytopenia as a cause of hemorrhage.

Low platelet count suggests a secondary cause of hemorrhage.

Required to rule out coagulopathy as a cause of hemorrhage.

If elevated, results suggest a secondary cause of hemorrhage.

Myocardial ischemia may complicate hemorrhagic stroke.

Confused, comatose, or aphasic patients may not be able to verbalize whether they have angina. Large inverted T waves in multiple coronary artery distributions suggest ECG changes of cerebral origin, rather than acute coronary syndrome.[55]Catanzaro JN, Meraj PM, Zheng S, et al. Electrocardiographic T-wave changes underlying acute cardiac and cerebral events. Am J Emerg Med. 2008 Jul;26(6):716-20. http://www.ncbi.nlm.nih.gov/pubmed/18606329?tool=bestpractice.com

Indicated to rule out aneurysm or AVM as a cause of bleeding.

In patients with lobar spontaneous intracerebral hemorrhage <70 years, deep/posterior fossa spontaneous intracerebral hemorrhage <45 years, or deep/posterior fossa and age 45 to 70 years without history of hypertension, acute CT angiogram plus consideration of venography is recommended to exclude macrovascular causes or cerebral venous thrombosis.[37]Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 Guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke. 2022 Jul;53(7):e282-361. https://www.ahajournals.org/doi/10.1161/STR.0000000000000407 http://www.ncbi.nlm.nih.gov/pubmed/35579034?tool=bestpractice.com

May be low yield in patients >45 years old with hypertension and hemorrhages in typical locations (i.e., basal ganglia, thalamus, brain stem, or cerebellum).

Higher spatial resolution than MR angiography.

Presence of "spot sign" (hyperdense contrast material in the hematoma bed on postinjection CT images) associated with greater risk of subsequent hematoma expansion.

Indicated to rule out aneurysm or AVM as cause of bleeding.

In patients with spontaneous intracerebral hemorrhage with a negative CT angiogram/venography, it is reasonable to perform MRI and MR angiography to establish a nonmacrovascular cause of intracerebral hemorrhage.[37]Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 Guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke. 2022 Jul;53(7):e282-361. https://www.ahajournals.org/doi/10.1161/STR.0000000000000407 http://www.ncbi.nlm.nih.gov/pubmed/35579034?tool=bestpractice.com

May be low yield in patients ages >45 years with hypertension and hemorrhages in typical locations (i.e., basal ganglia, thalamus, brain stem, or cerebellum).

Best test for identifying small AVMs or aneurysms.[37]Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 Guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke. 2022 Jul;53(7):e282-361. https://www.ahajournals.org/doi/10.1161/STR.0000000000000407 http://www.ncbi.nlm.nih.gov/pubmed/35579034?tool=bestpractice.com

Conventional invasive brain angiography (catheter intra-arterial digital subtraction angiography [DSA]) is recommended in patients with spontaneous intracerebral hemorrhage and a CT or MR angiogram suggestive of a macrovascular cause (e.g. arteriovenous malformation or aneurysm).[37]Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 Guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke. 2022 Jul;53(7):e282-361. https://www.ahajournals.org/doi/10.1161/STR.0000000000000407 http://www.ncbi.nlm.nih.gov/pubmed/35579034?tool=bestpractice.com

High diagnostic yield has been reported in: patients <70 years of age with lobar intracerebral hemorrhage; patients <45 years of age with deep or posterior fossa intracerebral hemorrhage; patients 45 to 70 years of age with deep or posterior fossa intracerebral hemorrhage and the absence of both history of hypertension and signs of small vessel disease on imaging; all patients with intracerebral hemorrhage with CT or magnetic resonance evidence of a macrovascular lesion; patients with primary intraventricular hemorrhage.[37]Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 Guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke. 2022 Jul;53(7):e282-361. https://www.ahajournals.org/doi/10.1161/STR.0000000000000407 http://www.ncbi.nlm.nih.gov/pubmed/35579034?tool=bestpractice.com

Best performed with gradient-recalled echo sequence with and without contrast.

Acute ischemic infarct appears bright on DWI.

MRI GRE sequence detects asymptomatic microbleeds in about 5% to 20% of stroke-free older patients.

If microbleeds are an incidental finding on MRI, a prompt evaluation for underlying causes and BP control should ensue to prevent intracranial hemorrhage.

Finding of multiple microbleeds restricted to lobar locations is suggestive of underlying cerebral amyloid angiopathy.

Sensitivity for hemorrhage equivalent to CT; may allow identification of secondary causes such as infarction, tumor, or cavernous malformation.

Contraindicated in patients with certain metallic implants (e.g., pacemakers).

In some specialized stroke centers, MRI is the initial imaging modality of choice.

A noncontrast study is preferred to allow for maximum interpretation. Facial bones can be included if the physical exam suggests possible injury.

Thorough and systematic exam of all bony structures, soft tissue, and airways is essential. It is important to confirm that films show full extent of cervical spine to C7-T1 junction before removing c-spine protection. The most common injury is to the C5-C6 level and then C6-C7. C1-C2 should also be looked at closely.

The extent and pattern of the white matter pathology can aid in prognostication.

Chest images form the foundation of the evaluation of the other body systems, and are useful in assessing late complications. This often includes ventilator-associated pneumonia in patients with extensive injuries.

Should be performed on high field (1 Tesla or above) magnet, with IV contrast. Almost all patients with MS will have abnormal cranial MRI, but the interpretation of the MRI may be difficult.

Sagittal FLAIR images distinguish between nonspecific white matter changes, such as seen in association with hypertension, diabetes mellitus, age >50 years, smoking, migraine, high cholesterol, and toxin exposures.

Also used subsequently to look for progression of disease activity or other diagnoses.[61]Solomon AJ, Arrambide G, Brownlee WJ, et al. Differential diagnosis of suspected multiple sclerosis: an updated consensus approach. Lancet Neurol. 2023 Aug;22(8):750-68. http://www.ncbi.nlm.nih.gov/pubmed/37479377?tool=bestpractice.com

Many MS patients will have cervical spinal cord lesions and the specificity of this finding is high. Also used subsequently in cases of progressive disease.[61]Solomon AJ, Arrambide G, Brownlee WJ, et al. Differential diagnosis of suspected multiple sclerosis: an updated consensus approach. Lancet Neurol. 2023 Aug;22(8):750-68. http://www.ncbi.nlm.nih.gov/pubmed/37479377?tool=bestpractice.com

Recommended in patients with long segments of spinal cord demyelination with or without optic neuritis, and also patients with recurrent optic neuritis with normal brain imaging.

Available from the Mayo Clinic, exact sensitivity and specificity is under study.

Due to the invasive nature of the testing, all other noninvasive tests should be pursued first.

CSF is tested for oligoclonal bands, which are an inflammation marker found in 75% to 85% of people with MS.[62]Freedman MS, Thompson EJ, Deisenhammer F, et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol. 2005 Jun;62(6):865-70. https://jamanetwork.com/journals/jamaneurology/fullarticle/788592 http://www.ncbi.nlm.nih.gov/pubmed/15956157?tool=bestpractice.com

Visual evoked potentials are most commonly abnormal, with somatosensory and auditory evoked potentials less so.[61]Solomon AJ, Arrambide G, Brownlee WJ, et al. Differential diagnosis of suspected multiple sclerosis: an updated consensus approach. Lancet Neurol. 2023 Aug;22(8):750-68. http://www.ncbi.nlm.nih.gov/pubmed/37479377?tool=bestpractice.com

Somatosensory evoked potentials can be painful for the patient, as well as technically difficult.

Measured when symptoms present or at conclusion of 72-hour fast.

After glucagon administration at conclusion of 72-hour fast, glucose increase >25 mg/dL is consistent with insulinoma or IGF-II secretion.

Ordered as a screening test once patient presents complaining of hypoglycemic symptoms.

Ordered as a screening test once patient presents complaining of hypoglycemic symptoms.

Measured when glucose <60 mg/dL or at the end of 72-hour fast. Should be undetectable.

Elevated value is consistent with factitious hypoglycemia or insulinoma.

Measured when glucose level <60 mg/dL or at the end of 72-hour fast.

Elevated if insulin is endogenous.

Measured when glucose level <60 mg/dL or at the end of 72-hour fast.

Elevated if insulin is endogenous, especially with insulinoma.

Measured at the time of hypoglycemic symptoms or at the end of 72-hour fast.

Excessive insulin or IGF-II inhibits ketogenesis and lowers beta-hydroxybutyrate.

Therefore, low beta-hydroxybutyrate would support diagnosis of mesenchymal tumor.

Presence indicates iatrogenic hypoglycemia. Test assays chlorpropamide, tolazamide, tolbutamide, glipizide, glyburide, acetohexamide, glimepiride, or gliclazide.

May be done to clarify the diagnosis if the clinical scenario is unclear and/or as an aid to determining prognosis.

Can be used to assess if there has been any muscle injury from prolonged compression.

Used to check renal function in cases where muscle damage with release of myoglobin might have caused renal impairment.

An enhanced study is needed only in cases of suspected tumor/abscess.

Todd paralysis is postictal and can last up to several days after the seizure has ended. Ictal paralysis has been described and attributed to continuing motor cortex activation.

Patients with suspected cerebritis or other infection, should be imaged, then undergo LP.

The test is predicated on the observation that you should enter true sleep more rapidly when sleep deprived.[90]Hersen M, Turner SM, Beidel DC, eds. Adult psychopathology and diagnosis. 5th ed. Wiley; 2007;380.

Parameters monitored include electroencephalogram (EEG), electrooculography (EOG), and pulse oximetry (SpO2).

A noncontrast CT head is standard for initial evaluation of all patients with potential intracranial trauma/hematoma. The subdural fluid collection is usually crescentic in shape and can cross suture lines. The age of the hematoma determines the density of lesion. There may be effacement of underlying sulci or midline shift, effacement of cisterns or other signs of herniation, or skull fracture or other intracranial hematomas.

Although CT has become the investigation of choice, plain skull x-ray may play a role as a screening tool in patients with GCS 13 to 15 and in pediatric populations. It is not sensitive or specific for intracranial hematomas. May be useful for identifying skull fractures or presence of intracranial shrapnel.

Used in some centers to elucidate degree of brain injury, such as parenchymal microhemorrhages or areas of ischemia or hypoperfusion. Not necessary for initial and routine evaluation of hematomas. Similar results as CT scan. Intensities of fluid collection differ according to age of hematoma.

This is the standard diagnostic test for SAH and should be ordered if SAH is suspected.[7]Scottish Intercollegiate Guidelines Network, Royal College of Physicians. National clinical guideline for stroke for the United Kingdom and Ireland. Apr 2023 [internet publication]. https://www.strokeguideline.org/app/uploads/2023/04/National-Clinical-Guideline-for-Stroke-2023.pdf

Modern, third-generation scanners will detect SAH in 93% of cases if the scan is performed in first 24 hours after the bleed. The sensitivity of CT in detecting SAH declines after the first 24 hours, to 68% on day 3 and 58% on day 5. CT may also show subdural or parenchymal hematoma, hypodensities, hydrocephalus, and sometimes the aneurysm(s) if large or thrombosed.

Coagulopathy complicates management and worsens prognosis.

Elevated in 20% to 28% of cases during the first 24 hours in the absence of CAD. This elevation in troponin I is an order of magnitude less than that usually seen in the setting of myocardial infarction.

Fifty percent of patients with SAH have an abnormal ECG on admission. Abnormalities include arrhythmias, prolonged QTc and ST segment/T wave abnormalities.

LP should be performed if CT is unrevealing. CSF opening pressure should be measured and CSF should be visually inspected for gross blood and xanthochromia, although visual inspection for xanthochromia is not always reliable. Spectrophotometry is most sensitive for xanthochromia.

Xanthochromia is an indicator of the presence of blood in the subarachnoid space. Xanthochromia is absent in the first 12 hours after SAH, which is the time necessary for RBCs to start lysing.

This is the most accurate test for visualizing aneurysms and should be carried out once the diagnosis of SAH is made based on CT and/or LP results. It also needs to be performed if suspicion is still high despite inconclusive CT and/or LP results.

Noninvasive. CT angiography has been used as the only method for diagnosing aneurysms; however, it has not widely replaced digital subtraction angiography, primarily because of sensitivity and specificity issues (a meta-analysis reported CT angiography to have a sensitivity of 92.7% and a specificity of 77.2%).

Noninvasive. However, it has not widely replaced digital subtraction angiography, primarily because of sensitivity and specificity issues.

Imaging of several levels above and below the level of deficit is standard, but the complete length of the spinal cord should be imaged when circumstances permit, particularly for patients with coagulopathies.

Ordered in all patients because of the possibility of surgery for the intraspinal clot; may reveal coagulopathy.

For suspected thoracolumbar fractures at least anteroposterior and lateral views are required. Chest and abdominal radiographs taken as part of trauma assessment are not adequate. For awake and alert patients with no evidence of thoracolumbar injury, there is no need for routine thoracolumbar radiographic imaging. Plain films are unable to reliably distinguish between burst fractures and compression fractures.

CT spine should be performed if the following is found on plain radiography of the thoracolumbar spine: increased interpedicular distance (as a sign of burst fracture); and transverse fracture (which may be associated with other significant injuries of the spine or pelvis). Provides better visualization of vertebral arches, facet joints, and neural canal.

Useful to identify intramedullary lesions (e.g., posttraumatic cysts, hematomas, edema); and extramedullary compressions (disk, hematoma, bone fragments). Also for assessment of posterior ligamentous complex.

Performed when MRI spine unavailable or contraindicated (e.g., due to ferromagnetic aneurysm clips, periocular metallic fragments, electronic implants/cardiac pacemakers, hemodynamic instability, severe claustrophobia).

Offers better soft tissue visualization than normal CT, as well as the ability to visualize disk prolapse.

Evaluation of patients with compressive vertebral fractures requires performing an MRI, including the STIR sequence to distinguish an already healed fracture from an unhealed fracture.

High cervical fractures (condyles or C1-C2) may be missed on plain films.

Patients with SCIWORA (spinal cord injury without roentgen abnormality) may have injury detected with this modality. Ligamentous injury can be diagnosed with T1 and T2 scans.

A routine test. An elevated WBC count occurs in most infectious causes of encephalitis. Depressed WBC counts and pancytopenia can be seen in HIV and immunomodulating/immunosuppressive drug use.

A relative lymphocytosis may occur in viral encephalitis. Rickettsial and viral fevers are associated with leukopenia and thrombocytopenia.

Eosinophilia is seen in drug-induced encephalitis and in certain parasitic infections (e.g., Baylisascaris procyonis).

It is preferable to collect blood for the smear at the time of a fever spike in cases of suspected malarial illness to increase the likelihood of finding the trophozoites. Cytoplasmic inclusions in monocytes are seen in ehrlichiosis infection.

Hyponatremia is typically seen in rickettsial infections and SIADH.

Should be obtained as part of the routine workup of a febrile illness. Arboviral cultures are rarely performed and are available only through specialized reference laboratories.

Cultures (and some antigen detection tests) are performed on throat swabs to detect enterovirus, poliovirus, CMV, adenovirus, mumps, measles, influenza, and parainfluenza.

Indicated particularly in patients with a febrile illness and pulmonary symptoms or signs.

Routinely performed as part of a febrile workup. May detect Mycoplasma, Legionella, influenza, parainfluenza, tuberculosis, Coccidioides, Histoplasma, blastomycosis, Coxiella burnetii, or sarcoidosis.

Used more as a screening tool due to its widespread availability and ease of acquisition in an uncooperative patient. It should be ordered in all patients with altered mental state. Postcontrast CT scans (if obtained) can demonstrate diffuse meningeal enhancement, which is a frequent co-occurrence in encephalitis.

HSV encephalitis: often normal or subtly abnormal. Later, hypodense lesions and mild mass effect in temporal lobes, insula, hemorrhage, and enhancement can be seen.

HIV-1: normal/mild atrophy with hypodense white matter lesions. Opportunistic infections and complications of HIV infection have their own characteristic findings.

Acute disseminated encephalomyelitis (ADEM): normal in 40% of patients, low density, flocculent, asymmetric multifocal punctuate or ring-enhancing lesions can be seen.

Highly recommended (preferably as an initial test) in suspected encephalitis. Invaluable in diagnosis. Early lesions in the form of signal abnormalities are seen in most cases. However, it has limited availability compared with CT.

HSV encephalitis: gyral edema on T1, high signal on T2, FLAIR and DWI (with increased diffusion on apparent diffusion coefficient [ADC] maps) in temporal lobe and cingulate gyrus.

HIV-1: atrophy and nonspecific white matter, high signal on T2 and FLAIR. Opportunistic infections and complications of HIV infection have their own characteristic findings.

Polio and Coxsackie: T2 hyperintensities in the midbrain and anterior horn of the spinal cord.

EBV: T2 hyperintensities in the basal ganglia and thalami.

West Nile: leptomeningeal periventricular enhancement.

Japanese encephalitis: T2 hyperintensities in bilateral thalami, brainstem, and cerebellum.

Acute disseminated encephalomyelitis: multifocal, bilateral, asymmetric, large hyperintense lesions of the white and gray matter on T2 and FLAIR. Ring-enhancing lesions may be seen on postcontrast T1 images. Rasmussen encephalitis: T2 hyperintensities in cortex and white matter, cortical atrophy of the frontoinsular region, enlargement of lateral ventricle and moderate atrophy of the caudate nucleus, all limited to one cerebral hemisphere.

Paraneoplastic limbic encephalitis: bilateral involvement of the medial temporal lobes and multifocal lesions on FLAIR and DWI.

Background slowing is an early and sensitive indicator of cerebral involvement but nonspecific.

Temporal lobe abnormalities are frequently seen in viral encephalitides.

Periodic lateralized epileptiform discharges can be seen in HSV encephalitis.

In subacute sclerosing panencephalitis, a typical generalized periodic EEG pattern repeating with intervals between 4 and 15 seconds, synchronous with the myoclonus of the patient may be seen.

LP is almost mandatory in suspected encephalitis provided a mass lesion in the brain has been ruled out by imaging and none of the standard contraindications exist (e.g., coagulation disorders or thrombocytopenia as seen in viral hemorrhagic fevers and local site infection).

Opening pressure: usually normal in viral encephalitis but can be increased especially when meningoencephalitis is present.

Color and clarity: variable, usually clear, can be mildly xanthochromic or blood-tinged in certain necrotizing and hemorrhagic encephalitis (HSV, acute hemorrhagic leukoencephalitis, listerial, and primary amoebic meningoencephalitis).

Protein: normal or mildly elevated in most cases of viral encephalitis. Moderately elevated in bacterial infections, autoimmune diseases, limbic encephalitis, and acute disseminated encephalomyelitis. Markedly elevated in TB.

Glucose: normal to low normal in viral encephalitis except mumps, lymphocytic choriomeningitis virus, late stages of HSV-1. Low glucose levels are also seen in bacterial, fungal, parasitic, and neoplastic etiologies.

Cell counts: in the absence of a traumatic tap, RBC count is usually normal. In cases of HSV (40%), acute hemorrhagic leukoencephalitis, listerial, and primary amoebic meningoencephalitis, RBC count of >500/mm^3 can be seen. WBC count is usually elevated in most cases. May be normal if there is a delay in analysis and in immunocompromised patients who cannot mount an inflammatory response. In viral encephalitis an initial polymorphonuclear (PMN) predominance followed by a mononuclear shift after 24 to 48 hours (except in West Nile virus) is seen. Lymphocytosis (viruses, TB); atypical lymphocytes (EBV, CMV, rarely in HSV); PMN leukocytosis (bacterial infections, acute disseminated encephalomyelitis, acute hemorrhagic leukoencephalitis, amebic infections, occasionally in some viruses such as West Nile virus).

Culture: useful in identifying bacterial and fungal etiologies. Only useful for a few viruses (mumps, enterovirus, lymphocytic choriomeningitis virus). Viral cultures are rarely positive and if negative do not exclude infection.

Antigen testing: useful in rapidly identifying bacterial and fungal etiologies of encephalitis.

Gram stain: detection of organisms in bacterial causes.

Acid fast stain: TB.

India ink: Cryptococcus.

Serologic indexing is required for definitive diagnosis and compares CSF with serum-specific antibody levels in reference to total CSF, serum albumin, or total immunoglobulin.

Viral cultures of urine are not routinely performed.

Not widely available. Obtained more frequently in children when GI symptoms precede the development of encephalitis. Stool culture may also be used to detect poliovirus.

Ordered when a viral cause for encephalitis is suspected. IgG and IgM antibodies directed against specific viral pathogens may be detected by serologic serum studies.

Ordered when a viral cause for encephalitis is suspected.

Ordered when an underlying cancer is suspected and a paraneoplastic etiology to the encephalitis is suspected.

Performed later in the clinical course as part of the clinical workup for suspected underlying cancers (e.g., lung, breast, or ovarian) that are associated with limbic or brainstem encephalitis.

Performed later in the clinical course as part of the clinical workup for suspected underlying cancers (e.g., lung, breast, or ovarian) that are associated with limbic or brainstem encephalitis.

In some diagnostically difficult cases, repeat LPs are performed to obtain fluid for more specialized tests. PCR has revolutionized the diagnosis of most viral encephalitides. The advantages are its high sensitivity and specificity, quick turn around time, and ability to perform a battery of tests on a small sample of CSF. However, for PCR to be useful, viral genomic particles should be present in the CSF.

The criterion standard for diagnosis. Not routinely performed because it is invasive, requires general anesthesia, and is associated with some morbidity. With the increasing availability of MRI and PCR-based diagnostic methods, the need for brain biopsy is decreasing. It is still useful in diagnostically challenging cases. Immunocytochemistry (ICC), in situ hybridization (ISH) and PCR can be performed on biopsy/autopsy specimens, and have had a profound impact on the ability to diagnose the various etiologies of encephalitis.

Classic encephalitic nodules are composed of a mixture of microglia, astrocytes, and lymphocytes around affected neurons, cytologic features such as inclusion bodies (intranuclear in HSV, VZV, progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, and cytoplasmic Negri bodies in rabies) and cytomegalic cell changes (CMV). In acute disseminated encephalomyelitis, multiple small demyelinated foci are arranged around small veins of the white matter, with infiltration by lymphocytes, macrophages, and microglia.

Available in specialist centers only. Obtained in patients with a clinical diagnosis of encephalitis, but in whom the etiology is obscure or if the diagnosis of encephalitis is suspected but cannot be differentiated from brain tumors.

Available in specialist centers only. Obtained in patients with a clinical diagnosis of encephalitis, but in whom the etiology is obscure or if the diagnosis of encephalitis is suspected but cannot be differentiated from brain tumors.

Available in specialist centers only. Obtained in patients with a clinical diagnosis of encephalitis, but in whom the etiology is obscure or if the diagnosis of encephalitis is suspected but cannot be differentiated from brain tumors.

Available in specialist centers only. Obtained in patients with a clinical diagnosis of encephalitis, but in whom the etiology is obscure or if the diagnosis of encephalitis is suspected but cannot be differentiated from brain tumors.

Elevated WBC count in 70% or less of cases of brain abscess. This test should be ordered as part of the initial workup of any patient with a suspected brain abscess. Platelet count and Hb/Hct are also critical preoperative labs.

Elevation in the WBC count favors abscess over tumor, especially if the patient has not yet received corticosteroids.

Ordered as part of the initial workup if abscess is suspected, or subsequent to the finding of a ring-enhancing lesion on neuroimaging.

ESR is elevated in >90% of brain abscess. Rarely elevated in CNS neoplasm.

Considered more sensitive than CRP or ESR for infections of extra-CNS origin. Good marker for assessing treatment efficacy.[28]Luzzani A, Polati E, Dorizzi R, et al. Comparison of procalcitonin and C-reactive protein as markers of sepsis. Crit Care Med. 2003 Jun;31(6):1737-41. http://www.ncbi.nlm.nih.gov/pubmed/12794413?tool=bestpractice.com [29]Schuetz P, Christ-Crain M, Müller B. Procalcitonin and other biomarkers for the assessment of disease severity and guidance of treatment in bacterial infections. Jan 2008 [internet publication]. https://www.researchgate.net/publication/268576263_Procalcitonin_and_Other_Biomarkers_for_the_Assessment_of_Disease_Severity_and_Guidance_of_Treatment_in_Bacterial_Infections

The absence of positive blood cultures does not exclude the diagnosis of brain abscess. Blood cultures are less likely to be positive if the patient has received antibiotics. Not useful in cases of parasitic or fungal brain abscesses.

Appropriate if high index of suspicion for HIV or immunocompromise.

Negative antitoxoplasma IgM rules out acute infection, but false positives are possible.

MRI with contrast is the initial radiographic test ordered in a patient with suspected brain abscess, unless a head CT has already been obtained.

Although MRI generally offers more detail than CT, it is more time consuming and expensive.

The use of contrast is important to outline the areas of altered blood-brain barrier, and to assess the degree of edema in planning/monitoring therapy.[60]Younis RT, Anand VK, Davidson B. The role of computed tomography and magnetic resonance imaging in patients with sinusitis with complications. Laryngoscope. 2002 Feb;112(2):224-9. http://www.ncbi.nlm.nih.gov/pubmed/11889374?tool=bestpractice.com

Less detailed but more cost- and time-efficient than MRI. CT is less sensitive than MRI for detection of posterior fossa lesions as well as abscesses in the early stages.

Often performed as the first radiographic study in patients with new neurologic findings. If a good-quality MRI has been obtained, CT is not necessary.

Only useful in infants with open fontanelle. Sonography allows for more frequent neuroimaging in infants, who are at a higher risk of sequelae from the radiation associated with CT scanning. This technique also screens for hydrocephalus in this high-risk age group.

Time consuming. It has been suggested that analysis of diffusion-weighted imaging sequences of traditional MRI may be more cost effective in most patients.

LP is performed with extreme caution and only if a lesion is small and Toxoplasma gondii is likely. In cases of T gondii abscess, the PCR is positive.

LP does not play a role when pyogenic abscess is suspected.

Polymorphonuclear pleocytosis indicates acute suppurative meningitis. Mononuclear cells are seen in viral infections (meningoencephalitis, aseptic meningitis), syphilis, neuroborreliosis, tuberculous meningitis, multiple sclerosis, brain abscess, and brain tumors.

Testing is not typically warranted unless exposure to enterovirus 71 (EV71) is a possibility. EV71 causes a more severe illness and requires greater vigilance to detect complications early.

Only used if exposure to enterovirus 71 (EV71) is a possibility (e.g., recent travel to East or Southeast Asia).

Culture from stool or vesicle fluid is preferred, although a throat swab may also be used.

Only used if exposure to enterovirus 71 (EV71) is a possibility (e.g., recent travel to East or Southeast Asia).

CSF WNV-specific IgM using MAC-ELISA is the test of choice for diagnosing neuroinvasive WNV infection.

Results usually available in 24 to 48 hours.

Occasionally, IgM antibodies may persist in CSF long after acute infection.

Sensitivity is nearly 100% after the eighth day of illness.

Diagnostic in patients with more severe symptoms, but no symptoms of neuroinvasive disease.

Can be performed in neuroinvasive disease if CSF cannot be obtained or if diagnosis is in doubt.

Positive IgM in a single serum sample indicates either acute or previous infection.

Serum IgM antibody can persist for >1 year.

One serum sample should be collected during initial presentation and another during the convalescent phase (7 to 14 days later).

Results usually available in 24 to 48 hours.

Sensitivity is nearly 100% after the eighth day of illness.

Ordered in patients presenting with symptoms suggestive of neuroinvasive disease.

Ordered in patients presenting with symptoms suggestive of neuroinvasive disease.

Can be ordered when moderate to severe abdominal pain (especially RUQ) or jaundice present. Elevated LFTs suggest hepatitis, a rare complication of WNV.

Can be ordered when moderate to severe abdominal pain (especially epigastric) or jaundice.

Elevated amylase suggests pancreatitis, a rare complication of WNV.

Used to confirm WNV infection if MAC-ELISA results equivocal or patient exposed to other closely related viruses that may cause false positive WNV MAC-ELISA.

Optimal test for WNV diagnosis, but not routinely recommended.

Virus isolation is difficult, of low yield, and requires laboratories with proper biosafety containment facilities. Moreover, the virus is often absent from blood at onset of illness.

Performed if suspicion of other causes of neurologic symptoms. MRI is preferred over CT; however, CT is usually more readily available.

Perform if suspicion of other causes of neurologic symptoms. Not diagnostic, but can help exclude other causes of meningitis, encephalitis, and flaccid paralysis. Also can identify stroke, abscess, or other mass.

MRI is preferred over CT; however, CT is usually more readily available.

Requires selective culture media such as tellurite blood agar, enriched Loeffler, Hoyle, Mueller, or Tindale media, therefore, advance preparation and liaison with a microbiologist is required.

Cultures should be obtained from nose and throat swabs in patients suspected of having diphtheria. If possible, swabs should also be taken from beneath the pseudomembrane.

If suspicion of diphtheria is high, the patient and all their close contacts should be swabbed. Cultures may be taken even if antibiotic treatment has been started, although it is less likely to be successful in this circumstance.

If diphtheria antibody levels are high, the disease is less likely to produce a severe illness. However, if antibodies are low (a nonprotective diphtheria antibody titer is <0.01 IU/mL), a diagnosis of diphtheria cannot be excluded.

Culture and isolation of Corynebacterium diphtheriae is often unsuccessful once antibiotic treatment has been initiated. PCR is helpful in this situation because it can detect nonviable C diphtheriae organisms from clinical specimens.

PCR may not be available in all centers. The CDC can provide testing if required.

May help to assess anterior horn involvement and inflammation of spinal cord as well as to rule out other conditions.

May be useful in paralytic poliomyelitis and in postpoliomyelitis syndrome.

Demonstrates presence of virus being shed from the GI tract; does not indicate paralytic poliomyelitis.

Although clinically not usually relevant, epidemiologically it can be useful to diagnose whether there is circulating poliovirus.

Classic finding is elevated CSF protein with normal WBC count (albuminocytologic dissociation). Occurs in up to 90% of cases at week 1 after symptom onset. CSF protein is usually normal within the first 2 to 3 days but then begins to rise quickly, reaching a peak at 4 to 6 weeks and then persisting at a variably elevated level for many weeks.

CSF protein level varies from 45 to 300 mg/dL, but levels as high as 1000 mg/dL can be seen. About 59% of patients with Bickerstaff brainstem encephalitis (BBE) variant have elevated protein in CSF.

Extremely high protein levels (1000 mg/dL) are associated with development of high intracranial pressure (ICP) and papilledema. About 10% of patients will not have a protein elevation and this includes patients with the Miller-Fisher variant. WBC counts are typically <5/mm^3. However, in 10% of patients, lymphocytosis of <50 cells/mm^3 may be present early on but quickly normalizes over a few days.

Hepatic aminotransferases may be elevated during the first few days in 10% to 20% of patients and often rapidly normalize by 1 to 2 weeks. Elevation of hepatic enzymes is associated with a more severe disease. The cause is unclear. EBV and CMV infection have been suggested; however, serologic markers are often negative.

Should be carried out at 6-hourly intervals initially at the bedside. ICU monitoring and elective intubation should be considered if: vital capacity is <20 mL/kg (odds ratio 15.0); maximal inspiratory pressure worse than -30 cm H2O; maximal expiratory pressure <40 cm H2O; reduction of 30% in vital capacity, maximal inspiratory pressure, or maximal expiratory pressure.

Shows patchy demyelination, slowing of nerve conduction velocities, reduced or absent sensory action potential response without slowing of conduction velocities, prolongation of distal and F-wave latencies, dispersed response on needle.

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP): patchy demyelination, slowing of motor nerve conduction velocities, prolongation of distal and F-wave latencies, and dispersed response on needle.

At least one of the following in 2 nerves, or at least 2 of the following in 1 nerve: motor conduction velocity <90% lower limit of normal (LLN; 85% if distal compound muscle action potential [dCMAP] <50% LLN), distal motor latency >110% upper limit of normal (ULN; >120% if dCMAP <100% LLN), proximal CMAP/dCMAP ratio less than 0.5% and dCMAP >20% LLN, F-response latency >120% ULN.

Acute motor and sensory axonal neuropathy (AMSAN): diminution of muscle and sensory action potentials. None of the features of AIDP except one demyelinating feature allowed in one nerve if dCAMP <10% LLN and sensory action potential amplitudes less than LLN.

Acute motor axonal neuropathy (AMAN): reduction in distally evoked motor action potential amplitudes, early signs of denervation on needle, normal action potential on sensory nerves and relatively preserved motor nerve conduction velocity. None of the features of AIDP except one demyelinating feature allowed in one nerve if dCMAP <10% LLN and sensory action potential amplitudes normal.

Miller-Fisher syndrome: reduced or absent sensory action potential response without slowing of sensory conduction velocity.

An increase in titers for infectious agents, including CMV, EBV, Mycoplasma, Haemophilus influenzae and Campylobacter jejuni may help in establishing etiology for epidemiologic purposes but is of limited clinical use. Some data suggest that positive serologic markers for Campylobacter jejuni are associated with worse prognostic outcome.

BBE may have antecedent infection in 92%.

Testing for C jejuni may be considered if there is an antecedent history of diarrhea or in a region where acute motor axonal neuropathy (AMAN) is prevalent.

Ordered in individuals at high-risk of HIV or with CSF lymphocytic pleocytosis (>20 cells/mm^3).

Sensitive but nonspecific.

Enhancement of the cauda equina nerve roots with gadolinium has been found to be 85% sensitive for acute GBS and present in 95% of typical cases. May be useful when diagnosis is unclear and electrophysiologic abnormalities are equivocal. Can exclude disease processes involving the spinal cord (i.e., epidural abscess, transverse myelitis, spinal stenosis, spinal cord stroke, or tumor). In a study of 24 patients with GBS scanned on day 13, enhancement of the cauda equina nerve roots with gadolinium on lumbosacral MRI was found to be 83% sensitive for acute GBS and was present in 95% of typical cases.

The ELISA test depends on the active, free antibodies to attach to the free antigens that have been embedded on the walls of the test tube. If the antibodies in the serum being tested are already attached to antigens, then the enzyme reaction cannot take place. Thus the testing has moderate sensitivity, but good specificity. The numbers are widely spaced in the literature.

The sensitivity of PCR is >80%, making it useful for the differential testing. Its speed is a major advantage over viral cultures.

Has a sensitivity of 60% in most studies. Specificity for type of carcinoma is also limited.

Cerebrospinal fluid ACE assay is insensitive (24% to 55%) but may be reasonably specific (94% to 95%) for CNS neurosarcoidosis.

This combination of testing increases the positive yield to 90%.

Real-time PCR for zoonotic organisms has high sensitivity and moderate specificity, but when combined with indirect fluorescent antibody testing, sensitivity is >96%.

Results may vary among laboratories and assay techniques.

Antibodies are detectable in 80% to 90% of patients with generalized MG and up to 50% of patients with ocular MG.

Sensitivity: >90% in generalized MG; 40% to 60% in ocular MG. Specificity: 99%.

If the result is negative or equivocal, proceed to anti-muscle tyrosine kinase (MuSK) antibody assay.

Indicated if shortness of breath and suspected MG crisis.

Serial measurements of FVC and negative inspiratory force (NIF) are taken. Indication for mechanical ventilation includes FVC 15 mL/kg or less (normal 60 mL/kg or greater) and NIF 20 cm H2O or less (normal 70 cm H2O or greater). Physicians should not wait for abnormal ABG as it occurs late in the course after clinical decompensation.

Not performed routinely in all patients.

These antibodies are rare in patients without thymoma.

Sensitivity, 79% in generalized MG, 50% in ocular MG. Specificity, 97%.

Brief exercise of a muscle before the test may enhance decrement response.

If the result is negative and clinical suspicion is high, proceed to single fiber EMG.

Positive decrement also seen in Lambert-Eaton myasthenic syndrome (LEMS) and amyotrophic lateral sclerosis (ALS).

Sensitivity of 86% to 92% and specificity of 70% to 96% in facial muscles in ocular MG; sensitivity and specificity of 98% in generalized MG.

Abnormal test may be seen in Lambert-Eaton myasthenic syndrome (LEMS) and amyotrophic lateral sclerosis (ALS), inflammatory myopathies, or patients injected with botulinum toxin.

Should be performed in all newly diagnosed patients to detect thymoma (which occurs in about 15% of patients with MG) or thymic hyperplasia (which occurs in 75% of MG).

Some studies have questioned the primary role of angiography in deference to MR angiography, but the clinical pattern is still to order an angiogram.

Although brain biopsy remains the definitive test in the diagnosis of CNS vasculitis, 25% of the time a brain biopsy will be negative even in the setting of true vasculitis.[68]Aviv RI, Benseler SM, Silverman ED, et al. MR imaging and angiography of primary CNS vasculitis of childhood. AJNR Am J Neuroradiol. 2006 Jan;27(1):192-9. http://www.ajnr.org/content/27/1/192.long http://www.ncbi.nlm.nih.gov/pubmed/16418382?tool=bestpractice.com

Required in all patients to exclude compressive myelopathy.

Detection of intrinsic cord lesion assists in confirmation of myelitis.

Partial/asymmetric cord lesion extending over 1 or 2 vertebral segments supports diagnosis of acute partial TM.

Complete TM with longitudinally extensive lesion (3 or more contiguous vertebral segments in length) supports diagnosis of longitudinally extending TM. Longitudinally extending TM suggests other causes, including idiopathic TM, neuromyelitis optica, infection, or connective tissue disease-associated TM.[70]Murthy JM, Reddy JJ, Meena AK, et al. Acute transverse myelitis: MR characteristics. Neurol India. 1999 Dec;47(4):290-3. http://www.neurologyindia.com/article.asp?issn=0028-3886;year=1999;volume=47;issue=4;spage=290;epage=3;aulast=Murthy http://www.ncbi.nlm.nih.gov/pubmed/10625901?tool=bestpractice.com

If initial MRI is negative, the diagnosis of myelopathy should be reconsidered, and a decision made whether to repeat MRI in 7 to 10 days.

Periventricular, brain stem, and juxtacortical lesions suggest MS in setting of acute partial TM.

Periaqueductal lesions or lesions involving the thalamic and hypothalamic region suggest neuromyelitis optica.

Normal results suggest neuromyelitis optica or idiopathic TM in setting of complete TM.

Increased cell count (WBC >5/mm^3) supports inflammatory myelitis.

Normal CSF does not exclude TM but if TM is strongly suspected, repeating LP in 7 to 10 days should be considered.

Most causes are associated with WBC 10 to 2000/mm^3. WBC >50/mm^3, and negative oligoclonal bands suggest neuromyelitis optica.

WBC <50/mm^3 with lymphocytic differential and presence of increased IgG index or oligoclonal bands in setting of acute partial TM suggest multiple sclerosis.

Negative in noninfectious TM; helpful when there are constitutional symptoms, fever and/or CSF pleocytosis.

Useful for detection of HSV-1, HSV-2, VZV, Borrelia burgdorferi (Lyme disease), CMV, EBV, West Nile virus.

Indicated if high clinical suspicion of malignancy.

May require up to 3 serial CSF exams to exclude false-negative results.

Positive CSF VDRL is virtually 100% specific for syphilis but a negative result does not exclude the diagnosis.

May detect pulmonary infection or mediastinal lymphadenopathy or other lung parenchymal abnormality consistent with sarcoidosis.

May detect pulmonary infection, or mediastinal lymphadenopathy, or other lung parenchymal abnormality consistent with sarcoidosis.

Acute and convalescent serologies may confirm recent infection in parainfectious or infectious TM.

Most people develop detectable antibodies about 30 days after infection, although some seroconvert later. The vast majority of people (99%) have detectable antibodies by 3 months after HIV infection.

Delayed conduction in anterior visual pathways supports recent or prior optic neuropathy/neuritis.

If the MRI and CSF studies support TM but all other studies are negative, empiric treatment with corticosteroids can be considered both to confirm that the disorder is steroid-responsive and to improve symptoms.

Clinical improvement during or shortly after corticosteroids confirms a steroid-responsive inflammatory TM in most cases, although the possibility of CNS lymphoma, which also responds to corticosteroids, should also be considered.

At this point, the evaluation can move from diagnosis to evaluation of risk for recurrent TM, neuromyelitis optica, or MS.

Biopsy should be considered in patients with severe TM, failure to improve, and an enlarging lesion despite empiric corticosteroids. Biopsy may allow differentiation of inflammatory TM from granulomatous disease (sarcoidosis), lymphoma, or other neoplasm.

The most sensitive and specific muscle-derived serum enzyme of disease activity.

Can be elevated as much as 50 times above normal, especially in polymyositis. Can be normal in active dermatomyositis and, rarely, in active polymyositis. Normal or only mildly elevated in inclusion body myositis.

When elevated, serial evaluation represents the most effective laboratory guide for monitoring disease progression in polymyositis and dermatomyositis, as well as treatment response.

Not helpful in inclusion body myositis.

The CK level may normalize with treatment, and yet objective clinical exams do not typically reveal any improvement.

Less specific than CK for monitoring disease activity because it is not only present in the muscle, but also in the liver and brain. Occasionally elevated in myositis when CK is normal.

A sensitive index of the integrity of muscle fibers.

May show myopathic motor units on voluntary activity. Typical pattern at rest may be present.

Mixed long and short duration, small and large amplitude, polyphasic, a pattern of early-firing units and increased amplitude of motor units may be present in any type, more often in inclusion body myositis due to muscle fiber regeneration and disease chronicity.

EMG pattern described above is not specific for and similar patterns can be seen in toxic, infectious, or metabolic myopathies.

Mandatory for definitive diagnosis.

For accurate results there are 3 essential prerequisites: proper choice of muscle; appropriate staining; and interpretation of results by an expert in myopathology.

Muscle involvement can be patchy and prior EMG (followed by biopsy from the contralateral muscle) or MRI to direct muscle biopsy may increase yield. This is of particular relevance in clinically amyopathic dermatomyositis. A very weak muscle should be avoided as the site of biopsy because of the high risk that the distinguishing characteristics of idiopathic inflammatory myopathies have been lost, yielding nonspecific end-stage myopathic changes. A moderately weak muscle offers the best chance of a positive biopsy.

In inclusion body myositis, inclusion bodies contain beta-amyloid that can be revealed by Congo-red staining.

Elevated level may be erroneously interpreted as a sign of liver disease.

Present in muscle, liver, and erythrocytes.

less specific than CK for muscle injury

Normal in about one half of patients with polymyositis and dermatomyositis.

Inaccurate indicator of disease activity; in most cases there is no correlation between ESR and degree of weakness.

Nonspecific and commonly positive in other connective tissue diseases where myositis may be a feature.

Further testing for autoantibodies against specific nuclear antigens (e.g., anti-ds DNA, anti-Ro, anti-La, anti-Sm, anti-RNP) is useful to help differentiate between dermatomyositis and other connective tissue diseases.

Two major groups exist. Anticytoplasmic antibodies against translational components (e.g., antisynthetase antibodies and anti-SRP (anti-signal recognition particle) antibodies) are usually associated with relatively severe muscle disease.

Antibodies against Mi-2 and Mas antigens are usually associated with relatively mild muscle disease. Up to 79% of patients with dermatomyositis have Mi-2 antibodies.

Required in all patients with suspected dermatomyositis to evaluate respiratory involvement and to screen for malignancy.

In early interstitial lung disease (ILD), x-ray changes may be minimal or nonspecific and ILD may be missed if further respiratory investigations are not performed.

Should be performed in all patients with respiratory symptoms or abnormal PFTs.

More sensitive than chest x-ray in detecting interstitial lung disease and provides information on prognosis not provided by chest x-ray. The presence of ground glass opacification is associated with a better prognosis compared with honeycomb fibrotic changes.

Should be performed in patients with suspected dermatomyositis who have dysphagia, nasal regurgitation of fluid, or dysphonia.

Silent aspiration may also occur and further assessment is indicated in patients presenting with lower respiratory tract infection.

Presence of urinary PBG can be confirmed in a single void urine specimen using a urinary PBG test kit. This is the most useful single screening test for acute porphyrias, with high sensitivity and specificity during or soon after acute attacks.

Results should be confirmed by later measurement of delta-aminolevulinic acid (ALA) and urinary PBG and total porphyrins in the same sample.

An initial test ordered in patients with advanced renal disease and suspected AIP. Provides a quantitative measurement of serum PBG.

Less sensitive than urinary PBG in patients with normal renal function.

Performed in patients with increased PBG to differentiate AIP from hereditary coproporphyria and variegate porphyria, in which fecal porphyrins are substantially increased.

Quantitative assessment.

Single void specimen or 24-hour collection used.

Less sensitive than urinary porphobilinogen.

Quantitative assessment.

Single void specimen or 24-hour collection used.

Less specific than urinary PBG.

May remain increased after ALA and PBG become normal.

Performed in patients with increased PBG to differentiate AIP from variegate porphyria, in which plasma porphyrins are substantially increased.

Helps differentiate AIP (predominantly uroporphyrin) from hereditary coproporphyria and variegate porphyria (both predominantly coproporphyrin).

Helps differentiate AIP (predominantly uroporphyrin) from hereditary coproporphyria (predominantly coproporphyrin III) and variegate porphyria (both predominantly coproporphyrin III and protoporphyrin).

Helps in confirming a diagnosis of AIP and in differentiating AIP from other acute porphyrias.

Also useful in identifying carriers of an AIP trait in families where the index case has confirmed AIP and decreased enzyme activity.

More useful in screening family members with latent AIP.

Sequencing may not detect some cryptic mutations and complete or large deletions.

Hyponatremia may be present due to syndrome of inappropriate ADH secretion (SIADH) reflecting hypothalamic involvement.

May be changes in enzymes during attacks reflecting underlying pathophysiology.[75]Cherian A, Baheti NN, Kuruvilla A. Muscle channelopathies and electrophysiological approach. Ann Indian Acad Neurol. 2008 Jan;11(1):20-7. http://www.annalsofian.org/article.asp?issn=0972-2327;year=2008;volume=11;issue=1;spage=20;epage=27;aulast=Cherian [76]Khan NA, Khan AU, Hasan MI, et al. Clinical profile of periodic paralysis. Mymensingh Med J. 2012 Jan;21(1):28-33. http://www.ncbi.nlm.nih.gov/pubmed/22314450?tool=bestpractice.com

Exercise-induced changes are commonly seen. There are characteristic patterns for the different ion channels.[75]Cherian A, Baheti NN, Kuruvilla A. Muscle channelopathies and electrophysiological approach. Ann Indian Acad Neurol. 2008 Jan;11(1):20-7. http://www.annalsofian.org/article.asp?issn=0972-2327;year=2008;volume=11;issue=1;spage=20;epage=27;aulast=Cherian [77]Dachowski LJ, DeLaney TF. Photodynamic therapy: the NCI experience and its nursing implications. Oncol Nurs Forum. 1992 Jan-Feb;19(1):63-7. http://www.ncbi.nlm.nih.gov/pubmed/1538989?tool=bestpractice.com

Insulin and glucose administration will drive potassium into the cells, producing symptoms/signs of hypokalemic paralysis.

Administration of potassium to raise serum potassium will provoke a hyperkalemic attack. These tests are only recommended for inpatients.

Patients have a reduced interference pattern or reduced recruitment. This is also true for other neuropathic conditions, for instance, peripheral neuropathy, thus reduced recruitment is not specific for ALS.[82]Harrington TM, Cohen MD, Bartleson JD, et al. Elevation of creatine kinase in amyotrophic lateral sclerosis: potential confusion with polymyositis. Arthritis Rheum. 1983 Feb;26(2):201-5. http://www.ncbi.nlm.nih.gov/pubmed/6824516?tool=bestpractice.com

Used to exclude other potential diagnoses.

Tests may be ordered on blood and urine samples to eliminate the possibility of other diseases as well as routine laboratory tests.

Consistent with Duchenne muscular dystrophy (DMD). Patients may not attain such levels until 1 year old. CK levels peak at 5 years old, and are often as high as 35,000 IU/L.

Unusual presentation of DMD includes asymptomatic elevation of serum CK. Serum levels of CK depend on race and sex, so it is difficult to give a normal value.

If no mutation is present, linkage analysis of the patient, parents, and sibling(s) should be performed to establish the genetic diagnosis.

If DNA studies for Duchenne muscular dystrophy (DMD) are negative, EMG and muscle biopsy should be considered. EMG can usually distinguish between neuropathic and myopathic pathology. After a myopathic EMG, muscle biopsy is usually the next step in diagnosis. A neuropathic EMG usually leads to initial consideration of spinal muscular atrophy.

When DNA analysis does not identify the mutation and the mother or other family members are unavailable for linkage studies, muscle biopsy demonstrating absence of dystrophin can establish the diagnosis.

It is important to check with the laboratory before sending the sample. It may be appropriate to request assay of a single enzyme (e.g., glucocerebrosidase if Gaucher disease is suspected), or of a group of enzymes (e.g., requesting leukocyte enzyme assay as a screen for mucopolysaccharidosis disorders). Specimens are subject to decay.

Plasma and leukocyte activity may need to be tested in some conditions (e.g., Fabry disease).

Cultured fibroblasts are a good source of enzyme to assay; DNA will also be available.

Urinary glycosaminoglycans will be elevated in the mucopolysaccharidosis disorders. Urinary levels of globotriaosylceramide (Gb3) are elevated in Fabry disease. Urinary Glc4 and plasma Hex4 levels are increased in patients with Pompe disease. Plasma levels of glucosylceramide are elevated in Gaucher disease.

It is important to check with the laboratory before sending the sample. The result needs to be considered in light of detailed clinical information and data on enzyme activity.

Some mutations are polymorphisms and may not be associated with disease. Many PCR tests only screen for common mutations; "private" mutations are only detected by sequence analysis in research laboratories.

Denaturing high pressure liquid chromatography is a method for rapid screening for single base mutations.

Carrier detection in X-linked disorders can only be reliably achieved by DNA analysis.

Not all mutations have been analyzed and some disorders will only be diagnosed in specialist laboratories; it is essential that specialist centers are consulted in the design and implementation of the diagnostic strategy for these rare diseases.

Anemia may be multifactorial due to chronic disease, renal impairment, feeding difficulties, marrow replacement.

Leukopenia typically due to splenomegaly.

Abnormal inclusions in leukocytes: for example, PAS positive lymphocytes in Pompe disease; abnormal leukocyte appearances in blood/marrow in Tay-Sachs.

Thrombocytopenia typically due to splenomegaly; disturbed platelet function in, for example, Hermansky-Pudlak syndrome.

Critical for infantile Pompe, adult Fabry, and many neonatal mucopolysaccharidosis disorders.

Critical for infantile Pompe, adult Fabry, and many neonatal mucopolysaccharidosis disorders.

Muscle biopsy is of diagnostic use in many lysosomal storage diseases (e.g., late-onset Pompe; however, appearances may be normal).

A low glucose level during fasting or acute illness is obtained. Glucose level should be obtained as part of the initial evaluation. Serial measurements are often useful.

A low bicarbonate level during fasting or acute illness is obtained. This test is essential for the characterization of GSD I.

A high lactic acid level during fasting or acute illness is obtained. This test is essential for the characterization of GSD I.

A high uric acid level during fasting or acute illness is obtained. This test is essential for the characterization of GSD I.

Elevated levels of triglycerides obtained during fasting or acute illness. This test is essential for the characterization of GSD I.

AST and/or ALT levels may be elevated at diagnosis or during an advanced disease stage. These tests are essential for the characterization of GSD I.

In addition to fasting studies, glucose and lactate responses to glucagon (30 micrograms/kg, maximum 1 mg, either intramuscularly or as an intravenous bolus), 4 to 6 hours after a meal or after the administration of oral glucose, is a valuable functional test to evaluate a child with suspected glucose storage disease.

Blood samples for measurement of glucose and lactate concentrations are obtained 1 minute before and then at 15, 30, 45, and 60 minutes after glucagon is injected.

In type 1 glucose storage disease, glucagon causes little or no increase in the blood glucose concentration. By contrast, the blood lactate level, which typically is already markedly increased, increases further.

Identification of GSD I mutations confirms the diagnosis. These mutations are inherited in an autosomal recessive manner.

Assessment of enzymatic activity in biopsy tissue may be necessary in a small minority of patients who do not have an identifiable gene mutation. This highly specialized test is offered at a few academic centers.

Peripheral neuropathy is a common neurotoxic effect of medications. Axonal or demyelinating neuropathies are associated with individual drugs, especially anticancer, HIV, and transplant medications.

Toxin-induced syndromes can occur with normal serum levels of an agent such as antipsychotics. Their presence can aid in the diagnostic reasoning for the presenting dysfunction.

Several pressure measurement devices are available for determining intracompartmental pressures. Pressure should be measured in all compartments and at multiple sites, particularly within 5 cm of the level of injury. Differential pressure (diastolic BP minus compartment pressure) of 20 mmHg or less strongly indicates need for fasciotomy. Care should be taken when using this criterion for patients who are receiving vasodilatory medications whose diastolic BP is low.

Most sensitive and specific imaging modality. Primary diagnosis tool for brain tumors.

Ordered if the presentation is acute and need to rule out other processes such as stroke and hemorrhage.

Also used when there is no MRI available or if patient has any contraindications to MRI.

Sensitivity of contrast-enhanced CT is 65% to 100%, and the specificity is 72% to 100%.

If the CT is normal but history and exam are suggestive of brain tumor, an MRI should be performed.

CT scan can be ordered to complement MRI when calcification is suspected in the lesion.

Used to help determine the grade of the tumor. The choline:NAA ratio is most useful for tumor identification, lactate for infracted/necrotic tissue, and lipids for determining infection.[87]Howe FA, Opstad KS. 1H MR spectroscopy of brain tumours and masses. NMR Biomed. 2003 May;16(3):123-31. http://www.ncbi.nlm.nih.gov/pubmed/12884355?tool=bestpractice.com [88]Usenius JP, Kauppinen RA, Vainio PA, et al. Quantitative metabolite patterns of human brain tumors: detection by 1H NMR spectroscopy in vivo and in vitro. J Comput Assist Tomogr. 1994 Sep;18(5):705-13. http://www.ncbi.nlm.nih.gov/pubmed/8089316?tool=bestpractice.com

The definitive diagnostic tool.

One of the limitations of the stereotactic biopsy is the sampling error in diffuse astrocytoma (different area of the tumor can show different histologic grade).

Ordered if there are specific complaints from the patient and/or specific findings on physical exam, or evidence of compression of optic chiasm on MRI.

This is the most sensitive test for all pathologies, especially disc, blood, ligaments, and paravertebral structures.

Dynamic motion films should be reserved until spinal attending physician is present.

May help to assess the amount of cognitive impairment, if response times are noted. Recall deficit can be distinguished from recognition deficit if responses improve when cues or multiple choices are offered.

Imaging with either CT or MRI is essential; absence of ventriculomegaly essentially eliminates the diagnosis of normal pressure hydrocephalus from the differential.

MRI is considered more sensitive and specific than CT for the diagnostic and subsequent therapeutic options in hydrocephalus. Enhanced images are useful if a tumor is suspected.

Imaging with either CT or MRI is essential; absence of ventriculomegaly essentially eliminates the diagnosis of normal pressure hydrocephalus from the differential.

CT is cheap, widely available and preferred for patients with pacemakers and automatic implantable cardioverter defibrillators. Its speed also makes it preferable for children.

Removal of 40 to 50 mL of CSF can be performed in outpatient setting without specialized equipment.

Predictive power for improvement from shunting: sensitivity 26% to 62%, specificity 33% to 100%.

No evidence to show relationship between opening pressure values and outcome in normal pressure hydrocephalus, but pressures higher than the expected range may indicate a secondary cause of hydrocephalus.

Large-volume removal of CSF, typically up to 10 mL/hour for up to 72 hours. This can predict potential response to shunting. Sensitivity: 50% to 100%; specificity: 60% to 100%.

Can provide predictive value in determining response to shunt (positive predictive value 83%); presence of specific B-wave subtypes (Great Symmetrical waves and Intermediate waves) may predict positive outcomes (limited evidence, has not been generalized to idiopathic normal pressure hydrocephalus patients).

For detection of shunt-responsive normal pressure hydrocephalus (NPH). Sensitivity: 46%, specificity: 87%. Positive predictive value: 56% to 96%. May be useful in identifying shunt-responsive NPH when tap test is negative.

Helpful, but not crucial. Stable, bilaterally symmetrical hearing results are expected. Conductive loss due to middle-ear infection or neoplastic lesions should be investigated. Ipsilateral sensorineural hearing loss should be investigated to rule out a cerebellopontine angle and/or internal auditory canal tumor.

Helpful, but not crucial. Absent reflexes along the efferent limb of the reflex arc are expected in moderate to severe facial paralysis. If the facial paralysis is severe, but the reflexes are normal, a lesion external to the temporal bone should be suspected, especially a malignant neoplasm of the parotid. Absent reflexes along the afferent limb are not expected and may suggest an eighth nerve tumor. In both cases, an MRI is necessary.

Helpful, but not crucial. Performed within the first 14 to 21 days. Neuropraxic (transient) lesions may not affect the CMAP. Neural degeneration results in a reduction in the CMAP correlating with the degree of presumed axon destruction. Nerve fiber regrowth can overcome some or nearly all the functional loss and return visible facial function to near normal. This becomes overwhelmed when the CMAP is reduced 95% or greater; in these cases, recovery is usually far less than normal. These data help to determine prognosis.

Helpful, but not crucial. Performed after the first 10 days. Fibrillation potentials and reduced or absent voluntary motor unit potentials are indicative of neuron/axon destruction. This is qualitatively informative, but it is difficult or impossible to quantitatively assess. These data help to determine prognosis.

Not generally performed unless tumor is suspected. Facial nerve or eighth nerve schwannomas, or other cerebellopontine angle or temporal bone tumors show tumor mass enhancement.

Expert consensus is that the formal diagnostic assessment for functional neurologic disorder should include a neurologist/neuropsychiatrist and/or another physician with neurologic exam expertise; therefore, specialist referral is typically required following an initial assessment.[23]Perez DL, Aybek S, Popkirov S, et al. A review and expert opinion on the neuropsychiatric assessment of motor functional neurological disorders. J Neuropsychiatry Clin Neurosci. 2021 Winter;33(1):14-26. https://neuro.psychiatryonline.org/doi/10.1176/appi.neuropsych.19120357 http://www.ncbi.nlm.nih.gov/pubmed/32778007?tool=bestpractice.com