Randolph W. Evans

Posttraumatic Headache: A Review

There has been intense controversy about postconcussion syndrome (PCS) since Erichsen’s publication in 1866 on railway brain and spine. Headache as a result of trauma is one of the most common secondary headache types. Posttraumatic headache (PTH) remains a very controversial disorder, particularly with relation to chronic PTH following mild closed-head injury. PTH is one of several symptoms of PCS, and therefore may be accompanied by additional cognitive, behavioral, and somatic problems. PTH also is an important public health issue due to its associated disability and often refractory clinical course. While current awareness of PTH has become more prominent due to increased scrutiny given to both combat-related and sports-related head injuries, directed treatment remains a difficult challenge for physicians. Because of the frequently associated medicolegal aspects, PTH is one of physicians’ least favorite types to treat. The article reviews both PCS and PTH.

A Dissociation of Positive Staircase (Bowditch) from Ouabain-Induced Positive Inotropism: Use of Verapamil

The effects of verapamil on myocardial contractility were examined in perfused rabbit ventricular preparations. Verapamil (0.2 μM) decreased the time derivative of developed force (dF/dt) of the preparations paced at 90 beats/min to 39 ± 3% (SE) of the control value. Partial reversal to 76 ± 5% of the control value was achieved by subsequent perfusion with drug-free Krebs solution. Verapamil hastened the decline and delayed the return of contractility in response to a cycle of calcium washout and reperfusion. It converted the response to increased heart rate from positive (Bowditch effect) to negative inotropism. Moreover, the sensitivity to the drug was frequency related; the drug concentration required to induce a 50% decrease in dF/dt was an inverse function of heart rate, suggesting that the drug altered contractility by interfering with a phenomenon associated with systole. Verapamil did not decrease the magnitude of the positive inotropic response to 0.5 μM ouabain, although a significant delay in the development of the response was observed. After 8 minutes of ouabain perfusion dF/dt had increased 35 ± 2% in the absence of verapamil but only 13 ± 1% in the presence of 1.0, μM verapamil. The maximum response to ouabain was a 39 ± 4% increase at 9 minutes in the absence of verapamil and a 34 ± 2% increase at 23 minutes in the presence of verapamil. These results suggest that the responses to increased frequency and to cardiac glycosides are not explained by a common mechanism such as sodium-calcium exchange occurring during diastole or any other diastole-related mechanism for calcium influx. However, the possibility that both events are mediated by some common mechanism occurring during systole has not been eliminated.

Persistent post-traumatic headache, postconcussion syndrome, and whiplash injuries: The evidence for a non-traumatic basis with an historical review

There has been intense controversy about postconcussion syndrome since Erichsens publication in 1866 on railway brain and railway spine. The fascinating history of this debate will be reviewed and then the non‐organic explanations for postconcussion syndrome, headaches after head injury, and chronic whiplash injuries and headaches will be explored including the following: psychogenic, psychosocial, sociocultural, base rate misattribution, chronic pain, compensation and litigation, and malingering.

A Rational Approach to the Management of Chronic Migraine

About 2% of the adult population has chronic migraine with only 20% diagnosed with this disorder. Those with medication overuse may improve with withdrawal of overuse medications. The intravenous dihydroergotamine regimen usually produces short‐term benefit for those with medically refractory chronic migraine. OnabotulinumtoxinA and topiramate have shown efficacy in large placebo‐controlled randomized trials. Sodium valproate, gabapentin, tizanidine, amitriptyline, fluoxetine, zonisamide, and possibly memantine may be alternative or possibly combined treatment options but with lesser levels of evidence supporting their use. Preliminary evidence suggests that nerve blocks might be beneficial. Acupuncture, biofeedback, relaxation therapy, and cognitive behavioral therapy might be of benefit. Surgical treatments including bariatric and deactivation of trigger points are of growing interest but not appropriate for most sufferers. Occipital nerve stimulation is a promising treatment with ongoing studies defining its use.

Cyclic Vomiting Syndrome and Abdominal Migraine in Adults and Children

The first pediatric descriptions of cyclic vomiting syndrome were provided in the French literature by Heberden in 1806 and in the English literature by Gee in 1882. An association of cyclic vomiting with migraine headaches was reported by Whitney in 1898. Described by Liveing in 1873 and Buchanan in 1921, Brams introduced the term “abdominal migraine” in 1922. We present 2 cases of cyclic vomiting syndrome and 3 cases of abdominal migraine in adults and provide a review.

A survey of headache medicine specialists on career satisfaction and burnout

Physicians report increasing rates of career dissatisfaction and professional burnout, which may be related to the practice environment and subspecialty. There has never been a survey of professional burnout among headache medicine specialists.

The risk and management of kidney stones from the use of topiramate and zonisamide in migraine and idiopathic intracranial hypertension

CASE HISTORY A 40-year-old woman has a 15-year history of migraine without aura that has been chronic for 5 years. While on TPM 100 mg daily for 2 years without side effects, her migraine frequency has decreased from 20 days per month to 6 days per month. She then developed a first-time kidney stone that passed spontaneously. Upon analysis, the stone was determined to be calcium phosphate. QUESTIONS What is the type of kidney stones that form and their pathophysiology? What is the frequency of kidney stones in migraineurs on TPM and ZNS and the general population? Is the risk dose and time dependent? Is a prior history of kidney stones a contraindication to use of either medication? Is formation of kidney stones a contraindication to ongoing use of TPM or ZNS? If migraineurs who develop a kidney stone(s) on TPM continue the drug, is there any way to prevent further stone formation? In patients with IIH, is the risk of kidney stone formation a contraindication to combined use of TPM and acetazolamide (ATZ)?

Migraine: A Question and Answer Review

Internists commonly treat migraine, which affects more than 29 million Americans yearly. This article reviews epidemiology, pathophysiology, comorbidity, clinical features, diagnostic testing, acute and preventive treatment, and womens issues. Physicians and migraineurs would like to see more effective and more tolerable medications.

Triptans and serotonin syndrome

Dear Sir I read the article, ‘Serotonin syndrome and rhabdomyolysis induced by concomitant use of triptans, fluoxetine and hypericum’ by Bonetto et al. with concern (1). Their conclusion that the patient had serotonin syndrome precipitated by the use of eletriptan was incorrect if the diagnosis was based upon meeting criteria and not conjecture. The authors do not state specifically which criteria they used for serotonin syndrome. Their patient does not meet the Hunter serotonin toxicity criteria (2). The patient fulfilled the clinical features, but did not meet the Sterbach criteria because other aetiologies were not ruled out (2). In this case, an infectious aetiology (meningoencephalitis) was not excluded by a lumbar puncture, serology or cultures. This case may very well have been due to an enterovirus meningitis such as group B coxsackievirus, which could have caused all of the symptoms and signs including the complications of seizure, rhabdomyolysis, and renal failure (3). The elevated D-dimer level, which the authors state is not a laboratory finding of serotonin syndrome, may also have been associated with the viral disease and complications. In 2006, the United States Food and Drug Administration (FDA) issued an alert to potentially lifethreatening complications from the combined use of triptans with selective serotonin re-uptake inhibitors (SSRI) or selective norepinephrine reuptake inhibitors (SNRI) based upon 27 cases reported worldwide (4). Following a Freedom of Information Act request, the FDA provided me all of the case information on 29 cases, not just 27 as described in the alert. On analysis, seven of the cases met the Sternbach criteria and no case met the Hunter criteria (5). The biological plausibility of the serotonin syndrome with combined use is not clear, as triptans are 5HT1B/5HT1D/5HT1F subtype receptor agonists, whereas serotonin syndrome is believed to be due to activation of the 5-HT1A and 5-HT2A receptors (6). Although the incidence of serotonin syndrome among patients on SSRI monotherapy has been estimated in the range of 0.5–0.9 cases per 1000 patient-months of treatment (7), there have been no reported cases of serotonin syndrome due to triptans taken alone (8). A prospective postmarketing safety study (9) for up to 1 year of subcutaneous sumatriptan use in 1784 migraineurs on SSRIs found no cases of serotonin syndrome. However, it is possible that additional definite cases may be reported with greater physician awareness of these potential drug interactions and serotonin syndrome. As Bonetto et al. concur, ‘The FDA recommends that patients treated concomitantly with a triptan and an SSRI/SNRI be informed of the possibility of serotonin syndrome’. This recommendation seems premature when more than 1 million patients have been exposed to the drug combinations (8) with only seven cases meeting just one set of criteria for serotonin syndrome. Routinely advising our patients may be a poor use of time, unnecessarily alarm some patients, and may be harmful when efficacious medications are not used.

The heterogeneity of new daily persistent headache

CLINICAL HISTORIES Case 1.—This is a 42-year-old woman who developed a right nuchal-occipital throbbing and vice-like headache with an intensity of 10/10 at the onset while sitting with nausea, vomiting, and a spinning sensation but no hearing loss, pressure in the ears, tinnitus, or other neurological symptoms 5 months previously. The headache had an intensity of 10/10 for about 3 weeks. Since then, she has had a constant headache described as a right nuchal-occipital and right hemicranial aching, throbbing, and stabbing with an intensity ranging from 4 to 8/10, with an average of 3-5/10 with nausea at times, and light and noise sensitivity, but no vomiting, visual symptoms, or vertigo since the first day. She had intermittent true vertigo lasting up to 30 minutes initially on a daily basis that did not totally resolve for about 6 weeks. She was taking baclofen 10 mg in the morning and 20 mg at bedtime that decreased the pain. She tried eletriptan 40 mg that dulled the pain. Three years previously, she had a mild head injury resulting in headaches for 3 weeks following but no other history of headaches. There was a past medical history of asthma. She initially saw her primary care physician who prescribed oral ketorolac and promethazine without benefit. A computed tomography (CT) scan of the brain without contrast 4 days after onset was negative. She then saw a neurologist who placed her on topiramate that was titrated up to 200 mg daily with mild benefit.A complete blood count, comprehensive metabolic panel, thyroid function tests, erythrocyte sedimentation rate (ESR), antinuclear antibody, and magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) scans of the brain were normal. She had a normal evaluation by an otorhinolaryngologist including an audiogram and electronystagmogram. I saw her in headache consultation 4 weeks after onset. A neurological examination and an MRA of the brain and neck, MRV of the brain, and MRI of the brain with and without contrast were normal. Topiramate was increased to 300 mg daily that mildly decreased the intensity of the pain, allowing her to work. Although consideration was given to a trial of From the Montefiore Headache Center, Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA (M.S. Robbins); Baylor College of Medicine, Houston, TX, USA (R.W. Evans).