Brimonidine Eye Drops within the Reach of Children: A Possible Foe.

Brimonidine, a selective alpha-2 adrenergic agonist used for the treatment of open-angle glaucoma, has been shown to cause neurological side effects such as unresponsiveness, lethargy, hypoventilation, and stupor, mimicking opioid toxicity. We report one case of transient encephalopathy in a toddler, in whom accidental brimonidine toxicity was suspected and then confirmed by a toxicology study. The healthy 8-month-old girl was taken to the pediatric ER since she was drowsy and hypotonic with miosis. The computed tomography scan of her brain and toxicological workup of her blood and urine were negative. Starting from the fourth hour, the child progressively improved, and by the sixth hour, she recovered to a normal state of consciousness. A survey of available drugs within the child's reach showed the presence of brimonidine. Thus, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to quantify the brimonidine in urine and plasma samples, showing levels of 8.40 ng/mL and 0.79 ng/mL, respectively. To our knowledge, this is the first report to determine brimonidine levels in urine and plasma using UPLC-MS/MS. Insufficient knowledge on the part of family members about the potential hazards of an apparently innocuous, topical medication such as eye drops may put children at a greater risk of poisoning. Necessary warnings should be given to parents with greater care when prescribing this medication.

Extended-release formulations in epilepsy.

In the past years, the extended-release antiepileptic drug formulations have been developed and then approved for the treatment of many types of epilepsy. Among these extended-release formulations of antiepileptic drugs, the main drugs are valproic acid, carbamazepine, and phenytoin. This review analyzes the chemical and structural characteristics of the extended-release formulations of these 3 antiepileptic drugs, analyzing their bioequivalence and the studies about their clinical use. The results of these studies are encouraging and suggest a good tolerability and efficacy of these extended-release formulations, although larger studies are needed.

Photosensitivity and epilepsy.

Photosensitive epilepsy is a well-known condition characterized by seizures in patients who show photoparoxysmal responses on electroencephalography (EEG) elicited by intermittent photic stimulation. Photoparoxysmal responses can be defined as epileptiform EEG responses to intermittent photic stimulation or to other visual stimuli of everyday life and are frequently found in nonepileptic children. The modern technologic environment has led to a dramatic increase in exposure to potential trigger stimuli; nowadays, television and video games are among the most common triggers in daily life. There is ample evidence for genetic transmission of photoparoxysmal responses; systematic family studies have provided data for an autosomal dominant mode of inheritance with age-dependent penetrance for photosensitivity. The age of maximum penetrance is between 5 and 15 years. The prognosis for control of seizures induced by visual stimulation is generally very good. The large majority of patients do not need anticonvulsant therapy, but, when needed, the drug of choice is valproate. Stimulus avoidance and stimulus modification can be an effective treatment in some patients and can sometimes be combined with antiepileptic drug treatment.

Photosensitivity and epilepsy: a follow-up study.

To understand the evolution of photosensitivity and to evaluate if its disappearance is related to the response to anticonvulsant therapy, we performed a long-term study of 42 patients (17 males, 25 females; age at onset 6 years 9 months, SD 5 years 2 months, range 5 years to 12 years 1 month) who had electroencephalography (EEG) evidence of photosensitive epilepsy. Of the patients, 36 were treated with valproate (VPA) monotherapy and four received VPA in combination with other antiepileptic drugs (AEDs), which were carbamazepine and lamotrigine. Two patients were given no drugs, but treated with stimuli avoidance. All patients were investigated with EEG by using intermittent photic stimulation. The photoparoxysmal response indicated the presence of photosensitivity. At the end of follow-up, the photoparoxysmal response had disappeared in 25 patients. Thirty-three patients became seizure-free. Our study confirms that photosensitive epilepsy has a good prognosis for seizure control that is independent of the persistence or disappearance of photosensitivity.

Intermittent oral diazepam prophylaxis in febrile convulsions: its effectiveness for febrile seizure recurrence.

In order to evaluate the effectiveness of diazepam for the reduction in the recurrence of febrile seizures we carried out a prospective study in two groups of children; Group A: 45 children (25 female, 20 male), receiving oral prophylaxis with diazepam, and Group B: 65 children (35 female, 30 male) who did not receive any oral prophylaxis. All subjects of both groups were followed for at least 4 years and finally re-evaluated at the mean age of 6.7+/-1.4 years. Among the patients of Group A, recurrent febrile seizures (FS) occurred in five of the 45 children (11.1%). Among the 65 children of Group B, 20 (30.7%) went on to have one or more additional episodes. In conclusion, our study demonstrates that oral diazepam, given only when fever is present, is an effective means of reducing the risk of recurrences of FS.

Diabetic neuropathy in children and adolescents.

Diabetic neuropathy (DN) represents a major complication of type 1 diabetes mellitus (T1DM) but there is considerable uncertainty as to its incidence, prevalence, diagnosis and prognosis in pediatric population. Generally, DN is classified as polyneuropathy, focal neuropathy and autonomic neuropathy. The latter seems to be detectable even in asymptomatic children and adolescents with diabetes and is associated with the most serious consequences, such as hypoglycemia unawareness and cardiovascular dysfunction. A near-normal control of blood glucose in the early years after onset of diabetes may delay the development of clinically significant nerve impairment and, therefore, children and adolescents with diabetes represent a critical target for primary prevention of this complication. The aim of this review is to focus on the main clinical, epidemiological and prognostic aspects of DN in children and adolescents with T1DM. Etiopathogenetic theories and diagnostic tools are also reviewed from in a pediatric perspective.

Benign focal epilepsy with onset in infancy in a patient with 18q-syndrome.

CASE REPORT: The 18q-syndrome is sometimes associated with epilepsy. We report a child with a 18q deletion who showed the typical manifestations of the syndrome. In addition, she had benign focal epilepsy with onset in infancy characterized by complex partial seizures with a frequency from 1 to 20 per day. This type of epilepsy is a rare condition and this is the first report of benign focal epilepsy with onset in infancy in a child with 18q-syndrome. The EEGs performed during sleep showed low-voltage spikes over the fronto-central region of the left hemisphere. The magnetic resonance imaging of the brain was normal. CONCLUSION: In conclusion, benign focal epilepsy with onset in infancy could be a condition associated with 18q-syndrome.

Risk factors for recurrence of epilepsy and withdrawal of antiepileptic therapy: a practical approach.

In epileptic patients, treated with anticonvulsant drugs (AEDs), the question when and how an attempt should be made to withdraw therapy is a crucial point in the management of these patients. In recent years, many studies have identified the main risk factors for seizure recurrence after discontinuation of AEDs. Patients are more likely to have recurrences if there is a definite symptomatic aetiology, two or more different types of seizures, an abnormal neurological examination and a seizure onset at adolescence or later. In contrast, abnormal EEG has not been proved as a risk factor for recurrence. Moreover, the classification of epilepsy syndromes is another important predictor of the outcome for these patients. In practice, most authors suggest that medication is discontinued after a seizure-free period of two years. In this review we analyse data from the literature and we suggest a practical approach for safe anticonvulsant withdrawal, although the decision should always be made individually, weighing risks and benefits.

Preventing microvascular diabetic complications in children and adolescents: looking beyond glycaemic control.

Type 1 diabetes mellitus is associated with the development of micro- and macrovascular disease, and diabetic angiopathy in children and adolescents. It is represented mainly by microangiopathy, characterised by structural changes in the eye, renal glomeruli and peripheral nerves. The pathogenesis of the vascular complications of diabetes is controversial, but without any doubt, endothelial dysfunction play an important role in the pathogenesis of glomerulosclerosis and atherosclerosis. Preventive strategies for these three major complications are discussed in this review. Appropriate surveillance for the earliest evidence of microvascular disease should begin at the onset of puberty, and after 3 - 5 years of diabetes. Therapeutic interventions, particularly excellent metabolic control, may be almost effective in preventing complication onset, or significantly retarding the rate of progression.

Anticonvulsant hypersensitivity syndrome in children: incidence, prevention and management.

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but potentially fatal, adverse reaction that occurs in patients, including children, who are treated with anticonvulsants. During metabolism of the anticonvulsant, toxic arene-oxide compounds are produced. AHS is associated with both cutaneous and systemic symptoms and is associated with multiorgan involvement. Liver damage, in particular, seems to be associated with fatal outcomes. The pathophysiology of AHS is still uncertain but it may be linked to a genetically determined inability to detoxify reactive drug metabolites. The prompt recognition of the first clinical signs of AHS, and the rapid withdrawal of the anticonvulsant, often avoids the progression of symptoms. Pharmacological treatment is essentially based on systemic corticosteroids in association with enteral nutrition, intravenous fluid augmentation, pain relief and ocular care. Intravenous immunoglobulins may also have a possible therapeutic role in some cases. Diagnostic tests, such as patch tests or in vitro assays, for AHS could help to identify patients at risk of developing the syndrome and could represent a first step of primary prevention when applied to relatives of patients.