What is the Epigenome? Most neurosurgeons have difficulty understanding the details of what the genome is—much less the Epigenome. In the last year, I became aware of articles on the Epigenome, about which I had known nothing. I learned that a supercontrolling mechanism called the Epigenome governs all the genes we have. This Epigenome is located in the histone core around which the DNA is wound and also in the DNA. The Epigenome determines which genes should be turned on or off. In addition, through mechanisms yet unknown, the environment in which we live can influence the Epigenome. Suddenly this discovery made sense; now there is a connection between our environment and our gene expression. To me, this information was an outstanding discovery. It can explain why some environments produce cancer and why behavior, under genetic influence, can be affected by the environment in which we live. So each organism is not a result of the automated translation of its DNA, but rather, the expression of each DNA-containing gene is controlled and can be turned on or off by environmental factors. So, even though animals and humans have DNA sequences that are similar, why are we different? And why do humans with similar DNA respond differently? How is the expression of our different genes controlled? The Epigenome will provide one of the answers. There may be other factors also. This discovery, in my opinion, will have profound implications on science in years to come. I asked John Zhang from the United States to write a short editorial on the subject for our readers. He and his colleague provide us with some insight into a phenomenon about which we will learn much more in the future.
During the year, Surgical Neurology receives a number of articles on the treatment of subdural hematomas, many of which are not accepted for publication. The article by Hong et al from South Korea addresses the biochemical mechanisms responsible for recurrent subdural hematomas (SDH). In a simple experiment, the authors have shown an increase in some protein factors that stimulate inflammation and angiogenesis in SDH, which may be the cause of recurrence. These factors are products of a genetic change leading to an increase in these protein components. More experiments will be necessary to help us understand why SDHs recur. However, it is not unreasonable to believe that molecular inhibitory factors can be used to fill the subdural cavity or be given intravenously to stop recurrence in highly suspect patients.
Toldo et al from Italy report a superb family study in which cavernous hemangiomas appear among multiple members of the family at different sites, including the spinal location. Figs. 1 and 2 in the article, showing the genetic defect and the family pedigree, respectively, are amazing. What does this report mean to neurosurgeons who see and operate on this disease? How will this gene defect be fixed in the future? Is it the cause of cavernous malformations that occur sporadically and in less numbers? Neurosurgeons operate on the phenotypic expression of this genetic mutation. What will happen to surgical treatment when this abnormal gene is eliminated?
Also, look at the Letter to the Editor from Newfoundland, Canada, in which the authors report a fascinating description of 6 large families with Von Hippel-Lindau disease, each with a different mutation. Because the patients are living longer, the expression of the disease is different.
Kapapa et al from Germany address the problem seen by neurosurgeons of bleeding that cannot be controlled in some surgeries. The authors report a series of patients in whom they used recombinant factor VII to stop the excessive bleeding caused by other methods that were not successful. The Discussion contains an excellent summary of the advantages and disadvantages of using recombinant factor VII. It will take time for a randomized study to be done. So, case reports as described are valuable for neurosurgeons facing this problem.
Fraioli et al from Italy report on their experience using radiofrequency thermocoagulation for patients with isolated third division trigeminal neuralgia. Their results are superb, better than any other treatment. Read the Abstract and the Discussion for a good overview of this subject.
Yoshida et al from Japan report on 109 cases of cerebellar metastases in a retrospective series covering 15 years. Surgery, surgery and radiation (RT), RT alone, and no treatment were all options from which to choose. The reasons for selection of a particular treatment are not indicated in their report. Yet, the data are good indicating that surgical resection and RT provide longer survival in this series with a median survival of 35 months. Read the comments by Ashby at the end. Look at Table 4 in the article for a quick summary.
Lorenzoni et al from Belgium and Chile report their results in using radiosurgery for brain stem metastases. It can be effective, leading to an 11-month median survival. This article comes from an experienced group in Belgium that has reported other studies on the management of brain stem lesions.
Abdulrahman et al from Saudi Arabia, United States, and Poland report an interesting study correlating the computed tomography (CT)-determined calcification in the carotid arteries in the neck of patients with their calculated stroke risk. The calculated stroke risk was based on studies used to relate stroke risk factors to actual stroke rate. Our cardiology colleagues around the world are using this technique of relating coronary calcifications to cardiac risk and cardiac atherosclerosis. In this study, the authors found a relationship between carotid calcification on CT and stroke risk in males. For some reason, this correlation did not appear in females. Read the comments by Rumboldt at the end, which are very good in providing a perspective on this research. This type of evaluation will be part of the future in selecting patients at risk for stroke. The method will change, but the principle will endure.
Pruthi et al from India report a retrospective analysis of patients presenting with extradural hematomas. They correlated the outcomes of these patients with the density of the hematoma seen on the admission CT scan. The real point of this article is that hematomas that are of mixed density (Fig. 3 of the article as an example) have that mixed density appearance because of active bleeding. The Discussion contains the supportive argument for this hypothesis. In fact, in the authors' experience, those patients with mixed density hematoma had larger volume extradural hematoma, lower Glasgow Coma Score on admission, and a poorer outcome even with more emergent surgery than those with hyperdense hematomas. So, how will this information change our management? To me, the patients need surgery with these size masses and a history of clinical deterioration anyway. The mixed density on the scan will tell me that there is active bleeding and may force me to place a burr hole in the emergency department unless I can get one done in the operating room in a very short time that is not likely.
Guzel et al from Turkey have a simple but informative study on what kind antibacterial agents to use in the presurgical scrub. In a randomized study of cranial and spinal surgeries, they found that after hair removal, the application of chlorhexidine scrub (Peridex or Corsodyl in the United Kingdom, Chlorhexamed in Germany, Savacol in Australia, Clohex in India, Perioxidina in Venezuela, Clorexil in Central America, or Hibiclens in the United States) for 3 minutes reduced the bacterial count by 72%. If this scrub was followed with povidone-iodine (Betadine) cleansing twice for 30 seconds total, a zero bacterial count was found. Read the comments by Cone at the end for an infectious disease expert's view of this study. Also, look at another Letter to the Editor from neurosurgeons in Iran about a previous Surgical Neurology article indicating that head shaving before a craniotomy is not necessary. The Iranians performed a randomized study to prove that head shaving before a craniotomy makes no difference in the infection rate.
The article by Prat et al from Spain on rebleeding in an arteriovenous malformation (AVM) after radiosurgery and angiographically documented obliteration of the AVM raises an interesting subject. Read the comments by Goodkin at the end, which are excellent. In 2005, Shin et al published an article in the Journal of Neurosurgery (102:842-846), reviewing the data on 4 patients with angiographically obliterated AVMs after radiosurgery who had recurrent hemorrhages. The authors found an area of enhancement around the AVMs on imaging, which at surgery, was found to contain small residual AVM vessels. So, if you have such a patient and the CT or magnetic resonance imaging is helpful in demonstrating an enhancing area at the edge of the AVM, there is a likelihood of finding an abnormal remnant of AVM vessels that should be resected. The authors in this article focused their surgery on the enhancing area with minimal surgery to reach the site and did not disturb the rest of the AVM.
Luo et al from Taiwan report their experience using endovascular catheter embolization to obliterate an indirect (meningeal) artery fed cavernous fistula. The authors used n-butyl-2-cynoacrylate glue in all 11 cases they report.
Fujimura et al from Japan report on the cause of delayed intracerebral hemorrhage in a Moyamoya patient after superficial temporal artery-middle cerebral artery bypass. This problem is found most commonly in ischemic brain in adults, in my experience, and not in patients in whom a bypass is being used on normal vessels for aneurysm management. The authors postulate and provide proof for hyperperfusion followed by edema at the anastomosis site. This is interesting information. I have encountered this bleeding problem in the past and did not have the tools to understand what was happening. The authors advocate controlling the blood pressure as the treatment of choice along with the use of steroids to control cerebral edema.
Refai et al from the United States report on a patient with a giant cell tumor of the thoracic spine and its management. Their literature review in the Discussion is worth reading. There are some other interesting case reports to read.
Clark Watts, a neurosurgeon, who also has been a lawyer for many years, has written an excellent editorial advising a neurosurgeon on what to do when he/she is sued. His advice is practical. This is good information to keep on file.
Finally, after being at neurosurgical meetings in 2 countries and discussing the problems that concern neurosurgeons, I have found that the problems I hear are the same for neurosurgeons everywhere. My editorial this month is about that subject, entitled, “If you do not take control of your life, someone else will.”
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