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Book Reading -Motor Neuron Disease
ReporterI1 林宜慧
Stories•冰桶挑戰• Tuesdays with Morie•霍金
Outline
Definition Classification
Diagnosis Treatment
Outline
Definition Classification
Diagnosis Treatment
* ALS* Other - SMA - Poliomyelitis* Less well-defined etiologies
* History* PE
* Laboratory* Electrodiagnosis
* Medication* Rehabilitation* Exercise* Disease– related impact
Definition Definition
• Dysfunction and degeneration of motor neurons. • ALS is the prototypical and the most common form in
adulthood.
Amyotrophic Lateral Sclerosis
Classifi-cation
Lou Gehrig's disease
ALS• Incidence : 1.4/100,000• Begin : 60-70y• Men : women = 1.6 : 1 Degeneration of both the UMNs and LMNsSparing of other neurons
Classifi-cation
ALS pathogenic Classifi-cation
• pathogenic mechanisms - undefined • Gene mutations for familial ALS (fALS) • clinical similarity • chromosome 9 : hexanucleotide repeat expansion • C9ORF72
ALS Classifi-cation
• accumulation of transcribed repeats may bind and sequester RNA-binding proteins and lead to abnormal RNA metabolism and processing.
ALS Classifi-cation
Primary Lateral Sclerosis Progressive muscular atrophy
leg amyotrophic diplegia
brachial amyotrophic diplegia
progressive bulbar palsy
ALS Classifi-cation
Primary Lateral Sclerosis Progressive muscular atrophy
leg amyotrophic diplegia
brachial amyotrophic diplegia
progressive bulbar palsy
預後
基準點
差好好
好 好
Primary Lateral Sclerosis Classifi-cation
• bulbar muscles related degeneration of UMNs• progressive spasticity and weakness of limb • Rare• 50y• etiology : unknown• fasciculations, cramps• LMN involvement.
PLS Classifi-cation
• 8 and 15 years after diagnosis • Charcot“the clinical description deserves to exist
alone.”
• unilateral leg spasticity • -> 1~2y -> the other leg • -> 3~4y -> upper limbs • -> 1~2y -> bulbar involvement
PLS Classifi-cation
• clinical diagnosis • exclude other possible diagnoses. • MRI - central nervous system disorders• Transcranial magnetic stimulation (TMS) : confirmatory
test• severe abnormalities • absent potentials
VCR
PLS Classifi-cation
• no disease-modifying treatment • no studies have shown efficacy of riluzole• Symptomatic treatment
Progressive Muscular Atrophy
ALS Classifi-cation
Primary Lateral Sclerosis Progressive muscular atrophy
leg amyotrophic diplegia
brachial amyotrophic diplegia
progressive bulbar palsy
PMA Classifi-cation
• LMN degeneration• signs of UMN degeneration • older men • atrophy and weakness (hands) • Reflexes are reduced or absent• EMG : fibrillation potentials, positive sharp waves• differential diagnosis : LMN-predominant ALS, other
MNDs
PMA Classifi-cation
• D/D: multifocal motor neuropathy (MMN) • immunomodulatory treatment
• Not respond to riluzole• supportive treatment• Average of living : ALS+1y
Regional ALS Variants
ALS Classifi-cation
Primary Lateral Sclerosis Progressive muscular atrophy
leg amyotrophic diplegia
brachial amyotrophic diplegia
progressive bulbar palsy
Regional ALS Classifi-cation
• remain restricted to certain regions• PBP, progressive bulbar palsy • bulbar symptoms • Older• poorer prognosis
Regional ALS Classifi-cation
• BAD, brachial amyotrophic diplegia • proximal prominent upper limb weakness • bulbar, thoracic, and lumbar : unaffected >12y
• LAD, leg amyotrophic diplegia • distal-predominant • delayed progression
• genetically defined ALS may have clinical features of these variant syndromes
Familial ALS
fALS Classifi-cation
• Superoxide dismutase 1 (SOD1) mutations • 10% of fALS • 1% of sporadic ALS
• D90A mutation of SOD1 • indolent course • 10+ y
• A4V mutation • 1y
fALS Classifi-cation
• C9ORF72 gene • hexanucleotide repeat • 40% of fALS • 5% of sporadic ALS
• 20 gene mutations associated
ALS-Plus Syndromes
ALS+ Classifi-cation
• involvement outside of the motor system • Parkinsonism/ frontotemporal dementia / sensory loss
• fALS - TAR DNA-binding protein (TARDBP) • parkinsonism
• ALS is a multi-system disease with predilection for UMN and LMN involvement
Other MND
Outline
Definition Classification
Diagnosis Treatment
* ALS* Other - SMA - Poliomyelitis* Less well-defined etiologies
* History* PE
* Laboratory* Electrodiagnosis
* Medication* Rehabilitation* Exercise* Disease– related impact
Spinal Muscular Atrophy Classifi-cation
• a group of genotypically and phenotypically diverse disorders associated with features of LMN loss• proximal SMA : autosomal recessive • 1/11,000 births• most common genetic cause of death in infants
• spectrum : onset of disease and severity
Proximal SMA• SMA type 1• most common form• onset before 6 m• sit upright is never
achieved
Classifi-cation
Proximal SMA• SMA type 2 • onset : 6-18m• (V) Sit, (X) stand
• SMA type 3 • onset > 18 months • stand or walk at least
temporarily
Classifi-cation
Proximal SMA Classifi-cation
出生 6m 18m 30y
SMA subtype
1 2(x)sit
3(x)stand
4 5
SMA Classifi-cation
• deletion or mutation of the survival motor neuron 1 (SMN1) gene • proximal predominant weakness and hypotonia• Reflexes : absent or reduced • Electrodiagnostic testing genetic testing • no effective therapies for any form of SMA • supportive care
Take home massage Classifi-cation
Primary Lateral Sclerosis Progressive muscular atrophy
leg amyotrophic diplegia
brachial amyotrophic diplegia
progressive bulbar palsy
預後
基準點
差好好
好 好
Take home massage Classifi-cation
出生 6m 18m 30y
SMA - LMN loss
1 2(x)sit
3(x)stand
4 5