A Woman With Muscle Weakness and Areflexia

A 52-year-old woman presented with a history of weakness and fatigue in the legs with difficulty going upstairs and downstairs for over 1 year. She also had burning paresthesias in the thighs and was treated with amitriptyline 50 mg every night for depression and fibromyalgia. She had a loss of appetite and had had a 20-lb weight loss.

Previous neurologic workup included an EMG that showed brief polyphasic motor unit potentials and increased insertional activity in proximal muscles; her serum creatine kinase was normal; a muscle biopsy showed type II muscle fiber atrophy; and a nerve biopsy was unremarkable. A CT scan of the chest showed benign hilar adenopathy. Other previous tests included a fluorescent antinuclear antibody titer of 1:160 homogenous pattern, normal thyroid function tests, acetylcholine receptor antibodies, protein electrophoresis, 24-hour heavy metals, porphyrins, extractable nuclear Ag, and C3 and C4.

She was treated with 30 mg of prednisone daily without benefit and was referred to us.

Past medical history included a hysterectomy and oophorectomy in the remote past. She smoked one pack of cigarettes a day and did not drink. She worked as a secretary. Family history was positive for a daughter with cystic fibrosis.

Neurologic examination revealed normal mentation and cranial nerves. The pupils, disks, extraocular movements, face, palate movement, and tongue strength were normal, but her tongue was dry. Strength examination showed mild proximal weakness without fatigue. She was areflexic. Vibration sense was diminished in the toes, but pinprick sensation was normal. Coordination was also normal. There was no evidence of muscle atrophy or fasciculations.

What is the Differential Diagnosis?

This patient presented with progressive muscle weakness mainly in the legs with paresthesias. For this, spinal stenosis is a consideration, although she did not have back pain. Another possibility would be an inflammatory myopathy such as polymyositis and inclusion body myositis, but she had normal serum creatine kinase, and both were ruled out by her muscle biopsy. Endocrine myopathies, such as from hypothyroidism or hyperparathyroidism, might manifest with predominant lower extremity weakness, and their muscle biopsies might show type II muscle fiber atrophy, as in this patient.

She had some clinical suggestion of a neuropathy, as she had paresthesias and was areflexic, but her previous nerve conduction test and EMG were against that diagnosis. The lack of fasciculations, the small motor units reported on the EMG, and the muscle biopsy findings are against a motor neuron disease.

Another possibility is a disorder of neuromuscular transmission, particularly because of her history of fatigue and lack of significant muscle atrophy. The lack of diplopia or ptosis and the areflexia are against myasthenia gravis, but not Eaton–Lambert syndrome. She also had a dry mouth as in that disorder, but this could have been caused by the amitriptyline.

An EMG Test was Performed

Motor Nerve Studies

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Peroneal Nerve L.	Normal ≤ 4.2	Normal ≥ 6	Normal ≥ 50
Ankle	3.9	2	–
Fibular head	10.6	2	42

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Ulnar Nerve L.	Normal ≤ 3.6	Normal ≥ 8	Normal ≥ 50
Wrist	3.0	2.5	–
Below elbow	7.7	2.5	50

F-Wave Studies

Nerve	Latency (ms)	Normal Latency ≤ (ms)
Peroneal nerve L.	53.8	54
Ulnar nerve L.	26.7	30

Sensory Nerve Studies

Nerve	Onset Latency (ms)	Normal Onset Latency ≤ (ms)	Peak Latency (ms)	Normal Peak Latency ≤ (ms)	Amp (μV)	Normal Amp ≥ (μV)	Conduction Velocity (m/s)	Normal Conduction Velocity ≥ (m/s)
Sural nerve L.	3.3	3.5	3.8	4.0	14	11	42	40
Ulnar nerve L.	2.1	2.6	2.4	3.1	15	13	57	50

EMG Data

Muscle	Insrt Activity	Fibs	Pos Waves	Fasc	Amp	Dur	Poly	Pattern
Cervical paraspinals L.	Norm	None	None	None	Norm	Norm	Norm	Full
Deltoid L.	Norm	None	None	None	Variable ^a	Norm	Norm	Red
Biceps brachii L.	Norm	None	None	None	Norm	Norm	Norm	Full
Gluteus medius L.	Norm	None	None	None	Norm	Norm	Norm	Full
Vastus lateralis L.	Norm	None	None	None	Variable ^a	Norm	Norm	Red
Tibialis anterior L.	Norm	None	None	None	Norm	Norm	Norm	Full
Peroneus longus L.	Norm	None	None	None	Norm	Norm	Norm	Full
Abductor hallucis L.	Norm	None	None	None	Norm	Norm	Norm	Red
Tibialis anterior R.	Norm	None	None	None	Norm	Norm	Norm	Full
Peroneus longus R.	Norm	None	None	None	Norm	Norm	Norm	Full
Gastrocnemius R.	Norm	None	None	None	Norm	Norm	Norm	Full