Effects of chronic lithium treatment on the peripheral nervous system.

BACKGROUND: Although lithium carbonate is widely used in the treatment of mood disorders, symptoms suggesting toxic effects on the peripheral nervous system may emerge even in subjects whose serum lithium levels remain within the recommended therapeutic range. METHOD: Electroneuronographic (ENG) parameters (motor nerve conduction velocity of peroneal and median nerves, sensory nerve conduction velocity of sural and median nerves, amplitude of motor potential of peroneal and median nerves, and amplitude of sensory action potential of the median nerve at the wrist and the sural nerve) were investigated in 2 groups (N = 34) of patients suffering from bipolar affective disorder (DSM-III-R, DSM-IV) undergoing maintenance treatment with lithium carbonate for at least 1 year (mean = 2.06 years) in monotherapy. For 12 patients, ENG results were compared with pretreatment values, whereas in the other 22 cases, only data relevant to posttreatment were available. Fifty-four healthy subjects and 20 patients with recurrent major affective disorder (unipolar and bipolar) never treated with lithium made up the comparison groups. RESULTS: Compared with the 2 comparison groups, patients on chronic lithium treatment showed significant reduction of motor nerve conduction velocity of peroneal and median nerves, sensory nerve conduction velocity of sural and median nerves, amplitude of motor potential of peroneal and median nerves, and amplitude of sensory action potential of the median nerve at the wrist and the sural nerve. The comparison with the assessment made prior to lithium treatment also showed significant changes; after a period of treatment with lithium varying from 2 to 8 years (mean = 5.2 years), significant reductions were found on motor and sensory nerve conduction velocity and on amplitude motor potentials and sensory action potentials. CONCLUSION: Chronic maintenance treatment with lithium affects the peripheral nerves, even if the impairment rarely is such as to warrant discontinuation of treatment. Monitoring of ENG results could be useful for the early detection of neurotoxicity of lithium.

Monitoring of somatosensory evoked potentials during carotid endarterectomy.

Somatosensory evoked potentials (SEPs) were monitored in the course of 368 carotid endarterectomies (CEAs) carried out in 312 patients. In an initial group of 26 patients the shunt was used routinely while in a second group, involving 342 CEAs, it was applied selectively on the basis of modifications which the SEP underwent during clamping. The criterion for shunting was the progressive reduction, up to 50%, of the N20-P25 amplitude. New postoperative neurological deficits appeared in 6 patients, all of whom displayed a transitory SEP flattening. The SEPs of 2 of these returned to normal by the time they awoke and both showed a clinical deficit homolateral to the operated side. In only 2 cases did the deficit fail to regress completely and their postoperative CT scans revealed ischaemic lesions. A positive relationship emerged between SEP changes and back pressure values; nonetheless, as many as 75% of the patients with low residual back pressure values (less than 25 mmHg) tolerated the clamping. SEP monitoring appears to provide a reliable basis for selectively applying a shunt when there is a high risk of haemodynamic ischaemia during clamping.

Transmission times from cutaneous and mixed nerves of lower limbs.

In each of 10 normal subjects, P28 and N31 far-field components as well as the cortical N37 and P40 waves were identified for both Sural (SN) and Posterior Tibial nerve (PTN) stimulation at the ankle. Peripheral conduction velocity along the popliteal fossa-L3 segment and spinal transmission velocity over the L3-Cv2 segment did not differ significantly for the two nerves. The average latencies of N37 and P40 to stimulation of PTN were 2.55 and 3.65 msec shorter than corresponding latencies from SN. If we consider the P28-N37 and P28-P40 intervals as central transmission times, only the former approaches upper limb CCT values closely enough to support the analogy between median nerve N20 and PTN N37. At the intracranial level, the P28-N37 inter-peak latency was significantly shorter for PTN than SN. The P28 component is generally attributed to lemniscal activity. Thus, the discrepancy in afferent transmission times from the leg's mixed and sensory nerves would appear to take place at a level that is supralemniscal but subcortical.

Effect of physiological and pathological aging processes on topographic bit-mapped cognitive evoked potentials in presenile subjects.

Bit-mapped multicomponent CNV complex and reaction time (RT) were recorded and measured in 24 presenile patients with initial symptoms of very mild to moderately severe primary mental deterioration without depression, and in 10 age-matched controls. All patients underwent CT and MRI examinations, EEG spectral analysis and a battery of psychometric test. Significant group differences were obtained for measures of some post-S1 ERP and CNV components, particularly of the post-S1 N1b, P300 and early and late pre-S2 CNV. P300 with increased latency, no significant CNV activity, very prolonged RTs, EEG slowing down and diffuse brain atrophy were observed in the majority of patients with probable presenile Alzheimer's dementia. These results suggest that CNV/RT and EEG activity changes similar to those observed in our patients may constitute a valuable clue for the study of brain dysfunction in the early stage of presenile idiopathic cognitive impairment.

Topographic CNV activity mapping, presenile mild primary cognitive decline and Alzheimer-type dementia.

The CNV complex evoked with a standard paradigm (S1-2 sec-S2-motor response) and reaction time (RT) to the imperative signal (S2) were recorded and measured in 12 patients with initial presenile idiopathic cognitive decline (PICD), 12 with presenile Alzheimer-type dementia (PAD) and 10 healthy age-matched controls. Significant group differences were obtained for measures of some CNV components, particularly of the late pre-S2 CNV. No significant CNV activity, very prolonged RTs and sometimes characteristic post-imperative negative variations (PINV) were observed in the majority of patients with PAD. These results suggest that similar CNV complex and RT changes to those observed in our patients may constitute a valuable clue in the study of pathophysiological brain functioning in the early stages of presenile idiopathic mental deterioration.

Long-term nervous system damage from radiation of the spinal cord: an electrophysiological study.

A group of 13 patients suffering from Hodgkin's disease who had undergone chemotherapy and radiotherapy (above and below the diaphragm) approximately 10 years earlier was studied. The total chemotherapeutic dose was similar for all patients; the radiotherapy dose, however, was standard for 7 patients, while the other 6 received much higher dosages over limited regions of the spinal cord. Although most of these patients appeared normal both clinically and on magnetic resonance imaging, a neurophysiological study was performed to determine whether there was any involvement of the central or peripheral nervous system. Motor conduction velocity and sensory conduction velocity were measured in the lower limbs as well as spinal- and scalp-recorded somatosensory evoked potentials (SEPs) in response to stimulation of the posterior tibial and sural nerves at the ankle. In addition, motor evoked potentials were recorded from the upper and lower limbs during cortical stimulation. All neurophysiological data were normal in patients who had received a standard radiation dose, while most of those who had been exposed to higher doses showed altered cortical SEPs and a slowing of central conduction time (D10-P1). Thus even though they were asymptomatic, these patients appeared to have sustained CNS damage, mainly at the level of the spinal cord.

Anesthetic induction with thiopental: its effect on scalp topography of median nerve somatosensory evoked potentials.

The effects on median nerve somatosensory evoked potentials (SEPs) of analgesic doses of fentanyl, meperidine or morphine and of sodium thiopental (STP) anesthesia (4 mg/kg) were tested in 36 surgical patients. We also explored changes in SEP components as a function of their scalp location. Before and after medication, responses were recorded from the scalp overlying the parietal cortex (ipsi- and contralateral to the stimulated arm) and the precentral (contralateral) cortex. None of the three opiates affected SEP latencies or amplitudes. The barbiturate increased the amplitudes of subcortical and early cortical components (N18, N20, P22, P25), whose latencies, however, were not significantly modified. The effect of STP on later SEP cortical components depended on their scalp topography: parietal N33 and P45 underwent significant changes in both latency and amplitude, whereas precentral N30 showed a significant amplitude increase only. Thiopental anesthesia produces clearer short-latency SEP recordings, from both parietal (components N20-P25) and precentral (P22, N30) areas.

Neurological damage in patients irradiated twice on the spinal cord: a morphologic and electrophysiological study.

We reviewed the files of 950 patients treated for Hodgkin's disease since 1966 and were able to find five patients treated with radiochemotherapy and irradiated twice on volumes including a cord segment, at various time intervals, and surviving until now. Seven patients with comparable clinical and therapeutic features, but not reirradiated on the cord, were chosen as a control group and were examined with the same diagnostic procedures. The cumulative cord dose in the reirradiated patients was recalculated and ranged from 50 to 70 Gy. All these patients and the control cases were followed up for more than 10 years and presented no or only minor neurological symptoms. We compare the results of both magnetic resonance imaging (MRI) and electrophysiological studies (spinal and scalp recorded somatosensory evoked potentials--SEPs) in an attempt to define the characteristics of the subclinical damage present in these patients. While no cord abnormality was demonstrated with MRI, electrophysiological studies evidenced a clear difference between cases and controls, as far as the D10-P1 conduction time and SEPs average amplitude are concerned. Advantages and drawbacks of a wider use of electrophysiological methods in research work on cord radiation damage are presented, along with the possible implications of the results obtained for the understanding of the pathogenesis and of the dose dependence of radiation myelitis (RM).

Selective shunting based on somatosensory evoked potential monitoring during carotid endarterectomy.

Somatosensory Evoked Potentials (SEPs), to median nerve stimulation, were continuously monitored in 58 patients undergoing carotid endarterectomy A first group of patients was shunted routinely; in a second group the shunt was selectively applied when inadequacy of collateral circulation was suspected based on stump pressure values and SEP changes. Both amplitude and latency modifications of SEPs occurred during surgery; however no post-operative neurological deficit was seen unless there was a complete flattening of cortical waves, even a transitory one. Inadequate collateral circulation and embolic ischemia affected SEPs differently. While the latter produced a disappearance of all cortical waves, the former led first to a progressive flattening of later cortical waves and then of N20 as well. For values of stump pressure ranging between 20 and 50 mmHg SEPs were unchanged in some patients and altered in others. These findings may explain the controversies existing about the usefulness of stump pressure for predicting tolerance to carotid clamping.

Effect of associated antiepileptic treatment on valproate-induced hyperammonemia.

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.