tips and tricks

presence of prominent respiratory involvement

Think of:

• Acute/Subacute:
  
  
  
  • Guillian–Barré syndrome
    
  • myasthenia gravis
  
  
• Chronic:
  
  
  
  • amyotrophic lateral sclerosis
    
  • acid maltase deficiency
    
  • Duchenne dystrophy
    
  • myotonic dystrophy

A brief screening mental status may be indicated. Cognitive impairment is seen as a primary feature of some neuromuscular diseases (Duchenne muscular dystrophy, congenital myotonic dystrophy, mitochondrial cytopathies, frontotemporal dementia in ALS or secondary to the complications of the disease – confusion secondary to chronic respiratory failure and hypercapnia). A relevant cranial nerve examination might include assessment of fundi because pigmentary retinopathy can be a feature of some mitochondrial disorders, pupils (not involved in myasthenia gravis compared with fixed with botulism), eyelids, and extraocular movements. Trigeminal neuropathy may be seen with Sjögren’s syndrome or other neuropathies. Facial weakness is prominent in a number of myopathies but may also be seen in some hereditary neuropathies. Subtle evidence of facial weakness may be an inability to bury the eyelashes. Sensorineural hearing loss may be evident in neuropathies and mitochondrial disorders. A high arched palate may be a clue to a longstanding, inherited disorder, and the quality of the voice, in addition to the elevation of the soft palate, highlights the involvement of nerves IX and X. In addition to tongue movement, the presence or absence of tongue atrophy (hypoglossal nerve involvement, ALS), hypertrophy (Duchenne muscular dystrophy, amyloidosis), and fasciculations should be noted. Neck flexion is often weaker than neck extension in many myopathies and myasthenia gravis, although there are exceptions.

A vigilant motor examination at the first assessment yields useful clues because the patterns of weakness are informative. This should be preceded by careful inspection of the muscle for spontaneous movements such as fasciculations and myokymia, and assessment of muscle bulk. Attention to tone and reflexes can help differentiate neurogenic from myopathic conditions, as well as ruling out the presence of an upper motor neuron component. Direct percussion of the muscles with a reflex hammer can induce rippling, mounding, or myotonia which are important diagnostic clues. A systematic approach that includes all muscle groups about the shoulder, elbow, wrist, hand including the long finger and thumb flexors, hip, knee, and ankle may shorten the differential diagnosis. In inclusion body myositis for example, the quadriceps muscles and finger flexors are preferentially involved early in the disease. And, finally, observing the posture, stance, and gait, including a functional assessment by having the patient lift the arms above the head, walk on heels, toes, hop on either foot, rise from a squat, climb a few stairs, or rise from the floor, often yields important diagnostic information. An individual with a marked lumbar lordosis and Trendelenburg gait has a chronic problem, even if he or she dates symptom onset only back several months.

A careful sensory assessment of all modalities requires mapping out the territories on face, arm, leg, or trunk for perception of pinprick (± temperature) and vibration threshold (± joint perception). This assessment reveals patterns of individual nerve, multiple nerves, plexus, root, proximal, distal, or central involvement in individuals with sensory, balance, and coordination complaints, e.g. a subacute stocking-and-glove sensory loss to all modalities with absent reflexes and preserved strength points to a sensory neuronopathy and prompts a return to the history to make further inquiries about pyridoxine intake, dry eyes and mouth, etc. if not revealed initially. Coordination testing with attention to Romberg’s sign and dysmetria are often abnormal in the face of marked large-fiber sensory deficits. Retained reflexes would be expected in the individual with painful, burning feet and a small-fiber neuropathy. The weal-and-flare “triple” skin response is often abnormal with small-fiber neuropathies affecting autonomic fibers. Attention to the skin, and any trophic (thinning, temperature, and color change) or sweating changes (absent or increased) in the feet may be early signs of the small thinly myelinated or unmyelinated fiber involvement.

Localization: Defines Your Differential and Investigations

Localization is most often apparent after a skilled history and physical exam are completed, although there are presentations that may still localize to several parts of the peripheral nervous system (e.g. proximal symmetrical weakness with absent reflexes may be nerve, neuromusculat junction, or muscle) and investigations will help to clarify.

Investigations: Selection Based on Pre-Test Probability

Healthcare costs have risen dramatically in the past few years, and it is the responsibility of each physician to select the appropriate tests based on the most likely diagnosis, taking into consideration how management will be affected. A creatine kinase and thyroid-stimulating hormone (TSH) test in muscle disease, acetylcholine receptor antibodies and TSH in neuromuscular junction disorders and fasting glucose, and a glucose tolerance test and serum protein electrophoresis with immunofixation in neuropathy are first-line lab tests in the investigation of common presentations of neuromuscular disease. Additional tests will depend on the clinical scenario and what the likely yield will be. For example, uncovering a low-titer antinuclear antibody in a middle-aged woman with a subacute sensorimotor neuropathy and no symptoms or signs of connective tissue or autoimmune involvement is of little benefit and may prompt unnecessary investigation. With a high pre-test probability, specific antibodies, and immune and paraneoplastic markers have their place (e.g. positive, high-titer serum, voltage-gated, potassium channel antibodies confirm a clinical diagnosis of neuro­myotonia).

Electrodiagnostic studies (nerve conduction studies, repetitive nerve stimulation, electromyography [EMG], somatosensory-evoked potentials, provocative testing) in skilled hands are generally always helpful in neuromuscular disorders. Electrodiagnostics will help confirm segmental lower motor neuron involvement in motor neuron disease, distinguish between axonal and demyelinating neuropathies, localize particular nerve roots or parts of the plexus, detect increment or decrement in neuromuscular junction disorders, and identify involved muscles in some myopathies to guide biopsy. It is important to note that electrodiagnostic studies are an extension of the history and physical exam, and rarely in and of themselves diagnostic. For example, the individual with the asymptomatic median neuropathy at the wrist on nerve conduction studies does not have carpal tunnel syndrome and the individual with small-amplitude, short-duration motor units with fibrillation potentials and positive sharp waves on EMG may have an inflammatory, toxic, or hereditary myopathy.

In many instances now, DNA analysis is clinically available for a number of disorders, in particular hereditary myopathies. It is appropriate, and less invasive, to confirm a clinical diagnosis with a genetic test in several hereditary myopathies including Duchenne/Becker muscular dystrophy, facioscapulohumeral muscular dystrophy (FSHD), myotonic dystrophy types 1 and 2, and oculopharyngeal muscular dystrophy. It is the responsibility of the ordering physician, however, to understand the sensitivity and specificity of tests ordered.

Muscle biopsy remains a critical investigation for diseases of muscle. However, the timing, site, and subsequent analysis and testing of the muscle, and the utility of a concomitant skin biopsy to generate fibroblast culture for enzymatic assays, are all decided based on the working diagnosis. Increasingly, in the literature, the use of magnetic resonance imaging to guide investigation of muscle disease is emerging; however, the benefits and costs over a careful history and examination in the clinical setting have yet to be determined. Nerve biopsies, on the other hand, are used infrequently in the investigation of neuropathies but remain critical in the diagnosis of vasculitic and amyloid neuropathies. A relatively new technique, punch skin biopsy for assessment of epidermal innervation, is helpful in the diagnosis of suspected small-fiber neuropathies that cannot be confirmed by electrodiagnostic testing.

Diagnosis: Putting the Story Together

Ultimately, an accurate diagnosis is needed to facilitate management. The needs of individual patients will vary from simple to complex. Having a confirmed diagnosis, however, facilitates discussions with patients and their families. Communication is the cornerstone of effective therapeutic relationships, regardless of whether there are effective treatments for a condition (e.g. Guillain–Barré syndrome, myasthenia gravis) or whether management remains supportive around education, planning and problem-solving (FSHD, hereditary neuropathies, etc.). When possible, interprofessional healthcare teams should be used because they improve quality of life. Lifestyle and behavior adaptation are often required, in addition to medical and surgical approaches.

References

Amato AA, Russell JA. Neuromuscular Disorders. New York: McGraw Hill, 2008.

Dyck PJ, Thomas PK. Peripheral Neuropathy, 4th edn. New York: Elsevier Saunders, 2005.

Engel AG, Franzini-Armstrong C. Myology, 3rd edn. New York: McGraw Hill, 2004.

Washington University’s Neuromuscular Home­page. http://neuromuscular.wustl.edu (a comprehensive, continually updated, reference for all neuromuscular disorders).