Bacterial CNS Infections

Bacterial infections of the CNS — meningitis, encephalitis, and brain abscess — produce some of the most distinctive and clinically urgent neuropathology. The findings range from purulent exudate in the subarachnoid space (bacterial meningitis) to focal collections of pus encapsulated by gliotic walls (brain abscess) to the granulomatous reaction of tuberculous meningitis. Recognition of pathology guides empirical and targeted antimicrobial therapy and identifies complications. This page covers the major bacterial CNS infections and their pathology.

Acute Bacterial Meningitis

Pathology

  • Purulent exudate in the subarachnoid space, predominantly over the convexities (S. pneumoniae, H. influenzae) or the basal cisterns (some others).
  • Neutrophil infiltration: dense polymorphonuclear infiltrate in subarachnoid space, sometimes extending into Virchow-Robin spaces.
  • Vasculitis: secondary inflammation of cortical and meningeal vessels; substrate of stroke complication.
  • Edema: cytotoxic + vasogenic; raised ICP.
  • Hydrocephalus: communicating (CSF absorption impaired) or obstructive (basal exudate blocking outflow).
  • Cranial neuropathies: from inflammation around nerves in subarachnoid space.
  • Secondary brain injury: cortical, hippocampal damage from edema/ICP/hypoperfusion.

Common Pathogens by Age

  • Neonates: Group B strep, E. coli, Listeria.
  • Infants/children: S. pneumoniae, N. meningitidis, H. influenzae (now rare with Hib vaccine).
  • Adults: S. pneumoniae (most common), N. meningitidis.
  • Elderly: S. pneumoniae, Listeria, gram-negative rods.
  • Immunocompromised: Listeria, gram-negatives, S. pneumoniae.
  • Post-neurosurgical / shunt: Staphylococcus (coag-negative and aureus), gram-negatives.

Gross Findings

  • Cloudy CSF in subarachnoid space.
  • Yellow-green exudate over convexities or base.
  • Brain swelling, flattening of gyri.
  • Sometimes ventriculitis with intraventricular pus.

Diagnosis

  • CSF: high opening pressure, neutrophilic pleocytosis, elevated protein, low glucose.
  • Gram stain, culture.
  • PCR for bacterial pathogens.
  • Blood cultures.

Complications

  • Hydrocephalus.
  • Stroke (arteritic).
  • Cranial neuropathies (especially CN VIII → hearing loss).
  • Subdural empyema, brain abscess.
  • Cortical damage with seizures or cognitive sequelae.
  • Death (10-30% with adult pneumococcal meningitis even with treatment).

Tuberculous Meningitis (TBM)

Pathology

  • Basal cistern predominance: thick gelatinous exudate around brainstem and basal vessels.
  • Granulomatous inflammation: caseating granulomas with epithelioid cells, Langhans giant cells, lymphocytes.
  • Vasculitis: of vessels traversing the basal exudate (lenticulostriate, perforators) → deep infarcts.
  • Hydrocephalus: common from basal exudate.
  • Tuberculoma: focal granulomatous mass; can present like tumor.
  • Acid-fast bacilli (AFB): in caseating material; identifiable with Ziehl-Neelsen or Fite stain.

Clinical

  • Subacute meningitis with fever, headache, cranial nerve palsies (especially CN VI from raised ICP, CN III, IV, VII).
  • Cognitive decline, behavioral change.
  • Strokes in lenticulostriate or perforator territory.
  • Hydrocephalus.
  • Often coexistent pulmonary TB.

Diagnosis

  • CSF: lymphocytic pleocytosis, very high protein, low glucose, sometimes neutrophils early.
  • CSF AFB stain (low sensitivity); culture (slow).
  • CSF PCR for M. tuberculosis (more sensitive).
  • CSF Xpert MTB/RIF (rapid).
  • Imaging: basal meningeal enhancement, hydrocephalus, deep infarcts, tuberculomas.

Brain Abscess

Pathology

Focal collection of pus surrounded by a fibrous capsule, with surrounding edema and reactive astrogliosis. Stages:

  1. Early cerebritis (1-3 days): localized inflammation, edema, perivascular neutrophil infiltration. No capsule.
  2. Late cerebritis (4-9 days): central necrosis, more inflammation, beginning of vascular proliferation around the lesion.
  3. Early capsule (10-13 days): ring of granulation tissue + fibroblasts forming.
  4. Late capsule (>14 days): well-formed collagenous capsule, central necrosis with pus, peripheral edema and gliosis.

Common Organisms

  • Streptococci (most common; oral, sinus, dental sources).
  • Staphylococcus aureus (skull infection, post-traumatic).
  • Gram-negatives.
  • Anaerobes (often polymicrobial).
  • Nocardia (in immunocompromised).
  • Fungi (immunocompromised).
  • Toxoplasma (HIV/AIDS).

Sources

  • Contiguous spread: sinusitis (frontal abscess), otitis/mastoiditis (temporal lobe / cerebellar), dental.
  • Hematogenous: endocarditis, pulmonary infection, septic emboli. Often multiple, at gray-white junction.
  • Direct inoculation: trauma, surgery, neurosurgical procedures.
  • Cryptogenic: 15-20%.

Imaging

  • Ring-enhancing lesion with central low signal.
  • Restricted diffusion centrally: pus restricts diffusion (key distinguishing feature from necrotic tumor, which often has bright ADC).
  • Vasogenic edema around lesion.
  • Often multiple in hematogenous source.

Treatment

  • Empirical broad-spectrum antibiotics covering streptococci, staphylococci, anaerobes, gram-negatives.
  • Surgical drainage (stereotactic aspiration or excision) for lesions >2.5 cm or progressive.
  • Treat source.

Subdural Empyema

Pus in the subdural space, usually from sinusitis or otitis extension. Spreads rapidly along subdural space. Surgical emergency. Pathology: purulent fluid between dura and arachnoid.

Epidural Abscess

Pus in the epidural space, usually from contiguous bony infection (vertebral osteomyelitis, sinusitis). Spinal epidural abscess is a treatable cause of progressive myelopathy. Surgical drainage + antibiotics.

Neurosyphilis

Stages of CNS Involvement

  • Asymptomatic neurosyphilis: abnormal CSF in early syphilis without symptoms.
  • Acute syphilitic meningitis: lymphocytic meningitis, sometimes with cranial neuropathies.
  • Meningovascular syphilis (months to years after primary): vasculitis (Heubner arteritis) → strokes. Pathology: lymphocytic perivascular infiltration with intimal proliferation.
  • General paresis (paretic neurosyphilis, late): chronic progressive dementia with iron pigment and cortical atrophy, especially frontal. Pathology: subependymal granular ependymitis, rod cells.
  • Tabes dorsalis (late): dorsal column degeneration → sensory ataxia, Argyll Robertson pupils, lightning pains, urinary incontinence. Pathology: posterior root degeneration + dorsal column atrophy.
  • Syphilitic gumma: granulomatous mass, rare.

Diagnosis

CSF VDRL (specific, low sensitivity), CSF FTA-ABS (sensitive). Serum RPR/VDRL + treponemal tests.

Treatment

IV penicillin G for 10-14 days.

Lyme Disease (Neuroborreliosis)

Pathology

  • Lymphocytic meningitis.
  • Cranial neuropathies (especially CN VII — Bell palsy is a classic Lyme presentation).
  • Radiculoneuritis (Bannwarth syndrome).
  • Chronic Lyme encephalopathy (controversial).

Treatment: IV ceftriaxone or oral doxycycline depending on syndrome.

Listeria Rhombencephalitis

Pathology

  • Brainstem (pons, medulla) predilection.
  • Microabscesses in brainstem.
  • Granulomatous inflammation.
  • Microglial nodules with neuronophagia.

Clinical

  • Fever + cranial nerve palsies + cerebellar / brainstem signs.
  • Often in immunocompromised or pregnant patients.
  • Patients over 50.

Treatment: ampicillin + gentamicin.

Toxoplasmosis

In immunocompromised hosts (HIV/AIDS, transplant, immunosuppressed).

Pathology

  • Ring-enhancing brain lesions, often multiple.
  • Basal ganglia predilection.
  • Necrotic lesions with surrounding inflammation.
  • Tachyzoites and bradyzoite-containing cysts visible with appropriate stains.

Treatment

Sulfadiazine + pyrimethamine + leucovorin. Empirical trial often initiated in HIV/AIDS patients with typical lesions (response within 2 weeks).

🔍 Did You Know?

The use of diffusion-weighted imaging (DWI) to distinguish brain abscess from necrotic tumor is one of the most clinically useful advances in modern neuroimaging. Both lesions appear as ring-enhancing masses on contrast-enhanced MRI, and conventional imaging can be ambiguous — yet the management differs enormously: abscess requires antibiotics and often surgical drainage, while tumor requires biopsy and oncologic management. The diffusion characteristics distinguish them: brain abscess pus restricts diffusion strongly (bright on DWI, dark on ADC), reflecting the high viscosity, cellular debris, and dense bacterial population. Necrotic tumor, by contrast, typically shows bright ADC (facilitated diffusion of free water in the necrotic center). This single MRI sequence often resolves the diagnostic dilemma and lets the clinician proceed confidently to drainage in an abscess (with culture) versus biopsy in a tumor. The principle has been validated in multiple studies and is now standard interpretation. The lesson: when you see a ring-enhancing lesion, look at the DWI. Restricted diffusion centrally = abscess. Facilitated diffusion centrally = necrotic tumor. Caveats exist (some lymphomas restrict; some tuberculomas can be ambiguous), but the rule holds in the vast majority of cases and has saved many patients from unnecessary biopsy or unrecognized abscess.

Pitfalls and Pearls

  • Acute bacterial meningitis: neutrophilic CSF + purulent subarachnoid exudate; emergent treatment.
  • S. pneumoniae: most common adult; basal preference variable.
  • N. meningitidis: petechial rash; convexity exudate.
  • Listeria: rhombencephalitis pattern; elderly, immunocompromised, pregnancy.
  • TBM: basal exudate + vasculitis + hydrocephalus + tuberculomas.
  • Brain abscess: ring enhancement + restricted diffusion centrally (key distinguisher from tumor).
  • Brain abscess stages: cerebritis → late cerebritis → early capsule → late capsule (>14 days).
  • Subdural empyema: usually sinusitis source; rapid spread; surgical emergency.
  • Spinal epidural abscess: progressive myelopathy + back pain + fever; MRI urgent.
  • Neurosyphilis: lymphocytic meningitis + vasculitis (Heubner arteritis) + general paresis + tabes dorsalis.
  • Lyme: Bell palsy + Bannwarth syndrome + meningitis.
  • Toxoplasmosis: ring-enhancing lesions in HIV/AIDS, often basal ganglia.
  • Mucor / Aspergillus: vessel-invasive fungi in immunocompromised; hemorrhagic infarcts.
  • Steroids + ceftriaxone + vancomycin: empirical first-line for adult bacterial meningitis; add ampicillin for Listeria coverage in elderly / immunocompromised.

References

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  2. van de Beek D, Brouwer M, Hasbun R, Koedel U, Whitney CG, Wijdicks E. Community-acquired bacterial meningitis. Nat Rev Dis Primers. 2016;2:16074.
  3. Thwaites GE, Bhavnani SM, Chau TT, et al. Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis. Antimicrob Agents Chemother. 2011;55(7):3244-3253.
  4. Brouwer MC, Tunkel AR, McKhann GM 2nd, van de Beek D. Brain abscess. N Engl J Med. 2014;371(5):447-456.
  5. Marra CM. Neurosyphilis. Curr Neurol Neurosci Rep. 2009;9(6):447-454.
  6. Halperin JJ. Lyme disease and the central nervous system. Continuum (Minneap Minn). 2018;24(5):1473-1493.