Outcomes of greater occipital nerve injections in pediatric patients with chronic primary headache disorders.

BACKGROUND: Chronic migraine is common in pediatrics and generally disabling. In adults, infiltration of the area around the greater occipital nerve can provide short- to medium-term benefit in some patients. This study reports the efficacy of greater occipital nerve infiltrations in pediatric patients with chronic primary headache disorders. METHODS: Retrospective chart review of patients <18 years with a chronic primary headache disorder undergoing a first-time injection. Infiltrations were unilateral and consisted of a mixture of methylprednisolone acetate, adjusted for weight, and lidocaine 2%. RESULTS: Forty-six patients were treated. Thirty-five (76%) had chronic migraine, 9 (20%) new daily persistent headache (NDPH), and 2 (4%) a chronic trigeminal autonomic cephalalgia. Medication overuse was present in 26%. Ages ranged from 7 to 17 years. Follow-up data were available for 40 (87%). Overall, 53% (21/40) benefitted, and 52% (11/21) benefitted significantly. Benefit onset ranged from 0 to 14 days, mean 4.7 (SD 4.3), with mean benefit duration of 5.4 (SD 4.9) weeks. In chronic migraine, 62% (18/29) benefitted, and 56% (10/18) significantly benefitted. In NDPH, 33% (3/9) benefitted; 33% (n = 1) significantly. Neither child with a chronic trigeminal autonomic cephalalgia benefitted. In logistic regression modeling, medication overuse, age, sex, and sensory change in the distribution of the infiltrated nerve did not predict outcome. There were no serious side effects. CONCLUSIONS: Greater occipital nerve injections benefitted 53% of pediatric patients with chronic primary headache disorders. Efficacy appeared greater in chronic migraine than NDPH. Given the benign side effect profile, a greater occipital nerve infiltration seems appropriate before more aggressive approaches.

Cranial autonomic symptoms in pediatric migraine are the rule, not the exception.

OBJECTIVE: The presence of cranial autonomic symptoms often leads to a misdiagnosis of "sinus headache" in adult migraineurs, leading to unnecessary treatments and delaying appropriate migraine therapy. In this study, we examined the frequency of cranial autonomic symptoms in pediatric/adolescent patients with migraine. METHODS: This cross-sectional study included all pediatric and adolescent patients with migraine evaluated by a single investigator at 4 different sites over the course of the study period. RESULTS: Of 125 pediatric migraineurs, 62% had at least one cranial autonomic symptom based on current International Classification of Headache Disorders, second edition (ICHD-II) criteria, and 70% based on proposed ICHD-III criteria. The majority had more than one cranial autonomic symptom and the symptoms tended to be bilateral. Age, sex, laterality of headache, presence of aura, and whether migraine was episodic vs chronic did not influence the likelihood of having cranial autonomic symptoms. CONCLUSIONS: In pediatric/adolescent migraine, the presence of cranial autonomic symptoms appears to be the rule rather than the exception. Clinicians should be careful to consider migraine when evaluating a child with headache and associated ocular or nasal symptoms so as to avoid giving a misdiagnosis of sinus headache.

Endocytic adaptors--social networking at the plasma membrane.

Receptor-mediated endocytosis is a dynamic process that is crucial for maintaining plasma membrane composition and controlling cell-signaling pathways. A variety of entry routes have evolved to ensure that the vast array of molecules on the cell surface can be differentially internalized by endocytosis. This diversity has extended to include a growing list of endocytic adaptor proteins, which are thought to initiate the internalization process. The key function of adaptors is to select the proteins that should be removed from the cell surface. Thus, they have a central role in defining the physiology of a cell. This has made the study of adaptor proteins a very active area of research that is ripe for exciting future discoveries. Here, we review recent work on how adaptors mediate endocytosis and address the following questions: what characteristics define an endocytic adaptor protein? What roles do these proteins fulfill in addition to selecting cargo and how might adaptors function in clathrin-independent endocytic pathways? Through the findings discussed in this Commentary, we hope to stimulate further characterization of known adaptors and expansion of the known repertoire by identification of new adaptors.

The F-BAR protein Syp1 negatively regulates WASp-Arp2/3 complex activity during endocytic patch formation.

BACKGROUND: Actin polymerization by Arp2/3 complex must be tightly regulated to promote clathrin-mediated endocytosis. Although many Arp2/3 complex activators have been identified, mechanisms for its negative regulation have remained more elusive. To address this, we analyzed the yeast arp2-7 allele, which is biochemically unique in causing unregulated actin assembly in vitro in the absence of Arp2/3 activators. RESULTS: We examined endocytosis in arp2-7 mutants by live-cell imaging of Sla1-GFP, a coat marker, and Abp1-RFP, which marks the later actin phase of endocytosis. Sla1-GFP and Abp1-RFP lifetimes were accelerated in arp2-7 mutants, which is opposite to actin nucleation-impaired arp2 alleles or deletions of Arp2/3 activators. We performed a screen for multicopy suppressors of arp2-7 and identified SYP1, an FCHO1 homolog, which contains F-BAR and AP-2micro homology domains. Overexpression of SYP1 in arp2-7 cells slowed Sla1-GFP lifetimes closer to wild-type cells. Further, purified Syp1 directly inhibited Las17/WASp stimulation of Arp2/3 complex-mediated actin assembly in vitro. This activity was mapped to a fragment of Syp1 located between its F-BAR and AP-2micro homology domains and depends on sequences in Las17/WASp outside of the VCA domain. CONCLUSIONS: Together, these data identify Syp1 as a novel negative regulator of WASp-Arp2/3 complex that helps choreograph the precise timing of actin assembly during endocytosis.

Syp1 is a conserved endocytic adaptor that contains domains involved in cargo selection and membrane tubulation.

Internalization of diverse transmembrane cargos from the plasma membrane requires a similarly diverse array of specialized adaptors, yet only a few adaptors have been characterized. We report the identification of the muniscin family of endocytic adaptors that is conserved from yeast to human beings. Solving the structures of yeast muniscin domains confirmed the unique combination of an N-terminal domain homologous to the crescent-shaped membrane-tubulating EFC/F-BAR domains and a C-terminal domain homologous to cargo-binding mu homology domains (muHDs). In vitro and in vivo assays confirmed membrane-tubulation activity for muniscin EFC/F-BAR domains. The muHD domain has conserved interactions with the endocytic adaptor/scaffold Ede1/eps15, which influences muniscin localization. The transmembrane protein Mid2, earlier implicated in polarized Rho1 signalling, was identified as a cargo of the yeast adaptor protein. These and other data suggest a model in which the muniscins provide a combined adaptor/membrane-tubulation activity that is important for regulating endocytosis.