Biomedical subjects

G Zaccara

Publications and source records attributed to G Zaccara.

At least 19 recordsLinked to original sources

PubMed2002

Bilateral motor cortex output with intended unimanual contraction in congenital mirror movements.

In congenital mirror movements (MM), it is unclear whether the "mirror" motor cortex (M1) produces output during intended unimanual movements. In two patients with MM, the cortical silent period (CSP) was abnormally short after focal transcranial magnetic stimulation (TMS) of either M1, but simultaneous bilateral TMS led to significant CSP lengthening. Thus, it is likely that the shortened CSP after unilateral TMS is caused by output from the nonstimulated M1, suggesting that both M1 produce output with intended unimanual movements in patients with MM.

Adolescent↗

PubMed2002

Cortical silent period in two patients with meningioma and preoperative seizures: a pre- and postsurgical follow-up study.

OBJECTIVES: Prolongation of the cortical silent period (CSP) following transcranial magnetic stimulation has been reported in patients with partial epilepsy involving the primary motor cortex (M1). This study aimed to investigate the relationship between the expected intraindividual variations in risk factors for seizures and CSP duration. METHODS: We studied a 59-year-old woman with a rolandic meningioma and simple motor partial seizures and a 71-year-old woman with a parietal/occipital meningioma and complex partial seizures. Both patients had seizure as their initial symptom with complete postsurgical remission. Repeated pre- and postoperative CSP recordings were made from both first dorsal interosseous muscles. We compared the results to those obtained in 13 normals. RESULTS: In the patient with simple motor partial seizures, the CSP was significantly prolonged in preoperative recordings and 3 weeks after surgery. This CSP lengthening partly subsided 3 months after surgery. Finally, the CSP was normal 6, 8, and 18 months after surgery. In the patient with complex partial seizures, no CSP change was observed. CONCLUSIONS: In our patient with a rolandic meningioma, CSP prolongation was observed when the risk of seizure relapse was supposed to be higher (preoperative and early postoperative periods). This supports the view that CSP changes reflect compensatory mechanisms in M1 epilepsy.

Adult↗

PubMed2002

Congenital hemiparesis: different functional reorganization of somatosensory and motor pathways.

OBJECTIVES: To investigate the reorganization of somatosensory and motor cortex in congenital brain injury. METHODS: We recorded motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SEPs) in a 41 year old man with severe congenital right hemiparesis but only mild proprioceptive impairment. Brain magnetic resonance imaging showed a large porencephalic cavitation in the left hemisphere mainly involving the frontal and parietal lobes. RESULTS: TMS showed fast-conducting projections from the undamaged primary motor cortex to both hands, whereas MEPs were not elicited from the damaged hemisphere. Left median nerve stimulation evoked normal short-latency SEPs in the contralateral undamaged somatosensory cortex. Right median nerve stimulation did not evoke any SEP in the contralateral damaged hemisphere, but a middle-latency SEP (positive-negative-positive, 39-44-48 ms) in the ipsilateral undamaged hemisphere, with a fronto-central scalp distribution. CONCLUSIONS: Our data show that somatosensory function of the affected arm is preserved, most likely through slow-conducting non-lemniscal connections between the affected arm and ipsilateral non-primary somatosensory cortex. In contrast, motor function was poor despite fast-conducting ipsilateral cortico-motoneuronal output from the primary motor cortex of the undamaged hemisphere to the affected arm. This suggests that different forms of reorganization operate in congenital brain injury and that fast-conducting connections between primary cortex areas and ipsilateral spinal cord are not sufficient for preservation or recovery of function.

Adult↗

PubMed2000

Reorganization of the motor cortex in a patient with congenital hemiparesis and mirror movements.

Abnormal branching of corticospinal fibers from the unaffected motor cortex is responsible for mirror movements in patients with congenital hemiparesis, but it is unknown which mechanisms enable these patients to lateralize motor activity. Using multiunit electromyographic analysis and transcranial magnetic stimulation, the authors provide evidence for nonbranched crossed and uncrossed corticospinal projections and intracortical inhibition of the mirror hand. They propose that this remarkable reorganization of the unaffected motor cortex helps these patients to reduce mirror movements.

Adult↗

PubMed2000

Event-related potentials in patients with total locked-in state due to fulminant Guillain-Barré syndrome.

A series of electrophysiological investigations were performed over a 6-month period in two patients affected by fulminant Guillain-Barré polyradiculoneuropathy, who developed an ascending paralysis leading, within 72 h, to flaccid quadriplegia, internal and external ophthalmoplegia, absence of all brainstem reflexes and no respiratory effort: the clinical state resembled brain death. Brain CTs were normal and spinal fluid examination revealed albuminocytological dissociation. All motor nerves tested were unexcitable, whereas sensory responses were markedly abnormal but present. Sequential EEG recordings revealed normal, partially reactive alpha rhythm in both patients. In one patient, normal auditory event-related potentials (ERPs: peak N1, P2, N2, P3, evoked in an 'oddball' paradigm) and CNV-like potentials could be recorded not earlier than the 20th day into the illness. In earlier recordings, N1 and P2 peaks as well as mismatch negativity (MMN) were present over the frontal and central scalp electrodes. This patient has now partially recovered motor functions and no cognitive defects are present, but he has little recollection of the events occurring in the first 2 weeks spent in the ICU, when he was completely paralyzed. The other patient generated normal N1 and P2 ERP peaks, but no N2, P3 and MMN were detected in a series of recordings. He died without having ever regained appropriate behavioral responses. The ERP abnormalities observed raise the matter of the origin of cognitive dysfunction in patients with severe and prolonged de-efferentation/de-afferentation. ERPs allow monitoring the level of alertness and attention and appear more specific than EEG in identifying a state of awareness in patients in which communication is severely impaired as a consequence of neurological disorders.

Adult↗

PubMed2000

Remote effects of cortical dysgenesis on the primary motor cortex: evidence from the silent period following transcranial magnetic stimulation.

OBJECTIVE: In cortical dysgenesis (CD), animal studies suggested abnormal cortico-cortical connections. Cerebral areas projecting to the primary motor cortex (M1) modulate the cortical silent period (CSP) following transcranial magnetic stimulation (TMS). Therefore, we used the CSP to investigate remote effects of CD on the M1. METHODS: A detailed investigation, including single-pulse TMS and electrical nerve stimulation, was performed in 3 consecutive adults with focal CD located outside the M1 and in 18 controls. Two patients with unilateral CD were epileptic and treated with anti-epileptic drugs. One patient with focal CD on both sides had no history of seizures. Neurological examination was normal in all patients. Recordings were made from both first dorsal interosseous muscles. RESULTS: In CD patients, the CSP was significantly lengthened contralaterally to the affected hemispheres. In treated patients with unilateral CD, the interside difference of the CSP duration was also significantly increased. In contrast, excitability threshold, peripheral and corticospinal motor conduction studies, and peripheral as well as ipsilateral silent periods were not significantly modified. CONCLUSIONS: Our findings indicate that focal CD outside the M1 may produce CSP modifications, which are likely due to changes of afferent control.

Adult↗

PubMed1999

Motor imagery in a locked-in patient: evidence from transcranial magnetic stimulation.

Motor evoked potentials (MEPs) to transcranial magnetic stimulation were evaluated in a case of locked-in syndrome due to a large pontine infarction. In this patient, magnetic resonance imaging (MRI) and somatosensory evoked potentials demonstrated a tegmental involvement. One month after the attack, no MEP could be recorded from the right abductor digiti minimi (ADM) or either tibialis anterior muscle. On the contrary, MEPs were obtained from the left ADM, although with a prolonged latency and a reduced amplitude. When the patient was requested to think about the abduction of her paralyzed left little finger, the latency and the elicitability of these responses improved as compared with the relaxed condition. These severe MEP alterations correctly predicted a poor recovery of motor function in the chronic stage. However, although the tegmental involvement raises the question of an insufficient cortical motor arousal, preserved motor imagery suggested a normal cortical motor area activation.

Cerebral Infarction↗

PubMed1999

Cost effectiveness of riluzole in amyotrophic lateral sclerosis. Italian Cooperative Group for the Study of Meta-Analysis and the Osservatorio SIFO sui Farmaci.

OBJECTIVE: In patients with amyotrophic lateral sclerosis, long term treatment with riluzole has been reported to improve survival or tracheostomy-free survival in comparison with placebo. We conducted a pharmacoeconomic analysis for estimating the cost per life-year gained using this drug. DESIGN: This study was an incremental cost-effectiveness lifetime analysis. SETTING: The clinical material was derived from 2 placebo-controlled randomised controlled trials comparing riluzole versus usual care without riluzole, which were identified through a literature search based on the IOWA and the Medline systems. PATIENTS AND INTERVENTIONS: The study included 633 patients with amyotrophic lateral sclerosis. Patient-level information was retrieved from 313 patients treated with riluzole and 320 patients assigned to placebo. Survival after randomisation was compared between the 2 groups using standard statistics (log-rank test and Cox analysis), whereas the lifetime survival gain was estimated using Gompertz extrapolation. Cost data relative to the expenditure for healthcare resources were obtained from published information (using the US average wholesale price for the acquisition cost of riluzole). Sensitivity testing assessed the impact of different cost-of-illness assumptions for treated and untreated patients. MAIN OUTCOME MEASURES AND RESULTS: Our primary analysis showed that treatment with riluzole significantly prolonged survival [death risk = 0.77; 95% confidence interval (CI): 0.62 to 0.96; p = 0.022]. The lifetime survival gain (including 3% annual discounting) was, on average, 2.3 months per patient, while the incremental cost was around $US12,000 per patient. Hence, the cost-effectiveness ratio of riluzole versus usual care without riluzole was $US62,609 per life-year gained (discounted dollars per discounted years; 95% CI: $US13,458 to $US205,714). The sensitivity analysis, considering different values of national cost for riluzole, suggested an interval for this parameter ranging from $US45,048 to $US62,609. CONCLUSIONS: Our study indicates that in patients with amyotrophic lateral sclerosis, riluzole has an unfavourable cost-effectiveness ratio or, at best, a borderline pharmacoeconomic profile.

Amyotrophic Lateral Sclerosis↗

PubMed1998

Eye movement abnormalities in anorexia nervosa.

The aim of the present study is to investigate smooth pursuit eye movement and saccadic performance in anorexia nervosa during a restored weight period and to determine if functional links can be made between eye movement performance and clinical features. SPEM parameters were recorded for 28 female anorectic out-patients (DSM IV), who had a body weight loss of up to 20% of ideal body weight. Twenty-eight comparison subjects were also tested. Clinically, each patient was assessed using the Eating Disorder Inventory (EDI), the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Structured Interview for Personality Disorders (SCID II), the Symptom Checklist-90-Revised (SCL-90-R) and the Hamilton Scale for Depression (HRSD). The anorectic patients performed slightly worse than the comparison subjects on a number of SPEM measures. No relationship was found between SPEM impairment and a global severity index of psychopathology (SCL 90-R GSI) or depressive symptoms. Moreover, OCD symptoms and scores on some EDI scales (such as perfectionism) appear related to the severity of the eye movement alterations. The evidence of SPEM abnormalities in a subgroup of anorectic patients during the remitted state and the relationship of the abnormalities to obsessive-compulsive symptoms are discussed. Results are in agreement with the hypothesis regarding the persistence of neurophysiological as well as psychopathological traits of disorder in anorectic patients.

Adult↗

PubMed1998

Adjunctive lamotrigine therapy in patients with refractory seizures: a lifetime cost-utility analysis.

OBJECTIVE: Lamotrigine as add-on treatment (500 mg per day) is effective in patients with refractory epilepsy, but its high cost requires a pharmacoeconomic analysis. We conducted a retrospective lifetime cost utility study in which clinical data were derived from a recent placebo-controlled clinical trial, cost-of-illness data were drawn from a previous ad-hoc study, and quality-of-life values were obtained by prospectively interviewing a separate group of 81 patients referred to our institution with epilepsy. RESULTS: Our analysis showed that chronic lamotrigine treatment implies an incremental lifetime cost of about $1,600,000 for every 100 patients. Incremental lifetime utility was around 40 quality-adjusted life-years (QALYs) for every 100 patients. On the basis of these data, adjunctive lamotrigine was estimated to cost approximately $41,000 per QALY gained. Sensitivity testing suggested a range of $25,000-$85,000 per QALY gained. CONCLUSION: Adjunctive lamotrigine (500 mg per day) in refractory epilepsy seems to have a worse pharmacoeconomic profile than many pharmacological treatments commonly used in areas other than epilepsy. Further data are needed to determine if lamotrigine can be equally effective at lower (and less costly) daily doses which could markedly improve its pharmacoeconomic characteristics.

Adjuvants, Pharmaceutic↗

PubMed1998

Interictal inhibitory mechanisms in patients with cryptogenic motor cortex epilepsy: a study of the silent period following transcranial magnetic stimulation.

The silent period (SP) following transcranial magnetic stimulation (TMS) of the motor cortex is mainly due to cortical inhibitory mechanisms. The aim of the present study was to investigate these inhibitory phenomena in primary motor cortex epilepsy. We studied the TMS-induced SP in both the first dorsal interosseous (FDI) muscles in 8 patients who suffered from cryptogenic partial epilepsy with seizures starting with clonic movements of the right upper limb. All patients were on chronic medication with antiepileptic drugs. Therefore, besides contrasting the results with 16 age-matched normal controls, we also studied 10 patients receiving similar antiepileptic treatments who suffered from cryptogenic partial epilepsy with seizures characterised by the absence of clonic manifestations. The duration of the SP was bilaterally increased in the patients with clonic seizures when compared with the two other groups of subjects. The SP was longer in the left FDI muscle (contralateral to the side of the clonic manifestation in all the patients). Our findings likely indicate enhanced interictal inhibitory mechanisms in patients with partial epilepsy involving the primary motor cortex. The resulting inhibitory effect could be greater in the intact hemisphere rather than in the affected one, in which the hyperexcitability of the epileptic focus had to be counterbalanced.

Adolescent↗

PubMed1997

Reversal of syphilitic hydrocephalus with intravenous penicillin.

BACKGROUND: CSF shunting procedures are generally considered the fundamental therapy of syphilitic hydrocephalus. METHODS: We followed up with CSF analysis and MR imaging a patient with progressive mental and gait disturbances and tetraventricular hydrocephalus due to tertiary syphilis who was treated for 14 days with high dose intravenous penicillin alone. RESULTS: Clinical and CSF abnormalities resolved within a few months, whereas the hydrocephalus disappeared only 30 months after therapy. CONCLUSIONS: Before consideration of a CSF shunting procedure, a trial of high dose intravenous penicillin is warranted for patients with syphilitic hydrocephalus.

Adult↗

PubMed1996

Smooth-pursuit eye movement and saccadic intrusions in obsessive-compulsive disorder.

Although several reports agree that smooth-pursuit eye movement (SPEM) is abnormal in some obsessive-compulsive disordered (OCD) patients, differences between treatments and lack of accuracy in control selection make the results controversial. Although reduced gain seems the most accepted abnormality, the characteristics of saccadic disruption of smooth pursuit are as yet unspecified. SPEMs in 21 OCD patients (DSM-III-R) and 21 healthy subjects recruited from the community were studied through a multiple target velocity task . The two groups were individually matched on age, gender, and level of education. None of the subjects had a history of substance dependence apart from the smokers who refrained from smoking in the 2 hours prior to the test. A significantly lower SPEM gain and increased number and frequency of anticipatory saccades (ASs) was found in OCD patients as compared with control subjects. No relationship emerged between eye movement abnormalities and clinical variables explored.

Adult↗

PubMed1996

Human heart rate variability and sleep stages.

With the aim of better understanding the dynamic changes in sympatho-vagal tone occurring during the night, human heart rate variability (HRV) during the various sleep stages was evaluated by means of autoregressive spectral analysis. Each recording consisted of an electroencephalogram, an electrooculogram, and electromyogram, and electrocardiogram, and a spirometry trace. All of the data were sampled and stored in digital form. Sleep was analysed visually, but HRV was analysed off-line by means of original software using Burg's algorithm to calculate the LF/HF ratio (LF: 0.04-0.12 Hz; HF: 0.15-0.35 Hz) for each sleep stage. Seven healthy subjects (four males; mean age 35 years) were enrolled in the study. Our findings show a progressive and significant reduction in the LF/HF ratio through sleep stages S1-S4, as a result of an increase in the HF component; this indicates the prevalence of parasympathetic activity during slow-wave sleep. During wakefulness, S1 and REM, the LF/HF values were similar and close to 1.

Adult↗

PubMed1993

Influence of single and repeated doses of oxcarbazepine on the pharmacokinetic profile of felodipine.

Eight healthy male volunteers (age 25-41 years) entered an open-label, within-subject study. They were treated for 13 consecutive days with felodipine (FEL) extended-release tablets, 10 mg daily. On day 6, oxcarbazepine (OXC) 600 mg was given in the morning, and from day 7 to 13, the daily dose was increased to 450 mg b.i.d. Blood samples for measurement of FEL and its pyridine metabolite (determined by gas-chromatography) were drawn just before dosing and at 2, 4, 6, 8, 10, 12, and 24 h after dosing on days 5, 6, and 13. Steady-state pharmacokinetic parameters of FEL and its pyridine metabolite were not influenced by the single dose of OXC. Repeated coadministration of OXC significantly reduced the area under the concentration-time curve (AUC0-24) of FEL by 28% and the FEL maximum plasma concentration (Cmax) by 34%. This reduction in FEL bioavailability is much smaller than that observed after co-administration of carbamazepine (CBZ) (i.e., 94%).

Administration, Oral↗

PubMed1993

Vigabatrin-induced decrease in serum phenytoin concentration does not involve a change in phenytoin bioavailability.

The possibility that vigabatrin (VGB) decreases serum phenytoin (PHT) concentration by lowering the oral bioavailability of PHT was investigated in 21 patients with epilepsy. Each patient was switched from oral to intravenous PHT for 5 days before and after combined treatment with VGB. After VGB (2-3.5 g day(-1) for at least 5 weeks), serum PHT concentrations decreased slightly from 87 +/- 25 to 76 +/- 31 micromol l(-1) (means +/- s.d., P < 0.05), but in a subgroup of seven patients the decrease was more prominent (from 72 +/- 22 to 49 +/- 17 micromol l(-1), P < 0.005). At baseline (before VGB), serum PHT remained unaffected (85 +/- 30 micromol l(-1)) after switching PHT dosage to the intravenous route, indicating that the oral availability of the drug was virtually complete. During VGB treatment, serum PHT was also unchanged (74 +/- 34 micromol l(-1)) after switching from oral to intravenous therapy, and this was also true for the subgroup of patients showing a prominent interaction (48 +/- 18 micromol l(-1)). The urinary recoveries of PHT and its metabolites pHPPH and mHPPH remained constant throughout the study. It is concluded that the oral availability of PHT is unaffected by VGB and that the VBG-induced decrease in serum PHT is mediated by alternative mechanisms.

Adolescent↗

PubMed1992

Smooth-pursuit eye movements: alterations in Alzheimer's disease.

Smooth-pursuit eye movements induced by targets moving at constant velocities (from 5 to 100 deg/sec) were recorded from 13 patients with Alzheimer's disease (AD) and from 11 healthy subjects. Four variables were evaluated to quantify the patients' response to the eye movement tests: (1) average peak velocity of smooth-pursuit; (2) percent target matching index after saccade removal (percent ratio between the area of the velocity curve of smooth-pursuit eye movement after saccade removal and the area of target velocity) which is related to the eye performance for each value of target velocity; (3) total amplitude of anticipatory saccades; (4) total number of anticipatory saccades. Compared to the controls, AD patients were found to have significantly lower values of average peak velocity of smooth pursuit and of percent target matching index and a significantly increased number and amplitude of anticipatory saccades. A discriminant stepwise analysis indicated that 5 oculographic variables were significantly associated with the patient's clinical condition (healthy volunteer or AD patient). These statistics yielded an equation for predicting the patient's status according to which the percentage of cases classified correctly was 82.6% in the overall group (n = 23). The predictive performance was similar between the healthy volunteers subgroup (81.8%, n = 11) and the AD subgroup (83.3%, n = 12). The discriminant score was significantly correlated with the score resulting from the MiniMental test (r = 0.67). A significant correlation was also found between the MiniMental score and the number of anticipatory saccades (r = -0.61). No significant correlation was present between the gain of smooth pursuit and the patients' cognitive decline.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Effects of oxcarbazepine and carbamazepine on the central nervous system: computerised analysis of saccadic and smooth-pursuit eye movements.

Oxcarbazepine (OXC) is a new anti-epileptic agent structurally related to carbamazepine (CBZ). OXC seems to have a similar efficacy and a better tolerability profile than CBZ. In the present study we compared the subclinical side-effects on the CNS of OXC and CBZ using a computerised analysis of saccadic and smooth-pursuit eye movements. Six healthy male volunteers (mean age 29 yrs) participated in the study, which was conducted by a double-blind cross-over design. Each subject was given a single dose of either CBZ 400 mg or OXC 600 mg (according to the random assignment) after which the drug effects on eye movements were evaluated. One week later, the trial was repeated using the other drug. The parametrisation of both saccadic and smooth-pursuit eye movements was carried out by measuring a series of performance parameters [e.g. the maximum saccade peak velocity (MSPV) and the typical target velocity (TTV)]. OXC was found to induce a lesser degree of alteration on the values of both MSPV (p = 0.07) and TTV (p less than 0.03) than CBZ. In particular, the TTV values were virtually unaffected by OXC administration, while the effects of CBZ on both variables were particularly evident at 8 and 10 h after dosing which correspond to the time at which the plasma concentrations of CBZ and of its 10,11-epoxide reach the peak. In conclusion, our preliminary results indicate that OXC induces negligible alterations, if any, on the eye movement parameters evaluated in our study.

Adult↗