Most patients with primary headache syndromes who have frequent attacks of pain have tenderness in the sub-occipital region. Injection of the greater occipital nerve (GON) with local anesthetic and corticosteroids has been widely used in clinical practice for many years, yet there is no clear understanding of its mechanisms of action. Moreover, there is no current gold-standard of practice regarding GON injections in the management of headache. We audited of our practice to generate hypotheses about the range of primary headaches that might benefit, to determine response rates to power future studies, and to assess whether we should continue to do this procedure. Twenty-six of fifty-seven injections in 54 migraineurs yielded a complete or partial response that lasted for the partial response a median of 30 days. For cluster headache 13 of 22 injections yielded a complete or partial response lasting for a median of 21 days for the partial response. Tenderness over the GON was strongly predictive of outcome, although local anesthesia after the injection was not. The presence or absence of medication overuse did not predict outcome. Apart from two patients with a small patch of alopecia the injection was well tolerated. GON injection is a useful tool in some patients that provides interim relief while other approaches are explored. It is remarkable that in all conditions in which an effect is observed the response time so much exceeds the local anesthetic effect that the mechanism of action may well be through changes in brain nociceptive pathways.

Objective: To establish the phenotypic spectrum of KIF5A mutations and to investigate whether KIF5A mutations cause axonal neuropathy associated with hereditary spastic paraplegia (HSP) or typical Charcot-Marie-Tooth disease type 2 (CMT2).Methods: KIF5A sequencing of the motor-domain coding exons was performed in 186 patients with the clinical diagnosis of HSP and in 215 patients with typical CMT2. Another 66 patients with HSP or CMT2 with pyramidal signs were sequenced for all exons of KIF5A by targeted resequencing. One additional patient was genetically diagnosed by whole-exome sequencing.Results: Five KIF5A mutations were identified in 6 unrelated patients: R204W and D232N were novel mutations; R204Q, R280C, and R280H have been previously reported. Three patients had CMT2 as the predominant and presenting phenotype; 2 of them also had pyramidal signs. The other 3 patients presented with HSP but also had significant axonal neuropathy or other additional features.Conclusion: This is currently the largest study investigating KIF5A mutations. By combining nextgeneration sequencing and conventional sequencing, we confirm that KIF5A mutations can cause variable phenotypes ranging from HSP to CMT2. The identification of mutations in CMT2 broadens the phenotypic spectrum and underlines the importance of KIF5A mutations, which involve degeneration of both the central and peripheral nervous systems and should be tested in HSP and CMT2. Neurology ® 2014;83:612-619 GLOSSARY CMT2 5 Charcot-Marie-Tooth disease type 2; HSP 5 hereditary spastic paraplegia; KHC 5 kinesis heavy chain; SPG10 5 spastic paraplegia type 10; WES 5 whole-exome sequencing.