Red Flags for early referral of people with symptoms suggestive of narcolepsy: a report from a national multidisciplinary panel.

OBJECTIVE: Narcolepsy is a lifelong disease, manifesting with excessive daytime sleepiness and cataplexy, arising between childhood and young adulthood. The diagnosis is typically made after a long delay that burdens the disease severity. The aim of the project, promoted by the "Associazione Italiana Narcolettici e Ipersonni" is to develop Red Flags to detect symptoms for early referral, targeting non-sleep medicine specialists, general practitioners, and pediatricians. MATERIALS AND METHODS: A multidisciplinary panel, including patients, public institutions, and representatives of national scientific societies of specialties possibly involved in the diagnostic process of suspected narcolepsy, was convened. The project was accomplished in three phases. Phase 1: Sleep experts shaped clinical pictures of narcolepsy in pediatric and adult patients. On the basis of these pictures, Red Flags were drafted. Phase 2: Representatives of the scientific societies and patients filled in a form to identify barriers to the diagnosis of narcolepsy. Phase 3: The panel produced suggestions for the implementation of Red Flags. RESULTS: Red Flags were produced representing three clinical pictures of narcolepsy in pediatric patients ((1) usual sleep symptoms, (2) unusual sleep symptoms, (3) endocrinological signs) and two in adult patients ((1) usual sleep symptoms, (2) unusual sleep symptoms). Inadequate knowledge of symptoms at onset by medical doctors turned out to be the main reported barrier to diagnosis. CONCLUSIONS: This report will hopefully enhance knowledge and awareness of narcolepsy among non-specialists in sleep medicine in order to reduce the diagnostic delay that burdens patients in Italy. Similar initiatives could be promoted across Europe.

Progressive cerebral white matter involvement in a patient with Congenital Cataracts Facial Dysmorphisms Neuropathy (CCFDN).

Congenital Cataracts with Facial Dysmorphisms and Neuropathy (CCFDN) is a complex autosomal recessive disorder characterized by bilateral congenital cataracts, developmental delay, peripheral; hypo-demyelinating neuropathy, mild facial dysmorphisms, and other rare signs. Cerebral and spinal cord atrophy is the main neuroimaging finding but other less common abnormalities have been previously described. We describe progressive focal lesions of supratentorial white matter in a 10-year-old boy affected by CCFDN. Other etiologies have been excluded and these lesions can be considered a new finding of the disease. We discuss a possible demyelinating mechanism affecting both peripheral and central myelin.

Preliminary report on effects of oxcarbazepine-treatment on serum lipid levels in children.

The aim of the present study was to assess serum lipid levels before and after treatment with oxcarbazepine (OXC) in children with epilepsy. We measured total cholesterol (TC), triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) in 28 patients whereas only TC levels in 11 patients, during baseline period and at 3 months after the beginning of therapy with OXC. During baseline period, median values were: 4.38 mmol/l (IQR = 4.12-5.03) for TC levels, 1.72 mmol/l (IQR = 1.42-2.01) for HDL-C levels and 1.54 mmol/l (IQR = 1.29-1.96) for TGs levels. At 3 months, median values were: 4.38 mmol/l (4.10-4.95) for TC levels (P < 0.05), 1.57 mmol/l (1.34-1.93) for HDL-C levels (P < 0.005) and 1.8 mmol/l (1.23-2.34) for TGs levels (P < 0.05). Median serum lipid levels remained in the normal range, despite an increasing-trend at 3 months of treatment with OXC. Further studies are necessary to confirm these results.

Open prospective study on oxcarbazepine in epilepsy in children: a preliminary report.

PURPOSE: To evaluate the long-term efficacy, tolerability, and safety of oxcarbazepine (OXC) in children with epilepsy. METHODS: We enrolled 36 patients (median age 7.75) with new diagnosis of partial epilepsy in an open prospective study. All type of epilepsy were included: 25 patients were affected by idiopathic epilepsy, eight by symptomatic epilepsy and three by cryptogenic epilepsy. Patients were then scheduled to come back for controls at 3 months (T1), 12 months (T2) and 24 months (T3) after the beginning of OXC-monotherapy (T0). At each control we evaluated patients through their seizure diary, a questionnaire on side effects, their level of 10-monohydroxy (MHD) metabolite and laboratory analysis. RESULTS: At T1, 21/36 patients (58.3%) were seizure-free, 3/36 patients (8.3%) showed an improvement higher than 50%, 3/36 (8.3%) lower than 50%, while 2/36 worsened (5.6%). In 7/36 (19.5%) patients, no improvement was reported. At T2 13/18 patients (72.2%) were seizure-free, 1/18 showed a response to therapy higher than 50% while 2/18 worsened (11%). In two patients no improvement was reported. A correspondence between MHD plasmatic levels and clinical response (r=0.49; p<0.05) was only registered at T1. An EEG normalization was observed in 25% of cases. Side effects were reported in 25% of cases, but symptoms progressively disappeared at follow-up. CONCLUSIONS: We can therefore conclude that OXC can be considered, for its efficacy and safety, as a first line drug in children with epilepsy.

Clinical features of benign infantile convulsions: familial and sporadic cases.

The authors describe the so-called benign convulsions of infancy and confirm the existence of benign nonfamilial infantile convulsions during the first 2 years of life and their benign course. The authors evaluated 58 patients: 17 subjects had a family history of benign epilepsy, and 41 did not. No clinical differences were observed between the two groups.

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.

X-linked neurodegenerative syndrome with congenital ataxia, late-onset progressive myoclonic encephalopathy and selective macular degeneration, linked to Xp22.33-pter.

Linkage analysis was performed in a previously described family segregating for an X-linked progressive neurological disorder [Bertini et al., 1992]. In three generations, the disease was inherited from the mothers in seven affected males (Fig. 1). Five had severe congenital hypotonia and died during the first year of life. Two other boys (maternal cousins) were found to have severe congenital ataxia, late-onset progressive myoclonic encephalopathy, and selective macular degeneration; brain CT-scan showed moderate cerebellar vermis hypoplasia. Linkage analysis was carried out in 12 informative relatives using 35 microsatellite markers (Généthon) evenly distributed on the X chromosome. A multipoint analysis showed a significant linkage (Z > 2) between the disease and three markers in the Xp22.33 region: DYS403 (Z = 2.37, theta = 0) which maps in the pseudoautosomal region, DXS7099 (Z = 2.45, theta = 0), and DXS7100 (Z = 2.48, theta = 0). Further linkage analysis with more telomeric markers will refine the location of this severe X-linked encephalopathy.

Band brain heterotopia. Case report and literature review.

The authors describe the case of an 11-year-old boy with a neuroradiologic pattern of band gray matter heterotopia, clinically characterized by epileptic seizures as well as normal psychomotor development. The clinical history and neurophysiological and neuroradiological investigations are reported. The diagnosis is based on brain magnetic resonance (MR) imaging, which has proved to be the most specific and sensitive test to describe neuronal migration disorders. Possible treatments are discussed.

Electroclinical diagnosis of Angelman syndrome: a study of 7 cases.

The authors describe 7 new cases of Angelman syndrome (AS: 3 males and 4 females) diagnosed on the basis of clinical features (dysmorphic facial features, severe mental retardation with absent speech, peculiar jerky movements, ataxic gait and paroxysms of inappropriate laughter) and neurophysiological findings. Failure to detect deletion of the long arm of chromosome 15 or the absence of epileptic seizure were not considered sufficient to exclude a diagnosis of AS. Feeding problems, developmental delay and early signs of ataxia, especially tremor on handling objects and unstable posture when seated, proved effective as clinical markers for early diagnosis of AS. The EEG patterns characteristic of AS were found within the first 2 years of life (under 18 months in the majority of cases). The authors conclude that AS should be included in differential diagnosis in a child aged under 12 months having cryptogenic psychomotor retardation with prevalent language compromise. Repeat EEG recordings are needed to check for the typical trace, and cytogenetic investigations are mandatory.

MRI and CT in Krabbe's disease: case report.

A case of infantile Krabbe's disease was first recognised as areas of relatively increased density on CT in the thalamus lateral geniculate body and dentate nucleus. These sites were subsequently shown on MRI to have a paramagnetic effect, being characterised by short T2 and T1. Subsequent examinations showed development of atrophy and high signal in white matter.

[The use of propofol in status epilepticus]. / L'impiego del propofol nello stato di male epilettico.

Three cases of status epilepticus not responsive to an aggressive treatment are described. The seizures and EEG activity were rapidly brought under control with a continuous infusion of propofol (3-6 mg/kg/hour), maintained between 21 hours and 7 days. Patient awakening at the end of the infusion period was rapid and without sequelae.