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Head trauma

There is little doubt that stem cells, along with genetics and computer science will revolutionize medicine. There are more than a dozen journals devoted to stem cell research and many general and speciality medical journals also publish research on stem cells, which means that a couple of hundred articles are published every month. At first, the research was stymied by the controversy about the fetal sources of stem cells. For the most part this problem has been circumvented by the discovery of other sources, such as umbilical cord, placenta, fat tissue, and other.

In neurology, multiple sclerosis, spinal cord injuries, and strokes have been the main targets of stem cell research. The latest study of stem cells for stroke victims conducted at Stanford by Gary Steinberg and his colleagues produced very encouraging results. This trial included only 18 patients, but they all had their stroke anywhere between 6 months and 3 years before the study – past the usual time where further recovery is expected. Improvement occurred in the majority of patients and the improvement was not affected by the age of the patient or the severity of the stroke. Although stem cells were injected directly into the brain through a small hole that was drilled in the skull, there were no serious complications or side effects. The researchers also noted that stem cells did not replace damaged cells but rather stimulated patients’ own repair mechanisms. This is at odds with the original idea that stem cells by their nature could turn into nerve cells or any other cells in the body to replaced damaged cells.

This stimulating (and anti-inflammatory) effect of stem cells was our reason for conducting a small pilot study of stem cells in patients with refractory chronic migraines, which was described in a previous post. We did not inject cells into the brain, but into the muscles around the head and neck. Three out of 9 patients showed some improvement. We used patients’ own cells extracted from their fat tissue, while the stroke study used cells derived from the bone marrow of a donor. The future of stem cell research clearly lies in the use of such off-the-shelf cells, which have been shown to be safe and are probably more effective than fat-derived cells.

Stem cell lines are being developed to treat different medical conditions – Asterias for spinal cord injury, Pluristem for radiation damage, and many other.

The same team of researchers and SanBio, Inc. the Japanese company that developed these stem cells are conducting another larger controlled trial. You can email stemcellstudy@stanford.edu for information about participating in this trial.

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Chronic pain is known to alter the structure of the brain. Mayo Clinic researchers used MRI scans to examine brains of 29 patients with post-traumatic headaches and compared their scans to those of 31 age-matched healthy volunteers. The average frequency of headaches was 22 days a month. Patients with post-traumatic headaches were found to have thinning of several areas of their cerebral cortex which are responsible for pain processing in the frontal lobes. Cortex covers the surface of the brain and contains bodies of brain neurons. Drs. Chiang, Schwedt, and Chong, who presented their findings at the annual meeting of the International Headache Society held last month in Vancouver, also discovered that the thinning was correlated with the frequency of headaches.

This study did not address possible treatments, but it would make sense that with better control of headaches, this brain atrophy might be reversible. To treat post-traumatic headaches we often use Botox injections, which have been shown to help posttraumatic headaches. Even though Botox is approved only for chronic migraines, many patients with post-traumatic headaches do have symptoms of migraines and can be diagnosed as having post-traumatic chronic migraines (without such a designation insurance companies may not pay for Botox). We also check RBC magnesium, CoQ10 and other vitamin levels, which are often low in chronic headache sufferers and if corrected, can lead to a significant improvement. Epilepsy drugs and anti-depressants can also help.

While the above mentioned treatments can help headaches and potentially could reverse brain atrophy, there is only one intervention that has been shown to increase the thickness of the brain cortex on the MRI scan. This intervention is meditation. And this effect was demonstrated in several studies. An 8-week course of mindfulness-based stress reduction led to a measurable increase in the gray matter concentration of certain parts of the brain cortex. A pilot study of migraine sufferers showed that meditation has a potential not only to restore thickness of the brain, but also to relieve migraines.

In one of my previous blog posts that described a sceintific study of meditation, I mentioned several ways to learn meditation: Free podcasts by a psychologist Tara Brach an excellent book, Mindfulness in Plain English by B. Gunaratana, and several apps – Headspace, 10% Happier, and Calm. You can also take an individual or a group class, which are widely available.

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Concussion, even when it is mild, can result in a post-concussion syndrome. The main symptom is a headache and it is present in 60% of people within the first year after a mild traumatic brain injury. In people with personal or family history of migraines these headaches are often post-traumatic chronic migraines. Post-traumatic headaches and other symptoms such as dizziness and difficulty with vision, concentration and memory are often difficult to treat. However, an effective treatment of headaches often leads to an improvement in other symptoms as well.

Treatment with epilepsy drugs (Topamax, Depakote, Neurontin), blood pressure medications (propranolol), or antidepressants (Elavil, Cymbalta) can be effective in some, but not in all and not without side effects. Botox injections have been very effective without any serious side effects in many of my patients and similar results have been published by other doctors (see here and here).

Dr. Sylvia Lucas of University of Washington in Seattle presented her experience with the treatment of posttraumatic headaches with Botox at the annual meeting of the American Headache Society held in Boston last month. She described 15 patients who sustained a mild traumatic brain injury and suffered from chronic migraines for an average of 8 months prior to being treated with Botox. After a series of three Botox treatments given every 3 months most patients had a significant improvement in the number of headache days, as well as improved physical and social functioning, emotional well-being, energy level and a reduction in pain. As expected, no patient experienced any serious side effects.

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Inhalation of pure oxygen under high flow is an effective treatment for an acute cluster headache, although not migraines. Headache is one of the most common symptoms of traumatic brain injury and postconcussion syndrome and there is evidence that oxygen under pressure can help those conditions.

A review article on the use of oxygen to treat mild and moderate traumatic brain injury and postconcussion syndrome was recently published in Neurology. THe authors reviewed 5 previously published studies and concluded that hyperbaric oxygen in fact does help patients with brain trauma and postconcussion syndrome.

While cluster headache patients can breathe in oxygen through a mask from a tank of oxygen delivered to their home, hyperbaric oxygen requires a special room or a chamber. Hyperbaric means that oxygen is under increased pressure, although the authors report that moderate pressure (between 1 and 2 ATA) may be better than high pressure. Even hyperbaric air, that is normal air under pressure, may have beneficial effects.

The authors conclude that, there is sufficient evidence for the safety and preliminary efficacy from clinical data to support the use of hyperbaric oxygen in mild to moderate traumatic brain injury and postconcussion syndrome. They also state that “It would be a great loss to clinical medicine to ignore the large body of evidence collected so far that consistently concludes that hyperbaric oxygen is effective in treatment of brain injuries.”

Fortunately, there are many hospitals and private clinics all around the country that offer hyperbaric oxygen. They often advertise its use for a variety of unproven indications, but if you suffer from a traumatic brain injury, this treatment may be worth trying. A major obstacle though could be the cost of treatment since insurance companies are not likely to cover this treatment.

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Postconcussion symptoms can be debilitating and can persist for long periods of time, both in kids and adults. Persistence of headaches, dizziness, difficulty concentrating and with memory is often compounded by depression and anxiety. The usual care consists of mild exercises, sleep medications, antidepressants, and other drugs.

A new study published in Pediatrics shows very promising results from cognitive-behavioral therapy (CBT) in teens with post-concussion symptoms. Children aged 11 to 17 years with persistent symptoms for more than a month after sports-related concussion were randomly assigned to receive collaborative care that included CBT (25 kids) or care as usual (24 kids). The children were assessed before treatment and after 1, 3, and 6 months.

Six months after the baseline evaluation 13% of children who received CBT and 42% of control patients reported high levels of postconcussive symptoms. Depression improved by at least 50% in 78% of the CBT group and 46% of control patients. Anxiety symptoms were at the same level in both groups.

CBT has been shown to be effective in children and adolescents with chronic migraines, so it is not surprising that it would also help with postconcussion headaches and other symptoms. And the effect is quite dramatic.

A major obstacle for wider adoption of CBT is the cost and difficulty in finding a qualified psychologist. In a previous post I mentioned two very effective and scientifically verified online programs, ThisWayUp and moodGYM. These do require persistence and discipline, which in case of teens, parents might be able to provide.

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With 13 million participants, soccer is the third most popular sport in the US after basketball and baseball. Worldwide, 250 million people play soccer. Unfortunately, a number of studies have linked playing soccer with neurological symptoms. The latest study from the Albert Einstein College of Medicine published in Neurology evaluated 222 amateur soccer players aged 18 and older (mostly in their 20s and 30s) over a two-week period.

The study suggests that playing soccer even without heading the ball is associated with symptoms of a concussion. Those who did not report heading the ball often had unintentional head impacts (head to head, elbow or knee to head, head kicked, etc) and were much more likely to have concussion-related symptoms which were rated as moderate or severe. These symptoms included headache, dizziness, feeling dazed, and other. Unintentional head impacts were experienced by 37% of men and 43% of women, while heading-related symptoms were reported by 20%.

Not all symptoms necessarily represent a concussion and some pain and dizziness could be neck-related, so additional large studies are needed. Some studies have detected brain changes in soccer players who frequently head the ball, but these findings are considered to be preliminary and not conclusive.

According to the US Soccer Federation children under the age of 10 should not be allowed to head the ball in practice or in games. Children aged 11 to 13 are allowed to head the ball only during practice. However, this new study suggests that soccer players of any age may be risking brain injury, mostly from heading and unintentional head injuries.

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Physical and mental symptoms can persist after a concussion and strangely, mild concussions are more likely to cause persistent symptoms than severe ones. In a previous post, Rest your brain after a head injury I described a study that involved 335 children and young adults. As the title indicates, cognitive rest was associated with a faster recovery.

Another post on concussion and post-concussion headaches mentioned that experts advocate physical rest as well. However, a new study of over 3,000 Canadian children between the ages of 5 and 18 with concussion suggests that the recovery is faster in those who get physically active within the first week of an acute concussion. Of the children who engaged in physical activity within the first week 29% had persistent post-concussive symptoms four weeks later compared to 40% of those who did not engage in any physical activity. This was true whether the child participated only in light aerobic exercise (33% of kids), sport-specific exercise (9%), noncontact drills (6%), full-contact practice (4%), or full competition (17%). I am very surprised that kids were allowed to return to full-contact practice and full competition before complete recovery.

These finding contradict all of the concussion guidelines, which recommend a period of physical and cognitive rest following a concussion until post-concussive symptoms such as dizziness, fatigue, and headaches have resolved. The guidelines also advise to increase the amount of physical activity only if symptoms do not worsen. These guidelines were developed without the benefit of large controlled studies, but rather by a consensus of experts.

The authors also think that children who rest for a long period of time may be unnecessarily deprived of physical activity’s benefits on the growing body. Too much rest may also lead to symptoms such as depression, anxiety, and social isolation.

“We may need to reconsider the current recommendations for strict conservative rest until patients are symptom-free,” study author Roger Zemek, MD, PhD, associate professor and director of research at the University of Ottawa in Canada, said in an interview with Neurology Today. “Patients should be encouraged to participate in some form of active physical rehabilitation following concussion as long as the activity does not put them at risk of re-injury.”

The study authors did caution that “Participation in activities that might introduce risk for collision or falls should remain prohibited until clearance by a health professional to reduce the risk for a potentially more serious second concussion during a period of increased vulnerability.”

Two prominent sports neurologists said that not much will change at their clinics, because programs like the one in the study are already in place. They generally prescribe an early, graduated, return to physical activity for children and adolescents who present with a sports-related concussion. (Phases include light activity like walking, moderate activity like jogging, and moderate-heavy activity like non-contact practice or drills.) Patients may return to full activity within one week, although they may not progress by more than one phase per day. These neurologists also felt that avoidance of all activity can be harmful – not just on physical health, but also on mental health.

They also agreed that kids must not be allowed to immediately return to full-contact sport or high risk activities before complete recovery because of the increased risk of re-injury.

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A new report presented at the last annual scientific meeting of the American Headache Society in San Diego showed that post-concussion symptoms can be helped by an intravenous infusion of magnesium.

Doctors at the department of neurology at UCLA described six patients with a post-concussion syndrome, who were given an infusion of 2 grams of magnesium sulfate. Three out of six had a significant improvement of their headaches and all had improvement in at least one of the following symptoms: concentration, mood, insomnia, memory, and dizziness.

This was a small study, but it is consistent with other studies that show a drop in the magnesium level following a concussion and also studies in animals that show beneficial effects of magnesium following a head trauma.

Our studies have shown that intravenous magnesium can relieve migraine and cluster headaches in a significant proportion of patients.

Considering how safe intravenous magnesium is and how devastating the effect of a concussion can be, it makes sense to give all patients with a post-concussion syndrome if not an intravenous infusion, at least an oral supplement. I usually recommend 400 mg of magnesium glycinate, which should be taken with food. For faster and more reliable effect, we routinely give patients with migraines, cluster, and post-concussion headaches an infusion of magnesium. Patients who do not absorb or do not tolerate (it can cause diarrhea) oral magnesium, come in to for monthly infusions.

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Post-concussion symptoms have long been thought to be more severe and prolonged in people who have pre-existing psychological problems. This has been shown to be the case in the military personnel. A new study confirmed this observation in the first prospective study. Over 2,000 high school and college athletes in Wisconsin were asked to answer 18 questions (Brief Symptom Inventory-18, or BSI-18) and then were followed for three years. The 18 questions, which are listed below, addressed the presence of anxiety, panic attacks, depression, and somatization (excessive bodily sensations). In the ensuing three years, 127 athletes sustained a concussion. The concussion had to be diagnosed by a licensed athletic trainer according to the Department of Defence definition, which includes alteration of mental status with associated headache, nausea, vomiting, balance difficulties, dizziness, cognitive difficulties, and other. These athletes were again evaluated two and six weeks later. Eighty percent of concussed athletes were men. The mean duration of symptoms was five days. Ninety five percent of them recovered completely within a month. High somatization score on the BSI-18 questionnaire predicted prolonged duration of symptoms, while no correlation was found with the years of playing a sport, the type of sport (most played football), number of prior concussions, migraines, ADHD, or the grade point average. Another factor that delayed recovery was the initial symptom severity after the concussion. Most of the concussions were mild with less than 10% of athletes losing consciousness.

An interesting and unexplained fact, not examined in this study, is that milder concussions tend to cause more severe symptoms than severe ones.

This was a very thorough study, but it was relatively small, so it is possible that other pre-concussion factors may also delay recovery. One such factor is pre-existing migraines. I see many patients, adults and children, who suffered from migraines and after a concussion have worsening of their migraines or new daily persistent headaches. If they themselves have never suffered from migraines, often their mother or siblings have a history of migraines, suggesting genetic predisposition to migraines.

Treatment of post-concussion symptoms, include typical therapies employed in migraine sufferers, including aerobic exercise, biofeedback, magnesium supplementation, Botox injections, and a variety of medications.

Brief Symptom Inventory-18

The Somatization dimension
01. Faintness or dizziness
04. Pains in heart or chest
07. Nausea or upset stomach
10. Trouble getting your breath
13. Numbness or tingling in parts of your body
16. Feeling weak in parts of your body
The depression dimension
02. Feeling no interest in things
05. Feeling lonely
08. Feeling blue
11. Feeling of worthlessness
14. Feeling hopeless about the future
17. Thoughts of ending your life
General anxiety
03. Nervousness or shakiness inside
06. Feeling tense or keyed up
15. Feeling so restless you couldn’t sit still
Panic
09. Suddenly scared for no reason
12. Spells of terror or panic
18. Feeling fearful

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Several presentations at the annual meeting of the American Headache Society held in Washington DC last weekend discussed the treatment of post-concussion symptoms in children (everything below also applies to adults). Among many topics, the speakers addressed the question of aerobic exercise after the concussion. Most experts agree that starting physical exercise too early can worsen the symptoms and delay recovery. At the same time, because aerobic exercise has so many benefits for the brain, it is prudent to begin aerobic exercise 2 to 4 weeks after the concussion. The child should begin exercising for short periods of time and at low intensity. Exercise should be stopped as soon as symptoms, such as headache or dizziness worsen. Brisk walking could be the first activity to be tried. The ideal duration is about 30 minutes and when this goal is achieved, the intensity of exercise can be gradually increased.

As far as the very common cognitive problems after a concussion, the experts also agreed that complete cognitive rest is not helpful. Just like with physical exercise, it is best to begin mild activities, such as reading for pleasure, and then slowly increase the load, as tolerated.

Several scientific presentations reported that the most common type of headaches that occurs after a concussion is migraine. When these post-concussion migraines last for more than 3 months and occur on more than 15 days each month, they are considered to be chronic migraines.

The treatment of post-concussion chronic migraines is the same as the treatment of chronic migraines that occur without a concussion. These treatments may include cognitive behavioral therapy, biofeedback, magnesium and other supplements (magnesium deficiency is found in up to 50% of migraine sufferers and magnesium is depleted by trauma), various preventive medications, and Botox injections.

Although the FDA has not yet approved Botox injections for the treatment of chronic migraines in children, Botox is safer than most drugs. We know about the safety of Botox in children because it has been widely used even in very young children who suffer from cerebral palsy and are unable to walk unless their stiff leg muscles are relaxed by Botox. Botox was approved by the FDA 26 years ago and some kids have been getting injections for over 20 years and so far there have been no long-term side effects observed.

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Post-concussion syndrome, which often includes headaches, can persist for many months especially after a minor injury (yes, mild injury is more likely to cause post-concussion syndrome than a severe one).
However, little is known about prognosis after the injury. The symptoms fall into three categories – cognitive (such as memory, concentration difficulties), somatic (headaches, dizziness, etc), and emotional (irritability, anxiety, depression). A study by French physicians recently published in JAMA Psychiatry, also took into account the fact that injuries are often sustained during psychologically distressing events (car accidents, assaults, falls) and looked for symptoms of post-traumatic stress disorder (PTSD) in those patients.

The authors conducted a study of patients seen at an emergency department for a mild head injury. They checked on these patients for persistent symptoms three months after the concussion. The study included 534 patients with head injury and 827 control patients with non-head injuries.

The study showed that three months after the injury, 21.2 percent of head-injured and 16.3 percent of nonhead-injured patients had post-concussion syndrome, while 8.8 percent of head-injured patients met the criteria for PTSD compared with only 2.2 percent of control patients.

Their conclusion was that it is important to differentiate post-concussion syndrome from PTSD because it has important consequences, in terms of treatment, insurance resource allocation and advice provided to patients and their families. They also stressed the importance of considering PTSD in all patients with mild traumatic brain injury who suffer persistent symptoms.

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Strenuous mental activity seems to delay recovery after a head injury, according to a new study published in Pediatrics .

Doctors have always recommended rest after a head injury, but it has never been clear how much to limit activities, what kind to limit (physical, mental, or both), and for how long.

Dr. William P. Meehan III, director of the Micheli Center for Sports Injury Prevention in Waltham, Massachusetts and his colleagues studied 335 patients (62% were males), aged 8 to 23 who came to a sports concussion clinic within three weeks of their injury between 2009 and 2011. Most of the concussions were sustained while playing ice hockey, football, basketball or soccer. The researchers asked them about their symptoms and how often they were reading, doing homework or playing games at each of their appointments.

Those with minimal cognitive activity were not reading or doing homework, and spent less than 20 minutes on the Internet or playing video games each day. They could have watched TV or movies or listened to music. Those with moderate or significant cognitive activity did some reading and some homework, but less than usual. Others had not limited their cognitive activities at all since their last clinic visit.

On average, patients took 43 days to fully recover from their concussions. Those with more minor concussions tended to get over their symptoms faster. So did those who did less with their brains while recovering.

Results showed that only those engaging in the highest levels of cognitive activity had a substantial increase in their symptom duration, while those at all lower activity levels seemed to recover at about the same pace.

According to Dr. Meehan, “This would suggest that while vigorous cognitive exertion is detrimental to recovery, milder levels of cognitive exertion do not seem to prolong recovery substantially”

In general, Meehan said, doctors recommend almost complete brain rest for three to five days after a concussion, followed by a gradual return to normal activities.

Athletes suspected of having a concussion should be seen by the most immediately available medical personnel, like an athletic trainer or team doctor, he said, with a follow-up visit to their primary care doctor.

I would also emphasize the importance of physical rest and complete avoidance of any activities that could result in another head injury before completely recovering from the first one. Complete recovery means no symptoms at all, including headaches, dizziness, mental fog, fatigue, difficulty concentrating, insomnia, anxiety, depression, and other. Taking a magnesium supplement can also help since animal studies show magnesium depletion following an injury. If rest alone does not lead to a complete recovery, cognitive behavioral therapy, medications (for anxiety, depression, and irritability), and Botox injections (for persistent headaches) are sometimes needed.

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