40 PRACTICAL NEUROLOGY Pract Neurol: first published as 10.1046/j.1474-7766.2003.00121.x on 1 February 2003. Downloaded from Enlarged periph Michael Donaghy Department of Clinical Neurology, University of Oxford, Radcliffe Infi rmary, Oxford OX2 6HE, UK Practical Neurology, 2003, 3, 40–45 Enlargement of peripheral nerve is a physical sign that all neurologists know about, but which, like pes cavus, is extremely diffi cult to recognize in its milder forms. It is associated principally with two conditions – leprosy and hereditary motor and sensory neuropathy. It has also been noted in a number of others (Table 1). http://pn.bmj.com/ DETECTING ENLARGED PERIPHERAL NERVES BY PALPATION Potential sites for palpating nerves are shown in Fig. 1, based on experience in leprosy. Attempts to palpate such nerves are best made using the on September 28, 2021 by guest. Protected copyright. tips of the index, middle and ring fi ngers rolled backwards and forwards across the long axis of the nerve. Sometimes you can try to pick up the nerve between the thumb and middle fi nger as in the case of the ulnar nerve in the upper arm. Table 1 Differential diagnosis of enlarged peripheral nerves Leprosy Hereditary motor and sensory neuropathy Neurofi bromatosis Refsum’s disease Perineuroma/localized hypertrophic neuropathy Figure 1 Sites of potentially palpable peripheral nerve enlargement in Nerve tumours leprosy [Fig. 14.5 from Leprosy 2nd Edn. (1994), Hastings RC, Opromolla Amyloidosis DVA (Eds.)]. © 2003 Blackwell Publishing Ltd FEBRUARY 2003 41 Pract Neurol: first published as 10.1046/j.1474-7766.2003.00121.x on 1 February 2003. Downloaded from NEUROLOGICAL SIGN heral nerves Only the most astute physician will be able to use his thumb to detect an enlarged superfi cial ra- dial nerve in the anatomical snuffbox of some- one with whom he is casually shaking hands. The best simile for an enlarged peripheral nerve is that it feels like a length of domestic electric cable. The ulnar nerve can be thickened to four or fi ve times its normal diameter in leprosy, not that unusual in the Indian subcontinent. Some normal nerves can be palpated eas- ily, without being enlarged in the pathological http://pn.bmj.com/ sense. Well known examples include the super- fi cial radial nerve running over the extensor pollicis tendon, the ulnar nerve behind the me- dial epicondyle at the elbow, the common pero- neal nerve around the fi bula head, and terminal on September 28, 2021 by guest. Protected copyright. sprigs of the peroneal nerve over the dorsum of the foot. It is extremely diffi cult to judge mild degrees of enlargement at these sites: other sites may be preferable, for example in some cases ulnar nerve enlargement may be better noted in the medial upper arm above the elbow. Nerve enlargement can lead to entrapment within canals of otherwise normal calibre. Ex- amples include the ulnar nerve in the cubital tunnel (Fig. 2) and the median nerve in the car- pal tunnel. In suspected leprosy it is necessary to compare carefully the same nerve on both sides of the body in making the decision about whether a nerve is enlarged or not (McDougall Figure 2 A hugely palpable ulnar nerve in the upper arm in leprosy. 1996). Leprosy workers can be trained to palpate Note that the nerve enlargement has led to suspected secondary nerves systematically, and scoring systems have compression in the cubital tunnel, hence the scar refl ecting surgical been developed: no enlargement (0); slightly release (courtesy of Dr Colin McDougall). © 2003 Blackwell Publishing Ltd 42 PRACTICAL NEUROLOGY Pract Neurol: first published as 10.1046/j.1474-7766.2003.00121.x on 1 February 2003. Downloaded from enlarged (1 +); moderately enlarged (2 +); very of course, is obvious, but it is quite striking enlarged (3 +) with additional note of nerve the number of times cases are diagnosed as tenderness or pain (Croft et al. 1999). leprosy with a remark that the ulnar nerve is enlarged, yet one can fi nd no such enlarge- LEPROSY ment. A good general rule is: if in doubt, the Leprosy is the only condition in which a pal- nerve is not enlarged’. pably hypertrophied peripheral nerve is often So technique is all-important, and those central to the diagnosis. At the lepromatous end working as diagnostic assistants in leprosy clin- of the spectrum, symmetrical involvement with ics in endemic countries should be taught reli- glove and stocking sensory loss due to dermal able methods for detecting enlarged nerves. nerve involvement, often with autonomic neu- Over half a million new cases of leprosy are ropathic features, is the usual fi nding. At the registered annually (WHO 2002). Of these, tuberculoid end of the spectrum, one or a few some 20% are at risk of developing a disability individual nerves tend to be picked out. Three because of nerve function impairment. This cardinal signs remain the basis for diagnosing 20% represents those patients whose nerve in- leprosy (Pfaltzgraft et al. 1994; Report of the volvement by leprosy bacilli and/or infl amma- International Leprosy Association Technical tory infi ltrate affects the main sensory, or mixed Forum 2002; WHO 1995): motor and sensory nerve trunks. Interestingly, • Anaesthetic skin lesions. These usually nerve function impairment commonly occurs consist of erythematous or hypopigmented for the fi rst time during or after multidrug macules and are often the fi rst clinical sign of antibiotic treatment (Heinhardt et al. 1994, disease, but papules (raised) and nodules are Croft et al. 2000). This distressing occurrence also seen. A skin lesion due to leprosy typi- may lead to non-compliance with treatment yet cally shows loss or diminution of sensation to can be treated with corticosteroids. Such nerve pin prick and/or light touch. function impairment occurring during treat- • Enlarged peripheral nerves. Nerve thicken- ment is considered to represent a hypersensitiv- ing usually appears later than the skin lesions. ity reaction. The presence of pre-existing nerve Depending on the delay in presentation and trunk enlargement is a powerful predictor of the clinico-immunological classifi cation, the subsequent treatment-related nerve function likelihood of detecting one or more enlarged impairment (Croft et al. 2000). nerves can vary from in as few as 20% of pa- tients, to as many as 96%. In over 90% of those HEREDITARY MOTOR AND SENSORY patients with nerve enlargement, it is detect- NEUROPATHY (HMSN) http://pn.bmj.com/ able in either the ulnar or the peroneal nerve. Palpable nerve thickening occurs in about 30% Nerve function impairment is evident in the of patients with type I (the demyelinated form) skin or muscles innervated by the enlarged but not in type II (the axonal form) of heredi- nerve. tary motor and sensory neuropathy (Harding & • Acid fast bacilli demonstrated on a skin Thomas 1980). The best nerve to palpate is the on September 28, 2021 by guest. Protected copyright. smear (in a small proportion of cases). How- greater auricular nerve, which cannot usually be ever, leprosy lesions in paucibacillary disease felt in normal people (Fig. 3). With the head in- are skin smear negative and this constitutes clined slightly away to tighten the neck muscles the majority of cases in most endemic coun- and skin, the fi ngers of the palpating hand can be tries. drawn across the side of the neck to try to feel the As a general rule one should be cautious about nerve. Sometimes an enlarged nerve is misdiag- accepting nerve thickening alone, without sen- nosed. I well remember a patient with HMSN sory loss, muscle weakness or skin changes, as a whose general practitioner’s referral letter reliable sign of leprosy (WHO 1995, 2002). stated that ‘his general health is otherwise good, The technique of palpating nerves in sus- apart from chronic cervical lymphadenopathy’. pected leprosy was eloquently described by R G This turned out to be a nerve. Nerve thickening Cochrane in 1964: in hereditary motor and sensory neuropathy is ‘Never squeeze the nerve fi rmly … remember thought to represent the summation of onion always to examine the corresponding nerve bulb formation around individual dysmyelin- on the other side; it is never safe to pronounce ated nerve fi bres, with all the associated redun- a nerve enlarged without comparing the dant Schwann cell processes and collagen which one on the other side. Gross enlargement, that entails. © 2003 Blackwell Publishing Ltd FEBRUARY 2003 43 Pract Neurol: first published as 10.1046/j.1474-7766.2003.00121.x on 1 February 2003. Downloaded from Figure 3 A visibly enlarged greater auricular nerve in hereditary motor and sensory neuropathy type I (given to me by the late Professor WB Matthews). It is my informal impression that nerve en- ataxia, retinitis pigmentosa and hearing impair- http://pn.bmj.com/ largement is not present in nearly as many as ment due to phytanic acid deposition. 30% of the HMSN type I patients whom I see in Infi ltration of a nerve with amyloid protein my peripheral nerve clinic. However, that may might be expected to cause palpable enlargement. be because it is most common in HMSN type However, this was only noted in 1 out of 31 pa- IA, which accounts for 70% of HMSN type I, tients with primary systemic amyloidosis (amy- on September 28, 2021 by guest. Protected copyright. and is associated with the 17p11.2 reduplication loid immunoglobulin light chain deposition) on chromosome 17 providing a double dose of (Kelly et al. 1979). There are only rare reports of the PMP22 gene. Modern molecular genetics palpable peripheral nerves in the various forms may mean that this diagnoses is made in general of familial amyloid polyneuropathy (Juliao et al.