Abstract: transverse myelitis. Following treatment with corticosteroids and intravenous

Transverse myelitis has been reported in association with vaccination,
including post  diphtheria, pertusis and
tetanus (DPTw)  vaccination. A 21 month old toddler presented with
loss of neck control after 27 days of DPTw booster vaccination. Child was
referred to the tertiary care service hospital. MRI of spine revealed cervical
longitudinally extensive transverse myelitis (LETM).  Extensive investigation effectively ruled out
causes other than vaccination- associated transverse myelitis. Following
treatment with corticosteroids and intravenous immune-globulin, the child made
a complete recovery.

Message:  (1)LETM may be associated with otherwise seemingly
harmless DPTw vaccination.

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(2)The investigation includes an early
MRI of nervous system for exact diagnosis and treatment.

(3)An early identification and prompt
treatment with immunotherapy is associated with good outcome.

(4) Treatment is either intra venous
immunoglobulin or methylprednisolone pulses and in relapsed cases other
immunomodulation may be tried.

Keywords: LETM,
Vaccine associated transverse myelitis, Immunotherapy, Intravenous
immunoglobulin, prognosis

myelitis (TM) is a focal inflammatory demyelinating disorder of the spinal cord
and is commonly due to an auto-immune process. Lesion extending more than 3
vertebral segments in length is diagnosed as Longitudinally Extensive
Transverse Myelitis (LETM). LETM have been rarely associated with post DPT
vaccination.The extensive involvement of cervical segment in this child
confirmed the diagnosis of a severe form of TM.(1)

History: A 21 month old female toddler referred from dependant hospital to
our centre with history of loss of control of neck of 1 day duration. There was
no history of difficulty in swallowing, breathing or difficulty in passing
urine or stool or history of altered sensorium. There was no history of fall,
trauma or antecedent history suggestive of gastroenteritis or upper respiratory
tract infection. There was history of booster DPTw vaccination 27 days prior to
presentation to dependant hospital. On examination child found to have non
significant cervical lymphadenopathy and pallor and full neck flop on general
examination. On central nervous system examination, child was conscious with Glasgow
Coma Scale (GCS) 15/15 and hypotonia in neck muscles. The power as per Muscle
Research Council (MRC) was 3/5 for neck flexors and 2/5 for neck extensors. Limb
powers in both upper and lower limbs were normal at all the joints. Reflexes
were normal in lower limbs however were poorly elicitable in bilateral upper
limbs. Plantar was flexor bilaterally and other superficial reflexes were
normal. There were no signs of cerebellar involvement or any signs of meningeal
irritation. There was no evidence of sensory or autonomic involvement. Her
fundus examination was normal. Other systemic examination was normal. On
laboratory investigation had AST of 364 IU/dl and ALT of 569 IU/dl which
normalized after 6 days of admission. Her Cerebro Spinal Fluid (CSF) examination
showed no cells, normal sugar (53 mg, with blood sugar of 92 mg/dl) and protein
of 22 mg/dl with absence of oligoclonal band. CSF culture for bacteria and
fungus were negative. Her initial MRI done in referring hospital was normal
however repeat MRI done  on sixth day of
presentation for spine and brain showed T2 hyper-intense signal in cord
parenchyma from C2 to C6. Rest of the spine and brain parenchyma revealed no
significant demyelinating changes. MRI images demonstrated LETM. (Fig 1)  She was worked up for tuberculosis, EBV,
entero virus PCR and anti-aquaporin 4 antibody in CSF which were all
negative.  Her serum anti-aquaporin 4
antibody ,ANA , C-ANCA and P-ANCA  for
vasculitis and work-up for human immune-deficiency virus, mycoplasma and
Epstein-Barr virus were also negative. Her Vit B12 level was 216pg/ml (Normal
200-600 pg/ml). In view of LETM child was started on immune-modulation with
intravenous immunoglobulin (IvIG) in doses of 2 gm/per kg over 2 days. Child
had shown only some clinical improvement in next 72 hours hence a 5 days pulse
of methylprednisolone at 30 mg/kg/day was given intra-venously followed by oral
prednisolone of 1 mg/kg/day. From 4th day of methylprednisolone  pulse, 
child started showing improvement and by 7th day of pulse
child recovered full range of neck movement and normal power at all groups of
neck muscles. VEP has been done at the time of discharge and was normal. Child
was discharged after 14 days of admission with advice to continue prednisolone
for 2 weeks followed by tapering over 3 weeks and monthly follow up in the OPD.


Figure 1:Saggital images of spine demonstrating high signal
intensity from C2-6 in T2W



TM is a focal inflammatory demyelinating disorder of the spinal
cord. LETM involves more than 3 spinal segments in length. Occasionally it
involves entire length of spinal cord which entails a severe forms of LETM.(2) Presently
a bimodal distribution is usually seen in children, under 5 years and older
than 10 years of age.(1, 3)

                Ever since
vaccination is being used to control infectious disease, the pitfalls and side
effects of vaccines which is called adverse effect following immunization (AEFI)
is being reported. Several complications related to neurological systems are
documented in literature like Transverse myelitis(TM), Guillian Barre Syndrome
(GBS), Neuro-myelitis Optica and Acute Demylinating Encephalomyelitis (ADEM)
are most common.(3) The diagnosis in the case is based on
excluding other causes and with epidemiological evidences. TMCWG (Transverse myelitis
consortium working group) have proposed diagnostic criteria for diagnosis of TM
which necessitates exclusion of idiopathic TM, bilateral sign and symptoms
(though not necessarily symmetric), exclusion of extra-axial compressive
etiology by neuro-imaging.(4) This case fits in these criteria and
also had MRI evidence of LETM in cervical segment C2-C6. Since it’s difficult
to pin point the exact causal relationship with vaccine, a hypothesis has been
proposed for possibility of TM following vaccination. Only few cases have been
published in literature due to post DPT vaccination till date.(3) Other vaccine which have been
implicated in TM are MMR, H1N1 and Hepatitis B vaccination. Its vaccine
adjuvant which has been specifically considered triggering agent for vaccine
associated Transverse Myelitis.(5, 6) Auto-immunity
theory  has been proposed  which is due cross reactivity of antibodies
and T cells to peripheral nervous system(PNS) or central nervous system (CNS).(7) The other hypothesis which has been
proposed is  “Molecular mimicry” which
portends that similar proteins of microbial pathogens with human proteins
result in immune response that damage the human organ system. (8) Diagnosis is clinical and
confirmed by MRI of the spine. Cervico-thoracic segment or thoracic segment is
usually commonest area of involvement.(9) The
treatment is essentially immune-modulation by steroid or IvIG (Class IV) or by
plasmapheresis. There are no randomized trial in children published in
literature to prove superiority of one over other, however a STRIVE trial
protocol has been published in 2015 and results are pending, therefore the
choice of drug is dependent on individual preferences, cost and availability.(9) Plasmapheresis
has been recently recommended by American Academy of Neurology   for subgroup of patients who fail to respond
to high dose corticosteroid treatment. This procedure is technically difficult
hence is not routinely done in the children. For relapsed cases or NMO related,
Cyclophosphamide ,Rituximab or ecluzimab have been tried occasionally.
Prognosis in TM is generally good in children however LETM lesions with
extensive involvement of ?7 spinal segments showed poor functional recovery in
at 3 month follow-up. In another study of 19 patients with TM, rapid
progression of symptoms, high level of deficit and spinal shock were associated
with poorer outcome. (10) In a study from north
India in Pediatric TM, spinal shock, severe weakness at onset with power ?1/5
on MRC scale, respiratory muscle involvement, greater mean time to diagnosis
and treatment had with poorer outcome during follow-up.(11, 12)

Conclusion: Transverse myelitis is an acute/sub-acute inflammatory
disorder of the spinal cord and may be due to cross reaction from vaccines.
This diagnosis is only by excluding other causes and with epidemiological
correlation. The early diagnosis and early treatment with immune-therpy yields
satisfactory results.