Concordant occipital and supraorbital neurostimulation therapy for hemiplegic migraine; initial experience; a case series.

INTRODUCTION: Hemiplegic migraine is a particularly severe form of the disease that often evolves to a debilitating chronic illness that is resistant to commonly available therapies. Peripheral neurostimulation has been found to be a beneficial therapy for some patients among several diagnostic classes of migraine, but its potential has not been specifically evaluated for hemiplegic migraine. MATERIALS AND METHODS: Four patients with hemiplegic migraine were treated with concordant, combined occipital and supraorbital neurostimulation over periods ranging 6-92 months. The clinical indicators followed included assessments of headache frequency and severity, frequency of hemiplegic episodes, functional impairment, medication usage, and patient satisfaction. RESULTS: All reported a positive therapeutic response, as their average headache frequency decreased by 92% (30 to 2.5 headache days/month); Visual Analog Score by 44% (9.5 to 5.3); frequency of hemiplegic episodes by 96% (7.5 to 0.25 hemiplegic episodes/month); headache medication usage by 96% (6 to 0.25 daily medications); and Migraine Disability Assessment score by 98% (249 to 6). All were satisfied and would recommend the therapy, and all preferred combined occipital-supraorbital neurostimulation to occipital neurostimulation alone. CONCLUSIONS: Concordant combined occipital and supraorbital neurostimulation may provide effective therapy for both the pain and motor aura in some patients with hemiplegic migraine.

Application of mass spectrometry to characterize localization and efficacy of nanoceria in vivo.

In vivo study of nanomaterials is complicated by the physical and chemical changes induced in the nanomaterial by exposure to biological compartments. A diverse array of proteins can bind to the nanomaterial, forming a protein corona which may alter the dispersion, surface charge, distribution, and biological activity of the material. Evidence suggests that unique synthesis and stabilization strategies can greatly affect the composition of the corona, and thus, the in vivo properties of the nanomaterial. Protein and elemental analyses techniques are critical to characterizing the nature of the protein corona in order to best predict the in vivo behavior of the nanomaterial. Further, as described here, inductively coupled mass spectroscopy (ICP-MS) can also be used to quantify nanomaterial deposition in tissues harvested from exposed animals. Elemental analysis of ceria content demonstrated deposition of cerium oxide nanoparticles (CeNPs) in various tissues of healthy mice and in the brains of mice with a model of multiple sclerosis. Thus, ICP-MS analysis of nanomaterial tissue distribution can complement data illustrating the biological, and in this case, therapeutic efficacy of nanoparticles delivered in vivo.

Peripheral neuromodulation and headaches: history, clinical approach, and considerations on underlying mechanisms.

Implantable peripheral neurostimulation was introduced in 1969 as a potential treatment for certain neuropathic pain syndromes, primarily involving the limbs. While a few early studies included implants for occipital neuralgia, serious interest in its potential as a treatment for head pain came only after our 1999 report of positive findings in a series of patients with occipital neuralgia. Subsequent investigators confirmed these initial findings, and then extended the application to patients with various primary headache disorders, including migraine. While most found a therapeutic response, the degree of that response varied significantly, and analysis suggests that the issue of paresthesia concordancy may be central, both in explaining the data, as well as providing direction for future endeavors. Therefore, while at present peripheral neurostimulation is gaining increasing acceptance as a treatment for chronic headaches, the precise clinical indications and procedures, as well as the underlying neurophysiological mechanisms, are still being worked out.

Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: results from a randomized, multicenter, double-blinded, controlled study.

BACKGROUND: Chronic migraine (CM) is a debilitating neurological disorder with few treatment options. Peripheral nerve stimulation (PNS) of the occipital nerves is a potentially promising therapy for CM patients. METHODS: In this randomized, controlled multicenter study, patients diagnosed with CM were implanted with a neurostimulation device near the occipital nerves and randomized 2:1 to active (n = 105) or sham (n = 52) stimulation. The primary endpoint was a difference in the percentage of responders (defined as patients that achieved a ≥50% reduction in mean daily visual analog scale scores) in each group at 12 weeks. RESULTS: There was not a significant difference in the percentage of responders in the Active compared with the Control group (95% lower confidence bound (LCB) of -0.06; p = 0.55). However, there was a significant difference in the percentage of patients that achieved a 30% reduction (p = 0.01). Importantly, compared with sham-treated patients, there were also significant differences in reduction of number of headache days (Active Group = 6.1, baseline = 22.4; Control Group = 3.0, baseline = 20.1; p = 0.008), migraine-related disability (p = 0.001) and direct reports of pain relief (p = 0.001). The most common adverse event was persistent implant site pain. CONCLUSION: Although this study failed to meet its primary endpoint, this is the first large-scale study of PNS of the occipital nerves in CM patients that showed significant reductions in pain, headache days, and migraine-related disability. Additional controlled studies using endpoints that have recently been identified and accepted as clinically meaningful are warranted in this highly disabled patient population with a large unmet medical need. TRIAL REGISTRATION: Clinical trials.gov (NCT00615342).

Sorption of unoprostone isopropyl to packaging materials.

This study investigated the stability of an ophthalmic solution formulation of unoprostone isopropyl (UI), a prostaglandin like compound, in two types of packaging materials, polypropylene (PP) and low-density polyethylene (LDPE). We determined the concentration of UI and its degradation products as a function of time and found that the rate of disappearance of drug was faster for the formulation stored in LDPE bottles than that stored in PP bottles. Further studies indicated that the inferior stability observed with the LDPE packaging was primarily due to the sorption of UI to the packaging material and to a lesser degree, chemical degradation. The sorption was temperature dependent, lowering the temperature reduced the sorption, thus improving the shelf-life of the product.

Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double-blind, crossover trial.

Amitriptyline (AT) relieves some patients with postherpetic neuralgia (PHN). Many patients suffer side effects and better therapies are necessary. The aim of this study was to evaluate the efficacy of maprotiline (MT) (noradrenergic) compared to AT (mixed noradrenergic and serotonergic) in this disorder. Thirty-five patients entered a randomized, double-blind, crossover trial of these two agents. We found that MT relieved PHN in many patients but was not as effective as AT. Side effects were troublesome with both agents. Relief of steady pain, brief pain and pain on tactile stimulation occurred. Four groups of responses were identified. Some patients reported relief with both agents, some with neither agent and others with only one of the drugs. Most patients were not depressed and analgesia was observed to occur without change in depression ratings in most patients who responded. This result provides evidence that in some patients AT may act via a selective noradrenergic mechanism in relieving PHN and that individuals may differ in the balance and type of neurotransmitters inhibiting pain. Selective noradrenergic agents may be effective if AT fails.