Fungal meningitis differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby; Prince Tano Djan, BSc, MBChB [2]

Overview

The differential diagnosis of fungal meningitis includes a range of medical conditions that can be broadly classified into infectious and non infectious. The cerebrospinal fluid analysis and radiological findings help distinguishing fungal meningitis from other causes of meningitis example bacterial meningitis, protozoal meningeal infection, viral meningeal infection, and non-infectious causes.

Differential Diagnosis

Fungal meningitis must be differentiated from other causes of meningeal irritation as shown below:

• Meningeal infection
  • Bacterial meningitis
  • Protozoal meningeal infection
  • Helminthic meningeal infection
  • Viral meningeal infection
• Non infectious causes
  • Behçet's syndrome
  • Chronic benign lymphocytic meningitis
  • Chemical meningitis
  • Drug hypersensitivity
  • Isolated granulomatous angiitis of the nervous system
  • Granulomatosis with polyangiitis (Wegener's)
  • Malignancy
  • Mollaret's meningitis
  • Sarcoidosis
  • Systemic lupus erythematosus
  • Vogt-Koyanagi-Harada syndrome

Differentiating fungal meningitis 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		+	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-specific CSF FTA-AbS -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 alcohol abuse	Ophthalmoplegia, confusion
CNS abscess		+	↑ leukocytes >100,000/ul, ↓ glucose and ↑ protein, ↑ 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 fungal meningitis from other causes of meningitis

Fungal meningitis may be differentiated from other causes of meningitis by cerebrospinal fluid examination as shown below:

Cerebrospinal fluid level	Normal level	Bacterial meningitis	Viral meningitis	Fungal meningitis	Tuberculous meningitis	Malignant meningitis
Cells/ul	< 5	>300	10-1000	10-500	50-500	>4
Cells	Lymphocyte:Monocyte 7:3	Granulocyte > Lymphocyte	Lymphocyte > Granulocyte	Lympho.>Granulocyte	Lymphocytes	Lymphocytes
Total protein (mg/dl)	45-60	Typically 100-500	Normal or slightly high	High	Typically 100-200	>50
Glucose ratio (CSF/plasma)	> 0.5	< 0.3	> 0.6	<0.3	< 0.5	<0.5
Lactate (mmols/l)	< 2.1	> 2.1	< 2.1	>3.2	> 2.1	>2.1
Others	ICP:6-12 (cm H2O)	CSF gram stain, CSF culture, CSF bacterial antigen	PCR of HSV-DNA, VZV	CSF gram stain, CSF india ink	PCR of TBC-DNA	CSF tumor markers such as alpha fetoproteins, CEA