Evaluation Guidelines Table211

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Neuroimaging. Magnetic resonance imaging (MRI) is useful for the evaluation of patients with focal or organ-specific autonomic syndromes. It can detect lesions that involve the frontal lobes (e.g., hydrocephalus) or the cervical, thoracic, or lumbar spine, producing different types of neurogenic bladder. It is also indicated for the detection of hypothalamic lesions, lateral medullary infarctions, syringomyelia, or lesions in the cavernous sinus that produce Horner's syndrome. MRI of the neck is required when a diagnosis of paragangliomas arising from the carotid body or the vagus nerve is considered in patients with severe baroreflex failure. MRI of the abdomen can localize pheochromocytomas arising from chromaffin cells in the adrenal medulla or elsewhere in the abdomen, and imaging of the neck, chest, and pelvis should be used when pheochromocytomas are considered.

Neuroimaging has a low yield in the evaluation of patients with generalized autonomic failure, although it may show atrophy of the basal ganglia, pons, or cerebellum in patients with multiple system atrophy. In these patients, areas of hypointensity in T2-weighted MRI images of the posterolateral putamen have been reported.

Electrophysiology. Electromyography (EMG) and nerve conduction velocities (NCVs) are useful in evaluating patients with peripheral neuropathy. However, the studies may be normal in conditions that selectively affect small nerve fibers. Small fiber function may be assessed using quantitative sensory testing to determine the sensory threshold for heat and cold sensation; these sensory modalities are mediated by the C and A-delta nerve fibers. This technique measures the intensity of a stimulus necessary

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TABLE 21-1 -- USEFUL STUDI

ES IN THE EVALUATION OF DISORDERS OF THE AUTONOMIC NERVOUS SYSTEM

Syndrome

Neuroimaging

Electrophysiology

Fluid and rissue Analysis

Neuropsychological Tests

Other Tests

PANDYSAUTONOMIA

Preganglionic disorders (multiple system atrophy)

MR1 brain: decreased putaminal signal intensity on T2-weighted images

EMG of anal sphineter: large motor units

Supine NE normal; no increase with standing

N/A

Cardiovagal and adrenergic innervation tests abnormal; TST abnormal

Autonomic ganglionic and postganglionic disorders

N/A

NCV/EMG: Abnormal in peripheral neuropathies with motor/sensory involvement

Supine plasma NE low; no increase with standing ANNA: paraneoplastic syndromes

N/A

Cardiovagal and adrenergic innervation tests abnormal; TST abnormal

Rectal biopsy:amyloiosis

PURE CHOLINERGIC DYSAUTONOMIA

N/A

EMG abnormal in botulism and LEMS

Normal plasma NE Antibodies to voltage-gated calcium channels: LEMS

N/A

GI motility studies

PURE ADRENERGIC DYSAUTONOMIA

N/A

N/A

Very low plasma NE

N/A

Test of adrenergic innervation abnormal; TST normal.

FOCAL DISORDERS

Telenecephalic

MRI brain

EEG monitoring for limbic seizures

N/A

Temporal lobe dysfunction

N/A

Diencephalic

MRI brain

N/A

Endocrinological tests for hypothalamic dysfunction

Elevated creatinine kinase

Memory Cognition

N/A

Brain stem

MRI brain

N/A

CSF abnormalities in MS

N/A

N/A

Spinal cord

MRI spinal cord

N/A

CSF abnormalities in MS

N/A

Bladder EMG or cystometrogram

MRI Magnetic resonance imaging: EMG, electromyography: NCv, nerve conduction velocity; LEMS, Lambert-Eaton myasthenic syndrome; ANNA, antineuronal nuclear antibody (anti-Hu); NE, norepinephnne; tSt, thermoregulatory sweat test; CSF, cerebrospinal fluid; MS, multiple sclerosis

MRI Magnetic resonance imaging: EMG, electromyography: NCv, nerve conduction velocity; LEMS, Lambert-Eaton myasthenic syndrome; ANNA, antineuronal nuclear antibody (anti-Hu); NE, norepinephnne; tSt, thermoregulatory sweat test; CSF, cerebrospinal fluid; MS, multiple sclerosis

to evoke a specific sensation. Electromyography and NCVs are used to evaluate peripheral nerve injuries that may result in focal autonomic abnormalities. Nerve conduction velocity studies may also be used to identify the cause of the predominantly cholinergic autonomic abnormalities that accompany the prejunctional disorders of neuromuscular transmission (e.g., botulism, the Lambert-Eaton myasthenic syndrome and the autonomic abnormalities that accompany paraneoplastic sensory ganglioneuronopathy). Finally, EMG of the external anal sphincter may show denervation in patients with lesions of the conus or cauda equina and in patients with multiple system atrophy.

Electrodermal activity is generated by the sweat glands and overlying epidermis and mediated by supraspinal sites that include the orbitofrontal cortex, the posterior hypothalamus, the dorsal thalamus, and the ventrolateral reticular formation. This response, which occurs spontaneously and can be evoked by stimuli such as respiration, startling, mental stress, and electrical stimuli, is referred to as the sympathetic skin response or peripheral autonomic surface potential. The sympathetic skin response is used in some EMG laboratories to assess sudomotor function. It consists of a slow change in the electrical potential of the skin of the palms and feet that depends on sweat production and is evoked reflexly by unexpected noise, deep inspiration, and electrical stimuli. Absence of the sympathetic skin response occurs in patients with autonomic failure, but it has limited specificity and no localizing value.

Microneurographic recordings of activity in sympathetic fibers innervating muscle and skin allow direct assessment of sympathetic vasoconstrictor and skin sudomotor outflows, respectively. However, because this technique is laborious and invasive and requires considerable expertise as well as a very cooperative patient, it remains only a research tool.y

Electroencephalography may show epileptiform activity in the temporolimbic areas, which may be associated with syncope or other paroxysmal autonomic phenomena. Sleep polysomnograms in patients with multiple system atrophy may allow the physician to make a diagnosis of sleep apnea.

Fluid and Tissue Analysis. Blood tests useful in the evaluation of patients with autonomic failure include blood glucose and glycosylated hemoglobin (diabetes), protein immunoelectrophoresis and genetic tests for the transthyretin variant (amyloidosis), vitamin B 12 (pernicious anemia), erythrocyte sedimentation rate, antinuclear antibody (connective tissue diseases), antineuronal nuclear (anti-Hu) antibody (paraneoplasia), human immunodeficiency virus (HIV) serology, and, in selected cases, porphyrins (acute intermittent porphyria) or alpha-galactosidase (Fabry's disease). y

Measurements of plasma cortisol in the morning and evening and, as previously mentioned, plasma catecholamines in the supine and standing positions may be helpful in the evaluation of patients with orthostatic hypotension.

Cerebrospinal Fluid. Cerebrospinal fluid examination may show albuminocytological dissociation with an elevated protein concentration and no pleocytosis in patients with Guillain-Barre syndrome and other acute pandysautonomias. Abdominal fat aspirate, rectal biopsy, or sural nerve biopsy should be considered in patients in whom amyloid neuropathy or Fabry's disease is suspected, and salivary or lacrimal gland biopsy should be done in patients in whom Sjoengren's syndrome is suspected.

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