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Biomedical subjects

R Michelucci

Publications and source records attributed to R Michelucci.

At least 37 records · Page 2Linked to original sources

Reduced plasma nisoldipine concentrations in phenytoin-treated patients with epilepsy.

PURPOSE: To assess whether phenytoin affects the pharmacokinetics of the dihydropyridine calcium antagonist nisoldipine. METHODS: Twelve patients with epilepsy receiving chronic phenytoin therapy and 12 healthy control subjects matched for age and gender received a single oral dose of nisoldipine (40 and 20 mg, respectively). Blood samples were collected for up to 48 h for estimation of plasma nisoldipine levels by capillary gas chromatography. RESULTS: Mean plasma nisoldipine concentrations were much lower in the patients. Geometric means for areas under the concentration-time curve (AUC0-tn) normalized to a 20-mg dose were 1.6 micrograms/L/h (95% confidence intervals, 0.6-3.8 micrograms/L/h) in the patients compared with 15.2 (10.7-21.6) micrograms/L/h in control subjects (p < 0.002). CONCLUSIONS: These results suggest that phenytoin increases the first-pass metabolism of nisoldipine to a clinically important extent. In view of the magnitude and variability of interaction, use of nisoldipine in patients receiving chronic phenytoin therapy is contraindicated.

Adult↗

Transcranial magnetic stimulation in partial epilepsy: drug-induced changes of motor excitability.

Single-pulse transcranial magnetic stimulation (s-TMS) with recording of motor evoked potentials (MEPs) from thenar muscles of both hands was performed on 84 patients with cryptogenic partial epilepsy and 50 healthy controls. We analyzed the cortical latency (CL), central conduction time (CCT), and threshold intensity (TI) required to elicit liminal MEPs at rest. In the patients, CL and CCT were normal, but TI was significantly higher than in the controls. Of the 84 patients, 65 were taking one or more antiepileptic drugs and 19 were untreated. The untreated patients had a significantly lower TI than the treated patients. In the treated patients, the TI increase paralleled the number of drugs taken. Additionally, in 2 subgroups of patients undergoing major modifications of antiepileptic treatment, TI dropped after partial withdrawal of medication and increased following the commencement of therapy. The results suggest that anticonvulsants depress the excitability of human motor pathways in epileptic subjects.

Adolescent↗

Electroclinical features of idiopathic generalised epilepsy with persisting absences in adult life.

OBJECTIVES: To describe the electroclinical features of typical absences persisting in adult life. METHODS: Twelve adult patients (aged 21 to 56 years) with idiopathic generalised epilepsy featuring typical absences as the prominent clinical feature were studied. All patients underwent a full clinical and neurophysiological investigation including ictal documentation of seizures. RESULTS: Neurological examination and neuroradiological investigations were normal in all cases. Clinical findings included a median age at onset of absences of 14 (range 4-32) years, almost constant tonic-clonic seizures (in 83% of patients), frequent episodes of absence status (in 33% of patients), and associated cognitive or psychiatric disturbances. Interictal EEG findings showed normal background activity, generalised paroxysms of spike waves or polyspike waves, and inconstant focal spikes (in five patients); runs of polyspikes were seen during non-REM sleep. Ictal EEG findings showed generalised spike waves at 3 Hz, sometimes preceded by multiple spikes, or more complex EEG patterns with sequences of polyspikes intermingled with spike waves or polyspike waves, showing discharge fragmentation or variation of intradischarge frequency. CONCLUSION: The results of the present study show that absences persisting in adult life may show particular clinical and EEG patterns, distinct from those in childhood or adolescence.

Adult↗

Epileptic negative myoclonus.

ENM is an etiologically heterogeneous disorder clinically evident as brief (less than 500 msec) lapses of tonic muscular contraction which seems to be related to lesions or dysfunction of different anatomofunctional levels of the CNS (Fig. 13). ENM can occur in heterogeneous epileptic disorders, ranging from benign syndromic conditions (such as BECTS) to focal static lesional epilepsy, as in neuronal migration disorders, and even to severe static or progressive myoclonic encephalopathies (PMEs). Neurophysiological studies in patients with ENM lead to the following conclusions: 1. A cortical origin of ENM is supported by EEG mapping and dipole analysis of spikes related to the ENM. In particular, our data suggest that the focal spike is a paroxysmal event involving, primarily or secondarily, the centroparietal and frontal "supplementary" motor areas. 2. A cortical inhibitory active mechanism for the genesis of ENM is supported by the occurrence of a decreased motor response to TMS, with preserved spinal excitability as demonstrated by the persistence of F waves. A "cortical motor outflow inhibition" related to spike-and-wave discharges was suggested by Gloor in his Lennox lecture (34). The cortical reflex negative myoclonus, described by Shibasaki et al. (16) in PME, is also consistent with a cortical active inhibitory mechanism. The spike associated with ENM raises new issues about the definition of "interictal" versus "ictal" EEG paroxysmal activity. A single spike on the EEG can be clinically silent (therefore, "interictal") or clinically evident as ENM (then viewed as "ictal"), depending on whether a given group of muscles is at rest or is showing tonic activity (see Fig. 4). These data, from a more general perspective, imply that the motor manifestation related to EEG paroxysmal events can depend not only on amplitude, topography, or intracortical distribution of seizure activity (35), but also on plasticity (36) and on the functional condition of the motor system (37). The variability of latency between the spike and the onset of the muscular inhibition (ranging from 15 to 50 msec, for the upper limbs), and the variability of duration of the ENM itself (from 50 to 400, or more, msec) indicate that ENM could be the result of inhibitory phenomena arising not only from a single cortical "inhibitory" area, but also from subcortical and pontine structures, as discussed by Mori et al. (this volume). The neurophysiological distinction between ENM and postmyoclonic periods of muscular suppression, mainly related to an EGG slow wave, as described by Lance and Adams (2) in the postanoxic action myoclonus is still a matter of discussion (38, 39). This is also the case for other movement disorders combining action myoclonus and epilepsy-as described in Ramsay Hunt syndrome (30), now better referred to as Unverricht-Lundborg syndrome (40) (Fig. 14). In these conditions, myoclonia and muscular silent periods are inconstantly associated with paroxysmal EEG discharges, suggesting a possible thalamocortical mechanism rather than a purely cortical one. In the most prolonged muscular inhibitions, both cortical and thalamocortical mechanisms might be implicated. Clearly, our knowledge of ENM is still very limited and gaining further insights into this complex phenomenon is a challenging problem.

Brain Mapping↗

PME of Unverricht-Lundborg type in the Mediterranean region: linkage and linkage disequilibrium confirm the assignment to the EPM1 locus.

Seven phenotypically homogeneous Mediterranean myoclonus families were studied using DNA markers from the genetically defined EPM1 region on chromosome 21. No recombinations between the disease phenotype and the markers studied were detected. Within the EPM1 region, the highest lod score value of 5.07 (at theta = 0.00) was reached at locus PFKL. Significant allelic association (P = 0.02) between the disease mutation and PFKL was detected suggesting a founder effect in Mediterranean myoclonus. However, haplotype data using four marker loci residing within 300 kb of each other and of EPM1 suggest the occurrence of more than one mutation. The data are compatible with Mediterranean myoclonus being caused by mutations in the EPM1 gene and strengthen the concept that a large subset of progressive myoclonus epilepsies conforms with Unverricht-Lundborg disease and that this subset is an etiologically homogeneous entity.

Adolescent↗

Rapid-rate transcranial magnetic stimulation and hemispheric language dominance: usefulness and safety in epilepsy.

We performed rapid-rate transcranial magnetic stimulation (r-TMS) in 14 epileptic patients, using a coil centered over nine different positions on each side of the scalp and while the subjects counted aloud. We obtained lateralized speech arrest, concordant with the site of manual preference, in only seven patients. There was transitory homonymous hemianopia (one patient), brief jerking of one arm (two patients), and affective (crying) reaction (three patients) after the end of a train of stimuli. In our experience, r-TMS is not as sensitive as previously reported for determination of hemispheric language dominance and may have undesirable side effects.

Adult↗

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↗

Transthyretin-related TTR hereditary amyloidosis of the vitreous body. Clinical and molecular characterization in two Italian families.

Two unrelated Italian families affected by hereditary amyloidosis are described. Molecular genetic characterization demonstrated different mutations of the transthyretin gene. In all patients belonging to the TTR Ala 49 family the vitreous body, the heart and the peripheral nervous system were massively infiltrated by amyloid matter. In the TTR Pro 36 family vitreous opacities were the long-standing isolated manifestations of the disease. Two different patterns of vitreous deposits can be observed in these two families. The authors' data support the hypothesis that different pathological transthyretin proteins may have different affinity for the connective tissue in the vitreous.

Adult↗

Identical genetic locus for Baltic and Mediterranean myoclonus.

Genetic linkage analysis shows that Baltic and Mediterranean myoclonus, two forms of progressive myoclonus epilepsy, are closely linked to marker D21S113 on the long arm of chromosome 21. Baltic and Mediterranean myoclonus are most probably due to mutations of the same gene.

Alleles↗

Slowly progressive familial dementia with recurrent strokes and white matter hypodensities on CT scan.

We describe 2 normotensive sisters presenting slowly progressive dementia associated with acute or subacute focal neurological symptoms, unilateral or bilateral motor signs, and dysarthria. Their father, who died in the seventh decade, had a similar clinical picture. Computerized axial tomography (CT) scan of the head showed symmetrical hypodensities in the periventricular white matter and mild to moderate hydrocephalus. In these patients a diagnosis of Binswanger's disease was based on the clinical features supported by white matter changes on CT scan. Our study suggests that genetic factors may play a role in the etiology of Binswanger's disease.

Adult↗

Multiple lesions in cerebral white matter in two young adults with thoracic extramedullary tumours.

Cranial MRI showed multiple lesions in white matter that were thought to be consistent with multiple sclerosis in two young adults presenting with symptoms of progressive myelopathy. MRI of the cervicothoracic spine around one and two years after onset showed the myelopathy to be due to mid-thoracic tumours. The tumours (an extradural meningioma and intradural neuroma) were resected with complete resolution of myelopathy in one patient but no recovery in the other. Spinal MRI (or myelography) should be performed in young patients presenting with signs of progressive myelopathy even when cranial MRI shows a picture typical of multiple sclerosis.

Adult↗

The electrical status epilepticus syndrome.

The authors review the clinical and electroencephalographic features of electrical status epilepticus during slow sleep (ESES) in children. The major points of debate regard the nosology and diagnosis of ESES. The relationship between ESES and the neuropsychological impairment is emphasized. It is concluded that ESES is a separate electro-clinical entity which deserves individual categorization.

Cerebral Cortex↗

The neurophysiological features of benign partial epilepsy with rolandic spikes.

SEPs were performed in 44 children with benign partial epilepsy with rolandic spikes (BERS). High-amplitude mid- or long-latency SEPs were recorded in 17 patients (38%). These giant responses showed normal latency values but reached an exceedingly high amplitude (up to 200 microV). They showed the same reactivity characteristic of normal long-latency SEPs. In a 3-year follow-up study, the giant responses were shown to disappear in some patients and to shift from side to side in others. Our study demonstrates that giant SEPs are relatively common in BERS and give further support to the concept of a functional nature of rolandic foci.

Adolescent↗

Vigabatrin.

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Adolescent↗

[The role of mitochondrial encephalopathies in progressive myoclonus epilepsy].

The authors compare the clinical, neurophysiological and evolutive features of progressive myoclonus epilepsy (PME) associated with mitochondrial encephalomyopathy with ragged-red fibers (MERRF), based on 49 cases from the literature, and the two well-described types of degenerative PME: Baltic myoclonus (BM), of which over 100 cases have been reported from Finland, and Mediterranean myoclonus (MM), based on a personal series of 43 patients. Degenerative PMEs are age-dependent, recessively inherited conditions with homogeneous clinical signs and course; there are no major clinical symptoms beside the cardinal symptoms: generalized epileptic seizures, predominantly action myoclonus and cerebellar dysfunction; mental deterioration when present, is slight and progresses very slowly; associated neurological symptoms are uncommon and limited to mild spino-cerebellar involvement. In MERRF, the transmission is maternal, the age of onset is variable, the evolution is not stereotyped and associated symptoms are many (deafness, muscle weakness, optic atrophy, short stature, sensory disturbances, spasticity, clinical or neurophysiological signs of peripheral neuropathy, absence of motor reflexes); muscle biopsy generally shows ragged-red fibers. The differential diagnosis between these conditions is usually easy, although pathological examination (i.e. muscle biopsy) should be performed.

Biopsy↗

The Ramsay Hunt syndrome revisited: Mediterranean myoclonus versus mitochondrial encephalomyopathy with ragged-red fibers and Baltic myoclonus.

Among progressive myoclonus epilepsies (PME), the nosography of the Ramsay Hunt syndrome (RHS) has been much debated. The authors report on a homogeneous group of 43 patients originating from around the western Mediterranean, with a large number of northern African subjects, who were followed up for a mean period of 11.6 years. Onset is between 6 and 17 years (mean: 11.2) and the transmission appears to be recessive. The clinical features include: action myoclonus, generalized epileptic seizures, mild cerebellar signs and lack of dementia. EEG features include normal background activity, spontaneous fast generalized spike-wave discharges, photosensitivity, lack of activation during nREM sleep and vertex/rolandic spikes during REM sleep. The prognosis is variable, even within families, but the progression seems to be slow in a majority of patients. This condition can be distinguished from mitochondrial encephalomyopathy and is less severe than Baltic myoclonus. The authors propose that this form of PME, formerly reported as RHS, be more properly described as Mediterranean myoclonus.

Adolescent↗

Transcranial magnetic stimulation in epileptic patients: usefulness and safety.

We studied 58 patients with partial or generalized epilepsy who had transcranial magnetic stimulation (TMS) of the brain motor regions. Short-term monitoring disclosed that the stimulation did not provoke seizures or EEG changes in any patient. Long-term follow-up disclosed that the epileptic condition was not made worse by TMS. TMS, as currently used for monitoring conduction in central motor pathways, does not induce seizures in drug-treated epileptic patients.

Adult↗