Sensory loss (Diagnostic approach) INTRODUCTION 1. Sensory loss may be due to disorders of CNS or PNS. As in most of neurology, initial goal when confronted with patient with sensory loss is localization of lesion using information from Hx and PE. This narrows differential diagnosis and directs further investigations. Localization requires understanding of anatomy of sensory system. ANATOMY 1. Perception of somatic sensation depends on detection of stimulus by specialized receptors in skin, muscle, or joint. Information from these receptors is then transmitted via peripheral nerves to CNS. With exception of mesencephalic nucleus, whose projections carry proprioceptive information from muscles of mastication, cell bodies of primary sensory 2. 3. 4. neurons that constitute peripheral nerves reside in ganglia outside of CNS. Projections from these ganglia then enter CNS to synapse with second order neurons. The peripheral nerves are made up of large myelinated fibers that transmit proprioceptive, vibratory, pressure, and touch, and small, poorly myelinated fibers that transmit pain, temperature, and touch. (Note that touch is transmitted by both large and small fibers.) Projections from cell bodies receiving pain, temperature, and touch stimuli enter spinal cord via dorsal nerve root. These fibers terminate in dorsal horns, fanning out over several segments. They synapse with 2nd order neurons in dorsal horns. These neurons then cross midline of cord in anterior commissure in front of central canal, and these second order neurons ascend (now on opposite side of spinal cord to peripheral nerve) in either anterior spinothalamic tract (touch) or lateral spinothalamic tract (pain and temperature) to VPL nucleus of thalamus. Here, they synapse with neurons which ascend to primary sensory cortex in parietal lobe. Projections from dorsal root ganglia that carry proprioceptive, vibratory, pressure, and touch stimuli directly enter dorsal columns from dorsal roots. The gracile column is medial and carries stimuli from lumbar and thoracic region; cuneate column begins laterally in cervical region, which it subserves. Thus, dorsal columns consist of first order neurons traveling ipsilateral to peripheral nerve from which they originate. These neurons synapse with second order neurons in cuneate and gracile nuclei of medulla. These second order neurons cross in dorsal midline of medulla and ascend through brainstem as medial lemniscus to VPL nucleus of thalamus where they synapse with 3rd order neurons which project through internal capsule and centrum semiovale to primary sensory cortex in parietal lobe. As with motor cortex, primary sensory cortex is arranged somatotopically, with face represented laterally, close to Sylvian fissure. The hand and arm are represented just above region for face and leg is represented medially, similar to layout of motor homunculus. DEFINITION 1. Sensory loss is categorized as follows. A. Hypoesthesia is diminished ability to perceive pain, temperature, touch, or vibration. B. Anesthesia is complete inability to perceive pain, temperature, touch, or vibration. C. Hypalgesia is decreased sensitivity to painful stimuli. D. Analgesia is complete insensitivity to painful stimuli. 2. Hyperpathia, hyperesthesia, and allodynia refer to increased sensitivity to sensory stimuli. EXAMINATION 1. The goal of sensory examination is to "localize lesion." This portion of examination tends to be subjective because it relies on patient's responses to various stimuli; thus, it is usually done following motor examination. With more objective data obtained from motor examination, 2. 3. examiner is often able to narrow down differential and proceed with more focused sensory examination, resulting in less frustration for both patient and examiner. The primary sensory modalities usually are examined first. These include touch, proprioception, vibration, temperature, and pain. Abnormalities in these sensations may occur with any sensory syndrome (peripheral nerve injury, radiculopathy, spinal cord syndromes, thalamic and cerebral hemispheric syndromes). A disproportionate loss of vibration sense and proprioception, compared with pain and temperature sensation, tends to occur with diseases of dorsal columns of spinal cord (tabes dorsalis, vitamin B12 deficiency, multiple sclerosis) and also with demyelinating neuropathies and sensory neuronopathies. Higher cortical sensation can be examined if touch sensation remains relatively preserved and patient is suspected of having cortical lesion. Examination of cortical sensation includes two point discrimination, graphesthesia, stereognosis, and extinction. A. Two point discrimination is ability to recognize 2 points applied simultaneously to skin as distinct from single point. B. Graphesthesia is ability of patient to identify numbers or letters drawn in palm of hand. C. Stereognosis is ability to recognize common objects such as keys, coins or paper clips by touching or handling them with one's eyes closed. D. Extinction is evaluated by simultaneously touching two separate points on either side of body. The test is abnormal if patient consistently identifies stimulus on only one side of body. Extinction is seen in relatively large parietal lesions. 4. Romberg is test of proprioception. It is positive when patient is able to stand with feet together and eyes open without losing his balance but is unable to remain steady with eyes closed. This occurs because patients are using their eyes to compensate for lack of sensory feedback they are receiving from their lower extremities. A functional correlate of this often comes out in history when patient notes that he loses his balance when he gets up at night in darkened room. PATTERN 1. Hx and PE are keys to determining cause of sensory loss. Ancillary studies may be helpful in 2. selected circumstances. Sensory loss that is confined to part of limb suggests injury to peripheral nerve, nerve plexus, or spinal root (mononeuropathy or radiculopathy). In contrast, sensory loss involving most of extremity or trunk suggests presence of other disorders that may be distinguished as follows. A. Involvement of both sides of body is consistent with polyneuropathy or spinal cord disease, while involvement of one side is consistent with contralateral disease of brainstem, thalamus, or cerebral cortex. B. A sensory level is consistent with spinal cord disease or, more rarely, lateral medullary infarction. C. D. E. Sensory loss of face suggests disease above spinal cord (brainstem, thalamus, or cerebral hemispheres). With lower brainstem disease (lateral medullary syndrome), sensory loss on face is typically opposite that of body, although ipsilateral sensory loss has also been reported; sensory loss is on same side of face and body with upper brainstem, thalamic, or hemispheric disease. "Stocking-glove" sensory loss is most commonly seen with length dependent axonal neuropathies, although other disorders may also present with this pattern. Disproportionate loss of vibration sense and proprioception, compared with pain and temperature sensation, tends to occur with diseases of dorsal columns of spinal cord (tabes dorsalis, vitamin B12, multiple sclerosis) and demyelinating polyneuropathy. 3. Neuropathy A. Mononeuropathy and radiculopathy i. Mononeuropathies refer to pathology affecting individual peripheral nerve. One common example is carpal tunnel syndrome; patients with carpal tunnel syndrome frequently complain of numbness and tingling in median nerve distribution that can be particularly bothersome at night, often awakening them from sleep. This may or may not be accompanied by wrist pain that can radiate up arm or into hand. Mononeuropathies are diagnosed clinically based on signs and symptoms that correlate with individual nerve distribution. ii. Radiculopathies refer to pathology affecting nerve root, resulting in S/S in corresponding dermatome and myotome. Because of overlap in nerve root innervation of both individual muscles and dermatomes, weakness and sensory loss can be mild and/or not involve entire region described on dermatome/myotome maps. Instead, smaller "signature zones" of sensory loss may define level of nerve root involvement (table 1). Although radiculopathies may not cause significant sensory loss, they characteristically result in paroxysmal severe lancinating pain that may be exacerbated by coughing, sneezing, or straining. iii. Occasionally it is difficult to differentiate mononeuropathy from radiculopathy clinically. As example, both peroneal nerve palsy and L5 root lesion can result in drop foot and numbness over lateral aspect of leg and dorsum of foot. Electrodiagnostic testing (NCS and EMG) are useful in distinguishing between these conditions. In peroneal palsy, NCS may demonstrate focal slowing in peroneal nerve at fibular head, while in L5 radiculopathy there may be evidence of denervation in L5 muscles outside of peroneal territory (tibialis posterior or flexor digitorum longus, both of which are innervated by tibial portion of sciatic nerve). B. Stocking-glove sensory loss i. Stocking-glove sensory loss is term used to describe sensory loss affecting distal lower and upper extremities that is most commonly seen in length-dependent axonal neuropathies. 1. Diabetes mellitus 2. Alcohol 3. Vitamin B12 deficiency 4. Syphilis 5. HIV 6. Lyme disease ii. 7. Uremia 8. Chemotherapy 9. Vasculitis 10. Paraneoplastic neuropathy 11. Amyloidosis With axonal neuropathies, the longest axons are affected first. Thus, symptoms start distally and progress proximally. Patients typically do not have noticeable numbness in their hands until sensory S/S has progressed to knee. iii. iv. v. vi. vii. viii. The examination usually reveals decrease in vibration threshold, pinprick, and temperature distally. Diminished proprioception at great toe is typically also evident on careful examination, but can be difficult to detect. In combined large and small fiber neuropathies, ankle jerk is frequently diminished or absent. Patients with pure small fiber neuropathies will primarily demonstrate loss of pinprick and temperature distally, although vibration perception can also be affected. Proprioception and DTR remain intact. Length dependent axonal neuropathies are generally very slowly progressive. Other etiologies need to be considered if patient presents with stocking-glove pattern of sensory loss in which symptoms present in hands and feet simultaneously, or if symptoms evolve quickly over several days to weeks. Occasionally patients with mononeuritis multiplex due to vasculitis do not seek medical attention unless their S/S progress to become confluent and resemble stocking-glove pattern. Hx and PE help to differentiate mononeuritis multiplex from length dependent axonal neuropathy: patient will give history of stepwise sensory loss in discrete nerve distributions (ulnar aspect of hand, then peroneal distribution in foot). Furthermore, weakness, which is not usually significant complaint in length dependent axonal neuropathies, typically accompanies sensory loss in mononeuritis multiplex. Patients with GBS may present with numbness or paresthesias affecting their feet and hands. In this situation, the symptoms will have been present only a short time before the patient presents to medical attention. There may or may not be a history of an antecedent infection. The patient develops progressive weakness soon after the onset of sensory loss or paresthesias. The examination should reveal areflexia or depressed reflexes. Sensory loss should be minimal in comparison to the weakness and predominantly affects the larger myelinated fibers carrying proprioception and vibration. Occasionally, patients with variant of CIDP present with history and examination that are most suggestive of length dependent axonal neuropathy. In this situation, symptoms and signs are predominantly distal and sensory as opposed to more common form of CIDP where symmetric proximal and distal motor weakness is predominant symptom. EMG and NCS are helpful in differentiating this variant of CIDP from axonal neuropathy. Central lesions affecting cervical spinal cord can also present with stocking-glove pattern of sensory loss. In younger population, this may be presenting symptom of demyelinating lesion in cervical cord. In older population, this is frequently caused by cervical spondylosis with cord impingement. Imaging studies are required to positively identify precise etiology. Hyperreflexia, spasticity (clonus, increased tone), and extensor plantar responses are helpful in pointing to central cause. C. Sensory neuronopathies i. Sensory neuronopathies are very rare causes of sensory loss. They result from degeneration at level of dorsal root ganglion and manifest with sensory ataxia, absent reflexes, and dysesthesias, as well as sensory loss. They are differentiated from length-dependent sensory neuropathies in several ways. 1. Sensory neuronopathies do not necessarily follow length-dependent pattern. In addition, they are frequently asymmetric. As example, patients may present with initial numbness in dermatomal distribution in one hand or even in face. 2. Sensory neuronopathies lack motor involvement. In contrast, patients with length dependent neuropathies may not complain of weakness, but mild motor abnormalities can often be found on detailed clinical examination ii. iii. and/or NCS. 3. Sensory neuronopathies tend to be much more disabling than length-dependent axonal neuropathies. As they progress, patients develop profound sensory ataxia, and almost always decline to point where mobility aids are required (cane, walker and/or wheelchair). Sensory neuronopathies are most often associated with paraneoplastic phenomenon. The latter is most commonly associated with SCLC and presence of anti-Hu antibodies. Other causes of sensory neuronopathy. 1. Sjogren's syndrome 2. Guillain-Barre syndrome variant 3. Chemotherapy-induced, especially platinum drugs 4. Vitamin B6 toxicity 5. Friedreich ataxia D. Investigation i. NCS and EMG can be helpful in characterizing neuropathies (axonal vs. demyelinating, acquired vs. hereditary). These studies are also helpful for discriminating whether sensory pathology is proximal or distal to DRG. As example, radiculopathies that are caused by pathology proximal to DRG result in sensory loss in corresponding dermatome, but NCS reveal normal sensory response. In contrast, ii. iii. axonal lesions distal to DRG result in low amplitude or absent sensory responses. Laboratory investigations are worthwhile to rule out treatable causes (DM, lymphoproliferative disorders, uremia, vitamin B12 deficiency, syphilis, HIV, and Lyme disease) if history, physical examination, and electrophysiologic workup reveal generalized sensorimotor axonal neuropathy (table 2). Unfortunately, etiology is not always identified. In 2 separate studies of patients referred to tertiary care neuromuscular clinics for evaluation of peripheral neuropathy, approximately 25% remained undiagnosed after extensive workup. 4. Spinal cord lesions A. Cape distribution sensory loss i. Cape distribution sensory loss is uncommon but well described pattern of sensory loss resulting from lesions of central cervical cord. The classic presentation involves diminution or loss of sensation for pinprick and temperature across upper back, shoulders, and upper arms resulting from lesions that involve spinothalamic neurons as they cross in anterior commissure in cervical cord. The differential diagnosis includes tumor, syrinx, and demyelination. B. Brown-Sequard syndrome i. Brown-Sequard syndrome results from lesion involving only one side of spinal cord. In this situation, patient presents with diminished proprioception, vibration, and weakness on side ipsilateral to lesion, and decreased pinprick and temperature sensation on contralateral side. Hyperesthesia or pain may also occur ipsilateral to lesion. Small lesions, such as those caused by demyelination, can result in isolated involvement of dorsal columns or spinothalamic tracts resulting in ipsilateral abnormalities in proprioception and vibration or contralateral abnormalities in pinprick and temperature. C. Imaging study i. MRI is imaging method of choice in suspected spinal cord lesions as it is far more sensitive than CT in this situation. When spinal cord lesion is suspected it is important to remember that sensory level found on examination indicates that 5. lesion itself is at or above that level. The spinal cord levels or dermatomes are presented for upper and lower extremities. It is not uncommon for patients to present with ascending pattern of sensory loss from cervical cord lesion. Depending on when patient is examined, different sensory levels will be found for same lesion. Thus, in working up suspected spinal cord lesions, the physician must image cord from the neck (cervical region) to sensory level found on examination. Brainstem lesion A. There are several classic patterns of sensory loss found with lesions at various levels of brainstem. Most brainstem lesions involve cranial nerves and/or their nuclei. The resultant signs and symptoms tend to be more useful in localizing lesion than are B. sensory findings in isolation. Wallenberg syndrome is probably the most well-known brainstem abnormality leading to sensory loss. It results from lesion of lateral medulla and was originally described as involving pain and temperature loss on ipsilateral face and contralateral limbs and trunk. However, several other patterns of pain and temperature loss have been described in association with this syndrome, including contralateral face and bilateral face involvement. Accompanying signs and symptoms include loss of vibration and proprioception as well as ataxia in ipsilateral limbs. An ipsilateral Horner's syndrome, vertigo, nystagmus, hoarseness, and dysphagia are often present. C. 6. 7. The optimal initial investigation when history and examination suggest brainstem lesion is brain MRI. Head CT are rarely useful as artifact resulting from skull base obscures brainstem images. Thalamic lesion A. Thalamic lesions may cause contralateral sensory deficit that involves all sensory modalities to varying degrees. Although tumors and abscesses can involve thalamus, typically onset of sensory loss in thalamic lesions is acute or subacute and is result of lacunar infarct. B. Thalamic pain syndrome, type of central post-stroke pain, has been well described and is not uncommon in recovery phase of these infarcts. Often sensory examination is normal but patient experiences severe pain that may be paroxysmal and exacerbated by touch over contralateral hemibody. Sensory cortex A. Discrete lesions of the sensory cortex are unusual. When they occur only small part of body is affected (corresponding to region of homunculus where lesion is found). Any lesion large enough to affect significant area of body will result in other associated symptoms. B. Cortical signs and symptoms, including aphasia, neglect, and/or cortical sensory loss (graphesthesia), are useful in placing lesion in cortex. However, cortical signs and symptoms can only be assessed in patients who have adequate sensation for primary modalities; profound alteration of primary sensory modalities, particularly touch, prevents sensory information from reaching cerebral hemisphere, thereby rendering cortical sensory tests inaccurate. C. Either head CT or MRI is useful initial investigation in workup of cortical or thalamic sensory loss, although MRI is more sensitive in diagnosis of demyelinating lesions (multiple sclerosis). SUMMARY 1. Is disease confined to part of a limb or most of an extremity or trunk? A. Disease that is confined to part of a limb is consistent with mononeuropathy or radiculopathy. i. Mononeuropathies may involve disorders of the upper extremity (median [carpal ii. tunnel syndrome], ulnar, radial nerves or brachial plexopathy) or lower extremity (peroneal, posterior tibial [tarsal tunnel], femoral, or lateral femoral cutaneous nerves [meralgia paresthetica]). Radiculopathies classically present with sensory loss in distribution of dermatome, and may be caused by structural spine disease (neck or lower back), infection (VZV, Lyme disease, CMV), leptomeningeal carcinomatosis, or focal extramedullary tumors. Sensory loss may be relatively mild with radiculopathies or may only involve small "signature zones" rather than entire dermatomes; paroxysmal severe lancinating pain is common. B. 2. Sensory alteration that involves most of an extremity or trunk is consistent with polyneuropathy, spinal cord disease, or central nervous system problems. For sensory loss that involves most of a limb or trunk, is one or both sides of the body involved? A. Polyneuropathy and spinal cord disease present with sensory loss on both sides of body. B. Polyneuropathy may be caused by a variety of systemic diseases, drugs, or toxins. Stocking-glove sensory loss is characteristic of a length dependent axonal polyneuropathy. The work-up of polyneuropathy is summarized in algorithm 1 and discussed in more detail separately. C. Spinal cord disease typically presents with a sensory level. A cape distribution of sensory loss is characteristic of disease of the central cervical spinal cord. Brown-Sequard syndrome is characterized by diminished proprioception, vibration, and weakness on side ipsilateral to the lesion, and decreased pinprick and temperature sensation on contralateral side. D. Sensory loss confined to one side of the body is characteristic of disorders of brainstem, thalamus, or cortex. i. Brainstem lesions are unique in that cranial nerves are usually also involved, and there may be sensory loss of the face that is opposite that of the body. ii. In contrast, disease of the thalamus or cortex may involve sensory loss of the face that is on the same side as sensory loss of body. E. Cortical signs and symptoms (aphasia, neglect, abnormalities of graphesthesia, stereognosis, two point discrimination, extinction) are useful for placing lesion in the cerebral cortex.