motor neurone disease

Question 1

what is motor neurone disease

Answer 1

adult onset neurodegenerative disorder

third commonest after AD and PD

mean survival 2-5 years

Question 2

what are the commonest symptoms of MND?

Answer 2

weakness of limbs, bulbar and respiratory muscles

Question 3

what are the three main types of MND?

Answer 3

Primary lateral Sclerosis

Amyotrophic lateral sclerosis (lou gherig’s)

progessive musclar atrophy

Question 4

what is the difference between an upper motor neuron and a lower motor neuron?

Answer 4

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.

Question 5

what are the UMN symptoms?

Answer 5

symptoms: 
weakness
stiffness
muscle spasm
pain
emotional lability
spastic gait

Question 6

what are the UMN signs?

Answer 6

signs:
pyramidal weakness
no wasting
increased tone
brisk reflexes 
extensor plantars
ankle clonus
brisk jaw jerk
pseudobulbar palsy

Question 7

what is the pattern of pyramidal weakness in UMN

Answer 7

upper limbs: extensors weaker than flexors

lower limbs: flexors weaker than extensors

fine movements worst affected

Question 8

what are the LMN symptoms

Answer 8

weakness
loss of muscle bulk
muscle twitches
cramps

Question 9

what are the LMN signs?

Answer 9

reduced power
muscle wasting
fasiculations limbs/tongue
decreased tone
reduced/absent reflexes
flexor plantars

Question 10

what LMN signs are prominent in MND?

Answer 10

wasting

weakness

fasiculations

Question 11

what is the difference between PLS, ALS & PMA?

Answer 11

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

Question 12

which motor neurons are generally not affected in MND?

Answer 12

occulomotor motor neurons
iii, iv, VI responsible for eye movement

motor neurons withing onuf’s nucleus:
sacral motor neurons serving pelvic floor muscles

Question 13

what epidemiological factors are associated with ALS

Answer 13

diet (what?)

electric shock

heavy metals

exercise

genetics

Question 14

what is the diagnostic criteria for ALS: (El Escorial)

Answer 14

[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

Question 15

what are the classifications of ALS

Answer 15

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

Question 16

what clinical features point to possible ALS

Answer 16

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

Question 17

what are the segmental variants of ALS

Answer 17

flail arm
flail leg
monomelic
proressive bulbar palsy

Question 18

what are some differentials for ALS:

Answer 18

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.

Question 19

what percentage of ALS are misdiagnosed?

Answer 19

7-8%

Question 20

what investigations can be conducted for MND/ALS

Answer 20

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

Question 21

what are some mechanisms as to why motor neurons die in ALS?

Answer 21

mitochondrial dysfunction

protein aggregation

excitotoxicity

axonal transport

oxidative stress

Question 22

what are some features of neurophysiological investigation in ALS/MND

Answer 22

denervation in bulbar muscles and thoracic paraspinals

conduction block

Question 23

what features differentiate kennedy’s from ALS/MND?

Answer 23

males only
pure LMN disorder

proximal symmetrical weakness

gynaecomastia

sensory changes

slow progression

tongue wasting out of proportion to dysarthria

Question 24

what are the clinical clues to differentiate CSM: cervical spondylotic myelopathy from ALS/MND

Answer 24

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
`
CSM can cause pure motor syndrome

Question 25

what features differentiate Multifocal motor neuropathy with conduction block from ALS/MND

Answer 25

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

Question 26

what features distinguish Inclusion body Myositis from MND?

Answer 26

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

Question 27

what are the fetures of thryrotoxicosis

Answer 27

may present with muscle weakness, wasting, fasiculations and weight loss

some patients appear to have concomitant UMN signs

Question 28

what are the features of benign cramp fasiculation syndrome?

Answer 28

1% of population

most common in middle aged men

calf muscles most commonly affected

no evidence of progression

Question 29

compressive pure motor focal neuropathies:

Answer 29

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