Davidson's Principles and Practice of Medicine Reference

1. Meningitis/Encephalitis
Dr Avatar Verma
KISTMCTH
2076/01/28

2. Anatomy: Meninges

5. Definition
• Meningitis: Inflammation of leptomeninges ( pia and arachnoid mater)
with or without suppuration of csf
• Encephalitis: Inflammation of brain parenchyma

6. • Acute meningitis presents with triad of pyrexia, headache and meningism
(headache, photophobia, stiffness of neck and other signs)
• The severity of clinical features varies with the causative organism,
as does the presence of other features such as a rash
• Abnormalities in the CSF are important in distinguishing the cause of
meningitis.

7. Causes
oInfective
Bacteria
Viruses
• Enteroviruses (Echo, Coxsackie, polio) • Mumps • Influenza
• Herpes simplex • Varicella zoster • Epstein–Barr • HIV
• Lymphocytic choriomeningitis • Mollaret’s meningitis

8. o Non-infective (‘sterile’)
 Malignant disease
• Breast cancer
• Bronchial cancer
• Leukaemia
• Lymphoma
 Inflammatory disease (may be recurrent)
• Sarcoidosis
• SLE
• Behçet’s disease
 Protozoa and parasites
• Cysticerci • Amoeba
 Fungi
• Cryptococcus neoformans • Candida •Histoplasma
• Blastomyces • Coccidioides • Sporothrix

10. Viral meningitis
• Viruses, most common cause of meningitis,usually resulting in a
benign and self-limiting illness
• Requires no specific therapy and much less serious than bacterial
unless encephalitis
• Occurs mainly in children or young adults, with acute headache (most
severe), irritability and rapid development of meningism
• There may be a high pyrexia but focal neurological signs are rare

11. • CSF: excess of lymphocytes with normal glucose and protein levels?
• Prior antibiotic?
• Usually benign and self-limiting
• Should be treated symptomatically and recovers within days, although
a lymphocytic pleocytosis may persist in the CSF
• Meningitis can be complication of a systemic viral infection such as
mumps, measles, infectious mononucleosis, herpes zoster and hepatitis

12. Bacterial Meningitis
• Usually part of a bacteraemic illness, although direct spread from an
adjacent focus of infection in the ear, skull fracture or sinus
• Early diagnosis and the prompt initiation of therapy determines prognosis
• Epidemics of meningococcal meningitis occur particularly in cramped
living conditions/ hot and dry climate
• The organism invades through the nasopharynx, producing septicaemia and
meningitis

13. Pathophysiology
• Infection stimulates immune response, meninges: congested and
infiltrated with inflammatory cells
• Then pus forms in layers, may later organise to form adhesions
obstructing the flow of CSF, leading to hydrocephalus, or damage the
cranial nerves at bases
• Hearing loss is a frequent

14. Clinical features
• Headache, drowsiness, fever and neck stiffness
• In severe: coma and later may be focal neurological signs
• Ninety percent with meningococcal meningitis will have two : fever,
neck stiffness, altered consciousness and rash
• When accompanied by septicaemia, it may present very rapidly, with
abrupt onset of obtundation due to cerebral oedema

15. • Chronic meningococcaemia is a rare condition in which the patient can be
unwell for weeks or even months with recurrent fever, sweating, joint pains
and transient rash usually occurs in splenectomised
• In pneumococcal and Haemophilus infections there may be an associated
otitis media
• Pneumococcal meningitis may be associated with pneumonia and occurs
especially in older patients and alcoholics, as well as those without
functioning spleens.
• Listeria monocytogenes is an increasing cause of meningitis in the
immunosuppressed, diabetics, alcoholics and pregnant women

16. Investigations
• Lumbar puncture is mandatory unless contraindicated (drowsy, focal neurological
signs, seizures, immunosuppressed, recent neurosurgery or head injury) ? CT
• If deferred or omitted, take blood cultures and start empirical treatment
• Lumbar puncture will help differentiate the causative organism: in bacterial meningitis
the CSF is cloudy (turbid) due to the presence of many neutrophils (often > 1000 × 10
cells/L), the protein content is significantly elevated and the glucose reduced
• Gram film and culture may allow identification of the organism
• PCR techniques can be used; useful in detecting meningococcal infection and in typing
the organism

19. Management
• Untreated mortality rate of around 80%, so swift
• If bacterial meningitis is suspected, parenteral benzylpenicillin
immediately (intravenous is preferable) and prompt hospital admission
should be arranged
• Adjunctive corticosteroid therapy is useful in both children and adults
in developed countries where the incidence of penicillin resistance is
low,
• In meningococcal disease, mortality is doubled if the patient presents
with features of septicaemia rather than meningitis

22. • Intensive care facilities: with cardiac, respiratory or renal involvement, and
CNS depression
• Early endotracheal intubation and mechanical ventilation protect the
airway and may prevent the development of the acute respiratory distress
syndrome
• Adverse prognostic features: hypotensive shock, a rapidly developing rash,
a haemorrhagic diathesis, multisystem failure and age over 60 years

23. Prevention of meningococcal
• Close contacts of patients with meningococcal infection should be given 2 days of
oral rifampicin
• In adults, a single dose of ciprofloxacin is an alternative
• If not treated with ceftriaxone, the index case should be given similar treatment to
clear infection from the nasopharynx before hospital discharge
• Vaccines are available for most meningococcal subgroups but not group B, which is
among the most common serogroup isolated in many countries

25. Tuberculous meningitis
• Common in developing countries and is seen more frequently as a
secondary infection in patients with AIDS
• Tuberculous meningitis most commonly occurs shortly after a primary
infection in childhood or as part of miliary tuberculosis
• Usual local source of infection is a caseous focus in the meninges or brain
substance adjacent to the CSF pathway
• Brain is covered by a greenish, gelatinous exudate, especially around the
base, and numerous scattered tubercles are found on the meninges

26. Clinical features
• Onset is slower than in other bacterial meningitis: 2–8 weeks
• If untreated, fatal in a few weeks but complete recovery is usual if
treatment is started at stage I
• When treatment is initiated later, the rate of death or serious
neurological deficit may be as high as 30%.

28. Investigations
• CSF is under increased pressure, usually clear but, a fine clot strand (‘spider web’) on
standing
• Contains up to 500 × 106 /L, predominantly lymphocytes, but can contain neutrophils
• There is a rise in protein and a marked fall in glucose
• The tubercle bacillus may be detected in a smear of the centrifuged deposit from the CSF but
a negative result does not exclude the diagnosis
• The CSF should be cultured but, as this result will not be known for up to 6 weeks, treatment
must be started without waiting for confirmation
• Brain imaging may show hydrocephalus, brisk meningeal enhancement or tuberculoma

29. Management
• As soon as the diagnosis is made or strongly suspected, chemotherapy should be
started
• 2HRZE plus 7HRE (12months of treatment)
• Corticosteroids improves mortality, if given early but not focal neurological
damage
• Surgical ventricular drainage may be needed if obstructive hydrocephalus
develops
• Skilled nursing is essential during the acute phase of the illness, and adequate
hydration and nutrition must be maintained

30. • Fungal meningitis: Usually occurs in patients who are immunosuppressed
and is a recognised complication of HIV infection
• CSF findings are similar to those of tuberculous meningitis, but the
diagnosis can be confirmed by microscopy or specific serological tests
• In some areas, meningitis may be caused by spirochaetes (leptospirosis,
Lyme disease and syphilis – rickettsiae (typhus fever) or protozoa
(amoebiasis ).

31. • Meningitis can also be due to non-infective pathologies
• This is seen in recurrent aseptic meningitis due to SLE, Behçet’s
disease or sarcoidosis, as well as a condition of previously unknown
origin known as Mollaret’s syndrome, in which the recurrent
meningitis is associated with epithelioid cells in the spinal fluid
(‘Mollaret’cells)
• Recent evidence suggests that this condition may be due to human
herpes virus type 2, and is therefore infective after all
• Meningitis can also be seen due to neoplastic cells

32. Viral encephalitis
• In Europe, the most serious herpes simplex which probably reaches the brain via the
olfactory nerves
• Varicella zoster is also an important cause
• Development of effective therapy for some forms of encephalitis has increased the
importance of clinical diagnosis and virological examination of the CSF
• In some parts of the world, viruses transmitted by mosquitoes and ticks (arboviruses)
are an important cause of encephalitis
• Japanese encephalitis has spread relentlessly across Asia to Australia, and there have
been outbreaks of West Nile encephalitis in Romania, Israel and New York
• HIV may cause encephalitis with a subacute or chronic presentation

33. Pathophysiology
• The infection provokes an inflammatory response involves the cortex,
white matter, basal ganglia and brainstem
• HSV: temporal lobes; Cytomegalovirus: areas adjacent to ventricles
• Inclusion bodies infiltration of polymorphonuclear cells in the
perivascular space
• Neuronal degeneration and diffuse glial proliferation, often associated
with cerebral oedema

34. Clinical features
• Headache, fever, focal neurological signs (aphasia and/orhemiplegia,
visual field defects) and seizures
• Disturbance of consciousness ranging from drowsiness to deep coma
supervenes early and may advance dramatically
• Meningism occurs in many patients

35. Investigations
• CT scan: low-density lesions in the temporal lobes but MRI is more sensitive
• CSF contains lymphocytes but polymorphonuclear cells may predominate in the early
stages, may be normal in up to 10% of cases
• West Nile virus, may have sustained neutrophilic CSF
• The protein content may be elevated but the glucose is normal
• The EEG is usually abnormal in the early stages, especially in herpes simplex:
periodic slow-wave activity in the temporal lobes
• Virological investigations of the CSF, including PCR for viral DNA, may reveal the
causative organism but treatment initiation should not await this.

36. Management
• Aciclovir 10 mg/kg IV 3 times daily for 2–3 weeks reduced mortality from
70% to 10%
• This should be given early to all patients suspected of suffering from viral
encephalitis
• Some survivors will have residual epilepsy or cognitive impairment
• Anticonvulsant treatment may be needed and raised intracranial pressure
may indicate the need for dexamethasone.

37. Brainstem encephalitis
• This presents with ataxia, dysarthria, diplopia or other cranial nerve
palsies
• CSF is lymphocytic, with normal glucose
• The causative agent is presumed to be viral
• However, Listeria monocytogenes may cause a similar syndrome with
meningitis (and often a polymorphonuclear CSF pleocytosis) and
requires specific treatment with ampicillin

38. Rabies
• Rhabdovirus that infects the central nervous tissue and salivary glands of a wide
range of mammals, and is usually conveyed by saliva through bites or licks on
abrasions or on intact mucous membranes
• Humans are most frequently infected from dogs and bats
• Incubation period minimum of 9 days to many months but is usually between 4
and 8 weeks
• Severe bites, especially on the head or neck, shorter incubation periods
• Human rabies is a rare disease, even in endemic areas

39. Clinical features
• At onset; fever, and paraesthesia at the site of the bite
• A prodromal period of 1–10 days, during which the patient becomes increasingly anxious, leads
to the characteristic ‘hydrophobia’
• Although the patient is thirsty, attempts at drinking provoke violent contractions of the
diaphragm and other inspiratory muscles
• Delusions and hallucinations may develop, accompanied by spitting, biting and mania, with lucid
intervals in which the patient is markedly anxious
• Cranial nerve lesions develop and terminal hyperpyrexia is common
• Death ensues, usually within a week of the onset of symptoms

40. Investigations
• During life, the diagnosis is usually made on clinical grounds but rapid
immunofluorescent techniques can detect antigen in corneal
impression smears or skin biopsies

41. Management
• Established disease: Only a few have survived
• All received some post-exposure prophylaxis and needed intensive care facilities
to control cardiac and respiratory failure
• Otherwise, only palliative treatment is possible once symptoms have appeared
• The patient should be heavily sedated with diazepam, supplemented by
chlorpromazine if needed
• Nutrition and fluids should be given intravenously or through a gastrostomy.

42. Pre-exposure prophylaxis
• Intradermal injections of human diploid cell strain vaccine, or two
intramuscular injections given 4 weeks apart, followed by yearly
boosters

43. Post-exposure prophylaxis
• The wounds should be thoroughly cleaned, preferably with a quaternary
ammonium detergent or soap; damaged tissues should be excised and the
wound left unsutured
• Rabies can usually be prevented if treatment is started within a day or two of
biting
• For maximum protection, hyperimmune serum and vaccine are required
• The safest antirabies antiserum is human rabies immunoglobulin
• The dose is 20 U/kg body weight; half is infiltrated around the bite and half is
given intramuscularly at a different site from the vaccine

44. • Human diploid cell strain vaccine; 1.0 mL is given intramuscularly on
days 0, 3, 7, 14, 30 and 90
• In developing countries, 0.1 mL of vaccine may be given intradermally
into eight sites on day 1, with single boosters on days 7 and 28

45. Poliomyelitis
• Subgroup of the enteroviruses
• Problem in the developing world, especially parts of Africa
• Infection usually occurs through the nasopharynx
• The virus causes a lymphocytic meningitis and infects the grey matter of the
spinal cord, brainstem and cortex
• There is a particular propensity to damage anterior horn cells, especially in
the lumbar segments

46. Clinical features
• Incubation period: 7–14 days
• Many patients recover fully after the initial phase of a few days of mild fever and
headache
• In other individuals, after a week of well-being, there is a recurrence of pyrexia,
headache and meningism
• Weakness may start later in one muscle group and can progress to widespread paresis
• Respiratory failure may supervene if intercostal muscles are paralysed or the medullary
motor nuclei are involved

47. • Epidemics vary widely in terms of the incidence of nonparalytic cases and in
mortality rate
• Death occurs from respiratory paralysis
• Muscle weakness is maximal at the end of the first week and gradual recovery
may then take place over several months
• Muscles showing no signs of recovery after a month will probably not regain
useful function
• Second attacks are very rare but occasionally patients show late deterioration in
muscle bulk and power many years after the initial infection (this is termed the
‘post-polio syndrome’).

49. Investigations
• CSF: lymphocytic pleocytosis, a rise in protein and a normal sugar content
• Cultured from CSF and stool
Management
Established disease:
• In the early stages, bed rest is imperative because exercise worsen the
paralysis
• Onset of respiratory difficulties, a tracheostomy and ventilation are required
• Subsequent treatment is by physiotherapy and orthopaedic measures.

50. Prophylaxis
• Prevention of poliomyelitis is by immunisation with live (Sabin) vaccine
• In developed countries where it is rare live vaccine

51. Herpes zoster (shingles)
• Reactivation of the varicella zoster virus that has lain dormant in a
nerve root ganglion following chickenpox earlier in life
• Reactivation may be spontaneous (as usually occurs in the middle
aged or elderly) or due to immunosuppression (as in patients with
diabetes, malignant disease or AIDS)

52. Subacute sclerosing
panencephalitis
• Rare, chronic, progressive and eventually fatal complication of
measles, presumably a result of an inability of the nervous system to
eradicate the virus
• Occurs in children and adolescents, many years after the primary virus
infection
• There is generalised neurological deterioration and onset is insidious,
with intellectual deterioration, apathy and clumsiness, followed by
myoclonic jerks, rigidity and dementia

53. • CSF: mild lymphocytic pleocytosis
• EEG: characteristic periodic bursts of triphasic waves
• Although there is persistent measles specific IgG in serum and CSF,
antiviral therapy is ineffective and death ensues within a few years

54. Progressive multifocal
leucoencephalopathy
• Originally described as a rare complication of lymphoma, leukaemia or carcinomatosis,
but has become more frequent as a feature of AIDS
• Infection of oligodendrocytes by human polyomavirus JC, which causes widespread
demyelination of the white matter of the cerebral hemispheres
• Clinical signs include dementia, hemiparesis and aphasia, which progress rapidly, usually
leading to death within weeks or months
• Areas of low density in the white matter are seen on CT but MRI is more sensitive,
showing diffuse high signal in the cerebral white matter on T2-weighted images
• Only treatment available is to restore the immune response (by treating AIDS or any
other cause of immunosuppression).

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