Differential Diagnosis in Neurology

12.5. Disorders with Continuous Motor Unit Activity (CMUA)

• General features of this heterogeneous group of diseases
  • Myotonia
  • Muscle stiffness
  • Pain (sensitization of deep muscle pain afferents)
  • Contracture
  • Cramps
  • Fasciculations
• Origin:
  • Spinal cord (stiff-man syndrome)
  • Peripheral nerve (neuromyotonia)
  • Muscle (myotonias)
• EMG:
  • Muscular myotonias:
    • Series of muscle fiber action potentials; positive sharp waves
    • brief spikes
  • Continuous motor unit activity:
    • Continuous motor unit action potentials
    • Decrementing
    • High amplitude

Stiff-man Syndrome

• Onset: sporadic disease of adult life
• May be immune mediated
• Insufficiency or dysfunction of GABA spinal cord inhibitory neurons
• Clinical presentation:
  • Involuntary painful extremity spasms
  • Exacerbated by movement and stress
  • Axial predominance (hyperlordosis); truncal musculature more involved than appendicular muscles
• Associated diseases:
  • Idiopathic diabetes mellitus
  • Hypothyroidism
  • Paraneoplastic
• Antibodies to glutamic acid decarboxylase (GAD-67)
• May occur following DDT poisoning

Chondrocyte Trophic Myotonia (Schwartz–Janpel Syndrome)

• Genetics: AD from
• Clinical presentation:
  • Short stature
  • Skeletal abnormalities:
    • Kyphoscoliosis
    • Short neck
    • Basilar compression
    • Dislocation of the hips
  • Facial dysmorphisms
    • Blepharophimosis
    • Pursing of the mouth
  • 20% of patients are mentally retarded
  • Stiffness of gait
  • Exercise intolerance
• EMG:
  • Continuous motor unit activity
  • Some myotonia

Isaac's Syndrome (Neuromyotonia)

• General Features:
  • Most common in adults; rare descriptions in infants
  • Antibody to potassium channels
• Clinical Presentations:
  • Insidious onset
  • Persistent muscle contractions
  • Distal > proximal muscle involvement
  • Trunk and facial muscles may be involved
  • Hyperhidrosis (often severe)
  • Erythema of the skin
  • Persistent contraction after exercise; rippling of the contracting muscles
  • Muscles may be painful with contractions
  • Dystonic flexed hand posture
  • Hypertrophy of continuously contracting muscle
• EMG:
  • Myokymic discharge of contracting muscle
  • Occasional superimposed neuromyotonic discharges

Morvan's Syndrome

• Clinical Features:
  • Clinical muscle features are similar to Isaac's syndrome
  • Additional signs and symptoms are:
    • Encephalopathy
    • Hallucinations
    • Insomnia
    • Confusion

Neuromyotonia and Myokymia

• General Features (definitions):
  • Myokymia is a spontaneous continuous undulating vermicular ("worm" like) movement of muscles that does not displace a joint. It may be focal.
  • Neuromyotonia is a generalized continuous contraction of muscle that causes stiffness, but also does not move joints
  • Both processes are channelopathies
  • Hereditary myokymia has been described
    • The locus for episodic ataxia and myokymia
  • Episodic ataxia and myokymia are on chromosome 12p13 (K⁺ channelopathy)
  • Isaac's and Morvan's syndrome are secondary to antibodies directed at potassium channels.
  • Acquired neuromyotonia in >50% of patients is secondary to voltage gated potassium channel antibodies
  • Associated illnesses:
    • MG
    • Penicillamine treatment
    • CIDP
    • Graft vs host disease
    • Thymoma
    • Paraproteinemia
    • Paraneoplastic processes
    • Lymphoma
    • CTS (rare); carpal tunnel syndrome
    • Radiculopathy (rare)
• Specific Associations:
  • Brainstem MS
    • Orbicularis oculi (myokymia)
  • Pontine glioma
    • Facial myokymia (VII)
  • Timber rattle snake envenomation
    • Generalized myokymia and neuromyotonia
  • X-RT
    • Focal to the site of treatment (orbicularis oculi neuromyotonia following pituitary X-RT) episodic diplopia
• EMG:
  • Myokymic discharges are bursts of single motor unit action potentials at 5–150 Hz
    • Pattern of firing is doublets, triplets or in multiples
    • Regular bursts or slightly irregular
  • Neuromyotonic discharge:
    • 150–300 Hz
    • Begin and end abruptly
    • Duration of a few seconds
    • May wax and wane in amplitude and frequency
    • Initiated by mechanical perturbation of the nerve
    • Occur with myokymic discharges

Differential Diagnosis of Morvan's and Isaac's Syndrome

• Snake envenomation (North American timber rattle snake)
• Hypocalcemia (tetany)
• CIDP (prominent sensory loss; depressed reflexes)
• Myotonic disorders (dysmorphisms and systemic involvement in dystrophic froms; hypertrophy of muscle with percussion myotonia in the benign froms)
• Stiff person syndrome (axial > appendicular involvement)
• SCA type 8 (vertigo and ataxia)
• Denervation with intense fasciculation
• Amyloidosis