An updated Italian normative dataset for the Stroop color word test (SCWT).

The Stroop color and word test (SCWT) is widely used to evaluate attention, information processing speed, selective attention, and cognitive flexibility. Normative values for the Italian population are available only for selected age groups, or for the short version of the test. The aim of this study was to provide updated normal values for the full version, balancing groups across gender, age decades, and education. Two kinds of indexes were derived from the performance of 192 normal subjects, divided by decade (from 20 to 90) and level of education (4 levels: 3-5; 6-8; 9-13; >13 years). They were (i) the correct answers achieved for each table in the first 30 s (word items, WI; color items, CI; color word items, CWI) and (ii) the total time required for reading the three tables (word time, WT; color time, CT; color word time, CWT). For each index, the regression model was evaluated using age, education, and gender as independent variables. The normative data were then computed following the equivalent scores method. In the regression model, age and education significantly influenced the performance in each of the 6 indexes, whereas gender had no significant effect. This study confirms the effect of age and education on the main indexes of the Stroop test and provides updated normative data for an Italian healthy population, well balanced across age, education, and gender. It will be useful to Italian researchers studying attentional functions in health and disease.

A normative study of the Italian printed word version of the free and cued selective reminding test.

According to the new research criteria for the diagnosis of Alzheimer's disease, episodic memory impairment, not significantly improved by cueing, is the core neuropsychological marker, even at a pre-dementia stage. The FCSRT assesses verbal learning and memory using semantic cues and is widely used in Europe. Standardization values for the Italian population are available for the colored picture version, but not for the 16-item printed word version. In this study, we present age- and education-adjusted normative data for FCSRT-16 obtained using linear regression techniques and generalized linear model, and critical values for classifying sub-test performance into equivalent scores. Six scores were derived from the performance of 194 normal subjects (MMSE score, range 27-30, mean 29.5 ± 0.5) divided per decade (from 20 to 90), per gender and per level of education (4 levels: 3-5, 6-8, 9-13, >13 years): immediate free recall (IFR), immediate total recall (ITR), recognition phase (RP), delayed free recall (DFR), delayed total recall (DTR), Index of Sensitivity of Cueing (ISC), number of intrusions. This study confirms the effect of age and education, but not of gender on immediate and delayed free and cued recall. The Italian version of the FCSRT-16 can be useful for both clinical and research purposes.

Subacute measles encephalitis in a young man immunosuppressed for ankylosing spondylitis.

Subacute measles encephalitis occurred 1 month after measles onset in a 26-year-old HIV-negative man undergoing immunosuppressive treatment for ankylosing spondylitis. He had seizures, a decline in mental status, and progressive impairment of consciousness, with a fatal outcome. Despite severely deficient cellular immunity, the elevated antimeasles antibody titers and CSF findings indicated that humoral immunity was not impaired. Histologic, electron microscopic, and immunocytochemical studies revealed the typical intranuclear inclusions of paramyxovirus nucleocapsids, and measles virus antigen in neurons and oligodendrocytes.

Further evidence for asymmetry of point localization in normals and unilateral brain damaged patients.

The properties of errors made by normals and unilateral brain damaged patients in localizing points in each half of a plane have been further investigated. A lesion of either hemisphere affects specifically the performance in the left half of the plane, where controls attain the highest degree of constancy. Consideration of the orientation of pathologic vectors may contribute to differentiation between damage of the two hemispheres.

Cerebrospinal fluid (CSF) findings in amyotrophic lateral sclerosis.

The cerebrospinal fluid (CSF) was examined in 90 amyotrophic lateral sclerosis (ALS) patients and in 50 age-matched normal controls. Total protein concentration was significantly higher in ALS patients than in normal controls. CSF IgG and albumin, quantitatively determined by single radial immunodiffusion, were significantly increased in ALS. No difference in serum concentrations was observed between ALS patients and normal controls. On isoelectric focusing a clearcut "fingerprint" pattern was observed in 11 of 12 cases. These findings support the hypothesis that blood-brain barrier damage occurs in ALS. The finding of a higher mononuclear cell count in young ALS patients is briefly discussed in the light of the hypothesis that an exogenous agent might be of some relevance in pathogenesis. An alteration of at least one of the CSF parameters considered was found in 45.5% of ALS cases.

Cerebrospinal fluid and neuropathological study in Devic's syndrome. Evidence of intrathecal immune activation.

Cerebrospinal fluid (CSF) was studied in 2 cases of Devic's syndrome (DS). In one of these cases autopsy was carried out. The main CSF feature in DS is the association of blood-brain barrier damage and intrathecal IgG synthesis. These findings are in keeping with our neuropathological observation of diffuse central nervous system vasculitis and leptomeningitis. As a whole, our CSF and neuropathological findings in DS are consistently different from those in multiple sclerosis.

Long-term observations on the clinical use of lamotrigine as add-on drug in patients with epilepsy.

We report open-label clinical observations of additional lamotrigine (LTG) in 16 adult patients with refractory epilepsy, aimed to assess the long-term efficacy and safety of LTG in clinical use. LTG was added to the current antiepileptic drug (AED) regimen at a daily dosage of 200-400 mg depending on the concomitant treatment. Ten patients completed one year's treatment and were followed up to an overall exposure ranging 15-38 months. Six patients (38% of the initial group) had a reduction of seizure frequency greater than 50% of pre-treatment baseline after one year; the further follow-up indicated some efficacy decline, since the percentage of improved patients dropped to 19% after 2 years and 13% after 3 years. The dropouts during the first year were due to seizure breakthrough (two patients), Steven-Johnson-like syndrome (one patient) and reasons unrelated to treatment (three patients); in one patient LTG treatment was stopped due to macrocytic anemia after 23 months. Other reported adverse events were dizziness, mild ataxia, diplopia and localized purpura. No other hematological or biochemical changes were noted. LTG was not associated with any significant changes in plasma concentrations of concomitant AEDs. These findings confirm the moderate efficacy and low toxicity of long-term LTG in severe epilepsy.

Vigabatrin in complex partial seizures: a long-term study.

The efficacy and safety of oral vigabatrin (VGB) as add-on therapy in the long-term treatment of poorly controlled epilepsy were evaluated in 19 patients with complex partial seizures, either with or without secondary generalization. The study was run with a single-blind, placebo-controlled, crossover design, and included 2 months of placebo and 13-15 months of treatment with VGB, at doses ranging from 1 to 4 g/day. Of the 14 patients who completed the trial, 2 were seizure free, in 5 seizure frequency dropped by more than 75% and in another 5 by more than 50% with respect to baseline. The decrease in seizure frequency in the group as a whole was significant at all observation points of the trial. Three patients were not entered into the long-term phase due to lack of improvement (an increase in seizure frequency was observed in one of them), and 2 were excluded later because improvement disappeared leading to unauthorized changes in comedication. Side effects were mild and never caused discontinuation of treatment. In conclusion, VGB showed a remarkable efficacy and safety in the long-term treatment of complex partial seizures.

GABA and phosphatidylserine in human photosensitivity: a pilot study.

Previous experimental studies have shown that the simultaneous administration of gamma-aminobutyric acid (GABA) and phosphatidylserine (PS) can exert an anticonvulsant activity in different seizure models; moreover, a preliminary trial showed some effect of the association GABA-PS in patients with absence seizures. The aim of this study was to investigate the antiepileptic properties of GABA-PS in the model of human photosensitivity. Nine patients with epilepsy associated with an EEG pattern of photoconvulsive response at intermittent photic stimulation entered a 3-day study. The photosensitivity range (PSR) was determined at hourly intervals both in basal conditions and after the administration of a single oral dose of GABA (3000 mg) and PS (600 or 1200 mg). The administration of GABA-PS was not associated with any systematic changes of PSR, nor with any significant differences of time course profiles on each daily session. No correlation was found between PSR percent deviations from baseline and GABA serum levels. These results indicate that a single acute administration of GABA-PS has no effect in the human photosensitivity model, and suggest that the efficacy of GABA-PS in human epilepsy, as shown by a preliminary investigation, may possibly require chronic administration.

Preliminary evaluation of the effect of GABA and phosphatidylserine in epileptic patients.

The effect of the combined administration of gamma-aminobutyric acid (GABA) and phosphatidylserine was evaluated in a pilot study of 42 patients with drug-resistant epilepsy. The group included patients with complex partial seizures, simple partial seizures and absence seizures. Patients with complex partial seizures and simple partial seizures showed no significant improvement; on the other hand, there was a remarkable decrease in absence seizures, linearly related to the dose of GABA and phosphatidylserine. Side effects occurred in 9 patients and were usually mild.

Orbital pseudotumor as a presenting sign of temporal arteritis.

Both unilateral proptosis (2 cases) and radiological evidence of orbital inflammatory pseudotumor in the absence of exophthalmos (1 case) have been separately described as presenting signs of temporal arteritis. We report a patient presenting with bilateral exophthalmos associated with CT and MRI signs of orbital inflammation, who had biopsy-proven temporal arteritis. Our case is unique in view of the association of the above clinical and radiological features, and the bilateral involvement of orbital tissues.

Delayed effects of a migrated foreign body (sewing needle) in the cervical spine: a case report.

STUDY DESIGN: A case report is presented. OBJECTIVE: This report documents one case of intraspinal migration of a metal foreign body. SUMMARY OF BACKGROUND DATA: The migration and penetration of foreign bodies into the spine have been described, but there are only three reports of a needle as the causative object. METHODS: This case report included a chart review, an examination of the patient, and a literature search. RESULTS: The patient successfully underwent surgery, in which the foreign body (a sewing needle) was removed. CONCLUSION: It is important to be aware of the possible delayed penetration of a foreign body into the spine even in patients with few or no symptoms.

Vigabatrin in chronic epilepsy: a 7-year follow-up study of responder patients.

Data on efficacy and safety of vigabatrin over very protracted treatment periods are still limited. This study reports the follow up of 23 responder epileptic patients who continued vigabatrin treatment after completion of the first year, to an overall long-term exposure ranging 21-84 months (median 60; mean 58.0 +/- 24.0 sd). The seizure frequency during the follow up was compared with that at the end of the first year on vigabatrin. The rates of patients who gained a further improvement and those who deteriorated were almost identical, ranging 33-45% and 33-46% respectively at individual time points. At the trial endpoint, nine patients (39%) were improved, five (22%) were unchanged and nine (39%) showed some deterioration. All patients still had a 14-100% decrease of seizure frequency as compared with pretreatment baseline. Two patients discontinued vigabatrin for occasional reasons. No patient experienced new adverse events during the follow up after the first year on vigabatrin. No significant effects were noted on any of the routine hematologic or metabolic screening assessments. Although reduction of concomitant treatment was rarely possible, the overall number of associated antiepileptic drugs dropped from 42 at entry to 40 at the trial endpoint. These findings indicate that vigabatrin retains its efficacy and safety in responder patients for periods up to 7 years.

MRI findings in epileptic patients on vigabatrin for more than 5 years.

Although vigabatrin is a promising new antiepileptic drug, its safety has been challenged by the report of dose-dependent central nervous system myelin vacuolation in some preclinical animal studies. Since it has been shown that vacuolation is associated with specific magnetic resonance imaging (MRI) findings in rats and dogs, MRI of the brain was performed in 11 patients with complex partial seizures who had been receiving vigabatrin for 64-78 months (mean 74.0 +/- 5.0 sd) as additional treatment for epilepsy, with a cumulative exposure ranging 4200 to 9360 g. In no case did MRI show white matter changes similar to the pathological findings of microvacuolation observed in animals. These results would appear to confirm that current doses of vigabatrin do not cause myelin vacuolation in humans, even for treatment periods of longer than 5 years.

The anticonvulsant effect of citalopram as an indirect evidence of serotonergic impairment in human epileptogenesis.

Some evidence would indicate that a serotonergic deficit may be involved in epileptogenesis. A preliminary trial of citalopram, a selective inhibitor of serotonin reuptake, was carried out. Citalopram 20mg/day was given to 11 non-depressed patients with poorly controlled epilepsy as an add on treatment with an open label design for 8-10 months. The median seizure frequency dropped by 55.6% in the whole group, with nine patients improving by at least 50%. No adverse reactions occurred with the exception of mild drowsiness. There were no changes of post-treatment as compared to pre-treatment AED serum concentrations. Although controlled studies are required to confirm the anticonvulsant effect of citalopram, these findings may be regarded as an indirect evidence of serotonergic impairment in human epileptogenesis.

Preliminary observations on the activity of progabide, administered as monotherapy in complex partial seizures.

Progabide (PGB), a gamma-amino-butyric acid receptor agonist, was administered, according to an open-label long-term design, to 40 adult patients suffering from complex partial seizures, with or without secondary generalization, whose response to carbamazepine (CBZ) monotherapy was unsatisfactory. A reference-baseline period of two months with carbamazepine monotherapy was followed by a two-month "add-on" period where increasing doses of progabide were added without modifying the CBZ regimen; then CBZ was withdrawn over 15-60 days and patients were followed up to 12 months' progabide treatment. Twenty-seven patients completed the trial but 12 of them had to be returned to CBZ + PGB bitherapy due to an increase of seizures following CBZ withdrawal. A definite therapeutic effect could be observed in nine patients on PGB monotherapy and in six patients on CBZ + PGB bitherapy. Side-effects of clinical relevance occurred in three cases and were represented by remarkable anxiety in two patients and a rise in serum glutamic oxalo-acetic acid and pyruvic transaminases with clinical symptoms of liver dysfunction in one, with rapid recovery following progabide discontinuation. In conclusion, progabide was effective against complex partial seizures in about 40% of patients not responding satisfactorily to available antiepileptic drugs. Although the withdrawal of previous antiepileptic drugs was not possible in all patients, progabide monotherapy was sometimes more effective than CBZ monotherapy, and several patients in whom bitherapy had to be restored benefited from the association of progabide.

Subependymoma of the lateral ventricle presenting with sudden onset.

A 52-year-old man presented with sudden onset of severe headache, fever, mental confusion and mild signs of left hemisphere dysfunction. Computed tomographic and magnetic resonance imaging findings suggested a preoperative diagnosis of subependymoma of the left lateral ventricle, which was subsequently confirmed by surgery. The neoplasm could be totally removed and the postoperative clinical course was favourable. The reported case is unusual because symptomatic subependymomas of the lateral ventricle are definitely rare, and almost invariably present with a progressive clinical course over a period of weeks to years.

May focal epileptic seizures be considered a marker of TIAs?

Late-onset focal epileptic seizures occurred in 8 patients with ischemic cerebro-vascular disease (ICVD) and were associated with TIAs in 6 of them. History, physical, laboratory, ancillary examinations and follow-up revealed no other disease which might be responsible for the seizures. Moreover, time of onset and appropriate signs of ICVD suggested that transient cerebral ischemia was the most likely cause of seizures.

Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study.

Chronic Fatigue Syndrome (CFS) represents a disabling condition characterized by persistent mental and physical fatigue, bodily discomfort and cognitive difficulties. To date the neural bases of CFS are poorly understood; however, mono-aminergic abnormalities, sleep-wake cycle changes and prefrontal dysfunctions are all thought to play a role in the development and maintenance of this condition. Here we explored in a group of 62 CFS subjects the impact on fatigue levels of agomelatine, an antidepressant with agonist activity at melatonin receptors (MT1 and MT2) and antagonist activity at serotoninergic 2C receptors (5HT2C). To tease out the relative effects of MT-agonism and 5HT2C antagonism on fatigue, we compared agomelatine 50mg u.i.d. with sustained release melatonin 10mg u.i.d. in the first 12-week-long phase of the study, and then switched all melatonin-treated subjects to agomelatine in the second 12-week-long phase of the study. Agomelatine treatment, but not melatonin, was associated with a significant reduction of perceived fatigue and an increase in perceived quality of life. Moreover the switch from melatonin to agomelatine was associated with a reduction of fatigue levels. Agomelatine was well tolerated by all enrolled subjects. Our data, albeit preliminary, suggest that agomelatine treatment could represent a novel useful approach to the clinical care of subjects with CFS.