Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Roy's Pathology (G3) > CNS Patho 3 (malformations + neurodegeneration + others) > Flashcards

CNS Patho 3 (malformations + neurodegeneration + others) Flashcards

1
Q

What are some aetiologies of CNS malformations?

A

Prenatal/Perinatal insults + Genetic Factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are some prenatal/perinatal insults?

A
  1. Nutritional deficiency (Folate): Neural tube defects
  2. Radiation: Neural tube defects + Anencephaly
  3. Drugs, toxins, infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the 3 types of CNS malformations?

A
  1. Neural Tube Defects
  2. Forebrain abnormalities
  3. Posterior fossa abnormalities
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are neural tube defects?

A

Failure of part of tube to close -> Causing reopening of tube –> Resulting in abnormalities of neural tissue and overlying bone/soft tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

When do neural tube defects occur?

A

3-4 week of embryogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the aetiology of neural tube defects?

A

Multifactorial (both genetic and environmental)
Eg. Folate deficiency leads to spinal bifida

Treatment: Folic acid 0.4mg during periconceptional period

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How do you detect neural tube defects?

A

Detection in-utero in
1. Amniotic Fluid
2. Maternal blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Neural tube defects are classified into…

A

1.Brain
–> Anencephaly
–> Encephalocele (extension of brain)
2.Spinal cord
–> Spinal bifida/Spinal dysraphism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

List the following about anencephaly (Pathogenesis, Predisposing factor)

A

Pathogenesis:
Due to failure of closure of anterior neural tube –> disrupted forebrain development –> absent brain and calvarium –> Area cerebrovasculosa is formed in place

Predisposing factor: Female> Male

Note: Posterior fossa is spared

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is Encephalocoele?

A

Failure of closure of posterior neural tube –> Extension of brain through defect in calvarium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the pathogenesis of spinal bifida?

A

Failure of closure of the spinal column

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the less serious form of spinal bifida

A

Spinal Bifida Occulta - Hairy patch on skin at the site of spinal bifida but no other signs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Clinical presentation of spinal bifida?

A
  1. LL weakness and paralysis
  2. Skeletal/Orthopaedic abnormalities (eg. club feet, hip dislocation)
  3. Bladder and bowel dysfunction, UTI
  4. Pressure Ulcers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the 3 different types of spinal bifida?

A
  1. Meningocoele
    –> Extension of meninges
  2. Meningo-Myelocoele
    –> Extension of meninges and spinal cord
  3. Syringo-Myelocoele
    –> Extension of central canal of spinal cord
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the 3 forebrain abnormalities?

A
  1. Polymicrogyria
  2. Lissencephaly
  3. Holoprosencephaly
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is polymicrogyria and its complications?

A

What: increase in number of gyri and size of gyri are smaller

Complications: Seizures, Mental retardation, Hemi/Quadriparesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is Lissencephaly and its complications?

A

What: Smooth brain appearance due to absence of normal gyri and sulci (folds and grooves) –> due to defective neuronal migration during development

Complications: Seizures, Severe psychomotor retardation, Difficulty swallowing/Aspiration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is holoprosencephaly and its complications?

A

What: Structural brain malformation resulting in incomplete separation of central hemispheres of forebrain across midline

Associated with: Trisomy 13, Maternal Diabetes

Complications: Facial midline abnormalities (eg. cyclopia), Early mortality, seizures, movement disorders, feeding problems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the posterior fossa anomalities?

A
  1. ARNOLD CHIARI MALFORMATION (CHIARI TYPE II MALFORMATION)
  2. DANDY WALKER SYNDROME
20
Q

What is Arnold Chiari Malformation?

A
  1. Characterised by small posterior fossa → causes cerebellar tonsils to displace through foramen magnum
  2. Commonly results in associated hydrocephalus due to CSF flow obstruction
  3. Can be associated with SPINA BIFIDA (specifically myelomeningocele)

Clinical Presentation:
1. Headaches especially on Valsalva maneuver (holding breath for 15-20 seconds before mouth breathing out to slow down heart rate → commonly used to stop supraventricular tachycardia)
2. Muscle weakness, fatigue
3. Severe - brainstem damage and death

21
Q

What is Dandy Walker Syndrome

A
  1. Characterised by enlarged posterior fossa → causes cerebellar vermis to be absent/shrunken + central open cyst
  2. Common in females

Clinical presentation:
1. Slow motor development in infants
2. Gradual enlargement of skull
3. Raised ICP → vomiting, irritability and convulsions
4. Poor coordination of eye and face muscles

22
Q

What is neurodegenerative diseases?

A

progressive loss of specific groups of neurons or brain areas

23
Q

Who is neurodegenerative diseases more common in?

A

Most common in elderly (>65 year olds)

24
Q

What are some examples of neurodegenerative diseases

A
  1. Dementia - Alzheimer Disease
  2. Movement Disorders
    –>Parkinson disease (substantia nigra neurones)
    –>Huntington chorea (basal ganglia)
  3. Motor Weakness - motor neurone disease
  4. Others
    –>Spinocerebellar degenerations
    –>Friedreich’s ataxia
25
Q

Alzheimer’s disease demographic?

A
  • Common in ageing population (20% in >80 year old age group)
  • ‘Early onset’ group (individuals who develop symptoms before target age) is rare
26
Q

What is the genetic basis of Alzheimer’s?

A
  1. Chromosome 21 - accumulation of APP (amyloid precursor protein) → production and deposition of A-beta (beta amyloid) peptides
  2. Chromosome 19 - Apo E4 subtype → tau hyperphosphorylation
27
Q

What are the clinical features of Alzheimer’s

A
  1. Cognitive decline
  2. Immobility (dyskinesia)
  3. Pneumonia
28
Q

Micro features in Alzheimer’s

A

Abnormal protein deposition in hippocampus, neocortex and amygdala

  1. Accumulation of amyloid plaques (neuritic/senile plaques)
    –>Collections of dilated, tortuous neuritic processes often surrounding a core of amyloid (A-beta = beta amyloid peptides) → disrupts cell communication → inflammation

2.Neurofibrillary tangles
–> Accumulation of hyperphosphorylated tau protein within neurons → neurofibrillary tangles → destabilises microtubules → neuronal damage and loss

29
Q

Macro features of Alzheimer’s

A
  1. Smaller, atrophied brain
  2. Temporal lobe most affected, frontal and parietal regions less
30
Q

Who is more likely to get Parkinson’s disease?

A

Common in middle-aged population (>45 year olds)

Genetic predisposition: Disorder of alpha-synuclein gene → accumulation of alpha-synuclein protein (lewy bodies)

31
Q

What are the 6 causes of Parkinsonism?

A

One of the most common causes of PARKINSONISM,
1. Idiopathic Parkinson’s Disease: Apoptosis of dopaminergic nigro-striatal neurons due to accumulation of alpha-synuclein in lewy bodies within dopaminergic neurons due to a disorder in the alpha-synuclein gene

  1. Neuroleptic medication
    –>Caution: Anti-emetcs block dopamine
    –>Contraindicated: First generation neuroleptics (Trifluoperazine, Haloperidol, Depot Flupentixol), Second generation neuroleptics (Risperidone, Olanzapine, Quetiapine, Clozapine)
  2. Parkinson plus syndromes
    –>Caused by groups of neurodegenerative diseases
    –>Examples:
    - Lewy Body Dementia - Parkinsonism + Hallucinations and cognitive deficits
    - Progessive Supranuclear Palsy - Parkinsonism + Eye movement abnormalities
    - Multiple System Atrophy - Parkinsons + Autonomic failure / Cerebellar disease
  3. Wilson disease
    –> Autosomal recessive inherited disorder of metabolism
    –> Defect in biliary copper excretion → deposition in basal ganglia, liver (cirrhosis), iris (KF rings)
    –>Diagnose through…
    - Demonstrating low levels of ceruloplasmin (copper transporter)
    - Demonstrating high copper urinary levels
    - Demonstrating kayser Fleischer rings
  4. Infective encephalitis
  5. Vascular parkinsonism
32
Q

What is the main pathology in Parkinson’s disease

A
  1. Loss of nigro-striatal neurons from the substantia nigra (midbrain):
    - Reduced dopamine to basal ganglia
    - Grossly: Pallor (loss of pigment) in substantia nigra
  2. Lewy bodies in neurones (alpha-synuclein protein accumulation)
33
Q

What are the main clinical presentations of Parkinsons’ disease

A
  1. Lead pipe rigidity (remember do not get confused with clasp knife rigidity in UMN issues)
    –> Cogwheel rigidity = Lead pipe rigidity + Tremor
  2. Bradykinesia (Hypomimia, Paucity of Blinking, Hypophonia, Decremental Bradykinesia such as micrographia and smaller arm swing, Festinant gait and smaller stride)
  3. Resting tremor (pill rolling)
34
Q

What are the other clinical presentations of Parkinson’s disease

A
  1. Psychiatric (Psychosis, Hallucinations, Depression)
  2. Sleep (Excessive daytime sleep, REM sleep disorders, Insomnia)
  3. Cognitive deficits (Progressive dementia, 6x more likely to develop cognitive defects)
  4. Autonomic dysfunction (Incontinence, Sialorrhea, Constipation, Postural hypotension)
35
Q

Treatment of Parkinsonism? (focus on medical treatment)

A
  1. Increase dopamine availability
    –> Sinemet/Maldopar are L-dopa + Carbidopa formulations (GOLD standard, 1st choice in older patients)

–>MAO inhibitors (Rasageline and Selegeline) - MOA: Prevent dopamine breakdown +U sed as adjuncts to L-dopa therapy

–> COMT inhibitors (Tolcapone and Entacapone) - MOA: Prevent dopamine breakdown +U sed as adjuncts to L-dopa therapy

  1. Stimulate dopamine receptors
    –> Dopamine agonists (Rotigotine, Ropinirole, Pramiprexole, Amantadine) (1st choice for younger patients + Administered to young patients first before resorting to L-dopa preparations when needed)
36
Q

What must we take note for L-dopa + Carbidopa Treatment? (+ ADVERSE)

A

1.Later on, when fluctuations are problematic, consider continuous infusion preparations - sc apomorphine or duodenal L-dopa
2. Prolonged treatment leads to diminished efficacy + more adverse effects
3. Short Term Adverse Effects (NIDIP) –> nausea, increased daytime sleepiness, dyskinesia, impulse control disorders, psychosis and hallucinations
4. Long Term Adverse Effects
–> on-off phenomenon, dyskinesia, freezing

37
Q

Why do we not just administer dopamine directly?

A

DO NOT administer dopamine as…
1. It is too large to cross BBB to reach target in brain
2. Positive inotrope - tachycardia and harder heart beating
3. Enhances and reduces blood flow to kidneys
4. Hypertension

38
Q

So how does L-dopa + Carbidopa work

A

Carbidopa (Dopa decarboxylase inhibitor) prevents the L-dopa from being converted to Dopamine when outside the CNS.

However, once L-Dopa enters the CNS, Carbidopa does not follow as it is too big to pass through the BBB, allows L-dopa to be converted to Dopamine in the CNS –> exert its function

39
Q

Pathogenesis fo Huntington disease/chorea

A
  1. Progressive neurodegenerative disorder caused by an inherited autosomal-dominant genetic mutation in the HTT gene
    Mutation in Huntingtin gene → increased trinucleotide repeats CAD → Huningtin protein accumulates in neurones of STRIATUM (caudate nucleus + putamen) and CORTEX

NOTE: Greater number of repeats = earlier age of onset, THEREFORE Spermatogenesis - Repeat expansions occur → paternal transmission is associated with anticipation (early onset in next generation)

40
Q

What are the clinical presentation of Huntington’s disease?

A
  1. Personality alterations
  2. Cognitive decline
  3. 15-20 year average duration (lifespan)
  4. Death from aspiration pneumonia + heart disease
  5. Can also cause dyskinesias
41
Q

What are the gross features of Huntington’s disease

A
  1. Small brain with atrophy of the caudate nucleus and frontal lobe
  2. (Later) Putamen and globus pallidus atrophied
  3. Dilated ventricles
42
Q

What are micro features of Huntington’s disease

A

**Atrophy and neuronal inclusions **

  1. Loss of striatal neurons → motor dysfunction
  2. Loss of cortical neurons → cognitive decline
43
Q

What are the metabolic and toxic diseases of the CNS?

A

Deficiencies
- Vitamin B1 (Thiamine) → Wernicke Encephalopathy
- Vitamin B12 → Subacute combined degeneration spinal cord

Storage Diseases
- Niemann Pick Disease
- Tay-Sachs Disease

Hepatic Encephalopathy

Carbon Monoxide Poisoning → Necrosis of globus pallidus + Diffuse cortical necrosis

Alcohol-related Diseases

44
Q

What are the consequences of thiamine (B1) deficiency

A

Thiamine deficiency → damage to medial thalamus + mammillary bodies + generalised cerebral atrophy

Wernicke Encephalopathy → acute development of psychotic symptoms or ophthalmoplegia
–> Morphology: haemorrhage and necrosis in mammillary bodies, walls of 3rd and 4th ventricles

Chronic alcohol abuse or severe malnutrition → Korsakoff’s syndrome/dementia/psychosis
–> Morphology: cystic spaces with hemosiderin laden macrophages

When Wernicke encephalopathy accompanies Korsakoff’s syndrome → Wernicke-Korsakoff syndrome

45
Q

What are the effects of alcohol on the brain

A
  1. Fetal Alcohol Syndrome (growth retardation and cerebral malformations)
  2. Acute Intoxication → respiratory depression → death
  3. Chronic Alcoholism
    - Cerebral cortical atrophy
    - Cerebellar atrophy
    - Wernicke Encephalopathy (Thiamine deficiency)
    - Korsakoff’s Psychosis
46
Q

Korsakoff’s Syndrome major symptoms (6)

A
  1. Anterograde amnesia
  2. Retrograde amnesia
  3. Confabultion - invented memories which are taken as true due to gaps in memories sometimes associated with blackouts
  4. Meager content in conversation
  5. Lack of insight
  6. Apathy - patients lose interest in things quickly and generally appear indifferent to change
47
Q

What are the histological features of the brain due to alcohol

A
  1. Atrophy of cerebellar vermis
  2. Haemorrhage in mammilary bodeies

Roy's Pathology (G3) (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions