Introduction: Evaluation of Patients with Neuromuscular Disorders

Medical History and Symptoms

The evaluation should include obtaining detailed medical and family histories as well as identifying possible complicating factors. In children, information should be obtained on the prenatal period and delivery, especially if the patient was a “floppy baby,” and details of the patient’s developmental milestones should be recorded ( ; ).

Identifying general medical problems is important because some NMDs are associated with other conditions, such as endocrine and connective tissue diseases that might affect other organs. Medications also should be considered, because many are known to produce neurologic complications.

Muscle weakness is a common symptom, except in patients with sensory or autonomic neuropathy or in some radiculopathies and entrapment syndromes. The rate of progression varies, and in some conditions, such as Guillain-Barré syndrome (GBS), electrolyte imbalance, toxic neuropathy, and myopathy associated with rhabdomyolysis, it is rapid ( Box 1.1 ). In disorders of neuromuscular transmission, such as myasthenia gravis (MG), weakness fluctuates during the day. In periodic paralysis, weakness is recurrent ( ), whereas in other disorders, such as muscular dystrophies, or in hereditary and some autoimmune neuropathies, it is subacute or chronic ( Box 1.2 ) ( ; ).

The distribution of weakness also is important in diagnosis; for example, it is proximal in spinal muscular atrophies and most myopathies, except for some disorders in which it is more distal, for example, inclusion body myositis (IBM) and Miyoshi myopathy. In myopathies, weakness usually is symmetric, although asymmetry can be seen in some diseases like fascioscapulohumeral dystrophy and IBM. In polyneuropathies, this characteristically begins in the legs but may initially manifest more prominently in the upper extremities, as in multifocal neuropathy, and also in brachial plexopathies, and cervical spinal canal disorders as well as in ALS. This follows the territory of roots or nerves in radiculopathies, focal neuropathies, ( ), mononeuritis multiplex, and entrapment neuropathies.

Dysphagia, diplopia, and ptosis also help to identify NMDs because they occur in some myopathies and also in disorders of neuromuscular transmission, such as MG. Symptoms of respiratory difficulty should be recognized and treated promptly because this can be the first manifestation of some disorders such as MG, GBS, ALS, and some myopathies, such as acid maltase deficiency, whereas in other disorders, it appears at later stages ( , ). During the evaluation, one should always inquire about sleep difficulties, as sleep apnea can be seen in some of these diseases.

Difficulty combing the hair and placing objects in high cabinets commonly occurs in patients with shoulder-girdle weakness, whereas difficulty writing and grasping objects indicates involvement of the forearm and hand muscles, as in ALS and IBM. Weakness of the hip extensors usually causes inability to rise from a low chair or a toilet seat, whereas difficulty ascending stairs indicates dysfunction of the hip flexors and quadriceps muscles. More severe weakness of the quadriceps muscles occurs in IBM, causing difficulty descending stairs ( ; ). When the distal muscles are affected, foot drop may cause a steppage gait and difficulty negotiating curves or changing courses, as seen in polyneuropathies, distal dystrophies, and ALS.

Muscle stiffness, tightness, and spasms occur as a result of spasticity in disorders affecting the upper motor neuron, but these also occur in patients with motor unit hyperactivity, such as “stiff-person” and Isaac syndromes and the myotonias. Those with inflammatory myopathies, polymyalgia rheumatica, fasciitis, and hypothyroidism also complain of stiff limbs. Cramping at rest or during exercise is a prominent symptom of the cramp-fasciculation syndrome ( ) and also some neuropathies. In metabolic myopathies, this usually occurs during or after exercise, or after fasting in some cases. Fatigue is common in disorders of neuromuscular transmission, such as Eaton-Lambert syndrome (ELS) and MG, but also in myopathies, even though weakness is the major symptom. In ELS, there may be temporary improvement after a brief exercise.

Decreased sensation as well as paresthesias and neuropathic pain are symptoms of peripheral neuropathies ( ). These symptoms are localized in the affected areas in those with radiculopathies, plexopathies, and entrapment neuropathies. Autonomic dysfunction can occur in some neuropathies and also in ELS, and the clinician should ask the patient for dysautonomic symptoms such as orthostatic hypotension and urinary and sexual dysfunction.

Physical Examination

A careful general physical examination is essential to arrive at a diagnosis, and the clinician should assess cardiac and lung function, examine the eyes for cataracts and retinal disease, and check for hearing loss and lipoma, which are often seen in mitochondrial disorders. Visceromegaly and skin changes are present in some patients with neuropathies, for example, those with POEMS ( p olyneuropathy, o rganomegaly, e ndocrinopathy, m onoclonal gammopathy, s kin changes) syndrome. Skin abnormalities can also be seen in connective tissue disorders, whereas patients with dermatomyositis have a characteristic rash, including the Gottron sign, carpenter fingers, and dilatation of the periungual capillaries ( Fig 1.2 ) (also see figures of patients in Chapter 22 ) ( ). High arches of the feet are seen in hereditary motor sensory neuropathy.

Clubbing of the fingers is seen in some chronic lung disorders, whereas Mees lines are seen in patients with arsenic and other poisoning ( Fig 1.3 ).

Intellectual function should be assessed because it could be impaired, such as in some cases of ALS and in myotonic dystrophy. Examination of posture and gait is useful to determine if there is hyperextension of the knees, if there is evidence of a waddling gait in myopathies, and if there is a spastic or ataxic gait, or the steppage seen in peripheral neuropathy and some distal dystrophies should test tandem gait which is abnormal in cerebellar disease. Difficulty walking on tiptoes is seen in people with gastrocnemius and soleus weakness, whereas walking on heels cannot be done in persons with foot dorsiflexor weakness. Patients should be asked to get up and down from a stool to determine if there is thigh muscle weakness. The examiner should also notice difficulty arising from the chair or going upstairs, and if the patient has the characteristic Gower maneuver, when arising from the floor, due to proximal muscle weakness ( Fig. 1.4 ), and should observe if there is hyperlordosis with proximal atrophy in myopathies and distal atrophy in neuropathies and whether it is symmetric or focal ( Figs. 1.5 and 1.6 ) or whether it affects the upper or lower extremities more prominently. The clinician should examine the patient for muscle hypertrophy, which is seen in some dystrophies and disorders of neuromuscular hyperactivity such as myotonia congenita ( Fig. 1.7 ). Examination of muscle tone also is important to determine whether there is hypotonia, particularly in infants ( Fig. 1.8 and Box 1.3 ), or spasticity and also to determine if there is limitation of passive joint movement like from muscle fibrosis that occurs in various myopathies ( Fig. 1.9 ).