Meningitis
Inflammation / infection of meninges
Encephalitis
Inflammation / infection of brain substance
Myelitis
Inflammation / infection of spinal cord
What is the classic triad of meningitis?
- Fever
- Neck stiffness
- Altered mental state
How do meningitis patients usually present?
Present with a short history of progressive headache associated with
- Fever (>38º) and
- Meningism (neck stiffness, photophobia, nausea and vomiting)
What should you look for on the skin in meningitis?
-Look for a petechial skin rash (Tumbler test)
It is hallmark of meningococcal meningitis, but can also occur in viral meningitis
What are the clinical features of meningitis?
- Classic triad
- Cerebral dysfunction (confusion, delirium, declining conscious level) is common and GCS is <14 in 69%
- Cranial nerve palsy (30%), seizures (30%), focal neurological deficits (10-20%) may also occur
What is the differential diagnosis for meningitis?
Infective
-Bacterial, viral, fungal
Inflammatory
-Sarcoidosis
Drug induced
-NSAIDs, IVIG
Malignant
-Metastatic, haematological
What bacterial causes of meningitis are there?
- Neisseria meningitidis (meningococcus)
- Streptococcus pneumoniae (pneumococcus)
What viral causes of meningitis are there?
Enteroviruses
What are the clinical features of encephalitis?
- Flu-like prodrome (4-10days)
- Progressive Headache associated with fever
- +/- meningism
- Progressive cerebral dysfunction
- Seizures
- Focal symptoms / signs
How can viral and bacterial encephalitis be differentiated?
Onset of a viral encephalitis is generally slower than for bacterial
meningitis and cerebral dysfunction is a more prominent feature
What progressive cerebral dysfunction may be present in encephalitis?
- Confusion
- Abnormal behaviour
- Memory disturbance
- Depressed conscious level
What is the differential diagnosis for encephalitis?
Infective
-Viral (most common HSV)
Inflammatory
-Limbic encephalitis (Anti VGKC, Anti NMDA receptor), ADEM
Metabolic
-Hepatic, uraemic, hyperglycaemic
Malignant
-Metastatic, paraneoplastic
Migraine
Post ictal
What 2 antibodies are associated with auto-immune encephalitis?
- Anti-VGKC (Voltage Gated Potassium Channel)
- Anti NMDA receptor
How does anti-VGKC auto-immune encephalitis present?
- Frequent seizures
- Amnesia (not able to retain new memories)
- Altered mental state
How does anti-NMDA receptor auto-immune encephalitis present?
- Flue like prodrome
- Prominent psychiatric features
- Altered mental state and seizures
- Progressing to a movement disorder and coma
How should meningitis be investigated?
- Blood cultures (bacteraemia)
- Lumbar puncture (CSF culture/microscopy)
- No need for imaging if no contraindications to LP
How should encephalitis be investigated?
- Blood cultures
- Imaging (CT scan +/- MRI)
- Lumbar puncture
- EEG
What are the contraindications for LP?
- Focal neurological deficit, not including cranial nerve palsies
- New-onset seizures
- Papilloedema
- Abnormal level of consciousness, interfering with proper neurological examination (GCS<10)
- Severe immunocompromised state
What do focal symptoms or signs suggest?
Focal brain mass
What does a reduced conscious level suggest?
Raised intracranial pressure
What is the opening pressure in bacterial meningitis?
Increased
What is the opening pressure in viral meningitis and encephalitis?
Norma/ increased
What is the cell count in bacterial meningitis?
High, mainly neutrophils
What is the cell count in viral meningitis and encephalitis?
High, mainly lymphocytes
What is the glucose level in bacterial meningitis?
Reduced
What is the glucose level in viral meningitis and encephalitis?
Normal (60% of BG)
What is the protein level in bacterial meningitis?
High
What is the protein level in viral meningitis and encephalitis?
Slightly increased
What will be seen on blood culture gram stain of bacterial meningitis?
Gram positive cocci in chains - looks like streptococci
What is streptococcus pneumonia sensitive to?
Penicillin
What is the commonest cause of encephalitis in Europe?
Herpes simplex virus
How is Herpes simplex encephalitis diagnosed?
Lab diagnosis by PCR of CSF for viral DNA
How is HSV encephalitis treated?
Treat with aciclovir on clinical suspicion
What is the prognosis of untreated HSV encephalitis?
Over 70% mortality and high morbidity if untreated
What do the 2 types of HSV cause?
- Cold sores (type 1»_space; 2)
- Genital herpes (type 1 & 2)
Where does the HSV remain latent?
-Virus remains latent in the trigeminal or sacral ganglion after primary infection (as with all herpesviruses, once infected, always infected)
What type of HSV is associated with encephalitis?
- Encephalitis is a rare complication of HSV
- Other than neonates, nearly all caused by type 1
What are enteroviruses?
Large family of RNA viruses
What do enteroviruses have a tendency to cause?
Tendency to cause CNS infections (neurotropic) Human infections, no animal reservoir
How are enteroviruses spread?
Faecal-oral route
What do enteroviruses NOT cause?
Gastroenteritis
What can many enteroviruses cause?
Non-paralytic meningitis
Give examples of enteroviruses
Include polioviruses, coxsackieviruses and echoviruses
How are arbovirus encephalitides transmitted?
Transmitted to man by vector (mosquito or tick) from non-human host
Give examples of arbovirus caused infection.
- West Nile virus
- St Louis Encephalitis
- Western Equine Encephalitis
- Tick Borne Encephalitis
- Japanese B Encephalitis
What are arbovirus encephalitides named after?
Generally relate to where first described and NOT to current geographical distribution
Where do arboviruses get their name from?
Called Arbo as arthropod borne
Brain abscess
Localised area of pus within the brain
Subdural empyema
Thin layer of pus between the dura and arachnoid membranes over the surface of the brain
What are the clinical features of brain abscess and empyema?
-Fever, Headache
-Focal symptoms / signs (Seizures, dysphasia, hemiparesis, etc)
-Signs of raised intracranial pressure (Papilloedema, false localizing signs,
depressed conscious level)
-Meningism may be present, particularly with empyema
-Features of underlying source (e.g dental, sinus or ear infection)
What is the differential diagnosis for brain abscess and empyema?
- Any focal lesion, but most commonly tumour
- Subdural haematoma
What can cause brain abscess and empyema?
- Penetrating head injury
- Spread from adjacent infection (Dental, Sinusitis, Otitis media)
- Blood borne infection (e.g. Bacterial endocarditis)
- Neurosurgical procedure
How is brain abscess and empyema diagnosed?
- Imaging: CT or MRI
- Investigate source
- Blood cultures
- Biopsy (drainage of pus)
What organisms are usually present in brain abscesses?
- Often a mix
- Streptococci in 70% of cases, especially the penicillin-sensitive “Strep milleri” group (Strep anginosus, Strep intermedius, Strep constellatus)
- Anaerobes in 40 - 100% of cases (Bacteroides, Prevotella)
How should brain abscess be managed?
- Surgical drainage if possible
- Penicillin or ceftriaxone to cover streps
- Metronidazole for anaerobes
- High doses required for penetration
- Culture and sensitivity tests on aspirate provide useful guide
- High mortality without appropriate treatment
What brain illnesses may indicate HIV?
- Cerebral toxoplasmosis
- Aseptic meningitis/encephalitis
- Primary cerebral lymphoma
- Cerebral abscess
- Cryptococcal meningitis
- Space occupying lesion of unknown cause
- Dementia
- Leucoencephalopathy
What brain infections are common in HIV patients with low CD4 counts?
- Cryptococcus neoformans
- Toxoplasma gondii
- Progressive multifocal leukoencephalopathy (PML)
- Cytomegalovirus (CMV)
- HIV-encephalopathy (HIV-associated dementia)
What diagnostics are there for HIV related brain infections?
- India Ink, cryptococcal antigen
- Toxoplasmosis serology (IgG)
- JC virus PCR
- CMV PCR
- HIV PCR
How are people exposed to Cryptococci infections?
Exposure occurs following inhalation of airborne organisms into the lungs.
What do most clinical cases of cryptococcal infections present with?
Most clinical cases present with meningoencephalitis
What are the risk factors for cryptococcal infection?
- Defects in immune function
- AIDS
- Transplant patients
What spirochaetes can cause CNS illness?
- Borrelia burgorferi
- Trepomena pallidum
- Leptospira interrogans
What is the causative agent of Lyme disease?
Borrelia burgorferi
What is the causative agent of syphilis?
Trepomena pallidum
What is the causative agent of leptospirosis?
Leptospira interrogans
What is the vector in Lyme disease?
Tick
How many stages are there in Lyme disease?
3
What is meant by Lyme disease being multi-system?
- Skin, rheumatological, neurological / neuropsychiatric, cardiac and ophthalmological involvement
- Untreated 80% will develop multi-system disseminated disease
What is stage 1 of Lyme disease?
- Early localized infection (1-30d)
- Characteristic expanding rash at the site of the tick bit known as erythema migrans
- 50% flu like symptoms lasting days (fatigue, myalgia, arthralgia, headache., fever, chills, neck stiffness)
What is stage 2 of Lyme disease?
-Early disseminated infection (weeks – months)
-One or more organ systems become involved
Haematologic or lymphatic spread
-Musculoskeletal and neurologic involvement most common
-Neurologic involvement (10-15%) untreated patients
What neurological involvement may there be in stage 2 Lyme disease?
PNS> CNS
- Mononeuropathy
- Mononeuritis multiplex
- Painful radiculoneuropathy
- Cranial neuropathy
- Myelitis
- Meningo-encephalitis
What is stage 3 of Lyme disease?
Chronic infection
-Months to years occuring after a period of latency
Musculoskeletal and neurologic involvement most common
Neurologic involvement
- As described for stage 2
- Subacute encephalopathy
- Encephalomyelitis
What does Lyme disease not cause?
Chronic fatigue syndrome
What is the investigation for Lyme disease?
- Complex range of serological tests
- CSF lymphocytosis
- PCR of CSF
- MRI brain / spine (if CNS involvement)
- Nerve conduction studies / EMG (if PNS involvement)
How should Lyme disease be treated?
- Prolonged antibiotic treatment
- Intravenous ceftriaxone
- Oral doxycycline
What are the stages of syphilis?
- Primary
- Secondary
- Latent
What is tertiary syphilis?
Tertiary disease (neurosyphilis) years/decades after primary disease - not common
What investigation is there for syphilis?
- Treponema specific and non-treponemal specific (VDRL) antibody tests
- CSF lymphocytes increased, evidence of intrathecal antibody production, PCR
How is syphilis treated?
High dose penicillin
What is poliomyelitis caused by?
- Poliovirus 1, 2 or 3
- All enteroviruses
How does poliovirus infection present?
- 99% of infections are asymptomatic
- Paralytic disease in ~1%
When does paralytic disease occur in poliovirus infection?
When it infects anterior horn cells of lower motor neurones
Why did the polio vaccine change from oral to injected administration?
- Risk of vaccine-associated polio from oral vaccine
- Indigenous polio due to wild (ie non-vaccine) polio eliminated from UK
- Given combined with other antigens (IPV)
What is rabies?
Acute infectious disease of CNS affecting almost all mammals
How is rabies transmitted?
Transmitted to human by bite or salivary contamination of open lesion
How does rabies present?
- Paraesthesiae at site of original lesion
- Ascending paralysis and encephalitis
How does the rabies virus spread in the body?
Neurotropic - virus enters peripheral nerves and migrates to CNS
How is rabies encephalitis diagnosed
- No useful diagnostic tests before clinical disease apparent
- Diagnosis: culture, detection or serology
What are important sources of rabies encephalitis?
- Dogs in Africa/Asia
- Bats in the developed world. In 2003 it was recognised that UK bats may carry a rabies-like virus, European Bat Lyssavirus 2 (EBL2).
What rabies pre-exposure prevention is there?
Active immunisation with killed vaccine
Who is the rabies immunisation given to in the UK?
- Bat handlers
- Regular handlers of imported animals
- Selected travellers to enzootic areas
What is the rabies post-exposure treatment?
- Wash wound
- Give active rabies immunisation
- Give human rabies immunoglobulin (passive immunisation) if high risk
What is the causative agent of tetanus?
Clostridium tetani
What is clostridium tetani?
-Anaerobic Gram positive bacillus, spore forming
How does tetanus present?
- Wound may not be apparent
- Rigidity and spasm (risus sardonicus)
What is the pathology behind tetanus?
Toxin acts at neuro-muscular junction and blocks inhibition of motor neurones
How is tetanus prevented?
- Immunisation (toxoid)
- Given combined with other antigens (DTaP}
- Penicillin and immunoglobulin for high risk wounds/patients
What is the causative agent of botulism?
Clostridium botulinum
What is clostridium botulinum?
Anaerobic spore producing gram positive bacillus
Where is clostridium botulinum naturally present?
Naturally present in soil, dust and aquatic environments
Why is clostridium botulinum considered a neurotoxin?
- Binds irreversibly to the presynaptic membranes of peripheral neuromuscular and autonomic nerve junctions
- Toxin binding blocks acetylcholine release
- Recovery is by sprouting new axons
What are the 3 modes of infection of clostridium botulinum?
- Infantile (intestinal colonization)
- Food-borne (outbreaks)
- Wound: Almost exclusively injecting or “popping” drug users
How does botulism present?
- Incubation period 4-14 days
- Descending symmetrical flaccid paralysis
- Pure motor
- Respiratory failure
- Autonomic dysfunction: Usually pupil dilation
How is botulism diagnosed?
- Nerve conduction studies
- Mouse neutralisation bioassay for toxin in blood
- Culture from debrided wound
How is botulism treated?
- Anti-toxin (A,B,E)
- Penicillin / Metronidazole (prolonged treatment)
- Radical wound debridement
Give an example of a post-infective inflammatory syndrome affecting the CNS
Acute disseminated encephalomyelitis (ADEM)
Give an example of a post-infective inflammatory syndrome affecting the PNS
Guillain Barre Syndrome (GBS)
What can precede a post infective inflammatory syndrome?
Preceding infection (viral, bacterial) or immunization
- “Molecular mimicry”
- Latent interval between the precipitating infection and onset of neurological symptoms
- Autoimmune
What is the causative agent of Creutzfeldt-Jakob Disease?
Transmissible Proteinaceous particle – Prion
What is the aetiology of CJD?
- Sporadic CJD
- New variant CJD
- Familial CJD (10-15%)
- Acquired CJD (<5%) (Cadeveric Growth Hormone, Dura matter grafts, Blood transfusion)
What is the epidemiologyof CJD?
Very rare: sporadic 1 per million per year (incidence)
When should sporadic CJD be considered?
Consider in any rapidly progressive dementia
What are the clinical features of sporadic CJD?
- Insidious onset (usually older than 60)
- Early behavioural abnormalities
- Rapidly progressive dementia
- Myoclonus
- Progressing to global neurological decline
- Motor abnormalities
- Cortical blindness
- Seizures may occur
What motor abnormalities may be present in sporadic CJD?
- Cerebellar ataxia
- Extrapyramidal: tremor, rigidity, bradykinesis, dystonia
- Pyramidal: weakness, spacticity, hyper-refexia
What is the differential diagnosis for sporadic CJD?
Alzheimer’s disease with myoclonus
-Usually more prolonged
Subacute sclerosing panencephalitis (SSPE)
-Very rare, chronic infection with defective measles virus
CNS vasculitis
Inflammatory encephalopathies
What is the prognosis of sporadic CJD?
- Rapid progression
- Death often within 6 months
Who is usually affected by new variant CJD?
Younger onset <40
What is new variant CJD linked to?
Linked to Bovine Spongiform Encephalopathy in Cattle
-Eating infected material
-Less cases than predicted
-No new cases last few years
-May be a genetic susceptibility (MM, MV, VV)
-Concern about a further wave
of infection
What length of course is associated with new-variant CJD?
Longer course (average 13 months)
What clinical feature is more prominent in new variant CJD?
Early behavioural changes more prominent
How is new variant CJD investigated?
- MRI
- EEG
- CSF
What may be seen on MRI of new variant CJD?
- Pulvinar sign in variant CJD
- Often no specific changes in sporadic CJD
What may be seen on EEG of new variant CJD?
- Generalised periodic complexes typical
- Often normal / non-specific in initial stages
What may be seen in the CSF of new variant CJD?
- Normal or raised protein
- Immunoassay 14-3-3 brain protein (non-specific, but very helpful in correct clinical context)
What is the causative agent of cryptococcal meningitis?
Cryptococcus neoformans
How does paralytic disease present in poliomyelitis?
- Asymmetric, flaccid paralysis, esp legs
- No sensory features