Assessment of polyneuropathy

polyuria, polydipsia, weight loss, may have blurred vision

retinopathy, Charcot's joints, hypertension

mental slowing, depression, dementia, fatigue, weight gain, constipation, dry skin, hair loss, cold intolerance, hoarse voice, irregular menstruation, infertility, muscle weakness, muscle pain

goitre, dry skin, hair loss, bradycardia, hypercholesterolaemia, hoarse voice, delayed return of deep tendon reflexes

memory loss, paraesthesias, gait unsteadiness, Lhermitte's sign (electric shock-like sensations extending down the cervical spine radiating to the limbs), nitrous oxide misuse; history of chronic gastrointestinal illness or surgery, advancing age, pregnancy, vegan diet, long-term use of certain medications (e.g., metformin, proton-pump inhibitors, and anticonvulsants), unexplained fatigue, memory loss; consider pernicious anaemia

ataxia, peripheral neuropathy, impaired memory, atrophic glossitis

history of alcohol-use disorder; medicine use (e.g., vinca alkaloids, platinum analogues, taxols, dapson, isoniazid, nitrofurantoin, fluoroquinolones, amiodarone, colchicine, phenytoin, statins, or thalidomide); exposure to toxins/heavy metals (e.g., arsenic, lead, thallium, mercury, acrylamide, carbon disulfide, methylbutyl ketone, or triorthocresyl phosphate)

often no distinguishing features; may be signs of ethanol misuse (e.g., hepatomegaly, tremor, spider anigomata), or heavy metal poisoning (e.g., Mees' lines)

age >40 years, very slow symptom progression; numbness and pain in feet, poor balance

impairment of sensation in distal lower extremities with few motor signs

neck or back pain which radiates into a limb along a dermatomal pattern; weakness, paresthesiae, and/or numbness along the distribution of the involved root(s); multiple adjacent radiculopathies may mimic polyneuropathy; once localised to the spinal nerve roots, the differential is broad

decreased strength and sensation in the distribution of the affected nerve root; depressed reflexes in a myotomal pattern, rather than a length dependent manner; features of chronic muscle atrophy may be present; positive Spurling or straight leg raise test may be present

rapid symptom progression (nadir often reached in 2 weeks); often occurs 1 to 3 weeks following a respiratory or gastrointestinal illness; may also follow infection with Zika virus which presents with rash, low grade fever, myalgia, and conjunctivitis; paraesthesias often precede the onset of weakness; ascending paralysis most common; Miller Fisher syndrome variant may present with areflexia, ataxia, and ophthalmoplegia

diffuse weakness (proximal and distal muscle groups); globally reduced or absent reflexes; sensory impairments may be mild; normal sphincter function

rapidly progressive numbness and weakness in the legs; loss of bladder and bowel function; back pain

severe; diffuse weakness and sensory impairment in the legs and perineum; absent reflexes in lower extremities; decreased anal sphincter tone; large post-void residual urine volume

subacute or step-wise progression; numbness and weakness is patchy; pain; weight loss; fevers

hypertension (possible consequence of vasculitis); palpable purpura; weakness and numbness in pattern of multiple single, large nerves (multiple mononeuropathies); reflexes only absent in affected regions

weakness (e.g., foot drop) usually prompts presentation to a physician; symptoms progress over weeks to months

moderate-to-severe muscle weakness; proximal muscle groups may be as weak as distal muscle groups, globally reduced/absent reflexes; sensory impairments may be similar in the upper and lower extremities (not a clearly distal or length-dependent pattern)

headaches, fatigue, visual disturbances, change in shoe size, carpal tunnel syndrome

coarsening facial features, frontal bossing, hypertension, hyperhidrosis, hypertrophic arthropathy, visual field loss, cranial nerve palsies, large hands and feet, protruding jaw, widely spaced teeth

exposure to blood/body fluids (e.g., history of drug misuse, blood transfusion, unprotected intercourse), weight loss >10%, fever and diarrhoea for at least 1 month[55]Mindel A, Tenant-Flowers M. ABC of AIDS: Natural history and management of early HIV infection. BMJ. 2001;322:1290-1293. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1120386/?tool=pubmed http://www.ncbi.nlm.nih.gov/pubmed/11375235?tool=bestpractice.com

lymphadenopathy; fever, oropharyngeal and anogenital ulceration

exposure to blood/body fluids (e.g., history of drug misuse, blood transfusion, unprotected intercourse), malaise

jaundice, ascites, Dupuytren's contracture, features of cryoglobulinaemia, mononeuritis multiplex, palpable purpura

low-grade fever, malaise, headache, sore throat

pharyngitis, stridor, wheezing, myocarditis

prolonged contact with affected individuals, prolonged stay in endemic areas (including Brazil, India, Pakistan, Africa or southeast Asia)

weakness and paralysis of the small muscles of the hands and feet and eyes, asymmetric/patchy weakness of the face, anaesthetic patches, contractures, skin lesions

dry eyes and mouth, blurred vision, difficulty swallowing food, cracking of lips and corners of the mouth, arthralgias, dry skin, cough[56]Vitali C, Moutsopoulos HM, Bombardieri S. The European Community Study Group on diagnostic criteria for Sjögren's syndrome. Oral involvement in Sjögren's syndrome. Sensitivity and specificity of tests for ocular and oral involvement in Sjogren's syndrome. Ann Rheum Dis. 1994;53;637-647. http://ard.bmj.com/cgi/reprint/53/10/637 http://www.ncbi.nlm.nih.gov/pubmed/7979575?tool=bestpractice.com [57]Carsons S. A review and update of Sjogren's syndrome: manifestations, diagnosis and treatment. Am J Manag Care. 2001;7(suppl 14):S433-S443. http://www.ncbi.nlm.nih.gov/pubmed/11605978?tool=bestpractice.com

conjunctivitis, mucous threads, angular cheilitis, tooth decay/loss, parotid and/or submandibular gland enlargement, dry mucosa, trigeminal neuropathy; distal polyneuropathy or painful small fibre neuropathy[12]de Greef BTA, Hoeijmakers JGJ, Gorissen-Brouwers CML, et al. Associated conditions in small fiber neuropathy - a large cohort study and review of the literature. Eur J Neurol. 2018 Feb;25(2):348-355. https://www.doi.org/10.1111/ene.13508 http://www.ncbi.nlm.nih.gov/pubmed/29112785?tool=bestpractice.com

fatigue, fever, weight loss, arthralgia, photosensitivity/skin rashes, Raynaud's phenomenon

arthritis, butterfly rash, alopecia, hepatomegaly, splenomegaly, cranial neuropathies, peripheral neuropathy

may have weakness

often no distinguishing features, a minority present with prominent, diffuse weakness and global areflexia (chronic inflammatory demyelinating polyradiculoneuropathy with monoclonal antibody of unknown significance)

depends on organs affected, fatigue, weight loss, carpal tunnel syndrome, easy bruising, impotence, orthostatic lightheadedness, constipation or diarrhoea, renal failure

primary (AL): oedema (nephrotic syndrome), CHF, autonomic polyneuropathy (postural hypotension), sensory polyneuropathy, hepatomegaly, macroglossia, splenomegaly (rare); secondary (AA): hepatomegaly, splenomegaly, rare cardiac involvement, no macroglossia; familial (e.g., mutation of the abundant plasma protein transthyretin--ATTR); prominent peripheral sensorimotor and autonomic neuropathy; no macroglossia

fatigue, decreased urine output, oedema, discoloured urine, vomiting, seizures; neuropathy may develop in pre-dialysis or post-dialysis settings

hypertension, oedema, pericarditis, encephalopathy

weight loss, night sweats, known malignancy

sensory ataxia, multifocal sensorimotor neuropathy or symmetric polyneuropathy; sensory loss may be non-length dependent if the dorsal root ganglion is affected

possible alcohol-use disorder or prior bariatric surgery, severe burning dysaesthesias, tends to be subacute-to-chronic progression but may occur over a few days

cardiomegaly, congestive heart failure, peripheral oedema, tachycardia; if concomitant Wernicke-Korsakoff's syndrome, confusion, nystagmus, ataxia, and ophthalmoplegia

skin changes, depression, irritability, chronic renal failure requiring peritoneal dialysis, alcohol-use disorder; deficiency associated with exposure to medications including isoniazid and hydralazine; toxicity may develop with excess iatrogenic repletion or over the counter supplementation

seborrhoeic dermatitis, atrophic glossitis, angular cheilitis, conjunctivitis, confusion

history of tick bite and ‘bulls-eye’ rash, monoarticular or oligoarticular arthritis, followed by variable neurological symptoms; prolonged stay in an endemic area (selected areas of northeast and midwest United States or central and eastern Europe)

erythema migrans, facial palsy, radiculoneuropathy, aseptic meningitis

history of cystic fibrosis, small bowel bacterial overgrowth, pancreatic insufficiency, gluten-sensitive enteropathy

spinocerebellar ataxia, retinopathy, myopathy

history of gastric surgery, zinc overdose

anaemia and leukopenia (in half of patients); sensory ataxia, brisk reflexes except for depressed ankle reflexes; Babinski's sign; impaired dorsal column sensation; may have Lhermitte's sign (electric shock-like sensations extending down the cervical spine radiating to the limbs)[64]Kumar N, Gross JB Jr, Ahlskog JE: Myelopathy due to copper deficiency. Neurology. 2003;61:273-274. http://www.ncbi.nlm.nih.gov/pubmed/12874423?tool=bestpractice.com

long-standing difficulty standing on heels or toes, unable to find shoes that fit, high arches, hammertoes

pes cavus, hammertoes, distal muscle atrophy (especially in distal calf and shin causing 'stork' or 'champagne bottle' appearance), weakness

family history (autosomal dominant); episodic (symptom free between attacks); abdominal pain, constipation, urinary retention, red-purple urine; paraesthesia, paralysis; psychiatric symptoms: psychosis, anxiety, depression, agitation, delirium; acute episode may be triggered by medicines such as barbiturates, carbamazepine, valproic acid, and ergot preparations

during attack: fever, tachycardia, elevated BP; predominantly motor peripheral neuropathy with marked involvement of proximal upper extremities; autonomic neuropathy

slow or clumsy gait, urinary and erectile dysfunction, urinary incontinence, poor balance, usually male

spastic paresis

headache, nausea, paresis, intellectual disability, ataxia, visual and hearing disorders

reduced or absent tendon refluxes

symptoms more common in males (X-linked disorder); neuropathic pain crises affecting hands and feet, may be exacerbated by stress, exercise, or temperature changes; abdominal pain, diarrhoea; syncope, exercise intolerance (suggesting cardiac manifestations)[65]Sun A. Lysosomal storage disease overview. Ann Transl Med. 2018 Dec;6(24):476. https://www.doi.org/10.21037/atm.2018.11.39 http://www.ncbi.nlm.nih.gov/pubmed/30740407?tool=bestpractice.com

angiokeratomas (skin and mucous membranes), corneal abnormalities, renal insufficiency[66]Brady RO, Schiffmann R. Clinical features of and recent advances in therapy for Fabry Disease. JAMA. 2000;284:2771-2775. http://www.ncbi.nlm.nih.gov/pubmed/11105184?tool=bestpractice.com

episodic psychiatric disturbance with crampy abdominal pain and painful neuropathy; generalised weakness

retinitis pigmentosa, blindness, anosmia, deafness, sensory neuropathy, ataxia[69]Wierzbicki AS, Lloyd MD, Schofield CJ, Feher MD et al. Refusm disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation. J Neurochem. 2002;80:727-735. http://www.ncbi.nlm.nih.gov/pubmed/11948235?tool=bestpractice.com

early manifestations of coronary artery disease

yellow discolouration of tonsils and adenoids, corneal opacification, retinal pigmentary changes

patients with sepsis and multiple organ failure may develop a rapidly progressive polyneuropathy; often first suspected when a patient fails to wean from ventilatory support[71]Hermans G, De Jonghe B, Bruyninckx F, et al. Clinical review: critical illness polyneuropathy and myopathy. Crit Care. 2008;12:238. http://www.ncbi.nlm.nih.gov/pubmed/19040777?tool=bestpractice.com

flaccid and usually symmetrical weakness is typical

gastrointestinal (GI) distress following consumption of gluten-containing foods; neuropathy may precede GI symptoms and is typically a sensorimotor axonal peripheral neuropathy.[24]Thawani SP, Brannagan TH 3rd, Lebwohl B, et al. Risk of Neuropathy Among 28,232 Patients With Biopsy-Verified Celiac Disease. JAMA Neurol. 2015 Jul;72(7):806-11. https://www.doi.org/10.1001/jamaneurol.2015.0475 http://www.ncbi.nlm.nih.gov/pubmed/25962148?tool=bestpractice.com [25]Zis P, Sarrigiannis PG, Rao DG, et al. Gluten neuropathy: prevalence of neuropathic pain and the role of gluten-free diet. J Neurol. 2018 Oct;265(10):2231-2236. http://www.ncbi.nlm.nih.gov/pubmed/30032386?tool=bestpractice.com Symptoms may improve with a gluten-free diet.

abdominal tenderness, hepatosplenomegaly, dermatitis herpetiformis rash

neck or back pain may be absent but hip or shoulder pain may be more prominent; symptoms are regional and do not fit a single nerve or nerve root; once localised to the plexus, the differential is broad

decreased strength and sensation and depressed reflexes involving multiple adjacent spinal levels or adjacent terminal nerves, rather than in a length dependent manner; features of chronic muscle atrophy may be present