COVID-19-associated headache: Difference between revisions

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Revision as of 15:34, 20 July 2020

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D. Syed Musadiq Ali M.B.B.S.[2]

Synonyms and keywords:

Overview

The association between COVID-19 and headache was made in 2020. COVID-19 associated headache may be caused by SARS-CoV-2 virus. There is no established system for the classification of COVID-19 associated headache. The exact pathogenesis of headache in COVID 19 patients is not fully understood. It is thought that headache is the result of cytokine release, direct invasion, metabolic disturbances, inflammation, dehydration, and hypoxia. COVID-19-associated headache must be differentiated from other diseases that cause headache, such as migraine, tension-type headache, cluster headache, seizure, meningitis, encephalitis, neurosyphilis, SAH, subdural hematoma, brain tumor, hypertensive encephalopathy, brain abscess, multiple sclerosis, hemorrhagic stroke, Wernickes encephalopathy, and drug toxicity. A positive history of fever and cough in addition to headache is suggestive of COVID-19-associated headache.

Historical Perspective

The association between COVID-19 and headache was made in December, 2019 during SARS-CoV-2 outbreak initiated in Wuhan, Hubei Province, China.^[1]

Classification

There is no established system for the classification of COVID-19 associated headache.

Pathophysiology

The exact pathogenesis of headache in COVID 19 patients is not fully understood.
It is thought that headache is the result of:^[2]^[3]^[4]^[5]
- Cytokine release
  - There is higher concentration on IL-6 and INF-gamma in patients infected with SARS/ CoV2.
  - Cytokines can disrupt blood brain barrier and cause tissue injury and cerebral edema.
- Direct invasion
- Metabolic disturbances
- Inflammation
- Dehydration
- Hypoxia

By Fahimeh Shojaei, M.D. / https://en.wikipedia.org/wiki/File:Migraine.jpg

Causes

COVID-19 associated headache may be caused by SARS-CoV-2 virus.

Differentiating COVID-19-associated headache from other Diseases

Epidemiology and Demographics

Incidence / Prevalence

WHO reported that more than 462,801 people have been infected worldwide, more than 380,723 of which are outside of China.^[6]
The incidence/prevalence of COVID-19-associated headache is still unknown.
Guan et al. recently reported 13 percent of COVID-19-associated headache among 1099 laboratory-confirmed cases.

Age

There is insufficient information regarding age-specific prevalence or incidence of COVID-19-associated headache.

Gender

There is insufficient information regarding gender-specific prevalence or incidence of COVID-19-associated headache.

Race

There is insufficient information regarding race-specific prevalence or incidence of COVID-19-associated headache.

Risk Factors

There are no established risk factors for COVID-19-associated headache.

Screening

There is insufficient evidence to recommend routine screening for COVID-19 associated headache.

Natural History, Complications, and Prognosis

Natural History

At this point natural history of COVID-19-associated headache is unknown.
Further studies are needed to better understand the COVID-19-associated headache.

Complication

Patients with a history migraine may experience headache as their first symptom, these patients experience more severe headache and are more disabled by the infection compared with age‐matched cohorts.
Further studies are needed to better understand complication.
Larger retrospective studies are needed for evaluating the experience of COVID‐19 in patients with a history of a primary headache disorder.

Diagnosis

Diagnostic Study of Choice

The diagnosis of COVID-19-associated headache is based on the clinical presentation

There are no established criteria for the diagnosis of COVID-19-associated headache.

History and Symptoms

The hallmark of COVID-19-associated headache is headache.

A positive history of fever and cough in addition to headache is suggestive of COVID-19-associated headache.

Physical Examination

Patients with COVID-19-associated headache usually appear normal.
Physical examination of patients with COVID-19-associated headache is usually remarkable for fever, cough, and malaise.

Laboratory Findings

Additional diagnostic tests like blood chemistry and urine analysis may be needed to rule out other medical conditions.

There are no diagnostic laboratory findings associated with COVID-19-associated headache.

Electrocardiogram

There are no ECG findings associated with COVID-19-associated headache.

X-ray

There are no x-ray findings associated with COVID-19-associated headache.

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with COVID-19-associated headache.

CT scan

There are no CT scan findings associated with COVID-19-associated headache.

MRI

There are no MRI findings associated with COVID-19-associated headache.

Other Imaging Findings

There are no other imaging findings associated with COVID-19-associated headache.

Other Diagnostic Studies

There are no other diagnostic studies associated with COVID-19-associated headache.

Treatment

Medical Therapy

Medical therapy for COVID-assocaited-headache is still controversial^[7].
The use of NSAIDs, who received treatment early in the disease causes worsening of COVID-19 symptoms according to some anecdotal evidences.
In March 11, 2020, Fang et al. reported the hypothesis that ibuprofen (40 mg/kg/dose)^[8] can increase the risk of developing severe and fatal COVID-19 since ibuprofen is known to upregulate ACE2 receptors^[9].
In March 23, 2020, US FDA announced that it is not aware of any evidence that NSAIDs such as ibuprofen could worsen COVID-19^[10].
The European Medicines Agency and World Health Organization (WHO) have not yet recommended that NSAIDs be avoided.
Despite this recommendation, as a precautionary measure many providers are avoiding NSAIDs in patients with COVID-19.
In practice, the decision to continue or stop NSAIDs in patients with COVID-19 is made in collaboration between the treating physician and the patient, after a brief discussion on the limited available evidence.
More data are needed before broad recommendations are made.

Surgery

Surgical intervention is not recommended for the management of COVID-19-associated headache.

Primary Prevention

There are no established measures for the primary prevention of COVID-19 associated headache.

Secondary Prevention

There are no established measures for the secondary prevention of COVID-19-associated headache.

References

↑ Meng X, Deng Y, Dai Z, Meng Z (June 2020). "COVID-19 and anosmia: A review based on up-to-date knowledge". Am J Otolaryngol. 41 (5): 102581. doi:10.1016/j.amjoto.2020.102581. PMC 7265845 Check |pmc= value (help). PMID 32563019 Check |pmid= value (help).
↑ Baig, Abdul Mannan; Khaleeq, Areeba; Ali, Usman; Syeda, Hira (2020). "Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms". ACS Chemical Neuroscience. 11 (7): 995–998. doi:10.1021/acschemneuro.0c00122. ISSN 1948-7193.
↑ St-Jean JR, Jacomy H, Desforges M, Vabret A, Freymuth F, Talbot PJ (August 2004). "Human respiratory coronavirus OC43: genetic stability and neuroinvasion". J. Virol. 78 (16): 8824–34. doi:10.1128/JVI.78.16.8824-8834.2004. PMC 479063. PMID 15280490.
↑ Rossi, Andrea (2008). "Imaging of Acute Disseminated Encephalomyelitis". Neuroimaging Clinics of North America. 18 (1): 149–161. doi:10.1016/j.nic.2007.12.007. ISSN 1052-5149.
↑ St-Jean, Julien R.; Jacomy, Hélène; Desforges, Marc; Vabret, Astrid; Freymuth, François; Talbot, Pierre J. (2004). "Human Respiratory Coronavirus OC43: Genetic Stability and Neuroinvasion". Journal of Virology. 78 (16): 8824–8834. doi:10.1128/JVI.78.16.8824-8834.2004. ISSN 0022-538X.
↑ Tu H, Tu S, Gao S, Shao A, Sheng J (2020). "Current epidemiological and clinical features of COVID-19; a global perspective from China". J Infect. 81 (1): 1–9. doi:10.1016/j.jinf.2020.04.011. PMC 7166041 Check |pmc= value (help). PMID 32315723 Check |pmid= value (help).
↑ Zhang J, Xie B, Hashimoto K (2020). "Current status of potential therapeutic candidates for the COVID-19 crisis". Brain Behav Immun. 87: 59–73. doi:10.1016/j.bbi.2020.04.046. PMC 7175848 Check |pmc= value (help). PMID 32334062 Check |pmid= value (help).
↑ MaassenVanDenBrink A, de Vries T, Danser A (April 2020). "Headache medication and the COVID-19 pandemic". J Headache Pain. 21 (1): 38. doi:10.1186/s10194-020-01106-5. PMC 7183387 Check |pmc= value (help). PMID 32334535 Check |pmid= value (help). Vancouver style error: initials (help)
↑ Fang L, Karakiulakis G, Roth M (2020) Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 8 (4):e21. DOI:10.1016/S2213-2600(20)30116-8 PMID: 32171062
↑ FitzGerald GA (2020) Misguided drug advice for COVID-19. Science 367 (6485):1434. DOI:10.1126/science.abb8034 PMID: 32198292

Template:WikiDoc Sources

[pmid32563019-1] Meng X, Deng Y, Dai Z, Meng Z (June 2020). "COVID-19 and anosmia: A review based on up-to-date knowledge". Am J Otolaryngol. 41 (5): 102581. doi:10.1016/j.amjoto.2020.102581. PMC 7265845 Check |pmc= value (help). PMID 32563019 Check |pmid= value (help).

[BaigKhaleeq2020-2] Baig, Abdul Mannan; Khaleeq, Areeba; Ali, Usman; Syeda, Hira (2020). "Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms". ACS Chemical Neuroscience. 11 (7): 995–998. doi:10.1021/acschemneuro.0c00122. ISSN 1948-7193.

[pmid15280490-3] St-Jean JR, Jacomy H, Desforges M, Vabret A, Freymuth F, Talbot PJ (August 2004). "Human respiratory coronavirus OC43: genetic stability and neuroinvasion". J. Virol. 78 (16): 8824–34. doi:10.1128/JVI.78.16.8824-8834.2004. PMC 479063. PMID 15280490.

[Rossi2008-4] Rossi, Andrea (2008). "Imaging of Acute Disseminated Encephalomyelitis". Neuroimaging Clinics of North America. 18 (1): 149–161. doi:10.1016/j.nic.2007.12.007. ISSN 1052-5149.

[St-JeanJacomy2004-5] St-Jean, Julien R.; Jacomy, Hélène; Desforges, Marc; Vabret, Astrid; Freymuth, François; Talbot, Pierre J. (2004). "Human Respiratory Coronavirus OC43: Genetic Stability and Neuroinvasion". Journal of Virology. 78 (16): 8824–8834. doi:10.1128/JVI.78.16.8824-8834.2004. ISSN 0022-538X.

[pmid32315723-6] Tu H, Tu S, Gao S, Shao A, Sheng J (2020). "Current epidemiological and clinical features of COVID-19; a global perspective from China". J Infect. 81 (1): 1–9. doi:10.1016/j.jinf.2020.04.011. PMC 7166041 Check |pmc= value (help). PMID 32315723 Check |pmid= value (help).

[pmid32334062-7] Zhang J, Xie B, Hashimoto K (2020). "Current status of potential therapeutic candidates for the COVID-19 crisis". Brain Behav Immun. 87: 59–73. doi:10.1016/j.bbi.2020.04.046. PMC 7175848 Check |pmc= value (help). PMID 32334062 Check |pmid= value (help).

[pmid32334535-8] MaassenVanDenBrink A, de Vries T, Danser A (April 2020). "Headache medication and the COVID-19 pandemic". J Headache Pain. 21 (1): 38. doi:10.1186/s10194-020-01106-5. PMC 7183387 Check |pmc= value (help). PMID 32334535 Check |pmid= value (help). Vancouver style error: initials (help)

[pmid32171062-9] Fang L, Karakiulakis G, Roth M (2020) Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 8 (4):e21. DOI:10.1016/S2213-2600(20)30116-8 PMID: 32171062

[pmid32198292-10] FitzGerald GA (2020) Misguided drug advice for COVID-19. Science 367 (6485):1434. DOI:10.1126/science.abb8034 PMID: 32198292

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@@ Line 37: / Line 37: @@
 ==Differentiating COVID-19-associated headache from other Diseases==
-COVID-19-associated headache must be differentiated from other diseases that cause headache, such as [[migraine]], [[tension-type headache]], [[Cluster headache (patient information)|cluster headache]], [[seizure]], [[meningitis]], [[encephalitis]], [[neurosyphilis]], [[Subarachnoid hemorrhage|SAH]], [[subdural hematoma]], [[brain tumor]], [[hypertensive encephalopathy]], [[brain abscess]], [[multiple sclerosis]], [[hemorrhagic stroke]], [[Wernicke's encephalopathy|Wernickes encephalopathy]], and [[drug toxicity]] etc.<ref name="pmid145039852">{{cite journal |vauthors= |title=National guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage |journal=Ann. Clin. Biochem. |volume=40 |issue=Pt 5 |pages=481–8 |date=September 2003 |pmid=14503985 |doi=10.1258/000456303322326399 |url=}}</ref><ref name="pmid237177982">{{cite journal| author=Le Rhun E, Taillibert S, Chamberlain MC| title=Carcinomatous meningitis: Leptomeningeal metastases in solid tumors. | journal=Surg Neurol Int | year= 2013 | volume= 4 | issue= Suppl 4 | pages= S265-88 | pmid=23717798 | doi=10.4103/2152-7806.111304 | pmc=3656567 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23717798  }}</ref><ref name="pmid243266182">{{cite journal| author=Chow E, Troy SB| title=The differential diagnosis of hypoglycorrhachia in adult patients. | journal=Am J Med Sci | year= 2014 | volume= 348 | issue= 3 | pages= 186-90 | pmid=24326618 | doi=10.1097/MAJ.0000000000000217 | pmc=4065645 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24326618  }}</ref><ref name="pmid228800962">{{cite journal| author=Leen WG, Willemsen MA, Wevers RA, Verbeek MM| title=Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice. | journal=PLoS One | year= 2012 | volume= 7 | issue= 8 | pages= e42745 | pmid=22880096 | doi=10.1371/journal.pone.0042745 | pmc=3412827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22880096  }}</ref><ref name="pmid106549482">{{cite journal| author=Negrini B, Kelleher KJ, Wald ER| title=Cerebrospinal fluid findings in aseptic versus bacterial meningitis. | journal=Pediatrics | year= 2000 | volume= 105 | issue= 2 | pages= 316-9 | pmid=10654948 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10654948  }}</ref><ref name="pmid206108192">{{cite journal| author=Brouwer MC, Tunkel AR, van de Beek D| title=Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 3 | pages= 467-92 | pmid=20610819 | doi=10.1128/CMR.00070-09 | pmc=2901656 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20610819  }}</ref><ref name="pmid27692742">{{cite journal |vauthors=Vermeulen M, Hasan D, Blijenberg BG, Hijdra A, van Gijn J |title=Xanthochromia after subarachnoid haemorrhage needs no revisitation |journal=J. Neurol. Neurosurg. Psychiatry |volume=52 |issue=7 |pages=826–8 |date=July 1989 |pmid=2769274 |pmc=1031927 |doi=10.1136/jnnp.52.7.826 |url=}}</ref><ref name="pmid158850532">{{cite journal |vauthors=Wasay M, Mekan SF, Khelaeni B, Saeed Z, Hassan A, Cheema Z, Bakshi R |title=Extra temporal involvement in herpes simplex encephalitis |journal=Eur. J. Neurol. |volume=12 |issue=6 |pages=475–9 |date=June 2005 |pmid=15885053 |doi=10.1111/j.1468-1331.2005.00999.x |url=}}</ref><ref name="pmid171092902">{{cite journal |vauthors=Glaser CA, Honarmand S, Anderson LJ, Schnurr DP, Forghani B, Cossen CK, Schuster FL, Christie LJ, Tureen JH |title=Beyond viruses: clinical profiles and etiologies associated with encephalitis |journal=Clin. Infect. Dis. |volume=43 |issue=12 |pages=1565–77 |date=December 2006 |pmid=17109290 |doi=10.1086/509330 |url=}}</ref><ref name="pmid214901812">{{cite journal |vauthors=Meltzer EO, Hamilos DL |title=Rhinosinusitis diagnosis and management for the clinician: a synopsis of recent consensus guidelines |journal=Mayo Clin. Proc. |volume=86 |issue=5 |pages=427–43 |date=May 2011 |pmid=21490181 |pmc=3084646 |doi=10.4065/mcp.2010.0392 |url=}}</ref><ref name="pmid19410102">{{cite journal |vauthors=Rasmussen BK, Jensen R, Schroll M, Olesen J |title=Epidemiology of headache in a general population--a prevalence study |journal=J Clin Epidemiol |volume=44 |issue=11 |pages=1147–57 |date=1991 |pmid=1941010 |doi=10.1016/0895-4356(91)90147-2 |url=}}</ref><ref name="pmid154476952">{{cite journal |vauthors=Kelman L |title=The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs |journal=Headache |volume=44 |issue=9 |pages=865–72 |date=October 2004 |pmid=15447695 |doi=10.1111/j.1526-4610.2004.04168.x |url=}}</ref><ref name="pmid266433782">{{cite journal |vauthors=Laurell K, Artto V, Bendtsen L, Hagen K, Häggström J, Linde M, Söderström L, Tronvik E, Wessman M, Zwart JA, Kallela M |title=Premonitory symptoms in migraine: A cross-sectional study in 2714 persons |journal=Cephalalgia |volume=36 |issue=10 |pages=951–9 |date=September 2016 |pmid=26643378 |doi=10.1177/0333102415620251 |url=}}</ref><ref>{{cite web | author=Charlotte E. Grayson and The Cleveland Clinic Neuroscience Center | title=Cluster Headaches  |url=http://www.webmd.com/content/article/46/1826_50688.htm | date=October 2004 | publisher=WebMD | accessdate=2006-09-22}}</ref><ref name="pmid78887472">{{cite journal |vauthors=Drummond PD |title=Sweating and vascular responses in the face: normal regulation and dysfunction in migraine, cluster headache and harlequin syndrome |journal=Clin. Auton. Res. |volume=4 |issue=5 |pages=273–85 |date=October 1994 |pmid=7888747 |doi=10.1007/BF01827433 |url=}}</ref><ref name="pmid166869022">{{cite journal |vauthors=Drummond PD |title=Mechanisms of autonomic disturbance in the face during and between attacks of cluster headache |journal=Cephalalgia |volume=26 |issue=6 |pages=633–41 |date=June 2006 |pmid=16686902 |doi=10.1111/j.1468-2982.2006.01106.x |url=}}</ref><ref name="pmid22454692">{{cite journal |vauthors=Ekbom K |title=Evaluation of clinical criteria for cluster headache with special reference to the classification of the International Headache Society |journal=Cephalalgia |volume=10 |issue=4 |pages=195–7 |date=August 1990 |pmid=2245469 |doi=10.1046/j.1468-2982.1990.1004195.x |url=}}</ref><ref name="pmid76977072">{{cite journal |vauthors=Sandrini G, Antonaci F, Pucci E, Bono G, Nappi G |title=Comparative study with EMG, pressure algometry and manual palpation in tension-type headache and migraine |journal=Cephalalgia |volume=14 |issue=6 |pages=451–7; discussion 394–5 |date=December 1994 |pmid=7697707 |doi=10.1046/j.1468-2982.1994.1406451.x |url=}}</ref><ref name="pmid75157932">{{cite journal |vauthors=Jensen R, Fuglsang-Frederiksen A |title=Quantitative surface EMG of pericranial muscles. Relation to age and sex in a general population |journal=Electroencephalogr Clin Neurophysiol |volume=93 |issue=3 |pages=175–83 |date=June 1994 |pmid=7515793 |doi=10.1016/0168-5597(94)90038-8 |url=}}</ref>
-{| class="wikitable"
-|+
-! rowspan="2" |Disease
-! colspan="13" |History and Physical Examination
-! rowspan="2" |PMHx
-! colspan="3" |Diagnostic approach
-|-
-!Bilateral
-!Throbbing character
-!Autonomic symptoms
-!Fever
-!Photophobia
-!Aphasia
-!LOC
-!Aura
-!Nause/
-Vomiting
-!Rash
-!Neck stiffness
-!Vision changes
-!Neurologic  deficits
-!Labs and CSF findings
-!CT/MRI
-!Gold standard test
-|-
-|[[Migraine]]
-|<nowiki>-</nowiki>
-|  +
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|  +
-|<nowiki>-</nowiki>
-|Trigger factors, family hx
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|Clinical assesment
-|-
-|[[Tension-type headache|Tension-type headache (TTH)]]
-|<nowiki>+</nowiki>
-|  -
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|  -
-|<nowiki>-</nowiki>
-|[[stress]], [[genetics]]
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|Clinical assesment
-|-
-|[[Cluster headache]]
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>-</nowiki>
-|episodic history
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|Clinical assesment
-|-
-|[[Seizure]]
-|<nowiki>+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|Hx of [[Seizure|seizures]]
-|prolactin level
-|<nowiki>+/- mass lesion</nowiki>
-|[[EEG]] <ref name="pmid11385043">{{cite journal| author=Manford M| title=Assessment and investigation of possible epileptic seizures. | journal=J Neurol Neurosurg Psychiatry | year= 2001 | volume= 70 Suppl 2 | issue=  | pages= II3-8 | pmid=11385043 | doi= | pmc=1765557 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11385043  }}</ref>
-|-
-|[[Meningitis]]
-|<nowiki>+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|Hx of [[fever]], [[malaise]]
-|[[Leukocytosis|<math>\uparrow</math>WBC]]
-<math>\uparrow</math>Protein
-<math>\downarrow</math>glucose
-|<nowiki>+/-</nowiki>
-|[[CSF analysis]]<ref name="pmid19398286">{{cite journal| author=Carbonnelle E| title=[Laboratory diagnosis of bacterial meningitis: usefulness of various tests for the determination of the etiological agent]. | journal=Med Mal Infect | year= 2009 | volume= 39 | issue= 7-8 | pages= 581-605 | pmid=19398286 | doi=10.1016/j.medmal.2009.02.017 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19398286  }}</ref>
-|-
-|[[Encephalitis]]
-|<nowiki>+</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|Hx of [[fever]], [[malaise]]
-|elevated WBC, low glucose
-|<nowiki>+</nowiki>
-|CSF PCR
-|-
-|[[Brain tumor]]<ref name="pmid10582668">{{cite journal| author=Morgenstern LB, Frankowski RF| title=Brain tumor masquerading as stroke. | journal=J Neurooncol | year= 1999 | volume= 44 | issue= 1 | pages= 47-52 | pmid=10582668 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10582668  }}</ref>
-|<nowiki>+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|[[weight loss]], [[fatigue]]
-|neuromarkers,
-Cancer cells<ref name="pmid21371327">{{cite journal| author=Weston CL, Glantz MJ, Connor JR| title=Detection of cancer cells in the cerebrospinal fluid: current methods and future directions. | journal=Fluids Barriers CNS | year= 2011 | volume= 8 | issue= 1 | pages= 14 | pmid=21371327 | doi=10.1186/2045-8118-8-14 | pmc=3059292 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21371327  }}</ref>
-|<nowiki>+/- mass</nowiki>
-|[[MRI]]
-|-
-|[[Subdural hematoma|Subdural hemorrhage]]
-|<nowiki>-/+</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|[[Trauma]], [[fall]]
-|Xanthochromia
-|<nowiki>+</nowiki>
-|CT w/o contrast
-|-
-|[[Subarachnoid hemorrhage]]
-|  -/+
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|[[thunderclap headache]]
-|<math>\uparrow</math>opening pressure, xanthochromia
-|<nowiki>+</nowiki>
-|CT w/o contrast
-|-
-|[[Hypertensive encephalopathy]]
-|<nowiki>+</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|[[Hypertension]]
-|UA +/-
-|<nowiki>+/-</nowiki>
-|clinical assessment
-|-
-|[[Brain abscess|CNS abscess]]
-|<nowiki>-/+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|History of [[drug abuse]], [[endocarditis]], [[immunosupression]]
-|'''↑''' [[Leukocytosis|leukocytes]], '''↓''' [[glucose]] and '''↑''' protien
-|<nowiki>+</nowiki>
-|[[MRI]]
-|-
-|[[Conversion disorder]]
-|<nowiki>-/+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|History of [[emotional stress]]
-|<nowiki>-</nowiki>
-|  -
-|Diagnosis of exclusion
-|-
-|[[Multiple sclerosis]]
-|<nowiki>-/+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|<nowiki>+/-</nowiki>
-|History of relapses and remissions
-|'''↑'''  [[CSF]] [[IgG]] levels
-(monoclonal bands)
-|<nowiki>+</nowiki>
-|[[MRI]]
-|-
-|[[Hemorrhagic stroke]]
-|<nowiki>-/+</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|[[Hypertension|HTN]]
-|<nowiki>-</nowiki>
-|<nowiki>+</nowiki>
-|[[CT scan]]  without contrast<ref name="pmid21694755">{{cite journal| author=Birenbaum D, Bancroft LW, Felsberg GJ| title=Imaging in acute stroke. | journal=West J Emerg Med | year= 2011 | volume= 12 | issue= 1 | pages= 67-76 | pmid=21694755 | doi= | pmc=3088377 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21694755  }}</ref><ref name="pmid21807345">{{cite journal| author=DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF et al.| title=ACR Appropriateness Criteria® on cerebrovascular disease. | journal=J Am Coll Radiol | year= 2011 | volume= 8 | issue= 8 | pages= 532-8 | pmid=21807345 | doi=10.1016/j.jacr.2011.05.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21807345  }}</ref>
-|-
-|[[Neurosyphilis]]<ref name="pmid22482824">{{cite journal| author=Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG et al.| title=Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients. | journal=J Neurol Sci | year= 2012 | volume= 317 | issue= 1-2 | pages= 35-9 | pmid=22482824 | doi=10.1016/j.jns.2012.03.003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22482824  }}</ref><ref name="pmid24365430">{{cite journal |vauthors=Berger JR, Dean D |title=Neurosyphilis |journal=Handb Clin Neurol |volume=121 |issue= |pages=1461–72 |year=2014 |pmid=24365430 |doi=10.1016/B978-0-7020-4088-7.00098-5 |url=}}</ref>
-|<nowiki>-/+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|[[Sexually transmitted disease|STI]]<nowiki/>s
-|'''↑''' [[Leukocytes]] and [[protein]]
-|<nowiki>+</nowiki>
-|CSF [[VDRL]]-specifc
-CSF FTA-Ab -sensitive<ref name="pmid22421697">{{cite journal| author=Ho EL, Marra CM| title=Treponemal tests for neurosyphilis--less accurate than what we thought? | journal=Sex Transm Dis | year= 2012 | volume= 39 | issue= 4 | pages= 298-9 | pmid=22421697 | doi=10.1097/OLQ.0b013e31824ee574 | pmc=3746559 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22421697  }}</ref>
-|-
-|[[Wernicke's encephalopathy|Wernicke’s encephalopathy]]
-|<nowiki>-/+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|History of alcohal abuse
-|blood ethanol levels
-|<nowiki>+/-</nowiki>
-|Clinical assesment and lab findings
-|-
-|[[Drug toxicity]]
-|<nowiki>-/+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|Medication hx
-|Drug levels
-|<nowiki>-</nowiki>
-|Drug screen test
-|-
-|[[Metabolic disorder|Metabolic disturbances]]
-|<nowiki>-/+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>+/-</nowiki>
-|Underlying [[CKD]], CLD
-|[[Hypoglycemia]], [[Hyponatremia|hypo]] and [[hypernatremia]], [[Hypokalemia|hypo]] and [[hyperkalemia]]
-|<nowiki>-</nowiki>
-|Cause dependent
-|-
-|[[Sinusitis]]
-|<nowiki>-/+</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>+/-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|<nowiki>-</nowiki>
-|[[allergies]], seasonal
-|[[leukocytosis]]
-|<nowiki>+</nowiki>
-|[[CT-scans|CT]]
-|}
-</small></small>
 ==Epidemiology and Demographics==