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Cervicocerebral arterial dissections are increasingly recognized as a cause of stroke, particularly in young people. The term “cervicocerebral arterial” refers to the arteries in the neck and brain, while the term “dissection” refers to a tear in the inner wall of a major artery. An arterial dissection leads to the intrusion of blood within the layers of the artery wall. Depending upon which layers blood collects, an arterial dissection can cause narrowing of the channel within the artery (termed stenosis), which restricts blood flow, or an aneurysmal dilation, meaning a localized, blood-filled bulge in the artery wall.

Although neck trauma preceding a cervicocerebral arterial dissection is common (including trivial injury such as vigorous nose blowing), several genetic connective tissue disorders are associated with cervicocerebral arterial dissections, including vascular Ehler-Danlos syndrome (EDS), an autosomal dominant disorder with mutations in the gene that encodes collagen, type I, alpha 1 (gene symbol COL1A1) [1] and fibromuscluar dysplasia (FMD), a non-inflammatory disease of medium sized arteries mainly affecting the carotid and renal arteries [2].

Cervicocerebral arterial dissections are most common between the ages of 35 and 50 years, with peak incidence in the 50’s [3], and account for up to 20% of strokes in patients less than 45 years of age [4].

Cervicocerebral arterial dissections include carotid artery dissections and vertebral artery dissections.

In each arterial system, the segment of artery involved can be extracranial, meaning a dissection involving the artery in the neck before it enters the brain, or intracranial, meaning a dissection involving the artery after it has entered the brain. Extracranial dissections are more common than intracranial, explained by the fact that extracranial artery segments are more mobile and prone to damage by the vertebrae. However, intracranial dissections are typically more severe and have a poorer prognosis than extracranial dissections.

Carotid artery dissections are at least three times more common than vertebral dissections [5]. Early detection is important, since cervicocerebral arterial dissections can cause neurological deficits, including weakness, paralysis of a limb or the entire body, impairment of hearing or vision, impairment or loss of speech, disturbance or loss of sensation, and tremors, due to thromboembolism (meaning the formation of a clot in a blood vessel that breaks loose and is carried by the blood stream to block another vessel) as well as hemodynamic failure due to arterial stenosis. Hemodynamic failure occurs when the brain is not receiving the normal amount of oxygenated blood.

Patients presenting with early dissection (with no related aneurysm or significant stroke) are treated with antithrombotic drug therapy to prevent thrombus formation, either with anticoagulation (e.g. warfarin, Coumadin) or antiplatelet (e.g. Plavix) agents. Surgical treatment is typically reserved for dissecting aneurysms and advanced stroke symptoms from the dissection. However, meta-analysis of controlled clinical trials assessing the efficacy of anticoagulants or antiplatelets for the treatment of extracranial internal carotid artery dissection, randomized controlled trials, and non-randomized trials failed to demonstrate evidence to support their routine use [6]. Indeed, the authors suggest that aspirin is likely to be effective and is safer than anticoagulents for patients with carotid artery dissection.

Arterial dissections are dynamic processes. Although the radiographic appearance may worsen during the acute phase of dissection, approximately 90% of stenoses eventually resolve, two-thirds of blockages open and one-third of aneurysms decrease in size [7]. Indeed, asymptomatic cervicocerebral dissections do not require any medical intervention and typically resolve on their own.

Cervical artery dissection and chiropractic neck manipulation

It seems every few years, the media focuses its attention on the relationship between chiropractic neck manipulation and cervical artery dissection. The first case of carotid artery dissection due to neck manipulation by a chiropractor was reported sixty years ago [8], and in the years following there have been a number of studies and case reports published.

A new study indicates that there is no increased risk of arterial dissection and stroke with chiropractic neck manipulation [9]. The findings, published in the journal Spine, elucidate the results of an earlier study that suggested that chiropractic neck adjustment resulted in some patients suffering a stroke after treatment [10]. Canadian researchers investigated the associations between chiropractic visits and vertebrobasilar artery stroke. Vertebrobasilar artery refers to the vertebral arteries, which are susceptible to compression with neck rotation, and the basilar artery (the artery formed by the junction of the two vertebral arteries). The researchers also compared their results with primary care physician visits and vertebrobasilar artery stroke.

The study included patients that had incident vertebrobasilar artery stroke and were admitted to Ontario hospitals between 1993 and 2002. Each case included four controls that were age and gender matched. Health billing records the year prior to the stroke date were used to determine case and control visits to chiropractors and primary care physicians.

Compared to the earlier study, which found that there is a one-in-5.85-million risk of stroke from chiropractic adjustment, Canadian researchers investigated the relationship between chiropractic visits and vertebral artery stroke and, as one type of control, compared the results to family doctor visits that preceded the same kind of stroke. Reviewing nine years worth of data, scientists found only 818 patients that had vertebrobasilar stroke. Patients less than 45 years of age were approximately 3 times more likely to see a primary care physician or chiropractor preceding their stroke than controls (meaning patients that did not have a stroke). Although there was no increased association between chiropractic visits and vertebrobasilar artery stroke in patients older than 45 years of age, positive associations were found between primary care physician visits and vertebrobasilar artery stroke in all age groups.

Although there was an increased association between chiropractic visits and stroke, it was the same as when patients visited a family doctor! Scientists interpret this surprising result to indicate that patients seeking either medical or chiropractic care for neck pain have already damaged the vertebral artery. Although a stroke occurred following the visit, the damage that caused the stroke was present prior to the medical or chiropractic visit.

The risk of arterial dissection is small when cervical spinal manipulation is performed. Nevertheless, patients who have other risk factors for cervicocerebral arterial dissection, including hypertension, migraines, use of oral contraception and smoking [11], should avoid chiropractic neck adjustment. Symptoms of vertebral artery dissection include headache and/or neck pain, vertigo, an abnormal sensation — typically tingling or pricking — on one side of the face, and visual field defects [12].

Although the risk of a vertebrobasilar artery dissection occurring after a chiropractic neck adjustment is small, it does happen. However, based upon these data, the risk of it happening is not any greater than after a primary care physician visit.

Have you ever had an arterial dissection? What do you think the relationship is between chiropractic neck adjustment and artery dissection?

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The American Society of Clinical Oncology (ASCO) recently published its third annual Clinical Cancer Advances report, Clinical Cancer Advances 2007: Major Research Advances in Cancer Treatment, Prevention and Screening [1]. It was developed under the guidance of a 21-person editorial board consisting of leading oncologists and cancer specialists, including specialty editors for each of the disease-specific and issue-specific sections. The report highlights 6 major advances in cancer research in 2007 and describes an additional 18 other findings of significant importance, demonstrating the pace of progress being made in cancer prevention, screening, treatment, epidemiology and survivorship.

The top 6 most important cancer advances of 2007

1. Magnetic resonance imaging (MRI) for breast cancer screening.

   Several recent studies have led to new guidelines regarding the use of MRI for breast imaging. The first study evaluated whether MRI could improve on clinical breast examination and mammography in the detection of breast cancer in the other breast soon after the initial diagnosis of cancer in one breast. Researchers found that patients recently diagnosed with unilateral breast cancer may benefit from MRI of the other breast to increase the chance of detecting additional cancers that may have been missed by mammography or clinical examination [2]. A second study found that MRI is significantly more sensitive for the detection of the most common type of noninvasive breast cancer in women, ductal carcinoma in situ (meaning the development of cancer within the milk ducts of the breast that has not moved out of the duct into surrounding tissue) [3]. Despite these findings, there are a number of limitations to MRI screening. MRI is expensive and there is a high rate of false positives (meaning the positive detection of cancer that really isn’t there). MRI screening has not yet been shown to improve the overall survival rate of patients with breast cancer.

2. Decreasing hormone replacement therapy (HRT) use linked to declines in breast cancer incidence.

   In 2007, two studies reported a link between the recent decrease in breast cancer incidence and the decline in the use of HRT in menopausal women [4-5]. Both studies examined large databases of patients, finding declines in breast cancer only in women aged 50 years and older. The declines were more significant in breast cancers that were estrogen receptor positive, the specific type of cancer whose growth could be fueled by the use of HRT. Other factors that could have played a role in the decreased incidence were analyzed, and while those factors could not be completely ruled out, the association with HRT was strong and warrants further study.

3. Sorafenib improves survival in liver cancer.

   Primary liver cancer is the third leading cause of cancer death, often progressing rapidly from initial diagnosis. A 2007 phase III study found that patients taking sorafenib (Nexavar) for hepatocellular carcinoma (the most common type of liver tumor) lived 44% longer than patients receiving placebo [6]. Sorafenib is currently approved by the U.S. Food and Drug Administration for the treatment of a form of advanced kidney cancer and is being evaluated in patients with other types of cancer.

4. Bevacizumab and interferon-alpha 2a for renal carcinoma.

   A recent large, multicenter study found that adding bevacizumab to an older kidney cancer drug called interferon-alpha 2a almost doubled progression-free survival (meaning the time during and after treatment when the cancer does not grow) [7]. In patients with metastatic kidney cancer, the combination therapy increased progression-free survival from 5.4 months to 10.2 months. One-third of tumors responded to the therapy compared to just 13% for the placebo. Bevacizumab is currently approved by the U.S. Food and Drug Administration for the treatment of metastatic colorectal cancer and non-small cell lung cancer.

5. The role of human papilloma virus (HPV) in head and neck cancers.

   In 2007, two studies increased our understanding of HPV infection and cancer. The first study evaluated the associations between HPV infection and oropharyngeal cancer in 100 newly-diagnosed patients and 200 control patients without cancer. The oropharynx is the middle part of the pharynx (throat) behind the mouth and includes the back one-third of the tongue, the soft palate, the side and back walls of the throat, and the tonsils. The study found that DNA from HPV-16, one of the strains of HPV most commonly associated with cervical cancer, was detected in 72% of tumors. Further, 64% of patients with cancer had antibodies for cancer-related proteins commonly found in HPV-16. The study thus demonstrates a strong association between oral HPV infection and oropharyngeal cancer [8]. Another study, a phase II clinical trial evaluating HPV infection and treatment response and survival outcome for patients with head and neck squamous cell carcinoma, found that cancers that are HPV-positive may have a better prognosis than patients that are HPV-negative [9]. Case in point: newly diagnosed patients with head and neck squamous cell carcinoma were treated with a combination of chemotherapy and radiation therapy. After a median follow-up of approximately 39 months, patients infected with HPV had a 72% lower risk progression and a 79% lower risk of death than those who were uninfected. Researchers suggest that HPV infection causes cancers that are biologically different than other cancers.

6. Preventive radiation therapy decreases brain metastases and prolongs survival for patients with advanced lung cancer.

   A 2007 clinical trial found that radiation therapy to the head for patients who responded to chemotherapy for advanced small cell lung cancer decreased the incidence of brain metastases and prolonged disease-free and overall survival [10]. The cumulative risk of brain metastases within 1 year was 14.6% in patients receiving head irradiation compared to 40.4% in the control group, thus extending patients’ lives.

Nancy E. Davidson, M.D., president of the American Society of Clinical Oncology (ASCO), said [11]:

This report demonstrates what many of us in the cancer research and practice community have known for some time. The long-term federal investment in cancer research is paying off. But this impressive pace of progress will slow if we don’t recommit to funding cancer research. Adjusted for inflation, cancer research funding has actually declined 12 percent since 2004 –this has never happened in our nation’s history. Without additional funding, the chance to build on the extraordinary new scientific knowledge, and provide new treatments for 1.4 million Americans diagnosed with cancer every year, will be delayed or lost.

Editors of the report reviewed studies published in peer-reviewed scientific journals and early research results presented at major scientific meetings from November 2006 to October 2007. Only studies that significantly altered the way a cancer is understood or had an important impact on patient care were included.

References

1. Gralow et al. Clinical cancer advances 2007: major research advances in cancer treatment, prevention, and screening–a report from the american society of clinical oncology. J Clin Oncol. 2008 Jan 10;26(2):313-25. Epub 2007 Dec 17.
   View abstract
2. Lehman et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007 Mar 29;356(13):1295-303. Epub 2007 Mar 28.
   View abstract
3. Kuhl et al. MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. Lancet. 2007 Aug 11;370(9586):485-92.
   View abstract
4. Glass et al. Breast cancer incidence, 1980-2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst. 2007 Aug 1;99(15):1152-61. Epub 2007 Jul 24.
   View abstract
5. Ravdin et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007 Apr 19;356(16):1670-4.
   View abstract
6. llovet et al. Randomized phase III trial of sorafenib versus placebo in patients with advanced hepatocellular carcinoma (HCC). Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL. 2007 June.
7. Escudier et al. A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-alpha 2a vs placebo/interferon-alpha 2a as first-line therapy in metastatic renal cell carcinoma. Presented at the 43rd Annual Meeting of the American Society of Clinical
   Oncology, Chicago, IL. 2007 June.
8. D’Souza et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May 10;356(19):1944-56.
   View abstract
9. Fakhry et al. Prognostic significance of human papillomavirus (HPV) tumor status for patients with
   head and neck squamous cell carcinoma (HNSCC) in a prospective, multi-center phase ii clinical trial.
   Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL. 2007 June.
10. Slotman et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72.
    View abstract
11. ASCO announces top cancer advances of 2007 in annual progress report. Hematology & Oncology News & Issues (HONI) online. 2007 Dec. 18.

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