Susac syndrome with a unique involvement of the thoracic spinal cord

Abstract

A woman in her late 20s presented with headaches and subacute encephalopathy. MRIs showed multiple punctate subcortical and periventricular white matter hyperintensities with diffusion restriction, infratentorial lesions, leptomeningeal enhancement of the cervical spinal cord, brainstem and cerebellum and two areas of high-signal abnormality at T4 and T6 raising suspicion for multiple sclerosis or acute disseminated encephalomyelitis.

Further studies and evolution of her symptoms during her hospital stay confirmed the clinical triad of encephalopathy, branch retinal artery occlusions and hearing loss pathognomonic for Susac’s syndrome.

While cervical spinal cord and cauda equina involvement have been reported in Susac’s syndrome previously, no thoracic spinal cord involvement has been reported.

We report the novel MRI finding of thoracic spinal cord involvement in Susac’s syndrome. In order to avoid misdiagnosis, neurologists and neuroradiologists should be aware that any part of the spinal cord can be involved in Susac’s syndrome.

Background

Patients with Susac’s syndrome (SuS) frequently present with migraine like headaches before encephalopathy. They can be underdiagnosed or initially misdiagnosed with migraines, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM) or another neuroinflammatory entity; especially in the presence of brain or spinal cord lesions on MRI.

The extent of nervous system involvement in SuS continues to evolve over the years. It was first described in 1979 by John Susac as a microangiopathy of the brain, retina and inner ears. Leptomeningeal involvement was later reported and only 2 cases of cervical cord and cauda equina involvement were reported in 2014. We report a case of thoracic cord involvement for the first time in SuS.

Case presentation

A woman in her late 20s presented to the emergency room on two consecutive days with posterior throbbing headaches more intense than her previous migraines and not responding to over-the-counter medications. Headaches were associated with nausea and dizziness described as imbalance with standing or walking. CT brain, CTA head and neck and blood work were unremarkable. Lumbar puncture was only significant for elevated protein=85 mg/dL. She was admitted to the hospital for worsening headaches, neck pain, unsteady gait and subacute encephalopathy. On examination, she appeared confused and was disoriented to time and place. She struggled to find words and had an ataxic gait. She had no psychiatric or personality changes, livedo reticularis, weakness, sensory or urinary symptoms. MRI brain showed punctate diffusion abnormalities in the deep white matter of the frontal and parietal lobes with involvement of the corpus callosum and brainstem (figure 1A–D).

Figure 1.

(A) Brain MRI sagittal T2 FLAIR showing an ‘icicle’ lesion in the superior genu of the corpus callosum (solid red arrow), a central corpus callosum ‘Snowball’ lesion at the posterior midbody (Dashed red arrow). T2 hyperintensities are seen at the splenium (light blue arrow), tectum (orange arrow) and within the vermis, just posterior to the fourth ventricle (dark blue arrow). (B) Axial diffusion-weighted imaging (DWI) sequence showing three splenial corpus callosum lesions with restricted diffusion (dashed light blue arrows). (C) Axial DWI demonstrating multiple punctate areas of restricted diffusion in the subcortical areas (pink arrows) and posterior periventricular area (Dashed green arrow). (D) Axial DWI demonstrating multiple punctate areas of restricted diffusion.

She was treated empirically for presumed autoimmune encephalopathy with 5 days of intravenous methylprednisolone with improvement of confusion and headaches. Then, 6 days after the last dose of intravenous methylprednisolone, she began reporting additional symptoms including right ear fullness, tinnitus, and hearing loss, a black spot in the left eye, burning or freezing like discomfort in both feet, constipation and urinary urgency with urge incontinence all presenting over a 5-day period. Intravenous immunoglobulins was initiated. Repeat MRIs showed leptomeningeal enhancement of the cervical spinal cord, brainstem, cerebellum and increased T2 signal within the right aspect of the thoracic cord at T4 and T6 (figure 2A–D). Repeat lumbar puncture showed an increase in protein from 85 mg/dL to 254 mg/dL and white blood cells from 3 to 12 with 74% lymphocytes (table 1). She was found to have profound hearing loss in the right ear and moderately severe hearing loss in the left ear on audiometry (figure 3) and bilateral branch retinal artery occlusions (figure 4A–D). The diagnosis of SuS was confirmed based on these findings.

Figure 2.

MRI of the cervical and thoracic spine: (A) sagittal T1 postcontrast of the cervical spine showing areas of leptomeningeal enhancement at the anterior pons/medulla and posterior vermis (green arrows). (B) Axial T2 of the thoracic spine at the level of T4 showing area of T2 intensity at the anterior right spinal cord (red arrows). (C) Sagittal T2 stir thoracic spine showing corresponding arrows for the T2 hyperintensities seen at T4 (red arrow) and T6 (yellow arrow). (D) Axial T2 of the thoracic spine at the level of T4 showing area of T2 intensity at the anterior right spinal cord (red arrows).

Table 1.

Imaging, CSF analysis and blood work

A. Imaging	At presentation	1 month later
MRI head w/wo Contrast	Innumerable non enhancing punctate FLAIR/T2 hyperintense lesions in the supratentorial and infratentorial brain in the periventricular margins, deep white matter, juxtacortical frontal and right parietal lobes, periaqueductal grey matter, right quadrigeminal plate and three splenium of corpus callosum lesions with mild restricted diffusion.	Several new punctate T2/FLAIR hyperintense foci in the periventricular and juxtacortical white matter and a small new diffusion restricting lesion in the juxtacortical right medial frontal lobe white matter.
MRI cervical spine with and without contrast	Leptomeningeal enhancement of the cervical spinal cord, brainstem and cerebellum
MRI thoracic spine with and without contrast	two non enhancing areas of increased T2 signal within the right aspect of the spinal cord at the level of T6 and T4.
B. Cerebrospinal fluid (CSF) analysis	At presentation	2 weeks Later
CSF clarity	Clear	Clear
CSF colour	Colourless	Colourless
CSF Xanthochromia	Absent	Absent
CSF WBC count	4	12 (H)
CSF RBC count	3	32
CSF neutrophils	<1%	3%
CSF lymphs	86% (H)	74%
CSF monocytes/ macrophages	14% (L)	21%
CSF eosinophils	<1%	2%
CSF total cells	100	100
Glucose CSF	61	56
Protein CSF	85 (H)	254 (H)
Inflammatory markers		three bands matched in CSF and serum, normal IgG index
Other CSF Studies	Negative meningitis/encephalitis panel, JC virus DNA PCR, autoimmune encephalopathy panel, paraneoplastic encephalopathy panel
C. Blood Work	Negative myelin oligodendrocyte glycoprotein and aquaporin four antibodies, ANA, HIV, RPR, autoimmune encephalopathy and paraneoplastic panel, normal B12, ACE, ESR, CRP.

CRP, C reactive protein; CSF, cerebrospinal fluid; ESR, erythrocyte sedimentation rate; RBC, red blood cells; WBC, white blood cells.

Figure 3.

Audiogram showing a moderately severe sensorineural hearing loss in the right ear and a moderate to severe down sloping left sided sensorineural hearing loss. Speech discrimination 0% for the right ear and 80% for the left ear.

Figure 4.

Colourfundus photographs of the right (A) and left (B) eyes showing patchy areas of retinal whitening due to ischaemia (arrows). Fluorescein angiography of the right (C) and left (D) eyes demonstrating branch retinal artery occlusions (dashed arrows).

Differential diagnosis

Migraines were ruled out due to the presence of restricted diffusion on MRI, encephalopathy, and increased protein in CSF. An inflammatory central nervous system disease was considered. Although ADEM was considered initially due to encephalopathy, the punctate lesions on MRI were not the typical large fluffy lesions seen with ADEM. MS was thought to be less likely due to the markedly elevated protein in CSF, headache and encephalopathy on presentation, the presence of punctate not the typical MS ovoid lesions and the central not typical of MS peripheral corpus callosum lesions. Testing for MOG demyelinating disease, neuromyelitis optica spectrum disorder was negative. The presence of bilateral BRAO and bilateral hearing loss was not consistent with ADEM, MS, and NMOSD. Of note, our patient presented at a time when there was a national shortage of COVID-19 testing equipment and the very first case of COVID-19 was reported in a different city that same month. The absence of fever, respiratory symptoms, community outbreak or sick contacts makes COVID-19 19 infection less likely as an aetiology. Our patient was determined to be clinically low risk for COVID-19 according to our infection control protocol on admission.

Treatment

She underwent physical therapy and received rituximab 1000 mg 2 weeks apart. She remained on prolonged oral steroid taper for 9 months and is currently on azathioprine and intravenous immunoglobulins initially every 3 weeks then gradually spaced out to 8 weeks in the hopes of discontinuing it by the end of the year.

Outcome and follow-up

The patient is doing well a year after diagnosis with resolution of headaches, dizziness, and gait instability. She underwent a cochlear implant for the hearing loss on the right side and uses a hearing aid on the left.

Discussion

SuS is an autoimmune endotheliopathy that affects mostly young women between the ages of 21 and 41 with a female predominance of 3–1.¹ The precapillary arterioles of the brain, leptomeninges, retinal artery, cochlea and semicircular canals are affected.²

Although SuS is classically characterised by the clinical triad of encephalopathy, branch retinal artery occlusions and hearing loss, only 13% present with the clinical triad at the onset of symptoms.³ The clinical triad may become complete after a delay of months to more than 2 years.⁴ This delay can lead to misdiagnosis, in particular an erroneous diagnosis of MS, the treatment of which has been linked to exacerbations in SuS.^{4 5}

Headache maybe the major presenting symptom for SuS, characterised as severe or even migrainous in nature. Another crucial symptom is encephalopathy which may present as confusion, memory impairment, cognitive changes and psychiatric disturbances.¹ Later, other manifestations develop including impaired cognition, memory loss, vertigo, dysarthria, ataxia, hemiparesis and sensory disturbance. These symptoms also occur commonly in MS.^{4 6}

In SuS, the supratentorial and infratentorial white matter can be affected. The typical lesions are small, multifocal and enhancing in 70% of cases during the acute stage.¹ T2/FLAIR shows tiny punctate periventricular and deep white matter hyperintensities in over 90% of cases. The lesions are usually distinguishable from the demyelinating lesions of MS, which are commonly larger and have an ovoid appearance.⁶ Imaging of the corpus callosum can yield particularly important diagnostic clues. In SuS, MRI always show corpus callosum involvement.^{7 8} Lesions typically involve the central fibres of the corpus callosum but typically spare the undersurface unlike MS and ADEM, which preferentially involve the periphery of the corpus callosum.^6–8 Central callosal holes and atrophy develop as the active lesions resolve and white matter lesions disappear.¹ Marrodan et al described several patterns of lesions in SuS including ‘snowball lesions’ which are central corpus callosum ischaemic infarcts. On diffusion-weighted imaging, ‘Spokes’, ‘icicles’, periventricular lesions and internal capsule ‘string of beads’ patterns were described.⁹ Seventy per cent show deep grey matter lesions within the basal ganglia and thalamus and 33% show leptomeningeal enhancement.¹ Leptomeningeal enhancement is an uncommon finding in MS and ADEM but can be seen in up to 30% of patients with SuS. Involvement of deep grey matter including basal ganglia is a common finding in SuS but unusual in MS.^{3 7} There is no clinical correlation between the number of lesions seen on MRI brain and the severity of encephalopathy.¹ Susac recommended that patients with ‘unexplained encephalopathy’ and abnormal lesions affecting the white matter, grey matter and leptomeninges should undergo a dilated funduscopic examination by a neuro-ophthalmologist or retina specialist to detect difficult to discover branch retinal artery occlusions. Ophthalmologic examinations should be repeated, as branch retinal artery occlusions may present later in the disease course.¹ Fluorescein angiography is the preferred test because it shows typical changes in SuS that are not always appreciated on direct funduscopic examination. Furthermore, even for patient without auditory or visual disturbances, tonal audiometry and fluorescein angiography are tools needed to help confirm the diagnosis.⁹

Cord involvement is rare in SuS. In 2014, two separate case reports were published reporting on two patients with SuS involving the spinal cord. Those case reports have been the only published reports of SuS with spinal cord involvement. One case reported involvement of the cervical cord with two focal areas of high signal abnormality at C2 and C3. The other case reported involvement of the cauda equina with diffuse lumbosacral nerve root enhancement seen on MRI.^{10 11} Our case establishes that SuS can involve the thoracic spinal cord and thus any part of the CNS.

With thoracic cord lesions being reported for the first time, it becomes evident that SuS can affect any level of the spinal cord like MS or other MS mimickers. We recommend that neurologists and radiologists pay special attention to the location of corpus callosum lesions in patients with spinal cord lesions and white matter hyperintensities presenting with symptoms not classic for MS such as migraines or encephalopathy. The location of lesions in the centre of the corpus callosum are key to early diagnosis on initial presentation. Other MRI features and the CSF examination can distinguish SuS from MS and ADEM as well. While splenium lesions, retinal artery occlusions and sensorineural hearing loss have been reported in COVID-19, the presence of these findings in our patient combined with central corpus callosum involvement and encephalopathy strongly support the diagnosis of Susac’s syndrome.^12–14 The absence of fever, respiratory symptoms, community outbreak or sick contacts makes COVID-19 19 infection less likely as an aetiology.

It is important that clinicians realise that spinal cord lesions can occur at any level in SuS. The diagnosis and treatment of SuS requires close cooperation between neurologists, radiologists, ophthalmologists and otorhinologists for early diagnosis, treatment and improved patient outcomes.

Learning points.

• Any part of the spinal cord including the cervical, thoracic cord and cauda equina can be affected in Susac Syndrome like multiple sclerosis (MS), acute disseminated encephalomyelitis and other MS mimickers but the appropriate clinical context, additional imaging features and central corpus callosum involvement are crucial to make a diagnosis.

• Susac syndrome should be strongly suspected when a patient with encephalopathy presents with lesions involving the central fibres of the corpus callosum and sparing the periphery.

• Branch retinal artery occlusions can be hard to find and may not be appreciated at presentation in Susac syndrome. Therefore, ophthalmological examinations and fluorescein angiography should be performed and repeated in patients presenting with encephalopathy and involvement of the brain, inner ear, leptomeninges and any part of the spinal cord.

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Consent obtained directly from patient(s).