Purpose The purpose of this paper is to review some of the causes of secondary headache particularly focusing on the subcategories of secondary headache in the International Classification of Headache Disorders, 3rd edition, the clinical features of these headaches, and their associated features and management. Overview Headache attributed to trauma or injury to the head and/or neck, headache attributed to cranial or cervical vascular disorder, headache attributed to non‐vascular intracranial disorder, headache attributed to a substance or its withdrawal, headache attributed to infection, headache attributed to disorder of homeostasis, and headache or facial pain attributed to disorder of the cranium, neck, eye, ears, nose, sinuses, teeth, mouth, or other facial or cervical structure are discussed in this paper. Discussion Headache is a common symptom of multiple medical conditions. Although a minority of headache patients have a secondary basis for their headaches, it is important to identify clinical features of secondary headache disorders including both the headache and non‐headache features of the condition, diagnose the secondary etiology correctly, and treat them appropriately.

Mutations in the presenilin (PS) genes are a predominant cause of familial Alzheimer’s disease (fAD). An ortholog of PS in the genetic model organism Caenorhabditis elegans (C. elegans) is sel-12. Mutations in the presenilin genes are commonly thought to lead to fAD by upregulating the expression of amyloid beta (Ab), however this hypothesis has been challenged by recent evidence. As C. elegans lack amyloid beta (Ab), the goal of this work was to examine Ab-independent effects of mutations in sel-12 and PS1/PS2 on behaviour and sensory neuron morphology across the lifespan in a C. elegans model. Olfactory chemotaxis experiments were conducted on sel-12(ok2078) loss-of-function mutant worms. Adult sel-12 mutant worms showed significantly lower levels of chemotaxis to odorants compared to wild-type worms throughout their lifespan, and this deficit increased with age. The chemotaxis phenotype in sel-12 mutant worms is rescued by transgenic over-expression of human wild-type PS1, but not the classic fAD-associated variant PS1C410Y, when expression was driven by either the endogenous sel-12 promoter (Psel-12), a pan-neuronal promoter (Primb-1), or by a promoter whose primary expression was in the sensory neurons responsible for the chemotaxis behavior (Psra-6, Podr-10). The behavioural phenotype was also rescued by over-expressing an atypical fAD-linked mutation in PS1 (PS1?S169) that has been reported to leave the Notch pathway intact. An examination of the morphology of polymodal nocieptive (ASH) neurons responsible for the chemotaxis behavior also showed increased neurodegeneration over time in sel-12 mutant worms that could be rescued by the same transgenes that rescued the behaviour, demonstrating a parallel with the observed behavioral deficits. Thus, we report an Ab-independent neurodegeneration in C. elegans that was rescued by cell specific over-expression of wild-type human presenilin.