Neurological phenotypes and treatment outcomes in Eagle syndrome: systematic review and meta-analysis.

Background: Eagle syndrome is caused by an elongated styloid process affecting carotid arteries and cranial nerves. Pain, dysphagia, tinnitus, paresthesia (classic subtype), and neurovascular events (vascular subtype) may be triggered by head movements or arise spontaneously. However, Eagle syndrome remains underappreciated in the neurological community. We aimed to determine the most common neurological and non-neurological clinical presentations in patients with Eagle syndrome and to assess the clinical outcome post-surgical resection in comparison to non-surgical therapies. Methodology: We conducted a systematic review of patient-level data on adults with Eagle syndrome, following PRISMA guidelines. We extracted data on demographics, presenting symptoms, neurological deficits, radiological findings, and treatments, including outcomes and complications, from studies in multiple indexing databases published between 2000 and 2023. The study protocol is registered with PROSPERO. Results: In total, 285 studies met inclusion criteria, including 497 patients with Eagle syndrome (mean age 47.3 years; 49.8% female). Classical Eagle (370 patients, 74.5%) was more frequent than vascular Eagle syndrome (117 patients, 23.5%, p < 0.0001). Six patients (1.2%) presented with both variants and the subvariant for four patients (0.8%) was unknown. There was a male preponderance (70.1% male) in the vascular subtype. A history of tonsillectomy was more frequent in classic (48/153 cases) than in vascular (2/33 cases) Eagle syndrome (Odds Ratio 5.2, 95% CI [1.2-22.4]; p = 0.028). By contrast, cervical movements as trigger factors were more prevalent in vascular (12/33 cases) than in classic (7/153 cases) Eagle syndrome (Odds Ratio 7.95, 95% CI [2.9-21.7]; p = 0.0001). Headache and Horner syndrome were more frequent in vascular Eagle syndrome and dysphagia and neck pain more prominent in classic Eagle syndrome (all p < 0.01). Surgically treated patients achieved overall better outcomes than medically treated ones: Eighty-one (65.9%) of 123 medically treated patients experienced improvement or complete resolution, while the same applied to 313 (97.8%) of 320 surgical patients (Odds Ratio 1.49, 95% CI [1.1-2.0]; p = 0.016). Conclusions: Eagle syndrome is underdiagnosed with potentially serious neurovascular complications, including ischemic stroke. Surgical treatment achieves better outcomes than conservative management. Although traditionally the domain of otorhinolaryngologist, neurologist should include this syndrome in differential diagnostic considerations because of the varied neurological presentations that are amenable to effective treatment.

Brimonidine eye drops reveal diminished sympathetic pupillary tone in comatose patients with brain injury.

BACKGROUND: There is an urgent need for easy-to-perform bedside measures to detect residual consciousness in clinically unresponsive patients with acute brain injury. Interestingly, the sympathetic control of pupil size is thought to be lost in states of unconsciousness. We therefore hypothesized that administration of brimonidine (an alpha-2-adrenergic agonist) eye drops into one eye should produce a pharmacologic Horner's syndrome if the clinically unresponsive patient is conscious, but not if the patient is unconscious. Here, in a first step to explore this hypothesis, we investigated the potential of brimonidine eye drops to distinguish preserved sympathetic pupillary function in awake volunteers from impairment of sympathetic tone in patients in a coma. METHODS: We enrolled comatose patients admitted for acute brain injury to one of the intensive care units (ICU) of a tertiary referral center, in whom EEG and/or neuroimaging for all practical purposes had ruled out residual consciousness. Exclusion criteria were deep sedation, medications with known drug interactions with brimonidine, and a history of eye disease. Age- and sex-matched healthy and awake volunteers served as controls. We measured pupils of both eyes, under scotopic conditions, at baseline and five times 5-120 min after administering brimonidine into the right eye, using automated pupillometry. Primary outcomes were miosis and anisocoria at the individual and group levels. RESULTS: We included 15 comatose ICU patients (seven women, mean age 59 ± 13.8 years) and 15 controls (seven women, mean age 55 ± 16.3 years). At 30 min, miosis and anisocoria were seen in all 15 controls (mean difference between the brimonidine-treated pupil and the control pupil: - 1.31 mm, 95% CI [- 1.51; - 1.11], p < 0.001), but in none (p < 0.001) of the 15 ICU patients (mean difference: 0.09 mm, 95% CI [- 0.12;0.30], p > 0.99). This effect was unchanged after 120 min and remained robust in sensitivity analyses correcting for baseline pupil size, age, and room illuminance. CONCLUSION: In this proof-of-principle study, brimonidine eye drops produced anisocoria in awake volunteers but not in comatose patients with brain injury. This suggests that automated pupillometry after administration of brimonidine can distinguish between the extremes of the spectrum of consciousness (i.e., fully conscious vs. deeply comatose). A larger study testing the "intermediate zone" of disorders of consciousness in the ICU seems warranted.

Nusinersen treatment of spinal muscular atrophy - a systematic review.

INTRODUCTION: 5q spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by insufficient survival motor neuron protein. Untreated SMA involves death or permanent respiratory support (type 1), inability to walk (type 2) or ability to walk (type 3). The incidence of SMA is 1 in 7,500 live births, equivalant to eight children being born with SMA in Denmark annually. METHODS: We undertook a systematic review of the efficacy of nusinersen as SMA treatment. We included randomised controlled trials and cohort studies. Our primary endpoints were survival without permanent respiratory support and change in motor function. RESULTS: We identified 658 articles and included 13 of these (two randomised controlled trials and 11 cohort studies). Nusinersen increased survival without permanent respiratory support in SMA type 1 and increased motor function development in types 1-3. Nusinersen treatment before symptom onset in children with presymptomatic SMA produced near-normal motor development. So far, nusinersen has only minor safety concerns mostly related to the lumbar puncture. CONCLUSIONS: Nusinersen increased survival without permanent ventilatory support in children with SMA type 1. Improvements in SMA type 2 and 3 were less evident. Better outcomes were seen in young children with a short disease duration, particularly in children receiving nusinersen before symptom onset. Newborn SMA screening may facilitate presymptomatic treatment with splice modification (nusinersen, risdiplam) or gene implantation therapy (AVXS-101, zolgensma).