Meningitis - Pathology Notes

Definition

• Chemical meningitis - reaction to an irritant (e.g., debris from a ruptured epidermoid cyst)
• Carcinomatous meningitis - metastatic cancer cells spreading to the subarachnoid space

Routes of CNS Entry

1. Hematogenous spread - most common; usually via arterial circulation, but retrograde venous spread via facial vein anastomoses can occur
2. Direct implantation - trauma, congenital malformations (e.g., meningomyelocele)
3. Local extension - from infected adjacent structures (sinuses, teeth, skull, vertebrae, mastoid, middle ear)
4. Peripheral nerve transport - viruses travel retrogradely (e.g., rabies, herpes zoster)

Classification

1. Acute Pyogenic (Bacterial) Meningitis

Organisms by Age Group

Clinical Features

• Systemic signs of infection + meningeal irritation + neurologic impairment
• Headache, photophobia, irritability, clouding of consciousness, neck stiffness
• Kernig sign, Brudzinski sign
• CSF: increased pressure, abundant neutrophils, elevated protein, reduced glucose

Gross Morphology (MORPHOLOGY)

• An exudate is evident within the leptomeninges over the surface of the brain
• Meningeal vessels are engorged and stand out prominently
• Distribution varies by organism:
  • H. influenzae: exudate tends to be basal
  • S. pneumoniae: densest over the cerebral convexities near the sagittal sinus
• Tracts of pus follow along blood vessels on the brain surface
• In fulminant cases: inflammation extends to the ventricles - ventriculitis
• The ventricles can be a portal for CSF involvement because the choroid plexus lacks a blood-brain barrier

Fig. 28.23 - Pyogenic meningitis: a thick layer of suppurative exudate covers the brain surface and thickens the leptomeninges. (Robbins PBD)

Microscopic Morphology

• Neutrophils fill the subarachnoid space in severely affected areas
• In less severe cases: PMNs are predominantly around leptomeningeal blood vessels
• Gram stain reveals variable numbers of bacteria in untreated cases
• The pia is rarely breached in bacterial meningitis
• In fulminant cases: inflammatory cells (mostly neutrophils) infiltrate walls of leptomeningeal veins and may extend focally into the brain parenchyma (cerebritis)
• Secondary vasculitis and venous thrombosis may lead to hemorrhagic cerebral infarction

Sequelae / Complications

• Leptomeningeal fibrosis - may follow pyogenic meningitis and cause hydrocephalus (due to obstruction of CSF flow at arachnoid villi or cisterns)
• Chronic adhesive arachnoiditis - especially in pneumococcal meningitis; large quantities of organism-derived capsular polysaccharide produce a gelatinous exudate that promotes arachnoid fibrosis

2. Acute Aseptic (Viral) Meningitis

Definition

Etiology

• Enteroviruses - most common, accounting for ~80% of cases with identified pathogen
• Other agents: influenza species, lymphocytic choriomeningitis virus (LCMV)
• The etiologic agent is identified only in a minority of cases overall

CSF Findings (distinguish from bacterial)

Course

• Less fulminant than pyogenic meningitis
• Usually self-limited, treated symptomatically

Chemical Meningitis (Aseptic variant)

• Caused by rupture of an epidermoid cyst into subarachnoid space, or introduction of a chemical irritant
• CSF: sterile, neutrophilic pleocytosis, increased protein, but normal glucose

3. Chronic Meningitis

Tuberculous Meningitis

• <50% of adults have a history of prior pulmonary TB
• Patients present with lethargy, stupor, or coma + nuchal rigidity
• May have a fulminant course despite being "chronic"

• Elevated opening pressure
• 1-500 WBC, predominantly lymphocytes/monocytes (resembles aseptic meningitis)
• Protein >100 mg/dL
• Glucose decreased (but rarely <20 mg/dL)
• Organisms seen on smear in minority; cultures take weeks; PCR sensitivity 25-80%

Listeria Meningitis

• Predominantly in immunocompromised patients
• Can cause a chronic infection lasting weeks
• Predilection for brainstem - cystic lesions/abscesses causing cranial neuropathies
• Key point: responds to ampicillin, not to many broad-spectrum antibiotics used for bacterial meningitis - always include ampicillin when Listeria is in the differential

4. Fungal Meningitis

Cryptococcal Meningitis (Cryptococcus neoformans)

• Most common in immunocompromised (e.g., AIDS patients)
• Imaging may show gelatinous pseudocysts in basal ganglia on T2 MRI
• Complications include: hydrocephalus, infarction, cryptococcoma
• CSF CrAg (cryptococcal antigen) test: rapid, specific, sensitivity >90%

CSF Analysis Summary Table

Key Complications of Meningitis

Waterhouse-Friderichsen Syndrome

• Bilateral adrenal hemorrhage associated with meningococcal (N. meningitidis) septicemia
• Fulminant course with purpuric rash (petechiae/purpura from DIC), septic shock, adrenal insufficiency
• Pathology: bilateral massive adrenal hemorrhage, DIC

Brudzinski's Sign

How to Elicit It

1. Patient lies supine
2. Examiner passively flexes the patient's neck (chin toward chest)
3. Positive sign: the patient involuntarily flexes both hips and knees in response

Mechanism

Alongside Other Signs of Meningeal Irritation

Clinical Significance

• All three signs (nuchal rigidity, Kernig's, Brudzinski's) are classic signs of meningeal irritation seen in meningitis and subarachnoid hemorrhage
• Important caveat: sensitivity is approximately 30% or lower for diagnosing acute bacterial meningitis in adults - they can be absent despite confirmed meningitis
• The classic triad of fever + stiff neck + change in mental status is initially present in only a subset of patients
• May be absent or reduced in:
  • Very young or elderly patients
  • Immunocompromised individuals
  • Patients with severely depressed mental status
• Cervical spine disease in older patients can cause false-positive nuchal rigidity

Confirmed By