Weakness: An Approach

• Mental fatigue
• bradykinesia
• Decreased range of motion
• Depression
• Movement limited by pain.

“Abnormal fatigability of striated muscle is the cardinal manifestation of disorders of the neuromuscular junction. Exercise-dependent weakness often affects the extraocular muscles first, causing ptosis or diplopia, as the motor units of these muscles contain only a small number of muscle fibers…. In contrast to myasthenia, the myopathies generally cause [only a] slowly progressive, non-exercise dependent weakness [without sensory or autonomic deficits, or fasciculation].”

Mathias Baehr, MD, et al. Duus’ Topical Diagnosis in Neurology, 5e (p. 72)

The patient history should include a meticulous search for possible causes or localizing signs or symptoms such as diarrhea, dysuria, arthralgias, rashes, and toxins.

• Infectious: sepsis, HIV, UTI, trichinosis, toxoplasmosis, and countless other
• Electrolytic: dehydration and electrolyte disturbances, particularly hypokalemia
• Organ system dysfunction or failure:  heart, lungs, brain, liver, renal, hematopoietic
• Toxic: excessive food (obesity!), statins, ETOH, glucocorticoids, heavy metals, antineoplastics, carbon monoxide, cyanide, methemoglobin (from nitrates, local anesthetics,  sulfonamides, and aromatics such as aniline dyes and phenazopyridine)
• Endocrinal: any, but especially hyper- or hypothyroidism, hyperparathyroidism, hyper- or hypoadrenalism, Cushing syndrome, acromegaly, or panhypopituitarism
• Autoimmune: polymyositis, dermatomyositis, inclusion body myositis
• Neuromuscular: Myasthenia gravis
• Nutritional: obesity, protein-energy malnutrition, hypovitaminoses
• Other: pregnancy, deconditioning, critical illness myopathy

Physical examination should include:

• Skin for pallor or jaundice
• Neurological examination with emphasis on ocular movements, pupils, eyelids, and deep tending reflexes
• Testing for fatigability
• Evaluation for muscle strength
• Evaluation for muscle bulk, particularly if weakness is chronic
• Evaluation for muscle tenderness

Workup

There is no generic workup for weakness. For starters, however, I would discontinue possible offenders (statins, etc.) and consider, at minimum, a CBC with differential, a comprehensive metabolic panel, calcium, magnesium, and phosphorus levels, and a pregnancy testing if applicable. In addition, I might consider a routine electrocardiogram, chest radiograph and urinalysis in the elderly.  Additional testing might include ESR, TSH, B12, ANA.

The remainder of the workup should be guided by the H&P.

Classic associations (and associated workups):

• If myasthenia gravis is suspected: anti-acetylcholine receptor (AChR) antibodies, muscle specific receptor tyrosine kinase (MuSK) antibodies, electromyography, CT of the thorax (to look for thymoma), neostigmine test
• Constipation: hypothyroid, hypercalcemia (TSH, calcium)
• Fatigability (worse as the day goes on and relieved with rest) ptosis, diplopia, dysarthria: myasthenia gravis. Check anti-acetylcholine antibody, muscle specific receptor tyrosine kinase antibody, CT chest (to evaluate for thymoma), EMG, neostigmine challenge.
• Proximal muscle/joint pain and stiffness weakness (trouble getting up from chair without using arms, stair climbing, brushing hair) with elevated ESR: polymyalgia rheumatica (ask about vision changes, palpate temporal artery, and get an ESR)
• Proximal, symmetric muscle weakness and muscle pain with elevated CK: polymyositis; for inflammatory myopathy, workup might include CK, ESR, CRP, anit-Jo-1, anti-Mi-2, EMG, muscle biopsy
• “Polymyositis” plus rash: dermatomyositis. Look for heliotrope rash (purple rash around eyes, with or without edema of the eyelids), Gottron’s papules (purple papules and papules overlying extensor surfaces, particularly PID and DIP joints), or shawl sign (V-shaped chest rash); consider electrocardiogram (for myocardial involvement) and screening for malignancy as guided by history
• Asymmetry and distal muscle weakness: inclusion body myositis
• Temporal arteritis: polymyalgia rheumatica
• Easy bruising, purple striae, negative CK: Cushing syndrome
• Rapidly progressive descending paralysis (early cranial nerve involvement): botulism, Descending GBS,  organophosphate poisoning, brainstem stroke
• Preceding flu-like or diarrheal illness, followed by ascending flaccid paralysis with hypoactive, then absent reflexes: Acute inflammatory demyelinating polyneuropathy (Guillain–Barré Syndrome). Consider telemetry (for autonomic instability), forced vital capacity, negative inspiratory flow, lumbar puncture (to look for increased protein without pleocytosis), EMG with nerve conduction studies; tick paralysis
• Contacts sick with weakness: organophosphate poisoning, botulism
• Botulism (3 distinct disease entities!):
  • Sick contacts eating from a common source, especially home-canned food that was not adequately preheated who develop nausea, vomiting, and diarrhea followed by descending cranial nerve paralysis: foodborne botulism
  • Wound: wound botulism
  • Infant with constipation, followed by poor feeding, swallowing, weak cry, poor head control, absence of fever: infant botulism
• Delayed deep tendon reflexes: hypothyroidism
• Salivation, abdominal cramping, diarrhea: organophosphate poisoning or overtreatment of myasthenia gravis with anticholinesterase medication such as pyridostigmine
• CN III ophthalmoplegia without loss of pupillary tone (“pupillary sparing”): diabetic neuropathy
• CN III ophthalmoplegia with loss of pupillary tone: increased intracranial pressure or aneurism of the posterior communicating artery
  • If isolated, needs angiogram
  • If accompanied by central nervous system depression, needs immediate brain CT to rule out increase intracranial pressure
• If accompanied by CNS depression, needs immediate brain imaging to rule out increase intracranial pressure
• Hyperpigmentation, hyperkalemia: primary adrenal insufficiency (electrolytes, blood pressure, cosyntropin stimulation study)
• Bronzing of skin, arthralgia: hemochromatosis
• Enlarging size of hat and coarsening of facial features: acromegaly (IGF-1, glucose and/or HbA1C)
• Heavy exertion, cocaine, urinalysis positive for “blood”: rhabdomyolysis (serum electrolytes, urinalysis)
• Elevated CK: inflammatory myopathies, hypothyroidism, statins (but not steroids!)

References:

1. Pocket Medicine 2010 (at 8-13)
2. Instant Workups: A Clinical Guide to Medicine (2008) (reviewed here)
3. Conrad Fischer MD. Master the Boards USMLE Step 3 (2012)
4. Habif, Thomas P, MD, Skin Disease: Diagnosis and Treatment (2011), 3e (reviewed here)
5. Baehr, Mathias, MD, et al. Duus’ Topical Diagnosis in Neurology, 5e

Please note that I routinely update posts in response to feedback, and as my understanding of the subject matter changes. Posted comments below may refer to an earlier iteration. Your feedback is welcomed and appreciated!