Weakness: Guidelines for a Cost-Effective Workup
Weakness: Guidelines for a Cost-Effective Workup
"Weakness" is a common presenting complaint. Physicians who evaluate patients with this symptom face a formidable diagnostic challenge, since the clinical possibilities are vast.
True neuromuscular weakness may result from pathological processes affecting any level of the neur- axis. Disease may involve the muscles (myopathy), neuromuscular junctions (neuromuscular transmission disorder), nerves (neuropathy), anterior horn cells (motor neuron disease), spinal cord (myelopathy), or more central processes. Weakness may portend a benign or life-threatening disorder. Effective treatments may exist and vary according to the specific disease. Accurate diagnosis is therefore essential.
Here we focus on issues related to diagnosis of the cause of true neuromuscular weakness in patients who present in an office setting. Guidelines are presented in the context of time and cost constraints.THE 4 QUESTIONS
In approaching the adult patient complaining of generalized weakness, 4 questions must be considered:
- Is there true weakness?
- Where does the primary pathological process reside?
- What are the diagnostic possibilities?
- What is the specific diagnosis?
As the 5 accompanying cases illustrate (see page 1269), the answer to the first question confirms the problem. The answer to the second question, the "anatomic localization," is determined by the findings on the neurological examination. The initial differential diagnosis is generated by the anatomic localization; this list is further refined by particular elements of the history, thereby providing an answer to the third question. Adjuvant laboratory tests can assist in establishing a final diagnosis.IS THERE TRUE WEAKNESS?
The first step in evaluating patients who complain of generalized weakness is to determine whether true weakness is present. Although many patients complain of "fatigue" and "weakness," many of those with true neuromuscular weakness do not actually use the word "weakness" to characterize their symptoms. Rather, they refer to task-specific dysfunction—eg, difficulty in climbing stairs, getting out of a chair, combing hair, opening jars, or using keys or "foot slapping."
Conversely, patients who do not have true weakness typically offer less specific complaints of "generalized fatigue and weakness" and report being unable to carry out their usual routine activities, such as housework or job-related responsibilities. Some may experience myalgias or depressive symptoms. They do not demonstrate true weakness on physical examination. Psychosocial factors often underlie these patients' difficulties, and effective treatment requires attention to those issues.
However, one must exercise caution in assigning the diagnosis of psychogenic weakness. Nonspecific "generalized fatigue" (in the absence of true neuromuscular weakness) may represent a manifestation of an underlying systemic illness, such as anemia, hypoxemia/hypercapnia secondary to hypoventilation or congestive heart failure, sleep disruption associated with sleep apnea, malignancy, or a low-grade systemic infection. Usually, however, such systemic conditions produce other symptoms or general physical findings that facilitate diagnosis.
In addition, while complaints of nonspecific "generalized fatigue" may not suggest neuromuscular disease, exercise-induced, task-specific "fatigability" is the hallmark of myasthenia gravis. Patients with this disorder may not appear severely weak during a cursory routine examination, but significant weakness may become apparent with repetitive maneuvers.
Other patients may complain of "weakness" in moving their limbs, when the cause is not true neuromuscular weakness. Pain or other mechanical factors may limit a patient's movement or restrict mobility of a joint. Stiffness or rigidity (for example, secondary to parkinsonism) may be perceived by the patient as "weakness." A careful physical examination will identify these conditions.
Finally, one must identify the patient who is malingering or has a conversion disorder. Such patients may offer diffuse or multiple complaints. There may be inconsistencies in the history: the patient may profess that he or she is unable to carry out a certain movement yet report no difficulty in engaging in other activities that require normal function of the muscle groups in question.
Similarly, inconsistencies may be evident in the physical examination: while lying flat, the patient may be "unable" to lift a leg off the bed, but have no difficulty with flexing the hip (elevating a bent knee) in a sitting position. The patient may appear unable to carry out a selected movement when the examination focuses on a specific task, but may perform the same maneuver smoothly and without difficulty when distracted. On formal strength testing, the patient may "give way" suddenly or yield in a "tremor-like" fashion when the examiner provides resistance rather than exerting a smooth, consistent effort. The patient's gait may appear wild, uncontrolled, and unsteady but never eventuate in a fall; the patient may reproducibly lurch into the arms of the examiner.
If such features are unequivocally demonstrated on examination (and no other abnormal physical findings are identified), management should focus on elucidating the relevant psychosocial factors contributing to the patient's difficulties. Further diagnostic evaluations are unwarranted and might actually serve to reinforce the patient's errant perception of physical illness. Since factitious illness and true illness may coexist in the same patient, however, it is important to accurately identify any true pathology before assigning a definite diagnosis of a conversion disorder or malingering.ANATOMIC LOCALIZATION: THE EXAMINATION
In neurological diagnosis, the history and physical examination are of paramount importance. When a patient is being evaluated, the history is taken first. However, when a differential diagnosis is being formulated for a patient with generalized weakness, the examination is considered first.
Assuming that the patient has true documented weakness, the next step is to characterize the pattern of weakness. Neurologists distinguish between paralysis or plegia (absence of movement) and paresis (partial weakness), although the terms are generally used interchangeably. Weakness of the arm and leg on one side is called hemiplegia; weakness of the legs only, paraplegia; and weakness of all 4 extremities, quadriplegia.
It is important to determine whether the weakness is generalized and symmetric, generalized but asymmetric, multifocal, proximally or distally predominant, and lower or upper extremity predominant. Establishing the location of the primary pathological process first requires defining the pattern of weakness, then assessing the patient for the presence of associated neurological findings, such as sensory loss, hypertonicity, hyporeflexia, hyperreflexia, pathological toe signs, or sphincter and cranial nerve dysfunction.
The physical findings seen in various neurological disorders are summarized in Table 1. Although exceptions exist, proximally predominant weakness suggests myopathy or a neuromuscular transmission disorder (eg, myasthenia gravis); distally predominant weakness, a neuropathy; and spinal segmental weakness, a motor neuron disease (eg, amyotrophic lateral sclerosis [ALS]). Hypertonicity indicates upper motor neuron dysfunction, which is seen in spinal cord lesions and often in motor neuron disease. Sensory loss or pain suggests neuropathy or spinal cord dysfunction. Hyporeflexia indicates neuropathy (also Lambert-Eaton myasthenic syndrome and, occasionally, lower motor neuron presentations of ALS); hyperreflexia and upgoing toes suggest myelopathies or anterior horn cell disorders. Bowel or bladder dysfunction indicates a spinal cord process.
Cranial nerve dysfunction is common in neuromuscular transmission disorders (diplopia, ptosis, dysarthria, dysphagia, bilateral facial weakness in myasthenia gravis) and motor neuron disease (dysarthria, dysphagia, tongue weakness in ALS). It is rare in neuropathies (with the exception of bilateral facial weakness in those with Guillain-Barré syndrome). It is also rare in myopathies (bilateral facial weakness occurs in myotonic dystrophy; ophthalmoplegia, in the rare oculopharyngeal dystrophies and selected mitochondrial disorders).
Certain physical examination patterns indicate central disease. A hemiparesis suggests a lesion in the brain. Neck pain indicates a disorder of the cervical spinal cord, whereas alterations of speech, attention, or cortical sensation suggest a hemispheric localization. A quadriparesis with brisk references and hypertonicity (in the absence of cerebral symptoms) suggests a cervical cord process. A paraparesis (sparing the arms) with spasticity and brisk reflexes suggests a disorder of the thoracic spinal cord. (A paraparesis with flaccidity and hypoactive reflexes indicates a peripheral disorder, unless the symptoms were of sudden recent onset [ie, spinal shock]). Bibrachial paresis, or weakness of the arms with sparing of the legs, is seen rarely following cerebral ischemia ("man-in-the-barrel syndrome") but more typically reflects lower motor neuron disease (eg, early ALS).DIFFERENTIAL DIAGNOSIS: THE HISTORY
Myopathies, neuromuscular transmission disorders, neuropathies, motor neuron diseases, and myelopathies each have their own differential diagnoses (Tables 2, 3, 4, 5, and 6). Some general principles can provide a framework for the initial evaluation of the patient.