motor neurone disease Flashcards
what is motor neurone disease
adult onset neurodegenerative disorder
third commonest after AD and PD
mean survival 2-5 years
what are the commonest symptoms of MND?
weakness of limbs, bulbar and respiratory muscles
what are the three main types of MND?
Primary lateral Sclerosis
Amyotrophic lateral sclerosis (lou gherig’s)
progessive musclar atrophy
what is the difference between an upper motor neuron and a lower motor neuron?
an upper motor neurone is a neuron that originates in the cerbral cortex or brain stem
a lower motor neuron is a neuron that originates in the anterior grey column of the spinal cord or anterior nerve roots
or cranial nerve nuclei of the brainstem.
what are the UMN symptoms?
symptoms: weakness stiffness muscle spasm pain emotional lability spastic gait
what are the UMN signs?
signs: pyramidal weakness no wasting increased tone brisk reflexes extensor plantars ankle clonus brisk jaw jerk pseudobulbar palsy
what is the pattern of pyramidal weakness in UMN
upper limbs: extensors weaker than flexors
lower limbs: flexors weaker than extensors
fine movements worst affected
what are the LMN symptoms
weakness
loss of muscle bulk
muscle twitches
cramps
what are the LMN signs?
reduced power muscle wasting fasiculations limbs/tongue decreased tone reduced/absent reflexes flexor plantars
what LMN signs are prominent in MND?
wasting
weakness
fasiculations
what is the difference between PLS, ALS & PMA?
PLS: almost pure upper motor neuron involvement
(survival longer than others)
ALS: Mixed UMN and LMN
prognosis 2-5 years
PMA: almost pure lower
prognosis similar to ALS
which motor neurons are generally not affected in MND?
occulomotor motor neurons
iii, iv, VI responsible for eye movement
motor neurons withing onuf’s nucleus:
sacral motor neurons serving pelvic floor muscles
what epidemiological factors are associated with ALS
diet (what?)
electric shock
heavy metals
exercise
genetics
what is the diagnostic criteria for ALS: (El Escorial)
[A] the presence of:
1) evidence of LMN degeneration by clinical, electrophysiological or neuropathological examination
2) evidence of UMN degneration by clinical examination and
3) progressive spread of symptoms or signs within a region or to other regions as determined by history or examination
[B] together with absense of:
1) electrophysiological and pathological evidence of other disease that might explain the signs of LMN and/or UMN degeneration
2) neuroimaging evidence of other disease processes that might explain the clinical and electrophysiological signs
what are the classifications of ALS
Definite ALS: UMN and LMN signs in 3 regions
probable: UMN and LMN signs in 2 regions with at least some UMN signs rostral to LMN signs
probably (lab supported): UMN signs in 1 or more regions and LMN signs defined by EMG in at least 2 regions
possible ALS:
UMN signs and LMN signs in 1 region (together with)
UMN signs in 2 or more regions
UMN and LMN signs in 2 regions with no UMN signs rostral to LMN signs
what clinical features point to possible ALS
combination of upper and lower motor neuron signs
absence of pain,
significant sensory signs, sphincter disturbance
preservation of or brisk reflexes in a limb severe muscular atrophy
dysarthria-typically mixed spastic/flacid
in the upper limbs: early involvement of intrinsic hand muscles. triceps and finger flexors remain relatively strong until late
lower limbs: early involvement of hip flexion and ankle dorsiflexion
quads and plantar flexion typically remain preserved until late
what are the segmental variants of ALS
flail arm
flail leg
monomelic
proressive bulbar palsy
what are some differentials for ALS:
Genetic: Kennedy’s disease, spinal muscular atrophy
infective: post-polio syndrome, lyme disease, HIV
metabolic/toxic:
lead and mercury poisoning, thyrotoxicosis
structural: foraman magnum lesions, spondylotic myelopathy
immunological/inflammatory:
polymyositis, Myasthenia gravis, Inclusion body myositis.
paraneoplastic: lymphoproliferative disease
others: cramp fasiculation syndrome.
what percentage of ALS are misdiagnosed?
7-8%
what investigations can be conducted for MND/ALS
neurophysiological to exclude changes explained by single nerve, root or plexus
imaging: MRI brain and spine, sometimes brachial plexus
bloods: ca, CK, thyroid, ACh-R Ab
CSF
genetic testing for familial disease
muscle biopsy (reserve for atypical cases of uncertainty or if CK >1000)
baseline resp function
what are some mechanisms as to why motor neurons die in ALS?
mitochondrial dysfunction
protein aggregation
excitotoxicity
axonal transport
oxidative stress
what are some features of neurophysiological investigation in ALS/MND
denervation in bulbar muscles and thoracic paraspinals
conduction block
what features differentiate kennedy’s from ALS/MND?
males only
pure LMN disorder
proximal symmetrical weakness
gynaecomastia
sensory changes
slow progression
tongue wasting out of proportion to dysarthria
what are the clinical clues to differentiate CSM: cervical spondylotic myelopathy from ALS/MND
natural history is important distinguishing feature
UMN signs caudal to LMN signs, lhermitte’s sign, pain, sensory symptoms
initially progressive phase then plateau
difficult as:
concommitant degenerative spine disease is common in MND
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CSM can cause pure motor syndrome
what features differentiate Multifocal motor neuropathy with conduction block from ALS/MND
No UMN signs
more males than females
weakness in non-wasted muscles
may have signal change on T2 MRI f brachial plexus and serum anti-GM1 ganglioside antibodies
amenable to treatment with IVig
what features distinguish Inclusion body Myositis from MND?
early prominent weakness of finger flexors and quadriceps- quite different to the pattern in MND
Dysphagia not accompanied by dysarthria
EMG may show neurogenic change
Muscle biopsy- creatine kinase levels
what are the fetures of thryrotoxicosis
may present with muscle weakness, wasting, fasiculations and weight loss
some patients appear to have concomitant UMN signs
what are the features of benign cramp fasiculation syndrome?
1% of population
most common in middle aged men
calf muscles most commonly affected
no evidence of progression
compressive pure motor focal neuropathies:
compression of the deep brance of the ulnar nerve:
can present with weakness and wasting of the intrinsic muscles of the hand in the absense of pain or sensory loss
(prolonged pressure: cycling, tools)
compression of posterior interosseous branch of radial nerve
presents with weakness of wrist extension with radial drift
