Biomedical subjects
Publications and source records attributed to W Trojaborg.
A case of X-linked recessive bulbospinal neuronopathy is reported. Neurophysiological findings were consistent with chronic partial denervation (motor axonopathy) and large fibre sensory axonopathy. DNA analysis showed an abnormal increased size of tandem CAG repeats.
We measured residual latency (RL), motor conduction velocity (MCV), and terminal latency index (TLI) in 15 patients with neuropathy and anti-MAG or SGPG antibodies and compared these to values obtained in 103 patients with other types of polyneuropathy (PN) and to 57 normal subjects. Ten patients had anti-MAG antibody titers of 25,600 or higher, and 5 had titers between 800 and 12,600. Patients with the highest titers had longer RL, slower MCV and shorter TLI than those with lower titers, acute or chronic inflammatory demyelinating PN, hereditary neuropathy, and metabolic or axonal neuropathy. In contrast F-wave latencies did not contribute to the differentiation between the groups of demyelinating neuropathies. RL and TLI correlated best with anti-MAG antibody titers, whereas there was a poor correlation with anti-SGPG titers suggesting that MAG more than SGPG may be the antigen in PN, and that the distal nerves are affected more than their proximal segments. The RL rather than TLI turned out to be the best variable to classify the demyelinating type of anti-MAG neuropathy. Sural nerve biopsy in 5 of the patients with the highest titer of anti-MAG antibodies showed deposits of IgM and C3 on the myelin sheaths, pronounced demyelination and widening of the myelin lamellae. In 4 of the patients with lower titers demyelination was absent or less pronounced.
Immune mechanisms have been implicated in the pathogenesis of motor neuropathy with conduction blocks and of acute axonal neuropathy, and GM1 ganglioside has been identified as a potential target antigen. In these experiments, the B subunit of cholera toxin (CT-B), which binds to GM1, was used to target an antibody response to GM1 in peripheral nerve. CT-B was injected into the sciatic nerves of rats, in which anti-CT antibodies were previously induced by immunization, so that the circulating anti-CT-B antibodies bound to the CT-B-GM1 complex in the nerve. Electrophysiological studies revealed the presence of conduction block, and in pathological studies there was axonal degeneration with little demyelination. Control animals, in which keyhole limpet hemocyanin was substituted for CT, did not develop conduction block or axonal degeneration. These studies indicate that antibodies directed at GM1 sites in peripheral nerve could cause an axonal neuropathy with conduction block.
Antibodies to myelin-associated glycoprotein (MAG) are found in patients with both monoclonal gammopathy and sensorimotor peripheral neuropathy but almost never in patients with amyotrophic lateral sclerosis (ALS). Ninety percent of patients with anti-MAG activity also have antibodies to sulfated glucuronic acid paragloboside (SGPG). We studied a patient with autopsy-proven ALS who had high titers of anti-SGPG but normal anti-MAG--one more unexplained immunologic abnormality in ALS.
The purpose of the study was to examine REM and delta sleep energy in adults with high and normal plasma growth hormone (GH) concentration by means of power spectrum EEG analysis. After a three-day regular sleep/waking schedule, all-night polysomnographic recordings were performed on two consecutive nights before as well as one year after treatment for acromegaly by adenomectomy. The sleep energy was calculated by power spectrum analysis. We studied nine patients aged 24-45 years with untreated active acromegaly. The same patients were re-examined one year after adenomectomy when plasma GH concentrations were normal. The acromegaly was verified biochemically by measuring basal plasma GH concentration and plasma GH during hyperglycaemia as well as insulin-like growth factor. Cerebral computer tomography (CT) and magnetic resonance (MR) scans revealed an intrasellar adenoma in all patients. The resulting sleep records obtained before and after adenomectomy were subjected to power spectrum analysis and a manually blinded sleep scoring. The power spectrum analysis showed that when circulating GH was elevated the energy in the REM sleep per minute was significantly higher compared to the REM energy/min after surgery when GH concentrations had normalized. A similar relation was found for delta sleep (stage three and four, deep sleep) where the energy per minute was higher before treatment than after. The study demonstrates that plasma GH concentration was correlated to sleep energy. During high GH concentration the REM and delta sleep energies were high and normalization of plasma GH was followed by normalization of REM and delta sleep energy per time unit.
We review clinical, neurophysiological, immunological, and experimental data concerning multifocal motor neuropathy (MMN), a newly recognized disorder that mimics MND. It is separated from MND by the presence of multifocal conduction block (CB) demonstrated electrophysiologically, and in some instances by the association of high titers of GM1 antibodies. The possible immunopathogenetic effect of GM1 antibodies is discussed. However, 70% of patients with MMNCB do not have elevated titers of GM1 antibodies, but may respond nevertheless to immunosuppressive treatment. Thus, so far unrecognized antibodies may react against some other epitopes in the paranodal region than those attacked by GM1 antibodies to cause CB.
The compound sensory action potential evoked by electrical stimulation provides a measure of the number and physiological properties of myelinated fibers in the nerve but does not allow evaluation of the most distal part of the sensory nerve. This study compares the compound sensory action potential, evoked by electrical and tactile stimuli, and recorded through needle electrodes placed close to the median and sural nerves of 22 normal males aged 16-51 years. The tactile probe, with a slight preindentation, delivered an indentation of the skin of 200 microns at a rate of 400 microns/ms at the tip of digit III and the dorsolateral side of the foot. The responses were recorded from the median nerve at wrist and elbow and from the sural nerve at the lateral malleolus and midcalf. The amplitudes of the responses averaged 0.5 microV and 0.7 microV in the sural and the median nerves (P < 0.02), respectively, which was only 5-10% of the amplitude evoked by electrical stimulation. The mean maximal conduction velocity determined by tactile stimulation was 54 m/s in the sural nerve compared with 65 m/s in the median nerve and similar to that calculated after electrical stimulation. In the median nerve the sensory conduction velocity was 8% faster than the motor conduction velocity. These findings indicated that only a fraction of the fibers in the nerve were activated by the probe and that the response was conducted along large myelinated sensory fibers. The latency of the tactile response was longer than that of the electrically evoked response due to the receptor delay and conduction along thin distal fiber portions. The delay at the mechanoreceptors was about 1 ms in the sural and 0.65 ms in the median nerve (P < 0.01).
In traumatic brachial plexus injuries a thorough neurological, electrodiagnostic, and radiological examination is essential to determine treatment and prognosis. The most important diagnostic question concerns the presence or absence of a preganglionic nerve root lesion. Electromyography and motor and sensory conduction studies were performed in 17 patients with traumatic plexus injuries who had myelographic evidence of nerve root avulsion; in 8 of these clinical and electrophysiological features confirmed the X-ray findings. However, in 9 cases there was a discrepancy between myelographic and neurophysiological data regarding the actual number and sites of roots avulsed. Thus, in 2 cases myelography showed avulsion of one more root than did conduction studies and EMG; in 2 others, there was discordance as to the specific roots avulsed; in 4 cases fewer nerve roots seem to be avulsed radiologically than predicted clinically, and in 1, none at all, although clinical and electrophysiological data were compatible with avulsion of four roots. In 6 cases recovery showed that avulsions indicated by clinical and electrophysiological considerations could not have occurred. When both EMG and myelography are misleading, surgical exploration should be considered.
We examined 8 men with X-linked recessive bulbospinal neuronopathy. Quantitative electromyography showed large amplitude motor unit action potentials of prolonged duration and increased polyphasia. There was a pronounced loss of motor units in all but one muscle at maximal volition even in muscles with normal or only mildly decreased force. Denervation activity was present in 53% sampled limb muscles, and fasciculation was recorded in 33% of limb muscles. Nerve conduction studies showed small amplitude sensory action potentials in 6 out of 8 patients. The motor and sensory conduction velocity was normal or borderline slow. The electrophysiologic findings were consistent with chronic partial denervation (motor axonopathy) combined with large fibre sensory axonopathy.
The neuropathic profile was studied in 26 patients with long-standing, insulin-dependent diabetes mellitus and end-stage nephropathy using tests to evaluate large and small nerve fibres and autonomic function. Clinically, 18 patients (69%) has symptoms and signs of peripheral neuropathy, 9 (35%) had symptoms of autonomic involvement. Vibratory sensation was impaired in 20 patients (77%) in the lower limbs and in 6 (22%) in the upper limbs; cold and warm sensation was equally often impaired in the feet and in the hands with no significant difference between patients with and without neuropathy. Heart rate variation was abnormal in 23 patients at rest (88%), in 24 (92%) during deep breathing and during the orthostatic test. Conduction studies revealed abnormalities in two or more nerves in all patients regardless of whether or not they had overt neuropathy clinically. Thus, the applied multimodal tests revealed evidence of impaired function in large or small nerve fibres or both in all patients independent of clinical findings.
From a series of 26 diabetics selected for combined pancreas and kidney transplantations 9 died before surgery was scheduled, one died after surgery and 4 rejected the transplants. The effect of pancreas or kidney transplantation or both on vibratory perception and thermal thresholds, various motor and sensory conduction parameters were studied in 9 of the remaining 12 patients. In 6 both the pancreatic and renal grafts were functioning, in 2 the pancreas was rejected, and in 1 the kidney. At an average follow-up of 41 months after surgery, the mean total score of clinical and electrophysiological improvement in 6 patients with successful combined transplantation was 5.5 +/- 1.6 compared with -4.3 +/- 2.5 in 3 patients with one surviving transplant (P < 0.001). Similarly, the average increase in nerve conduction velocity was 5.8 +/- 1.1 m/s in patients with two functioning grafts whereas it decreased 2.9 +/- 0.7 m/s in those with only one (P < 0.001). The quality of life was considered improved in patients with successful outcome of the two organ transplantations in contrast to the statements of those with only one.
We reviewed the clinical and electrophysiologic features of 36 patients with increased titers of IgM anti-GM1 antibodies. Mildly elevated titers of up to 3,200 were not associated with any particular clinical syndrome or disease. Clinically, 14 of 16 patients with highly elevated titers of 6,400 or higher had progressive weakness with lower motor neuron signs; six had active tendon reflexes and eight had absent reflexes, but none had definite upper motor neuron signs. Electrophysiologic studies showed spontaneous activity in all 14 patients, one or more motor conduction blocks in nine, slowed motor conductions in one, and normal conductions in four patients. None had abnormal sensory conductions. These patients presented with a syndrome that has features of, but is distinct from, both motor neuron disease and demyelinating neuropathy.
Explore the source record for details and available documents.
Sixty-six non-epileptic children with focal spikes in EEG and without cerebral palsy were followed for 16 to 35 years. The cumulative risk of developing one or more seizures was 33% when the first abnormal EEG was recorded, and increased to about 80% if abnormalities persisted three or more years. Focal spike activity was most persistent in children with retarded development or with organic brain diseases. We conclude that the presence of focal EEG spikes in children without epileptic seizures can be considered epileptogenic, especially if the abnormality is persistent and associated with clinical evidence of organic brain disorder.
Although conduction block indicates dysfunction of peripheral nerve, it may occur in patients with clinically typical motor neuron disease. There are no universally accepted criteria to identify conduction block, so diagnosis may be difficult. In some peripheral neuropathies, conduction block persists over long periods of time. If conduction block persists in motor neuron disease, then a more reproducible means for identification would be available. We repeatedly studied 9 patients with different forms of motor neuron diseases; conduction block was suspected because of excessive loss of the amplitude of motor evoked responses between distal and proximal stimulation sites. Five showed persistent amplitude loss at intervals between 12 and 36 months. All had focal loss of amplitude and area across a specific segment; all were men; none had definite upper motor neuron signs, 2 had probable and 3 had no upper motor neuron signs; 1 had IgM paraproteinemia, one elevated anti-GM1 titers; the duration of symptoms spanned 4-13 years. Four patients had transient loss of amplitude that was not reproduced in intervals between 3 and 13 months. None had focal loss of both amplitude and area; 2 were men; all had definite upper motor neuron signs and none had symptoms for more than 3-13 months; and none had immunological abnormalities. Thus, patients with persistent amplitude loss fulfill other criteria for conduction block, have prolonged survival but otherwise have clinical syndromes indistinguishable from ALS, except that definite upper motor neuron signs seem to be exceptional.
Electrical and mechanical responses to single shocks, slow and fast nerve stimulation (RNS), quantitated EMG, anti-acetylcholine receptor (AChR) and anti-striated muscle (SM) antibodies (ab) were determined in 145 patients with myasthenia gravis (MG). Anti-AChR ab were found in 93% of the myasthenic sera. Decrement of muscle and mechanical responses occurred in 72% and 49%, respectively, the diagnostic yield being positively related to severity of MG. Anti-AChR ab were found in 81% of patients without RNS abnormalities. Decrement at RNS occurred in 33% of the cases without anti-AChR ab compared with 78% of those with elevated titres. Regional curare test (RCT) was diagnostic in 75% of cases with normal RNS. As the combined diagnostic yield of RNS and anti-AChR ab was 96%, RCT and single fibre EMG are rarely indicated. Post-tetanic facilitation and exhaustion, and an abnormal staircase phenomenon occurred in 25%, 44% and 37%, respectively. None of these parameters correlated with severity, type or onset of MG. EMG evidence of myopathy, positively correlated with the presence of anti-SM ab, occurred in 19% of patients examined, 3 times more frequent in those with late onset of MG than in those with early onset; thus myopathy of possible autoimmune origin may coexist with MG. An adequate electrophysiological diagnostic strategy for MG patients is proposed.
Cisplatin is a widely used anti-neoplastic agent with dose-dependent sensory neuropathy as a major side-effect. The mechanism for the neuropathy is poorly understood; it may be caused by a lesion of the dorsal root ganglion cells or by a distal axonopathy. This distinction is important since regeneration in a neuronopathy is impossible, whereas recovery may occur if the axon is affected only distally. The most distal part of the sensory nerve fibre is, however, not accessible for conventional electrophysiological examination. To ascertain whether the distal receptor-associated part of the fibre is involved, we have used a method previously untested in patients with neuropathy. In 26 males treated with cisplatin for testicular cancer 3-6.5 years previously, and in 22 normal males, the compound sensory action potentials evoked by a tactile probe were recorded through needle electrodes placed close to the sural and median nerves. The responses were compared with action potentials evoked by electrical stimulation of the same nerves. Biopsies from the distal sural nerve at the dorsolateral aspect of the foot were obtained in three patients and in four subjects not treated with cisplatin. Sixteen patients had received a conventional dose (307-435 mg/m2) of cisplatin and 10 patients had received a high dose (553-1197 mg/m2). Two-thirds of the conventional dose patients and all the high dose patients had mild to severe sensory loss and reduced or absent tendon reflexes. The amplitude of the electrically evoked sensory action potential decreased with increasing dose of cisplatin and was correlated with the reduction of vibration sense. Tactile responses, probably originating mainly from Pacinian corpuscles, were, with the exception of two high dose patients, recorded from all sural and median nerves. The two high dose patients without a tactile response had a severely reduced or no electrically evoked response at the sural nerve. The sural nerve biopsies from high dose patients showed loss of large fibres; Pacinian corpuscles were obtained in two of these patients and contained normal axons. Our findings do not suggest that cisplatin causes a primarily distal lesion with sparing of more proximal parts of the peripheral nerve. We interpret the results as being consistent with a neuronopathy affecting primarily large sensory neurons. Brainstem and somatosensory evoked potentials and H-reflexes suggested that the spinal cord and brainstem were affected as well.
Turns-amplitude analysis of the electromyographic recruitment pattern was performed on-line in the brachial biceps muscle of 46 patients with neuromuscular disorders using the mean amplitude as an indicator of force. The parameters, peak-ratio (PR) and number of time intervals (TI) from 0 to 1.5 ms, were increased in patients with myopathy. In patients with neurogenic involvement, the characteristic pattern was a decreased PR and a decreased incidence of TI between 0 and 1.5 ms. The results indicate that the two parameters supplement each other as some of the patients were identified only by one or the other. In patients with myopathy, the method had a higher diagnostic yield than the individual motor unit action potential analysis. The method is objective, fast, and reliable.