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ObjectiveHow responsive neurostimulation (RNS) decreases seizure frequency is unclear. Stimulation may alter epileptic networks during inter-ictal epochs. Since fast ripples (FR) may be a substrate of the epileptic network, we examined whether stimulation of FR generating networks differed in RNS super- and intermediate-responders.MethodsIn 10 patients, we detected FR during sleep from stereo EEG (SEEG) contacts during the pre-surgical evaluation in patients with subsequent RNS placement. The normalized coordinates of the SEEG contacts were compared with that of the eight RNS contacts, and RNS stimulated SEEG contacts were defined as within 1.5 cm3of the RNS contacts. We compared the post-RNS placement seizure outcome to 1) the ratio of stimulated SEEG contacts in the seizure-onset zone (SOZ SR); 2) the ratio of FR events on stimulated contacts (FR SR); and 3) the global efficiency of the FR temporal correlational network on stimulated contacts (FR SGe).ResultsWe found that the SOZ SR (p=0.18) and FR SR (p=0.06) did not differ in the RNS super- and intermediate-responders, but the FR SGe did (p=0.02). In super-responders highly active desynchronous sites of the FR network were stimulated.SignificanceRNS that better targets FR networks, as compared to the SOZ, may reduce epileptogenicity more.Short summaryResponsive neurostimulation (RNS) may reduce seizures by altering the epileptic network. Fast ripples (FR) may be a substrate of the epileptic network. We investigated, in 10 patients, if RNS stimulation of FR generating brain differed in RNS super-responders and intermediate-responders. The RNS stimulated brain sites were defined as contacts in the pre-surgical stereo EEG implant within 1.5 cm3of the subsequently placed RNS stimulation contacts. FR events were more highly active and temporally desynchronous (p

This article is about one of the world’s most celebrated structures — the Brooklyn Bridge: what makes it beautiful, and why it has been loved by millions of people. It is based on this landmark principle, stated by Eli Siegel — poet, critic, and founder of the philosophy Aesthetic Realism: “All beauty is a making one of opposites, and the making one of opposites is what we are going after in ourselves.” Beginning with the effect of this bridge on such artists and poets as Joseph Stella and Hart Crane, it then describes each step of the design and construction of this magnifi cent structure, showing how the making one of opposites — Power and Grace, Heaviness and Lightness, Firmness and Flexibility, Simplicity and Complexity — is what makes it a great work of both engineering and art. For example, in Bridges and Their Builders, Steinman and Watson write: “The pierced granite towers, the graceful arc of the main cables, the gossamer network of lighter cables, and the arched line of the roadway combine to produce a matchless composition, expressing the harmonious union of power and grace”. Doesn’t every person want to be at once strong and graceful? The authors describe how, as people are affected by the beautiful sensible relation of opposing forces working together for one purpose in the Brooklyn Bridge, they feel more hopeful that these same opposites can make sense in their own lives.

ObjectiveTo update the 2004 American Academy of Neurology guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs).Methods2004 criteria were used to systemically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength.ResultsForty-two articles were included.RecommendationsThe following are established as effective to reduce seizure frequency (Level A): immediate-release pregabalin and perampanel for TR adult focal epilepsy (TRAFE); vigabatrin for TRAFE (not first-line treatment); rufinamide for Lennox-Gastaut syndrome (LGS) (add-on therapy). The following should be considered to decrease seizure frequency (Level B): lacosamide, eslicarbazepine, and extended-release topiramate for TRAFE (ezogabine production discontinued); immediate- and extended-release lamotrigine for generalized epilepsy with TR generalized tonic-clonic (GTC) seizures in adults; levetiracetam (add-on therapy) for TR childhood focal epilepsy (TRCFE) (1 month–16 years), TR GTC seizures, and TR juvenile myoclonic epilepsy; clobazam for LGS (add-on therapy); zonisamide for TRCFE (6–17 years); oxcarbazepine for TRCFE (1 month–4 years). The text presents Level C recommendations. AED selection depends on seizure/syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. This evidence-based assessment informs AED prescription guidelines for TR epilepsy and indicates seizure types and syndromes needing more evidence. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years of age and perampanel as monotherapy received FDA approval.

Objective: To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy (GE) with second- and third-generation antiepileptic drugs (AEDs). Methods: The 2004 AAN criteria was used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic–clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. Recommendations: Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years with new-onset focal epilepsy. Unless there are compelling adverse-effect–related concerns, ethosuximide (ETS) or valproic acid (VPA) should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (Level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.

Migraine is a common and intermittently disabling condition with a myriad of clinical presentations. A detailed understanding of the neurovascular pathology of migraine has translated into effective strategies for both prevention as well as acute treatment; however, knowledge of the varied presentations is necessary for accurate diagnosis and optimal use of treatment. Treatment may include both acute and preventative interventions and options that span lifestyle modification, nonprescriptive supplements, prescription medications, and other interventions.

Librarians working in clinical settings are challenged by clinicians’ lack of time for nonessential reading. At Pennsylvania Hospital, partnership between the clinical librarian and a senior physician resulted in an e-newsletter. After initially distributing via e-mail only, Dreamweaver was used to create an archive of past issues, and all subsequent issues were produced as HTML versions for instant archiving. The newsletter aims to provide medicine residents, faculty, medical school students, and other members of the Penn Medicine community with hand-selected educational reading material from both popular and scholarly sources. The ultimate goal is to encourage good reading habits for lifelong and professional learning.

A 67 year old female presented with generalized weakness, falls and recurrent high grade fevers for 5 - 6 weeks. Physical findings included high grade temperature, lower extremity weakness and diminished reflexes. An extensive work-up for fever of unknown origin (FUO), including PET-FDG scan, did not yield any occult infectious or neoplastic process. Ultimately a temporal artery biopsy was planned to rule out temporal arteritis. The histopathology of temporal artery was normal while the vein showed lymphoid proliferation consistent with Angiotropic large cell lymphoma (ALCL).

Musicogenic epilepsy, which is a form of reflex epilepsy, is characterized by the triggering of epileptic seizures by specific music experiences. Individuals with musicogenic epilepsy differ in the music trigger, but may have similar seizures. Typically, these seizures are focal dyscognitive and have a temporal-lobe origin with a limbic system distribution. As such, the music trigger is likely related to either an emotional or memory aspect of music perception. Investigations into musicogenic epilepsy may lead to a better understanding of seizure propagation within the brain and of neurologic aspects of the music experience. Successful treatment of medication-resistant musicogenic epilepsy has been achieved with anterior temporal-lobe resection.

To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies.A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003.Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking.The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Intravesical instillation of Bacillus Calmette-Guerin for the treatment of bladder carcinoma uncommonly causes miliary tuberculosis. We describe a case of pulmonary tuberculosis caused by BCG immunotherapy and review of 11 cases of miliary tuberculosis related to this form of treatment previously reported in the literature.

Infection of arterial reconstructions is associated with high rates of mortality and limb loss despite optimal treatment. Lower extremity revascularization procedures performed at a teaching hospital were reviewed to identify risk factors associated with wound infection. Medical records, postoperative infection surveillance forms, and a computerized vascular registry for lower extremity revascularizations involving a common femoral or more distal artery during a 3-year period were reviewed. There were 335 bypass operations (184 femoral-distal, 36 popliteal-distal, 17 aortofemoral, 13 femorofemoral, 11 axillofemoral, 74 graft revisions) and 30 other vascular procedures (arterial thrombectomy or endarterectomy). Factors analyzed included age, gender, diabetes mellitus, dialysis dependence, malnutrition, obesity, ipsilateral foot ulcer or gangrene, separate admissions within the month preceding surgery, length of hospital stay before surgery, length of operation, wound hematoma requiring reoperation, vein or prosthetic grafts, or redo surgery. Risk factors commonly thought to increase wound infection following lower extremity revascularizations, such as diabetes, obesity, renal failure, redo surgery, and prosthetic grafts, did not predict this complication in this series. Given the correlation of operative time with infection, efforts to minimize operative time by "double-teaming" staff participation in teaching cases may decrease infection rates, although this is speculative. Vascular services should institute strategies to ensure that appropriate prophylactic antibiotics are administered in a timely fashion before lower extremity revascularizations.

We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy.Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation.One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events.Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

Acyclovir-resistant herpes simplex virus (HSV) has become increasingly common, particularly among patients with human immunodeficiency virus (HIV). We present a case of acyclovir-resistant HSV treated with intralesional cidofovir.

This project seeks to develop superior new methods to monitor human alertness and fatigue in real time, using a suite of unobtrusive sensors and algorithms to assess and predict human behavioral capabilities.

A significant percentage of human immunodeficiency virus type 1 (HIV-1)-infected persons treated with highly active antiretroviral therapy (HAART) will develop plasma HIV-1-specific virion RNA levels

We report an unusual complication of oral-gastric lavage in a drug overdose patient. During the lavage procedure, the oral-gastric tube became impacted in the esophagus. Forceful removal of the tube resulted in an esophageal tear. The patient did well with conservative management and was discharged with no long-term sequelae.