Discussion:
Since March 2020, the World health organization (WHO) declared the
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections
to have reached pandemic proportions. Ever since, COVID-19 infections
have rapidly spread to reach more than 63.9 million reported cases to
date. The virus is well known with its portentous respiratory system
manifestations, but compelling evidence from experimental study and case
reports points towards its potential neurotropism[8][9].
SARS-CoV-2 has demonstrated a wide array of manifestation and its potent
ability to ignite a profound host immune response varying from ARDS seen
in 29% of cases to cytokine storms that warrant
immunotherapy.[10] Multiple neurological
manifestation is well recognized which could be gauged on a spectrum of
severity, from anosmia, headaches to stroke syndrome, encephalitis,
myelitis, and demyelination in close proximity to the
illness.[9]
V. Montalvan in May 2020, published a systematic review highlighting the
possible neuropathogenicity of the virus. It proposed possible invasion
of cerebral circulation endothelium via hematogenous spread of
SARS-CoV-2 from systemic circulation and potential viral propagation
through the cribriform plate and olfactory bulb.[8]
Neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin
oligodendrocyte glycoprotein (anti-MOG) syndromes are two distinct
conditions owing to their proposed pathophysiology and diagnostic
antibodies yet have compelling and over-lapping
features[11]. As both exhibit demyelinating and
inflammatory immune mediated responses on to the central nervous system
with predilection to involve the spinal cord and optic nerve bilaterally
which makes them well differentiated from multiple sclerosis (MS)[1].
It is estimated that NMOSD holds a prevalence of 0.5 to 10 per 100,000,
with well recognized ethnic and geographical discrepancies[12][13]. Like most of auto-immune conditions,
NMOSD is not an exception with incidence 10 times more common in
women.[11] Despite the fact, monophasic NMOSD
seems to affect both genders equally with a median age of onset is 32 to
41 years, yet cases in children and adolescent has been reported[12].
The hallmark of NMOSD is well recognized with its preferential
involvement of optic nerve and the spinal cord as acute transverse
myelitis associated with a longitudinally extensive transverse myelitis
(LETM) lesion on spinal MRI[14][15]16][17]. NMO-IgG discovery in
2004, lead to a spectrum of brainstem and diencephalic signs that are
well recognized to institute a pivotal part of the 2015 diagnostic
criteria [International Panel for NMO Diagnosis
[IPND][14].
Clinical analysis of the largest international cohort to date published[17] of AQP4-seropositive NMOSD, shows myelitis
was the initial manifestation in 48%, optic neuritis in 42%, and
simultaneous optic neuritis and myelitis in 4%[14][17]. Interestingly enough,
NMOSD-associated optic neuritis is extensive; it could manifest as
severe visual loss at onset, and bilateral involvement of the optic
nerves or optic chiasm. It is observed to exhibit a relapsing course
with poor response to IV corticosteroid pulses, poor recovery with
permanent visual deficits, with relatively unspecific lesions or normal
brain MRI. [14]
Anti-MOG syndromes are defined as AQP4-seronegative patients with a
phenotype of NMOSD [12][14][15]. On the
contrary, they have lower female to male ratio, with earlier age of
onset, when compared to sero-positive AQP4-IgG NMOSD as per major
published series. [14]
In 2017, a large cross-sectional study of 132 patients with non-MS
demyelinating disease, estimated that 73% fulfilled the diagnostic
criteria of 2015 International Panel for NMO diagnosis have aquaporin-4
antibodies (AQP4-IgG), around 11% were MOG-IgG seropositive and 16%
remained seronegative [16].
Despite the overlapping features between NMOSD and anti-MOG syndrome,
optic neuritis in the latter exhibits distinctive feature that could
help us distinguish it from optic neuritis in AQP4-IgG NMOSD and MS[14][17]. Bilateral optic neuritis with
radiographic evidence of longitudinally extensive lesions in the
retrobulbar and orbital segments of the optic nerve, with one third of
patients exhibiting perioptic contrast enhancement[14][18]. Chiasmal involvement is very rare in
anti-MOG syndromes as opposed to NMOSD [18].
Myelin oligodendrocyte glycoprotein constitutes 0.05% of total myelin
proteins; its significance was encountered with the introduction of
experimental autoimmune encephalomyelitis (EAE) as an animal model of
demyelination [19]. Recent evidence suggests that
anti-MOG antibodies are produced peripherally, making their way to the
CNS following a breakdown in the blood-brain barrier due to infections.
To support this notion, the absence of restrict oligoclonal bands in CSF
of patients with anti-MOG syndromes patients supports its peripheral
origin [20][21]. Molecular mimicry could
explain the pathophysiology in anti-MOG antibodies production, as 50%
of patient reported history of receding infectious
prodrome[21].
Since the early 1790, an etiologic correlation between prodromal viral
illness and parainfectious or postinfectious demyelinating syndromes is
well recognized, with the description of a 23-year-old woman developed
encephalomyelitis 1 week after a measles rash[22]. Anti MOG syndromes, Guillain–Barré
syndromes and NMOSD in SARS-Cov-2 infection is well reported in a number
of cases, with one for the prevailing mechanism of injury is likely to
involve molecular mimicry; with various viral antigens, trigger an
immune response toward endogenous CNS myelin proteins, including MOG[22][23].
On the other hand, idiopathic intracranial hypertension (IIH)
constitutes of a constellation of signs and symptoms of raised
intracranial pressure with fulfillment of Dandy’s criteria. IIH has an
annual incidence of 19.3 per 100,000 in those who weigh 20% or more
than their ideal body weight, with 90% affecting females[24]. Different pathophysiology varying from
vascular, hormonal, and increased CSF outflow resistance have been
proposed, which could be directly linked to common risk factors[24].
Recent evidence has linked interleukin-6 (IL-6) to disease activity in
NMOSD by mechanism of promoting survival of plasmablasts, stimulation of
AQP4-IgG secretion, altering integrity and functionality of BBB and
increasing differentiation and activation of pro-inflammatory
T-lymphocytes. In patients with NMOSD, IL-6 levels in the serum and CSF
are significantly increased [25]. Interlinking
this to elevated IL-6 levels in SARS-CoV-2 infection may explain the
underlying pathophysiology for occurrence of NMOSD in cases of recent
COVID-19 infection.
Our patient presented with a severe progressive headache after recent
COVID-19 infection, followed by rapid deterioration in her vision, with
severe optic disc edema and normal MRI head. Lumbar puncture (LP) showed
high opening pressure (45cmH2O) and normal CSF analysis, with headache
that improved with therapeutic LP and acetazolamide. MRI orbits was
pursued due to further deterioration of her vision, which showed
bilateral increased T2 signal involving optic nerve entire intra-orbital
segment extending anteriorly to the papilla with post-contrast optic
nerve and perioptic enhancement, thereby raising the suspicion of optic
neuritis due to anti-MOG syndrome or NMOSD in correlation with
SARS-CoV-2. With multiple sessions of IVIG, her visual acuity improved.