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Biomedical subjects

U Aguglia

Publications and source records attributed to U Aguglia.

At least 55 records · Page 3Linked to original sources
PubMed1996

Tolerance to anticonvulsant effects of some benzodiazepines in genetically epilepsy prone rats.

The development of tolerance to the anticonvulsant effects of clonazepam, clobazam, and diazepam were studied in genetically epilepsy-prone rats following intraperitoneal (IP) or oral administration. The anticonvulsant effects were evaluated on seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz). All compounds showed 60 min after IP injection antiseizure activity with ED50 against clonus of 0.24 mumol kg-1 for clonazepam, 0.72 mumol kg-1 for diazepam, and 3.9 mumol kg-1 for clobazam. After 120 min of oral administration the ED50 against clonus of 2.37 mumol kg-1 for clonazepam, 15.8 mumol kg-1 for diazepam, and 30 mumol kg-1 for clobazam. The dose chosen for the chronic treatment were 2.5 mumol kg-1 for clonazepam, 15 mumol kg-1 for diazepam, and 30 mumol kg-1 for clobazam. The animals were treated three times daily for 4 or 6 weeks. Auditory stimulation was administered 60 min after drug IP injection on various days. During treatment, tolerance was observed as a loss of drug anticonvulsant effects. No changes of occurrence of audiogenic seizures was observed in rats treated with vehicle. Tolerance to the anticonvulsant activity developed most rapidly during clobazam treatment, less rapidly following diazepam treatment, and most slowly during clonazepam treatment. Sixty minutes after IP injection on various days of chronic treatment the motor impairment induced by these benzodiazepines was also studied by means of a rotarod apparatus. The tolerance to the motor impairment developed more rapidly than the anticonvulsant effects. The response to auditory stimulation to benzodiazepines was stopped 24 and 48 h after chronic treatment with these compounds, showing no residual drug effects and that rats were still tolerant. The genetically epilepsy-prone rats is a reliable and sensitive model for studying long-term effects of anticonvulsant drugs.

Acoustic Stimulation↗
PubMed1996

Anticonvulsant activity of 5,7DCKA, NBQX, and felbamate against some chemoconvulsants in DBA/2 mice.

The anticonvulsant effects of felbamate (10-300 mg/kg, intraperitoneally, IP), and those of two representative antagonists of the excitatory amino acid receptors, 5-7 dichlorokynurenic acid (5-7DCKA; 0.6-30 nmol/mouse, intracerebroventricularly, ICV), and 2, 3-dihydroxy-6 nitro-7-sulfamoylbenzo (F) quinoxoline (NBQX; 1.1-33.6 mg/kg, IP) were studied in the DBA/2 mice. All drugs protected the animals from sound-induced seizures. The drugs were also effective against seizures induced by stimulation of the excitatory amino acid receptor complex using the agonists N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid (AMPA). In separate studies, felbamate protected mice from seizures induced by ICV administration of the activator of dihydropyridine-sensitive calcium channels, methyl-1, 4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate (Bay k 8644), with ED50 values of 26 and 46.9 mg/kg for tonus and clonus, respectively. Using Bay k 8644, NBQX (1-40 mg/kg IP) was uneffective, while 5,7DCKA (5-90 nmol/mouse, ICV) protected mice against tonus. Moreover, felbamate prevented seizures induced by blocking voltage-dependent K+ channels using alpha-dendrotoxin, with ED50 values of 22.6 mg/kg for tonus and of 34.8 mg/kg for clonus. Conversely, 5,7DCKA or NBQX did not significantly antagonize seizures induced by alpha-dendrotoxin. The present data indicate that felbamate is an effective anticonvulsant drug in DBA/2 mice with a broader anticonvulsant spectrum than 5,7DCKA and NBQX.

Acoustic Stimulation↗
PubMed1996

Functional preservation of benzodiazepine receptors of the primary somatosensory cortex in Creutzfeldt-Jakob disease: a pharmacologic-evoked potential study.

In previous studies, we demonstrated that the benzodiazepine (BZP) receptors of the visual system are functionally preserved in Creutzfeldt-Jakob disease (CJD). We hypothesized that such a functional preservation is not confined to the visual system. In a 74-year-old woman suffering from CJD, three consecutive recording sessions of somatosensory cortical evoked potentials (SEPs) by right median nerve stimulation were carried out: (a) basal condition, without any pharmacologic treatment; (b) 1 min after i.v. administration of 10 mg diazepam (DZP); (c) 2.5 min after i.v. administration of 3 mg FMZ, a high-affinity receptor benzodiazepine antagonist. DZP greatly decreased the amplitude of SEP early components, whereas flumazenil (FMZ) reversed such an effect. The results of this study, paralleling our previous findings on the visual system in CJD, demonstrated functional preservation of BZP receptors in the somatosensory pathways as well.

Aged↗
PubMed1996

Photic-induced epileptic negative myoclonus: a case report.

We present the first documented case of photic-induced epileptic negative myoclonus. A 17-year-old girl had experienced two generalized tonic-clonic seizures (GTCS) while watching television. The only EEG abnormality was a photoparoxysmal response (PPR), which was sometimes accompanied by loss of postural tone in both arms. Valproate was effective in abolishing photosensitivity. Negative myoclonus should be included among the ictal phenomena accompanying PPR.

Adolescent↗
PubMed1996

Autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheaths: clinical, electrophysiologic, and genetic aspects of a large family.

We describe 10 patients from a large family with early onset motor and sensory neuropathy. Six were still living at the time of the study. In all cases, early motor milestones had been achieved. Mean age at onset of symptoms was 34 months; these included progressive distal and proximal muscle weakness of lower limbs. Pes equinovarus developed in all patients during childhood. Slight facial weakness was present in four patients, and one of them also had bilateral facial synkinesia. Intellectual function was normal in all cases. There was no evidence of thickened peripheral nerves. All three adult patients (mean age, 27 years) were seriously handicapped and wheelchair-bound. Death occurred in the fourth to fifth decade of life and the duration of the illness varied from 27 to 39 years. Motor nerve conduction velocities ranged from 15 to 17 m/sec in the upper limbs of the youngest patients, and were undetectable in the adult patients. Sensitive action potentials were almost always absent. In all patients, auditory evoked potentials showed abnormally delayed interpeak I-III latencies. The most prominent pathologic finding was a highly unusual myelin abnormality consisting of irregular redundant loops and folding of the myelin sheath. The genealogic study gave strong evidence of autosomal-recessive inheritance. The molecular analysis failed to demonstrate either duplication in the chromosome 17p11.2-12, point mutations in the four exons of the PMP-22 (17p11.2) and the six exons of the Po (1q21-q25) genes, or linkage to chromosome 8q13-21.1.

Adult↗
PubMed1995

The subacute levodopa test for evaluating long-duration response in Parkinson's disease.

The clinical relevance of a long-duration response (LDR) to levodopa therapy in Parkinson's disease (PD) has not been widely recognized. In 25 patients with moderate PD, we measured LDR on motor function after short periods of treatment with levodopa (subacute tests). Each subacute test lasted 15 days and consisted of the oral administration of levodopa at various interdose intervals (IDIs) of 48, 24, 12, 8, 6, and 5 hours. The goal for a subacute test was to achieve a satisfactory antiparkinsonian effect before the last levodopa dose (day 15), i.e., an LDR greater than 50% of the maximal response following an acute levodopa test (LDR-endpoint). Twenty-one patients (84%) reached the LDR-endpoint. The IDI at which levodopa was administered clearly differentiated patients who were otherwise clinically indistinguishable when evaluated at baseline off medication or after an acute levodopa test. The IDI schedule that produced a satisfactory LDR was specific for each patient, since longer DIs failed to produce the required LDR, and a shorter IDI schedule (resulting in larger cumulative dosage of levodopa) did not significantly enhance the response. Also, the LDR decay rate after discontinuation of treatment was individual for each patient and independent of the cumulative amount of levodopa administered. Both the IDI schedule and the LDR decay rate may reflect the ability of nigrostriatal neurons to store and to release dopamine formed from the exogenous precursor. The assessment of the LDR to levodopa by subacute tests is useful for establishing the appropriate dose of the drug, as well as for developing levodopa sparing strategies in PD patients.

Aged↗
PubMed1995

De novo epileptic confusional status in a patient with cobalamin deficiency.

A 80-year-old man with cobalamin deficiency and no history of epilepsy developed a partial complex epileptic confusional status (ECS) unresponsive to acute i.v. diazepam. Brain CT scan and MRI investigation ruled out a focal cerebral lesion. Therapy with high doses (10,000 micrograms i.m. daily) of cobalamin alone was started, and the patient fully recovered in the following 72-hour. Control EEGs repeatedly performed days and weeks later showed progressive disappearance of the frontal interictal spiking, while the patient was on monotherapy with cobalamin (5,000 micrograms i.m. weekly). A month later the patient unfortunately discontinued replacement therapy and 13 weeks later he developed a fatal convulsive epileptic status. To our knowledge the association of ECS and cobalamin deficiency has not been previously reported.

Aged↗
PubMed1995

Negative myoclonus during valproate-related stupor. Neurophysiological evidence of a cortical non-epileptic origin.

We retrospectively reviewed clinical and neurophysiological data of 6 epileptic patients who developed negative myoclonus and stupor a few days after introduction of valproate (VPA). Prompt remission of clinical signs and symptoms followed valproate withdrawal. We attempted to elucidate the pathophysiological mechanism of VPA-induced stupor and provide further polygraphic and backaveraging EEG documentation of negative myoclonus. During VPA-induced stupor electroencephalograms revealed posterior background slowing in all patients. Interictal epileptiform discharges were present in 3 patients. In all 6 patients close examination using simultaneous video-polygraphic recording showed negative myoclonus which was not time-related to lateralized spike discharges. In 2 of 3 patients with no spikes on conventional EEG who underwent backaveraged EEG recordings we detected a large (5 microV) cortical positive-negative wave time-locked (30-40 msec) with the postural modification of the contralateral wrist. This cortical potential was similar to that observed in patients with asterixis secondary to metabolic or toxic encephalopathies. In one patient i.v. administration of 10 mg diazepam did not modify this cortical potential and did not reverse the clinical manifestations. In all patients the only abnormal laboratory finding was an increased level of venous ammonemia. Our findings are against an epileptic origin of VPA encephalopathy and provide further argument in favour of a cortical non-epileptic mechanism mediating negative myoclonus. Benzodiazepines should be avoided in the management of this condition.

Adult↗
PubMed1994

Excitatory amino acid neurotransmission through both NMDA and non-NMDA receptors is involved in the anticonvulsant activity of felbamate in DBA/2 mice.

The anticonvulsant activity of felbamate against sound-induced seizures was studied in the DBA/2 mouse model. Felbamate (10-300 mg/kg, i.p.) produced dose-dependent effects with ED50 values for the suppression of tonic, clonic and wild running phases of 23.1, 48.8 and 114.6 mg/kg, respectively. Felbamate also protected DBA/2 mice from N-methyl-D-aspartate (NMDA)-induced seizures with ED50 values of 12.1 and 29 mg/kg for tonus and clonus, respectively. Pretreatment with glycine, an agonist to the glycine/NMDA receptors, shifted the dose-response effect of felbamate to the right (ED50 = 56.8 against tonus and 94.8 mg/kg versus clonus). Similarly, D-serine, an agonist at the glycine site, shifted the ED50 of felbamate against the tonic component of audiogenic seizures from 23.1 to 78.1, and that against clonus from 48.8 to 90.3 mg/kg. Felbamate was also potent to prevent seizures induced by administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), an AMPA/kainate receptor agonist (ED50 = 11.8 and 20.9 mg/kg, against tonus and clonus, respectively). The data indicate that felbamate is an effective anticonvulsant drug in the genetic model of seizure-prone DBA/2 mice. Our findings suggest that the anticonvulsant properties of felbamate depend upon its interaction with neurotransmission mediated by both the glycine/NMDA and the AMPA/kainate receptor complex.

Acoustic Stimulation↗
PubMed1994

Chlorpromazine versus sleep deprivation in activation of EEG in adult-onset partial epilepsy.

We prospectively compared the activating effect of chlorpromazine (CHLP, 50 mg, i.m.) versus sleep deprivation (SD) in 41 patients with a clinical diagnosis of partial epilepsy. Patients were selected on the basis of both seizure onset in adulthood and normal interictal awake EEG recordings. Twenty out of 41 patients (group A) were not yet treated because of either recent onset of epilepsy or misdiagnosis. The remaining 21 patients (group B) were treated with antiepileptic drugs (AED). A control group consisted of 18 healthy, volunteers (group C). All EEG recordings were scored by one observer according to a fixed protocol. In group A, SD and CHLP activated sleep EEG in 12 (60%) and 19 (95%) patients, respectively. This difference reached the limit of statistical significance (P = 0.05, McNemar test). In group B, SD and CHLP activated sleep EEG in 12 (57%) and 13 (62%) patients respectively. There was a significant (P < 0.02, exact Fisher test) intergroup difference (95% vs 62%) with respect to the activating effect of CHLP. No false-positive results were found in 18 control subjects. SD or CHLP activating procedures did not provoke any epileptic seizures in any of the groups. In conclusion, EEG activation by either SD or CHLP is highly specific in the diagnosis of adult-on-set partial epilepsy. Moreover, CHLP is more sensitive than SD in untreated patients, whereas the activating effect of CHLP may be partially attenuated by AED.

Adolescent↗
PubMed1993

Functional integrity of benzodiazepine receptors of the geniculo-striate visual pathways in Creutzfeldt-Jakob disease. A pharmacological evoked potential study.

We evaluated the effects of flumazenil (FMZ), a high-affinity benzodiazepine receptor antagonist, on flash-evoked visual potentials (FEPs) in a patient with Creutzfeldt-Jacob disease (CJD). FEPs were recorded in three different consecutive sessions: (1) basal condition, without any pharmacological treatment; (2) 3.5 min after i.v. administration of 5 mg FMZ; (3) 1 min after i.v. administration of 10 mg diazepam (DZP). FMZ provoked a marked increase in the amplitude as well as evident shortening of the latency of early FEP components. DZP reversed these effects. These results are in agreement with our previous findings of anatomical and functional integrity of the geniculo-striate pathways in human CJD and demonstrate functional integrity of benzodiazepine receptors in this visual system in CJD.

Creutzfeldt-Jakob Syndrome↗
PubMed1992

Sleep electroencephalogram at the early stage of Creutzfeldt-Jakob disease.

We describe sleep EEG studies in three patients at the early stage of Creutzfeldt-Jakob disease. Little work has been devoted to the study of the sleep EEG in the course of the CJ disease: disorganized sleep architecture was noted, associated with a decrease in stage 4 and an almost complete disappearance of the REM stage. Our patients were considered to have normal stage 2; yet spindles and K complexes were rare at this stage. No evolution towards stage 4 was noted. The percentage of rapid eye movement sleep was significantly low in two cases and normal in one case. Sleep disturbances in the other dementing disorders are reported.

Aged↗
PubMed1991

Different susceptibilities of the geniculate and extrageniculate visual pathways to human Creutzfeldt-Jakob disease (a combined neurophysiological-neuropathological study).

Flash evoked visual potentials (FEPs) of 7 patients with advanced Creutzfeldt-Jakob disease (CJD) were compared with those recorded in 7 patients with senile dementia of the Alzheimer type (SDAT), in 13 age- and sex-matched healthy volunteers and in 7 neuropsychiatrically normal subjects whose occipital evoked responses were increased in amplitude (amplitude controls). Post-mortem examination was performed in 4 of 7 CJD patients in order to map pathological changes along the visual pathways, including the retino-geniculo-striate and extrageniculate pathways. Normal FEPs were typified by 2 constant early components (P1 and N2) followed by several (3 or more) late components that were characterized by marked interindividual variability. Amplitude controls had enlarged (from 14 to 44.8 microV, mean 25.7) P1 component. Both SDAT and CJD patients had normal early FEP waves (P1 and N2) and important alterations of the late FEP components. Moreover, a late positive component was responsible for abnormally enlarged FEPs (52.6 and 58.2 microV) in 2 CJD patients. Finally, electroretinograms, recorded in 1 CJD patient, were normal. These findings suggested relative functional integrity of the retino-geniculo-striate pathway associated with important dysfunction of the cortical visual processing in both SDAT and CJD patients. Pathological studies disclosed preservation of optic nerves, chiasmas, lateral geniculate nuclei and Gennari's strip of the striate cortex but associated with important spongiform change, neuronal loss and gliosis in the superior colliculi (layer II), pulvinar, extrastriate cortex and layers II-III, V and VI of the striate cortex. We conclude that different visual pathways have different susceptibilities to CJD: important functional and anatomical alterations of the intracortical and extrageniculate pathways contrast with relative preservation of the retino-geniculo-striate pathway.

Adult↗
PubMed1991

Sensory evoked potentials in herpes simplex encephalitis.

Flash visual potentials (FEPs), somatosensory evoked potentials (SEPs) and auditory brainstem responses (ABR) were recorded in a 66-year-old patient presenting with clinical, EEG and CT brain scan features of herpes simplex encephalitis (HSE). At the time of evoked potential study (10 days after onset of the disease) the patient was treated with iv barbiturate on controlled respiration (lidocaine and phenytoin were not utilized); core temperature was 37 degrees C and pupils were dilated and nonreactive. Cortical FEPs were not recognizable on 02 lead, whereas they were clearly evident on 01 with normal latency of early N1, P1, N2 waves and delayed P2 component. SEPs showed normal peripheral and central conduction times, but N20 peak was bilaterally absent with unrecognizable (on P3) or delayed (on P4) N33 wave. No ABR (including wave I) were found on stimulation of the right ear, whereas delayed wave V with prolonged interpeak I-V latency was found on stimulation of the left ear. In conclusion, changes in sensory evoked potentials in HSE seem to be caused either by necrotic-hemorrhagic damage (with the disappearance of some cortical responses), by coma (with alterations in middle-latency cortical responses) and by increased intracranial pressure (with subsequent ABR abnormalities).

Aged↗
PubMed1991

Sleep-induced masticatory myoclonus: a rare parasomnia associated with insomnia.

Tonic and rhythmic activity of the masticatory muscles accompanied by a loud and grating or clicking sound characterizes bruxism, a well-recognized parasomnia. We describe a 63-year-old man who complained of insomnia due to repeated tongue nibbling during sleep. Nocturnal polysomnographic recordings showed brief (50-100-ms) myoclonic jerks of myloioideus and masseter muscles occurring during phase 1 of sleep and leading to troublesome tongue nibbling with arousal of the patient. Hypnograms showed reduction of phase 2 and absent phases 3-4 and REM. Different pharmacological treatments including clomipramine, benzodiazepines, and carbamazepine were ineffective. A purposive interdental plate was placed to prevent jaw closings during sleep: masticatory myoclonus still persisted, but it did not provoke arousals; insomnia disappeared and night hypnograms improved.

Cerebral Cortex↗
PubMed1990

Triphasic waves and cerebral tumors.

Three patients with cerebral tumor involving diencephalic midline structures (2 malignant gliomas, 1 craniopharyngioma) and no metabolic abnormalities developed disorientation in time and place or coma with triphasic waves (TW) seen on electroencephalograms. Serial EEG recordings showed persistence or disappearance of TW depending on poor or good outcome of the antiedema treatment. TW have been described with disorders affecting the brain diffusely, as metabolic encephalopathies, dementing processes, cerebral carcinomatosis and baclofen intoxication. The findings described here demonstrate that TW may occur in patients with brain tumor involving subcortical midline structures.

Aged↗