Question 10

Clinical Features:                                                                                                               [3 marks]

Acute transverse myelitis is a clinical syndrome characterised clinically by rapid onset and progression of motor, sensory and autonomic dysfunction as a result of acute inflammation involving gray and white matter at one or adjacent levels in the spinal cord.

• History: recent vaccination, travel, recent infection (esp viral). History of motor, sensory or autonomic symptoms including pain, parathesiae.
• Clinical Findings:
  • Motor weakness, paraparesis.
  • Sensory level
  • Autonomic signs – e.g. incontinence

Differentials (i.e. diagnoses other than those specifically associated with ATM);

[2 marks for any 4 of below]

1. GBS
2. Vascular event -Anterior spinal artery syndrome.
3. Multiple sclerosis (similar but different immunopathogenesis – MS mediated through cell mediated immune aberration, ATM mediated through abnormal humoral immunity)
4. Acute Compressive myelopathy due to bleed (e.g. AVM) or abscess
5. Herpes zoster myelitis
6. Post-polio syndrome (even in countries where polio has been eradicated)
7. B12 deficiency (usually sub-acute)

Diagnostic work-up;

• CT spine to rule out compressive myelopathy, bleed
• MRI brain and spine with gadolinium contrast – MRI findings (T2 signal) may lag clinical findings
• CSF examination:
  • variable cellular response dependent on sub-aetiology
  • Culture and enterovirus PCR
  • Oligoclonal bands and specific immunology (NMO, ADEM) [2 marks]
• Blood tests for anti-CNS and systemic auto-antibodies (don’t expect fine print, bonus marks for candidates knowing association of NMO with acquaporin-4 IgG antibodies)
• Blood for B12 levels
• ENMG (neurophysiology), if possibility of neuropathy remains.

Note: Must include imaging (either CT scan or MRI) and CSF examination in this section to score full marks.

Specific Treatments to be initiated;                                                                                                               [3 marks]

– should be commenced awaiting definitive diagnosis

1. Pulse corticosteroids for ADEM, NMO and ATM associated with auto-immune diseases are usual care; trials lacking
2. Plasma exchange: for ADEM, NMO
3. IVIG described

Discussion

This question is a welcome evolution of Question 3 from the second paper of 2018, where (again) the trainees were asked to compare Guillaine-Barre syndrome to another lower motor neuron disease. 

Clinical features

• History and background:
  • Usually occurs as a postinfectious complication
  • Can fall within the spectrum of coexisting MS
  • Can coexist with acute disseminated encephalomyelitis
  • Autoimmune diseases are associated (eg. SLE, scleroderma, etc)
  • Often, very rapidly progressing
  • Weakness nadir is achieved within 4 hours in some cases (though some take as long as 21 days)
• Examination findings:
  • Power
    • Bilaterally decreased power 
    • Symmetrical
    • Weakness remains at and below the level of the lesion
    • "Pyramidal" preference: flexors of the legs and the extensors of the arms
  • Tone
    • Initially flaccid
    • Later, hypertonic spasticity
  • Reflexes
    • Depressed initially
    • Hyperreflexia subsequently
  • Sensation
    • Sensation is usually absent 
    • There is usually a distinct symmetrical sensory level
  • Cranial nerves
    • Usually, not involved
    • When it forms a part of the MS spectrum, there may be optic neuritis
  • Autonomic dysfunction
    • Usually, no dysfunction, unless the level of the lesion is high
    • High lesions may present with spinal shock

Differential diagnosis

• Vascular causes
  • spinal cord infarction
• Infectious causes
  • Polyomyelitis
  • Epidural abscess
  • Herpes zoster
• Neoplastic causes
  • Spinal canal tumour
• Drug-related causes
  • B12 deficiency
  • Steroid-induced myopathy
• Hereditary distal neuropathies
  • Spinobulbar muscular atrophy (Kennedy's disease)
  • genetically heterogeneous distal hereditary motor neuropathies
• Autoimmune/ immune-mediated diseases
  • Guillain-Barré syndrome
  • multifocal motor neuropathy (MMN)
  • Chronic inflammatory demyelinating polyneuropathy (CIDP)
  • Multiple sclerosis
  • Myasthenia gravis
  • Eaton-Lambert syndrome
  • Myositis and dermatomyositis
• Iatrogenic causes
  • Critical illness polyneuromyopathy

Initial diagnostic tests

• Bloods
  • B12 level
  • Aquaporin-4 IgG antibodies
• Lumbar puncture:
  • Expect to see raised protein and lymphocytosis
  • Test for viruses (zoster and enterovirus) 
  • Also, need culture and gram stain if an infection is still a serious differential
• Nerve conduction studies
  • Reduced amplitude sensory nerve action potential (SNAP)
  • Pathological F-wave responses
  • Decreased conduction velocity of motor and sensory nerves.
• Electromyography
  • Reduced amplitude of motor (MUP) action potentials
• MRI
  • Noncontrast MRI reveals cord oedema at the level of the lesion (but in 40%, looks totally normal)
  • Gadolinium-enhancing signal abnormality extending over one or more cord segments.
  • Lesions occupy most of the transverse diameter of the cord (2/3rds)

Management

• High dose steroids: though there are no clinical trials, generally people tend to recommend giving 1g/day of methylprednisolone for 3-7 days
• Plasmapheresis should be offered to those patients who do not respond to steroids: though this recommendation is also extrapolated form the fact that other demyelinating autoimmune diseases benefit from plasmapheresis. Beh et al (2013) recommended  1.5 plasma volumes for 5 treatments over 10 days (i.e. every second day). This should be offered early, within 15 days of diagnosis
• Cyclophosphamide is recommended occasionally
• Rituximab has been attempted
• IV immunoglobulin is not usually recommended, as there is insufficient evidence