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Peripheral neuropathy in older people Peripheral neuropathies are common in older people. Although the ageing process itself may play a part, there are multiple other causes. interferes with normal daily activities and leads to increased risk of falls, injury and poor quality of life. Management of peripheral neuropathy ofen needs a multidisciplinary team approach.

Siyum Strait, Specialist Registrar Acute Medicine, Great Western Hospital, Swindon Pippa Medcalf, Consultant Physician, Gloucester Royal Hospital, Great Western Road, Gloucestershire Email [email protected]

Peripheral neuropathy is one involvement, time course, type of (eg. diabetic distal symmetrical pattern of damage to the peripheral defcit or nature of the underlying ), purely nervous system.1 Physical signs of pathology.8 (Box 1) motor (eg. acute motor axonal peripheral neuropathy are common The patterns of neuropathy), mixed motor and in older people.2 Recognition involvement that occur include sensory (eg. Charcot-Marie-Tooth of these deficits is particularly mononeuropathy, multiple disease) and autonomic. important because peripheral mononeuropathy (mononeuritis Te responsible pathology may neuropathy may contribute to the multiplex), symmetrical be axonal, demyelinating or mixed vulnerability to falls that is common polyneuropathy, and axonal and demyelinating. in this age group.3,4 More than 30% . Peripheral neuropathies of all of patients aged over 65 years will Mononeuropathy refers to groups may involve large nerve fall at least once per year.5 involvement of major nerve trunks, fbres, small nerve fbre or both. Peripheral neuropathy singly or multiply. Radiculopathy Large nerve fibres are long, commonly causes impairment refers to involvement of nerve myelinated and enable fast of proprioception and balance, roots, again singly or multiply. conduction of impulses. They which can be identified from an Polyneuropathy affects terminal can afect motor function and the inability to maintain unipedal branches of multiple , sensory modalities of vibration, stance for 10 seconds, impaired often involving both legs and position sense and temperature. position sense at the great toe and arms and occurring bilaterally Small fbres may or may not decreased vibratory sense that (symmetrical polyneuropathy).9 be myelinated. Each type involves improves proximally.6 Distal symmetrical polyneuropathy different sensations. Involvement Recognition of the cohort of is the most common variety of of small fbres commonly produces patients with these deficits may polyneuropathy.10 pain and paresthesiae (often identify treatable causes and Te time course can be acute described as burning, lancinating or provide a better management plan (reaching maximal deficit in less “ice pick in the bone”). for patients prone to falling.6,7 than four weeks eg. Guillain-Barré Small fibre neuropathy syndrome), subacute (reaching is the most common type of maximal defcit in 4–8 weeks) or neuropathy in people over the Classifcation chronic (taking more than eight age of 50 years and typically weeks to develop). affects the lower limbs. It often Peripheral neuropathy can be Te resulting defcits may be precedes the development of large classifed by the pattern of nerve purely or predominantly sensory fibre neuropathy. This type of

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Multiple mononeuropathy Box 1: Classifcation of Multiple mononeuropathy Box 2: Classifcation of peripheral neuropathy (mononeuritis multiplex) is mononeuropathy caused by vascular, infammatory, Facial palsy infltration, immune reactions and Vascular Bell’s palsy trauma. (Box 3) Diabetes Sarcoidosis Polyarteritis nodosa Polyneuropathy Lyme disease Rheumatoid arthritis Causes of symmetrical Guillain-Barré syndrome polyneuropathy are more extensive Non-systemic vasculitis Chronic infammatory and complicated than those Infammatory demyelinating polyneuropathy of mononeuropathy, although Sarcoidosis Herpes zoster relatively few diagnoses account for Lyme disease a large number of cases (eg. diabetes Infltrations mellitus, alcohol over use). palsy Malignancy palsy Amyloidosis Meralgia paraesthetica Clinical evaluation Immune reactions Common peroneal nerve palsy Immunisation, foreign serum An accurate history and clinical and proteins examination remains vital in the Trauma neuropathy is ofen unrecognised clinical evaluation of a patient with Multiple nerve injuries by physicians and responds poorly peripheral neuropathy. or slowly to medication.9 Although large and small nerve History Patients may also have cramps fibres may be affected together, The history should address and spasms. only large fibre involvement symptoms, possible causes and Autonomic symptoms depend can be detected by conventional time course. It is important to note upon the system involved. Cardiac nerve conduction studies. Nerve the time period that has taken for involvement may give rise to heart damage due to inflammation or symptoms to evolve and progress. rate irregularities, orthostatic compression tends to sustain a Sensory nerve involvement hypotension and dizziness on more or less complete recovery commonly causes a sensation standing. Gastro-intestinal because of the ability of Schwann of wearing an invisible glove or involvement can commonly cause cells to proliferate and remyelinate sock, burning or freezing pain nausea, vomiting, constipation demyelinated axons. in the extremities, numbness, and diarrhoea. Genito-urinary tingling, pins and needles, band- involvement results in poor bladder like sensation around the wrist control and sexual dysfunction. Causes or ankles and unsteadiness Autonomic symptoms can be and stumbling. very disabling. Among adult patients referred Motor symptoms are usually In searching for probable for assessment of peripheral those of wasting and weakness. causative factors, enquiry should neuropathy, a specifc cause can be Te symptoms will depend upon routinely address recent infections, identifed in about 72% cases.2 the muscle groups affected and alcohol and drug intake, diet, whether those involved are distal or family history and symptoms of Mononeuropathy proximal, but include difculty in systemic disease. Mononeuropathy is usually due to turning keys in locks, unfastening direct compression or entrapment buttons and removing the tops of Clinical examination of the nerves but may be the bottles and jars, foot drop, difculty Motor signs include muscle wasting first manifestation of diabetic or climbing stairs, getting out of chairs and weakness, which in symmetrical vasculitic neuropathy. (Box 2) and standing from crouching. polyneuropathy is usually distal

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stocking distribution. Sensory serum proteins, vitamin B12, Box 3: Classifcation of testing should include light touch, TSH, auto antibodies, serum mononeuritis multiplex pinprick, vibration and joint protein electrophoresis and position. Distal tendon refexes are immunoelectrophoresis, serum Diabetes commonly absent. creatinine, liver function Idiopathic neuropathy The patient should be tests, chest radiographs and Connective tissue disease observed standing and walking, electrophysiological studies. rising onto their heels and If these investigations do not Systemic lupus erythematosus toes, the Romberg’s test and provide information that leads to Polyarteritis nodosa walking heel to toe. The skin a diagnosis, special investigations Rheumatoid arthritis should be examined for trophic may be required, such as Non-systemic vasculitis skin changes and ulcers in the cryoglobulins, HIV, anti Myelin- Inherited neuropathies extremities. Bony deformities Associated Glycoprotein (MAG) such as pes cavus and clawtoes antibodies, urinary heavy metals Infections may be present. Nerves should be and Lyme serology. HIV palpated for thickening. Malignancies Examination of the optic Nerve conduction studies Multiple myeloma fundus may reveal papilloedema Nerve conduction studies play Waldenstrom’s in chronic inflammatory a vital role in confirming the macroglobulinaemia demyelinating polyneuropathy presence of peripheral neuropathy and the retinal abnormalities of and establishing its cause. Tey Cryoglobulinaemia diabetes mellitus. help to determine whether a Monoclonal gammopathy of patient has a mononeuropathy, uncertain signifcance mononeuritis multiplex or a Paraneoplastic syndrome Investigations generalised neuropathy; whether Chemotherapy & drugs the neuropathy is symmetrical Metronidazole, nitrofurantoin, Te clinical features ofen suggest or asymmetrical; whether phenytoin, thalidomide, a likely underlying cause and both sensory and motor fibres vincristine point to the most appropriate are affected; and whether the investigations.11 General laboratory underlying pathology is of axonal Metabolic disorders tests and nerve conduction studies degeneration or demyelination. Tyroid disease should be performed as the first Motor conduction velocities Multiple nerve injuries stage of investigation in all patients. below 40m/s in the upper limb Uraemia Subsequent investigations will and 30m/s in the lower limb depend on the results of these indicate possible demyelination. Cirrhosis initial studies.11 Lesser degrees of slowing of Acromegaly nerve conduction velocity Defciencies indicate peripheral nerve damage, Tiamine+ General which could be due to axonal Pyridoxine laboratory tests loss as in axonal neuropathy or neuronopathy (pathology within Vitamin E Basic laboratory investigations the nerve cell body). Vitamin B12 that should be performed on all patients with peripheral Needle neuropathy of undetermined Electromyography is ofen useful and symmetrical. Occasionally aetiology include urinalysis, in confirming the presence of fasciculation may occur, haemoglobin, white cell axonal degeneration. However, particularly in radiculopathy. count, platelets, erythrocyte denervation potentials may not Sensory loss is also predominantly sedimentation rate, fasting blood appear until three weeks afer the distal, often in a glove and glucose, serum electrolytes, onset of axonal degeneration.

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Examination of cerebrospinal activities and negative feelings smoking are major risk factors fuid of self-worth. for the development of diabetic Cerebrospinal fluid (CSF) Occupational and polyneuropathy. examination is sometimes useful physiotherapy, as well as Diabetic polyneuropathy is in the investigation of peripheral psychosocial support, may primarily a distal, symmetrical neuropathy. For example, in reduce the impact of these sensory neuropathy. Sensory Guillain-Barré syndrome, CSF factors. Preservation of physical loss typically ascends from the protein concentration rises in the functions and maintenance peripheries in a “glove-stocking” frst week. In chronic infammatory of quality of life should be a pattern. This pattern reflects demyelinating polyneuropathy, priority in the management of damage according to axon length, oligoclonal IgG bands may be peripheral neuropathy. with the longest axons being present. An increase in white cell Neuropathic pain due to afected frst. Motor involvement count may be seen in HIV and small fbre neuropathy tends not is sometimes observed, but only Lyme disease. to respond well to treatment.12 later and in more severe cases. Te However, some benefit may be clinical signs are loss of vibratory Other specialised obtained by the use of drugs, such sense and proprioception refecting investigations as tricyclic anti-depressants (eg. large fibre loss. The small fibre Quantitative sensory testing, , dosulepin); anti- loss gives rise to impairment of autonomic function studies, epileptics (eg. sodium valproate, pain, light touch and temperature. molecular genetics and nerve carbamazepine), selective Reduced or absent ankle refexes biopsy (eg. sural) are some of the serotonin reuptake inhibitors occur early, but widespread loss of targeted investigations. However, (SSRI), narcotic analgesics (eg. reflexes and motor weakness are these are not routinely done and opiates) and topical agents (eg. late fndings. Diabetic dermopathy may need referral to a specialised capsaicin, patches). may occur as a manifestation unit for further assessment. Nerve blocks and local of diabetic polyneuropathy in anaesthetics may be used as a older patients. last resort to alleviate otherwise Diabetic polyneuropathy is Management intractable pain. a very significant risk factor for diabetic foot ulcers and a major Management of polyneuropathy reason for poor healing in such depends on the underlying cause Common ulcers. Diabetic polyneuropathy and its clinical presentations and neuropathies in also contributes to problems with implications. gait and balance, falls and fear Identifcation of the cause of older people of falling.14 Specifically, it can the peripheral neuropathy often cause postural instability, loss of leads to useful treatment even if it The older person is more likely ankle strength and diminished is only the removal of the causative to succumb to peripheral proprioception. agent (eg. stopping alcohol) neuropathy related to diabetes, In the UK, diagnosis of diabetic or treatment of the underlying paraproteinaemia-associated polyneuropathy is based on a two- condition (eg. diabetes, B12 malignancies and chronic part diagnostic test, consisting of defciency, HIV, Lyme disease).8 inflammatory neuropathies a symptom score and a physical It is important to identify the (eg. chronic inflammatory examination score.15 Peripheral impact of peripheral neuropathy demyelinating polyneuropathy). neuropathy is considered to be on a patient’s wellbeing. Aspects present if there are moderate or commonly missed in evaluation Diabetic polyneuropathy severe signs (≥ 6 points), even in the and management include anxiety Distal symmetric polyneuropathy is absence of symptoms, or if there are and depression, breakdown of the most common form of diabetic at least mild signs (≥3 points) in the social relationships and activities neuropathy.13 The duration and presence of moderate symptoms of daily life, sleep disturbances, severity of hyperglycaemia, presence (≥5 points). A neurologic sign inability to engage in recreational of dyslipidemia, hypertension and score of eight or more indicates

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that the patient’s feet are at high Confrmation of the diagnosis pathophysiology seems to be one risk for ulceration. depends on neurophysiological of sharing the same epitope of IgM The management of diabetic studies showing slowing of nerve MGUS and antibodies to Myelin- polyneuropathy has three main conduction. Corticosteriods, Associated Glycoprotein (MAG) elements: glycaemic control, intravenous immunoglobulin and other myelin proteins and foot care and treatment of (IVIg) and plasma exchange glycolipids. Testing for anti-MAG pain. Glycaemic control is the have all been found to be antibodies is widely available. Te most important factor in the benefcial in treatment. However, nerve conduction studies show a prevention and progression of sometimes, in pure motor chronic prolonged distal motor latency. diabetic polyneuropathy. For inflammatory demyelinating Te need for treatment in these optimal foot care, patients should polyneuropathy, symptoms worsen neuropathies is debatable because be educated to inspect their feet on corticosteroids so IVIg should they progress only very slowly. If on a daily basis to look for dry or be the frst line of treatment. necessary, cytotoxic drugs, such as cracking skin, fissures, plantar The usual regime for chlorambucil, can be used. callus formation and signs of early treatment of chronic infammatory infection between the toes and demyelinating polyneuropathy with around the toe nails. Fortunately, IVIg is infusion repeated every four Conclusion only a minority of patients weeks until maximum response with diabetic polyneuropathy is achieved. If the response to Peripheral neuropathies commonly will develop painful symptoms corticosteriods, IVIg and/or affect older people. Peripheral and sometimes pain symptoms plasma exchange is poor, cytotoxic neuropathy can be caused by axonal may resolve spontaneously. In drugs can be used. At present, damage or demyelination, as well as other cases, pain control may azathioprine is the commonest damage to large or small fbres. Te be achieved using one or more such drug in use in this situation. risk of falls and disabling symptoms of the drugs described earlier like pain are quite pronounced in under “management.” Paraproteinemic neuropathies the elderly, leading to poor quality Monoclonal gammopathy is a of life. Diabetes and heavy alcohol Chronic inflammatory common disorder, especially in use commonly cause symmetrical demyelinating older age. A small percentage of axonal . polyneuropathy these patients will develop overt Neurophysiological studies are Chronic inflammatory multiple myeloma.16 helpful in distinguishing axonal demyelinating polyneuropathy is Paraproteins may be from demyelinating neuropathies. the commonest acquired cause of associated with axonal neuropathy, However, in the presence of small chronic demyelinating neuropathy amyloid light (AL) chain amyloid fbre neuropathy, these tests ofen and typically causes symmetrical neuropathy and demyelinating are not useful. weakness and sensory changes in neuropathy.8 Monoclonal Usually, there are no the limbs, developing over a period gammopathy of undetermined specific treatments available. of more than eight weeks. It is significance (MGUS), solitary A multidisciplinary approach important to distinguish chronic myeloma or plasmacytoma with pain relief, physiotherapy, inflammatory demyelinating and POEMS (polyneuropathy, management of anxiety and polyneuropathy from chronic organomegaly, endocrinopathy, M depression are important in axonal neuropathy, because the protein band on electrophoresis, managing these patients. former, unlike the latter, responds skin hyperpigmentation) well to treatment. Te diagnosis syndrome can be associated with Conflict of interest: none is suggested by a history of a demyelinating neuropathy.8 declared. relapsing course, examination Te clinical picture is usually findings of proximal or distal of a very slowly progressive References available on weakness, and CSF findings of sensory or sensory and motor online version at www. increased CSF protein with normal demyelinating neuropathy. Ofen gmjournal.co.uk cell count.8 there is a postural tremor. The

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