The classification of chronic headache: room for further improvement?

In this commentary, the authors briefly discuss their views on some of the limitations in the current terminology and classification of chronic headache. Suggestions for consideration and further debate include the acceptance of chronic daily headache as the umbrella term for this group of headache disorders, a more consistent definition of 'chronic' and the use of a multi-axial classification approach.

Childhood chronic daily headache: a biopsychosocial perspective.

The aim of our observational study was to highlight some clinical observations on chronic daily headache (CDH) in children and adolescents. Data on patients < or =18 years aged presenting with CDH to the Pediatric Headache Clinic at the Royal University Hospital, Saskatoon, Canada, were collected prospectively and sequentially from February 2004 to July 2006. Standardized data sheets and definitions were used. Follow-up information on the 70 participants (22 males, 48 females) was current to February 2007. Fifty-four participants (77%) had had recurrent headaches before transformation to CDH. Comorbid chronic migraine and chronic tension-type headache was the most frequent subtype of CDH (37 participants; 53%). Anxiety and mood disorders were diagnosed in 17 and 15 children respectively. Stressors that precipitated or contributed to the maintenance of CDH were judged important in 44 (63%). The possibility of a somatoform disorder was considered in five children, a factitious disorder in one, and malingering in another. We suggest that CDH be viewed from a biopsychosocial rather than a narrow biomedical perspective and the classification improved to enhance clinical utility.

Effect of long-term vigabatrin administration on the immature rat brain.

PURPOSE: To determine whether the neuropathologic changes produced by vigabatrin (VGB; gamma-vinyl GABA) administration in the developing rat brain are reversible. METHODS: We injected rats daily with VGB (25-40 mg/kg/day, s.c.) from age 12 days for 2 weeks followed by 2 weeks of a drug-free period. Behavioral testing, magnetic resonance (MR) imaging, biochemical assays, and histologic technique were used to assess the adverse effect of VGB in developing brain and its reversibility. RESULTS: At the end of 2 weeks' VGB administration: (a) there was a hyperactivity and a shortened latency to escape out of cool water; (b) white matter appeared hyperintense in T2 and diffusion-weighted MR images with 4-15% increases in T2; (c) microvacuolation, TUNEL-positive nuclei, and swollen axons were observed in the corpus callosum; (d) myelin staining indicated a reduction in myelination, as did the reduction in activities of myelin and oligodendrocyte-associated enzymes and the decrease in myelin basic protein on Western blots. Two weeks after stopping VGB administration: (a) MR images were normal, and microvacuolation was no longer in the white matter; (b) reduction in myelination reversed partially; (c) the T2 relaxation time remained elevated in the hypothalamus; and (d) the behavioral response remained abnormal. CONCLUSIONS: Long-term VGB administration to young rats causes brain injury, which recovers partially on its cessation. The observed cell death, disrupted myelination, and alterations in behavior indicate a need for further safety assessment in infants and children.

Low-dose vigabatrin (gamma-vinyl GABA)-induced damage in the immature rat brain.

The antiepileptic drug, vigabatrin, inhibits GABA transaminase, thus elevating GABA levels in the brain. In adult animal experiments, high-dose (200 mg/kg/day) chronic vigabatrin administration is associated with potentially reversible myelin vacuolation, a phenomenon not documented in humans. We hypothesized that vigabatrin might adversely affect myelination in the developing brain. Rats were given vigabatrin in doses comparable to those used clinically (15-50 mg/kg/day), from age 12 to 16 days. The rats were killed at age 19-20 days. We observed decreased myelin staining in the external capsule, axonal degeneration in white matter, evidence of glial cell death in the white matter, and reactive astrogliosis in the frontal cortex. We did not detect myelin vacuolation. These findings indicate that vigabatrin can have adverse and potentially irreversible effects on the developing rat brain. The mechanism of damage could be direct toxicity of vigabatrin or an indirect effect mediated through elevated GABA levels. Vigabatrin has been recommended as a treatment for some forms of childhood epilepsy; therefore, further studies are needed to assess the risks in children.

Specificity of IHS criteria in childhood headache.

We prospectively assessed the relative specificity of the International Headache Society (IHS) criteria in 30 children referred to a pediatric neurologist. An important cause of headache, including raised intracranial pressure with slit ventricle syndrome, would have been missed in 4 children if one had relied on IHS criteria alone. Specific revisions have been proposed to minimize misclassification and further enhance the relevance of the IHS document for children.

International Headache Society classification and diagnostic criteria in children: a proposal for revision.

The authors have proposed specific revisions to current International Headache Society (IHS) criteria for the diagnosis of headache. They include: (1) the use of the terms 'clinically definite' and 'clinically probable' to preface the diagnosis of a particular headache disorder to distinguish between situations in which (a) all criteria for the disorder are fulfilled and (b) one or two criteria are not fulfilled; (2) a slight revision to the criteria for the diagnosis of migraine with aura; (3) acceptance by the IHS of a category 'co-existing migraine and tension-type headache'; (4) consistency in the use of terms and elimination of ambiguous phrases; and (5) the omission of rule 7. The authors trust that these suggestions will help make the recommendations of the IHS more applicable to paediatric practice.

Inter-observer agreement in the diagnosis of childhood headache.

We prospectively assessed inter-observer agreement in the diagnosis of recurrent headaches in children. Clinical letters containing information on 40 children with headaches (age 4.3 to 17.8 years, median 10.4 years) were given to four Pediatric Neurologists. One or more headache types could be checked off on a data sheet that listed the main types recognized by the International Headache Society and an additional one, "combined migraine and tension-type headache". There were six combinational pairs of neurologists. The six pairs yielded 240 sets of diagnoses. Percentage agreement ranged from 45% to 78%, Kappa values from 0.20 to 0.59, and weighted Kappa from 0.19 to 0.52 within the six pairs. Agreement was 76% when both neurologists in a pair assigned single headache types and 4% when one or both neurologists diagnosed multiple types. The International Headache Society suggests that patients may have multiple types of headache and recommends that all types be classified. We suggest that the option of diagnosing more than one headache type from data in clinical letters may reduce inter-observer agreement.

Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives.

We describe eleven mid-western Canadian aboriginal infants with a unique, progressive muscle disorder. All except one had muscle biopsy and/or autopsy. The infants were normal newborns who rapidly developed rigidity of all skeletal muscles, with early, respiratory insufficiency. Death occurred before 18 months of age. Electromyography showed increased insertion activity and profuse fibrillation potentials; motor unit potentials and interference pattern are normal until late in the course. Pathologic features include progressive, granular to powdery Z-band transformation, myofibrillar loss, and muscle regeneration. SDS-gel electrophoresis of one muscle sample revealed increased 54kDa and reduced 80kDa protein fractions. This disease differs from other conditions with Z-band alterations because of continuous muscle activity and relentless clinical progression. The clinical features, elevated serum creatine kinase, electromyographic and muscle biopsy findings suggest a dystrophic process. The recognition of this condition as an autosomal recessive disorder allows appropriate genetic counselling.

International headache society criteria and childhood headache.

The objective of this study was to determine whether the intuitive clinical diagnosis of a headache type made by paediatric neurologists would also have fulfilled International Headache Society (IHS) criteria for that type. Clinical information was recorded on data sheets. The neurologists made clinical diagnoses without referring to a fixed set of criteria. An independent physician then used the information on the data sheets to classify the child's headache by IHS criteria. Complete data sheets were available for 72 children, aged between four and 18 years. The intuitive clinical diagnosis was completely concordant with the criterion diagnosis of the IHS in 61 per cent, partially concordant in 31 per cent and at complete variance in 8 per cent. These data suggest that the IHS criteria can be applied to a majority of children in a referral-based population such as this, but that minor revisions to the criteria are necessary to make them even more applicable to children.

Contact thermography in the diagnosis of childhood migraine.

The objective of our prospective study was to assess the role of contact thermography in children with migraine. Contact thermograms were done in 54 children aged 4.2-16.5 years (median 10.5 years), who were seen for headache and on 10 age-matched controls, between July and December 1991. Thermograms were interpreted as definitely normal, equivocally normal, equivocally abnormal, and definitely abnormal by a radiologist who was blinded to clinical information. Forty-eight children had the test between headaches; of these, four out of 26 patients (15%) who had migraine without aura and 3 out of 14 children (21%) who had migraine with aura had definitely abnormal thermograms. Nine out of 10 normal controls had definitely normal thermograms. The sensitivity of contact thermography in the diagnosis of childhood migraine, when done between headaches, was low in our study.

Impact of genetic counselling after neonatal screening for Duchenne muscular dystrophy.

In a pilot neonatal screening programme for Duchenne muscular dystrophy (DMD) conducted in the Canadian province of Manitoba, a cohort of eight affected males was identified between 1 January 1986 and 31 December 1989. Demographic information, knowledge of DMD, reproductive outcome, and attitudes to prenatal diagnosis and neonatal screening for DMD were obtained through questionnaires distributed in May 1992 to the eight sets of parents of index cases, two high probability carrier aunts, and one high probability carrier sister. Personal interviews were subsequently conducted in the summer of 1992. Although there is overall consensus among the families in favour of routine neonatal screening for DMD, five of seven subsequent pregnancies reported in six women were not monitored by prenatal diagnosis and have resulted in the birth of two affected boys. In a comparable time interval, prenatal diagnosis was acceptable to carrier females whose affected male relatives were traditionally diagnosed at four or five years. We conclude that, although molecular genetic analysis now allows for precise diagnosis of DMD, highly accurate carrier testing and prenatal diagnosis, very early DMD carrier identification, and genetic counselling after the identification of DMD males in a population based neonatal screening programme may not be an effective way of decreasing the number of repeat cases of DMD within families or the overall population frequency of DMD.

Atypical features of the hepatic form of carnitine palmitoyltransferase deficiency in a Hutterite family.

We describe hepatic carnitine palmitoyltransferase (CPT I) deficiency in three children (a brother and sister and their second cousin) from an extended inbred Hutterite kindred. The patients were first seen between 8 and 18 months of age with recurrent episodes of hypoketotic hypoglycemia accompanied by a decreased level of consciousness and hepatomegaly. One patient had two Reye syndrome-like episodes. Abnormal organic acids were rarely detected in urine. Serum total and free carnitine levels were elevated in all three patients. Fibroblast acyl-coenzyme A dehydrogenase activities were normal in all, but palmitic acid oxidation, performed in fibroblasts from one patient, was less than 10% of control values. Activity of CPT I in cultured skin fibroblasts from the three patients was 10% to 15% of control levels; CPT II activity was normal. Activity of CPT I and CPT II in muscle from one patient was normal. Atypical features in two of these patients were greatly elevated levels of liver enzymes and creatine kinase during acute episodes. The patients have recently been successfully treated with medium-chain triglycerides and avoidance of fasting. Early identification and treatment of this disorder may avert potentially fatal episodes of hypoglycemia.

Benign neonatal sleep myoclonus. A differential diagnosis of neonatal seizures.

OBJECTIVE: To describe 10 infants with benign neonatal sleep myoclonus. DESIGN: Patient series, representing the experience of one pediatric neurologist. SETTING: Referral-based Pediatric Neurology Service at a Children's Hospital. PATIENTS: Sequential sample of 10 neonates referred for assessment of seizures and found to have benign neonatal sleep myoclonus. Neonates who did not have the events of concern during electroencephalography or in whom electroencephalography was not done were excluded even if the clinical features suggested the entity. RESULTS: Our patients met the criteria for the diagnosis. The myoclonus often increased with gentle restraint. The amplitude and duration of events mimicked convulsive status epilepticus and serial seizures in four neonates. In two of them the myoclonus worsened in spite of anticonvulsant therapy, decreasing substantially when such treatment was stopped. CONCLUSION: Benign neonatal sleep myoclonus, an entity characterized by (1) neonatal onset, (2) myoclonic jerks only during sleep, (3) abrupt and consistent cessation with arousal, (4) absence of concomitant electrographic changes suggestive of seizures, and (5) good outcome must be included in the differential diagnosis of neonatal seizures.

Discriminant analysis when all variables are ordered.

Determination of the equation that relates an ordered dependent variable to ordered independent variables is sought. One solution, non-parametric discriminant analysis (NPD), involves obtaining the best monotonic step function by means of a computer search procedure. Although one can use alternative selection criteria in obtaining the equation, the illustrative examples use absolute distance. This paper compares the prediction procedures obtained from NPD with those from linear discriminant analysis, linear regression (with and without transformed variables), and logistic regression. We show that NPD is analogous to regression tree analysis with incorporation of ordered variables and monotonicity. We use various prediction functions to predict the example data, the data using the leave-one-out technique, and a verification set. Consistently, non-parametric discriminant analysis performs as good as or better than the tested alternatives.

Inter-observer agreement in assessing comatose children.

Inter-observer agreement was evaluated for twelve items used in the neurological assessment of comatose children. Data were obtained prospectively on fifteen patients examined independently by two observers in a double-blind fashion. Observer variability was measured by using the Disagreement Rate and Kappa statistic. The Disagreement Rate ranged from 0.01 to 0.12 for all items. Values for Kappa statistic were generally in accordance with those for Disagreement Rate. The data suggest fair to almost perfect inter-observer agreement for the items used to assess comatose children in this study.

Electrical status epilepticus during slow-wave sleep: a review.

Electrical status epilepticus during sleep (ESES) is primarily an EEG-defined syndrome in children characterized by the occurrence of continuous spike and slow waves during non-rapid-eye-movement (non-REM) sleep, the paroxysmal abnormalities being substantially less frequent during the awake state and REM sleep. Etiologically, cases can be divided into symptomatic and cryptogenic varieties. Partial motor seizures, frequently nocturnal, precede the emergence of ESES, whereas absence seizures often occur during the phase of ESES. The emergence of ESES is associated with neuropsychological regression. The characteristic electrographic pattern and epilepsy generally disappear during adolescence and are associated with an improvement in neuropsychological function. However, if the cases reported in the literature are representative, then there is a high probability of considerable residual dysfunction. A number of factors, broadly termed ascertainment biases, likely contribute to the paucity of reports from North America and the greater recognition of the syndrome in Europe and Japan. The current information on ESES is critiqued in this review.

Phenotypic variability in glutaric aciduria type I: Report of fourteen cases in five Canadian Indian kindreds.

We describe 14 patients with glutaric aciduria type 1 in five Canadian Indian kindreds living in Manitoba and northwest Ontario. The patients had marked clinical variability of the disease, even within families. Eight followed the typical clinical course of normal early growth and development until the onset of neurologic abnormalities, often precipitated by infection, between 6 weeks and 7 1/2 months of age. Five patients had early developmental delay; one was thought to be normal until 8 years of age. Three patients died, seven are severely mentally and physically handicapped, and four have only mild mental retardation or incoordination. Six patients had macrocephaly in the neonatal period. Computed tomography was done for 12 patients, and findings were abnormal in 11. Glutaric acid and 3-hydroxyglutaric acid were detected in increased amounts in the urine of all patients, but the concentrations were much lower than those in most other reported patients. Glutaryl coenzyme A dehydrogenase activity in skin fibroblasts, interleukin-2-dependent lymphocytes, or both, ranged from 0% to 13% of control values. There was no correlation between clinical severity and urine glutaric acid concentration or level of residual enzyme activity. We recommend that organic acid analysis of the urine be done in patients with unexplained cerebral palsy-like disorders, especially if the computed tomographic scan is abnormal. If there is suspicion of glutaric aciduria, glutaryl-coenzyme A dehydrogenase should be measured in fibroblasts or lymphocytes even if glutaric acid is not increased in the urine.

Coma scales in pediatric practice.

Interobserver variability for six coma scales was assessed prospectively on a sample of 15 comatose children, by two physicians, in a double-blind fashion. The six scales were the Glasgow Coma Scale, the Simpson and Reilly Scale, the Children's Coma Score, the Children's Orthopedic Hospital and Medical Center Scale, the Jacobi Scale, and the 0 to IV Scale. Interobserver variability was measured by using disagreement rate and the kappa statistic. The results from both methods were generally concordant. The disagreement rate for the various items in the different scales ranged from a high of 0.20 to a low of 0.03. The disagreement rate was greater than 0.10 for verbal responses in the Children's Coma Score and Glasgow Coma Scale and for both items in the Children's Orthopedic Hospital and Medical Center Scale. The disagreement rate was 0.10 or less for the 0 to IV Scale and for all items in the Simpson and Reilly and Jacobi scales. The relatively high interobserver agreement for these scales makes them more suitable for the pediatric setting than the other three scales, since good agreement is essential for interpreting data reliably, both in clinical practice and for research.

Myopathy with hypophosphatasia.

Three children with hypophosphatasia also had muscle pains, stiffness, and symptoms of proximal lower limb muscle weakness that occurred early in the disorder and were the presenting features in two. A non-progressive myopathy may be an important sign of hypophosphatasia.