Selectivity of intramuscular stimulating electrodes in the lower limbs.

Intramuscular (IM) electrodes have been used safely and effectively for decades to activate paralyzed muscles in neuroprosthetic systems employing functional electrical stimulation (FES). However, the response to stimulation delivered by these and any type of electrode can be limited by a phenomenon known as spillover, in which the stimulus intended to produce a contraction in a particular muscle inadvertently activates another muscle, causes adverse sensation, or triggers undesired reflexes. The purpose of this retrospective study was to determine the selectivity of monopolar intramuscular stimulating electrodes implanted in the lower limbs of individuals with motor and sensory complete paraplegia secondary to spinal cord injury (SCI) and to catalog the most common electrode spillover patterns. The performance records of 602 electrodes from 10 subjects who participated in a program of standing and walking with FES in our laboratory over the past decade were examined. Sixty percent (358) of these electrodes were "stable" (i.e., stimulated responses were consistent during the first 6 months postimplant), and 32% of all stable electrodes (113) exhibited spillover as noted in clinical and laboratory records. Common spillover patterns for eight muscle groups were tabulated and analyzed in terms of their functional implications. The beneficial (activation of synergistic muscles) or deleterious (activation of compromising reflexes, antagonists, or adverse sensation) effects of spillover were highly context dependent, with several potentially useful spillover patterns in certain phases of gait becoming undesirable and limiting in others. Knowledge of the selectivity of intramuscular electrodes and the patterns of spillover they exhibit should guide surgeons and rehabilitationists installing lower-limb neuroprostheses during the implantation process and allow them to better predict the ultimate functional usefulness of the electrodes they choose.

Effects of stimulated hip extension moment and position on upper-limb support forces during FNS-induced standing--a technical note.

This study explores the effects of active hip extension moment produced by electrical stimulation on the support forces the arms must exert through an assistive device during quiet erect standing with functional neuromuscular stimulation (FNS) in individuals with spinal cord injuries (SCI). A static sagittal plane biomechanical model of human standing was developed to predict the effects of stimulated hip extension moment and sagittal plane hip angle on the arm support necessary to maintain an upright posture. Two individuals with complete thoracic SCI were then tested while they stood with continuous stimulation to the knee and trunk extensors. The steady-state active extension moment exerted at the hip was varied by activating different combinations of hip extensor muscles with continuous stimulation while steady-state support forces applied to the arms and feet during standing were measured. The steady-state support forces imposed on the arms during quiet standing decrease with increased stimulated hip extension moment and are highly dependent upon hip flexion angle, as predicted by the biomechanical simulations. Experimentally, the combination of gluteus maximus and semimembranosus stimulation produced three times more steady-state hip extension moment than did stimulation of the gluteus maximus and adductor magnus. This resulted in a ten-fold decrease in body weight supported on the arms. More vertical postures (smaller hip flexion angles) improve the effectiveness of the hip extensor muscles in reducing the support forces placed on the arms. A single Newton-meter of stimulated hip extension moment with the hips fixed at 5 degrees of flexion results in almost five times the reduction in arm support forces as with the hips at 20 degrees. To minimize the forces applied by the arms on an assistive device for support while standing with FNS, these preliminary results suggest that (1) efforts should be made to assume the most erect postures possible and (2) muscles and stimulation paradigms that maximize active hip extension moment should be chosen.

Surgical technique for installing an eight-channel neuroprosthesis for standing.

A standardized surgical procedure to implant an eight-channel functional neuromuscular stimulation system in the lower extremities for standing, exercise, and transfers for individuals with spinal cord injury has been developed. The implanted components include: (1) one eight-channel receiver-stimulator, (2) epimysial electrodes, (3) intramuscular electrodes, and (4) inline connectors. The development process included identifying the target muscle set for electrode placement and the corresponding surgical approaches, determining the stages of the surgical procedure, and assessing the effectiveness and stability of the implanted neuroprosthesis. The bilateral muscle set consists of the vastus lateralis, the gluteus maximus, the semimembranosus, and the erector spinae. Surgical approaches to the nerve entry points were developed through a series of cadaveric studies and intraoperative tests. Electrode placement is related to bony landmarks and based on standard orthopaedic approaches. The components of the neuroprosthesis are installed in one surgical session, with three stages. This procedure has been applied successfully in seven individuals, resulting in strong, isolated stimulated contractions adequate to raise and lower the body, maintain standing with a walker, and perform pivot transfers. The standardized surgical procedure is repeatable and teachable and will be used in upcoming multicenter clinical trials of the implanted neuroprosthesis.

Architecture of the rectus abdominis, quadratus lumborum, and erector spinae.

Quantitative descriptions of muscle architecture are needed to characterize the force-generating capabilities of muscles. This study reports the architecture of three major trunk muscles: the rectus abdominis, quadratus lumborum, and three columns of the erector spinae (spinalis thoracis, longissimus thoracis and iliocostalis lumborum). Musculotendon lengths, muscle lengths, fascicle lengths, sarcomere lengths, pennation angles, and muscle masses were measured in five cadavers. Optimal fascicle lengths (the fascicle length at which the muscle generates maximum force) and physiologic cross-sectional areas (the ratio of muscle volume to optimal fascicle length) were computed from these measurements. The rectus abdominis had the longest fascicles of the muscles studied, with a mean (S.D.) optimal fascicle length of 28.3 (4.2)cm. The three columns of the erector spinae had mean optimal fascicle lengths that ranged from 6.4 (0.6)cm in the spinalis thoracis to 14.2 (2.1)cm in the iliocostalis lumborum. The proximal portion of the quadratus lumborum had a mean optimal fascicle length of 8.5 (1.5)cm and the distal segment of this muscle had a mean optimal fascicle length of 5.6 (0.9)cm. The physiologic cross-sectional area of the rectus abdominis was 2.6 (0.9)cm(2), the combined physiologic cross-sectional area of the erector spinae was 11.6 (1.8)cm(2), and the physiologic cross-sectional area of the quadratus lumborum was 2.8 (0.5)cm(2). These data provide the basis for estimation of the force-generating potential of these muscles.

Preliminary performance of a surgically implanted neuroprosthesis for standing and transfers--where do we stand?

This paper describes the preliminary performance of a surgically implanted neuroprosthesis for standing and transfers after spinal cord injury (SCI) in an initial group of 12 volunteers with longstanding paralysis. The CWRU/VA standing neuroprosthesis consists of an 8-channel implanted receiver-stimulator, epimysial and surgically implanted intramuscular electrodes, and a programmable wearable external controller. After reconditioning exercise and rehabilitation with the system, most individuals with paraplegia or low tetraplegia were able to stand, transfer, and release one hand from a support device to manipulate objects in the environment or to perform swing-to ambulation in a walker. The effort and assistance required for transfers were reduced for users with mid-level tetraplegia, although the maneuvers were not independent. Neuroprosthesis users with tetraplegia and paraplegia alike benefited from the improvements in their general health derived from exercise, including reduced risk of decubiti and self-reported modulation of spasticity. Stimulated responses are stable and sufficiently strong for function, and implanted components are reliable with a 90% probability of epimysial electrode survival at 4 years post-implant. The techniques employed are repeatable and teachable, and suitable for multi-center clinical trial.

The use of selective electrical stimulation of the quadriceps to improve standing function in paraplegia.

Persons with spinal cord injury (SCI) can benefit significantly from functional neuromuscular stimulation (FNS) systems for standing if manual tasks can be performed while upright. Using FNS to sufficiently activate the knee extensors to rise from a sitting position often results in inadvertent activation of the rectus femoris and/or sartorius, which flex the hip. In this study, intramuscular electrodes implanted in the vastus lateralis and medialis of four subjects with SCI were used to activate these muscles individually and simultaneously to measure knee extension moment. Support forces applied to the arms and feet were measured while upright to quantify the effects of recruiting rectus femoris and/or sartorius. In three of the four subjects, vastus lateralis, by itself, generated adequate knee extension moment for rising from a chair and to maintain static standing. Simultaneous activation of the vastus lateralis and medialis using a bifurcated electrode generated adequate knee extension moment in one subject, and was within 10% of the required moment in another. While upright, activation of the rectus femoris resulted in arm support force increases of 4-11% body weight, while deactivation resulted in arm support force decreases of 6-9% body weight. The results indicate that selective activation of the vastus lateralis, individually or in combination with vastus medialis, can improve current FNS standing systems by reducing the arm support forces required to remain upright.

Implanted functional electrical stimulation system for mobility in paraplegia: a follow-up case report.

A 16-channel functional electrical stimulation (FES) system has been implanted in a person with T10 paraplegia for over a year. The system consists of two eight-channel radio frequency controlled receiver-stimulators delivering stimuli through a network of 14 epimysial and two intramuscular electrodes. Using this system and a walker for support, the subject was able to stand up for 8 min and walk regularly for 20 m. The standing duration was limited by arm fatigue since upper extremities supported an average of 25% of body weight. This was due to suboptimal hip extension and some undesired recruitment of rectus femoris and sartorius with stimulation of quadriceps electrodes. The left quadriceps exhibited rapid fatigue that limited walking distance and duration. The metabolic energy requirements were well within the aerobic limits of the sedentary paraplegic population. At one-year follow-up evaluation all electrodes are functional except one intramuscular electrode. The implant caused no adverse physiological effects and the individual reported health benefits such as increased energy and overall fitness as a result of the FES system use. With further improvements in muscle response through innovative surgical techniques, the 16-channel implanted FES system can be a viable addition to exercise and mobility function in persons with paraplegia.

Implantation of a 16-channel functional electrical stimulation walking system.

A 16-channel electrical stimulation system was implanted in a 39-year-old patient with T10 paraplegia to restore sit to stand, walking, and exercise functions. System implantation required two surgical sessions. In the first session, the posterior muscle set consisting of bilateral semimembranosus, adductor magnus, and gluteus maximus muscles were exposed and epimysial electrodes sutured at the point of greatest muscle contraction. Closed double helix intramuscular electrodes were implanted in the erector spinae. Two weeks later, epimysial electrodes were attached to the eight anterior muscles consisting of the tibialis anterior, sartorius, tensor fasciae latae, and vastus lateralis with all 16 electrode leads passed to the anterior abdominal wall. The electrodes were connected to two eight-channel stimulators placed in the iliac fossae, and the system was checked by activating the individual muscles. The implanted stimulators received stimulation instructions and power via a radio frequency link to an external control. Stimulation patterns for standing, walking, sitting, and exercise functions were chosen from a preprogrammed menu via a finger key pad. After 3 weeks of restricted patient activity, all electrodes stimulated either the target muscle or had an acceptable spillover pattern. The patient is undergoing a 16-week rehabilitation course of stimulated exercises gradually increasing in intensity. At the conclusion, the goal is to discharge the patient with the system for spontaneous use. Although long term followup is required to determine system reliability, preliminary clinical results indicate that targeted, repeatable, functional muscle contractions in the lower extremity can be achieved with a system consisting of epimysial electrodes.

Implanted Functional Neuromuscular Stimulation systems for individuals with cervical spinal cord injuries: clinical case reports.

OBJECTIVE: To determine the feasibility of providing the ability to stand and to facilitate the performance of standing transfers to individuals with cervical-level spinal cord injuries via functional neuromuscular stimulation (FNS). The applicability of implantable technology to this population was investigated, and the characteristics of the potential system users were explored. The effects of FNS on the effort and assistance required to stand and complete standing transfers were examined. SETTING: Institutional rehabilitation practice. DESIGN: Nonrandomized controlled trial. PATIENTS: Twenty-four individuals with low cervical spinal cord injuries were evaluated for inclusion in a program of lower extremity FNS, four of whom received the intervention. INTERVENTION: Chronically indwelling percutaneous intramuscular electrodes were used to exercise the hip, knee, and trunk extensors and develop activation patterns to produce standing function. These temporary systems were then replaced with silicone-enclosed helical wire electrodes suitable for eventual use with an eight-channel implantable receiver/stimulator. MAIN OUTCOME MEASURES: Full sensory and motor evaluations were performed and physical contraindications to stimulation were catalogued. For active subjects, American Spinal Injury Association Total Motor Scores with and without FNS were recorded, along with quadriceps strength and ability to complete exercise, standing, controlled sitting, and standing transfer maneuvers. Performances of implanted electrodes were determined by the stability of recruitment properties, impedances or surface potentials, and serial radiographs. RESULTS: Motor scores increased an average of nine points with stimulation over baseline volitional values. With FNS, all four volunteers were able to exercise, stand, and sit independently or with minimal assistance. Although they required varying degrees of assistance with the pivot phase of the transfer maneuver, all were able to raise and lower their body weight independently with stimulation and to use the system to facilitate standing transfers. One participant received the implantable receiver/stimulator, which remains operational at follow-up more than 3 years later. CONCLUSION: FNS can provide the ability to exercise, stand, and transfer to individuals with tetraplegia, even in the presence of medical complications and upper extremity impairment. FNS facilitates standing transfers by eliminating the heavy lifting usually required by a caregiver, thus decreasing the effort and assistance necessary to gain access to places impossible to approach with conventional sliding transfers.

Ultrastructural localization of a sialic acid-specific hemolymph lectin in the hemocytes and other tissues of the hard tick Ixodes ricinus (Acari; Chelicerata).

Lectins have been suggested to function as pattern-recognition molecules in invertebrate immune mechanisms. A lectin from the hemolymph of the tick Ixodes ricinus with main specificity for sialic acid was characterized and antibodies directed against this lectin were prepared. In this study, these antibodies were used to localize the lectin in the tissues of I. ricinus. Immunoreactivity with poly- and monoclonal antibodies was detected in the granules of both types of granular hemocytes, at the membrane of hemocytes, and at the basal laminae surrounding the hemocoel. Furthermore, cells attached to the midgut, invaginations of Géné's organ, and granular inclusions of nephrocytes were labeled. The immunoreactivity detected in hemocytes and the hemocoel lining supports the idea that the hemolymph lectin may function as a recognition molecule in the immune system of I. ricinus. Another function could be protection of eggs that are coated with secretions by Géné's organ. The lectin activity could also be involved in transmission of Borrelia burgdorferi, the causative agent of Lyme borreliosis, and the tick-borne encephalitis virus.

Novel agglutinin in the midgut of the tick Ixodes ricinus.

Haemagglutination activity (HA) was found and characterized in a midgut homogenate of Ixodes ricinus (L.). HA was induced by tick feeding; it was not detected in starved ticks. In a haemagglutination inhibition test, HA showed an affinity for some carbohydrates (N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, rhamnose, and dulcit) and glycoconjugates (especially lipopolysaccharides). Midgut protein components of 37, 60, 65, and 73 kDa were identified by immunoblotting as potential structural subunits of the new agglutinin.

Immunosuppression and feeding success of Ixodes ricinus nymphs on BALB/c mice.

The effect of repeated infestations of Ixodes ricinus (L.) nymphs on BALB/c mice was studied. Four successive infectations resulted in an increase of tick feeding success. Tick yield and mean engorged weight increased and the length of the feeding period was reduced significantly (P < 0.05-0.01). The increase of specific anti-tick antibodies was not significant (P > 0.05). The blastogenic response of spleen lymphocytes to T-cell mitogens (Con A and PHA-P) was unimpaired or slightly enhanced, whereas the response to B-cell activators (LPS and PWM) was suppressed, as was the total antibody generation in vitro. The numbers of mast cells in murine skin at the tick attachment sites slightly decreased during the third infestation. The suppression of B-cell competence and of antibody generation, together with decrease of skin mast cell numbers in tick attachment sits, are considered to be responsible for enhancement of tick feeding success.

Antigens and glycoproteins of larvae, nymphs and adults of the tick Ixodes ricinus.

Protein components of homogenates of unfed larvae and nymphs of Ixodes ricinus (L.), and of ovary, haemolymph, Malpighian tubules, rectal ampulla, fat body, integument, salivary glands and midgut of partially fed adult females were studied for their antigenicity and carbohydrate moieties using immunoblotting and lectin affinity blotting (LAB) techniques. Comparing the individual anti-larval, anti-nymphal and anti-adult immune sera for their capacity to recognize the specific and trans-stadially cross-reactive antigenic proteins, larval feeding induced the most effective humoral response. The majority of immunogens recognized by rabbit anti-tick immune sera are glycoproteins. Most of the glycosylated antigens were modified with N-type glycans; however, O-type glycans were also demonstrated in some antigens. The correlation of the type of glycosylation with antigenicity, and the sharing of common antigenic epitopes by various tissues, are discussed.

Humoral and cellular immune response of BALB/c mice to repeated infestations with Ixodes ricinus nymphs.

The capacity of female BALB/c mice to mount an immune response and effective resistance to repeated infestations with I. ricinus nymphs was studied. An anamnestic antibody response and transient in vitro responsiveness of spleen lymphocytes to tick antigens were demonstrated in repeatedly infested mice. On the other hand, the response to concanavalin A--a T-cell mitogen, was suppressed at the same time. In the presented experiment, BALB/c mice did not manifest tick resistance after three successive infestations (with a reinfestation period of 2 weeks). The possibility of an infestation-dependent modulation of immune response in BALB/c mice is discussed.

Age-dependent immune response of chickens to feeding by Argas persicus larvae.

Chickens of the dwarf Velsum breed acquired immunity to Argas persicus larvae during repeated infestations with 100 larval ticks in 2-week intervals, when primarily infested at the age of 10 weeks. This immunity was manifested by 74.6% and 75.9% rejection of larvae during secondary and tertiary infestations (P < 0.01), respectively, in relation to controls. The mean weight reductions observed were 16.5% and 12.2% in secondary and tertiary infestations, respectively (P < 0.05). Weak immunity also occurred after secondary and tertiary infestations in chickens infested first at the age of 6 and 8 weeks, but not in chickens aged 2 or 4 weeks at first infestation. No changes were observed in mean feeding periods of larvae engorged on chickens of all age groups (P > 0.05). A significant increase in the leucocyte counts in peripheral blood (P < 0.01 or P < 0.05), mostly of lymphocytes and heterophil granulocytes, followed each infestation in chickens of all age groups. Specific anti-tick circulating antibodies were detected by ELISA in the sera of 10-week-old chickens after primary infestations, in the 4-8-week chicken groups following secondary infestations when aged 6-10 weeks, and in the 2-week chicken group only after tertiary infestations, when the chickens reached the age of 6 weeks. A 53 kDa protein was recognized in the whole-body extract of larval ticks by immune serum during immunoblotting. This was probably the antigenic protein responsible for eliciting the circulating antibodies. The acquired immunity to ticks seen in chickens aged 6 weeks or more may be connected with maturation of the bursa of Fabricius and the development of complete immunocompetence, which is believed to occur in chickens at the age of 4-5 weeks.

Effect of repeated infestations of BALB/c mice with Ixodes ricinus nymphs on tick-borne encephalitis virus infection.

The effect of repeated infestations of BALB/c mice with Ixodes ricinus (L.) nymphs on tick borne encephalitis (TBE) virus infection was studied. Enhancement of nymphal feeding, occurring in noninfected mice during the quaternary infestations, was less apparent or absent in female nymphs engorged on TBE virus infected mice. The mice infected with TBE virus during quaternary tick infestation survived significantly longer (P < 0.01) than mice infected with TBE virus during the primary tick infestation. The mean titre of virus in murine blood (determined by plaque assay) was significantly lower (P < 0.01) and the number of nymphs acquiring virus was reduced (P < 0.05) when feeding on hosts infected during the quaternary infestation. The results indicate that repeated infestations of I. ricinus nymphs on BALB/c mice, although enhancing tick feeding, reduced infection with TBE virus when inoculated intraperitoneally.

Functional and structural identification of a new lectin activity of Borrelia recurrentis spirochetes.

1. Haemagglutinating activity (HA) was found and characterized in lysate of the spirochete Borrelia recurrentis. 2. The highest HA was observed using native rabbit red blood cells (RBC), especially oxidized rabbit RBC. 3. In a haemagglutination inhibition test the HA showed an affinity with monosaccharides D-glucosamine, D-galactosamine and N-acetyl-D-mannosamine and several glycoproteins and polysaccharides. 4. An inhibitory effect was also achieved by mouse monoclonal antibody H 9724, polyclonal antibodies from B. recurrentis infected mice and with rabbit polyclonal antibodies directed against B. recurrentis HA. 5. B. recurrentis proteins components of 29, 33, 41 and 55 kDa were identified by immunoblotting as structural subunits of complex binding activity of a new agglutinin.

Isolation and partial characterisation of an immunogen from the mite, Psoroptes cuniculi.

The immunological reactions of Psoroptes cuniculi protein components with antigen-specific rabbit antisera and with six plant lectins are described. In immunoblotting, the antisera from rabbits heavily and mildly infested with Psoroptes cuniculi recognized from two to five protein components. Affino-blotting analysis showed that eight mite components were glycoproteins with different types of glycan structures. The immunogenic antigen was isolated by both immunoaffinity chromatography and identified by crossed immunoelectrophoresis. It was a glycoprotein with a relative molecular mass of 48 kDa and with complex or high mannose type of oligosaccharides.

Ivermectin: its effect on the immune system of rabbits and rats infested with ectoparasites.

The influence of subcutaneously administered ivermectin on the specific immune response was studied in rabbits infested with mites (Psoroptes cuniculi) and in rats infested with lice (Polyplax spinulosa). A pronounced specific antibody activity and a change in immunoblotting pattern was observed in rabbits after the ivermectin treatment. However, in rats the antibody activity decreased and the profile of specific antibodies, tested by immunoblotting, remained the same as before the treatment. The specific immune response in rabbits artificially immunized with whole-body Psoroptes cuniculi extract was not affected by ivermectin. It was concluded that ivermectin has no direct effect on the immune response of rabbits and rats and that the enhanced immune response in the mite-infested rabbits was caused by the massive release of antigens associated with the synchronous death of the mites.

Immunization of rabbits with antigens from Psoroptes cuniculi, the rabbit scab mite.

Rabbits immunized with the whole body extract of Psoroptes cuniculi (Delafond, 1859) developed partial immunity to the infestation with this mite. These rabbits manifested P. cuniculi antigen-induced cell response and a high level of specific serum antibody after the immunization. Electrophoretic separation of the mite extract followed by immunostaining with various sera revealed differences between artificially immunized and naturally infested rabbits to most of the P. cuniculi antigens. However, the specific antibody pattern, that was developed by the immunized rabbits, was not changed after these rabbits were infested with the mites.