Surface electric fields during CNV activity.
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Biomedical subjects
Publications and source records attributed to R Zappoli.
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The cases of two epileptic identical twins are described, one of whom had presented an episode of valproate (VPA)-induced stupor associated with very high blood ammonia (NH3) concentrations. Both twins showed a similar marked increase of venous NH3 concentrations after the administration of a single loading dose of VPA (800 mg).
In five patients with initial idiopathic Parkinson disease AEPs (early and late components of auditory evoked potentials), SEPs (somatosensory evoked potentials) and arm ballistic movements (abduction of the humerus) were studied. Experimental sessions were conducted before starting treatment (L-Dopa plus Carbidopa) and at two and six month intervals. Before treatment evoked potential abnormalities were found in four out of five patients; EMG patterns underlying ballistic arm abduction movements were altered in all patients; corresponding prolonged duration of initial movements and low mean velocities were found. After treatment AEP and SEP showed a reduction of previously observed abnormalities and both EMG patterns and kinematic variables consistently improved. It is suggested that the electrophysiological investigations employed in this preliminary study may be a useful tool in clinical and pharmacological researches on Parkinson disease.
It has recently been shown that acute changes of venous blood ammonia (NH3) may predict short-term adverse effects of valproic acid (VPA). In the present study, the time course of NH3 concentration after a single oral dose of VPA (800 mg) was monitored in 68 epileptic patients. Patients were classified into four groups: previously untreated patients (group A, n = 21), patients under treatment with either phenobarbital (group B, n = 14) or phenytoin (group C, n = 13) or both (group D, n = 20). In each patient, venous blood for the NH3 assay was taken before the VPA dose (predose level) and at 1, 2, 3, and 4 h after the dose (postdose levels). While in patients receiving only VPA the postdose NH3 concentrations did not differ from the predose level, in each of groups B, C, and D the postdose concentrations appeared to be significantly higher than the predose concentration. The greatest increase was observed in group D. In the light of the data reported in the literature, those patients whose NH3 concentration after the VPA dose exceeds 100 micrograms/dl should be considered at higher risk for short-term, VPA-induced adverse effects during long-term therapy. Thus, our data suggest that caution should be exercised in adding VPA to anticonvulsant treatments including phenobarbital or phenytoin or both.
This chapter reviews the literature about intensive monitoring (IM) in status epilepticus (SE). The description of the newly developed and suitable monitoring techniques is followed by a few sections devoted to the clinical application of IM in SE. IM is mostly required to establish the correct diagnosis in SE, particularly in the nonconvulsive type. Similarly, the classification and the medical treatment of SE are greatly improved by IM. Although no definitive data exist, the practical relevance of IM in the prognosis of SE is discussed in detail. Furthermore, special emphasis is given to the value of neuroradiological monitoring in SE, as evidenced by a proper case report. It is concluded that a further development and a more widespread employment of monitoring techniques are needed to assist and improve the management of SE.
We report a case of hemorrhagic shock associated with an EEG pattern resembling pseudoperiodic lateralized paroxysmal discharges, repeated focal motor seizures on the opposite side of the prevalent EEG abnormalities and consciousness disturbances in the absence of a demonstrable cerebral lesion occurring in a 45 year-old woman without a personal or familial history of epilepsy. This unusual electroclinical picture appeared inexplicably several days after the hemorrhagic shock when the laboratory data had already normalized. The only cause of this picture seemed to be brain hypoxia and the metabolic disorders consequent upon hemorrhagic shock.
The Mullen and Foster method was prospectively applied for individualizing phenytoin dosage in 24 epileptic patients. Accuracy and reliability of the method were assessed by comparing predicted and measured values of plasma phenytoin steady-state concentration. The absolute difference between predicted and measured phenytoin levels was less than 15 percent in 22 of 35 cases (63 percent), between 15 and 25 percent in 8 of 35 cases (23 percent) and more than 25 percent in 6 of 35 cases (17 percent).
A functional assessment of the acoustic pathways in a group of 9 patients with Friedreich's ataxia was performed. In none of them was symptomatic auditory impairment noticeable. All patients were submitted to audiological tests and AEP recording. AEPs included early (BAEPs), middle (MLCs) and long (LLCs) latency components. The absence of one or more BAEP waves was observed in 5 out of 9 patients. N85 latency was significantly increased in all but one patient. MLCs, particularly P12, N15, P25 were often normal in amplitude and latency, scarcely showing a positive relationship with abnormalities of preceding and following waves. Pure tone audiometry revealed cochlear or neural impairment only in 2 patients. Speech audiometry showed deficits in all patients. These investigations, taken as a whole, showed a prevalent involvement of the brain-stem acoustic pathways, presumably at different levels, seldom associated with eighth nerve impairment. In some cases LLC (N85) abnormalities could not be interpreted as a consequence of impaired function in peripheral and brain-stem acoustic sites and might suggest a cortical dysfunction. Major BAEP abnormalities were observed in patients with longer disease duration, while N85 changes were unrelated to the duration and the severity of the illness. The former may prove to be a reliable means of monitoring the progression of the disease, the latter could be employed as a complementary procedure in its early diagnosis.
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Sodium valproate was administered to 38 patients, admitted to our unit in the last 18 months, and chosen because they had: (1) poor control of their seizures; (2) therapeutic concentrations in their plasma of at least two major antiepileptic drugs. In 8 of them, a therapeutic dosage of VPA caused modifications of the state of consciousness ranging from coma to drowsiness and stupor. These patients also showed gastrointestinal disturbances, asterixis, ataxia, tremor and a worsening of EEG abnormalities. The side effects of the drug were constantly associated with increased concentration of blood ammonia. Better penetration of ammonia into the CNS of patients undergoing frequent seizures and possibly having imperfectly functioning biological barriers, could explain our observations. In view of the unusually high percentage of patients suffering from serious VPA side effects, it is probably advisable to carefully monitor ammonemia in the first few days of VPA therapy in every patient treated with multiple anticonvulsants.
Valproic acid (VPA) was given to 24 epileptic patients who were already being treated with other antiepileptic drugs. A standardized loading dose of VPA was administered, and venous blood was sampled at 0, 1, 2, 3, and 4 hours. Ammonia (NH3) was higher in patients who, during continuous therapy, complained of drowsiness (7 patients) than in those who were symptom-free (17 patients), although VPA plasma levels were similar in both groups. By measuring VPA-induced changes of blood NH3 content, it may be possible to identify patients at higher risk of obtundation when VPA is given chronically.
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The purpose of this study was to evaluate the possible modifications of the plasma and urine short-chain-fatty acid (SCFA) patterns indiced by treatment with valproic acid (VPA). Increased amounts of SCFAs in patients under VPA treatment may explain the presence of VPA-induced hyperammonemia, toxic encephalopathies and rarer Rey-like syndromes recently observed. For this reason we assayed SCFA levels in the plasma and looked for propionic acid in the urine of 10 epileptic patients to whom it was decided to add VPA to their previously unsatisfactory anti-epileptic treatment. This was carried out prior to and during therapy with VPA. 5 of these patients developed toxic encephalopathy with hyperammonemia induced by VPA. Our data show that plasma and urine SCFAs are not modified by VPA treatment. This is so even in patients who have toxic encephalopathy with hyperammonemia indiced by this drug.
A right-handed 32-year-old woman had recurrent combined partial temporal and secondary generalized epileptic states almost constantly related to menstruations. During such more or less prolonged episodes sometimes the patient presented right adversive attacks with short postictal dysphasia. The catamenial status epilepticus observed in this cas was manifested in two clear-cut behavioral phases. The first phase was characterized by frequently recurrent left temporal epileptiform discharges without tendency to diffusion, progressively more prolonged and pseudorhythmic associated with a signalized feeling of intense fear without apparent impairment of consciousness or speech disturbances. The electroclinical features of the first phase suggest a depth origin of the paroxysms, probably due to a primary epileptogenic focus in the left amygdaloid-hippocampal complex. In the second phase the left temporal focal semirhythmic discharges associated with fear bouts became more frequent and prolonged and began to be followed by long-lasting generalized discharges resulting in a trance-like state with severe impairment of consciousness. The diffuse paroxysmal activity regularly preceded by the left temporal focal discharges was interpreted as a form of secondary bilateral synchrony constantly triggered from a focal pacemaker represented by the primary epileptogenic focus. During the very short transient periods of sudden cessation of the epileptiform activity the patient returned immediately to an apparent normal mental state. Good correlation could be established between different seizure patterns and predominant clinical signs. Intravenous diazepam rapidly decreased and then completely stopped the catamenial status epilepticus. Some problems related to the classification of these rare epileptic events are discussed.
A total of 70 selected patients affected by reversible ischemic attacks in the vertebrobasilar system were studied. 50 patients presented transient ischemic attacks (TIA), while the other 20 patients suffered from 1-2 protracted transient ischemic attacks (PTIA). All patients underwent brainstem acoustic evoked potentials (BAEP) and electrooculography (EOG) 7-20 days from the last reversible ischemic attack, when all signs and symptoms completely disappeared. The combination of BAEP and EOG gave objective evidence of brainstem dysfunction in 61 out of 70 patients. BAEP resulted abnormal in 26 patients (16 TIA, 10 PTIA), EOG in 49 (36 TIA, 13 PTIA). Serial controls at 3, 6, and 12 months were conducted in 27 patients. 5 patients showed a normalization for BAEP and 7 for EOG 12 months after the first examination.
A programmable calculator procedure allowing nonlinear least-squares fit to pharmacokinetic data conforming to the Michaelis-Menten model is described. Model parameter estimation is performed according to the iterative Gauss-Newton technique as modified by Hartley. This procedure thus employs the same theoretical approach used by most pharmacokinetic computer programs. No programming skill is needed to run the program described. The proposed procedure is discussed in detail and applied to some sets of pharmacokinetic data.