Central Nervous System Pathology

Cerebral Oedema and Raised Intracranial Pressure

= Brain and spinal cord are protected by rigid compartment of the skull – cerebral oedema, increases in CSF volume and focally expanding lesions can cause raised intracranial pressure (ICP)

Two types of oedema:

1. Vasogenic = blood-brain barrier disruption, increased vascular permeability. Can be localised or generalised. Seen in inflammation or neoplasm.
2. Cytotoxic = increase in intracellular fluid due to neuronal/ glial/endothelial cell injury. Seen in hypoxic/ ischaemic insults.

In practice, conditions with generalised oedema are associated with elements of vasogenic and cytotoxic oedema.

Hydrocephalus

= Accumulation of excessive CSF within ventricular system

Mostly due to impaired flow and reabsorption of CSF, rarely with overproduction

Two types:

1. Non communicating = only a portion of ventricular system is enlarged
2. Communicating = enlargement of entire ventricular system

Hydrocephalus ex vacuo = dilation of ventricular system with compensatory increase in CSF volume secondary to loss of brain parenchyma.

Raised ICP and Herniation

= Raised ICP leads to mass effect within the brain and herniation syndromes:

1. Subfalcine (cingulate gyrus) herniation = expansion of cerebral hemispheres displaces cingulate gyrus under the falx cerebri, can cause ACA compression
2. Transtentorial (uncinate) herniation = medial aspect of temporal lobe compresses against free margin of tentorium, cranial nerve III can be compressed
3. Tonsillar herniation = displacement of cerebellar tonsils through Foramen of Magnum, life threatening due to brainstem compression and compromise of respiratory/ cardiac centres in medulla

Traumatic CNS injuries

Skull fractures

Classification:

‘Displaced’ if the bone has moved into cranial cavity by a distance greater than the thickness of the bone.

‘Diastatic’ if crosses suture lines

Base of skull fracture is suspected if orbital/ mastoid haematoma, CSF rhinorrhoea/ otorrhea (increased risk of meningitis) or lower cranial nerve deficits.

Parenchymal injuries

Concussion

= Clinical syndrome of altered consciousness secondary to head injury

Sx: Instantaneous onset of transient neurologic dysfunction (loss of consciousness, temporary respiratory arrest, loss of reflexes) with persisting amnesia of events.

Direct

= Contusion or laceration of the brain due to transmission of kinetic energy to soft tissues

Results in tissue displacement, disrupted vascular channels, haemorrhage and oedema.

Crests of gyri, frontal and temporal lobes most susceptible.

Coup injury = contusion at point of contact

Contrecoup injury = contusion on brain surface diametrically opposite

Diffuse axonal injury

= Injury to deep white matter regions

Results in diffuse axonal swelling and focal haemorrhagic lesions.

Traumatic vascular injury

Epidural

= tearing of dural arteries (middle meningeal artery) causing haematoma to separate dura from inner skulls surface. Do not cross suture lines, convex shape. May expand rapidly and require prompt drainage.

Subdural

= rupture of bridging veins between inner surface of dura and outer arachnoid layer. Cross suture lines, characteristic crescentic shape.

 Common in elderly (brain atrophy) and infants (thin-walled veins). May be acute or chronic.

Subarachnoid

= rupture of berry aneurysm or extension of traumatic haemorrhage into subarachnoid space.

Intraparenchymal

= rupture of intraparenchymal vessel in basal ganglia/ thalamus/ cerebral hemispheres.

• Causes:
  • Trauma
  • Non traumatic (hypertension and cerebral amyloid angiopathy)

Spinal cord trauma

Associated with displacement of vertebral column.

Level of cord injury determines extent of neurologic sx –

Thoracic lesions = paraplegia.

Cervical lesions = quadriplegia.

Morphology:

Haemorrhage, necrosis and axonal swelling. Over time, lesion becomes cystic and gliotic with Wallerian degeneration.

Sequelae of trauma

Can cause broad range of neurologic symptoms over months or years.

Post traumatic hydrocephalus – obstruction of CSF resorption from haemorrhage into subarachnoid spaces.

Post traumatic dementia – following repeated head trauma during a protracted period (dementia pugilistica)

Post traumatic epilepsy

Tumours (meningioma) Psychiatric disorders

Cerebrovascular disease

Two main processes =

1. Hypoxia, ischaemia and infarction resulting from impairment of blood supply to CNS tissue.
2. Global cerebral ischaemia = generalised reduction in cerebral perfusion, due to cardiac arrest/ shock/ hypotension
   1. Neurons are most sensitive to ischaemia – especially those in with high metabolic requirements
   1. Border zone (watershed) infarcts occur in areas that lie in distal regions of arterial supply.
3. Focal cerebral ischaemia = reduction of blood flow to localised area of brain due to vessel disease (thromboembolic occlusion) or small vessel disease (vasculitis/ arteriosclerotic lesions)
   1. Adequacy of collateral flow will affect severity of infarct
   1. Arterial occlusion may be due to:
      1. Thrombosis due to atherosclerosis (common in carotid bifurcation, origin of MCA or basilar artery)
      1. Embolism from many origins (cardiac mural thrombi due to MI/ AF/ valvular disease, plaques in carotid arteries, PFO in children or air/fat/tumour embolism)
      1. Vasculitides include infectious vasculitis, polyarteritis nodosa and primary angiitis of CNS
   1. Infarcts are categorised as:
      1. Haemorrhagic (red) = associated with embolic events
      1. Non- haemorrhagic/ anaemic (white) = thrombosis
   1. Morphology: Ischaemic neuronal changes with cytotoxic and vasogenic oedema -> neurtrophil emigration -> macrophage activation -> (months later) gliosis.
4. Haemorrhage
5. Hypertensive cerebrovascular disease
   1. Affects small penetrating vessels that supply basal ganglia, hemispheric white matter and brain stem
   1. Vessels develop arteriolar sclerosis and may become occluded
   1. Consequences:
      1. Lacunar infarcts = multiple small, cavitary infarcts known as lacunae
      1. Slit haemorrhages = rupture of small calibre penetrating vessels
      1. Hypertensive encephalopathy = diffuse cerebral dysfunction due to malignant hypertension
6. Intraparenchymal haemorrhage
7. Subarachnoid haemorrhage

= Associated with rupture of berry aneurysm or extension of traumatic haemorrhage

Saccular ‘berry’ aneurysms:

• Most common type of intracranial aneurysm
• 90% are found at major arterial branch points of Circle of Willis such as 40% at ACOM/ACA, 34% MCA branches, 20% PCOM/MCA and 4% at basilar tip
• Pathogenesis unknown, most are sporadic. Known associations with polycystic kidney disease, Ehler’s- Danlos, neurofibromatosis and Marfan Syndrome.
• Clinical features: Rupture of aneurysm can occur at any time, 1/3 cases associated with acute raise in ICP (straining with stool or sexual orgasm) causing sudden, excruciating headache and loss of consciousness. 25-50% patients die with first rupture.
• Consequences: Vasospasm causing further ischaemic injury, meningeal fibrosis/ scarring and CSF obstruction.

CNS infections

= Haematogenous spread is most common, direct implantation in setting of trauma or local extension from adjacent air sinus/ infected tooth/ cranial or spinal osteomyelitis

Acute meningitis

Inflammation of leptomeninges and CSF within subarachnoid space

CSF sampling assists to determine cause –

Bacterial

Organisms:

Neonates – E Coli, GBS

Elderly – S pneumoniae, Listeria

Adolescents – N meningitidis

Morphology:

Cloudy, purulent CSF

Neutrophils fill subarachnoid space

Leptomeningeal fibrosis

Viral

Also known as aseptic because recognizable organisms are absent

Acute focal suppurative

Brain abscess

Subdural Empyema

Extradural abscess

Chronic meningoencephalitis

Bacterial

Organisms =

Tuberculosis

Neurosyphilis (Tertiary syphilis due to Treponema pallidum)

Neuroborreliosis (Lyme Disease)

Viral

Certain viruses have increased tropism to CNS cells

Latency of viruses is important facet for some infections (eg. Herpes Zoster)

Viruses =

Arbovirus

Herpes Simplex Type 1 (common in young adults and children, PCR CSF for dx)

Herpes Simplex Type 2 (50% neonates born to women with active primary genital HSV)

Varicella Zoster Virus (primary infection as chickenpox, following which virus enters latent stage within sensory neurons of DRG, reactivation causes shingles or in immunocompromised individuals, acute encephalitis)

Cytomegalovirus (foetus and immunocompromised patients)

Poliomyelitis

Rabies (Negri bodies = cytoplasmic inclusions are pathognomonic)

HIV

Progressive Multifocal Leukoencephalopathy due to JC polyomavirus (infects oligodendrocytes and causes demyelination)

Subacute Sclerosing Pancephalitis (SSPE) due to measles infection

Fungal

Primarily involves immunocompromised patients

Candida albicans

Mucor species

Aspergillus Cryptococcus

Other

Protozoal disease –

Malaria

Toxoplasmosis

Amebiasis

Trypanosomiasis

Rickettsial –

Typhus and Rocky Mountain Spotted Fever

Metazoal –

Cysticercosis

Echinococcosis

Last Updated on September 24, 2021 by Andrew Crofton