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A 28-year-old right hand-dominant mechanical engineer attended a number of neurologists because of several months of twitching in his thigh and calf muscles. His concern was that he may have developed motor neurone disease as he also had wasting of the muscles in his right thenar eminence. This had progressed over 3 years, with worsening grip strength, weakness and loss of dexterity in the right hand. There was no tenderness and no weakness elsewhere and no sensory, autonomic or systemic symptoms. His history included psoriasis, treated with oral methotrexate and corticosteroids.
On examination, there was significant wasting of the right thenar eminence with weakness of opposition and thumb abduction (figure 1). The remaining intrinsic muscles, all of the extrinsic muscles and sensory function of the hand were normal. There were brief fasciculations in the thighs and calves bilaterally, but none in the arms or tongue. Muscle bulk, strength and sensation were normal in the legs, and his reflexes were intact including the jaw jerk. There was no dysarthria, dysphagia or other cranial nerve deficits.
What is the differential diagnosis?
There are two dimensions to the presentation, which may or may not be related. First, the progressive right hand weakness with wasting and second, the fasciculations in the thighs and calves. Each of these is considered in turn.
Right hand weakness
Three years of weakness and wasting without spread beyond the thenar eminence favours a focal cause for right hand the symptoms, reflecting isolated distal median nerve involvement.
The most common site of compression of the median nerve is in the carpal tunnel, which normally manifests as weakness of the thenar muscles and dysaesthesia of the thumb, index, middle and radial half of the ring finger. The severity of the focal wasting and the lack of sensory features here indicate median nerve dysfunction distal to the carpal tunnel, specifically in the recurrent branch of the median nerve. Figure 2 shows the anatomy of the median nerve. Figure 1 shows the wasting of the thenar eminence; the weakness was confined to the abductor pollicis brevis, flexor pollicis brevis and opponens pollicis (figure 3).
It was also possible that he had a systemic or generalised neuropathic process restricted to a single clinically eloquent nerve (or local myopathic process). However, this would usually be accompanied by subclinical involvement of other nerves and evident on neurophysiological analysis. Multifocal motor neuropathy is a key differential diagnosis for focal and asymmetric weakness, although this diagnosis requires two or more affected nerves. The neurophysiological hallmark is conduction block, and about half of cases have serum anti-GM1 antibodies.
Could other focal peripheral nerve lesions explain this clinical picture? A form of carpal tunnel syndrome with entrapment of the recurrent motor branch has been described, with cases occurring alone or together with typical carpal tunnel manifestations.1 There was no weakness in movements facilitated by median nerve innervated muscles arising within the forearm—forearm pronation, wrist flexion and abduction—nor weakness of flexion of the index and middle fingers or loss of sensation in the thenar region. This all makes a median nerve deficit within the forearm much less likely. A lesion proximal to the forearm would typically also cause sensory symptoms, and if not, at least subclinical sensory abnormalities on neurophysiology. A C8 or T1 cervical radiculopathy or brachial plexopathy, from thoracic outlet syndrome affecting the lower trunk, for example, could compromise innervation to the thenar muscles before other intrinsic muscles of the hand and thereby mimic a median nerve lesion. Likewise, a proximal perineurioma specifically affecting a fascicle of nerves en route to the thenar muscles may also cause a restricted motor deficit. Hirayama’s disease is a form of focal amyotrophy precipitated by mechanical forces in the cervical spine and exiting nerve roots. It is often highly asymmetrical and most commonly affects young man. Neurophysiology in Hirayama’s disease shows chronic denervation, and MR imaging of the cervical spine may be abnormal with forward displacement of the dura.
Fasciculations, due to spontaneous discharge of a motor unit or part of a motor unit, may occur in a range of conditions, including motor neuropathies, peripheral nerve hyperexcitability, radiculopathies and motor neurone disease. Systemic factors such as anxiety, hyperthyroidism and electrolyte imbalances may also lead to fasciculations. Fasciculations can commonly occur physiologically, usually affecting the lower limbs, without associated neurological findings, and have a benign prognosis.2 Neuromyotonia can resemble fasciculations to the naked eye and may be autoimmune or paraneoplastic, but can be distinguished with neurophysiology.
What investigations would you organise?
Nerve conduction studies and electromyography (EMG).
Nerve conduction studies found normal amplitude, conduction velocity and median sensory responses but a reduced median motor amplitude response from wrist to abductor pollicis brevis on the right compared with the left (3.1 mV compared with 6.2 mV) with no slowing (latency 3.67 on right, 3.54 on left) and absent F waves on the right. Conduction velocities to the second lumbrical muscle were normal, excluding median nerve involvement proximal to the recurrent branch of the median nerve. These results are shown in table 1A,B. Conduction amplitudes and latencies were normal in all other nerves tested, confirming the absence of a more widespread neuropathic process. There was no evidence of conduction block. EMG of abductor pollicis brevis found occasional fibrillations and positive sharp waves, a moderate excess of polyphasic units of normal or increased duration and units firing at high rates in relative isolation. There were occasional fasciculations in right rectus femoris and gastrocnemius, but individual units had normal configuration and normal recruitment, indicating no evidence of acute denervation outside the right thenar eminence. These results are summarised in table 1 (C).
What is the most useful diagnostic test now?
Isolated involvement of the recurrent branch of the median nerve is unusual and imaging of the hand should be done to look for a local cause. MR neuronography is the most helpful next imaging modality.3 Figure 3 gives selected images, whichTable 2 show a homogenously enhancing nodular lesion intrinsic to the nerve. Based on the MR appearances, we suspected a neuroma.
Were neuronography of the recurrent branch of the median nerve to be normal, the same technique could be applied to more proximal portions of the median nerve could be used to identify a perineurioma compromising conduction within a particular fascicle of the median nerve.
What are the treatment options?
Neuromas are one of several non-neoplastic peripheral nerve tumours. They are commonly reactive, arising at the site of previous trauma and are tender when superficial. They comprise a mass of disorganised axons. Non-tumourous compressive lesions, malignant and benign nerve sheath and non-nerve sheath tumours can all present with similar clinical deficits.
Conservative management is an option as neuromas have a benign prognosis and are slow growing. Where there is functional compromise (as here), then surgical excision is definitive. We referred this patient to a specialist hand surgeon for excision of the neuroma. However, it was not feasible to shell out the neuroma and leave the nerve in continuity, as the pathology involved the entire segmental circumference of the diseased part of the nerve causing significant attenuation. Hence, the surgeon excised the segment containing the neuroma, mobilised the ends and directly anastomosed by microsurgical repair without much tension. Had direct anastomosis not been possible, a nerve graft would have been needed to breach the gap. In addition, the surgeon performed a functional tendon transfer using the ipsilateral palmaris longus tendon to abductor pollicis brevis to improve the patient’s functional outcome while the nerve was recovering. Figure 4 shows intraoperative images. Figure 5 illustrates the histopathology of the resected neuroma, with disorganised microfascicles of Schwann-type spindle cells.
This patient made an excellent functional recovery (figure 6) and was back to routine activities after 6 weeks following occupational hand therapy rehabilitation. His lower limb fasciculations have persisted. We found no underlying neurological, endocrine or metabolic cause and he was also diagnosed with benign fasciculation syndrome.
MR neuronography can help to identify the cause of peripheral nerve dysfunction, focused by clinical examination and nerve conduction studies to localise the site of nerve dysfunction.
Neuromas comprise one of many potential mimics of motor neurone disease.
Surgery can potentially radically improve function in muscles affected by neuromas.
Benign fasciculations are common and difficult to distinguish clinically from the fasciculations of motor neurone disease; they are signified by the absence of weakness, wasting or other neurological deficits.
Thank you to Dr Kieren Allinson, Neuropathologist at Cambridge University Hospitals NHS Foundation Trust for assistance with histopathology and to Anne Wadmore, Medical Illustrator for the preparation of figure 2.
Contributors SKA drafted the submission with neurophysiology from SC and radiology from SV. Information about surgery and patient photographs were provided by RC and RR. AR conceptulised and oversaw writing of the article. AR and RR led clinical care of the patient.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned. Externally peer reviewed by Haider Katifi, Southampton, UK
Data sharing statement No additional unpublished data is available.
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