Novel Interventional Nonopioid Therapies in Headache Management

Purpose of Review

Headaches encompass a broad-based category of a symptom of pain in the region of the head or neck. For those patients who unfortunately do not obtain relief from conservative treatment, interventional techniques have been developed and are continuing to be refined in an attempt to treat this subset of patients with the goal of return of daily activities. This investigation reviews various categories of headaches, their pathophysiology, and types of interventional treatments currently available.

Recent Findings

Injection of botulinum toxin has been shown to increase the number of headache free days for patients suffering from chronic tension-type headaches. Suboccipital steroid injection has been demonstrated as a successful treatment option for patients suffering from cluster headache. Occipital nerve stimulation (ONS) has been described as a treatment for all types of trigeminal autonomic cephalgias. Percutaneous ONS is a minimally invasive and reversible approach to manage occipital neuralgia performed utilizing subcutaneous electrodes placed superficial to the cervical muscular fascia in the suboccipital area. Radiofrequency lesioning is another commonly used treatment in the management of chronic pain syndromes of the head and neck. If a diagnostic sphenopalatine ganglion block successfully resolves the patient’s symptoms, neurolysis can be employed as a more permanent solution.

Summary

Although many patients who suffer from headaches can be treated with conservative, less-invasive treatments, there still remains at present an ever-increasing need for those patients who are refractory to conservative measures and thus require interventional treatments. These procedures are continually evolving to become safer, more precise, and more readily available for clinicians to provide to their patients.

     

Postpartum thyroid dysfunction: clinical assessment and relationship to psychiatric affective morbidity

OBJECTIVE: Postpartum thyroid dysfunction (PPTD), diagnosed using biochemical criteria, is usually transient with a wide range of reported prevalence rates. The specific clinical and psychiatric morbidity associated with PPTD is still uncertain. The aims of the study were to determine the point prevalence of PPTD in Australian women at 6 months postpartum and to assess the specific clinical and psychiatric morbidity in these women. DESIGN: Women who were Caucasian, aged 20-45 years and 4.5-5.5 months postpartum, were randomly selected and invited into the study. The respondents were assessed for biochemical and psychiatric morbidity. PPTD for this study was defined as TSH or free T4 outside the adult reference range. A double blind clinical assessment of PPTD women and their matched controls used standardized clinical hypo- and hyperthyroid clinical indices. PATIENTS: From the total randomly selected sample size of 1816 women, 748 participated. MEASUREMENTS: Biochemical measurements were serum TSH, free T4, microsomal antibody (MsAb) and thyroid peroxidase antibody (TPOAb), and thyroid receptor antibodies (only in women with low TSH). Psychiatric assessment involved screening all participants using the General Health Questionnaire 28, followed by classifying and quantifying severity of cases using DSM-III-R categories for depression and anxiety. Clinical signs and symptoms of hypo- and hyper-thyroidism were measured using weighted standardized indices. Thyroid size was assessed by palpation. Achilles tendon reflex time was measured by photomotograph. RESULTS: The prevalence of PPTD in the participants was 11.5% (95% CI 9.2-13. 8%), giving a minimum prevalence for the randomly selected sample of 4.7% (95% CI 3.7-5.7%). In the PPTD women, 54% had an elevated TSH, 30% had a suppressed TSH and the remainder had a low fT4 and normal TSH. Positive thyroid autoantibody titres in the PPTD group were 46. 5% for microsomal antibody (MsAb) and 63.9% for thyroid peroxidase antibody (TPOAb), and in the non-PPTD group were 1.7% and 4.9%, respectively. The 6 month point prevalence rates of depression, generalized anxiety disorder and panic disorder and/or agoraphobia were 9.4%, 1.4% and 3.1%, respectively. No relationship was found between PPTD status and the diagnosis of current depression or between thyroid antibody status and current depression. In women who were diagnosed as anxious at the time of assessment, the number of anxiety symptoms was higher in the PPTD group (P < 0.05). There was no difference in signs and symptom scores for the hypo- and hyper-thyroid clinical indices between PPTD women and their controls. CONCLUSION: This study has shown a high prevalence of postpartum thyroid dysfunction but there was no difference in the clinical and psychiatric signs and symptoms between cases and controls. In the social, psychological, physical and endocrine setting of the postpartum period, women with postpartum thyroid dysfunction are identifiable by the attending physician only by their abnormal thyroid function tests.     

Decreased signal transduction in rat parotid cell aggregates during aging is not due to loss of alpha 1-adrenergic receptors

Specific binding of the agonist, 3H-epinephrine, and antagonist, 3H-prazosin, to alpha 1-adrenergic receptors in both intact and broken rat parotid cell preparations was measured as a function of age in Wistar rats. Agonist binding exhibited approximately tenfold weaker affinity (Kd approximately 10 nM) for both intact and broken cells than did the antagonist (Kd approximately 1 nM). In addition, Bmax for the agonist was only 25 to 50% of that of the antagonist (7-10 fmol/mg protein vs. 15-30 fmol/mg protein) in both preparations. Binding affinity decreased significantly between ages 3 and 24 months for the antagonist but not the agonist in both intact and broken cells. The number of binding sites did not change with age in intact cells when measured with either agonist or antagonist, or when measured with agonist in broken cells, but increased markedly (approximately two fold) with age in broken cells for the antagonist. The latter results support the hypothesis that the aged rat parotid cell exhibits a naturally occurring, post-alpha 1-adrenoreceptor defect in signal transduction.     

The effect of syringe exchange use on high-risk injection drug users: a cohort study

OBJECTIVE: To determine whether syringe exchange program use is associated with cessation of syringe sharing among high-risk injection drug users. DESIGN AND METHODS: Between 1992 and 1996, street-recruited injection drug users were interviewed and received HIV testing and counseling semi-annually, as part of a dynamic cohort study. We examined a cohort of 340 high-risk injection drug users for whom two observations, 6-months apart, were available and who reported syringe sharing at the first interview. Multivariate logistic regression analysis was performed to determine the relationship between syringe exchange program use and cessation of syringe sharing, while controlling for confounding factors. RESULTS: At follow-up interview, 60% (204 of 340) reported quitting syringe sharing. High-risk injection drug users who began using the syringe exchange program were more likely to quit sharing syringes [adjusted odds ratio (AOR), 2.68; 95% confidence interval (CI), 1.35-5.33], as were those who continued using the syringe exchange program (AOR,1.98; 95% CI, 1.05-3.75) in comparison with non-syringe exchange program users, while controlling for confounding factors. CONCLUSIONS: The initiation and continuation of syringe exchange program use among high-risk injection drug users is independently associated with cessation of syringe sharing. Syringe exchange program use can be an important component in reducing the spread of blood-borne infectious diseases among high-risk injection drug users.     

Phannacokinetics of Intravenous Immunoglobulin in Neonates

Intravenous immunoglobulin (IVIG) may be a therapeutic adjunct to antibiotic treatment of neonatal infections. We examined the pharmacokinetics and safety of IVIG in human neonates. Thirty neonates with suspected sepsis were randomly assigned either to a treatment (receiving either 250, 500, or 1,000 mg/kg of IVIG plus antibiotics) or control (antibiotics alone) group. The 500 mg/kg dose produced a rise in total IgG for greater than 8 and in group B streptococcus (GBS) type-specific IgG for greater than 4-14 days. The type-specific antibody elevation varied with the amount of pathogen-specific antibody and dose of IVIG. Pharmacokinetic analysis suggests a Vdss of 42 ml/kg, Cl of 3.0 ml/kg/day, a biphasic elimination curve, and a terminal elimination half-life of 24.2 days. No toxicity was observed. These data may be valuable in determining optimal dosing schedules for IVIG in treating or preventing neonatal infections.     

IMMUNOGLOBULINS IN THE SKIN IN DERMATITIS HERPETIFORMIS AND CŒLIAC DISEASE

The unaffected skin of eighteen patients with dermatitis herpetiformis (D.H.), twenty-two patients with cœliac disease (C.D.), and eight controls were examined using direct immunofluorescence and class-specific fluorescein-conjugated anti-human IgA, IgM, and IgG antisera. All eighteen patients with D.H. showed IgA deposits in the skin: in seventeen the deposits were only found in the dermal papillæ, whilst in one it was found in a continuous line below the basement membrane, confirmed by immuno-electronmicroscopy. IgM deposits were also found in the dermal papillæ in three patients with D.H. and IgG deposits below the basement membrane in one patient. In cœliac disease, however, only one of the twenty-two patients showed papillary IgA deposits and one had continuous IgM deposits. These immunoglobulin deposits in D.H. and C.D. seem to be on the reticulin of the dermal papillæ. It is suggested that in D.H. there is a fault of the reticulin in the skin and small intestine, whilst in cœliac disease it is present in the small intestine but not in the skin. The reticulin cross-reacts with gluten complexes to give rise to an immunological reaction. In support of this hypothesis we have demonstrated cross-reactivity between gluten and reticulin.     

Regulation of intercellular biomolecule transfer–driven tumor angiogenesis and responses to anticancer therapies

Intercellular biomolecule transfer (ICBT) between malignant and benign cells is a major driver of tumor growth, resistance to anticancer therapies, and therapy-triggered metastatic disease. Here we characterized cholesterol 25-hydroxylase (CH25H) as a key genetic suppressor of ICBT between malignant and endothelial cells (ECs) and of ICBT-driven angiopoietin-2–dependent activation of ECs, stimulation of intratumoral angiogenesis, and tumor growth. Human CH25H was downregulated in the ECs from patients with colorectal cancer and the low levels of stromal CH25H were associated with a poor disease outcome. Knockout of endothelial CH25H stimulated angiogenesis and tumor growth in mice. Pharmacologic inhibition of ICBT by reserpine compensated for CH25H loss, elicited angiostatic effects (alone or combined with sunitinib), augmented the therapeutic effect of radio-/chemotherapy, and prevented metastatic disease induced by these regimens. We propose inhibiting ICBT to improve the overall efficacy of anticancer therapies and limit their prometastatic side effects.