Subarachnoid hemorrhage differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Syed Ahsan Hussain, M.D.[2] Sara Mehrsefat, M.D. [3]

## Overview

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## Differential diagnosis

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It is clinically difficult to distinguish subarchnoid hemorrhage from an ischemic stroke. However, the symptoms like headache, nausea, vomiting, and depressed level of consciousness should raise the suspicion for a hemorrhagic event compared to ischemic stroke.[1][2]

Disease | Findings

|

Ischemic stroke |

* Occurs when a clot or a mass clogs a blood vessel and cutting off the blood flow to the brain
* Present as a
* Thrombotic stroke (thrombus develops at the clogged part of the vessel)
* Embolic strokes (blood clot that forms at another locations usually the heart and large arteries of the upper chest and neck, and travels to the brain)
* Urgent evaluation with brain / neurovascular imaging (such as MRI, CT, CTA, MRA), cardiac, and metabolic evaluation is often necessary

transient ischemic attack (TIA) |

* Caused by a temporary clot which often called a “mini stroke”
* Occurs rapidly and presents as a sudden onset of a focal neurologic symptom/sign lasting less than 24 hours
* Urgent evaluation with brain / neurovascular imaging (such as MRI, CT, CTA, MRA), cardiac, and metabolic evaluation is often necessary

Acute hypertensive crisis/Malignant hypertension |

* Presents as significantly elevated blood pressure (systolic pressure ≥180 and/or diastolic pressure ≥120 mmHg) with or wihout acute end-organ injury
* Urgent evaluation with MRI and CT of the brain, serum creatinine, urinalysis, cardiac (EKG, chest x ray, and cardiac enzymes) and metabolic evaluation is often necessary

Sentinel headache[3] |

* Caused by small aneurysmal leaks into the subarachnoid space
* Presents as a episode of headache similar to that accompanying subarachnoid hemorrhage (days to weeks prior to aneurysm rupture) and focal neurologic symptoms and signs are usually absent

Sinusitis |

* Presents with acute and subacute headaches and facial pain

Hypoglycemia |

Pituitary apoplexy[4] |

* Caused by pituitary gland infarct or hemorrhage secondary to pitutiery adenoma
* Presents with acute headache, change in mental status, ophthalmoplegia, and decreased visual acuity
* Brain CT and MRI are the preferred imaging techniques

Cerebral venous thrombosis[5][6] |

* Presents with isolated gradual onset headache or in combination with papilledema, seizures, bilateral focal deficits, and change in mental status
* Brain MRI with venography should be considered

Colloid cyst of the third ventricle[7] |

* Caused by an acute obstructive hydrocephalus secondary to sudden obstruction in cerebrospinal fluid flow by the cyst
* Presents with an acute onset fronto-parietal or fronto-occipital headache which relieved by taking the supine position and may be associated with nausea, vomiting, mental status changes, seizures, coma
* Head CT or MRI of the brain are usually diagnostic

Cervical artery dissection[8][9] |

* It usulay occurs spontaneously or after head and neck injury
* Presents with gradual onset head and neck pain with a local manifestations (such as Horner syndrome, pulsatile tinnitus, bruit, or cranial neuropathies)
* Neuroimagings are usually preferred (brain MRI with MRA and cranial CT with CTA)

Reversible cerebral vasoconstriction syndrome |

* Occurs spontaneously and trigerred by sexual activity, exertion, emotion, and constriction of the cerebral arteries
* Presents with acute severe headache with or without focal deficits or seizures that resolves spontaneously within 12 weeks

Spontaneous intracranial hypotension[10][11] |

* Presents with orthostatic headaches, nausea, vomiting, dizziness, diplopia, interscapular pain
* Caused by cerebrospinal fluid (CSF) leakage from spinal meningeal defects or dural tears
* Brain MRI is the preferred imaging techniques

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[12][13] |  | ✔  | Cancer cells[14] | 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[15] |  | ✔  | Xanthochromia[16] | CT scan without contrast[17][18] | ✔  | ✔  | ✔  | ✔  | ✔  | ✔  | ✔  | ✔  | Trauma/fall  | Confusion, dizziness, nausea, vomiting
Stroke |  | ✔  | Normal  | CT scan without contrast  |  | ✔  | ✔  |  | ✔  | ✔  |  | ✔  | TIAs, hypertension, diabetes mellitus | Speech difficulty, gait abnormality
Neurosyphilis[19][20] |  | ✔  | ↑ Leukocytes and protein | CSF VDRL-specifc

CSF FTA-Ab -sensitive[21]

| ✔  | ✔  | ✔  | ✔  |  | ✔  |  | ✔  | 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

Subarachnoid hemorrhage should be differentiated from other diseases causing severe headache for example: [22][23][24][25][26][27][28][29][30][31]

Disease  | Symptoms  | Diagnosis

|
|

CT/MRI  | Other Investigation Findings
Subarachnoid hemorrhage |

* Severe headache (as a worst headache of the life)
* Headache is the main symptom (often starts suddenly and starts after a popping or snapping feeling in the head)
* Double vision
* Nausea and vomiting
* Symptoms of meningeal irritation
* Sudden decreased level of consciousness
* Rapid progression of symptoms

* The modality of choice for diagnosis of subarachnoid hemorrhage is noncontrast head computed tomography (CT), with or without lumbar puncture.[1]
* CT shows hyperattenuating material filling the subarachnoid space.

* Lumbar puncture (LP) is necessary when there is a strong suspicion of subarachnoid hemorrhage. LP will show:
* Elevated opening pressure
* Elevated red blood cell (RBC)
* Xanthochromia

Meningitis |

* Headache
* Neck stiffness
* Fever

* Photophobia (inability to tolerate bright light)
* Phonophobia (inability to tolerate loud noises)
* Irritability, altered mental status (in small children)

* CT scan of the head may be performed before LP to determine the risk of herniation.

* Diagnosis is based on clinical presentation in combination with CSF analysis.
* CSF analysis is the investigation of choice.
* For more information on CSF analysis in meningitis please click here.

Intracranial mass |

* Headache
* Nausea
* Vomiting
* Change in mental status
* Seizures
* Focal symptoms of brain damage
* Associated co-morbid conditions like tuberculosis, etc

* CT or MRI is the initial test to detect intracranial lesions.
* These imaging tests determine the location of intracranial mass lesion(s) and help in guiding therapy.

* Biopsy of the lesion is needed to identify the nature of the lesion such as:
* Tumor
* Abscess

* X- ray of the skull is a non specific test, but useful if any of the lesions are calcified.

Cerebral hemorrhage |

* Headache, vomiting, and depressed level of consciousness from increased intracranial pressure (ICP)

* Progression of focal neurological deficits over periods of hours

* CT scan without contrast is the initial test performed to diagnose ischemic stroke and rule out hemorrhagic stroke.
* CT is very sensitive for identifying acute hemorrhage which appears as hyperattenuating clot.
* Gradient echo and T2 susceptibility-weighted MRI are as sensitive as CT for detection of acute hemorrhage and are more sensitive for identification of prior hemorrhage.

* PT/ INR and aPTT should be checked to rule out coagulopathy.

Cerebral Infarction | The symptoms of an ischemic stroke vary widely depending on the site and blood supply of the area involved. For more information on symptoms of ischemic stroke based on area involved please click here.  |

* CT scan without contrast is the initial test performed to diagnose ischemic stroke and rule out hemorrhagic stroke. CT may show hypo-attenuation and swelling of involved area.
* MR diffusion weighted imaging is the most sensitive and specific test for diagnosing ischemic stroke and may help detect presence of infarction in few minutes of onset of symptoms.

* Carotid doppler may be done to check for patency of carotid arteries and blood supply to the brain.

* Cerebral angiogram is an invasive test and detect abnormalities of the blood vessels, including narrowing, blockage, or malformations (such as aneurysms or arterio-venous malformations).

Intracranial venous thrombosis |

* Headache: It is a common presentation (present in 90% of cases); it tends to worsen over a period of several days, but may also develop suddenly (thunderclap headache).[1] The headache may be the only symptom of cerebral venous sinus thrombosis.[2]
* Inability to move one or more limbs.
* Weakness on one side of the face.
* Seizures: 40% of all patients have seizure.
* Depressed level of consciousness and otherwise unexplained changes in mental status are common symptoms in the elderly.[4]

* The classic finding of sinus thrombosis on unenhanced CT images is a hyperattenuating thrombus in the occluded sinus.

* CT and MRI may identify Cerebral edema and venous infarction may be apparent.

* CT venography detects the thrombus, computed tomography with radiocontrast in the venous phase (CT venography or CTV) has a detection rate that in some regards exceeds that of MRI.

* Cerebral angiography may demonstrate smaller clots, and obstructed veins may give the "corkscrew appearance".

Migraine |

* Severe or moderate headache (which is often one-sided and pulsating) lasts between several hours to three days.
* Other symptoms include gastrointestinal upsets, such as nausea and vomiting, and a heightened sensitivity to bright lights (photophobia) and noise (phonophobia). Approximately one third of people who experience migraine get a preceding aura.[4]

* CT and MRI may be needed to rule out other suspected possible causes of headache.

| Migraine is a clinical diagnosis that does not require any laboratory tests. Laboratory tests can be ordered to rule out any suspected coexistent metabolic problems or to determine the baseline status of the patient before initiation of migraine therapy.
Head injury |

* Headache
* Confusion
* Drowsiness
* Personality change
* Seizures
* Nausea and vomiting
* Loss of consciousness
* lucid interval

* CT scan is the first test performed and identifies cerebral hemorrhage (appears as hyperattenuating clot) following head injury. CT scan is also less time consuming.

* MRI is more sensitive, takes more time and is done in patients with symptoms unexplained by CT scan.

* The Glasgow Coma Scale is a tool for measuring degree of unconsciousness and is thus a useful tool for determining severity of injury.
* The Pediatric Glasgow Coma Scale is used in young children.

Lymphocytic hypophysitis | Lymphocytic hypophysitis is most often seen in late pregnancy or the postpartum period with the following symptoms:

* Hypopituitarism
* Mass lesion effect such as headache or visual field defects

* CT & MRI typically reveal features of a pituitary mass.

* The most accurate test is pituitary biopsy which will show lymphocytic infiltration.

Radiation injury |

* Headache
* Impairment of mental function is the most prominent feature such as personality change, impairment of memory, confusion, learning difficulties.
* Focal neurological abnormalities and evidence of raised intracranial pressure.

CT & MRI will show:

* Focal radiation necrosis
* Diffuse white matter injury
* Contrast-enhancing mass surrounded by edema and mass effect

| PET scan

* Radiation necrosis is hypo metabolic and will have decreased uptake of fluorodeoxyglucose.

## References

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1. ↑ Linn FH, Rinkel GJ, Algra A, van Gijn J (1998). "Headache characteristics in subarachnoid haemorrhage and benign thunderclap headache". J Neurol Neurosurg Psychiatry. 65 (5): 791–3. PMC 2170334. PMID 9810961.CS1 maint: Multiple names: authors list (link)
2. ↑ Markus HS (1991). "A prospective follow up of thunderclap headache mimicking subarachnoid haemorrhage". J Neurol Neurosurg Psychiatry. 54 (12): 1117–8. PMC 1014694. PMID 1783930.
3. ↑ Polmear A (2003). "Sentinel headaches in aneurysmal subarachnoid haemorrhage: what is the true incidence? A systematic review". Cephalalgia. 23 (10): 935–41. PMID 14984225.
4. ↑ Dodick DW, Wijdicks EF (1998). "Pituitary apoplexy presenting as a thunderclap headache". Neurology. 50 (5): 1510–1. PMID 9596029.
5. ↑ de Bruijn SF, Stam J, Kappelle LJ (1996). "Thunderclap headache as first symptom of cerebral venous sinus thrombosis. CVST Study Group". Lancet. 348 (9042): 1623–5. PMID 8961993.CS1 maint: Multiple names: authors list (link)
6. ↑ Bousser MG, Chiras J, Bories J, Castaigne P (1985). "Cerebral venous thrombosis--a review of 38 cases". Stroke. 16 (2): 199–213. PMID 3975957.CS1 maint: Multiple names: authors list (link)
7. ↑ KELLY R (1951). "Colloid cysts of the third ventricle; analysis of twenty-nine cases". Brain. 74 (1): 23–65. PMID 14830663.
8. ↑ Mitsias P, Ramadan NM (1992). "Headache in ischemic cerebrovascular disease. Part I: Clinical features". Cephalalgia. 12 (5): 269–74. PMID 1423556.
9. ↑ Touzé E, Gauvrit JY, Moulin T, Meder JF, Bracard S, Mas JL; et al. (2003). "Risk of stroke and recurrent dissection after a cervical artery dissection: a multicenter study". Neurology. 61 (10): 1347–51. PMID 14638953.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
10. ↑ Rando TA, Fishman RA (1992). "Spontaneous intracranial hypotension: report of two cases and review of the literature". Neurology. 42 (3 Pt 1): 481–7. PMID 1549206.
11. ↑ Schievink WI, Wijdicks EF, Meyer FB, Sonntag VK (2001). "Spontaneous intracranial hypotension mimicking aneurysmal subarachnoid hemorrhage". Neurosurgery. 48 (3): 513–6, discussion 516-7. PMID 11270540.CS1 maint: Multiple names: authors list (link)
12. ↑ Soffer D (1976) Brain tumors simulating purulent meningitis. Eur Neurol 14 (3):192-7. PMID: 1278192
13. ↑ Invalid `<ref>` tag; no text was provided for refs named `pmid3883130`
14. ↑ 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.CS1 maint: Multiple names: authors list (link)
15. ↑ 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
16. ↑ Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction". Stroke. 6 (6): 638–41. PMID 1198628.CS1 maint: Multiple names: authors list (link)
17. ↑ Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.CS1 maint: Multiple names: authors list (link)
18. ↑ 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
19. ↑ 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
20. ↑ Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
21. ↑ 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.
22. ↑ Endrit Ziu & Fassil Mesfin (2017). "Subarachnoid Hemorrhage". PMID 28722987.
23. ↑ Benedikt Schwermer, Daniel Eschle & Constantine Bloch-Infanger (2017). "[Fever and Headache after a Vacation in Thailand]". Deutsche medizinische Wochenschrift (1946). 142 (14): 1063–1066. doi:10.1055/s-0043-106282. PMID 28728201.
24. ↑ Otto Rapalino & Mark E. Mullins (2017). "Intracranial Infectious and Inflammatory Diseases Presenting as Neurosurgical Pathologies". Neurosurgery. doi:10.1093/neuros/nyx201. PMID 28575459.
25. ↑ I. B. Komarova, V. P. Zykov, L. V. Ushakova, E. K. Nazarova, E. B. Novikova, O. V. Shuleshko & M. G. Samigulina (2017). "[Clinical and neuroimaging signs of cardioembolic stroke laboratory in children]". Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 117 (3. Vyp. 2): 11–19. doi:10.17116/jnevro20171173211-19. PMID 28665364.CS1 maint: Multiple names: authors list (link)
26. ↑ Sanjay Konakondla, Clemens M. Schirmer, Fengwu Li, Xiaogun Geng & Yuchuan Ding (2017). "New Developments in the Pathophysiology, Workup, and Diagnosis of Dural Venous Sinus Thrombosis (DVST) and a Systematic Review of Endovascular Treatments". Aging and disease. 8 (2): 136–148. doi:10.14336/AD.2016.0915. PMID 28400981.CS1 maint: Multiple names: authors list (link)
27. ↑ Priyanka Yadav, Alec L. Bradley & Jonathan H. Smith (2017). "Recognition of Chronic Migraine by Medicine Trainees: A Cross-Sectional Survey". Headache. doi:10.1111/head.13133. PMID 28653369.
28. ↑ S. Wulffeld, L. S. Rasmussen, B. Hojlund Bech & J. Steinmetz (2017). "The effect of CT scanners in the trauma room - an observational study". Acta anaesthesiologica Scandinavica. 61 (7): 832–840. doi:10.1111/aas.12927. PMID 28635146.CS1 maint: Multiple names: authors list (link)
29. ↑ Johnston PC, Chew LS, Hamrahian AH, Kennedy L (2015). "Lymphocytic infundibulo-neurohypophysitis: a clinical overview". Endocrine. 50 (3): 531–6. doi:10.1007/s12020-015-0707-6. PMID 26219407.
30. ↑ Makale MT, McDonald CR, Hattangadi-Gluth JA, Kesari S (2017). "Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours". Nat Rev Neurol. 13 (1): 52–64. doi:10.1038/nrneurol.2016.185. PMID 27982041.
31. ↑ Sato N, Sze G, Endo K (1998). "Hypophysitis: endocrinologic and dynamic MR findings". AJNR Am J Neuroradiol. 19 (3): 439–44. PMID 9541295.CS1 maint: Multiple names: authors list (link)

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