A Woman With Progressive Proximal Muscle Weakness

A 36-year-old Black woman presented with progressive muscle weakness of 8 months; she had had increasing difficulty climbing stairs and rising from a chair and later raising her arms above her head. She was treated with prednisone (100 mg/day for 3 months) and later azathioprine (150 mg/day) without improvement and was referred to us after she developed difficulty breathing.

She denied muscle cramps, myotonia, fasciculations, sensory difficulties, or pigmenturia. A sister died at age 39 after a 5-year course of progressive weakness that had been diagnosed and treated as polymyositis. A maternal aunt had had similar problems, stopped walking in her 20s, and died after several years without being evaluated.

Cardiovascular and respiratory examinations were unremarkable except for labored respiration that caused some difficulty with speech. There was no visceromegaly. Neurologic examination showed a waddling gait. There was generalized hypotonia and mild atrophy of proximal muscles. Neck flexor and extensor muscles were 4/5; deltoids, 3/5; and trapezius, 3+ to 4/5. Distal muscles of the arms and hands were 5/5. Iliopsoas strength was 2/5; quadriceps, 3/5; adductors, 2/5; glutei, 3−/5; hamstrings, 4/5; foot dorsiflexors, flexors, invertors, and evertors were 5/5. Reflexes were absent throughout except 2+ at the ankles. Sensation and coordination were normal. No fasciculations were seen. There was no grip or percussion myotonia. Cranial nerves were normal. There was no evidence of tongue atrophy or hypertrophy. ( Fig. 92-1 shows the patient after the disease progressed and she needed a cuirass respirator.)

What is the Differential Diagnosis?

This woman presented with progressive weakness that was assumed to be from polymyositis but did not respond to treatment. The positive family history of a sister and probably an aunt having the same problem suggested an inherited disorder. This presentation could suggest adult-onset familial spinal muscular atrophy; the absence of most reflexes is compatible with this disorder, but the lack of fasciculations is against. The lack of cranial nerve involvement, the atrophy, and the progressive nature of the disease are against a disorder of neuromuscular transmission.

A mitochondrial disorder should be considered, but the lack of extraocular involvement and systemic manifestations are against this. Proximal myotonic myopathy should also be considered, but in that disease, the inheritance is autosomal-dominant and she had no clinical myotonia. Assuming that the sister’s and aunt’s conditions were unrelated, other possibilities should include an endocrine myopathy and polymyositis, a condition rarely seen in families. For this, it would have to be assumed that the disease was refractory to treatment.

A limb-girdle muscular dystrophy and a metabolic myopathy, such as acid maltase deficiency (AMD), also are considerations.

What Tests should be Done?

Routine laboratory studies (including liver function tests and serum electrolytes) and thyroid-stimulating hormone test were normal. Serum creatine kinase level was 650 IU/L (normal, <200 IU/L), and erythrocyte sedimentation rate was 55 mm/h (normal, <30 mm/h).

An EMG Test was Performed

Motor Nerve Studies

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Peroneal Nerve R.	Normal ≤ 5.7	Normal ≥ 3	Normal ≥ 40
Ankle	5.1	8	–
Fibular head	11.4	8	46
Knee	13.2	8	44

Ulnar Nerve R.	Normal ≤ 3.6	Normal ≥ 8	Normal ≥ 50
Wrist	3.3	10	–
Below elbow	6.7	9	60
Above elbow	8.5	9	67

F-Wave Studies

Nerve	Latency (ms)	Normal Latency ≤ (ms)
Peroneal nerve R.	51.2	54
Ulnar nerve R.	26.4	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 R.	3.3	3.5	3.8	4.0	15	11	42	40
Ulnar nerve R.	2.2	2.6	2.7	3.1	22	13	54	50

EMG Data

Muscle	Insrt Activity	Fibs	Pos Waves	Fasc	Amp	Dur	Poly	Pattern
Deltoid R. ^a	Myot	3+	3+	None	Dec	Brief	Many	Full ^a
Biceps brachii R.	Inc	3+	3+	None	Dec	Brief	Many	Full ^a
Triceps R.	Inc	3+	3+	None	Dec	Brief	Few	Full
Brachioradialis R.	CRD	1+	1+	None	Dec	Brief	Few	Full
First dorsal interosseus R.	Inc	1+	1+	None	Dec	Brief	Few	Full ^a
Tensor fasciae latae R.	CRD	None	None	None	Dec	Brief	Few	Full ^a
Vastus lateralis R.	Myot	2+	2+	None	Dec	Brief	Few	Full
Tibialis anterior R.	Inc	2+	2+	None	Dec	Brief	Few	Full