Identical Horner Syndrome in Homozygotic Twins Caused by Non-Traumatic Internal Carotid Artery Dissection

ABSTRACT

Internal carotid artery dissection is an uncommon entity and the result of a spontaneous or traumatic tear in the vessel lining. We present two almost identical cases of Horner syndrome caused by spontaneous, non-traumatic internal carotid artery dissection within 4 months in two 52-year-old homozygotic twin brothers.

Case 1

A 52-year-old male was urgently referred to the ophthalmic department because of anisocoria and possible ptosis on the side of the smaller pupil. For 6 days, the patient had experienced a smaller than normal right pupil and right-sided pain. Visual analogue scale in his head and neck was 4 (VAS; a purely subjective pain scale, patients rating their degree of pain from 1–10). The pain did not respond to 1 g paracetamol thrice daily for 4 days.

His physical status was excellent, which was explained by regular running, swimming, and bicycling. He had completed several uneventful “iron man” competitions, the latest being 1 month before the onset of symptoms. He attended a chiropractor at regular intervals, but treatments did not include neck manipulations. His risk factors for cardiovascular disease included arterial hypertension treated with daily 300 mg irbesartan and cigarette smoking for 7 years from 15 to 22 years of age. He was born around gestation age 34 with a birth weight around 2,000 g and had not had any noteworthy childhood illnesses.

Examination showed anisocoria, the right pupil (4 mm) being smaller than the left (6 mm). Subsequent examination in our clinic showed isocoria (4.5 mm/4.5 mm) in standard room lighting conditions. In dim light, anisocoria was present (5 mm/6 mm) and 15 min after instilling cocaine 4% eye drops in both eyes, the anisocoria became significant in standard room lighting conditions also (4.5 mm/7 mm; Figure 1, left). We also found a 1 mm right-sided upper eyelid ptosis.

Figure 1.

Images of pupils before (top row) and 15 min after (bottom row) administration of a single eye drop of cocaine 4% in both eyes. Case 1 depictured in the left panels and case 2 in the right panels.

The patient was diagnosed with right-sided Horner syndrome and an acute computerised tomographic (CT) angiogram of the head and neck was performed. This revealed vessel calibre variation as a sign of internal carotid artery dissection (ICAD). Diagnosis was later confirmed by magnetic resonance imaging (MRI) the lesion being located at C2 level (Figure 2, left). All scans were negative for other intracranial pathology.

Figure 2.

T1-weighted fat saturated MRI of the brain in the subacute phase of right-sided Horner syndrome showing right-sided bleeding in the wall of the internal carotid artery consistent with dissection at C2 level in case 1 (left panel) and at C1 level in case 2 (right panel).

Dual-antiplatelet agent treatment was initiated and consisted of daily 75 mg aspirin and 75 mg clopidogrel.

Case 2

Four months earlier, the patient’s homozygotic twin brother was urgently referred to the neurological department of another hospital because of anisocoria and 1 mm upper eyelid ptosis found by a primary sector ophthalmologist. For 4 days, the patient had experienced a smaller than normal right pupil and right-sided pain (VAS 7) around his eye and in his neck, that did not respond to two consecutive doses oral paracetamol 1 g and diclofenac 50 mg.

His physical status was excellent, which was explained by regular running, swimming, and bicycling. He had completed several uneventful marathon competitions, the latest being 5 days before start of symptoms. He had a cough for 14 days before the marathon. He attended a chiropractor (not the same as his brother) at regular intervals, the latest treatment 3 days before symptoms started. This treatment session did not include neck manipulations. His risk factors for cardiovascular disease included arterial hypertension treated with daily 50 mg losartan and cigarette smoking for 7 years from 15 to 22 years of age. He was born around gestation age 34 with a birth weight around 2500 g and had not had any noteworthy childhood illnesses.

No exact pupil measurements are available from the primary ophthalmologist, but subsequent examination in our clinic at a later stage revealed anisocoria, the right pupil (3 mm) being smaller than the left (4.5 mm) in standard room lighting conditions. The anisocoria was more pronounced in dim light (3 mm/5 mm) and 15 min after instilling cocaine 4% eye drops in both eyes, the anisocoria became more significant (3 mm/5.5 mm; Figure 1, right). The ptosis was no longer present.

The patient was diagnosed with right-sided Horner syndrome and an acute CT angiogram of the head and neck was performed. The scan revealed vessel calibre variation as a sign of ICAD. Diagnosis was later confirmed by MRI, the lesion being located at C1 level (Figure 2, right). All scans were negative of other intracranial pathology.

Dual-antiplatelet agent treatment was initiated and consisted of a loading dose with 300 mg aspirin and 150 mg clopidogrel, continuing with daily 75 mg aspirin and 75 mg clopidogrel.

Discussion

ICAD is an uncommon entity and the result of a spontaneous or traumatic tear in the vessel lining wherein the intima separates from the media.^1,2 The incidence of spontaneous ICAD in a North American city setting is 2.14/100,000.³ ICAD presents initially with head, face, and neck pain, and a painful, postganglionic ipsilateral Horner syndrome was initially reported in as many as 36–58% of cases.⁴ Subsequent reports have found a lower incidence (25–29%),^3,5 possibly due to improved detection of ICAD without definite symptoms because of improved access to and widespread use of modern imaging techniques. It is one of the major causes of cerebrovascular accidents in patients younger than 45 years of age, accounting for 10–25% of ischaemic stroke cases.² Spontaneous ICAD can be preceded by minor trauma and influenced by an underlying connective tissue disorder, such as Marfan syndrome, Ehlers-Danlos syndrome, or osteogenesis imperfecta.^6,7 Amongst identified cervical artery dissections (CAD, including both ICAD, common carotid artery, and vertebral artery dissections), these known – but rare – syndromes constitute a minority of cases.⁸ In studies trying to correlate spontaneous CAD to other connective tissue aberrations, results have shown heterogeneity in both genotype⁹ and phenotype¹⁰ from collagen analysis of skin biopsies. Association between CAD and ultrastructural connective tissue abnormalities from skin biopsies was found in 55–57% of cases¹⁰ with identical alterations in the collagen tissue in some first-degree relatives with familial CAD, possibly with inheritance in an autosomal dominant pattern.^9,11

A recent genome-wide association study found one risk locus (at PHACTR1) and three other candidate loci for CAD.¹² Interestingly, the locus at PHACTR1 is, among other disorders, also a known risk factor for fibromuscular dysplasia,¹³ which is present in 3–15% of CAD patients.⁵

Reports have been published both of a familial occurrence of spontaneous CAD and of redissection in patients without known underlying arteriopathies.^14–16 There are also descriptions of a familial predilection for the dissection location (ICAD or vertebral artery dissection) and of the patient’s age when experiencing their (first) dissection.¹⁷ However, none of these studies reported the incidence of Horner syndrome.

Disclosure of interest

The authors report no conflict of interest.

Financial disclosures

None.