The evaluation of patients with suspected neurologic disease remains first and foremost a bedside exercise. Accurate diagnosis requires consideration of individual patient and disease differences. Despite the benefits of evidence-based medicine, conclusions are more relevant to populations than to individuals. Confounding variables that are part of the human experience may be overlooked or overemphasized by testing algorithms. This textbook will repeatedly emphasize the strongly held philosophy of its authors, that is, patient management flows from an accurate diagnosis. An accurate diagnosis is most likely to be obtained based on a differential diagnosis driven by clinical assessment and hypotheses. These hypotheses should be formulated on the basis of the principles of neurologic localization, the correlation of the chronologic course of symptom development with the behaviors of differing disease conditions, and the application of risk factor analysis. Ideally, the tests described in the subsequent two chapters and throughout the text would be utilized with the primary intent of resolving a clinically established differential diagnosis ideally to prove a working diagnosis. As all tests are potentially fallible, the credibility of their results diminishes when they are used as screening procedures. A laboratory abnormality, occurring without the context of clinical correlation, fails to establish the desired confidence in a cause and effect relationship with the patient’s complaint(s). Metaphorically, laboratory tests are analogous to a carpenter’s tools. They are of great value when placed in the hands of a skillful artisan, but are potentially damaging if used injudiciously.

In this book, a neuromuscular disorder will refer to any condition that affects the structure and/or function of any component of the neuromuscular system, beginning and working centrifugally from the cell bodies of the anterior horn and dorsal root ganglion. This will include disorders of nerve root, plexus, nerve, neuromuscular junction and muscle. In essence, with the exception of disorders affecting small, poorly, or unmyelinated nerve fibers such as the small fiber or pure autonomic neuropathies, a neuromuscular disorder may alternatively be defined as one that can be potentially detected by electromyography and nerve conduction studies. Disorders affecting the peripheral autonomic system or cranial nerves will be discussed only as necessary to better understand diseases affecting their somatic and spinal counterparts.

Many neuromuscular disorders are the result of or are influenced by single gene or complex genetic mutations. Many of these patients will not recognize the hereditary nature of their disease. This may be due to a recessive inheritance pattern, spontaneous mutation, false paternity, or incomplete or delayed penetrance. Frequently, it is due to a lack of familiarity with the medical issues of other family members. In suspected hereditary disease, acquisition of family history, particularly if done in a cursory fashion, may be insufficient. Examination of other family members, even if only briefly, is strongly recommended when heritable diseases are considered.

The differential diagnosis of disorders of the neuromuscular system is in part age-dependent. The differential diagnosis of neuromuscular conditions in infants, children, and adolescents is both overlapping and unique in comparison to their adult counterparts (Tables 1-1,1-2,1-3).^1,2 The applied diagnostic principles are similar although both the examination and review of symptoms may be hampered in infants. In the pediatric population, parents must be questioned with great care and sensitivity. The heightened concern of the parents may cause them to unconsciously omit important details of the patient’s status or assume a benign attribution as the cause of the symptom. Parents may also bring a considerable amount of guilt to the examination, which may limit their willingness to share information. The parents’ fears and associated guilt should be addressed. If necessary, professional counseling should be offered in addition to treating the patient. Often, when a child is ill, the entire family is affected, which can in turn have profound repercussions on the entire family from both a physical and a psychological standpoint.

The nature of neurologic practice is such that many patients evaluated by a neurologist will have complaints that are attributable neither to a specific neuromuscular disorder nor to the nervous system in general. Confidence in the ability to exclude neuromuscular disorders from consideration is enhanced by a thorough knowledge of how these conditions behave. The strategies outlined in this chapter are based on the general principle that diagnostic accuracy is enhanced by correlation of the patient’s signs and symptoms, with knowledge of the natural history and behavior of the ever-expanding menu of neuromuscular diseases. In our opinion, adherence to these principles will improve diagnostic accuracy. This chapter will attempt to focus on information that is important to elicit, and also on an organizational framework to allow accurate interpretation.

HISTORY TAKING

Neuromuscular diseases manifest themselves through some symptoms or combination of symptoms attributable directly or indirectly to the dysfunction of peripheral motor, sensory and autonomic nerves, neuromuscular junction or muscle. Motor symptoms are typically expressed in a “negative” fashion (weakness or atrophy). Occasionally, “positive” symptoms referable to overactivity [e.g., muscle cramps and fasciculations with LMN involvement and stiffness or flexor spasms in upper motor neuron (UMN) involvement] may dominate the clinical presentation. Sensory symptoms may also manifest with either a positive (e.g., paresthesia) or a negative (e.g., numbness or sensory ataxia) manner. Although pain may be considered a positive sensory symptom, it will be considered as an independent symptom in this text as it is neither a common or dominant feature in many neuromuscular conditions.

Neuromuscular disorders which manifest themselves solely within the domain of the motor system typically originate from anterior horn cells, the neuromuscular junction, muscle or rarely motor nerve fibers. Sensory symptoms typically imply a disorder of nerve root, dorsal root ganglion, plexus, or one or more peripheral nerve trunks. During history acquisition, there is considerable value in identifying both the location and the nature of the initial symptom(s), including the context in which that symptom developed. The subsequent evolution of symptoms should then be developed in a chronologic fashion with particular attention to the topographical distribution. The value of this approach may be illustrated with the example of multifocal neuropathy. At the time of their initial neurologic assessment, the patient’s deficits may have become confluent and indistinguishable from a length-dependent neuropathy and its far more extensive differential diagnosis. Identifying that the initial symptom occurred in a focal nerve distribution limits the differential diagnosis and improves diagnostic accuracy. The benefit of defining the chronologic course is that the differential diagnosis of acute neuromuscular disorders is notably disparate from that of its chronic counterparts (Tables 1-4,1-5,1-6).

In the history acquisition, it is imperative not to accept words at face value and to explore what that word means to a patient. For example, it is not uncommon for patients to say numb when they mean weak, and weak when they mean numb. The mechanism of impaired function should be explored. For example, questions should be formulated to determine whether a fall is due to proximal weakness resulting in failure of antigravity muscles, tripping due to a foot drop, or loss of balance due to impaired proprioception, vestibular function, or disordered postural reflexes originating at the central nervous system level. Detailed questioning may be required to determine whether the inability to get out of the chair is due to proximal weakness or impaired central nervous initiation.

It is important to identify symptoms not only referable to the peripheral neuromuscular system but to symptoms relating to impairment of higher cortical or cranial nerve function. In addition, a major discriminator in the development of a differential diagnosis is the presence or absence of symptoms referable to involvement of other organ systems. A careful system review is important in an attempt not only to achieve a diagnosis but also to fully anticipate the scope of its potential morbidity. For example, the recognition of orthostasis either by history or examination can provide insight that an evolving, otherwise nonspecific neuropathy pattern may be attributable to amyloidosis. Symptoms referable to cardiomyopathy or cardiac conduction defects, impaired GI motility, cutaneous change, and contractures may clarify the differential diagnosis in the heritable myopathies.

As muscle weakness is usually the most objective manifestation of neuromuscular disease, emphasis is placed not only on its existence but on its characteristics (e.g., upper or lower motor neuron) and on the pattern of involvement (Tables 1-4,1-5,1-6,1-7). The existence of weakness may be apparent either through history taking or, more commonly, by examination. Even though muscle weakness is the hallmark of neuromuscular disease, patients frequently identify weakness by its functional consequences. Patients with proximal upper extremity weakness commonly complain of activities of daily living (ADLs) that involve use of the arms at or above shoulder level. Shaving or drying hair, obtaining objects off shelves, or getting arms in coat sleeves are notable examples. Distal upper extremity weakness interferes with a wide variety of activities such as diminished grip strength, difficulty with opening flip tops on beverage cans, buttoning or using nail clippers. Patients with hip flexor weakness have trouble going up stairs or getting their legs into vehicles. Patients with hip or knee extensor weakness have troubles with stairs in either direction, getting up from a squat or a deep chair. Patients with foot dorsiflexion weakness may trip whereas patients with plantar flexion weakness cannot run or walk as fast and cannot reach for objects as effectively.

Conversely, the complaint of weakness is more commonly used by patients as a synonym for asthenia—a more pervasive, generalized complaint due to a number of different conditions. History taking pertaining to muscle weakness should focus on the identification of specific functions or activities that the patient finds difficult. If a patient who claims to be weak cannot describe a specific activity that is problematic for them, the existence of true muscle weakness remains suspect unless subsequently corroborated by the physical examination. Conversely, it is not rare for a disorder such as Lambert–Eaton myasthenic syndrome where credible functional impairments due to muscle weakness appear disproportionate to actual weakness found on bedside examination.

At times, weakness may present with pain rather than with symptoms directly attributable to weakness. For example, patients with trapezius weakness commonly present with shoulder pain, presumably due to traction on pain-sensitive structures resulting from their “shoulder drop.” Pain originating from strain on joints or soft tissues, as a secondary consequence of neuromuscular disease and the weakness it produces, is not uncommon.

UMN involvement needs to be considered in patients with potential neuromuscular disease, either as an alternative explanation for symptoms, or as a component of their neuromuscular condition. UMN pathology interferes with the synergistic functions of multiple muscle groups. As a result, functional activities highly dependent on coordinated muscle actions are commonly impaired early in the disease course. Impaired running and hand dexterity are notable examples. In addition, positive motor symptoms that occur commonly in UMN disease such as limb stiffness or spasms are readily recognized. They may complain of a tendency to drag one or both lower extremities. If the corticobulbar tracts are affected, swallowing and articulation are affected early and prominently, as these functions are dependent on the coordinated interplay of multiple muscle groups. The speech pattern that results is often halting, effortful, and “strangled” in its characteristics. Patients may lose their ability to effectively sniff or blow their nose. Patients with corticobulbar tract involvement may also develop lability of affect known as pseudobulbar palsy or forced yawning.

In contrast, as the final common pathway, lower motor neuron disorders express themselves in a limited number of ways, typically as a direct effect of functional loss due to weakness. Depending on a patient’s handedness, vocation or hobbies, this may not be noticed until the weakness is substantial. Less commonly, the patient’s initial complaints pertaining to lower motor neuron loss may reflect awareness of atrophy, fasciculations, or cramps.

Patients with weakness of hip flexion will have difficulty getting in and out of a car without manually lifting their thighs. Unless there is concomitant knee extensor weakness, patients will have more difficulty going upstairs than down as the former requires active hip flexion against gravity. Patients with weakness of hip abductors will waddle as a compensatory maneuver to maintain their center of gravity and balance. Patients with chronic weakness of hip extension will have difficulty rising from a chair and a tendency to have exaggerated lumbar lordosis as well, the latter resulting from posterior displacement of the shoulders for the same compensatory reasons. Knee extension weakness will result in difficulty getting up from a squat or out of deep chairs and commonly results in falls due to buckling of one or both knees. These patients may hyperextend their knees in order to prevent this while standing or walking (i.e., genu recurvatum). Ankle dorsiflexion weakness often results in tripping. Ankle plantar flexion weakness affects the efficiency of walking and deprives individuals from the ability to stand on their toes and run effectively.

In the upper extremity, people with weakness of the shoulder girdle will have difficulty with antigravity movements such as washing their hair, lifting heavy pans, inserting arms into coat sleeves, or retrieving objects from shelves. Weakness of elbow flexion and extension often goes unnoticed until fairly severe but may be recognized while attempting to open doors that require pull and push, respectively. Wrist and digit weaknesses interfere with grip and dexterity, which may impair multiple ADLs, including opening of bottles and cans, grasping zipper tabs, turning ignition keys, or buttoning buttons.

Neuromuscular disorders often affect the motor and to a lesser extent sensory functions of cranial nerves. Extraocular muscle involvement is a key discriminating factor in working through the differential diagnosis of neuromuscular disorders. For example, the extraocular muscles are rarely affected in motor neuron disease (MND), the majority of polyneuropathies or acquired inflammatory myopathies. Conversely, they may represent prominent manifestations of the inflammatory demyelinating polyneuropathies, disorders of neuromuscular transmission, and a finite list of muscle diseases, typically heritable in nature.

Patients typically become aware of ptosis by personal or family observation (Table 1-8). Occasionally, they first become aware when their vision is impaired by the drooping eyelid. Extraocular muscle involvement is typically expressed as diplopia, although patients with slowly progressive, symmetric involvement of the extraocular muscles such as in chronic progressive external ophthalmoplegia may have limited awareness of their deficit.

Patients with acute onset of unilateral facial weakness are usually very aware of the existence and nature of their problem. In many neuromuscular disorders, facial weakness is often chronic and symmetric, and as a result, the patient may not be aware of their deficit (Table 1-9). It is not rare for chronic bifacial weakness to be recognized for the first time on a routine neurologic examination. Questions pertaining to a tendency to sleep with eyes incompletely closed, the ability to blow up balloons or whistle may help to estimate the duration of a problem in situations such as these.

Symptomatic jaw weakness is an infrequent neuromuscular complaint. When present, it is often overshadowed by symptoms referable to muscles concomitantly affecting speech, swallowing, and breathing. Difficulty with chewing should nonetheless be inquired about, as it may sometimes be the initial or key symptom in a limited number of disorders such as myasthenia or Kennedy disease.

Symptoms referable to tongue weakness are common in many neuromuscular disorders. Patients typically become aware of tongue weakness as a result of dysarthria. Other issues may include the inability to manipulate food properly within their mouth. This kind of detail is uncommonly volunteered by the patient and is more frequently elucidated by detailed questioning.

Weakness of the neck muscles may be noticed by patients or their families when the neck extensors can no longer support the weight of the head and head drop develops by the development of head drop (Table 1-10). This is often accompanied by nuchal discomfort, presumably due to the constant and unaccustomed traction on posterior cervical ligamentous structures. Neck discomfort from head drop may be distinguished from other, more common causes of neck pain, by the relief allowed by neck support. Head drop may contribute to dysphagia as well. Trapezius weakness is most commonly symptomatic when acute and unilateral and is usually a result of a mononeuropathy of the accessory nerve. As discussed above, trapezius weakness is usually presents with shoulder pain as the index symptoms. Shoulder drop can be easily missed unless the patient is viewed from the rear, with the back exposed.

Weakness of the scapula can result from weakness of either the trapezius or serratus anterior muscles (Table 1-11). Scapular winging interferes with both shoulder-girdle strength and mobility. Patients may note either difficulty in raising an arm above the head or an inability to push with the accustomed force, for example, while doing pushups.