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Approach to Patients with Neuromuscular Disorders

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Approach to Patients with Neuromuscular Disorders Approach to Patients With Neuromuscular Disorders Anthony A. Amato, MD Chief, Neuromuscular Division and Director, Clinical Neurophysiology Laboratory Brigham and Women’s Hospital Associate Professor of Neurology Harvard Medical School Boston, Massachusetts INTRODUCTION a true sensory level is not evident in GBS but should be present in transverse myelitis and other structural abnormalities involving the The approach to patients with neuromuscular disorders is chal- spinal cord. lenging. As in other neurological diseases the key to arriving at the correct diagnosis is careful localization of the lesion. Weakness can The presence of motor and sensory symptoms and signs are helpful be the result of central lesions (brain or spinal cord processes—e.g., in distinguishing peripheral neuropathies from anterior horn cell brainstem infarct, central pontine myelinolysis, transverse myelopa- disorders, myopathies, and neuromuscular junction disorders. thy), anterior horn cell disease (e.g., amyotrophic lateral sclerosis However, some types of peripheral neuropathy are predominantly [ALS], poliomyelitis), peripheral neuropathy (e.g., Guillain-Barré or purely motor and thus can be difficult to distinguish these other syndrome [GBS]), neuromuscular junction defects (botulism, disease processes. Most neuropathies are associated with distal Lambert-Eaton myasthenic syndrome [LEMS], myasthenia gravis greater than proximal weakness. However, significant proximal [MG]), or myopathic disorders. The most important aspect of as- weakness can be seen in certain peripheral neuropathies (e.g., GBS, sessing individuals with neuromuscular disorders is taking a thor- chronic inflammatory demyelinating polyneuropathy [CIDP]). ough history of the patient’s symptoms, disease progression, and Further, although usually associated with proximal weakness, past medical and family history as well as performing a detailed certain myopathies and rarely even neuromuscular junction disor- neurologic examination. This is not to say that the electrodiagnos- ders can manifest with primarily distal weakness. tic (EDX) examination, laboratory data, and muscle biopsies are not important, but the physician’s clinical acumen based on the Amyotrophic lateral sclerosis is the result of degeneration of upper historical aspects of the disease and the clinical examination provide and lower motor neurons. The degeneration of lower motor neurons the guiding force for performing the most appropriate confirma- leads to muscle weakness, atrophy, and fasciculations, which typi- tory tests to most expeditiously arrive at a correct diagnosis. cally begins focally. Upper motor neuron involvement manifests as spasticity and pathologically brisk DTRs. While most patients over It is usually not difficult to distinguish generalized weakness sec- time develop both upper and lower motor neuron deficits, some ondary to a cerebral or brainstem insult from other causes of muscle patients continue to have pure lower motor neuron abnormalities, weakness, because in these central disorders weakness is accompa- while others have only upper motor neuron signs. Some of the nied by impaired consciousness. Myelopathies can be more trouble- hereditary spinal muscular atrophies present with generalized sym- some to diagnose. Compressive lesions of the involving spinal cord metrical, proximal greater than distal, weakness and can be difficult and the nerve roots can result in a combination of upper and lower to distinguish from myopathic disorders. motor neuron abnormalities which can mimic ALS and vice-versa. Acute transverse myelitis can be associated with rapid quadriparesis The key in distinguishing neuromuscular junction defects from in which the deep tendon reflexes (DTRs) are initially absent from myopathies is the fluctuation in symptoms and signs in the a “shocked cord.” Such cases are not uncommon initially as GBS. former. Patients with MG usually fatigue during repetitive activ- Although both conditions are usually associated with sensory loss, ity while patients with LEMS can actually improve with contin- Approach to Patients With Neuromuscular Disorders AANEM Course ued physical exertion. Neuromuscular junction disorders have a predilection to affect the extraocular muscles which are less com- Table 1 Differential diagnosis of the floppy infant monly affected in myopathies. The following discussion is a reasonable approach to evaluating Central nervous system disorders (most common etiology) patients with neuromuscular complaints. Anterior horn cell Spinal muscular atrophy type I and II MEDICAL HISTORY Peripheral neuropathy While obtaining the medical history, the clinician should attempt Congenital hypomyelinating/amyelinating neuropathy to define onset and course of the illness as well as the distribution CMT III (Dejerine-Sottas) of symptoms. The differential diagnosis of generalized weakness CMT type I and CMT type II (rare) presenting in infancy (Table 1) is different from that presenting Giant axonal neuropathy later in childhood or early adult life (Table 2) and those disorders manifesting in late adulthood (Table 3). The rate of disease pro- Neuromuscular junction gression is important to pursue with the patient. Certain disorders Infantile botulism progress acutely over days or weeks (Table 4), while others evolve Infantile myasthenia gravis more slowly over months (Table 5). The course of the disease may be chronic and progressive, monophasic, or relapsing. The increas- Congenital myasthenia ing health consciousness of some individuals presents a good op- Myopathy portunity to gauge the rate of disease progression with respect to distance previously run, weight lifted, or games played. A steady Congenital myopathies (all of them can present in infancy) reduction in these exercise-related parameters may be important Muscular dystrophies clues for establishing a pattern of gradual and progressive physical Congenital muscular dystrophies decline. Dystrophinopathy/sarcoglycanopathy (rare) The patients’ presenting symptoms are dependent upon the muscle Congenital myotonic dystrophy groups that are predominantly affected. Early manifestation of proximal Metabolic myopathies lower extremities weakness is progressive difficulty climbing stairs and Glycogen storage defects in arising from a chair, commode, or the floor. The patient may note Acid maltase deficiency that the upper extremities may now be required to provide assis- tance in pulling them up the stairs with a hand rail or in pushing Debrancher deficiency them up from a seat. Weakness of the anterior compartment of Branching enzyme deficiency the distal lower extremity results in foot drop. These patients will Myophosphorylase deficiency (rare) complain of frequent tripping or stubbing of the toes because of Disorders of lipid metabolism the inability to dorsiflex the foot when walking. Involvement of the posterior compartment of the distal legs leads to difficulty standing Carnitine deficiency on one’s toes. Fatty acid-Acyl-CoA dehydrogenase deficiencies Mitochondrial myopathies Weakness about the shoulder girdles may impact on the patient’s Benign and fatal infantile myopathy ability to perform activities of daily living, such as brushing hair and lifting objects. Distal upper extremity weakness usually pres- Leigh’s syndrome ents with progressive difficulty with grip. Patients will describe dif- Endocrine myopathies (e.g., hypothyroidism) ficulty opening jar tops and twisting or turning door knobs. CMT = Charcot-Marie-Tooth A patient with neck weakness will often complain of difficulty lifting their head off a pillow. Further, sudden braking or accelerat- ing in a car can cause the head to jerk back and forth. Involvement of cranial muscles may result in ptosis, diplopia, dysarthria, or dif- small intrinsic hand muscles. Alternatively, some muscle groups ficulty chewing and swallowing. may be noted to be enlarged. Some disorders are associated with fasciculations, myalgias, cramps, stiffness or myotonia, periodic The examiner should ask about the presence of extreme fluctuations paralysis, and myoglobinuria. If these symptoms are not offered by in strength during the day or associated with physical activities. Such the patient, their presence should be inquired by the clinician. fluctuations in strength are more typical of neuromuscular junc- tion disorders. Observant patients may also detect a progressive It is important to inquire about sensory symptoms. Patients may loss of muscle bulk about various aspects of their body, particularly complain of feeling “numb,” but this word has different meanings involving the anterior thigh, shoulder, and occasionally face and for different people. If not offered by the patient, the examiner AANEM Course Numbness, Tingling, Pain, and Weakness 3 Table 2 Weakness presenting in childhood or early adulthood Anterior horn cell Congenital muscular dystrophy (partial merosin deficiency) Spinal muscular atrophy type III Myotonic dystrophy Poliomyelitis Other dystrophies (e.g., FSHD, EDMD) Amyotrophic lateral sclerosis Metabolic myopathies Glycogen storage defects Peripheral neuropathy Acid maltase deficiency Acute or chronic inflammatory demyelinating polyneuropathy Debrancher and branching enzyme deficiency Hereditary neuropathies Disorders of lipid metabolism Neuromuscular junction Carnitine deficiency Botulism Fatty acid-Acyl-CoA dehydrogenase deficiencies Myasthenia gravis Mitochondrial myopathies Congenital myasthenia Periodic paralysis Lambert-Eaton myasthenic syndrome Electrolyte imbalance
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