Right Hemianopsia and Right-Limb Hypesthesia Associated With Vascular Ehlers-Danlos Syndrome and Antiphospholipid Syndrome

Dear Editor,

Vascular Ehlers-Danlos syndrome (EDS) is an inherited autosomal disorder that affects the connective tissue due to a mutation in the COL3A1 and leads to various vascular injuries.1 Antiphospsholipid syndrome (APS) is an autoimmune disorder that results in a hypercoagulable state.2 We describe a patient who presented with acute right hemianopsia and right-limb hypesthesia, and was diagnosed with both EDS and APS.

A 26-year-old Asian female presented to the emergency room reporting transient right hemianopsia for 4 hours following a neck massage. She also developed sudden-onset hypesthesia in her right upper and lower extremities. The patient presented with distinct facial features, including prominent eyes, thin lips, pinched nose, hollow cheeks, and lobeless ears. The patient’s skin was easily stretched and bruised (Fig. 1A).

Fig. 1
Clinical and imaging data of the patient. A: The patient’s skin was pale and could be easily stretched by more than 1.5 cm. B: Brain MRI with diffusion restriction sequences revealed acute infarction in the left thalamus (arrow) and occipital lobe. C: Brain magnetic resonance angiography revealed focal moderate stenosis in the left proximal PCA (arrowhead) and fusiform aneurysmal dilatation and stenosis involving both vertebral arteries (arrow). D: High-resolution vessel-wall MRI with the black-blood technique revealed an eccentric stenotic segment with minimal enhancement in the left PCA (arrowhead) and fusiform aneurysmal dilatations (arrow) in distal vertebral segments. MRI, magnetic resonance imaging; PCA, posterior cerebral artery.

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During childhood she had experienced multiple bruises that were slow to heal. During adolescence, the patient experienced multiple episodes of abdominal discomfort, which were ultimately variously diagnosed as spontaneous pneumothorax, bowel perforation, uterine rupture, and complete occlusion of the common hepatic and splenic arteries. Her physical appearance and history of recurrent spontaneous organ rupture with delayed wound healing suggested EDS, a condition that may predispose individuals to vascular rupture or dissection triggered by minor trauma or massage.

The patient’s visual symptoms fully resolved while in the emergency room, with no motor weakness and with normal gait and cerebellar function. However, the patient displayed 50% hypesthesia in pain and temperature in the right arm and leg, while vibration and proprioception remained intact, suggesting a lesion within the spinothalamic pathway. The sudden onset of neurological symptoms suggested a vascular origin, possibly involving the central nervous system supplied by the left posterior cerebral artery (PCA). Given that the patient was young and had experienced recurrent systemic embolic events, potential etiologies such as arterial dissection, cardioembolism, coagulopathy, and genetic disorders were considered.3

Initial brain magnetic resonance imaging (MRI) revealed acute infarction in the left thalamus and occipital lobe (Fig. 1B), focal moderate stenosis in the left proximal PCA, and fusiform aneurysmal dilatation and stenosis involving both vertebral arteries (Fig. 1C). High-resolution vessel-wall MRI with the black-blood technique was used to identify the etiology of the arterial stenosis, and revealed an eccentric stenotic segment with minimal enhancement in the left PCA and fusiform aneurysmal dilatations in both distal vertebral segments, suggesting a dissecting aneurysm (Fig. 1D).

Carotid Doppler ultrasonography, Holter monitoring, and echocardiography were performed, but they did not reveal any significant embolic source. A genetic evaluation identified the c.582+1G>C heterozygous pathogenic variant of COL3A1. Blood tests revealed normal glucose and lipid profiles, with triglyceride at 67 mg/dL and low-density lipoprotein cholesterol at 80 mg/dL. The initial titers showed anticardiolipin antibody IgG at 63.6 U/mL and anti-β₂-glycoprotein I IgG at 20.4 U/mL, raising suspicion of APS. Follow-up titers at 3 months showed elevated anticardiolipin IgG at 64.9 U/mL and anti-β₂-glycoprotein I IgG at 23.5 U/mL, leading to a definitive diagnosis of APS.

Considering the brain imaging and laboratory findings, the infarction in the left occipital lobe and thalamus in this patient may have resulted from either arterial dissection associated with EDS or an embolic event associated with APS.

The concomitant presence of both diseases posed a significant diagnostic and therapeutic challenge in our patient. EDS is a genetic disorder affecting the structural and functional integrity of the extracellular matrix, particularly in fibrillary collagen biosynthesis.1, 4 This condition can lead to intracranial aneurysms, subarachnoid hemorrhage, spontaneous dissection, and cavernous sinus fistula, in turn leading to stroke.1 In EDS there is concern about vascular rupture due to weakened connective tissue, and so antithrombotic therapy is generally avoided.5 In contrast, APS is an autoimmune disorder characterized by abnormal antiphospholipid antibodies that can cause an acquired hypercoagulable state, leading to deep vein thrombosis, ischemic stroke, and myocardial infarction6, 7 requiring anticoagulation based on the current guidelines.8 After careful consideration, we decided to continue aspirin monotherapy, and the patient did not experience another embolic or vascular rupture event during a 1-year follow-up.

EDS and APS may coexist due to shared mechanisms, including immune dysregulation leading to chronic inflammation. There have been observations of high levels of inflammation markers such as transforming growth factor-β and interleukin-8 in individuals with EDS,9 which can lead to tissue fragility and mechanical stress on blood vessels.1, 4 The chronic inflammation in the two conditions can potentially interact to worsen the symptoms. On the other hand, due to the extreme rarity of the conditions coexisting, it cannot be ruled out that APS and EDS may independently exist alongside each other.

Even though cases of these two diseases coexisting are extremely rare, further studies are required to investigate whether a mechanistic link between EDS and APS exists, since there has been another case report describing stroke in a young male with the two diseases.8 We performed vessel-wall MRI, which revealed a narrowed segment of the PCA with eccentric enhancement, as well as multifocal saccular protrusions in the vertebral arteries. Future studies are also needed to determine the optimal therapeutic approach for such cases.