Search

Objective: To assess frequency, types, and mechanisms of comorbidities in people with epilepsy and verify their association with disease features and outcome. Methods: This cohort study was performed in 13 Italian epilepsy centers with nationwide distribution and accurate records. Eligible patients were children and adults diagnosed before December 31, 2005, and followed for a minimum of 10 years. Two pairs of raters independently reviewed patients’ records and classified each comorbidity. In case of disagreement, a third reviewer made the final decision. Comorbidities were classified according to type (organ/system) and underlying mechanism (causal, shared risk factors, chance association). Comorbidity types and mechanisms were described in the entire sample and according to epilepsy prognostic patterns (sustained remission, relapsing-remitting course, no remission). Results: Of 1006 included patients, 266 (26.4%) had at least one comorbidity. The most common were developmental/perinatal (7.5% of cases), psychiatric (6.2%), cardiovascular (5.3%), and endocrine/metabolic (3.8%). Among 408 reported comorbidities, the underlying mechanisms were, in decreasing order, chance association (42.2%), shared risk factors (31.1%), and causal (26.7%). Psychiatric diseases were present in 13.3% of patients with no remission, 5.9% of patients with relapsing-remitting course, and 4.8% of patients with sustained remission (p =.016). The corresponding numbers for endocrine/metabolic diseases were respectively, 9.6%, 3.4%, and 2.9% (p =.013); for respiratory diseases were 3.6%,.3%, and.3% (p =.001), and for urogenital diseases were 3.6%,.7%, and 1.6% (p =.048). The association of endocrine/metabolic, psychiatric, and respiratory comorbidities with epilepsy prognosis was confirmed by multivariable analysis adjusted for the main demographic and clinical variables, with patients with these comorbidities showing a lower probability of achieving remission. Signifi

Objective: The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease. Methods: This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate. Results: Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of

Objective: To compare withdrawal of antiseizure medications (ASM) to continued treatment in newly diagnosed individuals achieving seizure freedom, and assess the risk of relapse and factors associated with relapse. Methods: This is a multicenter retrospective cohort study with long-term follow-up. Patients with newly diagnosed epilepsy were identified from the medical records of 13 Italian epilepsy centers and followed up until the most recent visit or death. Seizure-free patients discontinuing treatment were compared to patients who maintained treatment for baseline characteristics. Treatment was stopped upon clinical judgment. The probability of relapse was calculated with the Kaplan–Meier method. Demographic, clinical, and instrumental variables associated with relapse were assessed with Cox proportional hazards models. Results: One thousand and six patients aged 1 month to 72 years at diagnosis were enrolled and followed up for 17,892 person-years (median follow-up, 9.9 years). Three hundred and twenty patients (31.8%) underwent one or more treatment discontinuations. Factors associated with ASM withdrawal were younger age at remission and normal psychiatric examination. The probability of relapse after the first withdrawal was 16% at six months, 24% at 12 months, and 36%, 45%, and 53% at three, five, and ten years, respectively. The probability of remission after the first relapse was 59% at one month, 67%, 72, and 76% at three, six, and 12 months, respectively. Variables associated with relapse were age 14+ years, structural etiology, abnormal neuroimaging, ASM initiation after a single seizure, and symptomatic/cryptogenic epilepsy. Conclusions: About one half of seizure-free patients stopping ASM relapse in 10 years. However, the possibility of remission after relapse is high, particularly in children and patients with idiopathic/cryptogenic epilepsy. Treatment deprescription might be encouraged at least in these patients.

Purpose: The purpose of this study was to assess the priorities of patients with epilepsy and caring physicians and the correspondence between these priorities. Methods: In this multicenter cross-sectional study, patients with epilepsy attending 21 Italian epilepsy centers and their caring physicians filled anonymously questionnaires on the needs and priorities in the management of the disease. Included were questions on patients' demographics, diagnosis, treatment, and outcome of epilepsy. The concordance between patients and their physicians was assessed on various aspects of the diagnosis and care of the disease. Patients' satisfaction with communication, services, and patient–doctor relationship was also assessed. Results: Included were 432 women and 355 men aged 15 to 88 years (median: 41 years). Disease duration ranged from 6 months to 75 years. A structural/metabolic etiology predominated (52.7%), followed by a (presumed) genetic etiology (33.0%). Seizure remission was present in 56.5% of cases. Comorbidities requiring chronic treatment were present in 27.5%, and comorbidities affecting self-sufficiency in 9.5%. Psychiatric comorbidity was present in 35.0%. Patients' priorities included discovery of the cause (89.1%), use of right drug (98.7%), use of a drug without chronic side effects (94.0%), and a life without restrictions (90.4%). Physicians' priorities included choice of right drug (83.5%) and use of drugs without chronic side effects (86.8%). Priorities varied with patients' age, sex, education, and occupation. Patient–doctor relationships were at least good in most cases. The information imparted was considered unsatisfactory by 21–44% of cases on seizure circumstances and complications, side effects of drugs, limitations of daily activities, and management of physiologic or pathologic conditions. Patients declared overall satisfaction, except for appointments (21.5%) and emergencies (30.8%). Conclusion: Patients and physicians' priorities in the mana

Objectives To describe the long-term prognosis of epilepsy and prognostic patterns in a large cohort of newly diagnosed patients and identify prognostic factors. Methods Study participants were 13 Italian epilepsy centres with accessible records dating back to 2005 or earlier, complete data on seizure outcome and treatments, precise epilepsy diagnosis, and follow-up of at least 10 years. Records were examined by trained neurology residents for demographics, seizure characteristics, neurological signs, psychiatric comorbidity, first electroencephalogram (EEG) and MRI/CT, epilepsy type and aetiology, antiepileptic drugs (AEDs), and 1-year, 2-year, 5-year and 10-year seizure remissions. Five predefined prognostic patterns were identified: early remission, late remission, relapsing-remitting course, worsening course and no remission. Prognostic factors were assessed using multinomial logistic regression models. Results 1006 children and adults were followed for 17 892 person-years (median 16 years; range 10-57). During follow-up, 923 patients (91.7%) experienced 1-year remission. 2-year, 5-year and 10-year remissions were present in 89.5%, 77.1% and 44.4% of cases. 5-year remission was associated with one to two seizures at diagnosis, generalised epilepsy, no psychiatric comorbidity, and treatment with one or two AEDs during follow-up. 10-year remission was associated with one or two AEDs. The most common prognostic pattern was relapsing-remitting (52.2%), followed by early remission (24.5%). 8.3% of cases experienced no remission. Predictors of a relapsing-remitting course were <6 seizures at diagnosis, (presumed) genetic aetiology and no psychiatric comorbidity. Conclusions Few seizures at diagnosis, generalised epilepsy and no psychiatric comorbidity predict early or late seizure freedom in epilepsy. Achieving remission at any time after the diagnosis does not exclude further relapses.

Refractory status epilepticus (RSE) occurs in up to 30% of patients following resuscitation after cardiac arrest. The impact of aggressive treatment of postanoxic RSE on long-term neurological outcome remains uncertain. We investigated neurological outcome of cardiac arrest patients with RSE treated with a standardized aggressive protocol with antiepileptic drugs and anesthetics, compared with patients with other electroencephalographic (EEG) patterns. A prospective cohort of 166 consecutive patients with cardiac arrest in coma was stratified according to four independent EEG patterns (benign; RSE; generalized periodic discharges (GPDs); malignant nonepileptiform) and multimodal prognostic indicators. Primary outcomes were survival and cerebral performance category (CPC) at 6 months. Refractory status epilepticus occurred in 36 patients (21.7%) and was treated with an aggressive standardized protocol as long as multimodal prognostic indicators were not unfavorable. Refractory status epilepticus started after 3 ± 2.3 days after cardiac arrest and lasted 4.7 ± 4.3 days. A benign electroencephalographic patterns was recorded in 76 patients (45.8%), a periodic pattern (GPDs) in 13 patients (7.8%), and a malignant nonepileptiform EEG pattern in 41 patients (24.7%). The four EEG patterns were highly associated with different prognostic indicators (low flow time, clinical motor seizures, N20 responses, neuron-specific enolase (NSE), neuroimaging). Survival and good neurological outcome (CPC 1 or 2) at 6 months were 72.4% and 71.1% for benign EEG pattern, 54.3% and 44.4% for RSE, 15.4% and 0% for GPDs, and 2.4% and 0% for malignant nonepileptiform EEG pattern, respectively. Aggressive and prolonged treatment of RSE may be justified in cardiac arrest patients with favorable multimodal prognostic indicators. This article is part of the Special Issue “Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures"

We report a subtype of immune-mediated encephalitis associated with COVID-19, which closely mimics acute-onset sporadic Creutzfeldt-Jakob disease. A 64-year-old man presented with confusion, aphasia, myoclonus, and a silent interstitial pneumonia. He tested positive for SARS-CoV-2. Cognition and myoclonus rapidly deteriorated, EEG evolved to generalized periodic discharges and brain MRI showed multiple cortical DWI hyperintensities. CSF analysis was normal, except for a positive 14-3-3 protein. RT-QuIC analysis was negative. High levels of pro-inflammatory cytokines were present in the CSF and serum. Treatment with steroids and intravenous immunoglobulins produced EEG and clinical improvement, with a good neurological outcome at a 6-month follow-up.

Refractory nonconvulsive status epilepticus (NCSE) occurs in 10%-30% of patients following resuscitation after cardiac arrest. Both the optimal treatment and prognosis of postanoxic status epilepticus remain uncertain. We analyzed acute electroencephalographic changes, neurological outcome at 3 months, and adverse effects in consecutive postanoxic patients with super-refractory NCSE treated with add-on oral loading of perampanel. Eight postanoxic patients with super-refractory NCSE were treated with perampanel (dose range = 6-12 mg). All patients had continuous electroencephalographic monitoring showing definite generalized NCSE and favorable multimodal prognostic indicators (presence of brainstem reflexes, presence of bilateral N20 responses, absence of periodic discharges/generalized epileptic periodic discharges). In six patients (75%), status epilepticus resolved within 72 hours after administration of perampanel, without changing the comedication. Neurological outcomes at 3 months were return to normal or minimal disability in four patients (50%). A mild cholestatic liver injury, which required no specific treatment, was observed in five patients (62.5%). Perampanel 6-12 mg oral loading appeared to be an effective option in selected patients with postanoxic super-refractory NCSE with good prognostic indicators. In this patient population, our safety data indicate a risk of cholestasis.

ObjectiveTo investigate neurologic outcome of patients with cardiac arrest with refractory status epilepticus (RSE) treated with a standardized aggressive protocol with antiepileptic drugs and anesthetics compared to patients with other EEG patterns.MethodsIn the prospective cohort study, 166 consecutive patients with cardiac arrest in coma were stratified according to 4 independent EEG patterns (benign, RSE, generalized periodic discharges [GPDs], malignant nonepileptiform) and multimodal prognostic indicators. Primary outcomes were survival and cerebral performance category (CPC) at 6 months.ResultsRSE occurred in 36 patients (21.7%) and was treated with an aggressive standardized protocol as long as multimodal prognostic indicators were not unfavorable. RSE started after 3 ± 2.3 days after cardiac arrest and lasted 4.7 ± 4.3 days. A benign EEG pattern was recorded in 76 patients (45.8%); a periodic pattern (GPDs) was seen in 13 patients (7.8%); and a malignant nonepileptiform EEG pattern was recorded in 41 patients (24.7%). The 4 EEG patterns were highly associated with different prognostic indicators (low-flow time, clinical motor seizures, N20 responses, neuron-specific enolase, neuroimaging). Survival and good neurologic outcome (CPC 1 or 2) at 6 months were 72.4% and 71.1% for benign EEG pattern, 54.3% and 44.4% for RSE, 15.4% and 0% for GPDs, and 2.4% and 0% for malignant nonepileptiform EEG pattern, respectively.ConclusionsAggressive and prolonged treatment of RSE may be justified in patients with cardiac arrest with favorable multimodal prognostic indicators.

Objective: The new epilepsy definition adopted by the International League Against Epilepsy (ILAE) includes patients with one unprovoked seizure with a probability of further seizures, similar to the general recurrence risk after two unprovoked seizures, occurring in a 10-year period. Long-term follow-up of patients diagnosed after a single seizure is needed to assess the applicability of the new epilepsy definition in clinical practice. Methods: Patients with newly diagnosed epilepsy were recruited retrospectively with a minimum follow-up of 10 years. Patients were stratified in two groups depending on the occurrence of one (new definition, ND) or two or more unprovoked seizures (traditional definition, TD) at the time of epilepsy diagnosis and compared for disease characteristics and factors predicting seizure recurrence. The primary outcome was the occurrence of a new unprovoked seizure during follow-up in the ND group. The secondary outcome was the achievement of an early remission in both groups. Results: Among 1,006 patients with newly diagnosed epilepsy, 152 (15.1%) were diagnosed after a single seizure. Compared to patients diagnosed using the TD, patients diagnosed according to the ND showed a higher proportion of subjects with an abnormal neurologic examination (19.9% vs. 13.7%, p = 0.0504) and with focal seizures (69.3% vs. 60.4%, p = 0.0021). The two samples differed in the presence of at least one of the factors predicting seizure recurrence (focal seizures or abnormal findings in at least one among the following: neurologic examination, electroencephalography [EEG], and neuroimaging) (94.6% vs. 89.1%, p = 0.0376). Long-term recurrence in patients diagnosed with the new definition was 83.6% at 10 years and 89.1% at 15 years. The probability of early remission did not differ between the two groups. Significance: Our results support the applicability of the new epilepsy definition in clinical practice. Individual patient characteristics and a personalized

Purpose: To investigate the risk of illnesses in a cohort of patients with epilepsy and in matched nonepilepsy controls, by type and complications. Methods: A total of 951 children and adults with idiopathic, cryptogenic, or remote symptomatic epilepsy and 904 matched controls seen in secondary and tertiary centers in eight European countries (England, Estonia, Germany, Italy, the Netherlands, Portugal, Russia, Slovenia) were followed prospectively for 17,484 and 17,206 person-months and asked to report any spontaneous complaint requiring medical attention (illness), its type and complications (hospitalization, absence from work or school, medical action). Risk assessment was done by actuarial methods, relative risks (RR), and 95% confidence intervals (CIs). Results: During the study period 644 patients (68%) and 504 controls (56%) reported an illness (p<0.0001); 30% were seizure related. The cumulative probability of illness at 12 and 24 months was 49 and 86% in the cases and 39 and 75% in the controls (p<0.0001). The largest differences regarded disorders affecting the nervous system (NS) (RR, 3.3; 95% CI, 2.3-4.2) and ear, nose, and throat (ENT) (RR, 1.3; 95% CI, 1.0-1.6). In patients with epilepsy, an NS illness was more likely to be followed by hospital admission, work absence, or medical intervention. All risks were significantly reduced after excluding seizure-related events. Conclusions: Patients with epilepsy are at higher risk of NS and ENT illnesses and complications than the general population. However, the risk of illness is significantly reduced when seizure-related events are excluded

Purpose: To investigate the risk of accidents in a cohort of patients with epilepsy and in matched nonepilepsy controls, by type, circumstances, and complications. Methods: A total of 951 children and adults with idiopathic, cryptogenic, or remote symptomatic epilepsy and 904 matched controls seen in secondary and tertiary centers in eight European countries (England, Estonia, Germany, Italy, the Netherlands, Portugal, Russia, and Slovenia) were followed up prospectively for 17,484 and 17,206 person-months and asked to report any accident requiring medical attention, its site, and complications. Risk assessment was done by using actuarial methods, relative risks (RRs), and 95% confidence intervals (CIs). Results: During the study period, 199 (21%) patients and 123 (14%) controls reported an accident (p < 0.0001); 24% were seizure related. The cumulative probability of accidents at 12 and 24 months was 17 and 27% in the cases and 12 and 17% in the controls. The risk was highest for concussions (RR, 2.6; 9.5% CI, 1.2-5.8), abrasions (RR, 2.1; 95% CI, 1.1-4.0), and wounds (RR, 1.9; CI, 1.2-3.1). Domestic accidents prevailed in both groups, followed by street and work accidents, and were more common among cases. Compared with controls, patients with epilepsy reported more hospitalization, complications, and medical action. Disease characteristics associated with an increased risk of accidents included generalized epilepsy (concussions), active epilepsy, and at least monthly seizures (abrasions). Most risks decreased, becoming nonsignificant after excluding seizure-related events. Conclusions: Patients with epilepsy are at higher risk of accidents and their complications. However, the risk was substantially lower after exclusion of seizure-related events.

A total of 151 patients on chronic treatment with amiodarone and other antiarrhythmic drugs were subjected to standard clinical and electrophysiological investigation to assess the prevalence and specificity of polyneuropathy. Twenty two untreated patients with cardiac disorders and 246 normal subjects served as controls. Abnormal electrophysiological findings supporting the diagnosis of polyneuropathy were present in 38 subjects (25%) given antiarrhythmic drugs, with even distribution among drugs, and four untreated patients (18%). Concurrent clinical abnormalities were present in five treated patients (one each with amiodarone, propafenone, and flecainide, and two with multiple drugs). Therefore, electrophysiological abnormalities are a common, although non-specific, feature in patients taking antiarrhythmic drugs. Amiodarone users do not seem at higher risk of polyneuropathy than subjects treated with other drugs or even untreated patients with cardiac disorders

Goals of the case-control study is to evaluate the prevalence of PNES among persons referring to a secondary epilepsy center and to investigate through Rorschach Test the psychological traits of both the two groups: people with PNES only and people with PNES and epileptic seizures, compared with a control group of persons with epileptic seizures only. 240 persons have been screened with a semistructured questionnaire. 97 are considered at risk of PNES and 54 were observed by a psychiatrist consultant. All persons with PNES (7) suffer or suffered from an Anxiety Disorder and 57% have or had a Depressive Disorder. In the history of persons with epileptic seizures only these disorders were present in 33%. 19 people have been subjected to the Rorschach Test and it has been seen that persons with PNES tend to focus on their body as a vehicle to communicate a deep suffering

We investigated the possible use of clinical signs of chemotherapy-induced peripheral neurotoxicity (CIPN) or of nerve growth factor (NGF) circulating levels to predict the final outcome of CIPN. PATIENTS AND METHODS: Sixty-two women affected by locally advanced squamous cervical carcinoma treated with TP (paclitaxel 175 mg/m2 over a 3 h infusion plus cisplatin 75 mg/m2) or TIP (TP plus ifosphamide 5 mg/m2) were examined and scored according to the Total Neuropathy Score (TNS), before and during chemotherapy. RESULTS: A correlation with the final severity of CIPN was observed with vibration perception and deep tendon reflex evaluation, while pin sensibility, strength, and autonomic symptoms and signs were not informative. A highly significant correlation existed between the decrease in circulating levels of NGF and the severity of CIPN (r = -0.579; P < 0.001; 95% confidence limits -0.702 to -0.423). However, circulating levels of NGF were not effective as predictors of the final neurological outcome of each patient. CONCLUSION: Our study indicates that a precise clinical evaluation of the peripheral nervous system of patients treated with platinum and taxane combination polychemotherapy not only gives reliable information regarding the course of CIPN, but also can be used to predict the final neurological outcome of the treatment.

We investigated the possible use of individual Total Neuropathy Scale (TNS) items to predict the neurological outcome in patients undergoing cisplatin and paclitaxel combination chemotherapy in a series of thirty‐four women divided, according to the worst TNS score reached during the period of observation, into three groups, i.e. with a score <5 (n = 14), >5 but <10 (n = 5) or >10 (n = 15). At the visit performed before the onset of the worst neuropathy signs, 14 out of the 15 patients with the worst TNS had a change of 2 or more points in the sum of the semiquantitative vibration score (tuning fork) plus the DTR examination. In 12 of them the change was due to both vibration perception and DTR impairment. A change in the combined score was observed also in 7 out of the 14 patients with the better neurological outcome, but none of them had any change in the vibration perception. Early disappearance of DTR in the lower limbs (i.e. both ankle and patellar reflexes bilaterally) was observed in 7 out of the 15 patients with a worst outcome, while only 1 patient in the better outcome group had this clinical sign. The results of the VDT score obtained with a vibrameter did not improve the accuracy of the neurological assessment. Our study indicates that the accurate clinical evaluation of the patients treated with platinum and taxane combination polychemotherapy can be used to predict the final neurological outcome of the treatment

The authors compared clinically based neurotoxicity scales with the Total Neuropathy Scale, with the aim of improving the grading of the severity of chemotherapy- induced peripheral neuropathy ( CIPN). The severity of CIPN was evaluated in a series of 60 women treated with cisplatin- and paclitaxel- based chemotherapy. A reduced version of TNS ( TNSr) was also compared. The authors concluded that the TNS and TNSr can be used to assess the severity of CIPN effectively, and the results of this evaluation can be reliably correlated with the oncologic grading of sensory peripheral neurotoxicity.

We sought to assess whether epilepsy is associated with a higher risk of emotional reactions to frustrating stimuli, aggressive behavior, apathy, and depression, and whether these psychiatric patterns are specific to the epileptic condition. The study population consisted of referral patients 17 years and older with idiopathic or cryptogenic epilepsy (i.e., epilepsy not caused by a detectable brain lesion) without significant cognitive dysfunction. A first control was selected for each patient among patients with insulin-dependent diabetes and a second among normal blood donors. Aggressiveness in response to stressful stimuli was assessed with the Picture Frustration Study (PFS). Depression was tested by the Beck Depression Inventory. The Aggressive Behavior Scale (assessing irritability and rumination) and the Apathy Scale were also used. Odds Ratios (ORs) with 95% Confidence Intervals (95% CI) were used as the risk measure. Statistical analysis included between-group comparisons. In patients with epilepsy, the test scores were correlated to the main demographic (age, sex, education, marital status, and occupation) and clinical features (seizure types, disease duration, seizure control, and treatments). The sample included 55 patients with epilepsy, 56 diabetics, and 59 normal individuals. Patients with epilepsy and the two control groups had similar PFS scores and similar aggressiveness. Scores were also similar for the Aggressive Behavior and Apathy Scales, with similar numbers of individuals with aggressive conduct and excess rumination. Patients with epilepsy had higher depression scores. Moderate to severe depression was present in 9 cases (diabetes, 2; blood donors, 1) (P = 0.004). Relative to blood donors, the OR for moderate to severe depression (95% CI) was 2.1 (0.1-61.7) for diabetes and 11.3 (1.4-247.8) for epilepsy. No significant correlation was detectable between test scores and patient and disease characteristics.

Background: Hematopoietic toxicity of high-dose carboplatin (HD-CBDCA) chemotherapy can be managed effectively with autologous blood cell support, but no conclusive data are available on its the neuro- and ototoxicity. Patients and methods: We determined the neuro- and ototoxicity of HD-CBDCA in 10 patients affected by advanced ovarian cancer. HD-CBDCA was delivered as 24-hour continous infusion or as 5-day schedules. Each patient underwent an extended clinical and instrumental neurological and otological evaluation before, during and after treatment. Results: After HD-CBDCA only I patient had a clinically-evident peripheral neuropathy, while 3 additional patients had only distal paresthesias. Neurophysiological examination evidenced mild, although diffuse, sensory nerve impairment. Motor nerve impairment war also occasionally observed All the sensory and motor pathological changes had a favorable course during the follow-up period. Ototoxicity was more severe than neurotoxicity and, in one case it was dose-limiting and audiologic impairment tended to remain constant also in the follow-up period. Conclusions: HD-CBDCA treatment can be tolerated by most of the patients, but careful monitoring of neuro- and, especially, ototoxicity should be planned

Purpose: The social implications of epilepsy are ill-defined, and there are no comparative findings from different countries. A multicenter cohort study has recently been completed on the risk of morbidity and accidents. The main social issues in the study population (patients with epilepsy and control subjects) are investigated and correlated to the clinical features of the disease. Methods: Seven hundred six adult patients with idiopathic or remote symptomatic epilepsy and 662 matched controls without epilepsy were enrolled by secondary and tertiary centers in seven European countries (Italy, Germany, Spain, the Netherlands, England, Portugal, and Russia). At entry, patients and controls were interviewed, and data were collected on social variables (education, current occupation, marital status, driving, involvement in sports, and insurance). The main clinical features of epilepsy (seizure types, frequency and timing, disease duration, and syndrome) were also recorded. Results: The sample included 690 men and 678 women aged 18 to 86 years. The level of education (mostly basic or high school) was slightly higher among patients with epilepsy. More patients than controls were single (56% versus 50%) or unemployed (18% versus 13%). Fewer patients than controls held a driver's license (44% versus 67%) or practiced sports (30% versus 41%). The distribution of each social variable varied significantly across countries, but with few exceptions, the differences between patients and controls were fairly similar. Based on multivariate analysis, for patients with epilepsy the odds ratio for driving was 0.27, and the corresponding odds ratios for sports involvement, better education, better occupation, and insurance were 0.59, 1.30, 0.60, and 1.49. Among patients with epilepsy, social variables were correlated to seizure remission and selected clinical features. Conclusions: Comparative findings from different European countries support the concept that epilepsy has a consider

In recent years several authors have described a close con-elation between circulating antineuronal antibodies of different types and the occurrence of paraneoplastic neurological syndromes. Because this has not been widely accepted, we screened 300 serum samples from 181 ovarian cancer patients for the presence of circulating antineuronal antibodies by immunofluorescence. The findings were confirmed by immunoblotting. In 11 patients circulating antineuronal antibodies were detected. In 4 patients they were classified as anti-Yo and in 7 as anti-Ri, titres ranging from 1:400 to 1:204,800. All the patients underwent thorough neurological and neurophysiological investigations, with special regard to paraneoplastic syndrome. None of them had symptoms pointing to a paraneoplastic neurological syndrome, although patients were followed up to 2 years after the first examination. Thus the frequency of circulating antineuronal antibodies in ovarian cancer patients is higher than the frequency of paraneoplastic syndromes, and antibody positivity does not necessarily lead to the appearance of a neurological paraneoplastic syndrome.

To compare the neurotoxicity and ototoxicity of combination cisplatin plus paclitaxel versus cisplatin plus cyclophosphamide using extensive clinical and instrumental evaluation

Cisplatin sensory neuropathy is not equally severe in all patients and may progress even after drug withdrawal. A major goal in cisplatin chemotherapy would be the identification of early predictors of an unfavorable neurological outcome in order to adjust the schedules of administration. The final neurological outcome of 63 women treated with the same schedule of cisplatin (CDDP) was compared with the general demographic and oncological parameters and with the baseline neurological results. No definite association could be drawn between any of the parameters evaluated and peripheral neuropathy. Further studies are needed to investigate the individual factors which are at the basis of the remarkable variability of this severe side effect of CDDP

To assess the prognosis of the Guillain-Barré syndrome and identify the main prognostic indicators, 297 patients with Guillain-Barré syndrome recruited through a network of Italian centres were followed up for 24 months or until clinical recovery, whichever was earliest. For each patient the time to plateau, improvement, clinical recovery, or death was calculated, and prognostic indicators (age, sex, antecedent events, disability at admission and nadir, electrophysiological patterns) and treatments were noted. The mean duration of follow-up was 309 days. During this period, 212 patients (71%) recovered, 48 (16%) had residua and 33 (11%) died. The mean times to nadir, improvement and clinical recovery were 12, 28 and 200 days. Using life-tables and survival curves, the cumulative probability of achieving the plateau of symptoms was 73% by 1 week and 98% by 4 weeks. Improvement started during the first week in 36% of cases and within 4 weeks in 85%. The rates of clinical recovery at 1 and 4 weeks, 6, 12 and 24 months were 4, 24, 57, 70 and 82%, respectively. The chance of recovery was significantly affected by age, antecedent gastroenteritis, disability, electrophysiological signs of axonopathy, latency to nadir and duration of active disease. The main treatments did not seem to affect the chance of recovery

On the basis of experimental data showing the efficacy of glutathione (GSH) as a protective agent on cisplatin-induced neurotoxicity and the clinical evidence of the low incidence of neurotoxicity in high-dose cisplatin + GSH treated patients we evaluated the neuroprotective effect of GSH in a randomized phase II study. Thirty-three patients with relapsed ovarian cancer after a disease-free interval of at least 1 year and a cumulative dose of prior cisplatin ranging 450-650 mg m-2 were randomized to receive cisplatin 50 mg m-2 weekly +/- 2.5 g GSH for 9 consecutive weeks. Clinical and instrumental neurologic and otologic evaluations were made at the baseline and at the end of the study. Overall response rate in 31 evaluable patients was: 9/15 in group A and 12/16 in group B, including 4/15 vs 7/16 complete responses. The administered dose intensity of cisplatin was higher in the GSH treated patients (100% dose intensity was received by 56% vs 27%). A trend in terms of neuroprotection was detected in the GSH treated group, and no major difference was observed in the other toxicities between the two groups. It is concluded that possible benefit can be expected from the concomitant administration of GSH and cisplatin in patients at high risk of developing neurotoxicity, without decreasing the anti-tumor activity.

Background. Taxol is a new anticancer drug that acts as a tubulin polymeration enhancer. Its major toxicities are myelosuppression, hypersensitivity, and mucositis, but it also induces peripheral nerve damage. The use of taxol has recently been proposed for platinum-resistant cancers, but in these cases there is a possibility of cumulative toxicity in the peripheral nervous system. Methods. Twenty-two patients affected by a relapse of cisplatin-treated ovarian cancer were examined clinically and neurophysiologically to determine the evolution of taxol-induced peripheral somatic and autonomic neurotoxicity and the possible cumulative effect of a combination of taxol and cisplatin. Each patient was examined before, during, and after taxol treatment (using a dose of 135 or 175 mg/m(2) in 3 hours every 3 weeks). Results. No patients were excluded from the study because of unacceptable toxicities of any kind. The serial examinations demonstrated that taxol induced onset of (or worsening of preexisting) neuropathic symptoms and signs in almost all the patients, The features were those of a distal, symmetrical, sensory polyneuropathy due to an axonopathy. Motor nerves and the autonomic nervous system were unaffected. Taxol neurotoxicity appeared early in the course of the treatment (i.e., after three courses) and was not severely disabling, In most cases after the early onset of peripheral neuropathy, stabilization of this side effect occurred. Conclusions. Considering the low doses of taxol used in this study, the sensory nerve damage was unexpectedly severe. It appears that a cumulative, but not dose-limiting, neurotoxic effect occurs using taxol in patients previously treated with cisplatin

We evaluated clinically and neurophysiologically the immediate and long-term involvement of the peripheral nervous system in 22 selected patients with epithelial ovarian cancer successfully treated with DDP alone or in combination with non-neurotoxic drugs. While the motor nerves were unaffected, generally the involvement of sensory nerves was more severe at the examination performed several months after DDP discontinuation than at the evaluation performed after the "induction phase". We conclude that up to now the importance of long-term DDP-induced peripheral nerve damage has probably been underestimated. DDP-induced long-term damage is at least as severe as the immediate toxicity and, moreover, it is likely that complete recovery can occur, if ever, only years after DDP discontinuation

Cisplatin is known to induce a disabling sensory peripheral neuropathy. However, some authors have suggested that cisplatin may also cause motor impairment, raising doubts as to the pathogenetic hypothesis of primary damage to the dorsal root ganglia neurons induced by the drug. In order to clarify the real extent of motor nerve damage induced by cisplatin we performed a prospective neurophysiologic study on 33 patients affected by ovarian cancer in which cisplatin was administered as single anticancer agent. No motor nerve impairment ensued after cisplatin treatment and, therefore, we conclude that the occurrence of motor neuropathy during or immediately after, cisplatin treatment is probably coincidental and indicates the need for a careful search for concomitant causes of peripheral nerve damage

One hundred forty-one adult patients treated for no less than 6 months with standard daily doses of the commonest antiepileptic drugs (AEDs) were recruited in five Italian centers and submitted to intensive clinical and electrophysiologic investigation to assess the effects of AEDs on peripheral nerves. Eighty percent of the patients were receiving monotherapy. Carbamazepine (CBZ) was the most common AED (51 cases), followed by phenytoin (PHT) (46), phenobarbital (PB) (42), and valproate (VPA) (25). Fifty-three percent of the patients had one or more symptoms of polyneuropathy (paresthesias being the most common complaint). The neurologic examination was abnormal in 32%. Electrophysiologic findings in two or more separate nerves were abnormal in 77 patients (54.6%); of these, 27 (19.1%) had abnormal neurologic findings and 21 (14.9%) also had symptoms of polyneuropathy. Sensory functions were most frequently impaired. Sural nerve biopsy was performed in 4 patients receiving monotherapy with CBZ, PHT, PB, and VPA. Except in patients receiving VPA (in whom no morphologic abnormalities were detected), mild predominantly axonal damage with secondary myelin changes was noted. A correlation was noted between polyneuropathy, age of the patient and, to a lesser extent, receipt of two or more AEDs

The authors prospectively evaluated the effects of three different schedules of cisplatin (DDP) administration in 60 patients with advanced epithelial ovarian cancer. The individual total dose of DDP was 450 mg/m2 in all three groups, and the anti-cancer response at the end of treatment was similar for the different regimens. The clinical and neurophysiologic results confirmed that axonal sensory neuropathy occurred after the standard administration of DDP (75 mg/m2 in 3-week cycles) and probably not only the peripheral, but also the central sensory pathway, was involved. Although the total dose of the drug was identical, the two less conventional schedules were less neurotoxic. These results suggest that not only the total-dose intensity, but also the single-dose intensity are relevant in the onset of DDP-induced sensory neuropathy; therefore, the use of less neurotoxic schedules may prevent or reduce sensory nerve damage.

The use of high doses of cisplatin (DDP) in the treatment of different solid tumors is often prevented by the onset of a disabling sensory neuropathy. In an attempt to minimize DDP-induced neurotoxicity different schedules of DDP administration have been tested. Moreover, during the past few years some putative neuroprotective drugs have been reported as reducing DDP neurotoxicity. In this prospective, randomized study we evaluated in a series of 33 patients affected by relapsing ovarian cancer the effect on the sensory pathway of a non-conventional schedule of DDP administration as monochemiotherapy or in combination with one of the neuroprotective drugs (i.e. glutathione). The results of the neurophysiologic examinations performed before and immediately after chemotherapy suggest that these schedules besides being safe and effective in the treatment of the ovarian cancer, have an extremely low peripheral neurotoxicity, neurotoxicity of cisplatin

Sensorimotor polyneuropathy is the most common of the paraneoplastic syndromes involving the nervous system. Its incidence is high (more than 50%) in the patients undergoing neurophysiological investigation, and it is considered to be more frequent in subjects with lung and breast cancers. In this study we evaluated a series of 58 women with epithelial ovarian cancer at FIGO stages I and III. The aim of the study was to assess the incidence and characteristics of peripheral nerve involvement during the course of the disease both clinically and neurophysiologically. Our results suggest that in women with epithelial ovarian cancer (1) the incidence of subclinical polyneuropathy is high; (2) sensory involvement is predominant in stage I, but motor involvement is frequent in stage III; and (3) the incidence of peripheral nerve involvement increases with progression of the cancer

Adrenoleukodystrophy (ALD) is a sex-linked disorder characterized by very long chain fatty acid accumulation in different tissues, but mainly in the adrenal cortex, gonads and nervous system. The typical symptoms are hypoadrenalism, hypogonadism and central and peripheral nervous system impairment due to demyelination. On neurological grounds visual and hearing loss associated with quadriparesis are the most common symptoms, onset in childhood and a rapidly progressive course leading to a vegetative state and death. We report the case of a 31-year-old man affected by ALD, whose neurological symptoms started at the age of 12 and showed a markedly slow progression during the following years

We report the case of a patient affected by contralateral hemiplegia during herpes zoster ophthalmicus (HZO) evaluated both with serial CT scans and with MRI. We suggest that MRI examination of patients affected by HZO could be useful for the detection of early signs of cerebral arterial damage which are not yet clinically and radiologically apparent

The distribution of the motor impairment was correlated to the site and extension of the lesion of 18 patients with restricted lesions of the internal capsule, detectable with computerised tomography (CT). In three cases the lesion was located in the anterior limb of the internal capsule and the patients did not suffer any motor defect. Among the 15 patients with lesions in the posterior limb, 13 presented a distribution of the motor weakness consistent with a location of the corticobulbar fibres in the genu and corticospinal fibres in the anterior half of the posterior limb. Our CT study confirms the classical view on the location of the pyramidal tract in the internal capsule of man, but also evidences the possibility of individual variations

The classical thalamic syndrome of Dejerine and Roussy is very rare. Sensory disorder are almost constant but the thalamic hyperpathia had not been reported. Clinical findings are reported in 14 patients with restricted lesions of the thalamus visible with the CT scan. Occasionally aphasia was found in patients with left sided lesion (with Thalamic Neglect, apraxia, mainly of ideomotor type and the so-called "Central Dazzle"). Thalamic lesions can produce a great variability of signs and symptoms.

20 new cases of ataxic hemiparesis syndrome (AHS) are reported and the findings compared with those of published cases. AHS may be due to lesions either of the brainstem or of supratentorial structures, where motor fibers run together with the cerebro-cerebellar pathways. Specific syndromes related to the lesion site cannot be identified from the clinical signs. Ischemic infarct is the most frequent cause of the syndrome, but hemorrhagic, neoplastic and demyelinating lesions have also been reported