Pilot study evaluating treatment with sumatriptan for moderate to severe post-traumatic headache: A phase 2 open-label study.

OBJECTIVE: Our primary outcome was to determine the feasibility of patients with post-traumatic headache (PTH) keeping a daily headache diary and using sumatriptan as directed. Secondary outcomes include determining if sumatriptan is effective in aborting PTH and whether headache resolution is dependent on PTH phenotype. BACKGROUND: PTH is prevalent and persistent after traumatic brain injury, yet there have been few studies evaluating the effects of pharmacological treatments in individuals with PTH. METHODS: This is a single-arm, prospective, non-randomized phase 2 clinical trial registered at Clinicaltrials.gov (NCT01854385) and conducted from 2013 to 2017. Data analysis was completed in 2022. Of the 299 participants screened, 40 were enrolled in the study. Participants kept a headache diary documenting headache characteristics and severity. Headache characteristics were used to determine PTH phenotypes of migraine-like, probable migraine-like, or non-migraine-like. Participants reported whether sumatriptan was used for their headache, their response to the medication, if a second dose was taken, and their response to the second dose. RESULTS: A total of 15 participants out of the 40 enrolled (mean [SD] age, 41.9 [14.2] years, and 53% [21/40] male), met the criteria for the use of sumatriptan, and completed all assessments. Average headache diary compliance rate for the final month of the study was 80% (372/465). While sumatriptan was used for only 19% (122/654) of all reported headaches, 72% (88/122) of those headaches resolved within 2 h of taking the medication. Resolution of headaches with sumatriptan was not significantly different among headache phenotypes (migraine-like: 22/38 [58%], probable migraine-like: 24/29 [83%], non-migraine-like: 6/15 [40%]; p = 0.154). CONCLUSIONS: A daily headache diary is feasible for tracking headache symptoms. Preliminary results also suggest that sumatriptan, a migraine-specific medication, may be beneficial for the treatment of PTH of different clinical phenotypes. Future studies, such as a phase 3 clinical trial with a larger sample size, are needed to better understand the efficacy of sumatriptan in the treatment of PTH.

Postinjury Alcohol Use Is Associated With Prolonged Recovery After Concussion in NCAA Athletes.

OBJECTIVE: To determine whether alcohol use leads to prolonged clinical recovery or increased severity of concussion symptoms in National Collegiate Athletic Association (NCAA) athletes. DESIGN: Prospective observational study. SETTING: Clinical institutions. PARTICIPANTS: Athletes from the NCAA Concussion Assessment Research and Education consortium who sustained a concussion from 2014 to 2021. INTERVENTIONS: Athletes were divided into 2 groups, those reporting alcohol use postinjury and those reporting no alcohol use postinjury. MAIN OUTCOME MEASURES: Symptom recovery was evaluated as time (in days) from injury to clearance to return to unrestricted play (days until URTP). Severity of concussion symptoms was assessed using the Standardized Sport Concussion Assessment Tool (SCAT3) symptom severity, headache severity, difficulty concentrating, and difficulty remembering scores. These scores were taken a median of 6.6 [interquartile range (IQR) = 4.0-10] and 6 (IQR = 4.0-9.0) days after injury for those who did and did not consume alcohol postinjury respectively and compared with baseline SCAT3 scores. RESULTS: Four hundred eighty four athletes from the data set had complete data for exposure and outcome. The adjusted mean number of days until URTP for athletes reporting alcohol use postinjury [23.3; 95% confidence interval (CI), 20.0-27.2; days] was incidence rate ratio (IRR) 1.32 (95% CI, 1.12-1.55; P < 0.001) times higher than for athletes who reported no alcohol use postinjury [17.7 (95% CI, 16.1-19.3) days]. Postinjury alcohol was not associated with severity of concussion symptoms ( P 's < 0.05). CONCLUSION: Self-reported postinjury alcohol use is associated with prolonged recovery but not severity of concussion symptoms in collegiate athletes. This may inform future clinical recommendations regarding alcohol consumption after concussion.

Longitudinal follow-up of biopsy-proven small fiber neuropathy.

INTRODUCTION: Little is published on the prognosis of small fiber neuropathy (SFN). METHODS: A retrospective analysis of 101 patients with biopsy proven SFN. RESULTS: Study participants included 87 patients with length-dependent SFN and 14 patients with non-length-dependent SFN. The average duration of symptoms was 3.2 years prior to SFN diagnosis, and the average follow-up duration after diagnosis was 6.2 years. Neuropathic pain was present in 98% of patients and in 84.2% of patients at the final visit. The average total number of pain medications ever used was 4.4 per patient. Signs of autonomic dysfunction were initially present in 24.8% of patients, but improved in most. Large fiber involvement was seen in 11.9% of patients. Small fiber neuropathy affected employment and ambulation status in 5.3% and 6.3% of patients, respectively. DISCUSSION: Small fiber neuropathy tends to be stable and rarely affects ambulation and employment status. Effective pain control remains a challenge.

Common Primary and Secondary Causes of Headache in the Elderly.

OBJECTIVE/BACKGROUND: Headache in the elderly, defined as individuals aged 65 and older, although less prevalent than younger individuals, can present as a diagnostic challenge, given the increase in potentially fatal diseases within this population. METHODS: These individuals require a complete history, neurological examination, and assessment of potential secondary causes of headaches. RESULTS: Secondary causes include temporal or giant cell arteritis, subdural hematomas, central nervous system (CNS) tumors, strokes, and CNS infections. Once secondary conditions are ruled out, then primary causes of headache are considered such as tension-type headache, migraine, cluster headache, or hypnic headache. CONCLUSION: This article reviews the distinguishing characteristics of the most common types of headache in patients over the age of 65 years old, along with potential diagnostic tests and treatment.

Intravascular T-cell lymphoma: A rare, poorly characterized entity with cytotoxic phenotype.

Intravascular T-cell lymphomas are rare, poorly characterized lesions. We discuss the clinical, radiologic and especially the laboratory characteristics of a lesion which presented in a 62-year-old woman with a history of progressive CNS abnormalities. Throughout the course of the disease, radiologic findings consisted mainly of multifocal mixed areas of ischemia and vasogenic edema involving cortical and subcortical regions. A brain biopsy identified an abnormal T-cell population confined to lumens of vessels. These T-cells were abnormal cytotoxic cells, positive for CD3, CD8, and negative for CD2, CD4, CD5, CD7 and CD30. While flow cytometry and immunohistochemistry failed to identify a similar population in the blood or bone marrow, molecular studies showed a clonal T-cell population in both the brain and the bone marrow. No other organs were involved. In spite of aggressive treatment, the patient's medical condition continued to progress and she passed away. In conclusion, this abnormal population of cytotoxic T-cells with intravascular localization probably represents a specific type of T-cell lymphoma with specific clinical, radiologic, molecular and immunophenotypic characteristics.

Cerebrospinal fluid phospholipase C activity increases in migraine.

BACKGROUND: Adrenaline, serotonin, cannabinoid and estrogen receptors are involved in migraine pathophysiology. The signaling of these receptors change phosphatidylcholine-specific phospholipase C (PC-PLC) activity, but there have been no reported PC-PLC studies in migraine. METHODS: We identified PC-PLC activity in blood and cerebrospinal fluid (CSF), and quantified it in samples from ictal and interictal migraineurs without aura and healthy controls. RESULTS: Pre-incubation with a specific PC-PLC inhibitor, D609, inhibited enzyme activity (p < .0001) and confirms its presence in CSF. PC-PLC activity was higher in the CSF from ictal migraineurs compared to controls (mean relative fluorescence unit [RFU]/µg/min [standard deviation, SD] 13.1 [3.07] vs. 9.3 [1.97]; p = .002) and, in a paired analysis, in migraineurs during ictal compared to interictal states (11.7 [1.6] vs. 7.9 [1.5]; p = .02). CSF PC-PLC activity in the ictal state correlated negatively with migraine frequency (r = -0.82). Plasma PC-PLC activity was 250-300 times less than in CSF and did not increase in migraine, implicating the brain as the source of the CSF enzyme changes. CONCLUSION: This is the first report of PC-PLC activity in CSF and of its alteration in migraine. We propose that these PC-PLC changes in CSF reflect the overall receptor fluctuations in migraine.

Flying After Concussion and Symptom Recovery in College Athletes and Military Cadets.

Importance: Concussions are a common occurrence in young athletes. Hypobaric hypoxemia, such as that experienced during airplane travel, can potentially cause alterations to cerebral blood flow and increased neuroinflammatory response. It remains unknown whether flying early after a concussion may influence the clinical course of injury. Objective: To determine whether there is an association between concussion recovery and airplane travel in collegiate athletes and military cadets. Design, Setting, and Participants: This cohort study was conducted by the National Collegiate Athletic Association and US Department of Defense Concussion Assessment, Research, and Education Consortium from August 3, 2014, to September 13, 2018. Participant groups were categorized by those who flew within 72 hours of injury and those who did not fly. All participants included in the final analyses had complete data of interest and only 1 injury during the study. Data analysis was performed from September 2018 to March 2020. Main Outcomes and Measures: Recovery outcome measures were defined as time (in days) from injury to return to activity, school, and baseline symptoms. Symptom and headache severity scores were derived from the Sports Concussion Assessment Tool-Third Edition. Scores for both groups were taken at baseline and a median of 2 days after injury. Results: A total of 92 participants who flew (mean [SD] age, 19.1 [1.2] years; 55 male [59.8%]) and 1383 participants who did not fly (mean [SD] age, 18.9 [1.3] years; 809 male [58.5%]) were included in the analysis of symptom recovery outcomes (analysis 1). Similarly, 100 participants who flew (mean [SD] age, 19.2 [1.2] years; 63 male [63.0%]) and 1577 participants who did not fly (mean [SD] age, 18.9 [1.3] years; 916 male [58.1%]) were included in the analysis of symptom severity outcomes (analysis 2). No significant group differences were found regarding recovery outcome measures. Likewise, there were no group differences in symptom (estimated mean difference, 0.029; 95% CI, -0.083 to 0.144; P = .67) or headache (estimated mean difference, -0.007; 95% CI, -0.094 to 0.081; P = .91) severity scores. Conclusions and Relevance: Airplane travel early after concussion was not associated with recovery or severity of concussion symptoms. These findings may help guide future recommendations on flight travel after concussion in athletes.