Motor Neuron Disease Flashcards
Upper motor neuron signs
increased tone hyperreflexia extensor plantar response spastic gait exaggerated jaw jerk slowed movements
lower motor neuron signs
muscle wasting
weakness
fasciculations
absent or reduced deep tendon reflexes
upper motor neuron
brain and spinal cord
lower motor neuron
exiting spinal nerve
types of MND
Amyotrophic lateral sclerosis (ALS) Hereditary spastic paraplegia (HSP) primary lateral sclerosis (PLS) progressive muscular atrophy (PMA) Progressive bulbar palsy (PBP) pseudobulbar palsy Spinal Muscular Atrophy (SMA) Fredrich's ataxia
reflexes in UMN
higher inhibition over reflex arc is lost causing excessive firing from alpha motor neuron = exaggerated deep tendon reflexes
reflexes in LMN lesion
alpha motor neuron distally is injured, loop isn’t completed = no reflex
muscle bulk in LMN lesion
wasting as no innervation
muscle bulk in UMN lesion
muscle still contracts locally even if higher innervation lost, passive movement preserves bulk
tone in UMN lesion
exaggerated as modulation of gamma neuron is lost so nerve fires spontaneously
tone in LMN lesion
absence of innervation so flaccid tone
fasciculations in LMN lesion
LMN will erratically discharge its neurotransmitter
symptoms caused when cortex affected
any of others
symptoms caused by midbrain/pon involvement
dysphagia, dysarthria, dysphonia, pseudobulbar affect, hypersalivation
symptoms caused by medulla involvement
arm, trunk and leg symptoms
symptoms caused by cervical spinal cord involvement
poor dexterity/handwriting, weak grip, weak arms
symptoms caused by thoracic spinal cord involvement
symptoms of type 2 respiratory failure, early morning headaches, breathlessness on exertion, lethargy, drowsy
symptoms caused by lumbar spinal cord involvement
foot drop/tripping, stiffness, leg weakness, poor balance, falls
ALS is characterised by progressive loss of which regions?
frontotemporal, bulbar and ventral cord motor neurons
pathophysiology of ALS
glutamate toxicity - cause increased calcium entry = cell dysfunction, oxidative stress and cell death
protein misfolding - accumulation and aggregation of intracellular and membrane protein = formation of toxic oligomers, also interfere with apoptotic mechanisms
oxidative stress -superoxide radicals
microglial activation - with mutant SOD1 have altered protective mechanisms
mitochondrial dysfunction
cause of ALS
unknown
combination of genetic and environment
environmental factors related to ALS
military service, smoking, alcohol, lead exposure, previous trauma, sports
genetic factor related to ALSO
mutations in SOD1 gene
also 9ORF72, FUS, TARDBP
ALS - UMN or LMN
mixture of both
ALS symptoms
UMN and LMN features
normal sensation
frontal lobe - frontal dementia, emotional changes
Bulbar - dyspnoea, swallowing, slurred speech, sialorrhea and drooling
Weakness - extensors in upper limbs, flexors in lower limbs
diagnosis of definite ALS
UPPER AND LOWER MOTOR NEURON SIGNS IN BULBAR AND AT LEAST TWO SPINAL (LUMBOSACRAL, THORACIC, OR CERVICAL) REGIONS OR UPPER AND LOWER MOTOR NEURON SIGNS IN THREE SPINAL REGIONS
diagnosis of probable ALS
CLINICALLY PROBABLE – UPPER AND LOWER MOTOR NEURON SIGNS IN AT LEAST 2 REGIONS (BULBAR OR SPINAL) WITH SOME UMN SIGNS ROSTRAL TO THE LMN SIGNS
LAB SUPPORTED – CLINICAL EVIDENCE OF UMN AND LMN SIGNS IN ONE BODY REGION OR OF UMN SIGNS IN ONE REGION AND EMG FINDINGS OF LMN INVOLVEMENT IN AT LEAST 2 BODY REGIONS
UMN AND LMN SIGNS IN ONLY THE BULBAR OR ONLY ONE SPINAL REGION OR UMN SIGNS IN 2 OR MORE REGIONS OR LMN SIGNS ROSTRAL TO UMN SIGNS
investigations for ALS
EMG, nerve conduction studies, MRI, thyroid and calcium studies
Screen for paraproteinemia, lymphoreticular disease and hexosaminidase deficiency
riluzole is a type of which medication
anti-glutamic
management for ALS
physiotherapy, occupational therapy speech therapy nutritional needs respiratory needs Medication - riluzole (also anti-spasmic agents)
PLS is characterised by
progressive muscle weakness in voluntary muscles
PLS - UMN or LMN
UPPER MOTOR ALONE
PLS causes
unknown
combo genetic and environmental
Juvenile caused by ALS2
Clinical features of PLS
UMN features
gradual onset progressive lower extremity stiffness and pain
affects extremities, trunk, upper extremities and bulbar muscles
often asymmetrical
PMA - UMN or LMN
LMN only
PMA clinical features
LMN features
HSP characterised by
length dependent axonal degeneration
HSP involves which regions
crossed and uncrossed corticospinal tracts to the legs and fasciculus gracillis
spinocerebellar tract is involved to a lesser extent (pyramidal tract)
pathophysiology of HSP
mutations affecting: axonal pathfinding - L1CAM lipid metabolism - ATL1, BCL2, ERLIN2 myelin formation - PLP1, GFC2, FA2H endosomal trafficking - AP4b! mitochondrial function
causes in HSP
autosomal dominant inherited disorders
SPG gene
clinical features of HSP
progressive spasticity in the lower limbs
brisk reflexes
extensor plantar reflexes
lower limb muscle weakness, muscle tone lower limbs increased
bladder disturbances
abnormal gait
decreased vibrators sense at the ankles
paraethesia
upper extremity muscle tone and strength normal
Progressive Bulbar Palsy is
corticobulbar degeneration and lower cranial nerve motor nuclei involvement
regions affected in PBP
degeneration of motor neurons in the cerebral cortex, spinal cord, brain stem and pyramidal tracts
degeneration of corticobulbar pathways to V, VII, X, XI, XII cranial nerve motor nuclei
causes of PBP
SOD1 Mutation
Clinical features of PBP
WEAKNESS OF MUSCLES OF MASTICATION AND EXPRESSION (TROUBLE CHEWING AND FACE IS EXPRESSIONLESS)
EXAGGERATED JAW JERK
DIFFICULTY SWALLOWING
ATROPHY AND FASCILATIONS IN SUPPLIED MUSCLES
TONGUE APPEARS WASTED AND FOLDED
DROOLING
Spinal Muscular Atrophy is caused by
mutations in survival motor neuron 1 (SMN1) leading to defective splicing and therefore defective proteins causing LMN degeneration
SMN1 gene codes for what
survival motor neurone protein 1m an enzyme hat regulates global gene expression in cells. Its main function is in gene splicing.
clinical features of SMA
muscle weakness lack of motor development reduced muscle tone tongue fasciculations postural finger tremor loss of tendon reflexes
diagnosis of SMA
SMN1 gene testing
Friedreichs ataxia is…
autosomal recessive genetic disease that leads to neurological, cardiac and endrocrine manifestations
pathophysiology of Friedreichs ataxia
expansion of a guanine-adenine-adenine (GAA) trinucleotide repeat that leads to mitochondrial dysfunction
cause of Friedreichs
FRDA1 mutations
clinical features of Friedreichs ataxia
onset before the age of 25
progressive ataxia of limbs and gait
loss of knee and ankle reflexes
extensor plantar response
what is spinocerebellar ataxias
diverse group of autosomal dominant clinical syndromes whose core feature is progressive cerebellar ataxia
pathophysiology of spinocerebellar ataxia
similar to Friedreichs ataxia - caused by triplet expansion mutation of CAG in specific genes
