We report a case of new onset refractory
status epilepticus (NORSE) in an adult patient with acute
COVID infection who was ventilated for long with continuous
fits and finally responded dramatically to Immunoglobulin
therapy.
Keywords: NORSE, COVID 19,
Immunoglobulin therapy
Introduction
There is a broad range of neurologic manifestation which are
reported with Covid 19 infection. The central nervous system
complication can range from non specific manifestations to
encephalitis, myelitis, necrotising encephalopathy,
endothelitis and stroke. One of the mechanism for the
neurovirulence of Corona virus is related to the virus'
ability to induce proinflamatory cytokines and resultant
hyperimmune response.
Case report
A young lady with no premorbid illness, was diagnosed as
Covid-19 by PCR of nasal swab when she presented
with cough and mild fever. She was
home quarantined. 2 days later she developed sudden onset
tonic posturing of both upper and lower limbs with uprolling
of eyes. She was brought to emergency deparment where she
had multiple episodes of fits. She was given diazepam and
loading dose phenytoin. She was started empirically on
ceftriaxone and acyclovir in meningitic dose along with
dexamethasone. Since she was continuing to have seizures she
was intubated. Simultaneously she was being given parenteral
sodium valproate and Levetiracetam. After the patient
was mechanically ventilated she was started on midazolam
infusion. Lumbar puncture was was done on same day.
CSF (cerebrospinal fluid) was normal, less than 5 cells/mm3,
protein of 15 mg/dl, CSF gram stain was negative, no growth
in CSF culture and CSF viral panel was negative. CT
brain was normal. She was continuing to have subtle
seizures. On second day she had recurrent seizures with
twitching of face and mild clonic movements of hands. She
was started on phenobarbital infusion on third day and
continued on oral phenobarbitone. Still she continued to
have subtle seizures. She was subsequently given propafol
and thiopentone without much benefit. Her CT brain and CT
venogram of brain was normal. Her MRI brain could not
be done at the time since she had to be shifted out to
nearby facility which was not possible considering the
critical situation and continuous seizure. She continued to
have seizures with multiple medications. She was started on
ketamine also on day 10. Her CSF study was
repeated after 4 days of admission which was also
normal. Initially she was given ceftriaxone and
acyclovir for 5 days. It was discontinued when repeat
CSF also came as normal. She was given dexamethasone 6 mg
once daily for the initial 10 days. She was deteriorating
and could not be weaned from ventilator. So she was
tracheostomised.
Since the patient attender was not willing for auto immune
work up, it was not done. As there was no clinical
improvement regarding patient sensorium and seizure,
we planned to give trial of immunoglobulin. She was given
intravenous immunoglobulin at 0.4 g/kg for 5 days from
day 10 of admission. After 2 days of starting of
immunoglobulin no more seizures were noted. Her anaesthetic
medications were tapered and stopped. She gradually regained
consciousness and on fifth day of immunoglobulin she was
opening eyes and moving all limbs to painful stimuli. She
became fully conscious and began to obey commands
after 5 more days. There was no further seizures. Her
tracheostomy wound was closed later. 15 days after
immunoglobulin infusion she was discharged from hospital.
She was conscious, conversing normally and there was no
focal neurologic deficit. Her antiseizure drugs were
tapered. At the time of discharge she was on carbamazepine
600 mg, Levetiracetam 3000 mg and Clonazepam 2 mg. Also she
was on prednisolone 20 mg daily. She had few episodes of
focal seizures when she missed her medication. Her EEG done
after she recovered showed only ocassional theta slowing of
background. No epileptiform activity was present. MRI brain
showed flair hyperintensities in cortical areas -
right parasagittal and right anterior temporal cortex.
Discussion
Central Nervous System (CNS) manifestations of SARS
CoV 2 are diverse. Other than stroke, the COVID can present
as acute necrotising encephalopathy, encephalitis, Acute
Demyelinating Encephalomyelopathy (ADEM), endothelitis like
involvement, Toxic/ Wernicke like encephalopathy.
Mechanisms of CNS damage can be direct viral injury,
inflammatory mediated injury, thrombotic injury, hypoxia
mediated injury and encephalopathy of critically ill [1,3].
NORSE is a condition defined as the occurrence of refractory
status epilepticus in patients without active epilepsy and
without a clear acute or active structural, toxic or
metabolic cause. The most frequently identified cause of
NORSE is autoimmune encephalitis [2]. Antibodies
against NMDA receptor or voltage gated potassium
channels are the most common antibodies identified in an
adult [4]. Early treatment is recommended for NORSE due to
autoimmune encephalitis as delay can lead to irreversible
neurological sequelae.
In our patient although though we cannot rule out a direct
infectious mechanism of SARS CoV 2, since the CSF parameters
are normal, this is unlikely.There has been a few case
reports of NORSE associated with COVID. Our patient was
deteriorating daily but once initiated with IVIG she showed
dramatic improvement. This case report highlights the
importance of early initiation of IV immunoglobulin in
suspected immune mediated NORSE related to Covid to prevent
irreversible neuronal damage. If infectious, structural and
metabolic causes of NORSE are excluded by appropriate
investigations, patient should be initiated on
immunoglobulin.
Conclusion
The main implication is that physicians should be
aware of the Covid -19 infection presenting as encephalitis
or as refractory epilepsy due to activation of inflammatory
pathways and early initiation of treatment is critical to
avoid neurologic sequelae.
References
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Loddenkemper T, Navarro V, Specchio N, Lagae L, Rossetti AO,
Hocker S, Gofton TE, Abend NS, Gilmore EJ, Hahn C,
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Esteller etal, Increased CSF levels of IL-1β, IL-6, and ACE
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