Chapter 30: Infections of the central nervous system

Infections of the central nervous system cover general conditions such as meningitis and encephalitis and specific organisms such as syphilis and polio. This section is highlighted because the conditions that are difficult to diagnose can have morbid outcomes, especially if the conditions are misdiagnosed. They are representative of classic ‘not-to-be-missed’ conditions.

Key symptoms suggestive of cerebral infection are headache, seizures and altered conscious level.

Meningitis

Meningitis is inflammation of the meninges (pia and arachnoid) and the cerebrospinal fluid (CSF).

The classic triad is:

• headache

• photophobia

• neck stiffness

Other symptoms include malaise, vomiting, fever and drowsiness.

Causes (organisms)^1,2

Bacteria

• Streptococcus pneumoniae, Haemophilus influenzae (especially children), Neisseria meningitides (the big three)

• Listeria monocytogenes, Mycobacterium tuberculosis, Group B Streptococcus, Strep. agalactiae (common in newborn), Staphylococcus spp., Gram –ve bacilli, such as Escherichia coli, Borrelia burgdorferi, Treponema pallidum

Viruses

• Enteroviruses (Coxsackie, echovirus, poliovirus) mumps, herpes simplex HSV type 1, 2 or 6, varicella zoster virus, EBV, HIV (primary infection)

Fungi

• Cryptococcus neoformans or C. gattii

• Histoplasma capsulatum

Investigations

• Lumbar puncture (see TABLE 30.1)

• CT scan

• Blood culture—all patients with suspected meningitis

• CSF microculture/PCR (PCR useful even if antibiotics given)

• Specific serology, e.g. HIV, EBV

Note: If significant delay with these, do not withhold treatment.

Bacterial meningitis²

Bacterial meningitis is basically a childhood infection. Neonates and children aged 6–12 months are at greatest risk. Meningococcal disease can take the form of either meningitis or septicaemia (meningococcaemia) or both. Most cases begin as septicaemia, usually via the nasopharynx. The onset is usually sudden (see CHAPTER 96).

Clinical features (typical)

Infancy

• Fever, pallor, vomiting ± altered conscious and mental state

• Lethargy

• Increasing irritability with drowsiness

• Refusal to feed, indifference to mother

• Neck stiffness (not always present)

• Cold extremities (a reliable sign)

• May be bulging fontanelle

• Kernig sign (see FIG. 30.1): unreliable

• Brudzinski sign (see FIG. 30.2): more reliable sign of meningeal irritation

• Opisthotonos (see FIG. 30.3): rare

Children over 3 years, adolescents, adults

• Meningeal irritation more obvious (e.g. headache, fever, vomiting, neck stiffness)

• Later: delirium, altered conscious state

Note: Antibiotics may mask symptoms. Suspect meningitis if fever >3 days in reasonably well child on antibiotics.³

Fulminating

• Dramatic sudden-onset shock, purpura (does not blanch on pressure) ± coma

• Usually due to meningococcal septicaemia, also H. influenzae type B, Streptococcus pneumoniae, Listeria monocytogenes

Note: septic shock may ensue without signs of meningitis.

Treatment (suspected meningitis)⁴

First: oxygen + IV access and consult

• Take blood for culture (within 30 minutes of assessment)—ideally prior to hospitalisation

• For child give bolus of 10–20 mL/kg of N saline with added bolus up to total 60 ml/kg if signs of hypoperfusion

• Admit to hospital for lumbar puncture (preliminary CT scan to assess safety of LP in adults)

• Dexamethasone 0.15 mg/kg up to 10 mg IV (start at same time as antibiotics—shown to improve outcome)⁵

• Ceftriaxone 2 g (child >1 month: 50 mg/kg up to 2 g) IV statim then 12 hourly for 4 days

  or

  Ceftriaxone 2 g (child <1 month: 50 mg/kg up to 2 g) IV statim then 12 hourly for 4 days

  or

  cefotaxime 2 g (child: 50 mg/kg up to 2 g) IV 6 hourly for 3–5 days (note that IM injection is painful)

Note: IV preferable but IM or interosseous better than nothing.

Antibiotics of proven effectiveness are cefotaxime, ceftriaxone, meropenem and penicillin.

Treatment (meningococcaemia—all ages)

Treatment is extremely urgent once suspected (e.g. petechial or purpuric rash on trunk and limbs) (see FIG. 30.4). It should be given before reaching hospital. Empirical treatment is:

• benzylpenicillin 2.4 g (child: 60 mg/kg IV up to 2.4g) statim (continue for 5 days)

• if IV access not possible give IM

  or

• ceftriaxone 2 g (child >1 month 50 mg/kg up to 2 g) IV or IM 12 hourly for 5 days

Note: Penicillin dose guide for suspected meningitis in child: <1 year 300 mg, 1–9 years 600 mg, 10+ years 1.2 g.

Specific organisms—streptococcus pneumoniae: benzyl penicillin or cephalosporin; Group B streptococcus: benzyl penicillin; H influenza: cephalosporin.

Prevention

• meningococcal vaccines—B and ACWY given separately

Viral meningitis^1,6

This is basically a childhood infection. The most common causes are human herpes virus 6 (the cause of roseola infantum) and enteroviruses (Coxsackie and echovirus).

Most cases are benign and self-limiting, but the clinical presentation can mimic bacterial meningitis although there are fewer obvious signs of meningeal irritation. Lumbar puncture is important for diagnosis and also PCR for enterovirus. If positive it can allow early cessation of antibiotics if commenced empirically.² Treatment which is symptomatic includes rehydration and analgesics. Acyclovir is given for herpes meningitis. The immunocompromised require special management.

Encephalitis^1,6

Encephalitis is inflammation of the brain parenchyma. It is mainly caused by viruses although other organisms including some bacteria, Mycoplasma, Rickettsia and Histoplasma can cause encephalitis. Suspect it when a viral prodrome is followed by irrational behaviour, altered conscious state and possibly cranial nerve lesions.

Clinical features

These can vary from mild to severe.

• Constitutional: fever (not inevitable), malaise, myalgia

• Meningeal features: headache, photophobia, neck stiffness

• Cerebral dysfunction: altered consciousness—confusion, drowsiness, personality changes, irrational behaviour, seizures, coma

• Focal neurological deficit

Causes (viral organisms)

• Herpes simplex type 1 or 2, enteroviruses, mumps, CMV, EBV, HIV, measles, influenza, arboviruses, for example, Japanese B, West Nile, Murray Valley encephalitis, Ross River

• Consider cerebral malaria in the differential diagnosis

There are three forms of mediated viral encephalitis: direct, delayed (latent) and immune mediated (postinfectious encephalomyelitis).

Toxoplasma gondii

A protozoal infection seen in immunocompromised patients, especially HIV. Refer for specialist advice.

Investigations

• Lumbar puncture: CSF (usually aseptic meningitis)

• CSF PCR for viral studies, esp. HSV, toxoplasma

• CT scan—often shows cerebral oedema

• Gadolinium enhanced MRI

• EEG—characteristic waves

Treatment

Organise hospitalisation where treatment will be supportive. Suspected herpes simplex encephalitis should be treated with IV aciclovir immediately.

Note: Meningoencephalitis is meningitis plus some parenchymal involvement of brain substance.

Autoimmune encephalitis

This is a recently identified group of neuropsychiatric disorders seen typically in young people.⁷ There is a prodrome of fever and headache followed by days or weeks of psychiatric behavioural problems with bizarre symptoms and movements. It may be related to a paraneoplastic manifestation, e.g. ovarian cancer. Diagnosis is confirmed by blood and CSF antibody testing (anti-NMDA receptor). Specialist referral for diagnosis and specific immunotherapy is appropriate.

Brain abscess and subdural empyema^4,8

A brain (cerebral) abscess is a focal area of infection in the cerebrum or cerebellum. It presents as a spaceoccupying intracerebral lesion. Suspect in any patient with a raised intracranial pressure. The infection can reach the brain by local spread or via the bloodstream, for example, endocarditis or bronchiectasis. There may be no clue to a focus of infection elsewhere but it can follow ear, sinus, dental, periodontal or other infection and also a skull fracture. The organisms are polymicrobial, especially microaerophilic cocci and anaerobic bacteria in the non-immunosuppressed. In the immunosuppressed, Toxoplasma, Nocardia sp. and fungi.

Clinical features

Raised intracranial pressure

• Headache

• Nausea and vomiting

• Altered conscious state

• Papilloedema

Other

• Focal neurological signs such as hemiplegia, dysphasia, ataxia

• Seizures (30%)

• Fever (may be absent)

• Signs of sepsis elsewhere, e.g. teeth, endocarditis

Investigations

• MRI (if available) or CT scan

• FBE, ESR/CRP, blood culture

  Note: lumbar puncture is contraindicated.

• Consider endocarditis

Management

Management is urgent neurosurgical referral. Aspiration or biopsy is essential to guide antimicrobial treatment which may (empirically) include metronidazole IV and a cephalosporin, e.g. ceftriaxone IV. Nocardiosis is treated with other antibiotics.

Spinal subdural or epidural abscess⁹

These uncommon focal infections can be extremely difficult to diagnose so an index of suspicion is required to consider such an abscess. The usual organism is Staphylococcus aureus.

Clinical features⁶

• Back pain (increasing) ± radiculopathy

• Percussion tenderness over spine

• Evolving neurological deficit, e.g. gradual leg weakness and sensory loss ± fever (may be absent)

Causes

• Associated infection: furuncle, decubitus ulcer, adjacent osteomyelitis, discitis, other

• Back trauma with haematoma

• Post-subdural or epidural anaesthetic block

• One-third is spontaneous

Investigations

• Blood culture

• MRI scan to localise abscess and spinal cord pressure

Management

Urgent neurosurgical referral. Empirical therapy while awaiting culture results may include di/flucloxacillin IV, + gentamicin IV or vancomycin IV.

Prions are proteinaceous infected particles devoid of nucleic acid that can present with a wide spectrum of neurological presentations. The feature is transmissible spongiform encephalopathy (TSE), with Creutzfeldt–Jakob disease being the classic example. Other examples of TSE forms affecting humans are variant CJD, kuru (New Guinea) and fatal familial insomnia.

Creutzfeldt–Jakob disease

There are three distinct forms of CJD: sporadic (80–85%), familial (15%) and iatrogenic (1%). The annual incidence is one per million people. Usual transmission is from contaminated human tissue (e.g. corneal graft), cadaver pituitary human gonadotrophin or eating contaminated beef. There is no specific treatment for the disease.

Clinical features

• Progressive dementia (starts with personality change and memory loss—eventual loss of speech)

• Myoclonus/muscle spasms

• Fatigue and somnolence

• Variable neurological features (e.g. ataxia, chorea)

Diagnosis

• MRI: high signal intensity in thalami

• CSF: positive 14-3-3 protein immunoassay

• EEG

• Brain biopsy after death (ultimate confirmation)

Management

• Supportive: no proven specific treatment

Poliomyelitis¹¹

Polio is a highly contagious enterovirus (picornavirus) transmitted through the faeco-oral route and is a specific spinal cord anterior horn cell enterovirus. It remains endemic in the tropics. Most infections (95%) are asymptomatic. Note: myelitis means inflammation of the spinal cord.

Clinical features

• Flu-like syndrome, with fever and sore throat, then

• ‘Pre-paralytic’ stage: nausea and vomiting, headache, stiff neck (meningeal irritation)

• Paralytic (0.1%): LMN lesion (flaccid paralysis)—may include spinal polio especially of lower limbs and/or bulbar polio ± respiratory failure. No sensory loss.

There are 2 levels of polio: minor (recovery in a few days) and major.

Diagnosis

• Viral studies of throat and faeces—culture and PCR

• Serology

• CSF: leucocytosis, esp. lymphocytes

Management

Symptomatic paralytic patients should be referred to hospital. Prevention is through vaccination.

Post-polio syndrome

Many years after the primary infection (usually 20–40 years) this may present with new muscle weakness and pain as dysfunction of surviving motor neurones develops. Refer to specialist unit.

Non-viral causes of flaccid paralysis^12,13

• Borrelia burgdorferi (Lyme disease), Mycoplasma, diphtheria, botulism, transverse myelitis, syphilis

Syphilis

Neurosyphilis can present at any stage of syphilis. The main syphilitic syndromes affecting the CNS are:

• Asymptomatic syphilis: present during the interval between the secondary and tertiary stages of syphilis.

• Meningitis including acute basal meningitis and meningovascular syphilis. The latter can present with a cerebrovascular accident.

• Tabes dorsalis causing meningoradiculitis with degeneration of the parenchyma of the spinal columns of the spinal cord and involvement of the pupils. Features include lightning pains, Charcot joints, ataxia and neurotrophic ulcers, Argyll Robertson pupils.

• General paralysis of the insane with marked personality change, dementia, dysarthria and seizures.

OTHER INFECTIONS THAT CAN INVOLVE THE CNS

Tuberculosis

Neurological TB may include tuberculosis meningitis, tuberculoma (presenting as a cerebral abscess), spinal arachnoiditis and spinal involvement (Pott disease). Treatment with multiple antimicrobial agents is usually complex and prolonged.

Human immunodeficiency virus

HIV involvement may be direct with primary infection causing encephalopathy (‘AIDS’ dementia), myelopathy or acute atypical meningitis in addition to secondary opportunistic infection. The latter include CNS toxoplasmosis, cytomegalovirus, herpes simplex myelitis, varicella zoster and others (see CHAPTER 27).

Helminthic infections

Worm infestations that can (rarely) cause intracerebral lesions through the formation of cysts or granulomas include cysticercosis (tapeworms), Echinococcus (hydatid) and Schistosoma.

Other infections may present with seizures. These include:

• Botulism (see CHAPTER 29)

• Tetanus (see CHAPTER 29)

• Rabies (see CHAPTER 15)

• Hansen disease (leprosy) (see CHAPTER 15)

Hand-out sheets from Murtagh’s Patient Education 7th edition:

• Bacterial meningitis and meningococcus