Thalidomide-induced neuropathy: a ganglionopathy?
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Biomedical subjects
Publications and source records attributed to S Passero.
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Both dopamine agonists and levodopa may induce episodes termed "sleep attacks" in patients with PD. These episodes are well detailed behaviorally, but little is known about their neurophysiologic characterization. The authors performed a 24-hour polysomnography (PSG) in a PD patient taking pergolide in combination with levodopa, in which four of these diurnal sleep episodes occurred. PSG findings were followed up after pergolide withdrawal. Sleep episodes shared with narcolepsy both behavioral and EEG findings. However, pergolide partly restored a more physiologic sleep architecture, which was disrupted during therapy with levodopa alone.
OBJECTIVES: A neural system matching action observation and execution seems to operate in the human brain, but its possible role in processing sensory inputs reaching the cortex during movement observation is unknown. METHODS: We investigated somatosensory evoked potentials (SEPs), somatosensory evoked fields (SEFs) and the temporal spectral evolution of the brain rhythms (approximately 10 and approximately 20 Hz) following electrical stimulation of the right median nerve in 15 healthy subjects, during the following randomly intermingled conditions: a pure cognitive/attentive task (mental calculation); the observation of a motoric act (repetitive grasping) with low cognitive content ('Obs-grasp'); and the observation of a complex motoric act (finger movement sequence), that the subject had to recognize later on, therefore reflecting an adjunctive cognitive task ('Obs-seq'). These conditions were compared with an absence of tasks ('Relax') and actual motor performance. RESULTS: The post-stimulus rebound of the approximately 20 Hz beta magnetoencephalographic rhythm was reduced during movement observation, in spite of little changes in the approximately 10 Hz rhythm. Novel findings were: selective amplitude increase of the pre-central N(30) SEP component during both 'Obs-grasp' and 'Obs-seq', as opposed to the 'gating effect' (i.e. amplitude decrease of the N(30)) occurring during movement execution. The strength increase of the 30 ms SEF cortical source significantly correlated with the decrease of the approximately 20 Hz post-stimulus rebound, suggesting a similar pre-central origin. CONCLUSIONS: Changes took place regardless of either the complexity or the cognitive content of the observed movement, being related exclusively with the motoric content of the action. It is hypothesized that the frontal 'mirror neurons' system, known to directly facilitate motor output during observation of actions, may also modulate those somatosensory inputs which are directed to pre-central areas. These changes are evident even in the very first phases (i.e. few tens of milliseconds) of the sensory processing.
INTRODUCTION: Primary intraventricular haemorrhage (PIVH) is an uncommon type of intracerebral haemorrhage. Relatively little is known about clinical and imaging features, and even less about prognosis and predictors of mortality. MATERIAL AND METHODS: We analysed clinical and imaging features, causative factors and outcome of 26 patients with CT brain scan evidence of PIVH. A multivariate regression model of failure time data was used to assess predictors of in-hospital mortality. RESULTS: Loss of consciousness was the first manifestation of PIVH in six patients and occurred after all other symptoms in five. In other patients, onset was characterized by headache, vomiting, confusion and disorientation (n=8) or by headache with or without vomiting (n=7). Angiography revealed vascular malformations in eight patients (31%). Other possible causative factors were clotting disorder in one patient and arterial hypertension in 10. No cause was identified in seven patients. Early hydrocephalus was the most frequent complication and resolved spontaneously in a minority of patients. In-hospital mortality was high (42%): four patients died early of direct consequence of bleeding and seven died after clinical worsening because of increasing hydrocephalus or other adverse events. Multivariate analysis indicated Glasgow Coma Scale < or = 8 (OR 4.67; 95% CI 1.22-17.92) and early hydrocephalus (OR 4.93; 95% CI 1.13-21.59) as independent predictors of in-hospital mortality. CONCLUSION: In patients with PIVH, hydrocephalus seems to be a critical determinant of in-hospital mortality and this suggests the need for early treatment strategies.
The frequency of positive results of four conventional provocative tests (Phalen sign, Tinel sign, wrist extension and pressure provocation test) was evaluated in 179 patients with clinical and electrophysiological findings consistent with idiopathic carpal tunnel syndrome (CTS), 147 control subjects and 39 patients with polyneuropathy. The diagnostic accuracy was evaluated for each test alone and in combination and the sensitivity correlated with the clinical and electrophysiological severity of CTS. For comparison of the CTS group with the control group, none of the tests reached sufficient diagnostic accuracy. The same was found for comparison of the CTS group with the polyneuropathy group, the Tinel sign being the least accurate. The combination of signs was not found to be more useful than single signs. The sensitivity of all signs was much less in severe clinical stages of CTS, especially for tests that increase the intra-carpal canal pressure. Traditional provocative tests, such as those tested here, have limited or no value for distinguishing patients with and without CTS, one reason being that their sensitivity depends largely on the clinical and electrophysiological severity of CTS. This correlation may also explain the contradictory results in the literature.
OBJECTIVE: To evaluate the effects of mechanical compression of the brain-stem in patients with vertebrobasilar dolichoectasia (VBD). METHODS: In the framework of a prospective, observational study that collected clinical and laboratory data in patients with VBD, we studied 20 patients with compression of the brain-stem due to ectatic, tortuous basilar or vertebral arteries. Patients with cerebral lesions other than small lacunae in the white matter of the cerebral hemispheres were excluded from the study. Patients underwent vestibular and auditory function testing, including brain-stem auditory evoked potentials (BAEPs), blink reflex (BR), somatosensory evoked potentials (SEPs), and motor evoked potentials (MEPs). RESULTS: Almost all of the patients complained of auditory or vestibular symptoms and none had symptoms or signs of impairment of long tracts or the facial and trigeminal nerves. The most consistent findings were BR abnormalities with prolongation of ipsilateral R1 latency in cases of compression of the pons (10/16) and prolongation of the R2 and R2c latencies with compression of the medulla oblongata (5/15). Subclinical impairment of corticospinal pathways was found in 13 out of 25 instances of compression, and this was more frequent with compression of the pons. Abnormal BAEPs or SEPs were less frequently encountered, and only in cases with compression of the pons. CONCLUSIONS: Neurovascular compression of the brain-stem, even with severe distortion, is seldom associated with overt clinical signs, whereas subclinical dysfunctions are relatively frequent. The central pathways of the BR and the corticospinal pathways are more susceptible to compression than acoustic and sensory pathways. BR, MEP and BAEP data provide a functional evaluation of the brain-stem and some cranial nerves, which is lacking in imaging studies. Functional investigations may be useful in the long-term management of these patients, since VBD may be progressive and surgical correction may be required at some stage.
The distributions of intracerebral hemorrhage (ICH) according to place of onset, degree of physical activity at onset and potential triggering factors were analyzed in 848 patients with ICH. Patients were grouped according to the presumed cause of ICH: hypertensive ICH, secondary ICH and ICH of undetermined origin. The influence of demographic and temporal factors on the relative frequency of events was also assessed. In 30% of the cases, ICH occurred during inactivity or sedentary activity, in 50% during light exertion and in 20% during moderate/vigorous exertion. During inactivity or sedentary activity, hypertensive ICH was significantly less frequent than secondary ICH (OR 0.32; 95% CI 0.21-0.47) and undetermined ICH (OR 0.36; 95% CI 0.23-0.55), whereas during moderate or vigorous exertion hypertensive ICH was more frequent than secondary (OR 1.88; 95% CI 1.16-3.05) and undetermined ICH (OR 2.29; 95% CI 1.31-4.00) Potential triggering factors were observed in 27% of patients and were significantly more frequent in patients with hypertensive ICH than in patients with secondary ICH (OR 2.90; 95% CI 1.85-4.54) or undetermined ICH (OR 2.44; 95% CI 1.54-3.87). Our findings suggest that many potential external triggers that act mainly by raising blood pressure may interact, and their concurrence may favor cerebral hemorrhage, particularly in hypertensive patients. In many cases, these circumstances of increased risk may be mitigated by preventive measures.
BACKGROUND AND PURPOSE: The purpose of this study was to further analyze the temporal patterns of onset of intracerebral hemorrhage (ICH) and to determine whether or not subgroups with specific clinical characteristics exhibit different patterns of onset. METHODS: The daily, weekly, and yearly variations in occurrence of ICH together with the relationship between ICH occurrence and changes in air temperature were evaluated in 1018 patients. Patients were grouped according to the presumed etiology of ICH: hypertensive ICH, secondary ICH, and ICH of undetermined origin. The contribution of demographic and clinical factors to the temporal distributions of ICH was also evaluated. RESULTS: Marked differences in seasonal and diurnal patterns of ICH onset were observed in the different groups. The incidence of hypertensive ICH reflected seasonal and circadian changes in blood pressure, whereas the latter did not seem related to the onset of nonhypertensive ICH. The seasonal pattern was more evident in elderly patients with hypertensive ICH than in younger subjects. No significant weekly variations were observed; however, risk was greater on Monday in the working population. CONCLUSIONS: Our results suggest that the higher incidence of ICH in the colder months is due to the effect of low temperatures on blood pressure and that the clustering of ICH events in the morning is due to the increase in sympathetic tone, and consequent increase in blood pressure, on awakening.
OBJECTIVE: To verify whether the change in L-dopa plasma levels after a single dose of carbidopa/L-dopa 50/200 (controlled-release) transiently modifies frontal components of somatosensory evoked potentials (SEPs) in patients with PD in parallel with improvement of motor performance. BACKGROUND: Apomorphine, a potent dopamine-agonist drug, transiently increases frontal SEP components, which may be depressed in PD; however, relationships between clinical status, frontal SEPs, and therapy are still unclear. METHODS: Nineteen PD patients (mean age 65.9 years, range 52 to 77, responders to L-dopa therapy, were studied in the same day at times T0 (baseline predose level), T1 (presumed L-dopa peak time), and T2 (end of dose-induced motor response). The following were monitored: L-dopa plasma concentration, tapping test, reaction times, peak latency (with central conduction times), and amplitude of cervical, subcortical, as well as cortical parietal and frontal SEP components elicited by median nerve stimulation of the more clinically affected arm. RESULTS: The average amplitude of frontal components of PD patients was significantly reduced at T0 with respect to control subjects. A significant and transient amplitude increase of frontal SEPs was found at T1, in parallel with the L-dopa peak concentration and improvement in motor performance (tapping and reaction times), without significant changes in amplitude of parietal SEP waves. No latency shifts were observed in brain and spinal waves. CONCLUSIONS: L-Dopa may influence the responsiveness of the parkinsonian brain as assessed by frontal somatosensory evoked potentials. The time course of these modifications coincides with that of the clinical response in the motor performance.
OBJECTIVE: The aim of the study was to assess peripheral neural involvement induced by exposure to hand-arm vibration. METHODS: Twenty lumberjacks, working regularly with chain-saws and exposed to hand-arm vibration (group E) and 20 forestry workers performing heavy manual work and not exposed to vibration (group NE) were matched with a control group of 20 healthy non-manual workers (group C). The subjects of groups E and NE, all symptomatic, and of group C underwent extensive bilateral neurophysiological examination consisting of: sensory conduction (velocity and amplitude) of radial, median and ulnar nerves in digit-wrist segments; sensory conduction (velocity) of median nerve in wrist-elbow segment; mixed conduction (velocity and amplitude) of median and ulnar nerves in palm-wrist segments; motor conduction velocity, including distal motor latencies, and amplitude of median (elbow-wrist) and ulnar (elbow-wrist and across the elbow) nerves. RESULTS: Electrophysiological abnormalities were found in 85% of group E's limbs, versus 62.5% of group NE's limbs. The most frequent pathological pattern in group E was a 'multifocal' impairment (multiple sites of several nerve segments), with a prevalent involvement of sensory rather than motor fibres in the hand, seldom extending to the forearm. Multivariate analysis showed that the neurographic parameters which better characterized workers exposed to hand-arm vibration had a pattern different from that usually found in idiopathic carpal tunnel syndrome (CTS). CONCLUSION: These results suggest that vibration-induced neural involvement can be considered neither pure digital neuropathy, nor definite CTS, as previously described.
BACKGROUND AND PURPOSE: Vertebrobasilar dolichoectasia (VBD) may produce symptoms by direct compression of cranial nerves or the brain stem, by obstructive hydrocephalus, or by ischemia in the vertebrobasilar arterial territory. This study was undertaken to examine and characterize clinical and imaging findings in patients with stroke associated with VBD and compare these data with those for patients with VBD who did not have a stroke. METHODS: We studied 40 consecutive stroke patients with associated VBD. All were evaluated by CT scan (n=9), MRI (n=6), or both (n=25). The diameter of the basilar artery (BA), height of bifurcation, and transverse position were evaluated. Clinical and imaging findings were compared with those found in a group of 40 VBD patients without stroke. RESULTS: More than half of the patients (24 of 40) had infratentorial infarcts, located mainly in the midpons. Sixteen patients had supratentorial lesions localized in the thalamus (n=8) or in the superficial arterial territory of the posterior cerebral artery (PCA; n=8). The diameter and height of the bifurcation of the BA were correlated with the location of the lesion (PCA territory versus BA territory), in that severe ectasia and vertical elongation of the BA were significantly more often observed in patients with infarcts in PCA territory than in patients with infarcts in territories supplied by branches of the BA. Comparison of VBD patients with and without stroke showed that the incidence of arterial hypertension and the degree of ectasia and lateral displacement of the BA were not significantly different in the two groups. Patients with stroke more often had atherosclerotic changes of the posterior circulation (P=.0006) and a higher degree of vertical elongation of the BA (P=.025). CONCLUSIONS: In patients with VBD, superimposed atheromatous changes of the posterior circulation may have an important role in precipitating ischemia. However, other factors related to the severity of the dolichoectasia also favor ischemia and in some cases are the only factors responsible.
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Impairment of the auditory-vestibular system has been reported in patients with vertebrobasilar dolichoectasia (VBD), but little is known about the underlying cause of the symptoms. Auditory testing (pure tone audiometry, auditory brain stem response and stapedius reflex) and vestibular tests (assessment of nystagmus, eye tracking tests, caloric test and rotational test) were performed in 23 patients with auditory-vestibular symptoms and/or cranial nerve impairment associated with VBD. Specific evidence of auditory and/or vestibular system impairment was observed in 19 cases (83%). Among patients with abnormal test findings, 47% had evidence suggesting peripheral impairment, 16% evidence suggesting central dysfunction, and 37% evidence suggesting both peripheral and central dysfunction. Although compression of the vestibulocochlear nerve plays an important role in the genesis of the auditory-vestibular dysfunction in patients with VBD, mechanism such as brain stem-cerebellar ischemia and impaired blood supply to the vestibular labyrinth may be just as important.
The effect of oral treatment with acyclovir (ACV) on sensory axonal neuropathy, segmental motor paresis and postherpetic neuralgia (PHN) was studied in 105 patients with herpes zoster. Forty-seven patients were treated with ACV at a dose of 4 g/day in 5 doses for at least a week; the others did not undergo any kind of treatment. Electrodiagnostic examination of the nerves and muscles corresponding to the dermatomeric lesions was performed, including sensory and motor nerve conduction studies, blink reflex and electromyography (EMG). The patients treated with ACV showed a significant reduction in the number of cases in which there was electrophysiological evidence of axonal damage in afferent fibres of nerves arising from roots corresponding to affected dermatomes. The treated group also showed a smaller incidence of segmental motor neuritis, clinically evident or only detectable by EMG as denervation. However, there was no significant difference between groups as far as the incidence of PHN was concerned. Oral treatment with ACV therefore reduces peripheral sensory axonopathy due to ganglion damage and prevents the possibility of spread to anterior roots and spinal motoneurones. In this way it reduces the incidence of segmental motor neuritis, but does not reduce the incidence of PHN.
Somatosensory evoked potential (SEP) studies were performed in 14 patients with peripheral vascular disease who received epidural spinal cord stimulation (SCS) for chronic pain relief of the lower limbs. Signals were amplified and filtered between 20-2000 Hz and 200-2000 Hz to better identify activities in the high frequency range. In 7 patients bit-colour maps were also computed. In all the patients a homogeneous short-latency scalp evoked potential with a prevalent diphasic shape (P1-N1) was recorded. In all our scalp records, even with the wide bandpass, small short-latency positive deflections were observed on the descending front of the first major positive wave and they were better defined as a series of up to 6 wavelets, preceding the major negative scalp wave in the tracings filtered through the narrow bandpass. They appeared in an interval ranging from 5.5 to 15.6 msec. Bit-colour maps showed consistent positive fields, with a maximum at the vertex, starting mainly at about 5.5 msec; in 3 patients, a prominent positivity between 8.5 and 10.5 msec was recorded followed by smaller components preceding the major positive-negative (P1-N1) complex. More synchronous volleys during direct SCS produced clear short-latency SEPs. Although they were of larger amplitude, we regarded them as corresponding to those described by previous authors obtained by stimulation of nerves of the lower limbs, and probably arising from subcortical structures.
1. Twenty-six patients with major unipolar depression were rated clinically and regional cerebral blood flow (rCBF) determined prior to and after six months of treatment with 75-100 mg/day amitriptyline (n. 16) or 200 mg/day amineptine (n. 10). 2. rCBF was measured in 16 regions over each hemisphere by the Xenon 133 inhalation method and was computed as the initial slope index (ISI). The severity of depression was quantified by the Hamilton rating scale for depression. 3. Baseline rCBF values of depressed patients tended to be lower than those of normal subjects. Significant reductions were observed for all probes exploring the frontal region of the left hemisphere and for some probes exploring the frontal region of the right hemisphere. Chronic treatment with amitriptyline induced a significant increase in rCBF in the left frontal region. Similar results were obtained after treatment with amineptine. 4. Besides confirming frontal lobe dysfunction in depressed patients which is reversed by treatment with classic tricyclic antidepressants, the present results show that this dysfunction may also be reversed by treatment with dopaminergic drugs.
BACKGROUND AND PURPOSE: Rebleeding in patients with primary intracerebral hemorrhage is considered uncommon, but there are no precise data to support this opinion. The purpose of this study was to assess the incidence and predictors of recurrent bleeding in survivors of primary intracerebral hemorrhage. METHODS: As part of a prospective study, 112 survivors of a first primary intracerebral hemorrhage were followed up for a mean period of 84.1 months after their discharge. To ascertain risk factors that may influence rebleeding, several demographic, medical history, clinical, and laboratory variables were collected and analyzed. RESULTS: Twenty-four percent (27/112) of survivors experienced one or more rebleeding during the follow-up period, in 8 cases (30%) in the first year of follow-up; in the others recurrence occurred later, up to 11.5 years. Rebleeding had a high mortality rate: 70% of patients died as a consequence of their second or third hemorrhage. Univariate and multivariate analyses showed that lobar location of the first hemorrhage was the only significant predictor of rebleeding. Patients with rebleeding were more frequently older, more often had a history of previous transient ischemic attack or ischemic stroke, and less often had hyperlipidemia than patients without rebleeding, although these correlations did not reach statistical significance. During follow-up, poor control of arterial hypertension was found in 7% of hypertensive patients without rebleeding and in 47% of hypertensive patients with rebleeding. CONCLUSIONS: Our study showed that rebleeding after a first primary intracerebral hemorrhage is not as uncommon as is usually believed. The risk of rebleeding seems to be particularly high after hemorrhage at the junction of the gray and white matter, a site regarded as typical of hemorrhages due to amyloid angiopathy, and when arterial hypertension is poorly controlled.