Infections of the Nervous System Flashcards
What is meningitis?
Inflammation/ infection of the meninges
What is encephalitis?
Inflammation/ infection of brain substance
What is myelitis?
Inflammation/ infection of spinal cord
How strong is the destinction of meningitis, encephalitis and myelitis?
In reality the distinction is artificial and patients often have a mixture
What are the clinical features of meningitis
- “Classical triad”
- Present with short history of progressive headache associated with fever and meningism
- Cerebral dysfunction
- Cranial nerve palsy, seizures, focal neurological deficits may also occur
- Patechial skin rash
What is the “classical triad” in meningitis?
Fever
Neck stiffness
Altered mental status
What is meningism?
Neck stiffness
Photophobia
Nausea and Vomiting
How is neck stiffness examined?
Passively bendng the neck forward
Describe cerebral dysfunction in meningitis
Confusion, delirium, declining conscious level
Common
GCS
How many patients with meningitis have cranial nerve palsy?
30%
Cranial nerves pass through meninges so may be effected
How many patients with meningitis have seizures?
30%
How many patients with meningitis have focal neurological deficits?
10-20%
You should always look out for a skin rash in meningitis.
Give more information about this
Tumbler test
Hallmark of meningococcal meningitis, but cal also occur in viral meningitis
What is the differential diagnosis of meningitis?
Infective
-Bacterial, viral , fungal
Inflammatory
- Sarcoidosis
Drug induced
-NSAIDs, IVIG
Malignant
- Metastatic
- Haematological (e.g. leukaemia, lymphoma, meyloma)
What do the bacterial causes of meningitis include?
Neisseria meningitidis
(Meningococcus)
Streptococcus pneumoniae
(pneumococcus)
What do the viral causes of meningitis include?
Enterovirus
What are the clinical features of encephalitis?
Flu-like prodrome (4-10 days)
Progressive Headache associated with fever
- +/- meningism
- Progressive cerebral dysfunction
- Seizures
- Focal symptoms / signs
Describe progressive cerebral dysfunction in encephalitis
Confusion
Abnormal behaviour
Memory disturbance
Depressed conscious level
How does viral encaphalitis differ to bacterial meningitis in its presentation?
Onset of a viral encephalitis is generally slower than for bacterial meningitis and cerebral dysfunction is a more prominent feature
What is a prodrome?
An early symptom that might indicate the start of a disease before specific symptoms occur
What is the differential diagnosis for encephalitis?
Infective
-Viral (most common is HSV)
Inflammatory
- Limbic encephalitis
- ADEM
Metabolic
-Hepatic, Uraemic, Hyperglycaemic
Malignant
-Metastatic, Paraneoplastic
Migraine
Post ictal (after seizure)
What antibodies are involved with limbic encephalitis?
Anti VGKC (voltage gated potassium channels)
Anti NMDA
What is ADEM?
Acute Disseminated Encephalomyelitis
The disorder manifests as an acute-onset encephalopathy associated with polyfocal neurologic deficits and is typically self-limiting.
Bears a striking clinical and pathological resemblance to other acute demyelinating syndromes of childhood, including multiple sclerosis (MS).
Describe anti-VGKC Auto-immune encephalitis
Frequent seizures
Amnesia (not able to retain new memories)
Altered mental state
Decribe anti-NMDA receptor auto-immune encephalitis
Flu like prodrome
Prominent psychiatric features
Altered mental state and seizures
Progressing to a movement disorder and come
What is the priority in meningitis and encephalitis?
Treat infection
Then try to exclude infection with investigation
What are the investigations for meningitis?
Blood cultures (bacteraemia)
Lumbar puncture (CSF culture/ microscopy)
No need for imaging if no contraindications to lumbar puncture
What are the investigations for encephalitis?
Blood cultures
Imaging (CT scan +/- MRI)
Lumbar Puncture
EEG
What are the indications for CT scanning before a lumbar puncture?
Focal neurological deficit, not including cranial nerve palsies
-Raised ICP
New-onset seizures
Papilloedema
-Raised ICP
Abnormal level of consiousness, interfering with proper neurological examination (GCS
What are the CSF findings in bacterial meningitis?
Opening pressure
-Increased
Cell count
- High
- Mainly Neutrophils
Glucose
-Reduced
Protein
-High
What are the CSF findings in Viral meningitis and encephalitis?
Opening pressure
-Normal/ increased
Cell count
- High
- Mainly leukocytes
Glucose
-Normal (60% of blood glucose)
Protein
-Slightly increased
What should be looked at with the CSF extracted from a lumbar puncture?
- Opening pressure
- Cell count
- Glucose
- Protein
What is the most common cause of bacterial meningitis?
Streptococcus Pneumoniae
How common is herpes simplex virus as a cause of encephalitis?
Relatively rare, but commonest cause of encephalitis is europe
How do you diagnose HSV?
Lab diagnosis by PCR of CSF for viral DNA
How do you treat HSV?
Treat with aciclovir on clinical suspicion
Treat as soon as you suspect
What is the result if HSV encephalitis is missed?
Over 70% mortality and high morbidity if untreated
What are the two types of herpes simplex virus?
HSV types 1 and 2
- Cold sores (type 1»_space; 2)
- Genital herpes (type 1&2)
What is the herpes group of viruses?
Herpes simplex
Varicella Zoster Virus
Epstein Barr Virus
Cytomegalovirus
What happens to the herpes simplex virus after initial infection?
Virus remains latent in the trigeminal or sacral ganglion after primary infection
(as with all herpes viruses, once infected, always infected)
How does HSV cause encephalitis?
Its a rare complication of HSV
-Other than neonates, nearly all caused by type 1
What are enteroviruses?
Large family of RNA viruses
Tendency to cause CNS infections (Neurotropic)
Human infections, no animal reservoir
-Fecal oral route
Many can cause non-paralytic meningitis
What is included in the family of enteroviruses?
Polioviruses
Coxsackieviruses
Echoviruses
Enteroviruses cause gastroenteritis.
True or false?
False
Found in gut but DO NOT cause gastroenteritis.
Diarrhoea wont be enterovirus
How common is Arbovirus Encephalitides?
Common cause of encephalitis in other parts of the world
What is included in Arbovirus encephalitides?
Variety of virus groups?
Transmitted to man by vector (mosquito or tick) from non-human host e.g.:
- West nile Virus
- St Louis Encephalitis
- Western Equine Encephalitis
- Tick Borne Encephalitis
- Japanese B Encephalitis
How does the place name of Arbovirus encephalitis relate to where its geographic location is?
Generally relate to where first described and NOT to current geographical distribution
What is a brain abscess?
Localised area of pus within the brain
What is a 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 or subdural empyema?
Fever, Headache
Focal symptoms/ signs
-Seizures, dysphasia, hemiparesis etc
Signs of raised intracranial pressure
- Papilloedema, false localising signs
- Depressed conscious level
Meningism may be present (particularly with empyema)
Features of underlying source
-e.g. dental, sinus or ear infection
What are the differential diagnosis for brain abscess and empyema?
Any focal lesion, but most commonly tumour
Subdural haematoma
What are the causes of brain abscess and empyema?
Penetrating head injury
Spread from adjacent infection (dental, sinusitis, otitis media)
Blood borne infection
-e.g. Bacterial endocarditis
Neurological procedure
How do you diagnose brain abscess and empyema?
Imaging: CT or MRI
Investigate source
Blood cultures
Biopsy (drainage of pus)
What do you need to consider in biopsy of brain abscess and empyema?
Risk vs benefits
Need to consider the location (base may be risky)
Describe the organisms involved in brain abscess
Often mixtures of organisms present:
-Depend on predisposing condition
Streptococci in 70% of cases, esp penicillin-sensitive “Strep milleri” group
Anaerobes in 40-100% of cases
-Bacteroides, Prevotella
What is the management for 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 guidance
High mortality without appropriate treatment
What conditions should you consider HIV testing?
- Cerebral toxoplasmosis
- Aseptic meningitis/ encephalitis
- Primary cerebral lymphoma
- Cerebral abscess
- Cryptococcal meningitis
- Space occupying lesion of unknown cause
- Dementia
- Leucoencephalopathy
What brain infections can occur in HIV patients with low CD4 counts?
- Cryptococcus neoformans
- Toxoplasma gondii
- Progressive multifocal leukoencephalopathy (PML)
- Cytomegalovirus (CMV)
- HIV-ENCEPHALOPATHY (HIV- ASSOCIATED DEMENTIA
How can you diagnose HIV related neurological infections?
India Ink, Cryptococcal antigen
Toxoplasmosis serology (IgG)
JC virus PCR
CMV PCR
HIV PCR
What Spirochaete infections effect CNS?
Lyme disease (Borrelia Burgorferi)
Syphilis (Trepomena Pallidum)
Leptospirosis (Leptospira Interrogans)
How does lyme disease spread
Spirochaete (Borrelia Burgdorferi) spreads by Tick vector
Common in inverness and moray areas
Has 3 stages
What is Lyme disease?
Has 3 stages
Multi-system:
- Skin,
- Rheumatological,
- Neurological/ neuropsychiatric
- Cardiac
- Opthalmological involvement
Untreated 80% will develop multi-system disseminated disease
What is stage 1 of lyme disease?
lasts 1-30 days
Early localised infection
Characteristic expanding rash at the site of the tick bite: erythema migrans
50% flu like symptoms for 1 day to a week
-Fatigue, myalgia, arthralgia, headache, fever, chills, neck stiffness
What is stage 2 lyme disease?
lasts weeks to months
Early disseminated infection
One or more organ systems become involved
-Haematologic or lymphatic spread
Musculoskeletal involvement most common
Describe the neurologic involvement in stage 2 lyme disease
10-15% untreated patients
- Mononeuropathy
- Mononeuritis multiplex
- Painful radiculoneuropathy
- Cranial neuropathy
- Myelitis
- Meningo-encephalitis
Describe stage 3 lyme disease
months to years
Chronic infection:
-Occuring after a period of latency
Musculoskeletal and neurologic involvement most common
Describe the neurologic involvement in stage 3 lyme disease
As described for stage 2
Subacute encephalopathy
Encephalomyelitis
What is the relationship of lyme disease and chronic fatigue syndrome?
Lyme disease does NOT cause a chronic fatigue syndrome
What is the investigation for lymes disease?
Complex range of serelogical tests
CSF lymphocytes
PCR of CSF
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
Stage 1 doxycycline
Late stage IV ceftriaxone
Describe neurosyphilis
Syphilis (Treponema pallidum) has a similar 3 stage presentation to lyme disease
(Primary -> secondary -> tertiary)
Tertiary disease occurs years/ decades after primary infection (not common)
How do you investigate neurosyphilis?
Treponema specific and non-treponemal specific (VDRL) antibody tests
CSF lymphocytes increased, evidence of inthrathecal antibody production, PCR
How do you treat neurosyphilis?
High dose penicillin
What is poliomyelitis?
Caused by poliovirus types 1, 2 or 3
-all enteroviruses
99% of infections are asymptomatic
Paralytic disease in about 1%
-infects anterior horn cells of lower motor neurones
Asymmetric, flaccid paralysis, esp legs
No sensory features
What is rabies?
Acute infectious disease of CNS affecting almost all mammals
Transmitted to human by bite or slivary contamination of open lesion
Neurotropic - virus enters peripheral nerves and migrates to CNS
Parasthesiae at site of original lesion
Ascending paralysis and encephalitis
How do you diagnose rabies encephalitis?
No useful diagnostic tests before clinical disease apparent
Diagnosis:
- Culture
- Detection
- Serology
How do you manage rabies encephalitis?
Sedation
Intensive care
Death
What are important sources of human infection in rabies?
Dogs in Africa/ Asia
Bats in the developed world (even UK…)
What is the rabies pre-exposure prevention?
Active immunisation with killed vaccine
Given to:
- 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 immunoglobin (passive immunisation) if high risk
What is tetanus?
Infection with Clostridium tetani
Wound may not be apparent
Toxin acts at NMJ
- Blocks inhibition of motor neurones
- Rigidity and spasm (risus sardonicus)
What type of bacteria is clostridium tetani?
Anaerobic Gram positive bacillus
-Spore forming
How do you prevent tetanus?
Immunisation (toxoid)
Given combined with other antigens (DTap)
Penicillin and immunoglobulin for high risk wounds/ patients
What is clostridium botulinum?
Anaerobic spore producing gram positive bacillus
Naturally present in soil, dust and aquatic environments
Describe the botulinum neurotoxin
Binds irreversibly to the presynaptic membranes of peripheral neuromuscular an autonomic nerve junctions
Toxin binding blocks acetylcholine release
Recovery is by sprouting new axons
What are the 3 modes of infection for clostridium botulinum?
Infantile (intestinal colonisation)
Food-borne (outbreaks)
Wound: almost exclusively injecting or “popping” drug users
What is the clinical presentation for botulism?
Incubation period 4-14 days
Descending symmetrical flaccid paralysis
Pure motor
Respiratory failure
Autonomic dysfunction (usually pupil dilation)
How do you diagnose botulism?
Nerve conduction studies
Mouse neutralisation bioassay for toxin in blood
Culture from debrided wound
What is the treatment for botulism?
Anti-toxin (A, B, E)
-Fight toxin
Penicillin/ Metronidazole (prolongued treatment)
-Fight infection
Radical wound debridement
What should you suspect in an IVDA patient with pure motor descending paralysis?
Botulism until proven otherwise
What post infective inflammatory syndromes should you watch outfor after a neurological infection?
Preceding infection (viral, bacterial) or immunisation
- “Molecular mimicry”
- Latent interval between the precipitating infection and onset of neurological symptoms
- Autoimmune
Central nervous system
-Acute disseminated encephalomyelitis (ADEM)
Peripheral nervous system
-Guillain Barre Syndrome (GBS)
What is Guillain Barre Syndrome?
Rapid-onset muscle weakness after damage to the peripheral nervous system.
Many experience changes in sensation or develop pain, followed by muscle weakness beginning in the feet and hands.
The symptoms develop over 1/2 day to 2 weeks.
Acute phase -> disorder can be life-threatening
-About 25% developing weakness of the breathing muscles and requiring mechanical ventilation.
Some affected by changes in function of the autonomic nervous system -> dangerous abnormalities in heart rate and blood pressure.
What is Creutzfeldt-Jakob Disease (CJD)?
Transmissable Proteinaceous Particle (Prion)
What is the aetiology of Creutzfeldt-Jakob Disease?
Sporadic CJD (most common)
New variant CJD
Familial CJD (10-15%)
Acquired CJD (
How can you get acquired CJD?
Cadeveric Growth Hormone
Dura mater grafts
Blood transfusion
What is the incidence of Creutzfeldt-Jakob Disease?
Very Rare
Sporadic = 1 per million per year
When should you consider sporadic CJD?
Consider in any rapidly progressive dementia
What are the clinical features of Sporadic CJD?
- Insidious onset (usually over 60)
- Early behavioural abnormalities
- Rapidly progressive dementia
- Myoclonus
- Progressing to global neurological decline
- Motor abnormalities
- Cortical blindness
- Seizures may occur
What motor abnormalities may occur in sporadic CJD?
Cerebellar ataxia
Extrapyramidal:
-tremor, rigidity, bradykinesis, dystonia
Pyramidal:
-weakness, spacticity, hyper-reflexia
What is the differential diagnosis of 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 in sporadic CJD?
Rapid progression
Death often within 6 months
How does new varient CJD differ to sporadic CJD?
Younger onset
How do you investigate CJD?
MRI
- Pulvinar sign in varient CJD
- Often no specific changes in sporadic CJD
EEG
- Generalised periodic complexes typical
- Often normal/ non-specific in initial stages
CSF
- Normal or raised protein
- Immunoassay 14-3-3 brain protein (non-specific, but very helpful in correct clinical context)
