Moyamoya syndrome may result from psoriasis: Four case reports

Abstract

BACKGROUND

Moyamoya syndrome (MMS) is a group of diseases that involves more than one underlying disease and is accompanied by moyamoya vascular phenomena. Psoriasis is a chronic immune skin disease closely linked to high blood pressure and heart disease. However, psoriasis-related MMS has not been reported.

CASE SUMMARY

We collected data on patients with stroke due to MMS between January 2017 and December 2019 and identified four cases of psoriasis. Case histories, imaging, and hematological data were collected. The average age of the initial stroke onset was 58.25 ± 11.52 years; three cases of hemorrhagic and one case of ischemic stroke were included. The average duration from psoriasis confirmation to the initial MMS-mediated stroke onset was 17 ± 3.56 years. All MMS-related stenoses involved the bilateral cerebral arteries: Suzuki grade III in one case, grade IV in two cases, and grade V in one case. Abnormally elevated plasma interleukin-6 levels were observed in four patients. Two patients had abnormally elevated immunoglobulin E levels, and two had thrombocytosis. All four patients received medication instead of surgery. With an average follow-up time of 2 years, two causing transient ischemic attacks occurred in two patients, and no hemorrhagic events occurred.

CONCLUSION

Psoriasis may be a potential risk factor for MMS. Patients with psoriasis should be screened for MMS when they present with neurological symptoms.

Key Words: Moyamoya syndrome, Psoriasis, Stroke, Interleukin-6, Immune, Hypertension, Case report

Core Tip: As we all known that moyamoya syndrome (MMS) is a special subtype of intracranial arterial disease. Herein, we analyzed the clinical characteristics and prognosis of MMS-related ischemic and hemorrhagic stroke in patients with psoriasis retrospectively, and also, analyzed the probable mechanisms of psoriasis-related MMS, so as to make a reference for diagnosis and early etiology treatment. Finally we suspect that psoriasis may be a potential risk factor of MMS formation. Whereby, we considered that MMS should be screened in patients with psoriasis when they presented neurological symptoms.

INTRODUCTION

Moyamoya is classified as moyamoya disease (MMD) and moyamoya syndrome (MMS). MMD is characterized by unexplained intracranial arterial stenosis and the development of characteristic moyamoya-like vessels, primarily affecting the precerebral circulation, first reported by Suzuki and Takaku in 1969[1]. It is prone to transient ischemic attack (TIA), acute ischemic stroke and hemorrhagic stroke. Some patients have a younger age of onset and are prone to severe disability[2]. MMS is a secondary intracranial arterial disease with imaging similarities to MMD but different etiologies, such as atherosclerosis, autoimmune disease or rheumatoid arthritis[2]. However, psoriasis related MMS, especially MMS-mediated cerebral hemorrhage in adult psoriasis patients, has not been reported[3]. Psoriasis is a common, chronic, immune skin disease with a global incidence of about 2%-3% per year that usually presents as red spots and scales on the scalp and extremities. Psoriasis can induce many complications, including autoimmune diseases, cardiovascular and cerebrovascular diseases, and diabetes[4]. A previous study showed that psoriasis was an independent risk factor for stroke; The incidence of stroke in patients with mild or severe psoriasis is 1/4115 and 1/530 per year, respectively[5].

The value of reporting patients with psoriasis in combination with stroke due to MMS is to reveal possible synergistic effects between the two diseases and provide vital clues for a more comprehensive understanding of stroke pathogenesis.

CASE PRESENTATION

Chief complaints

Case 1: A 42-year-old male was admitted to the hospital with sudden weakness in the right hand and foot for 5 h.

Case 2: A 71-year-old man was admitted to the hospital with recurring left-sided limb weakness of 1 year's duration with 4 h recurrence.

Case 3: A 47-year-old man was admitted to the hospital with sudden onset of headache, vomiting, and weakness of the left hand for 2 h.

Case 4: A 65-year-old man was admitted to the hospital with sudden numbness of the left hand for 3 h.

History of present illness

Case 1: Sudden right limb weakness with persistent symptoms. No headache, nausea, vomiting, or impaired consciousness was observed.

Case 2: In the last year, episodic weakness appeared on the left side of the limbs, with only a gradual relief of symptoms within 1-2 h. This time, there was a second episode of persistent weakness in the left limbs. No limb twitching, headache, nausea, vomiting, or impaired consciousness were observed.

Case 3: The patient had sudden onset of headache, vomiting, and weakness of the left hand for 2 h, with persistent symptoms. No limb convulsions or impaired consciousness was observed.

Case 4: Although no limb weakness, convulsions, or impaired consciousness, the patient had a sudden onset of numbness in the left hand for 3 h, with persistent symptoms.

History of past illness

Case 1: Had psoriasis for 30 years.

Case 2: Had psoriasis for 52 years and hypertension for 3 years.

Case 3: Had psoriasis for 30 years and hypertension for 2 years.

Case 4: Had psoriasis for 35 years and hypertension for 3 years.

Personal and family history

None of the four patients had a personal or family history of the disease.

Physical examination

Neurological examination: (1) Case 1: Grade 4 muscle strength in the right upper and lower extremities and Grade 5 muscle strength in the left extremity were observed, and the remaining examination was normal; (2) Case 2: Grade 5 muscle strength was observed in all four limbs, and the rest of the examination was normal; (3) Case 3: Examinations revealed Grade 4 muscle strength in the left upper and lower limbs, Grade 5 in the right limbs, and positive meningeal irritation signs; the rest of the examinations were normal; and (4) Case 4: Hypesthesia in the left upper limb and Grade 5 muscle strength were observed in the left and right limbs, with remaining normal examination findings.

Skin examination: All four patients had red lesions on the lower limbs, with their backs covered with white or silvery-white scales.

Cardiopulmonary and abdominal examinations of all three patients showed no abnormalities or positive signs (Table 1).

Table 1 Demographic characteristics.

Items	Gender	Age of developing psoriasis (age)	Age at MMS-related stroke (age)	Duration of hypertension (yr)	Blood pressure at admission (mmHg)	Type of stroke	NIHSS on admission 0-42	Suzuki grade I-VI	mRS on admission 0-5
Case 1	Male	30	42	-	120/70	ICH	2	III	2
Case 2	Male	52	71	3	122/68	TIA	0	V	0
Case 3	Female	30	47	2	140/88↑	ICH	2	IV	2
Case 4	Male	35	65	3	190/100↑	ICH	1	IV	1

MMS: Moyamoya syndrome; NIHSS: National Institute of Health stroke scale; mRS: Modified Rankin scale; ICH: Intracerebral hemorrhage; TIA: Transient ischemic attack.

Laboratory examinations

Interleukin (IL)-6 was elevated in all cases. Patients 1 and 2 had elevated immunoglobulin E levels, and patient 3 had an elevated CD4 count. Patient 1 had elevated total cholesterol and low-density lipoprotein (Table 2).

Table 2 Data of blood tests.

Items	White blood cell (4-10, × 109/L)	Neutrophils (1.8-3.6, × 109/L)	Monocytes (0.1-0.6, × 109/L)	Platelet (100-300, × 109/L)	Interleukin-4 (0-3, pg/mL)	Interleukin-6 (0-5.3, pg/mL)	Immunoglobulin E (0-40, mg/L)	Treg cells (CD4+) (2.86-7.74, %)	Cholesterol (2.8-5.2, mmol/L)	LDL cholesterol (1.6-3.4, mmol/L)
Case 1	9.38	5.57	0.63↑	203	1.09	8.27↑	90.8↑	-	5.76↑	4.15↑
Case 2	7.67	4.95	0.51	244	1.22	7.63↑	68.9↑	-	4.04	3.18
Case 3	6.92	4.32	0.5	358↑	3.43	8.49↑	17.8	11.4↑	4.88	3.36
Case 4	9.4	7.5	0.74↑	338↑	0.35	8.86↑	16.9	-	4.84	2.44

The arrows indicated that the results were over the normal cutoff value.

Imaging examinations

Case 1: Cranial computed tomography (CT) showed a cerebral hemorrhagic lesion in the left basal ganglia. CT angiography (CTA) revealed severe stenosis of the bilateral middle cerebral arteries with puff of moyamoya-vessels.

Case 2: Cranial CT showed no abnormalities. Digital subtraction angiography exhibited occlusion of the right internal carotid artery with moyamoya-vessels.

Case 3: Cerebral hemorrhagic lesions in the right basal ganglia and lateral ventricle are seen on cranial CT. CTA showed severe stenosis of the bilateral ICAs with moyamoya-vessels.

Case 4: Hemorrhagic lesions were observed in the right thalamus, and foci of old softening were observed in the right basal ganglia. CTA showed severe stenosis of the ICAs with moyamoya-vessels bilaterally (Figure 1).

Figure 1 Cerebral arteriography or computed tomography angiography shows arterial stenosis and moyamoya-like vessels. Computed tomography shows cerebral hemorrhage, and limb imaging shows skin psoriasis. Arrows showed the intracerebral hematoma.

FINAL DIAGNOSIS

Case 1

Intracerebral hemorrhage, psoriasis, hypertension, hypercholesterolemia.

Case 2

TIA, psoriasis, hypertension.

Case 3

Intracerebral hemorrhage, psoriasis, hypertension.

Case 4

Intracerebral hemorrhage, psoriasis, hypertension.

TREATMENT

Patients 1, 3, and 4 were treated with medications to manage blood pressure and reduce intracranial pressure following the American Society of Anesthesiologists guidelines, whereas patient 2 received clopidogrel and calcium atorvastatin. No brain surgeries were performed.

After consulting with a dermatologist, glucocorticoids and carbotriol were prescribed for patients with psoriasis.

OUTCOME AND FOLLOW-UP

Case 1

The patient was discharged from the hospital with an National Institute of Health stroke scale (NIHSS) score of 0 and a modified Rankin score (mRS) of 0. During the 2-year follow-up, the patient experienced two TIA events and no further stroke events after the administration of aspirin and atorvastatin. The itchy skin recurred.

Case 2

The patient was discharged from the hospital with an NIHSS score of 0 and an mRS score of 0. After 2 years of follow-up, although the patient did not undergo a stroke or TIA, pruritus episodes recurred.

Case 3

The patient was discharged with an NIHSS score of 1 and mRS score of 1. At 1 years after discharge, the patient experienced a TIA and was administered clopidogrel and atorvastatin. No stroke occurred during the second year of follow-up. The itchy skin recurred.

Case 4

The patient was discharged with an NIHSS score of 1 and mRS of 1. After 2 years of follow-up, the patient experienced no further strokes. The itchy skin recurred.

DISCUSSION

According to our hospital's database, the prevalence of psoriasis in patients in the moyamoya study group was 1.9% (unpublished data), which is much higher than the prevalence of psoriasis in the Chinese population of 0.47%. Therefore, we hypothesized an association between psoriasis and MMS.

Histological inflammatory infiltration and immune response exist in the pathological mechanism of psoriasis and atherosclerosis, and they have certain similarities[6]. Psoriasis causes dermal skin damage, T cell infiltration and promotes systemic immune processes. Studies have found that the degree of histological infiltration of helper T1 and T17 lymphocytes is positively correlated with the degree of psoriasis and atherosclerosis[7].

All four patients had abnormally elevated plasma IL-6 levels in this study. Immunoglobulin E was abnormally elevated in 2 patients, platelet count was increased in 2 patients, and Treg cells were abnormally elevated in 1 patient (Table 2). Therefore, we speculate that the mechanism of psoriasis-mediated MMS may be that psoriasis activates a chronic T-cell-mediated immune-inflammatory process that damages the endothelial cell layer of the cerebral vasculature, leading to arterial inflammatory intervention stenosis and inducing stroke[3]. Patient 3 had a TIA event in the first year after discharge, and his blood CD4 count was above the normal range, possibly indicating the severity of immune dysfunction. Treatment against psoriasis may require using biological agents to organize psoriasis and stroke. Unfortunately, we did not administer specific immunotherapy to these patients to see if treating psoriasis would prevent stroke recurrence.

Kazumata et al[8] has reported a case of MMS-induced psoriasis in an 8-year-old female patient without stroke. There was only one adult male Chinese MMS combined with psoriasis previously reported[9], who presented with typical cerebral ischemia and symptoms of dizziness, tingling, and weakness of the extremities. A meta-analysis reported a 20% increased risk of stroke and myocardial infarction in patients with psoriasis, and a study by Gelfand reported a 44% increased risk of stroke in patients with severe psoriasis[10]. However, neither study provided a detailed classification of stroke subtypes. From our four cases it seems that haemorrhagic stroke was more likely. Abnormally high expression of IgG and S100A4 in the walls of intracranial vessels in patients with MMD suggests that MMD-associated arterial intimal injury releases IgG, which recruits smooth muscle cells through the intima gap, leading to intimal thickening, and that arterial stenosis in MMS has a similar mechanism[11]. It has also been shown that vascular endothelial progenitor cells are involved in MMS-related vascular stenosis. We know that endothelial progenitor cells can induce angiogenesis, monocyte chemotactic protein-1, tumor necrosis factor and vascular endothelial growth factor participate in the activation and proliferation of vascular endothelial progenitor cells, and accelerate angiogenesis. These factors may induce the formation of abnormal vascular networks and lead to stroke[12]. Although three of the four patients had mild hypertension, which may result in stroke, all their hypertension was under control. In this case series, the predominant risk factor of arterial stenosis was psoriasis-related MMS.

To date, this is the first report of cerebral hemorrhage and TIA secondary to psoriasis associated MMS. This study suggests that T cell-mediated immune damage may be involved in the pathogenesis of psoriasis associated MMS. However, the exact molecular mechanism needs to be confirmed with larger clinical samples and basic studies.

CONCLUSION

Therefore, psoriasis may be a potential risk factor for MMS. Thus, patients with psoriasis should be screened for MMS when they present with neurological symptoms.

ACKNOWLEDGEMENTS

We would like to appreciate all patients who participated in this research.