While traveling in Connecticut, a man from North Carolina in his mid-60s was admitted to a community hospital for new onset of diplopia, vertigo, truncal ataxia, and vomiting. Approximately 10 days before admission, the patient had been prescribed doxycycline for sinusitis. The physical examination at admission was notable for dilated, asymmetric (5 mm on the right and 4 mm on the left), sluggishly reactive pupils; cranial nerve IV palsy; bilateral proptosis (right more than left); bilateral peripheral facial weakness; and proximal left upper extremity weakness. Routine blood test results and imaging studies of head, brain, and orbits were unremarkable.
During hospital day 1, the patient experienced hypophonia, complete ophthalmoplegia, bilateral ptosis (right more than left), pupils unresponsive to light, dysphagia, and bilateral limb-girdle muscular weakness. His cognition remained intact, and no sensory deficits were documented. Cerebrospinal fluid contained 4 leukocytes/mm3, 70 mg glucose/dL, and 43 mg protein/dL; bacterial cultures were negative. Serum was negative for IgG and IgM against Borrelia burgdorferi, and rapid plasma reagin test results were negative. Test results for antibody levels against Campylobacter spp. and gangliosides (anti-GQ1b IgG) were negative.
On hospital day 2, the patient had difficulty breathing and bulbar signs progressed, followed by descending extremity weakness (left more than right) and areflexia. A diagnosis of Miller Fisher syndrome (MFS), a variant of Guillain-Barré syndrome, was considered, and treatment with intravenous immunoglobulin was begun.
The Connecticut Department of Public Health and the Centers for Disease Control and Prevention (CDC) were contacted for a botulism consultation. Botulinum antitoxin was not administered at that time because asymmetric neurologic deficits and lack of exposure to injection-drug use or home-preserved foods made botulism unlikely. Respiratory paralysis progressed, and on hospital day 3 the patient required mechanical ventilation. A diagnosis of botulism was reconsidered; however, antitoxin was not administered because an alternative diagnosis (MFS) was still likely. Serum was collected on hospital day 5 and sent to CDC for botulism testing; a stool sample was collected on hospital day 14 after resolution of ileus. Neurologic improvement was first noted on hospital day 7, consisting of improved upper-extremity strength. On hospital day 14, weaning from mechanical ventilation was complete.
Botulinum toxin type F was confirmed in the serum sample on hospital day 16. Treating physicians and CDC agreed that administration of antitoxin might still be beneficial because of potential clostridial intestinal colonization. On hospital day 17, investigational heptavalent (A–G) botulinum antitoxin was administered (5
). Stool sample was negative for botulinum toxin and botulinum toxin–producing Clostridium
spp. On hospital day 28, the patient experienced self-limited serum sickness. He was discharged to a rehabilitation center later the same day.
At the time of admission to the rehabilitation center, the patient was able to stand with assistance. At 6 weeks after symptom onset, he was able to keep his eyes open and walk with assistance, but dysphagia persisted. Subsequently, he continued to improve. Approximately 9 weeks after the illness had begun, the patient was found unresponsive; cardiopulmonary resuscitation was unsuccessful. Autopsy was limited to the brain and demonstrated inflammatory demyelination of cranial nerve tissue ().
Figure Postmortem cranial nerve tissue from a patient with botulism. A) Fragmentation of myelin sheaths and inflammatory infiltration of B and CD3+ T-cells within the nerve tissue (original magnification ×200). B) B-cell infiltration of nerve tissue; (more ...)
An epidemiologic investigation was conducted by state and local health departments in Connecticut and North Carolina. No contacts experiencing similar paralytic illness were identified. Two food items consumed by the patient were submitted for CDC analysis; both were negative for botulinum toxin and botulinum toxin–producing Clostridium spp.