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Brain tumor differential diagnosis

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

Overview

Overview

Brain tumors should be differentiated from essential tremors, stroke, chronic subdural hematoma, meningitis, orbital optic neuritis, arteriovenous malformation, intraocular optic neuritis, brain abscess, and neurosyphilis.

Differentiating brain tumor from other diseases

Differentiating brain tumor from other diseases


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[1][2] ✔ Cancer cells[3] 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[4] ✔ Xanthochromia[5] CT scan without contrast[6][7] ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ Trauma/fall Confusion, dizziness, nausea, vomiting
Stroke ✔ Normal CT scan without contrast ✔ ✔ ✔ ✔ ✔ TIAs, hypertension, diabetes mellitus Speech difficulty, gait abnormality
Neurosyphilis[8][9] ✔ ↑ Leukocytes and protein CSF VDRL-specifc

CSF FTA-Ab -sensitive[10]

✔ ✔ ✔ ✔ ✔ ✔ 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 tumors from other brain cystic lesions
Disease Prominent clinical features Lab findings Radiological findings
Neurocysticercosis
Brain abscess
  • 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.
Brain tumors
  • 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.[13]
Brain tuberculoma
  • Presentations are usually due to the pressure effect, not the T.B. bacilli.
  • Presenting symptoms and signs in order of occurrence:[14]
  1. Episodes of focal seizures
  2. Signs of increased intracranial pressure
  3. Focal neurologic deficits.
  • 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:[15]
  1. Cranial nerve neuropathies: Facial palsy is the most common presentation.
  2. Meningeal involvement: diffuse meningeal inflammation can cause diffuse basilar polyneuropathy in 40% of the patients. with neurosarcoidosis.
  3. Inflammatory spinal cord disease: Inflammatory span usually more than 3 spinal cord segments which helps to differentiate it from Multiple Sclerosis.
  4. Peripheral neuropathy: Asymmetric polyneuropathy or mononeuritis multiplex. It may also manifest as Guillain-Barré syndrome (GBS) like presentation.
  5. HPO axis involvement: may present as diabetes insipidus. More than 50% of the cases have no radiological signs.
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

Brain tumors must be differentiated from other causes of headache, seizures and loss of consciousness.

Diseases Symptoms Physical Examination Past medical history Diagnostic tests Other Findings
Headache ↓LOC Motor weakness Abnormal sensory Motor Deficit Sensory deficit Speech difficulty Gait abnormality Cranial nerves CT /MRI CSF Findings Gold standard test
Meningitis + – – – – + + – – History of fever and malaise – ↑ Leukocytes,

↑ Protein

↓ Glucose

CSF analysis[16] Fever, neck

rigidity

Encephalitis + + +/- +/- – – + +/- + History of fever and malaise + ↑ Leukocytes, ↓ Glucose CSF PCR Fever, seizures, focal neurologic abnormalities
Brain tumor[17] + – – – + + + – + Weight loss, fatigue + Cancer cells[3] MRI Cachexia, gradual progression of symptoms
Hemorrhagic stroke + + + + + + + + – Hypertension + – CT scan without contrast[6][7] Neck stiffness
Subdural hemorrhage + + + + + – – – + Trauma, fall + Xanthochromia[5] CT scan without contrast[6][7] Confusion, dizziness, nausea, vomiting
Neurosyphilis[8][9] + – + + + + – + – STIs + ↑ Leukocytes and protein CSF VDRL-specifc

CSF FTA-Ab -sensitive[10]

Blindness, confusion, depression,

Abnormal gait

Complex or atypical migraine + – + + – – + – – Family history of migraine – – Clinical assesment Presence of aura, nausea, vomiting
Hypertensive encephalopathy + + – – – – + + – Hypertension + – Clinical assesment Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy – + – – – + + + + History of alcohal abuse – – Clinical assesment and lab findings Ophthalmoplegia, confusion
CNS abscess + + – – + + + – – History of drug abuse, endocarditis, immunosupression + ↑ leukocytes, ↓ glucose and ↑ protien MRI is more sensitive and specific High grade fever, fatigue,nausea, vomiting
Drug toxicity – + – + + + – + – – – – Drug screen test Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder + + + + + + + + History of emotional stress – – Diagnosis of exclusion Tremors, blindness, difficulty swallowing
Metabolic disturbances (electrolyte imbalance, hypoglycemia) – + + + + + – – + – – Hypoglycemia, hypo and hypernatremia, hypo and hyperkalemia Depends on the cause Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Multiple sclerosis exacerbation – – + + – + + + + History of relapses and remissions + ↑ CSF IgG levels

(monoclonal bands)

Clinical assesment and MRI [18] Blurry vision, urinary incontinence, fatigue
Seizure + + – – + + – – + Previous history of seizures – Mass lesion Clinical assesment and EEG [19] Confusion, apathy, irritability,


References

References

  1. ↑ Soffer D (1976) Brain tumors simulating purulent meningitis. Eur Neurol 14 (3):192-7. PMID: 1278192
  2. ↑ Invalid <ref> tag; no text was provided for refs named pmid3883130
  3. ↑ 3.0 3.1 Weston CL, Glantz MJ, Connor JR (2011). “Detection of cancer cells in the cerebrospinal fluid: current methods and future directions”. Fluids Barriers CNS. 8 (1): 14. doi:10.1186/2045-8118-8-14. PMC 3059292. PMID 21371327.
  4. ↑ Yeh ST, Lee WJ, Lin HJ, Chen CY, Te AL, Lin HJ (2003) Nonaneurysmal subarachnoid hemorrhage secondary to tuberculous meningitis: report of two cases. J Emerg Med 25 (3):265-70. PMID: 14585453
  5. ↑ 5.0 5.1 Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). “Cerebrospinal fluid in cerebral hemorrhage and infarction”. Stroke. 6 (6): 638–41. PMID 1198628.
  6. ↑ 6.0 6.1 6.2 Birenbaum D, Bancroft LW, Felsberg GJ (2011). “Imaging in acute stroke”. West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.
  7. ↑ 7.0 7.1 7.2 DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF; et al. (2011). “ACR Appropriateness Criteria® on cerebrovascular disease”. J Am Coll Radiol. 8 (8): 532–8. doi:10.1016/j.jacr.2011.05.010. PMID 21807345.
  8. ↑ 8.0 8.1 Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG; et al. (2012). “Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients”. J Neurol Sci. 317 (1–2): 35–9. doi:10.1016/j.jns.2012.03.003. PMID 22482824.
  9. ↑ 9.0 9.1 Berger JR, Dean D (2014). “Neurosyphilis”. Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
  10. ↑ 10.0 10.1 Ho EL, Marra CM (2012). “Treponemal tests for neurosyphilis–less accurate than what we thought?”. Sex Transm Dis. 39 (4): 298–9. doi:10.1097/OLQ.0b013e31824ee574. PMC 3746559. PMID 22421697.
  11. ↑ Brouwer MC, Tunkel AR, McKhann GM, van de Beek D (2014). “Brain abscess”. N. Engl. J. Med. 371 (5): 447–56. doi:10.1056/NEJMra1301635. PMID 25075836.
  12. ↑ “Brain Abscess — NEJM”.
  13. ↑ 13.0 13.1 “Primary Brain Tumors in Adults – American Family Physician”.
  14. ↑ “The Journal of Association of Chest Physicians – Tuberculoma of the brain – A diagnostic dilemma: Magnetic resonance spectroscopy a new ray of hope : Download PDF”.
  15. ↑ 15.0 15.1 “Neurosarcoidosis”.
  16. ↑ Carbonnelle E (2009). “[Laboratory diagnosis of bacterial meningitis: usefulness of various tests for the determination of the etiological agent]”. Med Mal Infect. 39 (7–8): 581–605. doi:10.1016/j.medmal.2009.02.017. PMID 19398286.
  17. ↑ Morgenstern LB, Frankowski RF (1999). “Brain tumor masquerading as stroke”. J Neurooncol. 44 (1): 47–52. PMID 10582668.
  18. ↑ Giang DW, Grow VM, Mooney C, Mushlin AI, Goodman AD, Mattson DH; et al. (1994). “Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group”. Arch Neurol. 51 (1): 61–6. PMID 8274111.
  19. ↑ Manford M (2001). “Assessment and investigation of possible epileptic seizures”. J Neurol Neurosurg Psychiatry. 70 Suppl 2: II3–8. PMC 1765557. PMID 11385043.

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