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Clinical results of contralateral C7 root neurotization to the median nerve in brachial plexus injuries with total root avulsions.

This prospective study was carried out to assess motor and sensory recovery after contralateral C7 root to median nerve neurotization in brachial plexus injuries with total root avulsions. The survey was carried out from 1993 to 1995 and the patients were followed up for at least 3 years. There were 96 male patients with ages ranging from 13 to 48 years. All had a unilateral brachial plexus injury with avulsion of all roots. This was confirmed by clinical assessment and exploration. The anterior part of the contralateral C7 root was used for neurotization via a reversed pedicular ulnar nerve graft and the proximal end of the graft was connected to the median nerve. Furthermore, phrenic nerve to suprascapular nerve and spinal accessory nerve (via a sural nerve graft) to musculocutaneous nerve neurotizations were also carried out to obtain shoulder abduction and elbow flexion. At the 3 year follow-up, most patients had encouraging recovery of sensory function in the hand but motor function of the forearm and hand muscles was rather poor. Acceptable motor function was found in only 50 to 60% of the patients who were younger than 18 years.

Adolescent↗

Normalized Southern Hybridization to Enhance Testing for Charcot-Marie-Tooth Disease, Type 1A.

Background: Charcot-Marie-Tooth disease, type 1A (CMT,1A) is a common autosomal dominant neuromuscular disorder, which affects both motor and sensory function and is characterized usually by duplication of a region on chromosome 17 through unequal crossover. As a result, affected patients carry three copies of this region. Individuals inheriting the other deleted chromosome involved in the crossover have one copy of the region and manifest herditary neuropathy with susceptibility to pressure palsies (HNPP). One diagnostic approach to CMT,1A exploits Southern blot hybridization and the relative intensity for three polymorphic MspI restriction fragment lenth polymorphism bands within the duplicated area to judge whether patients have two or three copies of this region using a probe such as VAW409R3A. This is usually straightfoward and works well for the majority of samples that display polymorphisms. However, it is difficult to judge dosage for this region in patients who do not demonstrate polymorphic bands. Methods and Results: An assay has been developed in which a simultaneously hybridized probe (pH15), which detects a nonpolymorphic band on chromosome 22 generated by the same restriction enzyme used to digest genomic DNA, is used to normalize the signal from the CMT,1A probe after phosphorimager analysis. Normalized ratios for VAW409R3A-hybridizing Southern bands fell within discrete ranges for patients with three copies (2.72-3.69), two copies (1.60-2.40) and one copy (0.75-1.30) of this region in over 45 patient and control samples studied. Conclusions: This assay appears to provide a reliable and consistent method of analysis.

Journal Article↗

[Diagnosis and treatment of trauma to blood vessels around the knee joint (author's transl)].

Eighteen arterial reconstructions after trauma in the region of the knee joint were performed between 1970 and 1976. In seven cases there had been fracture of the distal femur, in five of the head of the tibia, in three dislocation of the knee joint or severe contusion of the popliteal artery. In 12 cases referral had been eight hours or later after injury. The concomitant vessel injury was not recognised in six. Vascular reconstruction by direct suture with a venous patch was performed in eight, interposition of a venous autograft in five, and saphenous vein bypass in four. Results depended upon length of ischaemia time and the level of the vascular injuries. Complete restitution to normal was achieved in only two cases, while in the remaining 12 there were defects of motor and sensory function as seen in the post-ischaemia syndrome. In four cases above-knee amputation was necessary despite successful reconstruction of the artery because there was irreversible ischaemic damage with tissue necrosis. To improve these results careful examination of blood vessels and, in questionable cases, angiography is recommended for every trauma victim.

Amputation, Surgical↗

[Diabetic somatic polyneuropathy. Pathogenesis, clinical manifestations and therapeutic concepts].

Diabetic polyneuropathy is the most frequent neuropathy in western countries. In Germany, there are 3.5 to 4 million diabetic patients. Diagnosis should rule out other polyneuropathies and assess two out of the five diagnostic criteria: neuropathic symptoms, neuropathic deficits, pathological nerve conduction studies, pathological quantitative sensory testing and pathological quantitative autonomic testing. So far, the pathophysiology of diabetic neuropathy remains to be fully understood. Among the various pathophysiological concepts are the Sorbitol-Myo-Inositol hypothesis attributing Myo-Inositol depletion to the accumulation of Sorbitol and Fructose, the concept of deficiency of essential fatty acids with reduced availability of gamma-linolenic-acid and prostanoids, the pseudohypoxia- and hypoxia-hypothesis attributing endothelial and axonal dysfunction and structural lesions to increased oxidative stress and free radical production. Obviously, the hyperglycemia induced generation of advanced glycation end products (AGEs) also contributes to structural dysfunctions and lesions. Elevated levels of circulating immune complexes and activated T-lymphocytes as well the identification of autoantibodies against vagus nerve or sympathetic ganglia support the concept of an immune mediated neuropathy. The reduction of neurotrophic factors such as nerve growth factor, neurotrophin-3 or insulin-like growth factors also seems to further diabetic neuropathy. The symmetrical, distally pronounced and predominantly sensory neuropathy is far more frequent than the symmetrical neuropathy with predominant motor weakness or the asymmetrical neuropathy. The painless neuropathy manifests with impaired light touch sensation, position sense, vibratory perception and diminished or absent ankle deep tendon reflexes. The painful sensory diabetic neuropathy primarily affects small nerve fibers and accounts for decreased temperature perception and paresthesias. The proximal, diabetic amyotrophy evolves subacutely or acutely, induces motor weakness of the proximal thigh and buttock muscles and is painful. Cranial nerve III-neuropathy is also painful and has an acute onset. Truncal radiculopathy follows the distribution of truncal roots and frequently causes intense pain. Autonomic neuropathy occurs with and without somatic neuropathy. The most important therapy is to attempt optimal blood glucose control, to reduce body weight and hyperlipidemia. Symptomatic therapy includes alpha-lipoic acid treatment, as the antioxidant seems to improve neuropathic symptoms. Aldose reductase inhibitors might reduce sorbitol and fructose production and normalize myo-inositol levels. However, there are no aldose reductase inhibitors available in Europe as yet. Evening primrose oil, containing gamma-linolenic acid, might improve nerve conduction velocities, temperature perception, muscle strength, tendon reflexes and sensory function. Substitution of nerve growth factor showed promising results in pilot studies but failed in a large-scale multicenter study. Symptomatic pain treatment can be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, anticonvulsants such as carbamazepine, gabapentin or lamotrigine, or anti-arrhythmic drugs such as mexiletine. Topical capsaicin application should reduce neuropathic pain but also induces local discomfort in the beginning of therapy. Vasoactive substances, so far have not proven to be of major benefit in diabetic neuropathy. Physical therapy and thorough footcare are of primary importance and allow prevention of secondary complications such as foot amputations.

Diabetic Neuropathies↗

Microsurgical posterior fossa exploration for trigeminal neuralgia: a study on 48 cases.

The authors present their experience in the microsurgical treatment of trigeminal neuralgia (TGN). Over the last five years 48 patients were explored and 34 (71 %) underwent microvascular decompression (MVD) for significant arterial or venous conflicts. The remaining 14 patients (29 %) underwent partial sensory rhizotomy (PSR) because of negative intraoperative findings (simple contact or no conflict). Excellent or good immediate outcomes were achieved in 87.5 and 12.5 % of patients, respectively. Of the three severe recurrences observed during the follow-up period (24.7 months; range: 7 - 65 months), two underwent percutaneous microcompression and one posterior fossa reexploration, which revealed teflon-induced recompression. None of the PSR cases experienced incapacitating face numbness. MVD, an extremely effective procedure in the immediate post-operative period, is burdened in the long term by 20 % recurrences, the majority occurring within two years from surgery. We believe that careful intraoperative evaluation of the conflict entity could be the key to achieve a significant reduction of recurrences: overestimation of simple vascular contact of doubtful etiologic relevance, may lead to ineffective decompression and unsatisfactory results. In our opinion PSR should be preferred to percutaneous treatments in cases of negative exploration (contact or no conflict). In accordance with others we observed that section of half or less of the inferolateral "portio major" allows long-lasting pain relief and good preservation of sensory function.

Adult↗

[Secondary nerve reconstruction in the upper extremity in children--results with respect to number of motor units].

After nerve injury, the therapy of choice is primary suture. If this, however, is not possible or inadequate, a secondary reconstruction must be carried out within a suitable period of time. This study shows results after nerve transplantation within a timeframe of six weeks. Seventeen children with peripheral nerve injuries of the upper extremity were treated. Secondary nerve reconstruction was accomplished by sural nerve transplantation. Eight children, aged from 5 to 13 years, were examined. The median nerve was affected in three and the ulnar nerve in five cases. The examination included clinical and electrophysiological assessments. The length of grafts was correlated with the clinical result. Besides the calculation of sensitive and motor nerve conduction velocity the number of motor units from the flexor pollicis brevis muscle or abductor digiti minimi muscle were determined by motor-unit-estimation (MUE) on both sides. The observation time period was on an average 2.9 years. Results were good to excellent. A persisting Hoffmann-Tinel's sign was found only once in median nerve lesion. Loss of sensitivity following harvesting of sural nerve was not noted as a problem by any of these children. Length of grafts did not affect the results. Standard values were reached in every case in the electrophysiological examination. The number of motor units of the abductor pollicis brevis muscle and abductor digiti minimi muscle decreased to approximately 50% compared to the healthy side. Sural nerve grafting resulted in good motor and sensory function. We recommend grafting within six weeks, as Wallerian degeneration is completed and regeneration from the proximal nerve stump is optimal. Although children have a very good regeneration potential, the examined cases did not achieve a complete restoration of all motor units of the muscles.

Action Potentials↗

Long-term results of toe transfer: retrospective analysis.

Between February 1966 and February 1994, 400 cases of toe transplantation were analyzed, to evaluate toe-transfer procedures in thumb and finger reconstruction. Techniques utilized included single second-toe transfer, with and without the metatarsophalangeal joint (299): second- and third-toe transfer (28); second-toe and third proximal phalanx transfer (1); second-toe with flap transfers (66); and hallux nail flap with second toe or second and third toe transfer (6). There was a survival rate of 96.5 percent, with 386 cases surviving and 14 failing. A more than 2-year follow-up was possible in 240 cases. Excellent motor and sensory function (more than 90 percent of normal) was achieved in the reconstructed fingers and thumbs, as well as satisfactory function (between 86 and 91 percent of normal) in the donor foot.

Adolescent↗

Salvage of wounds following failed tissue transplantation.

During the past 20 years, 972 microvascular transplantations have been performed for 783 patients, with an overall failure rate of 6.2 percent. Fifty-four of the 60 failed transplantations were available for long-term follow-up and were retrospectively reviewed with respect to the original indications for transplantation, the number, and the type of salvage procedures performed following transplant failure. This study illustrates that the choice of salvage procedures performed following transplant failure depends on the original indications, the location, and the severity of the resultant wound. Failure following transplantation for coverage of contour defects or unstable wounds can often be managed by non-microsurgical methods. In contrast, when the indications for transplantation included the transfer of specialized tissues for thumb or digit reconstruction, the restoration of motor or sensory function, or the coverage of a limb-threatening wound, requirements for reconstruction could be satisfied only by a second successful tissue transplant. Eighteen of the 54 cases underwent an additional transplantation, with an 89 percent success rate.

Adolescent↗

A case of replantation of a completely amputated digit after 26 hours of warm ischemia.

A seven-year-old-boy received a digit replantation after 26 hours of warm ischemia and showed good recovery of motor and sensory functions. In the case reported, replantation was performed after a much longer ischemic time than had been considered an indication for the procedure in previous reports. Successful replantation and revascularization can thus be achieved, even in cases of extensive warm ischemia.

Amputation, Traumatic↗

[Acute spinal syndromes in children and adolescents].

23 children with acute spinal syndromes are presented. The clinical signs were caused by trauma in 11 patients, by extramedullary tumors in 6, by operations (coarctation of the aorta, scoliosis) in 4 and by encephalomyelitis in 2. Motor signs (flaccid paraplegia or paraparesis, monoplegia, bilateral weakness) and changes of reflex intensities were always observed. Most children presented with disturbances of sensory functions and micturition, some exhibited ataxia. In addition to the neurological signs, plain films of the spine were of diagnostic importance after trauma, for tumors myelography and/or computerized tomography were most useful. The unfavourable prognosis of posttraumatic paraplegia may be improved by early application of corticosteroids in very high doses. The value of GM1-ganglioside is controversial. In cases of external compression by tumors a decompression of the spinal cord is urgent. "Spinal cord monitoring" can be used intraoperatively in surgery of scoliosis and coarctation of the aorta to detect neurological complications early. Differential diagnosis and therapies of encephalomyelitis and Guillain-Barré-Syndrome are discussed.

Adolescent↗

[Forensic evaluation of physical damage in the early Middle Ages--a comparison with current occupational disability guidelines].

The legal systems of the Germanic tribes in the early Middle Ages elaborated detailed catalogs of forfeits in compensation for certain physical injuries. The perpetrator had to pay the forfeit to the injured person, or in case of manslaughter, to the tribe of the dead. By doing so he could avert the feud which otherwise faced him. These catalogs of forfeits exactly reflect the relative value that was appointed to certain parts of the body and to sensory functions. The catalog of the Lex Saxonum (c. 802), in which physical injuries are listed, ranging from loss of single phalanges, differentiated between thumb, forefinger, small finger, and the other fingers, to death, is compared with modern grades of disability. There are surprising parallels and interesting contrasts. Bilateral deafness is put on a level with bilateral blindness, the loss of both hands, both feet, both testicles, and death.

Disability Evaluation↗

Intraoperative monitoring of median nerve somatosensory evoked potentials in cervical syringomyelia: analysis of 28 cases.

Intraoperative median nerve somatosensory evoked potentials (SEP) were monitored in 28 patients undergoing surgery for cervical or cervicothoracic syringomyelia. Analysis was focused on SEP components N13 (spinal cord), P14 (brain stem), and N20 (cortex). N13 was lacking in nearly 87% of the patients (due to a combined effect of syringomyelia and general anesthesia) and never recovered. P14 showed a significant (> 10%) intraoperative latency increase in two patients; this was irreversible in one patient who had a postoperative worsening of sensory function. N20 showed no relevant alterations. Pure motor deficits after surgery were not predicted by SEP monitoring. In conclusion, intraoperative P14 recording helped to identify harm to the dorsal columns and probably prevented the cord from irreversible damage in one case, whereas N13 recording did not contribute to the monitoring of spinal cord function during surgery for syringomyelia.

Adult↗

[Critical ischemia of the extremities caused by ergotism. Treatment with intra-arterial prostaglandin E1 infusion].

Severe ischaemia of the left upper limb developed in a 42-year-old woman (who had suffered from migraine since the age of 6 years) after the intake of 12 mg ergotamine tartrate (six suppositories of Cafergot within 5 hours). The left hand became very painful and pale with loss of touch sensation, and she could not move her fingers. Selective catheter angiography demonstrated typical signs of vascular ergotism: arterial spasms, corkscrew-like collaterals and segmental arterial occlusions. The patient's symptoms began to improve 10 minutes after starting an intraarterial infusion of prostaglandin E1 (0.34 ng/kg per min over 10 hours). Sensory function in the fingers was restored after 24 hours and reactive hyperaemia had occurred. Radiological examination after 48 hours showed complete recovery. This case emphasizes the need for obtaining an exact history regarding drug intake in any case of acute peripheral vascular disorder, but especially if there is no pointer to arterial thromboembolism. Angiography is of value in the differential diagnosis of suspected ergotism. Intraarterial infusion of prostaglandin E1 has few side effects and is immediately effective.

Adult↗

A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study.

Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurological examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eight hours of their injury had significant improvement as compared with those given placebo in motor function (neurologic change scores of 16.0 and 11.2, respectively; P = 0.03) and sensation to pinprick (change scores of 11.4 and 6.6; P = 0.02) and touch (change scores, 8.9 and 4.3; P = 0.03). Benefit from methylprednisolone was seen in patients whose injuries were initially evaluated as neurologically complete, as well as in those believed to have incomplete lesions. The patients treated with naloxone, or with methylprednisolone more than eight hours after their injury, did not differ in their neurologic outcomes from those given placebo. Mortality and major morbidity were similar in all three groups. We conclude that in patients with acute spinal-cord injury, treatment with methylprednisolone in the dose used in this study improves neurologic recovery when the medication is given in the first eight hours. We also conclude that treatment with naloxone in the dose used in this study does not improve neurologic recovery after acute spinal-cord injury.

Acute Disease↗

Enhancing aperiodic stochastic resonance through noise modulation.

We show that the conventional stochastic resonance (SR) effect for aperiodic signals in a model neuron can be enhanced by modulating the intensity of the input noise (which could be introduced artificially in bioengineering applications) with either the input signal or the unit's output rate signal. We analyze SR enhancement theoretically and numerically. We discuss how this work provides the theoretical foundation for the development of an optimal noise-based technique for enhancing sensory function. (c) 1998 American Institute of Physics.

Journal Article↗

An effective treatment protocol for intraarterial drug injection.

Between 1972 and 1988, 48 patients with extremity ischemia after an intraarterial drug injection were treated with the following protocol: heparin, dextran 40, dexamethasone, elevation, and early mobilization of the extremity. A tissue ischemia score, derived by assessing the color, capillary refill, sensory function, and temperature of the extremity, was used to assess the ischemic injury. Each sign was scored either normal = 0 or abnormal = 1; then summed to provide the tissue ischemia score (range, 0 to 4). Twenty-four (50%) patients had an extremity tissue ischemia score less than or equal to 2. After treatment 22 of the 24 patients had a normal extremity, and 2 required limited digital amputations. In this group, outcome was comparable regardless of the time interval from intraarterial drug injection to treatment. Ten of 24 (50%) patients with an extremity tissue ischemia score greater than 2 had a normal extremity, 3 had a functional deficit, and 11 required digital amputations. Twelve of the 24 patients were treated within 24 hours and had a significantly superior outcome when compared to the 12 who were treated more than 24 hours after intraarterial drug injection (p less than 0.001, Fisher's exact test). The tissue ischemia score is a useful predictor of extremity outcome in patients with intraarterial drug injection. The outlined treatment protocol is effective in minimizing tissue injury caused by intraarterial drug injection. Institution of treatment within 24 hours of intraarterial drug injection is particularly important in patients who manifest severe ischemia.

Adult↗

Dimerized Drosophila myosin VIIa: a processive motor.

The molecular mechanism of processive movement of single myosin molecules from classes V and VI along their actin tracks has recently attracted extraordinary attention. Another member of the myosin superfamily, myosin VII, plays vital roles in the sensory function of Drosophila and mammals. We studied the molecular mechanism of Drosophila myosin VIIa, using transient kinetics and single-molecule motility assays. Myosin VIIa moves along actin filaments as a processive, double-headed single molecule when dimerized by the inclusion of a leucine zipper at the C terminus of the coiled-coil domain. Its motility is approximately 8-10 times slower than that of myosin V, and its step size is 30 nm, which is consistent with the presence of five IQ motifs in its neck region. The kinetic basis for the processive motility of myosin VIIa is the relative magnitude of the release rate constants of phosphate (fast) and ADP (slow) as in myosins V and VI. The ATPase pathway is rate-limited by a reversible interconversion between two distinct ADP-bound actomyosin states, which results in high steady-state occupancy of a strongly actin-bound myosin species. The distinctive features of myosin VIIa (long run lengths, slow motility) will be very useful in video-based single-molecule applications. In cells, this kinetic behavior would allow myosin VIIa to exert and hold tension on actin filaments and, if dimerized, to function as a processive cargo transporter.

Animals↗

Single-molecule detection of structural changes during Per-Arnt-Sim (PAS) domain activation.

The Per-Arnt-Sim (PAS) domain is a ubiquitous protein module with a common three-dimensional fold involved in a wide range of regulatory and sensory functions in all domains of life. The activation of these functions is thought to involve partial unfolding of N- or C-terminal helices attached to the PAS domain. Here we use atomic force microscopy to probe receptor activation in single molecules of photoactive yellow protein (PYP), a prototype of the PAS domain family. Mechanical unfolding of Cys-linked PYP multimers in the presence and absence of illumination reveals that, in contrast to previous studies, the PAS domain itself is extended by approximately 3 nm (at the 10-pN detection limit of the measurement) and destabilized by approximately 30% in the light-activated state of PYP. Comparative measurements and steered molecular dynamics simulations of two double-Cys PYP mutants that probe different regions of the PAS domain quantify the anisotropy in stability and changes in local structure, thereby demonstrating the partial unfolding of their PAS domain upon activation. These results establish a generally applicable single-molecule approach for mapping functional conformational changes to selected regions of a protein. In addition, the results have profound implications for the molecular mechanism of PAS domain activation and indicate that stimulus-induced partial protein unfolding can be used as a signaling mechanism.

Anisotropy↗