A Case of Localized, Unilateral (Cephalic) Wound Botulism

Clinical Infectious Diseases, Jan 2018

We describe a rare presentation of botulism originally presenting with exclusively unilateral cranial nerve deficits following a puncture wound to the face. Cephalic tetanus was initially suspected but laboratory testing confirmed botulism. Botulism caused by local diffusion of toxin from a contaminated head wound can be confused with cephalic tetanus.

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A Case of Localized, Unilateral (Cephalic) Wound Botulism

A Case of Localized, Unilateral (Cephalic) Wound Botulism Kara Jacobs Slifka 1 2 Jo Ann Harris 0 Von Nguyen 1 2 Carolina Luquez 1 Tejpratap Tiwari 3 Agam K. Rao 1 0 Stormont-Vail Regional Health , Topeka, Kansas , USA 1 Division of Foodborne , Waterborne, and Environmental Diseases , Centers for Disease Control and Prevention , Atlanta , Georgia 2 Epidemic Intelligence Service 3 Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta , Georgia We describe a rare presentation of botulism originally presenting with exclusively unilateral cranial nerve deficits following a puncture wound to the face. Cephalic tetanus was initially suspected but laboratory testing confirmed botulism. Botulism caused by local diffusion of toxin from a contaminated head wound can be confused with cephalic tetanus. - Wound botulism and cephalic tetanus are both potentially fatal, toxin-mediated neurological illnesses. They require early clinical diagnosis and rapid treatment. Wound botulism occurs when Clostridium botulinum germinates in the anaerobic milieu of a wound and produces botulinum toxin, which enters the blood circulation and exerts its effect systemically [ 1 ]. Botulism is classically described as an acute-onset illness beginning with bilateral symmetric cranial nerve (CN) palsies, which may progress to descending flaccid paralysis [ 2 ]. Dysphagia, facial paralysis, ptosis, dysarthria, diplopia, and impaired gag reflex are among the manifestations of CN palsies that can be seen in patients with botulism. Rarely, asymmetric and even some unilateral CN palsies have been reported [ 3–5 ]. Symptoms result from blockade of voluntary motor and autonomic cholinergic junctions by botulinum toxin [ 1, 6 ]. Tetanus, a vaccine-preventable disease, is caused by wound colonization with Clostridium tetani and production of tetanus toxins that closely resemble botulinum toxin in amino acid sequence. Tetanus toxin acts at the myoneuronal junction of skeletal muscle and, eventually, the central nervous system, where it blocks inhibitory impulses, resulting in characteristic spastic paralysis of generalized and localized tetanus [ 5, 7 ]. Cephalic tetanus is a rare form of tetanus resulting from a head wound, and may cause, in contrast to generalized tetanus, flaccid palsies of CNs VII, III, IV, VI, and XII, usually presenting in a unilateral fashion. The exact pathophysiology of the flaccid paralysis is not fully understood [8]. Trismus (lockjaw) usually precedes facial paralysis and dysphagia; dysarthria and nystagmus may also be present. Progression to generalized tetanus occurs in about twothirds of cases and can result in respiratory compromise [ 6 ]. Cases of botulism are confirmed by specialized laboratory testing in reference laboratories. Wound botulism is confirmed by detection of botulinum toxin in serum, or isolation of C.  botulinum from a wound. Confirmatory testing for tetanus is uncommon; C. tetani yield on culture [ 9 ] and real-time polymerase chain reaction (PCR) assays for detection of C.  tetani neurotoxin gene fragments are not widely available [ 10 ]. CASE REPORT A 14-year-old boy playing stickball was wounded by a broomstick splinter that penetrated his right maxillary area under the eye. The boy experienced no fever, trauma to the right eye, vision changes, or drainage. Three days later, he visited his pediatrician, was diagnosed with cellulitis at the puncture site, and was prescribed oral cefadroxil. After 2 days, the boy complained of new-onset double vision, right-sided facial droop, and decreased sensation. Within 2 days, he had difficulty swallowing solids and his parents observed worsening facial swelling and difficulty speaking. A computed tomographic scan of the head showed a 3-cm foreign body deeply embedded in the right infratemporal fossa. Ten days after the injury, an otolaryngologist noted trismus, dysphagia, dysarthria, diplopia, and right-sided facial weakness; he was admitted for surgical removal of the splinter. On admission, the patient was afebrile. Examination showed diffuse cellulitis surrounding the right eye and a pinpoint puncture wound above the right malar eminence. Neurologic examination demonstrated unilateral, right-sided deficits including ptosis, decreased sensation in the area of swelling, weakness in the distribution of the facial nerve (CN VII), and impairment of lateral, superior, and inferior gaze consistent with CN III and VI palsies (Figure 1). Moderate trismus was again noted. Immunizations were up-to-date, including the 5-dose childhood tetanus toxoid series and a booster dose of a tetanus toxoid-containing vaccine 1  year before illness [ 11 ]. No sick contacts, injection drug use, or home-canned food consumption were reported. Unusual Wound Botulism • CID 2018:66 (Suppl 1) • S95 White blood cell count and lumbar puncture results were within normal limits. Ertapenem and vancomycin were initiated and the foreign body was removed in the operating room on hospital day (HD) 1; purulent material and the extracted splinter were cultured. Cephalic tetanus was the leading diagnosis based on unilateral CN impairments and trismus. Human tetanus immune globulin (500 units) was administered on HD2, HD4, and HD6. Electrodiagnostics performed on HD5 revealed unilateral findings; there was involvement of the right facial motor nerve with relative sparing of the left facial nerve and markedly decreased motor unit potentials on the right. Over the next few days, the patient developed worsening dysphagia. On HD7, the patient experienced severe respiratory distress and was transferred to the pediatric intensive care unit. A tracheostomy was performed to facilitate removal of respiratory secretions. By this day, the patient’s truncal tone was decreased and he was unable to extend his neck. For the first time on HD7, 17 days after the injury, physicians suspected bilateral CN XII impairment demonstrated by poor tongue mobility and CN XI impairment demonstrated by weakness of the right sternocleidomastoid muscle. They observed subtle left-sided ptosis on HD8 and loss of the left nasolabial fold on HD9. The patient’s extremities were not hyperreflexic. On HD7, cultures of 2 specimens obtained during surgery (a specimen obtained from a pocket of pus surrounding the wound and the broom splinter) grew a Clostridium species preliminarily identified as Clostridium species non-perfringens. Treating physicians, who maintained suspicion that C.  botulinum might have been the causative agent, sent serum and the 2 Clostridium cultures to the Centers for Disease Control and Prevention (CDC). CDC tested the serum specimen by mouse bioassay and the 2 cultures by botulinum neurotoxin gene realtime PCR and enzyme-linked immunosorbent assay. The serum S96 • CID 2018:66 (Suppl 1) • Jacobs Slifka et al Figure 2. Unilateral right-sided paralysis with inability to close the right eye due to tetanus toxin from wound on right forehead. Facial paralysis in the distribution of cranial nerve VII resulted in the inability to raise the right oral commissure and inability to close the right eye (Dan Higgins, illustrator). This artist rendition is modeled after a photograph depicting a patient with cephalic tetanus. specimen was negative for botulinum toxin, and the 2 cultures were positive for C. botulinum type A. These results were available 27 days after illness onset but by HD12, right-sided frontalis muscle function and extraocular muscle movements were improved, the patient was able to lift his head from the bed, and he was transferred from the hospital to a rehabilitation facility. Botulinum antitoxin was not indicated because of clinical improvement. DISCUSSION The boy’s illness began differently from the classically described appearance of botulism; all signs were unilateral and the trismus and CN deficits after a head wound were features consistent with cephalic tetanus (Figure  1). Risus sardonicus, which occurs with generalized tetanus, was absent; however, not all cases of cephalic tetanus progress to generalized tetanus, so this absence was not considered unusual. Continuous consideration of alternative diagnoses by the clinical team led to renewed suspicion for botulism, and laboratory testing confirmed it. All naturally occurring botulism syndromes are attributed to the systemic action of botulinum toxin that enters circulation to produce the classically described bilateral and symmetric CN palsies and flaccid paralysis of extremities [ 1, 6 ]. Seven (7%) patients with botulism due to toxin type A  in the United States during 2010–2013 had completely unilateral CN deficits on HD1, but all became bilateral within 2 days (CDC, unpublished data). The presence of a mix of unilateral and bilateral CN deficits has been reported rarely but, to our knowledge, we here describe the first confirmed case of botulism that became bilateral after several days of completely unilateral CN palsies. We speculate that the patient experienced localized paralysis resulting from slow diffusion of botulinum toxin from the injury site into facial, orbital, pharyngeal, and subsequently, cervical tissues—similar to the localized diffusion of botulinum toxin that occurs with cosmetic or therapeutic injection. The late-course postural manifestations of sternocleidomastoid and possibly trapezius weakness, along with mild contralateral CN deficits and respiratory symptoms, might have been due to slow diffusion of toxin from the postoperative wound site along fascial planes, or to toxin diffusion into circulation. While sensory deficits have sometimes been observed with botulism [ 12–14 ], in this case, these may be due to pressure on local sensory nerves from edema around the embedded splinter. The similarity in presentation of cephalic tetanus and botulism in a patient with a head or neck wound is illustrated in a previous report of a patient with atypical tetanus that was initially treated as wound botulism [ 15 ]. In that case, illness presented with flaccid paralysis and ptosis but progressed to generalized tetanus and, similar to our case, occurred in an adolescent immunized against tetanus. Typically, CN VII palsies are reported with cephalic tetanus; involvement of multiple CNs has been reported [ 5, 16 ]. Initial involvement of CNs III, IV, and VI are more commonly reported in botulism, which can involve other CNs [2]. As seen in Figure 1, the patient in our case had right facial paralysis with ptosis and loss of the nasolabial fold. In comparison, the patient in Figure 2, a 5-year-old boy with cephalic tetanus, had right facial paralysis and inability to close the right eye. The similarity of their appearances might be explained by a similar mechanism underlying cephalic tetanus and botulism. The botulism patient has multiple CN palsies including III and VI, which can occur with cephalic tetanus but is more common in botulism [ 2, 8 ]. During 2005–2014, 94% (207/220 cases) of wound botulism cases in the United States were due to limb wounds in intravenous drug abusers; 6% were due to wounds of other types [ 6 ]. The trauma-induced wound botulism described in this report is uncommon and resembles in some ways iatrogenic botulism from botulinum toxin injections. Licensed commercial preparations of botulinum toxins are increasingly injected for cosmetic or therapeutic purposes (eg, ablation of facial wrinkles and cervical dystonia relief). They produce limited unilateral paralysis of a target muscle through localized diffusion of the injected toxin and might present with clinical features similar to those in this case if diffusion of toxin occurs beyond the intended muscle. Rarely, systemic effects of injected toxin including bilateral CN deficits and paralysis have been described, presumably due to entry of toxin from high-dose injections into circulation. Whether the initial presentation was unilateral CN deficits is unknown [ 10 ]. To our knowledge, this is the first reported case of botulism initially presenting with persistent, completely unilateral CN palsies. However, 17 days after the injury the CN findings became bilateral. We attribute this presentation to local, ipsilateral diffusion of botulinum toxin from a contaminated facial wound. Given the expanded use of botulinum toxin injections for therapeutic purposes, it is possible that treatment-related cases similar to this case may occur. Botulinum toxin should be considered in addition to cephalic tetanus in a patient with unilateral CN palsies and a head wound or localized botulinum toxin injection. Notes Acknowledgments. We thank Dr Clifton Jones, Dr Daniel Katz, Dr Babak Marefat, and Dr Casey Cordts of Pediatric Hospitalists, Pediatric Intensive Care Team of Stormont Vail Health; Dr Anna Acosta of Division of Bacterial Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention (CDC); Dr James Sejvar of Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, CDC; Dr Jeremy Sobel of Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, CDC; and Dan Higgins, CDC illustrator. Disclaimer. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. Financial support. The findings and conclusions in this presentation are those of the author(s) and do not necessarily represent the official position of the CDC. Supplement sponsorship. This article appears as part of the supplement “Botulism,” sponsored by the Centers for Disease Control and Prevention. Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Unusual Wound Botulism • CID 2018:66 (Suppl 1) • S97 1. Shapiro RL , Hatheway C , Swerdlow DL . Botulism in the United States: a clinical and epidemiologic review . Ann Intern Med 1998 ; 129 : 221 - 8 . 2. Hodowanec A , Bleck T. Botulism (Clostridium botulinum) . In: Bennett JE, ed. Mandell, Douglas, and Bennett's principles and practice of infectious diseases . Philadelphia, PA: Elsevier Saunders, 2014 : 2763 - 7 . 3. Hughes JM , Blumenthal JR , Merson MH , Lombard GL , Dowell VR Jr, Gangarosa EJ . Clinical features of types A and B food-borne botulism . Ann Intern Med 1981 ; 95 : 442 - 5 . 4. 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Jacobs Slifka, Kara, Harris, Jo Ann, Nguyen, Von, Luquez, Carolina, Tiwari, Tejpratap, Rao, Agam K. A Case of Localized, Unilateral (Cephalic) Wound Botulism, Clinical Infectious Diseases, 2018, S95-S98, DOI: 10.1093/cid/cix828