Spinal Cord Stimulation for Failed Back Surgery Syndrome -- Patient Selection Considerations.

BACKGROUND: Failed back surgery syndrome (FBSS) refers to the condition where persistent pain is experienced by patients following back surgery. This condition is historically difficult to treat. Spinal cord stimulation (SCS) and its recent technical advances have opened the door to a promising treatment option for FBSS. However, critical appraisal of supporting and refuting data is necessary to identify the best patient population for this treatment modality. METHODS: In this systematic review, we review randomized controlled studies and cohort studies with matched controls to synthesize the data on the overall efficacy of spinal cord stimulation for FBSS. We further identify available data on outcome measurements based on working status, psychological status, smoking, sex, and race to provide insight on patient selection and identify needs for further research. RESULTS: The literature search identified 34 publications, of which 23 were excluded due to duplication and inclusion/ exclusion criteria, yielding a total of 11 publications for review. Seven out of eleven studies reviewed had sources of potential funding or affiliation bias. Three out of 4 studies with radiating leg pain relief as their primary outcome showed statistically significant improvement with SCS treatment, while 2 out of 5 studies with mixed radiating leg pain and axial back pain as the primary outcome showed statistically significant improvement with SCS. All randomized controlled trials that included functional status and quality of life outcome measures showed improvement after SCS, though scales utilized in each study varied. Six studies included work status as a patient descriptor with only three reporting inclusion of workers' compensation patients. There was limited data on the effect of psychological status, smoking, sex or race on SCS outcomes based on the studies reviewed. CONCLUSIONS: Evidence for the efficacy of SCS in FBSS is accumulating, with most studies demonstrating its efficacy especially for those patients with leg pain as the predominant symptom. However, a significant weakness in the current data includes potential bias based on the funding source for most studies. Additionally, it is clear that SCS provides short-term benefit, yet there is no solid evidence that SCS provides any benefit beyond two years of implantation. Another major concern is the significant placebo effect, which makes the true therapeutic response difficult to judge. Further, it is increasingly important to focus future studies on refining patient populations to those that may best respond to both SCS therapy in general, as well as specific stimulation techniques.

Ictal adipokines are associated with pain severity and treatment response in episodic migraine.

OBJECTIVE: To evaluate ictal adipokine levels in episodic migraineurs and their association with pain severity and treatment response. METHODS: This was a double-blind, placebo-controlled trial evaluating peripheral blood specimens from episodic migraineurs at acute pain onset and 30 to 120 minutes after treatment with sumatriptan/naproxen sodium vs placebo. Total adiponectin (T-ADP), ADP multimers (high molecular weight [HMW], middle molecular weight, and low molecular weight [LMW]), leptin, and resistin levels were evaluated by immunoassays. RESULTS: Thirty-four participants (17 responders, 17 nonresponders) were included. In all participants, pretreatment pain severity increased with every quartile increase in both the HMW:T-ADP ratio (coefficient of variation [CV] 0.51; 95% confidence interval [CI]: 0.08, 0.93; p = 0.019) and resistin levels (CV 0.58; 95% CI: 0.21, 0.96; p = 0.002), but was not associated with quartile changes in leptin levels. In responders, T-ADP (CV -0.98; 95% CI: -1.88, -0.08; p = 0.031) and resistin (CV -0.95; 95% CI: -1.83, -0.07; p = 0.034) levels decreased 120 minutes after treatment as compared with pretreatment. In addition, in responders, the HMW:T-ADP ratio (CV -0.04; 95% CI: -0.07, -0.01; p = 0.041) decreased and the LMW:T-ADP ratio (CV 0.04; 95% CI: 0.01, 0.07; p = 0.043) increased at 120 minutes after treatment. In nonresponders, the LMW:T-ADP ratio (CV -0.04; 95% CI: -0.07, -0.01; p = 0.018) decreased 120 minutes after treatment. Leptin was not associated with treatment response. CONCLUSIONS: Both pretreatment migraine pain severity and treatment response are associated with changes in adipokine levels. Adipokines represent potential novel migraine biomarkers and drug targets.

Migraine and estrogen.

PURPOSE OF REVIEW: The aim is to systematically and critically review the relationship between migraine and estrogen, the predominant female sex hormone, with a focus on studies published in the last 18 months. RECENT FINDINGS: Recent functional MRI (fMRI) studies of the brain support the existence of anatomical and functional differences between men and women, as well as between participants with migraine and healthy controls. In addition to the naturally occurring changes in endogenous sex hormones over the lifespan (e.g. puberty and menopause), exogenous sex hormones (e.g. hormonal contraception or hormone therapy) also may modulate migraine. Recent data support the historical view of an elevated risk of migraine with significant drops in estrogen levels. In addition, several lines of research support that reducing the magnitude of decline in estrogen concentrations prevents menstrually related migraine (MRM) and migraine aura frequency. SUMMARY: Current literature has consistently demonstrated that headache, in particular migraine, is more prevalent in women as compared with men, specifically during reproductive years. Recent studies have found differences in headache characteristics, central nervous system anatomy, as well as functional activation by fMRI between the sexes in migraine patients. Although the cause underlying these differences is likely multifactorial, considerable evidence supports an important role for sex hormones. Recent studies continue to support that MRM is precipitated by drops in estrogen concentrations, and minimizing this decline may prevent these headaches. Limited data also suggest that specific regimens of combined hormone contraceptive use in MRM and migraine with aura may decrease both headache frequency and aura.

Obesity and headache: Part II--potential mechanism and treatment considerations.

Obesity and headache are both associated with a substantial personal and societal impact, and epidemiologic studies have consistently identified a positive association between obesity and headache in general, as well as obesity and migraine specifically (see part I). In the current manuscript, we will discuss the potential mechanisms for the migraine-obesity association, with a focus on the central and peripheral pathophysiological pathways which overlap between migraine and those modulating the drive to feed. We then discuss surgical, behavioral, and pharmacological treatment considerations for overweight and obese migraineurs as well as for those with idiopathic intracranial hypertension. We close by briefly discussing where future research may be headed in light of this data.

Obesity and headache: part I--a systematic review of the epidemiology of obesity and headache.

Individually, both obesity and headache are conditions associated with a substantial personal and societal impact. Recent data support that obesity is comorbid with headache in general and migraine specifically, as well as with certain secondary headache conditions such as idiopathic intracranial hypertension. In the current manuscript, we first briefly review the epidemiology of obesity and common primary and secondary headache disorders individually. This is followed by a systematic review of the general population data evaluating the association between obesity and headache in general, and then obesity and migraine and tension-type headache disorders. Finally, we briefly discuss the data on the association between obesity and a common secondary headache disorder that is associated with obesity, idiopathic intracranial hypertension. Taken together, these data suggest that it is important for clinicians and patients to be aware of the headache/migraine-obesity association, given that it is potentially modifiable. Hypotheses for mechanisms of the obesity-migraine association and treatment considerations for overweight and obese headache sufferers are discussed in the companion manuscript, as part II of this topic.

Epidural lysis of adhesions for failed back surgery and spinal stenosis: factors associated with treatment outcome.

BACKGROUND: Failed back surgery syndrome (FBSS) is a challenging problem. One treatment advocated to treat FBSS is epidural lysis of adhesions (LOA). The results of studies examining LOA for FBSS have been mixed, but are limited because no study has ever sought to identify factors associated with outcomes. METHODS: We performed this multicenter, retrospective study in 115 patients who underwent LOA for FBSS (n = 104) or spinal stenosis (n = 11) between 2004 and 2007. Twenty-seven demographic, clinical, and procedural variables were extracted from medical records and correlated with the outcome, defined as ≥50% pain relief lasting ≥1 month. Univariable analysis was performed, followed by multivariable logistic regression. RESULTS: Overall, 48.7% (95% confidence interval [CI], 39.3%-58.1%) of patients experienced a positive outcome. In univariable analysis, those who had a positive outcome were older (mean age 64.1 years; 95% CI, 59.7-68.6 vs 57.2; 95% CI, 53.0-61.4 years; P = 0.02), while higher baseline numerical rating scale pain scores were associated with a negative outcome (mean 6.7 years; 95% CI, 6.0-7.3 vs 7.5; 95% CI, 6.9-8.0; P = 0.07). Use of hyaluronidase did not correlate with outcomes in univariable analysis (odds ratio [OR], 1.2; 95% CI, 0.6-2.5; P = 0.65). In multivariable analysis, age ≥81 years (OR, 7.8; 95% CI, 1.4-53.7), baseline numerical rating scale score ≤9 (OR, 4.4; 95% CI, 1.4-16.3, P = 0.02), and patients on or seeking disability or worker's compensation (OR, 4.4; 95% CI, 1.1-19.5, P = 0.04) were significantly more likely to experience a positive outcome. CONCLUSIONS: Considering our modest success rate, selecting patients for epidural LOA based on demographic and clinical factors may help better select treatment candidates. Procedural factors such as the use of hyaluronidase that increase risks and costs did not improve outcomes, so further research is needed before these become standard practice.

Why does vomiting stop a migraine attack?

Migraine is commonly associated with nausea and vomiting, though, interestingly, vomiting has also been reported by some patients to be therapeutic, and may actually stop a migraine attack. In this review, we will first discuss the epidemiology of nausea and vomiting in migraine. Further, we will briefly review the connections between the enteric nervous system, the autonomic nervous system, and the central nervous system as they pertain to understanding the question of "Why does vomiting stop a migraine attack?"

A comparison of spinal Iba1 and GFAP expression in rodent models of acute and chronic pain.

The treatment of acute and chronic pain is still deficient. The modulation of glial cells may provide novel targets to treat pain. We hypothesize that astrocytes and microglia participate in the initiation and maintenance of both, acute surgical and chronic neuropathic pain. Rats underwent paw incision, L5 nerve exposure or L5 nerve transection surgery. Behavioral mechanical allodynia was assessed using von Frey filaments. Immunohistochemistry was performed using anti-ionized calcium binding adaptor protein, Iba-1 (microglia), and anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) on day 1, 4 and 7 after surgery. Following paw incision and at spinal L5 segment GFAP expression was increased in laminae I-II and Iba1 in deep laminae on day 1, in the entire dorsal horn on day 4 and dissipated on day 7 after paw incision in parallel with the allodynia. L5 nerve transection induced mechanical allodynia from day 1 to 7 which correlated with Iba-1 increases on day 1, 4 (entire dorsal horn) and day 7 after nerve injury (deep laminae of the dorsal horn) at spinal L5 segment. Conversely, GFAP increased at later time points from day 4 (deep laminae) and on day 7 (entire dorsal horn). Our data demonstrates that astrocytes (GFAP expression) play a role in the initiation of acute pain and the maintenance of chronic pain while Iba-1 increases closely correlated with the early phase of neuropathic pain. Iba1 and GFAP increased rostrally, at L3 segment, after paw incision (day 4) and only Iba1 increased following L5 nerve transection (day 7).