A sequential study of the peripheral nervous system involvement in experimental Chagas' disease.

To search for the sequential compromise of the spinal cord, nerves, and skeletal muscle in mice chronically infected with Trypanosoma cruzi, animals were subjected to electromyographic investigation, end-plate recordings, and histological studies at 7, 15, 37, 60, 90, 120, 180, 270, and 360 days postinfection. Electromyographic studies showed signs of motor unit remodeling as early as 15 days postinfection, when diminished duration and amplitude of motor unit potentials pointing to a primary muscle involvement were found. Thereafter, certain features of denervation, reinnervation, and primary muscle involvement were often found to coexist. Low miniature end-plate potentials with normal frequency and acetylcholine quantum content were found in end-plate recordings made at the phrenic-diaphragm in vitro. Double end-plate potentials were observed in most of the tested muscle fibers from day 90 postinfection. All these features suggest post-synaptic damage of the end-plate and the presence of reinnervation after day 90 postinfection. Histological studies disclosed inflammatory infiltrates consisting of lymphocytes and macrophages, with vasculitis as the main lesion in the hamstring muscles; intracellular parasites were seen in 25% of the cases. Neuropathic features, as expressed by type fiber grouping and grouped muscle fiber atrophy, were found. On nerve examination epineural, perineural, and endoneural vasculitis were seen. Digestion chambers and myelin ovoids (axonal degeneration) were observed. In teased fiber preparations, segmental internodal and paranodal demyelination and remyelination were found. The lumbar inflammatory spinal cord failed to show grey or white matter infiltrates. However, spinal roots and dorsal root ganglia were densely affected by inflammatory cells.

Peripheral nervous system damage in experimental chronic Chagas' disease.

Electromyographic and histopathologic studies were performed in Rockland mice chronically infected with CA-I Trypanosoma cruzi strain. At 4 months post-infection the emg failed to show spontaneous activity, but a diminished interference pattern was detected in half of the infected group, while mean motor unit potential amplitude and duration were increased, compared with controls. An active denervation was observed at 6 months which persisted up to 9 months, when motor unit potential showed a significantly lower mean activity and duration. At 12 months most of the infected mice developed a reduced interference pattern, polyphasic motor unit potential increase with higher duration and amplitude than controls. Histopathologic studies showed myositis with perivascular involvement as well as intramuscular neuritis, especially at 4 and 12 months. Atrophic and hypertrophic fibers were seen. Few amastigote nests were detected. Inflammatory neuropathy with the demyelinated fibers and scanty axonal degeneration were the most common features in all infected mice. Mild myelinated fiber loss was only evident after 12 months. Endoneural parasites were seen only in the perineural macrophagic cells. These findings suggest that the neurogenic mechanism involved in the pathogenesis of muscle damage in this experimental model of chronic Chagas' disease consistently has been overlooked. The features registered here suggest that T. cruzi-infected mice developed a bimodal muscle denervation with an early acute period at any time before month 4, followed by reinnervation with a subsequent new acute denervation period by month 6, followed in turn by a slow later reinnervation.

Cu/Zn superoxide dismutase activity at different ages in sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive disorder resulting from degeneration of motor neurons in the brain and spinal cord. Sporadic ALS (SALS) accounts for the majority of patients and the familial form (FALS) represents fewer than 10% of all cases. Since it was found that there are Cu/Zn superoxide dismutase (SODI) gene mutations in 20% of FALS patients and that FALS and SALS patients show similar clinical features, it has been postulated that both may share a common physiopathological mechanism. We studied Cu/Zn SOD1 activity in cytosolic extracts of erythrocytes from 125 normal individuals and 40 SALS patients. We found that enzyme activity does not change with age in control subjects and tends to decrease in most SALS patients older than 60 years. A subpopulation of five SALS patients had significantly increased SOD1 activity; four of these patients over 70 years old. There was no correlation between enzyme activity and time of onset of the disease, or clinical forms of the illness. The variation in SOD1 activity in ageing SALS patients compared with younger patients suggests that they may undergo an oxidative disbalance contributing to the development of the disease.

A micrometric multiple electrode array for the exploration of gasserian and retrogasserian trigeminal fibers: preliminary report. Technical note.

The determination of the target for percutaneous thermocoagulation of the trigeminal rootlets has been generally based on the analysis of subjective clinical verbal and motor responses as assessed by freehand displacement of an electrode active at its straight or curved distal tip. In a previous report, we demonstrated that sensory and motor trigeminal evoked potentials are of practical value when attempting to localize the position of trigeminal electrodes. This report describes the technical features of a multiple electrode array designed to provide simultaneous access to various segments along a chosen trigeminal division or divisions, correlating at each segment clinical and electrophysiological data with radiological landmarks in the individual patient. The system consists of an outer needle with four windows at a distance of 15 mm from the tip. A multiple electrode array occludes the windows with four isolated caps for stimulation and recording. After correlating clinical verbal and motor responses with sensory and motor evoked potentials at each window and inter se, a target window is selected. A thermocouple fitted with a micromanipulator allows the accurate placement of the center of the active tip at the center of the chosen window. Preliminary data from 25 patients indicate that the technique provides a reliable sequential analysis of clinical, electrophysiological, and radiological data along the explored tract.

Familial congenital facial diplegia: electrophysiologic and genetic studies.

A 13-year-old boy with autosomal-dominant congenital facial diplegia was evaluated by electrophysiologic and genetic investigations. Thirteen members of his family were affected over 4 generations. The electrophysiologic studies revealed blink reflex abnormalities. Both R1 and R2 responses were prolonged on the left side after ipsilateral stimulation, while R2 was also delayed by contralateral stimulation. Ipsilateral R1 and R2 were of normal latencies when the right side was stimulated. A third ipsilateral response at 63 msec of latency could be obtained when stimulating the left side. These findings suggest functional damage to the brainstem. Further support for this interpretation was provided by the prolonged time between waves I and V, bilaterally, documented by study of brainstem auditory evoked potentials.

The effect of levodopa on the habituation of the acoustic-palpebral reflex in Parkinson's disease.

The aim of the present study was to assess the habituation of the blink responses evoked by repetitive auditory stimuli in patients with Parkinson's disease in different clinical states. We studied 28 parkinsonian patients. Eighteen patients without motor fluctuations were studied off and on levodopa, on two different sessions, one week apart. The remaining 10 parkinsonians had the wearing off phenomenon and were studied while being off their medication and while ON and OFF, as determined clinically, after a single dose of levodopa. Twelve age-matched controls were also studied in a single session. Unilateral auditory 1 kHz, 105 dB stimuli were delivered at a frequency of 0.2 Hz. The number of responses (R) from the orbicularis oculi was registered. R values were significantly smaller in controls and in treated parkinsonians than in untreated patients. R was also significantly smaller when ON than at baseline and when OFF in parkinsonians with the wearing off phenomenon. These results suggest a failure of the inhibition of the acoustic-palpebral reflex in Parkinson's disease. The improvement with levodopa and the similarities between the clinical and the electrophysiological changes suggest a dopaminergic role in the inhibition of this brainstem reflex.

Neuropathy in myotubular or centronuclear myopathy.

A detailed electrophysiological study has been made of the extensor digitorum brevis, thenar, hypothenar and soleus muscles in one patient with myotubular or centronuclear myopathy. The main finding was a noticeable reduction in the population of active motor units in all the investigated muscles. The remainer units showed normal sizes. The experimental observations have been interpreted in terms of a neuropathic process.

[Electrophysiological study of the variations in innervation of the hand muscles]. / Estudio electrofisiológico de las variaciones en la inervación de los músculos de la mano.

An electrophysiological study was carried out searching for variations in the innervation of the muscles of the hand. For this purpose a simple and non time-consuming technique was designed for stimulating the ulnar and median nerves at the elbow and wrist. Recordings were performed with surface electrodes at the abductor pollicis brevis, adductor digiti minimi and first dorsal interosseus muscles. Several anomalous innervation patterns of the intrinsic muscles of the hand were found, and the innervation of the first dorsal interosseus by the median nerve was the most frequent.

An electrophysiological investigation of skeletal muscles in polymyositis.

An electrophysiological study has been made of the extensor digitorum brevis, thenar and hypothenar muscles in 25 patients with chronic and acute polymyositis. It was found a reduction of the number of functioning motor units in some patients with chronic polymyositis and only in one of those affected by acute polymyositis and only in one of those affected by acute polymyositis. The sizes of the surviving units suggested that the results could be explained in terms of a primary muscle involvement mainly in acute polymyositis, while in chronic polymyositis a combination of primary and neurogenic involvement of muscle fibers might take place.

Cerebral evoked potentials in human chronic Chagas' disease.

Seventy five patients with the diagnosis of chronic Chagas' disease were studied by employing EPs techniques. Two of them had delayed arrival of the signal to the Erb's point and one to the spinal cord when looking at SEPs. Two patients had increment of the time interval between waves Ist and IIIrd, when studying PEATs. These findings were interpreted as due to peripheral nerve fibers damage, a feature described in previous papers. The most striking finding was the prolonged time interval between waves N13 and N20 (SEPs) found in two patients and between waves IIIrd and Vth (PEAT) seen in 7 affected subjects. These observations suggested the development of some sort of CNS involvement, perhaps related to myelin damage, in patients who reached the chronic state of the infection.

Peripheral nerve involvement in Bell's palsy.

A group of patients with Bell's palsy were studied in order to disclose the presence of subclinical peripheral nerve involvement. 20 patients, 8 male and 12 female, with recent Bell's palsy as their unique disease were examined. In all cases other causes of polyneuropathy were ruled out. Patients were investigated with CSF examination, facial nerve latencies in the affected and in the sound sides, and maximal motor nerve conduction velocities, as well as motor terminal latencies from the right median and peroneal nerves. CSF laboratory examination was normal in all cases. Facial nerve latencies were abnormal in all patients in the affected side, and they differed significantly from those of control group in the clinically sound side. Half of the patients showed abnormal values in the maximal motor nerve conduction velocities and motor terminal latencies of the right median and peroneal nerves. These results agree with previous reports which have pointed out that other cranial nerves may be affected in Bell's palsy. However, we have found a higher frequency of peripheral nerve involvement in this entity. These findings, support the hypothesis that in some patients Bell's palsy is the component of a more widespread disease, affecting other cranial and peripheral nerves.

Histological and histochemical changes of the skeletal muscle in human chronic Chagas' disease.

Gastrocnemius muscle biopsies were performed in 7 subjects with chronic Chagas' disease. On clinical and laboratory grounds the selected patients were judged to be healthy, being the only abnormality found the presence of positive serum tests for Chagas' disease. Fibre type grouping of either type I or type II was observed in 5 of the 7 patients. Furthermore, in 2 of the 5 patients showing muscle fibre groupings, angular fibres reacting with NADH and non-specific sterase were also found. These observations strongly suggest denervation associated with reinervation. This picture often can be observed in the skeletal muscle of patients with well compensated denervatory conditions who did not show clinical evidences of denervation.

An electrophysiological investigation of skeletal muscle in human chronic Chagas' disease.

An electrophysiological study has been made of the thenar, hypothenar, soleus and extensor digitorum brevis muscles and their inervation in 90 patients with chronic Chagas' disease. Some of them showed a reduced number of functional motor units with increased size of many of the surviving units. No decremental muscle response was found to repetitive nerve stimulation. Motor and sensory conduction velocities as well as motor terminal latencies were on the normal range. These findings suggested that the muscle changes resulted from a primary defect of the alpha spinal motoneurone soma.

[Evaluation of central and peripheral components of muscular fatigue in neuropathic and myopathic patients]. / Evaluación del componente central y periférico de fatiga muscular en pacientes neuropáticos y miopáticos.

In a group of patients chronically denervated and other with primary muscle involvement a search was made for mechanisms involved in the muscular fatigue. It was found that there was no major differences between patients chronically denervated and controls, while in those others with primary muscle disorders a loss of functional motor units during effort and a transient impairment of neuromuscular transmission play a role together with the central events normally occurring in fatigue.

Central motor conduction in human chronic Chagas' disease.

The possible involvement of spinal alpha motor neurons, dorsal root ganglia and sensory fibers in human chronic Chagas' disease was previously demonstrated. More recently neuropsychological and sensory evoked potentials studies suggest the existence of central nervous system abnormalities in these patients. We assessed the state of central motor pathways in 46 patients with chronic Chagas' disease and 30 healthy volunteers by means of percutaneous cortical and spinal electrical stimulation. No significative slowness in pyramidal tracts (PT) conduction was found when comparing both groups. Neither any individual patient exhibited abnormally delayed PT conduction values beyond the upper normal limit of the healthy volunteers. These results suggest that, in contrast with other neural systems, the large myelinated PT fibers are usually spared in human chronic Chagas' disease.

[Evaluation of central and peripheral factors in muscular fatigue]. / Evaluación del factor central y periférico en fatiga muscular.

Muscular fatigue was investigated in 13 healthy people by employing a simple device which comprises a computer on line with a conventional EMG equipment able to automatically measure the frequency and duration of free-run EMG recording. The procedure was carried out in the extensor digitorum brevis muscle by using surface electrodes throughout 10 minutes of voluntary maximal effort. The maximal M wave as well as the muscle response to repetitive nerve maximal stimulation was also explored at the beginning and at the end of the experiment. It was observed a decrease of the potentials frequency discharge and an increase of their duration without major changes in the M wave amplitude neither in the muscle response to the repetitive nerve discharge. The findings pointed out to the central factors as the mean responsible for the development of muscular fatigue.

[Evaluation of central and peripheral factors in muscular fatigue in patients with pyramidal lesions]. / Evaluación del factor central y periférico en fatiga muscular en pacientes con daño piramidal.

Muscular fatigue mechanisms were partially analyzed in patients with pyramidal lesions by using a computer device on line with a conventional electromyograph. Both the normal and the affected side were compared with control groups. The recordings were done throughout a ten minutes period and the maximal M wave was also measured at the starting and at the end of the procedure. The findings suggested that central events play a major role in the development of muscular fatigue in spastic muscles due to pyramidal damage.

Cognitive impairment in human chronic Chagas' disease.

UNLABELLED: We proposed to investigate subclinical cognitive impairment secondary to chronic Chagas' disease (CCD). No similar study was previously done. The neuropsychological performance of 45 chronic Chagasic patients and 26 matched controls (age, education place and years of residency in endemic area) was compared using the Mini Mental State Exam (MMSE), Weschler Memory Scale (WMS) and the Weschler Adult Intelligent Scale (WAIS). Non-parametric tests and Chi2 were used to compare group means and multivariate statistics in two way frequency tables for measures of independence and association of categorical variables with the disease. RESULTS: Chagasic patients showed lower MMSE scores (p < .004), poor orientation (p < .004), and attention (p < .007). Lower WMS MQ were associated with CCD (Chi2 5.9; p < .01; Fisher test p < .02). Lower WAIS IQ were associated with CCD (Chi2 6.3, p < .01; Fisher test p < .01) being the digit symbol (p < .03), picture completion (p < .03), picture arrangement (p < .01) and object assembly (p < .03) subtests the most affected. The impairment in non-verbal reasoning, speed of information processing, problem solving, learning and sequencing observed in chronic Chagas disease patients resembles the cognitive dysfunction associated with white matter disease.

[Diagnosis and treatment of myasthenia gravis: study of an inpatient population]. / Diagnóstico y tratamiento de la myasthenia gravis: estudio de una población hospitalaria.

Between 1974 and 1987 we have examined 50 patients with the diagnosis of myasthenia gravis. Female preponderance (2.5: 1) was found. Also, it was observed that most of the patients were aged between 20 and 49 years. Beside the clinical examination, the following tests were performed: (1) edrofonium test, (2) supramaximal repetitive nerve stimulation, (3) serum acetylcholine antibodies titers and (4) intraperitoneal passive transference of patient's sera to mice and recording of meepp's amplitude in the phrenic-diaphragm preparation in vitro. These four tests gave positive values for myasthenia in 90 to 100% of the cases. Thymus radiological examination was carried out by pneumomediastinography, which proved to correlate with the histological picture of the gland, and computed tomography, which disclosed some discrepances with the histology. Treatment was based on anticholinesterase drugs, corticosteroids and thymectomy, being the corticosteroids the most valuable therapeutical tool. Nine patients treated with steroids disclosed transitory worsening of their signs and symptoms at very early stages after onset of corticosteroid therapy, 6 of them had a disfavorable course in their follow-up. This observation seem to have value in the early prognosis of the disease.

Peripheral nervous system involvement in human and experimental chronic American trypanosomiasis.

An electrophysiological and histological study of the muscle and the peripheral nervous system (PNS) was carried out in chronic human American trypanosomiasis (Chagas' disease) and in an experimental Chagas' disease (Chd) mouse model. Altogether 995 patients with chronic Chd and 261 mice, experimentally infected with RA and CA-I parasite strains, were investigated. Results were compared with matched controls. Techniques employed in humans were: clinical assessment, conventional electromyography (EMG), estimated number of motor units, motor and sensory nerve conduction velocities, repetitive nerve stimulation and muscle and sural nerve biopsies. In mice conventional EMG, sciatic nerve conduction time, sciatic nerve action potential amplitude, in vitro miniature end-plate potentials (MEPPs) and end-plate potentials (EPPs) recordings, muscle, nerve and spinal cord histology and identification of cell phenotypes within the inflammatory infiltrates were the employed procedures. Out of 511 patients submitted to clinical examination, 52 disclosed signs and symptoms of mixed peripheral neuropathy. By employing electrophysiological techniques, it could be shown that about 30% of the investigated patients had one or more of the following features: diminished interference pattern, most of the remainder motor unit potentials being (MUPs) polyphasic; reduced number of functional motor units in the thenar, hypothenar, soleus and/or edb muscles; slow sensory and motor nerve conduction velocities; low sensory action potential amplitude and impairement of neuromuscular transmission. In mice, MUPs duration and amplitude were increased at later stages of the infection, nerve conduction was slow, nerve action potentials were of low amplitude, mepps were of low amplitude and double epps were frequently found. Muscle histology in humans with chronic Chd showed type I and type II grouping, atrophic angular fibers and targetoid muscle fibers. In mice perivascular mononuclear cells infiltrates, small round fibers, muscle fibers necrosis, atrophic angular fibers, type II muscle fibers grouping and grouped muscle fibers atrophy were found. Sural nerve samples showed segmental and paranodal demyelination and axonal loss. The same features were observed in mice nerves, also in this model mononuclear cells infiltrates at the nerve, dorsal root ganglia and meninges surrounding the spinal cord were observed. Muscle and nervous tissues infiltrates were mainly composed of T lymphocytes with predominance of CD8 or CD4 subsets according to the parasites strain employed for infecting the animals. These findings suggest that the skeletal muscle and the PNS may be involved in chronic American trypanosomiasis.