The Man Who Couldn’t Walk

Submitted by deb on Sun, 06/26/2011 – 00:00

A case study

Originally published in Lifeline; Newsletter of The California Chapter of the American College of Emergency Physicians Christopher Fee, MD and Susan B. Promes, MD FACEP Alameda County California Medical Center, Highland General Hospital

Acute weakness is a common patient complaint in the emergency department with a wide differential diagnosis, ranging from the manifestation of psychosocial stressors to potentially life-threatening neurologic, infectious, and metabolic illnesses. As with all patients in the emergency department, the emergency physician must rapidly recognize those with severe illness and assess the ABC’s and treat the patient appropriately.

A complete neurologic examination, including cranial nerves, cerebellar function, as well as a search for differences in motor and sensory function is crucial. Once this is complete, the next step is to identify the underlying illness and provide disease-specific therapy.

This case begins with a 41-year-old Salvadoran man who was brought to the hospital by his wife after awakening eight hours earlier unable to move his legs. The patient reported feeling completely healthy the night before. He had gone out to dinner with his wife and had an otherwise uneventful evening. The patient stated that he awoke at 3:00 a.m. to use the restroom and discovered he was unable to move his legs. He also reported feeling nauseated with four episodes of non-bloody, non-bilious emesis that morning. His symptoms had neither improved, nor worsened since awakening. The patient denied any shortness of breath, headaches, neck or back pain, fevers, chills, sweats, bowel or bladder complaints, numbness, tingling, or other sensory changes, and reported that his upper extremities had normal strength.

Additionally, the patient denied any trauma, recent camping or travel, insect bites, upper respiratory symptoms, canned foods, or immunizations. The patient denied any past medical history and had no prior episodes of weakness. He did not take any medications or herbal preparations and had no allergies. He did not smoke, drink alcohol, or use any illicit substances. His temperature was 97.7 degrees F, pulse was 122 beats per minute, blood pressure was 187/107 mm Hg, respirations were 20 per minute, and his pulse oximetry reading was 99% on room air.

On physical exam, the patient appeared mildly anxious. His HEENT exam was unremarkable. The patient’s neck had full range of motion, was non-tender, with no thyromegaly, masses, or nodules. His lungs were clear with good aeration. The cardiac exam revealed tachycardia, without murmurs, rubs, or gallops. The abdominal exam was normal. A rectal exam had normal tone and was negative for occult blood. His back was non-tender. The skin was normal, with no evidence of insect bites or ticks, and there was no lymphadenopathy. The extremities had normal muscle mass and tone, and there was no muscular tenderness. The patient was alert and oriented. Cranial nerves II though XII were intact. Fasciculation’s were noted in the patient’s quadriceps and calf muscles bilaterally.

The patient had 5/5 strength in both upper extremities. The patient’s hip flexion and extension was 2/5, as was knee flexion and extension. The patient had 4/5 ankle dorsiflexion, and 5/5 plantar flexion. Sensation to light touch, pinprick, and temperature was normal throughout. Deep tendon reflexes were 2 + globally and the toes were down going. Cerebellar function was intact. Gait could not be assessed due to the patient’s inability to stand. The patient’s blood glucose was 135 mg/dL.

An electrocardiogram showed sinus tachycardia with a rate of 103, first-degree atrioventricular block, normal QRS axis, a prolonged QT, and normal ST segments. A portable chest X-ray was normal. Dipstick urinalysis was unremarkable. Thirty minutes after presenting to the emergency department, the patient began to complain of mild shortness of breath. Exam was unchanged, as were all vital signs. Peak flows at that time were 270 L/min. An arterial blood gas was obtained on room air.

Any guesses on his ultimate diagnosis?

The differential diagnosis of symmetric motor weakness includes Guillain-Barre syndrome, myasthenia gravis, Eaton-Lambert syndrome, tick paralysis, botulism, medication and toxin induced weakness, spinal cord hemorrhage, spinal cord infarct, epidural abscess, and electrolyte disturbances, with particular attention to potassium, sodium, magnesium, phosphate, and calcium.

In the case presented here, Guillain-Barre is unlikely given the presence of deep tendon reflexes and the proximal nature of the weakness. The Miller-Fisher variant of Guillain-Barre is also unlikely in this patient with no ocular, bulbar, or upper extremity findings. Myasthenia gravis is less likely for the same reason, as well as the lack of fatigability. With no history of cancer, Eaton-Lambert syndrome can be taken off our list. Botulism is unlikely, again due to the lack of ocular or bulbar findings, and given no history of exposure.

Medications such as polymyxin, propranolol, procainamide, phenytoin, chlorpromazine, aminoglycosides, and D-penicillamine may cause neuromuscular blockade resembling myasthenia. Other medications can lead to potassium loss and resultant weakness, including diuretics, amphotericin, cisplatin, carbenicillin, and aminoglycosides. The patient in this case denied any medication use.

There was no history of exposure to ticks, and no ticks were found on exam, thus excluding tick paralysis as a cause. Spinal cord hemorrhage or infarct, and an epidural abscess are all unlikely in the absence of back pain or tenderness, sensory changes, or urinary retention. This leaves an electrolyte disturbance as the most likely etiology.

Let’s review his laboratory studies.

The patient had a WBC of 12,600/mm3 (86 % neutrophils, 9 % lymphocytes), a hematocrit of 52.9 %, and platelet count of 336,000/mm3. Results of the room air arterial blood gas included a pH of 7.38, pCO2 of 33mmHg, pO2 of 91mmHg, bicarbonate of 21, base excess of -4, and saturation of 98%. The patient had normal renal function and liver function tests.

The patient’s electrolytes were as follows: sodium of 146 mmol/L, potassium of 1.9 mmol/L, chloride of 107 mmol/L, carbon dioxide of 21 mmol/L, calcium of 8.0 mg/dL, and magnesium of 1.6 mg/dL. The patient was treated with 40 mEq KCl intravenously over two hours, 40 mEq KCl orally, and 2 g MgSO4 intravenously and was admitted to the medicine service on telemetry.

The patient’s symptoms resolved rapidly, with full recovery of motor function, return to a normal serum potassium level, and resolution of electrocardiogram abnormalities within 2 hours. Acute hypokalemic paralysis is a rare, but treatable, clinical syndrome characterized by acute systemic weakness and a low serum potassium (< 3.5 mmol/L).

Neuromuscular symptoms are the most prominent findings in hypokalemia, though the cardiovascular and gastrointestinal systems may be affected as well. Weakness is generally more profound in the lower extremities, with proximal muscles affected more than the distal musculature. Bulbar muscles are rarely affected. Deaths from respiratory failure and arrhythmia have been reported. Mental status and sensation are not affected. The reflexes may be normal or depressed.

Electrocardiogram changes are common, though they are not correlated with the severity of the hypokalemia, and consist primarily of varying degrees of atrioventricular blockage, flattening/inversion of the T-waves, presence of U-waves, and ST-segment sagging. Symptoms appear to be primarily due to an increase in the ratio of intracellular to extracellular potassium, which alters membrane polarization and excitability. Supportive care is the primary treatment.

These patients require cardiac monitoring and close observation of their respiratory status. If a patient with acute weakness requires mechanical ventilation, succinylcholine should be avoided as its use may produce severe hyperkalemia in the setting of denervated musculature. A small number of patients with periodic paralysis have hyperkalemia as a cause of their symptoms, which could prove potentially deadly if succinylcholine is used to intubate them.

Hypokalemia may result from total body potassium depletion (renal or extrarenal) or an alteration in transcellular distribution (most cases). Renal causes of potassium depletion include the renal tubular acidosis (type I or distal, and type II or proximal). Type I RTA is the final common pathway for hypokalemia in several disease processes, including medullary sponge kidney, Sjogren’s syndrome, and chronic toluene exposure, and is best treated by potassium repletion. Treating type II RTA, by repleting bicarbonate, exacerbates potassium loss, and often requires large doses of potassium to maintain normal serum levels. Other renal causes of hypokalemia include Fanconi’s syndrome, water intoxication, nephrotic syndrome, Barter’s syndrome, and the diuretic phase of acute tubular necrosis.

Extrarenal causes of potassium depletion include gastrointestinal losses (celiac disease, tropical sprue, acute gastroenteritis, and malabsorption due to short bowel syndrome), and several endocrinopathies. Primary hyperaldosteronism (Conn’s syndrome) may be treated by excision of the aldosterone-producing tumor, or with spironolactone, while pseudohyperaldosteronism (licorice intoxication) is treated by avoiding glycyrrhizic acid (the offending agent in licorice, also found in chewing tobacco) and repleting potassium.

Alteration in the transcellular distribution of potassium may be caused by medications (such as insulin, bicarbonate, and *-adrenergic drugs) and by the periodic paralyses. Familial periodic paralysis is autosomal dominant with a prevalence of 1:100,000. Patients are typically Caucasian with males affected more frequently than females. Symptoms generally manifest in the first two decades of life and may recur anywhere from daily to yearly, and last from 3 to 4 hours to more than a day. Attacks are typically precipitated by rest or sleep following exercise, but may also be triggered by high sodium or carbohydrate meals, cold, trauma, or surgery. The majority of acute attacks occur between the hours of 1 a.m. and 6 a.m..

Patients are most often hypokalemic, but may be hyperkalemic or normokalemic. Secondary causes of hypokalemia must be excluded. Total body potassium is normal, but a defective membrane protein causes intracellular shifts. Recommended treatment includes 0.2-0.4 mEq/kg PO q 15-30 minutes as needed, or 20meq KCl IV over 1 hour repeated as needed. The use of acetazolamide (250-750mg/day) or spironolactone (100-200 mg/day) has been shown effective as prophylaxis against attacks.

Thyrotoxic periodic paralysis, a true endocrine emergency, is the most common acquired form of hypokalemic periodic paralysis, and was first described in 1902 by Rosenfeld. Ninety percent of cases reported in the literature are in Asians and Hispanics, though case reports exist of Caucasian, Native American, Indian, African American, and Aborigine patients. There is a 20:1 male to female preponderance. The incidence may be as high as 25% in hyperthyroid males in Asia, though only 0.1-0.2% of thyrotoxic patients in North America present in this manner. As opposed to familial periodic paralysis, most patients do not present until their 2nd – 4th decades of life, when thyroid disease becomes prevalent. There is rarely a family history. Patients may have subtle or no signs of hyperthyroidism. Grave’s disease is the most common etiology. Patients only have attacks when hyperthyroid, and thus provocative testing with glucose and insulin will not induce an attack. The pathogenesis is unclear, though a decrease in calcium pump activity has been proposed. Hypophosphatemia, hypomagnesemia, and an elevated CPK are common.

Treatment is aimed at the underlying cause with propranolol and avoidance of extreme exertion, carbohydrates, and alcohol. Oral potassium is recommended for acute attacks, though the majority will resolve spontaneously in 8-12 hours, and 42% of patients who receive potassium will develop rebound hyperkalemia. Prophylactic potassium or acetazolamide are not effective in these patients. During his admission, the patient underwent studies to evaluate his hypokalemia. An abdominal CT scan to assess for adrenal tumor/hyperplasia was normal, as was a 24-hour urine analysis to rule out renal tubular acidosis. One day before discharge, the patient’s TSH returned at 0.002 mIU/mL (normal range 0.46-4.68), with a free T4 of 4.06 ng/dL (normal 0.78-2.19), clinching the diagnosis of thyrotoxic hypokalemic paralysis. The patient was placed on propranolol and PTU and discharged home, symptom free.

In summary, acute hypokalemic periodic paralysis, though rare in the United States, is likely to be seen with increasing frequency due to increased immigration of peoples from Asia and Latin America. These patients should be admitted for serial labs, cardiac monitoring, and close observation of their respiratory status. Caution must be taken with patients who require mechanical ventilation. Succinylcholine should be used with extreme caution, if the patient’s potassium level is unknown. Consideration should be given to using a non-specific beta-blocker, such as propranolol, if signs of hyperthyroidism are present. Gentle repletion of potassium, magnesium, and phosphorus should also be considered, with frequent electrolyte checks and neurologic exams. With supportive care, these patients generally do well.

References: 

• Ahlawat SK, Sachdev A. Hypokalaemic paralysis. Postgraduate Medical Journal. 1999; 75 (882):193-7. 
• Birkhahn RH, Gaeta TJ, Melniker L. Thyrotoxic periodic paralysis and intravenous propranolol in the emergency setting. The Journal of Emergency Medicine. 2000; 18 (2):199-202.
• Gutmann L. Periodic paralyses. Neurologic Clinics. 2000; 18 (1):195-202.
• Kodali VR, Jeffcote B, Clague RB. Thyrotoxic periodic paralysis: a case report and review of the literature. 199; 17(1):43-5.
• Kohn MS. Chapter 128: Weakness. In: Rosen, Barkin, Danzl, Hockberger, Ling, Markovchick, Marx, Newton, Walls, eds. Emergency Medicine: Concepts and Clinical Practice. St. Louis, Mo: Mosby-Year Book, Inc. 1998:2174-2183.
• Manoukian MA, Foote JA, Crapo LM. Clinical and metabolic features of thyrotoxic periodic paralysis in 24 episodes. 199; 159(6):601-6.
• Papadopoulos KI, Diep T, Cleland B, Lunn NW. Thyrotoxic period paralysis: report of three cases and review of the literature. 1997; 241(6):521-4.

Originally Published 12-11-2000 Used with permission Copyright retained by Lifeline 2000.