The
n e w e ng l a n d j o u r na l
of
m e dic i n e
clinical problem-solving Caren G. Solomon, M.D., M.P.H., Editor
Diagnosing One Letter at a Time Christopher Smith, M.D., Sanjay Saint, M.D., M.P.H., Raymond Price, M.D., Ammar Al-Zoubi, M.D., and Brian Callaghan, M.D. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors’ commentary follows.
A 45-year-old woman presented to a tertiary care center with weakness in the lower extremities. She first noted weakness in her ankles and feet 5 months previously. The weakness progressed to involve her knees and hips, and she had been unable to walk without support for the prior 2 months. She said that her grip strength had weakened and that she had numbness in her toes and fingertips. She also noted progressive swelling in her feet and ankles. She was coughing intermittently but said that she did not have sputum production, hemoptysis, dyspnea, or orthopnea. She reported losing several pounds unintentionally over a 6-month period but said that she did not have fever, chills, or sweats. Although this patient has symptoms affecting multiple systems, the most striking feature is her inability to walk because of proximal and distal leg weakness. These symptoms in the context of coexisting hand weakness and fingertip and toe numbness may localize to the cervical spinal cord, multiple nerve roots (as from a subarachnoid process), peripheral nerves, or some combination of these sites. The rate of symptom development and progression is often the most valuable historical feature used to differentiate among possible causes. This patient’s symptoms developed gradually, making most vascular and bacterial causes unlikely. Since the symptoms progressed over a 5-month period, neurodegenerative and inherited causes are also unlikely. Disease processes that typically develop and progress over a period of months include inflammatory, neoplastic, nutritional, toxic, and atypical infectious diseases. Moreover, the patient has systemic symptoms: peripheral edema, a nonproductive cough, and weight loss. These raise suspicion of systemic disease processes such as neoplasm, chronic infection, vasculitis, sarcoidosis, and amyloidosis. Another striking feature of her presentation is that her motor symptoms are more severe than her sensory symptoms. Conditions affecting the anterior horn cells or corticospinal tracts more than the sensory long tracts can have this pattern. Furthermore, hereditary, toxic, nutritional, and acquired inflammatory demyelinating neuropathies can cause motor symptoms that are more severe than sensory symptoms.
From the Veterans Affairs (VA) Ann Arbor Medical Center (C.S., S.S.) and the University of Michigan Medical School (C.S., S.S., A.A.-Z., B.C.) — both in Ann Arbor; and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia (R.P.). Address reprint requests to Dr. Smith at the VA Ann Arbor Medical Center, 2215 Fuller Rd., 11A, Ann Arbor, MI 48105, or at [email protected] .edu. N Engl J Med 2015;372:67-73. DOI: 10.1056/NEJMcps1308732 Copyright © 2015 Massachusetts Medical Society.
The patient had a 20-year history of hypothyroidism, hypertension, and seasonal allergies. Her medications included gabapentin (started for the paresthesias), levothyroxine, hydrochlorothiazide, and fexofenadine. She had no history of smoking, alcohol abuse, or illicit-drug use. She was married, unemployed, and lived in the midwestern United States. She had no family history of neurologic or autoimmune disease.
n engl j med 372;1 nejm.org january 1, 2015
The New England Journal of Medicine Downloaded from nejm.org at University of Texas at El Paso on December 31, 2014. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
67
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This information does not alter the differential diagnosis greatly. Thyroid dysfunction is associated with multiple peripheral nervous system processes, including a length-dependent sensory-motor polyneuropathy, which could explain the fingertip and toe numbness in this patient, and a myopathy, which could explain the proximal weakness. The severity of the neurologic symptoms and rate of progression of the symptoms, however, are atypical of mild thyroid dysfunction. If the hypothyroidism is immune-mediated (e.g., Hashimoto’s thyroiditis), this would increase the likelihood of a coexisting autoimmune disorder that might explain her symptoms. She is not taking medications that are neurotoxic. On physical examination, the patient was afebrile. The blood pressure was 128/68 mm Hg, and the heart rate 82 beats per minute. The respiratory rate was 15 breaths per minute, with an oxygen saturation of 100% while she was breathing ambient air. Examination of the neck showed no lymphadenopathy and a normal thyroid. Cardiovascular examination revealed a normal S1 and prominent S2, no S3 or S4, and a grade 1/6 systolic murmur at the left lower sternal border. The jugular venous pressure was 6 cm above the sternal angle. The lungs were clear on auscultation. The abdomen was minimally distended. The spleen tip was palpated below the costal margin. There was pitting edema up to the level of the ankles. The skin examination revealed no lesions, rash, abnormal pigmentation, or abnormality of the nails. Musculoskeletal examination showed normal tone and bulk. On neurologic examination, the patient was alert, oriented, and fluent. Cranial nerves II through XII were intact. On examination of muscle strength, her shoulder abduction, elbow flexion and extension, wrist flexion and extension, and finger abduction showed 5/5 strength (on the Medical Research Council scale), but there was 4/5 strength with hip and knee flexion and extension and 3/5 strength with plantar flexion and dorsiflexion of the ankles bilaterally. There was decreased vibratory sensation in the lower extremities, which was more marked distally than proximally, but proprioception and sensation of pinprick and temperature were retained in all extremities. Biceps and triceps reflexes were diminished, and brachioradialis, patellar, and Achilles reflexes were absent. The results of finger-to-nose and heel-to-shin coordination tests were normal. Her gait was unsteady and wide-based. Romberg’s sign was present. 68
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The diffusely diminished reflexes are the most informative findings in the physical examination. These findings suggest a peripheral nervous system process rather than a central nervous system process. Hyporeflexia in the upper arms with preserved arm strength indicates that the reflex is reduced because of involvement of the afferent (sensory) portion of the reflex arc. Therefore, even without the sensory examination, one can be confident that this disease process is affecting sensory-nerve fibers, localizing the disorder to the peripheral nerve. Although not definitive, the hyporeflexia beyond the areas of weakness and numbness, in addition to weakness in the presence of intact muscle bulk, also suggests a possible demyelinating peripheral neuropathy. The findings on sensory examination are consistent with a large-fiber neuropathy (impaired sensation of vibration with normal sensation of pinprick and temperature). The pattern of greater weakness in the distal lower extremities than in the proximal lower extremities, with relative sparing of the upper-extremity muscles, suggests a length-dependent motor neuropathy. Overall, the neurologic examination reveals hyporeflexia and a length-dependent neuropathy with the motor findings being more severe than the sensory findings. Notable additional findings on examination include pitting edema and splenomegaly, which could occur with cardiac, renal, or hepatic dysfunction or with neoplastic, inflammatory, or infectious causes. This patient’s weakness is probably caused by polyradiculopathy, polyneuropathy, or a combination of the two (polyradiculoneuropathy). Electrodiagnostic studies are indicated to assess the patient for a demyelinating process. Edema and splenomegaly may occur in the POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) and raise suspicion for this diagnosis, especially if demyelination is confirmed on electrodiagnostic testing. The serum white-cell count was 9600 per cubic millimeter, with 82% granulocytes, 9% lymphocytes, 8% monocytes, and 1% eosinophils. The hemoglobin level was 14.4 g per deciliter, the hematocrit 41.7%, and the platelet count 448,000 per cubic millimeter. The serum electrolyte levels, creatinine level, and results of liver-function tests, including total protein and albumin measurements, were normal. The thyrotropin level was 10.5 mU per liter (reference range, 0.30 to 5.50); the free thyroxine
n engl j med 372;1 nejm.org january 1, 2015
The New England Journal of Medicine Downloaded from nejm.org at University of Texas at El Paso on December 31, 2014. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
clinical problem-solving
level was 0.85 ng per deciliter (11 pmol per liter; reference range, 0.76 to 1.70 ng per deciliter [10 to 22 pmol per liter]). The erythrocyte sedimentation rate was 33 mm per hour (reference range, 0 to 20). The vitamin B12 level was 817 pg per milliliter (600 pmol per liter; reference range, 211 to 911 pg per milliliter [160 to 670 pmol per liter]). Serum antinuclear antibody and double-stranded DNA antibody tests were negative. Nerve-conduction studies of the left leg revealed the absence of sural-nerve sensory responses and tibial-nerve and peroneal-nerve motor responses (Table 1). The left arm showed normal median-nerve and ulnar-nerve sensory and motor amplitudes and distal motor latencies but reduced sensory and motor-nerve conduction velocities and prolonged F responses. There was no conduction block or temporal dispersion. The median-nerve terminal latency index (a ratio of the expected distal motor latency to the actual distal motor latency) was 0.39. Electromyography revealed neurogenic motor-unit morphologic features and recruitment with abnormal spontaneous activity in the distal muscles of the lower extremities but not in the proximal muscles. Magnetic resonance imaging (MRI) of the spine performed without the administration of contrast material revealed no evidence of a mass lesion. The sensory and motor nerve responses in the left lower leg and foot were absent. This finding suggests severe peripheral-nerve injury as seen in end-stage neuron loss, regardless of whether the inciting pathophysiological process was axonal or demyelinating. Since the responses were absent, the nerve-conduction studies in the lower extremities cannot provide diagnostic information about the underlying pathophysiological process. The results of the sensory and motor nerveconduction studies of the left upper extremity were relatively normal, aside from mildly reduced sensory and motor conduction velocities and prolonged F responses. Conduction velocity may be reduced by either demyelination or loss of large-diameter neurons; demyelination is diagnosed when the conduction velocity is reduced by more than 25%. The conduction velocities in this patient, although reduced, did not meet this criterion. F responses allow for an assessment of the entire nerve, including the most proximal segment, which is not assessed by routine motor nerve-conduction studies. Demyelination is suggested if the time for an F response to appear is
Table 1. Nerve-Conduction Studies.* Nerve Sural sensory
Amplitude NR
Latency
Conduction Velocity
m/sec
m/sec
NR
NR
Peroneal motor
NR
NR
NR
Tibial motor
NR
NR
NR
Median sensory
29.0 μV
3.7
48.3
Ulnar sensory
31.0 μV
3.6
48.3
Wrist
9.3 mV
4.1
—
Elbow
8.5 mV
9.1
43.4
—
44.3
—
Wrist
7.7 mV
2.9
—
Below elbow
6.7 mV
7.4
42.4
Above elbow
6.5 mV
9.5
47.6
—
42.3
—
Median motor
Median F response Ulnar motor
Ulnar F response
* Sensory and motor conduction velocities were mildly reduced. F responses were 136% (ulnar nerve) and 143% (median nerve) of the normal value. The patient’s F responses were prolonged more than the F estimate (median nerve, 38.0 msec; ulnar nerve, 37.7 msec). Conduction block and temporal dispersion were not seen. Sural-, tibial-, and peroneal-nerve responses were absent. The terminal latency index (a ratio of the expected distal motor latency to the actual distal motor latency) was 0.39. NR denotes no response.
greater than 130% of the normal value; the F responses in this patient were 136% (ulnar nerve) and 143% (median nerve) of the normal value. The observation that the patient’s F responses were prolonged more than the F estimate also suggests demyelination, specifically of the proximal segment (Table 1). Abnormal temporal dispersion and conduction block are specific but not sensitive electrodiagnostic findings of acquired demyelination and were not identified on the nerve-conduction studies. Electrodiagnostic studies cannot always classify a neuropathy definitively into an axonal or demyelinating category; that is the case in this patient, who has findings that suggest but are not diagnostic of demyelination. In cases such as this, the history and examination are essential in interpreting the results. With this patient’s subacute onset of weakness that was out of proportion to the sensory deficits and hyporeflexia observed on examination, the nerve-conduction studies suggest an acquired demyelinating polyneuropathy, as seen with either chronic inflammatory demyelinating polyneuropathy (CIDP) or a para-
n engl j med 372;1 nejm.org january 1, 2015
The New England Journal of Medicine Downloaded from nejm.org at University of Texas at El Paso on December 31, 2014. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
69
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protein-associated demyelinating polyneuropathy such as the POEMS syndrome. The lack of more definitive demyelinating features may be due to the degree of secondary axonal loss. Several electrodiagnostic features suggest that the POEMS syndrome is more likely than CIDP. A terminal latency index of 0.38 or more, indicating comparatively less distal demyelination, has good sensitivity and specificity for distinguishing the POEMS syndrome from the more common CIDP. Furthermore, the absence of conduction block, temporal dispersion, and sural-nerve sparing and the presence of denervation on needle examination, distal-predominant weakness, Figure 1. Plain-Film Image of the Pelvis. and unrecordable sural- and tibial-nerve responsA subtle sclerotic lesion is seen at the right ischium es all point to the POEMS syndrome over CIDP. (arrow). Patients with the POEMS syndrome usually have uniform demyelination, as suggested by the findings in this patient, whereas patients with CIDP The level of serum free light chains was minimally tend to have multifocal demyelination that is more elevated, with a normal ratio of kappa to lambda severe in the proximal and distal nerve segments. light chains. The urine showed no Bence Jones protein. A bone survey revealed no lytic lesions but did Serum protein electrophoresis with immunofixa- reveal a small area of sclerosis at the right ischium tion showed an IgA lambda monoclonal gammop- (Fig. 1). On bone marrow biopsy, there was an inathy (M-protein level, 0.3 g per deciliter). Quanti- terstitial plasmacytosis that was consistent with a tative immunoglobulin measurements showed an plasma-cell dyscrasia, with 4.8% lambda-restricted IgG level of 1000 mg per deciliter (reference range, plasma cells (reference value,
n e w e ng l a n d j o u r na l
of
m e dic i n e
clinical problem-solving Caren G. Solomon, M.D., M.P.H., Editor
Diagnosing One Letter at a Time Christopher Smith, M.D., Sanjay Saint, M.D., M.P.H., Raymond Price, M.D., Ammar Al-Zoubi, M.D., and Brian Callaghan, M.D. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors’ commentary follows.
A 45-year-old woman presented to a tertiary care center with weakness in the lower extremities. She first noted weakness in her ankles and feet 5 months previously. The weakness progressed to involve her knees and hips, and she had been unable to walk without support for the prior 2 months. She said that her grip strength had weakened and that she had numbness in her toes and fingertips. She also noted progressive swelling in her feet and ankles. She was coughing intermittently but said that she did not have sputum production, hemoptysis, dyspnea, or orthopnea. She reported losing several pounds unintentionally over a 6-month period but said that she did not have fever, chills, or sweats. Although this patient has symptoms affecting multiple systems, the most striking feature is her inability to walk because of proximal and distal leg weakness. These symptoms in the context of coexisting hand weakness and fingertip and toe numbness may localize to the cervical spinal cord, multiple nerve roots (as from a subarachnoid process), peripheral nerves, or some combination of these sites. The rate of symptom development and progression is often the most valuable historical feature used to differentiate among possible causes. This patient’s symptoms developed gradually, making most vascular and bacterial causes unlikely. Since the symptoms progressed over a 5-month period, neurodegenerative and inherited causes are also unlikely. Disease processes that typically develop and progress over a period of months include inflammatory, neoplastic, nutritional, toxic, and atypical infectious diseases. Moreover, the patient has systemic symptoms: peripheral edema, a nonproductive cough, and weight loss. These raise suspicion of systemic disease processes such as neoplasm, chronic infection, vasculitis, sarcoidosis, and amyloidosis. Another striking feature of her presentation is that her motor symptoms are more severe than her sensory symptoms. Conditions affecting the anterior horn cells or corticospinal tracts more than the sensory long tracts can have this pattern. Furthermore, hereditary, toxic, nutritional, and acquired inflammatory demyelinating neuropathies can cause motor symptoms that are more severe than sensory symptoms.
From the Veterans Affairs (VA) Ann Arbor Medical Center (C.S., S.S.) and the University of Michigan Medical School (C.S., S.S., A.A.-Z., B.C.) — both in Ann Arbor; and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia (R.P.). Address reprint requests to Dr. Smith at the VA Ann Arbor Medical Center, 2215 Fuller Rd., 11A, Ann Arbor, MI 48105, or at [email protected] .edu. N Engl J Med 2015;372:67-73. DOI: 10.1056/NEJMcps1308732 Copyright © 2015 Massachusetts Medical Society.
The patient had a 20-year history of hypothyroidism, hypertension, and seasonal allergies. Her medications included gabapentin (started for the paresthesias), levothyroxine, hydrochlorothiazide, and fexofenadine. She had no history of smoking, alcohol abuse, or illicit-drug use. She was married, unemployed, and lived in the midwestern United States. She had no family history of neurologic or autoimmune disease.
n engl j med 372;1 nejm.org january 1, 2015
The New England Journal of Medicine Downloaded from nejm.org at University of Texas at El Paso on December 31, 2014. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
67
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n e w e ng l a n d j o u r na l
This information does not alter the differential diagnosis greatly. Thyroid dysfunction is associated with multiple peripheral nervous system processes, including a length-dependent sensory-motor polyneuropathy, which could explain the fingertip and toe numbness in this patient, and a myopathy, which could explain the proximal weakness. The severity of the neurologic symptoms and rate of progression of the symptoms, however, are atypical of mild thyroid dysfunction. If the hypothyroidism is immune-mediated (e.g., Hashimoto’s thyroiditis), this would increase the likelihood of a coexisting autoimmune disorder that might explain her symptoms. She is not taking medications that are neurotoxic. On physical examination, the patient was afebrile. The blood pressure was 128/68 mm Hg, and the heart rate 82 beats per minute. The respiratory rate was 15 breaths per minute, with an oxygen saturation of 100% while she was breathing ambient air. Examination of the neck showed no lymphadenopathy and a normal thyroid. Cardiovascular examination revealed a normal S1 and prominent S2, no S3 or S4, and a grade 1/6 systolic murmur at the left lower sternal border. The jugular venous pressure was 6 cm above the sternal angle. The lungs were clear on auscultation. The abdomen was minimally distended. The spleen tip was palpated below the costal margin. There was pitting edema up to the level of the ankles. The skin examination revealed no lesions, rash, abnormal pigmentation, or abnormality of the nails. Musculoskeletal examination showed normal tone and bulk. On neurologic examination, the patient was alert, oriented, and fluent. Cranial nerves II through XII were intact. On examination of muscle strength, her shoulder abduction, elbow flexion and extension, wrist flexion and extension, and finger abduction showed 5/5 strength (on the Medical Research Council scale), but there was 4/5 strength with hip and knee flexion and extension and 3/5 strength with plantar flexion and dorsiflexion of the ankles bilaterally. There was decreased vibratory sensation in the lower extremities, which was more marked distally than proximally, but proprioception and sensation of pinprick and temperature were retained in all extremities. Biceps and triceps reflexes were diminished, and brachioradialis, patellar, and Achilles reflexes were absent. The results of finger-to-nose and heel-to-shin coordination tests were normal. Her gait was unsteady and wide-based. Romberg’s sign was present. 68
of
m e dic i n e
The diffusely diminished reflexes are the most informative findings in the physical examination. These findings suggest a peripheral nervous system process rather than a central nervous system process. Hyporeflexia in the upper arms with preserved arm strength indicates that the reflex is reduced because of involvement of the afferent (sensory) portion of the reflex arc. Therefore, even without the sensory examination, one can be confident that this disease process is affecting sensory-nerve fibers, localizing the disorder to the peripheral nerve. Although not definitive, the hyporeflexia beyond the areas of weakness and numbness, in addition to weakness in the presence of intact muscle bulk, also suggests a possible demyelinating peripheral neuropathy. The findings on sensory examination are consistent with a large-fiber neuropathy (impaired sensation of vibration with normal sensation of pinprick and temperature). The pattern of greater weakness in the distal lower extremities than in the proximal lower extremities, with relative sparing of the upper-extremity muscles, suggests a length-dependent motor neuropathy. Overall, the neurologic examination reveals hyporeflexia and a length-dependent neuropathy with the motor findings being more severe than the sensory findings. Notable additional findings on examination include pitting edema and splenomegaly, which could occur with cardiac, renal, or hepatic dysfunction or with neoplastic, inflammatory, or infectious causes. This patient’s weakness is probably caused by polyradiculopathy, polyneuropathy, or a combination of the two (polyradiculoneuropathy). Electrodiagnostic studies are indicated to assess the patient for a demyelinating process. Edema and splenomegaly may occur in the POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) and raise suspicion for this diagnosis, especially if demyelination is confirmed on electrodiagnostic testing. The serum white-cell count was 9600 per cubic millimeter, with 82% granulocytes, 9% lymphocytes, 8% monocytes, and 1% eosinophils. The hemoglobin level was 14.4 g per deciliter, the hematocrit 41.7%, and the platelet count 448,000 per cubic millimeter. The serum electrolyte levels, creatinine level, and results of liver-function tests, including total protein and albumin measurements, were normal. The thyrotropin level was 10.5 mU per liter (reference range, 0.30 to 5.50); the free thyroxine
n engl j med 372;1 nejm.org january 1, 2015
The New England Journal of Medicine Downloaded from nejm.org at University of Texas at El Paso on December 31, 2014. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
clinical problem-solving
level was 0.85 ng per deciliter (11 pmol per liter; reference range, 0.76 to 1.70 ng per deciliter [10 to 22 pmol per liter]). The erythrocyte sedimentation rate was 33 mm per hour (reference range, 0 to 20). The vitamin B12 level was 817 pg per milliliter (600 pmol per liter; reference range, 211 to 911 pg per milliliter [160 to 670 pmol per liter]). Serum antinuclear antibody and double-stranded DNA antibody tests were negative. Nerve-conduction studies of the left leg revealed the absence of sural-nerve sensory responses and tibial-nerve and peroneal-nerve motor responses (Table 1). The left arm showed normal median-nerve and ulnar-nerve sensory and motor amplitudes and distal motor latencies but reduced sensory and motor-nerve conduction velocities and prolonged F responses. There was no conduction block or temporal dispersion. The median-nerve terminal latency index (a ratio of the expected distal motor latency to the actual distal motor latency) was 0.39. Electromyography revealed neurogenic motor-unit morphologic features and recruitment with abnormal spontaneous activity in the distal muscles of the lower extremities but not in the proximal muscles. Magnetic resonance imaging (MRI) of the spine performed without the administration of contrast material revealed no evidence of a mass lesion. The sensory and motor nerve responses in the left lower leg and foot were absent. This finding suggests severe peripheral-nerve injury as seen in end-stage neuron loss, regardless of whether the inciting pathophysiological process was axonal or demyelinating. Since the responses were absent, the nerve-conduction studies in the lower extremities cannot provide diagnostic information about the underlying pathophysiological process. The results of the sensory and motor nerveconduction studies of the left upper extremity were relatively normal, aside from mildly reduced sensory and motor conduction velocities and prolonged F responses. Conduction velocity may be reduced by either demyelination or loss of large-diameter neurons; demyelination is diagnosed when the conduction velocity is reduced by more than 25%. The conduction velocities in this patient, although reduced, did not meet this criterion. F responses allow for an assessment of the entire nerve, including the most proximal segment, which is not assessed by routine motor nerve-conduction studies. Demyelination is suggested if the time for an F response to appear is
Table 1. Nerve-Conduction Studies.* Nerve Sural sensory
Amplitude NR
Latency
Conduction Velocity
m/sec
m/sec
NR
NR
Peroneal motor
NR
NR
NR
Tibial motor
NR
NR
NR
Median sensory
29.0 μV
3.7
48.3
Ulnar sensory
31.0 μV
3.6
48.3
Wrist
9.3 mV
4.1
—
Elbow
8.5 mV
9.1
43.4
—
44.3
—
Wrist
7.7 mV
2.9
—
Below elbow
6.7 mV
7.4
42.4
Above elbow
6.5 mV
9.5
47.6
—
42.3
—
Median motor
Median F response Ulnar motor
Ulnar F response
* Sensory and motor conduction velocities were mildly reduced. F responses were 136% (ulnar nerve) and 143% (median nerve) of the normal value. The patient’s F responses were prolonged more than the F estimate (median nerve, 38.0 msec; ulnar nerve, 37.7 msec). Conduction block and temporal dispersion were not seen. Sural-, tibial-, and peroneal-nerve responses were absent. The terminal latency index (a ratio of the expected distal motor latency to the actual distal motor latency) was 0.39. NR denotes no response.
greater than 130% of the normal value; the F responses in this patient were 136% (ulnar nerve) and 143% (median nerve) of the normal value. The observation that the patient’s F responses were prolonged more than the F estimate also suggests demyelination, specifically of the proximal segment (Table 1). Abnormal temporal dispersion and conduction block are specific but not sensitive electrodiagnostic findings of acquired demyelination and were not identified on the nerve-conduction studies. Electrodiagnostic studies cannot always classify a neuropathy definitively into an axonal or demyelinating category; that is the case in this patient, who has findings that suggest but are not diagnostic of demyelination. In cases such as this, the history and examination are essential in interpreting the results. With this patient’s subacute onset of weakness that was out of proportion to the sensory deficits and hyporeflexia observed on examination, the nerve-conduction studies suggest an acquired demyelinating polyneuropathy, as seen with either chronic inflammatory demyelinating polyneuropathy (CIDP) or a para-
n engl j med 372;1 nejm.org january 1, 2015
The New England Journal of Medicine Downloaded from nejm.org at University of Texas at El Paso on December 31, 2014. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
69
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
protein-associated demyelinating polyneuropathy such as the POEMS syndrome. The lack of more definitive demyelinating features may be due to the degree of secondary axonal loss. Several electrodiagnostic features suggest that the POEMS syndrome is more likely than CIDP. A terminal latency index of 0.38 or more, indicating comparatively less distal demyelination, has good sensitivity and specificity for distinguishing the POEMS syndrome from the more common CIDP. Furthermore, the absence of conduction block, temporal dispersion, and sural-nerve sparing and the presence of denervation on needle examination, distal-predominant weakness, Figure 1. Plain-Film Image of the Pelvis. and unrecordable sural- and tibial-nerve responsA subtle sclerotic lesion is seen at the right ischium es all point to the POEMS syndrome over CIDP. (arrow). Patients with the POEMS syndrome usually have uniform demyelination, as suggested by the findings in this patient, whereas patients with CIDP The level of serum free light chains was minimally tend to have multifocal demyelination that is more elevated, with a normal ratio of kappa to lambda severe in the proximal and distal nerve segments. light chains. The urine showed no Bence Jones protein. A bone survey revealed no lytic lesions but did Serum protein electrophoresis with immunofixa- reveal a small area of sclerosis at the right ischium tion showed an IgA lambda monoclonal gammop- (Fig. 1). On bone marrow biopsy, there was an inathy (M-protein level, 0.3 g per deciliter). Quanti- terstitial plasmacytosis that was consistent with a tative immunoglobulin measurements showed an plasma-cell dyscrasia, with 4.8% lambda-restricted IgG level of 1000 mg per deciliter (reference range, plasma cells (reference value,
