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Head trauma

A new study from Mayo Clinic researchers, published in The Journal of Headache and Pain, has examined the brain changes associated with acute post-traumatic headaches (PTH). These headaches can occur after a head injury or trauma and can be debilitating. The study involved 60 participants with acute PTH and 60 age-matched healthy controls. Using functional MRI (fMRI), the researchers found two key differences in the brains of PTH patients compared to healthy individuals.

Increased Iron Accumulation in Specific Brain Regions

First, the PTH patients showed higher levels of iron deposition in two brain areas: the left posterior cingulate and the bilateral cuneus regions. These areas are involved in various functions, including pain processing, attention, and visual processing. The accumulation of iron in these regions may disrupt normal brain function and contribute to the development and persistence of post-traumatic headaches.

Abnormal Functional Connectivity Patterns

Secondly, the researchers observed stronger functional connectivity between the bilateral cuneus (the visual processing area) and the right cerebellum (a region involved in motor control and coordination, and other functions) in PTH patients compared to healthy controls. Functional connectivity refers to the communication and synchronization between different brain regions. The abnormal connectivity patterns seen in PTH patients suggest disruptions in the brain networks responsible for processing sensory information, including pain signals.

Implications for Targeted Therapy

While these findings may have lacked utility in the past, they now have important implications for the treatment of post-traumatic headaches. We have been treating patients with repetitive transcranial magnetic stimulation (rTMS), a non-invasive technique that can modulate brain activity in specific regions. By stimulating the areas with abnormal connectivity, rTMS may help restore normal brain function and alleviate headache symptoms and other neurological and psychiatric symptoms. When possible, we perform fMRI scans on individual patients to identify the specific brain regions involved in their headache disorder. However, fMRI is still only a research tool, and when individual fMRI data is not available, studies like this one provide information on common brain changes associated with post-traumatic headaches that can be targeted with TMS.

 

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Nolan Williams has been at the forefront of developing breakthrough TMS protocols for the treatment of depression and other psychiatric indications. It was very stimulating and informative to discuss techniques, protocols, indications, and research into TMS for various neurological and psychiatric indications with the members of Nolan Williams’ lab Greg Sahlem and Ika Kaloiani. Thank you for sharing your knowledge.

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I am once again honored to participate in the annual meeting of the Headache Cooperative of the Northeast to be held March 7-9 at the Stamford Marriott Hotel and Spa in Stamford, CT.

You will get a chance to learn about the latest scientific breakthroughs from Rami Burstein, president of the International Headache Society. You will also hear from other prominent figures in the field, renowned for their pioneering work and extensive contributions over several decades – Drs. Steven Baskin, Elizabeth Loder, Thomas Ward, Morris Levin, Richard Lipton, Steven Silberstein, Allan Purdy, Alan Rapaport, Paul Rizzoli, Sait Ashina, and others.

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We use a neuronavigation system from Soterix (on the left) for precise targeting of transcranial magnetic stimulation (TMS). And we use the most advanced TMS machine from MagVenture (on the right) to treat chronic pain, migraines, fibromyalgia, and other neurological conditions.

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Medication overuse or rebound headaches can occur as the result of excessive intake of caffeine, opioid analgesics, and short-acting barbiturate drug, butalbital (contained in Fioricet, Esgic and similar drugs). These three substances not only worsen migraine headaches, they are also addictive.  Two of my patients with medication overuse headaches were able to stop the offending drugs with the help of repetitive transcranial magnetic stimulation (rTMS).

One patient, a 51-year-old man, had his migraines under control with Botox and infusions of eptinezumab (Vyepti) until he sustained a head injury with a skull fracture. His migraines worsened and he became disabled. A variety of therapies failed to reduce his pain. His pain was partially relieved by 60 mg of oxycodone a day, although he still was unable to work. After six weekly sessions of rTMS he was able to start reducing his oxycodone intake and after eight, he completely stopped it. He was able to return to work with the help of injections of fremanezumab (Ajovy).

Another patient, a 50-year-old woman, had been taking butalbital with caffeine and acetaminophen (Fioricet) for 20 years. The number of pills increased over time and for the previous several years, she had been taking 10 to 12 tablets every day. She was also receiving Botox injections, infusions of eptinezumab, and taking rizatriptan (Maxalt), 10 mg three times a day as well as 60 mg of nortriptyline, 12 mg of tizanidine nightly and atogepant, 60 mg. She had tried a wide variety of other treatments but was unable to reduce her Fioricet intake. Despite her persistent migraines, she was able to take care of her family. After three weekly sessions of rTMS she reduced her Fioricet intake to 3-4 a day, by the third month she was taking one a day, and after 6 months she was completely off it. She was also able to stop atogepant and tizanidine and reduced her nortriptyline to 25 mg.

In addition to helping relieve pain and migraines, rTMS has shown promise in the treatment of addiction, particularly in addressing withdrawal symptoms, depression, and cravings. While the use of rTMS for addiction is still relatively recent and not yet FDA-approved, some studies have demonstrated positive outcomes. For instance, a double-blind study showed that individuals receiving rTMS therapy for cocaine addiction had a higher rate of abstinence compared to those who received standard treatment. rTMS for addiction is still considered experimental, and more research is needed to fully understand its long-term effects and optimal treatment parameters.

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Neurologists frequently find themselves managing patients resistant to standard treatments due to limited proven therapies for many neurological conditions. Some patients cannot tolerate or have contraindications to medications, particularly for such common disabling conditions like migraine and chronic pain. 

One promising treatment is transcranial magnetic stimulation (TMS). It is a proven procedure for anxiety, depression, obsessive-compulsive disorder (OCD), smoking cessation, and acute migraines. TMS utilizes magnetic fields to stimulate nerve cells in the brain that are underactive or reduce the excitability of overactive cells. TMS can change the flow of information between different parts of the brain in various neurological conditions. Published reports show the potential benefit of TMS in fibromyalgia, neuropathic pain, cluster headaches, facial pain, trigeminal and other neuralgias, back pain, insomnia, memory disorders, tinnitus, post-concussion syndrome, post-traumatic stress disorder (PTSD), restless leg syndrome, and long COVID. The evidence for the efficacy of TMS for these neurological disorders, however, is still limited.

Single-pulse TMS is approved by the FDA for the acute treatment of migraines with aura. The patient uses a portable device during the aura phase to self-administer a single pulse of TMS to the back of the head. This can abort the attack. Repetitive TMS (rTMS) has been studied for the prevention of migraines and other types of pain. It appears effective, but compared to depression trials, migraine studies were relatively small and the FDA has not cleared rTMS for the treatment of migraines. This means that insurance companies are not likely to pay for this “off-label” use of TMS.

rTMS is generally considered safe and well-tolerated, with side effects typically mild and temporary, including scalp discomfort, headaches, and facial twitching. More serious side effects like seizures and mania are very rare. 

Before starting TMS, patients undergo a physical and mental health evaluation. The coil placement and dose are determined in the first session. During a TMS session, patients sit in a comfortable chair with earplugs. An electromagnetic coil is positioned near the scalp, delivering short magnetic pulses to specific brain regions involved in processing pain and other information. Patients feel and hear rapid tapping on their scalp that continues, on and off. Patients are awake and alert during the entire procedure. There are no limitations to activities before or after the treatment.

Treatment length varies from 20 to 45 minutes, depending on the stimulation pattern and number of sites stimulated. The frequency of treatments also varies – anywhere from daily for several weeks, to once a week. After the initial period of more frequent sessions, some patients require weekly or monthly sessions to maintain the effect. It may take a few weeks to see noticeable effects. 

TMS is a good choice for people who have not responded to multiple standard therapies, people who do not want to take drugs, those who also suffer from depression and anxiety, and pregnant women. Sufficient evidence suggests that TMS is as safe in children as it is in adults, with studies indicating its effectiveness in treating depression in adolescents.

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The annual course, “The Shifting Migraine Paradigm 2024” will be held February 15-17, 2024 at the Plaza San Antonio Hotel & Spa. This three-day conference offers an excellent update on the treatment of migraine and other headaches.

It is always an honor to be invited to speak at this event. The topic of my presentation is Supplements and Medical Foods.

 

 

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Researchers have identified four blood biomarkers that show promise in predicting, diagnosing, and monitoring treatment response for posttraumatic stress disorder (PTSD). These biomarkers could lead to more accurate methods of screening for PTSD, allowing for early intervention and prevention strategies. Additionally, they could help monitor treatment progress, identify different subtypes of PTSD, and enhance our understanding of the underlying mechanisms of the disorder.

The study was conducted by the PTSD Systems Biology Consortium, initiated by the Department of Defense, and involved approximately 45 researchers. The team analyzed blood samples from 1,000 active-duty Army personnel from the Fort Campbell Cohort (FCC), who were assessed before and after deployment to Afghanistan in 2014.

The researchers focused on four biomarkers: glycolytic ratio, arginine, serotonin, and glutamate. They categorized the participants into four groups based on their PTSD symptoms, resilience levels, and clinical assessments. The findings revealed that individuals with PTSD or subthreshold PTSD had higher glycolytic ratios and lower arginine levels compared to those with high resilience. Additionally, participants with PTSD exhibited lower serotonin and higher glutamate levels. These associations were independent of factors such as age, gender, body mass index, smoking, and caffeine consumption.

The study results require further validation. The researchers also aim to determine the optimal time to screen soldiers for PTSD, considering the psychological challenges that arise around 2 to 3 months post-deployment. Moreover, they recognize the need for gender-specific biomarkers to improve the clinical assessment of female soldiers, given the increasing number of women serving in combat roles.

Ultimately, these findings may apply to the civilian population experiencing PTSD.

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In a recent post, I mentioned a study in which researchers using functional MRI (fMRI) were able to link functional connectivity within the default mode network (DMN) and between DMN and executive control network (ECN) with the degree of disability in migraine patients.

In a new study published in the journal Pain, researchers examined the brains of patients with mild traumatic brain injury (mTBI) using fMRI imaging to understand the brain networks associated with early acute pain following a motor vehicle collision. Here are some key findings:

  • The properties of the brain’s white matter explained a significant portion of the variation in pain experienced after mTBI. This suggests that certain brain features make patients more likely to report higher levels of pain after the injury.
  • These white matter connections are associated with physiological and psychological characteristics related to pain sensitivity. The interactions between these connections and parameters of sensory testing and pain sensitivity can explain about one-third of the variability in pain.
  • The connectivity patterns in the brain’s white matter do not change over time, as observed up to a year after the injury. The same connectivity measures collected shortly after the injury and at six months post-injury can predict the level of pain reported by patients at the six-month mark.
  • The study further indicates that the strength of white matter connections in the sensorimotor, thalamic-cortical, and default-mode networks is associated with pain severity. These findings highlight the involvement of these brain networks in pain perception and suggest that connections within these networks can influence the experience of pain.

Over the past decade, scientists have been increasingly interested in functional connectivity, which is a way of finding networks in the brain that are related to particular activities, including resting. One of the most prominent networks is the default mode network.

The DMN is most active when the brain is at rest. When the brain is directed towards a task or goal, the default network deactivates. The DMN involves low-frequency oscillations of about one fluctuation per second.

The DMN is thought to be involved in a variety of cognitive functions, including self-awareness, social cognition, memory, thinking about the future, and daydreaming. The DMN is also thought to be involved in some psychiatric disorders, such as depression, post-traumatic stress disorder, obsessive-compulsive disorder, schizophrenia, and others.

The findings of this study suggest that the brain’s white matter networks plays an important role in pain perception, and that understanding these brain-pain relationships may lead to new treatments for pain in individuals with mTBI.

These brain networks are not fixed and we already have tools to improve their function. Meditation is one of the most effective and accessible such tools. Meditation has been shown to increase connectivity between different brain regions, including those involved in pain perception. It has also been shown to reduce the activity of pain-related brain regions. In addition to meditation, other things that people can do to improve the function of their brain networks and reduce pain include exercise and sleep.

 

 

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A new study published in JAMA Pediatrics found that engaging in screen time within the first 48 hours after concussion may prolong recovery time. The study was conducted by researchers at UCSF. They looked at data from 125 patients aged 12 to 25 who had recently been diagnosed with a concussion. The participants were divided into two groups: one group was allowed to use screens, and the other group was asked to abstain from screen time.

The study found that the group permitted to use screens had a significantly longer median recovery time of 8.0 days compared to 3.5 days in the group that abstained from screens. Additionally, individuals who used screens reported experiencing more symptoms such as headaches, dizziness, and fatigue. The screen time permitted group reported a median screen time of 630 minutes during the intervention period, while the screen time abstinent group reported 130 minutes.

The study’s authors concluded that avoiding screen time in the first 48 hours after concussion may help to shorten the duration of symptoms. However, this was a relatively small study and more research is needed to confirm these findings.

In a recent post, I mentioned a large Canadian study that showed that early return to school after a concussion was associated with better outcomes. These two reports are not contradictory. Most pediatric guidelines recommend 24 to 48 hours of physical and cognitive rest, followed by a gradual return to school with support and accommodations. Prolonged periods of complete physical and cognitive rest lasting one to two weeks can be detrimental.

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The traditional approach for managing concussions has been to recommend rest until post-concussion symptoms resolve. While many neurologists still advocate for this approach, several studies have suggested that an early return to activity after a concussion may lead to better outcomes.

Most pediatric guidelines recommend 24 to 48 hours of physical and cognitive rest, followed by a gradual return to school with support and accommodations.

The latest pediatric study was done in Canada. It examined data for 1630 children aged 5 to 18 with a mean age of 12 and of whom 38% were girls. The primary outcome was symptom burden at 14 days, measured with the Post-Concussion Symptom Inventory. Missing fewer than 3 days after concussion was defined as an early return to school.

An early return to school was associated with a lower symptom burden 14 days postinjury in the 8 to 12-year and 13 to 18-year age groups, but not in the 5 to 7-year age group.

Prolonged periods of complete physical and cognitive rest lasting one to two weeks can be detrimental, as it can be challenging for many people to remain inactive for such an extended period. This approach, which involves refraining from activities such as reading, writing, screen time, and exercise, can lead to depression, increased anxiety, and may even delay recovery.

After a brief period of rest lasting 24 to 48 hours, I typically recommend a gradual return to full activities. The key is to monitor for any exacerbation of post-concussion symptoms such as headaches, dizziness, brain fog, or fatigue. If an activity does not worsen symptoms, patients can continue to increase the level of physical and cognitive activities at a steady pace.

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Almost 1.5 million Americans visit emergency rooms every year for the treatment of head trauma. Headache, not surprisingly, is one of the most common symptoms of head trauma. What is very surprising is that until now, there have been no controlled studies of acute therapies for posttraumatic headaches.

Dr. Benjamin Friedman and his colleagues at the Montefiore Hospital in the Bronx just published a “Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache” in the journal Neurology. Emergency rooms often use metoclopramide (Reglan) as the first-line drug for the treatment of migraines. Diphenhydramine (Benadryl) was added to reduce the chance of side effects from metoclopramide. These side effects of restlessness and involuntary movements can be very unpleasant.

The study involved 160 patients. Their pain severity was measured on a 0 to 10 verbal scale. Patients who received a placebo reported a mean improvement of 3.8, while those receiving two medications improved by 5.2 points. Side effects occurred in 43% of patients who received medications and 28% of patients who received placebo.

My recent post was devoted to a study that showed dramatic similarities between migraines and posttraumatic headaches. The outcome of Friedman’s study, therefore, is not unexpected.

The overall efficacy of metoclopramide is fairly modest. It provides only partial relief that often does not last. And some patients get no relief at all. It also causes unpleasant side effects.

It is puzzling why emergency room doctors are not using a migraine-specific drug, sumatriptan for both migraines and posttraumatic headaches. An injection of sumatriptan works well within an hour for 70% of migraine patients. It has significantly fewer side effects than metoclopramide. Vials of sumatriptan (but not autoinjectors) are relatively inexpensive.

As far as the use of sumatriptan for posttraumatic headaches, we have only a few anecdotal reports. One of the reports, however, describes seven patients who did not respond to other drugs and had very good relief of their posttraumatic headaches with sumatriptan.

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