PH2113 - Neurodegenerative Disease and Epilepsy 7 Flashcards
What is the initial treatment for Multiple Sclerosis?
Gold standard
- high dose short term corticosteroids for relapsing-remitting
- intravenous methylprednisolone
- 500mg - 1g daily, 3 - 5 days
OR
- high dose oral methylprednisolone
- 500mg - 2g daily, 3 - 5 days
May help restore integrity of Blood-Brain Barrier, suppress inflammation, circulating immune cells (activated lymphocytes) and activity of toxic cytokines
Does NOT affect long-term course of disease
- reduce duration of a relapse by few weeks
- no effect on disability accrued
Side effects
- weight gain
- skin thinning
- hypertension
- diabetes
- osteoporosis
- Cushing’s syndrome
Gradual withdrawal needed if in long term use
What are the treatments for Multiple Sclerosis?
15 disease modifying agents for Relapsing-Remitting Multiple Sclerosis
- interferon beta (5)
- glatiramer acetate (2)
- monoclonal antibodies
- natalizumab
- alemtuzumab
- daclizumab
- ocrelizumab
- chemotherapeutic agents
- mitoxantrone
- small molecule oral agents
- fingolimod
- dimethyl fumarate
- teriflunomide
Give examples of interferon treatments for Multiple Sclerosis
Generally safe – only partially effective
Betaferon
- interferon beta-1b
- sub cut 0.25mg alternating days
Avonex
- interferon beta-1a
- intramuscularly 30ug once a week
Rebif
- interferon beta-1a
- sub cut 22 or 44ug 3 x a week
How does interferon-beta treat Multiple Sclerosis?
Thought to inhibit some of the downstream effects of interferon-gamma
- proinflammatory cytokine
Beneficial effect on Blood-Brain Barrier by inhibiting MMPs
- affecting migration of lymphocytes across Blood-Brain Barrier
- altering balance of pro-inflammatory Th1 response to suppressor Th2 response
What are the side effects of using interferon-beta to treat Multiple Sclerosis?
Flu-like symptoms
Injection site reactions
Nausea
Blood disorders
Depression
Mild lymphpaenia
What are the contraindications of using interferon-beta to treat Multiple Sclerosis?
Severe depressive illness
Liver disease
What is the mechanism of using Copaxone (a protein drug) to treat Multiple Sclerosis?
Mixture of polypeptides
- resembling MBP
- glutamic acid
- lysine
- alanine
- tyrosine
Sub-cut 20mg once per day
Thought to block interaction of activated T cells with myelin
Altering the balance of proinflammatory Th1 response to suppressor Th2
Induction of a specific Th2 (CD4+) population in the periphery
- may enter the CNS
- reactivated by cross reactivity with myelin antigens
Secrete anti-inflammatory cytokines
- damage the local inflammatory process
- bystander suppression
Response against one Ag is suppressed when it is presented in the context of an Ag to which tolerance is already established
What are the statistics for the onset and incidence of Huntington’s disease?
Typical onset
- 30 - 50 years of age
15 - 20 years from diagnosis to death
Incidence of 3-7 per 100,000
What are the main symptoms of Huntington’s disease?
Hallmark symptoms include:
Uncontrolled movement of the arms, legs, head face and upper body. Also causes a decline in thinking and reasoning skills, including memory, concentration, judgement and ability to plan and organise
First motor signs:
- Abnormal eye movements
- Inappropriate hand and toe movements
- General restlessness
Midcourse
- Onset of involuntary movements
- Hypertonic rigidity and dystonia
Late stage
- Impaired voluntary movements
- Rigidity
- Bradykinesia
- Convulsions
- Weight loss
What are the motor deficits of Huntington’s disease?
First motor signs
- abnormal eye movements
- inappropriate hand and toe movements
- general restlessness
Midcourse
- onset of involuntary movements
- chorea
- hypertonic rigidity and dystonia
- slow abnormal movements with increased muscle tone
Late stage
- impaired voluntary movements
- rigidity
- bradykinesia
- dystonia
- convulsions
- weight loss
Death
- pneumonia
- choking
- chronic skin ulcers
- nutritional deficits
What are the cognitive deficits of Huntington’s disease?
Executive function
- planning
- cognitive flexibility
- abstract thinking
- rule acquisition
Perceptual and spatial skills
- self
- surrounding environment
Memory
Learning
- new skills is affected
What are the psychiatric symptoms of Huntington’s disease?
Vary more than cognitive and physical
- blunting
- egocentrism
- anxiety
- depression
- aggression
- compulsion
- additions
- alcoholism
- gambling
- hypersexuality
What is the pathology of Huntington’s disease?
10 - 20% reduction in brain weight
Decreased striatal volume and cell death
Decreased cortical volume and cell death
Increased ventricle size
Proteinous inclusions throughout brain
- huntingtin protein
Loss of GABAergic medium spiny neurones
- especially in caudate and putamen
What is the pathway in Huntingtin’s disease?
Loss of neurones from the striatum to the globus pallidus
- chorea
Imbalance between D1 and D2 receptors
How is Huntington’s disease inherited?
Autosomal dominant gene mutation
- 50% chance of passing it on
- almost 100% penetrance
- gene affected encodes the protein huntingtin
- gene identified in 1993
