Damage to nervous tissue from direct injury by the infectious agent; or indirectly via microbial toxins, inflammatory response or immune-mediated.
Pyogenic Cerebritis and Abscess
Direct extension after trauma, surgery, sinusitis (frontal lobes), dental infection or otomastoiditis (temporal lobes, cerebellum). Haematogenous spread (most frontal and parietal MCA territory) at grey-white junction from lung, endocarditis, congenital heart disease, IVDU, sepsis. No predisposing factor in 25%. Mostly pre-adolescent and middle-aged, reflecting underlying causes, M>F. Anaerobics most common including bacteroides, peptostreptococcus, streptococcus. S.Aureus common after trauma or surgery. Others include gram negative rods (E.Coli, Kelbsiella, Proteus, Pseudomons, H.Influenzze), pneumococcus, streptococcus, listeria, nocadia, actinomycosis. Multiple organisms in 20%. HA, elevated WBC, lethargy, obtundation, nausea, vomiting, fever (absent in >50% esp if encapsulated abscess), meningeal signs (in 30%), focal neurologic deficits, papilloedema, nuchal rigidity, seizures. Symptoms develop over a few days. Four stages of evolution:
- Early cerebritis (<3 days) – Focal oedema, infiltrate of polymorphonuclear (PMN) cells, lymphocytes, plasma cells. Organisms in centre and periphery with ill-defined margins. Central necrosis develops by 3/7. CT normal or hyopdense, mild mass effect, high PD/FLAIR/T2, low T1, variable patchy/gyriform enhancement (increased with high-dose Gadolinium 0.3mL/kg or magnetisation transfer). Tx antibiotics.
- Late cerebritis (4-9/7) – Increased central necrosis with fewer detectable organisms. Peripheral vascular proliferation with inflammatory cells, fibroblasts, astrocytes. Rim enhancement, filling in centrally on delayed. Increased FLAIR/T2. Diffusion restriction centrally. Vasogenic oedema. No discrete low T2 capsule. Tx antibiotics.
- Early capsule (10-13/7) – Walled-off infection with low T2 capsule of collagen (limiting spread of infection, reduces antibiotic penetration, reduced with steroids), fibroblasts, reticulin, macrophages, phagocytes, neutrophils; surrounded by reactive gliosis with astrocytes. Very few organisms in necrotic centre. Capsule is well-defined, low T2, occasionally high T1, ?from paramagnetic free radicles, haemorrhage, marked diffusion restriction. Rim enhancement typically smoother on outside cf more irregular inside. Prominent vasogenic oedema; if not prominent consider granuloma, tumour or demyelination. Bright DWI (cytotoxic oedema, high protein, high viscosity, cellular pus). Tx stereotactic aspiration or surgical drainage/resection. If multiple or high surgical risk then antibiotics alone, with weekly imaging. At grey-white interface inner part of capsule is thinner than peripheral (reduced blood supply; cf uniform thickness in tumours), predisposing to rupture causing daugher abscess or intraventricular rupture -> ependymitis/ventriculitis with enhancing ependyma and high density CSF.
- Late capsule (>14/7) – Thinner, better defined enhancing rim (complete collagen abscess wall), reduced size of necrotic centre.
- Treated abscess – May enhance, high T2/FLAIR for >8/12.
Multiloculation common. On MRS high cytosolic amino acids (0.9ppm), acetate (1.92ppm), lactate (1.3ppm) and alanine (1.5ppm); no Cho, Cr or NAA peak. No elevation in rCBV (compared to high grade tumour).
DDx tumour, resolving haematoma. If rim enhancement thick/irregular/nodular consider tumour or atypical infection (eg fungus). Other DDx: MS, radiation necrosis, subacute haematoma, thrombosed aneurysm, TB. Complete ring on NECT usually mets, uncommon in abscess or glioblastoma. Haemorrhage rare in acute abscess except toxoplasmosis.
Septic emboli mostly from IVDU, endocarditis (S.aureus), pulmonary AVMs, pulmonary infection, infected catheters with cardiac septal defects, ECMO, occult infection. May also cause infarction with small rounded regions of enhancement and wedge-shaped cortical infarcts. Haemorrhage common. Typical capsule may not form due to poor blood supply, with a thicker more irregular ring of enhancement that may persist. Persistent mass effect, oedema and enhancement >6/52. Rarely does a plain infarct cause abscess. May cause mycotic aneurysm formation -> intraparenchymal or subarachnoid haemorrhage. May cause obliterative vasculitis. DWI smaller than typical strokes. DDx cardiac myxoma embolising to cause stroke with later tumour growth into vessel wall and aneurysm.
(Ependymitis). Isolated or as part of other infections eg meningitis. More common in neonatal meningitis, CMV. Ventriculomegaly, high T2/FLAIR in CSF and/or adjacent parenchyma, subependymal enhancement (characteristic, DDx lymphoma and other tumours), occasionally choroid plexus enhancement. May only have debris with no ependymal enhancement. May be bright on DWI if purulent. Occasional periventricular calcification after neonatal ventriculitis.
Choroid plexus is a conduit for infection to brain. Usually associated with encephalitis, meningitis or ventriculitis, rarely isolated. Esp Nocardia and Cryptococcus. Normal choroid plexus is iso-intense/dense with calcification and enhancement; xanthogranulomatous change causes high DWI, FLAIR with less enhancement.
Mild smooth dural or meningeal enhancment may persist for years postsurgery and in patients with a ventriculostomy tube, most likely chemical meningitis from haemorrhage. Intracranial hypotension (spontaneous or iatrogenic CSF leak) also causes smooth dural thickening and enhancement. Chemical meningitis from noninfectious irritant in the subarachnoid space eg haemorrhage, ruptured epidermoid cyst.
Leptomeningeal enhancement follows gyri/sulci and basal cisterns. From infection, SAH, metastases, stroke, sarcoidosis.
Pachymeningeal enhancement is thick, linear/nodular, doesn’t involve basal cisterns (dura widely seprated from pia). From infectious/inflammatory pachymeningitis, metastases, CSF leak, spontaneous intracranial hypotension, idiopathic hypertrophic cranial pachymeningitis, shunting.
- Idiopathic hypertrophic cranial pachymeningitis – Rare, peak 50s. Chronic severe HA, CN palsies, ataxia. Fibrotic syndrome similar aetiology of orbital pseudotumour, Tolosa-Hunt. Dura thickened (may be pseudotumour), avid enhancement, low T2, no brain involvement. DDx meningioma, sarcoid, TB, syphilis.
Acute pyogenic usually bacterial; aseptic usually acute viral (usually self-limiting); chronic usually TB, spirochetes or cryptococcus. In neonates E.coli and group B streptococci; children with URTI Haemophilus infuenze (usually basal), Strep pneumoniae (usually over convexities); adolescents/young adults Neisseria meningitidis; adults Streptococcus pneumoniae and Listeria monocytogenes; immunocompromised Klebsiella or anaerobics. From systemic bacteraemia or direct spread from sinusitis, surgery or penetrating trauma. Viral (aseptic) meningitis is 85% enteroviruses (esp coxsackie and echovirus), less commonly arboviruses, mumps, herpes (esp HSV2); usually self-limiting. Acute fever, neck stiffness, HA, declining mental status. CSF aspirate diagnostic; bacteria cause cloudy, increased neutrophils, protein, reduced glucose; viruses cause increased lymphocytes, mild elevation in protein, normal glucose. Leptomeninges spread to CSF via choroid plexus or circumventricular organs where there is lack of BBB. Waterhouse-Friderichsen syndrome – meningitis and septicaemia with haemorrhagic infarction of adrenal glands and cutaneous petechiae; esp meningococcal and pneumococcal meningitis.
Early congestion and hyperaemia of leptomeninges, initially scan normal then leptomeningeal enhancement (esp post-FLAIR). Later exudate with distended subarachnoid space (esp basal cisterns and interhemispheric fissure in children), high density/FLAIR CSF peripheral sulci > basal cisterns (cf SAH) esp in dependent regions, diffuse cerebral oedema, leptomeningeal thickening, echogenic sulci. DWI usually normal unless encephalitis.
- Hydrocephalus – Early or late (leptomeningeal fibrosis), usually communicating from reduced absorption.
- Vasculitis – Venous or arterial infarctions (more well-defined than cerebritis).
- Sterile subdural effusions – Esp H.infuenza in infants. Thin, iso-dense/intense to CSF.
- Epidural/subdural empyema
- Basilar adhesions/loculations of CSF. Chronic adhesive arachnoiditis esp pneumococcal with gelatinous polysaccharide encouraging arachnoid fibrosis.
- Septic thrombophlebitis of venous sinuses – May cause ICA pseudoaneurysm in cavernous sinus, haemorrhagic infarction.
- Labrynthitis ossificans – Late, from infiltrated chochlear channels.
- Late atrophy/encephalomalacia
- Neonatal infection from Escherichia coli, group B streptococcus or Listeria monocytogenes. ?From delivery, chorioamnionitis, immaturity or iatrogenic (catheters, lines etc). Often associated with severe parenchymal damage, later causing multicystic brain with hydrocephalus, multifocal encephalomalacia with multiple intraventricular and paraventricular cysts.
- Fungal meningitis usually thick meningeal enhancement (pachymeningitis) in basal cisterns, hydrocephalus. Infarct and spread is less common than TB or bacterial (except aspergillosis, mucormycosis).
- Racemose cysticercosis – Thick meningeal enhancement with cystic lesions in cisterns.
- Sarcoidosis (DDx) – In 14% at autopsy, but rarely neurological symptoms. Primarily leptomeninges with enhancement, occasionally focal parenchymal enhancing mass or nonenhancing small white matter lesions.
- Viral meningitis from enteroviruses, mumps, togavirus, herpex simplex, lymphocytic choriomeningitis virus, HIV. Neurologic deficits uncommon, imaging usually normal, most don’t require treatment.
Subdural and Epidural Infections
From penetrating injury, surgery, sinusitis, otitis media, mastoiditis, orbital infection, calvarial osteomyelitis, purulent bacterial meningitis or rarely haematogenous spread. Hyperdense to CSF, low/high T1, high T2/FLAIR, diffusion restriction (if empyema). May have rim enahancement from granulation tissue formed over time.
- Epidural collections are biconvex. May spread to subgaleal space via emissary veins or via osteomyelitis. Strong dural attachments prevent rapid expansion. May cause spinal cord compression if in the spinal epidural space.
- Subdural collections may be acute or chronic; sterile or infected at presentation. Empyema if purulently infected. May be caused by distended arachnoid villus rupturing into subdural space, phlebitic bridging veins (from meningitis), haematogenous or direct extension through necrotic arachnoid membrane from subarachnoid space or extracranial. May spread rapidly throughout the space (life-threatening). Causes cortical venous thrombosis in >10% with venous infarcts. DDx chronic SDH, but this doens’t cause inflammatory changes in underlaing brain or diffusion restriction.
Encephalitis is almost always associated with meningitis, occasionally myelitis.
Most congenital with transplacental transmission (in 30-50% if primary, 3% if reactivation), symptomatic disease in 5%. Hepatosplenomegaly, jaundice, psychomotor retardation, chorioretinitis, deafness, blindness. Most injury due to ischaemia from placentitis causing insufficiency. Infection favours ependymal and subependymal regions. Necrosis of germinal matrix and thus migration anomalies (agyria if <18/40, polymicrogyria or focal cortical dysplasia if 18-24/40). Delayed myelination, periventricular white matter lesions esp calcifications, parenchymal atrophy, cerebellar hypoplasia, ventriculomegaly/porencephaly, hydranencephaly, paraventricular cysts. Intranuclear inclusions within ependymal, subependymal and white matter cells causing ‘owl’s eye’.
CMV infection in adults is uncommon unless immunocompromised, when there is subacute encephalitis esp paraventricular subependymal regions with severe haemorrhagic necrotizing ventriculoencephalitis and choroid plexitis.
Herpes Simplex Virus (HSV)
Most commonly neonates during descent through birth canal in a mother with genital herpes (HSV 2); transplacental transmission usually causes spontaneous abortion. Transmited in up to 50% of mothers with active primary genital herpes. High morbidity and mortality. Severe encephalitis fatal or seizures (2nd-4th week), mental retardation, microphthalmia, retinal dysplasia. Early encephalitis diffuse swelling with reduced grey-white differentiation or bilateral patchy hypodensities/echogenicities/hyperintesities in white matter and cortex with relative sparing of basal ganglia, thalami and posterior fossa. May have gyriform diffusion restriction. Rapid enlargement, meningeal and gyriform enhancement, leading to necrosis, occasionally thalamic haemorrhage, calcifies (punctate to gyriform after 2-3/52); eventually multicystic encephalomalacia, porencephaly, ventriculomegaly, microcephaly, cortical grey matter hyperdensity/hypointense T2 (characteristic, ?increased blood volume with deoxyhaemoglobin, calcification, laminar necrosis or other paramagnetic ions).
Childhood and adult HSV infection may cause encephalitis or cranial neuritis; from reactivation of latent HSV type 1, primary in 1/3 (usually <18yo, ?entry via CN1). Only 10% have a history of prior herpes. Encephalitis causes personality change, disorientation, focal neurology, seizures, rapidly stupor and coma, fever in >95%, dysphasia (temporal lobe), localised spiked and slow wave pattern on EEG. Mortality >70% untreated, with only 2.5% normal function in survivors. CSF study often negative, requires PCR for HSV. Fulminant necrotizing meningoencephalitis with oedema, necrosis, haemorrhage and eventually encephalomalacia. CT usually negative < 5 days, MRI positive earlier. Ill-defined hypodensities and increased FLAIR/T2/DWI in limbic system: inferior and medial temporal lobes (virus latent within trigeminal ganglion which innervates anterior and middle cranial meninges), insular cortex, subfrontal, cingulate gyri, orbital gyri of frontal lobes. Sparing of the basal ganglia and putamen. Usually initially unilateral, tends to sequentially involve bilaterally. Swelling with mass effect, variable streaky enhancement. Negative DWI suggests possibility of reversibility. Marked necrosis, loss of all neural and glial elements then atrophic cystic change. Occasional early leptomeningeal enhancement. DDx MCA infarct (which often involves putamen), early bacterial cerebritis, other viral encephalitis. Tx acyclovir, many have permanent deficits.
HSV-2 infection in adults usually causes meningitis.
Herpes Varicella Zoster Virus (VZV)
Typically elderly or immunosuppressed (esp AIDS, lymphoma). Reactivation of latent VZV in cranial nerve and dorsal root ganglia along sensory nerves of trigeminal ganglion causing rash/shingles, severe pain and allodynia (sensitivity to touch). Most commonly thorax then face. Rarely encephalitis similar to hepes simplex. Cranial neuritis – involvement of any cranial nerve, with MR contrast enhancement around the nerve.
- Vasculitis causing high T2/FLAIR, hypodensity, mass effect and gyriform enhancement, multiple vascular constrictions/beading esp proximal ACA/MCA. Spherical white matter lesions.
- Small-vessel vasculitis in immunocompromised leads to progressive encephalitis. Multiple areas of high T2 involving cortex, grey-white junction and deep white matter, may be haemorrhagic. DDx PML, but VZV doesn’t enlarge.
- Primary angiitis of the CNS (granulomatous angiitis) – Immunocompromised esp lymphoproliferative disorders.
- Ventriculitis and meningitis causing pachymeningeal enhancement.
- Myelitis 1-2/52 after rash from neurotropic spread with paraparesis, sensory deficits. High T2 in dorsal root entry zone. Usually left with residual neurological deficit. May cause ipsilateral posterior column atrophy.
- Herpes zoster ophthalmicus (V1 shingles) – Initially involves V1 division then delayed contralateral hemiparesis.
- Ramsay Hunt syndrome (herpes zoster oticus) – Facial nerve with ear pain, facial paralysis, vesicular eruption around the ear.
- Rarely infarction of optic nerve.
Postvaricellar encephalitis – In children may cause HA, nausea, vomiting, fever, nuchal rigidity, cerebellar ataxia, parkinsonism 1-3/52 after chickenpox. Bilateral symmetric high T2 in caudate nuclei, basal ganglia, internal and external capsules, claustram. No enhancement except occasionally in grey-white matter lesions. DDx ADEM.
Subacute Sclerosing Panencephalitis (SSPE)
From variant of measles virus, usually children or young adults who had measles <2yo, after a 6-10y asymptomatic period. Now rare due to vaccination. M>F. Slowly progressive language and behavioural changes, ataxia, chorea, rigidity, seizures, myoclonus, ocular problems, finally severe autonomic dysfunction with coma and death within months-years. Patchy high T2 in periventricular, subcortical, basal ganglia (esp putamen), cerebellum, pons. Progression from cortex/subcortical -> periventricular with diffuse cerebral atrophy. Early enhancement and mass effect. Occasional involvement of splenium. No treatment.
Other Viral Encephalitis
- Arboviruses (arthropod-borne) – Endemic encephalitis esp tropical regions. Includes Eastern and Western equine, West Nile, Venezuelan, St. Louis, L Crosse, Japanese B (Far East), Murray Valley (Australia, New Guinea), tick-borne (Russia and Eastern Europe). All have animal hosts and mosquito vectors (except tick-borne). Seizures, confusion, delirium, coma, focal neurology. Meningoencephalitis esp perivascular, multiple areas of grey and white matter necrotic foci. Severe cases have necrotising vasculitis with haemorrhages. High T2 in brainstem, hippocampus, thalamus, basal ganglia, white matter. Occasional meningeal enhancement. Giant panda sign – high T2 in thalami, putamina and tegmentum while sparing red nuclei and corticospinal tract. Occasional haemorrhage, usually no enhancement. No treatment with high mortality.
- Epstein-Barr virus (EBV) – Can cause seizures, central/peripheral neuropathies, myelitis, aseptic meningitis, encephalitis. High T2 esp brainstem and cerebellum (DDX tumour, MS, ADEM).
- Infectious mononucleosis – From EBV causing pharyngotonsillitis, fever, generalised lymphadenopathy, usually resolves after 1-3/52. May cause airway obstruction, meningoencephalitis, Guillain-Barre syndrome, cranial nerve palsies (from enhancing high T2 inflammatory tissue compressing nerves in foramina).
- Poliomyelitis – Effectively eradicated by vaccination. Usually causes subclinical gastroenteritis. Occasional invades CNS at anterior horn motor neurons of spinal cord, may cause cavitation. Flaccid paralysis and muscle wasting. Post-polio syndrome 25-35yrs later is progressive weakness of unclear aetiology.
- Rabies – Transmitted by bite of rabid animal, usually dog or wild mammal. Severe encephalitis esp brainstem, basal ganglia, spinal cord, dorsal root ganglia. Negri bodies – eosinophilic cytoplasmic inclusions. Extraordinary CNS excitability.
Anaerobic gram positive bacillus, primarily immunocompromised (occasionaly otherwise healthy patients). From food-borne transmission in 20% (coleslaw, raw vegetables, seafood, pasteurised milk, cheese, raw hot dogs, undercooked chicken). Causes meningitis, meningoencephalitis and abscess. Predilection for brainstem. Listerial rhombencephalitis involves brainstem and cerebellum with abnormal signal and enhancement in white matter tracts, similar to ADEM.
Tuberculous meningitis – Haematogenous seeding to leptomeninges. Usually Mycobacterium tuberculosis, atypical eg M avium intracellulare in AIDS. Predilection for infants/children. CXR normal in 50%, tuberculin skin test also can be normal. CSF is almost always abnormal with elevated protein, reduced glucose. Subacute/insidious headache, malaise, weakness, apathy, focal neurology. Enhancing, thickened meninges (often marked pachymeningitis) esp basal cisterns (cf other bacteria), sylvian fissures. May have discrete nodules scattered over leptomeninges. Thick basal cistern gelatinous/fibrous exudate may extend into Virchow-Robin spaces causing obliterative endarteritis and infarcts, communicating hydrocephalus, cranial nerve palsies. Rarely calcification seen. Hydrocephalus usually doesn’t improve, due to dense adhesions, may also develop syringomyelia/syringobulbia.
Intracranial tuberculoma – In 5-10% of patients with TB esp children and elderly, AIDS. Haematogenous spread from lungs, only 50% have known history of TB. When cell-mediated immunity develops then forms small tuberculomas, walled-off by dense fibrous capsule with caseous necrotic core. CSF normal in 50%. In adults most supratentorial (frontal or parietal), in children 60% in posterior fossa (cerebellum). Multiple in 50%. Only 10% associated with tuberculous meningitis. Fever rare. Tumour-like intra- or xtra-axial. Iso- or slightly hyper-dense nodules/small masses with centre more dense than abscess due to caseous necrosis. The 1-2mm tuberculomas may coalesce into larger lesions. Target apparance with central calcification surrounded by rim enhancement is uncommon. Calcification in <20%, but common when lesions resolve. Variable T2, wall often low T2, solid nodular (noncaseating) or irregular/variable thickness rim enhancement (crenated appearance). Variable diffusion restriction. Mild oedema. May adhere to dura causing hyperostosis (DDx meningioma). Tuberculoma may be dormant for years, rupture into subarachnoid space (causing meningoencephalitis). DDx tumour, pyogenic abscess, fungal, parasites, sarcoidosis. Tx medical; surgery if diagnosis uncertain, failed medical Tx or large lesions.
Tuberculous abscess – Rare complication, pyogenic abscess in patients with impaired T-cell immunity. More rapid symptoms. Features similar to pyogenic abscess, often large, multiloculated, prominent oedema and mass effect.
Endemic infections are geographically restricted, usually immunosuppressed, but may be immunocompetent. Usually disseminated infection with haematogenous spread (usually from lungs) causing granulomatous meningitis. Focal parenchymal lesions unusual. Most granulomas are small with solid or thick rim enhancement. Abscesses similar to pyogenic abscesses. Meningeal enhancement is common. Hydrocephalus common esp coccidiodes.
- Coccidioidomycosis (Valley fever) – Spores inhaled with outbreaks after groundbreaking for construction in SW USA, normal Mexico. Most asymptomatic or mild respiratory symptoms, <1% develop disseminated infection after weeks-years involving bones or CNS. Thick basilar meningitis, meningeal and parenchymal granulomas (esp cerebellum), vasculitis, dilated Virchow-Robin spaces, ependymitis, communicating hydrocephalus.
- Blastomycosis – CNS involvement in 25% of disseminated cases with meningitis, parenchymal abscessses and granulomas more frequent than coccidioides. Epidural granulomas and absecess in head, spine, usually from direct extension from bone. Multiple brain lesions common.
- Histoplasmosis – Benign, asymptomatic, dissemination unusual with small risk of CNS involvement. Meningitis, occasionally multiple/solitary granulomas, abscesses uncommon.
Cosmopolitan infections occur worldwide, usually immunosuppressed, infants, elderly or chronically ill (except cryptococcosis). Usually meningitis, but parenchymal lesions common.
- Cryptococcosis – Most common, immunocompetent in 50%, 10% of patients with AIDS (3rd after HIV and toxoplasmosis). Yeast with polysaccharide capsule staining with India ink. Haematogenous spread from lungs. 90% have antigen in CSF or serum antiody. Usually meningitis, occasionally multiple granulomas, less commonly abscesses. CT usually N. Multiple small miliary solid or ring enhancing nodules involving basal leptomeninges, basal ganglia , choroid plexus in trigone, spinal cord and spinal nerve roots. Diffuse meningeal enhancement is unusual (cf TB and bacterial meningitis). Hydrocephalus (obstructing foramina of Luschka and Magendie), diffuse atrophy. Gelatinous pseudocysts with soap bubble appearance in basal ganglia (enlarged Virchow-Robin space filled with Cryptococcus), smooth, round, hypodense, follows CSF signal, most don’t enhance.
- Aspergillosis – CNS involved in 60-70% of disseminated disease, from haematogenous spread or direct extension from paranasal sinuses, usually immunocompromised. Meningitis or meningoencephalitis. Parenchymal disease usually abscess (esp basal ganglia, often multiple, irregular ring enhancement in crenated appearance), granulomas unusual. May not enhance due to vascular invasion and ischaemia. Aggressive aspergillosis invades blood vessles causing subcortical or cortical haemorrhagic infarctions. Mortality >85%.
- Mucormycosis – Usually inhaled, destroys nasal mucosa forming black crusts (classic eschar) ± bony destruction, spreading to paranasal sinuses, orbit, base of skull, cribriform plate -> anterior cranial fossa, occasionally haematogenous spread. 50% rate of intracranial extension. Almost all patients diabetic or immunocompromised (debilitated with burns, uremia, malnutrition), HIV with IVDU, deferoxamine (iron chelating agent abolishes fungistatic effect of serum on Mucor). Mortality >70%. Tends to invade blood vessels (esp cavernous ICA) with infarcts and haemorrhage, cavernous sinus thrombosis. Single or multiple mass lesions with varying peripheral enhancement depending on level of immunosuppression. Variable oedema. Often base of brain adjacent to sinuses.
- Candidiasis – Esp neutropenic patients on steroids. Usually meningitis, vasculitis, occasionally granulomas and small abscesses (esp MCA distribution), endophthalmitis. Usually haematogenous spread from lungs, GI. Can cause infarcts, hydrocephalus, large abscesses.
- Nocardiosis – Aerobic fungus, esp patients on steroids, pulmonary alveolar proteinosis, sarcoidosis, UC, intestinal lipodystrophy. Haematogenous spread from lungs causing brain abscesses, rarely meningitis. Enhancing capsule with multiple loculations.
Common in developing world, uncommon in developed.
- Cysticercosis (neurocysticercosis) – Larvae of pork tapeworm Taenia solium. Faecal-oral route – intestinal disease, eggs released into pig’s bowel stream, ingested by pig then forming oncospheres (primary larvae), hatching and haematogenously spread throughout the pig’s body forming cysticerci (secondary encysted larvae). In human intestinal tract larvae develop into adult tapeworm that release oncospheres during digestion and burrow through intestinal tract. They form cystercerci in CNS and other tissues, form cystic covering and scolex and cannot develop further in humans, eventually die. Those that reach CNS infect parenchyma, meninges, ventricles or spine. Endemic in Latin Mexico, Central/South America, Asia, Africa, Eastern Europe. Time from infection to symptoms (when larvae dies) varies form <1yr to 30yrs. Seizures in >90%, encephalitic symptoms. Tx anticystecercus drugs eg praziquantel, albendazole.
- Parenchymal cysticercosis – Progress through stages takes 2-10yrs. Vesicular (1st) stage: cyst viable as <10mm solitary/multiple, usually cortical or deep grey matter; small marginal nodule represents the scolex; minimal oedema/enhancement. Acute encephalitic phase (lasts 2-6/12): when the cyst dies fluid leaks causing inflammation, causing acute encephalitis with ring-enhancing lesions, surrounding oedema; cyst fluid is of increased density, higher T1 and T2. Colloidal vesicular (2nd) and granular nodular (3rd) stages: larvae die with cyst becoming turbid and smaller, may cause inflammatory reaction and encephalitis, nodular enhancement. Nodular calcified (4th) stage: scolex and cyst wall calcifies, hypodense cysts, occasionally enhance, oedema may be large despite size.
- Intraventricular cysticercosis similar to parenchymal. Cysts isodense, iso/high T1 to CSF, may see eccentric scolex. Esp 4th ventricle, may be free or adherent to wall causing subependymal high T2. Enhancement might not be present. May obstruct foramen of Monro, 3rd ventricle or cerebral aqueduct. Ventriculitis when cyst ruptures.
- Meningobasal/racemose (Latin = ‘clusters’) cysticercosis – Cysts mostly basal cisterns, grape-like clusters or conform to shape of cistern. No scolex, mural nodule or calcifications. Common mural enhancement, diffuse meningeal enhancement, hydrocephalus.
- Spinal cysticercosis (very rare) – Usually intradural, can be intramedullary (solid or ring-enhancing lesions similar to brain parenchyma) or extramedullary (analogous to racemose form).
- Echinococcosis (hydatid disease) – In Australia, South America, Africa, Central Europe, Middle East. Dog tapeworm (Echinococcus granulosus) with humans intermediate hosts. Ova hatch in gastrointestinal tract with embryos spreading throughout body, maturing into cystic larva (hydatic cyst). Hydatid cysts most common in lung and liver, brain involved in 5%. Usually solitary, unilocular, large, round, smooth, most supratentorial in MCA territory esp parietal lobe. May contain scolices and aggregates of scolices (hydatid sand) as dark whorls on MRI. Rarely mural calcification. Fluid isodense to CSF. Usually no oedema or enhancement unless ruptured, which causes inflamamtory reaction.
- Toxoplasmosis – Ubiquitous protozoan Toxoplasma gondii, congenital or acquired.
- Acquired in immunocompromised (10% of AIDS patients) – From reactivation causing vascular thrombosis or multiple abscesess (esp basal ganglia, corticomedullary junction, white matter, periventricular), calcification uncommon (except after treatment), occasionally haemorrhagic. Multiple high T2 with oedema and ring/nodular enhancement. Rapid response to antibiotics.
- Congenital – From pregnant woman eats poorly cooked meat or if infected by cat, causing diffuse encephalitis of foetal brain, usually with severe destruction, microcephaly, chorioretinitis, mental retardation, hydrocephalus (ependymitis cuasing aqueduct stenosis), calcifications (periventricular white matter, basal ganglia, cerebral hemispheres; cf CMV usually periventricular only).
- Amoebic meningoencephalitis – Amoeba enter nasal cavity of patient swimming in infested freshwater, direct extension through cribriform plate causing severe meningoencephalitis, usually fatal. Imaging usually underestimates severity. Meningeal and/or grey matter enhancement, then diffuse cerebral oedema. Occasional single/multiple ring or solid-enhancing abscesses with surrounding oedema, more common in immunosuppressed.
- Cerebral malaria – Plasmodium falciparum infected RBC occluding capillaries. Cortical infarction, high T2 in white matter, splenium.
- Sparganosis – Chronic granulomatous lesions causing cerebral atrophy, myelin loss, punctate/nodular calcifications, enhancing lesions. Dense collagenous walls line elongated/sinusoidal spaces which may contain the worm. Large enhancing lesion with oedema, changing location of enhancing nodule or deterioration on imaging suggest a live worm.
Gram negative helical/spiral shaped bacteria, free-living and anaerobic.
In 5-10% of untreated primary infection, usually in secondary or tertiary stages. Rare due to effective antibiotics, but increased with AIDS. Usually asymptomatic, aseptic meningitis, tabes dorsalis, general paresis or meningovascular disease.
- Meningovascular syphilis – Acute stroke syndrome or subacute illness with thickening of meninges and medium to large vessel arteritis, small infarcts (basal ganglia, white matter, cerebral cortex or cerebellum) which may have patchy or gyriform enhancement. Meningeal enhancement uncommon. Angiography shows multipe segmental constrictions/occlusions. May cause cerebral gummus (plasma cell-rich lesions) in meninges extending into parenchyma as small enhancing nodules with adjacent meningeal enhancement.
- Paretic neurosyphilis – Invasion of brain with progressive mental deficits, mood alterations then severe dementia. Esp frontal lobes with neuronal loss, microglia proliferation, gliosis, iron deposition. Hydrocephalus from damage to ependyma and proliferation of subependymal glia (granular ependymitis).
- Tabes dorsalis – Damage to sensory nerves in dorsal roots causing ataxia, loss of pain sensation, Charcot joints.
(Neuroborreliosis). Multisystem infection by Borrelia burgdorferi (found in deer, mice, raccoons and birds), spread to humans by Ixodes ticks. Stage 1: flulike illness, expanding skin lesion. Stage 2 after weeks/months: cardiac and neurological symptoms (in 10-15% including neuropathies, radiculopathies, myelopathies, encephalitis, meningitis, pain, cognitive disorders, movement disorders). Stage 3 after months-years: arthritis and chronic neurologic problems. MRI usually normal. Thick enhancing cranial nerves (CN3-8, esp CN7, from meningitis or mononeuritis multiplex), may cause optic neuritis, multiple small enhancing (ring or nodular) white matter lesions (similar to MS), meningeal enhancement. Tx antibiotics and corticosteroids.
Cat Scratch Disease
Inoculation of Bartonella henselae from animals esp kittens. Self-limited lymphadenopathy, fatigue, headache, anorexia. May cause encephalopathy esp involving thalami, vasculitis.
Rocky mountain spotted fever in South Atlantic USA, late spring-summer. Rash in 50% (less if >15yo). Meningoencephalitis and vasculitis with basal ganglia infarction, diffuse oedema, meningeal enhancement, dilated perivascular spaces. Mortality is 20% untreated.
AIDS and Immunocomprimise
CNS involvement of AIDS is common (up to 2/3), but reducing with highly active antiretroviral therapy (HAART). Can be divided into encephalitis, meningitis, pure white matter, mass lesions (infection, neoplastic), or atrophy. Commonly HIV encephalopathy, toxoplasmosis, cryptococcosis and other fungi, CMV and Herpes meningoencephalitis, mycobacterial, PML, meningovascular syphilis, primary CNS lymphoma, lymphoma metastases, gliomas, rarely Kaposi sarcoma.
- HIV encephalopathy (AIDS dementia complex ADC, progressive dementia complex) – HIV is neurotropic infecting brain in 90% at autopsy (prior to HAART), but symptomatic in minority. Subcortical dementia with cognitive, behavioural and motor deterioration in 10% of patients with AIDS. Infection of microglia (brain macrophages) with cytokines and excitatory compounds toxic on adjacent neurons, vasculopathy. Widely distributed microglial nodules. Diffuse atrophy (mostly central), ill-defined/hazy symmetrical focal or diffuse high T2 over a large area, or focal punctate lesions without mass effect or enhancement, demyelination, multinucleated giant cells esp centrum semiovale and basal ganglia, white matter calcifications. Involves supratentorial deep grey, subcortical and periventricular white matter. Cortical grey matter and U fibres usually spared. When severe, there is extensive signal throughought the periventricular white matter, brainstem, cerebellum. Early increased Cho, when severe reduced NAA. Resopnds to HAART.
- Toxoplasmosis – Common when CD4 count <100 cells/mm3. T.gondii is an obligate intracellular protozoan, from reactivation of previous infection. Usually necrotising encephalitis with thin-walled abscesses, multiple 10-40mm enhancing mass lesions with vasogenic oedema (small solid enhancement, larger ring-enhancement), lacks diffusion restriction, commonly haemorrhages. Basal ganglia, white matter and cortical lesions. DDx primary CNS lymphoma.
- Progressive multifocal leukoencephalopathy (PML) – Reactivation of polyomavirus (papova/JC virus) infecting oligodendrocytes (axonal support cells generating myelin). Most of the population has evidence of asymptomatic exposure to JC virus by 14yo. Reactivation only in immunosuppresed patients (AIDS, MS, lymphoma, organ transplant, disseminated malignancy). Demyelination and necrosis esp peripheral subcortical U fibres, less deep white matter (cf HIV, CMV). Solitary or multifocal, eventually coalescing. Spares cortex and deep grey matter. No significant mass effect. May be cystic in the setting of MS. Change in mental status, blindness, aphasia, hemiparesis, ataxia, progressive to death within months (improved with HAART). In non-AIDS predilection for parieto-occipital lobes, but in AIDS in any part of brain. Focal increased FLAIR/T2, decreased T1, hypodense, solitary or multifocal, rapidly coalescing into larger assymetric areas. Absent mass effect and enhancement. Reduced MTR.
- Primary CNS lymphoma – In 6% of patients with AIDS, also seen in other immunosuppresion (esp heart/kidney allograft). Solitary or multiple enhancing mass lesions, usually central (periventricular white matter, basal ganglia, thalamus), brainstem or cerebellar hemispheres, may have subependymal spread or extension across corpus callosum, variable T2/T1, usually isodense to grey matter (hypodense in AIDS). Unusual to have central necrosis except in AIDS. Almost always enhances (solid or ring). May rapidly increase in size. Very sensitive to steroids and radiotherapy, but prone to recurrence. Compared to toxoplasmosis tends to be larger and fewer, hyperdense, iso/low-T2, periventricular spread, encases ventricles (not seen in toxoplasmosis), solid rather than ring-enhancement, doesn’t haemorrhage (unless treated), incraesed choline and decreased NAA peaks (markedly high lactate and lipid in toxo), takes up Th201, increased perfusion (cf reduced in toxo). May coexist with toxoplasmosis and patient is often treated for both.
- Meningitis – Common including cryptococcosis, toxoplasmosis, TB, CMV. Usually mild due to reduced inflammatory response with little/no enhancement, normal imaging. Elevated cyrptococcal antigen in serum and CSF. May form gelatinous pseudocysts.
- Syphilitic meningovasculitis – Rare, widespread meningeal thickening, lymphocytic infiltration of perivascular spaces, Heubner arteritis of mid/large vessels (segmental constrictions/occlusions of supraclinoid ICA, proximal ACA/MCA, basilar a), small vessel Nissl arteritis, enhnacing parenchymal nodules (cerebral gumma), mesiotemporal high T2.
- Mycobacterial infections – Mostly in IVDU with pulomonary TB, CXR positive in 65%, high mortality. Mostly meningitis with communicating hydrocephalus, meningeal enhancement. Tuberculomas in 25%, abscesses less common.
- CMV – Commonly subclinical, unusual to cause frank tissue necrosis so imaging commonly normal. CMV meningoencephalitis can cause high T2 in periventricular white matter, subependymal enhancement, rarely ring-enhancing mass. Herpes and varicella more benign clinically and radiographically due to reduced immune response.
- Infarction – Common, esp basal ganglia. From altered vasoreactivity, drugs (esp cocaine), HIV vasculitis, infection, marantic endocarditis (non-bacterial), DIC, hypoxia.
- AIDS-associated myelopathy – Vacuolar myelopathy with lipid-laden macrophages. Insidious urinary incontinence, progressive paraparesis, sensory loss. Most commonly thoracic cord. Usually atrophy ± high T2, doesn’t enhance.
AIDS uncommon in paediatric patients, but high rate of CNS involvement with atrophy/acquired microcephaly (reduced brain weight for age), calcifications (basal ganglia, periventricular, frontal white matter, cerebellum), encephalitis, vascular ectasia/aneurysms and stenoses (likely from VZV vasculitis) associated with infarcts. Infections and lymphoma vey uncommon.
Creutzfeldt-Jakob Disease (CJD)
(Transmissible spongiform encephalopathy, prion disease). Prion (slow virus) causing conversion of normal α-helix protein PrPC to abnormal β-pleated sheats of PrPSC, which is resistant to proteases. This causes cytoplasmic vacuoles (spongiform change) and cell death. Rapidly progressive dementia, ataxia, myoclonus, death usually ~7/12 after onset of symptoms.
- Sporadic (sSJD, 95%) – 1:1 million incidence. CT normal in 80%, may show rapidly progressing atrophy. Diffusion restriction in cortex and lentiform, may also see on FLAIR. Later spread to all of basal ganglia, thalami, occipital cortex (Heidenhain variant), white matter; cerebral atrophy.
- Familial – Mutation in PRNP (gene encoding PrP). Familial CJD, fatal familial insomnia, Gerstmann-Straussler-Scheinker disease. Cortical ribbon high FLAIR and DWI, volume loss. Higher rate of PrP changes.
- Kuru – New Guinea brain-eating cannibal tribe.
- Iatrogenic – From contaminated grafts, transplants, blood.
- Variant (vCJD, bovine spongiform encephalopathy, mad cow disease) – Spread from scrapie in sheep, transmitted to humans via infected beef. Infected cows are apprehensive, hyperesthetic, uncoordinated. Diffusion restriction and FLAIR in caudate, putamen, bilateral thalamic pulvinar (pulvinar sign), dorsal medial nucleus of thalami (hockey stick sign), may also affect striatum and periaqueductal grey matter. Usually no atrophy due to rapid progression.
Noninfectious Inflammatory Disease
Infiltration of fibrocartilaginous stroma with polyclonal inflammatory cell infiltrates. This can be idiopathic, due to IgG4 or inflammatory myofibroblastic tumour (IMT). It is non-neoplastic, no granulomas, not due to vasculitis. Each demonstrate thickening and enhancement of pachymeninges (dura-arachnoid).
- Idiopathic: 50% due to chronic dural venous sinus occlusion. Predominantly involve the falx and tentorium (but can be diffuse). Low T2 due to fibrotic component. Eiffel-by-night sign – coronal C+ showing enhancing dural leaves of falx/SSS and tentorium/transverse sinus with central nonenhancing occluded venous sinus.
- IgG4: similar appearances to idiopathic, predominantly involving falx and tentorium.
- Inflammatory myofibroblastic tumour (IMT) – Also has proliferating spindle cells. Mass-like, may be nodular, anterior > posterior. 10% invasive into brain or skull base.
Diffuse pachymeningeal enhancement and thickening. Progressive thickened dura-arachnoid with fibrosis and chronic inflammation. Usually asymptomatic, but can cause headache.
- Secondary – including sarcoidosis (which may involve pia and perivascular spaces), infections, autoimmune disease, neoplastic, post-surgery
Note this is different to transient post procedure (eg lumbar puncture, surgery) pachymeningeal thickening, which is probably due to venous engorgement of the dura-arachnoid. DDx intracranial hypotension causing venous distention and pachymeningeal engorgement (the degree of imaging findings do not necessarily correte with clinical severity)
Systemic granulomatous disease of unknown aetiology involving nervous system in 5% (PNS and CNS). CNS involvement diagnosis of exclusion, biopsy nonspeific. Nodules may calcify, iso/hyper-dense. DDx tumour, meningioma, vasculitis, MS. 25% have anterior uveitis, posterior uveitis, lacrimal gland infiltration, optic nerve/sheath involvment, retrobulbar mass, exophthalmos, EOM thickening or visual pathway involvement; may mimic Tolosa-Hunt. May have dramatic response to steroids.
- Chronic basilar leptomeningitis – Involves hypothalamus, pituitary stalk, optic nerve and chiasm, occasionally convexities. Unilateral/bilateral CN (esp VII) palsies, endocrine/electrolyte imbalance. Communicating hydrocephalus common. May spread into Virchow-Robin spaces, invading and thrombosing vessels (granulomatous angiitis, similar to primary angiitis of CNS). Diffuse/focal/gyriform leptomeningeal and hypothalamic region enhancement, may be linear following Virchow-Robin spaces.
- Parenchymal sarcoid nodules – Granulomatous masses. Usually associated with arachnoiditis and microscopic granulomata throught parenchyma. May cause hydrocephalus if next to aqueduct. High T2 at grey-white junctions, may or may not enhance.
- In spinal cord may cause leptomeningeal coating or intramedullary mass. Occasionally involves cauda equina causing nodularity, thickening of nerve roots and polyradiculopathy.
Necrotising granulomas of multiple organs. Involves meninges and brain in 5% causing meningeal diffuse/focal thickening/enhancement, infarction, white matter high T2, intraparenchyma granuloma, atrophy, vasculitis, pituitary gland/stalk.
Multisystem vasculitis involving CNS in 5-10% with exacerbations and remissions, recurrent oral ulcerations, recurrent genital ulcerations, skull/eye lesions or positive pathergy test. Most >50yo. Common along Silk Road (Japan to Mediterranean). Associated with venous thrombosis in >1/3, but rarely dural sinus.
- Brainstem syndrome – Mesodiencephalic lesion with oedema extending alont tracts in brainstem and diaencephalon. Pontobulbar lesion. Atrophy when chronic.
- Meningoencephalitic syndrome
- Organic confusion syndrome
Chronic granulomatous involving GIT, CNS in 20%. ?Delayed hypersensitivity to Whipple bacterium (G pos Tropheryma whippelii). Periodic acid-Schiff and methenamine silver staning of macrophages which contain the bacilli. Myoclonus, ophthalmoplegia, progressive dementia, steatorrea, malabsorption, arthritis. Male 40-50yo. Involves grey matter, hypothalamus and thalamus with low T1 high T2 enhancing nodules.
?Viral-induced autoimmune reaction causing intractable seizures, progressive neurologic deficits. Mean 6-8yo. Usually affects one cerebral hemisphere with high T2 in basal ganglia and periventricular white matter, severe atrophy, large areas of reduced perfusion and hypometabolic on PET. Crossed cerebellar diaschisis – disruption of corticopontocerebellar system with reduced perfusion of contralateral cerebellar hemisphere. Reudced NAA, increased myoinositol, elevated Cho, glutamine and glutamate. Tx hemispherectomy.