Approach to General Weakness

Weakness is a common complaint, and it is important to determine whether a true decrease in muscle power is limiting activity, or whether it is some other factor such as shortness of breath, chest pain, joint pain, or fatigue. True muscle weakness is characterized by difficulties with specific tasks.

Key components of the history:
Is mental status depressed?
Which limbs are involved?  Unilateral vs bilateral
Is there sensory involvement? If so, is a sensory level deficit suggested?
Is there bladder involvement?
Does weakness primarily involve proximal or distal muscles? – the proximal muscle weakness typically found early in the course of a myopathy is suggested by difficulty walking up stairs or getting up from a chair (lower limbs involved) or difficulty with overhead activities e.g. combing hair (upper limbs involved)
Are there bulbar signs (involving tongue, jaw, face, or larynx)? – in NMJ disease
Does the degree of weakness fluctuate? – i.e. Myasthenia Gravis

Determining the location of the lesion:
Upper motor neuron (brain, spinal cord)

Signs: spasticity (rate and velocity-dependent rigidity), hyperactive reflexes, Babinski sign, distal weakness
Causes:
Brain: CVA, mass lesion
Spinal cord: demyelination, trauma, infection, vascular abnormality
Lower motor neuron (anterior horn cell, peripheral nerve)
Signs: atrophy, fasciculations, decreased tone, absent reflexes
Causes:
Anterior horn: ALS, infection (polio, West nile), lead poisoning
Peripheral nerve: structural (e.g. carpal tunnel), vasculitis, metabolic (B12, TSH, DM), multiple myeloma, HIV, demyelination (e.g. Guillain-Barre)

Neuromuscular junction
Signs: proximal weakness, bulbar symptoms, difficulties with neck flexion/extension
Causes: myasthenia gravis (antibody vs Ach receptor with ocular/bulbar symptoms that are worse after activity), Lambert-Eaton syndrome (antibody vs presynaptic Ca channel, with proximal muscle weakness and postexercise facilitation), organophosphate poisoning, botulism

Muscle
Signs: mild atrophy, typically proximal weakness, pain (suggests trauma, infection, or drug toxicity)
Causes: drugs (e.g. statins, fibrates, EtOH, cocaine, colchicine, antipsychotics, steroids), metabolic, endocrine (e.g. thyroid, Cushing’s), infection, autoinfarction, inflammatory myositis, muscular dystrophy

Stereotypical patterns of weakness:
Generalized weakness: myasthenia gravis, paraneoplastic, advanced motor neuron disease
Localized weakness:
- Symmetric:
- Proximal symptoms: difficulty getting up out of chair, going up stairs, combing hair, Gower’s sign suggests myopathy or LES
Distal symptoms: foot drop, weak grip, difficulty opening jar suggests early motor neuron disease or peripheral neuropathy
Asymmetric: CVA, structural lesion, mononeuritis multiplex
Fatigability: suggests myasthenia gravis; improvement with activity suggests LES

Overview of Polyneuropathy:
“Peripheral neuropathy” is often used interchangeably with “polyneuropathy” or even “neuropathy”,  but actually is a more general term referring to any disorder of the peripheral nervous system, including radiculopathies, mononeuropathies and polyneuropathies

Mononeuropathy refers to focal involvement of a single nerve, usually due to a local cause such as trauma, compression, or entrapment (ie. carpal tunnel syndrome)

Mononeuropathy multiplex refers to simultaneous or sequential involvement of noncontiguous nerve trunks, generally from a vasculitis process (ie. Polyarteritis Nodosa)

Polyneuropathy: a specific term that refers to a generalized, homogeneous process affecting many peripheral nerves, with the distal nerves usually affected most prominently
Peripheral nerves are susceptible to variety of toxic, inflammatory, hereditary, infectious, and parainfectious factors that can impair their function, leading to polyneuropathy
- characterized by symmetric distal sensory loss, burning, or weakness
- Symptoms vary significantly based on underlying pathophysiology:

Chronic axonal polyneuropathy: injury is related to axon length w/ longest axons affected first so presents in distal LE first; sensory symptoms present before motor. “stocking-glove” distribution 
Examples: DM, uremia, etoh, HIV, Lyme disease
Acute axonal polyneuropathy: similar to above, but with more acute and painful symptoms (can worsen over 2-3 weeks, then improve over months)
Examples: toxic exposures or porphyria

Acute demyelinating polyneuropathy: predominately affects motor nerves therefore weakness is more prominent than sensory loss
Examples: GBS

Chronic inflammatory demyelinating disorder (CIDP): like acute, only more insidious—both motor and sensory symptoms

Hereditary polyneuropathies: generally without pain or sensory symptoms, can be very slow and insidious, can present in childhood, or much later in life (up to 7th decade)
Examples: Charcot-Marie Tooth
Diagnosis: EMG should be the first study when there is suspicion of a polyneuropathy, as it can determine whether the nerve or muscle is involved, whether it is a polyneuropathy vs. radiculopathy, and whether it is an axonal or demyelinating

(Victoria Kelly MD, 5/26/11)