A 37-year-old man presented with a 1-year history of progressive weakness in the upper and lower extremities, difficulties raising his arms above his head, and difficulty combing his hair. He was unable to walk upstairs or arise up from a toilet. He had no sensory complaints or difficulty swallowing.
Past medical history was negative. He smoked occasionally and drank alcohol on weekends. He was referred with a diagnosis of a motor neuron disease. Family history was negative for neurologic disorders.
Examination showed normal mentation and cranial nerves. He was unable to raise his arms above his shoulders and to walk unassisted ( Fig. 52-1 ). No significant wasting was noted, except for the first dorsal interosseous muscles (see Fig. 52-1B ). He also had high foot arches (see Fig. 52-1C ). Motor examination revealed normal neck muscles; deltoids were 2+/5; biceps and triceps were 4/5; wrist and hand muscles, 3−/5; iliopsoas, 2/5; gluteus, 3/5; quadriceps, 3/5; and hamstrings, 2/5. Foot dorsiflexors and evertors were 2/5; flexors were 5. He was hyporeflexic all over and had diffuse fasciculations. Sensory examination to pinprick, touch, temperature, vibration, and position was normal. There were no Babinski signs or nerve hypertrophy.
What is the Differential Diagnosis?
This man had a recent onset of progressive symmetrical arm and leg weakness and fasciculations, but minimal atrophy. The fact that he has high arches raises the possibility of Charcot–Marie–Tooth (CMT) disease; however, the weakness was of recent onset and involved prominently proximal muscles. He had no sensory complaints, but patients with CMT may have only mild sensory deficits. It is also possible that the patient has familial spinal muscular atrophy and also some distal dystrophies which can present with high arches; but again, his weakness was of recent onset and was proximal as well as distal. It is indeed possible that high arches or hammertoes are not related and that he has two different conditions or that the weakness has been more long-standing than he reports. There are also reported cases of hereditary neuropathy that develop chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
Weakness with fasciculations and hyporeflexia could suggest a progressive spinal muscular atrophy. Amyotrophic lateral sclerosis is unlikely because he had no long tract signs, and no bulbar signs to suggest either this or Kennedy disease.
Multifocal motor neuropathy (MMN) presents with weakness, fasciculations, and little atrophy, but in this condition the weakness affects mainly the upper extremities, and it is asymmetric in the territory of individual nerves. Multifocal-acquired motor axonopathy (MAMA) has a similar presentation but without conduction blocks. Lewis–Sumner syndrome is also similar, but patients also have sensory deficits.
Symmetrical weakness affecting the upper and lower extremities occurs in CIDP, a disease in which there is large sensory fiber loss. There are, however, cases of a purely motor CIDP.
He was not exposed to toxins or medications that affect the peripheral nerves.
What Would One Do Next?
The workup included a complete metabolic panel, serum creatine kinase test, and thyroid studies that were normal, and an EMG was ordered.
An EMG Test was Performed
| Nerve and Site | Latency (ms) | Amplitude (mV) | Conduction Velocity (m/s) |
|---|---|---|---|
| Peroneal Nerve R. | Normal ≤ 5.7 | Normal ≥ 3 | Normal ≥ 40 |
| Ankle | 7.8 | 1.9 | – |
| Fibular head | 18.0 | 1.3 | 37 |
| Knee | 19.9 | 1.3 | 47 |
| Tibial Nerve R. | Normal ≤ 5.3 | Normal ≥ 4 | Normal ≥ 40 |
|---|---|---|---|
| Ankle | 6.2 | 1.8 | – |
| Pop. fossa | 20.2 | 1.2 | 37 |
| Peroneal Nerve L. | Normal ≤ 5.7 | Normal ≥ 3 | Normal ≥ 40 |
|---|---|---|---|
| Ankle | 12.1 | 0.6 | – |
| Fibular head | 25.1 | 0.3 | 24 |
| Knee | 27.3 | 0.3 | 41 |
| Median Nerve R. | Normal ≤ 4.2 | Normal ≥ 6 | Normal ≥ 50 |
|---|---|---|---|
| Wrist | 9.9 | 1.9 | – |
| Elbow | 14.8 | 1.0 | 51 |
| Ulnar Nerve R. | Normal ≤ 3.6 | Normal ≥ 8 | Normal ≥ 50 |
|---|---|---|---|
| Wrist | 5.0 | 4.4 | – |
| Below elbow | 10.0 | 2.9 | 45 |
| Above elbow | 13.4 | 2.3 | 35 |
| Axilla | 16.8 | 2.1 | 46 |
| Erb’s point | 24.6 | 0.4 | 27 |
| Nerve and Site | Latency (ms) | Amplitude (mV) | Conduction Velocity (m/s) |
|---|---|---|---|
| Ulnar Nerve L. | Normal ≤ 3.6 | Normal ≥ 8 | Normal ≥ 50 |
| Wrist | 7.0 | 2.1 | – |
| Below elbow | 13.8 | 0.9 | 35 |
| Above elbow | 19.1 | 0.3 | 23 |
| Axilla | 21.5 | 0.4 | 69 |
| Erb’s point | 24.8 | 0.5 | 61 |
| Musculocutaneous Nerve R. | |||
| Axilla | 7.4 | 4.5 | – |
| Erb’s point | 16.0 | 0.5 | 21 |
| Nerve | Latency (ms) | Normal Latency(ms) |
|---|---|---|
| Peroneal nerve R. | 62.7 | 54 |
| Tibial nerve R. | 83.0 | 54 |
| Peroneal nerve L. | NR | 54 |
| Median nerve R. | NR | 30 |
| Ulnar nerve R. | 45.9 | 30 |
| H-reflex R. | NR | 34 |
| H-reflex L. | NR | 34 |
| Nerve | Onset Latency (ms) | Normal Latency (ms) | Peak Latency (ms) | Normal Peak Latency (ms) | Amp (mV) | Normal Amp ≥ (mV) | Conduction Velocity (m/s) | Normal Conduction Velocity ≥ (m/s) |
|---|---|---|---|---|---|---|---|---|
| Sural nerve R. | 3.3 | 3.5 | 3.8 | 4.0 | 20 | 11 | 42 | 40 |
| Median nerve R. | 3.3 | 2.6 | 3.8 | 3.1 | 16 | 20 | 39 | 50 |
| Ulnar nerve R. | 2.2 | 2.6 | 2.7 | 3.1 | 18 | 13 | 55 | 50 |
| Ulnar nerve L. | 2.3 | 2.6 | 2.8 | 3.1 | 20 | 13 | 52 | 50 |
| Muscle | Insrt Activity | Fibs | Pos Waves | Fasc | Amp | Dur | Poly | Pattern |
|---|---|---|---|---|---|---|---|---|
| Sternocleido. R. | Norm | None | None | None | Norm | Norm | None | Full |
| Thoracic paraspinals R. | Inc | 1+ | 1+ | None | Norm | Norm | None | Full |
| Lumbar paraspinals R. | Norm | None | None | None | Norm | Norm | None | Full |
| Deltoid R. | Inc | 2+ | 2+ | None | Lg | Inc | None | Red |
| Biceps brachii R. | Inc | 2+ | 2+ | Few | Lg | Inc | Few | Red |
| Muscle | Insrt Activity | Fibs | Pos Waves | Fasc | Amp | Dur | Poly | Pattern |
|---|---|---|---|---|---|---|---|---|
| Flexor carpi radialis R. | CRD | 2+ | 2+ | None | Lg | Inc | None | Red |
| Flexor carpi ulnaris R. | CRD | 2+ | 2+ | Few | Lg | Inc | None | Red |
| 1st dorsal interosseous R. | Inc | 2+ | 2+ | Few | Lg | Inc | None | Red |
| Vastus lateralis R. | Inc | 2+ | 2+ | Few | Lg | Inc | None | Red |
| Tibialis anterior R. | Inc | 1+ | 1+ | None | Lg | Inc | None | Red |
| Extensor hallucis longus R. | Inc | 2+ | 2+ | None | Lg | Inc | None | Red |
| Gastrocnemius R. | Inc | 2+ | 2+ | None | Lg | Inc | None | Red |
What were the EMG Findings?
The nerve conduction velocity (NCV) test showed all the features of demyelinating neuropathy with velocity slowing, temporal dispersion of the compound muscle action potentials, prolonged distal latencies and F-responses, and no H-reflexes. He also had evidence of partial conduction blocks ( Fig. 52-2 ).
All the SNAPs were normal except for the median nerve that had prolonged latency, slow conduction velocity, and mildly decreased amplitude suggesting a mild median neuropathy at the wrist.
The needle tests showed diffuse denervation, indicating axonal degeneration, and there were also diffuse fasciculations.
Based on these findings, the differential diagnosis includes diseases that affect large myelinated fibers, such as CIDP, as well as CIDP associated with a monoclonal gammopathy of uncertain significance (MGUS), and with HIV. In these diseases, some diffuse or axonal degeneration can be seen. The lack of uniform slowing and the presence of conduction block are against a hereditary demyelinating neuropathy, such as CMT type 1, although this can be seen in CMT type X. Myelin-associated glycoprotein (MAG) neuropathy usually has distal numbness and weakness and is usually seen in older patients.
This patient had no exposure to drugs that cause a demyelinating neuropathy, such as amiodarone, nor did he have a history of weight loss or lymph node enlargement to suggest lymphoma. He was not a diabetic.
Vasculitis is usually asymmetric, as in mononeuritis multiplex, but can sometimes present with a diffuse sensorimotor neuropathy. Conduction block can also be seen due to focal edema. The diffuse symmetrical weakness with only motor involvement, along with the signs of demyelination seen on nerve conduction tests, makes that diagnosis unlikely.
What Other Tests Should Be Done?
Immunoelectrophoresis, erythrocyte sedimentation rate, fluorescent antinuclear antibody test, and HIV titers were normal. IgM GM 1 ganglioside antibody titers were 1:12,800, and the IgG was 1:3200 (normal, <1:800).
A muscle biopsy showed atrophic angular fibers and targets indicating denervation. A sural nerve biopsy was completely normal. A lumbar puncture showed spinal fluid with an elevated protein of 119 mg/dL (normal, <40 mg/dL) with no cells; the test was otherwise normal.
What Would You Do Next?
The patient was started initially on prednisone 60 mg by mouth per day with a marked worsening of symptoms, so this was discontinued. He received IgG infusions in doses of 2 g/kg with marked improvement. This was repeated monthly, but, as he later deteriorated, cyclophosphamide was added in doses of 200 mg daily, orally, with which he improved and stabilized ( Fig. 52-3 ). Because of the patient’s high arches, DNA tests for demyelinating CMT types 1 and X were done, and these were negative.
