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Neurology_Adams. As the patient with congenital athetosis or Huntington chorea stands or walks, there is a continuous play of irregular movements affecting the face, neck, hands, and, in the advanced stages, the large proximal joints and trunk. The position of the arms and upper parts of the body varies with each step, at times giving the impression of a puppet. There are jerks of the head, grimacing, squirming and twisting movements of the trunk and limbs, and peculiar respiratory noises. One arm may be thrust aloft and the other held behind the body, with wrist and fingers undergoing alternate nonrhythmic flexion and extension, supination, and pronation. The head may incline in one direction or the other, the lips alternately retract and purse, and the tongue intermittently protrudes from the mouth. The legs advance slowly and awkwardly, the result of superimposed involuntary movements and postures. Sometimes the foot is plantarflexed at the ankle and the weight is carried on the toes; or the foot


Neurology_Adams

Neurology_Adams. legs advance slowly and awkwardly, the result of superimposed involuntary movements and postures. Sometimes the foot is plantarflexed at the ankle and the weight is carried on the toes; or the foot may be dorsiflexed or inverted. An involuntary movement may cause the leg to be suspended in the air momentarily, imparting a lilting or waltzing character to the gait, or it may twist the trunk so violently that the patient may fall.


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Neurology_Adams. In dystonia musculorum deformans and focal dystonias, the first symptom may be a limp caused by inversion or plantarflexion of the foot or a distortion of the pelvis as discussed in Chap. 4. One leg may be rigidly extended or one shoulder elevated, and the trunk may assume a position of exaggerated flexion, lordosis, or scoliosis. Because of the muscle spasms that deform the body in this manner, the patient may have to walk with knees flexed. The gait may seem normal as the first steps are taken, the abnormal postures asserting themselves as the patient continues to walk. Prominence of the buttocks owing to a lumbar lordosis, combined with flexion of one or both legs at the hip, gives rise to the so-called dromedary gait of Oppenheim. In the more advanced stages, walking becomes impossible owing to torsion of the trunk or the continuous flexion of the legs.


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Neurology_Adams. Stiff-person syndrome, an unusual nondystonic disorder causing severe axial muscle spasm, causes stiffness of the legs and buttock muscles, slow propulsion, and lumbar lordosis; there is sometimes a mild superimposed ataxic disturbance of gait (see Chap. 46). Another unusual disorder affecting the body position during walking is camptocormia, a severe forward bending of the trunk at the waist that is symptomatic of either a dystonia, Parkinson disease, or one of several muscle diseases that focally weaken the extensors of the spine. Kyphosis due to spinal deformities does the same and all of these conditions cause the patient to walk while looking at the ground beneath the feet, but they rarely cause falling. Waddling (Gluteal, or Trendelenburg) Gait


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Neurology_Adams. Waddling (Gluteal, or Trendelenburg) Gait This gait is characteristic of the gluteal muscle weakness that is seen in the progressive muscular dystrophies, but it occurs as well in chronic forms of spinal muscular atrophy, in certain inflammatory myopathies, lumbosacral nerve root compression, and with congenital dislocation of the hips.


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Neurology_Adams. In normal walking, as weight is placed alternately on each leg, the hip is fixated by the gluteal muscles, particularly the gluteus medius, allowing for a slight rise of the opposite hip and tilt of the trunk to the weight-bearing side. With weakness of the glutei, however, there is a failure to stabilize the weight-bearing hip, causing it to bulge outward and the opposite side of the pelvis to drop, with inclination of the trunk to that side. The alternation in lateral trunk movements results in the roll or waddle. With unilateral gluteal weakness, often the result of damage to the first sacral nerve root, tilting and dropping of the pelvis (“pelvic ptosis”) is apparent on only one side as the patient overlifts the leg when walking.


Neurology_Adams

Neurology_Adams. In several of the muscular dystrophies, an accentuation of lumbar lordosis is often seen. Also, childhood cases may be complicated by muscular contractures, leading to an equinovarus position of the foot, so that the waddle is combined with walking on the toes (“toe walking”). This unusual fast tremor of the legs may devastate gait. As discussed in Chapter 4, “Disorders of Movement and Posture”, it is present only when the patient stands or exerts force with the legs while seated. The tremor ceases upon walking. In reaction to a perception of severe imbalance, which is characteristic of the disorder, the patient assumes a widened and often stiff-legged stance. Gait Disorder in Normal Pressure Hydrocephalus (See Also Chap. 29)


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Neurology_Adams. Gait Disorder in Normal Pressure Hydrocephalus (See Also Chap. 29) Progressive difficulty in walking is typically the initial and most prominent symptom of normal pressure hydrocephalus (NPH). However, the gait disturbance in NPH has few specific features. Certainly, it cannot be categorized as ataxic or spastic or what has been described as “apraxic” gait; nor does it have more than a superficial resemblance to parkinsonian gait. Its main early features—slowness in lifting the feet from the floor (called in some texts “magnetic gait”), reduced cadence, widened base, and short steps—may be misconstrued as compensations observed in patients with all manner of gait disorders. Patients with the gait disorder of NPH may complain of a sense of imbalance or vague dizziness, but most have difficulty in articulating the exact problem.


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Neurology_Adams. Like patients with disorders of frontal lobe function, they are better able to carry out the motions of stepping and cycling with the legs while supine or sitting but have difficulty in taking steps when upright or attempting to walk. They are helped by marching to a cadence or in step with the examiner, and by maintaining contact with the arm of another person. Turning may be impeded, performed in multiple steps, and have the appearance of a foot remaining stuck to the ground. If observed getting on and off an examining table and in and out of bed, they display poor management of the entire axial musculature, moving their bodies without shifting the center of gravity (en bloc turning) or adjusting their limbs appropriately. Changes in posture, even rolling over in bed, are made en bloc. The erect posture is assumed in an awkward manner—with hips and knees only slightly flexed and stiff and a delay in swinging the legs over the side of the bed.


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Neurology_Adams. Tone in the leg muscles of the NPH patient is often slightly increased, with a tendency to cocontraction of flexor and extensor muscle groups. Walking is perceptibly slower than normal, the body is held stiffly, arm swing is diminished, and there is a tendency to fall backward—features that are reminiscent of Parkinson and related diseases, although the lack of arm swing, a tendency to festination, and the stooped posture are more prominent in Parkinson disease than in NPH. We have been impressed that NPH causes parkinsonian shuffling only when the hydrocephalus is very advanced. In patients with untreated NPH, one observes a progressive deterioration of stance and gait—from an inability to walk to an inability to stand, sit, and rise from or turn over in bed. The neurologist is aided in diagnosis by the presence of incontinence and mental deterioration that are components of advancing NPH.


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Neurology_Adams. There is no hint of ataxia but a study of the mechanics of the gait in NPH by Stolze and colleagues described a widened base and slight outward rotation of the feet. Sudarsky and Simon quantified these defects by means of high-speed cameras and computer analysis. They reported a reduction in height of step, an increase in sway, and a decrease in rotation of the pelvis and counter-rotation of the torso. Unlike patients with the antalgic gait of hip or leg pain, the upper body in NPH is held stiffly and there is not avoidance of weight bearing. Frontal Lobe Disorders of Gait


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Neurology_Adams. Standing and walking may be severely disturbed by diseases that affect the frontal lobes, particularly their medial parts and their connections with the basal ganglia. This disorder is sometimes spoken of as a frontal lobe “apraxia of gait” among numerous other labels, because the difficulty in walking cannot be accounted for by weakness, loss of sensation, cerebellar incoordination, or basal ganglionic abnormality. The disorder should probably not be designated as an apraxia, in the sense of the original concept of loss of ability to perform a learned act, as walking is instinctual and not learned. Patients with the so-called apraxia of gait do not have apraxia of individual limbs; conversely, patients with apraxia of the limbs usually walk normally. More likely, the frontal gait disorder represents a loss of integration, at the cortical and basal ganglionic levels, of the essential elements of stance and locomotion that are acquired in infancy and often lost in old age.


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Neurology_Adams. Patients typically assume a posture of slight flexion with the feet placed farther apart than normal. They advance slowly, with small, shuffling, hesitant steps. At times they halt, unable to advance without great effort, although they improve if escorted, or if instructed to walk in step with the examiner or to a cadence. Walking and turning are accomplished by a series of tiny, uncertain steps that are made with one foot, the other foot being planted on the floor as a pivot. “Lower-half parkinsonism,” as mentioned earlier, has been applied to a pattern of slowed, sometimes shuffling gait in the absence of any abnormalities of the upper extremities, but the cause is rarely idiopathic Parkinson disease. The term “marche à petits pas” is also used as a description for an advanced form of the frontal lobe gait disorder and has been particularly associated with vascular damage to the white matter.


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Neurology_Adams. In frontal lobe disorders of gait there is a need to seek support from a companion’s arm or nearby furniture. The initiation of walking becomes progressively more difficult; in advanced cases, the patient makes only feeble, abortive stepping movements in place, unable to move his feet and legs forward; eventually, the patient can make no stepping movements whatsoever, as though his feet were glued to the floor. These late phenomena have been referred to as “magnetic feet” and the difficulty initiating gait as “slipping clutch” syndrome (Denny-Brown) or “gait ignition failure” (Atchison et al). In some patients, difficulty in the initiation of gait may be an early and apparently isolated phenomenon but invariably, with the passage of time, the other features of the frontal lobe gait disorder become evident. Finally, the resemblance to NPH is notable and these patients become unable to stand or even to sit; without support, they fall helplessly backward or to one side.


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Neurology_Adams. Until the late stages of the process, these patients, while seated or supine are able to make complex movements with their legs, such as drawing imaginary figures or pedaling a bicycle and, quite remarkably, to simulate the motions of walking, all at a time when their gait is seriously impaired. Eventually, however, all movements of the legs become slow and awkward, and the limbs, when passively moved, offer variable counterresistance (paratonia or gegenhalten). As with Parkinson disease, difficulty in turning over in bed may eventually become impossible.


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Neurology_Adams. These advanced motor disabilities are usually associated with dementia, but the gait and mental disorders need not evolve in parallel. Thus, some patients with Alzheimer disease may show a serious degree of dementia for several years before a gait disorder becomes apparent; in other conditions, such as NPH and Binswanger disease, the opposite pertains. Or both the dementia and gait disorder may progress more or less together. Grasping, groping, hyperactive tendon reflexes, and Babinski signs may or may not be present. The end result in some cases is a “cerebral paraplegia in flexion” (Yakovlev’s term), in which the patient lies curled up in bed, immobile and mute, with the limbs fixed by contractures in an attitude of flexion.


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Neurology_Adams. On the basis of bilateral but isolated frontal lobe infarction in the territory of the anterior cerebral artery (medial frontal lobes), the existence of a “gait center” has been proposed as mentioned in the introduction (see Della Sala). In the most severe and localized instance of complete gait failure from a frontal lobe stroke we have observed, the lesion was situated in the left pericallosal, medial supplementary motor area. Benson and colleagues have reported in an analysis of MRIs from a selected group of stroke patients that periventricular frontal and occipitoparietal ischemic lesions in the deep white matter are associated with deterioration of gait. Isolated pontine ischemic changes were associated with gait disequilibrium in another study by Kwa and colleagues of the Amsterdam Vascular Medicine Group. The clinical validity of all of these observations in regard to localization is uncertain but generally converges on the notion that ischemic damage at any of the


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Neurology_Adams. Amsterdam Vascular Medicine Group. The clinical validity of all of these observations in regard to localization is uncertain but generally converges on the notion that ischemic damage at any of the aforementioned sites in the white matter can alter walking.


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Neurology_Adams. In addition to NPH and Alzheimer disease, the causes of the frontal lobe gait disorder include large neoplasms (meningioma, infiltrating glioma—gliomatosis cerebri), subcortical arteriosclerotic encephalopathy (Binswanger disease; see Thompson and Marsden), frontotemporal lobar degeneration (formerly Pick disease), and frontal lobe damage from trauma, stroke, or the residual of a ruptured anterior communicating aneurysm. Gait of the Aged (See Also Chap. 28)


Neurology_Adams

Neurology_Adams. Gait of the Aged (See Also Chap. 28) An alteration of gait unrelated to overt cerebral disease is an almost universal accompaniment of aging and probably a variant of frontal lobe gait deterioration (Fig. 6-3). Lost with aging are speed, balance, and many of the quick and graceful adaptive movements that characterize the gait of younger individuals. The main objective characteristics are a slightly stooped posture, varying degrees of slowness and stiffness of walking, shortening of the stride, slight widening of the base, and a tendency to turn en bloc. The shortening of stride and widening of the base provide the support that enables the elderly individual to more confidently maintain his balance, but they result in a somewhat guarded gait, like that of a person walking on a slippery surface or in the dark.


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Neurology_Adams. Also lacking to a varying degree in the elderly is the ability to make the rapid compensatory postural changes (“rescue responses”) that are necessary to cushion or prevent a fall. A slight misstep, a failure to elevate the foot sufficiently, or tipping of the center of gravity to one side often cannot be corrected—features no doubt that account for the frequency of falls and fear of falling among the elderly. Most persons with this type of gait disturbance are aware of impaired balance and their need for caution to avoid falls (the “cautious gait”; see Nutt et al). As such, this gait lacks specificity, being combined with a general adaptive or defensive pattern of walking. Added to this, knee buckling that is attributable to quadriceps weakness from muscle loss of aging contributes to the problem, as discussed by Felson and colleagues. Furthermore, osteoarthritis, the almost inevitable accompaniment of aging, contributes to the disruption of gait as a result of pain and a reduced


Neurology_Adams

Neurology_Adams. the problem, as discussed by Felson and colleagues. Furthermore, osteoarthritis, the almost inevitable accompaniment of aging, contributes to the disruption of gait as a result of pain and a reduced range of motion and is a component of many gait disorders.


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Neurology_Adams. The nature of the elderly gait disorder is not fully understood. It may simply represent cerebral neuronal loss, attributable to aging itself, which in a severe form is the frontal lobe disorder of gait discussed above. Inadequate proprioception, slowness in making corrective postural responses, diminished vestibular function, and weakness of pelvic and thigh muscles are, as mentioned, probably contributing factors. However, Baloh and colleagues have found that changes in sensory function do not correlate well with deterioration in gait. Fisher remarked on the similarity of the senile gait to that of NPH and suggested that hydrocephalus underlies the gait disorder of some elderly. Cobalamin deficiency caused by gastric atrophy may contribute as well. The multiple contributors to gait deterioration, particularly vestibulopathy, in the aged is reflected in the survey by Fife and Baloh.


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Neurology_Adams. We emphasize here the common and vexing problem encountered so often in practice of an elderly person with gait disturbance but minimal dementia and without an obvious etiology. Factor and colleagues identify this as a primary freezing gait disorder of many etiologies and it conforms to “lower-half Parkinson” pattern as discussed earlier. Walking deteriorates over a period of months or years in an elderly individual, sometimes while residing in a nursing home, so that the tempo is unclear. The disturbance has most of the features of NPH or of a frontal gait disorder, but frontal atrophy is not marked, the ventricles are not enlarged, there is no response to drainage of CSF, and cervical spondylosis or neuropathy is not found. Sometimes, a functional imaging study such as positron emission tomography (PET) shows hypometabolism in the frontal lobes. Verghese and coworkers have emphasized the high incidence of subsequent dementia, and this is in accord with experience from our patients.


Neurology_Adams

Neurology_Adams. tomography (PET) shows hypometabolism in the frontal lobes. Verghese and coworkers have emphasized the high incidence of subsequent dementia, and this is in accord with experience from our patients. Presumably this reflects a degenerative process, perhaps of the frontotemporal variety. The changes in gait due to aging are nicely summarized in the text by Masdeu and colleagues and the review by Sudarsky.


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Neurology_Adams. Gaits of the Developmentally Delayed The array of peculiar gaits in these individuals defies easy analysis. An ungainly stance with the head too far forward or the neck extended and arms held in odd positions, a wide-based gait with awkward lurches or feet stomping the floor—each with his own ungraceful style—these are but a few of the patterns that meet the eye. One tries in vain to relate them to a disorder of proprioception, cerebellar deficit, or pyramidal or extrapyramidal disease.


Neurology_Adams

Neurology_Adams. The only plausible explanation that comes to mind is that these variants of gait are based on a change in the natural developmental sequence of cerebral and spinal mechanisms involved in bipedal locomotion, posture, and righting. The acquisition of the developmental refinements of locomotion—such as running, hopping, jumping, dancing, balancing on one foot, kicking a ball are also disrupted or delayed. The rhythmic rocking movements and hand clapping, odd mannerisms, waving of the arms, and other stereotyped patterns mentioned in the chapter on development, make gait even more maladroit. The Lincoln-Oseretsky scale is an attempt to quantitate these maturational delays in the locomotor sphere.


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Neurology_Adams. This may take several forms, often dramatic in appearance such as walking on stilts, extreme dystonic postures, or lurching wildly in all directions or collapsing legs, without falling to the ground, actually demonstrating by their gyrations a normal ability to make rapid and appropriate postural adjustments, all nicely summarized by Keane. The hysterical gait disorder may be accompanied by similarly exaggerated movements of the arms, as though to impress the observer with the great effort required to walk and maintain balance. Baik and Lang have emphasized the high frequency of coincident psychogenic movement and gait disorders in their specialty clinic.


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Neurology_Adams. Astasia-abasia was a term used to describe a psychogenic gait disorder in which patients, although unable to either stand or walk, display more or less normal use of their legs while in bed and have an otherwise normal neurologic examination and body carriage. When such patients are placed on their feet, they may take a few steps and then become unable to advance their legs; they lurch in all directions and crumple to the floor if not assisted. As noted below, astasia-abasia has causes other than psychogenic and the use of the term has been expanded to describe other forms of complete inability to stand and walk.


Neurology_Adams

Neurology_Adams. Also included in this category are hysterical monoplegias, hemiplegias, or paraplegias. In walking, the patient may hesitate and advance the leg in a grossly ataxic or tremulous manner. Typically, patients with a hysterical paralysis of the leg do not lift the foot from the floor while walking; instead, they tend to drag the leg as a useless member or push it ahead of them as though it were on a skate. In hysterical hemiparesis, the characteristic circumduction seen in bona fide spastic paresis of the leg is absent, as are hemiparetic postures, hyperactive tendon reflexes, and Babinski sign. The hysterical paraplegic cannot very well drag both legs and usually depends on canes or crutches or remains helpless in bed or in a wheelchair; after months or longer of immobilization, the muscles may be flaccid or rigid from shortening, with development of contractures. Leg movements in bed may be unimpaired or the patient may display a Hoover sign (described in Chapter 3), which belies


Neurology_Adams

Neurology_Adams. may be flaccid or rigid from shortening, with development of contractures. Leg movements in bed may be unimpaired or the patient may display a Hoover sign (described in Chapter 3), which belies genuine leg weakness. Some of the patients exhibit additional abnormalities of the voice and visual fields, tremors, and asthenic weakness of muscle contraction.


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Neurology_Adams. On the other hand, one should not assume that a patient who manifests a disorder of gait or inability to walk but no other neurologic abnormality necessarily has a psychogenic disorder. Lesions that are restricted to the anterosuperior cerebellar vermis may cause an ataxia or severe instability that becomes manifest only when the patient attempts to stand and walk; this is also true of very advanced NPH, frontal lobe disease, and various intoxications such as with alcohol or antiepileptic medications. Cases of severe peripheral neuropathy, particularly if there is prominent sensory loss, may also greatly impair the ability to stand or walk, and the unusual condition of orthostatic leg tremor (see the chapter on disorders of movement) that may produce buckling of the legs when the patient stands for some period of time, a situation often mistaken for hysteria. Similarly, the combination of ataxia and stiffness of the legs and buttocks that characterizes stiff-person syndrome may be


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Neurology_Adams. stands for some period of time, a situation often mistaken for hysteria. Similarly, the combination of ataxia and stiffness of the legs and buttocks that characterizes stiff-person syndrome may be easily mistaken for a psychogenic disorder.


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Neurology_Adams. Once the gait abnormality has been characterized, one should explore the possibility of rehabilitation by a combination of medical therapy and other corrective measures. The antispasticity agents baclofen and tizanidine are somewhat helpful when stiffness of the limbs exceeds weakness. They may reduce spasticity of the legs, but sometimes at the expense of exposing, to a greater degree than before, a loss of muscle power—the net effect being to the patient’s disadvantage. In extreme cases, a subarachnoid pump infusion of baclofen may be effective for spasticity.


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Neurology_Adams. Hypofunction of the labyrinths, as in drug-induced or idiopathic vestibulopathy, has greatly challenged physiatrists. Balance training and attention to postural correction and vision have helped some of these patients to be more steady and better able to function (see Baloh and Honrubia). Vestibular sedatives (e.g., meclizine) should be discontinued. Exercises to strengthen leg muscles can be beneficial in many circumstances, as can weight loss. Likewise, gait ataxia from proprioceptive defects can probably be corrected to some extent by careful attention to visual control and proper placement of the feet. Once dementia becomes conjoined with any of the gait disorders that occur in advanced age or with frontal lobe disease, rehabilitation stands less chance of success, since the ability to attend to small changes in terrain and posture is lost. Many patients have found exercises that emphasize balance, such as tai chi an yoga, to be helpful. Progression from the use of a cane, to a


Neurology_Adams

Neurology_Adams. to attend to small changes in terrain and posture is lost. Many patients have found exercises that emphasize balance, such as tai chi an yoga, to be helpful. Progression from the use of a cane, to a pronged cane, and finally to a four-posted walker allows patients with all types of gait disorders to maintain some mobility. The optimal use of these orthoses is best directed by experienced physical therapists and physiatrists.


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Neurology_Adams. Gait training with encouragement has been a useful maneuver to improve psychogenic gait disorders but some prove resistant. Atchison PR, Thompson PD, Frackowiak RS, Marsden CD: The syndrome of gait ignition failure: A report of six cases. Mov Disord 8:285, 1993. Baik JS, Lang AE: Gait abnormalities in psychogenic movement disorders. Mov Disord 22:395, 2007. Baloh RW, Honrubia V: Clinical Neurophysiology of the Vestibular System, 3rd ed. Oxford, Oxford University Press, 2001. Baloh RW, Ying SH, Jacobson KM: A longitudinal study of gait and balance dysfunction in normal older people. Arch Neurol 60:835, 2003. Benson RR, Guttman CR, Wei S, et al: Older people with impaired mobility have specific loci of periventricular abnormality on MRI. Neurology 58:46, 2002. Della Sala S, Francescani S, Spinnler H: Gait apraxia after bilateral supplementary motor area lesion. J Neurol Neurosurg Psychiatry 72:77, 2002. Denny-Brown D: The Basal Ganglia and Their Relation to


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Neurology_Adams. Denny-Brown D: The Basal Ganglia and Their Relation to Disorders of Movement. Oxford, Oxford University Press, 1962. Eidelberg E, Walden JG, Nguyen LH: Locomotor control in macaque monkeys. Brain 104:647, 1981. Factor SA, Higgins DS, Qian J: Primary freezing gait: A syndrome with many causes. Neurology 66:411, 2006. Factor SA, Jennings DL, Molho ES, et al: The natural history of the syndrome of primary progressive freezing gait. Arch Neurol 59:1778, 2002. Felson DT, Niu J, McClennan C, et al: Knee buckling: prevalence, risk factors, and associated limitations in function. Ann Intern Med 147:534, 2007. Fife TD, Baloh RW: Disequilibrium of unknown cause in older people. Ann Neurol 34:694, 1993. Fisher CM: Hydrocephalus as a cause of disturbances of gait in the elderly. Neurology 32:1358, 1982. JC: LIVING without a balancing mechanism. N Engl J Med 246:458, 1952. Keane JR: Hysterical gait disorders: 60 cases. Neurology 39:586, 1989.


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Neurology_Adams. JC: LIVING without a balancing mechanism. N Engl J Med 246:458, 1952. Keane JR: Hysterical gait disorders: 60 cases. Neurology 39:586, 1989. Kwa VI, Zaal LH, Verbeeten B, Stam J: Disequilibrium in patients with atherosclerosis: relevance of pontine ischemic rarefaction. Amsterdam Vascular Medicine Group. Neurology 51:570, 1998. Lawrence DG, Kuypers HGSM: The functional organization of the motor system in the monkey: II. The effects of lesions of the descending brainstem pathways. Brain 91:15, 1968. Martin JP: The basal ganglia and locomotion: Arris and Gale Lecture delivered at the Royal College of Surgeons of England on 3rd January 1963. Ann R Coll Surg Engl 32:219, 1963. Masdeu JC, Sudarsky L, Wolfson L (eds): Gait Disorders of Aging. Philadelphia, Lippincott-Raven, 1997. Murray MP, Kory RC, Clarkson BH: Walking patterns in healthy old men. J Gerontol 24:169, 1969. Olsson E: Gait analysis in hip and knee surgery. Scand J Rehabil Med Suppl 15:1, 1986.


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Neurology_Adams. Murray MP, Kory RC, Clarkson BH: Walking patterns in healthy old men. J Gerontol 24:169, 1969. Olsson E: Gait analysis in hip and knee surgery. Scand J Rehabil Med Suppl 15:1, 1986. Ropper AH: Refined Romberg test. Can J Neurol Sci 12:282, 1985. Stolze H, Kuhtz-Buschbeck JP, Drücke H, et al: Comparative analysis of the gait disorder of normal pressure hydrocephalus and Parkinson’s disease. J Neurol Neurosurg Psychiatry 70:289, 2001. Sudarsky L: Geriatrics: gait disorders in the elderly. N Engl J Med 322:1441, 1990. Sudarsky L, Simon S: Gait disorder in late-life hydrocephalus. Arch Neurol 44:263, 1987. Thompson PD, Marsden CD: Gait disorder of subcortical arteriosclerotic encephalopathy: Binswanger’s disease. Mov Disord 2:1, 1987. Tinetti ME, Williams CS: Falls, injuries due to falls, and the risk of admission to a nursing home. N Engl J Med 337:1279, 1997.


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Neurology_Adams. Tinetti ME, Williams CS: Falls, injuries due to falls, and the risk of admission to a nursing home. N Engl J Med 337:1279, 1997. Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ, Buschke H: Abnormality of gait as a predictor of non-Alzheimer’s dementia. N Engl J Med 347:1761, 2002. Yakovlev PI: Paraplegia in flexion of cerebral origin. J Neuropathol Exp Neurol 13:267, 1954. Figure 6-1. The normal gait cycle, based on the studies of Olsson and of Murray et al. See text for details. Figure 6-2. Schematic depiction of three of the main disorders of gait, described further in the text. A. Hemiplegic gait on the right. B. Spastic gait with close approximation of the feet and legs and flexion at the knees. C. Parkinsonian gait with forward position of the upper torso, flexion of the neck and elbows, and short-stepped gait. This may be contrasted with the similar but distinctive gait of aging (Fig. 6-3).


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Neurology_Adams. Figure 6-3. Diagram illustrating the changes in posture and gait that accompany aging (“senile gait”). With aging (figure on left), there occurs a decrease in the length of stride, excursion of the hip, elevation of the toes of the forward foot and the heel of the rear foot, shoulder flexion on forward arm swing, and elbow extension on backward swing. (Redrawn with permission from Murray et al.) Chapter 6 Disorders of Stance and Gait CHAPTER 8 Disorders of Non-Painful Somatic Sensation CHAPTER 10 Pain in the Back, Neck, and Extremities


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Neurology_Adams. Chapter 6 Disorders of Stance and Gait CHAPTER 8 Disorders of Non-Painful Somatic Sensation CHAPTER 10 Pain in the Back, Neck, and Extremities This section deals with pain and somatic sensations, all derived mainly from afferent impulses that arise in the organs, skin, blood vessels, connective tissues, muscles, and joints. Because of its overriding clinical importance, pain has been accorded a chapter of its own. The special senses—vision, hearing, taste, and smell—are considered in the next section, and visceral sensation, most of which does not reach consciousness, is considered with the disorders of the autonomic nervous system.


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Neurology_Adams. Pain is an important sign of illness and it stands preeminent among all the sensory experiences by which humans judge the existence of disease. Relatively few medical diseases do not have a painful phase. Moreover, the diagnosis of certain diseases rests heavily on a characteristic absence of pain. Headache and the pain derived from disorders of the spinal column and roots occupy a distinctive place in clinical practice and are elaborated in their own chapters.


Neurology_Adams

Neurology_Adams. To deal effectively with problems of pain and altered sensation requires familiarity with the anatomy of sensory pathways and the sensory innervation of body segments as well as insight into the psychological factors that influence the perception of and reaction to pain. Two major systems, designated by their tracts in the spinal cord, subserve these functions: spinothalamic pathways for pain and the posterior column-medial lemniscal pathways for touch, joint position, deep pressure, and vibration senses. Some basic facts are as follows: 1.


Neurology_Adams

Neurology_Adams. The spinothalamic system originates in free nerve endings that coalesce into lightly myelinated axons. These fibers represent the peripheral projections of neurons contained in the dorsal root ganglia. Their central projections are contained in the dorsal (posterior) roots that enter the spinal cord and synapse in the dorsal horns onto neurons. The axons of these neurons decussate and ascend as the spinothalamic tract, terminating in the thalamus. An analogous pathway called the spinal trigeminal tract subserves pain sensation in the face. 2.


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Neurology_Adams. 2. The posterior column-medial lemniscal system originates in several distinctive specialized receptors that give rise to heavily myelinated axons whose cell bodies are also contained in the dorsal root ganglia. Their central projections enter the dorsal roots and then the dorsal horn of the spinal cord, and without synapsing or decussating, ascend as the posterior columns. An analogous the anterior trigeminothalamic tract subserves somatic sensation in the face. 3. The problems of pain localized to the head and to the back (spine) represent special problems in neurology, as mentioned, because of the relationship of the dura, spinal nerve roots, and blood vessels, each of which can generate pain signals as a result of disease in the proximate structures of the brain, spinal cord, and vertebral column. The syndromes of headache and back pain occupy a large part of neurological and general practice.


Neurology_Adams

Neurology_Adams. The ambiguity with which the term pain is used is responsible for some of our difficulty in understanding it. One aspect, the easier to comprehend, is the transmission of impulses along certain pathways in response to potentially tissue-damaging stimuli, that is, nociception. Far more abstruse is its quality as a mental state intimately linked to emotion, the quality of anguish or suffering that defies definition and quantification, or “a passion of the soul,” in the words of Aristotle. This duality (nociception and suffering) is of practical importance, for certain drugs or surgical procedures, such as cingulotomy, may reduce the patient’s reaction to painful stimuli, leaving awareness of sensation largely intact. Further complexities are that the symptom of pain may persist despite interruption of neural pathways that abolish all sensation (i.e., denervation dysesthesia or anesthesia dolorosa), or that pain may continue to be perceived from the absent part of an amputated limb


Neurology_Adams

Neurology_Adams. interruption of neural pathways that abolish all sensation (i.e., denervation dysesthesia or anesthesia dolorosa), or that pain may continue to be perceived from the absent part of an amputated limb (“phantom pain”). Finally, pain can be evoked by almost any sensory modality, such as touch, pressure, heat, or cold, if it is intense enough.


Neurology_Adams

Neurology_Adams. It is apparent that few physicians are capable of handling difficult and unusual pain problems and it is sometimes to the neurologist that other physicians may turn for help with these matters. Although much has been learned about the anatomy of pain pathways, their physiologic mechanisms, and which structures to ablate in order to produce analgesia, the effective management of pain by medical and surgical means remains a considerable clinical challenge. The practice of pain medicine challenges every thoughtful physician, for it demands a high degree of skill in medicine, neurology, and psychiatry. More problematic are patients who seek treatment for pain that appears to have little or no structural basis; further inquiry may disclose that fear of serious disease, worry, or depression has aggravated some relatively minor ache or that the complaint of pain has become the means of seeking attention, drugs, or monetary compensation. There is also the “difficult” pain patient, in whom no


Neurology_Adams

Neurology_Adams. aggravated some relatively minor ache or that the complaint of pain has become the means of seeking attention, drugs, or monetary compensation. There is also the “difficult” pain patient, in whom no amount of investigation brings to light either medical or psychiatric illness. Further complicating almost all aspects of pain medicine is concern about narcotic dependence, tolerance, and addiction, which may be informed by societal and political forces. Finally, the physician must be prepared to manage patients who require relief from intractable pain caused by established and incurable disease.


Neurology_Adams

Neurology_Adams. For more than a century, views on the nature of pain sensation have been dominated by two major theories. One, the specificity theory, was from the beginning associated with the name of von Frey. He asserted that the skin consisted of a mosaic of discrete sensory spots and that each spot, when stimulated, gave rise to one sensation—either pain, pressure, warmth, or cold; in his view, each of these sensations had a distinctive end organ in the skin and each stimulus-specific end organ was connected by its own discrete pathway to the brain. A second theory was that of Goldscheider, who abandoned his own earlier discovery of pain spots to argue that they simply represented pressure spots, a sufficiently intense stimulation of which could produce pain. According to the latter theory, there were no distinctive pain receptors, and the sensation of pain was the result of the summation of impulses excited by pressure or thermal stimuli applied to the skin. Originally called the intensivity


Neurology_Adams

Neurology_Adams. were no distinctive pain receptors, and the sensation of pain was the result of the summation of impulses excited by pressure or thermal stimuli applied to the skin. Originally called the intensivity theory, it later became known as the pattern or summation theory.


Neurology_Adams

Neurology_Adams. In an effort to conciliate the specificity and pattern theories, Head and colleagues, in 1905, formulated a concept of pain sensation based on observations that followed the purposeful sectioning of the cutaneous branch of the radial nerve in his own forearm. The zone of impaired sensation contained an innermost area in which superficial sensation was completely abolished. This was surrounded by a narrower (“intermediate”) zone, in which pain sensation was preserved but poorly localized; extreme degrees of temperature were recognized in the intermediate zone but perception of touch, lesser differences of temperature, and two-point discrimination were abolished. To explain these findings, Head postulated the existence of two systems of cutaneous receptors and conducting fibers: (1) an ancient protopathic system, subserving pain and extreme differences in temperature and yielding ungraded, diffuse impressions of an all-or-none type; and (2) a more recently evolved epicritic system,


Neurology_Adams

Neurology_Adams. ancient protopathic system, subserving pain and extreme differences in temperature and yielding ungraded, diffuse impressions of an all-or-none type; and (2) a more recently evolved epicritic system, which mediated touch, two-point discrimination, and lesser differences in temperature, as well as localized pain. The pain and hyperesthesia that followed damage to a peripheral nerve were attributed to a loss of inhibition that was normally exerted by the epicritic upon the protopathic system. This theory was used for many years to explain the sensory alterations that occur with both peripheral and central (thalamic) lesions. It lost credibility for several reasons but mainly because Head’s original observations and deductions could not be confirmed (see Trotter and Davies; also Walshe). Nevertheless, both fast and slow forms of pain conduction were later corroborated (see below).


Neurology_Adams

Neurology_Adams. A later refinement of the pattern and specificity concepts of pain was made in 1965 when Melzack and Wall articulated their “gate-control” theory. They observed, in decerebrate and spinal cats, that peripheral stimulation of large myelinated fibers produced a negative dorsal root potential and that stimulation of small unmyelinated


Neurology_Adams

Neurology_Adams. C (pain) fibers caused a positive dorsal root potential. They postulated that these potentials, which were a reflection of presynaptic inhibition or excitation, modulated the activity of secondary transmitting neurons (T cells) in the dorsal horn and that this modulation was mediated through inhibitory (I) cells. The essence of this theory was that the large-diameter fibers excited the I cells, which, in turn, caused a presynaptic inhibition of the T cells; conversely, the small pain afferents inhibited the I cells, leaving the T cells in an excitatory state. Wall and Melzack emphasized that pain impulses from the dorsal horn must also be under the control of a descending system of fibers from the brainstem, thalamus, and limbic lobes.


Neurology_Adams

Neurology_Adams. At first the gate-control mechanisms seemed to offer an explanation of the pain of ruptured disc and of certain chronic neuropathies (particularly those with large fiber out-fall) and attempts were made to relieve pain by subjecting the peripheral nerves and dorsal columns (presumably their large myelinated fibers) to sustained transcutaneous electrical stimulation. Such selective stimulation would theoretically “close” the gate. In some clinical situations these procedures have indeed given relief from pain, but not necessarily as a result of stimulation of large myelinated fibers alone (see Taub and Campbell). In a number of other instances relating to pain in largeand small-fiber neuropathies, however, the clinical behavior has been quite out of keeping with what one would expect on the basis of the gate-control mechanism. As with preceding theories, weaknesses have been exposed in the physiologic observations on which the theory is based. These and other aspects of the


Neurology_Adams

Neurology_Adams. on the basis of the gate-control mechanism. As with preceding theories, weaknesses have been exposed in the physiologic observations on which the theory is based. These and other aspects of the gate-control theory of pain have been critically reviewed by Nathan.


Neurology_Adams

Neurology_Adams. During the last few decades there has been a significant accrual of information on cutaneous sensibility, demanding modification of earlier anatomic–physiologic and clinical concepts. Interestingly, much of this information is still best described and rationalized in the general framework of some of the older theories.


Neurology_Adams

Neurology_Adams. In terms of peripheral pain mechanisms, there is indeed a degree of specificity of pain conducting nerve fibers. In keeping with distinctions between nerve types, the sensory fibers have been classified according to their size and function (Table 7-1). It is well established that two types of afferent fibers in the distal axons of primary sensory neurons respond maximally to nociceptive (i.e., potentially tissue-damaging) stimuli. One type is the very fine, unmyelinated, slowly conducting C fiber (0.3–1.1 μ in diameter); the other is the thinly myelinated, more rapidly conducting A-d fiber (2–5 μ in diameter). The peripheral terminations of both of these primary pain afferents, or receptors, are free, profusely branched nerve endings in the skin and other organs; these are covered by Schwann cell cytoplasm but little or no myelin.


Neurology_Adams

Neurology_Adams. There is considerable evidence, based on physiologic responses, that a degree of subspecialization exists within these freely branching, nonencapsulated endings and their small-fiber afferents. Three categories of free endings or receptors are recognized: mechanoreceptors, thermoreceptors, and polymodal nociceptors. Each ending transduces stimulus energy into an action potential in the distal nerve membranes. The first two types of receptors are activated by innocuous mechanical and thermal stimulation, respectively; the mechanoeffects are transmitted by both A-d and C fibers and the thermal effects mostly by


Neurology_Adams

Neurology_Adams. C fibers. The majority of C-fiber endings are polymodal and are most effectively excited by noxious or tissue-damaging stimuli, but they can also respond to mechanical or thermal stimuli and to chemical mediators such as those associated with inflammation. Moreover, certain A-d fibers respond to light touch, temperature, and pressure as well as to pain stimuli and are capable of discharging in proportion to the intensity of the stimulus. The stimulation of single fibers by intraneural electrodes indicates that they can also convey information concerning the nature and location of the stimulus. These observations on the polymodal functions of A-d and C fibers would explain the observations of Lele and Weddell and of Weddell that modes of sensation other than pain can be evoked from structures such as the cornea, which is innervated solely by free nerve endings.


Neurology_Adams

Neurology_Adams. The manner in which painful stimuli are translated into electrical depolarizations in nerve endings is beginning to be understood. A number of specialized molecules, when activated by noxious stimuli, open cationic channels in membranes of the nerve ending. Opening of these channels activates voltage-gated sodium channels and generates an action potential in the sensory axon. It is of interest that numerous specialized ion channels are expressed only on some nociceptive nerve cells and their processes, but not in the brain or spinal cord; these include unique sodium, potassium, calcium channels, and other cation channels such as TRP (transient receptor potential) and ASIC (acid sensing ion channel). Benarroch has summarized the regulation and activation of these receptor molecules. Particular pain syndromes arise from mutations in these channels and from autoimmune diseases that interfere with their function.


Neurology_Adams

Neurology_Adams. The peripheral afferent pain fibers of both A-d and C types have their cell bodies in the dorsal root ganglia; central extensions of these nerve cells project, via the dorsal root, to the dorsal horn of the spinal cord (or, in the case of cranial pain afferents, to the spinal trigeminal nucleus, the medullary analogue of the dorsal horn). The pain afferents occupy mainly the lateral part of the root entry zone. Within the spinal cord, many of the thinnest fibers (C fibers) form a discrete bundle, the tract of Lissauer (Fig. 7-1A). Transection of the tract of Lissauer produces ipsilateral segmental analgesia, demonstrating that it is predominantly a pain pathway, but it does contain deep sensory and propriospinal fibers as well. Although it is customary to speak of a lateral and medial division of the posterior spinal nerve root (the former contains small pain fibers and the latter, large myelinated fibers), the separation into discrete functional bundles is not complete, and in humans


Neurology_Adams

Neurology_Adams. of the posterior spinal nerve root (the former contains small pain fibers and the latter, large myelinated fibers), the separation into discrete functional bundles is not complete, and in humans the two groups of fibers cannot be differentially interrupted by selective rhizotomy.


Neurology_Adams

Neurology_Adams. Dermatomal Distribution of Pain Fibers (See Fig. 8-1)


Neurology_Adams

Neurology_Adams. The sensory unit consists of the sensory nerve cell in the dorsal root ganglion, its central and peripheral extensions, and its cutaneous and visceral endings. The topography of the units maintains a consistent distribution throughout the sensory system from the periphery to the sensory cortex. The discrete segmental distribution of the sensory units permits the construction of clinically useful sensory maps (see Fig. 8-1). This aspect of sensory anatomy is elaborated in the next chapter, which includes maps of the sensory dermatomes and cutaneous nerves. However, as a means of quick orientation to the topography of peripheral pain pathways, it is useful to remember that the facial structures and anterior cranium lie in the fields of the trigeminal nerves; the back of the head, second cervical; the neck, third cervical; the epaulet area, fourth cervical; the deltoid area, fifth cervical; the radial forearm and thumb, sixth cervical; the index and middle fingers, seventh cervical; the


Neurology_Adams

Neurology_Adams. the neck, third cervical; the epaulet area, fourth cervical; the deltoid area, fifth cervical; the radial forearm and thumb, sixth cervical; the index and middle fingers, seventh cervical; the little finger and ulnar border of hand and forearm, eighth cervical–first thoracic; the nipple, fourth to fifth thoracic; the umbilicus, tenth thoracic; the groin, first lumbar; the medial side of the knee, third lumbar; the medial malleolus, the fourth lumbar; the great toe, fifth lumbar; the little toe, first sacral; the back of the thigh and lateral foot, second sacral; and the genitoanal zones, third, fourth, and fifth sacral segments.


Neurology_Adams

Neurology_Adams. The distribution of pain fibers from deep structures, although not fully corresponding to those from the skin, also follows a roughly segmental pattern. The first to fourth thoracic nerve roots are the important sensory pathways for the heart and lungs; the sixth to eighth thoracic, for the upper abdominal organs; the lower thoracic and upper lumbar, for the lower abdominal viscera; and lower pelvic organs such as the bladder and rectum, the second through fourth sacral roots. These areas of pain projection from visceral structures roughly correspond to the areas of skin innervation by the same roots, with some exceptions, such as the testicles, because of routing of sensory nerves to organs that migrate caudally with development.


Neurology_Adams

Neurology_Adams. Neurologically relevant maps of pain projection from the bones, ligaments, and adjacent musculoskeletal structures have been termed sclerotomes; they differ slightly in their distribution from the dermatomes. A further discussion of referred pain and a figure comparing sclerotomes and dermatomes is given later in the chapter. The Dorsal Horn


Neurology_Adams

Neurology_Adams. The afferent pain fibers, after traversing the tract of Lissauer, terminate in the posterior gray matter or dorsal horn, predominantly in the marginal zone. Most of the fibers terminate within the segment of their entry into the cord; some extend ipsilaterally to one or two adjacent rostral and caudal segments; and some project, via the anterior commissure, to the contralateral dorsal horn. The cytoarchitectonic studies of Rexed in the cat (the same organization pertains in primates and probably in humans) have shown that second-order neurons, the sites of synapse of afferent sensory fibers in the dorsal horn, are arranged in a series of six layers or laminae (Fig. 7-1B). Thinly myelinated (A-d) fibers terminate principally in lamina I of Rexed (marginal cell layer of Waldeyer) and also in the outermost part of lamina II; some A-d pain fibers penetrate the dorsal gray matter and terminate in the lateral part of lamina V. Lamina I is stated by several authorities to be the origin of


Neurology_Adams

Neurology_Adams. in the outermost part of lamina II; some A-d pain fibers penetrate the dorsal gray matter and terminate in the lateral part of lamina V. Lamina I is stated by several authorities to be the origin of half or more the spinothalamic fibers, discussed below. Unmyelinated (C) fibers also terminate in lamina II (substantia gelatinosa). Yet other cells that respond to painful cutaneous stimulation are located in ventral horn laminae VII and VIII. The latter neurons are responsive to descending impulses from brainstem nuclei as well as segmental sensory impulses. From these cells of termination, second-order axons connect with ventral and lateral horn cells in the same and adjacent spinal segments and subserve both somatic and autonomic reflexes. The main bundle of secondary neurons subserving pain sensation projects contralaterally (and to a lesser extent ipsilaterally) to higher levels; this constitutes the spinothalamic tract, discussed below.


Neurology_Adams

Neurology_Adams. A number of important observations have been made concerning the mode of transmission and modulation of pain impulses in the dorsal horn and brainstem. Excitatory amino acids (glutamate, aspartate) and nucleotides such as adenosine triphosphate (ATP) are the putative transmitters at terminals of primary A-d sensory afferents. Also, A-d pain afferents, when stimulated, release several neuromodulators that play a role in the transmission of pain sensation. Slower neurotransmission by C neurons involves other substances, of which the most important is the 11-amino-acid peptide known as substance P (“P” for powder extracted from animal tissue and urine by von Euler and Gaddum in 1931). In animals, substance P excites nociceptive dorsal root ganglion and dorsal horn neurons; furthermore, destruction of substance P fibers produces analgesia. In patients with the rare condition of congenital neuropathy and insensitivity to pain, there is a marked depletion of dorsal horn substance P.


Neurology_Adams

Neurology_Adams. The term “opiate” is used describe naturally occurring exogenous substances such as morphine that resemble the endogenous “opioids,” which are modulators of pain impulses as they are relayed through the dorsal horn and the nuclei in the medulla and midbrain. Opiates have been noted to decrease substance P; at the same time, flexor spinal reflexes, which are evoked by segmental pain, are reduced. Opioid receptors of three types are found on both presynaptic primary afferent terminals and postsynaptic dendrites of small neurons in lamina II. Moreover, lamina II neurons, when activated, release enkephalins, endorphins, and dynorphins—all of which are endogenous, morphine-like peptides that bind specifically to opiate receptors and inhibit pain transmission at the dorsal horn level. The subject of pain modulation by opiates and endogenous opioid substances such is elaborated further on. The (Anterolateral or Lateral) Spinothalamic Tract


Neurology_Adams

Neurology_Adams. As indicated above, axons of secondary neurons that sub-serve pain sensation originate in laminae I, II, V, VII, and VIII of the spinal gray matter. The principal bundle of these axons decussates in the anterior spinal commissure and ascends in the anterolateral fasciculus of the opposite side of the cord as the spinothalamic tract to terminate in brainstem and thalamic structures (Fig. 7-2). It is of clinical consequence that the axons carrying pain impulses from each dermatome decussate as they ascend one to three segments rostral to the level of root entry. For this reason, a discrete lesion of the lateral spinal cord creates a loss of pain and thermal sensation of the contralateral trunk, the dermatomal level of which is two to three segments below that of the spinal cord lesion. As the ascending fibers cross the cord, they are added to the inner side of the spinothalamic tract (the principal afferent pathway of the anterolateral fasciculus), so that the longest fibers from the


Neurology_Adams

Neurology_Adams. the ascending fibers cross the cord, they are added to the inner side of the spinothalamic tract (the principal afferent pathway of the anterolateral fasciculus), so that the longest fibers from the sacral segments come to lie most superficially and fibers from successively more rostral levels occupy progressively deeper positions (Fig. 7-3). This somatotopic arrangement was of importance to neurosurgeons, who performed an operation for pain relief, insofar as the depth to which the funiculus was cut governed the level of analgesia that was achieved; for the neurologist, it provides an explanation of the pattern of “sacral sparing” of pain and thermal sensation created by centrally placed lesions of the spinal cord. The termination of the spinothalamic tract, mainly in the thalamus, is described further on.


Neurology_Adams

Neurology_Adams. In addition to the anterolateral spinothalamic tract—a fast-conducting pathway that projects directly to the thalamus—the anterolateral fasciculus of the cord contains several more slowly conducting, medially placed systems of fibers. One such group of fibers projects directly to the reticular core of the medulla and midbrain and then to the medial and intralaminar nuclei of the thalamus; these fibers are referred to as the spinoreticulothalamic or paleospinothalamic pathway. At the level of the medulla, these fibers synapse in the nucleus gigantocellularis; more rostrally, they connect with nuclei of the parabrachial region, midbrain reticular formation, periaqueductal gray matter, and hypothalamus. A second, more medially placed pathway in the anterolateral cord ascends to the brainstem reticular core via a series of short interneuronal links. It is not clear whether these spinoreticular fibers are collaterals of the spinothalamic tracts, as Cajal originally stated, or whether they


Neurology_Adams

Neurology_Adams. reticular core via a series of short interneuronal links. It is not clear whether these spinoreticular fibers are collaterals of the spinothalamic tracts, as Cajal originally stated, or whether they represent an independent system, as more recent data seem to indicate. Probably both statements are correct. There is also a third, direct spinohypothalamic pathway in the anterolateral fasciculus.


Neurology_Adams

Neurology_Adams. The conduction of diffuse, poorly localized pain arising from deep and visceral structures (gut, periosteum, peritoneum) has been ascribed to these slow-conducting, indirect pathways. Melzack and Casey have proposed that this fiber system (which they referred to as paramedian), with its diffuse projection via brainstem and thalamus to the limbic and frontal lobes, subserves the affective aspects of pain, that is, the unpleasant feelings engendered by pain. It is evident that these spinoreticulothalamic pathways continue to evoke the psychic experience of pain even when the direct spinothalamic pathways have been interrupted. Also, the pathways for visceral pain from the esophagus, stomach, small bowel, and proximal colon are carried largely in the vagus nerve and terminate in the nucleus of the solitary tract (nucleus tractus solitarius [NTS]) before projecting to the thalamus, as described below. Other abdominal viscera still activate the NTS when the vagus is severed in animals,


Neurology_Adams

Neurology_Adams. of the solitary tract (nucleus tractus solitarius [NTS]) before projecting to the thalamus, as described below. Other abdominal viscera still activate the NTS when the vagus is severed in animals, probably transmitting impulses through the splanchnic plexus. However, it is the direct spinothalamic pathway, which projects to the ventroposterolateral (VPL) nucleus of the thalamus and thence to discrete areas of the sensory cortex, that subserves the sensory-discriminative detection of the location, quality, and possibly the intensity of the noxious stimulus.


Neurology_Adams

Neurology_Adams. It should be emphasized that the foregoing data concerning the cells of termination of cutaneous nociceptive stimuli and the cells of origin of ascending spinal afferent pathways have all been obtained from studies in animals (including monkeys). In humans, the specific cells of origin of the direct spinothalamic tract fibers have not been fully identified. Information about this pathway in humans has been derived from the study of postmortem material and from the examination of patients subjected to anterolateral cordotomy for intractable pain. What can be stated of clinical importance is that unilateral section of the anterolateral funiculus produces a relatively complete loss of pain and thermal sense on the opposite side of the body, extending to a level two or three segments below the lesion as noted earlier. After a variable period of time, partial sensibility for pain usually returns, probably being conducted by pathways that lie outside the anterolateral quadrants of the


Neurology_Adams

Neurology_Adams. the lesion as noted earlier. After a variable period of time, partial sensibility for pain usually returns, probably being conducted by pathways that lie outside the anterolateral quadrants of the spinal cord that gradually increase their capacity to conduct pain impulses. One of these is a longitudinal polysynaptic bundle of small myelinated fibers in the center of the dorsal horn (the dorsal intracornual tract); another consists of axons of lamina I cells that travel in the dorsal part of the lateral funiculus.


Neurology_Adams

Thalamic Terminus of Pain Fibers

Neurology_Adams. Thalamic Terminus of Pain Fibers


Neurology_Adams

Neurology_Adams. The spinothalamic fibers terminate in the ventral posterior nuclei, the most important of which are the ventroposterolateral (VPL) and ventroposteromedial (VPM) nuclei. These are the nuclei that project to the parietal and other areas of the cortex and subserve discriminative functions relating to pain. A contingent of medially projecting direct spinothalamic fibers terminates in the intralaminar complex of nuclei and in the nucleus submedius. These pertain to less-specific aspects of pain such as alerting and arousal. The indirect spinoreticulothalamic fibers also project onto the intralaminar thalamic nuclei and overlap with the terminations of the direct spinothalamic pathway. Projections from the dorsal column nuclei, which have a modulating influence on pain transmission, are mainly to the ventroposterior group of thalamic nuclei. Each of the thalamic nuclear groups has a distinct cortical projection and each is thought to play a different role in pain sensation (see below).


Neurology_Adams

Neurology_Adams. One practical conclusion to be reached from anatomic and physiologic studies is that, at thalamic levels, fibers and cell stations transmitting nociceptive impulses are not organized into discrete loci. In general, as one ascends from peripheral nerve to spinal, medullary, mesencephalic, thalamic, and limbic levels, the predictability of neuron responsivity to noxious stimuli diminishes. Thus it comes as no surprise that neurosurgical lesions that interrupt afferent pathways at progressively higher levels of the brainstem and thalamus become decreasingly successful.


Neurology_Adams

Neurology_Adams. Both ventroposterior nuclei project to two main cortical areas: the primary sensory (postcentral) cortex (a small number terminate in the precentral cortex) and the upper bank of the sylvian fissure. The thalamic projection to the primary sensory cortex that is distributed mainly along the postcentral gyrus of the anterior parietal lobe is shown in Fig. 8-6 (the “sensory homunculus”). The cortical representation allows for accurate localization of the site of origin of a painful stimulus but the notion that thalamic projections terminate solely in this region is an oversimplification. These cortical projections are described more fully in Chap. 8 but it can be stated that they are concerned mainly with the reception of tactile and proprioceptive stimuli and with all discriminative sensory functions, including pain. However, stimulation of these (or any other) cortical areas in a normal, alert human being does not produce pain, for which reason the extent to which cortical areas are


Neurology_Adams

Neurology_Adams. functions, including pain. However, stimulation of these (or any other) cortical areas in a normal, alert human being does not produce pain, for which reason the extent to which cortical areas are directly activated by thermal and painful stimuli remains uncertain.


Neurology_Adams

Neurology_Adams. The intralaminar nuclei, which also project to the hypothalamus, amygdaloid nuclei, and limbic cortex, probably mediate the arousal and affective aspects of pain and autonomic responses. Thalamic and cerebral cortical localization of visceral sensation is not well known. However, cerebral-evoked potentials and increased cerebral blood flow (by positron emission tomography [PET] studies) have been demonstrated in the thalamus and preand postcentral gyri of patients undergoing rectal balloon distention (Silverman et al; Rothstein et al).


Neurology_Adams

Neurology_Adams. The discovery of a system of descending fibers and way stations that modulate activity in nociceptive pathways has proved to be a major addition to our knowledge of pain. The endogenous pain control system that has been studied most extensively emanates from the frontal cortex and hypothalamus and projects to cells in the periaqueductal region of the midbrain and then passes to the ventromedial medulla. From there it descends in the dorsal part of the lateral fasciculus of the spinal cord to the posterior horns (laminae I, II, and V; see further discussion under “Endogenous Pain-Control Mechanisms”). Several other noradrenergic and serotonergic descending pathways, which arise in the locus ceruleus, dorsal raphe nucleus, and nucleus reticularis gigantocellularis, are also important modifiers of the nociceptive response. The clinical significance of these pain-modulating pathways, still under study, is discussed further on.


Neurology_Adams

Neurology_Adams. The stimuli that activate pain receptors vary from one tissue to another. The adequate stimulus for skin is one that has the potential to injure tissue, that is, pricking, cutting, crushing, burning, and freezing. These stimuli are ineffective when applied to the stomach and intestine, where pain is produced by an engorged or inflamed mucosa, distention or spasm of smooth muscle, and traction on the mesenteric attachment. In skeletal muscle, pain is caused by ischemia (the basis of intermittent claudication), necrosis, hemorrhage, injection of irritating substances, and by injuries of connective tissue sheaths. Prolonged contraction of skeletal muscle evokes an aching type of pain. Ischemia is also the most important cause of pain in cardiac muscle. Joints are insensitive to pricking, cutting, and cautery, but pain can be produced in the synovial membrane by inflammation and by exposure to hypertonic saline. The stretching and tearing of ligaments around a joint can evoke severe pain.


Neurology_Adams

Neurology_Adams. and cautery, but pain can be produced in the synovial membrane by inflammation and by exposure to hypertonic saline. The stretching and tearing of ligaments around a joint can evoke severe pain. Injuries to the periosteum give rise to pain but probably not to other sensations. Blood vessels are a source of pain when pierced by a needle or involved in an inflammatory process. Distention of arteries or veins, as occurs with thrombotic or embolic occlusion, may be sources of pain; other mechanisms, operative mainly in headache, relate to traction on arteries or inflammation of the meningeal structures by which they are supported. Pain from intraneural lesions probably arises from the sheaths of the nerves. Nerve root(s) and sensory ganglia, when compressed (e.g., by a ruptured disc), give rise to pain. The special subject of headache and its origins is taken up in Chap. 9.


Neurology_Adams

Neurology_Adams. With damage to tissue, there is a release of proteolytic enzymes, which act locally on tissue proteins to liberate substances that excite peripheral nociceptors. These pain-producing substances—which include histamine, prostaglandins, serotonin, and similar polypeptides, as well as potassium ions—elicit pain when they are injected intraarterially or intradermally. Other pain-producing substances such as kinins are released from sensory nerve endings or are carried there by the circulation. Local vascular permeability is also increased by these substances.


Neurology_Adams

Neurology_Adams. In addition, direct stimulation of nociceptors releases polypeptide mediators that enhance pain perception. The best studied of these is substance P, which is released from the nerve endings of C fibers in the skin during peripheral nerve stimulation. It causes erythema by dilating cutaneous vessels and edema by releasing histamine from mast cells; it also acts as a chemoattractant for leukocytes. This reaction, called neurogenic inflammation by White and Helme, is mediated by antidromic action potentials from the small nerve cells in the spinal ganglia and is the basis of the axon reflex of Lewis; the reflex is abolished in peripheral nerve diseases and can be studied electrophysiologically as an aid to clinical localization. The final pathway of activation of sensory nerves consists of opening of the various channels that are expressed on the surface of sensory endings and axons, as detailed in an earlier section. Perception of Pain


Neurology_Adams

Neurology_Adams. The threshold for perception of pain, that is, the lowest intensity of a stimulus recognized as pain, is approximately the same in all persons. Inflammation lowers the threshold for perception of pain by a process called sensitization. The pain threshold is, of course, raised by local anesthetics, centrally acting analgesic drugs, and by certain lesions of the nervous system. Mechanisms other than lowering or raising the pain threshold are important as well. Placebos reduce pain in about one-third of patients in which such effects have been studied (see further on for discussion of placebo). Distraction and suggestion, by turning attention away from the source of pain, reduce the awareness of and response to pain but not the threshold for its perception. Strong emotion (fear or rage) suppresses pain, presumably by activation of the above-described descending noradrenergic system. The experience of pain appears to be lessened in manic states and enhanced in depression. Anxious patients


Neurology_Adams

Neurology_Adams. pain, presumably by activation of the above-described descending noradrenergic system. The experience of pain appears to be lessened in manic states and enhanced in depression. Anxious patients in general have the same pain threshold as normal subjects but their reaction may be excessive or abnormal. The pain thresholds of frontal lobotomized subjects are also unchanged but they react to painful stimuli only briefly or casually if at all. Some of the terminology pertaining to abnormal pain perception is discussed below.


Neurology_Adams

Neurology_Adams. The conscious awareness or perception of pain occurs only when pain impulses reach the thalamocortical level. The precise roles of the thalamus and cortical sensory areas in this mental process are not fully understood. It was believed that the recognition of a noxious stimulus as such is a function of the thalamus and that the parietal cortex is necessary for appreciation of the intensity, localization, and other discriminatory aspects of sensation. This traditional separation of sensation (in this instance, awareness of pain) and perception (awareness of the nature of the painful stimulus) has evolved to the view that sensation, perception, and the various conscious and unconscious responses to a pain stimulus comprise an indivisible process. That the cerebral cortex governs the patient’s reaction to pain cannot be doubted. It is also likely that the cortex can suppress or otherwise modify the perception of pain; for example, it has been shown that central transmission in the


Neurology_Adams

Neurology_Adams. reaction to pain cannot be doubted. It is also likely that the cortex can suppress or otherwise modify the perception of pain; for example, it has been shown that central transmission in the spinothalamic tract can be inhibited by stimulation of the sensorimotor areas of the cerebral cortex. As indicated above, a number of descending fiber systems have been traced to the dorsal horn laminae from which this tract originates.


Neurology_Adams

Neurology_Adams. The functional imaging studies by Wager and coworkers have given insights into the ensemble of brain regions that are activated by painful stimuli. In addition to the expected thalamic and parietal sensory regions, the hypothalamus, and both insular and cingulate cortices, are prominently involved, in proportion to the intensity of the stimulus. These investigators have sought to develop an imaging “pain signature” that could, in the future, objectively measure the human pain response. Moreover, physical pain in their experiments could be differentiated from social and emotional pain.


Neurology_Adams

Neurology_Adams. An important contribution to our understanding of pain has been the discovery of a neuronal analgesia system that can be activated by the administration of opiates or by naturally occurring brain substances that share the properties of opiates. This endogenous system was first demonstrated by Reynolds, who found that stimulation of the ventrolateral periaqueductal gray matter in the rat produced a profound analgesia without altering behavior or motor activity. Subsequently, stimulation of other discrete sites in the medial and caudal regions of the diencephalon and rostral bulbar nuclei (notably raphe magnus and paragigantocellularis) was shown to have the same effect. Under the influence of such electrical stimulation, the animal could be operated on without anesthesia and move around in an undisturbed manner despite the administration of noxious stimuli. Investigation disclosed that the effect of stimulation-produced analgesia (SPA) is inhibition of the neurons of Rexed laminae I,


Neurology_Adams

Neurology_Adams. an undisturbed manner despite the administration of noxious stimuli. Investigation disclosed that the effect of stimulation-produced analgesia (SPA) is inhibition of the neurons of Rexed laminae I, II, and V of the dorsal horn, which are the neurons activated by noxious stimuli. In human subjects, stimulation of the midbrain periaqueductal gray matter through stereotactically implanted electrodes can also produced a state of analgesia. Other sites in which electrical stimulation is effective in suppressing nociceptive responses are the rostroventral medulla (nucleus raphe magnus and adjacent reticular formation) and the dorsolateral pontine tegmentum. These effects are relayed to the dorsal horn gray matter via a pathway in the dorsolateral funiculus of the spinal cord. Ascending pathways from the dorsal horn, conveying noxious somatic impulses, are also important in activating the modulatory network.


Neurology_Adams

Neurology_Adams. Opiates act preand postsynaptically on the neurons of laminae I and V of the dorsal horn, suppressing afferent pain impulses from both the A-d and C fibers as previously discussed. Furthermore, these effects can be reversed by the opioid antagonist naloxone. Interestingly, naloxone can reduce some forms of stimulation-produced analgesia. Levine and colleagues have demonstrated that not only does naloxone enhance clinical pain, but it also interferes with the pain relief produced by placebos. These observations suggest that the heretofore poorly understood beneficial effects of placebos may partly result from activation of an endogenous system that mutes pain through the release of endogenous opioids, or endorphins (see below). Prolonged pain and fear are the most powerful activators of this endogenous opioid-mediated modulating system. The same system is probably operative under a variety of other stressful conditions; for example, some soldiers, wounded in battle, require little or


Neurology_Adams

Neurology_Adams. endogenous opioid-mediated modulating system. The same system is probably operative under a variety of other stressful conditions; for example, some soldiers, wounded in battle, require little or no analgesic medication (“stress-induced analgesia”). The opiates also act at several loci in the brainstem, at sites corresponding with those producing analgesia when stimulated electrically and generally conforming to areas in which neurons with endorphin receptors are localized.


Neurology_Adams

Neurology_Adams. Soon after the discovery of specific opiate receptors in the central nervous system, several naturally occurring peptides that bind specifically to these receptors and have a potent analgesic effects were identified. These endogenous, morphine-like compounds are generically referred to as endorphins, meaning “the morphines within.” The most widely studied are b-endorphin, a peptide sequence of the pituitary hormone b-lipotropin, and two other peptides, enkephalin and dynorphin. They and their receptors are found in greatest concentration in the midbrain. At the level of the spinal cord, exclusively enkephalin receptors are found. Figure 7-4 illustrates a theoretical construct of the roles of enkephalin (and substance P) at the point of entry of pain fibers into the spinal cord. Different elements of the sensory system produce and release each of these peptides. A subgroup of dorsal horn interneurons that are in contact with spinothalamic tract neurons also contains enkephalin. Much of


Neurology_Adams

Neurology_Adams. of the sensory system produce and release each of these peptides. A subgroup of dorsal horn interneurons that are in contact with spinothalamic tract neurons also contains enkephalin. Much of the seminal early work in this field was summarized by Snyder.


Neurology_Adams

Neurology_Adams. Thus it appears that the central effects of a painful condition are determined by many ascending and descending systems using a variety of transmitters. Some aspects of opiate addiction and also the discomfort that follows withdrawal of the drug might also be accounted for in this way. Indeed, it is known that some of these peptides not only relieve pain but suppress withdrawal symptoms.


Neurology_Adams

Neurology_Adams. It should be noted that the descending pain-control systems contain, in addition to opiate connections, noradrenergic and serotonergic influences as well. A descending norepinephrine-containing pathway, as mentioned, has been traced from the locus ceruleus in the dorsolateral pons to the spinal cord, and its activation blocks spinal nociceptive neurons. The rostroventral medulla contains a large number of serotonergic neurons from which descending fibers inhibit dorsal horn cells concerned with pain transmission, perhaps providing a rationale for the use of certain antidepression serotonin agonist medications in patients with chronic pain. Finally, there is remodeling of the types and densities of surface receptors in the posterior horns as a result of nerve injury. These changes alter the effects of the above mentioned secondary modulating systems on pain pathways. This assumes importance in states of chronic pain after somatic and neural injury as discussed in the next sections.


Neurology_Adams

Neurology_Adams. Several terms related to the experience of altered sensations and pain are often used interchangeably but each has specific meaning. Hyperesthesia is a general term for heightened cutaneous sensitivity. The term hyperalgesia refers to an increased sensitivity and a lowered threshold to painful stimuli. Inflammation and burns of the skin are common causes of hyperalgesia. The term hypalgesia, or hypoalgesia, refers to the opposite state—that is, a decreased sensitivity and a raised threshold to painful stimuli. A demonstrable reduction in pain perception (i.e., an elevated threshold) associated with an increased reaction to the stimulus once it is perceived, is sometimes referred to as hyperpathia (subtly different from hyperalgesia). In this circumstance there is an excessive reaction to all stimuli, even those (such as light touch) that normally do not evoke pain, a symptom termed allodynia. The elicited allodynic pain may have unusual features, outlasting the stimulus and being


Neurology_Adams

Neurology_Adams. to all stimuli, even those (such as light touch) that normally do not evoke pain, a symptom termed allodynia. The elicited allodynic pain may have unusual features, outlasting the stimulus and being diffuse, modifiable by fatigue and emotion, and often being mixed with other sensations. The mechanism of these abnormalities is not clear but both hyperpathia and allodynia are common features of neuropathic or neurogenic pain, such as the pain generated by peripheral neuropathy. These features are also exemplified by causalgia, a type of burning pain that results from interruption of a peripheral nerve (see “Causalgia and Reflex Sympathetic Dystrophy”).


Neurology_Adams

Neurology_Adams. As indicated earlier, the nerve endings in each tissue are activated by different mechanisms, and the pain that results is characterized by its quality, locale, and temporal attributes. Skin pain is of two types: a pricking pain, evoked immediately on penetration of the skin by a needle point; or a stinging or burning pain that follows in a second or two. Together they constitute the “double response” of Lewis. Both types of dermal pain can be localized with precision. Compression of nerves by the application of a tourniquet to a limb abolishes pricking pain before burning pain because large fibers are more susceptible to pressure. The first (fast) pain is transmitted by the larger (A-d) fibers and the second (slow) pain, which is somewhat more diffuse and longer lasting, by the thinner, unmyelinated C fibers.


Neurology_Adams

Neurology_Adams. Deep pain from visceral and skeletomuscular structures is usually aching in quality; if intense, it may be sharp and penetrating (knife-like). Occasionally visceral derangements cause a burning type of pain, as in the “heartburn” of esophageal irritation and rarely in angina pectoris. The pain is felt as being deep to the body surface. It is diffuse and poorly localized, and the margins of the painful zone are not well delineated, presumably because of the relative paucity of nerve endings in viscera. Visceral pain produces two additional sensations. First, there is tenderness at remote superficial sites (“referred hyperalgesia”) and, second, an enhanced pain sensitivity in the same and in nearby organs (“visceral hyperalgesia”). This is a restatement of Head’s early observations, discussed above, and the referred “Head zones,” where somatic and visceral sensibility overlap as discussed below. The concept of visceral hyperalgesia has received considerable attention in a number of pain


Neurology_Adams

Neurology_Adams. above, and the referred “Head zones,” where somatic and visceral sensibility overlap as discussed below. The concept of visceral hyperalgesia has received considerable attention in a number of pain syndromes in reference to the transition from acute to chronic pain, particularly in headache.


Neurology_Adams

Neurology_Adams. The localization of deep pain of visceral origin raises a number of problems. Deep pain has indefinite boundaries and its location is distant from the visceral structure involved. It tends to be referred not to the skin overlying the viscera of origin but to other areas innervated by the same spinal segment (or segments). This pain, projected to some fixed site at a distance from the source, is called referred pain. The ostensible explanation for the site of referral is that small-caliber pain afferents from deep structures project to a wide range of lamina V neurons in the dorsal horn, as do cutaneous afferents. The convergence of deep and cutaneous afferents on the same dorsal horn cells, coupled with the fact that cutaneous afferents are far more numerous than visceral afferents and have direct connections with the thalamus, is probably responsible for the phenomenon.


Neurology_Adams

Neurology_Adams. Because the nociceptive receptors and nerves of any given visceral or skeletal structure may project upon the dorsal horns of several adjacent spinal or brainstem segments, the pain from these structures may be fairly widely distributed. For example, afferent pain fibers from cardiac structures, distributed through segments T1 to T4, may be projected to the inner side of the arm and the ulnar border of the hand and arm (T1 and T2) as well as the precordium (T3 and T4). Once this pool of sensory neurons in the dorsal horns of the spinal cord is activated, additional noxious stimuli may heighten the activity in the whole sensory field ipsilaterally and, to a lesser extent, contralaterally.


Neurology_Adams

Neurology_Adams. The regions of projection of pain that originate in the bones and adjacent ligamentous structures have been called by Kellgren, “sclerotomes.” His maps of pain referral patterns were established from studies of the injection of hypertonic saline into muscle and interspinous ligaments. Although dermatomes and sclerotomes overlap, the patterns are slightly different as shown in Fig. 7-5, which is taken from Inman and Saunders. These sclerotomatous projections are useful to neurologists in analyzing the origins of unusual pains of the cranium, spine, and limbs (see Chaps. 9 and 10).


Neurology_Adams

Neurology_Adams. Another peculiarity of localization is aberrant reference, explained by an alteration of the physiologic status of the pools of neurons in adjacent segments of the spinal cord. For example, cervical arthritis or gallbladder disease, causing low-grade discomfort by constantly activating their particular segmental neurons, may induce a shift of cardiac pain cephalad or caudad from its usual locale. Once it becomes chronic, any pain may spread quite widely in a vertical direction on one side of the body. On the other hand, painful stimuli arising from a distant site exert an inhibitory effect on segmental nociceptive flexion reflexes in the leg, as demonstrated by DeBroucker and colleagues.


Neurology_Adams

Neurology_Adams. Yet another clinical peculiarity of segmental pain is the reduction in power of muscle contraction that it may cause (known as reflex paralysis, or algesic weakness). The term “antalgia” is often used to describe this effort to avoid pain with movement, especially antalgic gait that arises from lumbar disc or other spinal or hip problems.


Neurology_Adams

Neurology_Adams. One of the most perplexing issues in the study of pain is the manner in which chronic pain syndromes arise. Several theories have been offered, none of which satisfactorily accounts for all the clinically observed phenomena. One hypothesis proposes that in an injured nerve, the unmyelinated sprouts of A-d and C fibers become capable of spontaneous ectopic excitation and afterdischarge and are susceptible to ephaptic activation. A second proposal derives from the observation that these injured nerves are also sensitive to locally applied or intravenously administered catecholamines because of an overabundance of adrenergic receptors on the regenerating fibers. These mechanisms are thought to be the basis of causalgia (persistent burning and aching pain in the territory of a partially injured nerve and beyond) and its associated reflex sympathetic dystrophy; either would explain the relief afforded in these conditions by sympathetic block. This subject is discussed in greater detail in


Neurology_Adams

Neurology_Adams. nerve and beyond) and its associated reflex sympathetic dystrophy; either would explain the relief afforded in these conditions by sympathetic block. This subject is discussed in greater detail in relation to peripheral nerve injuries (see “Peripheral Nerve Pain” and Chap. 43).


Neurology_Adams

Neurology_Adams. A third proposed mechanism is through central sensory structures, for example, sensory neurons in the dorsal horns of the spinal cord or thalamus, if chronically bombarded with pain impulses, may become autonomously overactive (being maintained in this state perhaps by excitatory amino acids) and may remain so even after the peripheral pathways have been interrupted. Peripheral nerve lesions have been shown to induce enduring derangements of central (spinal cord) processing (Fruhstorfer and Lindblom). For example, avulsion of nerves or nerve roots may cause chronic pain even in analgesic zones (anesthesia dolorosa or “deafferentation pain”). In experimentally deafferented animals, neurons of lamina V begin to discharge irregularly in the absence of stimulation. Later the abnormal discharge subsides in the spinal cord but can still be recorded in the thalamus. Consequently, painful states such as causalgia, spinal cord pain, and phantom pain are not abolished simply by cutting spinal


Neurology_Adams

Neurology_Adams. subsides in the spinal cord but can still be recorded in the thalamus. Consequently, painful states such as causalgia, spinal cord pain, and phantom pain are not abolished simply by cutting spinal nerves or spinal tracts.


Neurology_Adams

Neurology_Adams. It is likely that structural or physiologic changes in the spinal cord, of the type alluded to above, are able to produce persistent stimulation of pain pathways. Indo and colleagues review the molecular changes in the spinal cord that may give rise to persistence of pain after the cessation of an injurious episode. It is an open question whether the early treatment of pain may prevent the cascade of biochemical events that allows for both spread and persistence of pain in conditions such as causalgia, but it has been the experience of most clinical pain experts that preemptive treatment of certain painful conditions (e.g., herpes zoster) may reduce the risk of a chronic pain syndrome. None of these phenomena adequately explain the genesis of chronic pain in the absence of an ongoing painful stimulus.


Neurology_Adams

Neurology_Adams. Pain has several other singular attributes. It does not appear to be subject to negative adaptation—that is, pain may persist as long as the stimulus is operative—whereas other somatic stimuli, if applied continuously, soon cease to be perceived. Furthermore, prolonged stimulation of pain receptors sensitizes them, so that they become responsive to even low grades of stimulation, even to touch (allodynia). The Emotional Reaction to Pain


Neurology_Adams

Neurology_Adams. Another remarkable characteristic of pain is the strong feeling or affect with which it is endowed, nearly always unpleasant. Since pain embodies this element, psychologic conditions assume great importance in all persistent painful states. It is of interest that despite this strong affective aspect of pain, it is difficult to recall precisely, or to reexperience from memory, a previously experienced acute pain. Also, the patient’s tolerance of pain and capacity to experience it without verbalization are influenced by culture and personality. Some individuals—by virtue of training, habit, or phlegmatic temperament—remain stoic in the face of pain, and others react in an opposite fashion. In other words, there are inherent variations among individuals that determine the limbic system’s response to pain and their expression of it. In this regard, it is important to emphasize that pain may be the presenting or predominant symptom in a depressive illness (Chap. 48).


Neurology_Adams

Neurology_Adams. Price reviews this subject of the affective dimension of pain in detail, but it must be acknowledged that the models offered are largely theoretical. It is noteworthy, however, that on functional imaging studies, regions of the cerebrum that are activated by experimentally induced physical pain overlap to a limited degree with those for the experience of emotional pain, as reported by Wager and colleagues.


Neurology_Adams

Neurology_Adams. Finally, a comment should be made about the devastating behavioral effects of chronic pain. To quote from Ambroïse Paré, a sixteenth-century French surgeon, “There is nothing that abateth so much the strength as paine.” Continuous pain increases irritability and fatigue, disturbs sleep, and impairs appetite. Patients in pain may seem irrational about their illness and may make unreasonable demands on family and physician. Characteristic is an unwillingness to engage in or continue any activity that might enhance their pain. They withdraw from the main current of daily affairs as their thoughts and speech come to be dominated by the pain. Once a person is subjected to the tyranny of chronic pain, depressive symptoms are practically always added. A person’s entire identity may be dominated by the mixture of pain and depression (l’homme doloureux). Determining the cause and effect is usually a futile exercise.


Neurology_Adams

Neurology_Adams. One learns quickly that not all pain is the consequence of serious disease. Every day, healthy persons of all ages have pains that must be taken as part of normal sensory experience. To mention a few, there are the “growing pains” of presumed bone and joint origin of children; the momentary shock-like pains over an eye or in the temporal or occipital regions (“ice-pick” pain), which strike with such suddenness as to raise the suspicion of a ruptured intracranial aneurysm; inexplicable split-second jabs of pain elsewhere; the more persistent ache in the shoulder, hip, or extremity that subsides spontaneously or in response to a change in position; the fluctuant precordial discomfort of gastrointestinal origin, which conjures up fear of cardiac disease; and the breathtaking “stitch in the side” caused by intercostal or diaphragmatic cramp during exercise. These “normal pains,” as they may be called, tend to be brief and to depart as obscurely as they came. Such pains come to notice only


Neurology_Adams

Neurology_Adams. caused by intercostal or diaphragmatic cramp during exercise. These “normal pains,” as they may be called, tend to be brief and to depart as obscurely as they came. Such pains come to notice only when elicited by an inquiring physician or when experienced by a patient given to excessive worry and introspection. They must be distinguished from the pain of disease.


Neurology_Adams

Neurology_Adams. Whenever pain—by its intensity, duration, and the circumstances of its occurrence—appears to be abnormal or when it constitutes the chief complaint or one of the principal symptoms, the physician must attempt to reach a tentative decision as to its mechanism and cause. This is accomplished by a thorough interrogation of the patient, with the physician carefully seeking out the main characteristics of the pain in terms of the following: Mode and time of onset Associated features, e.g., nausea, muscle spasm


Neurology_Adams

Neurology_Adams. Knowledge of these factors, together with the physical examination, including maneuvers designed to reproduce and relieve the pain and ancillary diagnostic procedures, enable the physician to identify the source of most pains and the diseases of which they are a part. Nevertheless, the severity of pain is often difficult to assess reliably. Extreme degrees of pain are betrayed by the patient’s demeanor but lesser degrees can be roughly estimated by the extent to which the pain has interfered with the patient’s sleep, work, and other activities, or by the patient’s need for bed rest. Some physicians find it helpful, particularly in gauging the effects of analgesic agents, to use a “pain scale,” that is, to have the patient rate the intensity of his pain on a scale of zero (no pain) to 10 (worst pain) or to mark it on a line (the Visual Analog Pain Scale). It has been our experience that this effort to quantify pain is often unhelpful to the neurological analysis as patients rarely rate


Neurology_Adams

Neurology_Adams. pain) or to mark it on a line (the Visual Analog Pain Scale). It has been our experience that this effort to quantify pain is often unhelpful to the neurological analysis as patients rarely rate pain as trivial once they have decided to consult a physician about the problem. For most patients, pain that necessitates medical consultation is, by definition, considered to be serious. This general approach is put to use every day in the practice of general medicine.


Neurology_Adams

Neurology_Adams. In addition to the pains caused by the more common and readily recognized diseases of each organ system, there remain a significant number of chronic pains that fall into one of four categories: (1) pain from an obscure medical disease, the nature of which has not yet been disclosed by diagnostic procedures; (2) pain associated with disease of the central or peripheral nervous system (i.e., neurogenic, or neuropathic pain); (3) pain associated with psychiatric disease; and (4) pain of unknown cause.