Neuromuscular disease

Question 1

What do you tend to see with myopathies?

Answer 1

 generalised weakness and/or exercise intolerance – stiff stilted gait; neck ventroflexion
 usually no proprioceptive deficits (unless extreme weakness)
 normal spinal reflexes
 variable muscle tone and bulk
 generalised or focal

Question 2

What blood work may be useful?

Answer 2

 electrolytes – Ca, K, (Na)
 biochemistry – AST; CK
 haematology
 endocrine tests
• thyroid hormones
• ACTH stimulation test
 serology for IM diseases
• Ach receptor antibody titres
• Type 2M antibody titres
 serology for infectious diseases
• Toxoplasma gondii and Neospora caninum

Question 3

What ix tests may be required?

Answer 3

 electrodiagnostics:
 EMG – presence and distribution of lesions (does
not differentiate between muscle and nerve lesions)
 NCV – peripheral nerve function
- repetitive nerve stimulation and F waves
- muscle and/or nerve biopsies
 CSF analysis (polyradiculoneuritis)
 advanced imaging (some myopathies)

Question 4

Outline the VITAMIN D for neuropathies

Answer 4

V– ischaemic neuromyopathy
I – optic neuritis; acute polyradiculoneuritis; Toxoplasma and Neospora; cranial neuropathies (V, VII and VIII); chronic relapsing inflammatory demyelinating polyneuropathy
T – brachial plexus avulsion; tail pull injuries (cats); focal neuropathies; several toxins but rare (lead, organophosphates, vincristine)
A – optic nerve hypoplasia
M – diabetes mellitus; hypothyroidism; hyperadrenocorticism; hypoglycemia
I – distal denervating disease
N – peripheral nerve sheath tumour; lymphoma
D – motor neuron disease; neuroaxonal dystrophies; breed associated neuropathy; lysosomal storage diseases…

Question 5

Outline the VITAMIN D for myopathies

Answer 5

V– ischaemic neuromyopathy
I – Toxoplasma and Neospora; polymyositis; dermatomyositis; masticatory
muscle myositis
T – post-traumatic muscle contractures
A
M – hypokalaemia; hypocalcaemia; endocrine (hypothyroidism,
hyperadrenocorticism); mitochondrial myopathies
I
N – uncommon (lymphoma)
D – muscular dystrophy; Labrador retriever myopathy; myotonia; fibrotic myopathy; Great Dane inherited myopathy; breed associated episodic muscle hypertonicity…

Question 6

What are the main ddx for junctionopathies?

Answer 6

pre-synaptic
 botulism
 tick paralysis
 hypocalcaemia
post-synaptic:
 MG
 muscle relaxants
enzymatic
 organophosphates
 cholinesterase inhibitors

Question 7

What is acute polyradiculoneuritis and what are the sigsn?

Answer 7

 inflammation of nerves and nerve roots
 “Coonhound paralysis” – in US can be associated with contact with racoons; Guillain-Barré syndrome (humans)
 Clinical signs:
 acute and rapidly progressive
 PLs affected over 2-3d; then progresses to
TLs
 non-ambulatory tetraparesis (may affect respiratory muscles)
 mental status unaffected; no autonomic signs

Question 8

How do you dx/tx acute polyradiculoneuritis?

Answer 8

Diagnosis:
 clinical signs
 electrophysiology
 CSF analysis (lumbar tap) – raised protein
 negative infectious titres
Treatment
 supportive care
 physiotherapy
 human IV immunoglobulin (£££)
Prognosis
 fair (in cases with respiratory dysfunction the prognosis is poor)
 recovery to ambulation over several weeks

Question 9

What is tetanus and what are the signs?

Answer 9

 tetanus spores in anaerobic environment (necrotic wound)
 conversion into form that produces toxin
 PNs (α-motor neurons) transport tetanospasmine to CNS
 neurotoxin blocks fusion of synaptic vesicles with cell
membrane  stops neurotransmitter release at n-m junction, autonomic terminals and inhibitory neurons in CNS
 Clinical signs in 4 to 12 days
 rigidity, hyperextension of limbs, trismus, dysphagia, “risus sardonicus”, elevated tail and ears
 urinary and faecal retention
 hypersensitivity to external stimuli  muscle spasms
 seizures

Question 10

What is the tx for tetanus?

Answer 10

 Treatment:
 antibiotics (penicillin G, metronidazole)
• to stop toxin production
 identify and treat wound (if still present)
 anti-toxin (?) – neutralise toxin
 ACP, diazepam, phenobarbital
 supportive care:
• urinary retention, tracheostomy, “feeding tube”, calm and quiet environment
 Prognosis
 fair if treated aggressively

Question 11

What are the types of myasthenia gravis?

Answer 11

 congenital (JRT, Sp Spaniel, Smooth haired Fox
terrier, Gammel Dansk Honsehund, Dachshund,
cats)
 acquired form more common – antibodies against n-m junction (Ach recept)

Dogs:
 focal form in ~40% (MO; cranial nerve deficits)
 generalised form (often associated with
pharyngeal/laryngeal dysfunction)
 fulminant form (acute and rapidly progressive)

Cats:
 focal signs ~15% (pharyngeal/laryngeal
dysfunction)
 in association with thymomas ~25% of cases

Question 12

How do you dx/ tx myasthenia gravis?

Answer 12

Diagnosis:
 edrophonium test (neostigmine)
 antibodies anti-Ach receptors
 repetitive nerve stimulation

Treatment:
 pyridostigmine (cholinesterase inhibitor)
 immunosupression – controversial…
 thymoma removal
 can use Ab titres to guide treatment (if not using steroids)…

Prognosis:
 fair due to self-limiting nature of disease
 can be quite difficult to control (fulminant form)
 aspiration pneumonia when megaoesophagus and pharyngeal dysfunction

Question 13

What are the different severities of neuropathies?

Answer 13

 Neuropraxia – nerve conduction is affected but structure of axon remains intact; signs tend to resolve within a few days
 Axonotmesis – structure of axon is disrupted but the basal lamina remains intact working as a foundation for axon repair (1mm/day)
 Neuronotmesis – complete disruption of axon with destruction of basal lamina and of other connective tissues (epineurium, perineurium, endoneurium)

Question 14

Outline brachial plexus avulsion

Answer 14

 RTA, cats stuck in windows…
 brachial plexus dysfuntion – monoparesis, reduced to absent spinal reflexes in affected limb, ipsilateral cutaneous trunci cut-off, Horner’s syndrome
 cranial, caudal, complete
 bad prognosis when there is loss of pain perception

Question 15

Outline trigeminal neuritis

Answer 15

 bilateral inflammation of CN V
 idiopathic
Clinical signs:
 dropped jaw
 difficulty preheending food
Treatment:
 supportive care
 loose muzzle
 feeding tube
Prognosis:
 good, most recover within 3 weeks

Question 16

Outline trigeminal tumours

Answer 16

 most common cause of unilateral MM atrophy
 main DDx – neuritis (not idiopathic)
 very slow growth so signs can progress over
several months (to years)
 can affect any of 3 branches or all; eventually grows into brainstem and then signs progress
 unilateral temporal muscle atrophy
 reduced facial sensation
 reduced palpebral and corneal
 neurogenic corneal ulcers
 neuroparalytic keratitis
 intracranial signs
 head tilt
 nystagmus and strabismus
 proprioceptive deficits
 facial paralysis

Question 17

What is facial nerve paralysis and what are the signs?

Answer 17

 “idiopathic” – most common by far
 presence of abnormalities on MRI suggest possible inflammation of nerve
 commonly affects Cockers, Boxers, Springer Spaniels, CKCS
 brainstem lesions (other signs)
 middle ear disease
 Clinical signs:
 facial nerve paresis/paralysis
 usually unilateral (but may be bilateral); sometimes CN VIII also affected

Question 18

How do you dx/ tx facial nerve paralysis?

Answer 18

Diagnosis:
 rule out otitis media
 rule out hypothyroidism
Treatment:
 avoid KCC (eye lubrication)
Prognosis:
 extent of recovery is variable (permanent deficits not uncommon)
 usually occurs within several weeks (~8 weeks)

Question 19

What is hemifacial contracture?

Answer 19

 secondary to fibrosis resulting from chronic denervation
 up to 50% dogs after acute facial paralysis
 blepharospasm
 elevation of the ear
 deviation of the nose on affected side
 wrinkling of upper lip
 can be due to middle ear disease or brainstem lesions…

Question 20

Outline laryngeal paralysis

Answer 20

 inspiratory stridor, dyspnoea, dysphonia, exercise intolerance
 hereditary
 young dogs (≤1y)
 breed-specific (Bouvier de Flandres, Rotties, Perynean mountain dogs, Schnauzers, etc)
 acquired
 middle to old age dogs
 thought to be part of generalised neuropathy
 worse prognosis when generalised signs

Question 21

Outline polymyositis

Answer 21

 immune-mediated inflammation of several muscles
 Clinical signs (acute or chronic):
 exercise intolerance, generalised weakness, muscle atrophy
 dysphagia/regurgitation when oesophageal involvement
 Diagnosis:
 clinical signs, raised CK/AST, negative infectious disease titres
 EMG
 muscle biopsy
 Treatment:
 prednisolone +/- other immunosuppressive medications

Question 22

Outline masticatory muscle myositis

Answer 22

 auto-immune
Clinical signs:
 usually acute
 one or a combination of following signs:
• bilateral MM atrophy
• difficulty opening mouth
• pain
Diagnosis:
 raised CK levels (not always)
 EMG – MMs
 type IIM antibody titres
 biopsy (temporal m.)
Treatment:
 prednisolone (immunosuppressive doses); relapse not uncommon

Question 23

Outline infectious myositis

Answer 23

 Toxoplasma gondii & Neospora caninum
 Clinical signs of Neosporosis in puppies:
 PL hyperextension (starts in 1 limb and progresses to other)
 ascending paralysis of PLs with muscle contracture
 may affect several puppies in litter
Diagnosis:
 raised CK/AST
 EMG and muscle biopsies
 serology
Treatment:
 clindamycin or TMPS and pyrimethamine - sometimes leg function not regained and amputation required

Question 24

What are the signs of hypokalaemia myopathies and who gets them?

Answer 24

 cats with chronic renal disease
 inherited in Burmese kittens
- may be precipitated by stress or exercise
- clinical course: improvement followed by relapse
- often weeks between episodes

Clinical signs:
 stiff-stilted gait, reluctance to walk
 exercise intolerance
 ventroflexion of the neck
 muscle pain

Question 25

How do you diagnose hypokalaemia myopathy?

Answer 25

 low serum potassium  high CK  DNA test  renal parameters