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Biomedical subjects

C Krarup

Publications and source records attributed to C Krarup.

At least 19 recordsLinked to original sources

Peripheral sensory abnormalities in patients with multiple sclerosis.

Although multiple sclerosis primarily affects myelin within the central nervous system, both pathologic and physiological studies suggest that mild deficits in peripheral nervous system myelin may be common. To evaluate this question further, we performed near nerve studies on sural nerves of 14 patients with multiple sclerosis. Peak-to-peak amplitude and maximum conduction velocity were normal in 9 of 14 patients, while minimum conduction velocity, or the velocity of the slowest-conducting component of the sensory action potential, was abnormally reduced in 9 patients. In addition, the supernormal period was evaluated for patients and compared with a control sample; multiple sclerosis patients showed a significant reduction in the amplitude of supernormality. Both the reduction in minimum conduction velocity and the alteration in the supernormal period are consistent with a mild defect in peripheral myelin.

Action Potentials

Conduction studies of the normal sural nerve.

The sural nerve was studied orthodromically using the near-nerve technique in 273 normal subjects (155 females, 118 males) aged 5 to 90 years. The sensory action potential (SAP), evoked at the dorsum of the foot, was recorded at the lateral malleolus and midcalf, and at the midcalf when evoked at the lateral malleolus. In addition, the SAP was recorded at intermediate distal sites and at proximal sites at the popliteal fossa, the gluteal fold, and the S-1 root. The amplitude of the SAP recorded at midcalf was 32% higher in females than in males. This was probably due to volume-conduction properties, as differences between genders were less noticeable at more distal recording sites. The amplitude decreased steeply and exponentially with age. Conduction distance had a strong influence on the amplitude of the SAP, which decreased with increasing distance following a power relationship with an exponent of 1.4 to 1.7. This decrease was due to temporal dispersion with decreased summation and increased phase cancellation. The conduction velocity was slightly lower along the very distal course of the nerve than along more proximal segments.

Action Potentials

The influence of the stimulus on normal sural nerve conduction velocity: a study of the latency of activation.

Conduction along the sural nerve was studied in 64 normal subjects using near-nerve electrodes. Conduction velocities over the same nerve segments were calculated: (1) from the latency recorded from a site of stimulation to a site of recording (1R-method); and (2) from the difference in latency between 2 recording sites, the site of stimulation being situated elsewhere along the nerve (2R-method). Consistently faster velocities were seen with the 2R-method and could best be explained by a fixed delay of about 0.15 ms at the stimulus site (latency of activation, utilization time). This delay was markedly prolonged when a ramp rather than a rectangular stimulus was applied, though fast fibers were excited with both types of stimuli. The delay is thought to be dependent on the relationship between the density of current at the stimulus site and the threshold of responding fibers.

Adolescent

Recurrent potentials in human peripheral sensory nerve: possible evidence of primary afferent depolarization of the spinal cord.

To study slowly conducted components of the orthodromic compound sensory action potential (CSAP), the response evoked at the lateral malleolus in the sural nerve was recorded through near-nerve needles at two to four sites along the nerve at midcalf. When 500 to 2000 responses were averaged at high gain, components with latencies of 30 to 80 ms were often recorded. In contrast to the main component and late components with latencies of less than 15 to 20 ms, the latencies of these extremely late components diminished the closer to the spinal cord that they were recorded. This suggested that the components were conducted antidromically from proximal to distal. This assumption was supported by abolishing the components by local anesthesia of the nerve proximal to the recording electrodes. These antidromic potentials therefore appear to be due to recurrent discharges in the sural nerve. Recurrent discharges were recorded from 65% of 60 subjects (18 normal subjects and 42 patients with peripheral or central nervous system disorders). The latencies of the recurrent discharges allowed conduction to and back from the spinal cord. Although the origin of these potentials remains unknown, we suggest that they are due to dorsal root reflexes within the spinal cord. In this case, the responses may be a direct expression of primary afferent depolarization (PAD) seen in presynaptic inhibition, and may be of value in further studies on the physiology and pathophysiology of presynaptic inhibition of cutaneous fibers in man.

Action Potentials

Determination of the segmental sensory and motor innervation of the lumbosacral spinal nerves. An electrophysiological study.

The knowledge of the segmental innervation of the skin and muscles of the lower limb in man is inadequate. For this reason, sensory and motor segmental innervation of the lower extremities was examined by electrophysiological methods in 27 normal subjects, one patient with possible L5 radiculopathy and one with possible lumbosacral plexus affection. Needle electrodes were placed at root levels from L3 to S2 using bony landmarks. The electrode was then placed close to the spinal nerve as indicated by a low (less than or equal to 1 mA) threshold necessary to stimulate motor fibres. The position was controlled by X-ray in 10 subjects. Sensory innervation was determined by recording the sensory action potential evoked by stimulating the saphenous nerve at the medial epicondyle (mainly L3 and L4) and at the medial malleolus (mainly L4 and in some L3), the medial plantar nerve at the first plantar interstice (mainly S1, some L5 and S2), the deep peroneal nerve at the first dorsal interstice (mainly L5, some S1), the sural nerve at the dorsolateral aspect of the foot (mainly S1, some L5 and S2) and at the lateral malleolus (mainly S1, some L5 and S2), and the superficial peroneal nerve at the superior extensor retinaculum (mainly L5, S1). The motor innervation was determined by stimulating the spinal nerves supramaximally and recording the evoked responses from the medial and lateral vastus (mainly L3, L4), the anterior tibial (mainly L5), the peroneus longus (L5, S1), the extensor digitorum brevis (mainly S1), the gastrocnemius (mainly S1), the abductor hallucis (mainly S2) and the biceps femoris (mainly L5, S1). Sensory and motor conduction velocity measurements along the leg and across the lumbosacral plexus indicated that there was no difference in a disto-proximal direction, except for a 10% reduction along the most distal part of the sural nerve which, however, might be explained by utilization time. There was therefore no evidence of gradual tapering of nerve fibres in a distal direction. The proximal motor conduction velocity to the most distally placed muscle (abductor hallucis) was about 20% lower than to the proximally placed muscles (gastrocnemius and biceps femoris) suggesting a general difference in fibre calibre.

Action Potentials

[Chronic inflammatory demyelinating polyradiculoneuropathy].

During recent years chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) has been characterized on the basis of clinical and laboratory findings. Immune modifying treatment with glucocorticoids, plasma exchange and infusion of immune globulins has had a therapeutic effect in controlled studies. Decisive for increased therapeutic efforts against CIDP in Denmark is intensified electrophysiological search in patients with polyneuropathy with examination of several nerve segments for evidence of demyelination including conduction block, potential dispersion and reduction of conduction velocity by more than 40%.

Chronic Disease

[Immunomodulator therapy of chronic inflammatory demyelinating polyradiculoneuropathy].

A group of 6 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was treated with prednisone, azathioprine, plasma exchange and/or intravenous immunoglobulin. Three of the six patients improved during treatment with prednisone and two patients with severe CIDP both showed a remarkable therapeutic response to treatment with intravenous immunoglobulin.

Adjuvants, Immunologic

A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Slowly conducting myelinated fibers in peripheral neuropathy.

The main component of the compound sensory action potential reflects the activity of large myelinated sensory fibers with diameters of greater than 9 micron(s). By recording the averaged potential using a needle electrode placed close to the nerve, small late components can be measured. The latency of these late components can be used to calculate minimum conduction velocity (CV); in normal subjects, average minimum CV is 15 m/s, corresponding to conduction in fibers of about 4 micron(s) in diameter. Minimum CV was measured in median, ulnar, and sural nerves of 187 patients with mild to severe neuropathic symptoms. A reduction in minimum CV was a sensitive measure of peripheral nerve dysfunction, often showing abnormalities when measures derived from the main component were normal. Patients with isolated abnormalities in minimum CV tended to have neuropathic symptoms but no signs of neuropathy. In addition, reduced minimum conduction velocity has implications for the pathology of different types of neuropathy. Slowing conducting potentials may originate from regenerating fibers, which may be of particular relevance in patients with neuropathic pain.

Action Potentials

Abnormalities in the sensory action potential in patients with amyotrophic lateral sclerosis.

Sensory function in patients with amyotrophic lateral sclerosis (ALS) is thought to be normal; however, there is convincing morphologic evidence that sensory systems are affected in addition to motor systems. In this study, compound sensory action potentials were recorded with near nerve electrodes from 18 patients with ALS. Up to 1024 responses were averaged at high gain to determine minimum conduction velocity; that is, the conduction velocity of the slowest conducting component of the sensory action potential. Nine of 18 patients had abnormally reduced minimum conduction velocity, even when peak-to-peak amplitude and maximum conduction velocity (calculated from the latency to the initial positive peak) were normal. Only 3 of 18 patients showed abnormalities in peak-to-peak amplitude. Thus, subtle abnormalities in the sensory action potential can be detected in many patients with ALS.

Action Potentials

The carpal tunnel syndrome: diagnostic utility of the history and physical examination findings.

STUDY OBJECTIVE: To assess the value of a history and physical examination findings in diagnosing the carpal tunnel syndrome, and to determine whether constellations of clinical findings identify patients at high or low risk for the carpal tunnel syndrome. DESIGN: Comparison of diagnostic tests with neurophysiologic testing. SETTING: Patients with upper extremity complaints of diverse causes referred to a neurophysiology laboratory for diagnostic studies. METHODS: Before nerve conduction testing, a history, demographic and physical examination data, and a hand pain diagram were obtained from each patient. Diagrams were categorized as indicating the classic carpal tunnel syndrome, or as probable, possible, or unlikely to indicate the carpal tunnel syndrome. Associations between clinical data and nerve conduction results were examined in univariate and multivariate analyses. RESULTS: Of 110 patients in the study, 44 (40%) had the carpal tunnel syndrome. Individually, the best predictors were hand pain diagram rating (positive predictive value, 0.59; 95% CI, 0.48 to 0.68) and Tinel sign (positive predictive value, 0.55, CI, 0.45 to 0.65). The combination of a positive Tinel sign and a probable or classic diagram rating had a positive predictive value of 0.71; CI, 0.53 to 0.85. Other findings from physical examination and the history were less useful. Just 9% of patients under 40 years of age with possible or unlikely diagram ratings had the carpal tunnel syndrome. CONCLUSIONS: With the exceptions of age, Tinel sign, and hand pain diagram rating, findings from the physical examination and the history had limited diagnostic utility. Patients under 40 years of age with possible or unlikely diagram ratings were at low risk for the carpal tunnel syndrome. This finding, which should be confirmed in an independent population, suggests that subsets of patients may be managed without nerve conduction studies.

Adult

Nerve regeneration and reinnervation after limb amputation and replantation: clinical and physiological findings.

A 22-year-old male was studied 3 1/2-4 1/2 years after a traumatic section-avulsion amputation of the left upper extremity at the level of the distal humerus. The arm was reattached after a cold ischemia time of 4-5 hours and good vascularization was obtained. The ulnar nerve was repaired early with an end-to-end juncture while the median and radial nerves were repaired after seven months delay using a combination of vascularized radial nerve and nonvascularized sural nerve grafts. Some intrinsic hand muscle function had recovered. Pin-prick and touch sensation was present in all digits, although localization of touch stimulation was poor. Evoked motor responses had recovered by 25-50% of control amplitude in ulnar-innervated and by 10-25% in median-innervated muscles. Amplitudes of sensory responses from digit V had recovered by 25% and from digits I and III by 1-5%. Fast-adapting touch receptors had become reinnervated. There was electrophysiological evidence of aberrant sensory regeneration and of abnormal connections between sensory and motor fibers. Digital blood flow measurements suggested the presence of vascular obstruction in vessels of the replanted upper extremity. However, the digital vasoconstriction during cold exposure indicated regeneration of sympathetic nerve fibers.

Adult

A syndrome of asymmetric limb weakness with motor conduction block.

We describe 3 patients with asymmetric limb weakness, fasciculations (2 patients), relatively preserved reflexes, normal cranial nerves, and few or no sensory abnormalities. The symptoms had been progressive over 1 to 15 years. Detailed motor nerve conduction studies showed conduction block and slowing localized to sharply circumscribed areas 30 to 100 mm long in several nerves in each patient. By contrast, the sensory conduction studies over the same nerve segments were normal, indicating very selective involvement of motor fibers. Sural nerve biopsies showed minor changes that varied among the patients. One patient had high levels of anti-GM1 antibodies, 1 had mildly elevated levels, and 1 had high levels of only asialo-GM1 antibodies. Treatment with immune suppressive therapy has produced minimal improvement in 1 patient.

Electrophysiology

Perioperative nerve lesions.

The scenario is all too familiar. A patient has a surgical procedure. Anesthesia is uneventful and the procedure goes well. Nothing untoward is observed in the recovery room. Later that evening the patient complains of numbness, weakness, or pain, and a neurological deficit is found. A neurologist is called, examines the patient, and it is concluded that a nerve lesion has occurred, because of stretch, ischemia, compression, or laceration. A subsequent electromyogram and nerve conduction study confirm the clinical impression, but offer little in the way of explanation. Over the subsequent months, the patient makes a slow recovery but there has been a prolonged period of pain and disability. Liability issues loom. This scenario could reflect a number of different nerve lesions. This review illustrates the different modes of pathogenesis that may occur and the variable nature of the neurological deficits. We grouped these lesions according to the clinical setting in which they occur.

Brachial Plexus

Modulation of the bulbocavernosus reflex during voiding: loss of inhibition in upper motor neuron lesions.

The bulbocavernosus reflex (BCR) is a sacral segmental reflex which is suppressed throughout most of micturition. The BCR was evaluated by recording the associated EMG activity using a concentric needle electrode placed in the external urethral sphincter. The influence of the central nervous system (CNS) on the BCR was studied in 29 neurologically normal individuals and in 33 patients with upper motor neuron (UMN) lesions and voiding dysfunction. Ninety percent (26/29) of the neurologically normal patients did not have a BCR during most of micturition. By comparison, all the patients with an UMN lesion had a positive BCR beginning early during voiding. The finding of suprasegmental modulation of the BCR during voiding demonstrated by external urethral sphincter EMG was a more sensitive although slightly less specific sign of UMN bladder dysfunction than detrusor sphincter dyssynergia; uninhibited bladder contractions were neither sensitive nor specific for UMN lesions.

Adolescent

Conduction studies in peripheral cat nerve using implanted electrodes: III. The effects of prolonged constriction on the distal nerve segment.

Electrophysiological properties were monitored in detail in chronically constricted peripheral nerves by implanted, multicontact nerve cuff electrodes and correlated with morphometric histology in selected cases. The physiological and histological responses in nerve to a range of constricting cuffs of standard sizes were readily graded. The initial response to any significant constriction was a transient, focal conduction slowing or block at the constriction, followed by more protracted distal effects; the latter ranged from loss of excitability consistent with "dying-back" degeneration to reductions in conduction velocity consistent with histologically observed atrophy. Smaller myelinated fibers tended to have similar but less pronounced changes than larger diameter fibers. Recordings from ventral and dorsal roots showed that distal degeneration was more pronounced in motor than in sensory fibers of similar caliber. Electronmicroscopical measurements showed that basal laminas were relatively preserved around even the most atrophic and demyelinated axons. Perimeter measurements of the basal lamina could be used to estimate the diameter of the original nerve fiber.

Animals

Idiopathic brachial plexus lesion with conduction block of the ulnar nerve.

A 24-year-old male with idiopathic acute aching of the right wrist, weakness of ulnar innervated muscles of the forearm and hand, and numbness of the ulnar two digits, was examined electrophysiologically. Conduction studies showed almost complete conduction block of motor fibers of the ulnar nerve distally in the brachial plexus. Sensory fibers were less affected. The symptoms and pathophysiological findings improved over a period of 1-2 months and were normal at the final study performed 7 months after presentation. There was mild evidence of chronic partial denervation of the abductor digiti V and the flexor digitorum profundus of the two ulnar digits. There were additional mild EMG changes of the abductor pollicis muscle indicating minor involvement of the median nerve. There was no traumatic or other obvious cause for these findings. It is suggested that the patient had a mild and abortive form of brachial plexus neuropathy presenting as a demyelinating lesion rather than the more typical wallerian degeneration seen in most established cases.

Action Potentials

The unrecognized neuropathic bladder of infancy.

Four infants presented with hydroureteronephrosis and incomplete emptying of the bladder secondary to detrusor-sphincter dyssynergia. None of the patients had other signs suggestive of neurological dysfunction. It is presumed but not proved that these infants manifested a urodynamic reaction in response to a perinatal insult involving the brainstem area. Long-term followup has demonstrated a persistent but nonprogressive neurourological disturbance.

Electromyography