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Neurologic Back Pain: Myopathies, Neuromuscular Disease, Parkinson, and Dystonia
Asdrubal Falavigna and Carlo Domênico Marrone
■ Introduction
The International Association for the Study of Pain (IASP)1 defines pain as a disagreeable sensory and emotional experience associated with real or potential tissue damage. Back pain is a symptom that cannot be validated by an external standard or norm, and it is a multifactorial disorder with many possible etiologies.2 The annual incidence of chronic or recurring back pain varies from 35 to 79%.3
Neuromuscular pathologies trigger clinical signs and symptoms, because they compromise the peripheral nervous system or the skeletal striated muscles. The pathologies can affect the following: (1) lower motor neurons (e.g., amyotrophic lateral sclerosis and spinal muscle atrophy); (2) sensory ganglia (e.g., sensory neuronopathies); (3) nerve roots and peripheral or cranial nerves (e.g., Guillain-Barré syndrome, Charcot-Marie-Tooth disease); (4) nerve plexuses (e.g., Parsonage-Turner syndrome); (5) neuromuscular junction (e.g., myasthenia gravis); and (6) muscle (e.g., muscular dystrophies, inflammatory myopathies, drug-induced myopathies, etc.) (Table 7.1). The diseases that compromise the movement usually originate in the central nervous systems and comprise the dystonias and parkinsonian syndromes, the most common of them being Parkinson’s disease.
This chapter discusses the influence of the neuromuscular diseases, Parkinson’s disease, and dystonia on back pain.
■ Lower Motor Neuron Diseases
The group of lower motor neuron diseases represents hereditary or acquired etiologies, and is characterized by motor function disturbances that are not accompanied by disorders of reasoning, thinking, consciousness, cognition, preserved sensibility, or behavior, or by movements of the bowel, bladder, or eyes (Table 7.1).
Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving primarily motor neurons of the brain cortex, brainstem, and spinal cord that directly control the muscles and movements. Hence, the primary motor neurons, or the central and secondary or peripheral ones, are compromised. It is believed that there is an interaction of genetic defects increasing a person’s susceptibility to the disease.
The clinical presentation is usually nonspecific, as the beginning of the clinical picture depends on the neurologic area that has been primarily affected. The physician should suspect the disease during the history taking and examination of the patient when the following conditions are seen: (1) atrophy (e.g., of the first interosseous muscle of the hand); (2) distal muscle weakness (e.g., drop foot in the absence of root pain); (3) disseminated or focal fasciculation; (4) spasticity and signs that the first motor neuron is compromised; (5) progressive motor loss both for swallowing and for movements of the face and tongue; and (6) complaints of sometimes intense cramps, unrelated to physical effort and at less frequent sites (e.g., the submandibular region).
In one study, 78% of patients with ALS reported that the onset of pain occurred in the 24 hours prior to presenting to the physician, with a mean number of 3 points on the pain severity scale that varies from 0 (no pain) to 10 (pain as bad as you can imagine).4 Moderate to severe pain was found in 33% of the cases. The frequency and intensity of the pain correlated with a worsened function score and with a longer duration of the disease.5 Back pain affects 50% of patients, without radicular involvement.4 Other common places where pain appeared were the area of the shoulder and hip, suggesting as an etiologic factor the overload of joints due to the loss of the protective layer caused by muscle atrophy (Table 7.2).4,5
Spinal Muscle Atrophy
Spinal muscle atrophy (SMA) is an autosomal recessive genetic disorder of the motor neuron. The patient presents with progressive muscle weakness because of the loss of the lower motor neurons located in the anterior horns of the spinal cord and nuclei of the cranial nerves. As to genetics, the gene of motor neuron survival (MNS) is situated on the long arm of chromosome 5 (Sq11.13.3) that encodes the protein that carries its name. Each normal individual has two MNS genes, MNS1 and MNS2; a mutation, deletion, or rearrangement of MNS1 causes 95% of SMAs.6
There are many types of SMA, which can be classified according to their predominantly proximal or distal location. The proximal presentation is more frequent. SMA can also be classified, based on symptom onset, as severe, Werdnig-Hoffmann (type I); intermediate form (type II) (Fig. 7.1); juvenile form, Kugelberg-Wellander (type III); and the adult beginning form (type IV).
The clinical presentation of these forms has in common the following findings: progressive muscle weakness, deep myotatic areflexia, hypotonia, and preserved sensitivity, without the involvement of the central nervous system. In type I, symptoms begin early, such as intrauterus, at birth, or in the first 3 to 6 months of life. In these cases the clinical presentation is alterations in respiration and swallowing, and life expectancy is no longer than 2 years. In type II, symptoms begin at ages 6 to 18 months, and include decreased motor development. These patients are able to sit with or without support, and they may reach the stage of being able to stand, generally with external support, but they are unable to walk, and they demonstrate bulbar weakness and difficulty in swallowing. Over time, among other abnormalities, there are respiratory alterations, deformities, and scoliosis. In type III, symptoms begin after 18 months of age and either before the age of 3 (type IIIa) or at age 3 or older (type IIIb). Type IIIa patients are no longer walking by the age of 20 years, and type IIIb patients are no longer walking at some point after age 20 years, even with difficulty or the help of ortheses. In type IV, symptoms of muscle weakness and areflexia begin between the second and fourth decades of life.
The initial clinical and laboratory picture may be confused with that of other pathologies, especially myopathies due to elevation of creatine phosphokinase (CPK), a muscle marker, to at most five times above the normal value. Electroneuromyography shows a neurogenic pattern. The diagnosis is based on clinical presentation, laboratory findings, electrophysiological results, and molecular analysis showing the absence of exon 7 of the SMN1 gene.
In one study, 71% of adolescents with SMA type II or III had persistent or recurrent chronic pain in the previous 3 months; of these patients, 92% experienced pain for longer than 3 months.7 The pain lasted less than 1 hour in 46% of cases and between 1 and 12 hours in 36%. The most common site of pain, in 92% of cases, was the region of the neck or back, and was more severe in the nonambulating patients (Table 7.2).
None of the adolescents with SMA type II who were treated with spine surgery ambulated, whereas in SMA type III 57% could ambulate. Despite surgery, a large number still reported back pain and neck pain. A possible cause of this pain was osteoporotic fractures.7 The pain was exacerbated when the patients were being lifted and transferred (62%), when seated (46%), and during other activities (39%). Pain relief was observed from measures that did not involve drugs. Rest and change of position relieved pain in 62% of the cases, and, in patients who did not ambulate, change of position was the maneuver that gave the most relief.
Polyradiculoneuropathies
Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy that presents with muscle weakness and reduction or absence of deep myotatic reflexes. It has several subclassifications: acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute sensorimotor axonal neuropathy (ASMAN), and Miller Fisher syndrome.
Initially it was described as a demyelinating process, but other similar cases were described that affect the axon and the node of Ranvier. The disease is characterized by an immune-mediated disorder, usually preceded by an infection, that induces the production of antibodies that attack components of the nerve root and the nerve, especially components of the myelin sheath, such as gangliosides and glycolipids (e.g., GM1 and GD1b).
The triggering phenomenon may be a mild respiratory or intestinal infection 2 to 4 weeks before the symptoms begin. The clinical presentation generally includes paresthesia, as well as progressive muscle weakness, usually ascending, from the lower limbs to the upper limbs and trunk, and it can evolve within hours or days to dysfunction of the cranial nerves and of the innervation of respiratory muscles. The clinical picture generally reaches its worst point in 30 days, but the abnormalities may take days, months, or years to revert. Normally, 70% of patients recover within 12 months and 82% within 24 months. Unfortunately, some patients may have definitive sequelae or even die as a consequence of respiratory failure and autonomic alterations such as hypotension and cardiac arrhythmia.
The diagnosis is suspected from the clinical picture of paresis/flaccid ascending paralysis, sensory alteration on a smaller scale, and areflexia. The examination of cerebrospinal fluid after about 1 week shows a protein-cytological disproportion, with increase of proteins and normal white cellularity in 80 to 90% of patients. Electroneuromyography shows a demyelinating involvement from the third or fourth day onward, but generally with characteristic signs after the first and especially the second week of onset of the disease. Because myelin is responsible for speed in the transport of information, there is a slowdown in nerve conduction, with or without prolonged latency, as well as temporal dispersion, partial or total conduction blockage (generally motor), and prolonged late waves (F waves). When axonal involvement is more severe, there is an active denervation that is expressed by fibrillation and positive wave. Patients can be treated with plasmapheresis or intravenous human immunoglobulin. Respirator failure must be prevented by means of mechanical ventilation. Autonomic intercurrences are possible, especially when there is motor improvement, due to the risk of cardiac arrest and hypotension.
The onset of painful symptoms of moderate to severe intensity may occur in several parts of the body, generally in the back. Often pain begins in the lower back or lumbosacral region, and sometimes it radiates to the lower limbs, simulating sciatic pain, which is caused by the inflammatory radiculopathy. About 55% of patients present with back pain, and 72% complain of back pain during the course of the disease.8 The presence of back pain alone, independent of the lower limbs being radiated, is not a sign of GBS onset; other symptoms must also be present, such as flaccidity, lack of strength, paresthesias, or areflexia, in order to corroborate the diagnostic hypothesis of GBS (Tables 7.1 and 7.2).9
In children younger than 10 years of age, back pain may be the initial symptom in 20% of cases.10 However, back pain and lower limb pain may be present in 83% of children under the age of 6 at the beginning of the illness. In the acute phase, there is an association between back pain and the thickening and uptake of contrast in the nerve roots detected on magnetic resonance imaging (MRI) due to inflammation or compression of the nerve roots.10,11
Clinical evolution of acute or subacute back pain, with or without radiation to the lower limbs and an autonomic disorder such as bladder dysfunction for longer than 24 hours, probably is not GBS but rather a medullar lesion, such as myelitis, in which the sensory level has not yet appeared, or has been undervalued.
■ Myopathies
Myopathies are a heterogeneous group of diseases, in which muscle fibers, and their structures, channels, or metabolism, as well as the muscle interstice, are affected, resulting in muscle weakness.
The myopathies may present as hereditary or acquired. Hereditary myopathies generally evolve chronically; the acquired myopathies haven’t muscle involvement prior the initial signals presentation. Regarding the anatomopathology, muscle fiber necrosis may be present or possibly may have been replaced by inflammatory infiltrated fatty tissue proportional to the necrosis, and by increased connective tissue; these findings indicate the presence of dystrophy. In the myopathies, the structure of the muscle fibers is affected; in inflammatory myopathy, there is a predominance of inflammatory infiltrate.
The clinical picture typical of a myopathy is symmetrical and proximal muscle weakness without any sensory involvement, in contrast to peripheral neuropathies, which are distal and symmetrical to the sensory involvement (Tables 7.1 and 7.2).
Polymyositis and Dermatomyositis
Polymyositis and dermatomyositis are nonsuppurative and idiopathic inflammatory diseases of the muscles. In polymyositis only the muscles are involved, whereas in dermatomyositis both the muscles and the skin are involved.
The disease presents with proximal and symmetrical muscle weakness, often accompanied by pain that develops over weeks or months. Especially in polymyositis the “dropped head” sign can be seen, because of the weakness of the posterior cervical muscles and difficulty in swallowing. In dermatomyositis, the skin changes are characterized by edema and erythema of the eyelids (heliotrope), erythema on the extensor surfaces of the fingers (Gottron’s sign), and small dark-red points on the edge of the cuticles (periungual vasculitis). The muscle enzymes of CPK are elevated, and electroneuromyography identifies the myopathic and denervation pattern.
Muscle biopsy in polymyositis shows necrosis, degeneration, and regeneration of fibers, with an inflammatory infiltrate surrounding fibers that are generally not necrotic, such as those between the muscle fibers. This inflammatory infiltrate is composed of CD8 T lymphocytes, suggesting a cytotoxic process mediated by T cells against muscle antigens that have not been well defined. In contrast, in dermatomyositis there is a vasculitis, and this inflammatory infiltration includes predominantly B cells and CD4 helper lymphocytes, hence with humoral mediation. Perifascicular atrophy is found as a result of microinfarctions that are pathognomonic, in addition to degeneration, regeneration, and necrosis of muscle fibers.
The muscle inflammation observed may cause mild or moderate pain disseminated throughout the body, including the back.
Myopathy Caused by Statins
Statins are prescribed for treating dyslipidemias; they inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, ultimately helping reduce myocardial and cerebral infarctions. One of the side effects is muscle alteration. Patients who use statins have a 50% greater likelihood of having musculoskeletal pain and a 50 to 60% greater likelihood of having pain in the back and legs.12
The clinical manifestations can vary from minor complaints of muscle fatigue that does not interfere with the patient’s functioning to the very serious symptom of rhabdomyolysis. The American College of Cardiology (ACC)/ American Heart Association (AHA)/ National Heart, Lung, and Blood Institute (NHLBI) defined the following terms used for muscle symptoms of statin13: myalgia is muscle pain without an elevation of CPK; myopathy is any muscle disease; myositis is muscle symptoms with increased CPK; and rhabdomyolysis is muscular symptoms in association with a CPK elevation more than 10 times the normal upper limit, the elevation of creatinine, and the occasional presence of myoglobinuria.
Myalgia is expressed clinically by muscle weakness, pain in the proximal muscles, and/or back pain. The mean time to onset of myalgia after beginning statin use is still under discussion, but it usually occurs after about 1 month. The myopathic picture appears to be well correlated with the statin dose and to be independent of cholesterol reduction.14
Case Study
A 52-year-old man, a smoker with prior myocardial infarction, was prescribed a statin. After 3 months, he started to experience serious lower back pain, with mild radiation to the lateral and anterior portion of the right thigh, without a deficit of strength or a change in sensitivity. An extensive examination was performed of the hip and urinary system, as well as determining the possibility of radicular alterations, and the patients medications were reviewed. Nothing was found to explain his discomfort. After the statins were withdrawn, the lower back pain disappeared in 5 to 10 days.
Because statin-induced muscle abnormalities are common, physicians must seriously weigh the risk of muscle symptoms against the statin’ benefit of preventing a myocardial infarction or cerebrovascular accident.
Dystrophinopathies
Dystrophin is a protein essential to the muscle structure. It is located subsarcolemmally, connecting the actin to the sarcolemma. The gene that encodes dystrophin is located on the short arm of chromosome X (locus Xp21) and it is the largest gene in humans, with 79 exons. Mutations of this gene cause a partial or total dysfunction of this protein, giving rise to two important muscular dystrophies, DMD and BMD.
Both DMD and BMD appear in boys because they are limited to chromosome X. DMD begins earlier and is more severe, and BMD is milder with a later onset. DMD can begin as early as around 18 months, but it is generally noticed around the age of 4 years. There is proximal muscle weakness, especially in the lower limbs, pseudohypertrophy of the calves, anserine gait, and Gowers’s sign, with a rise from a sitting to a standing position by grasping and pulling on body parts from the knees to hips until reach an erect position (laborious escalade on itself). These findings reflect muscle involvement in general, and are not pathognomonic of the dystrophinopathies. Over time, the picture becomes more severe, with progressive difficulties until the patient stops walking between the ages of 9 and 13 years. Later there are difficulties with the upper limbs as well as scoliosis, especially in wheelchair users.
The elevation of CPK in the blood is more than 10 times the upper limit for the patient’s age, and sometimes may be 50 to 100 times the upper limit. Because the transaminases rise, many children undergo liver investigation, including liver biopsies, and it must be remembered that transaminases are also part of the muscle enzymes. In more advanced cases, due to the simple fact that there is no more muscle to be degraded, the muscle enzymes may become normal. Electroneuromyography has a myopathic pattern, with normal neuroconduction, and the needle exam shows short duration and short range potentials, often polyphasic, and increased paradoxical recruitment. Muscle biopsy shows a dystrophic pattern, with immunocytochemistry evidencing almost complete absence of dystrophin in muscle fibers (Fig. 7.2). Molecular analysis by polymerase chain reaction (PCR) shows an abnormality in 60 to 70% of cases, and it is useful to identify the abnormality by sequencing the dystrophin gene.
A BMD presents with milder defects in dystrophin, so that although the protein is truncated, it is partially functional. The clinical picture is similar to that observed in DMD, but with a later onset of symptoms, after the age of 5 to 7 years, or sometimes in adolescence (Fig. 7.3a). Enzymatic alterations may be small, with a CPK that is less than 10 times the normal level or even normal. The electroneuromyographic alterations are similar to those in DMD, and the muscle biopsy may reflect the same dystrophic pattern, but in immunocytochemistry there is the partial presence of dystrophin (Fig. 7.3b,c). The molecular analysis by PCR may be normal.
In one study, 41% of patients with DMD/BMD experienced pain in the previous 3 months,7 and of these patients, 76% had neck and back pain. Similar to the findings reported with SMA, nonambulating patients had more pain, especially back pain. The factors that most exacerbates the pain were sitting position in 52%, and daily activities in 44%; the factors that relieved pain were rest in 88%, change of position in 80%, and massage in 64%. The causes of the pain, both in ambulating and nonambulating patients, are the same described above for patients with SMA.
Improved patient care, especially mechanical ventilation, increases the survival of these patients, and in one study 85% reached the age of 30 years.15 The incidence of pain was 73.5% in patients with DMD over the age of 20 years who were nonambulators and on mechanical ventilation; 24.1% had back pain and 11.4% neck pain.16 Of patients with a poor quality of life, 80% reported experiencing pain and fatigue, whereas of patients with a good quality of life, the prevalence of pain was 70%.
