Seminars in Pediatric Neurology

An 11-year-old girl presented with a syndrome of inappropriate antidiuretic hormone secretion, which was transitory and, initially, of obscure origin. Subsequently, the patient's hypothalamic disorder emerged as a component of a steroid-responsive relapsing encephalomyelitis with cerebral pathology restricted to the basal ganglia and brainstem. Where such a disorder fits in the spectrum from acute disseminating encephalomeylitis to multiple sclerosis is discussed.

Partial complex seizures are often refractory to antiepileptic medications and may require epilepsy surgery for control. With the use of contemporary neuroimaging techniques the number of children with "idiopathic" partial complex seizures has declined. A presurgical neuroimaging evaluation for refractory partial complex seizures is discussed.

A 13-year-old boy with Lennox-Gastaut syndrome characterized by absence, myoclonic, complex-partial, and secondarily generalized tonic-clonic seizures, presents with progressive obtundation and loss of motor and verbal skills over a 2-day period. Initial evaluation revealed therapeutic phenytoin serum concentrations. This article discusses the differential diagnosis and management approach used in this setting, as well as the appropriate interpretation of antiepileptic drug serum concentrations.

The differential diagnosis of chorea or hemichorea in an adolescent boy is discussed. Sydenham's chorea, still the most common cause of chorea in childhood, is only one of many important diseases in the differential diagnosis in this clinical situation.

The evaluation of mental retardation is a frequent and challenging problem in pediatric neurology. Often clues obtained on history or by physical examination will help to direct the evaluation in the appropriate channel. This 16-year-old boy had clinical features which suggested the appropriate diagnostic studies.

Mental retardation (MR) is a life long condition that affects 6 million American and 560,000 Canadian children under the age of 14. This review discusses the definition of MR, an approach to investigation, common comorbidities, and a general approach to management.

Despite an effective vaccine for rubella and reliable serological methods for detecting syphilis, these pathogens remain important potential causes of congenital infections. This article describes the epidemiological factors that have contributed to the reemergence of these disorders and summarizes the clinical features, microbiological diagnosis, and strategies for treatment or prevention of congenital rubella and congenital syphilis.

Velocardiofacial syndrome, also called Shprintzen syndrome or DiGeorge sequence, is one of the most common genetic disorders in humans. Caused by a microdeletion on chromosome 22, it manifests in a remarkable variety of symptoms in multiple systems. The most frequent anomalies involve palatal function, facial features and congenital cardiac defects. In addition, learning disabilities and psychiatric issues are common. The aim of this article is to provide a concise review of the clinical characteristics of this complex disorder. Recognition of the features associated with velocardiofacial syndrome allows for an inclusive diagnosis and more comprehensive care.

The case of a young man with multiple brain and somatic anomalies that presented diagnostic difficulties, is discussed in this report. A majority of his features were suggestive of Joubert syndrome--although it was felt that he did not fully meet diagnostic criteria. The subsequent evaluations included a magnetic resonance image of the brain, that was found to be consistent with pontine tegmental cap dysplasia. Chromosomal microarray studies showed a 2q13 deletion. A gene associated with Joubert syndrome, NPHP1, is within this region. This case highlights several important aspects of the diagnosis and nosology of malformations of the mid-hind brain.

Primary generalized seizures occur in half of all children with epilepsy. Correct classification carries important diagnostic, therapeutic, and prognostic information. Approximately half of all patients with generalized juvenile myoclonic epilepsy may have a partial semiology or focal electroencephalographic features although similar findings have not been described in absence epilepsy. Two examples, one with semiology characteristic of focal seizures and the other with a video-electroencephalogram documented partial seizure emanating after the completion of typical 3-Hz generalized spike-wave absence epilepsy, are discussed.

In parallel to recent developments of genetic techniques, understanding of the syndromes of neurodegeneration with brain iron accumulation has grown considerably. The acknowledged clinical spectrum continues to broaden, with age-dependent presentations being recognized. Postmortem brain examination of genetically confirmed cases has demonstrated Lewy bodies and/or tangles in some forms, bridging the gap to more common neurodegenerative disorders, including Parkinson disease. In this review, the major forms of neurodegeneration with brain iron accumulation (NBIA) are summarized, concentrating on clinical findings and molecular insights. In addition to pantothenate kinase-associated neurodegeneration (PKAN) and phospholipase A2-associated neurodegeneration (PLAN), fatty acid hydroxylase-associated neurodegeneration (FAHN) NBIA, mitochondrial protein-associated neurodegeneration, Kufor-Rakeb disease, aceruloplasminemia, neuroferritinopathy, and SENDA syndrome (static encephalopathy of childhood with neurodegeneration in adulthood) are discussed.

Neurodegeneration with brain iron accumulation (NBIA) includes a heterogeneous group of genetically defined disorders characterized by progressive extrapyramidal deterioration and iron accumulation in the basal ganglia. Current medical options for these disorders remain largely unsatisfactory and do not prevent the disease from progressing to a severe and disabling state. In select cases, surgical techniques, such as deep brain stimulation, may be effective in ameliorating some of the symptoms of the disease. The availability of chelating agents with specific properties that have been demonstrated to be effective in other disorders with regional iron accumulation as well as magnetic resonance imaging techniques that allow for quantitative assessment of iron have stimulated interest in the use of chelating agents in NBIA. This review aims to describe the role of surgical therapies in NBIA, discuss the use of chelating agents in NBIA, and presents new therapeutic approaches under consideration.

Neurodegeneration with brain iron accumulation (NBIA) encompasses at least 7 genetically distinct disorders, and additional causative genes likely await identification. Recent advances have included the characterization of new genes associated with new subtypes of NBIA and also highlighted the phenotypic heterogeneity of this class of disorders. Herein, we summarize current concepts of NBIA pathogenesis and discuss important gaps in current knowledge, outlining key questions in the field. Semin Pediatr Neurol 19:51-56 Published by Elsevier Inc.

Neurodegeneration with brain iron accumulation (NBIA) defines a wide spectrum of clinical entities characterized by iron accumulation in specific regions of the brain, predominantly in the basal ganglia. We evaluated the presence of FA2H and C19orf12 mutations in a cohort of 46 Italian patients with early onset NBIA, which were negative for mutations in the PANK2 and PLA2G6 genes. Follow-up molecular genetic and in vitro analyses were then performed. We did not find any mutations in the FA2H gene, although we identified 3 patients carrying novel mutations in the C19orf12 gene. The recent discovery of new genes responsible for NBIA extends the spectrum of the genetic investigation now available for these disorders and makes it possible to delineate a clearer clinical-genetic classification of different forms of this syndrome. A large fraction of patients still remain without a molecular genetics diagnosis, suggesting that additional NBIA genes are still to be discovered.

The diagnosis of neurodegeneration with brain iron accumulation (NBIA) can be challenging, particularly given recent advances in NBIA genetics and clinical nosology. Although atypical cases continue to challenge physicians, by considering clinical features along with relevant neuroimaging findings, the diagnosis of NBIA can be made confidently. In addition, the identification of genetically distinct forms of NBIA allows clinicians to better provide prognostic and family counseling services to families and may have relevance in the near future as clinical trials become available. We describe a heuristic approach to NBIA diagnosis, identify important differential considerations, and demonstrate important neuroimaging features to aid in the diagnosis.

Neurodegeneration with brain iron accumulation comprises a clinically and genetically heterogeneous collection of disorders that share key features. These include progressive neurological disease accompanied by high basal ganglia iron and axonal dystrophy. To date, 2 genetic forms have been associated with mutations in PANK2 and PLA2G6, both of which encode proteins that are critical to membrane integrity. The intersection of pathways perturbed by defects in these 2 genes now enables us to test hypotheses of a common pathogenesis and ask why iron accumulates. The mechanisms implicated may contribute to our understanding of more common neurodegenerative disorders with iron dyshomeostasis, including Parkinson and Alzheimer disease.

Epidemiologic frequencies of pediatric white matter disorders as a class have not been well defined. This is particularly true of genetic disorders of the white matter of the brain. In this study, ICD-9 codes were used to estimate relative incidence rates and descriptive statistics of leukodystrophies, other genetic leukoencephalopathies and acquired demyelinating disease among children residing in the Washington, D.C. metropolitan area. Children being treated at US children's hospitals between January 1, 2004, and December 31, 2009, for acquired demyelinating disease or genetic white matter disorders were captured using the Pediatric Health Information System and the Physician Practice Management system and validated with local electronic medical records. Comparisons were made between genetic white matter disorders and acquired demyelinating disorders, to determine differences in incidence, age, gender, ethnicity, and mortality. Genetic causes of white matter disease identified with ICD-9 codes had an estimated incidence of 1.2/100,000 children in the Washington, DC area. What was of interest was nearly 5 out of 10 cases of pediatric white matter disease of any etiology were attributable to genetic causes. When only progressive white matter diseases were considered, 7 out of 10 cases were attributable to genetic causes, and only 3 out of 10 to progressive acquired demyelinating disease such as multiple sclerosis. These findings signify the important contribution of heritable white matter disorders to pediatric neurologic disease in the Washington, DC, metro area as well as throughout the United States. Continued research of these understudied disorders should compare disease incidence and determinants to validate these findings in different populations.

Infection with the human immunodeficiency virus type 1 (HIV-1) remains a major potential cause of neurological disorders in children and adults throughout the world. This article provides an overview regarding the epidemiology, clinical manifestations, and neuropathogenesis of perinatally acquired HIV-1 infection. Insights regarding the mechanisms of neuroinvasion and neuropathogenesis may allow novel strategies for treating or preventing the devastating consequences of HIV-1 infection of the central nervous system (CNS).

The occurrence of an asymmetrical motor dysfunction is an event that frequently results in referral to the pediatric neurologist. The differential diagnosis is not extensive but is somewhat larger than superficial evaluation might indicate. This 4-year-old boy developed intermittent painful motor dysfunction of the right arm over a 1-year period of time resulting from an unusual cause of unilateral motor dysfunction.

Acquired childhood aphasia is rare but has important conceptual implications for developmental neuropsychology. The last 15 years have seen major changes in their clinical description, which have led to the awareness that the syndromes in acquired childhood aphasia are more similar to the syndromes in adult aphasia than previously thought. This article briefly discusses the definition and differential diagnosis of acquired childhood aphasia from the point of view of the child neurologist and adds new perspectives afforded by neurolinguistic examinations. It reviews the main causes and syndromes of acquired childhood aphasia. Prognosis is less favorable than usually supposed, in terms of both language sequellae and academic failure. Finally, suggestions regarding the basis for aphasic children's nonverbal deficiencies are presented.

Neuropsychological deficits are the common "hallmark" of acquired epileptic aphasia and epilepsy with continuous spike-waves during sleep. Findings from various sources (eg, clinical cases, electrophysiological and positron emission tomography studies) indicate that the aphasia or the behavioral and intellectual deterioration are closely linked to a particular sustained focal epileptic activity. This leads to a wider concept of prolonged cognitive impairment of epileptic origin.

Neurocysticercosis, prevalent wherever pigs are raised in the presence of poor sanitation, is the most common identifiable cause of new-onset epilepsy throughout the developing world. As immigration patterns have changed, children with neurocysticercosis are seen throughout the United States. Acute cysticercosis, the most common manifestation in children, reflects the host response to the dying parasite. Children typically present with seizures and have an excellent prognosis. Neuroimaging demonstrates a single ring or nodular enhancing lesion surrounded by edema. Short-term anticonvulsant therapy is indicated, but treatment with antiparasitic agents is not required. Other forms, such as active cysts (intact organism), intraventricular or subarachnoid racemous cysticercosis, and cysticercal meningoencephalitis, are less common manifestations of parasitic infection. Toxoplasmosis, caused by the parasite Toxoplasma gondii, can be acquired by ingestion of infected undercooked meat or from oocytes shed in cat feces. Acquired cerebral toxoplasmosis, due to primary or reactivated infections, rarely occurs in immunocompetent children. In children who are immunodeficient as the result of AIDS, chemotherapy, tissue transplantation, or congenital immunodeficiency, toxoplasmosis may be difficult to distinguish from cerebral lymphoma. A variety of techniques, including neuroimaging, Thallium-201 SPECT, polymerase chain reaction analysis of CSF, and special histological methods, may be used to diagnose acquired toxoplasmosis. Antiparasitic therapy, using pyrimethamine and sulfadiazine, and serial neuroimaging often enable clinicians to differentiate toxoplasmosis from other central nervous system lesions. Toxoplasmosis may respond to other antimicrobials, including macrolide antibiotics, dapsone, clinidamycin, and atovaquone. Suppressive treatment is generally required for life in immunodeficient patients. Immunodeficient children with acquired toxoplasmosis have high rates of mortality and neurological sequelae.

The acquired epileptiform aphasias, with Landau-Kleffner's syndrome as the example, represent an important group of syndromes in our quest to understand the relationship between epilepsy, language, and behavior. The controversy that truly frames the literature on the acquired epileptiform aphasias is the role of epileptiform activity on language, behavior, and cognition. This review expands the model of Landau-Kleffner's syndrome to include two other encephalopathies with language and behavioral regression in association with an epileptiform electroencephalogram. Both of these encephalopathies, autistic epileptiform regression and disintegrative epileptiform regression, are associated with an acquired language disorder. The developmental period in which the acquired language disorder begins, the type of language disorder, and the location and type of the epileptiform activity are all important variables that may affect clinical manifestations and prognosis.

Long before they start talking, children are skilled at using eye contact, facial expression, and nonverbal gestures to communicate with other people. They also are able to discriminate speech sounds from an early age. Vocabulary learning builds on the child's knowledge about objects, actions, locations, properties, and stages gained as a result of sensorimotor development. Early word combinations allow children to express semantic relationships between these various referents. During the period from 2 to 4 years of age, children move from expressing their ideas in simple telegraphic speech to being able to ask questions, use negation, talk about past and future events, and describe complicated situations using sentences constructed according to complex grammatical rules.

Hyperactivity/impulsivity, aggression, self injury, and irritability are disruptive behaviors that frequently accompany autism spectrum disorders (ASD). The psychostimulants and atypical antipsychotics have been used with some success to manage hyperactivity, but neither drug group is fully satisfactory and clinical response to the stimulants varies. For other disruptive symptoms (irritability, aggression, self injury), both older antipsychotics and newer atypical antipsychotics have been shown to have helpful effects. Because of potential side effects, atypical antipsychotics should ordinarily be preferred over older agents. A small group of studies suggests that selective serotonin reuptake inhibitors may be helpful in managing symptoms related to aggression, self injury, and the like. A small and largely imperfect literature suggests that beta blockers, mood stabilizers, and alpha-2 agonists may also have some role for treating such symptoms. More research is needed on the management of all of these target symptoms, both for new agents (e.g., atomoxetine) and for established psychoactive medicines.

Herpes simplex virus type 2 (HSV-2) is known to cause acute retinal necrosis (ARN). The availability of HSV-2-specific polymerase chain reaction tests for diagnostic analysis has greatly increased our ability to discriminate ARN caused by HSV-2 from ARN caused by either herpes simplex virus type 1 or varicella zoster virus (VZV). Of great interest, HSV-2 appears to be the most common cause of viral ARN in children and adolescents. Although a few children with ARN are known to have had neonatally acquired herpes infection, most children lack a history of known herpes disease. Thus, the origin of the HSV-2 infection is a mystery. The hypothesis of this review is that HSV-2 ARN in children and adolescents may be the first sign of a previously undiagnosed and asymptomatic neonatal HSV-2 infection, which has reactivated several years later from latency in a cranial nerve and entered the retina. The review brings together 7 previously published ARN cases, plus one new case is added. Thus, this review also expands the spectrum of complications from neonatal HSV-2 infection.

Several new agents have recently become available for the long-term treatment of epilepsy. Until now, there has been little change for the acute management of seizures. Three new agents may alter our present practice. Fosphenytoin has recently been approved as a substitute for parenteral phenytoin. It provides similar efficacy without the risk for infusion site injury while allowing greater flexibility in intravenous solutions. Intravenous valproate adds flexibility for patients on valproate, allowing patients to be rapidly loaded. In addition, it will prevent patients from having to change seizure medications when intervening medical illness or surgery do not allow medications by mouth. Viscous diazepam solution for rectal administration will allow for safe and effective treatment for seizures at home and will potentially decrease emergency department services and hospitalization.

We report a 10-year-old child with Robinow's syndrome who had a 2-week history of headaches and dizziness. On the day of admission, he developed a focal onset seizure with rapid secondary generalization. The seizures were intractable despite adequate doses of benzodiazepine, phenytoin, and phenobarbital, requiring a pentobarbital drip. Continuous electroencephalogram (EEG) monitoring showed persistence of the epileptiform discharges for 13 days. Cerebrospinal fluid and brain biopsy studies were unrevealing. Mycoplasma pneumonia titers showed elevation of both immunoglobulins G and M that doubled during the tenth hospital day. High-dose methylprednisolone was begun, and within 12 hours of initiation the patient sat up and began to follow commands appropriately. The overall EEG background markedly improved. Central nervous system Mycoplasma pneumoniae infection should be suspected in patients with an encephalopathy of unclear etiology.

This review discusses diagnostic evaluation and management of chorea in childhood. Chorea is an involuntary, hyperkinetic movement disorder characterized by continuous, jerky, or flowing movement fragments, with irregular timing and direction. It tends to be enhanced by voluntary actions and generally causes interference with fine motor function. The diagnostic evaluation begins with accurate classification of the movement disorder followed by consideration of the time course. Most previously healthy children presenting with acute/subacute chorea have an autoimmune etiology. Chronic chorea usually occurs as part of encephalopathies or diseases causing more global neurologic symptoms. We review the management of acute/subacute and chronic choreas, with special emphasis on Sydenham chorea and benign hereditary chorea.

A 12-month-old boy with acute onset hemichorea and dystonia following a gastroenteritis has abnormal signal intensities of his basal ganglia on brain magnetic resonance imaging (MRI). A rigorous laboratory investigation is successful in diagnosing his rare condition. A discussion of the differential of abnormal basal ganglia on MRI is presented to help illustrate this case.

Multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) are conditions whose closely related pathology suggests shared pathophysiological elements, but whose clinical courses are usually, but not always quite dissimilar. The former is largely a disease of adulthood, the latter of childhood. Optic neuritis, demyelinative transverse myelitis, and Devic's syndrome are neurological syndromes that may occur as manifestations of either MS or ADEM. Patients with Miller-Fisher syndrome and encephalomyelradiculoneuropathy usually have features suggesting ADEM in combination with acute demyelinative polyneuropathy. These various conditions and other forms of ADEM share an indistinct border with encephalitides, granulomatous, and vasculitic conditions. MS, ADEM, and the pertinent syndromic subtypes, their differential diagnosis, treatment, and prognosis are considered in this review. Acute cerebellar ataxia is a syndrome that is likely to be pathophysiologically distinct from ADEM, although its occurrence as a postinfectious illness suggests a distant kinship. It is also reviewed.

A 4-month-old male infant presented to the emergency room with a history of choking while bottle feeding at home, and was found by emergency medical services (EMS) to be apneic and pulseless. He subsequently developed disseminated intravascular coagulopathy and died. Computed tomography (CT) and magnetic resonance imaging (MRI) showed subdural hemorrhages (SDHs), subarachnoid hemorrhage (SAH), and retinal hemorrhages (RHs), along with findings of hypoxic-ischemic encephalopathy (HIE). The caretaker account appeared to be inconsistent with the clinical and imaging features, and a diagnosis of nonaccidental injury with "shaken baby syndrome" was made. The autopsy revealed diffuse anoxic central nervous system (CNS) changes with marked edema, SAH, and SDH, but no evidence of "CNS trauma." Although NAI could not be ruled out, the autopsy findings provided further evidence that the child's injury could result from a dysphagic choking type of acute life threatening event (ALTE) as consistently described by the caretaker.

Pediatric neurologists frequently treat acute pain in children. A broad range of medication options is available including nonsteroidal anti-inflammatory drugs, opioids, and other analgesic adjuvants, such as antidepressants and antiepileptics. This article reviews the physiology underlying the experience of pain and compares the pharmacologic mechanisms and properties of these medications, providing a framework for developing effective multimodal medical treatment approaches to pain in children.

Headache is the third leading cause of referral to a pediatric emergency room. It is imperative for providers to be able to rule out rare but possible life-threatening disorders, such as meningitis, intracranial hemorrhage, brain tumor, or hydrocephalus. Most of the presenting headaches are secondary to viral illnesses followed by primary headache and migraine. A detailed initial evaluation is essential to guide toward necessary testing as well as diagnosis.

This article reviews the form and function of cranial sutures across the temporal and spatial scales. The temporal scale spans 530 million years, from ostracoderms to contemporary humans. The spatial scale spans eight orders of magnitude, from the macroarchitectural level (the entire cranium), through the mesoarchitectural (the local/regional bone-suture-bone complex) and microarchitectural levels (tissues and cells), to the nanoarchitectural level (molecules within and outside the cells). A mechanomorphologic loop, or cycle, exists. The mechanical strain experienced by the sutures eventually alters the morphology of the sutures. In turn, these morphological changes affect the strain distribution within and around the sutures. At the microarchitectural level, the responses of bone and sutural cells to environmental perturbations depend on the content (what that perturbation is), the context (the other coexisting extrinsic and intrinsic factors), and the history of the perturbation (how often and for how long).

Children with epilepsy have a significant risk for problems with attention and/or attention deficit hyperactivity disorder. Clinical studies suggest a prevalence of 30% to 40%. Inattention is more common than hyperactivity and impulsivity. Additional central nervous system dysfunction and intractable seizures are major risk factors. Treatment should include psychoeducational interventions and medication. Stimulant drugs are safe and effective in children with epilepsy and currently are first-line agents for treatment of attention problems in this population.

Migraine is a commonly occurring headache syndrome in children and adolescents. Half of all individuals destined to have migraine begin their attacks before age 20 years. It is characterized by paroxysmal headache, nausea, vomiting, and desire to sleep. On occasion, dramatic neurological symptoms and signs accompany the headache. The epidemiology, pathophysiology, clinical characteristics, evaluations, and management of migraine are reviewed.

The triptans are medications that are the most important advance, to date, in the treatment of migraine. Their use in adolescents is highlighted, including indications, dosages, benefits, and adverse effects.

During an evaluation for complicated migraine, a 14-year-old adolescent female was found to have a left frontoparietal cortical infarction on magnetic resonance imaging study. A transthoracic echocardiogram was normal, but a transesophageal echocardiogram, with contrast study, showed occasional right to left shunting through a patent foramen ovale. The role of cardiac anomalies in the pathogenesis of migraine-associated stroke is discussed.

A 15-year-old girl with the "MASS" phenotype (meeting several of the minor criteria for Marfan syndrome) presents with a new onset low-pressure postural headache. Clinical features and magnetic resonance imaging suggested intracranial hypotension, which was confirmed with lumbar puncture. The pathophysiology and treatment of spontaneous intracranial hypotension are discussed.

The importance of a thorough evaluation of each patient with headache is stressed. Details of the data base, pertinent information regarding the physical examination, and thoughts concerning selection of laboratory tests are provided. The majority of headache types seen in pediatric practice can correctly be identified using these methodologies.

Data concerning status migrainosus in children and adolescents is sparse. The varied clinical presentations, diagnostic evaluation, and treatment modalities are discussed.

This article reviews headache syndromes that are uncommon and not discussed in previous articles in this issue. Cluster, temporal-mandibular joint dysfunction, occipital neuralgia, and indomethacin responsive headache, as well as several other syndromes, are discussed. Proper identification of these disorders often leads to specific treatment, resulting in dramatic relief of discomfort and pain.

Headache is common in children and adolescents. A thorough history, examination, and a neurologic evaluation with charting of the temporal pattern of the headache and evaluation of psychosocial factors will allow the correct diagnosis to be made. Laboratory testing in most instances is unnecessary but should be tailored to the specific headache syndrome. Psychological factors are important in all forms of headache and should be evaluated in each and every ease. A comprehensive approach to the patient's problem, including medical and psychological interventions, will usually result in improvement.

A majority of the children presented for evaluation of headache complaints, will have one of the primary headache disorder such as tension-type or migraine. During the course of the evaluation, consideration must be given to the diverse collection of other medical and systemic disorders which may also cause headache in children and adolescents. The purpose of this article is to review the spectrum of secondary headaches. In majority of the instances, a thorough medical and headache history coupled with physical and neurologic examination will uncover clues to the presence of these other disorders. This will also guide clinical decision making regarding the need for further diagnostic testing, including neuroimaging, electrophysiological testing, or specific laboratory testing.

Headache is a common symptom in childhood and adolescence. Effective therapy for this symptom is based on the specific headache syndrome. This article presents examples of the four recognized Indomethacin-responsive headache syndromes encountered in pediatrics including exertional headache, cyclic-cluster migraine, chronic paroxysmal hemicrania, and hemicrania continua. Although uncommon conditions, successful treatment depends on recognition of these indomethacin-responsive headache syndromes.