Abordagem diagnóstica e terapêutica da meningite crônica no Brasil: uma revisão narrativa

Silva, Guilherme Diogo; Guedes, Bruno Fukelmann; Junqueira, Ióri Rodrigues; Gomes, Hélio Rodrigues; Vidal, José Ernesto

Guilherme Diogo Silva Address for correspondence Guilherme Diogo Silva, (e-mail: dr.guilhermediogo@gmail.com).

drafted the original manuscript

study design

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil.

https://orcid.org/0000-0001-9764-3763

Bruno Fukelmann Guedes

revised the manuscript for intellectual content

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil.

https://orcid.org/0000-0001-8391-2117

Ióri Rodrigues Junqueira

drafted the original manuscript

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil.

https://orcid.org/0000-0002-3899-5256

Hélio Rodrigues Gomes

revised the manuscript for intellectual content

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil.

https://orcid.org/0000-0003-4461-0305

José Ernesto Vidal

revised the manuscript for intellectual content and designed the work

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Doenças Infecciosas, São Paulo SP, Brazil.

Instituto de Infectologia Emílio Ribas, Departamento de Neurologia, São Paulo SP, Brazil.

https://orcid.org/0000-0001-7830-8716

Address for correspondence Guilherme Diogo Silva, (e-mail: dr.guilhermediogo@gmail.com).

Conflict of Interest

The authors have no conflict of interests to declare.

	Country	Infectious causes	Non-infectious causes
Anderson, 1987³	New Zealand (n = 55)	Tuberculosis 33 Cryptococcal 6 Syphilitic 2 Leptospiral 1 Eosinophilic 4 Herpes 1	Malignant 7 Sarcoid 1
Helbok, 2005⁶	Thailand (n = 110)	Cryptococcal 61 Tuberculosis 43 Streptococcus sp 2 Eosinophilic 1	Malignant 3
Erdem, 2017⁷	United States (n = 77)	Tuberculosis 37 Syphilis 24 Borrelia 10 Brucella 6	Not included
Total	n = 242	Tuberculosis 113 Cryptococcal 67 Spirochetes 27 Other agents 24 (viruses, parasites, uncommon bacteria)	Malignant 10 Autoimmune 1 (Sarcoid)

Common		Uncommon
Infectious	Tuberculosis	Spirochetes(Syphilis, Borrelia, Leptospirosis)
Infectious	Cryptococcosis	Intracellular bacterias (Brucella, Bartonella, Nocardia) Uncommon gram positive bacteria (Streptococcus sp) Non cryptococcus fungi (Histoplasma, Candida, Aspergillus) Parasites(Cysticercosis, Toxocara, Angiostrongylus) Viruses(Herpes family, HIV and recently described virus associated with chronic meningitis – e.g., astrovirus)
Noninfectious	Carcinomatosis	Sarcoidosis, IgG4-related diseases, Colagenosis (i.e., rheumatoid arthritis)

	Investigation	Finding	Potential diagnoses
Clinical History	Geographic region of residence/recent travel	Northeastern MG, southern BA	Neuroschistossomosis
		Southest region (SP, PR, RS)	Paracoccidioidmycosis
		Rural areas	Cysticercosis, hystoplasmosis, paracoccidioidomicosis
		Caving	Hystoplasmosis
	Immune status	HIV	Cryptococcosis, tuberculosis, syphilis
	Immune status	Immunossupressant use	Cryptococcosis, listeriosis
	Socieconomic	Incarcerated	Tuberculosis
		Drinking well water	Cisticercosis
		MSM, sex workers	Syphilis, HTLV, HIV
		Flood and sewer exposure	Leptospirosis
Investigation outside the CNS	Skin lesions	Ulcerated nodules	Sporotrichosis, cryptococcosis
		Eritema nodosum	Sarcoidosis, tuberculosis, systemic lupus
		Eritema migrans	borreliosis
	Ear nose and throat	Chronic sinusitis	Saprophitic fungi (Rhizopus, Rhizomucor and others), granulomatosis with polyangiitis
	Arthritis	Present	Rheumatoid arthritis, borreliosis, sarcoidosis
	Lymphadenopathy	Single, nonsupurative	Lymphoma
		Single, supurative	Tuberculosis, cryptococcosis
		Polyadenopathy	autoimmune disease (lupus, sarcoidosis), leukemia
	Hepatosplenomegaly	Present	Schistossomiasis, lymphoma, leukemia
	Lungs	Migrating nodules (Löefler syndrome)	Schistossomiasis, strongiloidiasis
		Fixed nodules	Sarcoidosis
		Ground-glass opacities	Autoimmune disease
		Miliary nodules	Tuberculosis
	Eyes	Retinal cisticercci	Cisticercosis
		Uveitis	Autoimmune disease, tuberculosis
		Chorioretinitis	Syphilis, cat-scratch disease
Neuroimaging	Magnetic resonance or computed tomography of the brain	Basilar enhancement	Tuberculosis
		Mild leptomeningeal enhancement	Autoimmune disease, syphilis, cryptococcosis, tuberculosis
		Pachymeningeal enhancement and thickening	IgG-4-related-disease, sarcoidosis, granulomatosis with polyangiitis
		Meningeal nodules	Sarcoidosis
		Cerebral calcifications, cystic lesions	Cysticercosis
CSF analysis	CSF cell count and differentials, protein, and glucose levels	Eosinophilic leukocytosis	Histoplasmosis, strongiloidiasis, schistossomiasis
		Neutrophilic leukocytosis	Early tuberculosis, bacteria
		Very high protein	Tuberculosis
		Mild changes	Autoimmune disease
		Low glucose	Carcinomatosis, tuberculosis, bacteria

Tests for most common causes of chronic meningitis

○
CSF smear and culture for tuberculosis, M. tuberculosis polymerase chain reaction (or GeneXpert Ultra when available)
○
CSF smear and culture for fungi, LFA CrAg
○
CSF smear and culture for bacteria
○
CSF oncotic cytology
○
Serological testing for HIV and Treponema pallidum

Cerebrospinal fluid analysis and serological testing for uncommon causes

○
Blood and CSF immunological testing for uncommon agents: Paracoccidoides, Histoplasma, Aspergillus, Cysticercus, Borrelia, Brucella, and Bartonella – based on epidemiology.
○
Autoimmune serological testing: ANA, RF, ANCA, IgG4 levels.

Advanced investigation for undiagnosed cases

○
Multidisciplinary diagnostic rounds
○
Whole-body imaging (FDG-PET-CT)
○
Meningeal and brain biopsy
○
Next-generation sequencing metagenomics

[1] Address for correspondence Guilherme Diogo Silva, (e-mail: dr.guilhermediogo@gmail.com).

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Abordagem diagnóstica e terapêutica da meningite crônica no Brasil: uma revisão narrativa

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