20 - MN disease

Question 1

signs of MN degeneration: upper vs. lower

Answer 1

upper = some weakness, normal bulk, no fasiculations, increased tone and reflexes aka spasticity. lower = lots of weakness, atrophy, fasiculations, decreased tone and reflexes

Question 2

3 anatomic syndromes

Answer 2

UMN = primary lateral sclerosis. LMN = progressive muscular atrophy. upper and lower = ALS

Question 3

clinical features of ALS? what is affected? what is spared? survival?

Answer 3

muscle wasting, weakness, fasiculations, spasticity, cramps. limb, bulbar and respiratory affected. spared: sensation, sphincter function. 2 - 5 years.

Question 4

bulbar clinical features

Answer 4

speech. chewing. swallowing. coughing, chocking, excess saliva. weight loss. dehydration.

Question 5

lower extremity clinical features

Answer 5

foot drop. difficulty with chairs and stairs

Question 6

upper extremity clinical features

Answer 6

hand: find motor activities like writing. shoulder: frozen shoulder, proximal arm weakness. axial: stooped posture

Question 7

respiratory clinical features

Answer 7

dyspnea aka shortness of breath. orthopnea aka difficulty breathing when lying down. sleep disordered breathing

Question 8

cognitive clinical features? prevalence? results?

Answer 8

frontotemporal: executive dysfunction and behavioural impairment. up to 50%. impacts decision making capacity + reduced survival.

Question 9

VBM in findings in ALS?

Answer 9

decreased grey matter volume in motor cortex, frontal and temporal lobes

Question 10

MRS findings in ALS?

Answer 10

decreased NAA (neuronal marker). increased glial marker mI. decrease NAA to mI ratio. so degeneration, but increase glia.

Question 11

extra-motor pathology: where?

Answer 11

frontotemporal lobar degeneration

Question 12

spectrum of ALS and FTD: linked by?

Answer 12

molecular link: ubiquinated cytoplasmic inclusions in FTD and ALS both contain TDP 43 protein

Question 13

most common genetic cause

Answer 13

C9ORF72

Question 14

MRI findings for ALS?

Answer 14

qualitative: low sensitivity + specificity but will see atrophy, hyperintensity of corticospinal tract and hypointense ribbon in motor cortex

Question 15

goal of disease management?

Answer 15

maximize quality of life + death

Question 16

disease modifying treatment: drug name? effect?

Answer 16

riluzole: antiglutamatergic, prolongs survival 3 - 6 months

Question 17

3 important interventions in ALS

Answer 17

BiPAP (ventilation). PEG (feeding tube). multisiciplinary care.

Question 18

ceftriaxone: what? effects?

Answer 18

beta-lactam antibiotic: stimulates glutamate transporter. didn’t work in clinical trials but had been promising in in vivo/vitro neuroprotection

Question 19

no effective treatment yet…what is required?

Answer 19

objective, sensitive + indirect measure of disease burden and drug efficacy: biomarkers

Question 20

take home: ALS is a ___ disease? what poses challenges to finding treatment?

Answer 20

multisystem disease. clinical and pathogenic heterogeniety pose challenges to finding treatment.

Question 21

take home: important goal? 4 important interventions?

Answer 21

maximize quality of life. riluzole, biPAP, PEG, multidisciplinary care