Module 2: Neurological and Psychiatric Disorders of the Central Nervous System Flashcards
Lecture 1, Cerebral ischaemia and pathogenic mechanisms
Why is Stroke important?
Stroke is a major cause of disability.
- Circulatory diseases (heart disease & stroke) are the second most common causes of death in England & Wales after cancer.
- and the second most common cause of death and major cause of disability worldwide according to the WHO
- In the first month following a stroke there is a 10% mortality and up to half of those who survive have a significant loss of independence
- 152,000 strokes per anum in UK/17 million worldwide
- 1.2 MIllion Stroke survivors in the UK
Lecture 1, Cerebral ischaemia and pathogenic mechanisms
How can we improve outsome of stroke?
- Rapid intervention STROKE
- increase specialist units in the UK to provide thrombolysis necessary within 3 hours to improve outcome, this increases outcome by 5% in the UK
- develop new neuroprotective drugs
- increase public awareness of the symptoms and prognosis
Lecture 1, Cerebral ischaemia and pathogenic mechanisms
What are the types of Acute Stroke?
What is their treatment and prohylaxis?
Acute stroke is the occlusion or haemorrhage of cerebral blood vessels, including:
- transient cerebral ischaemia (TIA)
- cerebral ischaemic stroke (CI) ~ 80%
- primary intracranial cerebral haemorrhage (ICH)
- subarachnoid haemorrhage (SAH)
Treatments: current acute treatments:
- CI improve bloodflow.
- Tissue plasminogen activator (tPA), thrombolysis, used on the minority of patients since there are saftey concerns after 4.5 hours.
- Aspirin, anti-platelet
Prophylaxis:
- cholesterol lowering statins (atherosclerosis)
- ACE inhibitors
- anti-platelet agents (aspirin, dipyridamole)
- anti-hypertensives
Lecture 1, Cerebral ischaemia and pathogenic mechanisms
How do the spatial and temporal issues relate to stroke’s effect on the brain?
- when blood flow via the major arteries is disturbed, blood flow predominantly from the Circle of Willis can compensate.
- If this is insufficient, resistance vessels begin to dilate due to autoregulatory mechanisms and anaerobic metabolism produces lacticacidosis and CO2, which further intensifies pH-mediated vasodilation
- Ischaemia initially diminishes functional brain activity, but not structural integrity; this can be seen as EEG & evoked potential are
impaired while cells remain viable. - However, it subsequently affects metabolic activity and structural integrity as well, resulting in disturbance of membrane ion
gradients and cell death:
|nfarct Core - consisteing of cells closest to the infract that demostrate both functional and structural damage
_The Penumbra -_is the surrounding cells that are functionally but not structurally damaged, these cells are still viable and can be restored if treated rapidly. The Penumbra represents tissue at risk of infarction where perfusion is adequate to maintain cell viability but not adequate for normal neuronal function
Lecture 1, Cerebral ischaemia and pathogenic mechanisms
What are the rates of blood flow in cerebral ischaemia?
Blood flow in cerebral ischaemia
- > 50 ml/100g/min Normal
- > 22 < 50 ml/100g/min olighaemia - Hypoperfusion but likely to survive depending on factors such as collateral flow
- < 22 ml/100g/min ischaemic penumbria - Misery perfusion likely to progress to infarction
- < 10 ml/100g/min rapid cell death
Lecture 1, Cerebral ischaemia and pathogenic mechanisms
What are the 5 time depended stages of ischaemia?
1) Energy failure (minutes)
2) Excitotoxicity (minutes)
3) Induction of immediate early genes (hours)
4) Inflammation (hours/days)
5) Programmed cell death / apoptosis (days)
Lecture 1, Cerebral ischaemia and pathogenic mechanisms
What does this graph tell you about cerebral ischaemia?
Proteinsynthesis is the first to go when you have reduced blood flow, in order to save energy
After 20ml/mg/min you get a very rapid loss of ATP
Lecture 1, Cerebral ischaemia and pathogenic mechanisms
What is the teraptuic window?
Lecture 1, Cerebral ischaemia and pathogenic mechanisms
Penumbra represents tissue at risk of infarction where perfusion is adequate to maintain cell viability but not adequate for normal neuronal function
What causes cell death in the penumbra?
Glutamate is the trigger, causing the ischaemic cascade
Lecture 1, Cerebral ischaemia and pathogenic mechanisms
What are the events that happen during energy failure?
- Reduced blood flow means cells are unable to conduct oxidative phosphorylation in aerobic metabolism since they need glucose and oxygen
- ATP is hence reduced (esp. bad because 20% of total Oxygen consumption is used by the brain, though only 2% body weight)
- Ion gradients & ATP-driven Na+ pumps become imbalanced so membrane potential is not maintained
- extracellular glutamate is elevated and energy-dependent glutamate transporters are inactivated
- Further acidosis occurs -> provokes free radical formation and impairs Na+/K+-ATPase and Ca2+/H+-ATPase pumps, and Na+/Ca2+ transporters
- Na+ and Cl- entry is accompanied by passive H2O entry
- Cellular swelling leads to oedema
Ischaemia affects extracellular neurotransmitiers:
- glutamate levels increase
- GABA levels increase
- adenosine levels increase
Lecture 2, Stroke
Fill in the types of stroke and beifly describe them.
- AIS = Acute ischaemic stroke
- Lacunar = that results from occlusion of one of the small penetrating arteries that provides blood to the brain’s deep structures.
- AVM = Aterial Venous Malformation
- PICH = primary intracerebral haemorrhage
- EDH = Extra dural haemorrhage
- AIS = You can get a haemorrhagic stroke secondary to an ischaemic stroke. 5-10% of AIS transform into haemorrhagic stokes. This can affect treatment.
- SDH = Subdural Haemorrhage, resulting from chronic trauma. So common in the elderly and alcoholics.
- CVST=contical venous sinus thrombosis
Lecture 2, Stroke - Classification
Draw a table for Stroke Classification
Lecture 2, Stroke
What is Virchow’s Triad?
Lecture 2, Stroke
Which factors are the mort important for aterial and venous stroke?
Generally, the most important factor for arterial stroke is endothelial damage and for venous it is due to stasis. However this is not to say that stasis is not important in arterial strokes, since 20/25% of ischemic stroke is due to thromboembolism resulting from atrial fibrillation. These each have different factors.
Lecture 2, Stroke
Where are most strokes? What symptoms does each location give rise to?
Most strokes are in the internal capsule/striatum. This is the main region of the middle cerebral artery (MCA). Accounting for ½ to ⅔ of strokes this is the most important type.
ACA strokes affect the legs worse than the limbs due to the layout of the somatosensory and motor cortex and their respective blood supplies. The ACA supplies more medial aspects of the motor and somatosensory cortex.
PCA visual deficits are usually homonymous hemianopia.
Lecture 2, Stroke
What are the main types of Brainstem strokes?
Posterior inferior cerebellar infarct (PICA) Happens in the dorsolateral medulla. Gives a very particular set of symptoms and signs. It is the most frequent type of brainstem stroke. Gives rise to crossed signs:
Facial symptoms that are opposite to the symptoms in the rest of the body
This is since the neural tracts for the body’s nerves have crossed whereas the facial nerves have not.
PONS stroke causes locked in syndrome, since the pons is supplied by the basilar artery you get bilateral deficits. This is the worst type of stroke.
Lecture 2, Stroke
What are the main types of Ischaemic stroke and their pathopysiology?
Thromboembolism: Fairly self explanatory, a clot either forms in the vessel (thrombus) or will be formed elsewhere (embolism).
Hypoperfusion: When there is a deficit on the blood supply from one particular vessel (usually due to atherosclerosis) and other vessels in the area are able to pick up the slack. This however makes the patient highly susceptible to drops in blood pressure. The regions furthest away from the two main vessels are the first to be affected. This creates a “watershed”/border zone infarction.
Lacunar infarction: When one of the penetrating arteries that provides blood to the brain’s deep structures (smaller than 5 mm) is occluded.
Lecture 2, Stroke
Lecture 2, Stroke
Lecture 2, Stroke
What are the main types of Haemorrhagic Stroke?
- Primary intracerebral Haemorrhage Causes include Hypertension, Amyloid angiopathy and AVM. They are typically from branches of the MCA.
- Subarachnoid Haemorrhage Causes include Anursyms (hypertension or genetic), dissection or trauma. The secondary vasospasm in subarachnoid stroke can lead to secondary ischaemia
- Subdural Haemorrhage Subdural is between the dura and the arachnoid membrane.
- Extradural Haemorrhage Extradural will present with initial drowsiness then a “lucid period”.
Lecture 2, Stroke
What are the main methods of investigation?
Methods of investigation:
- MRI/Perfusion CT
- MRA - radiation
- Bubble Echocardiogram
- 24 hour ECG - needed to pick up paroxysmal atrial fibrillation
- Carotid dopplers - pick up carotid artery stenosis
Lecture 3, Prion Disease: Clinical and Pathological features
LO: What were the factors that lead to the emergance of Varient CJD?
Variant CJD
- first seen in 1995, theorised that its genesis is from a chnge in the processing of meat. A reduction in the temperature of sausage meat production possibly gave rise to the ability for endocanibalism (as similar in Kuru) to allow transmission of the PrPp protein.
- from BSE-infected beef (bovine to human transmission of BSE)
- mostly in younger ppl (<45 years old) who were more susceptible and only affected those with methionine at polymorphic codon 129 homozygously in the PRNP gene.
- longer duration than CJD, like kuru which had an incubatino of roughly 40 years.
Lecture 3, Prion Disease: Clinical and Pathological features
Outline the neuropathology of Prion diseases
Neuropathology
• spongifom change
- these are ringed vacuoles?
- clinical presentation is different than alzheimers disease, but some cases are missed and only picked up in pathology
- this is the cerebellum with 3 layers; there’s widespread vacuolar change in this layer of the cerebellum (Purkinje layer)
• neuronal and synaptic loss
- massive enlargement of ventricles including lateral ventricles
- massive lost of substance in insular system and all of the cortex
- not as stereotypical as alzheimers in the specifics of the atrophy; it’s just very generalised
• astrogliosis
- you can see lots of reactive astroglial cells
• accumulation of PrPp
- you can use antibodies against prion
- some people with prion disease also have alzheimer like changes and that makes it confusing
- here are prion protein plaques in the cerebellum
Lecture 3, Prion Disease: Clinical and Pathological features
What are prions?
LO: Identify the key neuropathological features of prion disease
Prions are composed of abnormally folded and aggregate forms of a normally expressed protein called Prion protein (PrP)
- it is called prion because there is a proteinaecous infection only
- this can lead to human diseases e.g. Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker (GSS) syndrome, Fatal Familial Insomnia (FFI)
- and also animal diseases e.g. scrapie (in sheep), Bovine Spongiform Encephalopathy (BSE, in caile, “mad cow disease”), feline spongiform encephalopathy
Lecture 3, Prion Disease: Clinical and Pathological features
What happens to the Prp protein in Prion diseases?
normal = PrPc, scrapie isoform = PrPsc, abnormal human isoform = PrPp (is actually the same as PrPsc)
- prion protein is a cell surface glycoprotein, its funtion is not well know but thought to be involved in signal transduction and vesicle trafficing
- it’s resistant to degradation by proteinase K
- the pathological isoform PrPp is present in prion disease and the infectious agent.
- There is a conversion from alpha helix into beta pleated sheet that is more tightly bound and is the stucture for all amyloids.
- This deposits insoluble protiens in the brain
Lecture 3, Prion Disease: Clinical and Pathological features
What are the clinical presentations of different types of Prion disaese?
LO: Compare and contrast the clinical presentations of prion disorders with those of the more common neurodegerative disorders
Rapid progression of a clinical hisotry consistent with dementia or movement disorder
Sporadic CJD
- rare but accounts for 80% of prion diseases
- affects both genders equally
- the mean age of onset is 57-66 years but it can also occur at 17 years or 80 years
- progression is rapid:
- declines in cognitive and motor function over a few weeks (progressive dementia),EEG changes like in dementia
- motor signs (ataxia, bradykinesia and spasticity) due to corticospinal tract dysfunction
- memory deficits
- cognitive deficits
- visual disturbances
Iatrogenic CJD
- you can also get CJD iatrogenically, through transplantations, for example:
- dural transplant
- growth hormone (ground up brains used to harvest GH)
Gerstmann-Straussler-Scheinker (GSS) Syndrome
- slow progression (duraEon = 4-5 years)
- mild demenEa occurs late in the disease
- mean age of death is 50
Fatal Familial Insomnia (FFI)
- characterised by insomnia
- demenEa occurs late in the disease
Lecture 3, Prion Disease: Clinical and Pathological features
What is the importance of Glycosylation patterns?
There are 3 bands depending on how many polysaccharide chains are attached
- the nature of attached glycan is also important
- four patterns:
- types 1 and 2 = sporadic CJD
- type 3 = iatrogenic CJD
- type 4 = variant CJD
Lecture 4, CNS Trauma
Outline the progress of head injury
Lesions in fatal non-missile head injury
- *• Primary**
- skull fracture (75%)
- surface contusions (95%)
- diffuse axonal injury (30%)
- intracranial haematoma (60%)
- *• Secondary**
- brain swelling (53%)
- ischaemic brain damage (55%)
- infection (4%)
- due to raised ICP (75%)
Lecture 4, CNS Trauma
What are the features of secondary traumatic damage?
LO: Observe the differences between primary and secondary trauma damage
Brain swelling
- causes raised ICP
• vasodilatation and increased cerebral bloood volume (congestive)
• blood vessel damage (vasogenic oedema)
• increased water content of cells (cytotoxic cerebral oedema)
Can lead to uncle herniation if there is supratentorial pressure
Lecture 4, CNS Trauma
What are the main features of primary trauma damage?
LO: Observe the differences between primary and secondary trauma damage
Fractures:
-can lead to otorrhea or rhinorrhea
- there’s a risk of infection
- signs of a skull-based fracture:
• Baile’s sign (bruise beneath ear)
• Raccoon eyes
Contusions:
When the brain is in collision with the skull, surface bruising occurs since the anterior fossa is not smooth, any movement can cause localised bleeding.
Coup or countercoup injury can occur (the brain rebounding within the skull)
Diffuse axonal injury (DAI):
Happens at the moment of injury, has shear and tensile forces affecting axons.
Commonest cause of coma (when no bleed)
Midline stuctures are particularly vulnerable
DAI grading:
• grade 1: parasagital frontal, internal capsule, cerebellum
• grade 2: grade 1 + corpus callosum
• grade 3: grade 2 + dorsal brainstem
Pathogenesis- Primary axonomy = axolemma damage, allowing Ca2+ influx and eventually development of swelling. Causeing cytoskeleton dyruption and functional impairment. Secondary axonomy = increased neuron sensitivity to excitotic and hypoxic damage.
Traumatic axonal injury- at least some is present in neary all head injuries
Intracranial haematoma - 66% of fatal non-missile head injury. 10%extradural and 56% subdural,subarachnoid, intracerebral
Lecture 4, CNS Trauma
LO: Critically appraise the literature supporting the concept of chronic traumatic encepalopathy (CTE)
Dementia pugilistica (aka. Chronic Traumatic Encephalopathy, CTE)
definition of CTE pathology = presence of:
• foci of perivascular neurofibrillary tangles (NFT) and astrocytic tangles
• irregular cortical distribution of NFTs and astrocytic tangles particularly in the depths of the sulci.
• clusters of subpial and periventricular astrocytic tangles in the cerebral cortex, diencephalon, basal ganglia and brainstem
• neurofibrillary tangles in the cerebral cortex located preferentially in the superficial layers
• tau pathology in AD vs CTE
- the most important thing is that astrocytic tangles are not present in Alzheimer’s disease but prominent in CTE
Evidence
- now it’s generally accepted that head injury can promote the generation of Aß deposits diffusely in the brain; epidemiological studies showed that troops with head injuries in WWII showed significantly increased risk of dementia after 50 years (including vascular dementias)
- since the 1920s it had been known that the repetative brain trauma associated with boxing may produce a progressive neurological deterioration
- microscopically, there are extensive tau immunoreactive neurofibrillary tangles, astrocytic tangles and spindelshaped/ threadlike neurites throughout the brain
- proposed as a tauopathy
- in a study of 85 subjects with a history of repetitive mild TBI, who were athletes and military personnel, 68 of them showed some degree of CTE pathology.
Environmental and genetic risks:
Apolipoprotein E4 allele is associated with more Ab protein plaques follwoing head injury
Lecture 4, CNS Trauma
What are the 2 major clinical presentations of CTE?
Behvioural/mood varients (generally younger onset)
cognitive impairments (generally older onset)
Lecture 26, Alzheimer’s Neruopathology
What are Amyloid-ß peptide and APP?
Amyloid-ß peptide - is the protien that forms Amyloid plaques, it is PART OF Amyloid PRECURSOR PROTIEN
Amyloid Precursor Protien (APP) - APP is a membrane bound glycoprotein, its processing can be NON-AMYLOIDOGENIC or AMYLODOGENIC. The latter is the pathological pathway that leads to Amyloid-ß peptide production outside the cell membrane
- APP processing can be broken down in 2 ways either with
- on a neuronal cell membrane, there are 3 proteins involved in the processing of APP
- in normal conditions, alpha secretase breaks down APP and releases solid APP-alpha; then one of the fragments (83-aa) is broken down by gamma secretase and removed
- in Alzheimer’s, beta secretase cuts beta amyloid at a different site to form a 99-aa fragment, which is broken down by gamma secretase again
- this makes a beta amyloid monomer, which aggregates in toxic forms (in proto-fibrils to fibrils to clumped plaques)
- these get deposited on the neuronal cells
- this causes neuronal damage, by activating the inflammatory cascade
- maybe these plaques are just an end-stage process and it’s just a way of dumping the protein outside, and it’s actually the oligomers or monomers that are the most harmful
Lecture 26, Alzheimer’s Neruopathology
What are the various intracelluar effects of the Amyloid-B Peptide produced?
The Amyloid-B Peptide forms dimers which then form oligomers and eventually fibrils. Effects include:
- Hyper-phorsphorylating TAU the million $$$$ question in HOW DOES THIS HAPPEN
- Affecting the proteosome to prevent normal cell breakdown
- Calcium regulation disruption
- affecting the mitochondria to produce Reactive Oxygen Species
- Moving the Amyloid plaques outside the cell which is thought to be toxic
Lecture 28, Fronto-temporal Dementias (FTDs)
LO: Catagorise the Molecular Subtypes of FTDs
Lecture 28, Fronto-temporal Dementia
LO: What are the clinicopathological features of FTLD?
- in the years prior to presentatoin, they had word-finding difficulties, language impairments and later progressive personality change (since it affects the frontal lobe)
- there were also neuropsychiatric changes in facial recognition, verbal fluency, etc.
Lecture 28, Fronto-temporal Dementias
Exaplain how a Western Blot diagram can help in the molecular diagnosis of Tauopathies
The TAU protien can have 6 isoforms
It can either have 3 or 4 microtubule binding domains (R), and 0,1 or 2 unknown function inserts (N)
Alzheimer’s is a 3R and 4R Tauopathy
CBP and PSP (parkinson plus disorders) are 4R Tauopathies
Picks is a 3R Tauopathy
Lecture 28, Fronto-temporal Dementias
Outline the Neuropathologicaly diagnostic pathway for a clinical History consistent with Dementia or movement disorder
Lecture 28, Fronto-temporal Dementia
LO:What are the Neuropathological Features of FTDs?
LO: What is the overlap between FTD and Motor Neuron Disease?
- Pick bodies are very obvious, and there are some probably agerelated
tau tangles as well
- one brain section was stained with TDP43 (not progranulin antibodies) and they found that the pathology was quite unique and included:
- cat’s eyes (intranuclear inclusions)
- other neuritic inclusions
- C9ORF72 mutation in chromosome 9p:
- you can see cats eyes and neuritic pathology
- inclusions are usually found in the cerebrum, but it’s uncommon for them to be in the granular cell layer of the cerebellum; that are positive for ubiquitin but negative for TDP43 and tau
- is it like alpha synuclein, where there are cytoplasmic granular aggregations?
- will the things aggregate into a body like in FTLD?
- current insights into the C9ORF72 repeat expansion diseases of the FTLD/ALS spectrum suggest there’s clinical phenotypic heterogeneity and it’s very confusing to figure out what the diagnosis is
- Involvement of TDP-43 in both FTLD-TDP and MND/ALS also provided a firm molecular link between FTLD and MND/ALS underpinning the notion that these two large groups of neurodegenerative disorders represent two, often overlapping ends of a disease spectrum
- This is also supported by clinical data indicating that about 30% of patients with FTD develop clinical signs of MND/ALS and that 50% of MND/ALS patients show some evidence of cognitive deficits
Lecture 5, Multiple Sclerosis Clinical Features
What are the other risk factors for MS?
Virus
Risk of MS is twice as high in those who have has EBV. Disease severity and risk of MS corrlate with antiEBV antibodies titres.
Genetic
first degree relatives have a 10-25x greater risk of MS. 25% to 30% concordance rate in monozygotic twins. Only 30% of the disease is attributed to genes.
HLA-class II genes exert the strongest effect, accounting for 20-60% of the genetic risk,
Hormones
Women are twice as likely to get MS than men, relapsing rates are much higher around preganancy.
Lecture 5, Multiple Sclerosis Clinical Features
What are the MS subtypes?
RR MS
Mean age of onset is 30 (F:M = 2/3:1), optic neuritis and sensory distrubances are common onest symptoms. 70% of patients have at least a 5 year relapse free period. Annulaized relapse rate decreases over time (17% less every 5 years).
85% of relapsing remmiting MS patients convert to secondary progressive MS after 25 years from onest.
SP MS and PP MS
Primary progressive MS and Secondary progressive MS start at the same age.
Lecture 5, Multiple Sclerosis Clinical Features
What is the prognosis of MS?
What are prognostic indicators?
Mean time to EDSS 6 (need assistance to walk) is 20 years
No features can predict the outcome in the single patient. Age at onset and progressive course from onset are the most adverse prognostic factors.
Good prognostic indicators:
- young onset
- female
- optic neuritis or only sensory symptoms at onset
- low frequency of early attacks
- complete symptom remission
- long first inter attack interval
Bad prognostic indicators
- older than 40 years at onset
- male
- insidious pyramidal tract involvement
- prominent cerebellar involvement
- frequent early attacks
- rapid development of fixed disability
Discuss how recent research developments in amyotrophic lateral sclerosis have increased our understanding of the pathological mechanisms underlying this disorder.
Definition, clicical phenotype and basic pathology, epidemiology
Discuss how recent research developments in amyotrophic lateral sclerosis have increased our understanding of the pathological mechanisms underlying this disorder.
Intro to FALS and pathological mechanisms identified
Discuss how recent research developments in amyotrophic lateral sclerosis have increased our understanding of the pathological mechanisms underlying this disorder.
RNA processing : TDP43 and FUS
Discuss how recent research developments in amyotrophic lateral sclerosis have increased our understanding of the pathological mechanisms underlying this disorder.
Repeat expensions
Discuss how recent research developments in amyotrophic lateral sclerosis have increased our understanding of the pathological mechanisms underlying this disorder.
Protein quality control system: SOD1, VAPB, Sequestrome 1
Discuss how recent research developments in amyotrophic lateral sclerosis have increased our understanding of the pathological mechanisms underlying this disorder.
Protein quality control system: VCP, OPTN
Discuss how recent research developments in amyotrophic lateral sclerosis have increased our understanding of the pathological mechanisms underlying this disorder.
Conclusion
Discuss how recent research developments in amyotrophic lateral sclerosis have increased our understanding of the pathological mechanisms underlying this disorder.
Why do motor neurons die in ALS?
What are the animal models of Parkinson’s Disease and how do we induce them? Pros and cons. What is their resemblence to clinical PD?
Definition of PD, epidemiology, clinical phenotype and basic pathology
. What are the animal models of Parkinson’s Disease and how do we induce them? Pros and cons. What is their resemblence to clinical PD?
Animal models and toxin models
. What are the animal models of Parkinson’s Disease and how do we induce them? Pros and cons. What is their resemblence to clinical PD?
6OHDA
. What are the animal models of Parkinson’s Disease and how do we induce them? Pros and cons. What is their resemblence to clinical PD?
MTTP
. What are the animal models of Parkinson’s Disease and how do we induce them? Pros and cons. What is their resemblence to clinical PD?
Lactacystin
. What are the animal models of Parkinson’s Disease and how do we induce them? Pros and cons. What is their resemblence to clinical PD?
Genetic models intro
. What are the animal models of Parkinson’s Disease and how do we induce them? Pros and cons. What is their resemblence to clinical PD?
Overexpression of alpha synuclein
. What are the animal models of Parkinson’s Disease and how do we induce them? Pros and cons. What is their resemblence to clinical PD?
LRKKs
. What are the animal models of Parkinson’s Disease and how do we induce them? Pros and cons. What is their resemblence to clinical PD?
MitoPark
Clinical and pathological evidence that MS is an inflammatory condition. Describe treatment approaches and how they work with the pathology.
Definition, clinical presentation, epidemiology
Clinical and pathological evidence that MS is an inflammatory condition. Describe treatment approaches and how they work with the pathology.
Clinical evidence
Clinical and pathological evidence that MS is an inflammatory condition. Describe treatment approaches and how they work with the pathology?
Pathological evidence
a) What are the 4 main mechanisms and 2 examples of current drugs used and what mechanism they use?
b) What is the lifetime risk and what is the current population prevalence?
c) What are the causes of death in Epilepsy?
d) What are the 4 main mechanisms and 2 examples of current drugs used and what mechanism they use.
