Infections of the Nervous System Flashcards
What is inflammation of the meninges called?
Meningitis
What is inflammatio of the brain substance called?
Encephalitis
What is inflammation of the spinal cord called?
Myelitis
Do patients normally present with inflammation of only one part of the nervous system?
No, they present with a mixture of meningitis, encephalitis and myelitis
What are the clinical features of meningitis?
- Classical triad
- Fever, neck stiffness and altered mental status
- Present with a short history of progressive headache associated with
- Fever (>38 degrees)
- And meningism (neck stiffness, photophobia, nausea and vomiting)
- Cerebral dysfunction
- Confusion, delirium, declining conscious level)
- GCS <14 in 69%
- Cranial nerve palsy (30%), seizures (30%), focal neurological deficits (10-20%)
- Petechial skin rash (look for with Tumbler test)
- Hallmark of meningococcal meningitis but can also occur in viral meningitis
What is the classical triad of clinical features for meningitis?
- Fever, neck stiffness and altered mental status
What is meningism?
Clinical syndrome of headache, neck stiffness, and photophobia, often with nausea and vomiting
What cerebral dysfunction can patients with meningitis present with?
Confusion
Delirium
Declining conscious leve
GSC < 14
What is the differential diagnosis for meningitis?
- Infective
- Bacterial, viral, fungal
- Inflammatory
- Sarcoidosis
- Drug induced
- NSAIDs
- IVIG
- Malignant
- Metastatic
- Haematological
- Such as leukaemia, lymphoma, myeloma
What are some bacterial causes of meningitis?
- Neisseria meningitidis (meningococcus)
- Streptococcus pneumoniae (pneumonococcus)
What is the most common viral cause of meningitis?
Enteroviruses
What are the clinical features of encephalitis?
- Flu like prodrome (4 to 10 days)
- Progressive headache associated with fever
- With or without meningism
- Progressive cerebral dysfunction
- Confusion
- Abnormal behaviour
- Memory disturbance
- Depressed conscious level
- Seizures
- Focal symptoms/signs
What progressive cerebral dysfunction can patients with encephalitis display?
- Confusion
- Abnormal behaviour
- Memory disturbance
- Depressed conscious level
Is the onset of viral encephalitis faster or slower than the onset of bacterial meningitis?
Slower
Is cerebral dyfunction worse with viral encephalitis or bacterial meningitis?
Viral encephalitis
What is the differential diagnosis for encephalitis?
- Infective
- Viral (most common is HSV)
- Inflammatory
- Limbic encephalitis (anti VGKC anti NMDA receptor)
- ADEM
- Metabolic
- Hepatic
- Uraemic
- Hyperglycaemic
- Malignant
- Metastatic
- Paraneoplastic
- Migraine
- Post ictal (after seizure)
What are 3 different kinds of encephalitis?
Viral encephalitis
Autoimmune encephalitis
What are 2 important antibodies associated with autoimmune encephalitis?
- Anti-VGKC (voltage gated potassium channel)
- Frequent seizures
- Amnesia (not able to retain new memories)
- Altered mental state
- Anti-NMDA receptor
- Flu like prodrome
- Prominent psychiatric features
- Altered mental state and seizures
- Progressing to a movement disorder and coma
How does the clinical presentation differ between autoimmune encephalitis associated with anti-VGKC and anti-NMDA?
- Anti-VGKC (voltage gated potassium channel)
- Frequent seizures
- Amnesia (not able to retain new memories)
- Altered mental state
- Anti-NMDA receptor
- Flu like prodrome
- Prominent psychiatric features
- Altered mental state and seizures
- Progressing to a movement disorder and coma
When dealing with someone who presents with meningitis/encephalitis like symptoms, what is the priority?
Exclude and treat infection
What investigations are done for meningitis?
- Blood cultures (bacteraemia)
- Lumbar puncture (CSF culture)
- No need for imaging if no contraindications to lumbar puncture
What investigations are done for encephalitis?
- Blood cultures
- Imaging
- CT scan with or without MRI
- Lumbar puncture
- EEG
What are indications for CT scan before lumbar puncture (contraindications to lumbar puncture)?
- Focal neurological deficit, not including cranial nerve palsies
- Suggests a focal brain mass
- New-onset seizures
- Papilloedema
- Abnormal level of consciousness, interfering with proper neurological examination (GCS < 10)
- Reduced conscious level suggests raised intracranial pressure
- Severe immunocompromised state
How does the CSF differ between bacterial meningitis and viral meningitis/encephalitis in terms of:
- opening pressure
- cell count
- glucose
- protein
What is done to identify the bacteria responsible for bacterial meningitis?
What does HSV stand for?
Herpes simplex virus
What is required to diagnose HSV encephalitis?
- Lab diagnosis by PCR of CSF for viral DNA
What is HSV encephalitis treated with?
- Treat with aciclovir on clinical suspicion
What are the different herpes group of viruses?
VZV
EBV
CMV
What are the 2 different kinds of HSV?
Type 1
Type 2
What kind of sores are caused by HSV types 1 and 2?
- Cold sores (type 1 more than 2)
- Genital herpes (type 1 and 2)
Where does HSV remain latent after primary infection?
Virus remains latent in the trigeminal or sacral ganglion after primary infection:
- As with all herpes viruses, once infected, always infected
Does type 1 or type 2 HSV more commonly cause encephalitis as a complication?
Type 1
What are enteroviruses?
Are a large family of RNA viruses
Human infections with no animal reservoir
By what route are enteroviruses spread?
Spread by the faecal-oral route
What are examples of enteroviruses?
- Polioviruses
- Coxsackieviruses
- Echoviruses
What are some other, less common causes of encephalitis?
Arbovirus encephalitis
Brain abscess and empyema
How is arbovirus transmitted?
- Transmitted to man by vector (mosquito or tick) from non-human host
- Is arthropod borne
- Relevant to travel
- Travel history important
- Some preventable by immunisation
What is a brain abscess?
- Brain abscess is localised area of pus within the brain
What is subdural empyema?
- Subdural empyema is a thin layer of pus between the dura and arachnoid membranes over the surface of the brain
What are clinical features of brain abscess and empyema?
- Fever, headache
- Focal symptoms/signs
- Seizures dysphagia, hemiparesis
- Signs of raised intracranial pressure
- Papilloedema, false localising signs
- Depressed conscious level
- Meningism may be present, particularly with empyema
- Features of underlying source
- Such as 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 are some causes of brain abscess and empyema?
- Penetrating head injury
- Spread from adjacent infection
- Dental, sinusitis, otitis media
- Blood borne infection
- Bacterial endocarditis
Neurosurgical procedure
How is a brain abscess and empyema diagnosed?
- Imaging
- CT or MRI
- Investigate source
- Blood cultures
- Biopsy (drainage of pus)
What organs are normally present in a brain abscess?
Often mixture of organisms present (polymicrobial) which depends on predisposing condition
Streptococci is present in 70% of cases, especially the penicillin-sensitive “strep milleri” goup:
- Strep anginosus, Strep intermedius, Strep constellatus
Anaerobes in 40-100% of cases:
- Bacteroides
- Prevotella
What organisms are most commonly present in a brain abscess?
Streptococci is present in 70% of cases, especially the penicillin-sensitive “strep milleri” goup:
- Strep anginosus, Strep intermedius, Strep constellatus
Anaerobes in 40-100% of cases:
- Bacteroides
- Prevotella
What is the management of a brain abscess?
- 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 are examples of HIV indicator illnesses in the brain?
- Cerebral toxoplasmosis
- Aseptic meningitis/encephalitis
- Primary cerebral lymphoma
- Cerebral abscess
- Cryptococcal meningitis
- Space occupying lesion of unknown cause
- Dementia
- Leukoencephalopathy
What is done to diagnose HIV indicator brain illnesses?
- Cryptococcal antigen
- Toxoplasmosis serology
- CMV PCR
- HIV PCR
What are examples of spirochaetes in the CNS?
- Lyme disease
- Borrelia burgdorferi
- Syphillis
- Trepomena pallidum
- Leptospirosis
- Leptospira interrogans
What bacteria causes lyme disease?
- Borrelia burgdorferi
What bacteria causes syphillis?
- Trepomena pallidum
What bacteria causes leptospirosis?
- Leptospira interrogans
How is lyme disease transmitted?
- Vector borne
- Tick (wooded areas)
What are the stages of lyme disease?
- Stage 1
- Early localised infection (1-30 days)
- Characteristic expanding rash at the site of the tick bite (erythema migrans)
- 50% flu like symptoms (days to 1 week)
- Fatigue, myalgia, arthralgia, headache, fever, chills, neck stiffness)
- Stage 2
- Early disseminated infection (weeks to months)
- One or more organ system becomes involved
- Haematologic or lymphatic spread
- Musculoskeletal and neurological involvement are most common
- Neurological involvement occurs in 10-15% of untreated patients
- Mononeuropathy
- Mononeuritis multiplex
- Painful radiculoneuropathy
- Cranial neuropathy
- Myelitis
- Meningo-encephalitis
- PNS > CNS
- Stage 3
- Chronic infection
- Months to years
- Occurring after a period of latency
- Musculoskeletal and neurologic involvement most common
- Neurologic involvement
- As described for stage 2
- Subacute encephalopathy
- Encephalomyelitis
- Does not cause a chronic fatigue syndrome
- Chronic infection
What is stage 1 on lyme disease?
- Early localised infection (1-30 days)
What is the clinical presentation of stage 1 lyme disease?
- Characteristic expanding rash at the site of the tick bite (erythema migrans)
- 50% flu like symptoms (days to 1 week)
- Fatigue, myalgia, arthralgia, headache, fever, chills, neck stiffness)
What is stage 2 lyme disease?
- Early disseminated infection (weeks to months)
- One or more organ system becomes involved
- Haematologic or lymphatic spread
What is the clinical presentation of stage 2 lyme disease?
- Early disseminated infection (weeks to months)
- One or more organ system becomes involved
- Haematologic or lymphatic spread
- Musculoskeletal and neurological involvement are most common
- Neurological involvement occurs in 10-15% of untreated patients
- Mononeuropathy
- Mononeuritis multiplex
- Painful radiculoneuropathy
- Cranial neuropathy
- Myelitis
- Meningo-encephalitis
- PNS > CNS
What is stage 3 lyme disease?
- Chronic infection
- Months to years
- Occurring after a period of latency
What is the clinical presentation of stage 3 lyme disease?
- Musculoskeletal and neurologic involvement most common
- Neurologic involvement
- As described for stage 2
- Subacute encephalopathy
- Encephalomyelitis
- Does not cause a chronic fatigue syndrome
How is lyme disease a multi-system disease?
- Skin, rheumatological, neurological, cardiac and ophthalmological involvement
Untreated 80% will develop multi-system disseminated disease
What investigations are done for lyme disease?
- Complex range of serological tests
- CSF lymphocytosis
- MRI brain/spine (if CNS involvement)
- Nerve conduction studies/EMG (if PNS involvement)
What is the treatment for lyme disease?
- Prolonged antibiotic treatment
- Intravenous ceftriaxone
- Oral doxycycline
What is neurosyphillis caused by?
Caused by Treponema pallidum
What is the 3 stage presentation of neurosyphillis?
- Primary
- Secondary
- Latent
What investigations are done for neurosyphillis?
- Treponema specific and non-treponemal specific antibody tests
- CSF lymphocytes increased
- Evidence of intrathecal antibody production
What is the treatment for neurosyphillis?
Treatment is high dose penicillin
What are some examples of important vaccines?
- Poliomyelitis
- Rabies
- Tetanus
- Botulism
What is poliomyelitis caused by?
- Caused by poliovirus types 1, 2 or 3:
- All enteroviruses
Where does poliovirus infect to cause poliomyelitis?
- Infects anterior horn cells of lower motor neurons
What is the clinical presentation of poliomyelitis?
- Asymmetric, flaccid paralysis, especially legs
- No sensory features
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
What is the pathogenesis of rabies?
Neurotropic meaning virus enters peripheral nerves and migrates to CNS
What is the clinical presentation of rabies?
Paraesthesia at the site of original lesion
Ascending paralysis and encephalitis
How is rabies encephalitis diagnosed?
- Diagnosis is by PCR and serology
What are the possible outcomes of rabies encephalitis?
- Possibilities are sedation, intensive care or death
Who is the rabies vaccine given to in the UK?
- Bat handers
- Regular handlers of important animals
- Selected travellers to enzootic zones
What is some rabies post-exposure treatment?
- Wash wound
- Give active rabies immunisation
- Give human rabies immunoglobin (passive immunisation) if high risk
What are important sources of rabies infection?
- Dogs in Africa/Asia
- Bats in developed world
What infection causes tetanus?
- Infection with Clostridium tetani
- Anaerobic gram positive bacillus, spore forming
Where do the toxins that cause tetanus act?
- Toxins act at neuro-muscular junction
- Blocks inhibition of motor neurons
What is the clinical presentation of tetanus?
- Rigidity and spasm (risus sarconicus)
What can be done to prevent tetanus?
- Immunisation (toxoid)
- Given combined with other antigens (DTaP)
- Penicillin and immunoglobin for high risk wounds/patients
What kind of vaccine is used for rabies?
Killed vaccine
What kind of vaccine is used for tetanus?
Toxoid
What is botulism caused by?
Caused by Clostridium botulinum:
- Anaerobic spore producing gram positive bacillus
- Neurotoxin
- Binds irreversibly to the presynaptic membranes of peripheral neuromuscular and autonomic nerve junction
- Toxin binding blocks acetylcholine release
- Recovery is by sprouting new axons
Naturally present in soil, dust and aquatic environments
How does the botulism toxin act?
- Neurotoxin
- Binds irreversibly to the presynaptic membranes of peripheral neuromuscular and autonomic nerve junction
- Toxin binding blocks acetylcholine release
- Recovery is by sprouting new axons
Where is clostridium botulinium naturally found?
- Naturally present in soil, dust and aquatic environments
What are the 3 modes of infection of clastridium botulinium?
- Infantile (intestinal colonisation)
- Food-borne (outbreaks)
- Wound
- Almost exclusively by injecting drug users
What is the clinical presentation of botulism?
- Incubation period 4-14 days
- Descending symmetrical flaccid paralysis
- Pure motor
- Respiratory failure
- Autonomic dysfunction
- Usually pupil dilation
What is done to diagnose botulism?
- Nerve conduction studies
- Mouse neutralisation bioassay for toxin in blood
- Culture from debrided wound
What is the treatment of botulism?
- Anti-toxin (A, B, E)
- Penicillin/metronidazole (prolonged treatment)
- Radical wound debridement
What book is good to refer to for immunisatoin against infectious disease?
Green book
What are examples of post infective inflammatory syndromes?
Central nervous system:
- Acute disseminated encephalomyelitis (ADEM)
Peripheral nervous system:
- Guillain Bare Syndrome (GBS)
What does ADEM stand for?
- Acute disseminated encephalomyelitis (ADEM)
What does GBS stand for?
- Guillain Bare Syndrome (GBS)
Does guillain bare syndrome affect the CNS or PNS?
PNS
Does acute disseminated encephalitis affect the CNS or PNS?
CNS
What classification of disease are post infetive inflammatory syndromes?
Autoimmune
What does CJD stand for?
Creutzfeldt-Jakob Disease
What are the different kinds of Creutzfeldt-Jakob Disease (CJD)?
Sporadic CJD
New varient CJD
Familial CJD
Acquired CJD
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
- Cerebellar ataxia
- Extrapyramidal
- Tremor
- Rigidity
- Bradykinesis
- Dystonia
- Pyramidal
- Weakness
- Spasticity
- Hyper-reflex
- Cortical blindness
- Seizures
What is the differential diagnosis for sporadic CJD?
- Alzheimer’s disease with myoclonus
- Usually more prolonged
- Subacute sclerosing panencephalitis (SSPE)
- CNS vasculitis
- Inflammatory encephalopathies
What is the prognosis of sporadic CJD?
- Rapid progression
- Death often within 6 months
Does new varient CJD have younger or older onset?
Younger onset
What investigations are done for CJD?
- MRI
- Pulvinar sign in variant CJD
- Often no specific changes in sporadic CJD
- EEG
- Generalised periodic complexes typical
- Often normal/non-specific in early stages
- CSF
- Normal or raised protein
- Immunoassay 14-3-3 brain protein (non-specific, but very helpful in correct clinical context)
How does CJD impact the CSF proteins?
- Normal or raised protein
