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Year 4 - PAN > Neurology - Neurological infections > Flashcards

Neurology - Neurological infections Flashcards

1
Q

How do bacteria gain access to the CNS?

A

CNS is normally sterile - 3 routes:

1) Direct spread from adjacent focus of infection - e.g. paranasal sinus, middle ear, or open skull fracture
2) Blood borne spread as a consequence of septicaemia or from a septic emboli elsewhere e.g. bacterial endocarditis or bronchiectasis
3) Iatrogenic infection - introduction of organisms following an LP. Low grade meningitis can occur in 20% of patients with a ventricular shunt (skin commensals)

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2
Q

What is pachymeningitis?

A

Meningitis as a clinical term usually means inflammation within the subarachnoid space involving the arachnoid and pia mater

Pachymeningitis = inflammation predominantly involving the dura mater

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3
Q

What causes pachymeningitis?

A

Usually caused by direct spread from an adjacent focus of infection from the bones of the skull following otitis media or mastoiditis

Specific organisms include:

  • Gram negative bacilli from middle ear
  • Alpha or beta haemolytic strep from paranasal sinuses
  • Mixed organisms from skull fracture

An epidural or subdural abscess usually results

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4
Q

Epidural abscess

A

Caused by suppuration between the dura mater and the skull or vertebral column

Act as a SOL and require drainage

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5
Q

Subdural abscess

A

This is an uncommon lesion because pus can readily spread within the subdural space to form a subdural empyema

If subdural vessels are involved then cerebral cortical thrombophlebitis with infarction can occur

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6
Q

Leptomeningitis

A

This is “classic” meningitis caused by inflammation in the subarachnoid space between the arachnoid and pia

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7
Q

What causative organisms most commonly cause bacterial meningitis in neonates?

A

Group B strep (e.g. strep agalectiae) is most common followed by

  • E. coli
  • Listeria

Risk is increased in:

  • Prematurity
  • Prolonged membrane rupture
  • Traumatic delivery
  • Congenital malformations

NB - Listeria can also affect susceptible individuals (e.g. pregnant women, alcoholics, immunocompromised etc), rapidly progressing picture resembling brainstem encephalitis + focal signs + meningism, treat with ampicillin

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8
Q

What is the most common cause of bacterial meningitis in 3 months - 3 year age group?

A

H. influenza type B related to nasopharyngeal colonisation

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9
Q

In which age group is Neisseria meningitis most common?

A

Children and young adults

Nasopharyngeal colonisation leads to haematogenous dissemination and meningitis, occurring in epidemics

Low complement increases risk

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10
Q

In what group is S. pneumoniae causative for bacterial meningitis?

A

Elderly and alcoholics (also consider Klebsiella) - increased with age dependent reduction in immunity

Also post traumatic as S.pneumoniae part of normal flora of URT - increased risk with cerebrospinal fluid fistula

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11
Q

What agents are post neurosurgical patients at risk of for bacterial meningitis?

A
  • Staph epidermidis
  • Staph aureus
  • Enterobacteriaecae
  • Pseudomonas
  • Pneumococci
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12
Q

Pathology of bacterial meningitis - what structures can be damaged/ involved?

A

Blood brain barrier limits host defences

Bacteria in CSF trigger inflammatory reaction in vascular pia - causes exudate of blood proteins and PML migration

Thrombosis of superficial veins causes brain infarction

Accumulation of exudate can obstruct CSF (especially in the basal cisterns where it can obstruct the 4th ventricle exit foramina)

Penetration of the arachnoid causes subdural inflammation and effusions

Structures in the subarachnoid space such as the cranial nerves can become damaged; deafness (damage to VIIIth CN in the basal cisterns) is a common complication of meningitis in children

Retrograde spread from CSF into ventricles can cause centriculitis

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13
Q

Symptoms of bacterial meningitis

A

The classic triad is fever, neck stiffness and headache

Patients may have a prodrome phase

  • Resp infection or otitis media
  • Associated muscle pain (myalgia)

Other symptoms include coma, drowsiness, vomiting, generalised seizures

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14
Q

Signs of meningitis

A

Signs of meningeal irritation:
- Neck stiffness on forward flexion, inability to completely extend legs (Kerning’s sign)

Bulging of anterior fontanelles in neonates/ infants

Petechial and purpuric rash with circulatory collapse - characteristic of Waterhouse-Friderichsen syndrome in meningococcal disease

Look for sepsis elsewhere:

  • Ears
  • URT
  • Lung
  • Heart valves
  • CSF leak (post traumatic and post surgical patients)
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15
Q

What are the lumbar puncture findings in bacterial meningitis?

A

LP is THE investigation of choice to confirm meningitis

  • Raised opening pressure (20-40mm H2O)
  • Cloudy/ turbid
  • PML pleocytosis
  • Elevated protein
  • low glucose (under 40% that of simultaneously measured blood glucose)

Bacteria may be visible under gram stain
PCR can be used to detect bacterial antigens in partially treated meningitis

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16
Q

Other investigations in meningitis?

A
  • Increased WCC with left shift
  • Blood and throat cultures: source of infection and evidence of systemic sepsis
  • Imaging: CT/ MRI to exclude principle differentials for meningitis (subdural empyema, brain abscess and encephalitis)
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17
Q

Can an LP be performed without a prior CT scan?

A

LP must be preceded by a CT (or MRI) if there is any evidence of impaired of consciousness, focal neurology, or prior seizure due to the risk of tonsillar herniation or coning

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18
Q

Meningitis is a neurological emergency. What antibiotics are used to treat neonatal bacterial meningitis?

A

Either:

  • Ampicillin + Third generation cephalosporin, or
  • Ampicillin + gentamicin

(Remember 3rd gen cephalosporins have “t” or “tri” in their name)

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19
Q

Antibiotics used to treat bacterial meningitis in older children and adults

A

Ceftriaxone or cefotaxime + ampicillin (if Listeria suspected)

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20
Q

What antibiotics are used in patients over 50 or alcoholics with bacterial meningitis?

A

Third generation cephalosporin (e.g. ceftriaxone) + IV vancomycin

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21
Q

Should you wait for CSF microbiology to come back before starting antibiotics if you suspect meningitis?

A

Meningitis is a medical emergency requiring urgent antibiotics. These should be commenced as soon as possible when the disease is suspected, preferably after the CSF sample has been taken provided it does not interfere with treatment

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22
Q

Complications of meningitis

A
  • Cerebral infarction
  • Obstructive hydrocephalus
  • Cerebral abscess
  • Subdural empyema
  • Epilepsy
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23
Q

What is the prognosis of meningitis?

A

Neonatal meningitis carries a mortality rate of 50% - of the survivors, 50% have permanent sequelae

S. pneumoniae meningitis - 25%

N. meningitidis - 10%

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24
Q

How is the CNS affected by tuberculosis?

A

CNS tuberculosis is always secondary to infection elsewhere, usually the lungs

CNS involvement takes 2 forms:

(i) Tuberculous meningitis
(ii) Tuberculomas

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25
Q

What causes TB meningitis?

A

Usually results from haematogenous spread from a primary (children and adults) or secondary complex (adults) in the lungs

Rarely, it can result from direct spread of infection from a vertebral body to the meninges

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26
Q

Characteristics of tuberculous meningitis

A

Thick gelatinous exudate which is most marked around the basal cisterns (basal meninges are worst affected) and within cerebral sulci

On microscopy meningeal involvement consists of granulomas with central caseation and giant cells

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27
Q

CSF findings of tuberculous meningitis

A
  • Increased polymorphs initially then lymphocytes
  • Increased protein
  • Decreased or absent glucose
  • Clear or opalescent with fibrin webs

Acid fast bacilli present on MC&S

28
Q

What are the clinical features of tuberculous meningitis?

A

Majority of patients are adults, TBM is rare in children now
- Stage 1: non specific symptoms, fever, malaise

  • Stage 2: Confusion, isolated CN palsies, meningism, vasculitis (causing focal neurology - e.g. hemiparesis, ataxia, dysarthria)
  • Stage 3: coma
29
Q

What is a tuberculoma?

A

These are focal areas of granulomatous inflammation with caseation surrounded by a dense fibrous capsule

Tuberculoma’s usually present with symptoms of raised intracranial pressure - features of meningitis rarely occur

30
Q

Treatment for tuberculous meningitis

A

2 months of:

  • Rifampicin
  • Isoniazid
  • Pyrazinamide
  • Ethambutol

4 months of:

  • Rifampicin
  • Isoniazid
31
Q

What is Pott’s disease?

A

This is chronic epidural infection following tuberculous osteomyelitis of the vertebral bodies

Normally arises in the lower thoracic vertebra but can spread to several segments and may spread via the intervertebral foramina into the pleura, peritoneum or psoas muscle (causing a abscess)

32
Q

What is tuberculous meningomyelitis?

A

Inflammation of the leptomeninges (arachnoid and pia) results in an exudate that encases the spinal cord and nerve roots

Patients present with back pain, paraesthesia, lower limb weakness and loss of bladder and bowel function

This disorder is more common in AIDs patients

33
Q

What are spirochetes and which ones cause meningitis?

A

= Gram negative spiral shaped bacteria

1) Syphilis - treponema pallidum
2) Lyme disease - borrelia
3) Leptospirosis - leptospira

34
Q

Manifestations of neurosyphilis

A

Occurs in about 8% of untreated cases - 5 common presentations:

1) Asymptomatic neurosyphilis
2) Subacute meningitis (CSF shows high lymphocyte count)
3) Meningovascular syphilis
4) Tabes dorsalis (dorsal column and posterior root damage)
5) General paresis of the insane

35
Q

Lyme disease

A

Disease caused by Borrelia - transmitted by tick bites

Characterised by:

  • Relapsing remitting arthralgia
  • Characteristic skin rash (erythema chronicum migrans)
  • Neurological features
36
Q

What are the clinical features of Lyme disease?

A

Only a minority of patients who get bitten by an infected tick develop the disease

3 stages:
- Stage 1 - tick bite leads to arthralgia, flu like symptoms and a rash, antibiotics are usually curative

  • Stage 2 - several weeks/ months later; lymphocytic meningoencephalitis with facial nerve palsy + peripheral neuropathy
  • Stage 3 - several months/ years later: arthritis + diffuse CNS involvement with focal brain disease

Treatment is with IV penicillin G

37
Q

What is leptospirosis?

A

Spirochete infection caused by leptospira species
Transmitted by infected urine of domestic animals

Only 10% of patients develop jaundice and haemorrhage complications (Weil’s disease)

38
Q

Clinical features of leptospirosis

A

Incubation period for 10-12 days

Then leptospiraemia (5-7 days): pyrexia, myalgia, rigors, hepatosplenomegaly, lymphadenopathy

Followed by immune phase (variable duration): lymphocytic meningitis, cranial nerve palsies, encephalitis and (in Weil’s disease) hepatic and renal failure

39
Q

What parasites infect the CNS?

A

Parasitic infection of the CNS is rare except in countries where human parasites are endemic

Several cause neurological infection but 2 important ones are:

i) Toxoplasma gondii - toxoplasmosis
ii) Plasmodium falciparum - one form of malaria

40
Q

How is toxoplasmosis transmitted?

A

Eating uncooked meat or contact with faeces of an infected dog or cat

41
Q

What are the 2 forms of toxoplasmosis?

A

1) Congenital = previously unaffected woman contracts the infection during pregnancy; transplacental spread results in foetal infection
- Hydrocephalus
- Aqueduct stenosis
- Microcephaly

2)Acquired = symptomatic infection uncommon but may be associated with immunosuppression - e.g. AIDS

42
Q

How does malaria infect the CNS?

A

Plasmodium falciparum causes cerebral malaria

Infected RBCs adhere to vascular endothelium and block the microcirculation

Endothelial damage produces cerebral oedema

Patients develop confusion, focal signs, convulsions and coma

43
Q

Fungal CNS infections

A

Rare

Most are consequences of haematogenous spread from the lungs or paranasal sinuses

44
Q

Do all fungal infections occur in immunocompromised patients?

A

No - most CNS fungal infections occur in the immunocompromised, by cryptococcus neoformans is capable of producing disease in healthy individuals

Cryptococcal infection usually presents as a subacute meningitis with a mild inflammatory reaction

45
Q

Opportunistic fungal infections of the CNS

A

Candida albicans
Aspergillus fumigatus

Both are usually secondary to respiratory infection
Both cause meningitis with haemorrhage due to vascular invasion and characteristically produce multiple cerebral abscesses

46
Q

What is a rare fungal infection of the CNS that typically affects uncontrolled diabetics?

A

Mucormycosis

Produces granulomatous mass in the paranasal sinuses that extends through the skull and frontal lobes

Vascular invasion may result in cerebral infarction

47
Q

What are the lumbar puncture findings of fungal meningitis?

A

Same as TB

  • High lymphocyte count (lymphocytosis)
  • High opening pressure
  • High protein
  • Low glucose
48
Q

What stain is used to identify cryptococcus in CSF?

A

India ink preparation

Confirmed by positive latex agglutination test for cryptococcal polysaccharide antigen

49
Q

Viral spread to the CNS

A

i) Haematogenous spread as part of systemic infection with viraemia, usually causing meningitis or encephalitis

ii) Neural spread along peripheral sensory nerves by retrograde axonal transport
- Certain viruses exhibit neurotropism = a tendency to spread specifically to the CNS from the initial site of infection - e.g. polio from the gut

50
Q

Clinical features of viral meningitis

A

Presents with prominent headache and less obvious signs of meningeal irritation than in bacterial infections

The causative organism is identified (PCR, CSF or serology) only 50% of the time - often enterovirus

Viral meningitis is usually less severe than bacterial

51
Q

Name some causes of viral meningitis

A
  • Echovirus 7, 11
  • Coxsackie B1-5
  • Coxsackie A9
  • Mumps

NB - many childhood exanthemata such as measles and chickenpox may be accompanied by meningitic illness which are usually mild and rarely life threatening

52
Q

CSF features of viral meningitis

A
  • Normal CSF opening pressure
  • Mildly elevated or normal protein
  • Lymphocytosis
  • Normal glucose
53
Q

What is encephalitis? What are the clinical features?

A

= Infection of the brain parenchyma itself (rare)

Clinical features are fever (not universal), headache, and a diffuse (i.e. confusion, drowsiness up to coma) rather than focal disturbance of cerebral function

Others include: seizures, wandering, behavioural change, and frank psychotic symptoms

54
Q

How is encephalitis diagnosed?

A

Combination of clinical features + lymphocytosis in CSF

CSF findings in encephalitis:

  • CSF pressure raised or normal
  • Protein mildly elevated or normal
  • Lymphocytosis
  • Normal glucose
55
Q

What other investigations are supportive in encephalitis?

A
  • Focal inflammation on MRI
  • Focal slow wave activity on EEG
  • Organism detection (PCR, serology, culture)

NB - large number of viruses can cause encephalitis and there is marked geographical variation (e.g. Japanese B in Far East, and West Nile in the USA) so a travel history is vital

Cause is only identified in 30% of cases

56
Q

Herpes simplex virus encephalitis

A

Most treatable cause of encephalitis, but:

  • Rare: causes 20% of viral encephalitis
  • Presents with a viral prodrome followed by behavioural changes with amnesia and sometimes dysphasia
  • Rapid evolution into coma may occur
  • EEG shows repetitive epileptic discharges in the temporal lobe
  • CT/MRI shows necrotising inflammation in the temporal lobe
57
Q

What is the treatment for HSV encephalitis?

A

Immediate high dose aciclovir

Prognosis is poor and long term sequelae are common:

  • 10% die acutely
  • 10% are severally impaired (requiring institutionalisation)
  • 20% are left dependent
  • 60% recover but with neuropsychological deficits (most do not function at their premorbid levels)
58
Q

Key features and agents of temporal lobe encephalitis

A

Herpes simplex most common
Dysphasia and memory loss
Diagnose by CT scan, LP (and PCR of CSF)
Treat early (

59
Q

Key features and agents of brainstem encephalitis

A 
Can be bacterial (Listeria) or viral
Ataxia, dysarthria, diplopia 
Cranial nerve palsies
Diagnose with MRI, LP 
Treat with antibiotics (ampicillin if Listeria)
60
Q

Herpes zoster infection

A

Latent viral infection

Caused by reactivation of latent varicella zoster virus within sensory ganglia in the CNS (infection established following chickenpox in childhood)

Reactivation occurs during intercurrent infection or immunosuppression

Acute inflammation of the sensory ganglion (usually thoracic dorsal route or trigeminal ganglion) causes pain and hyperalgesia along the nerve distribution followed by erythema and vesicle formation

61
Q

What is progressive multifocal leucoencephalopathy?

A

Rare infection caused by the JC papovirus

Most cases occur in immunosuppressed patients - e.g. in AIDS

Virus causes cytolytic infection of oligodendrocytes resulting in demyelination of the white matter - usually fatal

62
Q

What is subacute sclerosing pan encephalitis?

A

Uncommon disease affecting children aged 7-10

Progressive neurological deficit with dementia and myoclonus leading to death

SSP is caused by measles virus that is usually acquired before the age of 1 - large numbers of measles virus inclusion bodies present in neurones

63
Q

What viruses can cause antenatal infections?

A

Fetal CNS can be damaged during the first trimester of pregnancy following maternal infection with:

  • Toxoplasmosis
  • Other (e.g. syphilis)
  • Rubella
  • Cytomegalovirus
  • Herpes simplex virus 2

Cytomegalovirus and Rubella cause necrotising encephalitis leading to developmental damage and microcephaly

64
Q

Pathology of HIV CNS infection

A

HIV infects microglial cells forming multinucleate giant cells (of macrophage/ monocyte lineage)

80% of AIDS patients have CNS pathology at the time of death:

  • Cerebral HIV infection (causing progressive dementia)
  • Multiple opportunistic infections (e.g. Toxoplasma)
  • Other viral infections
  • Primary cerebral lymphoma
65
Q

What is acute disseminated encephalomyelitis?

A

This is an infrequent complication of measles, mumps and rubella infections (may also occur following vaccination for small pox and rabies)

Onset is very sudden, usually 5-14 days after initial infection caused by T cell mediated delayed hypersensitivity response to a protein component of myelin

Acute haemorrhage leucoencephalitis is a more severe related disorder - immune complex deposition in cerebral vessel walls

Year 4 - PAN (43 decks)

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