The costs of childhood epilepsy in Italy: comparative findings from three health care settings.

PURPOSE: To determine the direct costs of epilepsy in a child neurology referral population, stratified by disease, duration, and severity, comparing three different health care settings [i.e., teaching or clinical research (CR) hospitals, general hospitals, and outpatient services]. METHODS: Patients were accepted if they had confirmed epilepsy and were resident in the center catchment area. Eligible subjects were grouped in the following categories: (a) newly diagnosed patients; (b) patients with epilepsy in remission; (c) patients with active non-drug-resistant epilepsy; and (d) those with drug-resistant epilepsy. Over a 12-month period, data regarding the consuming of all resources (i.e., consultations, tests, hospital admissions, drugs), were collected for each patient. Using the Italian National Health Service tariffs, the unit cost of each resource was calculated and indicated in Euros, the European currency. RESULTS: A total of 189 patients was enrolled by two teaching-CR hospitals, two general hospitals, and two outpatient services. The patients were evenly distributed across the four categories of epilepsy. The mean annual cost per person with epilepsy was 1,767 Euros. Drug-resistant epilepsy was the most expensive category (3,268 Euros) followed by newly diagnosed epilepsy (1,907 Euros), active non-drug-resistant epilepsy (1,112 Euros), and epilepsy in remission (844 Euros). Costs were generally highest in teaching-CR hospitals and lowest in outpatient services. Hospital services were the major cost in all epilepsy groups, followed by drugs. CONCLUSIONS: The cost of epilepsy in children and adolescents in Italy tends to vary significantly depending on the severity and duration of the disease Hospitals services and drugs are the major sources of costs. The setting of health care plays a significant role in the variation of the costs, even for patients in the same category of epilepsy.

Add-on lamotrigine treatment in children and young adults with severe partial epilepsy: an open, prospective, long-term study.

We evaluated the efficacy and safety of lamotrigine in 41 children and young adults (age range, 3-25 years; mean, 12 years) with drug-resistant, partial epilepsies, based on a prospective, add-on study. Patients had severe symptomatic/cryptogenic partial epilepsies (mean seizure frequency = 3.6/day), resistant to one to four major antiepileptic drugs. Mean seizure frequency significantly decreased (P < .001) throughout the period of treatment. A good response (>50% seizure reduction) was observed in 15 patients of whom 6 were seizure-free (follow-up: 12-48 months). Higher responder rate was found among cryptogenic epilepsies and epilepsies symptomatic of cerebral malformation, whereas patients with posthypoxic-ischemic perinatal damage were poor responders. Lamotrigine discontinuation was mainly due to lack of efficacy (46% of patients), whereas only 2 patients developed a transient skin rash and did not drop out. Lamotrigine represents a valuable treatment for severe partial epilepsies of childhood that have proved resistant to previous antiepileptic drugs.

Hepatocyte proliferation rate is a powerful parameter for predicting hepatocellular carcinoma development in liver cirrhosis.

AIMS: A sound predictive test is lacking for the identification of cirrhotic patients at high risk of developing hepatocellular carcinoma. The present study evaluates the measurement of hepatocyte expression of silver stained nucleolar organiser region (AgNOR) proteins as a risk factor for the development of hepatocellular carcinoma in cirrhosis. METHODS: Liver biopsies from 176 cirrhotic patients included in a follow up surveillance programme for hepatocellular carcinoma development were evaluated prospectively for hepatocyte AgNOR protein quantity. The follow up programme consisted of clinical and biochemical assessment every three months, and ultrasound scanning and serum alpha-fetoprotein (alpha FP) assessment every six months. Histological sections from the needle biopsies performed at enrollment were stained selectively for AgNOR proteins and the percentage of hepatocytes with an AgNOR protein area > or = 7 micron 2, indicative of a proliferative state (AgNOR proliferation index (AgNOR-PI)), was measured. RESULTS: During the mean (SD) follow up time of 65.5 (36.29) months (range, 12-143; median, 67), hepatocellular carcinoma was diagnosed in 48 of 176 patients (27.3%). The AgNOR-PI of the whole series ranged from 0% to 5% (median, 0.9%), and was significantly higher in patients with liver cell dysplasia and hepatitis B surface antigen (HBsAg) positivity (p < 0.0001 and p = 0.0002, respectively). The 176 patients were divided into two groups according to their AgNOR-PI scores; a cut off value of 2.5% defined by the receiver operating characteristic curve and the Youden index was used. Forty two patients were included in the high AgNOR-PI (< 2.5%) group, and 134 patients the low AgNOR-PI (< 2.5%) group. In the high AgNOR-PI group, 25 of 42 patients developed hepatocellular carcinoma, in contrast to only 23 of 134 patients (17.2%) in the group with a low AgNOR-PI (p < 0.0001). Hepatocellular carcinoma development was also significantly more frequent in patients with liver cell dysplasia and HBsAg positivity. Multivariate analysis using AgNOR-PI, liver cell dysplasia, HBsAg positivity, and hepatitis C virus (HCV) infection as covariates demonstrated that the AgNOR-PI parameter was the only significant predictor of hepatocellular carcinoma development. CONCLUSIONS: These results demonstrate that a high hepatocyte proliferation rate is a major risk factor for hepatocellular carcinoma development in the cirrhotic liver. Therefore, the evaluation of the hepatocyte proliferation rate is very important to identify patients requiring a more strict follow up programme for early diagnosis of hepatocellular carcinoma.

New autosomal recessive syndrome of mental retardation, coarse face, microcephaly, epilepsy and skeletal abnormalities.

We describe two sibs, one male and one female, presenting a new autosomal recessive multiple congenital anomalies/mental retardation syndrome of 'coarse face', microcephaly, moderate to severe mental retardation, epilepsy and skeletal abnormalities.

Idiopathic photosensitive occipital lobe epilepsy.

We studied 10 neurologically normal patients (8 females, 2 males) aged 8-30 years (mean 17 years) who had recurrent episodes if visually induced occipital seizures. Television and computer screens were the main triggers. Seizure onset occurred between the ages of 5 and 17 years (mean 11 years). All seizures were stimulus related and began with elementary visual symptoms, followed in most patients by a slow clustering of cephalic pain, epigastric discomfort, and vomiting, with either normal of only mildly impaired responsiveness. EEG features included normal background activity, occipital spikes and waves, and a photoparoxysmal response which could be occipital, generalized, or both. Four patients also showed spontaneous generalized epileptiform abnormalities, and 3 had rolandic spikes. An Oz electrode was critical in identifying epileptiform activity in some patients. Complete seizure control was achieved in most patients with monotherapy, although occasional stimulus-related seizures occurred in 3 patients who showed a wider range of photosensitivity. These patients have an idiopathic localization-related epilepsy with age-related onset and specific mode of precipitation. Although this type of epilepsy has been reported previously, it has remained underrecognized, probably because it is difficult to differentiate clinically from migraine or from nonreflex childhood idiopathic occipital epilepsy.

[Lymph-node inflammatory pseudotumor with granulomatous component. Report of a case and review of the literature]. / Pseudotumore infiammatorio del linfonodo con componente granulomatosa. Descrizione di un caso e revisione della letteratura.

A case of inflammatory pseudotumor of lymph node in a 65 year-old man is described. The case is striking because of a granulomatous component within the lesion, a finding unpreviously described. This lesion, benign by nature, should not be misinterpreted as a neoplastic process, especially lymphomas or soft tissue tumors; problems related to the differential diagnosis are also discussed.

Occipitotemporal seizures with ictus emeticus induced by intermittent photic stimulation.

We recorded occipitotemporal seizures induced by intermittent photic stimulation in three children with brain injuries, aged 10 to 13 years. All had a history of seizures and showed occipital spikes on EEG, but were seizure free and were not being treated at the time of investigation. In all, photic stimulation induced seizures in the right occipital lobe. They were followed by clinical and EEG signs suggesting infrasylvian spreading to ipsilateral mesiotemporal limbic structures and by vomiting, appearing at late stages of the attacks. Seizure spread was very slow in two patients in whom attacks lasted 16 and 25 minutes. Patients with occipital epileptiform abnormalities presenting with ictal vomiting are often diagnosed as having vague migraine-epilepsy syndromes. We conclude that vomiting can be a late ictal phenomenon resulting from temporal lobe spread of seizures originating in the occipital lobe.

[Proposal for a semiqualitative evaluation method for AgNORs (rap score)]. / Proposta di un metodo di valutazione semiquantitativa delle AgNORs (rap score).

Nucleolar Organiser Regions (NORs) can be stained in paraffin embedded specimens by a simple silver technique: the black dots formed, called AgNORs, have usually been counted only by eye with "careful focusing", a time-consuming and subjective method. Therefore we propose a new semiquantitative approach based on three patterns of AgNORs configuration of increasing malignancy as previously described by Crocker et al: 1) AgNORs fully aggregated to form a solitary argyrophil structure (pattern RESTING: -R-); 2) AgNORs lying within nucleolus and nucleoplasm (Pattern ACTIVATED: -A-); 3) Numerous small AgNORs distributed through the nucleoplasm, without nucleolar structures (Pattern PROLIFERATING: -P-). We assigned a numerical value to each pattern: R = 1; A = 2; P = 3. These values are multiplied by the relative rate in 100 cells. Eventually we obtain a score (range 100-300): this method shows significant correlation (r = 0.8363: regression equation) compared to the usual count obtained "by eye", tested on a sample of 150 breast cancer. Further studies are under way to validate this method which may represent a cheap and useful tool in AgNORs evaluation.

[The evolution of epilepsy in the most common genetic forms with mental retardation (Down's syndrome and the fragile X syndrome)]. / Evoluzione dell'epilessia nelle più frequenti forme genetiche con ritardo mentale (sindrome di Down e sindrome dell'X fragile).

Some chromosomal abnormality syndromes carry a higher risk of seizures than that found in the general population. Down's syndrome is considered to be the first and the most frequent chromosomal abnormality causing mental retardation. In spite of numerous reports and epidemiological surveys, the outcome of epileptic syndromes in patients with Down's syndrome (DS) is still largely unknown. We retrospectively studied 34 DS patients with epilepsy (14M; 20F). Epileptic syndromes were classified as: infantile spasms, 10 cases, i.e. 31%; Lennox-Gastaut syndrome, 5 cases, 15.5%; symptomatic generalized epilepsy, 1 case; idiopathic generalized epilepsy, 6 cases, 17.6%; partial symptomatic epilepsy, 10 cases, i.e. 31%. In 2 patients the epilepsy was unclassifiable. In all the patients the following evolutive particularities were noted: a) the infantile spasms to have a relatively mild prognosis, as 8/10 patients remained seizure-free, 3 of whom without treatment; b) no patient experienced febrile convulsions prior to the onset of epilepsy; c) Lennox-Gastaut syndrome had a relatively late onset (mean age 10 years, range 8-11.5); d) 7 patients (20.6%) developed reflex seizure. The fragile X syndrome is considered to be the second most frequent chromosomal abnormality causing mental retardation. The prevalence of epilepsy varies from 9.1% to 45% in the different series. In order to evaluate the prevalence rate of epilepsy and the previously hypothesized association with a particular electroclinical picture, we retrospectively studied 90 fragile X syndrome patients (80M, 10F) aged 4 to 25 years (mean age 13y6m).(ABSTRACT TRUNCATED AT 250 WORDS)

[Cognitive and psychological profiles in dysmorphic syndromes]. / Profili cognitivi e psicologici nelle sindromi dismorfiche.

The recognizable patterns of human malformations have recently received much attention, particularly because of the decline of other diseases. Patients with a congenital malformation syndrome come to the Child Neuropsychiatrist for various reasons, such as: mental retardation of variable degree, learning disabilities, speech delay or absence of speech, behaviour disorders, various neurological impairment. Parents, however, seem to be mainly concerned about the prognosis of cognitive and psychological aspects. We have studied 83 patients with a specific pattern of malformations (35 affected by the Sotos syndrome; 25 by the Williams syndrome; 9 by the Cohen syndrome; 8 by the Cornelia De Lange syndrome; 6 by the Rubinstein-Taybi syndrome) and have particularly investigated their cognitive and psychological profiles. 13/83 showed a normal cognitive level (9 Sotos syndrome; 4 Williams syndrome), while 70/83 showed a cognitive deficit ranging from mild-moderate (56 cases) to moderate-severe (14 cases). Linguistic deficits are prominent in the Sotos, Cornelia De Lange, and Rubinstein-Taybi patients, while practo-gnosic deficits are frequent in the Williams and particularly in the Cohen syndrome patients. The personality structure is characterized by immaturity and anxiety in all but the Williams syndrome patients, where some peculiar neurotic traits may be observed. All patients showed good communicative abilities.

Maternal decidua and fetal membranes contain immunoreactive neuropeptide Y.

The aim of the present study was to evaluate whether the various intrauterine tissues contain immunoreactive neuropeptide Y (NPY). Previous observations showed that human placenta produces NPY and that it may play a local role. Using a polyclonal NPY antiserum and an immunofluorescent technique, sections of maternal decidua, amnion and chorion collected from a pregnant women at parturition were studied. An intense positive staining for NPY was observed in epithelial amnion cells and in chorionic cytotrophoblast. Some of the maternal decidual cells showed a weaker signal of immunoreactive NPY. In evaluating whether NPY may coexist with other hormones in these tissues, adjacent slices of decidua, amnion and chorion were stained with activin beta B subunit antiserum. In the various tissues a relevant number of cells showed positive signals for both NPY and activin. The present findings showed that the various intrauterine tissues contain NPY and that in a large number of cells of amnion, chorion and decidua the neuropeptide is colocalized with immunoreactive activin. In view of the physiological implications of NPY in the regulation of uterine contractility and of placental hormonogenesis, the present findings indicate a large distribution of NPY in the various intrauterine tissues.

Double-blind placebo-controlled trial of flunarizine as add-on therapy in refractory childhood epilepsy.

Flunarizine (FLN) has been suggested as an add-on treatment in drug-resistant epilepsy patients. In view of the discordant experiences and of the paucity of controlled trials in children, we studied its effectiveness in 20 patients aged 6 to 18 years (10 males and 10 females), affected by drug-resistant epilepsy. 14 had symptomatic generalized epilepsy (the Lennox-Gastaut syndrome in 10; other forms in 4); 3 had cryptogenic generalized epilepsy (the Lennox-Gastaut syndrome in 2; myoclonic absences epilepsy in 1); 3 had symptomatic partial epilepsy (temporal lobe epilepsy). 7 of them were withdrawn: only 1 because of side effects. An initial four-month baseline pretrial period was followed by two four-month periods of administration of FLN or a placebo, under double blind conditions, in a randomized sequence. Preexisting antiepileptic (AEDs) medication was maintained at a constant dose throughout the study. FLN was administered as drops in a single evening dose of 5 mg (patients less than 10 years) or 10 mg. (patients greater than 10 years). During the pretrial phase, after phase 1 and phase 2, a waking EEG was recorded and blood samples were taken for hematology, hepatic-function tests, and AED serum levels. The evaluation of the activity of FLN was based on the total number of seizures. A 30-60% reduction in seizure frequency was found in 5 out of the 13 patients completing the trial (no changes occurred in the remainders). This result did not appear to be due to changes in the plasma levels of the AEDs. No significant differences were seen in the EEG paroxysmal activity in the three phases of the study. Side effects were rare. The serum FLN levels ranged between 16.4 and 109 ng/ml. It seems that the antiepileptic properties of FLN need further validation, particularly in childhood.

[Gastric lymphoma. Anatomo-clinical and prognostic correlations]. / Linfoma gastrico. Correlazioni anatomo-cliniche e prognostiche.

In order to assess the prognostic value of some clinicopathological factors of Gastric Lymphoma the authors reviewed 37 consecutive cases observed between 1973 and 1985 with 48 months follow up at least. Age, sex, gross features, site, histological subtype, depth of gastric wall invasion, regional lymph nodes involvement weren't useful parameters. Notable difference exists in survival according to the treatment carried out (surgery and chemoradiotherapy 100% alive & well, surgery and chemotherapy 29% a&w, surgery 17% a&w). The authors compared inflammatory cell population reactive to neoplasm to survival as possible meaningful parameter.

Liver cell dysplasia in cirrhosis. A serologic and immunohistochemical study.

Liver cell dysplasia (LCD) was investigated for hepatitis B virus (HBV) markers, alpha-fetoprotein (AFP) and ferritin by serologic and immunohistochemical methods in 101 patients with cirrhosis. LCD was found in 30 cases (29.7%), with the highest incidence in cases of posthepatitic cirrhosis (67%). In the group of dysplastic cirrhosis (DC) 46.6% of the patients had active HBV infection (hepatitis B surface antigen [HBsAg] serum positivity) compared with 7% of the patients with nondysplastic cirrhosis (NDC) (P less than 0.01). The mean serum AFP concentration was significantly raised in the DC group compared with that in the NDC group (P less than 0.05). In seven patients with LCD at the initial biopsy, the histologic followup showed the persistence of LCD in all cases, and the development of hepatocellular carcinoma (HCC) in three cases. In serologic HBsAg-positive cases, dysplastic cells, at variance with the surrounding liver parenchyma, were almost always negative for tissue HBsAg, and always negative for tissue hepatitis B core antigens (HBcAg). AFP was never detected in either normal or dysplastic cells. Ferritin was found in all cases, but dysplastic foci displayed a lesser amount of this protein. These serologic and immunohistochemical data strongly suggest a preneoplastic significance of LCD. The importance of monitoring cirrhotic patients with LCD and particularly those with HBV infection and/or increased AFP levels with more aggressive follow-up is also stressed.