Undifferentiated Weakness: ED-Focused Approach and Management

Author: Laryssa Patti (EM Chief Resident, Robert Wood Johnson EM) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

You are three-quarters of the way through your shift in the emergency department (ED) and your next patient has one of the most dreaded chief complaints.  The triage note states that your patient is a 75-year-old female with three days of WEAKNESS. Even the most experienced provider would want to sneak that triage note back in the rack without anyone noticing. Weakness can be a sign of any pathology and this article attempts to provide some steps toward evaluating and managing the weak patient.

Step 1: Define the weakness

Patients may have a difficult time defining their weakness. Patients may state that “I just do not feel right” or “I am lethargic”. Assess if the symptoms are acute, sub-acute, or chronic. Was a traumatic injury involved? Determine if the weakness is focal or non-focal. Narrow down any specific body part(s) affected – is it unilateral or bilateral? Does it involve a single extremity or both? Does it involve one side of the body? Does it affect a single nerve or group of nerves (1)?

Next, determine how the weakness manifests. For example, is the patient dropping things or having difficulty with fine motor tasks? Or is the patient having difficulty with large motor groups such as walking, taking the stairs, or getting out of chairs? Is the weakness continuous, or does the patient notice that symptoms are worse at certain times of day or in certain scenarios? Are they having difficulty with balance?

Check for other associated symptoms. Is there sensory involvement? Is there a change in mental status?  Does the patient have a headache? Does the patient actually mean that he or she is fatigued rather than weak? Finally, ask the patient if there are any areas of pain associated with his or her weakness (2).

Step 2: Remember that common things are common and can be serious

In a 2010 study by Nemec et al. (3), 218 elderly ED patients with non-specific complaints such as weakness and dizziness were examined for serious 30 day outcomes. The researchers found that nearly 60% of this elderly population had a serious condition diagnosed in the 30 day follow up period. The 30-day mortality rate was 6%. Thus, generalized complaints such as weakness and dizziness can be serious and should be kept in mind when evaluating these complaints in the ED.

Conduct a careful history and physical examination to evaluate for the more common etiologies of weakness. One should always include a neurological exam, as Nickel et al. (4) suggested that up to 76% of elderly patients presenting the ED with complaints of localized weakness had a final diagnosis of transient ischemic attack, cerebral ischemia, or intracerebral hemorrhage.  CT of the brain should be considered when clinically indicated. Also consider delirium in the differential.

Always check an ECG, a blood glucose level, electrolytes, and urinalysis.

Hypoglycemia is an easily diagnosed etiology of weakness and a cannot-miss for emergency physicians. In patients who present with hypoglycemia, make sure to determine why the patient is hypoglycemic. Did he or she not eat? Is it medication induced? Or is it due to another cause such as sepsis?

Electrolyte abnormalities, especially in the elderly population, can also be causes for weakness. A 2013 study by Mannesse et al. (5) found hyponatremia as a reason for admission in up to 22% of geriatric ward admissions.  In addition, Chao et al. (6) found acute or acute on chronic kidney injury in the geriatric population to be associated with increased complications during hospitalization, including GI bleeding, new electrolyte imbalance, and hospital-associated infections. Similarly, a 2014 study by Rohrig et al. (7) found that in a retrospective review of over 1000 patients over the age of 70, 36.4% of outpatients admitted through the emergency department were anemic, which most certainly can contribute to weakness.

 Rule out acute MI and arrhythmias as causes of weakness. In a 2002 chart review, Gupta et al. (8) noted 4% patients with chief complaints of weakness were diagnosed with acute ST elevation MI in the emergency department. Similarly, it is important to rule out conduction delay, bradycardia, and tachycardia as potential causes of weakness.

Consider an infectious cause as a possibility for generalized weakness and fatigue. This may include meningitis to a simple viral syndrome.  Something as simple as a urinary tract infection in an elderly patient can cause debilitating symptoms. Additional imaging, such as a chest x-ray, should be considered if clinically indicated.

One should also consider toxic and pharmacologic causes of weakness in patients presenting to the emergency department. In the elderly population, think about polypharmacy as a possible contributor. In Hohl et al. (9), patients 65 years of age or older were taking on average 4.2 different medications and adverse drug reactions contributed to 10.6% of their ED visits. Similarly, if patients have an acute or acute on chronic kidney injury, their metabolism of renally excreted medications may be compromised. Consider digoxin toxicity, which is partially excreted by the kidneys and dependent on urine flow. Similarly, consider patients unintentionally omitting or increasing doses of their maintenance medications.

Step 3: Consider pathologies that affect the spinal cord

If you are not seeing a pattern consistent with cerebral infarction, consider spinal cord ischemia as a possible cause of weakness. While a rare cause of central nervous system (CNS) infarction, it can be serious. The posterior one third of blood supply to the anterior two-thirds of the spinal column comes from the anterior spinal artery and two posterior spinal arteries. The anterior spinal artery arises from branches of the vertebral arteries and the posterior spinal arteries arrive from the cerebellar arteries. The thoracolumbar spinal column is reliant on the artery of Adamkiewicz, which stems from the thoracic aorta.  In rare cases, these arteries can become occluded, dissected, or hypoperfused (10).

Central cord syndrome

The most common of the incomplete spinal cord injuries is acute traumatic central cord syndrome, classically characterized by upper extremity weakness greater than lower extremity weakness with variable sensory loss below the level of injury. A loss of pain and temperature sensation may extend in a “cape-like” distribution over the shoulders and upper arms (11, 12, 13). Some patients may have “burning” sensations in the upper extremities. The suspected etiology of central cord syndrome is due to hyperextension of the neck. However, the affected population is bimodal. In those under 30 years old, symptoms may be secondary to high velocity injuries, whereas in elderly patients, symptoms may be due to lower impact injuries in the setting of pre-existing cervical stenosis (14). In either case, the ligamentum flavum protrudes inward, causing acute spinal canal narrowing and contusion to the spinal column. Diagnosis can be made via magnetic resonance imaging (MRI). Initial treatment is supportive and includes management of the airway, immobilization of the spine and maintenance of systolic blood pressure above 90 mmHg. In mild cases, management can be non-operative. However, more severe cases require decompression and spinal fusion (13, 15, 16).

Anterior cord syndrome

In anterior cord syndrome, the anterior two-thirds of the spinal column is affected. Patients present with paralysis and decreased pain sensation below the level of the lesion. Because the posterior columns are preserved, there is no change in sensation of light touch, position, or vibration (14). The etiology of anterior cord syndrome is suspected to be secondary to flexion injuries or occlusion of the anterior spinal artery (15). Prognosis for this syndrome is poor, with minimal recovery in function.

Conus medullaris and cauda equina syndromes

The conus medullaris is found at the terminal end of the spinal cord (approximately L1 in adults), whereas the cauda equina is the collection of lumbar and sacral nerve roots that pass distal to the conus medullaris in the dural sac (15). Compression of these structures can occur secondary to central disk herniation, neoplasm, or trauma. When compression occurs, patients may present with urinary retention and overflow incontinence, sexual dysfunction, sphincter impairment, distal motor weakness, and saddle anesthesia. According to Jalloh and Minhas 2007 (16), over 90% of patients who were eventually diagnosed with cauda equina syndrome presented with low back pain and urinary symptoms.

Transverse myelitis

Transverse myelitis is an inflammatory disorder of the spinal cord that can occur at multiple levels and interrupt sensory, motor, and autonomic functions. Symptoms are typically secondary to infection, immune insult, or autoimmune disorder – 60% of the cases in children follow infection or vaccination (17). When symptom onset is sudden, patients may present with severe weakness and areflexia, and can be confused with Guillain Barre Syndrome; typically, reflexes are hyperacute and the Babinski reflex is preserved. During the acute phase, lesions of the spinal column may enhance with gadolinium. Cerebrospinal fluid studies can help in narrowing down an etiology (for example, oligoclonal bands in multiple sclerosis, versus positive cerebrospinal fluid (CSF) cultures in an infectious etiology). Corticosteroids are first line treatment, although some patients may respond to plasma exchange (18). If there is cervical spine involvement, patients may require intubation for airway protection (17).

Step 4: Always think about the “Zebras”

Tick bite paralysis

Tick bite paralysis should be considered in patients who live in tick-endemic areas. It most commonly affects children between the ages of 1 and 5 and is typically due to the bite of the mature female tick, (species D. andersoni, A. americanum, and I. scapularis in the United States or the I. holocyclus in Australia). Seasonal incidence corresponds to when the female ticks are mature, and therefore tick bite paralysis is most common in the late spring and summer months (19).

The characteristic prodrome of tick bite paralysis is an unsteady gait associated with restlessness and irritability that begins 4 to 7 days after the tick attaches. After these initial symptoms, an ascending, symmetrical flaccid paralysis occurs. In severe cases, there can be bulbar involvement and respiratory paralysis. These symptoms are secondary to tick-secreted ixobotoxin, which disrupts sodium transport at the neuromuscular junction (20, 21).

Treatment of tick bite paralysis includes removing the tick and supporting any systems affected by the paralysis. A thorough exam should be performed to find the tick, as frequently it is found in the scalp. In most cases, the paralysis will resolve rapidly after tick removal. However, in cases due to the bite of the I. holocyclus species, paralysis may worsen for 24-48 hours after tick removal, followed by a rapid improvement. Most children will return to a baseline level of function and return of muscle strength, although some have persistent ataxia or cerebellar abnormalities. An anti-toxin is available to treat tick paralysis, but as a hyper-immune serum prepared from dogs, it carries a high risk of acute allergy and serum sickness (20, 21).

Guillain-Barre syndrome

Frequently, tick bite paralysis is confused with Guillain-Barre syndrome (GBS), as they both can present with ascending paralysis. An infectious syndrome precedes onset of GBS in up to 75% of cases, most commonly with Campylobacter jejuni, cytomegalovirus, Epstein Barr virus, Mycoplasma, or Human Immunodeficiency virus. Because of this, it is hypothesized that the body creates antibodies to the antigens within the offending infectious agent that correspond to epitopes within lipopolysaccharides in peripheral nerve tissues (22).  GBS incidence has a bimodal distribution, occurring most commonly in young adults and the elderly and is more prevalent in the winter months (23).

The characteristic acute neuropathy involved in GBS weakness of the proximal and distal muscle groups and an early loss of deep tendon reflexes. Sensation may remain somewhat intact. Respiratory muscle involvement is affected in one-third of cases, and is most accurately assessed by following vital capacity. Note that blood gases and oxygen saturation may not predict declining respiratory status until the patient enters overt respiratory failure (24). Confirmation of clinical diagnosis is made via nerve conduction studies. In some cases, there may be an increased in CSF protein, although this can be nonspecific.

Treatment of GBS can vary. The majority of patients with GBS should be admitted for inpatient management as some may require ventilator assistance. Patient should also be treated for pain and given prophylaxis for deep venous thrombosis (DVT) and pulmonary embolism (PE) development. Intubation is indicated if the patient is unable to lift his or her head, has a vital capacity of less than 60% of expected, a forced vital capacity of less than 20 mL/kg or a negative inspiratory force (NIF) of less than 30 cm H2O (25).  A 2002 Cochrane Review showed plasma exchange therapy to be superior to supportive treatment alone when treating GBS. Plasma exchange has shown to be most beneficial if given within 7 days of onset of symptoms (26). A second Cochrane review in 2014 showed that intravenous immunoglobulin (IVIG) started within 2 weeks of symptom onset can improve recovery as well as plasma exchange. IVIG is also more likely to be completed than plasma exchange (27).

Myasthenia gravis

Myasthenia gravis (MG) is characterized by fluctuating or fatigable weakness that is frequently associated with ocular symptoms such as diplopia and ptosis). Classically, the muscle weakness is worse with exercise, better at rest, and progressive as the day goes on. The first muscles affected are the ones that are most often used, hence the predominance of ocular symptoms (28). Patients with myasthenia gravis often find that their symptoms are aggravated by fever, physical/emotional stress, infection, and exposure to specific medications. A myasthenia gravis pattern can be related to a drug effect in patients, especially following treatment with penicillamine, alpha interferon, or bone marrow transplantation (as a type of graft versus host disease). Diagnosis can be made by edrophonium test, also known as a tensilon test.  This test exposes a patient with MG to edrophonium. Edrophonium is an acetylcholinesterase inhibitor that will improve symptoms in patients with MG by allowing more acetylcholine to exist in the neuromuscular junction (29). The diagnosis can also be made by screening for acetylcholine receptor antibodies or via an electromyelogram. For all cases, supportive management is key. As weakness can include the diaphragm and respiratory muscles, intubation is recommended when vital capacity is less than 1 liter or NIF less than 20 cm H2O. Of note, patients with MG have resistance to the depolarizing effects of neuromuscular blocking agents, and may require 2-3 times the dose of succinylcholine to achieve appropriate paralysis for rapid sequence intubation (RSI). Conversely, they are sensitive to nondepolarizing neuromuscular blocking agents, and can require only one-tenth of the dose typically required. For acute cases, treat with high dose IVIG and corticosteroids for rapid improvement (29, 30).

Lambert Eaton Syndrome

Lambert Eaton Syndrome (LES) presents similarly to myasthenia gravis. However, in myasthenia gravis, antibodies are created to the acetylcholine receptor whereas LES is a presynaptic disease. Patients report chronic fluctuating weakness of proximal limb muscles. The weakness is characterized by difficulty with ambulation, climbing stairs, or standing from a chair, that improves with sustained or repeated exercise. A classic exam finding is Lambert’s Sign, where handgrip in affected individuals improves after 5 seconds. Patients with LES less commonly present with ptosis or diplopia, but can complain of myalgias or muscle stiffness. Patients with LES are typically older and female and over half will have an underlying malignancy. LES symptoms can precede malignancy by one to two years in these cases. In the remainder of patients without malignancy, LES can be a manifestation of autoimmune disease. Treatment involves addressing any primary malignancy and administering pyridostigmine. Pyridostigmine is a cholinesterase inhibitor that increases acetylcholine release. Immunotherapy has also been shown to be a treatment as well (28, 29, 30, 31).

Botulism

Botulism classically presents after ingestion of food contaminated with a toxin produced by the Clostridium botulinum bacterium. The botulinum neurotoxin (BoNT) irreversibly binds to cholinergic receptors within the presynaptic cell membrane (30). Symptoms begin 12-48 hours after ingestion, and are characterized by initial bulbar symptoms (diplopia, ptosis, blurred vision, dysarthria), followed by weakness from upper to lower limbs. This is also known as a “descending paralysis”. The diagnosis of botulism is made by nerve conduction studies and stool/serum toxin polymerase chain reaction (PCR). Treatment of botulism is mostly supportive. In severe cases, patients may require intubation and mechanical ventilation when their functional vital capacities are less than 15 mL/kg or less than 1 L. A trivalent botulinum antitoxin exists, but its use is controversial. It may shorten illness, but it carries many side effects. The overall mortality of botulism is 5-10% (typically secondary to respiratory complications or sepsis), but eventual recovery is near complete if patients survive.

Note that a special subset of botulism cases exists and this is the group of patients who are 6 weeks to 6 months of age. Because of the immature gut flora in this population, only a small number of botulinum spores (like that in honey) are needed to produce severe illness. These patients present with generalized weakness, constipation, and cranial nerve muscle weakness. Finally, a generalized descending paralysis occurs. Treatment is similarly supportive, although intravenous botulism immunoglobulin is frequently administered (32, 33, 34).

The Bottom line

Do a careful history and physical examination. As difficult as it may be, try to elicit specifically what the “weakness” entails. Tailor your work up to those complaints, but if your work up to date is negative and you still have concerns, consider debilitating spinal cord pathology and other rare causes of weakness.

References / Further Reading

  1. Anderson RS and Hallen SAM. Generalized weakness in the geriatric emergency department patient. Clinics in Geriatric Medicine 2013, 29(1):91-100.
  2. Swenson, Rand. “Evaluation of Patient with Weakness.” In Reeves & Swinton: Disorders of the Nervous System. Dartmouth Medical School. Available online: https://www.dartmouth.edu/~dons/part_2/chapter_12.html.
  3. Nemec M., et al. Patients presenting to the emergency department with non-specific complaints: The Basel Non-specific Complaints (BANC) Study. Academic Emergency Medicine 2010, 17:284-292.
  4. Nickel CH, Nemec M, and Ringisser R. Weakness as a presenting symptom in the emergency department. Swiss Medicine Weekly 2009, 139(17-18):271-272.
  5. Mannesse CK et al. Prevalence of hyponatremia on geriatric wards compared to other settings over four decades: A systematic review. Ageing Res. Rev. 2013, 12, 165–173.
  6. Chao C-T et al. The severity of initial acute kidney injury at admission of geriatric patients significantly correlates with subsequent in-hospital complications. Scientific Reports 2015; 5:13925.
  7. Rohrig G et al. Prevalence of anemia among elderly patients in an emergency room setting. European Geriatric Medicine 2014, 5(1): 3-7.
  8. Gupta M et al. Presenting complaint among patients with myocardial infarction who present to an urban, public hospital emergency department. Annals of Emergency Medicine 2002, Volume 40, Issue 2, 180 – 186.
  9. Hohl CM, Dankoff J, Colacone A, and Afialo M. Polypharmacy, adverse drug-related events, and potential adverse drug interactions in elderly patients presenting to an emergency department. Annals of Emergency Medicine 2001, 38(6):666-671.
  10. Weidauer S et al. Spinal cord ischemia: aetiology, clinical syndromes and imaging features. Neuroradiology 2015, 57(3):241-257.
  11. Molliqaj G et al. Acute traumatic central cord syndrome: comprehensive review. Neurochirurgie 2014, 60(1):5-11.
  12. Levi ADO, Tator CH, and Bunge RP. Clinical syndromes associated with disproportionate weakness of the upper versus the lower extremities after cervical spinal cord injury. Neurosurgery 1996, 38:179-185.
  13. Schneider RC, Cherry G, and Pantek H. The syndrome of acute central cervical spinal cord injury; with special reference to the mechanisms involved in hyperextension injuries of cervical spine. Journal Neurosurgery 1954, 11:546-577.
  14. Schneider RC, Thompson JM, and Bebin J. The syndrome of acute central cervical spinal cord injury. J Neurol Neurosurg Psychiatry 1958 Aug; 21(3): 216–227.
  15. McKinley W et al. Incidence and outcomes of spinal cord injury clinical syndromes. Journal of Spinal Cord Medicine 2007, 30: 215-224.
  16. Jalloh I and Minhas P. Delays in the treatment of cauda equina syndrome due to its variable clinical features in patients presenting to the emergency department. Emerg Med J. 2007 Jan; 24(1): 33–34.
  17. Frohman EM and Wingerchuck DM. Transverse Myelitis. N Engl J Med 2010; 363:564-572.
  18. Weinshenker BG, O’Brien PC, Petterson TM, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999;46:878-886.
  19. Diaz JH. A comparative meta-analysis of tick paralysis in the United States and Australia. Clinical Toxicology 2015, 53(9):874-883.
  20. Edlow JA and McGillicuddy DC. Tick paralysis. Infectious Disease Clinics of North America 2008, 22(3):397-413.
  21. Grattan-Smith PJ et al. Clinical and neurophysiological features of tick bite paralysis. Brain 1997, 120, 1975–1987.
  22. Yuki N. Molecular mimicry between gangliosides and lipopolysaccharides of Campylobacter jejuni isolated from patients with Guillain-Barré syndrome and Miller Fisher syndrome. J Infect Dis1997;176(suppl 2):S150-3.
  23. Winer JB. Clinical Review: Guillain-Barre syndrome. BMJ 2008;337:a671.
  24. Chevrolet JC, Deleamont P. Repeated vital capacity measurements as predictive parameters for mechanical ventilation need and weaning success in the Guillain-Barré syndrome. Am Rev Respir Dis1991;144:814-8.
  25. Hughes RA et al., Multidisciplinary Consensus Group. Supportive care for patients with Guillain-Barré syndrome. Arch Neurol2005;62:1194-8.
  26. Raphael JC et al. Plasma exchange for Guillain-Barre Syndrome. Cochrane Database Syst Rev. 2002;(2):CD001798.
  27. Hughes RAC et al. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database of Systematic Reviews 2014, Issue 9. Art. No.: CD002063. DOI: 10.1002/14651858.CD002063.pub6.
  28. LeBaron AC. Myasthenia gravis and Lambert-Eaton Syndrome. In Faust’s Anesthesiology Review. Ed. Murray MJ.
  29. Sanders DB and Guptill JT. Myasthenia gravis and Lambert-Eaton myasthenic syndrome. CONTINUUM: Lifelong Learning in Neurology 2014, 20(5): 1413–1425.
  30. Pascuzzi RM. Pearls and pitfalls in the diagnosis and management of neuromuscular junction disorders. Semin Neurol 2001; 21(4): 425-440.
  31. Hulsbrink H and Hashemolhosseini S. Lambert-Eaton myasthenic syndrome – Diagnosis, pathogenesis and therapy. Clinical Neurophysiology 2014, 125(12): 2328–2336.
  32. Rosow LK and Strober JB. Infant Botulism: Review and Clinical Update. Pediatric Neurology 2015, 52(5):487-492.
  33. Thajeb T et al. Botulism: A frequently forgotten old malady. International Journal of Gerontology 2007, 1(3): 118-124.
  34. Chalk CH, Benstead TJ, Keezer M. Medical treatment for botulism. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD008123. DOI: 10.1002/14651858.CD008123.pub3.

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