Physicians increasingly depend on laboratory tests and imaging, sometimes at the expense of a careful history and physical, to rule in and rule out one diagnosis or another.¹ Perhaps no presentation in medicine depends more on careful history taking and physical examination than acute motor weakness. Here, I’ll outline a practical and efficient six-step approach to help narrow your differential diagnosis for the patient who presents to the emergency department with acute motor weakness. It is my hope that by using this approach, you will arrive at a diagnosis well before any tests are considered.

Step 1: Determine if Weakness Represents a True Loss of Motor Power

The chief complaint of “weakness” is often vague and can mean malaise or fatigue or anhedonia to some people and true loss of motor power to others.² It is incumbent upon the emergency physician to elucidate whether a complaint of weakness represents a true loss of motor power. Some history-taking tips include asking about what activity of daily living or specific function has been lost or made more difficult. For example, patients may complain of being unable to pick up and control a coffee cup, or they may say they had difficulty standing up from a seated position. The word “power” is preferred when communicating with patients and other physicians, as it is more specific to neuromuscular strength than the word “weakness.”

Step 2: Find Pattern of Motor Power Loss

Outside of diffuse weakness, there are five patterns of loss of motor power that each correlate with a specific neuroanatomical source. Diffuse loss of motor power may be caused by systemic problems such as hypo- or hyperkalemia or thyrotoxicosis as well as polymyositis and dermatomyositis.² Paraplegia suggests a lesion in the thoracic or lumbar spinal cord or peripheral nerves, quadriplegia suggests a lesion in the cervical spine, and hemiplegia suggests a lesion in the contralateral cerebral cortex. A bilateral ascending pattern that starts at the feet and progresses toward the head suggests a peripheral polyneuropathy such as Guillain-Barré syndrome or a spinal cord lesion such as transverse myelitis, while a bilateral descending pattern suggests neuromuscular junction disease such as myasthenia gravis or a presynaptic disease such as Lambert-Eaton syndrome.³

Step 3: Investigate Timing, Course, and Fatigability

The onset of loss of power may help narrow the differential diagnosis. An abrupt onset should be considered an acute vascular event such as an ischemic stroke until proven otherwise. That said, small vessel lacunar infarcts may present in a gradual stuttering fashion over hours or even days; thus, a gradual onset should not rule out the possibility of a stroke.⁴ An onset over minutes to hours could also be caused by metabolic abnormalities or toxic exposures. Peripheral neuropathies, neuromuscular junction disease, and myopathies tend to develop over many hours to days. A fluctuating or relapsing course of illness suggests myasthenia gravis, multiple sclerosis, or periodic paralysis, while transient motor loss may be caused by peripheral nerve entrapment or a complex hemiplegic migraine. Finally, fatiguability or worsening motor weakness with repeated muscle contraction, such as chewing or talking, that seems to be more difficult through the day suggests a neuromuscular junction disease such as myasthenia gravis.⁵