A Rare Fatal Cause of Acute Areflexic Quadriparesis in the Tropics
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.299153
Source of Support: None, Conflict of Interest: None
Keywords: Acute fulminant hepatic failure, acute kidney injury, ascending quadriparesis, Crimean–Congo hemorrhagic fever, Guillain–Barre syndrome, tick paralysis
Progressive ascending paralysis of limbs with or without fever is a recurring neurological conundrum encountered in practice. Amongst various differential diagnoses, the commonest are Guillain–Barre syndrome (GBS), porphyrias, acute myopathies (infective, inflammatory, or metabolic), myasthenia, Lymes disease, poliomyelitis, and myelopathies. Relevant historical details, neurological examination and laboratory, and electrophysiological evaluations serve as guides for appropriate therapy.
Crimean–Congo hemorrhagic fever (CCHF) is an emergent zoonotic viral illness recently described from western India. Though first recognized in Crimea in 1944, the first viral isolation from humans was in the Democratic Republic of Congo and hence the illness bears both names. The CCHF virus, belonging to family Bunyaviridae, genus Nairovirus, is predominantly found in Ixodid hard ticks, particularly belonging to genus Hyalomma that can infect domesticated animals such as cattle, buffalo, sheep, and goats, frequently subclinically while persisting in lungs, liver, and spleen., Humans are the only host of this pathogen that manifests clinical disease. Transmission occurs by bite, crushing of infected ticks, direct contact with blood, body fluids, or tissues with occasional nosocomial transmission.,, CCHF typically is a rapidly progressing acute febrile illness with severe hepatorenal dysfunction and association with myalgias and myoglobinuria. We describe a previously unreported presentation of CCHF from India and review the existing literature.
An 18-year-old male, resident of Jaisalmer district in western part of Rajasthan, presented with nonradicular low back pain followed by weakness of both lower limbs for 3 three days, rapidly progressing from distal to proximal limb girdle, causing recurrent buckling of knees without loss of bladder and bowel control. A brief episode of low-grade fever with nausea lasting a day occurred ten days before presentation. There was no muscle pain, stiffness, abdominal pain, high-colored urine, or recent travel. He was undergoing treatment for rheumatic heart disease with severe mitral and aortic regurgitation since three months and was on diuretics. There was no history of similar illness in family and neighbourhood.
Vitals and general physical examination were unremarkable. There was no organomegaly or lymphadenopathy, and higher mental functions and cranial nerves were intact. Generalized hypotonia with decreased power (neck flexor—4/5, upper limbs across all joints—4/5, handgrip—70%, across hip and knee joints—3/5, ankle joint—2/5), decreased (1+) tendon jerks in upper limbs, and absent knee and ankle jerks were noted. Plantar responses were flexor. No sensory loss or muscle tenderness was noted. A differential diagnosis of areflexic quadriparesis including GBS, hypokalemia, and Lyme's disease was considered.
Arterial blood gases and serum potassium (5.02 meq/L) were normal. Nerve conduction study of both upper and lower limbs at admission showed slightly reduced CMAP amplitude in both ulnar and peroneal nerves with normal conduction velocities [Table 1] and impersistent F waves in bilateral peroneal and tibial nerves [Figure 1] suggesting early polyradiculoneuropathy. CSF analysis was clear with protein—33 mg/dL, sugar—74 mg/dL (blood sugar—123 mg/dL), and no cells. A day later, the patient started deteriorating rapidly over hours with increasing limb weakness, labored respiratory pattern, and drowsiness. Liver and kidney functions were significantly deranged [Table 2] leading to acute liver failure, hepatic encephalopathy, and acute kidney injury two days after admission. Creatine kinase was 3843 U/L and serum ammonia 341 mmol/L along with metabolic acidosis and hyperkalemia. No myoglobulinuria was noted. By day 3, additionally thrombocytopenia and deranged coagulation profile were reported [Table 2]. Hemodialysis was started and hepatic encephalopathy was managed medically.
At this stage, the neurological illness at presentation took a back seat as acute hepatorenal syndrome deserved aggressive management. From days 4–5, patient developed petechial hemorrhages in skin, bleeding gums, recurrent upper gastrointestinal and intrabronchial bleed, and was intubated. Now, differentials of viral hemorrhagic fever with acute hepatorenal syndrome like viral hepatitis, leptospirosis, scrub typhus, malaria, and dengue were kept. Serology for hepatitis A, hepatitis B, hepatitis C, hepatitis E, HIV, EB virus, CMV, scrub typhus, and leptospirosis were negative. Malarial antigen and dengue NS 1 rapid tests were negative. By day 7, stool for occult blood was positive, fibrinogen was 71.2 mg/dL, and platelet counts progressively fell to 21,000/mm3.
Panel for viral hemorrhagic fever was assessed at the ICMR National Institute of Virology, Pune. History of exposure to ticks, rodents, and abbatoirs was reassessed. The patient lived with his family who had farmlands, cattle, and sheep, one of whom had died recently of apparently natural causes with no similar affliction in the family or neighborhood. Reexamination of patient did not reveal any eschar or ticks. The patient continued to worsen clinically despite continuous renal replacement therapy, high bowel wash, lactulose, rifaximin, and l-ornithine l-aspartate. Though ribavirin was considered, it could not be given due to severe hepatic and renal dysfunction. Bleeding was controlled with fresh frozen plasma and platelet transfusions. Paralytic ileus developed after seven days of admission and he was successfully resuscitated from three episodes of sudden unexplained asystole (echo—no evidence of endocarditis or myocarditis). On day 13, the virology report suggested positive anti-CCHF virus IgM response by ELISA, while qRTPCR for CCHFV was negative. Finally, the patient died after 14 days due to diffuse alveolar hemorrhage with refractory hypovolemic shock and multiorgan failure.
CCHF is endemic in areas in Africa, Asia, south-eastern Europe, and Middle East, including bordering Pakistan and western China with about 50 cases annually from Pakistan. CCHF antibodies have been detected sporadically in livestock in Kerala, Puducherry, Jammu and Kashmir, Rajasthan, Maharashtra, and West Bengal since 1976. Since 2011, sporadic outbreaks of CCHF have been noted, predominantly in border states of Gujarat and Rajasthan, in addition to a single case from Uttar Pradesh in India [Figure 2].,, Most affected persons are involved in agriculture, animal husbandry, veterinary services, abattoirs, or are health-care workers., Our index case hailed from Jaisalmer, one of the previously involved districts, after probable exposure at his farms.
Incubation period of CCHFV in humans is 1–13 days and dependent on route of inoculation and viral load, with shorter interval in nosocomial transmission. Usual manifestations of CCHF include fever with headache, abdominal pain, and vomiting. This rapidly progresses to hemorrhages from skin, mucous membranes, gastrointestinal, genitourinary tracts as well as venipuncture sites. Changes in mood, aggression, and confusion may be seen. Apart from myalgias and elevated creatine kinase, neurological manifestations are seldom observed., The index case presented without fever or myalgias. Instead, there was acute ascending areflexic quadriparesis and impersistent F waves on nerve conduction studies consistent with early GBS, although CSF was normal. While rapid progression to quadriplegia was noted, overwhelming emergence of hepatorenal dysfunction led to change in approach. An additional possibility in this setting could be tick paralysis., However, no tick was found on the patient on later reassessment. Tick paralysis, a sporadic disorder produced by neurotoxic effects of salivary secretions of hard ticks, can manifest symptoms of paresthesias, ataxia, ascending symmetrical flaccid paralysis, and bulbar, facial, and/or extraocular paralysis.
In the tropics, rapidly deteriorating patients with fulminant hepatic failure and multiorgan dysfunction in the setting of fever entail the exclusion of viral hepatitis A and E, leptospirosis, scrub typhus, falciparum malaria, dengue, and Hanta virus infection. Apart from hepatorenal dysfunction, cardiopulmonary dysfunction is also seen. Our patient had three episodes of unexplained cardiac asystole. Thrombocytopenia, at times treatment resistant, is observed. As highlighted here and in literature, CCHF should also be considered especially with history of contact and exposure to zoonotic vectors or suspected nosocomial transmission.,
Treatment of CCHF is limited and largely symptomatic. As demonstrated in our case, medical management of fulminant hepatic failure, renal replacement therapy for acute kidney injury, blood product transfusions for bleeding diathesis, and ventilation remains the cornerstone for management of CCHF. Oral or intravenous ribavirin has been tried for treatment and prophylaxis though substantial favorable evidence is lacking. Compared to animals human afflictions are associated with high viral load and high case fatality rate (9–80%).,, In a recent meta-analysis, fatality rates were lower in Africa (22.0%) than Asia (33.5%) and Europe (33.8%). Some of the predictors of mortality included platelet count (≤20 × 109/L), aspartate aminotransferase level (≥200 U/L), alanine aminotransferase (≥150 U/L), activated partial thromboplastin time (≥60 s), or fibrinogen levels (≤110 mg/dL). All these parameters were also observed in our index case. Unfortunately, no vaccine has been developed till date.
CCHF being an emerging endemic in certain regions of India with high mortality, case surveillance, and contact tracing in hospital and community is of utmost importance as low seroprevalence for CCHF in humans (0.5%) in endemic areas makes them susceptible to outbreaks. Standard infection control and use of personal protective equipment may prevent nosocomial spread to health-care workers unlike the 2011 outbreak in Gujarat. Similarly, disposal of the dead should be accomplished by spraying with 1:10 liquid bleach, packing in leakproof bags, disinfection of hearse van or ambulance, and appropriate burial of the body without production of infected aerosols by burning.
Tick-borne diseases like CCHF should be considered while dealing with acute fever with hepatorenal failure. Rapidly progressive areflexic paraparesis or quadriparesis without fever or myalgia is an unusual presentation of CCHF. Though highly fatal, early suspicion and diagnosis may help aggressive therapy and early convalescence, thereby underlining the need to increase awareness amongst health-care workers along with public health initiatives such as screening for ticks and sero-surveillance in animals in high-risk regions.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The authors thank Dr. Pragya D Yadav, Scientist “E” and In-charge, Indian Council of Medical Research-National Institute of Virology, Sus Road, Pashan, Pune 411021, India, for her invaluable laboratory support in the diagnosis of CCHF in the patient and screening of contacts.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]