Clinical Examination of a Patient with Possible Neuropathic Pain

Home , Hyperesthesia, Hypoesthesia, Neurological examination, Referred pain

Maija Haanpää, MD, PhD18 Helsinki University Hospital, Department of Neurosurgery, Helsinki, Finland; Etera Mutual Pension Insurance Company, Helsinki, Finland

Educational Objectives Th is chapter explains the crucial role and practical performance of the bedside examination of a pain 1. State the defi nition of neuropathic pain and de- patient with suspected neuropathic pain. Despite the scribe grading methods to determine clinical cer- development of neurophysiological and neuroimaging tainty of neuropathic pain. methods, taking a history and performing a clinical ex- 2. Give an overview of the clinical examination for di- amination of a patient, using simple tools, remain the agnosing neuropathic pain. most important step in the diagnostic process. Basic knowledge of neuroanatomy, suffi cient practical train- 3. Discuss the limitations and challenges of clinical ing in neurological examination, and an analytic ap- examination in diagnosing neuropathic pain and in proach in the patient are needed. Th e accompanying diff erentiating it from other types of pain. chapters by Truini and Meier review laboratory tools, quantitative sensory testing, and confocal corneal mi- Th e Rationale for Diagnosing croscopy in assessing patients with possible neuropath- Neuropathic Pain ic pain. Neuropathic pain causes suff ering and disability for Defi nition of Neuropathic Pain many patients and is a well-known public health prob- lem. Neuropathic pain diff ers from nociceptive pain IASP defi nes neuropathic pain as “pain caused by a le- in terms of symptoms, mechanisms, and therapeutic sion or disease of the somatosensory system.” Com- management [2]. Early diagnosis is a prerequisite for pared to the former defi nition, “pain initiated or caused adequate management. Hence, the basics of clinical ex- by a primary lesion or dysfunction of the nervous sys- amination of a patient with suspected neuropathic pain tem,” the current defi nition is more restrictive and pre- should be familiar to all clinicians treating pain patients. cise by necessitating “a lesion or disease” instead of In specialized pain centers, more extensive skills should the obscure “dysfunction” and by locating it in the “so- be available for diagnosing pain conditions, including matosensory system” instead of the broader “nervous skilled clinical examination and the availability of labo- system.” For example, the new defi nition excludes pain ratory examinations needed to confi rm or exclude sus- secondary to increased muscle tone in pyramidal or ex- pected cause of the pain state. trapyramidal motor system diseases from neuropathic

Pain 2014: Refresher Courses, 15th World Congress on Pain Srinivasa N. Raja and Claudia L. Sommer, editors 201 IASP Press, Washington, D.C. © 2014 202 Maija Haanpää pain [9,14]. Th e lack of structural abnormalities in pain (non-painful visceral percepts). Descending tracts are states such as fi bromyalgia or complex regional pain also part of the somatosensory system. Th ese tracts syndrome, type I, currently excludes them from neuro- originate in cortical, subcortical, and brainstem regions, pathic pain, although there may be subgroups in these importantly including the midbrain periaqueductal diagnostic categories that fulfi ll the requirement of a gray and rostroventral medial medulla. Th e projections recognized lesion in the nervous system [20]. With ad- from the brainstem are both inhibitory and facilitatory. vances in neuroscience, new conditions are now includ- Th e variable nature of neuropathic pain is not surpris- ed in the concept of neuropathic pain, such as primary ing, considering the complexity of the somatosensory erythromelalgia, a painful condition caused by a muta- system and the myriad of ways it may be aff ected by tion in the SCCN9A gene that codes for the voltage-gat- disease or injury. Th e literature on neuropathic pain ed sodium channel NaV1.7 [6]. overemphasizes conscious perception of sensory in- Neuropathic pain is a syndrome caused by formation from the skin. However, we lack standard- a range of diff erent diseases or lesions. Neuropathic ized methodology for the assessment of pain from deep pain can arise from damage to the nerve pathways at tissues (such as muscles and joints) and from viscera, any point from the terminals of the peripheral noci- which are the more dominant areas of complaint from ceptors to the cortical neurons in the brain. It is not patients. [11] known why the same condition is painful in some patients and painless in others. Neuropathic pain is clas- Aims and General Principles sifi ed as central (originating from damage to the brain of Assessment of a Pain Patient or spinal cord) or peripheral (originating from damage to a peripheral nerve, plexus, dorsal root ganglion, or Assessment of a patient with possible neuropathic root). Of note, the term “central pain” should never be pain aims at (1) recognizing what type of pain the pa- used to describe chronifi cation of an acute pain (de- tient has—nociceptive pain, neuropathic pain, a com- spite producing central changes), as it is reserved for bination of them (called “mixed pain”) [2], or neither neuropathic pain associated with lesion(s) in the cen- of them; (2) diagnosing the disease(s) or event(s) that tral nervous system. caused the pain; and (3) recognizing the functional limitations, possible comorbidities, and other impor- Neuroanatomy of Neuropathic Pain tant aspects related to tailoring the management of the patient. Th e best clinical tools in pain assessment Th e somatosensory system comprises mechanorecep- are the clinician’s capacity to listen to patients as they tion, thermoreception, nociception, proprioception, tell their story, careful observation, and thorough and visceroception functions, providing conscious physical examination. perception of sensory information from the skin, the Medical history. It is best to initiate the med- musculoskeletal system, and the viscera [5]. Th e so- ical history by permitting patients to fully describe matosensory system can be divided into the dorsal their pain experience as they understand it. Th e his- column-lemniscal system and the spinothalamic tract tory should include questions about the location, in- system. Th e former subserves mechanoreception and tensity, character, temporal profi le, and possible exac- proprioception, and the latter thermoreception, noci- erbating factors of the pain. Concomitant symptoms ception, and visceroception. Th e two systems project should also be queried. Past medical and surgical his- via the ventrobasal and intralaminar groups of tha- tory, psychosocial history, and functional history (i.e., lamic nuclei into a network of somatosensory cortex the impact of symptoms on level of mobility, activities areas, which include the primary and secondary so- of daily living, relation with others, sleep, and mood) matosensory cortex, posterior parietal cortex, pos- are also important. terior and mid-insula, and mid-cingulate cortex. Be- Conscious observation of patients from the sides these two main systems, other pathways have very fi rst moment of the appointment—their way of been suggested to be involved in mediating somato- expressing themselves, cognition, movement, gait, and sensory functions, such as the dorsal spinocerebellar general behavior—is important in giving the physician tract (lower limb proprioception), postsynaptic dorsal a general impression and clues about any functional column pathway (pelvic organ pain), and vagus nerve impairment they may have. During the history the Clinical Examination of a Patient with Possible Neuropathic Pain 203 physician formulates hypotheses about the type of pain the nociceptive submodality. In addition, allodynia to the patient has and the possible causes of pain. light moving tactile stimuli (dynamic mechanical al- Physical examination then tests these hy- lodynia), gentle pressure (static mechanical allodynia), potheses and hence verifi es or rejects the suggested innocuous warmth (heat allodynia), or cold (cold allo- explanations for the pain. In neurological examination dynia) may occur. It is helpful to document the extent the fi ndings should be consistent when tested multiple of each abnormal sensory fi nding on a body template. times in multiple ways, and they should be consistent Depending on the patient’s symptoms, specifi c with the pre-examination observation of behavior. If tests such as straight leg testing or Tinel’s test are per- there is any discrepancy between the patient’s perfor- formed. Guidelines and review articles are recommend- mance during the history and clinical examination, tested for specifi c clinical entities such as low back pain ing needs to be repeated or modulated so that the clini- [15,16], facial pain [21,25], or peripheral neuropathy [7]. cian can titrate out the real impairment from possible functional variation due to malingering or conversion Character of Neuropathic Pain syndrome. In addition to general examination, the pain Neuropathic pain is characterized by spontaneous and area is inspected and palpated. Next, neurological ex- provoked pain and negative signs (sensory defi cits) re- amination is performed to an adequate extent. Assess- fl ecting neural damage. Many patients with neural ment of cranial nerves, motor function, deep tendon damage only have negative symptoms, but some pa- refl exes, muscle tone, coordination, gait, and balance tients also have positive symptoms such as paresthesias is performed in the usual sequence. Sensory examina- and dysesthesias, because particular pathological pro- tion, which is the most important part of the exami- cesses are engaged that increase pain sensitivity or drive nation in case of suspected neuropathic pain, is per- spontaneous activation of the nociceptive pathway. It formed next. Touch can be assessed by gently applying is not possible to draw conclusions about the etiology cotton wool to the skin, pinprick sensation by the re- of neuropathic pain from the clinical characteristics of sponse to sharp pinprick stimuli, thermal sensation by the pain [1]. Additionally, there may be other symp- warm and cold objects (e.g., water-fi lled tubes), and toms and clinical fi ndings (e.g., motor paresis, muscle vibration sensation by a 128-Hz tuning fork. Th e fi nd- cramps, and autonomic nervous symptoms) depending ings in the painful area are compared with the fi ndings on the site of the lesion. in the contralateral area in unilateral pain and in other Although neuropathic pain is often described sites on the proximal-distal axis in bilateral pain. Th e as burning, no single feature of pain is diagnostic for relation between a stimulus and the perceived sensa- neuropathic pain. However, combinations of certain tion may be changed quantitatively (hypo- or hyper- symptoms, pain descriptors, and bedside fi ndings in- phenomena), qualitatively, spatially, and temporally crease the likelihood of neuropathic pain. Screening (Table II), and in an individual patient the somatosen- tools, comprising simple questionnaires, either patient- sory fi ndings are a mosaic of aberrations in diff erent or clinician-completed, can be used to alert a clinician modalities. Sensory loss should be specifi ed with re- to the need for careful examination in search of neuro- spect to the somatosensory submodalities involved— pathic pain [3] (Table I). However, a screening tool can- tactile, thermoreceptive, or nociceptive—to pinpoint not replace careful clinical examination [11]. the type of somatosensory pathways that are damaged. Sensory gain (hyperphenomena) is basically limited to Grading of Level of Certainty of

Table II the Diagnosis of Neuropathic Sensory abnormalities found in patients with neuropathic pain Pain Quantitative Qualitative Spatial Temporal Hypoesthesia Allodynia Poor localization Abnormal latency Th e neuropathic pain grading system, summarized Hyperesthesia Paresthesia Abnormal radiation Aftersensation in Fig. 1 (modiﬁ ed from [23]), provides for three lev- Hypoalgesia Dysesthesia Summation els of certainty regarding the presence or absence Hyperalgesia of neuropathic pain in an individual patient. In all Source: Modified from [18]. cases, there should be a neuroanatomically plausible 204 Maija Haanpää

Table I Common items in neuropathic pain screening tools Item LANSS DN4 NPQ painDETECT ID Pain Pricking, tingling x x x x x Electric shocks, shooting x x x x x Hot, burning x x x x x Numbness x x x x Pain evoked by light touch x x x x Painful cold, freezing pain x x Autonomic changes x Brush allodynia x x Raised soft touch threshold x Raised pinprick threshold x x Source: Modified from [3]. Abbreviations: DN4, Douleur neuropathique 4 questions ; LANSS, Leeds Assessment of Neuropathic Symptoms and Signs; NPQ, Neuropathic Pain Questionnaire. pain distribution and a clinical history suggesting a rele- Is the Location of Pain vant lesion or disease. For defi nite neuropathic pain, the Neuroanatomically Plausible? abnormal sensory fi ndings are confi ned to the innerva- All neuropathic pains are projected; they are perceived tion territory of the lesioned nervous system structure, within the innervation territory of the damaged nerve, AND diagnostic test(s) confi rm a nervous system lesion root, or pathway owing to the somatotopic organization or disease that could explain neuropathic pain. If only of the primary somatosensory cortex. Pain drawings one prerequisite is fulfi lled, neuropathic pain is proba- are a good tool to document the distribution of pain ble, and if neither of them is fulfi lled, the certainty level (Fig. 2). Th e area of pain does not necessarily need to of neuropathic pain is unconfi rmed. Th e levels “defi nite” be identical to the innervation territory of a peripheral and “probable” indicate that the presence of neuropath- nerve or root, but it should be in a distribution that is ic pain has been established. Th e level of “possible” im- typical for the underlying disorder. A patient with a dis- plies that the presence of neuropathic pain has not yet tal nerve entrapment may also complain of pain proxi- been established. mally to the entrapment site because of referred pain.

Working hypothesis: possible neuropathic pain, if pain distribution is neuroanatomically plausible and history suggests relevant lesion or disease

Confirmatory tests: a: Negative or positive sensory signs, confined to innervation territory of the lesioned nervous structure (either in bedside sensory testing or in quantitative Neither Unconfirmed as sensory testing) neuropathic pain b: Diagnostic test confirming lesion or disease explaining neuropathic pain (e.g., neuroimaging or neurophysiological methods)

Both One

Definite Probable neuropathic pain neuropathic pain

Fig. 1. Grading system for neuropathic pain (modiﬁ ed from [23]). Clinical Examination of a Patient with Possible Neuropathic Pain 205

A B Fig. 2. Examples of pain drawings of neuropathic pain patients. (A) Radicular pain of the right C6 dermatome. (B) Painful polyneuropathy.

It is not always easy to recognize the neuroana- non-neuropathic pains from neuroanatomically plau- tomical plausibility of the pain. Th is diffi culty may re- sible distribution of neuropathic pain. In addition, result from the coexistence of diff erent pains; the patient peated testing may be helpful; the outcome of repeated draws several pains in the body template, and the loca- testing during one session should be reproducible. Posi- tion of pain is not neuroanatomically logical. Further tive sensory phenomena (allodynia and hyperalgesia) are questions about the character and occurrence of the common in nociceptive pain states, especially in infl am- pain in diff erent areas and careful clinical examination matory conditions. Even in neuropathic conditions, the can clarify the situation. In some cases the pain area area of allodynia may be extensive compared with areas may be small with regard the site of the lesion and ex- of other sensory fi ndings, refl ecting central sensitization. tent of sensory abnormality. A patient may complain of In addition, the clinical evidence of thermal and nocicep- pain in the left hand and knee, whereas clinical examina- tive hypoesthesia may be diffi cult to detect at the bedside tion reveals hemibody sensory loss and MRI scan shows because it is frequently hidden by tactile allodynia. vascular lesions in the right hemisphere [24]. Th is exam- In some cases sensory fi ndings on bedside ex- ple highlights the importance of full neurological exami- amination may be normal (although quantitative sen- nation instead examining only the pain area. sory testing may reveal mild abnormality). Classical trigeminal neuralgia is an example; abnormal fi ndings on Are Th ere Sensory Abnormalities, and bedside sensory testing strongly raise the suspicion of Are Th ey Neuroanatomically Plausible? secondary trigeminal neuralgia [10]. Clinical examina- When performing sensory testing and interpreting sen- tion alone is less sensitive than several complementary sory fi ndings, the clinician should be aware of the com- tests to document the presence of a somatosensory le- plexity of sensory aberrations. Regional areas of numb- sion [7,8]. For example, electroneuromyography is supe- ness are commonly associated with regional soft tissue rior to clinical examination alone for the diagnosis of pe- pain, especially in the presence of muscle tightness and ripheral neuropathy. Overlap of dermatomes, especially spasm. Th ese features do not necessarily mean that there in the trunk, explains normal sensory fi ndings in a lesion is a neurological dysfunction related to pain. Negative of a single intercostal nerve. In cases where neuropathic sensory phenomena (hypoesthesia and hypoalgesia) pain is caused by somatosensory pathways lacking a cu- have been reported in non-neuropathic pain, such as taneous distribution, bedside examination is unable to muscular pain [17]. It is crucial to survey the borders of show sensory aberration. Currently, validated methods sensory dysfunction to differentiate diffusely located to test sensitivity in deeper tissues are lacking. 206 Maija Haanpää

Th e location of sensory abnormalities may not [5] Cruccu G, Aminoff MJ, Curio G, Guerit JM, Kakigi R, Mauguiere F, Rossini PM, Treede RD, Garcia-Larrea L. Recommendations for the perfectly resemble published diagrams of an innervated clinical use of somatosensory-evoked potentials. Clin Neurophysiol 2008;119:1705–19. territory. Th ere are several reasons. First, there is great [6] Dib-Hajj SD, Cummins Tr, Black JA, Waxman SG. From genes to pain: variance in nerve distribution among individuals. Sec- NaV 1.7 and human pain disorders. Trends Neurosci 2007;30:555–63. [7] England JD, Asbury AK. Peripheral neuropathy. Lancet 2004;363:2151–61. ond, the area of pain and abnormal sensations can vary [8] England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, at diff erent appointments depending on pain intensity Asbury AK, Szigeti K, Lupski JR, Latov N, Lewis RA, Low PA, Fisher MA, Herrmann DN, Howard JF Jr, Lauria G, Miller RG, Polydefkis M, [19], which refl ects the dynamic modulation of sensory Sumner AJ; American Academy of Neurology. Practice parameter: evaluation of distal symmetric polyneuropathy: role of autonomic testing, function. In addition, bilateral sensory abnormalities nerve biopsy, and skin biopsy (an evidence-based review). Report of the are possible in neuropathic pain conditions regarded as American Academy of Neurology, American Association of Neuromus- cular and Electrodiagnostic Medicine, and American Academy of Physi- unilateral, such as postherpetic neuralgia [12,13]. cal Medicine and Rehabilitation. Neurology 2009;72:177–84. [9] Geber C, Baumgärtner U, Schwab R, Müller H, Stoeter P, Dieterich M, Sommer C, Birklein F, Treede RD. Revised defi nition of neuropathic Is Th ere a Need for Further Examination? pain and its grading system: an open case series illustrating its use in clinical practice. Am J Med 2009;122(10 Suppl):S3–12. Finally, it is important to emphasize that the clinical ex- [10] Gronseth G, Cruccu G, Alksne J, Argoff C, Brainin M, Burchiel K, Nur- mikko T, Zakrzewska JM. Practice parameter: the diagnostic evaluation amination can never prove any pain to be of neuropath- and treatment of trigeminal neuralgia (an evidence-based review): re- ic origin, but can only provide supporting evidence for port of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. altered function of the nervous system. Th e fi nal diag- Neurology 2008;71:1183–90. nosis is always a result of the interpretation of all avail- [11] Haanpää M, Attal N, Backonja M, Baron R, Bennett M, Bouhassira D, Cruccu G, Hansson P, Haythornthwaite J, Iannetti G, Jensen T, Kauppi- able information. la T, Nurmikko T, Rice A, Rowbotham M, Serra J, Sommer C, Smith B, Treede R-F. NeuPSIG guidelines on neuropathic pain assessment. Pain Th e need for further investigations is consid- 2011;152:14–27. ered individually, depending on the clinical question [12] Haanpää ML, Laippala PA, Nurmikko TJ. Th ermal and tactile perception thresholds in acute herpes zoster. Eur J Pain 1999;3:375–86. and available consultation services. Tests in a special- [13] Haanpää M, Laippala P, Nurmikko T. Allodynia and pinprick hypesthe- sia in acute herpes zoster, and the development of postherpetic neural- ized center may include conventional electrophysio- gia. J Pain Symptom Manage 2000;20:50–8. logical procedures, quantitative somatosensory testing, [14] Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice AS, Treede RD. A new defi nition of neuropathic pain. Pain 2011;152:2204–5. neuroimaging, blood and cerebrospinal fl uid samples, [15] Kreiner DS, Hwang SW, Easa JE, Resnick DK, Baisden JL, Bess S, Cho and less conventional laboratory tools to assess the no- CH, DePalma MJ, Dougherty P 2nd, Fernand R, Ghiselli G, Hanna AS, Lamer T, Lisi AJ, Mazanec DJ, Meagher RJ, Nucci RC, Patel RD, Sem- ciceptive pathways in the peripheral as well as central brano JN, Sharma AK, Summers JT, Taleghani CK, Tontz WL Jr, Toton JF. An evidence-based clinical guideline for the diagnosis and treatment nervous system. of lumbar disc herniation with radiculopathy. Spine J 2014;14:180–91. Even after relevant clinical examination and [16] Lee J, Gupta S, Price C, Baranowski AP; British Pain Society. Low back and radicular pain: a pathway for care developed by the British Pain So- further examinations, pain may remain without a spe- ciety. Br J Anaesth 2013;111:112–20. [17] Leffl er AS, Hansson P. Painful traumatic peripheral partial nerve inju- cifi c explanation. Medically unexplained symptoms ry-sensory dysfunction profi les comparing outcomes of bedside exami- refer to symptoms for which no clear or consistent or- nation and quantitative sensory testing. Eur J Pain 2008;12:397–402. [18] Lindblom U. Analysis of abnormal touch, pain and temperature sensa- ganic pathology can be demonstrated (although organ tion in patients. In: Boivie J, Hansson P, Lindblom U, editors. Touch, temperature and pain in health and disease. Progress in pain research dysfunction may be an integral part of the symptom) and management, vol. 3. Seattle: IASP Press; 1994. p. 63–84. [4]. Th e term is purely descriptive and does not imply [19] Moriwaki K, Yuge O. Topographical features of cutaneous tactile hy- poesthetic and hyperesthetic abnormalities in chronic pain. Pain psychogenesis. In these cases it is important to fi nd a 1999;81:1–6. balance between excluding and treating organic causes [20] Oaklander AL, Herzog ZD, Downs HM, Klein MM. Objective evidence that small-fi ber polyneuropathy underlies some illnesses currently la- and overinvestigating. Supportive care is mandatory, beled as fi bromyalgia. Pain 2013;154:2310–6. [21] Siccoli MM, Bassetti CL, Sándor PS. Facial pain: clinical diff erential di- and it is important to acknowledge the patient’s suff er- agnosis. Lancet Neurol 2006;5:257–67. ing, as is the case for all pain patients [22]. [22] Stone L. Explaining the unexplainable: crafting explanatory frame- works for medically unexplained symptoms. Aust Fam Physician 2011;40:440–4. [23] Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffi n References JW, Hansson P, Hughes R, Nurmikko T, Serra J. Redefi nition of neuropathic pain and a grading system for clinical use: consensus statement on clinical and research diagnostic criteria. Neurology 2008;70:1630–5. [1] Attal N, Fermanian C, Fermanian J, Lanteri-Minet M, Alchaar H, Bou- [24] Vestergaard K, Nielsen J, Andersen G, Ingeman-Nielsen M, Arendt- hassira D. Neuropathic pain: are there distinct subtypes depending on Nielsen L, Jensen TS. Sensory abnormalities in consecutive, unselected the aetiology or anatomical lesion? Pain 2008;138:343–53. patients with central post-stroke pain. Pain 1995;61:177–86. [2] Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophys- [25] Zakrzewska JM. Diff erential diagnosis of facial pain and guidelines for iological mechanisms, and treatment. Lancet Neurol 2010;9:807–19. management. Br J Anaesth 2013;111:95–104. [3] Bennett MI, Bouhassira D. Epidemiology of neuropathic pain: can we use the screening tools? Pain 2007;132:12–3. [4] Burton C. Beyond somatisation: a review of the understanding and Correspondence to: Maija Haanpää, MD, PhD, Helsinki Uni- treatment of medically unexplained physical symptoms (MUPS). Br J versity Hospital, Department of Neurosurgery, PO Box 266, Gen Pract 2003;53:231–9. 00029 HUS, Finland. Email: maija.haanpaa@etera.fi .