A case of longitudinally extensive transverse myelitis with coinfection of scrub typhus and leptospirosis

INTRODUCTION

Both scrub typhus and leptospirosis are widely found diseases in tropical and subtropical regions. Orientia tsutsugamushi is the organism behind scrub typhus infection and is transmitted by bites of infected chiggers (larval mites). On the other hand, leptospirosis is caused by pathogenic strains of Leptospira interrogans and transmitted by indirect/direct contact with water, soil, or urine of infected animals.^[1] As both diseases share common epidemiological factors related to host (like outdoor activities), reservoir (rodent), and seasonal spread, isolated cases of coinfection have been reported in previous literature.^[1] Presentation of longitudinally extensive transverse myelitis (LETM) in both infections is quite rare and uncommon. We report a case where a 36-year-old man had concurrent leptospirosis and scrub typhus infection, presenting as an acute onset of upper motor neuron type of paraparesis with imaging showing LETM.

CASE REPORT

A young male of 36 years with no pre-existing comorbidities presented with fever with chills for the past 4 days. Fever was continuous with headache but without having vomiting. On the 2^nd day of illness, he noticed weakness of both lower limbs, which started distally. Gradually, it ascended to have proximal weakness of both lower limbs. He had incontinence of urine and bowel constipation. No history of seizure or behavioral abnormality was present. No eschar was found. On examination, he was conscious but disorientated. No meningeal signs were present. His power in the upper limbs was 5/5 but lower limb power was 3/5. Deep tendon reflexes were exaggerated, and plantar reflexes were extensor. Sensory was normal. His routine blood examination showed leukocytosis. Liver function showed direct hyperbilirubinemia but enzymes were normal. Renal functions were normal. Cerebrospinal fluid (CSF) examination showed a high protein level (84 mg/dL) with mild pleocytosis (10 cells/uL, all lymphocytes). CSF adenosine deaminase levels were normal. CSF Gram stain, Indian ink, and acid-fast bacillus stain were negative. Japanese encephalitis serology and herpes simplex virus polymerase chain reaction were negative. Both the Leptospira and scrub typhus enzyme-linked immunosorbent assay tests were positive. CSF aquaporin 4 antibody and myelin oligodendrocyte glycoprotein antibody were negative. Malarial parasite (Pf/Pv), dengue serology, and Weil–Felix test were negative. His brain magnetic resonance imaging (MRI) was normal as seen in Figure 1. Spine MRI showed T2 hyperintensities in the lower cervicodorsal cord, more pronounced at D4 to D6 vertebral level [Figure 2 a-c]. Post gadolinium sagittal T1 image showed patchy enhancement in the cord lesion [Figure 2d]. Axial T2-weighed images of lower cervical and dorsal cord show T2 hyperintensities in the central and bilateral paramedian locations of the cord substances [Figure 3].

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Figure 1:

a) Axial T2W, b) FLAIR and c) T1W images shows normal appearances of the brain parenchyma.

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Figure 2:

Sagittal T2W and STIR images (a-c) of cervico dorsal spine shows patchy ill-defined T2 hyperintensities in the lower cervico-dorsal cord, more prounced at D4 to D6 vertebral level (White arrow). Post gadolinium SAG T1 image (d) showed patchy enhancement in the cord lesion (white arrow).

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Figure 3:

Axial T2W images of lower cervical and dorsal cord (a-c) shows T2 hyperintensities in the central and bilateral paramedian locations of the cord substances (Black arrows).

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He was initiated on intravenous ceftriaxone and doxycycline. However, his power in the lower limbs was further deteriorated to 2/5. A course of intravenous methylprednisolone (1 g/day) was given for 5 days. Gradually, his lower limb power improved. The antibiotics were continued for 10 days. At the time of discharge, his power improved to 4/5 and he could walk without support. His bowel and bladder control were also regained.

DISCUSSION

Leptospirosis and scrub typhus share common epidemiological factors related to host (like outdoor activities), reservoir (rodents), and seasonal spread. In the rainy season (July to September), the incidence of leptospirosis increases because of waterlogging which leads to contact with animal’s urine. Similarly, the incidence of scrub typhus also increases due to an increase in trombiculid mite populations.^[1] As they share common epidemiological patterns, there is a possibility of dual infections but very few cases were reported from India.^[1,2]

Leptospirosis classically presents as a biphasic illness with an initial phase known as the septicemic phase. It is followed by a brief afebrile period after which the immune phase (also known as Weil’s syndrome) occurs which is characterized by hepato-renal involvement. Although asymptomatic meningitis and encephalitis are the most common presentations of neuroleptospirosis, it can involve any part of the neuraxis. Myeloradiculopathy, Guillain–Barré syndrome-like presentation, intracerebral bleed, cerebellar dysfunction, and extrapyramidal symptoms are less common presentations of the disease.^[3] Myelitis leading to paraparesis is very rare.^[4] Panicker et al. reported paraparesis as the initial presentation in 17 patients out of which myelopathy was seen in seven patients.^[4] All these cases presented in the septicemic phase of the disease. However, it can be found in the immune phase of illness also along with severe hepato-renal syndrome.^[5]

In scrub typhus infection, an eschar at the site of a chigger bite is visible in 40% of patients which is often pathognomonic. Neurological involvement can be found in 12.5–26% of the affected patients.^[6] The most common clinical manifestations were meningitis or meningoencephalitis, similar to leptospirosis.^[6] Other less common manifestations reported include delirium, myelitis, cerebral hemorrhage, isolated cranial nerve palsy, trigeminal neuralgia, opsoclonus, myoclonus, extrapyramidal involvement, myelitis, brachial plexopathy, polyneuropathy, acute disseminated encephalomyelitis, etc.^[6]

LETM is an immune-mediated clinicoradiological syndrome characterized by contiguous involvement over three or more spinal cord segments on MRI, with clinical presentation consisting of paraparesis or quadriparesis, sensory disturbances, and bladder and bowel dysfunctions.^[7] It is classically described in neuromyelitis optica. However, similar clinicoradiological findings were also described in various infections such as Borrelia, Chlamydia, Cytomegalovirus, mumps, coxsackie virus, Mycobacterium tuberculosis, Mycoplasma, enterovirus 71, hepatitis C virus, Brucella, Ascaris, Toxocara, and Schistosoma.^[8] Both direct infection of the spinal cord and through post-infectious immune-mediated injury can lead to various infection-related myelitis.

In our patient, co-infection with scrub typhus and Leptospira were detected in serum. The patient lived in a sporadic area of both infection. In our case, myelitis is most likely immune-mediated as the patient responded to steroids along with antibiotics. In both infections, there is evidence of immune-mediated vasculitis accompanied by perivascular mononuclear cell infiltration.^[4,6] Usually, coinfection is suspected who respond poorly to particular antibiotics or who present with severe and atypical symptoms like myelitis as present in the case.^[1,2] As the patient does not have any particular pathognomonic clinical presentation (like eschar in scrub infection), it is difficult to ascertain which organism is most likely. Furthermore, we have initiated ceftriaxone and doxycycline (drug of choice for leptospirosis and scrub typhus infection) from the day of presentation. Whether a coinfection can cause more severe myelitis compared to isolated infection is difficult to predict, as there are no previous case reports or studies available in the literature.

CONCLUSION

Although rare, LETM with coinfection of this type should be suspected when there is the presence of fever with atypical symptoms. Early clinical suspicion and serological diagnosis are important because of excellent response to treatment, which not only avoids antimicrobial resistance in the community but also decreases neurological morbidity and complications.