A Man With Muscle Twitching and Poor Balance

A 37-year-old man presented with a 2-year history of loss of balance and weakness. He also had muscle cramps, twitching, and difficulty in speaking. Previous workup showed a normal magnetic resonance imaging (MRI) of the brain and visual, auditory, and somatosensory-evoked responses. He also had normal spinal fluid studies, HIV and human T-lymphotropic virus 1 titers, complete blood count, and chemistry profile. He was referred for a possible motor neuron disease.

Past medical history was unremarkable. His father and paternal uncle were diagnosed with possible multiple sclerosis (MS) as they had weakness and ataxia. The patient did not smoke or drink and had not been exposed to toxins.

Neurologic examination revealed normal mental status with a score of 30/30 on the mini-mental state examination. He was mildly dysarthric. Visual fields were normal. There was mild limitation of the medial and lateral gaze and upward gaze. At times, he had a tendency to squint while looking forward ( Fig. 37-1 ). He had fasciculations in the face. Other cranial nerves were normal, including facial strength. The tongue appeared normal and showed no atrophy or weakness. Gag reflex and jaw jerk were increased. Although he complained of weakness, his muscle strength was normal on testing. Reflexes were hyperactive with positive Hoffmann signs bilaterally, but no Babinski signs. There were scattered muscle fasciculations in the limbs without atrophy. Vibration sense was diminished in the toes, but position sense, pain, and touch sensation were normal. He had difficulty with tandem gait. The finger-to-nose test was normal, but the heel-to-shin test was poorly done.

An EMG Test was Performed

Motor Nerve Studies

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Peroneal Nerve L.	Normal ≤ 5.7	Normal ≥ 3	Normal ≥ 40
Ankle	4.6	12	–
Fibular head	10.9	11	49
Knee	12.9	11	50

Tibial Nerve L.	Normal ≤ 5.3	Normal ≥ 4	Normal ≥ 40
Ankle	3.4	17	–
Pop. fossa	11.9	16	48

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Ulnar Nerve R.	Normal ≤ 3.6	Normal ≥ 8	Normal ≥ 50
Wrist	2.9	12	–
Below elbow	6.1	12	61
Above elbow	8.1	12	60

F-Wave and Tibial H-Reflex Studies

Nerve	Latency (ms)	Normal Latency ≤ (ms)
Peroneal nerve R.	47.4	54
Tibial nerve L.	50.1	54
Ulnar nerve R.	26.3	30
H-reflex R.	30.3	34

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.	3.5	3.5	4.0	4.0	12	11	40	40
Ulnar nerve R.	2.6	2.6	3.1	3.1	13	13	50	50

EMG Data

Muscle	Insrt Activity	Fibs	Pos Waves	Fasc	Amp	Dur	Poly	Pattern
Tongue	Norm	None	None	None	Norm	Norm	None	Full
Masseter R.	Norm	None	None	Few	Lg	Inc	None	Full
Deltoid R.	Norm	None	None	Few	Lg	Inc	None	Full
Biceps brachii R.	Norm	None	None	None	Lg	Inc	Few	Full
1st dorsal interosseous R.	Norm	None	None	None	Lg	Inc	None	Red
Vastus lateralis R.	Norm	None	None	Few	Lg	Inc	None	Red
Tibialis anterior R.	Norm	None	None	None	Norm	Norm	None	Full
Gastrocnemius R.	Norm	None	None	None	Norm	Norm	Few	Full
Tibialis anterior L.	Norm	None	None	None	Norm	Norm	None	Full
Gastrocnemius L.	Norm	None	None	None	Norm	Norm	None	Full

What were the EMG Findings?

The electrophysiologic studies revealed normal motor and sensory nerve conduction velocities, latencies, and amplitudes of the compound muscle action potentials and sensory nerve action potential (SNAPs). There were large motor unit potentials with decreased recruitment in the lower extremities, with fasciculations but no denervation potentials. Scattered fasciculations without denervation were also seen on the face but not in the tongue. The findings seemed to indicate a mild chronic motor neuron disorder.

What is the Differential Diagnosis?

This patient was initially referred for fasciculations and weakness. He has a positive family history of “possible MS,” but likely that diagnosis was incorrect as, although there is an increased incidence of MS in families, autosomal dominant inheritance is rare. Furthermore, the fasciculations in the face and limbs are unusual for this disease. Fasciculations, however, not only occur in motor neuron diseases but also can sometimes be seen in neuropathies; localized limb fasciculations are seen in radiculopathy. They are seen diffusely in a number of other diseases, including multifocal motor neuropathy, some spinocerebellar degenerations, Kennedy’s disease, Jakob–Creutzfeldt syndrome, and debrancher enzyme deficiency. This patient’s presentation with fasciculations and hyperreflexia with scattered large motor unit potentials on electromyography suggests a relatively benign chronic motor neuron syndrome. The apparent autosomal dominant inheritance could suggest a hereditary amyotrophic lateral sclerosis (ALS) which is usually more rapidly progressive, but the extraocular abnormalities and leg ataxia indicate a more widespread disorder; furthermore, the lack of denervation potentials makes the diagnosis of ALS or similar diseases unlikely. Facial fasciculations can be seen in Kennedy’s syndrome and Machado–Joseph spinocerebellar degeneration. Patients with Kennedy’s disease might have systemic manifestations, show SNAP abnormalities, and have elevated serum creatine kinase, which are not seen in this case. The mode of inheritance, ataxia, lack of tongue atrophy, and abnormalities of the extraocular movements are not characteristic of this disorder.

Multisystem degeneration might present with weakness, fasciculations, and tremor but without extraocular involvement or significant ataxia. Those, however, occur in spinocerebellar degenerations. The autosomal dominant inheritance, age of onset, hyperactive reflexes, lack of significant proprioceptive sensory deficits, up-going toes, scoliosis, fasciculations, and normal SNAPs rule out the possibility of a later-onset Friedreich’s ataxia. An acquired autoimmune or toxic cause seems unlikely.

The history and findings in this patient are suggestive of an autosomal dominant spinocerebellar ataxia (SCA). The lack of atrophy on the initial MRI could be related to the recent onset of the disease. Of the SCAs, Machado–Joseph disease (MJD) is an important consideration in this case, particularly because of the facial fasciculations.

What Tests Should Be Done?

A repeated MRI showed cerebellar atrophy ( Fig. 37-2 ). DNA tests for autosomal dominant spinocerebellar degenerations by protein catabolic rate amplification were performed in blood, and the patient had one allele with 27 CAG repeats and one with 78 (normal, <40), diagnostic of MJD or autosomal dominant SCA type 3.