Focal weakness

I. Problem/Condition.

Weakness is among the most common complaints of patients presenting to the clinic and the hospital, Generalized weakness is very nonspecific, with a long list of potential causes. However, pursuing a rigorous history and neurologic exam using a framework for localizing the source of weakness can help to narrow the differential dramatically.

Muscular weakness must first be distinguished on the history and physical from fatigue (lack of energy), abulia (lack of interest, usually in the context of depression), and asthenia (motor impairment that is due to joint disease or pain). Then the weakness should be categorized. Focal weakness usually denotes asymmetry or predominance of upper versus lower extremities. Focality should alert the clinician to potential neurologic etiology, sometimes requiring urgent intervention. For the purposes of discussion, focal weakness here will include symmetric weakness.

Using symmetric versus asymmetric, localized versus generalized, proximal versus distal, and upper motor neuron (UMN) versus lower motor neuron (LMN) as descriptors is more informative and helps the clinician consider the appropriate differential diagnosis.

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This chapter focuses on localized motor weakness, symmetric and asymmetric. For the hospitalist, the primary consideration when encountering localized muscle weakness is whether the patient is having an emergent neurologic event that requires immediate intervention (acute stroke, impending respiratory failure that is due to muscle weakness, or cord compression) or whether more time is available to evaluate the patient fully and identify a causative mechanism.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

The best strategy for identifying the source of localizing weakness is to think critically about what part of the nervous system is affected and then consider a differential diagnosis for diseases or states that affect that segment.

For the hospitalist, a useful framework is to consider whether the weakness is symmetric or asymmetric. If it is symmetric, is it predominantly proximal or distal? If it is asymmetric, is it predominantly UMN or LMN? On the basis of just these determinations, many potential etiologies are discarded, and relevant confirmatory testing can be obtained.

In general, symmetric causes of weakness arise from peripheral nerve, neuromuscular junction (NMJ), or intrinsic muscular disorders; CNS or UMN diseases are uncommon. Asymmetric causes tend to arise from central nervous system (CNS) lesions, or compression or inflammation of peripheral nerves. NMJ and intrinsic muscle disease are uncommon causes of asymmetric weakness. Occasionally systemic processes can lead to localized weakness. These include hypoglycemia, periodic paralysis, seizures (Todd’s paralysis), and infections (that lead to recrudescence of symptoms after remote strokes).

Symmetric weakness can be divided into proximal and distal disease.

Symmetric proximal weakness tends to be due to myopathy, including inflammatory muscle disease (dermatomyositis, polymyositis, inclusion body myositis, or myositis related to a systemic illness like scleroderma or lupus), drug-induced disease (statin-induced/corticosteroid-induced myopathy, alcohol, or illicit drug-induced myopathies), or endocrinopathies (thyroid or adrenal disease). It can also be caused by diseases of the neuromuscular junction (NMJ), such as myasthenia gravis and Lambert-Eaton syndrome.

Symmetric distal weakness is often accompanied by sensory changes, reflecting a polyneuropathy that can be due to endocrine causes (diabetes, B12, or folate deficiency), toxic effects (e.g., from alcohol use), or inflammation (Guillian-Barre or chronic inflammatory demyelinating syndrome, cryoglobulinemia, vasculitis). Patients with symmetric distal weakness and sensory changes should undergo nerve conduction studies (NCS) to help determine whether the damage is axonal (found with most endocrine or toxic causes) or demyelinating (seen with most inflammatory causes) and further narrow the differential diagnosis.

Asymmetric weakness can be divided into weakness with UMN signs and LMN signs.

Asymmetric weakness with UMN signs is due to a focal lesion in the CNS (brain or corticospinal tracts in the cord). It has an extensive differential diagnosis, including infection, inflammation, neoplasm, and ischemic disease. However, the distribution of the weakness is helpful in determining where the lesion is, and coupled with a detailed history and confirmatory imaging, it can lead to a diagnosis.

Asymmetric weakness with LMN signs is usually caused by a compression neuropathy or mononeuritis multiplex. Examples of the former include median (carpal tunnel), ulnar, or radial neuropathy, while mononeuritis is usually caused by diabetes (which can also cause a symmetric distal polyneuropathy) or vasculitis.

Patients with weakness without clear UMN or LMN signs (preserved reflexes, normal tone) likely have NMJ disease or intrinsic muscle disease, although the exam can be similar early in the course of UMN/LMN-predominant disease.

Although these guidelines apply to most patients, some diseases, such as myasthenia gravis, can have protean manifestations and symptoms that fall into more than one category.

B. Describe a diagnostic approach/method to the patient with this problem

The hospitalist should be immediately concerned about two kinds of patients:

1) Those who present with localized asymmetric weakness, especially if the patient is at risk for cerebrovascular disease (because acute ischemic stroke may be ameliorated with thrombolytic therapy), and

2) Those who present with symmetric, progressive weakness (for example, those with Guillain-Barre or myasthenia gravis), who may be approaching respiratory insufficiency that is due to weakness, and patients with cord compression.

For those who present with localized asymmetric weakness, a quick neurologic assessment and rapid head imaging (CT without contrast to rule out an acute bleed) in consultation with an acute stroke team is prudent; for those who present with symmetric, progressive weakness, measurement of respiratory muscle force (forced vital capacity and negative inspiratory force) and early intubation, if indicated, may be life-saving. In the case of cord compression, early intervention may prevent paralysis (see below).

In other patients, after localizing the lesion (whether symmetric or asymmetric, and whether UMN or LMN), it is then useful to consider the usual causes of neurologic disease in the context of the patient in question: could genetic/hereditary, inflammatory, infectious, neoplastic, toxic/drug-related, or metabolic/endocrine disorders be at work?

Finally, if a diagnosis is suspected, determine the best confirmatory test.

1. Historical information important in the diagnosis of this problem.

The history is most important for eliminating other conditions masquerading as motor weakness (abulia, asthenia, and fatigue, as above), determining the chronicity of the problem, determining the distribution of the weakness, and identifying relevant past medical history, medications, or toxic exposures that may suggest whether the etiology of the weakness in question.

Even in inflammatory myopathies, pain is an uncommon association with muscle weakness, so it should lead to investigation of asthenic joint or bone involvement. Further, asthenic patients often will complain of “weakness,” whereas patients with true weakness often complain of their inability to do certain tasks (get out of a chair, comb their hair) or “heaviness” of their limbs when doing such tasks. Patients with abulia complain predominantly of lethargy or lack of energy.

Understanding the chronicity of the problem can be helpful: an abrupt onset suggests a vascular event or new toxic/metabolic disturbance, whereas subacute onset over days to weeks is more commonly associated with neoplastic, infectious, or inflammatory sources of weakness. Weakness that is even more gradual – increasing over months to years – has a degenerative, endocrinologic, or, rarely, neoplastic basis.

The course of the illness over time is also helpful; ischemic stroke tends to be most severe at onset and improve, while hemorrhagic conversion may have progressively worsening deficits. Episodes of weakness with periods of improvement over days to weeks suggest vascular or inflammatory causes, while a steadily progressive course is more consistent with a degenerative or neoplastic etiology. Rapid fluctuations over short periods of time is characteristic of myasthenia gravis.

Proximal muscle weakness leads to difficulty with going up or down stairs, getting up from sitting or squatting, or trouble with reaching over the head (e.g., to comb one’s hair). Distal weakness tends to be described by patients as “clumsiness,” especially with fine motor tasks such as using buttons or shoelaces or grasping objects. Distal weakness of the lower extremities usually presents with complaints of frequent tripping or falling over the feet.

Care should be taken to question the patient closely about symptoms of bulbar weakness, including diplopia, difficulty chewing, drooling, difficulty swallowing, or dysarthria, which may herald more severe or proximal motor dysfunction.

2. Physical examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Hospitalists should have a basic neurologic examination they perform on most patients, which will be sufficient for many patients with weakness. However, hospitalists should be attuned to several aspects of weakness that they may not traditionally emphasize:

1) Muscle appearance – Are atrophy or fasciculations present, suggesting LMN/muscle disease?

2) Muscle tone – what is the resistance to passive movement of the muscles? Spasticity is an increase in tone that affects muscle groups to variable extents (e.g., increased tone in flexors over that of extensors in the arms or the reverse in the legs). A clue to finding spasticity may be that tone is high at the beginning of a passive movement and then drops away (the so-called “clasp-knife phenomenon”). Spasticity is a clue to UMN disease. Rigidity (increased resistance that affects all muscles the same way) indicates extrapyramidal disease, rather than muscle weakness. Hypotonia, on the other hand, suggests LMN, NMJ, or muscular disease. Pain with palpation of the muscle occurs in viral myositis and rhabdomyolysis but is otherwise uncharacteristic of motor disease.

3) Muscle power – This is where weakness is best defined in the exam, using a 0-5 scale. The hospitalist may find it useful to remember that a strength score of 0-1 represents no or trace muscle contraction, 2 represents movement with gravity eliminated, 3 is movement against gravity only, 4 is decreased power against resistance, and 5 is normal strength.

4) Reflexes – Hyperreflexia (including clonus and a positive Babinski sign) and hypo/areflexia are helpful in determining whether a lesion is UMN or LMN, and they are especially helpful when they are asymmetric. For example, focal reflex deficits often relate to peripheral nerve lesions as a result of compressive neuropathy, while distal reflex deficits with preserved proximal reflexes usually accompany a length-dependent polyneuropathy.

After examining these aspects of weakness, the hospitalist should feel confident in whether the weakness is symmetric or asymmetric, and if symmetric, whether it is proximal or distal. The location of the lesion can be confirmed in the nervous system by the presence or absence of UMN signs (weakness, spasticity, hyperreflexia, positive Babinski, lack of atrophy) or LMN signs (weakness, hypotonia and areflexia, wasting and fasciculations). If the weakness is thought to be due to a LMN lesion, only those muscles that are supplied by a given nerve are weak, so careful testing of the involved muscle groups will pinpoint the lesion.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Testing will be defined by the pattern of weakness.

For proximal symmetric muscle weakness, testing should focus on systemic disease that may be responsible for the pattern, such as a TSH, cortisol level, CK and aldolase, serum electrolytes, and autoimmune tests if an inflammatory source is suspected. Look for a positive urine dipstick for blood in the absence of red cells for a clue to myoglobinuria.

For distal symmetric muscle weakness, laboratory testing is an adjunct (B12, HgbA1c) to the primary diagnostic test, which is usually NCS and electromyography (EMG). NCS and EMG are useful only when the site of the lesion is suspected to be in the peripheral nervous system, the NMJ, or the muscle itself.

Asymmetric weakness also relies heavily on EMG and NCS for presumed compression neuropathies. Disease with UMN signs should prompt the hospitalist to consider imaging the spinal cord (MRI is preferred over CT or myelography) or CNS (MRI is preferred because of its improved visualization of corticospinal tracts) and, when indicated, lumbar puncture. In patients with suspected vasculitic asymmetric weakness, testing for ANCA, hepatitis B and C, and cryoglobulins may prove fruitful.

Muscle biopsy can reveal of intrinsic muscle disease, vasculitis, or congenital enzyme abnormalities/storage diseases. MRI or EMG can indicate the best sampling location preoperatively.

C. Criteria for diagnosing each diagnosis in the method above.

The list of diagnostic possibilities in localizing weakness is too long to list the conclusive criteria for diagnosis of each entity; however, the hospitalist who is able to localize the lesions and instigate an appropriate workup will confirm the diagnosis or maximize the useful information available to a consultant, who can then use specific diagnostic tests (e.g., EMG/NCS) to confirm the diagnosis.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

Clearly defining the location of the lesion avoids unnecessary testing, such as imaging of the CNS in LMN disease or EMG/NCS in UMN disease. Diagnostic testing should be performed in the context of the most likely possibilities, given the demographics and comorbidities of a certain patient; long lists of autoimmune antibodies may be checked and come back positive by chance, but they are unlikely to reflect underlying disease without suggestive history and physical.

III. Management while the Diagnostic Process is Proceeding

A. Management of focal weakness.

Immediate management of patients with asymmetric localized weakness is required, given concern for cerebrovascular event. In such a situation, engaging an acute stroke team and early imaging give the patient the best chance for functional recovery.

Immediate management of patients with progressive symmetric muscle weakness is also required if there is concern for respiratory muscle insufficiency, as these patients are likely to have normal arterial blood gas testing until complete respiratory collapse. Hence, regular measurement of negative inspiratory forces and vital capacity are necessary to monitor for this event. Patients who carry a diagnosis of myasthenia gravis are particularly susceptible if they are hospitalized for another reason, as the stress of the illness can precipitate myasthenic crisis, which may require intubation, plasmapheresis, and/or IVIg therapy.

Finally, immediate management of patients with concern for cauda equina syndrome or cord compression is required; early imaging is required to delineate the lesion, but corticosteroids and radiation therapy or laminectomy may be emergently indicated. Emergent management is required because treatment is rarely associated with recovery of function; rather, the neurologic exam when treatment starts for cord compression or cauda equina syndrome is often the best outcome one can expect after treatment. If this neurologic exam is severely compromised at treatment onset treatment may be of limited benefit.

B. Common Pitfalls and Side Effects of Management of this Clinical Problem

Common pitfalls in the correct diagnosis and management of localized muscle weakness include the failure to identify the location of the lesion in the motor pathway so pursuing testing that is not indicated, and failure to involve a neurologic consultant sufficiently early in the diagnostic workup, particularly when vascular disease is suspected. Hospitalists must also keep in mind that patients with myasthenia gravis, motor disease with bulbar involvement, amyotrophic lateral sclerosis, Gullain-Barre, and CIDP can become dramatically worse because of other medical stressors, and suspicion must be high for respiratory collapse.

One can imagine the pitfalls if the location of the lesion is not identified accurately, such as when a patient is being considered for LMN disease who undergoes MRI imaging of the brain or spine. Many nonspecific abnormalities will be identified in older patients, so how should the ordering physician know where to intervene? Conversely, a patient may not thank an ordering provider for a nondiagnostic EMG, which can be painful. This is an area of medicine where the history and physical exam are essential for an accurate, informative laboratory and imaging workup.

IV. What's the evidence?

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William Wesley, Campbell, DeJong, Russell N., Haerer, Armin F.. . 2012.

Abrahm, JL, Banffy, MB, Harris, MB. “Spinal cord compression in patients with advanced metastatic cancer: "all I care about is walking and living my life"”. . vol. 299. 2008 Feb 27. pp. 937-46.

Spillane, J, Beeson, DJ, Kullmann, DM. “Myasthenia and related disorders of the neuromuscular junction”. . vol. 81. 2010 Aug. pp. 850-7.

Sathasivam, S. “Statin induced myotoxicity”. . vol. 23. 2012 Jun. pp. 317-24.

Khan, S, Christopher-Stine, L. “Polymyositis, dermatomyositis, and autoimmune necrotizing myopathy: clinical features”. . vol. 37. 2011 May. pp. 143-58.

van der Worp, HB, van Gijn, J. “Clinical practice. Acute ischemic stroke”. . vol. 357. 2007 Aug 9. pp. 572-9.