Stiffness syndromes

Introduction

Muscle stiffness may be the presenting symptom in many disorders of the motor nervous system and muscles ( Table 21.1 ). Spasticity is the most common, and the others must be distinguished from it. In this chapter, therefore, spasticity is the primary topic and considered first. The pathophysiologic process of rigidity, muscle stiffness in parkinsonism, is discussed in Chapter 2 . The important entities of stiff-person syndrome and its variants and neuromyotonia, syndromes of continuous muscle activity, are both autoimmune in nature and are considered in Chapter 23 . Continuous muscle activity can also arise from situations in which the pathophysiologic features lie in the muscle, nerve, or anterior horn cell. These conditions will also be considered in this chapter.

Stiffness is assessed by the amount of force required to make an object move. Tone, the more general clinical term, can be defined as the resistance to passive stretch of a joint. Stiffness is a sign and not a symptom. Patients may well mistake their weakness or bradykinesia as being stiff. Normal tone is very low, and it is difficult to appreciate a decrease in tone, but some authorities say that they can detect hypotonia in cerebellar dysfunction. Increased tone, hypertonia, is characteristic of several different states and can come from three theoretical mechanisms: (1) altered mechanical properties of the muscle or joint, (2) background co-contraction of muscles acting on the joint, and (3) increase in reflex response to the stretch opposing the movement ( ). Background muscle activity is often the most important of the three. The mechanical characteristic of muscle that describes its resistance to stretch is thixotropy. The most severe change of altered mechanical properties is contracture. Increased background contraction is often seen with difficulty in relaxation, such as commonly characterizes Parkinson disease. In most patients with dystonia, there is increased tone only when there is dystonic activity of a muscle. Background contraction is also obviously the main cause of increased tone in patients with continuous muscle activity syndromes. There are many different reflexes that can occur in response to stretch, and these can help differentiate different states of hypertonia. In differentiating spasticity and rigidity, in simple terms, spasticity shows exaggerated short latency reflexes and rigidity shows exaggerated long latency reflexes ( Table 21.2 ).

Spasticity

Spasticity is a form of hypertonia with a number of characteristic features ( ; ; ; ; ; ; ). The increased resistance to stretch is velocity sensitive; there is more resistance the faster the joint is moved. There also might be a spastic catch, in which there is a sudden increase in tone in the middle of a fast stretch. There may be a clasped-knife phenomenon in which the resistance increases and then suddenly gives way. There are also several other “positive” features such as increased tendon jerks, clonus, increased flexor reflexes, spontaneous flexor spasms, and abnormal postures (spastic dystonia) ( ). Importantly, there are also “negative” features, including weakness (in a “pyramidal distribution”), fatigue, loss of coordination, and a decrease of some cutaneous reflexes. It can be noted that the increased stiffness can be valuable to a patient with significant weakness, because it might, for example, allow the patient to stand.

Loosely, neurologists usually say that spasticity arises from a lesion in the pyramidal tract or that it is from damage to the “upper motor neuron.” The first is false, and the second is vague. Supraspinal control of movement is complicated and consists of many tracts. Briefly, those fibers that go through the pyramid arise from the cortex and go to the spinal cord also can be called the corticospinal tract ( ). Approximately 30% of those fibers arise from the primary motor cortex; but there are also significant contributions from premotor cortex and sensory cortex. The fibers largely cross in the pyramid, but some remain uncrossed. Some terminate as monosynaptic projections onto alpha-motoneurons, and others terminate on interneurons, including those in the dorsal horn. Other cortical neurons project to basal ganglia, cerebellum, and brainstem; these structures can also originate spinal projections. Particularly important is the reticular formation that originates several tracts with different functions ( ). The dorsal reticulospinal tract may have particular relevance for spasticity and is normally inhibitory onto the spinal cord ( , ; ). There is cortical innervation of the reticular formation, and this is called the cortico-reticulo-spinal tract. Lesions of the primary motor area alone and lesions of the pyramid alone do not cause spasticity ( ). It appears that premotor damage is necessary and likely involvement of cortico-reticulo-spinal pathways. Dysfunction of the dorsal reticulospinal tract will disinhibit the spinal cord and may give rise to the hyperexcitability characteristic of spasticity ( ). Then there could be secondary changes in the spinal cord itself (Trompetto et al., 2014). The term “corticofugal syndrome” has been suggested to indicate that “spasticity” has important negative and positive features and that the lesions involve descending tracts other than the corticospinal tracts ( ). This term, however, has not been commonly used.

The clinical and physiologic features of spasticity differ to some degree depending on whether the lesion is cortical or spinal. Spasticity observed in hemiparesis differs from that seen with spinal cord lesions. For example, exaggeration of flexor reflexes is much more likely with spinal lesions. This certainly must be derived from the difference in the exact pattern of damage to the descending tracts.

Clinical features of spasticity that help with the diagnosis, in addition to the velocity-dependent increased tone, include brisk tendon reflexes, the Babinski sign, the Hoffman reflex (indicating brisk finger flexor reflexes), and loss of cutaneous abdominal reflexes. The negative features often will be seen as well, with weakness in the lower extremities of flexors more than extensors and in the upper extremities of extensors more than flexors. In the clinical neurophysiology laboratory, there will be increased H reflexes, identified with an increase of the maximum amplitude H reflex compared with the M wave (muscle response to direct supramaximal stimulation of the nerve), called the H/M ratio (Hallett, 2012). There is also a diminished decrease of the H reflex with vibration of the body part. Characteristics of the tonic stretch reflex also can be assessed for threshold and gain to stretches of varying velocity. In spasticity, there is some controversy, but both lowered velocity threshold and an increased gain have been found ( ; ; ). It is important to recognize that there are both reflex and nonreflex contributions to spastic hypertonia ( ). As noted earlier there are both neural and nonneural components; there are instrumental methods that can help in this differentiation ( ).

The neurologic syndromes in which spasticity can be seen are numerous. These include stroke ( ), spinal cord injury, brain trauma, cerebral palsy, and demyelinating illnesses such as multiple sclerosis. Spasticity also can be a part of degenerative disorders, such as amyotrophic lateral sclerosis, and is the major symptom in primary lateral sclerosis. In the hereditary spastic paraplegias (HSPs) spasticity is the primary feature, and it is interesting to note the important overlap between the HSPs and the ataxias ( ). Indeed, some mutations can cause spasticity, ataxia, or both, and some of the cell biologic pathways for the two entities are shared ( ). SPG7 is particularly common in complex ataxias.

More than 80 mutations have been identified for the HSPs ( ). The entities have been divided into pure HSP and complicated or complex HSP ( ). Pure cases have slowly progressive weakness and spasticity with possible sphincter disturbance and/or sensory loss. Complex forms have additional ataxia, neuropathy, cognitive impairment, epilepsy, myopathy, external ophthalmoplegia, parkinsonism, dystonia, or psychiatric disorders. Nonneurologic manifestations may be ophthalmologic abnormalities, such as cataracts or retinitis pigmentosa, dysmorphic features, and orthopedic abnormalities. There can be a wide variety of magnetic resonance imaging (MRI) findings from mild white matter changes to leukodystrophy, thin corpus callosum, spinal cord or cerebellar atrophy, brain iron accumulation, and hydrocephalus ( ), and these changes can be genotype specific ( ). Genetically, they can be dominant, recessive, X-linked, and mitochondrial ( ). The most common autosomal dominant entities are SPG4, SPG3A, and SPG31, and the most common autosomal recessive entities are SPG11 and SPG15. The protein products of all of these genes have function in relation to organelle shaping ( ). Looking over all the HSPs, the defective genes seem to play key roles in axon development and maintenance, including organelle shaping and biogenesis, membrane and cargo trafficking, mitochondrial function, nucleotide metabolism, and lipid/cholesterol metabolism ( ).

Many methods are used to treat spasticity ( Table 21.3 ), but this must be done carefully because correction of the positive features may not be all that helpful, and, as noted before, may even be detrimental ( ; ). For many patients, the much more important aspects of their corticofugal syndrome are the negative features, such as the weakness, and these cannot be dealt with easily. Increased tone can be improved with a variety of oral agents, including benzodiazepines, baclofen, and tizanidine ( ; ; ). Baclofen can be given intrathecally by pump, and this can be much more efficacious, likely because of the ability to increase the dose at the target tissue without side effects ( ; ; ; ; ; ). Tolperisone has been evaluated in patients after stroke ( ) and might be another consideration ( ). Medical cannabis might be useful in some circumstances ( ; ; ; ), and systematic reviews, including one from the American Academy of Neurology, concluded that oral cannabis extract is, and tetrahydrocannabinol probably is, effective in the treatment of spasticity in the setting of multiple sclerosis ( ; ; ; ). Approach to pharmacological management of spastic cerebral palsy has received specific attention ( ).

Direct blockade of muscle contraction with agents such as phenol has been used for some time, and the introduction of botulinum toxin (BTX) for this purpose has been welcomed with enthusiasm ( ). Evidence-based reviews give BTX high recommendation for treatment in both adults and children ( , ; ; ). For poststroke spasticity, there is very good evidence for reduction of spasticity ( ; ). Evidence is developing for an increase in functional ability ( ; ; ; ), and can be enduring ( ), but this benefit might be only short term ( ) or limited ( ; ). Improvement might be better with higher doses than have commonly been used ( ). Children with cerebral palsy can be much improved ( ; ; ; ; ; ; ; ), but are a vulnerable population and need to be treated with care ( ). Several evidence-based reviews document the utility of BTX for this indication ( ; ). It is interesting to note that the effect of BTX is mediated not only on the alpha-motoneuron neuromuscular junction but also via the gamma-motoneuron effect on the muscle spindle ( ). Reduction of gamma-motoneuron activity will lead to slackness of the muscle spindle, reduction of muscle afferent activity, and reduced reflex contribution to increased tone. Surgical methods such as rhizotomy also can be used in some cases for symptomatic relief of severe spasticity ( ; ; Ailonr et al., 2015; ; ; ).

Of course, physical therapy is also important. In the end, a multifaceted approach with a multidisciplinary team may well be necessary ( ; ; ; ).