Reversible cerebral vasoconstriction syndromes and primary angiitis of the central nervous system: clinical,imaging, and angiographic comparison

Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. However, prompt and accurate diagnosis remains challenging. Here we compared the features of 159 RCVS to 47 PACNS patients and developed criteria for prompt bedside diagnosis. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS‐spectrum disorders. In patients without TCH and positive angiography, neuroimaging can discriminate RCVS (no lesion) from PACNS (deep/brainstem infarcts). Ann Neurol 2016;79:882–894     

Reversible cerebral vasoconstriction syndrome or primary angiitis of the central nervous system?

BACKGROUND: Reversible Cerebral Vasoconstriction Syndrome (RCVS) may present as thunderclap headache (TCH), accompanied by reversible cerebral vasospasm and focal neurological deficits, often without a clear precipitant. RCVS may be mistaken for Primary Angiitis of the Central Nervous System (PACNS) due to the presence of similar angiographic features of segmental narrowing of cerebral arteries. We discuss the clinical features of a young female migraine patient who developed TCH and was found to have RCVS following initial treatment with corticosteroids for PACNS, in the context of a systematic review of the available medical literature. METHODS: A Medline search was performed to identify all case reports since 1966 describing RCVS and PACNS that provide sufficient clinical detail to permit diagnostic classification according to published criteria. RCVS included case studies in which there was angiographic or transcranial Doppler ultrasound evidence of near-to-complete resolution of cerebral vasoconstriction in the absence of a well-recognized secondary cause. PACNS included reports of histologically confirmed PACNS either through biopsy or necropsy. RESULTS: Reversible Cerebral Vasoconstriction Syndrome occurs primarily in females and is characterized by sudden, severe headache at onset, normal CSF analysis, vasoconstriction involving the Circle of Willis and its immediate branches, and angiographic or TCD ultrasound evidence of near-to-complete vasospastic resolution within 1-4 weeks. It occurs typically in the context of vasoconstrictive drug use, the peripartum period, bathing, and physical exertion. CONCLUSION: Initial and follow-up (within 4 weeks) non-invasive angiographic studies are indicated in patients who present with TCH or who have clinical presentations that could be consistent with RCVS or PACNS in the absence of a well-recognized secondary cause, such as subarachnoid haemorrhage. Early reversibility of cerebral vasospasm is the key neuroradiological feature that supports the clinical diagnosis of RCVS.     

CADASIL mimicking primary angiitis of the central nervous system

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and primary angiitis of the central nervous system (PACNS) share several clinical and radiological features. However, digital subtraction angiogram (DSA) is generally reported as normal in CADASIL, whereas lumen irregularities in distal cerebral arteries indicate PACNS. OBJECTIVE: To describe a potential pitfall of DSA interpretation, which led to the tentative diagnosis of PACNS in a CADASIL patient. PATIENT AND METHODS: Single case observation. RESULTS: A 47-year-old man sustained recurrent subcortical infarcts. He had mild hypercholesterolemia and migraine. His family history was unremarkable. The underlying cause of stroke could not be elucidated. Transcranial Doppler sonography revealed decreased intracranial blood flow velocities compatible with CADASIL. Lumen irregularities of several peripheral intracranial arteries were seen on DSA, which suggested PACNS. CADASIL was confirmed by results from skin biopsy and genetic testing. CONCLUSIONS: First, in patients with CADASIL, DSA can show segmental lumen irregularities in distal cerebral arteries suggestive of PACNS. Second, the potential role of transcranial Doppler sonography to distinguish CADASIL from PACNS deserves further testing.     

Follow-up examinations by transcranial Doppler ultrasound in primary angiitis of the central nervous system

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare disease. The definite diagnosis is made upon proof of mononuclear inflammation of the vessel wall on brain biopsy. The diagnosis can also be established on clinical grounds, typical findings on intra-arterial angiography and other investigatory grounds excluding other diseases. Therapy comprises an aggressive immunosuppressive approach. Close monitoring of the patients is mandatory. Transcranial Doppler ultrasound (TCD) has not yet been used to follow up the vasculitic lesions in PACNS. CASE: We report on a 32-year-old female with massive cerebral infarctions secondary to multiple large-vessel stenoses because of probable PACNS. The patient was followed closely by means of TCD. During therapy the cerebral blood flow velocities normalized as displayed by TCD. Clinical improvement followed several days after normalization of cerebral blood flow. CONCLUSIONS: TCD is a valuable noninvasive bedside tool to monitor cerebral blood flow velocities and therapy response in patients with cerebral vasculitis, if large arteries are involved.     

Primary angiitis of the central nervous system: report of eight cases from a single Italian center

The primary angiitis of the central nervous system (PACNS) is a rare and potentially fatal form of vasculitis with unknown etiology. Headache and encephalopathy are the most frequent symptoms. Neuroimaging plays an important role in the diagnosis, but the pattern of abnormal findings is not specific. In some cases brain biopsy is mandatory. PACNS is often described as a diagnostic and therapeutic challenge for clinicians considering the lack of univocal diagnostic criteria and paucity of studies evaluating the long-term outcome. This brief work reports how we managed eight patients with PACNS from diagnosis to long-term follow up treatment. Headache and focal acute neurological deficits were the most common symptoms. Magnetic resonance imaging (MRI) was abnormal in all patients with different patterns of infarctions or intraparenchymal/subarachnoid hemorrhages or their combination. Cerebral angiography demonstrated pathological findings compatible with vasculitis in all cases. Other causes of encephalopathy were ruled out. Patients with severe clinical and neuroradiological findings were treated with steroids and immunosuppressive therapy using cyclophosphamide/methotrexate. Patients with less aggressive PACNS, were treated with steroids only. In one case with multiple relapses infliximab was used after first-line immunosuppressive therapy failure. PACNS suspicion is based on the combination of demographic/clinical and MRI findings and the exclusion of other causes of multifocal encephalopathy. A positive angiography has a diagnostic value in an adequate clinical field. A strict collaboration of neurologists, neuroradiologists, and immunoreumatologists is essential in the management of PACNS both in the diagnostic and therapeutic phases.     

缘于可逆性脑血管收缩综合征的头痛研究进展

可逆性脑血管收缩综合征（reversible cerebral vasoconstriction syndrome，RCVS）是一种脑血 管疾病，霹雳性头痛是其最主要的临床表现。缘于RCVS的头痛发病机制尚未明确。本文介绍了缘于 RCVS的头痛可能与血管张力失调和内皮功能障碍有关，同时从临床表现和鉴别诊断方面进行疾病的 早期识别，从而早期干预以利于疾病的预后转归。     

A pediatric case of reversible cerebral vasoconstriction syndrome with cortical subarachnoid hemorrhage

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare disorder characterized by acute onset, severe headache, with reversible vasoconstriction of cerebral arteries often accompanied by additional neurological symptoms. This syndrome is seen mainly in middle-aged adults, predominantly women. Herein, we report on a pediatric case of RCVS with cortical subarachnoid hemorrhage (SAH). A 12-year-old boy developed acute, severe headache with paralysis of lower extremities causing gait disturbance after administration of eletriptan. Brain magnetic resonance angiography (MRA) revealed multifocal narrowing of the cerebral arteries, whereas magnetic resonance imaging (MRI) demonstrated sulcal hyperintensity on fluid-attenuated inversion recovery, consistent with cortical SAH. The patient's clinical symptoms resolved spontaneously after a few days and the MRI and MRA findings disappeared 3months later, suggesting a diagnosis of RCVS. Eletriptan might cause vasoconstriction of cerebral arteries. Although most patients with RCVS are adults and pediatric cases are rare, RCVS should be considered in a child complaining of severe headache.     

原发性中枢神经系统血管炎的临床特点

目的探讨原发性中枢神经系统血管炎(PACNS)的临床特点。方法对27例PACNS患者的临床资料进行分析。结果PACNS好发于中青年,呈急性或亚急性起病,临床表现以头痛、大脑皮质功能减退、局灶性神经功能缺损及癫疒间样发作为主;头颅MRI示病灶处呈长T1、长T2改变,多有强化;脑组织病理检查示软脑膜血管炎性改变。经糖皮质激素以及抗血小板聚集、清除自由基、降低颅内压、改善微循环等综合治疗,病情明显改善。结论PACNS临床表现多样,综合临床表现、影像学及脑组织活检可作出诊断;应用糖皮质激素治疗可显著提高疗效。     

原发性中枢神经系统血管炎的多学科诊治意义探讨（附1例报道并文献复习）

目的 探讨原发性中枢神经系统血管炎（PACNS）的病因、临床特点、诊断、治疗方法以及多学科协作在其诊治过程中的相关意义。方法 回顾性分析1例PACNS的多学科联合诊治过程,并复习相关文献,总结治疗经验。结果 最开始,结合临床表现、影像学表现及活检结果,考虑炎性脱髓鞘病,甲强龙冲击治疗无效;请神经内科、影像科、病理科会诊,再次活检结果仍为炎性病变,结合炎性脱髓鞘治疗过程,基本排除炎性脱髓鞘。经北京宣武医院病理科诊断为PACNS,再次请神经内科会诊,进行系统免疫治疗（甲强龙+免疫抑制剂他克莫司）,3个月后复查头部MRI增强示病变明显缩小,病人神志清楚,失语症状较前改善,左侧中枢性面瘫较前好转,左侧肢体肌力较前恢复。结论 PACNS是一种罕见病,其临床表现、影像学表现无特异性,目前病理活检是其主要诊断手段,治疗过程中,多学科协作,可明显提高诊治效率,大幅提高诊治水平。     

Isolated thunderclap headache during sex: Orgasmic headache or reversible cerebral vasoconstriction syndrome?

Orgasmic headache (OH) is an “explosive” headache that occurs at orgasm. Historically, it was considered benign with no treatment needed. Reversible cerebral vasoconstriction syndrome (RCVS) refers to a group of disorders characterized by recurrent thunderclap headache (TCH) and multifocal vasoconstriction. Patients who have RCVS often recover completely, but some may have persistent neurological deficits. We report a 34-year-old woman who presented with isolated and recurrent TCH at orgasm, which fulfilled the diagnosis of OH. However, she was post-partum and had recent exposure to ecstasy, making her symptoms highly suggestive of RCVS. Brain magnetic resonance angiography showed segmental vasoconstriction. We concluded that she could be considered to have either OH or RCVS. This patient suggests the theory that OH could be a presentation of RCVS. Given that RCVS is potentially treatable, early recognition by clinicians is vital in order to prevent devastating complications.     

Die primäre Angiitis des ZNS (PACNS)

Primary angiitis of the CNS (PACNS) is a rare inflammatory disease affecting middle-aged patients. The angiitis is focal and segmental in distribution, involving small and medium-sized leptomeningeal and intracranial vessels. The most frequent presenting symptoms are headaches, focal neurologic deficits, and confusion. In addition, aphasia, neuropsychological deficits, and seizures may occur. The paper presents a review of the literature. In addition, a typical case of PACNS is presented. This case demonstrates that diagnosis of PACNS is difficult and brain biopsy is essential to confirm it.     

Reversible Cerebral Vasoconstriction Syndrome: A Review of Recent Research

Reversible cerebral vasoconstriction syndrome (RCVS) is a collective term used for transient noninflammatory, nonatherosclerotic segmental constriction of cerebral arteries. The angiopathies of RCVS have previously been defined by several nomenclatures. Current opinion favors the unification of these pathophysiologically related angiopathies because of their similar angiographic features and clinical course. RCVS typically presents acutely as headache, delirium, seizure, cerebral ischemia, and/or hemorrhage. The angiographic features make RCVS an important mimic of CNS vasculitides. In contrast to CNS vasculitis, RCVS is typically a transient condition with relatively good clinical outcomes. Although a complete understanding of the etiological and pathological features of RCVS has not yet been achieved, alterations in vascular tone lead to the observed arterial changes. In this review, we aim to provide a summary of RCVS and provide insight into current perspectives of the underlying pathophysiological processes, diagnosis, and treatment.     

Role of High-Resolution Magnetic Resonance Imaging in the Diagnosis of Primary Angiitis of the Central Nervous System

Background

Primary angiitis of the central nervous system (PACNS) is a rare disorder and is often difficult to diagnose due to the lack of a confirmatory test. PACNS can generally be diagnosed based on typical angiographic findings. We describe herein a patient diagnosed with PACNS despite the presence of normal findings on conventional angiography.

Case Report

A 44-year-old man with a recent history of ischemic stroke in the right posterior cerebral artery territory developed acute-onset vertigo. Diffusion-weighted imaging revealed an acute infarction within the left posterior inferior cerebellar artery. His medical history was unremarkable except for hyperlipidemia; the initial examination revealed mild gait imbalance. During the 10 days of hospital admission, the patient experienced four recurrent ischemic strokes within the posterior circulation territory (occipital lobe, pons, and cerebellum). He was diagnosed with recurrent cerebral infarctions due to PACNS. The basilar artery exhibited no demonstrable luminal stenosis, but there were direct imaging signs of central nervous system angiitis including wall thickening and contrast enhancement. High-dose intravenous steroid therapy followed by oral prednisolone was administered. There was no further stroke recurrence and follow-up imaging of the arterial walls showed normalization of their characteristics.

Conclusions

The present case emphasizes the importance of wall imaging in the diagnosis and treatment of PACNS.     

Thunderclap headache and benign angiopathy of the central nervous system: a common pathogenetic basis

Thunderclap headache (TCH) is a head pain that begins suddenly and is severe at onset; TCH might be the first sign of different neurological illnesses, and primary TCH is diagnosed when no underlying cause is discovered. Patients with TCH who have evidence of reversible, segmental, cerebral vasoconstriction of circle of Willis arteries and normal or near-normal results on cerebrospinal fluid assessment are thought to have reversible cerebral vasoconstriction syndrome (RCVS). Herein, we discuss the differential diagnosis of TCH and offer pathophysiological considerations for TCH and RCVS.

     

External carotid artery branches involvement in reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by segmental vasoconstriction and dilatation of intracranial arteries, usually revealed by headaches, which spontaneously resolve in few weeks. We report a patient with RCVS, revealed by thunderclap headaches, involving both internal and external carotid artery (ECA). She received fluoxetin for depression and took a great amount of cannabis in the last months. While angio-MR, transcranial Doppler and CSF analysis were normal, cerebral angiography disclosed stenoses and dilatations of the middle cerebral artery. It also showed an involvement of maxillary arteries. Fluoxetin and cannabis were stopped. After few days, she had no more headaches. At 8th week, angiography was normalized confirming the RCVS. ECA angiogram may help reaching a diagnosis in patients with suspected RCVS when intracerebral abnormalities are minor or absent.     

Brain biopsy in primary angiitis of the central nervous system.

To determine the yield of brain biopsy and the predictive value of clinical features and ancillary studies, we retrospectively analyzed hospital chart data from 61 consecutive patients suspected of having primary angiitis of the CNS (PACNS). Biopsies disclosed PACNS in 22 (36%), alternative diagnoses in 24 (39%), and no diagnosis in 15 (25%). Clinical indicators and angiography were not useful predictors of PACNS. Brain biopsy should be the primary diagnostic tool in this setting because of the poor reliability of other indicators and because of the high yield of alternative diagnoses requiring different management.     

Primary angiitis of the central nervous system: report of eight cases from Southern China

Background and purpose:  This study is to report the clinical, neuroimaging and pathological characteristics of patients with primary angiitis of the central nervous system (PACNS) from Southern China.
Methods:  Eight patients with PACNS admitted between August 1995 and April 2006 were retrospectively studied. Records of clinical features, neuroimaging, brain biopsy and therapy were analyzed.
Results:  Primary angiitis of the central nervous system occurred predominantly in youth and middle-aged adults. Headache, hemiplegia and speech disturbance were the most predominant manifestations. The cerebrospinal fluid (CSF) was slightly abnormal in only one case, MRI was abnormal in seven, magnetic resonance angiography in seven, diffusion-weighted imaging in five and digital subtraction angiography in four. Brain biopsy in four cases revealed lymphocytic angiitis. All cases had good outcome with the treatment of single corticoid or cyclophosphamide.
Conclusion:  We report eight cases of PACNS from Southern China associated with neurological and neuroimaging abnormalities; these patients presented a mild to moderate inflammatory disease that was correlated with few CSF abnormalities and good response to single steroid or cyclophosphamide treatment without relapses. Although brain biopsy represents the gold standard for diagnosis of PACNS, considering the difficulty and challenge of identification of this disease, combination with other examinations might be necessary to arrive at an early and definitive diagnosis.     

Repetitive use of intra-arterial verapamil in the treatment of reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome (RCVS) typically presents with recurrent thunderclap headaches and neurological deficits that are usually self-limiting. The intra-arterial (IA) use of vasodilators for RCVS has been reported for severe cases. Patients with RCVS have the potential for serious and permanent neurological deficits. It is a rare disorder, with a recent surge in the number of reports, and probably continues to be under-diagnosed. We report two patients with RCVS with severe neurological sequelae, treated in a large tertiary hospital. Both patients received high-dose cortico steroids due to the possibility of angiitis of the central nervous system, but they deteriorated neurologically, which suggests that steroids may have a deleterious effect in RCVS. Treatment with IA verapamil resulted in reversal of vasoconstriction, but multiple treatments were necessary. Therefore, IA administration of verapamil is a possible treatment for severe RCVS, but there is only limited sustained improvement in vasodilation that may require repetitive treatments with a currently undetermined optimal treatment interval.     

Reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome (RCVS) is an under-recognised condition. It is characterised by sudden and severe headaches (of “thunderclap” type) associated with multifocal reversible narrowing of the intracranial arteries on neuroradiology. The diagnosis is often established with the resolution of headaches and vasoconstriction. We report two patients with RCVS and review the available literature, to clarify the diagnostic criteria and discuss the treatment options.