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Grouping of the EMG response produced by quick stretches of contracting muscles has been thought to reflect 'long loop reflexes' through cerebral cortex adding to the segmental stretch reflex. Our recordings from human muscle spindle afferents responding to such stretches show that these discharges also tend to be grouped. EMG grouping may therefore be a consequence of successive segmental reflexes rather than of additional delays in long loop reflex arcs.

1. Different techniques were used to generate sudden ramp extension movements of the wrist while the subjects were either relaxed or maintaining a weak voluntary contraction in the wrist flexors. Afferent responses to the displacements were recorded with a tungsten micro-electrode inserted into a fascicle of the median nerve supplying one of the wrist flexor muscles, and e.m.g. responses were recorded with needle electrodes inserted into the same muscle.2. With the wrist flexors either relaxed or contracting, extensions at 100-200 degrees /sec for 60-70 msec (generated by either an hydraulic motor or a torque motor) produced segmented afferent responses with two to four afferent bursts, separated by intervals of 20-30 msec. The successive neural peaks, occuring during the stretch phase, were correlated to mechanical vibrations sensed by a strain gauge and sometimes also by a wrist goniometer. With the flexor muscles contracting, the successive peaks in the neurogram were followed by similar peaks in the e.m.g, the delay between neural and e.m.g. peaks being 20-25 msec.3. Small abrupt extension movements of 1-2 degrees lasting only 10-15 msec often produced segmented afferent responses with one neural burst occuring during the stretch phase and another 15-20 msec later, corresponding to a mechanical oscillatory event succeeding the stretch. The oscillation and the second neural burst were not present with small extension movements of smooth onset and halt. With the flexor muscles contracting, stimuli producing one afferent burst produced only one e.m.g. peak, whereas double-peaked afferent discharges produced double-peaked e.m.g. responses, the delay between individual neural e.m.g. peaks being 20-25 msec.4. Similar segmentation of the neural stretch responses was seen when abrupt displacements were produced by electrically induced muscle twitches, by manual pulls on a spring attached to the hand or by the subject making fast voluntary wrist extensions. This grouping of afferent discharges was seen in both multi-unit and in single-unit recordings from fibres identified as group Ia afferents.5. It is concluded that mechanical vibrations in the moving parts are initiated by abrupt joint movements and that these vibrations are sensed by the primary endings. With initial background contraction in the stretched muscles, synchronous volleys of spindle discharges produce, via segmental reflex arcs, modulation of the e.m.g. with the appearance of two or three e.m.g. peaks separated by intervals of 20-30 msec. Possible causes for the mechanical oscillations are discussed.6. For imposed movements with a duration of 60-70 msec the successive e.m.g. peaks caused a fused reflex contraction, appearing as a torque trace deflexion, starting at about the time when the movement ended and reaching its peak within about 40 msec. With longer-lasting movements the mechanical reflex response accompanying the successive e.m.g. bursts, appeared as a decelerative force, starting to oppose the ongoing movement about 60 msec after its start. Mechanical consequences of stretch reflex contractions starting after, rather than during, the stretch movement are discussed.

Microneurographic studies were made of normal human muscle spindle afferent activity to evaluate the role played by these endings, and by the segmental stretch reflex, in various types of physiological tremor. Primary endings are sufficiently sensitive to respond to the minute tremulous movements normally seen in contracting muscles. Human muscle spindle endings appear to possess the same non-linear sensitivity to small stretches as has been reported for cat muscle spindles. The findings also support the notion that the segmental stretch reflex plays an important role in enhanced physiological tremor, in so far as it tends to synchronize the motor outflow in such a way as to produce rhythmical contractions properly timed to reinforce the mechanical resonant properties of muscle spindle endings, the stretch reflex also serves to damp the larger oscillations of finger or hand which result from a brisk tap or muscle twitch. There is no evidence for alpha-gamma co-activation in these enhanced physiological tremors.

Late response (H reflex and F response) and sural conduction studies were used in addition to conventional motor and sensory conduction to detect peripheral neuropathy in 30 randomly selected patients with chronic renal failure (18 receiving hemodialysis), five of whom had no clinical evidence of peripheral neuropathy; 30 age-matched control subjects were also studied. Conventional motor (median, ulnar, peroneal, and tibial) and sensory (median and ulnar) nerve conduction studies showed abnormalities of motor conduction in 25 (83%) and of sensory conduction in 26 (87%) patients. Abnormalities of sural nerve conduction and of late responses were present in all 30 patients. Five patients (17%) who had normal routine motor conduction showed abnormalities of late responses in the same nerve distribution. All electrophysiologic abnormalities were significantly more evident in lower limbs. Studies of late responses and sural conduction, in addition to improving the diagnostic yield, provide a method whereby effects of dialysis and medical management can be followed quantitatively in patients whose neuropathy would otherwise be undetectable.

Motor conduction velocities of median, ulnar, peroneal, and tibial nerves and sensory conduction velocities of median and ulnar nerves were studied in 30 alcoholic subjects and a similar group of control subjects. The results were compared to sural nerve conduction velocities and late response latencies (H reflex, F response). The latter two techniques improved the diagnostic yield by 20%: Whereas 73% of our patients showed an abnormality of conduction with conventional techniques, 93% had an abnormality of sural nerve conduction, late response latencies, or both. Abnormalities of motor and sensory conduction, which were more prominent in the lower limbs than the arms, could be documented in patients who did not have any clinical evidence of peripheral neuropathy. The electrophysiologic studies performed in the present study suggest that "axonal degeneration" is the underlying pathologic process in alcoholic peripheral nerve disease.

The purpose of this study was to derive numerical data concerning the probability of diagnosing myasthenia gravis by electrical tests, employing repetitive stimulation of motor nerves. This was done by recording the compound muscle action potential (CMAP) from 80 patients with clear-cut myasthenia gravis, using a number of different, reportedly useful, testing techniques. In 95% of these patients, the diagnosis could be documented by the careful application of rather simple methods, providing several muscles, including a proximal one such as deltoid, were studied.

Brainstem auditory evoked responses (BAERs) were recorded from 202 patients with definite, probable, or possible multiple sclerosis (MS). Definitions of abnormality were based only on interwave separations and the wave I/wave V amplitude ratio. Thirty-two percent of the patients had abnormal BAERs, and the presence of clinically unsuspected lesions was revealed by BAER abnormalities in 7.4%. Thirty-five percent of the patients who had nystagmus and 53% of those who had internuclear ophthalmoplegia at the time of testing had BAER abnormalities. Forty-five percent of the abnormalities were elicited with stimulation of one ear only, stressing the importance of monaural stimulation. Click rates faster than 10 per second did not reveal abnormalities undetected at slower rates. BAERs were normal by these criteria in patients with labyrinthine diseases and amyotrophic lateral sclerosis. Thus, the BAER in MS can (1) confirm the presence of central lesions in patients with suspected brainstem involvement, (2) document the presence of clinically unsuspected lesions, and (3) be followed over time to provide possible assistance in evaluating the effectiveness of therapeutic measures. The BAER is a useful tool in the diagnosis and management of MS.

Motor axons supplying lumbrical muscles are less severely affected than axons supplying thenar muscles in the carpal tunnel syndrome; sometimes lumbrical motor fibers are less affected than digit 2 sensory fibers. This pattern is consistent with compression of both the anterior and posterior aspects of the median nerve in the carpal tunnel because nerve fibers responsible for thenar, lumbrical, and digit 2 functions lie in an anterior-posterior gradient within the distal median nerve. Recognition of lumbrical sparing supports the electrodiagnosis of carpal tunnel syndrome when the distal latency to thenar muscles or the palm-to-wrist mixed median nerve conduction velocity is normal.

Fifty-one patients with clinically pure optic neuritis (ON) and 149 with possible, probable, or definite multiple sclerosis (MS) were tested with pattern shift visual evoked responses (PSVER) and compared with a group of 43 normal subjects. Attention was paid to response latency, intereye latency difference, as well as differences in amplitude or duration of the major positive peak (P100). Abnormal PSVER cannot be recorded from everyone with confirmed ON. Abnormal responses were recorded from 91% of all patients (including those with MS) who had a history of ON, 57% of all MS patients, and 36% of patients without a history of ON or an abnormal eye examination. Measurements of amplitude and duration proved to be of little value in this setting. Though abnormalities of PSVER are not "specific" for ON or MS, because they also result from other disease processes, they afford more reliable, quantitative documentation of abnormal conduction in visual pathways than any other clinical test.

F responses were elicited from both hands of patients shortly after they sustained unilateral cerebrovascular lesions. In 17 of 29 patients, significant abnormalities were found; F responses occurred with decreased persistence and/or amplitude on the clinically involved side, a change which was seen only in patients studied within 4 weeks of the ictus. The most prominent changes (in comparison with the clinically uninvolved side) occurred with extensive lesions. The abnormalities of F response correlated clinically with severity of the weakness, decrease in tone, and decrease in deep tendon reflexes. These changes in F response are consistent with a decreased "central excitatory state" at the spinal segmental level during the early phase after a supratentorial stroke.

Blink reflexes were obtained in a total of 34 different patients with cerebrovascular lesions; 28 were studied within 1 week of the ictus and 11 were eventually restudied. In 13, the latency of the first component of the reflex on the clinically involved side was significantly delayed (greater than 1.5 msec). This was an acute phenomenon that usually resolved within the first week after the ictus, correlated clinically with the severity of the hemiparesis and decrease in tone, and may be seen with lesions restricted to the pyramidal tract. The second component was absent in 17 of 34 patients during the early phase after stroke, and was associated with a decreased corneal response. These changes, which reflect decreased excitability of certain brainstem structures (rather than a lesion within those structures), are therefore potentially important for documenting CNS pathophysiology.

The clinical and EEG findings in patients in the literature with Creutzfeldt-Jakob disease (CJD) were reviewed and compared with findings in 36 patients with CJD at the Massachusetts General Hospital (MGH). Twenty-one of the 36 MGH cases had histopathology, all with findings consistent with CJD. EEGs in 18 patients studied pathologically and in 10 without pathological investigation (28 of the 36) had periodic sharp wave complexes (PSWC) at some time during the clinical course. Of the other eight patients, two had only a single EEG early in the course of the illness, four experienced unusually long clinical courses, and two never showed PSWC despite numerous EEGs. PSWC made their appearance within 12 weeks of onset of clinical symptoms in 25 of 27 in whom EEGs were done during that period. In the early stages, EEGs in 14 of 28 showed focal PSWC or amplitude asymmetries of PSWC that corresponded well with focal myoclonus or other focal neurological abnormalities. In the literature, PSWC occurred within 12 weeks of the onset of the illness in 66 of 75 patients (88%) with CJD who had comparable clinical and neuropathological findings and adequate EEG data during the first 3 months of the illness. In the approximately 10% of patients who experienced unusually long courses, PSWC occurred in only about 55%. The presence of PSWC in association with the appropriate clinical, biochemical, cerebrospinal fluid, and neuroradiological findings is diagnostic of CJD. Brain biopsy is, therefore, unnecessary even when clinical therapeutic trials are undertaken and certainty of diagnosis is required. The absence of PSWC in the EEG after 12 weeks' duration of illness is a point strongly against the diagnosis of CJD unless it is a rare subtype of long duration. Only those patients without PSWC need to be biopsied.

In view of recent evidence that physiological tremor can be enhanced by positive feedback via the segmental stretch reflex, several manoeuvres and procedures were employed to enhance the finger and hand tremor of healthy subjects--the purpose being to determine if tremorogenic effects, at least in part, are due to increase efficacy of the stretch reflex servo. Mechanical events during tremor (and during voluntary or electrically induced muscle twitches) were recorded together with EMG activity from wrist and finger flexor muscles and discharges from primary spindle endings in these muscles. Physiological tremor can be enhanced not only by manoeuvres which increase the gain of segmental stretch reflexes (Jendrassik manoeuvre) but also by manoeuvres which increase the contrast in spindle firing during stretch versus shortening phases of tremor, thus enhancing reflex modulation. Effects of the latter type can be achieved by procedures which alter mechanical twitch properties of extrafusal fibres (isoproterenol infusions and fatigue) and by procedures which involve application of spindle stimuli acting preferentially during stretch phases of tremor movements (muscle vibrations). Physiological tremor, which can be temporarily enhanced by an externally applied muscle perturbation, also becomes accentuated by those small "pseudo-myoclonic" jerks which occur in all normal subjects attempting to perform slow, smooth movements.

Asterixis is a disorder of motor control characterized by irregular myoclonic lapses of posture affecting various parts of the body independently. These lapses are caused by involuntary 50- to 200-msec silent periods appearing in muscles (even antagonistic groups of muscles) which are tonically active. That is, the silent periods and postural lapses occur in muscles that have been contracting for a time whether or not there has been slow shortening or lengthening but probably do not occur during or immediately after a sudden movement at a joint. What constitutes a sudden as opposed to a slow movement remains to be defined. When bilateral asterixis is present, one cannot rule out the possibility of a focal lesion (see Table 2), but it is almost always due to a metabolic encephalopathy (with a wide variety of possible causes). Unilateral asterixis is due to a localized lesion, perhaps otherwise not clinically evident, in the contralateral cerebral hemisphere. This episodic dysfunction within neural circuits which are normally concerned with maintenance of sustained or tonic muscle contraction may be released by focal lesions only in specific CNS areas (such as ventrolateral thalamus) or by a more generalized neurochemical imbalance (metabolic encephalopathies of various kinds). The system, a lesion or metabolic dysfunction which produces asterixis, is presumably an anatomically and/or pharmacologically distinct one; asterixis is not the result of a nonspecific disorder any more than are seizures. Presumably, those aspects of each of the different factors (e.g., subdural hematomas, drugs, electrolyte imbalance, cerebrovascular accidents, intracerebral tumors) that may produce asterixis or a seizure are mediated through some fundamental neuronal or neural systems process. To label asterixis or seizures nonspecific results of CNS disorders or results of nonspecific CNS disorders may be simply to avoid confronting our ignorance of the specific pathophysiologic mechanisms involved. Although the anatomy, neurochemistry, and physiologic function of this asterixogenic system remain to be elucidated, observations that asterixis may be caused by discrete anatomic or pharmacologic (e.g., phenytoin) lesions should tell us something important about mechanisms underlying sustained muscle contraction in humans. Unfortunately clinicoanatomic correlations alone cannot provide precise answers because even those reasonably focal vascular lesions that cause asterixis are too gross to permit localization or identification of the neural systems involved.(ABSTRACT TRUNCATED AT 400 WORDS)

To study the mechanisms by which propranolol suppresses essential tremor, accelerometric recordings were made from four normal subjects and eight patients with that tremor, and small amounts of isoproterenol and propranolol were infused intravenously or into one brachial artery. Intra-arterial isoproterenol increased tremor amplitude selectively in that arm in normal subjects and in patients with essential tremor (range, 1.85 to 3.50 with mean 2.74 times the base-line level). Intra-arterial or intravenous propranolol quickly blocked the enhanced action tremor in both groups. It did not simultaneously affect the underlying essential tremor, whereas long-term oral propranolol therapy did diminish the amplitude of the essential tremor in each patient. Peripheral beta-adrenergic tremorogenic receptors function normally even in patients with essential tremor; their function is not necessary for the production of essential tremor, and the efficacy of chronic propranolol therapy in the suppression of essential tremor is not mediated via its peripheral beta-adrenergic blocking action.

A method is described to measure reproducibly stiffness, and therefore "tone", at the elbow of patients with Parkinson's disease using a torque motor. In Parkinsonian versus normal patients (previously reported) it was observed that: the neutral angle in Parkinson's disease patients was significantly smaller (92 degrees +/- 15 degrees) than in normals (107 degrees +/- 10 degrees), and in Parkinson's disease patients, even with relatively mild symptoms, the upper limb was stiffer than normals in the totally relaxed state with no electromyographic activity present. Our results suggest that changes in the passive mechanical properties of the upper limb affected by Parkinsonian rigidity may have taken place, accounting for the more flexed neutral elbow angle and greater passive stiffness. Using this technique, response to antirigidity therapy and natural progression of illness can be quantitatively assessed and followed.

Electron-microscopic, morphometric, histochemical and biochemical studies were carried out on muscle biopsies from a patient with the characteristic clinical and pathological findings of nemaline myopathy. The mean fiber diameter was decreased, and the vastus lateralis muscle biopsy consisted exclusively of slow twitch (Type I) fibers. Quantitative biochemical investigations revealed significantly low calcium uptake and ATPase activity of the fragmented sarcoplasmic reticulum and decreased myosin ATPase activity. The electrophoretogram of myosin showed an abnormality in the light chain pattern which could not be explained by a disproportion of normal fiber types.

Spasticity has been defined as velocity-dependent hyperactivity of stretch reflexes; it is therefore only one aspect of the complex syndrome produced by a lesion of the upper motoneuron. Although spasticity may be partially responsible for joint contractures, it does not produce most of the functional disability experienced by patients with upper motoneuron lesions. Paresis, fatigability, lack of dexterity, etc., account for most of these patients' complaints. The pathophysiology of spasticity is poorly understood but appears to be related to an increased excitatory state at the segmental spinal level; there is no evidence for increased sensitivity of muscle spindles in spastic patients. Several mechanisms for this increased excitability within the spinal cord have been proposed. There are different types as well as degrees of spasticity. Clinical neurophysiologic recordings of reflex activity in patients with spasticity provide the means to differentiate among the various types of spasticity, to select the therapy most likely to be effective in a particular patient, and to see the results of its employment objectively. The latter will prove whether a specific therapy is useful or not. Ablative treatment at the level of the peripheral nerve or dorsal root may be useful, particularly when spasticity is severe. Drugs such as baclofen or diazepam relieve flexor spasms but are not particularly effective against spasticity itself. Dantrolene acts to weaken muscles, but that is not often helpful. Rarely do any of these therapies increase function; there are no effective cures for paresis or related negative manifestations of chronic spasticity.

Baclofen (a gamma aminobutylic acid derivative) and a placebo were compared for their efficacy in relieving certain symptoms in patients with long-standing spinal cord lesions and "spinal spasticity." In a double-blind, cross-over clinical investigation, 22 patients with chronic spinal cord disease were studied. Baclofen regularly alleviated involuntary flexor or extensor spasms and increased resistance to passive movement of the legs but did not alter strength, gait, stretch reflexes, or clonus. Side effects were mild and transient. This study demonstrates that (1) baclofen is useful for the treatment of flexor spasms and (2) in evaluating a new mode of therapy, one must consider selectively the response of individual components of such global syndromes as "spasticity."

A study of data on 30 patients with cervical spondylosis was carried out to determine whether short-latency somatosensory-evoked responses (SEPs) to median, ulnar, radial, and peroneal nerve stimulation provided additional information to that obtained by electromyography (EMG), late responses, and peripheral conduction studies. Peripheral studies, EMG results and SEPs were within normal limits in ten patients with pain, but without objective neurological deficit. By contrast, of ten patients who had objective signs of root compression, conventional EMG results were normal in nine, but abnormalities of the SEPs from radial nerve stimulation were obtained in only five patients, and were normal from ulnar and median nerve stimulation. In ten patients with clinical features of myelopathy, seven had abnormal median SEPs and all had abnormal peroneal SEPs, whereas EMG results were abnormal in only five patients. It is suggested that SEPs and EMG are both of limited use in patients with only symptoms of root compression. In patients with signs of root compression, EMG is the most sensitive procedure; however, some additional information can be obtained from superficial radial SEPs. In patients with cervical myelopathy, SEP was the most useful procedure, especially when upper and lower limbs were studied.

Five patients with essential tremor had a dramatic diminution in tremor amplitude within 15 minutes of ingesting small doses of ethyl alcohol. The same patients were given equivalent amounts of ethyl alcohol infused into a brachial artery, and there was no decrease in tremor amplitude in the perfused limb. It is concluded that, in patients with essential tremor, ethanol acts in a specific fashion on sensitive structures within the central nervous system and has no effect on peripheral tremorogenic mechanisms. This provides additional evidence for a central mechanism in essential tremor, distinguishing it from other tremors arising primarily from oscillation in peripheral servo-loops.

Patients with Parkinson's disease performed several different stereotyped elbow flexion tasks, and the electromyographic (EMG) patterns from biceps and triceps were compared with previously established normal standards. The EMG pattern during a smooth flexion task was almost always abnormal and was characterized by alternating activity in biceps and triceps. The EMG patterns during a fast flexion task were also usually abnormal although they were always composed of bursts of EMG activity of normal duration appearing alternately in the agonist and antagonist muscles. These bursts, associated with movements of the limb, have a superficially similar appearance to the EMG bursts seen with tremor-at-rest, but certain physiological differences are demonstrated. This study demonstrates that both slow (ramp) and fast (ballistic) movements are clearly abnormal in these patients with disease of the basal ganglia. In a task designed to investigate antagonist inhibition before agonist activity, a majority of the patients performed normally. This suggests that, contrary to previous claims, slowness of movement (akinesia/bradykinesia) is not due either to failure to relax or to rigidity of antagonist muscle.

Physiological and pharmacological studies of more than 150 patients with movement disorders are reported. Particular attention is paid to the differentiation of various types of tremor on the basis of rate, rhythm, and pattern of EMG activity in antagonistic muscles. The typical 'tremor-at-rest' of Parkinson's disease--3-7 Hz activity which alternates between antagonistic muscles--is suppressed, at least briefly, during voluntary activity, at which time typical 8--12 Hz 'physiological tremor' may be seen. Essential tremor and its familial or senile variants also have a characteristic EMG pattern during voluntary activity--5-8 Hz bursts of activity which are synchronous in antagonistic muscles. This type of tremor may also be present in patients with Parkinson's disease and in certain kinships with a Charcot-Marie-Tooth polyneuropathy. Other tremors in association with polyneuropathy ('neuropathic tremor') have different physiological characteristics. Myoclonus is of essentially two types ('positive' with EMG bursts and 'negative' with brief pauses in ongoing activity, as with asterixis) and may, at times, mimic tremor. Certain specific tremors respond predictably to specific pharmacological therapy.

One type of flexor reflex, that recorded from the tibialis anterior muscle in response to electrical stimulation of the sole of the foot, was studied in normal subjects and patients with several neurological disorders. Normally this reflex consists of two components, the second of which is related to the actual withdrawal. The first component, normally of lower threshold, is difficult to evoke in patients with chronic spinal cord or discrete cerebral lesions, whereas it has an unusually low threshold and is very clearly seen in those with Parkinson's disease. In patients with spinal cord disease, the exaggerated flexor reflexes are seen at long latencies after relatively small stimuli. During the early phase of recovery from spinal transection, both components may be seen and are, therefore, spinal in origin. Studies of patients with the sensory neuropathy of Friedreich's ataxia suggest that the afferent fibres responsible for these flexor reflexes are the small myelinated fibres. Recovery curves demonstrate very long-lasting changes in flexor reflex excitability in normal subjects and patients with `spasticity' from spinal lesions. This differs in patients with `spasticity' from lesions rostral to the brain-stem. Examples in man of such physiological phenomena as reciprocal inhibition, local sign, habituation, temporal and spatial summation are discussed.

Differential blocking of conduction in mammalian nerve fibers has been produced by irradiation of the whole nerve with focused ultrasound. The smallest (C) fibers are the most sensitive; the largest (A-alpha) fibers are the least vulnerable. Fully reversible blocking can be obtained with carefully graded doses of ultrasound.