W5 - MS and Alzheimer's Flashcards
Discuss the epidemiology and prevalence of MS.
Worldwide:
- Affects ~2.3 million people
- Females make up at least 50% of cases
- Most people diagnosed between 25-35
- Affects all parts of world, however prevalence tends to increase with latitude (more common further from equator), however many exceptions
- Increased prevalence in Sardinians, Parsis and Palestinians. Decreased in Chinese, Japanese, African blacks.
Australia:
- Females 75% of cases
- ~23,700 people with MS (2009)
- Prevalence in Tas 5x greater than QLD
Discuss the aetiology and pathogenesis of MS.
Geography/environment
- Hypothesis arisen from observed geographical distribution.
- May be due to environmental factors in specific areas such as viral or bacterial infections, exposure to chemicals, lack of sun exposure and different genetics
Genetics
- Only modest effect (concodance for monozygotic twins =25-35%)
- Presence of predisposing non-Mendlian risk factors (eg environmental effects etc) thought to play big role
- 1st degree family members 7x higher risk of developing MS
- HLA-DRB1 and class 2 MHC HLA-DR2 genes increase MS susceptibility
- Molecular mimicry - T cells in peripheral blood become activated to attack foreign Ag and attack brain proteins with similar epitopes
Viral ifections
- May infect immune system, activating self-reactive T cells → Enter CNS and attack myelin sheath of nerve cells
- Periodic reactivation of these viruses may cause acute exacerbations of MS
- Epstein-Barr virus (EBV) specifically implicated
Vit D deficiency
- Vit D helps to decrease proinflammatory cytokine production and increase anti-inflammatory cytokine production. Low Vit D = Increased inflammation.
- Increased Vit D associated with decreased risk of developing MS
Write notes on the MS plaque. Which are the most common sites of plaque development?
Process of MS plaque development:
- Individual’s geographic location/environment exposes individual to risk factors (genetics, viral infection, Vit D deficiency etc)
- Acute inflammation (due to predisposing factors) causes activation of self-reacting T-lymphocytes that spread to CNS –> Acute plaque formation
- Acute inflammation dies down, causing chronic plaque formation.
Plaque characteristics:
Acute plaque (early lesion)
- 0.1 to several cm’s in diameter
- Often occurs in periventricular areas of CNS (periventricular infiltration and accumulation of inflammatory cells eg. T-cells and plasma cells)
- Soft and pink, ill-defined borders
- Oedema
- Histologically: Observe breakdown of myelin and phagocytosis by macrophages
Chronic plaque (late lesion)
- Induration of affected tissues causes sclerosis and scarring
- Reactive fibrillary gliosis
- Sharply defined (no inflammation), grey/translucent (no dilated blood vessels) areas of demyelination
- Few/absent oligodendrocytes
Most common sites:
- Periventricular areas of CNS (surrounding the ventricles)
- Periventricular areas include: Optic nerve, brain stem, cerebellar peduncles and pyramidal tracts
- Can develop anywhere in brain and spinal cord
Which are the most common presenting symptoms and signs of MS?
A presenting symptom is the very first clinical manifestation of the disease.
- Limb weakness (40%)
- Paraesthesia (20%)
- Optic neuritis (20%)
- Diplopia (10%)
- Bladder dysfunction (5%)
- Vertigo (5%)
Which are most common symptoms of MS, overall?
Muscle weakness – 96% Ocular disturbance – 85% Urinary disturbance – 82% Gait ataxia – 60% Paresthesia – 60%
Which are the most common signs of MS, overall?
Muscle weakness – 96%
Dysarthria/scanning speech – 54%
List five (5) symptoms or signs which are considered to be extremely characteristic of MS. Briefly describe each of these manifestations.
- Lateral internuclear ophthalmoplegia – Inability of one eye to move laterally upon lateral gaze. Occurs due to damage of the MLF which connects CNIII and VI.
- Bilateral internuclear opthalmoplegia – Inability of both eyes to move laterally (as above)
- Lhermitte’s sign – An electric shock sensation going down spine and into limbs upon neck flexion. Occurs due to scar tissue formation altering conduction pathway.
- Retrobulbar neuritis – inflammation of the optic nerve that results in eye pain and blurred/reduced vision.
- Uhthoff’s phenomenon – Exacerbation of ssx when body temperature is raised.
How is MS diagnosed?
MS may be diagnosed based on the clinical picture:
- Definite MS: Consistent course with >2 bouts separated by >1 month. Documented neurologic signs of lesions in >1 area of CNS. Onset of Ssx between 10–50yo. Absence of other neurologic explanation.
- Probable MS: Hx of remitting Ssx, one current sign of MS, documented single bout of ssx, good recovery, absence of other neurologic explanation.
- Possible MS: Hx of remitting Ssx, no documentation of signs establishing more than one white matter lesion, absence of other neurologic explanation.
Lab tests:
- Electrophysiological studies – delayed nerve conduction (not specific for MS though 95% sensitive).
- CSF examination: normal/mild increase in lymphocytes, slight increase in protein, electrophoresis shows oligoclonal Ab’s (90% of pt’s), increased IgG (60%).
- CT scan – shows hypodense areas of demyelination
- MRI – shows areas of increased (bright) signals.
Discuss the clinical course of MS.
Typical onset: 20-40 years, observing episodic relapses and remissions.
Extremely variable clinical course:
- Severe disease – 5% pt’s die within 5 years, sometimes within months.
- Moderate – 80% of patients. Progression over decades, incomplete recovery from each episode. 1 attack every couple of years.
- Mild – 15% of pt’s, Patients have one or a few episodes with complete recovery.
Discuss the prognosis of MS.
- Average duration of disease from Ssx onset – 20 years
- Life expectancy only mildly decreased
- 60% of pt’s fully functional 10 years after 1st attack and 30% after 30 years
- Events ass with poor prognosis: Onset with motor ssx, onset at earlier age
- Events ass with better prognosis: Onset with sensory ssx, onset in middle age
List the complications of MS. Why do these complications occur?
- UTIs
- Chest infections
- Pressure sores
- Acute respiratory failure due to weakness of ventilator muscles
All complications mainly associated with being chronically bedridden.
Define the term dementia.
An umbrella term for a decrease in cognitive function due to an organic loss of cortical neurons.
Global impairment of intellect, reason, memory, personality and emotions occurs, without impairment of consciousness and other “lower brain” functions.
Briefly discuss the aetiology of dementia.
Many conditions are associated with the development of dementia.
- Primary degenerative disorders affecting the CNS
→ Alzheimer’s, Pick’s disease, Huntington’s disease, Parkinson’s disease.
- Disorders causing secondary changes in the CNS which result in dementia
→CVD, infections (HIV, syphilis), ISOLs, Hydrocephalus, Drugs/toxins (alcohol), Metabolic disease (hyperthyroidism etc), vitamin deficiencies (B1, B2, B12).
Briefly define the term “Alzheimer’s dementia” (AD). Is it a common condition?
A dual “clinicopathological entity” defined by a specific pattern of cognitive changes and structural/biological changes. The most common form of dementia.
Yes, it is a common condition.
Dementia statistics:
- >298000 Aus with dementia in 2011 (projected to be 900,000 by 2050)
- >1700 new dementia cases per week (1 case every 6mins)
- 3/10 people >85yo, 1/10 people over 65yo
- 3rd leading cause of death in Aus in 2010
Note: AD accounts for 50-70% of dementia cases.
Discuss the macroscopic changes which occur in the brains of Alzheimer’s dementia patients.
Cortical atrophy (especially in the frontal and temporal lobes) causes following macroscopic changes:
- Brain weight decreased
- Wider fissures and thinner gyri
- Loss of both grey and white matter
- Secondary hydrocephalus (due to ventricular enlargement)
Note: Hind brain and spinal cord usually appear normal.
