Brain abscess differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Farwa Haideri [2]

Overview

Brain abscess must be differentiated from metastatic tumors, necrotic tumors, and lymphomas.

Differential Diagnosis

Brain abscess must be differentiated from:

• Metastatic tumors
• Necrotic tumors
• Lymphomas

Metastatic Tumor

• The big differential is that the abscess is often located in watershed regions, and tumors often enhance diffusely with contrast.

Necrotic Tumor

• Diagnosis of brain abscesses and necrotic tumors is often impossible without conventional MR imaging.
  • Several studies demonstrate the utility of Diffusion-weighted imaging (DWI) to differentiate between necrotic or cystic lesions and brain abscesses.
  • DWI has a sensitivity and specificity of over 90% for distinguishing abscess (low ADC) from necrotic tumors (high ADC).

Lymphoma

• Some studies suggest that indium scans can help differentiate abscess from CA, and thallium SPECT scans can distinguish CNS toxoplasmosis from lymphoma.

Despite these differences, the true diagnosis is sometimes not made until biopsy.

Diseases	Diagnostic tests				Physical Examination					Symptoms			Past medical history	Other Findings
	Na+, K+, Ca2+	CT /MRI	CSF Findings	Gold standard test	Neck stiffness	Motor or Sensory deficit	Papilledema	Bulging fontanelle	Cranial nerves	Headache	Fever	Altered mental status
Brain tumour		✔	Cancer cells	MRI		✔	✔	✔	✔	✔		✔		Cachexia, gradual progression of symptoms
Delirium tremens		✔		Clinical diagnosis		✔	✔		✔	✔	✔	✔	Alcohol intake, sudden witdrawl or reduction in consumption	Tachycardia, diaphoresis, hypertension, tremors, mydriasis, positional nystagmus,
Subarachnoid hemorrhage		✔	Xanthochromia	CT scan without contrast	✔	✔	✔	✔	✔	✔	✔	✔	Trauma/fall	Confusion, dizziness, nausea, vomiting
Stroke		✔	Normal	CT scan without contrast		✔	✔		✔	✔		✔	TIAs, hypertension, diabetes mellitus	Speech difficulty, gait abnormality
Neurosyphilis		✔	↑ Leukocytes and protein	CSF VDRL-specifc CSF FTA-Ab -sensitive	✔	✔	✔	✔		✔		✔	Unprotected sexual intercourse, STIs	Blindness, confusion, depression, Abnormal gait
Viral encephalitis		✔	Increased RBCS or xanthochromia, mononuclear lymphocytosis, high protein content, normal glucose	Clinical assesment	✔	✔	✔		✔	✔	✔	✔	Tick bite/mosquito bite/ viral prodome for several days	Extreme lethargy, rash hepatosplenomegaly, lymphadenopathy, behavioural changes
Herpes simplex encephalitis		✔		Clinical assesment			✔	✔	✔	✔	✔		History of hypertension	Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy			Normal				✔	✔			✔		History of alcohal abuse	Ophthalmoplegia, confusion
CNS abscess		✔	↑ leukocytes >100,000/ul, ↓ glucose and ↑ protien, ↑ red blood cells, lactic acid >500mg	Contrast enhanced MRI is more sensitive and specific, Histopathological examination of brain tissue	✔	✔	✔		✔	✔	✔	✔	History of drug abuse, endocarditis, ↓ immune status	High grade fever, fatigue,nausea, vomiting
Drug toxicity											✔	✔		Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder				Diagnosis of exclusion		✔		✔		✔	✔	✔		Tremors, blindness, difficulty swallowing
Electrolyte disturbance	↓ or ↑			Depends on the cause						✔		✔		Confusion, seizures
Febrile convulsion			Not performed in first simple febrile seizures	Clinical diagnosis and EEG					✔	✔	✔	✔	Family history of febrile seizures, viral illness or gastroenteritis	Age > 1 month,
Subdural empyema		✔		Clinical assesment and MRI	✔	✔	✔	✔	✔			✔	History of relapses and remissions	Blurry vision, urinary incontinence, fatigue
Hypoglycemia	↓ or ↑			Serum blood glucose HbA1c		✔				✔		✔	History of diabetes	Palpitations, sweating, dizziness, low serum, glucose

Differentiating brain abscess in immunocompromised host

Brain abscess is common among immunocompromised patients who are at high risk for other fungal, bacterial, and viral infections. It should be differentiated from the following diseases:

Disease	Differentiating signs and symptoms	Differentiating tests
CNS lymphoma	Patient is immunocompetent Focal symptoms indicative of a mass lesion Seizure	Single solitary ring enhancing lesion on CT or MRI
Disseminated tuberculosis	Prior history of residence in an endemic area Chronic cough, weight loss, hemoptysis	PCR of CSF for tuberculosis Mycobacterial culture of CSF Brain biopsy for acid-fast bacilli staining Culture and acid stain positive for acid-fast bacilli CXR shows cavitations
Aspergillosis	Pulmonary lesions in addition to CNS lesions Symptoms may include cough, chest pain, and hemoptysis	CSF fungal culture, galactomannan
Cryptococcosis	Symptoms include cough, chest pain, and hemoptysis	Cryptococcal antigen from CSF and serum CSF fungal culture
Chagas disease	History of residence in Central or South America Acute infection is rarely symptomatic Encephalitis or focal brain lesions Myocarditis Chronic infections in immunocompromised patients develop into encephalitis with necrotic brain lesions causing a mass effect	Trypanosoma cruzi in blood, tissue, or CSF, PCR of tissue or body fluids, and serologic tests
CMV infection	Most common CNS opportunistic infection in AIDS patients Presents with encephalitis, retinitis, progressive myelitis, or polyradiculitis In disseminated disease, it involves both the liver and kidneys	Brain CT/MRI/biopsy: location of lesions is usually near the brain stem or periventricular areas PCR of CSF with detectable virus is diagnostic Brain biopsy with + staining for CMV or evidence of owl's eyes is also diagnostic, but it is rarely performed because of the location of brain lesions
HSV infection	Seizures, headache, confusion and/or urinary retention can be seen in disseminated disease, which usually affects only the immunocompromised or acute infections In pregnant women, it may be associated with concurrent genital/oral lesions; can be spread to the neonate during acute infection in the mother, or via viral shedding in the birth canal Neonatal HSV can range from localized skin infections to encephalitis, pneumonitis, and disseminated disease	Brain CT/MRI/biopsy: location of lesions is usually the medial temporal lobe or the orbital surface of the frontal lobe. PCR of CSF with detectable virus is diagnostic
Varicella Zoster infection	Multifocal involvement has subacute course, usually only in immunosuppressed, with headache, fever, focal deficits, and seizures. Unifocal involvement is more typically seen in immunocompetent hosts, occurring after contralateral cranial nerve herpes zoster, with mental status changes, TIAs, and stroke Disseminated varicella zoster virus can occur in adults during primary infection, presenting with pneumonitis and/or hepatitis Disease is a vasculopathy with hemorrhage and stroke	PCR of CSF with detectable virus is diagnostic
Brain abscess	Associated with sinusitis (abutting the sinuses) or with bacteremia Signs and symptoms includes fever and necrotizing brain lesions with mass effect	CSF culture or culture of brain abscess
Progressive multifocal leukoencephalopathy	Symptoms are often more insidious in onset and progress over months. Symptoms include progressive weakness, poor coordination, with gradual slowing of mental function. Only seen in the immunosuppressed. Rarely associated with fever or other systemic symptoms	PCR of CSF for JC virus Biopsy reveals white matter lesions and not well-circumscribed lesions.

Differentiating brain abscess from other brain cystic lesions

Disease	Prominent clinical features	Lab findings	Radiological findings
Neurocysticercosis	Presenting symptoms differ according to the site of the cysticerci. Parenchymal neurocysticercosis causes all the symptoms and signs of space occupying lesions. Extraparenchymal neurocysticercosis causes manifestations of increased intracranial pressure if cysts are present in the subarachnoid space or in the ventricles, manifestations of spinal cord compression if present in the spinal cord or causes eye disease if cysts are present in the orbit.	CDC's immunoblot is based on detection of antibody to one or more of 7 lentil-lectin purified structural glycoprotein antigens from the larval cysts. It is 100% specific and has a sensitivity superior to that of any other test yet evaluated	Computerized tomography (CT) is superior to magnetic resonance imaging (MRI) for demonstrating small calcifications. However, MRI shows cysts in some locations (cerebral convexity, ventricular ependyma) better than CT, is more sensitive than CT to demonstrate surrounding edema, and may show internal changes indicating the death of cysticerci.
Brain abscess	Headaches are the most common symptom. Usually, headaches occur on the same side of the abscess and tend to be severe (not responding to analgesics). Fever is not a reliable sign.	Lumbar puncture is contraindicated but when done, it was variable between patients. Culture from the CT-guided aspirated lesion helps in identifying the causative agent.	Contrast enhanced CT provides rapid assessment of the size and number of the abscesses. MRI: Diffusion-weighted imaging (DWI) MRI can differentiate brain abscesses from cystic brain lesions with sensitivity and specificity of 96%.
Brain tumors	Most common presenting symptom is dull aching headache. Usually, it's associated with other symptoms of increased intracranial pressure (ICP) as seizures, visual disturbances, nausea, and vomiting.		CT may be used in localizing the tumor and getting a rough estimate on the dimensions. MRI: Gadolinium-enhanced MRI is the preferred imaging modality for assessing the extension of the tumor and its exact location.
Brain tuberculoma	Brain tuberculomas has insidious onset of symptoms as compared to tuberculous meningitis. Presentations are usually due to the pressure effect, not the T.B. bacilli. Presenting symptoms and signs in order of occurrence: Episodes of focal seizures Signs of increased intracranial pressure Focal neurologic deficits.	T.B. should be investigated everywhere else in the body (e.g. peripheral lymphadenopathy, sputum and blood culture)	CT: Contrast-enhanced CT scan shows a ring enhancing lesion surrounded by an area of hypodensity (cerebritis) and the resulting mass effect. MRI: Better than CT scan in assessing the site and size of the tuberculoma. Gadolinium-enhanced MRI shows a ring enhancing lesion between 1-5 cm in size (In NCC, the wall is thicker, calcifications are eccentric and the diameter is less than 2 cm)
Neurosarcoidosis	70% of the patients present with the neurological symptoms rather than the presentation of systemic disease. Common presentations are: Cranial nerve neuropathies: Facial palsy is the most common presentation. Meningeal involvement: diffuse meningeal inflammation can cause diffuse basilar polyneuropathy in 40% of the patients. with neurosarcoidosis. Inflammatory spinal cord disease: Inflammatory span usually more than 3 spinal cord segments which helps to differentiate it from Multiple Sclerosis. Peripheral neuropathy: Asymmetric polyneuropathy or mononeuritis multiplex. It may also manifest as Guillain-Barré syndrome (GBS) like presentation. HPO axis involvement: may present as diabetes insipidus. More than 50% of the cases have no radiological signs.	Noninvasive tests have low sensitivity and specificity. Serum ACE levels are elevated in 25% of the cases Lumbar puncture shows elevated CSF proteins together with mild-moderate pleocytosis. It is usually accompanied by oligoclonal bands.	MRI with contrast shows enhancement of the inflamed areas (i.e. cranial nerves, meninges or HPO axis)

MRI brain showing brain abscess - Case courtesy of A.Prof Frank Gaillard, https://radiopaedia.org/ From the case https://radiopaedia.org/cases/4933"	MRI brain showing Glioblastoma multiforme - Case courtesy of A.Prof Frank Gaillard, <a href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/28272">rID: 28272</a>	MRI brain showing tuberculoma - Case courtesy of Dr G Balachandran, https://radiopaedia.org/ From the case https://radiopaedia.org/cases/5489"	MRI brain showing Neurosarcoidosis - Case courtesy of A.Prof Frank Gaillard, https://radiopaedia.org/ From the case https://radiopaedia.org/cases/4364S