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Headaches


 

Headaches are one of the most common reasons people seek medical attention. While headaches can represent a malignant condition, they usually do not, and are generally highly treatable. If you have a persistent headache that is not responding well to medication, then you need to be evaluated.

Recently, Botox has been FDA-approved for chronic migraines (see below, also the separate section on Botox). This has been a game-changer and can eliminate or come close to eliminating headaches for weeks and months at a time. This enables migraine sufferers to get on with their lives without needing to take pills every day, keeps them off expensive medications, and keeps them out of the Emergency Room.

Furthermore, it is of great importance that it has no known effects on pregnancy. Since many of those who suffer from migraines are young women, this is an enormous advantage of Botox over all other pharmacological interventions.

Primary Headaches

Primary headaches are those for which no specific structural etiology has been found, and chief among these are migraines.

Migraine was first described by Hippocrates 2,500 years ago. It is usually on one side of the head, and is often associated with visual disturbance and nausea. Hippocrates also noted an association with the muscles of the neck, something that had been largely forgotten until recently. Migraines are much more common in women than in men, and the female preponderance increases with the frequency and severity of headaches. Almost all of those with daily migraines are women. There is a wide variety of treatment options including low doses of tricyclics and some anticonvulsants. Blood pressure medications are sometimes advocated, but are rarely effective and potentially dangerous. Medications in the “triptan” class raise serotonin levels abruptly, and can be used to eliminate an acute migraine quickly and safely. Recently butulinum toxin (Botox) has been FDA approved for chronic migraines. This is discussed under the heading “Botox.”

Cluster Headache may be thought of as the male variant of migraines. Although it occurs in women – it is usually associated with a more classic migraine – in its textbook form it is probably more common in men, and there is usually a first degree relative with migraines. Typically cluster headaches occur every day for a period of time – although they can be sporadic – are usually associated with an intense pain in one eye, and can be associated with tearing and nasal discharge (rhinorrhea). The eye itself is often red and irritated. The classic cluster often awakens the patient in the early morning and is therefore sometimes referred to as an “alarm clock headache.” Medications for migraines are also useful for cluster.

Hemicrania Continua is a headache syndrome that superficially resembles cluster. It is distinguished by its persistence – being present continuously for days at a time – and also by the fact that only one eye is ever affected. It is important to distinguish clinically from cluster because medications for migraine are rarely very effective. Strikingly, an old non-steroidal anti-inflammatory agent – indomethacin – can be extremely effective, and response to this medication is diagnostic.

Trigeminal Neuralgia is not typically thought of as a migraine, but probably should be. Clinical experience shows that it is common in those who suffer from migraines, or who have first-degree relatives who have migraines. It is a pain felt in the lower jaw (sometimes the upper jaw), on one side, exacerbated by chewing and brushing of the teeth. It responds more to anticonvulsants, sometimes tricyclics, and often a mixture of both. In extreme cases, it may respond to neurosurgical intervention with gamma knife focused on the trigeminal ganglion. Recently, in our hands, Botox injections of the masseter and temporalis muscles have proven effective.

Secondary Headaches

Secondary headaches are the result of some other condition, such as a tumor or hemorrhage. The brain itself has no specific pain receptors, and headache must, therefore, arise from other structures within the skull that do. These structures include the blood vessels and also the layers of connective tissue which surround the brain, known as meninges.

We can understand secondary headaches as any condition which affects either the blood vessels or the meninges, or both. Thus:

Brain tumors stretch the meninges and cause a dull, progressive headache.

Aneurysms are a ballooning and weakening of the wall of an artery. Since these arteries run between meningeal layers, when they rupture blood pours into the meningeal spaces causing a sudden, very intense, headache. Because aneurysms run inside the meningeal space known as the arachnoid layer, such hemorrhages are called:

  • Subarachnoid Hemorrhage: treatment is surgical placement of a clip around the neck of the aneurysm, or endovascular placement of a sleeve within the arterial wall.
  • Subdural Hemorrhage: the superficial cerebral veins run inside the outermost layer of connective tissue, known as the dura, and when they rupture they cause a subdural hemorrhage. Usually, this occurs as the result of trauma. It is common in the elderly, who present with a headache on one side that has progressed over several days. Treatment and cure is surgical evacuation, a relatively simple procedure
  • Epidural Hemorrhage: the middle cerebral artery, a division of the external carotid artery, runs outside the dura. Rupture of this artery causes an epidural hemorrhage. This is usually the result of head trauma and is seen mainly in children because the skull is thin. It is a rapidly evolving headache, a medical emergency, and treatment is prompt surgical evacuation.

Dehydration headaches or “morning after” headaches, are the result of overindulgence with alcohol. The brain shrinks with diuresis caused by heavy alcohol consumption, and this stretches the meninges causing a dull diffuse headache, familiar to anyone who has suffered a hangover.

Vasculitis causes focal headaches due to inflammation of blood vessels. The classic syndrome is temporal arteritis. These headaches respond to corticosteroids.

Venous sinus headaches are typically seen in younger people. They are due to obstruction by blood clots of the veins that drain the brain. They may be the result of an identifiable clotting abnormality or a recent viral infection. Because they are associated with brain swelling, the meninges are stretched and the pain is dull, continuous and progressive. These headaches, therefore mimic tumors in some respects but are distinguishable by the fact that the pain is usually nonfocal.

Arterial dissection is the result of peeling off of the inner layer of tissue (endothelium) in an artery. This is usually the carotid artery, but may also be the vertebral or basilar arteries. These are the arteries that supply the brain with blood. Dissections can be the result of trauma, but are more commonly spontaneous. They can be associated with stroke, headache, or both. The associated headache can easily be mistaken for migraine, tension or temporal arteritis. For any patient with new onset of severe unilateral headache, an MRI of the head is mandatory. Close inspection of the skull base with such an MRI will reveal changes in the blood vessels associated with narrowing, blood products or both. If the pain is sudden in onset then an MR Angiogram of the intracranial vessels is important to exclude aneurysms. If there is pain in the neck then an MR Angiogram of the neck arteries is mandatory.

Treatment of Migraine

The following is a partial list of medications that can be used in the treatment of migraines:

1. Reversal of sporadic migraines

  • Triptans
  • Firoricet
  • Non-steriodal anti-inflammatory drugs
  • Steroids
  • Ergot alkaloids

2. Prevention of chronic migraines

  • Anticonvulsants (topiramate, depakote)
  • Tricyclic antidepressants (amitriptyline, nortriptyline)
  • Antihypertensives (propranolol, verapamil)
  • Clonazepam
  • Botox

Of these - the newest, and we believe by far the most effective treatment, is Botox.

Botox

Botulinum toxin is a protein manufactured in nature by the species Clostridium, a bacterium found in the soil. A highly purified version of this protein is manufactured artificially by Allergan, without using Clostridium, and marketed under the brand name Botox. Botox is a potent muscle relaxant which works by inhibiting the release of the neurotransmitter acetylcholine at the neuromuscular junction. This results in a slight relaxation of the injected muscle. For muscles in spasm, the tone of the muscle is diminished and the spasm is eliminated.

Botox is most famous because of its cosmetic applications since it can be used to remove wrinkles. However long before this application, Botox was approved by the FDA for a number of serious conditions including torticollis, blepharospasm, excessive sweating, and spastic bladder. It “removes” wrinkles by means of its muscle relaxing properties. By relaxing the muscle under the skin, the striations are diminished and the wrinkles disappear.

The application to migraines is far more interesting. What was becoming increasingly clear 20 years ago was that injecting Botox into the musculature of the neck and temples decreases the severity and frequency of migraines. We have been performing such injections since 1994.

However, no-one did a double blind placebo-controlled study until Allergan performed one in 2009. In the Botox-treated group, the frequency of headache was decreased by about 40%, and this was statistically significant, leading the FDA to grant approval for this indication in 2010.

Allergan currently advocates the template for muscle injections that was used in this study. This template appears to be used by most physicians who treat migraine with Botox, however as good as it is, we have found it inadequate. Each patient is different, and it is important to explore the musculature of the neck rather than apply a “one-size-fits-all” policy. Trigger points are routinely found in muscles, such as the splenius capitis, that are not on the Allergan template.

We have achieved, on average, an 89% reduction in headache frequency, which is far greater than that seen in the Allergan study. In almost half (44%) of those with daily migraines, the headaches are eliminated completely. In the 56% with occasional residual headaches, the headaches are much less severe and often easy to eliminate with simple medications such as Advil and Tylenol.

Mechanisms of Botox

Botox is a pure muscle relaxant, and although Allergan has attempted to show that it may also work in pain pathways, nevertheless all efforts have so far proved unsuccessful. So how can relaxation of a muscle in the neck lead to elimination of a headache in the temples? Neck muscles are innervated by a nerve known as Cranial Nerve XI – the Accessory Nerve – which issues from the base of the brainstem, a structure known as the medulla. On the other hand, the facial muscles are innervated by Cranial Nerve V – the Trigeminal Nerve – whose nucleus originates in the middle of the brainstem, approximately 1.5 inches above the medulla. However the trigeminal nerve nucleus is unique among brainstem nuclei in that it extends down through the medulla to the spinal cord. This extension is known as the spinal trigeminal.

We think that sensory efferent nerves, from the muscles of the neck, enter the medulla, and, in genetically susceptible people, trigger the spinal trigeminal. This causes a headache in the facial musculature. When the neck muscle is relaxed by means of Botox injections, these efferents are less active, the trigeminal nerve is no longer triggered, and the headache disappears.

This also illustrates a famous feature of neuroanatomy, namely that representations in the brain tend to be upside down and back to front. Thus, the left side of the brain controls the right side of the body, and vice-versa. The lower spinal trigeminal controls the upper part of the face, the upper trigeminal innervates the lower face.

Trigeminal neuralgia, TMJ, and Fibromyalgia

This brings us to other craniofacial pain syndromes such as trigeminal neuralgia, TMJ syndrome, and fibromyalgia. We now believe that all of these conditions are part of the migraine syndrome, since all are associated with spasm of the muscles of the neck. In particular, trigeminal neuralgia and TMJ may be associated with the masseter, or chewing, muscles and patients with these conditions tend to grind their teeth at night and during the day. We have found that injections of Botox in the masseter muscles help relieve both TMJ and trigeminal neuralgia. Meanwhile what had traditionally been called fibromyalgia, a condition of muscle spasm in the neck seen most commonly in women, is often associated with migraine, and also responds to Botox.

Michael Hutchinson, MD, PhD

Dr. Hutchinson is a board-certified neurologist and senior faculty at the Icahn School of Medicine, Mount Sinai, Manhattan. His clinical interests include headaches, dementia, concussion, traumatic brain injury (TBI), Parkinson's Disease, multiple sclerosis, epilepsy, anxiety, and REM sleep disorders.  He has an extensive scientific background and brings a science-based approach to solving clinical problems.

During his residency at the University of Washington, Hutchinson used his knowledge of chaos theory to propose a new way of treating status epilepticus, the most lethal form of epilepsy. The treatment proved successful and is now standard-of-care in the US. Hutchinson later did a sabbatical at Queen Square, London, where Ian McDonald was pioneering the use of beta interferon as the first treatment for multiple sclerosis.

 

After residency training, Hutchinson underwent a neuroimaging fellowship in Los Angeles.

 

After arriving at NYU in 1994, Hutchinson pioneered the use of cholinesterase inhibitors as a treatment for the dementia of Parkinson's disease. At the time this was considered forbidden because it might make the patient physically worse, but Hutchinson argued that this premise was ill-conceived. Today, cholineserase inhibitors are standard-of-care in Parkinson's dementia. Hutchinson later developed a new way of treating acute relapses in multiple sclerosis, which puts the patient in charge, and has yielded impressive long-term results.

 

During his time at NYU, Hutchinson made early contributions to functional MRI, discovering that regional brain activations during cognitive tasks are accompanied by widespread deactivations.  In structural imaging, Hutchinson combined physics, neuropathology, and image processing to develop a robust MRI biomarker for Parkinson's disease.

 

In addition to certification in neurology, Hutchinson is certified in neuroimaging (MRI and CT of the brain and spine), which combines neuroanatomy, neuropathology, and neurophysiology, fields that form the unique base of clinical neurology.

 

Dr. Hutchinson holds a Ph.D. in molecular physics and is the inventor of spatial sensitivity encoding for MRI - sometimes referred to as parallel MRI - which is now the acknowledged standard for clinical MRI. He is currently exploring a possible extension of this to ultrafast imaging.

Michael Hutchinson, MD, PhD

Dr. Hutchinson is a board-certified neurologist and senior faculty at the Icahn School of Medicine, Mount Sinai, Manhattan. His clinical interests include headaches, dementia, concussion, traumatic brain injury (TBI), Parkinson's Disease, multiple sclerosis, epilepsy, anxiety, and REM sleep disorders.  He has an extensive scientific background and brings a science-based approach to solving clinical problems.

During his residency at the University of Washington, Hutchinson used his knowledge of chaos theory to propose a new way of treating status epilepticus, the most lethal form of epilepsy. The treatment proved successful and is now standard-of-care in the US. Hutchinson later did a sabbatical at Queen Square, London, where Ian McDonald was pioneering the use of beta interferon as the first treatment for multiple sclerosis.

 

After residency training, Hutchinson underwent a neuroimaging fellowship in Los Angeles.

 

After arriving at NYU in 1994, Hutchinson pioneered the use of cholinesterase inhibitors as a treatment for the dementia of Parkinson's disease. At the time this was considered forbidden because it might make the patient physically worse, but Hutchinson argued that this premise was ill-conceived. Today, cholineserase inhibitors are standard-of-care in Parkinson's dementia. Hutchinson later developed a new way of treating acute relapses in multiple sclerosis, which puts the patient in charge, and has yielded impressive long-term results.

 

During his time at NYU, Hutchinson made early contributions to functional MRI, discovering that regional brain activations during cognitive tasks are accompanied by widespread deactivations.  In structural imaging, Hutchinson combined physics, neuropathology, and image processing to develop a robust MRI biomarker for Parkinson's disease.

 

In addition to certification in neurology, Hutchinson is certified in neuroimaging (MRI and CT of the brain and spine), which combines neuroanatomy, neuropathology, and neurophysiology, fields that form the unique base of clinical neurology.

 

Dr. Hutchinson holds a Ph.D. in molecular physics and is the inventor of spatial sensitivity encoding for MRI - sometimes referred to as parallel MRI - which is now the acknowledged standard for clinical MRI. He is currently exploring a possible extension of this to ultrafast imaging.


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