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Biomedical subjects

Mark J Stillman

Publications and source records attributed to Mark J Stillman.

5 recordsLinked to original sources

Testosterone replacement therapy for treatment refractory cluster headache.

OBJECTIVES: To describe the clinical characteristics and laboratory findings of cluster headache patients whose headaches responded to testosterone replacement therapy. BACKGROUND: Current evidence points to hypothalamic dysfunction, with increased metabolic hyperactivity in the region of the suprachiasmatic nucleus, as being important in the genesis of cluster headaches. This is clinically borne out in the circadian and diurnal behavior of these headaches. For years it has been recognized that male cluster headache patients appear overmasculinized. Recent neuroendocrine and sleep studies now point to an association between gonadotropin and corticotropin levels and hypothalamically entrained pineal secretion of melatonin. RESULTS: Seven male and 2 female patients, seen between July 2004 and February 2005, and between the ages of 32 and 56, are reported with histories of treatment resistant cluster headaches accompanied by borderline low or low serum testosterone levels. The patients failed to respond to individually tailored medical regimens, including melatonin doses of 12 mg a day or higher, high flow oxygen, maximally tolerated verapamil, antiepileptic agents, and parenteral serotonin agonists. Seven of the 9 patients met 2004 International Classification for the Diagnosis of Headache criteria for chronic cluster headaches; the other 2 patients had episodic cluster headaches of several months duration. After neurological and physical examination all patients had laboratory investigations including fasting lipid panel, PSA (where indicated), LH, FSH, and testosterone levels (both free and total). All 9 patients demonstrated either abnormally low or low, normal testosterone levels. After supplementation with either pure testosterone in 5 of 7 male patients or combination testosterone/estrogen therapy in both female patients, the patients achieved cluster headache freedom for the first 24 hours. Four male chronic cluster patients, all with abnormally low testosterone levels, achieved remission. CONCLUSIONS: Abnormal testosterone levels in patients with episodic or chronic cluster headaches refractory to maximal medical management may predict a therapeutic response to testosterone replacement therapy. In the described cases, diurnal variation of attacks, a seasonal cluster pattern, and previous, transient responsiveness to melatonin therapy pointed to the hypothalamus as the site of neurological dysfunction. Prospective studies pairing hormone levels and polysomnographic data are needed.

Adult↗

Treatment of primary headache disorders with intravenous valproate: initial outpatient experience.

OBJECTIVES: To evaluate the effectiveness of intravenous valproate in managing moderate to severe headaches. BACKGROUND: Despite major strides in the understanding of primary headache disorders, there have been few additions to acute headache management other than introduction of the triptans. An intravenous antiepileptic preparation, sodium valproate, has been reported to be effective in the management of status epilepticus and acute headache. METHODS: Between March 13, 2000 and October 11, 2000, we prospectively treated, in a nonrandomized and open-label study, every patient with a moderate to severe headache (4 or greater on a visual analog scale of head pain from 1 to 10) who wanted treatment with intravenous valproate. Using a verbal visual analog scale for pain (0 = no headache and 10 = most severe headache), we measured head pain before treatment and at time of discharge. The treating nurse monitored vital signs and side effects. A positive response was defined as a 50% or greater reduction at discharge in baseline pain. Information was collected regarding patient demographics, type of headache (according to criteria of the International Headache Society and that recently proposed for chronic headache), observation time in the treatment suite, cumulative dose of valproate, and use of concurrent medications. Univariable and multivariable correlates of response to treatment were identified using logistic regression analysis. RESULTS: One hundred thirty treatments were given to 89 women and 17 men, aged 17 to 76 years; 92 patients received only one treatment. Valproate doses ranged between 300 and 1200 mg. Thirty-three patients (31%) presented with episodic migraine, with or without aura; 45 patients (42%) presented with chronic daily headache with a history of episodic migraine, with or without aura (transformed migraine); 22 (21%) with unclassifiable chronic headache; 2 (2%) with episodic cluster headache; and 4 (4%) with chronic tension-type headache. For first treatments only, 61 patients (57.5%) responded to treatment, whereas for all treatments, 82 patients (63.1%) responded. Age and gender did not affect likelihood of response, whereas increasing duration of treatment (P=.003) and the additional use of analgesics (P=.021) were each negatively associated with response. Among headache types, unclassifiable chronic headache segregated from all other classified headaches in terms of poor response. Aside from rare dizziness (n = 2) and one spell interpreted as a pseudoseizure, no side effects were noted. CONCLUSIONS: Intravenous valproate is a safe, rapidly effective, abortive headache agent. It appears to be an effective analgesic for identifiable primary headaches, especially episodic headache, and less effective for unclassifiable chronic headache. Randomized, double-blind, controlled studies are warranted.

Adolescent↗

New developments in the pharmacotherapy of tension-type headaches.

The first International Headache Society classification defined tension-type headaches (TTHs) by itemising those characteristics of migraines TTHs did not possess [1]. As a result, TTHs, both episodic and chronic, remain the most nonspecific of all the commonly observed primary headaches. Until recently, there has been little impetus on the part of the pharmaceutical industry to investigate TTHs; many of the potentially useful drugs are now generic and unprofitable. In addition, few investigators have pursued the study of TTHs in lieu of its more glamorous neighbour, migraine. As a result, there are few well-designed studies on the pharmacotherapy of TTHs. The few studies that exist support the use of age-old standard drug classes, the tricyclic antidepressants and the NSAIDs. New research is now emerging that points to the potential utility of botulinum toxin type A, NMDA-receptor antagonists including Mg(2+) and nitric oxide synthase inhibitors. More scientifically rigorous clinical studies are needed.

Analgesics↗

Pharmacotherapy of tension-type headaches.

The first International Headache Society classification defined tension-type headaches by itemizing characteristics of migraines that tension-type headaches did not possess. As a result, tension-type headaches (episodic and chronic) remain the most nonspecific of all the commonly observed primary headaches. Until recently, there has been little impetus on the part of the pharmaceutical industry to investigate tension-type headaches; many of the potentially useful drugs are now generic and unprofitable. In addition, few investigators have pursued the study of tension-type headache because of its more glamorous neighbor, migraine. As a result, there are few well-designed studies on the pharmacotherapy of tension-type headaches. The few studies that exist support the use of age-old standard drug classes, the tricyclic antidepressants and the nonsteroidal anti-inflammatory drugs. New research is emerging that points to the potential use of botulinum toxin and nitric synthase inhibitors. More scientifically rigorous clinical studies are needed.

Humans↗