Case 22

Published on 03/03/2015 by admin

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Case 22

HISTORY AND PHYSICAL EXAMINATION

A 60-year-old woman presented with a 5- to 10-year history of leg weakness and a sense of unsteadiness of insidious onset. Recently, she had become aware of mild impairment of sensation over the tips of the fingers and toes. She had mild low back pain with no radicular pain. For many years before this, she had aching discomfort in both feet, which worsened with activity and weight bearing.

Her medical history was benign, except for hypertension and chronic anxiety disorder. Her medications included alprazolam (Xanax®) and diltiazem (Cardizem®). Family history was relevant for a 30-year-old son with hammer toes, high-arched feet, and “thin legs” since childhood. She had a daughter and a maternal cousin with high-arched feet. Parents were deceased, with no definite history of neuromuscular disease.

The general examination was relevant for bilateral pes cavus deformities without hammer toes. There were no skin trophic changes. On neurologic examination, the fundi were normal without retinal pigmentary changes. Cranial nerves were normal. There was atrophy of all intrinsic muscles of both hands. Distal legs were thin with inverted-champagne bottle appearance. She could not wiggle her toes. Manual muscle examination revealed bilateral symmetrical weakness, worse distally. Toe flexors and extensors were 0/5 (Medical Research Council [MRC]), ankle dorsiflexors and plantar flexors were 4-/5, and hand intrinsics 4+/5. Deep tendon reflexes were +1 in the upper extremities but absent in the legs. Sensation revealed decreased position and vibration sense at the toes, and to a lesser extent at the ankles. Pin and touch sensation was relatively decreased in all four extremities, symmetrically worse distally with a stocking-and-glove distribution. Gait was steppage due to foot weakness. She could not walk on heels or toes. Romberg test was negative.

An electrodiagnostic (EDX) examination was performed.

Please now review the Nerve Conduction Studies and Needle EMG tables.

QUESTIONS

1. The EDX findings observed in this patient are common to all of the following disorders except:

A. Refsum disease.
B. Charcot-Marie-Tooth disease type I.
C. Metachromatic leukodystrophy.
D. Diabetic polyneuropathy.
E. Adrenomyeloneuropathy.

2. Characteristics of hereditary demyelinating motor and sensory neuropathies include all of the following except:

A. Conduction blocks.
B. Symmetrical slowing of latencies and velocities.
C. Uniform slowing of velocities in different segments of the same nerve.
D. Onion bulb formation on histological evaluation of nerve.

3. Characteristics of Charcot-Marie-Tooth disease type 1 (CMT1) include all of the following except:

A. Has a common subtype that is associated with tandem duplication on chromosome 17.
B. Commonly is associated with pes cavus and hammer toes.
C. Has wide phenotypic variability.
D. Has abnormal sensory nerve action potentials (SNAPs).
E. Has low-amplitude compound muscle action potentials (CMAPs), with slight slowing of distal latencies and conduction velocities.

Case 22: Nerve Conduction Studies

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Case 22: Needle EMG

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EDX FINDINGS AND INTERPRETATION OF DATA

Relevant EDX findings in this case include:

1. Absent SNAPs throughout the upper and lower extremities.
2. Absent CMAPs and F waves in both lower extremities.
3. Marked slowing of motor distal latencies, conduction velocities, and F wave latencies in the upper extremities, along with moderate reduction of distal CMAP amplitudes (Figure C22-1). Distal latencies are 200 to 300% of the upper limit of normal values, conduction velocities are 45 to 50% of the lower limit of normal, and F wave latencies are 154 to 168% of the upper limit of normal values.
4. Motor slowing is uniform (affecting all motor nerve segments equally) and symmetrical (affecting motor nerves equally in both upper extremities). Also, there is no evidence of conduction block or significant temporal dispersion (see Figure C22-1).
5. Needle EMG reveals neurogenic changes that are mostly distal and symmetrical, but highly chronic, based on very large motor unit action potentials (MUAPs).
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Figure C22-1 Right median and ulnar motor conduction studies in an age-matched normal control (A) compared with patient (B). Note the significant slowing of distal and proximal latencies and the slight reduction of compound muscle action potential (CMAP) amplitudes in the patient. There is minimal temporal dispersion and no conduction block.

These findings are compatible with a chronic, demyelinating, sensorimotor peripheral polyneuropathy. Uniform and symmetrical slowing of motor conduction studies and the absence of conduction blocks are more consistent with an inherited, rather than an acquired, demyelinating polyneuropathy.

Based on the clinical manifestations, family history, and EDX findings, this case is consistent with an inherited demyelinating, sensorimotor peripheral polyneuropathy, as is seen with autosomal dominant hereditary motor sensory neuropathy (HMSN) type I (Charcot-Marie-Tooth disease type I).

DISCUSSION

Classification

Hereditary neuropathies are a heterogeneous group of peripheral nerve disorders (Figure C22-2). Some have a known metabolic basis and potential therapies (Table C22-1). The hereditary neuropathies that are not based on known specific metabolic defect are classified into three clinical groups: (1) hereditary motor and sensory neuropathies (HMSNs); (2) hereditary sensory and autonomic neuropathies (HSANs); and (3) hereditary motor neuropathies (HMNs).

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Figure C22-2 Classification of hereditary neuropathies.

(Adapted, with revisions, from Thomas PK. Classification and electrodiagnosis of hereditary neuropathies. In: Brown WF, Bolton CF, eds. Clinical electromyography, 2nd ed. Boston, MA: Butterworth-Heinemann, 1993, pp. 391–425.)

Table C22-1 Classification of Hereditary Neuropathies Associated With Specific Metabolic Defects

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The hereditary motor and sensory neuropathies (HMSNs) were classified by Dyck and Lambert into three predominant types (1) HMSN I, a demyelinating type; (2) HMSN II, a neuronal (axonal) type; and (3) HMSN III (Dejerine-Sottas disease), a severe demyelinating neuropathy of infancy and early childhood. HMSN I and II are characterized by skeletal deformities (pes cavus, hammer toes, scoliosis), insidious onset of distal lower more than upper extremities weakness, atrophy and sensory loss, and reduced or absent deep tendon reflexes. Based on clinical examination, these disorders are difficult to distinguish from each other because of similar phenotypes. With the recent influence of chromosomal linkage and gene identification, the term Charcot-Marie-Tooth disease (CMT) reemerged which created some confusion in the nomenclature and classifications of these disorders.

Charcot-Marie-Tooth disease (CMT) is subdivided into six major types with some but not perfect correlation to the HMSN classification (Table C22-2). CMT1 and CMT2 are interchangeable with HMSN I and HMSN II. The name Dejerine-Sottas syndrome (DSS, Dejerine-Sottas disease) is preserved and is the same condition as HMSN III. The term CMT3 is not commonly used since the genes involved with DSS are the same as CMT1. CMT4 is a new designation for a group of autosomal recessive CMT and should not be confused with HMSN IV which is Refsum disease. CMTX is an X-linked disorder and hereditary neuropathy with liability to pressure palsy (HNPP) is a distinct disorder characterized by recurrent mononeuropathies.

Table C22-2 Charcot-Marie-Tooth Disease (CMT, Hereditary Motor and Sensory Neuropathy, HMSN) Subtypes, Its Variants and Their Genetic Causes

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Disorder Locus/Gene Protein
Charcot-Marie-Tooth Disease Type 1 (CMT1, HMSN I, Autosomal-Dominant, Demyelinating)
CMT1A 17p11.2-12/PMP22* Peripheral myelin protein 22
CMT1B 1q22-23/MPZ Myelin protein zero
CMT1C 16p13.1-12.3/LITAF SIMPLE
CMT1D 10q21.1-22.1/EGR2 Early growth response protein 2
Charcot-Marie-Tooth Disease Type 2 (CMT2, HMSN II, Autosomal-Dominant, Axonal)
CMT2A 1p35-36/KFI1B Kinesin-like protein Mitousin 2
CMT2B 3q13-22/RAB7 Ras-related protein
CMT2C 12q23-24/? ? (unknown)
CMT2D 7p15/GARS Glycy-tRNA synthetase
CMT2E 8P21/NEFL Neurofilament triplet L protein
CMT2F 7q11-21/HSP27 Small heat shock protein
CMT2 1q22/MPZ Myelin protein zero
Dejerine-Sottas Syndrome (DSS, HMSN III, CMT3, Autosomal-Dominant or Recessive, Demyelinating)
DSS A 17p/PMP22 Peripheral myelin protein 22
DSS B 1q/MPZ Myelin protein zero
DSS C 10q/EGR2 Early growth response protein 2
DSS D 8q23 Unknown
Charcot-Marie-Tooth Disease Type 4 (CMT4, Autosomal-Recessive, Axonal or Demyelinating)
CMT4A 8q13-21/GDAP1 Ganglioside-induced differentiation-associated protein-1
CMT4B1 11q22/MTMR2 Myotubularin-related protein-2
CMT4B2 11p15/MTMR13 Myotubularin-related protein-13
CMT4C 5q23-33/KIAA1985 −

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