Li-xin Zhou,Jun Ni,Shan Gao,Bin Peng,and Li-ying Cui＊

Department of Neurology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100730,China

TAKAYASU arteritis (TA) is a chronic inflammatory disease of unknown etiology,affecting large vessels,most markedly,the aorta and its branches.1It is rare in Europe and North America,but relatively common in Asia.2TA usually presents first with non-specific symptoms,such as fever,night sweats,malaise and arthralgia.After a time lag of months and sometimes years,symptoms of organ ischemia may develop (e.g.renovascular hypertension,coronary artery disease,and stroke).Approximately 10%-20% of TA patients will have ischemic stroke or transient ischemic attacks.3Recently,some researchers have reported new unusual neurological manifestations of TA,such as epileptic seizures,reversible posterior encephalopathy syndrome (RPES),and spinal cord compression.4-6The present study retrospectively analyzes the clinical neurological manifestations of TA patients.

PATIENTS AND METHODS

Patients selection

Sixty-three consecutive patients with TA were admitted to the Department of Neurology,Rheumatology and Vascular Surgery of Peking Union Medical College Hospital from January 2009 to May 2010.The diagnosis of TA was assessed according to the Criteria for the Classification of TA by American College of Rheumatology.7The presence of 3 and more than 3 of the following 6 criteria is consistent with a diagnosis of TA:onset age≤40 years;claudication of an extremity;decreased brachial artery pulse;difference in systolic blood pressure between arms ≥10 mm Hg;a bruit over the subclavian arteries or the aorta;and arteriographic evidence of narrowing or occlusion of the entire aorta,its primary branches,or large arteries in the proximal upper and lower extremities.

A standardized neurological examination was performed.The following clinical features were recorded:age,sex,age at onset of symptoms,blood pressure,affected vessels,and current therapy.

Examination methods

Computed tomography angiography (CTA) with the aorta arch,subclavian,and carotid arteries was performed in all the patients to get information about stenoses and occlusions.An extracranial carotid arteries Doppler examination was performed in all the patients following a standardized protocol.Transcranial Doppler sonography (TCD) was performed in 17 patients to examine collateral pathways and possible additional intracranial artery pathologies.Cerebral computed tomography (CT) or magnetic resonance imaging (MRI) (T1-weighted,T2-weighted,and proton density-weighted images) was performed in 14 patients.

RESULTS

Demographic data

In the 63 TA patients,27 (42.9%) patients with neurological manifestations were enrolled in the present study.Most included patients were females (24/27,88.9%).The mean age was 27.9±11 years (range,7-53 years).The mean age at onset of neurological symptoms was 25±10 years (range,7-44 years).13 (48.1%) patients had high blood pressure;3 patients had tuberculosis.

Clinical neurological manifestations

The neurological manifestations detected in the patients included headache,dizziness,visual disturbance,epileptic seizures,ischemic stroke,and RPES (Table 1).Dizziness and visual disturbance were the most common symptoms.Six patients had suffered from ischemic stroke.In all the 6 patients,cerebral MRI demonstrated ischemic lesions that were presumably of vascular origin.Six patients suffered from transient ischemic attacks,in which 4 patients suffered from ischemic stroke simultaneously.Two (7.4%)patients were diagnosed of RPES based on the presence of typical clinical manifestations including headache,seizures,and sever hypertension,combined with typical imaging manifestations in cerebral MRI (Fig.1).CTA of 2 patients demonstrated severe stenoses of renal arteries.

Table 1.The clinical neurological manifestations of TA patients

DISCUSSION

TA is an idiopathic,chronic inflammatory vascular disease which may mainly involve the aorta and its major branches.It has a much higher incidence in women than in men and is most frequently found in Asian population.8The clinical symptoms of TA vary widely depending on the site and degree of arterial lesions.Neurological manifestations range from asymptomatic disease to catastrophic neurological impairment.

Neurological manifestations are reported to occur in up to 50% TA patients.9In our study,the prevalence of neurological involvement is 42.9%,similar to the proportion in the previous reports.Neurological manifestations are uncommon in children and in the early stage of the disease,but usually presented in the chronic phase.10These manifestations include headache,dizziness,visual disturbance,epileptic seizures,ischemic stroke,and RPES.Headache and dizziness are the commonest neurological manifestations found in the present study.These symptoms may develop because of either arterial hypertension or cerebral ischemia.11

Figure 1.Magnetic resonance imaging (MRI) findings of RPES in a 17-year-old female patient with Takayasu arteritis.

About 10%-20% of patients with TA have ischemic stroke or transient ischemic attacks due to the decreasing of blood flow in the involved carotid and vertebral arteries.12,13Some studies have found that one fourth of the patients with ischemic stroke presented with microembolus during TCD monitoring,suggesting an embolic mechanism in the pathogenesis of cerebral ischemia in TA.14Unfortunately，TCD monitoring for microembolus was not performed in the present study,thus providing no evidence supporting the microembolus hypothesis.

According to previous reports,seizure is a rare neurological complication of TA.1,4However,seizure was relatively usual in the TA patients in the present study.Seizures may be caused by ischemic stroke,hypertensive encephalopathy,RPES,and unknown reason.Antiepileptic treatment has been reported effective.4In those patients with hypertension who suffered seizures in the present study,decreasing the blood pressure may be another effective method to control the seizures.

In the present study,2 cases of RPES associated with TA were diagnosed.RPES is a rare phenomenon in TA patients,with only few cases being reported recently.5RPES is a new clinico-radiological entity,manifested radiologically by reversible vasogenic edema in the cortical and subcortical white matter of the parieto-occipital lobes.Headache,seizures,and mental changes are the prime clinical manifestations.15,16RPES can be associated with hypertensive encephalopathy,renal failure,blood transfusion,and eclampsia,and may also be caused by drugs such as immunosuppressive drugs,interferon alpha,cytotoxic chemotherapy,and corticosteroids.17Moreover,RPES has been identified in several connective tissue diseases such as systemic lupus erythematosus.18The 2 patients with RPES in the present study developed headache and seizures with a rapid increase of blood pressure caused by renal artery stenosis.Cerebral MRI demonstrated cortical and subcotical reversible vasogenic edema.The reasons why RPES occurs in TA have not been fully understood.In addition to endothelial injury associated with TA,hypertension may play the most important role in triggering RPES in those cases.19,20In the cases in this study,decreasing blood pressure immediately was effective to stop headache and seizures.And white matter lesions almost disappeared on follow-up MRI after several weeks.Therefore,we considered that it is essential to recognize RPES appropriately and promptly,because any delay in diagnosis and treatment may cause irreversible changes in the brain.

In conclusion,neurological manifestations are common symptoms in TA patients in chronic phase.Neurological symptoms are variable,among which dizziness,visual disturbance,and headache are the most common ones.Epileptic seizure is a relatively usual symptom,especially in TA patients with ischemic stroke or hypertension.We suggested including RPES in the differential diagnosis of acute neurological changes in TA.

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