A case of tetanus presenting with catatoniaSima Mohseni Ahangar1, Sussan Moudi2, Hadi Ahmadi Juybari3, Maria Yazdani4, Babak Yeganeh5, Masoud Ghasemi6, Maryam Vajdi7, Seyedeh Mahboobeh Mirtabar8*1MD, Infection Diseases and Tropical Medicine Research Center, Babol University of Medical Sciences, Babol, Iran. Orchid: 0000-0001-0201-7952Email: simamohseni6010@yahoo.com2MD, Associate Professor of Psychiatry, Fellowship of Psychosomatic Medicine, Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Orchid: 0000-0002-6573-8861 Email:sussan.mouodi@gmail.com3MD, Infection Diseases and Tropical Medicine Research Center, Babol University of Medical Sciences, Babol, Iran. Orchid: 0000-0001-6630-0100Email: dr.h.ahmadi.j@gmail.com4MD, Infection Diseases and Tropical Medicine Research Center, Babol University of Medical Sciences, Babol, Iran. Orchid: 0009-0009-4659-2455Email: Mariayazdani3255@gmail.com5MD, Infection Diseases and Tropical Medicine Research Center, Babol University of Medical Sciences, Babol, Iran. Orchid: 0009-0000-5426-7569Email: babak74ids@gmail.com6MDAssistant Professor of Anesthesiology, Department of Anesthesiology, School of MedicineBabol University of Medical Sciences, Babol, Iran. Orchid: 0009-0004-2816-0513Email: masoud.ghasemi.dr@gmail.com7MDAssistant Psychiatric Student, Clinical Research Development Unit of Yahyanejad Hospital, Babol University of Medical Sciences, Babol, Iran. Orchid:0009-0004-7528-3786Email: Maryamvajdi1991@gmail.comCorresponding author: 2PhD for By Research Clinical Psychology, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Orchid: 0000-0003-2679-5449. Email:seyedehm.mirtabar@gmail.comKey Clinical MessageTetanus is a potentially life-threatening disease that, although largely controlled in most parts of the world through childhood vaccination programs, remains a significant challenge in developing countries. We report a case of generalized tetanus presenting atypically with catatonia and complicated by aspiration pneumonia, who astonishingly survived.IntroductionTetanus is a potentially life-threatening disease presenting with muscle spasm and usually ending with death. However, it has been controlled to a great extent in most regions of the world as a result of childhood vaccination program. Yet, tetanus is still a challenging problem in developing nations with low socioeconomic level, contaminated environment, inadequate immunization coverage, and improper management1. The clinical diagnosis of tetanus is usually straightforward and is made by demonstration of body stiffness, trismus and dysarthria. Nonetheless, atypical presentations can be overlooked, delay the diagnosis and management and consequently worsen the outcome2. Herein, we report a case of generalized tetanus presenting atypically with catatonia and complicated by aspiration pneumonia, who astonishingly survived.Case presentationA 39-year-old male patient was admitted to the emergency department of the psychiatric hospital with a 2-3 weeks history of Catania-like changes. His complaints began after a family dispute with fatigue, weakness and lethargy, dysphoric mood, decreased ability to walk, loss of interest and refusal to eat and talk, desire to drink fluids, and social withdrawal, which prompted him to see a psychiatrist. An initial diagnosis of adjustment disorder was made and he was started on sertraline, propranolol, and clonazepam, but no significant improvement was achieved. Due to the lack of improvement in symptoms, he was referred to a neurologist, and brain imaging and necessary tests were performed, which were normal. After 2 weeks, his condition worsened, leading to hospitalization in the psychiatric department. The patient had no history of trauma, alcohol/substance abuse, or medical illness. However, his brother had an opiate use disorder. During the visit, the patient had general body tremors, sweating, upper limb tremors, inability to speak, retardation, drowsiness, rigidity, and increased DTR. He had no delusions or hallucinations. On examination, his pupils were of normal size and reaction to light. His vital signs were as follows: blood pressure 110/70 mmHg, heart rate 84 beats/min, respiratory rate 18 breaths/min, and body temperature 36.9°C. Physical examination revealed no significant abnormalities. He was alert and cooperative in psychiatric evaluation. His mood was anxious. Assessment of content and thought process was not possible. A complete clinical and necessary laboratory examination was performed. The patient’s blood tests were within normal limits, except for elevated creatine phosphokinase (CPK) (1313 units/L), lactate dehydrogenase (LDH) (570 units/L), aspartate aminotransferase (AST) (69 units/L), and aldolase (72 mIU/L).On day 1 of hospitalization, he developed akinesis and rigidity of upper and lower extremities; thus, neurological consult was done which advised cervical and thoracic vertebra and brain magnetic resonance imaging (MRI), and started the patient on bromocryptin, baclofen and diazepam. Moreover, testing for HTLV1 and 2 antibodies was recommended. Brain computed tomography (CT) scan was normal except for a nonsignificant left maxillary sinus opacification; however, lumbosacral MRI revealed bilateral spondylolysis at L5 and anterolisthesis between L5-S1.two days after admission, he developed fever and headache. Thus, infectious diseases consultation was requested. He was subsequently transferred to infectious diseases service with suspected meningoencephalitis. On physical examination, there was no meningioma’s but mutism, waxy flexibility and rigidity were evident. He was started on acyclovir, vancomycin and meropenem and underwent lumbar puncture (LP). Cerebrospinal fluid (CSF) parameters were normal except for elevated protein (61.7 mg/dl) level. Test results for human herpes virus (HSV) polymerase chain reaction (PCR) was negative in the CSF. Moreover, other workup for human immunodeficiency virus (HIV) and malaria did not provide conclusive results. Echocardiography and abdominopelvic ultrasound were also normal. Anti-nuclear antibody (ANA), anti-neuronal antibody panel for autoimmune encephalitis and anti-myositis antibody were negative, all of which excluded rheumatologic and autoimmune neurologic disorders. Meanwhile, the patient developed trismus, severe muscle spasms, dysphonia and dysphagia, which along with evidence of autonomic lability such as diaphoresis was consistent with signs of tetanus. The differential diagnosis of serotonin syndrome was also given. Thus, past history was again questioned which revealed no history of acute trauma, but the patient recalled a sole puncture with a nail with spontaneous resolution about 2 months prior to his symptoms initiation. Furthermore, it was found that his childhood immunization was complete but he had not received any booster dose of tetanus vaccine since then. Based on history and clinical manifestations, the likely diagnosis of tetanus was made. He was admitted to the intensive care unit (ICU) for further treatment. Antimicrobial and antiviral agents were discontinued except metronidazole which was prescribed 500 mg intravenously every 6 hours based on Centers for Disease Control and Prevention (CDC) guidelines. Blood was drawn for investigations including tetanus serology. This was followed by the administration of one tetanus toxoid dose, intramuscular (IM) tetanus immune globulin (TIG) for 6 times and two 5-day series of intravenous immunoglobulin (IVIG). Electroencephalography (EEG) was normal. Electrodiagnostic examination including nerve conduction study (NCS) was normal except for reduced amplitudes with distal stimulation; however, voluntary activity of muscles was not evaluable with needle electromyography. Muscle biopsy was performed to exclude neuromuscular disorders which demonstrated the presence of focal neurogenic atrophy with no vasculopathy, inflammation or myopathy. The spasms gradually ameliorated over 45 days of hospital stay but trismus was persistent and the patient was still listless. However, a single dose of tetanus toxoid was given as a booster and he was planned to be discharged home when he developed dyspnea and lowering of consciousness. Chest CT scan revealed consolidation and air-bronchogram in posterior right upper lobe and basal segments of both lungs suggestive for aspiration pneumonia. Due to the patient’s condition and arterial blood gas (ABG) results, he was intubated and remained in the ICU. He was restarted on broad-spectrum antibiotic therapy. Tracheal aspirate culture was positive for Pseudomonas aeroginosa and Klebsiella pneumonia which were both pan-drug resistant. Meanwhile, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels also increased significantly. This nosocomial infection led to an extra 2 months of hospitalization which fortunately ended with the patient’s improvement and systemically good condition for discharge. He was sent home and advised to institute physical therapy and receive the third toxoid dose in 2-4 months. His clinical condition was stable over the following weeks and he had full recovery with no spasms and trismus at the 2-month follow-up visit.DiscussionTetanus is a potentially lethal infection caused by the neurotoxin produced by Clostridium tetani. This gram-positive pathogen is ubiquitous and its spores can survive for long periods particularly in soil 3. Global tetanus vaccination programs reduced tetanus incidence and the associated morbidity and mortality all over the world; nonetheless, incomplete vaccination coverage in underdeveloped countries and also neglect in receiving tetanus-toxoid vaccine boosters even in developed and developing nations are causes of sporadic tetanus reports in various parts of the world especially in resource-limited countries. In fact, inadequate vaccination and decreased immunogenicity are thought to be the main reasons of tetanus incidence in the unvaccinated and vaccinated individuals, respectively4. Puncture wounds and injecting drug use have been among the most common routes of tetanus transmission; however, similar to our patient, tetanus can be transmitted through minor injuries by even a rusty nail 5.Clinical manifestations of tetanus is dependent upon the forms which include cephalic, localized, generalized, and neonatal ones6. Our patient presented with the generalized form of tetanus which is characterized by muscle rigidity predominantly in the extensor muscle groups, hypertonic reflexes, signs of cranial nerve involvement like facial muscle spasm (risus sardonicus), trismus, laryngeal spasm, and dysphagia. Any stimuli including auditory, tactile, or visual may trigger the tonic contractions 7. In addition, signs of autonomic dysfunction, such as hypersialosis, diaphoresis, hypertension, tachycardia and tachypnea may be evident8.Diagnosis is primarily based upon history and clinical manifestations; however, atypical presentations can result in overlook or mistake of tetanus for other medical conditions and delay the diagnosis9. Our patient presented with a long duration of depressive mood which had been managed with anti-depressant agents. Similar to our patient, wounds may not be apparent due to the long time passed since the traumatic event 10.Laboratory tests do not commonly aid in the diagnosis of tetanus. However, certain changes which may support the diagnosis include neutrophilic leukocytosis, and elevated CPK, LDH and AST levels. Moreover, there is a possibility of acute renal failure due to rhabdomyolysis, which did not fortunately occur in our patient11, 12.Although electromyographic testing should be delayed in order to prevent disease progression, but prolonged electrical discharges with normal nerve conduction velocities are predicted to be present in tetanus13.Any suspected case of tetanus should undergo aggressive workup and rapid management. Therapy is consisted of both generalized and specific care. Generalized care is consisted of supportive therapy and symptomatic care which include wound debridement, and administration of antibiotics to cover C. tetani and sedatives for muscle spasms. Antimicrobial agents are administered to eliminate the clostridial spores in order to prevent further toxin production. Metronidazole is the antibiotic of choice with good anaerobic tissue penetration and anti-spore activity14 . Our patient did not have any apparent wound but he was started on metronidazole. He was nutritionally supported and placed in a dark and quiet environment in order to avoid any stimulus like light and noise to trigger further spasms 15. In addition, diazepam and baclofen was administered without the use of narcotics to prevent respiratory depression 16. Magnesium was also started to regulate muscle contraction and relaxation and control autonomic dysfunction. Moreover, magnesium sulfate reduced our patient’s need to sedation, dispense him of the need to ventilatory support and improved his tolerance of enteral feeding17.Specific care includes antitoxin to neutralize the circulating toxin. Human TIG is the currently recommended antitoxin licensed for IM use. This immunoglobulin is only effective prior to toxin transportation into nerve cell; thus, it should be promptly administered as soon as when the toxin is present in the blood. However, it is suggested that intrathecal administration of immunoglobulin can be effective even when the toxin has penetrated the central nervous system (CNS) 15,18Since the clinical disease does not induce lifetime immunity, the infected patient should be routinely vaccinated post infection15. Thus, we started the patient on 3-dose series of tetanus toxoid and advised him to receive the third dose after discharge.The prognosis of tetanus is unfavorable, particularly in the untreated generalized form which is followed by cardiovascular collapse or respiratory failure 19. Fortunately, our patient did not develop any electrolyte abnormalities or end organ damage during the long period of hospitalization until aspiration pneumonia intervened which led to tracheal intubation and the need to ventialtory support.There is no doubt that national immunization programs have indeed abolished almost all cases of tetanus in developed countries. However, there are still a small number of cases, which present with ambiguous or non-specific symptoms such as dysphagia, neck stiffness, and other oropharyngeal symptoms portraying a prodromal state of the illness, which could eventually lead to full-blown generalized tetanus. Once developed or allowed to progress, it ultimately leads to respiratory or autonomic dysfunction necessitating long-term intensive care or even death in more severe cases.Another diagnostic challenge lies in the distinction between localized and other forms of this disease. The former involves muscle spasms limited to specific body areas with generally good outcomes, but rare cases go on to involving vital structures such as the cranial nerves leading to cephalic tetanus and increasing the risk of developing generalized tetanus with high mortality rates 7.Moreover, there have been reports of similar cases in the past whereby partially or completely immunized individuals have been misdiagnosed as suffering from illnesses other than tetanus and physicians have taken their immunization status for granted [8]. This highlights an important aspect of diagnosing this rare infection, considering some cases may even present without an acute wound as evident in our case and in another case series 9.Treatment of tetanus involves wound debridement, antibiotics to decrease bacterial load, and supportive care. Some studies have shown metronidazole to be more efficacious when compared to penicillin, as penicillin is thought to enhance inhibitory effects on neuromuscular junctions aggravating the disease further 10.The second step and the most vital aspect of managing this disease is the administration of tetanus immunoglobulin, which greatly reduces the mortality from generalized tetanus. It is generally recommended that tetanus accelerated immunization course should include immunization when the patient presents or is at high risk, at discharge, and 4 weeks later to confer concrete immunity and greatly reduce further risks.ConclusionThis case report acknowledges that tetanus is still a probability particularly in developing countries and in individuals who neglect to receive booster vaccine doses. In addition, this article signifies the fact that tetanus can present with atypical manifestations such as that happened for our patient who presented with psychiatric features; thus, a high index of suspicion should be undertaken for any patient with compatible findings.AcknowledgmentNot applicable.Conflict of interest:No conflict of interest was declared by the author.Author contributions:SM: took the lead in patient management and supervised work.ZM: conducted literature search on the topic and drafted and revised the paper.SMM: was responsible of the patient follow-up and wrote the drafts and final article.All authors read and approved the final manuscript.Ethical approval:Consent:Written informed consent was obtained from the patient to publish this case report in accordance with the journal’s patient consent policy.Reference:1. Thwaites CL, Loan HT. Eradication of tetanus. British medical bulletin . 2015;116(1):69.2. Mahmoud TM, Shawky JA, Abdelwahab NA. 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