Chapter 12 - Evaluation of the Patient with Weakness
Weakness is a common presenting concern in neurology. This chapter will discuss the evaluation of the weak patient. It will build on the chapter on examination of the motor system (Chapter 10) and will defer to the chapter on neuromuscular disorders (Chapter 21) for detailed discussion of many of the conditions.
The evaluation of the patient complaining of weakness must proceed in an orderly fashion. In the history, it is important to determine exactly what the patient means by "weak"; what are the specific muscle groups that are weak; whether there are associated findings with the weakness; and what has been the timing of onset of the weakness. Additionally, family history, the presence or absence of systemic signs and symptoms and the association of the weakness with other symptoms (such as pain) are relevant. Additionally, information about exposure to medications or toxins and potential exposure to infectious agents may be relevant. The examination can be helpful in determining whether the weakness is of upper or lower motor neurons or whether disease of the myoneural junction or of the muscles is present. Specialized testing, such as laboratory tests and electrodiagnostic testing may be of use in confirming the level of damage and focusing on an etiologic diagnosis.
What does the patient mean by “weakness?” You many be surprised to find that the patient is using the term to denote something other than what you understand to be the meaning of the term. In neurologic practice, weakness means the loss of strength or power, manifesting in the inability to generate normal force. The complaint of "fatigue" or general lack of energy rarely results from disturbance of the neuromuscular system and is not what this chapter is about. These complaints are often part of more systemic disorders, and are a common end result of many diseases, including rheumatologic disorders, endocrine, infectious and neoplastic disorders, not to mention psychiatric conditions. Complaints of "fatigue" may result from such diverse processes as sleep disorders or chronic fatigue and fibromyalgia syndrome. Although complaints of "fatigue" are rarely due to neurologic disease, it can occur as a result of multiple sclerosis and Parkinson disease (although rarely without other evidence of the condition). Therefore, the first step in evaluation is to determine whether the patient is truly weak and the history can begin to address this issue.
Occasionally, patients with other disorders of the motor system, such as rigidity or incoordination, may describe themselves as being weak because they have difficulties in performing motor acts. In this context, weakness may simply be a surrogate term for motor abnormality. Therefore, it is critical to determine whether the patient has actually lost power in performing certain actions. Simple questions, such as whether the patient can rise from a chair without assistance or climb a step, or whether they can lift up a gallon of milk from the refrigerator may help in determining whether strength and power are actually lost. A more open-ended question such as "what could you do that you no longer can do" may be a very helpful question in patients who are aware of their situation.
Spatial distribution of weakness. The next question that history can begin to answer relates to the particular pattern of weakness. For example, is the weakness mostly of proximal muscles or is it predominantly of distal muscles? Is the weakness on one side of the body or both and is it in the distribution of a particular nerve or group of nerves? Broad areas of weakness are more likely to be either damage to the central nervous system or a systemic disease that is attacking nerves. Weakness of a single limb can result from a large range of conditions, including spinal cord or multiple nerve roots, versus plexus lesions. Weakness of proximal muscles, that is weakness of shoulder and hip girdle muscles, is suggestive of a myopathic process (a process directly damaging muscles), while distal weakness is more likely to be a generalized polyneuropathy. If weakness of a limb is associated with lower facial weakness on the same side, the problem is above the brainstem, while if there is weakness of muscles on one side of the head and opposite limb, then a lesion in the brainstem is suggested.
Associated symptoms. Certain associated symptoms may help localize the part of the nervous system that is damaged, while other symptoms may put the condition in the larger context of disease. For example, the presence or absence of associated atrophy or fasciculations suggest damage to anterior horn cells or motor axons (i.e., lower motor neurons). Of course, any such report by the patient should be confirmed by examination. The presence of symptoms of systemic diseases may be a critical clue to diagnosis. For example, certain rheumatologic disorders can attack peripheral nerves. Several endocrine disorders, particularly those affecting thyroid or adrenal function, can present with weakness, while metabolic disorders such as diabetes mellitus often damage nerves. Hints regarding the presence of underlying neoplasia or infectious disorders may also be obtained from history.
Associated symptoms may provide important clues to whether other portions of the nervous system have been effected in addition to motor damage. Complaints of “numbness” or tingling, vision disturbance or vertigo suggest broader damage to the nervous system. The presence of such symptoms may indicate the level of damage to the nervous system or alert you to the presence of a neurologic syndrome. A change in character of the voice or problems swallowing (usually choking on water) suggests that the weakness may involve the pharyngeal muscles or those of the palate. Myelopathy (damage to the spinal cord) often produces bilateral symptoms below a certain level on the body. This may be attended by urgency of bladder function. Another common feature of damage to spinal cord, or peripheral nerves for that matter, is the combination of sensory and motor complaints. Some complaints can indicate a potentially serious neurologic disorder requiring urgent action. This includes rapidly progressive weakness of both lower extremities, which can be due to acute myelopathy, compressive lesions of the cauda equina (“cauda equina syndrome”) or Guillain-Barre syndrome. In any of these cases urgent evaluation is appropriate due to the need for prompt treatment.
Temporal characteristics. The tempo of onset and progression of the weakness is important, as is the question of whether the weakness is intermittent. Certain conditions have clear timing of onset and rapid progression. These include most vascular, infectious, inflammatory or traumatic disorders. Most degenerative conditions or those related with chronic conditions (such as metabolic or hereditary disease) develop insidiously. When conditions are intermittent, it is important to determine whether there are particular things that precipitate or worsen it. For example, if repeated activity tends to worsen the weakness (for example, if there are things that patients can’t do at the end of the repeated activity that they could at the beginning), this suggests a diagnosis of myasthenia gravis (a neuromuscular disease). If there are particular movements or postures that results in the weakness, this suggests some mechanical or orthopedic problem such as entrapment neuropathy, radiculopathy or localized vascular occlusive problem. If there are particular times of the day that symptoms are present, or if there are definite associations with eating, an ion channel disorder should be considered. Finally, if the symptoms happen at random, with recovery after five to 30 minutes, transient ischemia of the central nervous system should be considered.
Family history. Family history may be important in detecting hereditary neuropathies and myopathies. Additionally, some of the familial periodic paralysis problems that are associated with ion channelopathies may be hereditary.
Pain. Pain can be a particularly difficult symptom to assess in the weak patient. First of all, a highly specific pain pattern may indicate nerve root damage or damage to a particular peripheral nerve. On the other hand, many patients with pain report “weakness” that has nothing to do with nervous system damage. There are both voluntary mechanisms and unconscious mechanisms that limit the use of a painful body part. This can be perceived by the patient as weakness, despite a completely normal and intact neural and neuromuscular mechanism. On examination of such patients, there appears to be intermittent effort and “break-away” type weakness and the patient may be perceived to be “faking it.” This assessment should be made with great caution, especially in the case of painful syndromes.
Once the history has been obtained, the examination is focused on confirming the pattern of weakness and determining the type of weakness. True weakness can be caused by problems affecting upper motor neurons, lower motor neurons, the neuromuscular junction or the muscle itself. Upper motor neurons represent the neurons in the brain, whose axons descend the brain stem and spinal cord to contact the anterior horn cells. In practice, many of these are corticospinal (pyramidal) neurons. In many ways, these can be thought of as the "command neurons” for movement. The lower motor neurons are the anterior horn cells, along with their axons. These axons course through the ventral root, plexi and peripheral nerves, in order to reach their targets in the muscles. The myoneural junction is the cholinergic synapse between the lower motor neurons and muscle fibers, which represent the final contractile element.
Upper motor neuron. Upper motor neuron weakness presents in a rather characteristic pattern. First of all, it tends to affect broad areas of the body. This is because axons are quite tightly packed when they are in the brain stem and spinal cord. Typically, weakness is accompanied by an increase in deep tendon reflexes such as the biceps, triceps, patellar or ankle jerks. There is usually a decrease in superficial reflexes such as the abdominal, cremasteric reflex or the normal plantar response. There may well be the appearance of pathological responses, such as the Babinski response. Finally, upper motor neuron lesions are characterized by relatively minimal atrophy, and do not lead to the fasciculations. It is noteworthy that some atrophy may take place due to disuse, since the affected body part is unlikely to be exercised regularly. There may be increased tone of a spastic nature associated with heightened muscles stretch reflexes. This increased tone tends to appear in a "clasp knife" pattern. One caveat in the evaluation of upper motor neuron problems is that very large and acute injuries may produce a period of generally diminished tone and responses that has been termed "spinal cord shock" since this is usually seen with acute traumatic spinal cord injuries.
Lower motor neuron. Lower motor neuron weakness may result from damage to the anterior horn or its axon anywhere along its course from the CNS to the muscle that is weak. Lower motor neuron disease tends to result in decreased muscle tone, decreased reflexes in the affected area, atrophy and, possibly, fasciculations. Fasciculations are most prominent when the anterior horn cell is affected. They result from the random and spontaneous depolarization of a motor neuron or motor axon and results in a visible twitch of the skin over the muscle. Of course, there are benign fasciculations that most people have had at one time or another due to local irritation of motor nerve fibers in an overused muscle (these are temporary). Some individuals have more persistent benign fasciculations (usually in the calves). However, in the case of benign fasciculations the twitches are not associated with any other sign of lower motor neuron damage. Electromyography can be used to confirm this, if necessary.
Lower motor neuron damage within a peripheral nerve results in a distribution of symptoms that reflect of the motor distribution of the peripheral nerve (see table 10-5). The diseases that damage anterior horn cells are generally more widespread and do not follow the distribution of a single nerve (although they can focus on one limb, especially early in the course).
Neuromuscular disease. Neuromuscular disease is characterized by fluctuating strength based on muscle use. For example, myasthenia gravis results in decreasing power with continuous contraction. On the other hand, Lambert-Eaton myaesthetic syndrome (LEMS) results in increased strength with repeated contraction.
Myopathy. Muscle diseases are generally proximal and symmetrical. These often result in particular difficulties arising from the chair or holding up one's arm against gravity. There is usually minimal atrophy until late in the course and muscle stretch reflexes typically remain normal. An exception to this general rule is myotonic dystrophy, which tends to affect the muscle of the distal extremity most prominently. This condition is associated with myotonia, which is recognized by the inability to rapidly relax a muscle after tonic contraction (for example, problems opening the hand quickly after making a tight fist).
There are some unusual diseases that produce intermittent weakness of muscle contraction, most notably the familial periodic paralyses. These conditions are associated with abnormal ion channels and can be particularly difficult to diagnose. Patients often show abnormal serum potassium (some low and some high) during the episode of weakness and symptoms often follow a period of exercise or follow a heavy carbohydrate meal. Examination in between attacks may be completely normal until late the condition.
Various laboratory tests may aid in diagnosis. If peripheral nerve disease is anticipated, testing of complete blood count, glucose level, sedimentation rate, serum protein electrophoresis, antinuclear antibody levels, VDRL/RPR, vitamin B12 level, and Lyme titer may be useful. In the right setting, testing of heavy metal exposure, or firms or HIV status may be appropriate. Muscle disease often results in an increase in creatine kinase levels in the blood, although this is quite nonspecific in terms of etiologic diagnosis.
Blood tests for antibodies against acetylcholine receptors or certain other muscular antigens may be indicated when neuromuscular disease is suspected. These are not 100% sensitive, however.
When the location or distribution of weakness is in question, electromyography and nerve conduction studies may be extremely helpful (See the discussion on electrodiagnosis). This testing is particularly good at identifying signs of damage of nerves to muscle and nerve conduction studies often localize the specific point of nerve injury. Needle electromyography is the single most sensitive test at detecting lower motor neuron damage and may give important information as to whether this is recent or old. Newer techniques, such as transcranial cortical magnetic stimulation, may effectively examine the central motor pathways, as well.
Neuromuscular disease can also be studied electrodiagnostic testing. Repeated nerve stimulation may either show a decrease with repetition (myasthenia gravis) or an increase in contraction (LEMS). While these are not very sensitive tests, they are quite specific. Single fiber electromyography is a highly specialized procedure, but increases the sensitivity of electrodiagnostic testing for suspected neuromuscular disease
There are many potential causes of weakness. Each of these conditions is explained in greater detail in the third section of the book and we will only briefly touch on the differential diagnosis once a decision has been made as to whether the weakness is due to damage to upper motor neurons, lower motor neurons, the neuromuscular junction or the muscle.
Muscle diseases. Muscle diseases are most often productive of proximal and symmetrical weakness. As described in the previous section, there may be EMG abnormalities and creatine kinase levels are often elevated. Some of these conditions are primary, with the pathologic process essentially restricted to the muscle, and some secondary, where the muscle is affected by the systemic disease. The finding of a secondary myopathy often leads to a specific treatment, so it is important to consider these early in the evaluation. Causes of secondary myopathy include: infection (such as trichanosis), connective tissue disease, endocrine abnormality (particularly thyroid and adrenal dysfunction), paraneoplastic processes or may be related to drug or toxin exposures (for example statins). Primary myopathies can be broadly broken into subcategories of congenital or hereditary myopathies (dystrophies), inflammatory myopathies, and metabolic myopathies. These are discussed in greater detail in Chapter 21. The inflammatory myopathies are occasionally recognized by systemic signs, along with blood chemistry findings of muscle damage and inflammation (although inclusion body myositis may be insidious and without these other features). The dystrophies and metabolic myopathies (which are due to some deficit in critical muscle enzymes) tend to be more slowly progressive and often require invasive and specific genetic testing for confirmation. Table 21-5 lists conditions that should be considered in the differential diagnosis of myopathy.
Neuromuscular junction. Neuromuscular junction disorders may result from drugs and toxins or from diseases such as myasthenia gravis or Lambert-Eaton myaesthenic syndrome. Toxins such as botulinum toxin, certain snake venom's or tick-borne toxins are rare, but enter the differential diagnosis of neuromuscular disease. Drugs that affect neuromuscular transmission or certain pesticides can work in a similar way to block neuromuscular transmission. However, myasthenia gravis, and LEMS represent the majority of potential causes of neuromuscular conduction blockade. These are described in some detail elsewhere in the book. Briefly, myasthenia gravis, produces a decrement in strength with continued contraction, and most commonly affects the muscles of the eye and pharynx. Lambert-Eaton myasthenic syndrome, which typically affects hip girdle mussels, results in increased strength following repeated contraction.
Lower motor neuron. Lower motor neuron problems may result from several processes, including those affecting peripheral nerves, plexi, nerve roots or the anterior horn cells in the brainstem and spinal cord. Polyneuropathy results from a systemic condition damaging peripheral nerve. This may be due to toxic, metabolic, nutritional, infectious, hereditary, or immune/inflammatory conditions. The diagnosis of the patient with polyneuropathy is discussed in Chapter 21 although most of the potential causes are listed in table 21-4. One particularly important condition producing polyneuropathy is acute inflammatory demyelinating polyradiculoneuropathy (AIDP; Guillain-Barré syndrome). This condition should be considered in any patient with acute or subacute progression of weakness with loss of reflexes. A waxing and waning, chronic form of inflammatory polyradiculoneuropathy also exists (CIDP).
Many cause of lower motor neuron symptoms are due to local compression or trauma to nerves or nerve roots. These are recognized by the pattern of weakness (table 10-5). Compressive neuropathies and traumatic injuries tend to occur at specific sites along the peripheral nerves (see: Chapter 21)
Radiculopathy usually results from conditions in and around the spine, including intervertebral disc disease, spinal stenosis, neoplasms, radiation or chronic forms of meningitis can damage peripheral nerve roots either singularly or multiply (polyradiculopathy). These are often recognized as producing radiculopathic pain, which is frequently, though not always, provoked by particular movements or positions (such as the straight leg raise or Spurling’s maneuver (fig 1-4; fig 1-5).
Anterior horn cell disease typically produces significant fasciculations and atrophy. These conditions are usually degenerative, traumatic or infectious, though occasionally other causes of damage to the spinal cord (such as neoplasms, radiation or vascular insufficiency) can present with amyotrophy. Degenerative conditions include a range of conditions, generically termed “motor neuron diseases.” The prototype for the family of conditions is amyotrophic lateral sclerosis. Infections can also damage the anterior horn cells. The prototype for these conditions is poliomyelitis. However, a range of infectious processes, including cytomegalovirus and Lyme disease, may also attack the anterior horn cell and result in lower motor neuron damage. Compressive disorders of the spinal cord, whether chronic and due to degenerative spinal stenosis or subacute (such as with tumors or mass lesions) can preferentially affect the gray matter of the spinal cord and produce anterior horn cell damage. Spinal cord radiation, vascular occlusive disease in the spinal cord (quite rare) or infiltrating tumors of the spinal cord (also quite rare) are additional considerations. Fortunately, magnetic resonance imaging has made the evaluation of expensive segments of the spinal cord much easier.
Upper motor neuron disease. Finally, a finding that weakness results from upper motor neuron damage requires consideration of all disorders that can damage the cerebral cortex or axons extending through the brainstem and spinal cord. These include cerebrovascular disease, vascular malformations, tumors, trauma, infection, demyelination, degenerative conditions, congenital problems, toxic disorders, metabolic disorders, developmental problems or radiation damage.
In summary, the evaluation of the weak patient needs to be systematic. History can help determine whether the patient is truly weak, and the pattern of weakness. It can also help determine whether hereditary disorders or other associated metabolic or endocrine conditions are high on the list of possibilities. Medications and toxic potential toxic exposures should be explored as part of the history and an understanding of the tempo of the condition must be obtained. Examination is focused on helping to determine whether the weakness is likely to result from upper motor neuron problems, lower motor neuron problems, myoneural junction problems or myopathy. Electromyographic studies may be useful in confirming the impression of neuropathy, anterior horn cell disease or myoneural junction disorder. Blood tests may aid in ascertaining a cause. Finally, narrowing down the cause of the weakness requires considering the list of possible conditions that can produce the type of weakness being manifested by the patient.
- Monrad-Krohn, G.H. and Refsum, S.: The Clinical Examination of the Nervous System, ed. 12, London, H.K. Lewis & Co., 1964.
Define the following terms:fatigue, rigidity, myopathy, neuromuscular junction/myoneural disease, upper motor neuron, lower motor neurons, polyneuropathy, Charcot-Marie Tooth, Lambert-Eaton myasthenic syndrome, paraneoplastic syndrome, myasthenia gravis, nerve conduction study, electromyography.
12-1. What are the levels of the nervous system that can produce true weakness?
12-2. How is strength graded?
12-3. How can strength be tested functionally?
12-4. Other than actual weakness, what other symptoms might the patient be describing when they use the term “weak”?
12-5. What is suggested by proximal, symmetrical distribution of weakness (hip and shoulder girdle)?
12-6. What is suggested by distal, symmetrical distribution of weakness (feet and/or hands)?
12-7. What does it mean if there atrophy out of proportion to the degree of disuse?
12-8. What would be suggested by fatigability of muscles?
12-9. What conditions can cause transient weakness?
12-10. What is suggested by a story of severe, global weakness associated with heavy meals or periods of exercise?
12-11. What systemic conditions can produce weakness?
12-12. How can pain affect the diagnosis of the patient with weakness?
12-13. What conditions can present as bilateral weakness of the lower limbs?
12-14. What is the likely cause of weakness of one side of the body that is associated with a lower facial weakness on the same side?
12-15. What is the likely cause of weakness of one side of the body that is associated with weakness on the opposite side of the head (tongue, jaw, palate or eyes)?
12-16. What procedure can be used to objectively demonstrate whether nerves to a muscle are damaged?
12-17. What is the effect of upper motor neuron damage upon muscle bulk, tone, deep tendon reflexes and superficial reflexes?
12-18. What is the effect of lower motor neuron damage upon muscle bulk, tone, deep tendon reflexes and superficial reflexes?
12-19. What is the effect of muscle or neuromuscular disease on muscle bulk, tone, deep tendon reflexes and superficial reflexes?
12-20. What kinds of problems produce diffuse muscle damage (myopathy).
12-21. What kinds of conditions damage or block the neuromuscular junction?
12-22. What differences would be expected between myasthenia gravis and Lambert-Eaton myasthenic syndrome (LEMS).
12-23. What is the effect of lower motor neuron damage upon muscle bulk, tone, deep tendon reflexes and superficial reflexes?
12-24. What disorders can damage peripheral nerves?
12-25. What kinds of conditions damage nerve roots?
12-26. What kinds of conditions damage anterior horn cells?
12-27. What kinds of problems are associated with upper motor neuron damage?