Infections of the Nervous System Flashcards
Definition of meningitis
Inflammation/infection of meninges
Definition of encephalitis
Inflammation/infection of brain substance
Definition of myelitis
Inflammation/infection of spinal cord
Presentation of meningitis
Fever (>38C) Neck stiffness Altered mental status Short progressive headache Photophobia Nausea and vomiting Cranial nerve palsy (30%) Seizures (30%) Focal neurological deficits (10-20%) Petechial skin rash
What is the classic triad of meningitis?
Fever
Neck stiffness
Altered mental status
What is the petechial skin rash a hallmark of?
Meningococcal meningitis
But can also occur in viral
Differential diagnosis of meningitis
Infective; bacterial, viral, fungal
Inflammatory; sarcoidosis
Drug induced; NSAIDs, IVIG
Malignant; metastatic, haematological e.g. leukaemia, lymphoma, myeloma
Bacterial causes of meningitis
Neisseria meningitidis (meningococcus) Stretococcus pneumoniae (pnuemococcus)
Viral causes of meningitis
Enteroviruses
Presentation of encephalitis
Flu like prodrome (4 - 10 days) Progressive headache Fever \+/- meningism Progressive cerebral dysfunction (confusion, abnormal behaviour, memory disturbance, depressed conscious level) Seziures Focal symptoms/signs
Main differences of viral encephalitis vs bacterial meningitis
VE = Slower onset and cerebral dysfunction more prominent feature
Differential diagnosis of encephalitis
Infective; Viral (most common HSV)
Inflammatory; limbic encephlaitis (Anti VGKC Anti NMDA receptor). ADEM
Metabolic; hepatic, uraemic, hyperglycaemic
Malignant; metastatic, paraneoplastic
Migraine
Post ictal
What does post ictal mean?
Post seizure
What are the two important antibodies recognized in autoimmune encephalitis?
Anti-VGKC
Anti-NMDA receptor
What does anti-VGKC stand for?
Voltage gated potassium channels
Presentation of Anti-VGKC Autoimmune encephalitits
Frequent seizures
Amnesia
Altered mental state
What is amnesia?
Not able to retain new memories
Presentation of anti-NMDA receptor autoimmune encephalitis
Flu like prodrome
Prominent psychiatric features
Altered mental state and seziures
Progressive to movement disorder and coma
Investigations for meningitis
Blood cultures (bacteraemia) LP (CSF culture/microscopy)
Investigations for encephalitis
Blood cultures
Imaging (CT scan +/- MRI)
LP
EEG
Contraindications to 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 and signs suggest?
A focal brain mass
What does reduced consciousness level suggest?
Raised intracranial pressure
CSF findings in bacterial meningitis
Opening pressure increased
Cell count high, mainly neutrophils
Glucose reduced
Protein high
CSF findings in viral meningitis and also encephalitis
Opening pressure normal or increased
Cell count high, mainly lymphocytes
Glucose normal (60% of BG)
Protein slightly increased
How do you assess the level of glucose in the CSF?
Compare it to the level of glucose in the blood
Which bacterial cause of bacterial meningitis is sensitive to penicillin?
Culture streptococcus pneumoniae
If not pyrexial, does the patient need a blood culture?
No
How common is HSV Encephalitis?
Relatively rare
Commonest cause of encephalitis in Europe
Investigations of HSV Encephalitis
CSF - PCR for Viral DNA - Lymphocytosis - elevated protein CT - medial temporal and inferior frontal lobe changes (e.g. petechial changes) MRI (better) EEG
Treatment of HSV Encephalitis
Aciclovir on clinical suspicision
Types of HSV
Type 1
Type 2
What do both types of HSV cause?
Cold sores (type 1 > 2) Genital herpes (both types)
Where does the HSV virus lie in the body?
Remains latent in the trigeminal or sacral ganglion after primary infection
What type of HSV usually causes HSV encephalitis?
Type 1 (other than neonates)
What type of viruses are enteroviruses?
RNA viruses
Spread of entero-viruses
Faecal oral route
What do enteroviruses have the tendency to cause?
CNS infections (neurotrophic)
Do enteroviruses also cause gastroenteritis?
NO
Examples of enteroviruses
Polioviruses
Coxsackieviruses
Echoviruses
Causes of encephalitis
HSV
Enteroviruses
Arbovirus
Where is arbovirus encephalitis common?
Certain areas of the world where there is certain types of ticks/mosquitos - therefore have to have travel history
Types of arbovirus encephalitis
West nile virus
St Louis encephalitis
Tick borne encephalitis
Japanese B encephalitis
Definition of brain abscess
Localized area of pus within the brain
Definition of subdural empyema
Thin layer of pus between the dura and arachnoid membranes over the surface of the brain
Presentation of brain abscess/empyema
Fever Headache Focal symptoms - seizures - dysphagia - hemiparesis Signs of raised ICP - papilloedema - false localising signs - depressing conscious level Meningism may be present, particularly with empyema Features of an underlying source - dental, sinus or ear infection
Differential diagnosis of brain abscess/empyema
Any focal lesion but most commonly tumour
Subdural haematoma
Causes of brain abscess/empyema
Penetrating head injury Spread from adjacent infection - dental - sinusitis - otitis media Blood borne infection e.g. bacterial endocarditis Neurosurgical procedure
Investigations for brain abscess and empyema
Imaging; CT or MRI
Investigate source
Blood cultures
Biopsy (drainage of pus)
Causative organisms of a brain abscess
Often a mixture present - depends on predisposing condition Streptococci (70% of cases) - Strep anginousus - Strep intermediuss - Strep constellatus Anaerobes in 40-100% of cases - bacteriodes - prevotella
Treatment of brain abscess
Surgical drainage if possible
Penicillin or ceftrixazone to cover streps
Metronidazole for anaerobes
HIGH DOSES REQUIRED FOR PENETRATION
HIV indicator illnesses of the brain
Cerebral toxoplasmosis Aseptic meningitis/encephalitis Primary cerebral lymphoma Cerebral abscess Cryptococcal meningitis Space occupying lesion of unknown cause Dementia Leucoencephalopathy
Brain infections in HIV patients with low CD4 counts
Cryptococcus neoformans
Toxoplasma gondii
Progressive multifocal leykoencephalopathy (PML)
CMV
HIV encephalopathy (HIV-associated dementia)
Investigations of brain infections in HIV patients with low CD4 counts
India ink, cyptococcal antigen Toxoplasmosis serology (IgG) JC virus PCR CMV PCR HIV PCR
Causative organisms of cryptococcal infections
Cryptococcus neoformans
Exposure of cryptococcus organisms is due to what?
Inhalation of airborne organisms into the lungs
Most clinical cases of cryptococcal infections present with what?
Meningoencephalitis
What do most patients with cryptococcal infections also have?
Defects in immune function
Major risk factor for cryptococcal infections
AIDs
Risk factors for cryptococcal infections
AIDs
Immunosuppressive medications
- particularly in the setting of solid organ transplantation
What spirochaeates can be found in the CNS?
Borrelia Burgorferi
Trepomena pallidum
Leptospira interrogans
What does borrelia burgorgeri cause?
Lymes disease
What does trepomena pallidum cause?
Syphillis
What does leptospira interrogans cause?
Leptospirosis
How do you get lyme disease?
Vector borne; tick (wooded areas)
3 stages of lymes disease
Stage 1 , 2, 3
Presentation of stage 1 lymes disease
Early localised infection (1 - 30 days)
Characteristic expanding rash at the site of the tick bites - erythema migrans
50% flu like symptoms (days - 1 week)
- fatigue, myalgia, arthralgia, headache, fever, chills, neck stiffness
Presentation of stage 2 lymes disease
Early disseminated infections (weeks - months)
One or more organ systems involved - hematological or lymphatic spread
MSK and neurological involvement most common
Neurological involvement in 10 - 15% of untreated patients
- mononeuropathy
- mononeurtis multiplex
- painful radiculoneuropathy
- cranial neuropathy
- myeltiis
- meningo-encephalitis
PNS > CNS
When does stage 3 lymes disease occur?
Chronic infection - months to years
Occurring after a period of latency
Presentation of stage 3 lymes disease
MSK and neurological involvement most common
Neurological involvement as per stage 2 plus
- subacute encephalopathy
- encephalomyeltiis
Does stage 3 lymes disease cause chronic fatigue syndrome?
NO
Investigations for lymes disease
Serological testing CSF Lymphocytosis PCR of CSF MRI brain spine if CNS involvement Nerve conduction studies/EMG if PNS involvement
Treatment of lymes disease
IV ceftrixazone
Oral doxycycline
Stages of syphillis
Primary
Secondary
Latent
What stage of syphillis can affect the CNS? When does this occur?
Tertiary disease (neurosyphillis) Years / decades after primary disease
Investigations of syphillis
Treponema specific and non teponema specific (VDRL) antibody tests
CSF lymphocytes increased
Evidence of intrathecal antibody production
PCR
Treatment of syphillis
High dose penicillin
What is poliomyelitis caused by?
Poliovirus types 1, 2 or 3
What % of poliomyelitis infections are asymptomatic? What happens to the symptomatic group?
99%
1% symptomatic - paralytic disease as infects anterior horn cells of LMNs
Presentation of symptomatic poliomyelritis
Asymmetric, flaccid paralysis, especially on the legs
No sensory features
In the UK, what is done to prevent poliomyelitis?
Polio immunization against all 3 poliovirus types
What is rabies?
Acute infectious diseases of the CNS affecting almost all mammals
How are rabies transmitted from animal to human?
Bite
Salivary contamination of an open lesion
Features of the rabies virus
Neurotropic
Virus enters peripheral nerves and migrates to the CNS
Presentation of rabies
Paraesthesia at site of original lesion
Ascending Paralysis
Encephalitis
Investigations of rabies encephalitis
No useful diagnostic tests before clinical disease apparent
Culture
Detection or serology
What animals often carry rabies?
Dogs in Asia/Africa
Bats in developed world
What can be done for rabies pre-exposure prevention?
Active immunization with killed vaccine
Who is the rabies vaccine given to in the UK?
Bat handlers
Regular handlers of imported animals
Selected travelers to enzoonotic areas
Rabies post exposure treatment
Wash wound
Give active rabies immunisation
Give human rabies immunoglobulin (passive immunisation) if high risk
What is the causative organism of tetanus?
Clostridium tetani
Pathology of tetanus
Toxin acts at the NMJ
Blocks the inhibition of motor neurones
Presentation of tetanus
Rigidity and spam (risus sarconicus)
Prevention of tetanus
Immunisation (toxoid)
Given combined with other antigens (DTaP)
Penicillin and immunoglobulin for high risk wounds/patients
What is the causative organism for botulism?
Clostridium Botulinium
Pathology of botulism
Neurotoxin binds irreversibly to the presynaptic membranes of peripheral neuromuscular autonomic nerve junctions
Toxin binding blocks acetylcholine release
Recovery is by sprouting new axons
Where is clostridium botulinium naturally present?
Soil
Dust
Aquatic environments
Three modes of infection of clostridium botulinium
Infantile (intestinal colonisation)
Food-borne (outbreaks)
Wound; almost exclusively injecting or “popping” drug users
Presentation of botulism
Incubation period 4-14 days
Descending symmetrical flaccid paralysis
Pure motor
Resp failure
Autonomic dysfunction - usually pupil dilation
Investigations of botulism
Nerve conduction studies
Mouse neutralisation bioassay for toxin in the blood
Culture from debrided woud
Treatment of botulism
Anti-toxin (A,B,E)
Penicillin/Metronidazole (prolonged treatment)
Radical wound debridement
Example of a CNS post infective inflammatory syndrome
Acute disseminated encephalomyeltitis (ADEM)
Example of a PNS post infective inflammatory syndrome
Guillian Barre Syndrome (GBS)
What does CJD stand for?
Cretuzfeldt-Jakob Disease
Types of CJD
Sporadic
New variant
Familial
Acquired
How do patients get acquired CJD?
Cadaveric growth hormone
Dura mater grafts
Blood transfusion
Who should sporadic CJD be considered in?
Rapidly progressive dementia
Presentation of sporadic CJD
Insidious onset (usually older than 60) Early behavioral abnormalities Myoclonus Rapidly progressive dementia Motor abnormalities - cerebellar ataxia - extrapyramidal - pyramidal Cortical blindness Seizures may occur
Features of extrapyramidal motor abnormalities
Tremor
Rigidity
Bradykinesis
Dystonia
Features of pyramidal motor abnormalities
Weakness
Spasticity
Hyper-reflexia
Differential diagnosis of sporadic CJD
Alzheimer’s disease with myoclonus - usually more prolonged
Subacute sclerosing panencephalitis (SSPE)
CNS vasculitis
Inflammatory encephalopathies
Prognosis of sproadic CJD
Rapid progression
Death often within 6 months
What age do people get new variant?
< 40 y/o (usually < 25 y/o)
How do people get new variant CJD?
Linked to Bovine Spongiform Encephalopathy in cattle
- eating infected material
Investigations of CJD
MRI - pulvinar sign in variant CJD - no specific changes in sporadic CJD EEG - generalised periodic complexes typical CSF - normal or raised protein - immunoassay 14-3-3 brain protein (non specific but helpful in a clinical context)
What lobes does HSV encephalitis tend to affect?
Temporal lobes
Inferior frontal lobe
Presentation of HSV encephalitis
Fever Headache Psychiatric symptoms Seizures Vomiting Focal features e.g. aphasia
What is CJD caused by?
Prion proteins
Features of CJD
Rapidly progressive dementia
Myoclonus
Investigations of CJD
CSF = normal
EEG
MRI
Presentation of new variant CJD
Younger patients Psychological symptoms - anxiety - withdrawal - dysphonia
Median survival for new variant CJD
13 months
What is the most common complication of meningitis?
Sensorineural hearing loss
