Peripheral neuropathies in the elderly

Peripheral neuropathies are one of the most common clinical presentations in older people. The prevalence of peripheral neuropathies is approximately about 8,000 per 100,000 (8%) in the elderly population.¹

In Europe, diabetes mellitus is the most common underlying aetiology and tropical infections, including leprosy, remain a common underlying cause for neuropathies in South East Asia, Africa and India.² This complex condition can present as a medical or geriatric emergency. Certain acute, or sub-acute conditions such as Guillain Barre Syndrome can be fatal if there is a delay in accurate diagnosis and appropriate management. Additionally, other neuropathic conditions including vasculitic neuropathy can cause profound psychological and physical distress and may also severely restrict patients’ mobility and activities of daily living.

The underlying aetiologies of peripheral neuropathies in the elderly can be classified and described as idiopathic sensory peripheral neuropathies

About 50% of people above the age of 85 years can present with mild sensory impairment in the feet and reduced or absent ankle jerks as a result of the ageing process. However, this non-pathological idiopathic cause of neuropathies can increase the risk of postural instability and falls in older people and appropriate multi-disciplinary team based intervention is required.³

Acute cause of polyneuropathies

Guillain-Barre syndrome (GBS), also known as acute post-infective polyneuropathy or acute inflammatory demyelinating polyradiculoneuropathy, can present with progressive limb weakness and/or numbness from peripheral to proximal course. This ascending neuropathy affects respiratory muscles in approximately 20% of cases and can ultimately induce respiratory failure. Campylobactor jejuni and cytomegalovirus infections are well-recognised causes of GBS. Diagnosis is based on clinical presentations and additional confirmatory investigations include a  significantly raised cerebrospinal fluid (CSF) protein (generally >1g/l) with normal CSF cell count and glucose level. Intravenous gamma-immunoglobulin or plasmapheresis is the mainstay of management.The management plan must include urgent neurological input and serial monitoring of ventilation with regular vital capacity measurements and arterial blood gas analysis.⁴

Diabetes mellitus, the commonest aetiology of peripheral neuropathies in this age group, can cause symmetrical distal sensory polyneuropathies, acute painful neuropathy, mononeuritis multiplex, diabetic amyotrophy and autonomic neuropathy. Symmetrical sensory polyneuropathy is commonly seen as diabetic related polyneuropathy in middle and old age.

Clinical features include sensory loss in a glove and stocking distribution, loss of vibration sense and temperature sensation. Neuropathic arthropathy (Charcot’s joints) may form in ankles and Romberg’s sign may be positive. Sensory impairments in older people contribute to the risk of injuries and burns in the feet with neuropathic, painless ulcerations occurring mainly on plantar surfaces. Sensory ataxia can cause unsteadiness, poor confidence in mobility  and falls in the elderly.⁴

Malignancies

Unexplained polyneuropathies can be the presenting feature of an occult malignancy in old age. Anti-Hu antibodies could be positive in these cases. The common haematological malignancies of old age include multiple myeloma and Monocloncal Gammopathy of Undermined Significance (MGUS), which are both associated with peripheral neuropathies.

The rare and complex combination of polyneuropathies, MGUS, organomegaly (mainly hepatomegaly), gynaecomastia and skin hyperpigmentation, is known as POEM syndrome.⁴

Vasculitis

Any systemic vasculitis could cause multifocal neuropathy and/or symmetrical sensorimotor polyneuropathies. Therefore, a vasculitic screen is mandatory in the investigation of polyneuropathies in elderly people.⁴

Drugs

Polypharmacy is an ever increasing challenge and drug-related neuropathies are common in older people. Medications that potentially cause polyneuropathies in old age are anticonvulsants such as phenytoin, antibiotics such as metronidazole and nitrofurantoin, anti-arrthymatic agents such as amiodarone, anti-tuberculosis drugs such as isoniazid and others such as gold salt (a disease-modifying agent used in the treatment of rheumatoid arthritis).⁴

Alcohol and vitamin deficiencies

Alcohol excess can cause polyneuropathies due to acute alcohol intoxication or chronic use leading to thiamine deficiencies. Unless patients drink alcohol multi-vitamin deficiencies such as Vit B1, B6 and B12 should be considered as important differential aetiologies in old age. Malnutrition is a common and important problem in frail, elderly people, those with cognitive impairment and also with feeding difficulties.⁴

Metabolic causes

Thyroid disease including hypo and hyperthyroidism can cause sensorimotor polyneuropathies. This may present with vague non-specific symptoms including nausea, vomiting, abdominal discomfort and symptoms of peripheral neuropathies. The classical signs and symptoms of thyrotoxicosis may be absent (apathetic hyperthyroidism).⁴

Other causes

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a cause of  sensorimotor polyneuropathies. It develops over weeks or months and can present with a relapsing and remitting course over years. Clues to its diagnosis will be found in the history and clinical presentation, with supporting investigations including a raised CSF protein and nerve conduction studies showing axonal degeneration or peripheral demyelination patterns. Other less common aetiologies are amyloidosis, porphyria and heavy metal poisonings especially lead. HIV and syphilis should always be considered in the differential diagnosis of polyneuropathies.⁴

A comprehensive history is of course essential. Older people generally have multiple comorbidities, complex social issues and polypharmacy. Therefore the comprehensive geriatric assessment (CGA) tool should be applied appropriately in assessing an older patient with peripheral neuropathies.^3,5 The CGA focuses on the nature of presenting complaint, relevant past medical history, medication history, pre-admission social circumstances, mobility, activities of daily living and cognitive function.⁵ Collateral history from carers and or families is valuable, especially in patients suffering cognitive impairment, hearing or speech deficits. A complete neurological examination with appropriate systematic reviews should follow detailed history.

Positive findings from history and examination should appropriately guide specific investigations. These include haematinics, inflammatory markers, thyroid function test, vasculitic screen, cerebrospinal fluid (CSF) examinations and blood glucose.^3,4 Radiological investigations include chest x rays and CT/MRI scans and neurophysiological studies are central in the investigation of peripheral neuropathies.^3,4

Management of peripheral neuropathies

Multi-disciplinary team based management is vital. The provision of appropriate interventions to minimise the effects of neuropathies is required in this group of patients. The expertise of different professionals including geriatricians, physiotherapists, occupational therapists, dieticians, social workers and the community geriatric team should be employed in integrated care of these patients.⁵ Specialist neurological input should be sought as required. The mainstay of treatment is related to addressing the aetiology of neuropathies. For example, optimal glycaemic control is essential in an older patient with diabetic peripheral neuropathies.⁴ We would like to discuss the management of peripheral neuropathies now with the illustration of two case reports.

Case 1

A 71 year old woman initially presented as “off legs” after an accidental fall at home. She had background history of CREST syndrome, osteoporosis and previous use of homeopathic medications for her CREST. MRI spine showed T8 and T10 vertebral collapse but no cord compression. She had left sided weakness (power 3/5 in distal muscles and 4/5 in proximal muscles of both left arm and legs) with distal patchy sensory impairment in left hand and forearm. Tendon reflexes were reduced in left arm and leg but no extensor planter response was noted. CSF examination, nerve conduction studies, CT chest, abdomen and pelvis were normal. p-ANCA was strongly positive and a 24 hour urinary protein collection confirmed proteinuria. The diagnosis was peripheral mixed motor and sensory neuropathies secondary to systemic vasculitis. Her neuropathies resolved with considerable clinical improvement after a three days course of intravenous methylprednisolone followed by the commencement of two weekly intravenous cyclophosphamide infusions as advised by the rheumatology team. On discharge she was mobilising with a Zimmer frame. Community physiotherapy sessions, joint rheumatology and geriatric medical follow up were arranged. At three months follow up she was mobilising with one stick and her clinical condition returned to her baseline.

Case 2

A 77 year old man presented with a three month history of difficulty in walking. He complained of weakness in both legs and could only stand with assistance. He smoked ten cigarettes per day. He had a history of previous alcohol excess, but had been abstinent for three years. His neurological symptoms were initially attributed to his previous excessalcohol intake.

However his symptoms continued to progress and he was referred to the geriatric medicine out-patient clinic for further evaluation. On examination he had reduced tone bilaterally, power 3/5 distally, brisk knee reflexes bilaterally and reduced sensation to the mid-thigh in both legs. No extensor plantar response or other neurological deficit were noted. Gait was not examined as he refused to attempt to walk. The impression was of a mixed motor and sensory polyneuropathy.

All other diagnostic work up including MRI brain and spine, nerve conduction studies and vasculitic screen were normal. Of note his full blood count demonstrated a haemoglobin of 10.9g/dl (normal range 11.5-16.5g/dl) with normal MCV and MCH and ESR 29mm/hr (normal range 1-12mm/hr). CSF analysis showed high protein at 2.76g/l (normal range 0.10-0.40g/l). Serum protein electrophoresis detected monoclonal IgG lambda with normal level of IgG, IgA and IgM. Serum paraprotein quantity was less than 2g/l. Urinary electrophoresis detected monoclonal kappa light chains (Bence-Jones protein). These biochemical parameters were consistent with features of Monoclonal Gammopathy of Undetermined Significance (MGUS). He was given a three day course of intravenous methylprednisolone 1g OD after discussion with the haematology team. His neurological symptoms resolved with subsequent examination demonstrating motor power in lower limbs 5/5 with normal sensation. He was able to mobilise independently on discharge. The skeletal survey radiographs did not show any lytic lesions.

Conclusion

In the elderly, peripheral neuropathies can present as an iceberg feature with complex underlying aetiology. Its natural history may be slow but can induce rapid decline of mobility. A consideration of broad differential diagnoses and diagnostic work up is crucial in obtaining the correct diagnosis and initiating appropriate treatment. Additionally, comprehensive geriatric assessment and multi-disciplinary team based management are imperative in the management of  older patients with neuropathies.

Conflict of interest: none declared

References

1. Martyn CN, Hughes RAC. Epidemiology of peripheral neuropathy. J Neurol Neurosurg Psychiatry 1997; 62: 310-18
2. Hughes RAC. Peripheral neuropathy. BMJ 2002; 324(7335): 466-69
3. Bowler LK, Price JD, Smith SC. Peripheral neuropathies. Oxford Handbook of Geriatric Medicine. Oxford University Press 2006. 184-85
4. Kumar P, Clarke M. Polyneuropathies. Clinical Medicine 5th edition. 1212-15
5. Ellis G, Whitehead MA et al. Comprehensive geriatric assessment to older adults admitted to hospital. Cochrane Library 2011. Issue 7. www.thecochranelibrary.com