Performance of an intramuscular electrode during functional neuromuscular stimulation for gait training post stroke.

The goal of rehabilitation for stroke patients in this research was to improve the volitional coordination of the swing phase and stance phases of gait. Functional neuromuscular stimulation (FNS) is a promising rehabilitation tool for restoring motor control. For our gait training protocols, FNS systems with surface electrodes were impractical. For the rehabilitation protocols that we defined, available implantable electrode designs did not meet desired criteria regarding fracture rate, invasiveness of placement procedures, and maintenance of position at the motor point. The criteria for the new intramuscular (IM) electrode design included minimally invasive electrode placement technique, accurate placement of electrodes, good muscle selectivity, consistency of muscle activation, good position maintenance of the electrode at the motor point, comfortable stimulus, and practical donning time for the system. A percutaneous electrode was designed for placement beneath the skin at the motor point of seven paralyzed or paretic muscles in the lower limb. A single-helical coil lead, a double-helical coil electrode, and fine wire barbs were design features that enhanced the anchoring capability of the electrode. A polypropylene core enhanced electrode durability. Implantation tools were custom-designed to enable accurate electrode placement without incision. We studied 17 subjects with a total of 124 electrodes. With the use of IM electrodes, FNS was provided for 1,413.8 electrode months. During this time, no instances of infection occurred. The measure of electrode integrity showed a 99% electrode survival rate. Throughout the treatment protocols, 93% of the electrodes delivered a good muscle response; 7% (nine electrodes) moved from the motor point and delivered a poor muscle response during the treatment protocol. Anchoring performance was higher for electrodes implanted in muscles that moved the hip (96.0%) and ankle joints (97.45%) compared with electrodes implanted in muscles that moved the knee joint (88.5%). Ninety-seven percent of the electrodes delivered a comfortable stimulus. Three percent delivered a stimulus that was uncomfortable at therapeutic levels and therefore were not used. We achieved gains in subject impairment and disability measures. The system proved to be practical for use in both clinical and home environments.

Feasibility of gait training for acute stroke patients using FNS with implanted electrodes.

Following stroke, many patients do not regain a normal, safe gait pattern even after receiving conventional physical therapy. One promising technique is functional neuromuscular stimulation (FNS) with intramuscular (IM) electrodes (FNS-IM). Five subjects were admitted into the study at 3 weeks to 3 months following the stroke. For each subject, electrodes were placed intramuscularly at the motor point of up to seven lower extremity paretic muscles. Subjects were treated for 6 months, twice weekly with FNS-IM for exercise and gait training. The stimulator and software provided individualized stimulation patterns, with flexible stimulus parameters and activation timings of multiple muscles. Outcome measures were active joint movement, coordination (Fugl-Meyer scale), balance (Tinetti scale), gait (Tinetti scale), activities of daily living (functional independence measure), and therapist and subject satisfaction (survey instrument). Subjects tolerated well the placement of IM electrodes with no adverse effects, and subjects lost no conventional rehabilitation time. Therapists and subjects were satisfied with the FNS-IM system as a rehabilitation tool. Post treatment, subjects demonstrated improvements in impairment and disability in active joint movement, coordination, balance, gait and activities of daily living. Considered together with prior research for chronic stroke subjects, this research suggests that FNS-IM can be successfully and efficaciously utilized for gait training for those with acute stroke.

Response of prolonged flaccid paralysis to FNS rehabilitation techniques.

PURPOSE: The purpose of this study was to investigate the response of muscles with prolonged flaccid paralysis (a year after stroke) to two types of treatment: (1) functional neuromuscular stimulation (FNS) with surface electrodes; and (2) FNS with intramuscular (IM) electrodes (FNS-IM). A second purpose was to compare FNS-gait versus volitional gait (no FNS activation). METHOD: We used a single case study design; our patient was age 72, with flaccid paralysis of knee flexors and ankle dorsiflexors. RESULTS: Following four months of treatment with surface-stimulation, there was no change in muscle function or gait. Following treatment with FNS-IM, the patient regained partial volitional control of knee flexors and dorsiflexors; untreated muscles did not change. CONCLUSION: FNS-gait provided more normal knee and ankle dorsiflexion during swing phase versus volitional gait swing phase (no FNS activation).

Electrically induced recovery of gait components for older patients with chronic stroke.

OBJECTIVE: To compare the gains for chronic stroke patients in volitional gait pattern attained from treatment with functional neuromuscular stimulation (FNS) and intramuscular electrodes (IM) with gains attained using conventional therapy, including treatment with FNS using surface electrodes (surface-stim). DESIGN: This single-subject research design consisted of a series of two subjects. Three months of conventional therapy and surface-stim were followed by treatment using the FNS-IM system. Two stroke patients had cerebrovascular accident 1 or 4 yr before the study and ambulated with a cane. Interventions consisted of 3 months of conventional exercise and gait training including surface-stim, followed by 7-14 months of treatment with the FNS-IM system. Treatments occurred up to 3 times/wk for 1-hr sessions and a home program. Outcome measures consisted of six kinematic gait components, as measured by a six-camera video-based data-acquisition system. Coordination of isolated joint movement was measured according to the Fugl-Meyer scale. RESULTS: Both subjects improved during conventional therapy to some degree. During FNS-IM treatment, gains were made beyond those attained during conventional therapy. Statistically significant differences were found between conventional and FNS-IM therapy. CONCLUSIONS: For these two subjects, gains in volitional control of gait were made during conventional treatment (including surface-stim); for these two subjects during FNS-IM treatment, additional gains were made in volitional gait pattern, beyond those attained during conventional therapy.

Effects of temperature on slow and fast inactivation of rat skeletal muscle Na(+) channels.

Patch-clamp studies of mammalian skeletal muscle Na(+) channels are commonly done at subphysiological temperatures, usually room temperature. However, at subphysiological temperatures, most Na(+) channels are inactivated at the cell resting potential. This study examined the effects of temperature on fast and slow inactivation of Na(+) channels to determine if temperature changed the fraction of Na(+) channels that were excitable at resting potential. The loose patch voltage clamp recorded Na(+) currents (I(Na)) in vitro at 19, 25, 31, and 37 degrees C from the sarcolemma of rat type IIb fast-twitch omohyoid skeletal muscle fibers. Temperature affected the fraction of Na(+) channels that were excitable at the resting potential. At 19 degrees C, only 30% of channels were excitable at the resting potential. In contrast, at 37 degrees C, 93% of Na(+) channels were excitable at the resting potential. Temperature did not alter the resting potential or the voltage dependencies of activation or fast inactivation. I(Na) available at the resting potential increased with temperature because the steady-state voltage dependence of slow inactivation shifted in a depolarizing direction with increasing temperature. The membrane potential at which half of the Na(+) channels were in the slow inactivated state was shifted by +16 mV at 37 degrees C compared with 19 degrees C. Consequently, the low availability of excitable Na(+) channels at subphysiological temperatures resulted from channels being in the slow, inactivated state at the resting potential.

Insulin acts in hypokalemic periodic paralysis by reducing inward rectifier K+ current.

OBJECTIVE: To define how insulin acts in hypokalemic periodic paralysis (HypoPP). BACKGROUND: HypoPP results from point mutations of the skeletal muscle L-type Ca2+ channel. Attacks of flaccid paralysis are associated with hypokalemia and triggered by insulin. A persistent inward current causes depolarization-induced paralysis. The relationships of the Ca2+ channel mutations to the persistent inward current and how insulin triggers paralytic attacks are not yet known. METHODS: Intercostal muscle fibers from HypoPP and normal subjects were studied in vitro at 37 degrees C using two electrodes to determine action potential thresholds and a three-electrode voltage clamp to study membrane currents. RESULTS: HypoPP fibers were depolarized in bathing solution with 4 mM K+. Reducing K+ from 4.0 mM to 2.5 or 1.0 mM depolarized HypoPP fibers but hyperpolarized normal fibers. Adding 12 mU/mL of insulin to bathing fluids increased the depolarization of HypoPP fibers and increased the hyperpolarization of normal fibers. Depolarized HypoPP had increased action potential thresholds. The fraction of excitable muscle fibers decreased with increasing fiber depolarization. Blocking Na+ channels or L-type Ca2+ channels did not prevent depolarization induced by hypokalemia or by insulin. Insulin reduced the conductance of the inward rectifier K+ channel for outward-flowing currents. CONCLUSIONS: Insulin potentiates depolarization of hypokalemic periodic paralysis (HypoPP) fibers by reducing inward rectifier K+ conductance. The Ca2+ mutations in HypoPP indirectly derange membrane excitability by altering the function of other membrane channels.

Disorders of neuromuscular junction ion channels.

Ion channel defects produce a clinically diverse set of disorders that range from cystic fibrosis and some forms of migraine to renal tubular defects and episodic ataxias. This review discusses diseases related to impaired function of the skeletal muscle acetylcholine receptor and calcium channels of the motor nerve terminal. Myasthenia gravis is an autoimmune disease caused by antibodies directed toward the skeletal muscle acetylcholine receptor that compromise neuromuscular transmission. Congenital myasthenias are genetic disorders, a subset of which are caused by mutations of the acetylcholine receptor. Lambert-Eaton myasthenic syndrome is an immune disorder characterized by impaired synaptic vesicle release likely related to a defect of calcium influx. The disorders will illustrate new insights into synaptic transmission and ion channel structure that are relevant for all ion channel disorders.

Electrophysiology of postsynaptic activation.

The safety factor for neuromuscular transmission depends upon the amount of ACh released from the nerve terminal, the number of AChRs, and the concentration of Na+ channels at the end plate potential. The postsynaptic end plate membrane of the neuromuscular junctions is specialized in three ways: (1) AChRs, Na+ channels, ChE, NOS, and other membrane-associated proteins are concentrated at the end plate; (2) the end plate cytoskeleton has a different composition of proteins as compared with extrajunctional membrane; and (3) the end plate membrane is mechanically different as compared with extrajunctional membrane. A blockade of neuromuscular transmission occurs when ACh release is inadequate or the end plate response to ACh is too small to trigger an AP. A safety factor for neuromuscular transmission exists because the EPP is larger than the threshold for generating an AP. The high concentration of Na+ channels at the end plate increases the safety factor for neuromuscular transmission by reducing the threshold depolarization required to initiate an AP. In MG, the safety factor is reduced due to loss of AChRs and loss of Na+ channels. The loss of AChRs reduces the EPP and the Na+ channel loss increases the threshold for triggering an AP.

Pneumatic sequential compression reduces the risk of deep vein thrombosis in stroke patients.

OBJECTIVE: To determine if pneumatic sequential compression devices (SCDs) combined with subcutaneous heparin and antiembolic hose reduce the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in stroke patients. BACKGROUND: DVTs and PEs are serious complications among hospitalized stroke patients. Subcutaneous heparin and SCDs have both been used to prevent DVT. It is not known if SCDs combined with subcutaneous heparin can improve the protection afforded by heparin alone. METHODS: The study group was comprised of nonhemorrhagic stroke patients admitted to the neurology service from October 1988 through June 1996. From October 1988 through April 1991 (233 patients), and during February 1993 (16 patients), patients received 5,000 U subcutaneous heparin twice daily and antiembolic hose. From June 1991 through January 1993 and from March 1993 through June 1996 (432 patients) all nonambulatory stroke patients had SCDs applied to both legs in addition to subcutaneous heparin and antiembolic hose. RESULTS: Twenty-three of 249 patients (9.2%; 21 of 233 and two of 16 patients) treated with heparin alone developed DVT and six patients (2.4%) developed PE (six of 233 and zero of 16). Half the PE cases (three of six) were fatal and all PEs were in patients with DVT. Eighty-three of the 249 patients were nonambulatory. Twenty-two of the 23 DVTs and all the PEs developed in nonambulatory patients. Only one DVT (0.23%) and no PEs occurred among the 432 patients (148 nonambulatory) treated with SCDs as well as heparin. The addition of SCDs resulted in more than a 40-fold reduction in the risk of DVT. CONCLUSIONS: Nonambulatory stroke patients have an increased risk for DVT and PE. Adding SCDs to treatment with subcutaneous heparin and antiembolic hose reduced the risks of DVTs and PEs. SCDs should be considered for adjunctive DVT prophylaxis in nonambulatory stroke patients.

End-plate voltage-gated sodium channels are lost in clinical and experimental myasthenia gravis.

This study examined the loss of voltage-gated Na+ channels as well as acetylcholine receptors (AChRs) from the end-plate region in patients with acquired myasthenia gravis (MG) and in rats with experimental autoimmune passively transferred MG (PTMG). Rats received a monoclonal IgG antibody directed against an extracellular epitope of the nicotinic acetylcholine receptor of muscle (AChR) to produce PTMG. At the end-plate border we examined miniature end-plate potentials (MEPPs), sodium current (INa) amplitude, and action potential (AP) properties; the latter two were also examined on the extrajunctional membrane. In the normal situation, the safety factor for neuromuscular transmission is ensured by the large INa at the end plate, which reduces the AP threshold. Among different fiber types, INa was largest for type IIb fibers and smallest for type I fibers. When end-plate border properties of fibers from 3 MG patients and 15 PTMG rats were compared with controls, INa was reduced, AP thresholds were higher, and rates of AP rise were reduced. Amplitudes of MEPPs and INa at the end plate indicated that loss of AChRs was greater than loss of Na+ channels in patients with MG and rats with PTMG; INa was reduced to about 60% of control values, whereas MEPPs were reduced to less than 30% of control values. On the extrajunctional membrane, INa and AP thresholds and rates of rise were similar for MG patients, PTMG rats, and controls. This evidence for loss of voltage-gated Na+ channels at the motor end plate in both patients with MG and in rats with PTMG reveals a hitherto unrecognized consequence of the end-plate damage initiated by the binding of complement-fixing IgG to end-plate AChRs.

Endocrine neuromyopathies.

The myopathies associated with endocrine disorders range in clinical presentation from the relatively nonspecific pattern of proximal muscle weakness of glucocorticoid excess states to specific presentations of contractions produced in tetany. All endocrine neuromyopathies emphasize the role of skeletal muscle in protein, carbohydrate, and electrolyte metabolism. Hormonal abnormalities tend to compromise muscle force generation by indirect effects on muscle function. The recognition and effective treatment of all these disorders require the identification of the underlying hormonal imbalances and awareness of general medical problems produced by the endocrine disorders.

Serological survey for diseases in free-ranging coyotes (Canis latrans) in Yellowstone National Park, Wyoming.

From October 1989 to June 1993, we captured and sampled 110 coyotes (Canis latrans) for various diseases in Yellowstone National Park, Wyoming (USA). Prevalence of antibodies against canine parvovirus (CPV) was 100% for adults (> 24 months old), 100% for yearlings (12 to 24 months old), and 100% for old pups (4 to 12 months old); 0% of the young pups (< 3 months old) had antibodies against CPV. Presence of antibodies against canine distemper virus (CDV) was associated with the age of the coyote, with 88%, 54%, 23%, and 0% prevalence among adults, yearlings, old pups, and young pups, respectively. Prevalence of CDV antibodies declined over time from 100% in 1989 to 33% in 1992. The prevalence of canine infectious hepatitis (ICH) virus antibodies was 97%, 82%, 54%, and 33%, for adults, yearlings, old pups, and young pups, respectively. The percentage of coyotes with ICH virus antibodies also declined over time from a high of 100% in 1989 to 31% in 1992, and 42% in 1993. Prevalence of antibodies against Yersinia pestis was 86%, 33%, 80%, and 7%, for adults, yearlings, old pups, and young pups, respectively, and changed over time from 57% in 1991 to 0% in 1993. The prevalence of antibodies against Francisella tularensis was 21%, 17%, 10%, and 20%, for adults, yearlings, old pups, and young pups, respectively. No coyotes had serologic evidence of exposure to brucellosis, either Brucella abortus or Brucella canis. No coyotes were seropositive to Leptospira interrogans (serovars canicola, hardjo, and icterohemorrhagiae). Prevalence of antibodies against L. interrogans serovar pomona was 7%, 0%, 0%, and 9%, for adults, yearlings, old pups, and young pups, respectively. Antibodies against L. interrogans serovar grippotyphosa were present in 17% of adults and 0% of yearlings, old pups, and young pups. Many infectious canine pathogens (CPV, CDV, ICH virus) are prevalent in coyotes in Yellowstone National Park, with CPV influencing coyote pup survival during the first 3 months of life; eight of 21 transmitted pups died of CPV infection in 1992. The potential impact of these canine pathogens on wolves (C. lupus) reintroduced to Yellowstone National Park remains to be documented.