Hi, I'm Dr. Marilyn Pacheco. I'll be presenting spasticity and upper motor neuron syndrome pathophysiology. I do not have relevant financial relationships to disclose. At the end of this presentation, participants will be able to distinguish between negative and positive signs of upper motor neuron syndrome and also the third sign. Know the definition of spasticity, differentiate upper motor neuron syndrome manifestation and describe the pathophysiology of spasticity. Let us review the overall pathophysiology of impairment after damage to the central nervous system. Damage to the higher centers will cause dysfunction in several descending pathways, among which is the corticospinal tract involved in voluntary movement. This dysfunction of the corticospinal tract will provoke immediately a paralysis that would leave muscles immobilized, some of them in a shortened position. This will be chronologically the first factor of muscle shortening, that is contracture. On the other hand, the damage to the higher centers will provoke an imbalance in spinal reactivity through a modification of the descending input received by spinal neurons. After a variable period of time, spinal circuits will undergo plastic rearrangements that will lead to abnormal muscle contractions and abnormal reflex responses, some of which will meet the classical definition of spasticity. Then a reciprocal potentiation is likely to occur between spasticity and muscle shortening. The impact of any muscle overactivity on muscle length, including spasticity, has been well known since the 1930s and the works of Pollock and Davis. A reciprocal impact from muscle shortening to spasticity has been established in both animals and in humans. For damaging upper motor neurons, weakness and loss of dexterity are immediately apparent. Other signs can be hypotonia and loss of muscle stretch reflexes. These signs are known as negative features of the upper motor neuron syndrome. Sometime later, other signs appear characterized by overactivity, including spasticity, increased muscle stretch reflexes, clonus, extensor spasms, flexor spasms, Babinski sign, positive support reaction, co-contraction, spastic dystonia, and associated reactions. These signs are known as positive signs of upper motor neuron syndrome. Among them, the only one that tends to appear soon after deletion together with the manifestation of negative sign is the Babinski sign. The third sign is the presence of stiffness and contracture leading to disability. This slide shows the definition that was agreed upon in a meeting organized in Scottsdale, Arizona in 1979. The definition is a long sentence that may appear confusing. In 1980, Lanz published this frequently cited definition. Spasticity is a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes, which is muscle tone, with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex as one of the components of the upper motor neuron syndrome. This definition emphasizes the fact that spasticity is just one component of upper motor neuron syndrome. It is important to note that the expression tonic stretch reflex actually means a tonic muscle response to vibratory stretch. Thus, the definition only means that spasticity is the increase in muscle response to phasic stretch in a velocity-dependent manner. In routine practice at bedside, the two ways of assessing spasticity by phasic stretch are passive mobilization at different speeds and tendon taps. The core feature of spasticity is the exaggeration of stretch reflexes. The result is velocity-dependent increase in resistance of passively stretched muscle or muscle group. Besides the dependence from velocity, spasticity is also a length-dependent phenomenon. An example is the quadriceps. Spasticity is greater when the muscle is short than when it is long. This is probably one of the mechanisms underlying the so-called clasp-knife phenomenon. Bending the knee at first when the muscle is short, a greater resistance is met. Then when quadriceps lengthen, the resistance suddenly disappears. Another mechanism underlying the clasp-knife phenomenon could be the excitation of the higher threshold muscle receptors group 3 and 4 belonging to the flexor reflex afferens. On the contrary, in the flexor muscles of the upper limb and in the ankle extensors, spasticity is greater when the muscle is long. Spasticity is more often found in flexor muscles of the upper limb and in the extensors of the lower limb. However, there are several exceptions. For example, we observe patients in whom spasticity is prevalent in the extensor muscles of the forearm. Hypermotor Neuron Syndrome is complex where spasticity is one of the components. The hyperexcitability of the stretch reflex produces spasticity, clonus, and increase of muscle stretch reflexes. The phenomenon commonly associated with spasticity are abnormal and exaggerated cutaneous and nociceptive responses such as the elevation of the great toe when rubbing the external edge of the sole of the foot. On the contrary, co-contraction and associated reactions do not depend on spinal reflexes, therefore they are efferent phenomenon. Also, spastic dystonia is thought to depend on efferent drive. Associated reactions are involuntary movements due to the activation of paretic muscles which occur during voluntary activation of unaffected muscles or during involuntary events such as yawning, sneezing, and coughing. An example of associated reaction is the elbow flexion and arm elevation often seen in hemiplegic patients during walking. Co-contraction is the simultaneous contraction of both the agonist and antagonist muscles around a joint. An example would be your wrist flexors and extensors. In healthy subjects, the voluntary output from the motor cortex activates the motor neurons targeting the agonist muscles and through the 1A interneurons inhibits those innervating the antagonist muscles. In the upper motor neuron syndrome, co-contraction is due to the loss of reciprocal inhibition during voluntary command. This is likely to be the most disabling form of muscle overactivity in patients with upper motor neuron syndrome as it hampers the generation of force or movement. Spastic dystonia is a very important form of overactivity. Spastic dystonia refers to the tonic contraction of a muscle or muscle group when a subject is at rest. It can be described as relative inability to relax muscles. Spastic dystonia can alter resting posture contributing to the hemiplegic posture. The upper limb is flexed and adducted. The lower limb is extended. Although not induced by muscle stretch, spastic dystonia is sensitive to muscle stretch and length. It can be triggered by muscle stretch even though prolonged stretch can reduce it. The common view is that spastic dystonia is an efferent phenomenon mediated by an abnormal pattern of supraspinal descending drive. The inability to relax the muscle is the central feature in spastic patients and is likely to be connected to the prolonged firing of the alpha motor neurons in a well-documented phenomenon in patients with upper motor neuron syndrome. Pathological antagonistic co-contraction or spastic co-contraction is an abnormal contraction occurring in an antagonist muscle when the agonist is involved in a voluntary effort. It has been established that these co-contractions are aggravated when the antagonist muscle is under tonic stretch. Spastic dystonia and spastic co-contraction are two different types of muscle overactivity. One is present at rest and the other is present during voluntary movement. Both are influenced by the degree of recruitment of stretch receptors. Plantar segmental co-contractions are the abnormal contractions occurring at distance from the muscles involved in the voluntary efforts. An example would be contraction of your plantar flexors when the patient tries to elevate his sporadic arm. In this slide, we will be discussing about flexor and extensor spasms and abnormal cutaneous reflexes. An increased excitability in the physiological flexor withdrawal reflex produce flexor spasms in the lower limb. This commonly is seen after spinal cord injuries. The release of primitive reflexes is the cause of Babinski sign and the positive support reaction. The Babinski sign is a cutaneous reflex while positive support reaction is a proprioceptive reflex. As mentioned earlier, there are other types of muscle overactivity associated with spasticity. An example that was mentioned earlier is the contraction of the elbow and forearm flexors during yawning or the plantar flexor during yawning and heavy breathing. Muscle shortening is a consequence of both immobilization and overactivity. Motor weakness accounts for a part of the functional impairments in these patients. In summary, muscle shortening, motor weakness, and stretch-dependent forms of muscle overactivity, in particular spastic co-contraction and spastic dystonia are probably the most disabling features in spastic patients. In therapy, there will be three logical solutions. Muscle lengthening to address contractures, motor training to address the lack of motor power in these muscles that are mostly weak and hypoactive, and local muscle weakening in those muscles that are overactive. In the next half of this lecture, we will be discussing the pathophysiology of spasticity, which is not completely elucidated. It probably involves both abnormal descending pathways and plastic rearrangement in the spinal cord. This slide illustrates a simplified schema of some of the elements that contribute to the stretch-reflex pathway. There are likely to be many more pathways, neuronal elements, and neurotransmitters that contribute to the final output from the motor neuron. In healthy subjects, stretch reflexes are mediated by excitatory connections between 1A afferent fibers from the muscle spindles and alpha motor neurons innervating the same muscles from which they arise. Passive stretch of the muscles excites the muscle spindles, leading 1A fibers to discharge and send inputs to the alpha motor neuron through the mainly monosynaptic but also oligosynaptic pathways. The alpha motor neurons in turn send an efferent impulse to the muscle, causing it to contract. One may consider the motor neuron within the spinal cord to be discrete entity with influences from the segmental spinal levels as well as those resulting from upper and lower regions. The segmental neuronal structures include motor neurons and interneurons. Some of the descending pathways which modifies excitability of the stretch reflex include vestibular spinal, reticular spinal, and monoaminergic pathways. Previous EMG recordings in a normal subject at rest clearly show that passive muscle stretches performed at velocities used in the clinical practice to assess muscle tone do not produce any reflex contraction of the stretch muscle. For instance, recording of the EMG of elbow flexors during imposed elbow extension, no stretch reflex appear in the biceps when the passive displacement occur at the velocities usually used during clinical examination of muscle tone, that is, 60° to 180° per second. It is only above 200° per second that a stretch reflex can be usually seen. Therefore, stretch reflex is not the cause of muscle tone in healthy subjects. The muscle tone in healthy subjects is completely due to biomechanical factors. Different from healthy subjects, in patients with spasticity evaluated at rest, a positive linear correlation between EMG activity of the stretch muscles and velocity was found using a range of displacement velocities similar to that used in clinical practice to evaluate muscle tone. When the passive stretch is slow, the stretch reflex tends to be small, low in amplitude, and the tone may be perceived relatively normal or just increase. When the muscle is stretched faster, the stretch reflex increases and the examiner detects an increase in muscle tone. Therefore, spasticity is due to an exaggerated stretch reflex. Although spasticity is velocity dependent, surface EMG recordings show that in many cases, if a stretch is maintained, the muscle still keeps contracting, at least for a time. Although spasticity is considered classically dynamic, there is also an isometric tonic muscle contraction after the stretch reflex elicited in a dynamic condition. Let's discuss the established mechanisms to be factors of increase in the stretch reflexes. The first one is a change in muscle active properties that was shown by Edstrom in the 1970s and followed by others. It showed that there is a proportional increase in type 1 slow tonic fibers versus type 2 fast fibers. As a result, for the same amount of EMG, a greater amount of torque is developed. The second one is that establishment of the extensibility of spastic muscles is reduced in both animals and in humans. This reduction in passive muscle extensibility involves both a reduction in numbers of sarcomere as Tardot has demonstrated in the 70s and an accumulation of connected tissue inside the extrafusal fibers. This increase in connective tissue allows for a better stretch transmission to spindles. The next one would be a decrease in presynaptic inhibition, at least in paraplegic patients. There is an increased activity of gamma or alpha motor neuron. The microneurography studies looking at gamma motor neuronal activity have brought no demonstration of increased gamma motor activity. As for the alpha motor neuron activity, it is impossible to directly access in humans. The next established mechanism is the one affecting the reflex arc. There is a decrease in reciprocal 1A inhibition on the extensor muscles, which could explain overactivity of these muscles in the lower limbs. There is also a decreased nonreciprocal 1B inhibition that could participate in the mechanism of co-contraction. Finally, there is a decreased inhibition from the flexor reflex afferents that could also participate in the hyperexcitability of the stretch reflex arc. Another way of looking at this is dividing it into spasticity, the spinal model pathophysiology, and spasticity, the cerebral model pathophysiology. In both areas have excitatory and inhibitory pathophysiology. Spinal excitatory mechanism includes increased FUSI motor drive, primary hyperexcitability, of alpha motor neurons following spinal lesions, and enhanced cutaneous reflexes. Spinal inhibitory mechanisms include presynaptic inhibition of the 1A afferent terminals, disynaptic reciprocal 1A inhibition from the muscle spindle 1A afferents of the antagonist muscles, recurrent inhibition via motor axon collaterals and rential cells, nonreciprocal 1B inhibition from the Golgi tendon organs, and inhibition from the muscle spindle group 2 afferents. The supraspinal excitatory mechanisms involve vestibulospinal pathway and medial reticulospinal track. Supraspinal inhibitory mechanisms involves the corticospinal pathway, the corticoreticular pathways, and the dorsal reticular spinal track. In upper motor neuron syndrome, hyperexcitability of the stretch reflex can result in A. Babinski reflex, B. Associated reaction, C. Spastic dystonia, and D. Co-contraction. The correct answer is A. The hyperexcitability of a stretch reflex produces spasticity, clonus, and the increase of muscle stretch reflexes. The phenomenon commonly associated with spasticity are abnormal and exaggerated cutaneous and nociceptive responses, such as the elevation of the great toe when rubbing the external edge of the sole of the foot. The Babinski sign is a cutaneous reflex that results from the stretch reflex hyperexcitability. Co-contraction and associated reactions do not depend on spinal reflexes. Therefore, they are efferent phenomenon. Also, spastic dystonia is taught to depend upon the efferent drive. Let us summarize what we've learned in this short presentation. We have learned that upper motor neuron lesion can lead to positive, negative, and third signs. Positive signs are muscle overactivity, while negative signs are weakness. Third sign is the stiffness and contracture that happens. Muscle overactivity can be divided into dynamic and static. Muscle overactivity phenomenon includes spasticity, spasms, co-contraction, clonus, associated reaction, flexor and extensor withdrawal, and spastic dystonia. All of these can lead to impaired infunction. We have also learned the pathophysiology of spasticity in this lecture. And these are the references for this short presentation. Thank you for listening.

spasticity

upper motor neuron syndrome

corticospinal tract

muscle paralysis

plastic rearrangements

treatments