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