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Immunotherapy Attacking Cancer’s Sweet Cloak: Opportunities and Challenges

Dr. Shih-Pin Chen, Dr. Kun-Hsien Chou and Dr. Shuu-Jiung Wang, from the Headache Research Group of Taipei Veterans General Hospital (TVGH) and National Yang-Ming University (NYMU) have identified the dynamics of white matter hyperintensity lesions (WMH) in reversible cerebral vasoconstriction syndrome (RCVS). The discovery may help to elucidate the pathogenesis of RCVS. The results were published in JAMA Neurology on September 1, 2018.

 

 Reversible cerebral vasoconstriction syndrome is one of the most serious and dangerous headache disorders. The major clinical presentation of RCVS is recurrent abrupt-onset severe headaches (namely thunderclap headaches) with constriction of cerebral arteries. These thunderclap headaches are often provoked by common daily activities such as straining at stool, exertion, bathing or showering, orgasm upon sexual activities or abrupt emotional change. These explosive headaches are not only highly disabling and terrifying, they are also associated with high risks of ischemic stroke, intracerebral hemorrhage or brain edema, leading to a great burden to the sufferers and healthcare system.

 

The term RCVS was formally proposed for this enigmatic neurovascular disorder since 2007. Most physicians, even including neurologists, and the general population are still unfamiliar with the disease. The pathogenesis of RCVS is largely unknown. The TVGH-NYMU Headache Research Group has held a leading position regarding the researches in RCVS. Physicians in this group have established the largest RCVS patient cohort in the world. Their works have contributed significantly to the understanding of the clinical features, pathophysiology and therapeutic strategies of RCVS. These works have been published in renowned scientific journals such as Annals of Neurology, Neurology, and Cephalalgia, etc. Recently, they focused on investigating the WMHs in patients with RCVS and have had a major breakthrough.

 

Previous large-scale meta-analysis has indicated that WMHs in general population is associated with risks of ischemic stroke, dementia and even mortality. WMHs are commonly seen in patients with RCVS; whether these tiny brain lesions are also associated with long-term prognosis is an issue highly concerned by the physicians and patients. However, the spatial distribution, temporal evolution and clinical significance of WMHs in RCVS are totally unknown. Investigators in the Headache Research Group utilized cutting-edge neuroimaging techniques and developed novel analytic tools to investigate these WMHs. They found that the lesion loads are significantly higher in patients with RCVS during the ictal stage, 10 times higher than that noted in general population. These RCVS-associated WMHs have disease-specific spatial distribution and temporal evolution, which have never been seen in other physiological (such as aging) or pathological conditions (such as hypertension, diabetes, nephrotic diseases or migraine). Remarkably, the volume of the WMHs is highly corrected (correlated?) with the severity of cerebral vasoconstriction, indicating that these lesions are disease severity marker that can be “visualized”. Hence, in addition to conventional invasive angiography studies, this analytic tool provided a novel way that clinicians can easily use to evaluate disease severity. Most important of all, long-term follow up found that these WMHs will be partially resolved when the vasoconstrictions normalized, not only providing important information to the physicians but also quite reassuring to the patients. In addition, the study also investigated the pathogenesis of these WMHs using hemodynamic studies, finding that these WMHs might be attributed to cerebral hypoperfusion and excessive central pulsatile flow owing to autonomic dysfunction. This finding might be beneficial for developing disease-targeting therapy in the future.
 

Currently, the TVGH-NYMU headache research group are implementing in-depth studies to interrogate the pathophysiology of RCVS. Their recent achievement include identifying the vascular wall pathology using high-resolution vascular wall imaging (published in the Journal of Headache and Pain, the official journal of European Headache Federation) and disclosing that climatic parameters might contribute to the incidence of RCVS (published in Headache, the official journal of American Headache Society). Currently, they are dedicating themselves in discovering disease-specific biomarkers in the blood, urine and cerebrospinal fluid, as well as genetic studies in patients with RCVS, hoping that these researches could help identifying novel therapeutic and preventive strategies that are beneficial to the patients.

 

Media Contact

Alice L. Yu

Institute of Stem Cell and Translational Cancer Research,12JChang Gung Memorial Hospital at Linkou, No.5, Fu-Shin St., Kuei Shang, Taoyuan 333, Taiwan

Tel: 03-3281200 #5218

Email: aliceyu@ucsd.edu

 

Jung-Tsun Chien

Postdoc

Department of Life Sciences, MOST

+886-2737-7990

jtchien@most.gov.tw

 

Last Modified : 2019/05/01