Sodium is the main determinant of serum osmolality (Osm) and extracellular fluid volume. Neurologic symptoms are dependent on the time lag necessary for the brain to compensate for rapid changes in serum Na⁺ concentration, and Osm.

1. I. Hyponatremia: Acute decreases of Na⁺ levels to 130 mEq/L may produce symptoms, whereas chronic changes to 115 mEq/L may be asymptomatic. Acute hyponatremia (< 115 mEq/L) with seizures carries a high mortality rate and necessitates rapid (over a 6-hour period) correction to 120 to 125 mEq/L (with hypertonic saline or normal saline and furosemide). Rapid correction to levels greater than 120 to 125 mEq/L may result in central pontine myelinolysis, a disorder described in alcoholics but also occurring in children and adults with liver disease, severe electrolyte imbalances, malnutrition, anorexia, burns, cancer, Addison disease, and sepsis.
   There is symmetrical focal myelin destruction predominantly involving the basal central pons. Asymptomatic chronic hyponatremia usually requires no immediate intervention and is managed by correction of the underlying condition.
   
2. II. Hypernatremia: Neurologic symptoms develop when the serum Na⁺ level rises above 160 mEq/L or serum Osm is greater than 350 mOsm/kg. Level of consciousness correlates well with the degree of hyperosmolality. Sudden increases in serum Osm may produce decreased brain cell volume, with mechanical traction on cerebral vessels causing subcortical, subdural, or subarachnoid hemorrhage. Cerebrospinal fluid protein levels may be high without pleocytosis, and the electroencephalogram (EEG) is normal or mildly slowed. Hypernatremia resulting from diabetes insipidus may occur with tumors involving the hypothalamus or pineal region, as well as with basilar meningitis, encephalitis, ruptured aneurysms, sarcoidosis, trauma, or surgery. Treatment for hypernatremia includes isotonic solutions to reduce the serum Na⁺ level by no more than 1 mEq/L every 2 hours during the first 2 days of treatment. Rapid infusion of hypotonic solutions may cause cerebral edema and seizures.

Almost 60% of total body K⁺ is located within muscle; therefore, predominantly muscular symptoms occur with altered K⁺ levels.

1. I. Hypokalemia most commonly occurs with diuretic use but also occurs with gastrointestinal losses, mineralocorticoid excess, and rarely, thyrotoxicosis. Muscle weakness usually develops with serum levels of 2.5 to 3.0 mEq/L, with structural muscle damage occurring at levels below 2.0 mEq/L. Hypokalemia and hypocalcemia frequently coexist, with cancellation of neuromuscular manifestations. Treatment of one condition in isolation may produce symptoms of the other. Electrocardiogram (ECG) and cardiac abnormalities are common and may require intensive care unit (ICU) monitoring and treatment. Treatment includes increasing dietary K⁺, supplements of potassium chloride (KCl), and the use of K⁺-sparing diuretics.
   
2. II. Hyperkalemia is relatively uncommon but may occur in familial hyperkalemic periodic paralysis (see Periodic Paralysis). Quadriparesis may develop with levels greater than 6.8 mEq/L, and levels greater than 7.0 mEq/L are life-threatening due to cardiac toxicity. Potassium levels greater than 6.0 mEq/L require ICU monitoring and immediate therapy with administration of glucose and insulin, cation exchange resins, or calcium gluconate.

Plasma Ca²⁺ is a stabilizer of excitable membranes in the central and peripheral nervous systems and in muscle. Ca²⁺ concentrations are closely controlled through the combined effects of parathyroid hormone, calciferol, and calcitonin on intestine, kidney, and bone.

1. I. Hypocalcemia occurs in neonates, patients with renal failure, and after thyroid or parathyroid surgery. The “tetany syndrome” originates in the peripheral nerve axon and initially becomes evident with distal and perioral tingling. Distal tonic spasms (carpopedal spasms) may progress to laryngeal stridor and opisthotonus if severe. The EEG is diffusely slow with an exaggerated response to photic stimulation. ECG abnormalities are also common. Treatment consists of oral calcium supplements. Acute treatment of hypocalcemia with tetany or seizures may require 10% IV solutions of calcium gluconate or CaCl. Underlying disorders should be corrected, if possible. Hypocalcemia often coexists with hypomagnesemia. In such cases, total serum calcium levels may be normal, but ionized calcium levels may be low.
   
2. II. Hypercalcemia: Malignant neoplasms are the most common cause of increased serum Ca²⁺ levels. Mental status alterations occur with total serum levels greater than 14 mg/dL. Serum calcium levels need to be adjusted for serum albumin levels which are often low in chronically ill patients. Myopathy or carpal tunnel syndrome may occur in association with hyperparathyroidism.

Treatment: Saline hydration and furosemide are recommended. Occasionally, mithramycin (suppresses bone resorption) or calcitonin (suppresses bone resorption and increases urinary Ca^2 + excretion) are required.

Ninety-eight percent of Mg^2 + is intracellular. Magnesium is necessary for the activation of various enzymes. Extracellular Mg²⁺ affects central and peripheral synaptic transmission. Acute changes in serum levels may not reflect total body stores.

1. I. Hypomagnesemia occurs most commonly as a result of excess renal loss (chronic alcoholism, diuretics), but may also be the result of decreased intake or absorption. Neurologic symptoms usually develop at levels below 0.8 mEq/L. The presence of seizures requires treatment with parenteral MgSO₄. Oral Mg^2 + supplements may suffice in less severe cases. Calcium gluconate should be available when giving IV MgSO₄, as transient hypermagnesemia may cause respiratory muscle paralysis (see also hypocalcemia, above).
   
2. II. Hypermagnesemia, an uncommon disorder, usually occurs with increased intake and renal failure. Deep tendon reflexes may be lost at levels of 5 to 6 mEq/L, and CNS depression occurs at levels above 8 to 10 mEq/L. Muscular paralysis is due to neuromuscular blockade.

Paralysis treatment may be accomplished by small amounts of parenteral calcium gluconate and hydration. Otherwise, discontinuation of Mg⁺-containing preparations is indicated. If renal function is severely impaired, dialysis may be necessary. Magnesium infusions are often given as treatment for seizures associated with eclampsia. Serum magnesium levels need to be closely monitored in this situation.

Hypophosphatemia is often complicated by multiple abnormalities of electrolytes, nutrition, and acid-base balance. The syndrome commonly occurs in malnutrition and chronic alcoholism, especially after the infusion of glucose or hyperalimentation solutions.

Acute hypophosphatemia may not reflect decreased total body stores and may produce neurologic symptoms if severe (< 1.5 mEq/L). Chronic hypophosphatemia is usually moderate (1.5–2.5 mEq/L) and may not be symptomatic unless acute stresses (alcohol withdrawal, burns, binding of phosphate in the gut) cause sudden decreases below the moderate level.

Motor NCS involve stimulating a peripheral nerve and recording the action potential from a muscle innervated by that nerve—because this induced action potential conducts in the same direction as physiologic motor nerve signals, it is referred to as “orthodromic.” Compound muscle action potential (CMAP) is signal recorded as results from depolarization of all muscle fibers innervated, hence it is termed compound.

Sensory NCS are usually done antidromically, by stimulating a peripheral nerve proximally and recording from a distal site innervated by that nerve; for some sensory nerves, orthodromic recording is also possible. The recorded response is called a sensory nerve action potential (SNAP).

The amplitude, duration, shape, and latency of CMAPs or SNAPs are all noted for comparison to expected normalized values or morphology. Conduction velocities are calculated for SNAPs by dividing the distance between stimulating and recording electrodes by the time required for action potential conduction. For CMAPs, because the latency recorded includes not only nerve transmission velocity but also neuromuscular junction transmission time, conduction velocity is calculated by dividing the distance between two stimulation sites (proximal and distal) by the difference in conduction time between the distal stimulus site and the recording site. Normal values of NCS vary with different physiologic factors, most importantly with temperature and age. Normal nerve conduction velocities are approximately 50 m/second in the upper limbs and 40 m/second in the lower.

F waves are low-amplitude late responses due to antidromic activation of motor neurons (anterior horn cells) following peripheral nerve stimulation, which then cause orthodromic impulses to pass back along the involved motor axons, also called backfiring of axons. It is called the F wave because it was first noted in intrinsic foot muscles. The latency of the F wave is usually 25 to 32 milliseconds in the upper limbs and 45 to 56 milliseconds in the lower. F waves are useful for evaluating peripheral neuropathies with predominantly proximal involvement, such as the acute and chronic inflammatory demyelinating polyneuropathies, in which distal conduction velocities may be normal early in the disease. The H reflex is the other clinically recordable late response. It is the electrical homologue of checking ankle-jerk reflex on physical exam. It is the result of a monosynaptic reflex arc with an afferent component mediated by large, fast-conducting group 1a fibers, and an efferent component mediated by alpha motor neurons. For practical and anatomic reasons, the only routinely tested H reflex is in the S1 segment, recorded after tibial nerve stimulation in the popliteal fossa. Typical latency is 30 milliseconds. The loss of the H reflex is nonspecific—it can be simply a function of age (it is normally absent over age 60), or it can result from a very large number of disorders.

EMG records electrical activity in individual and collective muscle fibers, yielding more information on the localization and pathophysiology of peripheral nervous system disorders. NCS on the other hand record electrical activity from entire nerves at once and cannot study individual neurons. An EMG evaluation requires the examiner to carefully select the appropriate muscles to test on the basis of a thorough history and physical examination, and results of NCS.

For each of the muscles being studied, the first part of the examination is to assess insertional and spontaneous activity at rest. Once the insertional and spontaneous activity has been assessed, the examiner will ask the patient to slowly contract the muscle, and the motor unit action potentials (MUAPs) are evaluated. MUAPs are assessed for duration, amplitude, and numbers of phases. Then, the number of MUAPs and their relationship to the firing frequency (recruitment and activation pattern) are evaluated.

Insertional activity occurs when a needle is quickly moved through the muscle and creates depolarization of muscle fibers which is visualized on the monitor as high-frequency, positive and negative spikes (with an associated “crisp” noise). Normal insertional activity typically lasts only a few hundred milliseconds. Decreased insertional activity is seen in muscle atrophy because fewer muscle fibers are available to respond to needle insertion. Any electrical activity lasting longer than 300 milliseconds is considered increased insertional activity which may be seen in neuropathic disorders that result in denervation and several myopathic conditions that result in necrosis of the muscle fibers, such as inflammatory myopathies.

Recognition of abnormal spontaneous activity can provide helpful information for the diagnosis:

1. 1. The distribution of abnormal spontaneous activity may suggest the neuroanatomic localization of the lesion (e.g., mononeuropathy, radiculopathy).
   
2. 2. Certain types of spontaneous activity are associated with specific disorders, for example, myotonic discharges in myotonic dystrophy and hyperkalemic periodic paralysis (see below).
   
3. 3. The amount of spontaneous activity or the presence of spontaneous activity may provide information regarding the time course and severity of the lesion (e.g., presence of fibrillation potentials begins 2 to 3 weeks after the acute nerve injury).

Spontaneous activity may originate from individual muscle fibers, or from entire motor units.

Fibrillation potentials and positive sharp waves are brief, rhythmic discharges from individual denervated muscle fibers, and indicate acute or ongoing impaired innervation. They are not seen on EMG testing until 2 weeks or more after denervation occurs. They are usually graded on a scale from zero to four, where zero means that no such potentials are present and 4 + means that these spontaneous potentials fill the entire screen. They can be seen in neurogenic disorders (neuropathies, radiculopathies, motor neuron disease, etc.), myopathic disorders (especially in inflammatory myopathy and muscular dystrophies), and in severe disorders of the neuromuscular junction (such as botulism or therapeutic chemodenervation with botulinum toxin).

Complex repetitive discharges (high-frequency, regular-firing, multiserrated repetitive discharges with abrupt onset and termination, creating a characteristic “machine-like” sound) result from the depolarization of a single muscle fiber followed by ephaptic spread to adjacent denervated fibers. This occurs in a wide variety of chronic neurogenic disorders (poliomyelitis, motor neuron disease, radiculopathies, and neuropathies) and myopathic disorders (Duchenne and limb-girdle dystrophy, polymyositis, and hypothyroidism). These potentials are usually not seen on EMG testing until 6 months or more after an injury.

Myotonic discharges are characterized by waveforms with waxing and waning amplitude and frequency, creating a “dive bomber” sound on the recording. They arise from single muscle fibers, but many fibers may fire myotonic discharges simultaneously. They are typically seen in myotonic dystrophy, myotonia congenita, paramyotonia congenita, hyperkalemic periodic paralysis, acid maltase deficiency, diazocholesterol toxicity, clofibrate toxicity, and rarely in polymyositis and colchicine toxicity.

Fasciculations are random single spontaneous discharges from a whole motor unit. On EMG, fasciculations have the morphology of single MUAP. They can appear as normal MUAPs, or they can be complex and large if they represent a pathologic motor unit. Fasciculations are nonspecific, and can be seen in radiculopathies, entrapment neuropathies, motor neuron disease such as amyotrophic lateral sclerosis (ALS), metabolic disorders such as thyrotoxicosis, and anticholinesterase overdoses. Although fasciculations involving superficial muscles can be visible on clinical examination, EMG helps record fasciculations from deeper muscles that are not clinically visible.

Myokymic discharges are rhythmic, grouped, spontaneous repetitive discharges of the same motor unit. These repeating bursts of MUAPs have a characteristic sound like that of soldiers marching. They may be recorded in facial muscles (facial myokymia) associated with Bell palsy or brainstem lesions resulting from multiple sclerosis, brainstem glioma, or vascular disease. Appendicular myokymia is associated with radiation plexopathy. Rarely, it may be seen in Guillain-Barré syndrome, radiculopathy, chronic entrapment neuropathy, and gold toxicity.

Neuromyotonic discharges are high-frequency (150–250 Hz) decrementing, repetitive discharges of a single motor unit that create a characteristic “pinging” sound on EMG recording. These are rare and are seen only with chronic neuropathic diseases (e.g., poliomyelitis and adult-onset spinal muscular atrophy) and syndromes of continuous motor unit activity, such as in Isaac syndrome.

Cramps are sustained involuntary muscle contractions caused by the activation of multiple motor units that occur in normal subjects (especially in distal lower extremity muscles) and in many neurogenic and metabolic disorders, including ALS, electrolyte imbalances, hypothyroidism, pregnancy, and uremia (see Cramps). Electrically, cramps are high-frequency discharges of motor units.

Once the muscle has been assessed for insertional and spontaneous activity, the motor units are analyzed by asking the patient to slowly contract the muscle. The pattern of MUAP abnormalities will allow determination of whether the disorder is a neuropathic or a myopathic process and often helps to ascertain the time course and severity of the lesion. Assessment of MUAPs involves evaluation of the morphology or shape of individual units, and the timing of unit firing—that is, MUAP recruitment and activation.

The morphology of MUAPs provides much information into the health of the muscle being studied. Although the normal appearance of MUAPs will vary slightly from muscle to muscle, a typical MUAP is about 5 to 15 milliseconds in duration, between 0.1 and 2 mV in amplitude, and has 2 to 4 phases.

Short-duration, small-amplitude, polyphasic MUAPs occur in disorders with atrophy or loss of muscle fibers in the motor unit. Thus, they are present in myopathic disorders and in severe cases of neuromuscular transmission disorders (e.g., botulism). In early reinnervation, after severe denervation in which the newly sprouting axons only begin to reinnervate a few muscle fibers, the MUAP will also be small, short duration, and polyphasic but with reduced recruitment (“nascent” MUAP).

Long-duration, large-amplitude, polyphasic MUAPs occur with increased number or density of muscle fibers, or a loss of synchrony of fiber firing within a motor unit such as in chronic neuropathic processes (e.g., motor neuron disease, chronic radiculopathies, chronic axonal neuropathies, and chronic entrapment neuropathy).

MUAPs are considered polyphasic if they have 5 or more phases. Polyphasia is a measure of synchrony of the firing of muscle fibers within the same motor unit. This is a nonspecific measure and may be abnormal in both myopathic and neuropathic disorders. In normal muscles, up to 5% to 10% of MUAPs may be polyphasic (up to 25% in the deltoid).

Unstable MUAPs are MUAPs that change in morphology from one instance to the next. This may occur due to blocking of individual muscle fiber action potentials within the motor unit. This may be seen in disorders of neuromuscular transmission, myositis, muscle trauma, reinnervation, and rapidly progressive neurogenic atrophy.

The temporal characteristics of MUAP recruitment and activation are also important in the analysis of an EMG. Recruitment and activation are two different processes that the nervous system uses to increase the force of a contraction.

In activation, individual motor units are driven to fire at a faster rate. Poor activation of MUAPs is recognized by motor units firing slowly. As this process is centrally mediated, reduced activation is attributable to upper motor neuron lesions or lack of effort.

Recruitment refers to the orderly addition of motor units as activation increases. Decreased recruitment presents as a small number of units firing with a high frequency. Decreased recruitment occurs when there is a decreased number of available motor units; the remaining motor units will fire at a faster frequency to increase the muscle force. This occurs in any peripheral neuropathic process, including neuropathies, radiculopathies, motor neuron disease, and trauma. The term “early recruitment” is used to describe the recruitment pattern seen in myopathies; when the force generated by each individual motor unit is decreased, more motor units must be recruited to generate the same amount of force.

The normal firing rate of most motor units, before additional units are recruited, is 10 Hz. Recruitment ratio is another term used to describe the firing rate of a motor unit. This ratio is the rate of firing of the most rapidly firing motor unit (in Hz) divided by the number of units firing. A recruitment ratio of over 8 is considered abnormal and suggests a neurogenic process.