Phenytoin-induced isolated chronic, nocturnal dry cough

AbstractWe report a 72-year-old man with a four-year history of dyscognitive seizures (with occasional secondary generalization) who developed isolated, nocturnal dry cough immediately after being started on PO phenytoin. The cough was not accompanied by any other symptom or sign as his physical exam was completely normal. Further investigation with chest CT and spirometry was unremarkable. This symptom persisted for six months and did not resolve until we weaned him off of phenytoin. According to the Naranjo Adverse Drug Reaction Probability Scale, his cough was classified as being probably (score +6) related to the use of this antiepileptic drug. To our knowledge, there has been only one study that reported phenytoin-triggered cough. It described a postoperative patient who developed cough and bronchospasm after receiving IV phenytoin. By reporting our case and discussing the literature on this specific topic, we have essentially two goals. First, we intend to remind clinicians that isolated persistent cough can be an adverse reaction to phenytoin. Second, we hope to encourage further studies that will be able to elucidate the association presented herein

Cerebral Venous Thrombosis with Migraine-Like Headache and the Trigeminovascular System

Cerebral venous thrombosis- (CVT-) associated headache is considered a secondary headache, commonly presenting as intracranial hypertension headache in association with seizures and/or neurological signs. However, it can occasionally mimic migraine. We report a patient presenting with a migraine-like, CVT-related headache refractory to several medications but intravenous dihydroergotamine (DHE). The response to DHE, which is considered to be an antimigraine medication, in addition to the neurovascular nature of migraine, points out to a probable similarity between CVT-headache and migraine. Based on experimental studies, we discuss this similarity and hypothesize a trigeminovascular role in the genesis of CVT-associated headache

Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy

IMPORTANCE: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. OBJECTIVE: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. DESIGN, SETTING, AND PARTICIPANTS: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013-November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group. INTERVENTIONS: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). MAIN OUTCOMES AND MEASURES: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, -22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, -4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. RESULTS: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen and -11.2% with placebo (difference, -70.4% [95% CI, -75.2% to -65.7%]; P < .001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P < .001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P < .001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. CONCLUSIONS AND RELEVANCE: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10