Vernal Keratoconjunctivitis: an update focused on clinical grading system.

INTRODUCTION: Vernal keratoconjunctivitis (VKC) is a severe disease with a prevalence of < 1 case out of 10,000 in Europe, which occurs mainly in pediatric age and is characterized by a severe and often bilateral chronic inflammation of the ocular surface. The diagnosis is generally confirmed by the finding at the ocular examination of conjunctival hyperemia, papillary hypertrophy in the tarsal conjunctiva, giant papillae, papillae in the limbus region. OBJECTIVE: Aim of this review is to provide an updated overview on the disease focused on clinical grading system, searching papers published in the last decade on VKC in scientific databases. RESULTS: Currently there are no standardized criteria for diagnosis of VKC and there is no uniformity to define disease severity, which makes difficult to diagnose and treat the disease. CONCLUSIONS: Given the wide overlap of the symptoms of VKC with the allergic conjunctivitis, criteria of probable, possible or improbable diagnosis are needed, providing pediatricians with parameters useful for deciding whether to drive the patient to the ophthalmologist for diagnostic confirmation.

Electroclinical findings and long-term outcomes in epileptic patients with inv dup (15).

OBJECTIVE: To define the electroclinical phenotype and long-term outcomes in a cohort of patients with inv dup (15) syndrome. MATERIAL AND METHODS: The electroclinical data of 45 patients (25 males) affected by inv dup (15) and seizures were retrospectively analysed, and long-term follow-up of epilepsy was evaluated. RESULTS: Epilepsy onset was marked by generalized seizures in 53% of patients, epileptic spasms in 51%, focal seizures in 26%, atypical absences in 11% and epileptic falls in 9%. The epileptic syndromes defined were: generalized epilepsy (26.7%), focal epilepsy (22.3%), epileptic encephalopathy with epileptic spasms as the only seizure type (17.7%) and Lennox-Gastaut syndrome (33.3%). Drug-resistant epilepsy was detected in 55.5% of patients. There was a significant higher prevalence of seizure-free patients in those with seizure onset after the age of 5 years and with focal epilepsy, with respect to those with earlier epilepsy onset because most of these later developed an epileptic encephalopathy (69.2% vs 34.4%; P = .03), usually Lennox-Gastaut Syndrome in type. In fact, among patients with early-onset epilepsy, those presenting with epileptic spasms as the only seizure type associated with classical hypsarrhythmia achieved seizure freedom (P < .001) compared to patients with spasms and other seizure types associated with modified hypsarrhythmia. CONCLUSIONS: Epilepsy in inv dup (15) leads to a more severe burden of disease. Frequently, these patients show drug resistance, in particular when epilepsy onset is before the age of five and features epileptic encephalopathy.

Neuroimaging Changes in Menkes Disease, Part 2.

This is the second part of a retrospective and review MR imaging study aiming to define the frequency rate, timing, imaging features, and evolution of gray matter changes in Menkes disease, a rare multisystem X-linked disorder of copper metabolism characterized by early, severe, and progressive neurologic involvement. According to our analysis, neurodegenerative changes and focal basal ganglia lesions already appear in the early phases of the disease. Subdural collections are less common than generally thought; however, their presence remains important because they might challenge the differential diagnosis with child abuse and might precipitate the clinical deterioration. Anecdotal findings in our large sample seem to provide interesting clues about the protean mechanisms of brain injury in this rare disease and further highlight the broad spectrum of MR imaging findings that might be expected while imaging a child with the suspicion of or a known diagnosis of Menkes disease.

Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study.

PURPOSE: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions. PATIENTS AND METHODS: This Italian multicenter retrospective observational study was performed in 16 paediatric epilepsy centres. Inclusion criteria were: (i) ≤18 years of age, (ii) history of refractory epilepsy, (iii) a follow-up ≥5 months of PER add-on therapy. Exclusion criteria were: (i) a diagnosis of primary idiopathic generalized epilepsy, (ii) variation of concomitant AEDs during the previous 4 weeks. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline. RESULTS: 62 patients suffering from various refractory epilepsies were included in this study: 53% were males, the mean age was 14.2 years (range 6-18 years), 8 patients aged <12 years. Mean age at epilepsy onset was 3.4 years and the mean duration of epilepsy was 10.8 years (range 1-16), which ranged from 2 seizures per-month up to several seizures per-day (mean number=96.5). Symptomatic focal epilepsy was reported in 62.9% of cases. Mean number of AEDs used in the past was 7.1; mean number of concomitant AEDs was 2.48, with carbamazepine used in 43.5% of patients. Mean PER daily dose was 7.1mg (2-12mg). After an average of 6.6 months of follow-up (5-13 months), the retention rate was 77.4% (48/62). The response rate was 50%; 16% of patients achieved ≥75% seizure frequency reduction and 5% became completely seizure free. Seizure aggravation was observed in 9.7% of patients. Adverse events were reported in 19 patients (30.6%) and led to PER discontinuation in 4 patients (6.5%). The most common adverse events were behaviour disturbance (irritability and aggressiveness), dizziness, sedation and fatigue. CONCLUSION: PER was found to be a safe and effective treatment when used as adjunctive therapy in paediatric patients with uncontrolled epilepsy.

Clinical dissection of childhood occipital epilepsy of Gastaut and prognostic implication.

BACKGROUND AND PURPOSE: Our aim was to describe the clinical and electrical features and the long-term evolution of childhood occipital epilepsy of Gastaut (COE-G) in a cohort of patients and to compare long-term prognosis between patients with and without other epileptic syndromes. METHODS: This was a retrospective analysis of the long-term outcome of epilepsy in 129 patients with COE-G who were referred to 23 Italian epilepsy centres and one in Austria between 1991 and 2004. Patients were evaluated clinically and with electroencephalograms for 10.1-23.0 years. The following clinical characteristics were evaluated: gender, patient age at seizure onset, history of febrile seizures and migraine, family history of epilepsy, duration and seizure manifestations, circadian distribution and frequency of seizures, history of medications including the number of drugs, therapeutic response and final outcome. RESULTS: Visual hallucinations were the first symptom in 62% and the only manifestation in 38.8% of patients. Patients were subdivided into two groups: group A with isolated COE-G; group B with other epileptic syndromes associated with COE-G. The most significant (P < 0.05) difference concerned antiepileptic therapy: in group A, 45 children responded to monotherapy; in group B only 15 children responded to monotherapy. At the end of follow-up, the percentage of seizure-free patients was significantly higher in group A than in group B. CONCLUSIONS: Childhood occipital epilepsy of Gastaut has an overall favourable prognosis and a good response to antiepileptic therapy with resolution of seizures and of electroencephalogram abnormalities. The association of typical COE-G symptoms with other types of seizure could be related to a poor epilepsy outcome.

The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features.

Spinal neurofibromatosis (SNF) is a related form of neurofibromatosis 1 (NF1), characterized by bilateral neurofibromas (histologically proven) of all spinal roots (and, eventually, of all the major peripheral nerve branches) with or without other manifestations of classical NF1. By rigorous application of these criteria to the 98 SNF cases published, we developed: (i) a cohort of 49 SNF patients (21 males and 28 females; aged 4-74 years]: 9 SNF families (21/49), 1 mixed SNF/NF1 family (1/49) and 27 of 49 sporadic SNF patients (including 5 unpublished patients in this report); and (ii) a group of 49 non-SNF patients including: (a) 32 patients with neurofibromas of multiple but not all spinal roots (MNFSR): 4 mixed SNF/MNFSR families (6/32); (b) 14 patients with NF1 manifestations without spinal neurofibromas, belonging to SNF (8/49) or MNFSR families (6/32); (c) 3 patients with neurofibromas in one spinal root. In addition to reduced incidence of café-au-lait spots (67% in SNF vs 56% in MNFSR), other NF1 manifestations were less frequent in either cohort. Molecular testing showed common NF1 gene abnormalities in both groups. The risk of developing SNF vs NF1 was increased for missense mutations [p = 0.0001; odds ratio (OR) = 6.16; confidence interval (CI) = 3.14-13.11], which were more frequent in SNF vs MNFSR (p = 0.0271).

Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS.

Efficacy and tolerability of add-on lacosamide in children with Lennox-Gastaut syndrome.

OBJECTIVE: Available data on the efficacy of lacosamide in children with Lennox-Gastaut syndrome (LGS) are scarce and controversial. We present our experience with lacosamide therapy in children affected by LGS. MATERIAL AND METHODS: Medical charts of all children affected by LGS receiving oral lacosamide adjunctive therapy in six paediatric neurology centres were retrospectively evaluated. Efficacy was determined according to the frequency of countable seizures during the 4 weeks prior to treatment and the frequency in the last 4 weeks of observation. Patients whose seizure frequency was reduced by at least 50% were defined as responders. RESULTS: Eighteen children (mean age 12.3 years) were identified. After a mean follow-up period of 9 months, 33% of patients were responders. None of them was seizure-free during the study period. The overall seizure reduction rate was 29%. The percentage reductions from baseline in tonic seizures and drop-attacks rates were 31% and 20%, respectively. Adverse reactions occurred in 44% of patients. The drug was discontinued in four (22%) patients because of increased seizure frequency (three cases) and walking instability (another patient). CONCLUSIONS: A third of children with LGS were responders after lacosamide adjunctive therapy. Although caution is still necessary when the drug is used in children with LGS, our preliminary observations suggest that lacosamide might be effective and represent a possible therapeutic option in children affected by LGS.

Early-onset absence epilepsy: SLC2A1 gene analysis and treatment evolution.

BACKGROUND AND PURPOSES: To determine the prevalence of SLC2A1 mutations in children with early-onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure-free with anti-epileptic drug (AED) monotherapy (group I) and those who needed add-on treatment of a second AED (group II). METHODS: We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of SLC2A1 was performed in each patient. RESULTS: Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in SLC2A1 was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first-degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month follow-up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II (P = 0.008). CONCLUSIONS: We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure-free with add-on treatment of a second AED.

Antiepileptic drug withdrawal in childhood epilepsy: what are the risk factors associated with seizure relapse?

BACKGROUND: In recent years, several studies have been conducted to determine the risk of relapse after antiepileptic drug (AED) withdrawal: there is no general agreement on criteria that can predict safe discontinuation or seizure recurrence. AIMS: To evaluate prospectively the relapse rate of epilepsy associated to AED withdrawal in epileptic children and to determine the risk factors of seizure recurrence. METHODS: One hundred-sixty-eight children with epilepsy who were seizure-free for at least 2 years were enrolled and all children were proposed to stop AED treatment and were followed. In all children electroencephalograms (EEGs) were performed before the withdrawal of AEDs and after discontinuation of the treatment. RESULTS: A total of 48 (28.6%) children relapsed; half of these patients relapsed while reducing the AED dose and the other half after the AED was withdrawn; after 2 years without AEDs, the risk of relapse was very low. Data evaluated by multivariable analysis showed that the children receiving polytherapy before AED withdrawal, having a history of febrile seizures and suffering from multiple seizure types relapsed more frequently. The presence of abnormal post-withdrawal EEG recordings was associated with a higher risk of seizure recurrence. CONCLUSIONS: Epileptic children, after a seizure-free period of 2 years, have a low risk of seizure recurrence. The potential risk factors of relapse, are multiple seizure types previous polytherapy, history of febrile seizures and abnormalities in post-withdrawal EEG.

Effects of the abrupt switch from solution to modified-release granule formulation of valproate.

BACKGROUND: A new modified-release (MR) granule formulation of valproate (VPA) has been recently developed for the treatment of children with epilepsy. It consists of tasteless microspheres that can be sprinkled on soft foods and easily swallowed. There are no data on the effectiveness of this formulation in pediatric age. AIM OF THE STUDY: To evaluate the effects of the abrupt switch from solution to VPA MR granules in children undergoing chronic treatment. METHODS: We enrolled children receiving VPA solution as sole or adjunctive therapy and switched them to MR granules at identical dosages. VPA blood level, treatment efficacy (clinical and EEG data), tolerability (adverse reactions), palatability, ease of administration, and compliance were evaluated before switching (T0) and after 4 weeks (T1). RESULTS: Out of 112 enrolled children, 108 (96.4%) completed the evaluation. We observed no significant differences between the patients at T0 and T1 in VPA blood levels, treatment efficacy, tolerability, and compliance. MR granules were judged more palatable (P < 0.05) and easier to administer (P < 0.05) than solution by children and parents. At 6-month follow-up, all patients continued to use MR granules. CONCLUSION: Modified-release granule formulation of VPA may be a reliable alternative to solution for its convenience of use.

Early add-on immunoglobulin administration in Rasmussen encephalitis: the hypothesis of neuroimmunomodulation.

Rasmussen encephalitis (RE) is a chronic inflammatory disease leading to unilateral hemispheric atrophy, associated with progressive neurological dysfunction and intractable seizures. The best approach to RE is hemispherectomy. However long-term immunotherapy seems to prevent or slow down hemispheric tissue loss and the associated functional decline. We describe a girl with epilepsia partialis continua (EPC) and progressive neurological dysfunction compatible with RE. The brain MRI showed a lesion that was initially interpreted as focal cortical dysplasia. Combined antiepileptic and immunomodulation were administered for two years with initial beneficial effects. The follow-up MRI, 4 year later showed. atrophic change in right parietal region. The association of antiepileptic and immunomodulation therapies may inhibit pathogenetic mechanisms responsible for neuronal loss in RE, slowing down the progression of the disease.

Evaluation and management of nonsyndromic craniosynostosis.

UNLABELLED: Craniosynostosis (craniostenosis) is premature fusion of the sutures of the cranial vault. Several factors can affect the growth of the cranial vault during embryonic life and after birth, leading to different types of craniosynostosis; these can be classified on the basis of the specific sutures that are fused. Prognosis is improved by early diagnosis, and it is important to establish the correct approach to these patients on the basis of clinical and neuroradiological investigation. The first priority is to identify the type of craniosynostosis and to distinguish between the types that require surgical intervention and those that do not. We report on the different forms of nonsyndromic craniosynostosis, their clinical and neuroradiological diagnoses, and surgical strategies. CONCLUSION: The aim of this review is to provide to paediatricians a correct diagnostic approach and management of children affected from nonsyndromic craniosynostosis, for which a careful physical, ophthalmological and neurological examination is fundamental, whereas brain Computed tomography and magnetic resonance imaging are necessary for patients in which the diagnosis is uncertain or for cases of syndromic craniosynostosis.

Rufinamide in refractory childhood epileptic encephalopathies other than Lennox-Gastaut syndrome.

BACKGROUND: To report on the first multicenter Italian experience with rufinamide as adjunctive drug in children, adolescents and young adults with refractory childhood-onset epileptic encephalopathies other than Lennox-Gastaut syndrome. METHODS: Thirty-eight patients (19 males, 19 females), aged between 4 and 34 (mean 13.7 ± 8.3, median 12.5), all affected by different types of childhood-onset refractory epileptic encephalopathies other than Lennox-Gastaut syndrome, were treated with rufinamide as adjunctive drug for a mean period of 11.4 months (range 3-26 months). RESULTS: Fifteen of 38 patients (39.5%) had a ≥ 50% seizure reduction in countable seizures. Complete seizure freedom was achieved in one of these patients (2.6%). Three patients (7.9%) had a 25-49% seizure reduction, whilst seizure frequency remained unchanged in 15 (39.5%) and increased in five patients (13.1%). Eleven patients (28.9%) reported adverse side effects. Vomiting was reported in five patients (13.1%); drowsiness, decreased appetite and irritability with migraine manifested in other four patients. They were transient and mild in all cases. CONCLUSION: Rufinamide may be an effective and well-tolerated adjunctive drug for the treatment of refractory childhood-onset epileptic encephalopathies other than Lennox-Gastaut syndrome. Rufinamide was most effective in patients with drop-attacks and (bi)frontal spike-wave discharges.

Epileptic nystagmus: description of a pediatric case with EEG correlation and SPECT findings.

Epileptic nystagmus (EN) describes repetitive eye movements that result from seizure activity. We describe a patient with EN and vertigo first noted at the age of 4 yr and 10 mo. Brain MRI did not show anomalies. Ictal EEG recordings revealed epileptic activity during three episodes of horizontal, left-beating nystagmus not crossing the midline. Ictal 99mTc-ECD SPECT demonstrated the presence of active foci in multiple cerebral regions including bilateral prefrontal, bilateral parieto-temporo-occipital and the left parieto-insular-vestibular areas. A wide area of hypoperfusion was also evident in the right hemisphere, prevailing in the parieto-occipital regions and the medial prefrontal gyrus. Topiramate was started at a dose of 2 mg/kg/d with complete seizure control after 14 d. EEG and SPECT were repeated after a seizure-free period of 1 mo; disappearance of epileptic activity and modification of cerebral perfusion were evident. This case reaffirms the cortical origin and involvement of temporo-occipital and frontal cortex in the genesis of saccadic epileptic nystagmus. Rapid complete control of clinical events coincided with the normalization of EEG and improvement of the SPECT pattern.

Color vision and macular recovery time in epileptic adolescents treated with valproate and carbamazepine.

Visual dysfunction has been reported in patients diagnosed with epilepsy. Some of these visual disturbances may be attributable to either the disease process, or the anticonvulsant therapy prescribed to control the seizures. The aims of our study were to evaluate whether color vision and macular function are impaired in epileptic adolescents, to study if the monotherapy with valproic acid (VPA) and carbamazepine (CBZ) can affect color vision and macular function and to determine the possible relationship between color vision, retinal function and antiepileptic drugs (AEDs) dosage and their serum concentrations. We examined 45 (16 male and 29 female, mean age +/- SD, 15.71 +/- 2.01 years) Caucasian epileptic patients suffering from various types of cryptogenic epilepsy before the beginning of therapy and after 1 year of VPA or CBZ monotherapy and 40 sex- and age-matched healthy controls. Color vision was assessed by Farnsworth Munsell (FM) 100-hue test and total error score (TES) was evaluated. This test consists of colored caps: the testee has to arrange the caps according to their colors macular function was assessed by nyctometry evaluating initial recovery time (IRT) and summation method (SM). This test evaluates visual acuity after a period of intense illumination of macula. Analysis of variance was used to evaluate the difference between controls and patients; moreover, Pearson's correlation test have been performed. Before the beginning of therapy, there were no differences in color vision and macular function between controls and epileptic patients. After 1 year, the patients, treated with VPA or CBZ, showed a deficit in FM 100-hue test. At nyctometry, all patients showed no significant variation of macular function between baseline evaluation and second evaluation at end of the follow-up. Our study demonstrates that, in our group of epileptic patients, epilepsy per se does not affect color vision and retinal function. In contrast, after 1 years of therapy with VPA and CBZ these patients showed a deficit in FM 100-hue test although nyctometry evaluation continued to be normal allowing to exclude an impairment in macular function. Further investigations are required to determine the pathophysiological alteration(s) that are at the basis of color perception defects.

Efficacy and safety of levetiracetam: an add-on trial in children with refractory epilepsy.

The aim of this multicentric, prospective and uncontrolled study was to evaluate the efficacy and safety of levetiracetam in 110 children with refractory epilepsy, of whom 21 were less than 4 years old. After a median follow-up period of 7 months, levetiracetam administration was effective (responders with >50% decrease in seizure frequency) in 39% of children, of whom 10 (9%) became seizure-free. The efficacy was higher in patients with localization-related epilepsy (58% of responders) than in those with generalized epilepsy (37% of responders). Levetiracetam was well tolerated. The main side effects of somnolence and irritability occurred in 14% of patients. In one patient acute choreoathetosis occurred after few doses of levetiracetam. Overall, the adverse effects were not severe. Children younger than 4 years were particularly tolerant. In conclusion, the present study confirms that levetiracetam is effective and well tolerated as an add-on treatment in children with refractory epilepsy. Our preliminary data also indicate that levetiracetam may be a valid therapeutic option for epilepsy in infants and young children.