Longitudinally extensive transverse myelitis (LETM) in a ... · weakness in JE has been observed and even quadriparesis ... An approach to the diagnosis of acute transverse myelitis.

Japanese encephalitis (JE) is a mosquito borne dis-ease caused by a virus belonging to the Flaviviridae fam-ily. It is endemic in northern India and generally occurs in the monsoon season. Even though vaccination has been introduced in India, there’s not much reduction in the in-cidence1. It causes acute encephalitis syndrome and has been rarely associated with myelitis. The disease has a high mortality and is associated commonly with long term neurological sequelae.

Case definition of a suspected case of acute encepha-litis syndrome (AES) is described as a case of acute onset fever (5–7 days) with change in mental status with or with-out seizures2. Longitudinally extensive transverse myeli-tis is a variant of acute transverse myelitis (ATM) which involves three or more vertebral segments. It is most com-monly associated with neuromyelitis optica (NMO)3.

We report a case of a young male with altered senso-rium and quadriparesis, and diagnosed to have JE with longitudinally extensive transverse myelitis (LETM).

Case Report A 35-yr-old male resident of Delhi presented with a

history of fever and altered sensorium for five days, and two generalised tonic-clonic convulsions. There was no history of recent travel or vaccination. On examination, the pulse rate was 84/min, blood pressure was 130/90 mmHg and glasgow coma score (GCS) was E1VTM1. Neurological examination revealed generalised hypoto-nia, weakness and areflexia. Plantars were mute and there were no signs of meningeal irritation. No rash or eschar was visible. After a lumbar puncture, he was started on antibiotics (according to meningitis protocol), acyclovir; antimalarials (artesunate) and antiepileptics (levetirace-tam). A clinical diagnosis of suspected AES was made with pending investigations.

Routine haematological, biochemical and metabol-ic parameters were normal. Cerebrospinal fluid (CSF) showed 40 ×106 leucocytes/l (55% lymphocytes and 45% polymorphs), sugar and protein of 4.44 mmol/l (corre-

sponding blood sugar of 6.11 mmol/l) and 1.10 g/l respec-tively. Serum tests were negative for malaria, dengue, chikungunya, scrub typhus and HIV. The CSF was found negative for herpes virus, cryptococcal antigen and tuber-culosis (gene Xpert test). However, both the serum and CSF samples were found to be positive for IgM against Japanese B virus. Accordingly, the patient was managed for JE.

MRI of the brain revealed features of encephalitis (Fig. 1). Over the next two days, the patient’s fever subsided and sensorium gradually improved to a GCS of E4VTM1. His quadriplegia and areflexia however per-sisted. A nerve conduction velocity and electromyogra-phy were normal, but the MRI spine showed cord oede-ma and altered signal involving segments from C2 to C6 level (Fig. 2). With the diagnosis of transverse myelitis, the patient was given a pulse of methylprednisolone for five days.

The patient remained on mechanical ventilation how-ever, the muscle power did not show significant improve-ment and the patient succumbed to ventilator acquired pneumonia two weeks later.

DISCUSSION

Japanese encephalitis causes an array of neurologi-cal manifestations and does not have specific antiviral therapy. The mortality rate in India varies from 20–40%4 . Clinical manifestations includes fever, altered sensorium, seizures, movement disorders and brainstem involvement5. Rare findings include paralysis, dystonia and dysarthria6. Multiple seizures, respiratory pattern changes, flexor or extensor posturing and abnormalities of the papillary and occulocephalic reflexes are associated with poorer prognosis7.

The diagnosis was done by using JE specific IgM antibody capture enzyme linked immunosorbent assay (MAC-ELISA) as recommended by WHO8. IgM against the virus is detected in CSF by four days and in serum by

Longitudinally extensive transverse myelitis (LETM) in a case of Japanese encephalitis with an unexpected complication

Srikant Mohta1, Animesh Ray1, S.K. Sharma1 & Surabhi Vyas2

1Department of Medicine; 2Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India

Key words Diaphragmatic palsy; Flavivirus; quadriparesis

J Vector Borne Dis 54, September 2017, pp. 291–293

J Vector Borne Dis 54, September 2017292

Fig. 2: T2 weighted sagittal section of the MRI cervical spine with cord swelling and altered signal involving segments from C2 to C6 level.

Fig. 1: MRI of brain showing altered signal intensity involving the basal ganglia and thalami (bilaterally) appearing hyperin-tense on T2W image (a); with restricted diffusion on diffusion weighted imaging (DWI) (b); and apparent diffusion coeffi-cient (ADC) map (c).

(a)

(b)

(c)

7–9 days after clinical illness9. It may show cross reactiv-ity with other Flavivirus, but presence of CSF antibody is a more accurate way to confirm CNS infection of the virus; as in the present case. Also, the test for dengue was negative.

The patient’s sensorium improved, but the quadriparesis persisted likely due to myelitis. He could not be weaned-off mechanical ventilation, as he continued to have type-II respiratory failure, likely due to the bilateral diaphragmatic palsy caused by cervi-cal cord involvement. Even with steroids, the patient did not show significant improvement in muscle power over the first week, and developed ventilator acquired pneu-monia. The high dose of steroids may have predisposed the patient to super added infection. The role of steroids in idiopathic transverse myelitis is well documented10,

but there are few such records in case of acute infectious myelitis.

Acute transverse myelitis, an inflammatory myeli-tis, has been reported to be associated with autoimmune, infectious and inflammatory pathologies11. When associ-ated with acute encephalitis or encephalopathy, the dif-ferential diagnoses include non-infectious causes like acute disseminated encephalomyelitis (ADEM), NMO, post-vaccination encephalomyelitis, neurolupus, ex-traglandular Sjogren’s syndrome and rarely neoplasms. Infectious causes which must be considered are mostly viruses (including herpes family, flaviviridae, enterovi-rus and retrovirus), cerebral malaria, neurocysticercosis, CNS aspergillosis and rarely bacterial infections. These

293Mohta et al: Longitudinally extensive transverse myelitis (LETM) in a case of Japanese B encephalitis

causes were excluded in this case systematically, till a di-agnosis was confirmed. Association of ATM with JE is rare, and to the best of our knowledge it is only the third case where it has been documented6,12. Both the earlier described cases showed signal alternations in the cervical region of spinal cord and were treated by a short course of intravenous methylprednisolone. One of the cases was of the parainfectious variety likely due to autoimmuni-ty, which occurred after three weeks of infection while the second was in the acute phase of illness which may indicate an alternate pathogenesis, possibly acute infec-tious myelitis. Hence, myelitis may present in the acute phase or few weeks later in the parainfectious form. Motor weakness in JE has been observed and even quadriparesis is known which has been shown to occur due to anterior horn cell damage13. In the present case anterior horn cell damage was ruled out by the normal electromyography (EMG) and nerve conduction velocity (NCV), and by the abnormalities seen in MRI.

The present case is also unique, for the way, the pa-tient required prolonged mechanical ventilation due to his diaphragmatic involvement, and this complication led to a change in the patient’s clinical outcome.

In conclusion, Japanese B virus infection can cause spinal cord involvement in the form of LETM with a predilection for the cervical cord, even in the acute phase as observed in this as well as other reported cases12. Associated complications like diaphrag-matic palsy may also occur. The current treatment for my-elitis remains early initiation of high dose steroids (when specific antibiotic therapy is not available) but further research is required to determine its efficacy and role of other modalities like plasma exchange, cyclophospha-mide, etc.

Conflict of interest There is no conflict of interests to declare.

Ethical statementConsent was taken from the patient’s kin for the treat-

ment administered and for publication of the case.

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Correspondence to: Dr Animesh Ray, Assistant Professor, Room No. 3070, III Floor, Department of Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi–110 029, India. E-mail: [email protected]

Received: 2 March 2017 Accepted in revised form: 27 June 2017