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Disorders of the Spinal Cord the site of injury. Performance of a detailed sensory examina- tion, with ascending pinprick testing throughout the entire torso and neck, is essential. Gait is abnormal in most patients with myelopathy; a sensory ataxia or spastic gait sometimes can be an isolated presenting sign. Involvement of the distal spinal cord and lower roots (cauda equina syndrome) results in decreased muscle tone, areflexia, and loss of perianal sensation. Many patients with myelopathy report pain at the level of the compressive disease. Squeezing or banding sensations around the chest or abdomen near the level of spinal cord compression may be reported. Focal tenderness to percussion over the spinal column may be elicited. Disruptions in bowel and bladder function and loss of sphincter tone also are often noted. These varied symptoms may lead to unnecessary car- diac, pulmonary, gastrointestinal, or urinary tract evaluations and to a delayed diagnosis. e Corticospinal tract injury results in spastic paresis or paralysis, with weakness, hyperreflexia, muscle spastic- FIGURE 28. MRI of the spine showing metastatic cancer with collapse of the ity, and extensor plantar responses; there is often loss of vertebral body and compression of the spinal cord from the posteriorly displaced sensation at or below the site of injury. bony fragments (red arrow). ¢ Injury to the distal spinal cord and lower roots (cauda and bladder impairment. Some with lumbar stenosis describe equina syndrome) results in decreased muscle tone, symptoms similar to vascular claudication (pseudoclaudica- areflexia, and loss of perianal sensation. tion), with exertional groin, thigh, or buttock pain and possi- bly also weakness or numbness. Compressive Myelopathy Clinical Presentation Diagnosis Spinal cord compression often presents with neck or back pain, Initial MRI of the spinal cord at the suspected region of injury

¢ Injury to the distal spinal cord and lower roots (cauda and bladder impairment. Some with lumbar stenosis describe equina syndrome) results in decreased muscle tone, symptoms similar to vascular claudication (pseudoclaudica- areflexia, and loss of perianal sensation. tion), with exertional groin, thigh, or buttock pain and possi- bly also weakness or numbness. Compressive Myelopathy Clinical Presentation Diagnosis Spinal cord compression often presents with neck or back pain, Initial MRI of the spinal cord at the suspected region of injury followed by weakness, sensory changes, and bladder or bowel is the preferred means of diagnosing compressive myelopathy dysfunction. Examination typically reveals upper motor neuron and will often reveal the cause. Imaging should be performed signs (weakness, spasticity, hyperreflexia, and extensor planar emergently in cord compression thought to be secondary to responses), but lower motor neuron signs (atrophy, hypore- abscess or malignancy because neurologic compromise can flexia) sometimes can occur near the level of compression or progress rapidly. CT myelography can show compressive mye- after acute injury. Specific signs and symptoms can provide lopathy when MRI is not feasible but often does not reveal the clues as to the cause of compression. The presence of fever and cause of compression. Additionally, this type of imaging may be focal back pain and tenderness, especially in patients who have difficult to arrange emergently and is problematic in patients had recent back instrumentation or have a history of intrave- with allergies to contrast dyes or impaired kidney function.

clues as to the cause of compression. The presence of fever and cause of compression. Additionally, this type of imaging may be focal back pain and tenderness, especially in patients who have difficult to arrange emergently and is problematic in patients had recent back instrumentation or have a history of intrave- with allergies to contrast dyes or impaired kidney function. nous drug use, may indicate an epidural abscess (see MKSAP 19 Infectious Disease for more information on cranial and spinal e In patients with compressive myelopathy, a history of epidural abscesses). A history of neoplasia and focal back pain neoplasia and focal back pain should arouse concern for should raise concern for metastatic disease (Figure 28) or patho- metastatic disease; the presence of fever and focal back logic vertebral fracture. Anticoagulant use raises the risk of pain and tenderness may indicate an epidural abscess. compression from an epidural hematoma, particularly in the setting of recent back instrumentation. e An initial MRI of the spinal cord at the suspected region of injury is the preferred means of diagnosing compres- Patients with chronic spinal stenosis due to osteoarthritic degenerative spinal disease frequently present with chronic sive myelopathy and will often reveal the cause. myelopathic symptoms. Compressive myelopathy should thus be considered in older patients with gait dysfunction or weak- Treatment ness. Degenerative spinal disease often affects the cervical and Surgical decompression is typically required to treat spinal lumbar regions, but thoracic cord involvement is quite rare. cord compression, but medical therapies can complement Most patients with chronic compressive myelopathy initially surgical treatment, depending on the underlying cause. report progressive leg weakness, spasticity, distal numbness, Emergent treatment usually is indicated to prevent further 72

Disorders of the Spinal Cord neurologic decline, but full neurologic function is rarely For chronic cervical or lumbar stenosis or acute disk her- regained. niation, symptomatic management can control symptoms in Adjunctive therapy is important; an epidural hematoma most patients. Surgical decompression may be required for may first require management of the bleeding diathesis, and patients with myelopathy refractory to medical management. cord compression caused by epidural abscess requires antibi- See MKSAP 19 General Internal Medicine 1 for more informa- otics. Glucocorticoids generally are not indicated with hema- tion about treating neck and back pain. toma and abscess. The use of glucocorticoids in traumatic KEY POINT spinal cord compression is controversial. Although initial trials e Spinal cord compression from metastatic disease in acute traumatic spine injury suggested benefit, later studies requires emergent use of high-dose glucocorticoids and and reanalysis of initial trial data have suggested a lack of urgent surgical decompression, followed by radiation definitive benefit and potential harm of glucocorticoids. For for most tumor types. this reason, the long-standing practice of using glucocorti- coids immediately after traumatic spinal cord compression has been abandoned at most institutions. Spinal cord compression from metastatic disease Noncompressive Myelopathy requires emergent use of high-dose glucocorticoids and Noncompressive myelopathy can be caused by many inflam- urgent surgical evaluation. Trial evidence suggests that surgi- matory, infectious, metabolic, vascular, and genetic disorders. cal decompression followed by radiotherapy is most benefi- Inflammatory causes are most common, including multiple cial for patients younger than 65 years who have a single area sclerosis (see Multiple Sclerosis), neuromyelitis optica spec- of compression, paraplegia with a duration of less than trum disorders (typically characterized by optic nerve and 48 hours, and a predicted survival of greater than 6 months. spinal cord demyelination and the presence of aquaporin-4

neurologic decline, but full neurologic function is rarely For chronic cervical or lumbar stenosis or acute disk her- regained. niation, symptomatic management can control symptoms in Adjunctive therapy is important; an epidural hematoma most patients. Surgical decompression may be required for may first require management of the bleeding diathesis, and patients with myelopathy refractory to medical management. cord compression caused by epidural abscess requires antibi- See MKSAP 19 General Internal Medicine 1 for more informa- otics. Glucocorticoids generally are not indicated with hema- tion about treating neck and back pain. toma and abscess. The use of glucocorticoids in traumatic KEY POINT spinal cord compression is controversial. Although initial trials e Spinal cord compression from metastatic disease in acute traumatic spine injury suggested benefit, later studies requires emergent use of high-dose glucocorticoids and and reanalysis of initial trial data have suggested a lack of urgent surgical decompression, followed by radiation definitive benefit and potential harm of glucocorticoids. For for most tumor types. this reason, the long-standing practice of using glucocorti- coids immediately after traumatic spinal cord compression has been abandoned at most institutions. Spinal cord compression from metastatic disease Noncompressive Myelopathy requires emergent use of high-dose glucocorticoids and Noncompressive myelopathy can be caused by many inflam- urgent surgical evaluation. Trial evidence suggests that surgi- matory, infectious, metabolic, vascular, and genetic disorders. cal decompression followed by radiotherapy is most benefi- Inflammatory causes are most common, including multiple cial for patients younger than 65 years who have a single area sclerosis (see Multiple Sclerosis), neuromyelitis optica spec- of compression, paraplegia with a duration of less than trum disorders (typically characterized by optic nerve and 48 hours, and a predicted survival of greater than 6 months. spinal cord demyelination and the presence of aquaporin-4 In patients not meeting these criteria, surgical intervention antibodies), and sarcoidosis (see MKSAP 19 Pulmonary and may be of little benefit, and radiotherapy alone may be used. Critical Care Medicine and MKSAP 19 Rheumatology). Furthermore, certain radiosensitive tumor types, such as leukemia, lymphoma, myeloma, and germ cell tumors, may Idiopathic Transverse Myelitis not require initial surgical decompression and instead may Idiopathic transverse myelitis (ITM) (Figure 29) is a monopha- be treated urgently with radiation therapy. For more infor- sic, inflammatory, and demyelinating disorder of the spinal mation on spinal cord compression due to metastatic disease, cord. ITM typically affects only one region of the spinal cord see MKSAP19 Oncology. and is considered to be a para- or postinfectious inflammatory

In patients not meeting these criteria, surgical intervention antibodies), and sarcoidosis (see MKSAP 19 Pulmonary and may be of little benefit, and radiotherapy alone may be used. Critical Care Medicine and MKSAP 19 Rheumatology). Furthermore, certain radiosensitive tumor types, such as leukemia, lymphoma, myeloma, and germ cell tumors, may Idiopathic Transverse Myelitis not require initial surgical decompression and instead may Idiopathic transverse myelitis (ITM) (Figure 29) is a monopha- be treated urgently with radiation therapy. For more infor- sic, inflammatory, and demyelinating disorder of the spinal mation on spinal cord compression due to metastatic disease, cord. ITM typically affects only one region of the spinal cord see MKSAP19 Oncology. and is considered to be a para- or postinfectious inflammatory ’ FIGURE 29. MRI of the cervical spine in a patient with transverse myelitis. Sagittal T2-weighted (/eft) and axial T12-weighted (right) images both demonstrate hyperintensity within the parenchyma of the spinal cord (red arrows). 73

Disorders of the Spinal Cord response. Affected patients frequently experience subacute Subacute Combined Degeneration weakness, sensory changes, and bladder or bowel dysfunc- Severe and prolonged vitamin B,, deficiency can result in tion. Some patients experience an initial prodrome of back subacute combined degeneration, which refers to a dys- pain or a thoracic banding sensation. function of the corticospinal and dorsal sensory tracts of The diagnostic criteria for ITM require presence of the spinal cord that manifests as spastic paresis with clinical features of the syndrome, evidence of inflamma- reduced vibration and position sense and ataxia. MRI can tion (either cerebrospinal fluid leukocytosis or contrast show increased signal in the affected white-matter path- enhancement on spinal cord MRI), and exclusion of other ways without associated inflammatory changes. Laboratory potential causes. Those with complete myelitis (symptoms study results show a low serum vitamin Bj, level with referable to complete rather than partial cord transection), elevated levels of serum methylmalonic acid and homo- a lack of elevated oligoclonal bands or IgG index in the cysteine. Macrocytic anemia may be present, but the cerebrospinal fluid, and no lesions on brain MRI are much neurologic manifestations of B,, deficiency may precede more likely to have ITM than other disorders, such as mul- development of anemia. The clinical symptoms of vitamin tiple sclerosis. This is a crucial distinction because ITM is By, deficiency can sometimes occur with low-normal not a recurrent disorder and does not require long-term serum Bj, levels, and thus supportive laboratory studies immunomodulatory therapy. Recurrence of symptoms or with measurement of methylmalonic acid and homocyst- new symptoms beyond a 30-day period should arouse sus- eine should be performed in patients with a high index of picion for multiple sclerosis or other recurrent disorders. clinical suspicion. Vitamin B,, replacement usually halts The presence of a longitudinally extensive (> 3 spinal seg- progression of the disease but may not necessarily reverse ments) cord lesion should arouse suspicion for neuromyeli- existing symptoms. tis optica spectrum disorders, and testing for aquaporin-4 Nitrous oxide abuse also can cause a relative vitamin By» and myelin oligodendrocyte glycoprotein antibodies should deficiency that results in subacute combined degeneration. be performed. Supplementation of vitamin B,, in those circumstances with- The consensus-based treatment of ITM is intravenous out cessation of the drug may impede improvement in methylprednisolone, 1 g/d for 3 to 7 days. This therapy is symptoms. intended to stop inflammatory damage of the spinal cord and Copper deficiency (due to malabsorption, nutritional allow for recovery of neurologic function. Patients whose dis- deficiency, or zinc toxicity) can also cause subacute combined ease is refractory to glucocorticoids may benefit from plasma- degeneration. This entity should be considered in patients pheresis and/or cyclophosphamide. with suggestive symptoms who have normal vitamin B,, levels. Infectious causes of transverse myelitis should always Myelopathy from such nutritional deficiencies should specifi- be considered when evaluating patients for possible ITM. cally be considered in patients with previous bariatric surgical Herpes simplex virus, varicella zoster virus, West Nile virus, procedures. human T-lymphotropic virus, Lyme disease, and neuro- syphilis infections can affect the spinal cord. HIV infection can cause a transverse myelitis—like syndrome at the time of e Severe and prolonged vitamin B,, deficiency can seroconversion or result in a chronic degenerative vacuolar result in subacute combined degeneration; in patients

response. Affected patients frequently experience subacute Subacute Combined Degeneration weakness, sensory changes, and bladder or bowel dysfunc- Severe and prolonged vitamin B,, deficiency can result in tion. Some patients experience an initial prodrome of back subacute combined degeneration, which refers to a dys- pain or a thoracic banding sensation. function of the corticospinal and dorsal sensory tracts of The diagnostic criteria for ITM require presence of the spinal cord that manifests as spastic paresis with clinical features of the syndrome, evidence of inflamma- reduced vibration and position sense and ataxia. MRI can tion (either cerebrospinal fluid leukocytosis or contrast show increased signal in the affected white-matter path- enhancement on spinal cord MRI), and exclusion of other ways without associated inflammatory changes. Laboratory potential causes. Those with complete myelitis (symptoms study results show a low serum vitamin Bj, level with referable to complete rather than partial cord transection), elevated levels of serum methylmalonic acid and homo- a lack of elevated oligoclonal bands or IgG index in the cysteine. Macrocytic anemia may be present, but the cerebrospinal fluid, and no lesions on brain MRI are much neurologic manifestations of B,, deficiency may precede more likely to have ITM than other disorders, such as mul- development of anemia. The clinical symptoms of vitamin tiple sclerosis. This is a crucial distinction because ITM is By, deficiency can sometimes occur with low-normal not a recurrent disorder and does not require long-term serum Bj, levels, and thus supportive laboratory studies immunomodulatory therapy. Recurrence of symptoms or with measurement of methylmalonic acid and homocyst- new symptoms beyond a 30-day period should arouse sus- eine should be performed in patients with a high index of picion for multiple sclerosis or other recurrent disorders. clinical suspicion. Vitamin B,, replacement usually halts The presence of a longitudinally extensive (> 3 spinal seg- progression of the disease but may not necessarily reverse ments) cord lesion should arouse suspicion for neuromyeli- existing symptoms. tis optica spectrum disorders, and testing for aquaporin-4 Nitrous oxide abuse also can cause a relative vitamin By» and myelin oligodendrocyte glycoprotein antibodies should deficiency that results in subacute combined degeneration. be performed. Supplementation of vitamin B,, in those circumstances with- The consensus-based treatment of ITM is intravenous out cessation of the drug may impede improvement in methylprednisolone, 1 g/d for 3 to 7 days. This therapy is symptoms. intended to stop inflammatory damage of the spinal cord and Copper deficiency (due to malabsorption, nutritional allow for recovery of neurologic function. Patients whose dis- deficiency, or zinc toxicity) can also cause subacute combined ease is refractory to glucocorticoids may benefit from plasma- degeneration. This entity should be considered in patients pheresis and/or cyclophosphamide. with suggestive symptoms who have normal vitamin B,, levels. Infectious causes of transverse myelitis should always Myelopathy from such nutritional deficiencies should specifi- be considered when evaluating patients for possible ITM. cally be considered in patients with previous bariatric surgical Herpes simplex virus, varicella zoster virus, West Nile virus, procedures. human T-lymphotropic virus, Lyme disease, and neuro- syphilis infections can affect the spinal cord. HIV infection can cause a transverse myelitis—like syndrome at the time of e Severe and prolonged vitamin B,, deficiency can seroconversion or result in a chronic degenerative vacuolar result in subacute combined degeneration; in patients myelopathy in patients with chronic low CD4 cell counts. with suggestive symptoms of this disorder and nor- Mycobacterium tuberculosis can infect the meninges and mal vitamin B,, levels, copper deficiency should be

response. Affected patients frequently experience subacute Subacute Combined Degeneration weakness, sensory changes, and bladder or bowel dysfunc- Severe and prolonged vitamin B,, deficiency can result in tion. Some patients experience an initial prodrome of back subacute combined degeneration, which refers to a dys- pain or a thoracic banding sensation. function of the corticospinal and dorsal sensory tracts of The diagnostic criteria for ITM require presence of the spinal cord that manifests as spastic paresis with clinical features of the syndrome, evidence of inflamma- reduced vibration and position sense and ataxia. MRI can tion (either cerebrospinal fluid leukocytosis or contrast show increased signal in the affected white-matter path- enhancement on spinal cord MRI), and exclusion of other ways without associated inflammatory changes. Laboratory potential causes. Those with complete myelitis (symptoms study results show a low serum vitamin Bj, level with referable to complete rather than partial cord transection), elevated levels of serum methylmalonic acid and homo- a lack of elevated oligoclonal bands or IgG index in the cysteine. Macrocytic anemia may be present, but the cerebrospinal fluid, and no lesions on brain MRI are much neurologic manifestations of B,, deficiency may precede more likely to have ITM than other disorders, such as mul- development of anemia. The clinical symptoms of vitamin tiple sclerosis. This is a crucial distinction because ITM is By, deficiency can sometimes occur with low-normal not a recurrent disorder and does not require long-term serum Bj, levels, and thus supportive laboratory studies immunomodulatory therapy. Recurrence of symptoms or with measurement of methylmalonic acid and homocyst- new symptoms beyond a 30-day period should arouse sus- eine should be performed in patients with a high index of picion for multiple sclerosis or other recurrent disorders. clinical suspicion. Vitamin B,, replacement usually halts The presence of a longitudinally extensive (> 3 spinal seg- progression of the disease but may not necessarily reverse ments) cord lesion should arouse suspicion for neuromyeli- existing symptoms. tis optica spectrum disorders, and testing for aquaporin-4 Nitrous oxide abuse also can cause a relative vitamin By» and myelin oligodendrocyte glycoprotein antibodies should deficiency that results in subacute combined degeneration. be performed. Supplementation of vitamin B,, in those circumstances with- The consensus-based treatment of ITM is intravenous out cessation of the drug may impede improvement in methylprednisolone, 1 g/d for 3 to 7 days. This therapy is symptoms. intended to stop inflammatory damage of the spinal cord and Copper deficiency (due to malabsorption, nutritional allow for recovery of neurologic function. Patients whose dis- deficiency, or zinc toxicity) can also cause subacute combined ease is refractory to glucocorticoids may benefit from plasma- degeneration. This entity should be considered in patients pheresis and/or cyclophosphamide. with suggestive symptoms who have normal vitamin B,, levels. Infectious causes of transverse myelitis should always Myelopathy from such nutritional deficiencies should specifi- be considered when evaluating patients for possible ITM. cally be considered in patients with previous bariatric surgical Herpes simplex virus, varicella zoster virus, West Nile virus, procedures. human T-lymphotropic virus, Lyme disease, and neuro- syphilis infections can affect the spinal cord. HIV infection can cause a transverse myelitis—like syndrome at the time of e Severe and prolonged vitamin B,, deficiency can seroconversion or result in a chronic degenerative vacuolar result in subacute combined degeneration; in patients myelopathy in patients with chronic low CD4 cell counts. with suggestive symptoms of this disorder and nor- Mycobacterium tuberculosis can infect the meninges and mal vitamin B,, levels, copper deficiency should be spinal cord and present with a transverse myelitis-like syn- considered. drome. This infection warrants prompt treatment with appropriate antimicrobial agents. The addition of glucocor- ticoids to treat these disorders is controversial but may be Vascular Disorders indicated when infections are associated with significant Infarcts in the territory of the anterior spinal artery typically

spinal cord and present with a transverse myelitis-like syn- considered. drome. This infection warrants prompt treatment with appropriate antimicrobial agents. The addition of glucocor- ticoids to treat these disorders is controversial but may be Vascular Disorders indicated when infections are associated with significant Infarcts in the territory of the anterior spinal artery typically spinal cord edema. present as sudden-onset flaccid paralysis with preservation of vibration and position sense because of the lack of dorsal col- umn involvement. Prolonged hypotension during cardiovas- e Patients with complete myelitis, lack of elevated oligo- cular or aortic surgery can also sometimes result in lack of clonal bands or IgG index in the cerebrospinal fluid, and perfusion to watershed regions of the spinal cord, especially in no lesions on brain MRI are much more likely to have the area where the anterior spinal artery meets the most idiopathic transverse myelitis than multiple sclerosis. prominent radicular artery (artery of Adamkiewicz) in the ¢ Treatment of idiopathic transverse myelitis is intrave- upper thoracic cord. nous methylprednisolone; secondary causes of trans- Dural arteriovenous fistulas of the spinal vascular sup- verse myelitis, including infection, should first be ply can either result in chronic myelopathy due to venous excluded. congestion or cause infarction of the cord due to altered vascular dynamics or thromboses. Fistulas are most 74

Neuromuscular Disorders common in men older than 50 years and in persons with previous spinal surgery. Abnormal vascular flow voids Neuromuscular Disorders often are seen on careful review of spinal MRIs. Diagnosis Overview is often challenging and typically requires digital subtrac- Peripheral and central nervous system disorders can be dif- tion angiography of all radicular vessels along the entire ferentiated on the basis of history and neurologic examination spine. findings (Table 44). Neuromuscular disorders include myopa- thies, neuromuscular junction disorders, peripheral neuropa- Genetic Disorders thies, plexopathies, radiculopathies, and motor neuron dis- Although rare, several genetic disorders can result in eases (Table 45 and Table 46). chronic myelopathy. Some of these disorders have clear familial inheritance, but others may result from de novo mutations. Hereditary spastic paraplegia comprises heredi- tary disorders that result in chronic, progressive, ascending Peripheral Neuropathies weakness and spasticity, often beginning in childhood or Classification, Findings, and Diagnosis adolescence. Genetic screening is available, but no treat- Symptoms of peripheral neuropathy include negative (sen- ment currently exists. Female carriers of X-linked adreno- sory loss) or positive (paresthesia, dysesthesia, and pain) leukodystrophy sometimes develop adrenomyeloneuropa- sensory symptoms, weakness, or autonomic dysfunction.

common in men older than 50 years and in persons with previous spinal surgery. Abnormal vascular flow voids Neuromuscular Disorders often are seen on careful review of spinal MRIs. Diagnosis Overview is often challenging and typically requires digital subtrac- Peripheral and central nervous system disorders can be dif- tion angiography of all radicular vessels along the entire ferentiated on the basis of history and neurologic examination spine. findings (Table 44). Neuromuscular disorders include myopa- thies, neuromuscular junction disorders, peripheral neuropa- Genetic Disorders thies, plexopathies, radiculopathies, and motor neuron dis- Although rare, several genetic disorders can result in eases (Table 45 and Table 46). chronic myelopathy. Some of these disorders have clear familial inheritance, but others may result from de novo mutations. Hereditary spastic paraplegia comprises heredi- tary disorders that result in chronic, progressive, ascending Peripheral Neuropathies weakness and spasticity, often beginning in childhood or Classification, Findings, and Diagnosis adolescence. Genetic screening is available, but no treat- Symptoms of peripheral neuropathy include negative (sen- ment currently exists. Female carriers of X-linked adreno- sory loss) or positive (paresthesia, dysesthesia, and pain) leukodystrophy sometimes develop adrenomyeloneuropa- sensory symptoms, weakness, or autonomic dysfunction. thy, a degenerative condition of the spinal cord and Neuropathies are classified on the basis of distribution of peripheral nerves. These patients can be diagnosed through sensorimotor deficits (symmetric versus asymmetric, distal alterations in the serum very-long-chain fatty acid profiles versus proximal, focal versus generalized), pathology (demy- or genetic testing. Genetic counseling is indicated in such elinating versus axonal), family history, and autonomic settings. involvement (Figure 30).

thy, a degenerative condition of the spinal cord and Neuropathies are classified on the basis of distribution of peripheral nerves. These patients can be diagnosed through sensorimotor deficits (symmetric versus asymmetric, distal alterations in the serum very-long-chain fatty acid profiles versus proximal, focal versus generalized), pathology (demy- or genetic testing. Genetic counseling is indicated in such elinating versus axonal), family history, and autonomic settings. involvement (Figure 30). TABLE 44. Features Distinguishing Peripheral from Central Nervous System Disorders | Features PNS Disorder CNS Disorder ' Onset Subacute or insidious Sudden (stroke) or gradual (mass lesions) Pattern of weakness Focal or multifocal (in the territory of the affected Entire limb, unilateral, ora pyramidal pattern of nerve, plexus, or root) or generalized weakness? | Atrophy Yes (at times prominent) No (or mild, and related to disuse) Fasciculations Yes No Tone Decreased or normal Increased (spasticity or rigidity?) or normal Pattern of sensory Focal or multifocal (in the territory of the affected Entire limb or unilateral symptoms nerve, plexus, or root) or stocking-glove in distribution

Tone Decreased or normal Increased (spasticity or rigidity?) or normal Pattern of sensory Focal or multifocal (in the territory of the affected Entire limb or unilateral symptoms nerve, plexus, or root) or stocking-glove in distribution | Type of sensory Positive symptoms (paresthesia, dysesthesia, or Negative symptoms more frequent, but positive | symptoms allodynia‘) more frequent, but negative symptoms symptoms possible (numbness) possible Dissociated sensory Pain/temperature and vibration/proprioception Dissociation of pain/temperature and vibration/ loss deficits travel together proprioception deficits possible with spinal and brainstem lesions Deep tendon reflexes Diminished or normal Increased Pathologic reflexes Absent Present, including extensor plantar response, Hoffman sign,? knee cross adduction response, jaw jerk reflex, snout reflex, and clonus Additional localizing Cramps Headache, seizures, and visual and language-related symptoms symptoms EMG Abnormal Normal CNS = central nervous system; EMG = electromyography; PNS = peripheral nervous system.

Additional localizing Cramps Headache, seizures, and visual and language-related symptoms symptoms EMG Abnormal Normal CNS = central nervous system; EMG = electromyography; PNS = peripheral nervous system. *Pyramidal weakness is caused by upper motor neuron lesions and affects extensors more than flexors in the upper limbs and flexors more than extensors in the lower limbs. ®Spasticity is a direction- and velocity-dependent increase in tone and is associated with pyramidal lesions; rigidity is an increase in tone that is independent of velocity and direction and is associated with extrapyramidal lesions. ‘Paresthesia is an abnormal spontaneous sensation, such as tingling, burning, or electrical sensation. Dysesthesia is an unpleasant sensation provoked by neutral stimuli, such as light touch or contact of clothes. Allodynia is pain provoked by nonnoxious stimuli. | ‘Hoffman sign is positive if the thumb is flexed in response to a flicking or snapping of the distal phalanx of the middle finger. 75

Neuromuscular Disorders TABLE 45. Classification of Neuromuscular Disorders | Type Features Examples | Myopathy | Acquired Proximal greater than distal weakness, absence of Inflammatory, toxic, systemic, and endocrine sensory and autonomic symptoms, symmetric, late myopathies hyporeflexia after atrophy, adult onset | Inherited Similar to acquired myopathy, onset in childhood or Muscular dystrophies; mitochondrial, metabolic, and | | early adulthood, positive family history, some congenital myopathies possibly associated with distal or multifocal (scapuloperoneal, oculopharyngeal) weakness and atrophy, myotonia, or exercise-induced pain Neuromuscular Fluctuating weakness; fatigue; absence of sensory Myasthenia gravis, Lambert-Eaton myasthenic | junction disorder and autonomic symptoms; symmetric, bulbar, and syndrome respiratory involvement Peripheral neuropathy Axonal Symmetric distal sensory and sensorimotor Diabetic, toxic, hypothyroid, uremic, and nutritional impairment, possible involvement of autonomic polyneuropathy nerves, early or late hyporeflexia Demyelinating Proximal and distal symmetric or multifocal GBS, CIDP, hereditary (CMT1) weakness with variable sensory loss, early areflexia, low back radicular pain; hereditary forms associated with foot deformities and slow progression

Demyelinating Proximal and distal symmetric or multifocal GBS, CIDP, hereditary (CMT1) weakness with variable sensory loss, early areflexia, low back radicular pain; hereditary forms associated with foot deformities and slow progression Mononeuropathy Sensory and motor deficits within the distribution of Carpal tunnel syndrome, ulnar neuropathy, radial a single nerve, symptoms distal to site of neuropathy, peroneal neuropathy compression Plexopathy Motor and sensory deficits in multiple contiguous Idiopathic brachial plexitis, idiopathic lumbosacral nerves in upper or lower extremities, asymmetric, radiculoplexus neuropathy, diabetic amyotrophy, severe pain at onset with autoimmune and diabetic postradiation and carcinomatous plexopathy types Radiculopathy Motor, sensory, and reflex deficits in the area Cervical and lumbar radiculopathy innervated by affected nerve root, radicular pain and paresthesia, neck or low back pain Ganglionopathy Severe loss of vibration and joint position sense in Paraneoplastic and autoimmune ganglionopathy single limb, no motor deficit _ Motor neuron disease Concomitant signs of upper motor neuron Amyotrophic lateral sclerosis (hyperreflexia, pyramidal signs, and spasticity) and lower motor neuron (weakness, atrophy, and fasciculation) dysfunction, no sensory deficit, asymmetric onset, bulbar and respiratory involvement

_ Motor neuron disease Concomitant signs of upper motor neuron Amyotrophic lateral sclerosis (hyperreflexia, pyramidal signs, and spasticity) and lower motor neuron (weakness, atrophy, and fasciculation) dysfunction, no sensory deficit, asymmetric onset, bulbar and respiratory involvement Myelopathy? Lower motor neuron signs at the level of compression Cervical cord compression and upper motor neuron signs below it, sphincter dysfunction, sensory symptoms present, sensory level | CIDP = chronic inflammatory demyelinating polyradiculoneuropathy; CMT1 = Charcot-Marie-Tooth disease type 1; GBS = Guillain-Barré syndrome. *Myelopathy is a key differential diagnosis for neuromuscular disorders.

Myelopathy? Lower motor neuron signs at the level of compression Cervical cord compression and upper motor neuron signs below it, sphincter dysfunction, sensory symptoms present, sensory level | CIDP = chronic inflammatory demyelinating polyradiculoneuropathy; CMT1 = Charcot-Marie-Tooth disease type 1; GBS = Guillain-Barré syndrome. *Myelopathy is a key differential diagnosis for neuromuscular disorders. For all patients with a suspected peripheral neuropathy, a prolonged, whereas in myopathy, these potentials are low complete blood count, an erythrocyte sedimentation rate amplitude and brief. If neuropathy is present, EMG also can determination, serum protein electrophoresis with immune determine whether it is demyelinating or axonal. In demyeli- fixation, thyroid function tests, hemoglobin A,,./fasting plasma nating neuropathies, velocity of nerve conduction decreases, glucose determination, and vitamin B,, measurement are nec- but in axonopathy, velocity remains unchanged. The presence essary. In specific clinical settings, additional tests, including of weakness, asymmetry, proximal findings, rapid course, or CSF analysis, genetic testing, and other specialized laboratory atypical features should prompt EMG testing. In patients with testing, can help clarify the diagnosis (Table 47). a slowly progressive distal symmetric sensory neuropathy Electromyography (EMG), including both nerve conduc- with negative family history, however, EMG may not be tion studies and needle electrode examination, can differenti- required. ate neuropathy from other neuromuscular disorders. In Nerve biopsy should only be considered in rare settings in neuropathy, motor unit potentials are high amplitude and which concern for a vasculitic, infectious, or infiltrative 76

Neuromuscular Disorders TABLE 46. Common Symptoms and Signs of Neuromuscular Disorders | Symptoms and Signs Differential Diagnosis Weakness Distal extremities Diabetic, toxic and systemic polyneuropathy, hereditary neuropathy Proximal extremities Myopathy, polyradiculopathy, inflammatory demyelinating neuropathy, diabetic amyotrophy Multifocal with pain (mononeuropathy multiplex) Vasculitis, rheumatoid arthritis, diabetes Focal asymmetric ALS, inclusion body myositis, radiculopathy, mononeuropathy, multifocal motor neuropathy Fluctuating Myasthenia gravis Muscles of eye movement Myasthenia gravis, mitochondrial myopathy, thyroid disease Bulbar (tongue, palate, lips) ALS, myasthenia gravis, inclusion body myositis Cranial nerves (especially seventh and third) Diabetes, Lyme disease, sarcoidosis, HIV infection, Sjogren syndrome, tuberculosis Neck extensors ALS, myasthenia gravis (especially with anti-MuSK antibody), inflammatory myopathy Fasciculation ALS, radiculopathy, benign fasciculation syndrome | Sensory | Stocking-glove gradient Diabetic, toxic, systemic, or cryptogenic polyneuropathy; hereditary neuropathy Dermatomal pattern Radiculopathy, mononeuropathy Distal pain without hyporeflexia Small fiber neuropathy (diabetes mellitus, alcoholism, Sjagren syndrome, sarcoidosis, HIV, hepatitis C) Marked proprioceptive loss in single limb Dorsal root ganglionopathy (paraneoplastic, Sjsgren syndrome, HIV)

Distal pain without hyporeflexia Small fiber neuropathy (diabetes mellitus, alcoholism, Sjagren syndrome, sarcoidosis, HIV, hepatitis C) Marked proprioceptive loss in single limb Dorsal root ganglionopathy (paraneoplastic, Sjsgren syndrome, HIV) Autonomic Orthostatic hypotension, resting tachycardia, Diabetes, alcoholism, amyloidosis, autoimmune dysautonomia with anti- excessive or impaired sweating, gastroparesis, ganglionic acetylcholine receptor antibody, paraneoplastic antibodies constipation, erectile dysfunction ALS = amyotrophic lateral sclerosis; MuSK = muscle-specific kinase.

Orthostatic hypotension, resting tachycardia, Diabetes, alcoholism, amyloidosis, autoimmune dysautonomia with anti- excessive or impaired sweating, gastroparesis, ganglionic acetylcholine receptor antibody, paraneoplastic antibodies constipation, erectile dysfunction ALS = amyotrophic lateral sclerosis; MuSK = muscle-specific kinase. neuropathy exists. Autonomic tests, including quantitative Carpal Tunnel Syndrome sudomotor axon reflex and tilt table tests, can help confirm Carpal tunnel syndrome results from focal compression of the autonomic neuropathy but are rarely performed in practice. median nerve at the wrist. Most often, paresthesia and pain are experienced in the first three digits but may radiate to the entire hand or proximally. With milder symptoms, diagnosis of HVC e Electromyography (EMG) can differentiate neuropathy carpal tunnel syndrome can be made clinically, and treatment from other neuromuscular disorders, and if neuropathy is supportive, including neutral positioning, wrist splints, and is present, EMG can determine whether it is axonal or pain control. The presence of weakness, thenar atrophy, demyelinating. refractory pain, or active denervation evident on EMG should e The presence of weakness, asymmetry, proximal find- prompt surgical decompression. See MKSAP 19 General ings, a rapid course, or atypical features should prompt Internal Medicine 1 for further information about carpal tun- testing with electromyography in a patient with a sus- nel syndrome. pected peripheral neuropathy.

neuropathy exists. Autonomic tests, including quantitative Carpal Tunnel Syndrome sudomotor axon reflex and tilt table tests, can help confirm Carpal tunnel syndrome results from focal compression of the autonomic neuropathy but are rarely performed in practice. median nerve at the wrist. Most often, paresthesia and pain are experienced in the first three digits but may radiate to the entire hand or proximally. With milder symptoms, diagnosis of HVC e Electromyography (EMG) can differentiate neuropathy carpal tunnel syndrome can be made clinically, and treatment from other neuromuscular disorders, and if neuropathy is supportive, including neutral positioning, wrist splints, and is present, EMG can determine whether it is axonal or pain control. The presence of weakness, thenar atrophy, demyelinating. refractory pain, or active denervation evident on EMG should e The presence of weakness, asymmetry, proximal find- prompt surgical decompression. See MKSAP 19 General ings, a rapid course, or atypical features should prompt Internal Medicine 1 for further information about carpal tun- testing with electromyography in a patient with a sus- nel syndrome. pected peripheral neuropathy. Ulnar, Radial, and Peroneal Mononeuropathies Mononeuropathies Ulnar mononeuropathy presents with paresthesia and numb- Mononeuropathies involve a single nerve and can cause both ness in digits 4 and 5, and in severe cases with weakness and motor and sensory symptoms within the territory of the atrophy of intrinsic hand muscles. Site of compression is com- affected nerve. Sequential involvement of multiple nerves monly at the medial epicondyle because of frequent leaning on may be seen in mononeuropathy multiplex, a condition most the elbow. Management includes education to avoid pressure often associated with pain and caused by vasculitis. on the nerve, elbow splinting, and, in patients with persistent Plexopathies originate at the level of the brachial or lumbosa- pain and progressive weakness, decompression surgery. cral plexus and involve multiple sensory and motor nerves Radial mononeuropathy presents as wrist drop and simultaneously. finger extensor weakness caused by compression of the

Ulnar, Radial, and Peroneal Mononeuropathies Mononeuropathies Ulnar mononeuropathy presents with paresthesia and numb- Mononeuropathies involve a single nerve and can cause both ness in digits 4 and 5, and in severe cases with weakness and motor and sensory symptoms within the territory of the atrophy of intrinsic hand muscles. Site of compression is com- affected nerve. Sequential involvement of multiple nerves monly at the medial epicondyle because of frequent leaning on may be seen in mononeuropathy multiplex, a condition most the elbow. Management includes education to avoid pressure often associated with pain and caused by vasculitis. on the nerve, elbow splinting, and, in patients with persistent Plexopathies originate at the level of the brachial or lumbosa- pain and progressive weakness, decompression surgery. cral plexus and involve multiple sensory and motor nerves Radial mononeuropathy presents as wrist drop and simultaneously. finger extensor weakness caused by compression of the 77

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Neuromuscular Disorders TABLE 47. Laboratory Testing in Peripheral Neuropathy Underlying Cause Clinical Presentation Laboratory Testing Diabetes mellitus, impaired glucose Distal symmetric polyneuropathy, Fasting plasma glucose level, glucose tolerance mononeuropathy, lumbosacral tolerance test, hemoglobin A,, radiculoneuropathy measurement Uremia, thyroid disease, anemia, liver Distal symmetric polyneuropathy Serum creatinine, TSH, and free thyroxine disease (T,) levels; hematocrit, liver chemistry tests Connective tissue disease, polyarteritis Vasculitic mononeuropathy multiplex, ESR and rheumatoid factor determination; nodosa, vasculitis, Sjogren syndrome, Sjogren ganglionopathy antinuclear antibody, ANCA, anti-Ro/SSA cryoglobulinemia, lgG4-related disease antibody, anti-LA/SSB antibody, cryoglobulin, and serum IgG4 level measurements | Syphilis Posterior column disease resembling RPR, CSF, VDRL large-fiber neuropathy MGUS, amyloidosis, multiple myeloma, Paraproteinemic neuropathy SPEP, UPEP, IFE, serum free light chain lymphoproliferative disease, POEMS assay syndrome

| Syphilis Posterior column disease resembling RPR, CSF, VDRL large-fiber neuropathy MGUS, amyloidosis, multiple myeloma, Paraproteinemic neuropathy SPEP, UPEP, IFE, serum free light chain lymphoproliferative disease, POEMS assay syndrome Vitamin By, folate, vitamin E, or copper Myeloneuropathy with brisk reflexes Serum copper, vitamin B,y, folate, vitamin E, deficiency methylmalonic acid/homocysteine levels CIDP, GBS Subacute or acute progressive symmetric CSF cells and protein, serum proximal and distal motor and sensory antiganglioside antibodies polyradiculoneuropathy Miller-Fisher variant of GBS Ophthalmoplegia, ataxia, areflexia Serum anti-GQ1B antibody Multifocal motor neuropathy Asymmetric pure motor weakness Serum anti-GM1 antibody Distal acquired demyelinating symmetric Distal sensory loss, tremor, sensory ataxia SPEP, IFE, serum anti-MAG antibody neuropathy

Miller-Fisher variant of GBS Ophthalmoplegia, ataxia, areflexia Serum anti-GQ1B antibody Multifocal motor neuropathy Asymmetric pure motor weakness Serum anti-GM1 antibody Distal acquired demyelinating symmetric Distal sensory loss, tremor, sensory ataxia SPEP, IFE, serum anti-MAG antibody neuropathy Amyloidosis Autonomic and small-fiber neuropathy Serum free light chains, abdominal fat pad_| biopsy, transthyretin gene testing (familial) | Infectious neuropathy Variable, cranial nerve palsy, myelopathy Fourth-generation combination HIV assay, with flaccid weakness in West Nile virus serum Lyme antibody with Western blot confirmation, CSF West Nile virus antibody, skin biopsy in leprosy, IGRA, CSF acid-fast smear

Amyloidosis Autonomic and small-fiber neuropathy Serum free light chains, abdominal fat pad_| biopsy, transthyretin gene testing (familial) | Infectious neuropathy Variable, cranial nerve palsy, myelopathy Fourth-generation combination HIV assay, with flaccid weakness in West Nile virus serum Lyme antibody with Western blot confirmation, CSF West Nile virus antibody, skin biopsy in leprosy, IGRA, CSF acid-fast smear Toxic neuropathy Symmetric sensory or sensorimotor Serum lead, arsenic, mercury, and thallium neuropathy, acute motor neuropathy (lead) measurements; 24-hour urine toxicology; history of exposure to ethanol, chemotherapy agents, colchicine, amiodarone, quinolones Celiac disease Sensory neuropathy and ataxia IgA tissue transglutaminase antibodies

Toxic neuropathy Symmetric sensory or sensorimotor Serum lead, arsenic, mercury, and thallium neuropathy, acute motor neuropathy (lead) measurements; 24-hour urine toxicology; history of exposure to ethanol, chemotherapy agents, colchicine, amiodarone, quinolones Celiac disease Sensory neuropathy and ataxia IgA tissue transglutaminase antibodies Porphyria Acute painful polyradiculopathy Urine porphobilinogen and 6-aminolevulinic acid Paraneoplastic disease Subacute progressive sensory neuropathy, Serum anti-Hu and anti-CRMP5 asymmetric ganglionopathy measurement; CSF oligoclonal bands determination; assessment for underlying malignancy

Porphyria Acute painful polyradiculopathy Urine porphobilinogen and 6-aminolevulinic acid Paraneoplastic disease Subacute progressive sensory neuropathy, Serum anti-Hu and anti-CRMP5 asymmetric ganglionopathy measurement; CSF oligoclonal bands determination; assessment for underlying malignancy ANCA = antineutrophil cytoplasmic antibody; CIDP = chronic inflammatory demyelinating polyradiculoneuropathy; CRMP5 = collapsin response mediator protein 5; CSF = cerebrospinal fluid; ESR = erythrocyte sedimentation rate; GBS = Guillain-Barré syndrome, IFE = immune fixation electrophoresis; |GRA = interferon-y release assay; MAG = myelin- associated glycoprotein; MGUS = monoclonal gammopathy of unknown significance; POEMS = polyneuropathy, organomegaly, endocrinopathy, monoclonal protein plasma cell disorder, and skin lesions; RPR = rapid plasma reagin; SPEP = serum protein electrophoresis; SSA = Sjégren syndrome-related antigen A; SSB = Sj6gren syndrome-related antigen B; TSH = thyroid-stimulating hormone; UPEP = urine protein electrophoresis; VDRL= Venereal Disease Research Laboratory test.

ANCA = antineutrophil cytoplasmic antibody; CIDP = chronic inflammatory demyelinating polyradiculoneuropathy; CRMP5 = collapsin response mediator protein 5; CSF = cerebrospinal fluid; ESR = erythrocyte sedimentation rate; GBS = Guillain-Barré syndrome, IFE = immune fixation electrophoresis; |GRA = interferon-y release assay; MAG = myelin- associated glycoprotein; MGUS = monoclonal gammopathy of unknown significance; POEMS = polyneuropathy, organomegaly, endocrinopathy, monoclonal protein plasma cell disorder, and skin lesions; RPR = rapid plasma reagin; SPEP = serum protein electrophoresis; SSA = Sjégren syndrome-related antigen A; SSB = Sj6gren syndrome-related antigen B; TSH = thyroid-stimulating hormone; UPEP = urine protein electrophoresis; VDRL= Venereal Disease Research Laboratory test. nerve near the axilla as it crosses the humerus. This is often further assessed by EMG and lumbosacral imaging because caused by prolonged immobility in comatose or intoxicated proximal lesions may mimic peroneal palsy. patients (“Saturday night palsy”); spontaneous recovery is typical. e In patients with carpal tunnel syndrome the presence of HVC Peroneal nerve palsy presents as foot drop and is caused weakness, thenar atrophy, refractory pain, or active den- by compression of the nerve at the head of the fibula, which ervation evident on electromyography should prompt usually results from crossing of the legs, immobility, or trauma. decompression surgery. Patients who do not improve within 3 months should be

nerve near the axilla as it crosses the humerus. This is often further assessed by EMG and lumbosacral imaging because caused by prolonged immobility in comatose or intoxicated proximal lesions may mimic peroneal palsy. patients (“Saturday night palsy”); spontaneous recovery is typical. e In patients with carpal tunnel syndrome the presence of HVC Peroneal nerve palsy presents as foot drop and is caused weakness, thenar atrophy, refractory pain, or active den- by compression of the nerve at the head of the fibula, which ervation evident on electromyography should prompt usually results from crossing of the legs, immobility, or trauma. decompression surgery. Patients who do not improve within 3 months should be 79

Neuromuscular Disorders Bell Palsy may affect either large nerve fibers (and lead to impaired Bell palsy is idiopathic paralysis of the facial nerve (cranial proprioception, hyporeflexia, and weakness) or small nerve nerve VII) that leads to unilateral paralysis of upper and lower fibers (and cause pain, dysesthesia, and dysautonomia). facial muscles. In contrast, upper facial muscles are spared in Additionally, they may be primarily axonal or demyelinat- central facial weakness (stroke) because of their bilateral ing. If axonal, the distal axonal segments are affected first, innervation. Periauricular pain, altered taste, and hyperacusis which leads to a length-dependent stocking-glove pattern also may occur. Between 70% and 90% of patients with Bell of involvement. A sensory-predominant distal symmetric palsy fully recover within a few weeks. In classic Bell palsy, neuropathy is typically seen with metabolic, toxic, and brain imaging and laboratory testing are not required. systemic neuropathies. Demyelinating neuropathies, which Treatment with a 10-day course of oral prednisone, started result from injury to the myelin sheath of the peripheral within 72 hours of onset, is recommended to expedite both the nerve, can cause non-length-dependent weakness and rate and speed of full recovery. The utility of adding antiviral sensory loss. treatment to prednisone is controversial, but there may be a small benefit to adding antiviral treatment in patients with Neuropathies of Diabetes Mellitus and Impaired severe palsy. Use of an eye patch and artificial tears to prevent Glucose Tolerance corneal dryness is recommended. Synkinesis (concomitant Diabetes mellitus causes various types of neuropathy movement of perioral and periorbital muscles) may result (Table 48). The most common presentation is symmetric dis- from aberrant reinnervation after Bell palsy. tal neuropathy involving small and large sensory fibers and, Secondary causes for facial nerve palsy include diabetes to a lesser extent, distal motor nerves. Clinical examination

movement of perioral and periorbital muscles) may result (Table 48). The most common presentation is symmetric dis- from aberrant reinnervation after Bell palsy. tal neuropathy involving small and large sensory fibers and, Secondary causes for facial nerve palsy include diabetes to a lesser extent, distal motor nerves. Clinical examination mellitus, Lyme disease, sarcoidosis, HIV, vasculitis, and malig- may reveal length-dependent loss of light touch, pinprick nancy. Ifa secondary cause is suspected on the basis of history and vibration sensations, loss of the ankle reflex, and—in (subacute onset over days, comorbidities, rash) or clinical advanced disease—distal weakness. Pain and paresthesia may examination (deficits unrelated to the facial nerve such as predominate, especially when small fibers are involved. weakness in extraocular, masticatory, or lingual muscles), Patients with a pure small-fiber variant of symmetric distal additional testing is indicated, and prednisone is typically neuropathy may have normal distal sensory and reflex find- avoided. Brain MRI with contrast also is recommended in ings on examination and normal results on EMG at presenta- patients with lingering or worsening weakness after 2 months. tion; this pattern also can be seen even in patients with impaired glucose tolerance. Between 11% and 25% of patients with glucose intolerance have evidence of small-fiber neu- HVC ¢ In classic Bell palsy, brain imaging and laboratory test- ropathy on specialized testing, but only a minority (5%-10%) ing is not required; treatment with a 10-day course of are symptomatic. oral prednisone, started within 72 hours of onset, may Autonomic diabetic neuropathy can cause orthostatic expedite both the rate and speed of full recovery. hypotension, erectile dysfunction, abnormal hidrosis, and gastroparesis. Dysautonomia also can mask symptoms of

patients with lingering or worsening weakness after 2 months. tion; this pattern also can be seen even in patients with impaired glucose tolerance. Between 11% and 25% of patients with glucose intolerance have evidence of small-fiber neu- HVC ¢ In classic Bell palsy, brain imaging and laboratory test- ropathy on specialized testing, but only a minority (5%-10%) ing is not required; treatment with a 10-day course of are symptomatic. oral prednisone, started within 72 hours of onset, may Autonomic diabetic neuropathy can cause orthostatic expedite both the rate and speed of full recovery. hypotension, erectile dysfunction, abnormal hidrosis, and gastroparesis. Dysautonomia also can mask symptoms of Brachial and Lumbosacral Plexopathies hypoglycemia and may predispose patients to silent myo- Common causes of brachial and lumbosacral plexopathy cardial infarction. Diabetic mononeuropathy can involve include diabetes, malignancy, radiation, and trauma. Imaging the cranial nerves (especially II, VI, and VII) and truncal is mandatory to rule out structural lesions and malignancy. nerve roots (with a dermatomal pattern of pain and pares- Idiopathic brachial plexitis (also known as neuralgic amyotro- thesia in the chest or abdomen) and predispose patients phy) presents with subacute severe scapular pain followed by to entrapment neuropathies, such as carpal tunnel pronounced weakness and atrophy in shoulder-girdle and syndrome. upper extremity muscles. It is likely immune mediated, and a Diabetic amyotrophy, also known as proximal lumbosa- triggering event, such as infection or surgery, usually precedes cral radiculoneuropathy, is associated with subacute painful this presentation, although the infection or surgery is not in involvement of the lumbosacral plexus followed by resolution the region of the brachial plexus. EMG can confirm the diag- of pain and onset of marked asymmetric weakness with atro- nosis, and imaging can rule out alternative causes. Treatment phy and weight loss. Spontaneous recovery over 1 to 3 years is is supportive. Gradual recovery (90% by 3 years) is common. typical but may be incomplete. Idiopathic lumbosacral radiculoplexus neuropathy is immune Tight glycemic control, exercise, and management of dys- mediated and very similar in presentation to diabetic amyotro- lipidemia, obesity, and metabolic syndrome can slow the pro- phy. (See Neuropathies of Diabetes Mellitus and Impaired gression and improve the symptoms of diabetic polyneuropathy. Glucose Tolerance.) Management of diabetic amyotrophy consists of supportive measures, physical therapy, and pain control but does not Polyneuropathies involve immunosuppression. See MKSAP 19 Endocrinology Polyneuropathies arise from various disorders causing and Metabolism for further information about diabetic neu- injury to peripheral nerves (see Table 47). Polyneuropathies ropathy, including neuropathic pain treatment.

Brachial and Lumbosacral Plexopathies hypoglycemia and may predispose patients to silent myo- Common causes of brachial and lumbosacral plexopathy cardial infarction. Diabetic mononeuropathy can involve include diabetes, malignancy, radiation, and trauma. Imaging the cranial nerves (especially II, VI, and VII) and truncal is mandatory to rule out structural lesions and malignancy. nerve roots (with a dermatomal pattern of pain and pares- Idiopathic brachial plexitis (also known as neuralgic amyotro- thesia in the chest or abdomen) and predispose patients phy) presents with subacute severe scapular pain followed by to entrapment neuropathies, such as carpal tunnel pronounced weakness and atrophy in shoulder-girdle and syndrome. upper extremity muscles. It is likely immune mediated, and a Diabetic amyotrophy, also known as proximal lumbosa- triggering event, such as infection or surgery, usually precedes cral radiculoneuropathy, is associated with subacute painful this presentation, although the infection or surgery is not in involvement of the lumbosacral plexus followed by resolution the region of the brachial plexus. EMG can confirm the diag- of pain and onset of marked asymmetric weakness with atro- nosis, and imaging can rule out alternative causes. Treatment phy and weight loss. Spontaneous recovery over 1 to 3 years is is supportive. Gradual recovery (90% by 3 years) is common. typical but may be incomplete. Idiopathic lumbosacral radiculoplexus neuropathy is immune Tight glycemic control, exercise, and management of dys- mediated and very similar in presentation to diabetic amyotro- lipidemia, obesity, and metabolic syndrome can slow the pro- phy. (See Neuropathies of Diabetes Mellitus and Impaired gression and improve the symptoms of diabetic polyneuropathy. Glucose Tolerance.) Management of diabetic amyotrophy consists of supportive measures, physical therapy, and pain control but does not Polyneuropathies involve immunosuppression. See MKSAP 19 Endocrinology Polyneuropathies arise from various disorders causing and Metabolism for further information about diabetic neu- injury to peripheral nerves (see Table 47). Polyneuropathies ropathy, including neuropathic pain treatment. 80

Neuromuscular Disorders TABLE 48. Peripheral Nerve Dysfunction in Diabetes Mellitus Classification Sign and Symptoms Diagnosis Management Autonomic neuropathy Orthostatic hypotension, early Orthostatic blood pressure Fludrocortisone; midodrine; satiety, nausea and vomiting determination, QSART, tilt table compression stocking; small (gastroparesis), constipation frequent meals for (colonic dysmotility), erectile gastroparesis; supportive dysfunction, hyperhidrosis or management of bowel, hypohidrosis bladder, and sexual symptoms; glycemic control | Diabetic lumbosacral Severe pain followed by Clinical examination, EMG, Pain control, physical therapy, radiculoneuropathy (diabetic weakness and muscle wasting lumbar spinal MRI, CT of supportive measures, not | amyotrophy) in proximal lower extremities; abdomen and pelvis (to rule out associated with level of weight loss, with or without retroperitoneal hematoma) glycemic control, not proximal sensory loss responsive to immunotherapy

| Diabetic lumbosacral Severe pain followed by Clinical examination, EMG, Pain control, physical therapy, radiculoneuropathy (diabetic weakness and muscle wasting lumbar spinal MRI, CT of supportive measures, not | amyotrophy) in proximal lower extremities; abdomen and pelvis (to rule out associated with level of weight loss, with or without retroperitoneal hematoma) glycemic control, not proximal sensory loss responsive to immunotherapy _ Mononeuropathy Sensory loss; paresthesia or Clinical examination, EMG, brain Avoidance of compressive pain in the distribution of a MRI positions, bracing, pain control, single nerve, followed by decompressive surgery, weakness (median or peroneal observation in cranial palsies | nerve); cranial nerve palsy | (especially cranial nervesIll, VI, | or VII) | Radiculopathy Sensory loss, pain, and Clinical examination, EMG, MRI Pain control, glycemic control, weakness in the distribution of of nerve roots (to rule out root observation nerve roots; thoracic compression) radiculopathy causing patchy truncal numbness is common

| Radiculopathy Sensory loss, pain, and Clinical examination, EMG, MRI Pain control, glycemic control, weakness in the distribution of of nerve roots (to rule out root observation nerve roots; thoracic compression) radiculopathy causing patchy truncal numbness is common | Sensorimotor peripheral Asymptomatic (sometimes), Clinical, EMG Regular monitoring of feet, neuropathy distal length dependent, supportive measures, sensory loss and weakness, neuropathic pain medication often painful, possible loss of (see Small-fiber neuropathy ankle reflex below) | Small-fiber neuropathy Burning distal extremity pain Clinical, QSART, skin biopsy Pregabalin, duloxetine, | without weakness, may be non- (intraepidermal nerve fiber tapentadol (all FDA-approved); length-dependent, sparing of density) gabapentin, tricyclic ankle reflex antidepressants, venlafaxine, oxcarbazepine, topical capsaicin, tramadol EMG = electromyography; QSART = quantitative sudomotor axon reflex test.

| Small-fiber neuropathy Burning distal extremity pain Clinical, QSART, skin biopsy Pregabalin, duloxetine, | without weakness, may be non- (intraepidermal nerve fiber tapentadol (all FDA-approved); length-dependent, sparing of density) gabapentin, tricyclic ankle reflex antidepressants, venlafaxine, oxcarbazepine, topical capsaicin, tramadol EMG = electromyography; QSART = quantitative sudomotor axon reflex test. sensory loss without pain or paresthesia. Foot deformities, such as hammer toes, high arches, and distal leg atrophy, are e The most common form of neuropathy secondary to dia- common (Figure 31). EMG typically reveals a uniform slow- betes is a symmetric distal neuropathy involving small ing of nerve conduction velocities, and genetic testing is and large sensory fibers and, to less extent, distal motor confirmatory. nerves; examination may reveal length-dependent loss of light touch, pinprick and vibration sensations, loss of the Inflammatory Polyradiculoneuropathies ankle reflex, and—in advanced disease—distal weakness. Guillain-Barré Syndrome e Tight glycemic control, exercise, and management of Guillain-Barré syndrome (GBS) is an acute autoimmune dyslipidemia, obesity, and metabolic syndrome can slow demyelinating polyradiculoneuropathy that presents with the progression and improve the symptoms of diabetic rapidly progressive flaccid weakness. Onset is often preceded polyneuropathy. by a respiratory or gastrointestinal infection, triggering a T-cell-mediated autoimmune attack against peripheral nerve Hereditary Neuropathies and root myelin. Weakness is ascending, starting in the lower Charcot-Marie-Tooth disease consists of more than 70 genetic extremities, spreading to the upper limbs and bulbar and res- disorders in which peripheral neuropathy is the only or main piratory muscles, and reaching its nadir in less than 4 weeks. clinical manifestation. The most common inherited neuropa- The weakness may occur first in the proximal muscles. thy, Charcot-Marie-Tooth disease type 1 is an autosomal Paresthesia and early low back pain are common. dominant demyelinating neuropathy presenting with early Dysautonomia can be severe and predispose patients to labile onset, slowly progressive distal weakness, areflexia, and blood pressure and arrhythmias. Progressive respiratory and

sensory loss without pain or paresthesia. Foot deformities, such as hammer toes, high arches, and distal leg atrophy, are e The most common form of neuropathy secondary to dia- common (Figure 31). EMG typically reveals a uniform slow- betes is a symmetric distal neuropathy involving small ing of nerve conduction velocities, and genetic testing is and large sensory fibers and, to less extent, distal motor confirmatory. nerves; examination may reveal length-dependent loss of light touch, pinprick and vibration sensations, loss of the Inflammatory Polyradiculoneuropathies ankle reflex, and—in advanced disease—distal weakness. Guillain-Barré Syndrome e Tight glycemic control, exercise, and management of Guillain-Barré syndrome (GBS) is an acute autoimmune dyslipidemia, obesity, and metabolic syndrome can slow demyelinating polyradiculoneuropathy that presents with the progression and improve the symptoms of diabetic rapidly progressive flaccid weakness. Onset is often preceded polyneuropathy. by a respiratory or gastrointestinal infection, triggering a T-cell-mediated autoimmune attack against peripheral nerve Hereditary Neuropathies and root myelin. Weakness is ascending, starting in the lower Charcot-Marie-Tooth disease consists of more than 70 genetic extremities, spreading to the upper limbs and bulbar and res- disorders in which peripheral neuropathy is the only or main piratory muscles, and reaching its nadir in less than 4 weeks. clinical manifestation. The most common inherited neuropa- The weakness may occur first in the proximal muscles. thy, Charcot-Marie-Tooth disease type 1 is an autosomal Paresthesia and early low back pain are common. dominant demyelinating neuropathy presenting with early Dysautonomia can be severe and predispose patients to labile onset, slowly progressive distal weakness, areflexia, and blood pressure and arrhythmias. Progressive respiratory and 81