Motor Neuron Disease

• Definition: progressive degeneration of neurons in the motor cortex, cranial nerve nuclei
and anterior horn cells, upper and lower motor neurons are affected but there is no loss of
sphincter or sensory function (unlike MS or polyneuropathies). MND affects external eye
movements [CNIII, IV and VI] (unlike myasthenia gravis).
• Epidemiology: most common neurodegenerative disease of the motor system affects 2.6 in
100,000. M:F 1.5:1, Affects young and middle aged adults.
• Aetiology:
o Unknown

Ubiquitin-proteoasome system: Inclusions

Neurofilament disruption

Neurotransmitter system disruption
• Neurotrophic factors
• Heavy metals
• Oxidative stress
• Hypoxia responsiveness (VEGF, ANG etc)
o Familial 10% of cases: AD with Mendelian pattern of inheritance. 10-20% mutation in
copper/zinc-binding superoxide dismutase gene SOD1
o Western Pacific ALS: Ingestion of food products derived from the false sago palm
Cycas micronesica is thought to cause ALS.
• Risk factors: Family history, smoking[probable risk factor]
• Pathology:
o Degeneration of the upper motor neurons  loss of myelinated fibres in the
corticospinal tract
o Occasionally there is atrophy of the pre-central gyrus
• History & Exam
o Symptoms depend on where it starts:

Slurred speech, swallowing difficulties, breathing difficulties
• 45% of Irish ALS patients have some difficulty swallowing
• 81% have swallowing dysfunction at time of death
• Bedside assessment
o Dysphagia scales
o Duration of meals
o Weight loss (>10% of baseline)
o Videofluoroscopy
o FEES

Clumsy hand

Limp

Tripping / Falling

Cramping
o 3 clinical patterns:
o Bulbar palsy:

Palsy of the tongue, muscles of chewing/swallowing and facial muscles

Signs of LMN lesion: flaccid fasciculating tongue, jaw jerk is normal or
absent, speech is quite, hoarse or nasal.
o Amyotrophic lateral sclerosis (50%):

Upper motor neuron signs
• Emotional lability
• Slurred speech
 • Spasticity
• Paresis, clonus
• Decreased fine movements
• Brisk DTJs, Upgoing plantars

Lower Motor Neurone Signs
• Wasting
• Weakness
• Fasciculations
o Progressive muscular atrophy (25%): anterior horn cell lesion; distal muscles are
affected before proximal.
• Investigations:
o Exclude the disease through:

Clinical or electrophysiological evidence of another condition that could
explain the findings (e.g.hx of poliomyelitis)

Neuroradiological evidence of a condition that could otherwise account for
the clinical syndrome (e.g. evidence of cervical myelopathy)

Failure of the condition to progress

Symmetrical Signs

Pure upper or pure lower motor neurone syndrome

Upper motor signs caudal to lower motor neurone signs, with no bulbar
involvement

Development of sensory signs

Development of sphincter disturbances
o Bloods: to exclude other diagnoses

FBC  leucocytosis (infection)

U&E  electrolyte disturbances (Ca, K)

LFTs & Coags  Cirrhosis?

TFTs  Hypothyroidism?

LP  meningitis? MS?
o Electrophysiological studies:

Electromyography:
• Measures motor unit potentials
• Normal muscle silent at rest. On activation EMG records motor unit
pattern
• Denervated muscle shows fibrillation potentials and large motor
units
• 4 limb EMG and EMG of bulbar muscles:

o
o Fibrillations and positive sharp waves
o Large polyphasic units (partial reinnervtion)
o Reduced interference pattern

Nerve conduction studies:
• Detailed nerve conduction studies should be normal
• Search for conduction block (Should not be present)
• Sensory nerve action potentials should be normal
o Imaging:

MRI of the brain and spinal cord: to exclude other diseases.

Do MRI brain
• if predominantly upper motor neurone signs

MRI spine
• if with upper motor neurone signs caudal to lower motor neurone
signs
• & no bulbar features
o Invasive:

Muscle biopsy:

•
• Fibre size variation on H&E staining

•
• On ATPase: Angulated fibres & grouped atrophy
o “El Escorial Criteria” is only useful in research, not practical.
• Management:
o Multidisciplinary approach; neurologist, palliative nurse, hospice, OT, physio,
dietician, speech therapist & social services; this has been shown to improve survival
by 6 months
o Early intervention is favoured
o Disease modifying therapy:

Riluzole: antiglutamate; monitor LFTs every month for 3 months then every
3 months for 9 months then annually, SE: vomiting, weakness, headache,
vertigo, pain, deranged LFTs.
• Improves survival by 3 months
o Symptomatic management:

Spasticity
• Baclofen, Tizanidine

Cramping & fasciculation
• Quinine sulphate

Salivation & drooling
• Amitriptyline,Scopolamine, irradiation

Pseudobulbar affect
• Amitriptyline

Nutritional Supplementation

Respiratory Decline
• Recognition, early intervention
• Sniff nasal inspiratory Pressure is more accurate predictor of survival
than FVC.
• Management
o End of life decisions

Advance directives encouraged

Risks of unintended invasive ventilation discussed

Benefits of home / hospital based palliative care
explained
 o Non invasive ventilation

Criteria for initiation of NIV in ALS not well
established
• Symptoms of hypoxemia
• FVC, SNP
• Oximetry
• Arterial Blood Gases


o Invasive mechanical ventilation

• Complications:
o Progressive inability to perform activities of daily living (ADLs), including handling
utensils for self-feeding
o Deterioration of ambulation
o Aspiration pneumonia
o Respiratory insufficiency
o Complications from being wheelchair-bound or bedridden, including

decubitus ulcers and

skin infections (While rare in patients with ALS, these complications can
emerge if appropriate padding is not used.)

Deep vein thromboses and pulmonary emboli (these are rare)
• Prognosis: death within 3 years.