Autoimmune diseases of NS Flashcards
dESCRIBE MS and epidemiology, RFs,evo.
Multiple Sclerosis
Episodes of demyelination affecting areas of the central nervous system separated by space and time (disseminated by time and location).
#### Multiple Sclerosis - Epidemiology
- Prevalence varies between 20 and 100 per 100,000 in Australia
- More common in women (f:m ~ 3:1)
- Younger age of onset ~ 20-40 years
- Racial predilection
- Genetic component: non-Mendelian
- Distance from equator – vitamin D (risk in first 14 years and remains, T cell behaviour, maturation)
- Life expectancy reduction has reduced
- Evolution: predilection and triggers, hygiene hypothesis, EBV; preclinical inflammation; relapsing remitting MS with reduced reserve; then progressive (primary or secondary)
- RFs: obesity, smoking, EBV, vitamin D
Describe immmunology of MS
- Unregulated immune system – genetic, Vit D, smoking, viral trigger (EBV) - resembles myelin
- Triggered attach on CNS myelin, with resultant plaque
- Repair with remyelination but risk of neuronal loss esp. with repeated insults
- Repeated insults to white matter and some cortical damage and atrophy
- Secondary neurodegeneration ? Oxidative stress
- Inflammation most an issue early in disease
- Why some get more atrophy and not always: correlated with white matter lesions
Evolution of demyelinating plaque
- immune engagement
- acute inflammatory damage
- repair
- post-inflammatory gliosis
- further remyelination limited by gliosis
List the steps of immune activation in MS
- Autoreactive myelin specific T helper cells (Th1 and Th17) normally controlled by regulatory T cells
- Failure of regulation when autoreactive T cells stimulated by antigens
- T cells express adhesion molecules to BB barrier and penetrate. Th1 secrete IFN gamma and Th17 secrete IL-17
- Activated T cells re-encounter myelin and activate microglia
- Microglia express class II molecules which further promotes T cells, microglia and PMN
List MS presenting features and describe clinical course
- Optic neuritis
- Sensory symptoms
- Motor deficit
- Cerebellar
- Brainstem (esp. diplopia)
- Transverse myelitis (motor, sensory or bladder)
- Fatigue
Clinical Course of MS
- 70% relapsing-remitting
- 10% benign relapsing-remitting with no progression
- 20% primary progressive
List poor MS prognostic factors
- Male sex
- Older age at onset
- Motor or cerebellar signs at onset
- Short interval between initial and second attack
- High relapse rate in early years
- Incomplete remission after first relapses
- Early disability
- High lesion load detected by early magnetic resonance imaging of the brain
Describe how MS is diagnosed and some DDxs
- At least 1 clinical episode
- Clinical episodes separated in time and place
- Ancillary tests used to prove asymptomatic episode
- MRI
- CSF
- Evoked Potentials looking for white matter tract issues
- Visual
- Somatosensory
- Brainstem
- Important to exclude other causes
Differential Diagnosis Of MS
- Other demyelinating disorders
- Acute disseminated encephalomyelitis (ADEM), Neuromyelitis optica (NMO)
- Autoimmune diseases
- Sjogren’s, SLE, Behcet’s, sarcoid, antiphospholipid
- Vascular disorders
- AV fistula, cavernomas, CNS vasculitis, CADASIL
- Infections
- HIV, Lyme disease, syphilis
- Metabolic disorders
- B12, leukodystrophies
- Genetic syndromes
- Mitochondrial, Spinocerebellar ataxias, hereditary spastic paraplegia
- Neoplasms
- CNS lymphoma, paraneoplastic syndromes, spinal cord tumours
- Others
- Conversion disorders, Chiari malformations, spondylosis
List MS treatment aims
- Reduce relapses – immune modulatory and immune suppressant agents
- Prevent permanent disability
- Above agents
- Shorten symptoms from acute attacks
- Pulse methylprednisone – but no evidence it reduces long term disability
- Symptomatic treatment
Describe NMO and diagnosis
- More common in Far East and Africa
- Monophasic or recurrent
- Predilection for spinal cord and optic nerves
- More severe than MS
- Associated with higher inc. of auto-antibodies, mainly ANA and Sjogrens in 50%
- Aquaporin-4 Antibodies
Revised Diagnostic Criteria for Neuromyelitis Optica
1. Optic neuritis
2. Acute myelitis
Plus at least two out of the following three supporting criteria:
- Brain MRI at onset not meeting Paty’s criteria for multiple sclerosis
- Contiguous lesion extending over three or more vertebral segments on spinal cord MRI
- NMO-IgG seropositive status
NMO
- Long spinal lesions (>3 levels)
- Symmetrical cerebral lesions
- Often brainstem with extension to thalami
- Acute attacks respond to plasmapharesis but not steroids
- Long term Rx with immunosuppression (e.g., prednisolone, azathioprine, rituximab) aka B cell therapy
Describe MOGA
- Similar presentation to NMO
- 10% incidence of NMO
- More males
- Better prognosis
- More conus lesions
Describe GBS
- Acute post infectious autoimmune peripheral neuropathy e.g. Campylobacter
- Incidence 0.6 to 4 per 100,000 - country and culture variation esp. handling poultry
- Progresses for no more than 4 weeks then plateaus though recovery slow
- Most age groups except very extremes of age.
- Ascending paralysis most common presentation
Describe GBS pathogenesis and triggers
- Exposure to infectious illness – antigen presentation
- Host response – genetic factors
- Inflammatory activation targeting myelin or axonal components
- Inflammatory response causing secondary axonal loss even in primary demyelinating disease
- Self-limiting immune activation
- Remyelination and axonal regeneration
Triggers for GBS
- Infections
- Most commonly viral
- Vaccinations
- Surgery
- Nil
List some GBS types
Depends in nerve afflicted
- Acute inflammatory demyelinating polyradiculopathy (AIDP). Facial diplegic variant.
- Acute motor and sensory axonal neuropathy (AMSAN)
- Acute motor axonal neuropathy (AMAN)
- Miller Fischer syndrome
- Bickerstaff Brainstem Encephalitis
- Idiopathic cranial polyneuropathy
- Pharyngeal-cervical-brachial
- Paraparetic GBS
- Acute sensory neuronopathy/ganglionopathy
- Acute small fibre neuropathy
- Acute autonomic neuropathy
Describe presenting symptoms of GBS
- Pain (especially children)
- Numbness
- Paraesthesia
- Weakness
- Ascending
- Facial
- Respiratory
- Autonomic
- Tachycardia
- Postural hypotension
- Weakness
- LL>UL>facial>respiratory
- Paucity of sensory signs
- JPS most common
- Areflexia
- May have reflexes early
- Autonomic
- Miller Fisher variant
- Bickerstaff’s encephalitis
Describe GBS investigations and management
Investigations of GBS
- Establish diagnosis
- Exclude other diagnoses
- Related to general medical care
- Understanding causation
Investigations – Establish diagnosis
- CSF
- Nerve conduction studies
CSF and Guillain Barre Syndrome
- Cytoalbuminaemic dissociation: cell to protein off (high protein low cell)
- Rises with time, peaking at 7 days
- Raised WCC think of specific infections as triggers
- Oligoclonal bands can be seen
- 80% of cases will have raised protein
- WCC < 10
Respiratory Monitoring in GBS
- Deafferented lungs feel SOB and RR late
- Desaturate just prior to respiratory failure/arrest – ABGs poor assessment
- Intubation at 15ml/kg of FVC
- PEFR and spirometry can be affected by facial weakness
- Check frequently, but depends on rate of decline
Ancillary Management in GBS
- DVT management – PTE major cause of death
- Cardiac monitoring – autonomic instability
- BP – postural instability
- Pressure sore management
List prognostic factors for GBS
- Older age
- Campylobacter infection - target axons vs myelin, harder to repair
- CMV worse
- EBV better
- Axonal variant
- Intubation
- Bed bound
