Deep Brain Stimulation as a Treatment for Refractory Epilepsy: Review of the Current State-of-the-Art.

Epilepsy affects ∼ 1% of the global population, and 33% of patients are nonresponsive to medication and must seek alternative treatment options. Alternative options such as surgery and ablation exist but are not appropriate treatment plans for some patients. Neurostimulation methods such as vagal nerve stimulation, responsive neural stimulation, and deep brain stimulation (DBS) are viable alternatives for medically refractory patients. DBS stimulation has been used in the treatment of Parkinson's disease, dystonia, and pain management. For the treatment of epilepsy, DBS has been found to be an effective treatment plan, with promising results of reduced seizure frequency and intensity. In this review, we discuss DBS surgery and equipment, mechanisms of DBS for epilepsy, and efficacy, technological specifications, and suggestions for future research. We also review a historical summary of experiments involving DBS for epilepsy. Our literature review suggests that further studies are warranted for medically refractory epilepsy using DBS.

Electrostimulation for Refractory Epilepsy: A Review.

Epilepsy is a neurological disorder that has been diagnosed in approximately 1% of the world's population. In North America alone, more than 3 million individuals suffer from epilepsy. Antiepileptic drugs are not fully effective in some patients, and most drugs have adverse side effects. Recently, several stimulation techniques (responsive neural, vagal nerve, transcranial magnetic, and deep brain) have been used as adjunct therapies to treat medically refractive seizures. Since its Food and Drug Administration approval in 2013, responsive neural stimulation (RNS), a closed-loop electrical stimulation system, has emerged as a potential therapeutic alternative to treat patients with epilepsy (PWE). RNS consists of a cranially implantable neurostimulator that sends electrical pulses using depth electrodes to epileptic foci/focus after the device senses irregular electrical activity, thus avoiding the onset of a seizure. In a long-term study that lasted 7 yr and involved more than 245 patients using RNS, results showed that16% of patients were seizure free, 60% had 50% or greater seizure reduction, and 84% had some improvement. Quality of life improved in 44% of the patients by the end of the second year. There is a need for more, larger, well-designed, randomized, controlled trials to validate and optimize efficacy and safety of invasive intracranial neurostimulation treatments in PWE. This article highlights the effects of treating patients with medically refractive seizures using RNS.

Transcranial Magnetic Stimulation in Migraine: A New Therapy and New Insights into Pathogenesis.

Transcranial magnetic stimulation (TMS) was first found to be effective in acute migraine 12 years ago, and subsequent studies have confirmed this benefit in approximately two -thirds of treated patients. High response rate, ease of application, and freedom from adverse effects combine to make TMS a natural front-line treatment for migraine, and its use should therefore be encouraged. In relation to the pathogenesis of migraine, the prompt relief of symptoms often observed with TMS is considered incompatible with an underlying neuroinflammatory process and with spreading depression as a cause of aura. Instead, the available evidence points to hyperexcitability of cortical neurons as the immediate cause of headache and any associated symptoms, although the factor(s) leading up to the hyperexcitability remain unclear.

The Migraine Aura: A Problem for Vision Theory?

The scintillating zigzag pattern that a migraine patient may see as an illusion before the onset of headache offers a unique investigative approach to visual mechanisms. The likeliest interpretation of these zigzags is that they are the spontaneous discharges of the orientation-selective neurons first described in the striate cortex by Hubel and Wiesel (Hubel DH, Wiesel TN. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J Physiol (Lond). 1962 Jan;160:106-54; and Hubel DH, Wiesel TN. Receptive fields and functional architecture of monkey striate cortex. J Physiol (London). 1968 Mar;195(1):215-43). Although these cells appear to lie in rows in V1, as Hubel and Wiesel found, very few angles in the visual field are represented; this, and the coarseness of the representation, makes it unlikely that the cells act as feature detectors. The orientation-selective cells could, however, monitor the amount of light falling on the retina and thereby enable color constancy to be achieved. The cells may also serve as coarse movement detectors. The new model of cell organization in human V1 enables us to determine the approximate sizes of the receptive fields of the orientation-selective cells.

Air Pollution's Effects on the Human Respiratory System.

The World Health Organization defines air pollution as "any chemical, physical or biological agent that modifies the natural characteristics of the atmosphere." The most common pollutants include particulate matter, carbon monoxide, ozone, nitrogen oxide, and sulfur dioxide. The two types of air pollution, indoor and ambient, both contribute to a host of cardiac and respiratory illnesses. Exposure to excess levels of air pollution is significantly associated with a variety of acute and chronic respiratory illnesses, such as chronic obstructive pulmonary disease, asthma, respiratory allergies, and lung cancer. The effects of air pollution disproportionately impact the extremes of the age distribution, perhaps due to altered immune responses. Athletes and those who exercise outdoors are at greater risk for the respiratory effects of air pollution. This article discusses the epidemiology, types of respiratory diseases, and mechanisms involved in exposure to excess levels of air pollution. Biomedical engineering can contribute to the identification of air pollutants through the design of novel instrumentation using materials based on nanotechnology. Mathematical models can also be developed to characterize the physiological effects of air pollution.

Cortical spreading depression in migraine-time to reconsider? / Depressão alastrante cortical na enxaqueca – hora de reconsiderar?

New evidence concerning the pathophysiology of migraine has come from the results of therapeutic transcranial magnetic stimulation (tTMS). The instantaneous responses to single pulses applied during the aura or headache phase, together with a number of other observations, make it unlikely that cortical spreading depression is involved in migraine. tTMS is considered to act by abolishing abnormal impulse activity in cortical pyramidal neurons and a suggestion is made as to how this activity could arise.

Novas evidências referentes à fisiopatologia da enxaqueca são o resultado de estimulação magnética transcraniana terapêutica (tTMS). As respostas imediatas a pulsos simples aplicados durante as fases de aura ou de cefaleia, em associação a diversas outras observações, tornam improvável a ideia de que a depressão alastrante esteja envolvida na enxaqueca. Considera-se que tTMS tenha sua ação abolindo atividade anormal de impulsos em neurônios corticais piramidais, sugerindo que esta atividade tenha um papel desencadeante.

Cortical spreading depression in migraine-time to reconsider?

New evidence concerning the pathophysiology of migraine has come from the results of therapeutic transcranial magnetic stimulation (tTMS). The instantaneous responses to single pulses applied during the aura or headache phase, together with a number of other observations, make it unlikely that cortical spreading depression is involved in migraine. tTMS is considered to act by abolishing abnormal impulse activity in cortical pyramidal neurons and a suggestion is made as to how this activity could arise.

GERD and obesity: is the autonomic nervous system the missing link?

Gastroesophageal reflux disease (GERD) is a common chronic condition that not only impairs the quality of life of those who are affected by it but also poses a significant economic burden. It encompasses a wide spectrum of symptoms as a result of gastric content moving into the esophagus. The most common cause of GERD, other than a hiatus hernia, is considered to be transient lower esophageal sphincter relaxation. The lower esophageal sphincter (LES) normally has a higher resting tone than the stomach, thus preventing the reflux of gastric contents into the esophagus. The greater prevalence of GERD and GERD symptoms in obese individuals has generated significant interest in understanding the association between these 2 conditions and the underlying physiological mechanisms. The potential relationship between GERD and obesity and the exact mechanism by which obesity may cause reflux, however, remains uncertain. It has been proposed that patients with GERD have altered autonomic nervous function and, more specifically, have reduced parasympathetic activity. Obese individuals also have shown diminished parasympathetic activity, which may be reversed after weight reduction through exercise, diet control, and bariatric surgery. Given that contraction and relaxation of the LES are vagally mediated, the question that arises is whether the autonomic nervous system is, in fact, the missing link between obesity and GERD. In this article we examine the current evidence and hypothesize that the potential imbalance in sympathovagal stimulation to the LES is a key contributing factor to the increased prevalence of GERD symptoms in obese individuals.

Transcranial magnetic stimulation for migraine: clinical effects.

The objective was to assess the impact of transcranial magnetic stimulation (TMS) on pain and the autonomic nervous system (ANS) in migraine. Forty-two people [mean age 41.43+/-11.69 (SD) years, 36 females] were randomised into high vs. low TMS stimulation groups and received 2 brief pulses of TMS. Thirty-three (33/42) individuals had heart-rate variability assessed, before and after stimulation. No group effects were found. Pain decreased by 75%; 32% of people after 1 treatment reported no headache after 24 h. Mean heart rate decreased from 79.05+/-10.27 to 72.89+/-11.35 beats/min. The low-frequency (LF) and the high-frequency (HF) areas derived from power spectral analyses increased [mean 6522+/-1277 to 8315+/-1009 beats/min(2) (LF) (p=0.001) and mean 5600+/-1568 to 8755+/-3071 beats/min(2) (HF) (p=0.001)]. The LF:HF ratio decreased from mean 1.31+/-0.51 to 1.13+/-0.48 (NS). TMS produces immediate, sustained reductions in pain and modification of the ANS.

Optimal electrical stimulation modality for cortical esophageal evoked potentials: transmural or intraesophageal?

Esophageal electrical stimulation using short and a relatively small number of (200 micros, 0.2 Hz, n = 25) electrical pulses generates a characteristic and well defined cortical evoked potential response (EP). There are two methods of stimulation: either through intraesophageal electrodes or with transmural electrodes. The objective of this paper is to compare EP response, sensations and heart rate variability power spectra elicited by both stimulation modalities in healthy volunteers. Our results suggest that transmural stimulation is more accurately perceived and at lower intensities, produces more reproducible peaks of higher amplitude than during intraesophageal stimulation. During either mode of esophageal stimulation, power within the high-frequency component of the heart rate variability power spectrum is enhanced.

A comparison of algorithms for detection of spikes in the electroencephalogram.

Identification of the short transient waveform, called a spike, in the cortical electroencephalogram (EEG) plays an important role during diagnosis of neurological disorders such as epilepsy. It has been suggested that artificial neural networks (ANN) can be employed for spike detection in the EEG, if suitable features are provided as input to an ANN. In this paper, we explore the performance of neural network-based classifiers using features selected by algorithms suggested by four previous investigators. Of these, three algorithms model the spike by mathematical parameters and use them as features for classification while the fourth algorithm uses raw EEG to train the classifier. The objective of this paper is to examine if there is any inherent advantage to any particular set of features, subject to the condition that the same data are used for all feature selection algorithms. Our results suggest that artificial neural networks trained with features selected using any one of the above three algorithms as well as raw EEG directly fed to the ANN will yield similar results.

Laser tattoo removal.

The availability of Q-switched ruby Nd:YAG and alexandrite lasers has revolutionized the treatment of tattoos. These modalities offer significant advantages over all previously available treatments and are currently the standard of care for the cosmetic removal of unwanted tattoos.

800 nanometer diode laser hair removal in African American patients: a clinical and histologic study.

BACKGROUND: Although numerous lasers are available for laser assisted hair removal, their use in individuals with a dark skin type presents many challenges due to competition from epidermal melanin. OBJECTIVE: Our aim was to evaluate two 800 nm diode lasers (Lightsheer) with 30 msec and 100 msec pulse durations in the treatment of African American patients with skin types V and VI. Histologic studies, efficacy and side effects were examined in an effort to optimize laser hair removal procedures in this patient population. METHODS: Facial, neck and axillary areas were treated using 800 nm diode lasers at 30 and 100 msec pulse durations with fluences between 15 J/cm2 and 40 J/cm2. RESULTS: Both lasers could be used safely in skin type V and VI African American patients. Longer pulse durations enabled the delivery of higher fluences with minor and acceptable postoperative complication profiles. CONCLUSION: The Lightsheer diode laser (Coherent Medical, Santa Clara, CA, USA) operating at 30 msec and 100 msec can be safely used in hair removal procedures in African American patients.

Laser therapy of spider leg veins: clinical evaluation of a new long pulsed alexandrite laser.

BACKGROUND: The response of spider leg veins to laser or intense pulsed light therapy has generally been characterized by varying degrees of success and frequently inconsistent clinical response rates. OBJECTIVE: The purpose of this study was to examine the effectiveness of the 755 nm long pulsed infrared alexandrite (LPA) laser for the treatment of leg telangiectasias. METHODS: This study was constructed in four phases. Phase I examined 28 patients with variable sized telangiectasias using 5 treatment parameters (15 J/cm2 x 1 pulse, 20 J/cm2 x 1 pulse, 20 J/cm2 x 2 pulses, 20 J/cm2 x 3 pulses, or 30 J/cm2 x 1 pulse). Each patient received 3 treatments at 4 week intervals with the LPA. Patient diaries were obtained to examine the effects of the treatments. Subjective grading was performed at each follow-up visit by the investigators. Blinded objective grading was performed at the conclusion of the study by trained observers. Phase II examined the effects of these treatment parameters on varying vessel diameters. Vessels were grouped into small (<0.4 mm), intermediate (0.4-1.0 mm), and large (1.0-3.0 mm) subsets. Phase III examined the effects of a combination of LPA treatment followed by 23.4% hypertonic saline sclerotherapy. Subjective and blinded objective grading was used to determine improvement after a single treatment with the LPA at 20 J/cm2, single pulsed with a pulse duration of 5 or 10 msec followed by treatment with 23.4% hypertonic saline injected 3, 7, 14, or 28 days after laser therapy. Phase IV involved biopsies after LPA treatment alone at time intervals of immediately posttreatment and 5 and 21 days posttreatment. RESULTS: These evaluations revealed that the optimal treatment parameters for LPA therapy alone appeared to be 20 J/cm2, double pulsed at a repetition rate of one Hz. After 3 treatments at 4 week intervals, subjective grading indicated a 63% reduction in leg telangiectasias. Medium diameter vessels responded best with small vessel diameters responding poorly, if at all. The addition of 23.4% hypertonic saline sclerotherapy performed 3 to 7 days after laser therapy (LPA at 20 J/cm2, single pulsed with a pulse duration of 5 msec) produced 87% reduction in leg telangiectasias. Biopsies after LPA treatment revealed vessel wall endothelial cell necrosis at 5 days with fibrosis occurring at 3 weeks. The optimal clinical "window" for sclerotherapy seems to coincide with the period of endothelial cell necrosis. CONCLUSION: LPA therapy is most effective for leg telangiectasias 0.4-3.0 mm in diameter. This LPA technique is significantly improved with the addition of sclerotherapy.

Pulsed carbon dioxide and erbium-YAG laser resurfacing: a comparative clinical and histologic study.

BACKGROUND: The recent introduction of pulsed erbium-YAG (Er:YAG) laser technology has been accompanied by relatively few clinical studies with widely varying claims regarding post-operative healing, clinical side effects and efficacy. OBJECTIVE: The aim was to evaluate comparatively pulsed CO2 and Er:YAG lasers with regard to clinical side effects, post-operative healing and efficacy when equivalent depths of histologic damage were produced. METHODS: Bilateral periocular or perioral sites were treated using a pulsed CO2 laser on one side and a pulsed Er:YAG laser on the opposite side. Attempts were made to produce equivalent depths of coagulation (CO2) and ablation (erbium). RESULTS: Results showed almost equivalent post-operative healing. However, the pulsed CO2 laser proved more effective in the treatment of moderate and deep rhytids. CONCLUSION: When equivalent depths of coagulation and ablation are compared, the healing time is similar. CO2 proved to be more efficacious in the treatment of perioral and periocular rhytids.

Pulsed carbon dioxide and long pulse 10-ms erbium-YAG laser resurfacing: a comparative clinical and histologic study.

BACKGROUND: The recent introduction of pulsed erbium-YAG laser technology has been accompanied by relatively few clinical studies with widely varying claims regarding postoperative healing, clinical side-effects and efficacy. We evaluated a new long (10 ms) pulsed erbium-YAG laser in order to determine safety and clinical efficacy in comparison with a pulsed carbon dioxide laser. OBJECTIVE: Our objective was to comparatively evaluate a pulsed CO2 and long-pulsed erbium-YAG laser with regard to clinical side-effects, postoperative healing and efficacy in the reduction of rhytids. METHODS: Bilateral periocular or perioral sites were treated using a pulsed CO2 (UltraPulse) laser on one side and long-pulsed erbium-YAG laser (CO3) on the opposite side. Histologic specimens were also studied in order to compare tissue effects of both lasers. RESULTS: Results showed equivalent postoperative healing and lack of complications. In addition, the long-pulsed erbium-YAG laser showed significant efficacy in the treatment of mild and moderate rhytids. CONCLUSION: The long-pulsed (10 ms) erbium-YAG laser appears to be of significant benefit in the treatment of facial rhytids. Tissue studies show a greater degree of thermal damage in the dermis when compared to traditional 350 microseconds erbium-YAG lasers which may underlie the beneficial effects of this laser in the treatment of aging skin.

Treatment of leg telangiectasias using a long-pulse frequency-doubled neodymium:YAG laser at 532 nm.

BACKGROUND: At the present time a large variety of vascular lesion lasers are available for the treatment of both congenital and acquired disorders of blood vessels. Although most vascular lesions lasers are variably effective in the treatment of facial telangiectasias, port-wine stains, hemangiomas, and other vascular anomalies, their use in the treatment of leg veins has been disappointing. Histologic, anatomic, and other variables have been associated with a poor response of leg veins to currently available vascular lesion lasers. OBJECTIVE: This study examines the use of a new long pulse frequency-doubled Neodymium (Nd):YAG laser emitting radiation at 532 nm for the treatment of leg veins. METHODS: Fifty patients with leg telangiectasias of varying diameters were treated using a variable pulse width frequency doubled Nd:YAG laser. This laser delivers energy through a novel water-cooled chill tip, which appears to limit epidermal damage during laser treatment. RESULTS: Sixty-two treatment sites were evaluated in 50 patients. Seventy-three percent of patients had greater than 50% improvement after one treatment. Eight-three percent were graded with clearances of better than 50% after two treatments, with 63% showing greater than 75% improvement. CONCLUSION: The VersaPulse variable pulse width laser appears to be an effective modality for the treatment of leg telangiectasias. The relative lack of patient discomfort combined with a high degree of patient satisfaction may indicate a fairly high level of patient acceptance of this new form of therapy for the treatment of leg telangiectasias.