27.2 CNS trauma and raised intracranial pressure293
27.3 Cerebrovascular disease294
27.4 Degenerative and demyelinating diseases295
27.5 Congenital malformations and genetic disease of the CNS297
Diseases of the central nervous system (CNS) – particularly strokes, head injuries and dementia – are major causes of morbidity and mortality. Neurones do not divide in post-natal life (they are ‘permanent’ cells), and neuronal cell death is repaired by proliferation of supporting cells and ‘gliosis’ (the CNS equivalent of scarring). Children and young adults are not immune to serious CNS pathology – meningitis, congenital malformations, birth injuries, multiple sclerosis and certain neoplasms can particularly affect this population group.
The fixed available volume within the rigid skull means that an expanding mass lesion often results in raised intracranial pressure, which is frequently fatal without prompt medical intervention. Primary and secondary tumours are not uncommon in the CNS, and again the anatomical confines of the skull and vertebral column are important factors in prognosis, due to the effects of raised intracranial pressure and the physical limitation imposed on surgical resection.
27.1. Infection and inflammation
You should:
• know the spectrum of organisms that can cause meningitis and encephalitis
• understand the pathology of acute bacterial meningitis and the information that can be obtained from investigation of cerebrospinal fluid in suspected meningitis
• be aware of how human immunodeficiency virus (HIV) infection can manifest in the CNS
• understand the basic pathology of spongiform encephalopathies.
Intracranial infection
Intracranial infection can affect the arachnoid and pial membranes (meningitis) or the underlying brain itself (encephalitis). Viral, bacterial, protozoal, fungal and protein (prion) agents all contribute. Routes of entry into the CNS include:
• blood-borne spread from distant site of infection
• direct inoculation of organisms (traumatic or iatrogenic)
• local extension of sepsis (e.g. dental or sinus infection)
• via the peripheral nervous system (viral agents including herpes simplex and rabies).
Meningitis can be:
• pyogenic (bacterial)
• aseptic (viral)
• chronic (bacterial or fungal).
The microorganisms likely to be responsible vary with age and immunocompetence. Clinical symptoms include headache, neck stiffness, photophobia, irritability and altered consciousness. A skin rash may only be present with certain strains of meningococcal bacteria causing systemic sepsis. Biochemical analysis and microscopic examination of cerebrospinal fluid (CSF) obtained at lumbar puncture is helpful in discriminating the causative agent (Table 64). Bacteria and protozoa may be directly identified by microscopy.
| Infectious agent | Predominant cell content | Protein | Glucose |
|---|---|---|---|
| Pyogenic bacteria | Neutrophil polymorphs | Increased | Marked decrease |
| Viral | Lymphocytes | Mild increase | Normal, occasionally decreased |
| Tuberculosis | Lymphocytes | Marked increase | Decreased or normal |
Acute bacterial meningitis
This can be fatal if not treated at an early stage. Complications include:
• extension of infection into brain tissue with abscess formation
• venous thrombosis with cerebral infarction
• meningeal fibrosis with hydrocephalus.
The infective organisms vary with the age of patients and immunisation status but include: Escherichia coli, group B streptococci and Haemophilus influenzae in infants; Neisseria meningitidis and Streptococcus pneumoniae in older children and young adults; and Listeria monocytogenes in the elderly.
Viral meningitis
Viral meningitis is clinically less important and usually self-limiting.
Chronic meningitis
Tuberculous meningitis is rare, but is increasing in frequency among acquired immune deficiency syndrome (AIDS) patients. The onset is clinically more insidious with non-specific symptoms such as headache, confusion and vomiting. Chronic meningeal inflammation with granuloma formation and fibrosis can cause hydrocephalus and cranial nerve damage. Syphilis is a rare cause of neurological disease in the UK today, but a small percentage of those with tertiary syphilis develop chronic meningitis, sensory spinal cord damage (tabes dorsalis) or brain infection (dementia, Argyll Robertson pupils). The risk of developing neurosyphilis is increased in AIDS.
Viral encephalitis
Viral infections can cause encephalitis, with lymphocytic inflammation of the brain parenchyma and proliferation of glial cells. Intraneuronal inclusions may be seen in herpes simplex type 1 (HSV-1), cytomegalovirus (CMV) and rabies encephalopathy. Viral infections can be particularly damaging if acquired in fetal life (e.g. rubella, CMV-related congenital malformations) or during delivery (e.g. HSV-2-related neonatal sepsis).
Specific areas of the brain may be damaged, for example HSV-1 encephalitis particularly affects the temporal lobe.
Human immunodeficiency virus infection
HIV infects CNS macrophages and microglial cells. HIV infection and AIDS can cause numerous neurological lesions including:
• mild meningitis at seroconversion
• dementia-like illness
• spinal cord damage
• neuropathies
• congenital AIDS (microcephaly, motor delay and learning disabilities)
• opportunistic infections
• toxoplasmosis
• CMV
• cryptococcal meningitis
• progressive multifocal leucoencephalopathy (PML) – a papovavirus infection, which affects oligodendrocytes, causing demyelination and multifocal white-matter damage.
Rabies virus
The rabies virus gains entry to the brain by ascending along peripheral nerves. Symptoms arise weeks after initial infection and include abnormal CNS excitability (excessive pain on light touch, convulsions), paralysis, mania, stupor and coma. Local paraesthesia around the entry wound is a diagnostic pointer.
Poliomyelitis
Poliomyelitis is now very rare in industrialised countries. It initially occurs in the gut but in a small number of cases there is spread to lower motor neurones in the spinal cord, leading to muscle wasting and paralysis. Death can occur acutely due to a myocarditis or chronically due to respiratory muscle involvement.
Fungal infections of the CNS
Fungal infections of the CNS mainly occur in immunocompromised patients. The responsible organisms include Candida, Mucor, Aspergillus and Cryptococcus.
Spongiform encephalopathies
Spongiform encephalopathies are characterised by spongiform change (vacuolation) in the cerebral white matter. They are transmitted by prion protein, an abnormal form of a cellular protein that has undergone a conformational change and is able to induce a further conformational change in native protein when inoculated into previously normal cells. The prion protein gene is located on chromosome 20. It is highly conserved across species, and infectious particles in one species can corrupt the normal protein in other species. Spongiform encephalopathies include:
• scrapie in sheep
• bovine spongiform encephalopathy (BSE) in cattle
• transmissible encephalopathy in mink
• Creutzfeldt–Jakob disease (CJD), new variant CJD and kuru in humans.
Prions are neither destroyed by most normal disinfectants nor by formalin fixation.
Until the past decade, the incidence of CJD was approximately 1 per million, occurring sporadically in older adults. Iatrogenic transmission via corneal grafts, cadaveric growth hormone extracts or implanted electrodes has been documented. Recently there has been extensive debate about new variant (nv)CJD, which is thought to represent human infection by BSE transmitted by ingestion of contaminated meat products. Both CJD and new variant disease are characterised by rapidly progressive dementia with movement disorder (myoclonic jerks) and death usually occurs within 2years of symptom onset. The eventual number of individuals likely to be affected by nvCJD remains unknown.
Brain abscesses
The bacteria responsible are usually streptococcal or staphylococcal. Clinical symptoms include progressive focal neurological deficit and raised intracranial pressure.
27.2. CNS trauma and raised intracranial pressure
Mechanisms of traumatic brain injury
Contusion
Brain tissue is bruised on impact with the bony skull surface. A ‘coup’ injury occurs to the brain tissue underlying the point of external injury. A ‘contre-coup’ injury affects an area of brain directly opposite the impact. For example, a fall backwards onto the occiput causes contre-coup injury to inferior frontal lobes and inferior poles of temporal lobes (which is often more severe and clinically significant than the coup injury to the occipital lobe directly underlying the point of impact).
Laceration
Brain substance is torn, usually as a result of penetrating injury.
Diffuse axonal injury
Deceleration and rotational forces to the brain cause shearing injury to neurones and axonal processes. If extensive, this can cause coma and death. Diffuse axonal injury (DAI) is graded according to the extent of damage and the presence of grossly visible brain haemorrhage. Severe DAI can occur in the absence of any externally evident head trauma.
Tissue displacement following head injury damages blood vessels, causing haemorrhage and oedema with consequent mass effect (see below). Vascular injury and subsequent haemorrhage can be extradural, subdural, subarachnoid or intraparenchymal.
Intracranial haemorrhage
Extradural haemorrhage
Extradural haemorrhage is classically seen in association with a skull fracture involving the temporal bone with laceration of the middle meningeal artery. The typical clinical history includes a ‘lucid interval’ of several hours between the injury and neurological deterioration.
Subdural haemorrhage
Subdural haemorrhage usually originates from tearing of bridging veins that pass through the subdural space between the brain and the dural sinuses. The elderly are at increased risk, as brain atrophy increases stretching of the bridging veins and allows greater movement of the smaller brain within the skull following trauma. The precipitating head injury may be so trivial so as to have gone unnoticed. Subdural haemorrhage usually becomes clinically evident within hours, with non-specific signs (diminishing consciousness, headache) but may present chronically. Re-bleeding is common, and may occur from vascular granulation tissue within the organising haematoma.
Subarachnoid haemorrhage (SAH)
Subarachnoid haemorrhage occurring after trauma is usually secondary to brain tissue disruption. Non-traumatic SAH is more common and is discussed later in Section 27.3.
Raised intracranial pressure
The fixed skull volume allows very little room for the intracranial contents to expand in the presence of haemorrhage, tumour, abscess or oedema. Therefore a mild increase in intracranial mass can lead to increased intracranial pressure with serious consequences. Brain tissue becomes displaced (herniation). The site of herniation partly depends on whether mass increase is focal or diffuse (Figure 72):
• uncal gyrus (inferior temporal lobe) can herniate under the tentorium cerebelli and compress the midbrain (leading to altered consciousness), oculomotor nerve, contralateral cerebral peduncle, aqueduct and posterior cerebral artery
• cerebellar tonsils can herniate through the foramen magnum, compressing the brainstem (‘coning’).
Compression of blood vessels supplying the midbrain causes venous stagnation with haemorrhage, necrosis and irreversible neuronal injury in this vital area.
Cerebral oedema
Cerebral oedema can be focal or diffuse. Oedema often makes a significant contribution to the mass effect of tumours and abscesses. The development of cerebral oedema indicates impaired function of blood–brain barrier, which normally tightly controls fluid movement within the brain. Mechanisms of cerebral oedema include:
• increased vascular permeability (vasogenic oedema)
• altered cell regulation of fluid (cytotoxic oedema)
• movement of fluid from the ventricular system into the brain.
Hydrocephalus
Hydrocephalus describes an increased volume of cerebrospinal fluid, usually due to a blockage in the CSF pathway. If occurring prior to the fusion of skull bone sutures in young children, hydrocephalus will result in head enlargement. The development of hydrocephalus may result from blood, post-inflammatory fibrosis or tumour blocking cerebrospinal fluid (CSF) flow. Apparent hydrocephalus in older adults due to atrophy of brain tissue and expansion of the ventricular system is sometimes called ‘hydrocephalus ex vacuo’.
27.3. Cerebrovascular disease
Cerebral infarction
Normal brain function ceases within a few seconds of loss of oxygen supply; irreversible neuronal damage occurs after 6–8 minutes of anoxia. Most cerebrovascular disease results from focal impairment of blood supply causing cerebral infarction. This manifests clinically as a ‘stroke’ – a neurological deficit of sudden onset but lasting more than 24 hours, caused by vascular insufficiency (neurological symptoms caused by lack of blood flow but resolving within 24 hours are known as transient ischaemic attacks or ‘TIA’). Stroke can be due to thrombosis or embolus.
Thrombotic stroke usually complicates atherosclerosis in the basilar artery, proximal middle cerebral artery or at the carotid bifurcation. As thrombotic stroke arises on a background of atheroma, risk factors include hypercholesterolaemia, hypertension, diabetes mellitus and ischaemic heart disease.
When stroke occurs secondary to embolism, the source of the embolus is usually the heart. Cardiac mural thrombus can complicate myocardial infarction and atrial fibrillation. Thrombus may also embolise from abnormal heart valves, arterial walls (especially atherosclerotic carotid arteries) or from sites of cardiac surgery. Less commonly the embolus may consist of fat, air or tumour. Cerebral fat embolus should be suspected when neurological signs develop following non-head trauma with multiple bone fractures. Most embolic strokes affect the middle cerebral artery territory. Identification of the embolus at post mortem is often not possible, as a high percentage will have lysed.
Cerebral infarction can be haemorrhagic or non-haemorrhagic, as demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The distinction is of therapeutic importance, as anticoagulation therapy is contraindicated in the presence of intracerebral bleeding. Thrombotic strokes are not usually complicated by bleeding. Haemorrhage can be secondary to reperfusion following an embolic stroke, but is more commonly seen in spontaneous intracerebral haemorrhage (ICH) associated with hypertension. ICH usually arises in:
• deep white matter of cerebral hemispheres/basal ganglia (>50%)
• pons (10%)
• cerebellum (10%).
Microscopically, the small arterial branches that rupture may show fibrinoid necrosis of the vessel wall and formation of microaneurysms known as Charcot–Bouchard aneurysms. Severe bleeding can cause rapid mass effect with an acute fatal rise in intracranial pressure. Haemorrhage may rupture internally into the ventricular system or externally into the subarachnoid space.
Hypertension can also result in small, often multiple lacunar infarctions (<15mm in diameter) in the basal ganglia, deep white matter and pons. In accelerated or malignant hypertension, an encephalopathy may develop with headaches, vomiting, convulsions and altered conscious level.
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