Neuromyelitis optica – a cause for longitudinally extensive transverse myelitis: a rare case report from Nepal and literature review

Abstract

Introduction:

Neuromyelitis optica is a rare autoimmune condition, which is manifested by inflammation of optic nerve (optic neuritis) and spinal cord (myelitis). Longitudinally extensive transverse myelitis (LETM) is a neurological disorder leading to contiguous inflammatory spinal cord lesion, seen as T2 hyperintensity that extends over three or more vertebral segments on MRI of spine. Here, the author presents a case report on LETM from Western Nepal.

Case presentation:

The author reports a case of 21-year-female with no known comorbidities who presented to neuro OPD with complaint of progressive bilateral lower limb weakness for 2 weeks, associated with bowel and bladder incontinence for 3 days. There is no significant past or family history.

Discussion:

A detailed history, clinical examination, radiological findings, and interventions like lumbar puncture, MRI is critical to intervene for the cause of LETM. Treatment of patient depends upon underlying etiologies. In this case, patient is managed by IV methylprednisolone. Regular assessment and evaluation help in determining the prognosis of patient.

Conclusion:

Neuromyelitis optica spectrum disorder (NMOSD), being more common in middle-aged group (30–45 years); can occur in younger age group as per our case. Specialized AQP4 detection is often constrained in many parts of Nepal which is a big challenge, especially in resource-limited settings. This case highlights that positive AQP4 testing helps in reaching a definitive diagnosis and timely initiation of high-dose steroids and immunosuppressive therapy that brings out substantial recovery at 2 months – consistent with literature showing that early aggressive therapy prompts to better outcomes.

Introduction

Neuromyelitis optica (NMO) (also known as Devic’s Disease) is an autoimmune disease characterized by the formation of autoantibodies [like aquaporin 4, anti-myelin oligodendrocyte glycoprotein (MOG) antibody] directed against the optic nerve and spinal cord, which clinically presents with features of optic neuritis and myelitis. NMO has clinical features similar to multiple sclerosis (MS) which can be differentiated based on clinical picture, MRI findings, and more specifically by detection of cerebrospinal fluid (CSF) or blood anti-aquaporin 4 antibody.

HIGHLIGHTS

• Neuromyelitis optica, a rare autoimmune condition, manifests with features of myelitis and is extremely rare in young patients.

• Establishing a diagnosis in resource-limited settings is a huge challenge in diagnosis and treatment.

• Initial diagnosis and aggressive treatment prompts to better prognosis and leads to good outcome.

In this case report, we highlight:

1. Resource-limited setting: Access to specialized antibody testing is often constrained in many regions including parts of Nepal. In this case, positive AQP4 testing allowed a definitive diagnosis and prompt initiation of appropriate immunotherapy, demonstrating that targeted testing can change management even in constrained settings.

2. Young age: Neuromyelitis optica spectrum disorder (NMOSD) is more common in adults aged 30–45 years, but this case highlights that severe longitudinally extensive transverse myelitis (LETM) can occur in younger adults.

3. Good short-term recovery: Despite severe presentation, early high-dose steroids and prompt maintenance immunosuppression were associated with substantial recovery at 2 months – consistent with literature showing that early aggressive therapy improves short-term outcomes.

We present the case of a 21-year-old female patient with a diagnosis of NMO based on antibody markers. This case has been reported as per SCARE criteria^[1].This case report has been reported in line with the CARE checklist^[2]. This case report has been reported in line with the TITAN checklist^[3].

Case presentation

A 21-year-old female with no known comorbidities visited the Department of Medicine with a chief complaint of progressive bilateral lower limb weakness for 2 weeks, which initially started with a tingling sensation in bilateral lower leg and later involved weakness of both legs leading to inability in movement of both lower limbs. Paraparesis is associated with bowel and bladder incontinence for 3 days. She also experienced similar symptoms and presented to another center where symptomatic care was given.

On physical evaluation, the patient was ill looking; vitals were stable. On neurological examination, she was conscious, cooperative and well oriented to time, place and person, with a glasgow coma scale of 15/15, and pupils bilaterally round, regular and reactive. The tone of muscle was normal in bilateral upper extremities, while increased in lower extremities; power was 5/5 in bilateral upper limb extremities and 2/5 in bilateral lower limb extremities, while reflexes were intact with Grade 2 + in bilateral upper limbs and hyperreflexia with clonus; Grade 4 + reflex was present in bilateral lower limbs. Plantar reflex was bilaterally down going. Sensory examination was bilaterally intact and equal over all the dermatomes; Cranial nerve examination was normal, and meningeal signs were absent. Per rectal examination showed loss of sphincter control. Fundus examination was normal. All other physical findings were normal.

Initial investigations like complete blood count, erythrocyte sedimentation rate, renal function test, and liver function test were all normal; HIV serostatus, VDRL test, serum antinuclear antibody, ENA panel, APLA panel were all negative. CSF analysis showed scattered lymphocytes only (4-5/HPF); glucose = 99 mg/dL; protein = 34.6 mg/dL; LDH = 42.0 mg/dL; ADA = 7.9; no gram stain reaction/AFB; No growth after 48 hours of CSF culture, and CSF oligoclonal bands were negative.

Contrast enhanced MRI of cervical spine was done as shown in Figure 1. Then brain MRI and screening of dorsal and lumbar spine (Sagittal T2 images) were done as shown in Figure 2 and Figure 3. Based on the suspicion of NMO, NMO panel (anti-aquaporin 4 and MOG Ab) was sent where anti-aquaporin 4 antibody was seen positive. Following diagnosis of NMO, the patient is started on IV 1 g of methylprednisolone once a day for 5 days, followed by oral prednisolone 40 mg per day (1 mg/kg/day) and oral azathioprine 150 mg once a day for 4 months. After the treatment and with continued physiotherapy, her weakness improved progressively, and at 2 months follow-up she started walking by herself and her overall condition improved.

Figure 1.

Contrast enhanced-MRI cervical spine: Sagittal TIW, T2W, FAT SAT; coronal STIR; and axial TIW, T2W, and MERGE images. Post-Gd images reveal a longitudinally extensive T2 hyperintensity extending from the cervicomedullary junction to the lower endplate of D5 vertebral body. It appears hypointense in Ti WI and hyperintense in T2 WI & STIR images. On post-contrast study, there is patchy enhancement predominantly in posterior aspect of spinal cord.

Figure 2.

MRI of the brain: Axial T1, 12, ELAIR: Coronal 12 and sagittal T1-weighted images. Post-Gd images reveal no abnormality in the brain.

Figure 3.

Contrast enhanced-MRI of the spine: Revealed a longitudinally extensive T2 hyperintensity extending from the cervicomedullary junction to the lower endplate of the D5 vertebral body. It appears hypointense in Ti WI and hyperintense in T2 WI & STIR images. On the postcontrast study, there is patchy enhancement predominantly in the posterior aspect of the spinal cord.

Discussion

LETM is characterized clinically by recurrent episodes of paraparesis/tetraparesis, sensory alteration, bowel and/or bladder disturbances^[4]. Radiologically, it is defined as T2 hyperintensity involving three or more vertebral segments. LETM comes up with a vast majority of etiologies. Therapeutic intervention and prognosis of the patient vary as per etiologies. Hence, evaluation of these differentials is critical^[5].

Etiological causes of LETM:

• NMO

• Multiple sclerosis

• Other causes: Postinfectious myelitis (COVID-19^[6], syphilis, neuroborreliosis), systemic lupus erythematosus (SLE)^[7], Sjogren syndrome^[8], traumatic spinal injury, AV malformation, neoplastic disorder, and vitamin and mineral deficiency.

Clinical findings, radiological investigations, and laboratory markers like CSF fluid Analysis, specific markers like aqua4, MOG ab, and oligoclonal bands help in evaluating these differentials.

Neuromyelitis Optica (NMO):

NMO is a rare autoimmune, neurological disease with a female predominance (F:M – 9:1), mean age group being 30–45 years, and prevalence of 0.5–4 per 100 000 population which differs as per racial and geographical variation with the highest mortality among Africans and Asians^[9,10]. Though less common, it can also be seen in the younger age group, as per our case and existing literature^[7].

The pathophysiology involves the binding of the antibody to the aquaporin 4 channel present in the foot processes of astrocytes. The binding of the antibody to these astrocytes results in increased permeability of the blood–brain barrier, perivascular inflammation, ultimately resulting in demyelination of white matter and cavitation formation^[10,11]. Noteworthy, these aquaporin 4 channels are also found at other sites like collecting tubules of the kidney, secretory glands, parietal cells of the stomach, skeletal muscle, and airways. However, due to local complement inhibitory effect, this antibody-mediated inflammatory response is suppressed and thus, systemic manifestations are rare. Recently, MOG protein has been discovered as a target protein in NMO. MOG protein is found on oligodendrocytes, and binding of Ab leads to demyelination; the mechanism is poorly understood^[12]. Unlike MS, the demyelination seen in NMO is a secondary event occurring as a consequence of primary damage to astrocytes.

Diagnosis

Diagnosis of NMO is based on the 2015 Diagnostic criteria for NMSOD^[13] as shown in Table 1, which is confirmed by the presence of two of the three supporting criteria: LETM, MRI findings of the brain not suggestive of MS, and presence of antibodies against aquaporin 4. CSF findings show fluctuating WBC count, often with a lymphocytic profile. AQP4 is commonly expressed in spinal cord, optic nerve, dorsal medulla, brain stem, and thalamus/hypothalamus. Thus, a patient with clinical features of acute myelitis, optic neuritis, area postrema syndrome, brain stem syndrome, and diencephalic clinical syndrome.

Table 1.

Differences between NMOSD and multiple sclerosis

Features	Multiple sclerosis	NMOSD
Peak age	20–40 years	40–60 years
Male: Female ratio	1:2	1:9
Common clinical presentation	Presents with features of optic neuritis, myelitis, progressive cortical neuropathy may be seen.	Presents with core features like acute myelitis, optic neuritis, area postrema syndrome.
		Cerebral feature is less likely.
Pathology	Involves white matter; necrosis/cavitation – rare.	Involves gray matter and white matter; necrosis and cavitation are common.
Disease course	Mild, often progressive type.	Attack is often progressive, reaches nadir within a week. Progression – rare.
Coexisting autoimmune condition	Rare.	Common, associated with Sjogren syndrome, SLE.
Brain MRI	Nonspecific findings: lesions involve the peri-ependymal region, area postrema, fourth ventricle; occasionally pencil-thin ependymal enhancement.	Shows oval-shaped lesions around ventricles (Dawson configuration) and can also be seen in the infratentorial region.
Optic nerve MRI	The imaging shows a longitudinally extensive lesion involving >50% of the posterior segment of the optic nerve tract.	The imaging shows multiple lesions involving the anterior segment of the optic nerve tract.
Spinal cord MRI	Imaging shows multiple lesions of a small segment which involves the peripheral cord, specifically the dorsal and lateral tracts.	A typical pattern of longitudinally extensive transverse myelitis involving three or more vertebral segments is seen. The lesion is centrally located.
Specific marker	CSF analysis reveals oligoclonal bands in 30% of individuals.	AQP4 is positive in the majority of cases; however, MOG-Ab positivity is seen in some cases.
Treatment	Disability is usually seen in a later progressive course. Hence, a short course of steroids is indicated for severe acute relapses.	Attack-related disability is seen. Thus, high-dose steroid is indicated for every attack.

Acute myelitis manifests in the form of paraparesis/tetraparesis, bowel and bladder incontinence^[14], intense itching (due to involvement of spinothalamic tracts), or tonic spasm (leading to painful abnormal posturing of affected limb). In a cross-sectional study of 60 patients diagnosed with NMOD done by Mutch et al (50 female and 10 male), 78% reported bowel and bladder symptoms, and 87% reported either bowel or bladder symptoms, which is parallel to our case report^[15].

LETM is highly specific to NMO, in which MRI spine shows involvement of three or more vertebral segments. Optic neuritis mainly involves the posterior segment of the optic tract and presents as bilateral, painful, severe visual loss (<6/60) with poor recovery^[8]. Area postrema syndrome occurs due to involvement of the rhomboid fossa of the 4th ventricle, leading to intractable hiccups, vomiting. Brainstem syndrome presents in the form of oculomotor dysfunction like diplopia; it can even present with other cranial nerve palsies. NMO, affecting hypothalamic incretin function, occasionally manifests as narcolepsy. Since AQP4 is highly dominant in peri-ependymal region; lesions involving these regions help in diagnosing NMSOD. Symptoms of NMO widely vary, while 50% of patients present with features of myelitis and 35% of them present with features of optic neuritis; in contrast, our case shows features of myelitis in the form of paraparesis and bowel/bladder incontinence without any features of optic neuritis^[7].

Features of NMO resemble those of MS and can be differentiated as shown in Table 2. MRI is an important diagnostic modality in identifying NMSOD. MRI features specific to MS (lesions adjacent to the body of the lateral ventricle and in the inferior temporal lobe, S-shaped, U-fiber lesion, and presence of Dawson finger-like projections) help in distinguishing it from NMSOD. NMO is found to be associated with other autoimmune conditions like SLE, Sjogren syndrome; thus, anti-Ro and anti-La are diagnostic. Certain investigations like Visually Evoked Potential and Computed Tomography are found useful in NMO^[16].

Table 2.

2015 International consensus diagnostic criteria

If AQP4-antibody status	Diagnostic criteria
If AQP4-antibodies are positive, the diagnostic criteria are:	At least 1 core clinical characteristic.
	Positive test for AQP4-IgG using best-available detection method (cell-based assay strongly recommended).
	Exclusion of alternative diagnoses.
However, if AQP4-antibodies are not determined or negative, the diagnostic criteria will be:	At least two fundamental clinical features occurring as a result of one or more clinical attacks and fulfilling all of the following requirements:
	A minimum of 1 core clinical characteristic should be optic neuritis, acute myelitis with LETM, or area postrema syndrome.
	Dissemination across space (two or more distinct clinical characteristics).
	Meeting of additional MRI requirements that may be necessary.
	Negative test for AQP4-IgG using best-available detection method or test unavailable.
	Exclusion of alternative diagnoses.
Core clinical characteristics include:	Optic neuritis.
	Acute myelitis.
	Area postrema syndrome: Episodes of otherwise unexplained hiccups, nausea, or vomiting.
	Acute brainstem syndrome.
	Acute diencephalic clinical syndrome with NMOSD characteristic of diencephalic MRI lesions or symptomatic narcolepsy.
	Symptomatic cerebral syndrome with brain lesions characteristic of NMOSD.
Additional MRI requirements for NMOSD without AQP4-IgG and NMOSD with unknown AQP4-IgG status.	Acute optic neuritis: requires brain MRI showing (a) normal findings or only nonspecific white matter lesions, or (b) optic nerve MRI with a T2-hyperintense lesion of a T1-weighted gadolinium-enhancing lesion extending over >1/2 optic nerve length or involving optic chiasm.
	Acute myelitis: requires an associated intramedullary MRI lesion extending ≥3 contiguous segments (LETM) or ≥3 contiguous segments of focal spinal cord atrophy in patients with a history compatible with acute myelitis.
	Corresponding dorsal medulla/area postrema lesions are necessary for area postrema syndrome.
	Acute brainstem syndrome requires peri-ependymal brainstem lesions.

The diagnosis of NMO can be established either with one of the core clinical features and positive AQP4 antibody detection with exclusion of alternative diagnoses. One can establish the diagnosis based on the presence of one of six core clinical characteristics, dissemination in space, and fulfillment of all MRI features even if the AQP4 antibody is absent^[17]. In individuals with NMSOD, 10% of all show positive for MOG Ab detection. Amongst seronegative NMSOD, this percentage is significantly higher, leading to 31% among Asians and 34.3% among the European population^[18].

MOG-Ab NMOSD, in contrast to AQP4 has a higher predilection for the anterior segment of the optic nerve tract with better visual outcomes and has a monophasic course; though relapses can occur. On the other hand, AQP4-positive NMOSD typically has a relapsing course with more severe attacks and higher risk of permanent disability; thus, long-term immunosuppression is indicated^[18,19].

As per a Cohort study done by Du et al., out of 594 patients, 517 were AQP4-positive, 26 were MOG-Ab-positive, and 51 were double seronegative. Patients with MOG-Ab and double seronegativity had less severe clinical attacks with better outcomes compared to those who were AQP4-positive^[20].

Diagnostic evaluation

Careful history taking and examination is initial for assessment of patient suspectable for LETM; imaging involves MRI which includes sagittal T2-weighted turbo-spin-echo (TSE) and pre-contrast and post-contrast, T1-weighted sequences, as well as axial T2-weighted TSE and post-contrast T1-weighted sequences^[5]. Prognosis interpretation is done based on improvement of clinical symptoms following treatment but can be influenced by multiple confounders (prior/subclinical episodes, socioeconomic factors). However, the patient is on regular follow-up; recent (2 months after discharge) follow-up showed improvement in symptoms of myelitis and eradication of bladder and bowel incontinence.

Definitive diagnosis of NMO requires imaging and a specific antibody marker (NMO panel -aquaporin 4, MOG Ab) which is challenging due to the unavailability of the test and financial constraints. Thus, clinical suspicion of NMO is indicated in a patient presenting with features of myelitis and optic neuritis.

Therapeutic workup: The therapeutic intervention for LETM depends upon the underlying etiology. Diagnosis of NMO or other cause of LETM is a time-consuming process; therefore, for a transient period of time, the patient is given pragmatic treatment.

Treatment for NMO is started with a pulse high dose of intravenous methylprednisolone 1 g per day for 5 consecutive days, followed by oral prednisolone. If the patient shows partial or no response, then a steroid pulse dose can be started from 2 g IV methylprednisolone. Following the induction phase, the patient is switched to oral prednisolone 1 mg/kg/day which can then be tapered gradually to a minimal dose^[21]. Long-term immunosuppressive agents like azathioprine, mitoxantrone, and rituximab is also recommended^[22]. If the patient diagnosed with NMO or NMO spectrum disorder is unresponsive to steroid therapy, plasma exchange and/or immunoadsorption therapy is an alternative option^[23]. Relapses are necessary to be treated aggressively to prevent residual disability^[24]. Therapeutic options for MS include immunomodulatory agents such as interferon-β, glatiramer acetate as well as monoclonal antibodies like natalizumab^[25].

Limitations

Single case, short follow-up (2 months). Socioeconomic and prior health events may confound outcome interpretation; we explicitly acknowledge these limitations and avoid overgeneralizing prognosis.

Conclusion

NMO, being the most common cause for LETM, is an autoimmune condition presenting with features of myelitis and optic neuritis which can occur in young female individuals. Diagnosis is done based on the 2015 international consensus diagnostic criteria. Treatment involves high doses of pulse IV methylprednisolone followed by continuation with oral steroids and immunosuppressive agents. NMO follows with recurrent attacks which can lead to residual disability, thus demanding immediate intervention during each episode of attack. Hence, diagnosis of the cause for LETM is crucial which requires detailed clinical ideas and knowledge, and is a big challenge especially in resource-limited settings. In resource-limited contexts, high clinical vigilance for NMOSD and targeted antibody testing, where available, are critical. This case illustrates successful short-term recovery after standard treatment in a young AQP4-positive patient and underscores the importance of appropriate dosing and follow-up.

Ethical approval

The Institutional Review Board of the Manipal College of Medical Sciences, Nepal does not mandate the ethical approval for writing or publication of case reports/case series consent was obtained. Informed written consent was obtained from the patient before writing this case report.

Consent

Patient consent: Written informed consent was obtained from the patient and patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Sources of funding

No source of funding was received for the study.

Authors contributions

Conceptualization, writing – original draft, writing – review and editing, project administration – U.S., A.T., S.S., and S.P.: Review, editing, and acquisition of data – A.B.: and A.J.:Review and editing – A.M., A.K.Y., and S.R.N.

Conflicts of interest disclosure

Not applicable.

Research registration unique identifying number (UIN)

Name of the registry: None; Unique identifying number or registration ID: None; Hyperlink to your specific registration (must be publicly accessible and will be checked): None.

Guarantor

Ujwal Sah.

Provenance and peer review

Not commissioned.

Name of department and institution where work was done (required)

Department of Medicine, Manipal College of Medical Sciences, Nepal.

Declaration about informed consent (required)

Patient consent: Written informed consent was obtained from the patient publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.