The link between reversible cerebral vasoconstriction syndrome and transient global amnesia.

Reversible cerebral vasoconstriction syndrome (RCVS) and transient global amnesia (TGA) are acute and self-limiting intra-cerebral conditions. Although previously studied as independent phenomena, there are increasing reports of co-occurrence of these two pathologies. We report a 55-year-old male who presented to the hospital with recurrent thunderclap headaches over the course of 1 week with sudden onset of anterograde memory loss. His medications included a selective serotonin reuptake inhibitor and intermittent use of pseudoephedrine. On examination he was amnestic to recent events and notably perseverating. Magnetic resonance imaging of the brain without contrast showed a small, punctate focus of restricted diffusion in the left hippocampus. He was diagnosed with TGA based on his clinical presentation. His headaches and amnesia resolved over the next 12 h throughout the course of his stay with acetaminophen and oral verapamil and he was discharged. Repeat computed tomography angiogram at 2 weeks revealed diffuse and segmental narrowing of the anterior and posterior intracranial circulation, which resolved on follow-up imaging at 3 months, confirming RCVS. The acute and reversible nature of these conditions and increasing reports of co-occurrence suggests a common pathophysiologic link. We review the literature highlighting similar cases and the presumed pathophysiology.

Sex Differences in Photic Entrainment and Sensitivity to Ethanol-Induced Chronodisruption in Adult Mice After Adolescent Intermittent Ethanol Exposure.

BACKGROUND: Evidence supports a role for the circadian system in alcohol use disorders, but the impact of adolescent alcohol exposure on circadian timing later in life is unknown. Acute ethanol (EtOH) attenuates circadian photic phase-resetting in adult, but not adolescent, rodents. However, nearly all studies have focused on males and it is unknown whether this adolescent-typical insensitivity to EtOH persists into adulthood after adolescent drinking. METHODS: Circadian activity was monitored in C57BL/6J mice receiving adolescent intermittent EtOH (AIE) exposure (15% EtOH and water every other day throughout adolescence) or water alone followed by 24 days wherein EtOH was not available (washout). Mice then received a challenge dose of EtOH (1.5 g/kg, intraperitoneal) or saline 15 minutes prior to a 30-minute phase-delaying light pulse and then were released into constant darkness (DD). To control for possible phase-shifting by EtOH challenge alone, a separate group of mice underwent AIE exposure (or water-only) and washout and then received an EtOH or saline injection, but did not receive a light pulse prior to DD. RESULTS: Striking sex differences in nearly all measures of circadian photic entrainment were observed during adolescence but AIE effects were subtle and few. Only EtOH-naïve adult male mice showed attenuated photic phase-shifts with EtOH challenge, while all other groups showed normal phase-resetting responses to light. AIE-exposed females showed a persistent delay in activity offset. CONCLUSIONS: Adult male AIE-exposed mice retained adolescent-like insensitivity to EtOH-induced suppression of photic phase-resetting, suggesting AIE-induced "lock-in" of an adolescent behavioral phenotype. Adult AIE-exposed females showed delayed initiation of the rest phase. Our results also indicate that intermittent EtOH drinking has subtle effects on circadian activity in mice during adolescence that differ from previously reported effects on adult males. The observed sex differences in circadian activity, EtOH consumption and preference, and responses to EtOH challenge merit future mechanistic study.

Differential Sensitivity to Ethanol-Induced Circadian Rhythm Disruption in Adolescent and Adult Mice.

BACKGROUND: Growing evidence supports a central role for the circadian system in alcohol use disorders, but few studies have examined this relationship during adolescence. In mammals, circadian rhythms are regulated by the suprachiasmatic nucleus, a biological clock whose timing is synchronized (reset) to the environment primarily by light (photic) input. Alcohol (ethanol [EtOH]) disrupts circadian timing in part by attenuating photic phase-resetting responses in adult rodents. However, circadian rhythms change throughout life and it is not yet known whether EtOH has similar effects on circadian regulation during adolescence. METHODS: General circadian locomotor activity was monitored in male C57BL6/J mice beginning in adolescence (P27) or adulthood (P61) in a 12-hour light, 12-hour dark photocycle for ~2 weeks to establish baseline circadian activity measures. On the day of the experiment, mice received an acute injection of EtOH (1.5 g/kg, i.p.) or equal volume saline 15 minutes prior to a 30-minute light pulse at Zeitgeber Time 14 (2 hours into the dark phase) and then were released into constant darkness (DD) for ~2 weeks to assess phase-resetting responses. Control mice of each age-group received injections but no light pulse prior to DD. RESULTS: While adults showed the expected decrease in photic phase-delays induced by acute EtOH, this effect was absent in adolescent mice. Adolescents also showed baseline differences in circadian rhythmicity compared to adults, including advanced photocycle entrainment, larger photic phase-delays, a shorter free-running (endogenous) circadian period, and greater circadian rhythm amplitude. CONCLUSIONS: Collectively, our results indicate that adolescent mice are less sensitive to the effect of EtOH on circadian photic phase-resetting and that their daily activity rhythms are markedly different than those of adults.

Diagnostic Challenges of Lyme Neuroborreliosis in Inpatient Neurology: A Case Series.

Lyme disease is a multisystem disorder transmitted through the Ixodes tick and is most commonly diagnosed in northeastern and mid-Atlantic states, Wisconsin, and Minnesota, though its disease borders are expanding in the setting of climate change. Approximately 10%-15% of untreated Lyme disease cases will develop neurologic manifestations of Lyme neuroborreliosis (LNB). Due to varying presentations, LNB presents diagnostic challenges and is associated with a delay to treatment. We discuss three cases of LNB admitted to our referral center in a traditionally low-incidence state to highlight clinical pearls in LNB diagnosis. Three patients from low-incidence areas with prior diagnostic evaluations presented in August with neurologic manifestations of radiculoneuritis, cranial neuropathies, and/or lymphocytic meningitis. MRI findings included cranial nerve, nerve root, and leptomeningeal enhancement leading to broad differential diagnoses. Lumbar puncture demonstrated lymphocytic pleocytosis (range 85-753 cells/uL) and elevated protein (87-318 mg/dL). Each patient tested positive for Lyme on two-tiered serum testing and was diagnosed with LNB. All three cases were associated with a delay to health care presentation (mean 20 days) and a delay to diagnosis and treatment (mean 54 days) due to under-recognition and ongoing evaluation. With the geographic expansion of Lyme disease, increasing awareness of LNB manifestations and acquiring detailed travel histories in low-incidence areas is crucial to prompt delivery of care. Clinicians should be aware of two-tiered serum diagnostic requirements and use adjunctive studies such as lumbar puncture and MRI to eliminate other diagnoses. Treatment with an appropriate course of antibiotics leads to robust improvement in neurological symptoms.

Caffeine Delays Light-entrained Activity and Potentiates Circadian Photic Phase-resetting in Mice.

Caffeine is widely used to reduce sedation and increase alertness. However, long-term caffeine use may disrupt circadian (daily, 24-h) rhythms and thereby negatively affect health. Here, we examined the effect of caffeine on photic regulation of circadian activity rhythms in mice. We found that entrainment to a standard 12-h light, 12-h dark (LD) photocycle was delayed during oral self-administration of caffeine. Both acute, high-dose caffeine and chronic, oral caffeine exposure potentiated photic phase-delays in mice, suggesting a possible mechanism by which entrainment to LD was delayed. The effect of caffeine on photic phase-resetting was mimicked by administration of adenosine A1, but not A2A, receptor antagonist in mice. Our results support the hypothesis that caffeine interferes with the ability of the circadian clock to respond normally to light.