Differential Diagnosis in Neurology

4.7. Autoimmune Causes of Spinal Cord Dysfunction

• General considerations:
  • Maybe ethnically and genetically determined; more common in African American and Asian patients than Caucasians
  • Axonal destruction in the spinal cord greater than demyelination
• Clinical features:
  • Bilateral optic neuritis
  • Affects young patients
  • Severe spastic paraparesis
  • Axonal injury appears early

Multiple Sclerosis

• General considerations:
  • Spinal cord involvement may be predominant feature in middle aged women; almost always occurs in all forms of MS. The MRI coils to evaluate spinal cord pathology are not as well developed or accurate as those for cerebral imaging
• Clinical features:
  • The process is most often relapsing remitting which slowly evolves into secondary progressive disease; primary progressive and variants occur
  • The spinal lesions are most often occurring at cervical levels which cause a dropped sensory level to T4–T6 rather than at a thoracic level
  • The demyelinating lesions are often longitudinal rather than transverse and occur over several levels
  • Paresthesias of the palms rather than the fingers (the latter more characteristic of nerve or brachial plexus sensory loss)
  • Lower extremity spasticity
  • Bladder involvement:
    • Neurogenic
    • Dyssynergy between detrusor contraction and sphincter opening
  • Associated neurological findings:
    • Intranuclear ophthalmoplegia
    • Afferent pupillary defect
    • Bilateral cerebellar ataxia
    • Bilateral corticospinal tract dysfunction
    • Cognitive decline
    • Early loss of superficial abdominal reflexes

Acute Disseminated Encephalomyelitis

• General considerations:
  • 75% evolve into multiple sclerosis
• Clinical features:
  • One episode of demyelination
  • May follow a viral illness
  • Brunt of the demyelination is in the brain
  • Age of all lesions is similar
  • Spinal cord involvement is manifest by spasticity, bladder dysfunction and weakness
  • Optic nerve may be involved
  • Adrenocorticoid stimulating hormone may be more effective than intravenous steroids for treatment
  • A great percentage evolve into MS

Acute Hemorrhagic Leukoencephalitis

• General considerations:
  • Hyperacute demyelination
• Clinical features:
  • One clinical episode
  • Usually affects the left cerebral hemisphere
  • CSF may have up to or greater than 150 RBC cells/mm³
  • Spinal cord maybe affected

Post Vaccination Myelitis

• General considerations:
  • Occurs 7–14 days following vaccination
  • Measles and hepatitis B virus are the most common viral vaccinations. Rabies is a rare cause now due to recombinant vaccines.
• Clinical features:
  • More common in children
  • Associated with cerebral periventricular demyelination
  • Longitudinal myelitis occurs most frequently at cervical levels

Acute and Chronic Acquired Demyelinating Inflammatory Polyradiculopathy

• General considerations:
  • The major autoimmune attack is on peripheral myelin
  • GQ1b and other epitopes identified
  • Molecular mimicry is a possible mechanism; overlap between peripheral and central antigens (same epitopes) are responsible for the central manifestations
• Clinical features:
  • Longitudinal myelitis at cervical levels
  • Rarely brainstem and cerebral demyelination occurs

Systemic Lupus Erythematosus

• General considerations:
  • Spinal cord involvement occurs in association with arthralgia, skin and visceral involvement
  • Usually systemic markers of activity are high
• Clinical features:
  • Longitudinal myelitis at cervical levels
  • Maybe recurrent
  • Usually a dropped sensory level at T4–T6
  • Corticosplinal tract dysfunction

Sarcoid

• General considerations:
  • Lung, cardiac, joint, muscle and nerve involvement
• Clinical features:
  • Dural involvement is common
  • Primarily affects the thoracic cord
  • Compression myelopathy more common than parenchymal vasculitis
  • CSF:
    • Sugar 30–40 mg%
    • Protein 80–150 mg%
    • Lymphocytic cellular response
    • Associated cranial nerve and CNS involvement

Stiff Man Syndrome

• General considerations:
  • Slightly more common in females (50%)
  • Associated with diabetes mellitus, hyper and hypothyroidism, epilepsy in 10% of patients
  • GAD 67-kD isoform appears to be the antigen
  • May be associated with breast cancer; the antigen may be a non-intrinsic membrane protein of 128 kD (amphiphilic)
• Clinical features:
  • Fluctuating progressive muscle stiffness and painful spasms of the trunk
  • Insidious onset; 4th to 5th decades
  • Axial musculature affected more than appendicular; lower extremities are more affected than the upper
  • Respiratory, facial and bulbar muscles are affected in advanced disease
  • Patients have normal strength and sensation; reflexes maybe increased
  • Lumbar hyperlordosis occurs
  • Hereditary form has been described:
    • Stiffness is present at birth; resolves by age 3 and returns in adolescence
    • Stiffness precipitated by movement
  • Muscle spasms maybe induced by acoustic, somatosensory or emotional stress
• EMG:
  • Continuous motor unit activity in at least one axial muscle; normal silent period after a painful stimulus

Variants of Stiff Man Syndrome

• Progressive encephalomyelitis with rigidity
  • Rare
  • Rapidly progressive (few months) to death
• Stiff limb syndrome:
  • Rigidity and abnormal fixed posturing
  • Painful spasms of distal lower extremities
  • Sphincter and brainstem involvement in 50% of patients
• Women with breast cancer
  • Antibodies to synaptic vesicle protein amphiphilin I
• Jerking Stiff Main Syndrome
  • Myoclonic jerking is prominent

Differential Diagnosis of Stiff Man Syndrome

The symptom complex is rigidity of axial greater than appendicular musculature, action induced spasms and continuous motor unit activity:

• Isaac's syndrome
• Corticobasal ganglionic degeneration
• Focal spinal cord lesions
• Tetanus
• Encephalomyelitis

Sjögren's Syndrome

• General considerations:
  • Antibodies to salivary and lacrimal glands; red eyes and serosal surface irritation
  • Peculiar Vth nerve involvement (numb face)
• Clinical features:
  • Primarily posterior column involvement
  • Associated with primary progressive multiple sclerosis

Differential Diagnosis of Autoimmune Diseases Associated with Longitudinal Myelitis

• Wegener's granulomatosis (severe sinopulmonary involvement; mononeuritis multiplex)
• Rheumatoid arthritis (small muscle involvement of the hands, C1–C2 spondylolisthesis with spinal cord compression)
• Mixed connective tissue disease (elements of polymyositis, scleroderma and SLE). The latter component frequently associated with transverse myelitis.
• Regional enteritis (usually associated with stroke or cerebral sinus thrombosis loss of clotting factors through the gut causes a prothrombotic state)
• Ulcerative colitis (most often associated with cerebrovascular accidents, cerebral sinus thrombosis, eye and joint involvement).
• Relapsing polychondritis (most often associated with disc disease, collapses of the larynx or optic neuritis)

Differential Diagnosis of Arteritic Syndromes Affecting the Spinal Cord

• Syphilitic proliferative end arteritis
  • Occlusion of the vertebral or anterior spinal arteries
  • Meningoencephalitis (stage II)
  • In association with HIV (all stages appear simultaneously)
  • Pachymeningitis cervicalis
• Anti-phospholipid syndrome
  • Primary
  • In association with SLE
• Takayasu's disease
  • Vertebral artery and anterior spinal artery occlusions
  • Anterior > posterior spinal artery syndromes
• Isolated angiitis of the spinal cord
  • No associated features or laboratory evidence of systemic arteritis
• Giant cell arteritis
  • Rarely can affect all arteries of the internal carotid system
  • A component of the aortic arch syndrome (both carotids and vertebral arteries may slowly be occluded)
• Köhlmeier–Degos Disease
  • Characteristic atrophic skin lesions
  • Severe retinal arterial spasm
  • Spinal cord infarction

Paraneoplastic Syndromes

• Anti -Hu antibody (ANNAI)
  • Primarily an antinuclear antibody
• Associated with limbic encephalitis
• Associated primarily with small cell cancer of the lung
• Burning sensory neuropathy and limbic encephalitis
• Longitudinal myelitis

Vitamin Deficiencies

• B12
• Vitamin E deficiency
  • General considerations:
    • Dietary (associated with severe diarrhea and malabsorption)
    • Alpha tocopherol transporter deficiency
  • Clinical features:
    • Primarily dorsal column dysfunction
    • Associated cerebellar ataxia and large fiber neuropathy