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Objective: To study the prevalence of, and identify possible risk factors for, the development of post-traumatic epilepsy in a cohort of children with severe head injury treated in an inpatient rehabilitation unit., Methods: The hospital and community medical case notes of all children admitted prospectively to the unit and the records of the clinical EEG department over a seven year period were reviewed to identify those children who had developed late epilepsy after head injuries., Results: 102 children received inpatient rehabilitation between 1 June 1991 and 28 February 1998. Follow up of these patients ranged from 18 months to over eight years. Nine patients (9%) developed post-traumatic epilepsy between eight months and over five years after the head injury. Three of the nine patients had experienced early tonic-clonic seizures in the first week after the injury. Other risk factors examined included the age of the patient, the cause of the head injury, initial Glasgow coma scale score, neuroimaging findings, and duration of ventilatory support. Only the presence of early seizures (p = 0.002) and possibly the Glasgow coma scale score (p = 0.043) were found to be specific risk factors for late late epilepsy., Conclusions: Post-traumatic epilepsy appears to be uncommon, even in children with severe head injuries. Early seizures may indicate increased risk of developing late post-traumatic epilepsy in this study population.

West syndrome (WS) is commonly associated with a poor long-term outcome including a small but significant mortality, infantile spasms that are resistant to treatment, the development of other seizure types and impaired cognitive and psychosocial functioning. It is important to understand that the families of these children also experience significant psychosocial morbidity, which is usually, but not invariably, correlated with persisting seizures beyond the first or second year of life. One of the fundamental points about the prognosis of this epilepsy syndrome is that the natural history (i.e. the outcome of spasms without any medical or surgical intervention) is not known. Numerous factors have been implicated as being important in influencing the long-term prognosis of children with WS. However, the majority of these factors have been identified from retrospective and markedly heterogeneous studies, including different populations and different treatment regimes. The most important prognostic factors are generally recognised to be the underlying aetiology of the syndrome and the presence or absence of pre-existing seizures and/or developmental abnormalities. The rapidity with which the diagnosis is made and treatment started from the onset of spasms (often termed the 'treatment lag') is a possible, though controversial and as yet unproven, factor in the prognosis of WS.

We describe two unrelated children with almost identical clinical illnesses comprising of severe, burning dysesthesia, allodynia, hypertensive encephalopathy, and laboratory evidence of both sympathetic and parasympathetic autonomic disturbance after a nonspecific viral illness. No underlying etiology was identified. Both patients displayed complete resolution of their clinical and radiologic findings after a number of months, and there was no recurrence over a follow-up period of 17 months to 4 years. Treatment of the patients' dysesthesias proved difficult, requiring multiple analgesics and intensive physiotherapy. We speculate that their illnesses may represent a pure autonomic variant of Guillain-Barré syndrome.

A 14-year-old boy presented with a 3-year history of a skin rash typical of juvenile dermatomyositis, and a 2-month history of mild proximal weakness, myalgia, and weight loss. A quadriceps biopsy showed perifascicular fibre atrophy, focal necrosis and regeneration, immunohistochemical labelling for HLA-1 on the surface of the fibres, and focal C5-9 deposition in capillaries. Macrophages with diastase-resistant, PAS-positive cytoplasm were present. Ultrastructural studies showed electron dense and membranous debris. The patient's symptoms responded to intravenous immunoglobulin and oral prednisolone. Four months after discontinuing prednisolone, the patient developed cardiac failure, ventricular tachycardia, and a recurrence of his rash. The 16S ribosomal RNA specific for Tropheryma whippelii was identified by polymerase chain reaction (PCR) analysis in skeletal and cardiac muscle. The myalgia and skin rash responded to prednisolone and oral co-trimoxazole, and the tachycardia is controlled by oral verapamil. This patient appears to have a novel association of juvenile dermatomyositis and Whipple's disease.

Purpose: Vigabatrin (VGB) has been shown to be an effective drug in the treatment of infantile spasms (West syndrome) in predominantly retrospective and open but also in prospective studies. This prospective, randomised, and placebo-controlled trial of VGB in infantile spasms was considered to be justified and feasible to confirm or refute these previous findings., Methods: Forty children with newly diagnosed infantile spasms received either VGB or placebo for 5 days in a double blind, placebo-controlled, parallel-group study, after which all the infants continuing in the study were treated openly with VGB for a minimum of 24 weeks., Results: Compared with baseline, at the end of the double-blind phase, the patients treated with VGB had a 78% (95% confidence interval, 55-89%) reduction in spasms compared with 26% (-56-65%) in the group treated with placebo (p = 0.020). Seven VGB-treated patients and two placebo-treated patients were spasm free on the final day of the double-blind period (p = 0.063). At the end of the study, 15 children (38% of the original 40 patients or 42% of the 36 patients who entered the open phase) were spasm free with VGB monotherapy. No patient withdrew from the study because of an adverse event., Conclusions: This unique randomized, placebo-controlled study is the first to demonstrate the efficacy of a specific drug in the treatment of West syndrome and supports the results of previously published open and prospective trials. It further confirms that VGB could be considered as the drug of first choice in treating infantile spasms.

All children who presented in a convulsion, including convulsive status epilepticus, to the accident and emergency department over a 12-month period and who required treatment, were reviewed retrospectively to identify the effectiveness and safety of a specific treatment protocol. This protocol recommends the initial use of one, or if necessary, two doses of rectal or intravenous diazepam (0.4 mg/kg) followed by the simultaneous administration of phenytoin (18 mg/kg) and rectal paraldehyde (0.4 mL/kg), with instructions for maximum doses and timings of administration. Eighty-one evaluable children (52 male) were audited. The mean age of the study population was 4.1 (range 0.1 to 14.9) years. Overall, the presenting convulsion was successfully terminated in 76 children (94%) within the accident and emergency department. In 69 children (85% of the entire study population) this was after a single dose of diazepam (rectal in 41 and intravenous in 28). In only an additional two children did the presenting convulsion stop after a second dose of diazepam. In five of the 10 children (50%) who received paraldehyde and phenytoin as a combination, the convulsion stopped. Nine patients (11%) required admission to the intensive-care unit, five because of persisting convulsive activity, and four because of respiratory depression. The results of this retrospective audit suggest that the current treatment protocol appears to be effective and relatively safe in treating acute convulsions, including convulsive status epilepticus. The audit is to be repeated prospectively to either confirm or refute these findings before recommending any changes to the protocol.

Myotubular myopathy frequently presents in male infants with severe generalised muscular hypotonia and weakness associated with ventilatory insufficiency, and is diagnosed on biopsy by the presence of many fibres with central nuclei and mitochondrial aggregation. In a 6-year period, we have investigated five unrelated patients with clinical and pathological features suggesting an X-linked myotubular myopathy, including one female patient. In one male infant, a biopsy of vastus lateralis showed less than 2% centrally-nucleated fibres, while biceps brachii showed up to 15% centrally-nucleated fibres. Immunohistochemical expression of the neural cell adhesion molecule (CD56) was more intense in the biceps muscle than in vastus lateralis, while expression of desmin and vimentin was similar. Morphometric evaluation of tissue from each of the patients revealed a wide spread of values for the number of centrally-nucleated fibres per microscopic field, and variation in the extent of immunohistochemical expression of NCAM, utrophin, laminin alpha 5 chain, vimentin and HLA1 antigen. These variations in the manifestations of myotubular myopathy have not been previously described, and will need to be correlated with the increasing knowledge of the mutations in the MTM1 gene coding for myotubularin.

Metabolic disorders are a relatively uncommon, but important, cause of childhood seizures. Routinely searching for a metabolic disorder in epilepsy is usually unrewarding. Children and adolescents with epilepsy can be selected for appropriate biochemical investigation by considering the seizure type, age of onset, EEG appearance, family history, clinical findings and the results of brain imaging. A limited number of biochemical screening tests can be used to categorize the more common metabolic disorders associated with seizures.

Sudden, unexpected death in epilepsy (SUDEP) remains a controversial and enigmatic syndrome, particularly in children where the incidence, prevalence and risk factors may, and probably do, differ from adults. This study demonstrates (and further reinforces) the difficulties and inability of retrospective and coroner/death certificate-derived data in identifying the frequency of SUDEP in children.

Epilepsy starting in childhood frequently persists through adolescence and into adult life, and an onset in adolescence itself is common. The management of the teenager with epilepsy is important but often inadequate. In 1991, a specific clinic for teenagers with epilepsy was established in Liverpool to address the unique needs and concerns of this age group and, importantly, to facilitate a smooth hand-over of specialist epilepsy care from paediatric to adult services. An additional and crucial benefit of this clinic has been to provide a further, and hopefully final, screen to confirm (or refute) the diagnosis of epilepsy, to corroborate, or correctly identify, the specific epilepsy syndrome and to ensure that the most appropriate antiepileptic drug (AED) is being prescribed and when, if possible, the drug can be withdrawn. Of 120 consecutive patients referred to the teenager clinic, 12 (10%) did not have epilepsy, and 26 (22%) were being treated with an inappropriate AED. The main issues and concerns voiced by the teenagers included choices of further education and career, the possibility and risks of withdrawing anticonvulsants, driving regulations, the inheritance of epilepsy and pregnancy/contraception. This teenager clinic could serve as a model for both other 'epilepsy centres' and also for managing other chronic disorders with an onset in childhood.

We report the use of repeat electroencephalography (EEG) in the management of 69 patients with childhood-onset absence epilepsy (CAE). Electro-clinical absences were demonstrated in seven children who were felt clinically to have persisting absences. In three of the remaining 62 patients who were thought to be seizure-free, repeat EEG showed electro-clinical absences; revision of AEDs in these three children resulted in clinical and EEG control. EEG is a useful adjunct to the (usual) subjective monitoring of the response to treatment, and should be repeated routinely in all patients with CAE.

There are a large number of well recognised syndromes comprising cerebellar ataxia in association with other neurological features. We report three family members who presented with a relapsing, early onset cerebellar ataxia, associated with progressive optic atrophy and sensorineural deafness. All three patients have areflexia (in the absence of a peripheral neuropathy), a pes cavus deformity, and show varying degrees of severity. Extensive neurological investigations have been normal, and the aetiology and pathophysiology of this disorder remain unclear. This may represent a separate syndrome of early onset cerebellar ataxia with associated features ("cerebellar ataxia plus"), which is likely to either have an autosomal dominant or maternal mitochondrial pattern of inheritance. The recognition of this association under the acronym of CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural deafness) may help in the delineation of a new syndrome.

Epilepsy in children is frequently accompanied by learning, behavioural and psychological difficulties. These difficulties may be compounded by the ignorance and stigma which exists within the community health care and education services. The management of epilepsy in children therefore extends far beyond the use of antiepileptic drugs and must address these additional problems. The establishment of a nurse specialist service in paediatric epilepsy within our hospital has provided a more satisfactory and comprehensive management of these children and, in addition, has facilitated a close liaison with schools, community health personnel and support groups; as a result this has dispelled much of the local ignorance, misunderstanding and stigma surrounding epilepsy.

Four children with evolving Guillain-Barré syndrome were treated with a five-day course of intravenous immunoglobulin. No patient showed further progression of the condition and all made a rapid and complete recovery with no evidence of relapse over a six- to 24-month follow-up period. The early use of immunoglobulin in this disorder may prevent further progression of the disease and accelerate short-term recovery, with resulting medical, social and financial implications.

Previous research into non-epileptic attack disorder (NEAD) has focused on the individual. We report a teenager with non-epileptic seizures which highlights the importance of the family in the development and maintenance of such attacks. The authors propose that in children and adolescents the focus of therapeutic intervention should be the individual within the context of the family.

Epilepsy, a common childhood condition, is largely managed by general paediatricians. To assess whether recent management guidelines are being met, we undertook a prospective questionnaire-based survey of children with epilepsy, attending the general paediatric out-patient clinic, at the Royal Liverpool Children's Hospital, Alder Hey. Ninety-one children were identified over seven months-giving a prevalence of epilepsy in this out-patient population of 13.7/1000. Fifty-four per cent were diagnosed as having tonic-clonic, 16% partial and 5% typical absence seizures. Forty-two per cent received carbamazepine and 33% sodium valproate, as monotherapy, and 7% were treated with multiple antiepileptic drugs (AEDs). Correlation between AED and seizure type was often inappropriate as was the routine measurement of blood level of AEDs. Correlation between seizure frequency and clinic visits was generally acceptable with those children experiencing frequent seizures attending most often. Specialist paediatric neurologist advice was sought in only 14% of children; 19 of the 28 children with the most poorly controlled seizures were not referred for a specialist opinion. This study has demonstrated a poor understanding of seizure/syndrome classification; the frequent inappropriate use of AEDs and their blood level measurement and inadequate referral for specialist advice. Recognized guidelines are not being followed, nor are standards being met by many general paediatricians. There is a clear indication for more extensive education and the need to provide clear recommendations for the management of epilepsy in children.

An audit of 165 requests for electroencephalography (EEG) was undertaken before and after the introduction of guidelines and recommendations, 12 months apart. Inadequate clinical information was provided in requests in both surveys; 40% of requests were considered to be unnecessary, and approximately 50% of clinicians felt that EEG could diagnose epilepsy.

The interpretation of the results of the use of vigabatrin (VGB) in generalized seizures and epilepsies in children has been difficult. Most studies have assessed patients on the basis of both seizure type and epilepsy syndrome and the numbers of patients have been small. Some 'generalized' epilepsy syndromes (specifically the Lennox-Gastaut syndrome) are characterized by multiple seizure types which are frequently not analysed individually in terms of drug response. By contrast West syndrome is easier to evaluate as the spasms are the only, and characteristic, seizure type. Vigabatrin has been used as both add-on, and monotherapy in the treatment of spasms. The results of add-on studies suggest that symptomatic spasms respond best, with 40-100% of children becoming spasm-free and many others showing a reduction in seizures of over 50%. The limited, reported data on VGB-monotherapy in West syndrome have been encouraging with over 50% of patients experiencing a total and sustained control of seizures with minimal or no adverse events; however, the pattern of response (symptomatic cases responding better than cryptogenic cases), has not, as yet, been confirmed. The 'non-progressive' myoclonic epilepsies tend to be exacerbated with 25-50% of patients experiencing an increase in seizure frequency; this is an interesting observation in view of the improvement seen in infantile spasms, which are also classified as a myoclonic seizure. The use of VGB in other generalized seizures and epilepsy syndromes has been neither assessed, nor reported. This reflects the fact that these seizures/syndromes are easily and well controlled using the 'older' anti-epileptic drugs.

Epilepsy in children is frequently misdiagnosed and inappropriately managed with major medical, social, and educational consequences. The advent of the newer anti-epileptic drugs has paradoxically, and in contrast to what was expected, contributed to a therapeutic confusion, which in certain instances, has perpetuated this unsatisfactory management. The purpose of this paper is to address some of the diagnostic and management issues and outline drug regimens for specific seizures types and epilepsy syndromes. Alternative and surgical therapies, and the treatment of neonatal and 'febrile seizures' and status epilepticus will not be discussed in detail, as these particular aspects fall outside the remit of this paper.

Five unrelated patients are described with the clinical and electrical features of eyelid myoclonia with absences (EMA). In this syndrome brief, typical absences occur with rapid eyelid myoclonia associated with retropulsive movements of the eyeballs and occasionally of the head. The seizures are of shorter duration than in childhood absence epilepsy, and are accompanied by less profound impairment of consciousness. The electroencephalogram demonstrates high amplitude discharges consisting of spikes, multiple spikes and slow waves at a fluctuating frequency of 3-5 Hz and following eye closure, which disappear in darkness. Photosensitivity is also seen. Onset is in early childhood and EMA appears to persist into adult life. Treatment is sodium valproate in combination with either ethosuximide or a benzodiazepine. On the basis of the clinical features, EEG findings, and the response to treatment and prognosis, it is suggested that EMA be classified as a specific epilepsy syndrome.

More than 360 children with intractable epilepsy have been treated with vigabatrin in single-blind or open, add-on studies. Approximately 50% or more of patients with West syndrome and partial seizures have shown a 50% or greater reduction in seizure frequency with the use of vigabatrin. A less consistent response has been found between studies evaluating vigabatrin in children with Lennox-Gastaut syndrome, although, overall, approximately 50% of these patients have also shown a greater than 50% decrease in seizures. The use of vigabatrin in idiopathic localization-related epilepsy, idiopathic generalized epilepsy, and the Landau Kleffner syndrome have not been reported, but its evaluation in these conditions may be warranted based on the relatively excellent safety profile of vigabatrin. Vigabatrin has been shown to aggravate "nonprogressive myoclonic epilepsies." Vigabatrin has been well tolerated in children, with mild drowsiness and agitation being the most commonly reported side effects.

A young boy presented with loss of speech and behaviour disturbance and was thought to be deaf. He was subsequently found to have the Landau-Kleffner syndrome (LKS), or acquired aphasia with epilepsy. Children with this disorder commonly present to an audiology or ENT clinic. Early recognition is important to initiate supportive, speech and educational care.

A persistent focal abnormality was observed in 157 (16%) electroencephalograms undertaken in 964 consecutive children with epileptic and non-epileptic seizures seen over one year. CT head scans were performed in 121 (77%) of the 157 children with a focus on the EEG; 26 (21%) showed an abnormality, and 21 (81%) of the abnormalities were localised. There was no difference in the proportion of abnormal scans associated with a delta or slow wave focus compared with a spike or sharp wave focus. An abnormal scan was uncommon after a single seizure. In only two patients (1.7% of all scans) did the findings on CT alter or greatly influence subsequent management.

The effects of vigabatrin were studied over a 6-month period in 43 patients with intractable epilepsy. Children with complex partial seizures, with or without secondary generalization, responded best with more than one-half achieving a greater than 50% reduction; generalized tonic-clonic seizures also improved but there was no significant change in absence or myoclonic seizures. Four patients are seizure-free on monotherapy with vigabatrin. The drug was well tolerated with few side effects.

Horner syndrome may be caused by a neuroblastoma involving the cervical sympathetic nervous system. A two-year-old girl presented with Horner syndrome and a discrete, distant neuroblastoma, suggesting that these two conditions represent a more widespread dysgenesis of the sympathetic nervous system.

A Duchenne muscular dystrophy patient who displayed near-normal dystrophin staining at the sarcolemma with N-terminal, but not with C-terminal, anti-dystrophin monoclonal antibodies was found to have a frameshift deletion of exons 42 and 43. This deletion introduces an early termination codon, and a 225-kD protein was detected by western blotting with N-terminal antibodies only. The results suggest that an N-terminal truncated dystrophin fragment encoded by exon 1-41 is able to associate with the muscle cell membrane. The current idea that the C-terminal domains of dystrophin are important or essential for its integration with the sarcolemma may have to be reexamined in the light of these observations.