A 53-Year-Old Woman With Sudden-Onset Dysphonia and Paresis

Medscape

a day ago

Editor's Note:
The Case Challenge series includes difficult-to-diagnose conditions, some of which are not frequently encountered by most clinicians, but are nonetheless important to accurately recognize. Test your diagnostic and treatment skills using the following patient scenario and corresponding questions. If you have a case that you would like to suggest for a future Case Challenge, please email us at [e-mail] with the subject line "Case Challenge Suggestion." We look forward to hearing from you.
A 53-year-old woman comes to the emergency department (ED) in the middle of the night with a 1-day history of diffuse, constant, and worsening abdominal pain. The pain is not associated with fever, nausea, vomiting, constipation, diarrhea, or urinary symptoms. Her review of symptoms is positive only for visual blurriness and xerostomia.
The patient takes atorvastatin and atenolol/chlorthalidone. She has no recent history of trauma or hospitalization. Past surgeries include an appendectomy at age 10 years and a hysterectomy at age 42 years.
She lives with her husband and adult son. When asked about possible contributory environmental or vocational exposures, she states they all work from home selling homemade crafts and jewelry online and at regional festivals. She adds that they have recently taken workshops on fruit and vegetable canning and ornamental fish aquaculture to expand their business. Her husband and son are not ill, although they have generally shared the same environment and food.
Physical Examination and Workup
The patient's initial vital signs in the ED include a temperature of 98.6 °F, heart rate of 102 beats/min with sinus tachycardia, blood pressure of 116/50 mm Hg, and respiration rate of 18 breaths/min. Her oxygen saturation level is 99% on room air. Her Glasgow Coma Scale score is 15. She rates her level of pain at 7 out of 10.
Once the patient is undressed and placed in a gown, a physical examination is performed. The results are normal except for a mildly distended abdomen with voluntary guarding along the lower quadrants. No rebound tenderness is noted. Her mucous membranes are slightly dry. The results of the neurologic examination are grossly intact.
An intravenous (IV) line is inserted, and blood is drawn for laboratory studies. The results of a CBC count, comprehensive metabolic panel, and urinalysis are normal. Plain abdominal radiography reveals distended loops of bowel and air-fluid levels. Similar radiographic findings from a different patient are shown below (Figure 1).
Figure 1.
An abdominal CT scan with IV contrast confirms the dilated loops of small bowel but reveals no evidence of a mechanical obstruction. Figure 2 shows an example of an intestinal obstruction on a CT scan in a different patient.
Figure 2. Intestinal obstruction. Color-enhanced coronal CT scan.
After a consultation finds no evidence of an acute abdomen requiring surgery, the patient is sent to the ED observation unit for placement of a nasogastric tube, IV hydration, analgesia, and monitoring.
Over the course of 4-5 hours in the observation unit, the patient develops diplopia and her speech becomes less intelligible. She also reports dyspnea. Her temperature is 98.2 °F, heart rate 52 beats/min, blood pressure 92/52 mm Hg, and respiration rate 28 breaths/min. Her oxygen saturation level is 97% on room air. Her Glasgow Coma Scale score is 14-15. She rates the level of her pain at 2 out of 10.
The physician on duty is unable to see the patient immediately and orders a CT scan of the brain, repeated blood tests, and arterial blood gas analysis. The results of the brain CT scan are normal. The arterial blood gas analysis demonstrates moderate respiratory acidosis. The findings are:
Arterial blood pH: 7.32 (reference range, 7.35-7.45)
Partial pressure of oxygen (PO 2 ): 94 mm Hg (reference range, 75-100 mm Hg)
): 94 mm Hg (reference range, 75-100 mm Hg) Partial pressure of carbon dioxide (PCO 2 ): 56 mm Hg (reference range, 35-45 mm Hg)
When the physician returns to see the patient, he notes bilateral ptosis, dysphonia, dysarthria, and bilateral cranial nerve VI paresis.
Discussion
Tolosa-Hunt syndrome is a granulomatous inflammatory process near the cavernous sinus or within certain areas of the orbits. The disease manifests with one or more episodes of unilateral ocular pain in addition to paralysis of cranial nerves III, IV, and/or VI. In contrast to this patient's presentation, there is typically no gastrointestinal prodrome or progression of the neurologic manifestations beyond the ocular nerves.
Symptoms of lead toxicity can include anorexia, constipation, abdominal pain, nausea, and vomiting; other features may include renal dysfunction and neurological symptoms.[1] This patient's gastrointestinal symptoms did not include nausea, vomiting, or constipation; her comprehensive metabolic panel was within normal limits; and her neurological function was grossly intact.
In North America, tick paralysis is common during the spring and summer when ticks are most active. When this patient was undressed and placed in a gown in the ED, a tick would likely have been discovered. The neurologic manifestations occur while the tick is attached. Once the tick is removed, the paralysis resolves. The prodrome is an influenzalike illness, and acute abdominal pain is not a typical presentation. The second stage is an ascending paralysis, not a descending paralysis. Patients are ataxic and exhibit lower extremity muscular weakness. Notably, however, tick paralysis can cause diplopia, difficulty swallowing, and speaking, as in this case, highlighting that it is an important item on the differential diagnosis.
Botulism is a neuromuscular disease caused by toxins generated by the anaerobic, gram-positive bacterium Clostridium botulinum (Figure 3). Six syndromes are recognized: infant, foodborne, wound, adult colonization, inhalational, and iatrogenic. Of the eight neurotoxins (A to H), toxins A, B, and E (F, rarely) affect humans; types C and D are associated with disease in animals.[2,3] Type H was discovered in 2013.[4] Botulinum neurotoxins are considered the most potent biologic poison known.[2,3]
Figure 3. Color-enhanced image of Clostridium botulinum bacteria (botulism bacillus).
Of the eight C botulinum toxins (A to H), the ones that are likely to be poisonous to humans are A, B, and E, and rarely F. Type A produces the most severe syndromes. Type E is usually associated with botulism caused by consumption of aquatic food. Neurotoxin H was the last one discovered in 2013.[2]
Condition Overview
From 2011 to 2015, 162 cases of botulism were reported annually (mean)[3]; infant botulism, foodborne botulism, and wound botulism occurred in 71%-88%, 1%-20%, and 5%-10% of these cases, respectively. For foodborne botulism, the incubation period from first exposure to symptom onset can be from 12 to 72 hours (range, 2 hours to 8 days). The classic manifestations begin with a symmetrical paresis or paralysis starting from head to toe. The initial symptoms of botulism poisoning include ptosis, dysphonia, dysphagia, dysarthria, xerostomia, and visual difficulties (ie, bulbar manifestations).[2,3]
Although death was a frequent outcome in the past, it rarely occurs today. Before 1950 or so, foodborne botulism carried a mortality rate of 60%-70%. That rate dropped to 3% for all the different types of botulism between 1975 and 2009.[3] Two principal causes of early death are complete airway obstruction from a food bolus as the muscles of deglutition become paralyzed and respiratory failure with paralysis of the diaphragm and intercostal muscles.[2]
Once introduced into the body, the toxin enters the neuronal cells at the voluntary motor and autonomic neuromuscular junctions. There, it disrupts the release of neurotransmitter (acetylcholine) across the junction. With acetylcholine transmission blocked, the receptor sites of the motor and autonomic cells lie vacant. Flaccid paralysis occurs.[2,3] This process cannot be reversed. It may take months for the regeneration of the neurotransmitter mechanics.[2]
The initial manifestations of botulism may be misleading. A patient who presents at the early stage may be alert and afebrile. The patient may sense the minute anatomic changes, but these subjective concerns are subtle and may be attributed to more typical maladies. Common misdiagnoses at this stage include alcohol or drug intoxication and psychiatric disorders.[2] Later, the neurologic signs become dominant, and botulism may be misdiagnosed as stroke, Tolosa-Hunt syndrome, meningitis, myasthenia gravis, tick paralysis, or Guillain-Barré syndrome, among other conditions.[1,2,5-7]
Rarely, the gastrointestinal manifestations of botulism may predate or obscure the classic neurologic symptoms.[2,3] Botulism has been mistaken for acute bowel obstruction.[8,9] It is not until the neurologic manifestations come to the forefront that the correct diagnosis is made. In the patient in this case, the early ptosis was mistaken for lack of sleep and the xerostomia for dehydration. Nevertheless, the workup for a bowel obstruction (ie, abdominal radiographs and a CT scan of the abdomen with contrast) was reasonable because it is a more common disorder.
In-depth questioning of this patient revealed that several days before she came to the ED, she opened and tasted a batch of canned jalapeño peppers she had made a few months earlier. She was planning to take them to a parish food drive. Her husband and son did not consume any of the peppers.
With blockade of acetylcholine transmission, motor and autonomic cells lie vacant, leading to flaccid paralysis; this process cannot be reversed and regeneration of neurotransmitter mechanics may take months. Only rarely do the gastrointestinal manifestations of botulism predate or obscure the classic neurologic symptoms, but this has resulted in botulism being mistaken for acute bowel obstruction. Botulism is characterized by symmetrical paresis or paralysis starting from head to toe (descending paralysis).
Reporting Responsibilities and Treatment
Once botulism is included in the differential diagnosis, three actions must occur. First, the patient's status must be NPO to prevent aspiration; nasogastric tube feeding or total parenteral nutrition can be considered in cases with severe ileus. Second, assessment of respiratory capabilities is critical. It can be accomplished through various measurements, such as negative inspiratory force, vital capacity, blood gas analysis, or capnography.[1,2] Carbon dioxide retention requires immediate consideration of aggressive airway management to counter respiratory paralysis and cardiorespiratory arrest. Third, the local public health department and the Centers for Disease Control and Prevention (CDC) must be notified. Any case of botulism in a community is a public health emergency. An urgent epidemiologic investigation must begin to search for additional cases and the source of the outbreak (eg, restaurants).[2]
Electrodiagnostic studies may be used to evaluate muscle weakness.[2] Laboratory studies to confirm botulism include testing for neurotoxin in the serum, stool, and gastric juices; identifying clostridia in stool or wound cultures; and investigating the suspected sources of the toxin release. The mouse bioassay remains the criterion standard. Real-time polymerase chain reaction and mass spectrometry are also helpful.[2] However, waiting for the results of these studies cannot delay communication with the CDC once botulism is suspected.
The CDC has the responsibility for releasing Botulinum Antitoxin Heptavalent (A, B, C, D, E, F, G) (Equine) (BAT). It is free and is available to clinicians 24 hours a day, 7 days a week.[2] Early administration of the antitoxin is associated with fewer days in the hospital and intensive care unit and a reduced need for mechanical ventilation support.[2,10,11] BAT neutralizes only the toxin circulating in the bloodstream that has yet to be incorporated into the cells.[1] In 2015, at a botulism mass casualty incident at a potluck meal in Lancaster, Ohio, the antitoxin was requested at 10 AM but did not arrive until midnight.[12,13] Therefore, the CDC should be contacted expeditiously. Note that Botulism Immune Globulin Intravenous (Human) (BIG-IV) (BabyBIG), the specific immunoglobulin G for infants with botulism who are younger than 1 year, is requested through the California Department of Public Health Infant Botulism Treatment and Prevention Program.[2,14]
The patient in this case received the botulinum antitoxin, and her clinical manifestations resolved almost completely within 24 hours. She did not need intubation or mechanical ventilation support.
BabyBIG is an orphan drug that consists of human-derived anti–botulism toxin antibodies. It has been approved by the US Food and Drug Administration for the treatment of infant botulism types A and B in infants younger than 1 year. The treating physician can obtain BabyBIG by contacting the California Department of Public Health's Infant Botulism Treatment and Prevention Program. It has been administered to more than 1500 infants with botulism and, compared with control patients, resulted in a 3.5-week decrease in length of hospitalization.[10,14]
Proactive Strategies
Any patient with a presumptive diagnosis of botulism may require invasive airway management, owing to impending paralysis. Patients who may have a difficult airway should be identified early. Such patients include those who have short necks, obvious nuchal and/or facial abnormalities, or disconcerting results on an airway assessment tool (eg, the Mallampati score). For this type of patient, elective intubation is safer than emergency intubation.
Another situation that must be planned for is a community-wide outbreak with limited healthcare resources. Between 1977 and 2015, there were six foodborne botulism outbreaks involving multiple patients. The smallest outbreak (16 people) occurred in Texas in 2001 and was caused by contaminated chili at a church function. The highest caseload was 58 patients in Michigan in 1977. In this outbreak, home-canned peppers served at a local restaurant contained the botulinum toxin (Figure 4).[12]
Figure 4.
The mouse bioassay remains the criterion standard. Real-time polymerase chain reaction and mass spectrometry are also helpful, but these methods are not widely available and generally are limited to the CDC and reference laboratories. Important to note is that awaiting the results of these studies should not delay communication with the CDC once botulism is suspected. Stool culture is considered the criterion standard for confirming conditions such as Escherichia coli (Shiga toxin) infection and salmonellosis.
Outbreak Strategies
As patients involved in an outbreak arrive at an ED, there may be a paucity of respiratory therapists and equipment to evaluate progressive respiratory failure expediently. One solution is the single-breath counting test (SBCT).[15] It is useful because its functionality is not limited by skill set, equipment needs, or geography. To perform the SBCT, the clinician asks the patient to sit upright, take a deep breath, and then begin counting upward at a rate of two numbers per second in their normal speaking voice; they should continue as long as possible while exhaling.[2] Studies involving myasthenia gravis indicate that the SBCT has a moderate correlation to forced vital capacity and that reaching 25 or higher is indicative of normal respiratory muscle function.[2] The next step is to triage certain patients to outlying institutions to avoid compromising healthcare capabilities at the initial hospital. Reverse triage may be the safest method — that is, transporting the intubated patients whose condition is less likely to deteriorate en route.
Botulism is a complicated disease for both patients and their communities. It must be managed with equal measures of skill and flexibility.