Faculty Bibliography

BACKGROUND:Posttraumatic stress disorder (PTSD) is both prevalent and debilitating. While deep transcranial magnetic stimulation (dTMS) has shown preliminary efficacy, exposure therapy remains the most efficacious, though limited, treatment in PTSD. The medial prefrontal cortex (mPFC) is implicated in extinction learning, suggesting that concurrent mPFC stimulation may enhance exposure therapy. In this randomized controlled multicenter trial, the efficacy and safety of mPFC dTMS combined with a brief exposure procedure were studied in patients with PTSD. METHODS:Immediately following exposure to their trauma narrative, 125 outpatients were randomly assigned to receive dTMS or sham. Twelve sessions were administered over 4 weeks, with a primary end point of change in 5-week Clinician-Administered PTSD Scale for DSM-5 score. This clinical study did not include biological markers. RESULTS:Clinician-Administered PTSD Scale for DSM-5 score improved significantly in both groups at 5 weeks, though the improvement was smaller in the dTMS group (16.32) compared with the sham group (20.52; p = .027). At 9 weeks, improvement continued in Clinician-Administered PTSD Scale for DSM-5 score in both groups but remained smaller in dTMS (19.0) versus sham (24.4; p = .024). CONCLUSIONS:Both groups showed significant PTSD symptom improvement, possibly from the brief script-driven imagery exposure. While our design was unable to rule out placebo effects, the magnitude and durability of improvement suggest that repeated ultrabrief exposure therapy alone may be an effective treatment for PTSD, warranting additional study. The surprising and unexpected effect in the dTMS group also suggests that repeated mPFC stimulation with the H7 coil may interfere with trauma memory-mediated extinction. Our results provide new insight for dTMS approaches for possible future avenues to treat PTSD.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help to treat addictions, but evaluation in multicenter randomized controlled trials (RCTs) is needed. We conducted a multicenter double-blind RCT in 262 chronic smokers meeting DSM-5 criteria for tobacco use disorder, who had made at least one prior failed attempt to quit, with 68% having made at least three failed attempts. They received three weeks of daily bilat-eral active or sham rTMS to the lateral prefrontal and insular cortices, followed by once weekly rTMS for three weeks. Each rTMS session was administered following a cue-induced craving procedure, and participants were monitored for a total of six weeks. Those in abstinence were monitored for additional 12 weeks. The primary outcome measure was the four-week continuous quit rate (CQR) until Week 18 in the intent-to-treat efficacy set, as determined by daily smoking diaries and verified by urine cotinine measures. The trial was registered at ClinicalTrials.gov (NCT02126124). In the intent-to-treat analysis set (N=234), the CQR until Week 18 was 19.4% following active and 8.7% following sham rTMS (X² =5.655, p=0.017). Among completers (N=169), the CQR until Week 18 was 28.0% and 11.7%, respectively (X² =7.219, p=0.007). The reduction in cigarette consumption and craving was significantly greater in the active than the sham group as early as two weeks into treatment. This study establishes a safe treatment protocol that promotes smoking cessation by stimulating relevant brain circuits. It represents the first large multicenter RCT of brain stimulation in addiction medicine, and has led to the first clearance by the US Food and Drug Administration for rTMS as an aid in smok-ing cessation for adults.

We report two cases of a previously unrecognized clinical entity: concurrent adenoviral and herpetic ocular infection. The first case was recognized clinically by the presence of herpetic keratitis and findings attributable to epidemic keratoconjunctivitis (EKC) including lid swelling, pseudomembranous and follicular conjunctivitis, subconjunctival hemorrhages, preauricular lymphadenopathy, and corneal infiltrates. Only Herpes simplex virus was recovered by culture. In the second case of apparent EKC (again initially only Herpes simplex was isolated) after maintaining virus cultures long enough to isolate adenovirus, the diagnosis of concurrent infection was established when the second virus was isolated

The various surgical managements of herpes simplex keratitis are listed. Our management is 'atraumatic' keratoplasty, if vision is reduced, if the disease is protracted, or if perforation occurs. Our preoperative care is aimed at the production of a quiet eye with no active virus infection, by the use of antiviral drops, steroids, antibiotics, and bandage contact lenses. Removal of all corneal disease is desirable, but not mandatory. Perforations are managed in the same manner, but the host window is started at the perforation. Postoperative management is characterized by the use of therapeutic modalities necessary to prevent or treat complications, including steroids and frequent observation to check for complications of treatment. Our understanding of herpes simplex virus infections as they relate to surgical management is presented. The results of treatment warrant continuation of our efforts--but lead to the conclusion that it would be most helpful if latent virus infection could be eradicated