Test
NE10 Other neurological disorders
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Preguntas del test (16)
1By the end of this lecture you will be able to:
1. Describe the pathophysiology of motor neurone disease and multiple sclerosis
2. Describe available treatments for these disorders
• Mechanisms of action
• Main unwanted effects
[blank_start]OK[blank_end]- AOK
2Motor neurone disease is [blank_start]progressive degeneration[blank_end] of motor neurons. The most affected group is [blank_start]middle aged males[blank_end].
Motor neurons - Upper ones originate in brain, lower ones originate in spinal cord. MND affects [blank_start]both[blank_end] upper and lower. Also know as:
• [blank_start]Lou Gehrig's[blank_end] Disease
• Charcot's Disease (in Europe).
• Amyotrophic Lateral [blank_start]Sclerosis[blank_end] (in US)- Aprogressive degeneration
- Bmiddle aged males
- Cboth
- DSclerosis
- ELou Gehrig's
3Which of these is NOT a presentation of MND?
- AStumbling
- BDropping, difficulty holding things
- CHoarse voice/slurred speech
- DMuscle cramps
- EDysphagia
- FFatigue
- GBehavioural/emotional changes
- HSevere cognitive difficulties
4What causes MND?
Most cases [blank_start]sporadic[blank_end]...
• [blank_start]Viral[blank_end] infection
• [blank_start]Immune[blank_end] mediated damage
• Premature motor neuron [blank_start]aging[blank_end]
• Loss of [blank_start]growth factors[blank_end]
[blank_start]5-10[blank_end]% hereditary ([blank_start]SOD[blank_end] mutation).
Pathophysiology?
• TDP-43 [blank_start]RNA splicing[blank_end] dysfunction
• Excessive [blank_start]glutamate R[blank_end] activation
• Intracellular [blank_start]Ca2+ overload[blank_end]
• Mitochondrial damage
• [blank_start]Excitotoxic[blank_end] cell death
• Oxidative stress ([blank_start]free radicals[blank_end])- Asporadic
- BViral
- CImmune
- Daging
- Egrowth factors
- F5-10
- GSOD
- Hglutamate R
- ICa2+ overload
- JExcitotoxic
- Kfree radicals
- LRNA splicing
5Tx for motor neurone disease:
1. Riluzole
Slows progression, prolongs median survival time by [blank_start]2-3 months[blank_end]
Multiple effects on [blank_start]glutamate[blank_end] neurotransmission.
Presynapic: inhibits [blank_start]release[blank_end] - inhibits [blank_start]voltage gated Na+[blank_end] channels
Postsynaptic: prevents [blank_start]action[blank_end] - non competitive [blank_start]blockade of NMDA[blank_end] Rreceptors
Contraindicated: hepatic impairment
Caution: [blank_start]neutropenia[blank_end] (fever, sore-throat, malaise)
2. Endaravone (not available in NZ). First FDA approved MND therapy in [blank_start]22[blank_end] years. Free [blank_start]radical[blank_end] scavenger.- A2-3 months
- Bglutamate
- Cvoltage gated Na+
- Drelease
- Eaction
- Fblockade of NMDA
- Gneutropenia
- H22
- Iradical
6Which of these is not a common unwanted effect of riluzole?
- ANausea and vomiting
- BLethargy
- CDizziness
- DDiarrhoea
7Multiple Sclerosis is an [blank_start]autoimmune[blank_end] disorder that affects nerve [blank_start]conduction[blank_end]. There are multiple areas of [blank_start]scarring[blank_end] in the brain, and spinal cord. Inflammation causes relapse. [blank_start]Demyelination and axon damage[blank_end] cause:
Optic neuritis, weakness, spasticity, ataxia, [blank_start]bladder and bowel[blank_end] dysfunction.
Epidemiology:
- Affects 1 in 1000
- [blank_start]Young[blank_end] adults (average age 37 years old)
- [blank_start]Women[blank_end] three times more than men
• [blank_start]Caucasians[blank_end]
• People in [blank_start]cooler[blank_end] climates- Aautoimmune
- Bconduction
- Cscarring
- DDemyelination and axon damage
- Ebladder and bowel
- FYoung
- GWomen
- HCaucasians
- Icooler
8Pathology of MS:
Trigger = [blank_start]peripheral[blank_end] immune response. Primed [blank_start]T and B[blank_end] lymphocytes cross [blank_start]BBB[blank_end]. Upregulation of [blank_start]integrins[blank_end] causes [blank_start]adhesion[blank_end],
Inflammation -
[blank_start]Th1 lymphocytic[blank_end] autoimmune response involving INF-g, IL-17, TNF-b.
[blank_start]B[blank_end] cell mediated [blank_start]antibodies[blank_end] - [blank_start]Initiate[blank_end] myelin destruction
[blank_start]Macrophages[blank_end] -
Destroy myelin [blank_start]sheath[blank_end], damage [blank_start]oligo[blank_end]dendrocytes. Demyelination leads to [blank_start]axon[blank_end] damage- Aperipheral
- BT and B
- CBBB
- Dintegrins
- Eadhesion
- FTh1 lymphocytic
- GB
- Hantibodies
- IInitiate
- JMacrophages
- Ksheath
- Loligo
- Maxon
9Drug treatment for MS:
Reduction of symptoms.
15% of patients have [blank_start]primary[blank_end] progressive MS, 85% [blank_start]relapsing- remitting[blank_end] MS ([blank_start]secondary[blank_end] progressive MS).
• Modulating immune response early reduces [blank_start]disability[blank_end]- Aprimary
- Brelapsing- remitting
- Csecondary
- Ddisability
10Fingolimob
• Oral [blank_start]prodrug[blank_end] (reversible [blank_start]phosphorylation[blank_end])
• Agonist of [blank_start]sphingosine-1-phosphate[blank_end] R
• Then internalisation prevents [blank_start]lymphocyte[blank_end] egress, reduced [blank_start]migration[blank_end] to lesions
Immunomodulator - [blank_start]infections[blank_end] risk
UEs: Headache, migraine, [blank_start]dizziness, paraesthesia, depression[blank_end]
Caution: patients with [blank_start]CV[blank_end] risk – transient bradycardia, heart block.- Aprodrug
- Bphosphorylation
- Csphingosine-1-phosphate
- Dlymphocyte
- Emigration
- Finfections
- Gdizziness, paraesthesia, depression
- HCV
11Teriflunomide
• Immunomodulator, anti-inflammatory
• Selective, [blank_start]irreversible[blank_end] inhibition of dihydro-orotate dehydrogenase
• Key [blank_start]enzyme[blank_end] in de novo [blank_start]pyrimidine[blank_end] synthesis
• Reduced [blank_start]proliferation[blank_end] of activated T and B cells (without cell death)
Contraindicated: [blank_start]blood[blank_end] disorders, severe [blank_start]immunodeficiency[blank_end]
Caution: >65 years, significant [blank_start]alcohol[blank_end] consumption- Airreversible
- Benzyme
- Cpyrimidine
- Dproliferation
- Eblood
- Fimmunodeficiency
- Galcohol
12Dimethyl fumarate
• Immunomodulatory
• Anti-[blank_start]oxidative[blank_end]
• Anti-[blank_start]inflammatory[blank_end]
• MMF upregulates nuclear factor (erythroidlike)2 (Nrf2) pathways
• Activated by oxidative-stress
Unwanted effects: [blank_start]flushing, abdominal pain, rash, itching[blank_end], GI - [blank_start]diarrhoea, N&V[blank_end]- Aoxidative
- Binflammatory
- Cflushing, abdominal pain, rash, itching
- Ddiarrhoea, N&V
13[blank_start]Natalizumab[blank_end] - humanized monoclonal antibody
• Selective for [blank_start]a4 integrin[blank_end]
• Prevents [blank_start]interaction[blank_end] with R
• Cant cross [blank_start]BBB[blank_end]
Unwanted effects ([blank_start]infusion[blank_end] related): flushing, rigors, fatigue, fever, arthralgia, sore throat…[blank_start]hypersensitivity[blank_end] reactions (1%)- ANatalizumab
- Ba4 integrin
- Cinteraction
- DBBB
- Einfusion
- Fhypersensitivity
14Interferons
Reduce immune response (directed @ [blank_start]myelin[blank_end]) to reduce [blank_start]frequency[blank_end] of relapses
Unwanted effects:
• [blank_start]Flu-like[blank_end] symptoms common
• [blank_start]Ulceration[blank_end] @ injection site- Amyelin
- Bfrequency
- CFlu-like
- DUlceration
15Glatiramer acetate - Used when interferon effectiveness reduced.
• Synthetic [blank_start]tetra peptide immunomodulator[blank_end]
Unwanted effects:
• [blank_start]Lipoatrophy[blank_end]
• Post injection reaction: shortness of [blank_start]breath[blank_end], [blank_start]chest[blank_end] tightness, flushing (15-30 mins)- Abreath
- Bchest
- CLipoatrophy
- Dtetra peptide immunomodulator
16Ocrelizumab - Not funded, under consultation
[blank_start]Humanised[blank_end] monoclonal that targets [blank_start]CD20+ B cells[blank_end]
Unwanted effects:
- [blank_start]Infusion[blank_end] related reactions
- [blank_start]URTIs[blank_end]
- Oral herpes reactivation, neoplasms- AHumanised
- BCD20+ B cells
- CInfusion
- DURTIs
Información
- Descripción
- El usuario ha eliminado su información de asignaturas Test sobre NE10 Other neurological disorders, creado por Usuario eliminado el 11/10/2019.
- Autor
- Usuario eliminado
- Idioma
- English
- Visitas
- 58
- Historial
- Creado el 11 oct 2019 · actualizado el 11 oct 2019
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