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.

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.

Levetiracetam monotherapy for childhood occipital epilepsy of gastaut.

OBJECTIVES: The aim of this open label pilot study was to evaluate the efficacy and tolerability of levetiracetam (LEV) as 'de novo' monotherapy in children and adolescents with late onset childhood occipital epilepsy-Gastaut type (COE-G). MATERIAL AND METHODS: Twelve patients suffering from COE-G were enrolled in this prospective study. The age of seizures onset ranged from 6.1 to 16.2 years with a peak of frequency at mean (+/-SD) 10.54 +/- 2.77 years. Therapy with LEV was started at 10 mg/kg/day and, after titration, the final dose was generally achieved within 4 weeks and ranged from 20.7 to 45.2 mg/kg/day. RESULTS: At the 6 month evaluation, 11 (91.6%) of the 12 patients studied were seizure free, and one (8.3%) showed four additional episodes. Electroencephalography (EEG) activity was normal in six (54.5%) patients, unchanged in two (18.1%) children, and in four (33.3%) patients sporadic occipital abnormalities persisted. At the 12-month evaluation all patients were completely seizure free. Four patients (33.3%) continued to show some EEG abnormalities, while eight (72.8%) patients had normal EEG. At the 18-month evaluation all patients were seizure free and 10 patients (83.3%) showed a complete normalization of EEG abnormalities. DISCUSSION: Monotherapy with LEV was effective and well tolerated in patients with COE-G. Nevertheless, prospective, large, long-term double-blind studies are needed to confirm these findings.

Early-onset hereditary neuropathy with liability to pressure palsy.

The clinical onset of hereditary neuropathy with liability to pressure palsy (HNPP) in childhood is rarely reported. On the basis of a 5-year-old affected patient, we reviewed the cases reported in the literature to evaluate the clinical and genetic characteristics of patients with an early onset (<10 years) of HNPP.

Update of the medical treatment of West syndrome.

West syndrome is a generalized epilepsy syndrome composed of infantile spasms and onset is usually within the first year of life. Although West syndrome is well known clinical epileptic syndrome, there is no agreement about the first- and second-line treatments. In the last years a great progress in the development of new antiepileptic drugs allow us to have a large choice of treatment options to control the seizures. This review outlines the usefulness of the different antiepileptic drugs for the treatment of West syndrome.

Levetiracetam monotherapy for children and adolescents with benign rolandic seizures.

To assess the efficacy, tolerability and safety of Levetiracetam (LEV) therapy, we identified 21 (15 male; 6 female) patients with a history of benign epilepsy with centrotemporal spikes (BECTS), with and without secondarily generalization in children and adolescents aged between 5.0 and 12.1 years. LEV was administered as a first drug (number of patients=9) or converted after previous treatment with other AEDs (number of patients=12). The patients were subdivided into two groups: "newly diagnosed" patients and "converted" patients. Patients were followed up for 12 months and all patients were able to continue on LEV treatment. At the end of follow-up (12 months), all patients were seizure free or showed a reduction of seizures >50%. LEV dosage ranged from 1000 to 2500mg/daily. Overall, 100% of patients completed the 12 months study, without any important side effect. Somnolence and irritability occurred in two (9.5%) patients. Our results support findings that LEV monotherapy is effective and well tolerated in children with BECTS. Prospective, large, long-term double-blind studies are needed to confirm these findings.

Topiramate in frontal lobe epilepsy.

BACKGROUND: Frontal lobe epilepsy (FLE) is a type of epilepsy that is difficult to treat and there are few studies about the use of topiramate (TPM). AIM OF THE STUDY: To evaluate the efficacy and tolerability of TPM monotherapy in FLE. METHODS: The study group consisted of 55 (33 male; 22 female) patients. TPM was administered as a first drug (n = 16) or converted after previous treatment (n = 39). All patients were followed every 3 months for at least 1 year. The patients were subdivided into two groups: 'newly diagnosed' patients and 'difficult-to-treat' patients. RESULTS: Overall, all patients completed the 1-year study. At the end of follow-up, 10 patients showed disappearance of seizures and 33 patients showed improvement in seizure frequency. In particular, among the newly diagnosed patients 6/16 patients showed complete cessation of seizures and 5/16 patients showed very good response; in the other group, 4/39 patients showed complete cessation and 4/39 patients showed a very good response. No patients of both groups had worsening of seizures. No treatment-limiting adverse events associated with TPM were reported. CONCLUSIONS: TPM is effective in newly diagnosed patients with FLE; TPM can be considered for the treatment of FLE.

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.

Leptin, ghrelin, and adiponectin in epileptic patients treated with valproic acid.

The authors studied 40 epileptic patients treated with valproate and 40 healthy controls for at least 2 years. At the end of follow-up, 15 epileptic patients (37.5%) had development of obesity. They showed circulating leptin and insulin levels significantly higher and ghrelin and adiponectin levels significantly lower than those of patients who did not gain weight.

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.

Earliest clinical manifestations and natural history of neurofibromatosis type 2 (NF2) in childhood: a study of 24 patients.

BACKGROUND: Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterised by the development of multiple nervous system tumours, ocular abnormalities, and skin tumours. Although classically considered a disease of adults, initial signs and/or symptoms may be evident in childhood and are often unrecognised. OBJECTIVES: The aim of this study was to identify the earliest clinical presentations of NF2 and to characterise the clinical course and outcome in children with NF2. METHODS: We have performed a retrospective (years 1990-1998) and prospective (years 1998-2004) study of 24 patients (10 males, 14 females; currently aged 4 to 22 years) fulfilling the revised (Manchester) NF2 criteria seen at the Universities of Catania and Rome, Italy. RESULTS: Causes of referral prior to a definitive diagnosis of NF2 were: 1) Ophthalmologic problems: early onset lens opacities (n = 3); strabismus (n = 3) and amblyopia (n = 3) (due to underlying cranial nerves and/or brain tumours); 2) Otolaryngology problems: hearing loss and tinnitus (n = 2) in early teens disregarded or treated as ear infections; hoarse (n = 1) or bitonal (n = 1) voice; 3) Neurological dysfunction: seizures secondary to intracranial meningioma (n = 1) or vestibular schwannomas (VS) (n = 1), neurological dysfunction related to brainstem and/or spinal cord tumours (n = 7), isolated and multiple cranial nerve deficits (n = 10), and peripheral neuropathy secondary to schwannomas (n = 4); 4) Skin manifestations: schwannomas misdiagnosed as neurofibromas because of associated café-au-lait spots (n = 2); café-au-lait spots (n = 8) and skin tumours (n = 3). A family history was relevant in 20 % of the patients. Molecular genetic analysis of the NF2 gene revealed typical truncating mutations in all the 5 familial cases and in 2/10 sporadic cases analysed. CONCLUSIONS: Children with NF2 often first come to medical attention because of ocular, subtle skin, or neurological problems the significance of which is realised when they later present with more classical symptoms due to bilateral VS or other intracranial tumours. The clinical course at this young age is highly variable, depending on tumour burden, early surgical intervention, surgical outcome after tumour resection, and complications.

Ophthalmological manifestations in segmental neurofibromatosis type 1.

AIMS: To study the ophthalmological manifestations in individuals with the typical features of neurofibromatosis type 1 (NF1) circumscribed to one or more body segments, usually referred to as segmental NF1. METHODS: Visual acuity and colour tests, visual field examination, slit lamp biomicroscopy of the anterior segment, and a detailed examination of the retina by indirect ophthalmoscopy were performed at diagnosis and follow up in 72 consecutive subjects (29 males, 43 females; aged 1-64 years; mean age 14.6 years) seen at the university departments of paediatrics in Catania and Rome, Italy, during years 1990-2003, who had in restricted body areas: (1) typical pigmentary manifestations of NF1 (cafe au lait spots and freckling) only (n = 48); (2) NF1 pigmentary manifestations and neurofibromas alone (n = 2); (3) neurofibromas only (n = 15); and (4) plexiform neurofibromas only (n = 7). RESULTS: None of the 72 patients had Lisch nodules in the iris irrespective of age at eye examination or hypertelorism (a "minor" NF1 feature) and none developed typical associated ophthalmological NF1 complications. An additional child had an isolated optic pathways glioma (OPG), which behaved both biologically and radiographically as an NF1 associated OPG. CONCLUSIONS: This represents the first systematic study reporting on eye involvement in the largest series of individuals at different ages having segmental NF1. As one of the postulated mechanisms to explain segmental NF1 is somatic mosaicism for the NF1 gene (so far demonstrated only in two patients) the present findings could be explained either by the fact that the eye is too far from the mutated area with NF1 lesions in most cases or by the NF1 (or other "predisposing" or "cooperating") gene mutation restricted to too few cellular clones or to tissues embryologically different from the eye.

Multiple sclerosis in children under 10 years of age.

Despite the consistent amount of information accumulated in recent years on multiple sclerosis (MS) in childhood, many clinicians still view this condition as an exclusively young adult-onset disease and do not consider that it may occur and manifest even during infancy and pre-school age, suggesting that the number of MS cases in the paediatric age group may have been underestimated. Thus, the need to have practical parameters for therapeutic, counselling and educational purposes in such settings as caring for patients whose onset of disease is at very early ages may increasingly arise for practising clinicians. In addition, the clinical and radiographic criteria for the diagnosis of MS have not been validated in a paediatric MS population; accordingly, inclusion age at onset (such as for research purposes) is generally over 10 years. To highlight the peculiarities that characterise MS when it begins at this young age we have reviewed the literature and summarised our preliminary results with the national registry of the Italian Society of Paediatric Neurology (SINP) Study Group on Childhood MS in the group of MS patients with the earliest onset of disease (i.e., <10 years of age).

Seizures in paediatric Chiari type I malformation: the role of single-photon emission computed tomography.

UNLABELLED: Chiari type I malformation is one of the posterior fossa maldevelopments with which different clinical manifestations have been associated. Seizures have only recently been associated with Chiari type I malformation. This study reports on 4 children with epilepsy (2M, 2F; age range 8-15 y) diagnosed with Chiari type I malformation by brain magnetic resonance imaging (MRI), in whom no cortical structural involvement was observed. In these patients an interictal ethylcysteinate-dimer-single-photon emission computed tomographic (ECD-SPECT) study was performed to define more precisely the relationship between Chiari type I malformation and seizures. In these patients the hypoperfusion area correlated with electroencephalographic (EEG) focal abnormalities. These hypoperfusions may represent the functional aspect of a cerebral microdysgenesis; seizures and EEG epileptic anomalies may also be linked to the complex network connection between cortices and cerebellar hemispheres. A cerebellar hypoperfusion was also detected in two of the four examined patients, indicating a functional or structural involvement. CONCLUSION: Interictal SPECT scans are helpful for the clarification of seizures in patients with Chiari type I malformation.

Ictal single photon emission computed tomography in absence seizures: apparent implication of different neuronal mechanisms.

Absence seizures represent a complex group of epilepsy, characterized by lapse of consciousness with staring. Bilateral, synchronous, and symmetric bursts of 3-Hz spike-and-wave discharges are observed on the electroencephalogram, whereas interictal background activity is normal. This kind of epilepsy has to be differentiated from other generalized epilepsies such as juvenile absence epilepsy and juvenile myoclonic epilepsy. Moreover, absence seizures, together with generalized spike-and-wave discharges, may coexist with other types of epilepsy such as frontal lobe epilepsy, temporal lobe epilepsy, benign epilepsy with centrotemporal spikes, and childhood epilepsy with occipital paroxysms. We have carried out ictal single photon emission computed tomography (SPECT) in 10 patients with clinical evidence of absence seizures with the aim to better understand and to distinguish this kind of seizure as primarily or secondarily generalized to a specific area and to obtain more information on the neuronal mechanisms involved in the different types of seizures, usually not identifiable at the first appearance. During the long follow-up period (9 months to 14 years), 7 of the 10 examined patients underwent interictal SPECT when they became seizure free. Our data permitted, in two patients, the diagnosis of childhood absence seizures; in three patients, they suggested the possibility of later appearance of other seizure types, on the basis of focal hyperperfusion indicating a possible focal firing. In three of the examined patients, the diagnosis of idiopathic localization-related epilepsies mimicking childhood absence seizures could be performed. In the last two patients, the hypothesis of a coexistence of absences with partial and generalized seizures was considered. From our results, it can be presumed that ictal SPECT findings may contribute to the physiopathologic classification of the different types of epilepsies. Moreover, anticonvulsant treatment more appropriate to the different forms of seizures can be used.

Functional neuroradiologic investigations in band heterotopia.

Band heterotopias are an example of genetic generalized neuronal migration disorders that may be present in patients with mild epilepsy and normal or slightly impaired intellect, as well as in patients with intractable epilepsy and mental retardation. The case of a 17-year-old left-handed female patient with epilepsy and normal cognitive development is reported in whom single-photon emission computed tomography (SPECT), proton magnetic resonance spectroscopy, and functional magnetic resonance imaging (fMRI) were performed. MRI revealed the presence of bilateral asymmetric band heterotopia. SPECT revealed a left frontoparietal and occipital hypoperfusion, demonstrating a good correlation with the electroencephalogram abnormalities. Because of the appearance of new types of seizures, the patient underwent a second MRI investigation together with a proton magnetic resonance spectroscopy (MRS) study. MRI confirmed bilateral band heterotopia characterized by greater thickness in the left hemisphere at the frontal and occipital level. MRI and SPECT findings were in agreement with left occipital electroencephalogram abnormalities and with occipital seizure type. Qualitative results of proton MRS revealed normal spectra profiles in the examined left frontal and occipital heterotopic area and in the normal overlying cortex. Later, fMRI was performed. The finger-tapping test of the right hand yielded the activation of both normal left sensory-motor cortex and the facing band heterotopia. In the right hemisphere, only the activation of the sensory-motor neocortex was observed; no involvement of the right misplaced brain tissue was present. This functional behavior could be considered the consequence of poor neuronal representation. On the contrary, the involvement of both band heterotopia and normal cortex observed in the left hemisphere could be the result of many synaptic interconnections. Functional investigations may have an important role in defining the activity of band heterotopia per se and in relation to the overlying neocortex.