Fasciculations masquerading as minipolymyoclonus in bulbospinal muscular atrophy.

Minipolymyoclonus has been described in both anterior horn cell disorders and central nervous system degenerative conditions. While its etiology remains unclear and speculative, a central generator has been previously proposed. We describe a case of bulbospinal muscular atrophy (Kennedy's disease), where minipolymyoclonus-like movements corresponded to fasciculations in neurophysiological studies. Our novel finding suggests that the etiologies of minipolymyoclonus in central and peripheral nervous system disorders are distinct, despite outward clinical similarity. The term "minipolyfasciculations" may be more reflective of the underlying process causing minipolymyoclonus-like movements in lower motor neuron disorders.

Introduction

Minipolymyolonus is a term used to describe the involuntary, jerky, irregular, small amplitude tremor-like movements, most commonly seen in the hands, occurring in patients with degenerative anterior horn cell diseases. However, similar twitches have also been reported in patients with a variety of central nervous system (CNS) disorders. While the etiology of minipolymyoclonus remains speculative, a central generator has been proposed. We describe a patient with genetically proven bulbospinal muscular atrophy (Kennedy's disease) with minipolymyoclonus-like movements, demonstrated neurophysiologically to be due to frequent fasciculations.

Case Report

A 54-year-old man presented to the neuromuscular clinic with a 6-year history of gradual left upper extremity weakness, mainly manifested as trouble lifting his left arm above his head, followed 3 years later by slowly progressive bilateral lower extremity weakness, heralded by inability to climb stairs. He denied any pain or sensory complaints. He also noticed bilateral facial muscle twitching and shortness of breath on exertion. Past medical history included type-2 diabetes mellitus and hypertension. He had a maternal uncle with a “muscle disease” of unknown nature who was wheelchair-bound by the age of 60 years. General physical examination was significant only for gynecomastia. There was mild weakness of facial muscles, as well as the masseter, pterygoid, and sternomastoid muscles bilaterally, with prominent tongue atrophy. He had significant weakness and atrophy of the bilateral upper extremity proximal muscles, left worse than the right, and mild weakness of the intrinsic hand muscles. Medical research Council (MRC) muscle strength grading was as follows (right/left): Rhomboids 5/5, deltoids 4−/3, shoulder internal rotators 5/5, shoulder external rotators 4/3, biceps brachii 4−/3, triceps 4−/4, brachioradialis 4/3, brachialis 4/3, wrist extensors 5/4, wrist flexors 4/5, all intrinsic hand muscles (including first dorsal interosseous [FDI] and abductor pollicis brevis [APB]) 4+/4. In the lower extremities, there was mild weakness of the bilateral hip and thigh muscles (MRC muscle strength grading 4 or better in the iliopsoas, quadriceps, hamstring, gluteal, hip abductor, and hip abductor muscles bilaterally), with relatively intact distal muscle strength. Diffuse areflexia and a normal sensory examination were noted. There were fasciculations in the tongue, facial, proximal upper extremity as well as rectus abdominis muscles bilaterally.

There were involuntary, multifocal, irregular, non-rhythmic, occasionally jerky-appearing small amplitude muscle contractions in various parts of the body, appearing tremulous at times. These twitches mostly involved the fingers and caused visible movements in multiple planes (various combinations of flexion/extension, abduction/adduction), seen at rest but accentuated by holding the arms outstretched and with sustained action, resembling minipolyoclonus [Video 1]. In the face, they involved the lips and orofacial muscles. They also occurred less frequently in the toes, at times appearing similar to the movements seen in “painless limbs moving toes” syndrome.

Work-up included magnetic resonance imaging (MRI) of the cervical spine showing mild disc bulging at multiple levels from C3 through C6, and right neuroforaminal stenosis at C3-C4. MRI of the brain was unremarkable. Nerve conduction studies showed normal amplitudes, conduction velocities, F-wave latencies and distal latencies in the bilateral median, ulnar, peroneal, and tibial motor nerves, and normal amplitudes and conduction velocities in the bilateral median, ulnar, radial, and sural sensory nerves. Electromyography (EMG) of the left vastus lateralis, tibialis anterior, medial gastrocnemius, biceps brachii, triceps, FDI, thoracic paraspinals, frontalis, nasalis, and tongue muscles all showed spontaneous activity (2-3 + fibrillations and positive sharp waves) suggesting ongoing denervation as well as motor units demonstrating chronic neurogenic changes (large, polyphasic, long duration potentials with decreased recruitment, suggesting denervation and collateral re-innervation). A disease process of the motor neurons was suspected; subsequent genetic testing revealed a mutation of the androgen receptor gene with 46 CAG repeats, confirming a diagnosis of bulbospinal muscular atrophy.

Materials and Methods

To better characterize these muscle contractions, we performed polymyographic recordings using surface electrodes from the bilateral FDI and extensor digitorum communis (EDC), right APB and extensor digitorum brevis muscles. In addition, simultaneous concentric needle EMG was performed in the right FDI and EDC muscles. All recordings were performed using Viking Select eight-channel EMG equipment using a bandpass filter of 150 Hz-5 KHz. We recorded near-continuous, irregular, asynchronous muscle bursts on the surface EMG channels, which corresponded to fasciculations on the concentric needle EMG channels in those muscles where both were recorded simultaneously [Figure 1]. The duration of the muscle bursts ranged from 11-44 msecs, with the majority of the bursts lasting between 11-22 msecs.

Figure 1

One-second polymyographic recording from our patient. Note simultaneous occurrence of fasciculations in needle electromyography (EMG) channels (1, 4) and muscle bursts in the surface EMG channels (2, 5) in muscles where both were performed concomitantly. Other channels have irregular, asynchronous discharges, the right extensor digitorum brevis surface EMG channel (R EDB-S) shows relative quiescence. An “S” suffix represents a surface channel, and an “ N” suffix represents a needle EMG channel. FDI, first dorsal interosseous APB = Abductor pollicis brevis, EDC = Extensor digitorum communis

We also performed electroencephalography (EEG)-EMG correlation by back-averaging EEG signals recorded with scalp electrodes placed on Fz, Cz, and C3 regions according to the 10-20 international EEG nomenclature with a linked A1-A2 reference. The EEG filtering band pass was set at 0.2 Hz-5 KHz. The EEG electrode impedances were set below 5 KOhms. The period of analysis ranged from-1000 to + 1000 milliseconds relative to the onset of the rectified EMG signal using a band pass filter of 150 Hz-5 KHz obtained from right APB as the trigger. A minimum of 50 twitches were averaged. We did not observe an EEG time-locked prepotential preceding the muscle contractions. When the patient performed a voluntary contraction of the right APB muscle, a slowly rising negative potential (Bereitschafts potential) occurred approximately 1000 msecs before the contraction.

Discussion

There have been references in the literature from the 1930s to “fasciculate tremor” or “voluntary fasciculations” in patients with various forms of juvenile spinal muscular atrophy (SMA).[12] However, the term “minipolymyoclonus,” first used by Giblin, was only defined by Spiro in 1970.[1] He described two patients with childhood-onset SMA who had “generalized tremulousness” consisting of irregular, intermittent muscle contractions producing visible and palpable movements of the head and distal joints of the hands and the fingers. These movements were non-rhythmic and unequal in the agonists and antagonists (distinguishing them from tremor), were present at rest, worsened by movement and stress, and alleviated by relaxation and sleep. Spiro considered minipolymyoclonus a manifestation of peripheral neurogenic disease without elaborating on the distinction between minipolymyoclonus and fasciculations. Similarly, while both were mentioned as occurring in a recent series of patients with monomelic amyotrophy, their relationship remained unclear.[3] Though usually described in SMA, minipolymyoclonus appears to be a nonspecific marker of motor neuron damage. Although seen with nemaline rod myopathy and syringomyelia, it was attributed to coexistent lower motor neuron dysfunction.[45]

Minipolymyoclonus-like, small jerky movements in the hands and fingers also occur in degenerative CNS disorders. Wilkins et al.,[6] performed EMG-EEG correlation (back averaging) in a series of patients with CNS impairment (Lennox-Gastaut syndrome, cerebral palsy, familial myoclonic epilepsy and Alzheimer's disease) and bilaterally synchronous finger twitches often discharging simultaneously in antagonistic muscle pairs. They detected bifrontal or bifrontocentral negative slow waves preceding the myoclonic jerks, at times associated with bifrontal sharp waves or a bilateral alpha-range rhythm. They proposed a subcortical focus projecting downwards to spinal motor neurons to produce the motor activity (resulting in minipolymyolonus), and upwards to excite the cortex.

While Wilkins et al., thus demonstrated a central origin for minipolymyoclonus-like jerks in central neurodegenerative disorders, our findings of a correlation between finger jerks and fasciculations in a degenerative condition of the motor neurons suggests that despite an outward clinical similarity, minipolymyoclonus has fundamentally different etiologies in central and peripheral conditions. In Wilkins et al.’s series, no muscle bursts were shorter than 20 msecs in duration, with the range being 20-50 msecs, fulfilling duration criteria for cortical myoclonus. In contrast, the duration of most bursts in our patient was in the expected range for motor unit discharges (up to 20 msecs), consistent with fasciculations arising from the anterior horn cell; the longer duration of some of the bursts was likely due to the chronic neurogenic changes in the motor unit as noted in the prior EMG study. In addition, with the CNS disorders, jerks were bilaterally synchronous in agonist-antagonist pairs, apposite in the context of a proposed subcortical origin, whereas in our patient, the bursts were irregular and asynchronous. The absence of a preceding time-locked cortical prepotential on EEG-EMG correlation with back averaging, which was observed by Wilkins et al., rules out a cortico-subcortical generator in our patient.

Based on our novel findings, we propose that minipolymyoclonus in patients with motor neuron diseases is the clinical manifestation of frequent fasciculations, and thus occurs at the level of the anterior horn cell. The degree of fasciculations that is apparently necessary to produce minipolymyoclonus may explain the infrequent observation of minipolymyoclonus in these patients. Nevertheless, although minipolymyoclonus in central disorders may be clinically indistinguishable from that occurring in lower motor neuron dysfunction, our observations demonstrate that the mechanisms responsible in the latter setting are distinctly different from those previously described with CNS disorders. Using the term “minipolyfasciculations” to describe the minipolymyoclonus-like movements occurring with degenerative motor neuron disorders may lend greater clarity to the nature of the underlying process.