Vol 20 * No2 + 1996 NEUROLOGY REPORT 31 Guillain-Barré Syndrome and Exercise Guidelines Clare C Bassile, EdD, PT Columbia University New York, NY As physical therapists rehabilitating individuals with Guillain-Barré syndrome (GBS), it is imperative that we un- derstand the physiology of exercise responses in healthy and pathologic states. The purpose of this review is to identify the assumptions regarding exercise precautions in this patient pop- ulation. The scientific evidence that supports or refutes these assumptions will be discussed. Clinicians will have some guidelines for exercise prescription in these patients after read- ing this article. For the research scientist, it is my hope that the questions identified throughout the article will be explored in this patient population. Thus in the future, the clinician will no longer need to apply guidelines from a questionably related pathology’s literature base. Guillain-Barré syndrome will have its own literature base dealing with muscle physiology, dener- vation, demyelination, remyelination, reinnervation, and exer- cise effects Pathophysiology Guillain-Barré syndrome is an autoimmune disorder of the peripheral nervous system causing progressive weakness of the limbs with diminished/absent tendon reflexes.’ Although the etiology of the inflammatory polyradiculoneuropathy remains unknown at this time, the campylobacter jejune virus has been implicated in the more severe cases of GBS. Irrespective of etiology, the inflammatory process affects the Schwann cells. Macrophages attack Schwann cells resulting in primary de- ‘myelination of the axon while usually leaving the axon intact The process of remyelination occurs rapidly. Alternatively, the patient may also experience secondary axonal damage. Due to Iymphoeytic infiltration, cytodestructive events in the axon oc- cur resulting in Wallerian degeneration of the distal axon. Thus, the process of axonal regrowth and remyelination must occur. The regrowth rate is slow, approximately 1 mm/day: Therefore, it is likely that patients with GBS, who had quadraplegia and were acutely ventilator-dependent for a pro- longed period of time, have some axonal damage along with primary demyelination. Despite profound deficits and paralyis, these patients have a 65% chance of a full recovery.* Assumptions From the Literature Rehabilitation textbooks and anecdoctal case reports dis- cussing the exercise guidelines for the recovering patient with GBS have identified three parameters that the physical thera- pist should use when retraining/exercising these patients. They are: (1) avoidance of overwork, (2) avoidance of eccentric con- tractions, and (3) waiting until the musculature is antigravity strength before stressing."* The first two parameters are related. and will be discussed together. As discussed elsewhere in this, issue (Curtis and Weir), “Overwork weakness is a prolonged weakness in the absolute strength and endurance of a muscle due to excessive activity.” Anecdotal evidence from single-case subjects supporting the detrimental effects of overuse in GBS for both the early (acute) phase! as well as the later phase of the rehabilitation process’ can be found. There is no physiologi- cal evidence to date that uncovers the etiology of overwork weakness in GBS. In order to develop guidelines for exercise prescription in the GBS population, the overwork literature in the healthy, postpotio, and myopathic populations is typically used. Possible Mechanisms for Excessive Muscular Activity (One of two things must happen to increase force production in a muscle. Either a temporal summation of the alpha-motor neurons or an increase in the number of recruited alpha-motor neurons must take place."" When an alpha-motor neuron depo- larizes, the action potential (AP) travels swiftly down the myelinated axon via saltatory conduction to all the terminals and releases acetylcholine (ACh). The ACh permeates the muscle fibers innervated by that motor neuron and causes a contraction. Because GBS affects the peripheral nerves, an im- pairment in motor-unit recruitment occurs because of a trans- mission problem. Either there is damage to the myelin resulting in conduction block, or the axon itself is destroyed. As a consequence, there are fewer numbers of successfully re- cruited muscle fibers available to produce sufficient forces for functioning. Hence, those recruited muscle fibers are at risk for overworking. Three possible explanations for the presumptive excess muscle activity in GBS are supported by the literature: (1) spotty/patchy demyelination, (2) abnormal remyelination, and (3) partial denervation. In a recent review paper on demyelina- tion in spinal-cord injury and multiple sclerosis, Waxman ide tified the unmasking of fast potassium channels or the blocking of sodium channels at the nodes of Ranvier as two of several possibilities for the conduction block seen in CNS demyelina- tion." Recent work suggests that interference in sodium chan- nel functioning may be a potential mechanism for the nerve conduction block in GBS." In addition, Waxman suggests, that the morphology of remyelination must be similar 10 nor- mal myelin in order to eliminate the subclinical reductions in conduction that affect normal functioning. Regardless of the demyelination or the remyelination process, if there is slow- ness or failure of the AP to travel down the axon, the ultimate yield is little or no recruitment of motor units. This analogy32 NEUROLOGY REPORT can also be employed in GBS where the peripheral nerves are affected. If demyelination is spotty/patchy or the remyelination is abnormal along a particular nerve, fewer muscle fibers will contract, resulting in only partial muscle recruitment by the ‘motor neuron, and a decrease in force production may be seen. ‘The hypothesis that spotty/patchy demyelination or abnormal remyelination results in partial recruitment of motor units and decreased force production has not been sufficiently explored in the population with GBS.” ‘The same risk of excessive activity may be present with par- tial denervation. Here again, if partial recruitment of the mus- cle is seen, then those muscle fibers innervated have the potential to be overworked. It is the peripheral denervation process that links GBS to the polio and peripheral neuropathy literature. Irreversible increases in weakness believed to be due to muscle damage have been observed in some patients with polio following unsupervised strenuous activity."*"” However, the mechanism for overwork in the postpolio patient remains controversial (see McDonald, this issue). In addition, recent in- vestigations on animal models of peripheral neuropathy have demonstrated some short-term detrimental effects of intense exercise on reinnervation efficacy (numbers of myclinated fibers and diameter size)." These effects have not been empir- ically demonstrated in the population with GBS. Regardless of where the damage is occurring, this concept of avoidance of ‘overwork has been transferred to the population with GBS. Complete electrodiagnostic testing is of primary impor- tance in determining the neuropathology of GBS. These tests, determine the severity of axonal damage. However, some tra- ditional testing methods are too invasive for the patient with GBS. Although nerve conduction velocities are assessed through surface recordings, the integrity of the motor units in 1 specific muscle is assessed via inserted needle electrodes.” However, McComas, Galea, and deBruin have recently pro- posed a computer-based technique for estimating the number of motor units in a particular muscle by using surface record- ings of compound action potentials (CAP). The computeriza- tion of the technique surpasses the manual acquisition of CAP by eliminating the subjectivity of the testing procedure. These researchers have reported motor unit estimates for healthy con- trol subjects and patients with peripheral neuropathy.” The technique has also been employed longitudinally to investigate ‘motor unit drop out in patients with postpolio syndrome.” Although manual CAP testing has been employed in clini- cal neurology." it appears that computer-based CAP testing may be very enlightening in the patient with GBS. Collection of CAP daia in conjunction with traditional needle electrode recordings and nerve conduction velocity data has been used in patients with GBS early in the disease process to classify severity and type of axonal injury and to prognosticate recov- ery." Therefore, not only would computer-based CAPs quan- tify the degree of initial axonal injury by estimating the number of intact motor units, but CAPs may help determine the efficacy of treatment. Using CAPs throughout the rehabil- itation process may help to elucidate relationships between the Vol 20 + No2 + 1996 degree of motor unit integrity and the risk for overwork weakness. ‘Although there is theoretical support for demyelination o denervation leading to overuse, neither condition has demonstrated empirically in GBS. Having completed the gis. cussion on the proposed mechanisms that might predispose the patient with GBS toward excessive muscular activity, a discus. sion of the physiological processes underlying overwork mus. cle damage and its relationship to eccentric muscle contraction follows. Recognizing Overwork Weakness Overwork symptoms include delayed onset muscle sore- ness, peaking between days 1 and 5 postactivity and a reduc. tion in maximum force production that gradually recovers. ‘The probability of injury in humans is greatest for exercise with eccentric contractions compared with isometric and con- ‘centric contractions. A review paper by Faulkner and col- leagues details the sequence of events for skeletal muscle contraction-induced injury.” The initial injury following eccentric contraction has been hypothesized to be caused by myofibrillar disruption and Z- line streaming A mechanical injury to the individual sar- comeres occurs when they are stretched beyond overlap Patients would have to submit to a muscle biopsy and the mus- cle fibers would have to be examined histologically to suppor this hypothesis in individuals with GBS. This painful, invasive procedure may not be a realistic one in the population with GBS. Indirect evidence of muscle damage may be obiained, however. The peak for muscle soreness occurs between days | ‘and 5 postactivity and is associated with a reduction in relative ‘maximum isometric force production.” These are believed to be caused by an inflammatory process resulting in a secondary ‘muscle injury. Also, increases in calcium ion influx to the mus- cle occur concurrently, yielding an increase in serum creatine kinase (CK) levels. Creatine kinase levels are checked rou- tinely for patients with inflammatory muscle diseases (cg, polymyositis) to monitor the deleterious effects of an exercise regime.” However, there is a great deal of variability in CK levels, and this muscle damage marker may become insensitive with repeated bouts of exercise.” Therefore, identification of specific muscle injury through regular muscle testing with iso- metric dynamometry® or global injury with routine screening of blood CK levels or other identified markers of muscle dam- ‘age (eg, 3-methylhistadine, myoglobin)” are assessments that should be evaluated in the patient recovering from GBS. Both of these assessments can be performed easily in the rehabilita- tion setting, where patients are seen daily for exercise and bloods are drawn routinely. ‘The Relationship Between Eccentric Muscle Contractions and Muscle Damage ‘The overwork literature in healthy muscle states intense =~ centric activity has been shown to be associated with a higherVol 20 + No2 + 1996 NEUROLOGY REPORT 33 incidence of muscle damage compared with isometric and con- centric/shortening activity.®* Also, most of the scientific in- quiry into the mechanisms of overwork damage have investigated eccentric training regimes. Furthermore, excessive eccentric activity has been hypothesized to cause the predom- inant weakness pattern seen in patients with myopathies (sym- metrical proximal weakness pattern) This hypothesis has been transferred to the population with GBS without any em- pirical evidence; no clinical studies have evaluated eccentric activity in GBS. This assumption has lead to the avoidance of eccentric contraction training in the clinic. Are we sending our patients home to function in their communities unprepared for everyday life? Most functional activities require eccentric contractions. Edwards discusses the role of eccentric contractions of the scapular muscles during arm movements and the hip abductors during upright postures.* If one looks to the biomechanics lit- erature on ambulation, it is clear that many muscles in the lower extremity function eccentrically during ambulation.” ‘The anterior tibialis and quadriceps femoris during initial con- tact and the gastrocsoleus during stance perform eccentric con- tractions during particular phases of the gait cycle. Muscle damage should be expected to occur if we do not adequately prepare patients for the frequency and intensity of eccentric contractions in daily life. ‘A number of investigators propose that healthy muscles can be trained eccentrically to resist muscle damage.” We know from the specificity of training literature that strength im- provements are specific to the contraction type used in the taining regime.** Therefore, physical therapists should be performing strength training with these patients eccentrically if they are to recover to preinjured functional levels. However, ‘we must be cautious and scientific in our development of cri- teria for initiation of this training, protocols for progression, and clear objective tests for determining presence/absence of muscle damage in this population. None of these measures is, currently in place for clinicians. Therefore, a multidisciplinary team approach consisting of clinicians and scientists is re- quired to develop guidelines for an eccentric training program. ‘The team should assess the effectiveness of the program on the recovery of patients with GBS from multiple levels of analysis (pathology, impairment, and functional limitation). Until that time, the advancement of therapeutic strategies must rely on the tools of scientific inquiry that the rehabilitation team pos- Avoid Stressing Musculature With Less Than Ai Strength Stress avoidance may be an important parameter, but the clinical implementation is jeopardized because of its ambigu- ity. To improve strength in a muscle, that muscle must be over- loaded (see Curtis and Weir, this issue). Does this constitute stressing? When the muscle does not have antigravity strength, even activity in a gravity-neutral environment is stressing the muscle, so what are our guidelines for progressing? wvity Antigravity strength is going to recover at different times for Jones DA, Rutherford OM. Human muscle strength training: the effects or thre diferent regimes and the nature of the resultant changes. J Physi, 1987:391:1-11 Jones DA, Rutherford OM, Parker DF. Physiological changes in stele ‘muscle a a result of strength training. QJ Exp Physiol. 1989:74:233.256 +» Grinby G, Eiarsson G, Hedberg M, Aniansson A. Muscle adaptive changes postpolio subject. Scand J Rehabil Med. 1989:21:19-2. « Lovelace RE, Myers Si. Nerve conduction and neuromuscular transissio, Inv Downey JA, Myers SJ, Gonzales EG, Lieberman JS, eds. The Physiological Basis of Rehabilitation. Boston, Mass: Butterworth. Heineman; 1994:215-242, « Piteti KH, et al. Endurance exercise traning in Guillain-Barré Syndrome, ‘Arch Phys Med Rehabil, 1993:14:761-168. «© Karper WB. Effects of iow intensity aerobic exercise on one subject with ‘Chrdnicelapsing Guillain-Barré syndrome. Rehab Nursing. 1991;16:96-58, «© ‘Aitkens SG, MeCrory MA, Kilmer DD, Beraver EM. Moderate resistance xercise program: its effet in slowly progressive neuromuscular disease ‘Arch Phys Med Rehabil, 1993:74:711-7115, Kilmer DD, MeCtory MA, Wright N, Athens SG, Bemauer EM. The ees ofa high resistance exercise program in slowly progressive neuromuscular disease. Arch Phys Med Rehabil. 1994;75:360-563. ‘© Winstein Cl, etal. Standing balance training: effect on balance and leo motion in hemiparetic adults. Arch Phys Med Rehabil. 1989:70:755-762, $10,000 STIPEND UNIVERSITY OF FLORIDA DEPARTMENT OF PHYSICAL THERAPY ‘A new program with an opportunity to obtain an ‘advanced degree in Physical Therapy. The program is specifically designed for those thera interested in NEURO-REHABILITATION ‘Support For: 1) Payment of tuition and fees for full-time students 2) Appointment as a graduate assistant with a stipend for living expenses Admission Requirements: 1) GRE scores of 1000 2) One year of clinical experience in physical therapy 3) Three letters of professional recommendation For further information contact: Denis Brunt, EdD, PT Department of Physical Therapy Box 100154 University of Florida Gainesville, FL 32610 (904) 395-0085