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Neurology_Adams. and not from within; the pressure waves propagate syrinx fluid caudally with each heartbeat. This hardly exhausts the list of hypotheses that have been offered over the years but none of them has been confirmed.


Neurology_Adams

Neurology_Adams. The authors favor the type of hydrodynamic mechanism as postulated originally by Gordon Holmes and elaborated by Ball and Dayan. In this view, a relationship exists between basal cranial, cervical spine, the cerebellospinal Chiari malformation, syringomyelia, and disturbed hydrodynamics of perispinal CSF. Logue and Edwards documented several cases of syringomyelia in which the foramen magnum was obstructed by a lesion other than a Chiari formation, for example, by dural cyst, localized arachnoiditis, atlantoaxial fusion, simple cerebellar cyst, and basilar invagination (see Williams for a review of the numerous hypotheses of causation).


Neurology_Adams

Neurology_Adams. Irrespective of its mode of origin, the syrinx first occupies the central gray matter of the cervical portion of the spinal cord, usually independent of the central canal but sometimes extending into it. It interrupts the crossing pain and temperature fibers in the anterior commissure at several successive cord segments. As the cavity enlarges, it extends symmetrically or asymmetrically into the posterior and anterior horns and eventually into the lateral and posterior funiculi of the cord. It may enlarge the spinal cord. The cavity is lined with astrocytic glia and a few thick-walled blood vessels, and the fluid in the cavity is clear and in our patients, has had relatively low protein content, like intracranial CSF.


Neurology_Adams

Neurology_Adams. The cavitation nearly always arises in the cervical portion of the cord and can only reach the thoracic and lumbar portions by its extension from the cervical region, sometimes by a small, flat and thin, and eccentrically placed. Either a cavity or a glial septum may extend asymmetrically into the medulla, usually in the vicinity of the descending tract of the fifth cranial nerve to create a syringobulbia. The clinical picture of syringomyelia is so characteristic that diagnosis is seldom in doubt. Now one can obtain spectacular demonstrations of the syrinx, either traumatic or developmental (Fig. 42-14), Chiari malformations, and other foramen magnum lesions by MRI of the sagittal planes of the brain and spinal cord (see Fig. 37-4). Also, hours after a CT myelogram, contrast material fills the syrinx and the central canal directly, possibly by diffusion from the surface of the cord.


Neurology_Adams

Neurology_Adams. Certain rare polyneuropathies (amyloid, Tangier disease, and Fabry disease) that preferentially affect small fibers in the nerves of the upper extremities can reproduce the dissociated sensory loss that is characteristic of a syrinx (“pseudosyringomyelic” deficit), but motor abnormalities are not prominent in these neuropathic cases. These diseases are discussed in Chap. 43. For cases originating in a tumor, typically ependymoma in adults, resection of the tumor and some degree of decompression of the syrinx cavity can be undertaken to prevent progression of symptoms. The cyst fluid may be high in protein and viscid (unlike the low-protein fluid of the usual syrinx).


Neurology_Adams

Neurology_Adams. The only therapy of lasting value for type I syringomyelia (related to Chiari malformation) is surgical decompression of the foramen magnum and upper cervical canal. Headache and neck pain are helped most; ataxia and nystagmus tend to persist, but these are related to the Chiari process. The cavity tends to at least cease enlarging. Radiation therapy, which was formerly recommended, is of no benefit. The operation advised by Gardner, of plugging the connection between the fourth ventricle and the central canal of the cervical cord, has been abandoned. There were complications of this operative procedure, and the results were no better than those obtained from simple decompression. The decompression operation also carries some risk, especially if there is an attempt to excise the tonsillar projections of the cerebellum. In the series of Logue and Edwards, comprising 56 cases of type I syringomyelia, the occipitocervical pain was relieved by decompression in most patients, but the


Neurology_Adams

Neurology_Adams. projections of the cerebellum. In the series of Logue and Edwards, comprising 56 cases of type I syringomyelia, the occipitocervical pain was relieved by decompression in most patients, but the shoulder-arm pain usually persisted. Upper motor neuron weakness of the legs and sensory ataxia were often improved, whereas the segmental sensory and motor manifestations of the syringomyelia were not. Hankinson, in the past, had reported good results from decompression in 75 percent of type I cases of syringomyelia. In the retrospective review of 141 adult patients by Stevens and colleagues, good surgical outcome was achieved in 50 percent of those with minor degrees of descent of the cerebellar tonsils, but in only 12 percent of those with major cerebellar ectopia. A distended syrinx also led to a more favorable outcome. Whether the long-term course of these diseases is altered has not been determined. Other surgical series of Chiari-syrinx are discussed and cited in Chap. 37.


Neurology_Adams

Neurology_Adams. Syringotomy or shunting of the cavity has been performed in type I and some of the type II (idiopathic) cases, but the results have been unpredictable. Love and Olafson, who performed this procedure in 40 patients of both types (mainly type II), stated that 30 percent had an excellent outcome. Schurch and coworkers obtained improvement of pain and motor weakness in 5 of their 7 cases by stabilization of the spine and syringotomy with placement of a T-tube within the syrinx. In a more recent and comprehensive study of 73 patients with a developmental syrinx operated by Sgouros and Williams (1995), one-half remained clinically stable for a 10-year period; 15 percent had serious complications from the surgery, however. Our experience with this procedure has not persuaded us of its lasting value; most of these patients, even those who reported some improvement originally, soon relapsed to their preoperative state, and the disease then progressed in the usual way. An enlarged cervical cord


Neurology_Adams

Neurology_Adams. most of these patients, even those who reported some improvement originally, soon relapsed to their preoperative state, and the disease then progressed in the usual way. An enlarged cervical cord with progressive clinical worsening may nonetheless justify an attempt to shunt the cavity. Other comments are found in Chap. 37.


Neurology_Adams

Neurology_Adams. Surgery for the posttraumatic cases has given only slightly more favorable results. With incomplete myelopathy, syringotomy relieved the pain in all 10 patients of Shannon and associates. Where they found the myelopathy to be complete, the cord was transected and the upper stump excised. Sgouros and Williams (1996) studied 57 such patients and recommend decompressive laminectomy and reconstruction of the subarachnoid space as the most effective of the several procedures used in the management of traumatic cavities. An extensive review of surgical approaches to syringomyelia can be found in the article by Brodbelt and Stoodley, who tentatively recommend lysis of arachnoidal adhesions as preferable to shunting or filleting of the cord, but acknowledge that the current state of treatment is unsatisfactory.


Neurology_Adams

Neurology_Adams. The infrequent case of symptomatic purely hydromyelia may benefit from ventriculoperitoneal shunts of hydrocephalus, and a few excellent results are reported. This procedure has also been attempted in type I developmental cases, with unimpressive results unless there is an associated hydrocephalus. Draining the central canal by amputation of the tip of the sacral cord has been unsuccessful and can be harmful. Most patients with hydromyelia do not require treatment.


Neurology_Adams

Neurology_Adams. It is always well to remind oneself that of the more than 30 diseases of the spinal cord, effective means of treatment are available for many of the common ones: spondylosis, extramedullary spinal cord tumors, epidural abscess, hematoma and granuloma (tuberculous, fungal, sarcoidosis), myelitis, syringomyelia, and subacute combined degeneration and other forms of nutritional myelopathy. Many of the inflammatory myelopathies respond well to immune-modulating measures. The physician’s major responsibility is to determine whether the patient has one of these treatable diseases. Adams CBT, Logue V: Studies in cervical spondylotic myelopathy. Brain 94:557, 569, 1971. Allen AR: Surgery of experimental lesions of the spinal cord equivalent to crush injury of fracture dislocation of the spinal column: A preliminary report. JAMA 57:878, 1911. American Spinal Injury Association: Standards for Neurological Classification of Spinal Injury Patients. Chicago, American


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Neurology_Adams. American Spinal Injury Association: Standards for Neurological Classification of Spinal Injury Patients. Chicago, American Spinal Injury Association, 1984. Aminoff MJ, Logue V: The prognosis of patients with spinal vascular malformations. Brain 97:211, 1974. Angeli CA, Boakye M, Morton RA, et al: Recovery of over-ground walking after chronic motor complete spinal cord injury. N Engl J Med 379:1244, 2018. Antoni N: Spinal vascular malformations (angiomas) and myelomalacia. Neurology 12:795, 1962. Avrahami E, Tadmor R, Cohn DF: Magnetic resonance imaging in patients with progressive myelopathy following spinal surgery. J Neurol Neurosurg Psychiatry 52:176, 1989. Baker AS, Ojemann RG, Swartz MN, Richardson EP Jr: Spinal epidural abscess. N Engl J Med 293:463, 1975. Bakshi R, Kinkel PR, Mechtler LL, et al: Magnetic resonance imaging findings in 22 cases of myelitis: Comparison between patients with and without multiple sclerosis. Eur J Neurol 5:35, 1998.


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Neurology_Adams. Bakshi R, Kinkel PR, Mechtler LL, et al: Magnetic resonance imaging findings in 22 cases of myelitis: Comparison between patients with and without multiple sclerosis. Eur J Neurol 5:35, 1998. Ball MJ, Dayan AD: Pathogenesis of syringomyelia. Lancet 2:799, 1972. Ballantine HT, Ojemann RG, Drew JH: Syringohydromyelia. In: Krayenbuhl H, Maspes PE, Sweet WH (eds): Progress in Neurological Surgery. Vol 4. New York, Karger, 1971, pp 227–245. Barnett JHM, Foster JB, Hudgson P: Syringomyelia. Philadelphia, Saunders, 1973. Bartleson JO, Cohen MD, Harrington TM: Cauda equina syndrome secondary to long-standing ankylosing spondylitis. Ann Neurol 14:662, 1983. Bell HS: Paralysis of both arms from injury of the upper portion of the pyramidal decussation “cruciate paralysis.” J Neurosurg 33:376, 1970. Berkowitz AL, Samuels MS: The neurology of Sjogren’s syndrome and the rheumatology of peripheral neuropathy and myelitis. Pract Neurol 14:14, 2014.


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Neurology_Adams. Queiroz L de S, Nucci A, Facure NO, Facure JJ: Massive spinal cord necrosis in schistosomiasis. Arch Neurol 36:517, 1979. Reagan TJ, Thomas JE, Colby MY: Chronic progressive radiation myelopathy. JAMA 203:106, 1968. Rezai AR, Woo HL, Lee M, et al: Disseminated ependymomas of the central nervous system. J Neurosurg 85:618, 1996. Riddoch G: The reflex functions of the completely divided spinal cord in man, compared with those associated with less severe lesions. Brain 40:264, 1917. Robertson CE, Brown RD, Wijdicks EFM, Rabenstein AA: Recovery after spinal cord infarcts: Long-term outcome in 115 patients. Neurology 78:114, 2012. Roobol TH, Kazzaz BA, Vecht CJ: Segmental rigidity and spinal myoclonus as a paraneoplastic syndrome. J Neurol Neurosurg Psychiatry 50:628, 1987. Ropper AE, Cahill KS, Hanna JW, et al: Primary vertebral tumors: A review of epidemiologic, histologic, and imaging findings, Part I: Benign tumors. Neurosurgery 69:1171, 2011.


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Neurology_Adams. Ropper AE, Cahill KS, Hanna JW, et al: Primary vertebral tumors: A review of epidemiologic, histologic, and imaging findings, Part I: Benign tumors. Neurosurgery 69:1171, 2011. Ropper AE, Ropper AH: Acute spinal cord compression. N Engl J Med 376:1358, 2017. Ropper AH, Poskanzer DC: The prognosis of acute and subacute transverse myelitis based on early signs and symptoms. Ann Neurol 4:51, 1978. Roze E, Bounolleau P, Ducreux D, et al: Propriospinal myoclonus revisited: Clinical, neurophysiologic, and neuroradiologic findings. Neurology 72:1301, 2009. Rossier AB, Foo D, Shillito J: Posttraumatic cervical syringomyelia. Brain 108:439, 1985. Rowland LP: Surgical treatment of cervical spondylotic myelopathy: Time for a controlled study. Neurology 42:5, 1992. Sandson TA, Friedman SH: Spinal cord infarction: Report of 8 cases and review of the literature. Medicine (Baltimore) 68:282, 1989.


Neurology_Adams

Neurology_Adams. Sandson TA, Friedman SH: Spinal cord infarction: Report of 8 cases and review of the literature. Medicine (Baltimore) 68:282, 1989. Sanyal B, Pant GC, Subrahmaniyam K, et al: Radiation myelopathy. J Neurol Neurosurg Psychiatry 42:413, 1979. Sato T, Coler-Reilly AL, Yagishita N, et al: Mogamulizumab (Anti-CCR4) in HTLV-1–associated myelopathy. N Engl J Med 378:529, 2018. Savitsky N, Madonick MJ: Statistical control studies in neurology: Babinski sign. Arch Neurol Psychiatry 49:272, 1943. Schneider RC, Cherry G, Pantek H: The syndrome of acute central cervical spinal cord injury. J Neurosurg 11:546, 1954. Schurch B, Wichmann W, Rossier AB: Posttraumatic syringomyelia (cystic myelopathy): A prospective study of 449 patients with spinal cord injury. J Neurol Neurosurg Psychiatry 60:61, 1996. Scrimgeour EM, Gajdusek DC: Involvement of the central nervous system in Schistosoma mansoni and S. haematobium infection. Brain 108:1023, 1985.


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Neurology_Adams. Scrimgeour EM, Gajdusek DC: Involvement of the central nervous system in Schistosoma mansoni and S. haematobium infection. Brain 108:1023, 1985. Sgouros S, Williams B: A critical appraisal of drainage in syringomyelia. J Neurosurg 82:1, 1995. Sgouros S, Williams B: Management and outcome of posttraumatic syringomyelia. J Neurosurg 85:197, 1996. Shannon N, Simon L, Logue V: Clinical features, investigation, and treatment of posttraumatic syringomyelia. J Neurol Neurosurg Psychiatry 44:35, 1981. Sloof JH, Kernohan JW, MacCarty CS: Primary Intramedullary Tumors of the Spinal Cord and Filum Terminale. Philadelphia, Saunders, 1964. Spencer PS, Roy DN, Ludolph A, et al: Lathyrism: Evidence for role of the neuroexcitatory amino acid BOAA. Lancet 2:1066, 1986. Spiller WG: Thrombosis of the cervical anterior median spinal artery: Syphilitic acute anterior poliomyelitis. J Nerv Ment Dis 36:601, 1909.


Neurology_Adams

Neurology_Adams. Spiller WG: Thrombosis of the cervical anterior median spinal artery: Syphilitic acute anterior poliomyelitis. J Nerv Ment Dis 36:601, 1909. Stevens JM, Serva WA, Kendall BE, et al: Chiari malformation in adults: Relation of morphologic aspects to clinical features and operative outcome. J Neurol Neurosurg Psychiatry 56:1072, 1993. Stiell IG, Clement CM, McKnight RD, et al: The Canadian C-spine rule versus the NEXUS low-risk criteria in patients with trauma. N Engl J Med 349:2510, 2003. Stoltmann HF, Blackwood W: The role of the ligamenta flava in the pathogenesis of myelopathy in cervical spondylosis. Brain 87:45, 1964. Stookey B: Compression of the spinal cord due to ventral extradural cervical chondromas. Arch Neurol Psychiatry 20:275, 1928. Swann KW, Ropper AH, New PFJ, Poletti CE: Spontaneous spinal subarachnoid hemorrhage and subdural hematoma. J Neurosurg 61:975, 1984.


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Neurology_Adams. Swann KW, Ropper AH, New PFJ, Poletti CE: Spontaneous spinal subarachnoid hemorrhage and subdural hematoma. J Neurosurg 61:975, 1984. Symon L, Kuyama H, Kendall B: Dural arteriovenous malformations of the spine: Clinical features and surgical results in 55 cases. J Neurosurg 60:238, 1984. Thomas JE, Miller RH: Lipomatous tumors of the spinal canal. Mayo Clin Proc 48:393, 1973. Thompson TP, Pearce J, Chong G, et al: Surfer’s myelopathy. Spine 29:E353, 2004. Toossi S, Josephson SA, Hetts SW, et al: Utility of MRI in spinal arteriovenous fistula. Neurology 79:25, 2012. Tosi L, Rigoli G, Beltramello A: Fibrocartilaginous embolism of the spinal cord: A clinical and pathogenetic consideration. J Neurol Neurosurg Psychiatry 60:55, 1996. Uttley D, Monro P: Neurosurgery for cervical spondylosis. Br J Hosp Med 42:62, 1989. Uygunoglu U, Zeydan B, Ozguler Y, et al: Myelopathy in Beçhet disease: The bagel sign. Ann Neurol 82:288, 2017.


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Neurology_Adams. Uttley D, Monro P: Neurosurgery for cervical spondylosis. Br J Hosp Med 42:62, 1989. Uygunoglu U, Zeydan B, Ozguler Y, et al: Myelopathy in Beçhet disease: The bagel sign. Ann Neurol 82:288, 2017. Vallee B, Mercier P, Menei P, et al: Ventral transdural herniation of the thoracic cord: Surgical treatment in four cases and review of the literature. Acta Neurochir (Wien) 141:907, 1999. Watters MR, Stears JC, Osborn AG, et al: Transdural spinal cord herniation. AJNR 19:1337, 1998. Weidauer S, Nichtweiss M, Lanfermann H, et al: Spinal cord infarction: MR imaging and clinical features in 16 cases. Neuroradiology 44:851, 2002. Weisman AD, Adams RD: The neurological complications of dissecting aortic aneurysm. Brain 67:69, 1944. Whitely AM, Swash M, Urich H: Progressive encephalomyelitis with rigidity. Brain 99:27, 1976. Wilkinson M: Cervical Spondylosis, 2nd ed. Philadelphia, Saunders, 1971.


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Neurology_Adams. Whitely AM, Swash M, Urich H: Progressive encephalomyelitis with rigidity. Brain 99:27, 1976. Wilkinson M: Cervical Spondylosis, 2nd ed. Philadelphia, Saunders, 1971. Wilkinson PA, Valentine A, Gibbs JM: Intrinsic spinal cord lesions complicating epidural anaesthesia and analgesia: Report of three cases. J Neurol Neurosurg Psychiatry 72:537, 2002. Willeit J, Kiechl S, Kiechl-Kohlendarfer U, et al: Juvenile asymmetric segmental spinal muscular atrophy (Hirayama’s disease): Three cases without evidence of “flexion myelopathy.” Acta Neurol Scand 104:320, 2001. Williams B: The cystic spinal cord. J Neurol Neurosurg Psychiatry 58:649, 1995. Williams CS, Butler E, Roman GC: Treatment of myelopathy in Sjögren syndrome with a combination of prednisone and cyclophosphamide. Arch Neurol 59:815, 2001. Winkelman MD: Neurological complications of thermal and electrical burns. In: Aminoff MJ (ed): Neurology and General Medicine. New York, Churchill Livingstone, 1994, pp 915–929.


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Neurology_Adams. Winkelman MD: Neurological complications of thermal and electrical burns. In: Aminoff MJ (ed): Neurology and General Medicine. New York, Churchill Livingstone, 1994, pp 915–929. Winkelman MD, Adelstein DJ, Karlins NL: Intramedullary spinal cord metastases: Diagnostic and therapeutic considerations. Arch Neurol 44:526, 1987. Woltman HW, Adson AW: Abscess of the spinal cord. Brain 49:193, 1926. Woolsey RM, Young RR (eds): Neurologic Clinics: Disorders of the Spinal Cord. Philadelphia, Saunders, 1991. Wyburn-Mason R: Vascular Abnormalities and Tumors of the Spinal Cord and Its Membranes. St. Louis, Mosby, 1944. Yogananden N, Larson SJ, Gallagher M: Correlation of microtrauma in the spine with intraosseous pressure. Spine 19:435, 1994. Zimmerli W: Vertebral osteomyelitis. N Engl J Med 362:1022, 2010. Zwimpfer TJ, Bernstein M: Spinal cord compression. J Neurosurg 72:894, 1990.


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Neurology_Adams. Zimmerli W: Vertebral osteomyelitis. N Engl J Med 362:1022, 2010. Zwimpfer TJ, Bernstein M: Spinal cord compression. J Neurosurg 72:894, 1990. IIIIIIIIIIIIIIIIIIVIVIVVVVVIVIVIVIIVIIVIIIIXIXXXXIXIXIILIIIIIIIVVVIVIIIIILIXIIVIIVIIITITIVIIVIVIVIIIIIC12345678T123456789101112L12345S12345Coc.1C12345678234567891011122345S12345L1T1 Figure 42-1. The relationship of spinal segments and roots to the vertebral bodies and spinous processes. The cervical roots (except C8) exit through foramina above their respective vertebral bodies, and the other roots issue below these bodies. (From Haymaker W, Woodhall B: Peripheral Nerve Injuries, 2nd ed. Philadelphia, Saunders, 1953, by permission.) Figure 42-2. MRI of spinal epidural abscess compressing the dorsolateral cervical spinal cord. Sagittal (left) and axial (right) T1 gadolinium-enhanced images show the peripherally enhancing pyogenic collection (arrows) which extends over several vertebral segments.


Neurology_Adams

Neurology_Adams. Figure 42-3. Sagittal T2-weighted MRI in Pott tuberculous spine disease. The angulated deformity of the thoracic spine is highly characteristic. (Courtesy of Dr. Randall Edgell, New York University Medical Center.) Figure 42-4. T2-weighted MRI of acute postinfectious myelitis in the sagittal (A) and axial (B) planes. There is abnormal T2 hyperintensity within the dorsal spinal cord and the cord is mildly enlarged. Mild enhancement following gadolinium infusion was noted (not shown). Figure 42-5. MRI of necrotic myelopathy in a patient with neuromyelitis optica. Note the long extent of the lesion and thinning of the cord as the acute illness subsides. Posterior Spinal A.Anterior Spinal A.Penetrating A.Sulcal A.Radicular A.Segmental A.AortaRadiculomedullaryartery of Adamkiewicz(at T10-L1 level)


Neurology_Adams

Neurology_Adams. Posterior Spinal A.Anterior Spinal A.Penetrating A.Sulcal A.Radicular A.Segmental A.AortaRadiculomedullaryartery of Adamkiewicz(at T10-L1 level) Figure 42-6. Anterior view of the spinal cord with its segmental blood supply from the aorta. (Reproduced with permission from Prasad S, Price RS, Kranick SM, et al: Clinical reasoning: A 59-year-old woman with acute paraplegia. Neurology 69:E41, 2007.) Figure 42-7. Spinal cord infarct: Sagittal (left) and axial (right) T2 MRI of a man who experienced sudden onset of bilateral flaccid arm weakness. Note the abnormal T2 hyperintensity restricted to the ventral spinal cord, including both ventral horns.


Neurology_Adams

Neurology_Adams. Figure 42-8. Dural arteriovenous fistula of the cord. A. Sagittal T2-weighted MRI of the lower spinal cord of a 50-year-old man with progressive myelopathy. Cord edema (T2 hyperintensity at the conus medullaris) and multiple vascular flow voids surrounding the spinal cord and extending up to the mid-thoracic vertebral levels are seen, both the result of the arteriovenous fistula. B. Angiographic injection of the left T12 radicular artery from the patient whose MRI is shown in A, demonstrating abnormal early filling of veins surrounding the spinal cord, confirming the presence of an arteriovenous fistula. The fistula was repaired and the patient’s symptoms partially improved.


Neurology_Adams

Neurology_Adams. Figure 42-9. Sagittal T2 MRI in a patient with symptomatic cervical spondylosis. The spinal cord is severely compressed at the C5-C6 intervertebral disc space. Faint abnormal T2 hyperintensity of the spinal cord can be seen at the point of compression. Following surgical decompression, the patients myelopathic symptoms partially improved. Figure 42-10. Sagittal (left) and axial (right) gadolinium-enhanced T1-weighted MRI of an intraspinal meningioma that displaced and compressed the spinal cord, causing incontinence and leg weakness. As in intracranial meningiomas, homogenous contrast enhancement and a dural attachment are seen. Figure 42-11. Sagittal T2-weighted MRI of a primary glioma of the thoracic spinal cord in a middle-aged man. Note the expansion of the spinal cord.


Neurology_Adams

Neurology_Adams. Figure 42-11. Sagittal T2-weighted MRI of a primary glioma of the thoracic spinal cord in a middle-aged man. Note the expansion of the spinal cord. Figure 42-12. Sagittal T1-weighted MRI showing multiple spinal metastases from carcinoma of the lung. The metastases exhibit low signal intensity due to tumor replacement of bone marrow, which is normally T1 hyperintense. Figure 42-13. Sagittal T2 MRI of an intramedullary metastasis from breast cancer. The expansile lesion is at the T2 vertebral level (arrow) and the adjacent edema extends superiorly and inferiorly over a great length of the spinal cord. Figure 42-14. Sagittal T2-weighted MRI showing a developmental syringomyelia without Chiari malformation. The cervical spinal cord is greatly expanded but there were only signs of spinothalamic sensory loss over the arms. Chapter 42 Diseases of the Spinal Cord Diseases of the Peripheral Nerves


Neurology_Adams

Neurology_Adams. In this single chapter, an attempt is made to provide an overview of the very large and difficult subject of peripheral nerve disease. Because the structure and function of the peripheral nervous system are relatively simple, one might suppose that our knowledge of its diseases would be fairly complete. Such is not the case. For example, when a group of patients with chronic polyneuropathy were investigated intensively in a highly specialized center for the study of peripheral nerve diseases several decades ago, a suitable explanation for their condition could not be found in 24 percent (Dyck et al, 1981) and equally discouraging figures prevail in our clinics today despite genetic testing. Moreover, the physiologic basis of many neuropathic symptoms continues to be elusive and in several of the neuropathies the pathologic changes have not been fully determined. However, rapidly advancing techniques in the fields of immunology and genetics are now clarifying entire categories of


Neurology_Adams

Neurology_Adams. of the neuropathies the pathologic changes have not been fully determined. However, rapidly advancing techniques in the fields of immunology and genetics are now clarifying entire categories of neuropathic disease. Also, effective forms of treatment for several peripheral neuropathies have been introduced, making accurate diagnosis imperative. For these reasons, clinicians now find the peripheral neuropathies among the most challenging and gratifying categories of neurologic disease.


Neurology_Adams

Neurology_Adams. It is important to have a clear concept of the extent of the peripheral nervous system (PNS) and the mechanisms by which it is affected by disease. The PNS includes all neural structures lying outside the pial membrane of the spinal cord and brainstem with the exception of the optic nerves and olfactory bulbs, which are special extensions of the brain. The nerves within the spinal canal and attached to the ventral and dorsal surfaces of the cord are the spinal roots, which continue to form the numbered spinal nerves; those attached to the ventrolateral surface of the brainstem are the cranial nerve roots, or cranial nerves.


Neurology_Adams

Neurology_Adams. The dorsal, or posterior (afferent, or sensory), spinal roots consist of central axonal processes of the sensory and cranial ganglia. On reaching the spinal cord and brainstem, the roots extend for variable distances into the dorsal horns and posterior columns of the cord and into the spinal trigeminal and other tracts in the medulla and pons before synapsing with secondary sensory neurons, as described in Chaps. 7 and 8 that are devoted to the neurology of pain and sensation. The peripheral axons of the dorsal root ganglion cells are the sensory nerve fibers. They terminate as freely branching or specialized corpuscular endings—that is, the sensory receptors—in the skin, joints, and other tissues. The sensory nerve fibers vary greatly in size and in the thickness of their myelin covering; based on these dimensions, they are classified as type A, B, or C, as discussed in Chap. 7.


Neurology_Adams

Neurology_Adams. The ventral, or anterior (efferent, or motor), roots are composed of the emerging axons of anterior and lateral horn cells and motor nuclei of the brainstem. Large, heavily myelinated fibers terminate on muscle fibers and smaller unmyelinated ones terminate in sympathetic or parasympathetic ganglia. From these autonomic ganglia issue the axons that terminate in smooth muscle, heart muscle and conducting system, and glands. Traversing the subarachnoid space, where they lack well-formed epineurial sheaths, the cranial and spinal roots (both sensory and motor) are bathed in and are susceptible to substances in the cerebrospinal fluid (CSF), the lumbosacral roots having the longest exposure (Fig. 43-1).


Neurology_Adams

Neurology_Adams. The vast extent of the peripheral ramifications of cranial and spinal nerves is noteworthy, as are their thick protective and supporting sheaths of perineurium and epineurium that are endowed with a vascular supply through longitudinal arrays of richly anastomosing nutrient arterial branches. The perineurium comprises the connective tissue sheaths that surround and separate each bundle of nerve fibers (fascicles) of varying size, each fascicle containing several hundred axons. The sheath that binds and surrounds all the fascicles of the nerve is the epineurium. As the nerve root approaches the cord, the epineurium blends with the dura (see Fig. 43-1). The fine connective tissue covering of individual nerve fibers is the endoneurium. Longitudinally oriented and widely anastomotic endoneural vessels also nourish the nerve fibers and are susceptible to disease.


Neurology_Adams

Neurology_Adams. The nerves traverse narrow foramina (intervertebral and cranial) and a few pass through tight channels peripherally in the limbs (e.g., the median nerve between the carpal ligament and tendon sheaths of flexor forearm muscles that make up the carpal tunnel; the ulnar nerve in the cubital tunnel). These anatomic features explain the sites of susceptibility of certain nerves to compression and entrapment and also to ischemic damage.


Neurology_Adams

Neurology_Adams. The axons themselves contain a complex internal microtubular apparatus for maintaining the integrity of their membranes and for transporting substances such as neurotransmitters over long distances between the nerve cell body and the distant reaches of the nerve fiber. As discussed in Chap. 7 the long axons of sensory nerves can properly be considered to be dendrites but we use the term “axon” in this and other chapters to denote all the neuronal processes of peripheral enrves. Nerve fibers (axons) are coated with short segments of myelin of variable length (250 to 1,000 µm), each of which is enveloped by a Schwann cell and its membrane that constitute the myelin sheath. In fact, the PNS may be accurately defined as the part of the nervous system that is invested by the cytoplasm and membranes of Schwann cells. Each myelin segment and Schwann cell has a symbiotic relationship to the axon but is morphologically independent. The structure of the axonal membrane in the gaps between


Neurology_Adams

Neurology_Adams. membranes of Schwann cells. Each myelin segment and Schwann cell has a symbiotic relationship to the axon but is morphologically independent. The structure of the axonal membrane in the gaps between segments of the myelin sheaths (nodes of Ranvier) is specialized, containing a high concentration of sodium channels and permitting the saltatory electrical conduction of nerve impulses as described in Chap. 2. Unmyelinated fibers, more numerous in peripheral nerves than myelinated ones, also arise from cells in dorsal root and autonomic ganglia. Small bundles of these naked (unmyelinated) axons are enveloped by a single Schwann cell; delicate tongues of Schwann cell cytoplasm partition these bundles and separate individual axons. Each sensory nerve fiber terminates in a specialized ending which is designed to be especially sensitive to certain natural stimuli as discussed in Chaps. 7 and 8.


Neurology_Adams

Neurology_Adams. The features described previously enable one to conceptualize the possible avenues by which disease may affect the peripheral nerves. Pathologic processes may be directed at any one of the several groups of nerve cells whose axons constitute the nerves, that is, the cells of the anterior or lateral horns of the spinal cord, the dorsal root ganglia, or the sympathetic and parasympathetic ganglia. Each of these cell types exhibits specific vulnerabilities to disease, and if destroyed—as, for example, the motor nerve cells in poliomyelitis—there is secondary degeneration of the axons and myelin sheaths of the peripheral fibers of these cells. Neuropathic symptoms are also induced by alterations of function and structure of the ventral and dorsal columns of the spinal cord, which contain the fibers of exit and entry of anterior horn and dorsal root ganglion cells, respectively. The myelin of these centrally located fibers is constituted differently from that of the peripheral nerves,


Neurology_Adams

Neurology_Adams. the fibers of exit and entry of anterior horn and dorsal root ganglion cells, respectively. The myelin of these centrally located fibers is constituted differently from that of the peripheral nerves, being enveloped by oligodendrocytes rather than Schwann cells and the nerve fibers are supported by astrocytes rather than fibroblasts.


Neurology_Adams

Neurology_Adams. Because of the intimate relation of the nerve roots to the CSF and to specialized arachnoidal cells (the arachnoidal villi), a pathologic process in the CSF or leptomeninges may damage the exposed spinal roots. Diseases of the connective tissues affect the peripheral nerves that lie within their sheaths. Diffuse or localized arterial diseases may injure nerves by occluding their nutrient arteries. In a large category of immune-mediated neuropathies, the damage is the result of a cellular or humoral attack on various components of myelin. A subset of these is characterized by the binding of circulating antibodies to the specialized regions at the nodes of Ranvier, causing a block of electrical conduction. A complement-dependent humoral immune reaction against the radicular or peripheral axon is also known. Toxic or immunologic agents that selectively damage the Schwann cells or their membranes cause demyelination of peripheral nerves, leaving axons relatively intact, or a toxin may


Neurology_Adams

Neurology_Adams. axon is also known. Toxic or immunologic agents that selectively damage the Schwann cells or their membranes cause demyelination of peripheral nerves, leaving axons relatively intact, or a toxin may specifically affect axons and dendrites by poisoning their cell bodies, the axolemma, or the lengthy and complex axonal transport apparatus.


Neurology_Adams

Neurology_Adams. Finally, one might correctly suppose that axons of the motor or sensory nerves, sympathetic fibers of varying diameter and length, or the end organs to which they are attached would each have its own particular liability to disease. At present we can cite only a few examples of diseases that cause disease through these mechanisms exclusively: for example, diphtheria, in which the bacterial toxin acts directly on the membranes of the Schwann cells near the dorsal root ganglia and adjacent parts of motor and sensory nerves (the most vascular parts of the peripheral nerve); polyarteritis nodosa, which causes occlusion of vasa nervorum, resulting in multifocal nerve infarction; tabes dorsalis, in which there is a treponemal meningoradiculitis of the posterior roots (mainly of the lumbosacral segments); poisoning by arsenic, which combines with the axoplasm of the largest sensory and motor nerves via sulfhydryl bonds; and vincristine toxicity, which damages the microtubular transport


Neurology_Adams

Neurology_Adams. segments); poisoning by arsenic, which combines with the axoplasm of the largest sensory and motor nerves via sulfhydryl bonds; and vincristine toxicity, which damages the microtubular transport system. Analogous anatomic pathways are probably implicated in other diseases by mechanisms that remain to be discovered.


Neurology_Adams

Neurology_Adams. Among the genetically determined neuropathies, the altered gene products are known in some cases to lead to defective myelination, which greatly slows conduction along nerves. In other genetic diseases it is known that structural components of the axon are disrupted, leading to axonal degeneration and impaired electrical conduction. Pathologic Reactions of Peripheral Nerve Several distinct histopathologic changes are recognized in the peripheral nerve, although they are not disease-specific and they may be present in varying combinations in any given case. The three main ones are segmental demyelination, wallerian degeneration, and axonal degeneration (diagrammatically illustrated in Fig. 43-2).


Neurology_Adams

Neurology_Adams. The myelin sheath is the most susceptible element of the nerve fiber, for it may break down as part of a primary process involving the Schwann cells or of the myelin itself, or it may be damaged secondarily as a consequence of disease affecting its axon. Focal degeneration of the myelin sheath with sparing of the axon is called segmental demyelination. The characteristic change of segmental demyelination is the disappearance of the sheath over segments of variable length, bounded on each end by one side of a node of Ranvier and an adjacent preserved segment of myelin. This exposes long segments of the axon to the interstitial environment. Myelin may also degenerate from axonal disease in a general process that may occur either proximal or distal to the site of axonal interruption.


Neurology_Adams

Neurology_Adams. Common to many lesions of the peripheral nerve is wallerian degeneration, a reaction of both the axon and myelin distal to the site of disruption of an axon. Wallerian degeneration might be described as “dying forward,” a process in which the nerve degenerates from the point of axonal damage outward. In contrast, when the axon degenerates as part of a “dying-back” phenomenon in a more generalized metabolically determined polyneuropathy, it is termed axonal degeneration. Here, the axon is affected progressively from the distal-most site to the proximal, with dissolution of myelin that occurs roughly in parallel with the axonal change. One possible explanation for this process is that the primary damage is to the neuronal cell body, which fails in its function of synthesizing proteins and delivering them to the distal parts of the axon. Certain toxic and metabolic processes affect axons uniformly along their length or impair anterograde axonal transport to the periphery; the functional


Neurology_Adams

Neurology_Adams. them to the distal parts of the axon. Certain toxic and metabolic processes affect axons uniformly along their length or impair anterograde axonal transport to the periphery; the functional impairment is then proportional to the size and length of the blocked axons.


Neurology_Adams

Neurology_Adams. Destruction of a proximal spinal motor root results in a gradual dissolution of the distal motor nerve and its myelin sheath (a form of wallerian degeneration). The neuronal motor cell body that gives rise to the motor fiber undergoes characteristic retrograde morphologic changes described below but does not die. Similar destruction of the dorsal spinal root produces secondary wallerian degeneration of the posterior columns of the spinal cord, but not of the peripheral sensory nerve because the dorsal root ganglion cell maintains the integrity of the distal axon. In other words, destruction of axons results within several days in wallerian degeneration of the myelin distal to the point of injury but not transgressing the neuronal cell body. The myelin breaks down into blocks or ovoids in which lie fragments of axons (digestion chambers of Cajal). The myelin fragments are then converted, through the action of macrophages, into neutral fats and cholesterol esters and carried by these


Neurology_Adams

Neurology_Adams. which lie fragments of axons (digestion chambers of Cajal). The myelin fragments are then converted, through the action of macrophages, into neutral fats and cholesterol esters and carried by these cells to the bloodstream.


Neurology_Adams

Neurology_Adams. Certain diseases affect the neuron primarily rather than the axon and cause either a motor or sensory neuronopathy. In the former case, more properly considered a myelopathy, the anterior horn cell is affected by a disease process (motor neuron disease, or motor neuronopathy) and in the latter, the sensory ganglion cell (ganglionopathy) is destroyed. A type of wallerian distal degeneration of the respective nerve fibers follows.


Neurology_Adams

Neurology_Adams. Some of these pathologic reactions are more easily understood if one considers certain features of cytoskeletal structure and function of nerve cells and their axons. The axon contains longitudinally oriented neurofilaments and microtubules, which are separated but interconnected by cross-bridges. Their main function involves the transport of substances from nerve cell body to axon terminal (anterograde transport) and from the distal axon back to the cell body (retrograde transport). Thus, when the axon is severed, organelles cannot be transmitted to the distal axon for the purpose of renewing membrane and neurotransmitter systems. By means of retrograde axonal transport, the cell bodies receive signals to increase their metabolic activity and to produce growth factors and other materials needed for axonal regeneration. In an incompletely defined way, the axon also creates a local environment that allows the Schwann cell to maintain the integrity of the adjacent myelin sheath. Loss of


Neurology_Adams

Neurology_Adams. needed for axonal regeneration. In an incompletely defined way, the axon also creates a local environment that allows the Schwann cell to maintain the integrity of the adjacent myelin sheath. Loss of this trophic influence leads to dissolution of the myelin sheath, but not of the Schwann cell itself.


Neurology_Adams

Neurology_Adams. There are also highly characteristic histopathologic changes in the nerve cell body termed chromatolysis as a secondary consequence of axonal interruption. These retrograde changes consist of swelling of the cell cytoplasm and marginalization and dissolution of the Nissl substance. The important point again is that despite the destructive changes in the nerve fibers, the nerve cells, while altered in histologic appearance, are left intact with preservation of the apparatus required for recovery.


Neurology_Adams

Neurology_Adams. In segmental demyelination, recovery of function may be rapid because the intact but denuded axon needs only become remyelinated. The newly formed internodal segments are initially thinner than normal and of variable length. By contrast, recovery is much slower with wallerian or axonal degeneration, often requiring months to a year or more because the axon must first regenerate and then reinnervate the muscle, sensory organ, or blood vessel before function returns. When the regenerating axon first becomes myelinated, the internodal myelin segments are short, the length of one normal internode being replaced by 3 or 4 shorter new ones. Recurrent demyelination and remyelination lead to “onion bulb” formations and enlargement of nerves, the result of proliferating Schwann cells and fibroblasts that encircle the axon and its thin myelin sheath. If nerve cells are destroyed, no recovery of function is possible except by collateral regeneration of axons from intact nerve cells. Interruption


Neurology_Adams

Neurology_Adams. that encircle the axon and its thin myelin sheath. If nerve cells are destroyed, no recovery of function is possible except by collateral regeneration of axons from intact nerve cells. Interruption of a nerve fiber by severing or by crude destruction usually prevents continuity from being reestablished. Regenerating axon filaments take aberrant courses and, with fibroblastic scar formation, they may form a disorganized clump of tissue termed pseudoneuroma.


Neurology_Adams

Neurology_Adams. These relatively few pathologic reactions do not, in themselves, differentiate the many dozens of diseases of the peripheral nerves, but when they are considered in relation to the selective effects on various types and sizes of fibers, the topography of the lesions, and the time course of the process, they furnish criteria for fairly accurate diagnosis. Moreover, the identification of these basic reactions is of great value in the inspection of pathologic material obtained from biopsy or autopsy.


Neurology_Adams

Neurology_Adams. There are additional special pathologic changes, not specifically neural in nature that characterize certain diseases of the peripheral nervous system. These involve inflammatory or vascular changes or deposition of material in the interstitium of the nerve. For example, acute demyelinative polyneuritis of the Guillain-Barré type is characterized by endoneurial infiltrations of lymphocytes and other mononuclear cells in the nerves, roots, and sensory and sympathetic ganglia. Deposition of amyloid in the endoneurial connective tissue and walls of vessels affecting the nerve fibers is the distinctive feature of inherited and acquired amyloid polyneuropathy. Diphtheritic polyneuropathy is typified by the demyelinative character of the nerve fiber change, the location of this change in and around the roots and sensory ganglia, the subacute course, and the lack of inflammatory reaction. A number of neuropathies are characterized by the deposition of antibodies and complement on the myelin


Neurology_Adams

Neurology_Adams. the roots and sensory ganglia, the subacute course, and the lack of inflammatory reaction. A number of neuropathies are characterized by the deposition of antibodies and complement on the myelin sheath or on elements of the axon. These changes can be demonstrated by immunohistopathologic techniques. Many other polyneuropathies (paraneoplastic, nutritional, porphyric, arsenical, and uremic) are topographically symmetrical and represent forms of axonal degeneration but cannot be easily distinguished from one another on histopathologic grounds.


Neurology_Adams

Neurology_Adams. Concerning the pathology of the mononeuropathies, our knowledge is somewhat more complete. Compression of nerve or nerve roots, local or segmental ischemia, stretch, and laceration of nerves are understandable mechanisms and their pathologic changes can be reproduced experimentally. Tumor infiltration and importantly, vasculitis with ischemic infarction of nerve account for a proportion of cases. Of infections and granulomas localized to single nerves, leprosy, sarcoid, and herpes zoster represent identifiable disease states. For most of the acute mononeuropathies that are a result of transient compression, the pathologic changes have yet to be fully defined, as they are usually reversible states that provide no opportunity for complete pathologic examination. Experimental models of nerve compression indicate disruption of tubular transport and local demyelination. The common symptoms of compression such as paresthesias are explained, as discussed further on, by exposure of sodium


Neurology_Adams

Neurology_Adams. compression indicate disruption of tubular transport and local demyelination. The common symptoms of compression such as paresthesias are explained, as discussed further on, by exposure of sodium channels along denuded axons and spontaneous and ectopic electrical discharges.


Neurology_Adams

Neurology_Adams. There are a number of motor, sensory, reflex, autonomic, and trophic symptoms and signs that are typical of peripheral nerve disease. Grouping them into syndromes based on their temporal and topographic features has proved to be of great value in clinical diagnosis. Although motor, sensory, reflex, and trophic changes are taken together to determine specific diagnosis, each element of the neuropathic diseases is given in the following pages. Impairment of Motor Function


Neurology_Adams

Neurology_Adams. It is not surprising that weakness in various patterns and degrees is a feature of almost all neuropathies. The degree of weakness is proportional to the number of axons or motor neurons affected. Polyneuropathies that are the result of axonal damage are characterized foremost by a relatively symmetric distribution of weakness that is, moreover, distal because the pathologic changes begin in the far distal parts of the largest and longest nerves and advance along the affected fibers toward their nerve cell bodies (dying-back neuropathy, or “distal axonopathy”). The muscles of the feet and legs are typically affected earlier and more severely than those of the hands and forearms. In milder forms of axonal disease, only the feet and lower legs are involved. Truncal and cranial muscles are usually the last to yield, and then only in severe cases. This represents the “length-dependent” pattern that is typical of axonal degeneration. The nutritional, metabolic, and toxic neuropathies


Neurology_Adams

Neurology_Adams. are usually the last to yield, and then only in severe cases. This represents the “length-dependent” pattern that is typical of axonal degeneration. The nutritional, metabolic, and toxic neuropathies assume this predominantly distal “axonal” pattern. An exception is porphyria, an axonal process in which there may be mainly proximal weakness. By contrast, in demyelinating polyneuropathies, the multifocal nature of lesions and blockage of electrical conduction often leads to weakness of proximal limb and facial muscles before or at the same time as distal parts are affected.


Neurology_Adams

Neurology_Adams. Another pattern of neuropathic weakness is one in which all the muscles of the limbs, trunk, and neck are involved almost simultaneously, often including respiratory paralysis, therefore making it impossible to determine if the axons or myelin, or both, have been damaged. The best characterized of these processes is the Guillain-Barré syndrome (GBS). Less common causes of generalized paralysis include diphtheria, tick paralysis, and certain toxic polyneuropathies. Fatalities, when they occur, are usually a result of respiratory failure.


Neurology_Adams

Neurology_Adams. A predominantly bibrachial paralysis is an unusual presentation of neuropathic disease but may occur in the inflammatory-demyelinating polyneuropathies, as well as in Sjögren syndrome, chronic immune or paraneoplastic neuropathies, lead neuropathy, Tangier disease, and in a familial type of brachial neuritis. (A more frequent cause of bibrachial palsy is disease of the motor neurons themselves namely, motor system disease, or a lesion placed centrally in the cervical cord that damages these same neurons.) Paraparesis is not typical of the generalized polyneuropathies, but it is observed with infections and inflammations of the cauda equina, as occurs with Lyme disease, cytomegalovirus, herpes simplex, and with neoplastic infiltration of the nerve roots. Bifacial and other cranial nerve paralyses are likely to occur in GBS, neoplastic invasion, with connective tissue diseases, HIV and herpes virus infection, sarcoidosis, Lyme disease, or one of the rare metabolic neuropathies (e.g.,


Neurology_Adams

Neurology_Adams. paralyses are likely to occur in GBS, neoplastic invasion, with connective tissue diseases, HIV and herpes virus infection, sarcoidosis, Lyme disease, or one of the rare metabolic neuropathies (e.g., Refsum, Bassen-Kornzweig, Tangier, and Riley-Day). These are discussed in Chap. 44 on diseases of the cranial nerves and in respective chapters on infections and metabolic diseases of the nervous system.


Neurology_Adams

Neurology_Adams. Atrophy of weak or paralyzed muscles is characteristic of chronic disease of the motor neuron or motor axon and conversely, demyelinating neuropathies relatively spare muscle bulk because of the absence of denervation. Atrophy proceeds slowly over several weeks and months, the degree being proportional to the number of damaged motor nerve fibers. The maximum degree of denervation atrophy after an acute injury to the axons occurs in 90 to 120 days and reduces muscle volume by 75 to 80 percent. Atrophy may also be a consequence of disuse; it occurs over many weeks but in itself does not reduce muscle volume by more than 25 to 30 percent. In chronic axonal neuropathies, the degrees of paralysis and atrophy tend to correspond. As mentioned previously, atrophy does not coincide with weakness in acute paralysis caused by the demyelinative neuropathies in which the nerve fiber is relatively less affected than is the myelin. Ultimately in muscle atrophy, there is degeneration and loss of the


Neurology_Adams

Neurology_Adams. acute paralysis caused by the demyelinative neuropathies in which the nerve fiber is relatively less affected than is the myelin. Ultimately in muscle atrophy, there is degeneration and loss of the denervated muscle fibers. This process begins in 6 to 12 months; in 3 to 4 years, most of the denervated fibers will have degenerated. If reinnervation takes place within a year or so, motor function and muscle volume may be restored.


Neurology_Adams

Neurology_Adams. As a rule, neuropathies are associated with a reduction or loss of tendon reflexes. Most often, this is the result of an interruption of the afferent (sensory) portion of the monosynaptic reflex arc. The reflexes may be diminished if muscular function is impaired, but this occurs mainly in the case of extreme atrophy, in which there are too few muscle fibers to manifest a contraction. There are, of course, many other processes that reduce the tendon reflexes, but it is the neuropathies with which loss of reflexes is most closely associated. An exception is the group of small-fiber neuropathies, in which tendon reflexes may be retained, even with marked loss of perception of painful stimuli. This discrepancy is attributable to the dependence of the afferent component of the tendon reflex arc on the large, heavily myelinated fibers that originate in muscle spindles. Conversely, in neuropathies that affect the largest diameter and most heavily myelinated fibers, the tendon reflexes are


Neurology_Adams

Neurology_Adams. arc on the large, heavily myelinated fibers that originate in muscle spindles. Conversely, in neuropathies that affect the largest diameter and most heavily myelinated fibers, the tendon reflexes are diminished early and disproportionately to weakness. Slowing of conduction in sensory fibers may also abolish the reflex by dispersing the afferent volley of impulses initiated by the tendon tap. There is generally a concordance between areflexia and a loss of proprioceptive and joint-position senses; that is, the large nerve fibers from spindle afferents are of the same type and size as those mediating these forms of sensation. Furthermore, loss of sensory functions that are dependent on these large fibers in the presence of preserved reflexes implicates the central projections of the sensory ganglion cells, that is, a lesion in the posterior columns of the spinal cord that does not interrupt the afferent tendon reflex arc. Regional loss of a reflex is usually a sign of a radiculopathy.


Neurology_Adams

Neurology_Adams. in Chap. 8) Most polyneuropathies cause impairment of both motor and sensory functions, but one is often affected more than the other. In the toxic and metabolic neuropathies, sensory loss usually exceeds weakness. These differences are emphasized in the descriptions of individual peripheral nerve diseases in later parts of the chapter.


Neurology_Adams

Neurology_Adams. In the axonal polyneuropathies, sensation is affected symmetrically in the distal segments of the limbs and more in the legs than in the arms, owing to the length-dependent nature of most diseases that affect peripheral nerves. In most types, all sensory modalities (touch-pressure, pain and temperature, vibratory and joint position senses) are impaired or eventually lost, although one modality is often affected disproportionately to the others; for example, temperature sensation (small afferent fibers) may be impaired more than joint position and vibration (larger fibers). As an axonal neuropathy worsens, there is spread of sensory loss from the distal to more proximal parts of the limbs and eventually, to the anterior abdomen, thorax, and the face. An “escutcheon” pattern of sensory loss over the anterior abdomen and thorax in severe axonal neuropathy may be mistaken for the sensory level of a spinal cord lesion if the back is not examined. Another characteristic form of sensory loss


Neurology_Adams

Neurology_Adams. over the anterior abdomen and thorax in severe axonal neuropathy may be mistaken for the sensory level of a spinal cord lesion if the back is not examined. Another characteristic form of sensory loss affects the trunk, scalp, and face and later, the trunk and limbs; this is the pattern of a sensory ganglionopathy that is the result of simultaneous dysfunction of all parts of the sensory nerve.


Neurology_Adams

Neurology_Adams. Most often, universal sensory loss is attributable to an acquired disease affecting the sensory ganglia (sensory neuronopathy); a paraneoplastic process or certain toxic or immune diseases are usually responsible (e.g., Sjögren disease, scleroderma). Paresthesias, Pain, and Dysesthesias


Neurology_Adams

Neurology_Adams. These symptoms were described in Chaps. 7 and 8. Sensory symptoms tend to be especially marked in the hands and feet. “Pins and needles,” “falling asleep,” “stabbing,” “tingling,” “prickling,” “electrical,” and “Novocain-like” are the adjectives chosen by patients to describe these positive sensory experiences. In some neuropathies, paresthesias and numbness are the only symptoms and objective sensory loss is lacking or minimal. Certain neuropathies characteristically cause pain, which is described as burning, aching, sharp and cutting, or crushing and at times may resemble the lightning pains of tabes dorsalis. Perversion of sensation (allodynia) is also commonplace in some polyneuropathies—for example, tingling, burning, stabbing pain, or just an uncomfortable dysesthesia is induced by tactile stimuli. Under these conditions a stimulus induces not only an aberrant sensation but also one that radiates to adjacent areas and persists after the stimulus is withdrawn. As remarked in


Neurology_Adams

Neurology_Adams. by tactile stimuli. Under these conditions a stimulus induces not only an aberrant sensation but also one that radiates to adjacent areas and persists after the stimulus is withdrawn. As remarked in Chap. 8, the reactions of a patient with allodynia may seem to indicate hypersensitivity (“hyperesthesia”), but more often the sensory threshold is actually raised and it is the sensory experience or response that is exaggerated (hyperpathia).


Neurology_Adams

Neurology_Adams. Painful paresthesias and dysesthesias are particularly common in diabetic, alcoholic–nutritional, and amyloid neuropathies. Mainly they affect the feet (“burning feet”) and less often the hands. In herpes zoster, they are confined to dermatomal regions of the body. A particularly intense form of burning pain typifies the causalgia of a partial nerve lesion (usually traumatic) of the ulnar, median, posterior tibial, peroneal, or occasionally some other nerve (see Chap. 7 and further on in this chapter).


Neurology_Adams

Neurology_Adams. The mechanism of thermal and painful dysesthesias is not fully understood. It has been theorized that a loss of large touch-pressure fibers disinhibits the pain-receiving nerve cells in the posterior horns of the spinal cord. An argument against this explanation is the lack of pain in Friedreich ataxia, in which the larger neurons degenerate, and also in certain purely sensory polyneuropathies, where only the perception of tactile stimuli (large fibers) is lost. A more likely explanation, supported by microneurographic recordings, is that dysesthetic pain results from ectopic discharges arising at many sites along surviving intact or regenerating nerve fibers or their terminal receptors. It has been postulated, on uncertain grounds, that the deep, aching neuropathic pain of sciatica or brachial neuritis (nerve trunk pain) arises from irritation of the normal endings (nervi nervorum) in the sheaths of the nerve trunks themselves (Asbury and Fields). These considerations are discussed


Neurology_Adams

Neurology_Adams. neuritis (nerve trunk pain) arises from irritation of the normal endings (nervi nervorum) in the sheaths of the nerve trunks themselves (Asbury and Fields). These considerations are discussed in Chap. 7.


Neurology_Adams

Neurology_Adams. Proprioceptive deafferentation with retention of a reasonable degree of motor function may give rise to ataxia of gait and of limb movement as discussed in Chap. 8. Dysfunction of the spinocerebellar fibers of the peripheral nerves is probably the source of the ataxia. Some of the most severe ataxias of this type occur with sensory ganglionopathy, as commented further on.


Neurology_Adams

Neurology_Adams. Ataxia without weakness is also characteristic of tabes dorsalis, a purely posterior root disease, but this syndrome can be duplicated by a type of diabetic polyneuropathy, which affects posterior roots (diabetic pseudotabes) and by a variant of GBS (termed Fisher syndrome). The ataxia is indistinguishable from that caused by cerebellar diseases, but other features of cerebellar dysfunction such as dysarthria and nystagmus are lacking. Characteristic of the sensory-ataxic gait are brusque, flinging, slapping movements of the legs. Loss of proprioception may also give rise to small wavering, fluctuating movements of the outstretched fingers—called pseudoathetotic, or “dancing fingers.” An action tremor of fast-frequency type may also appear during certain phases of a polyneuropathy;


Neurology_Adams

Neurology_Adams. An action tremor of fast-frequency type may also appear during certain phases of a polyneuropathy; Shahani and coworkers had the impression that it is a result of loss of input from the muscle-spindle afferents. Corticosteroid therapy enhances this fast tremor. A particularly severe form of slower action tremor is combined with clumsiness of movement in the neuropathies caused by the autoimmune, anti-myelin-associated glycoprotein (anti-MAG) polyneuropathy and in some cases of chronic inflammatory demyelinating polyneuropathy (CIDP). The tremor may be so coarse as to resemble the intention tremor of cerebellar disease and all movements are rendered useless. However, a tremor at rest is not found in these afferent-sensory neuropathies. The neuropathic type of tremor is also discussed in Chap. 4.


Neurology_Adams

Neurology_Adams. In a few of the chronic polyneuropathies, the feet, hands, and even the spine may become progressively deformed. This is most likely to occur when the disease begins during childhood. Austin pointed out that foot deformity is found in 30 percent of patients with hereditary polyneuropathy, and spine curvature is found in 20 percent. In early life, the feet are pulled into a position of talipes equinus (plantar deviation) because of disproportionate weakness of the pretibial and peroneal muscles and the unopposed action of the calf muscles. Weakness of the intrinsic foot muscles during the period of life when the bones are forming allows the long extensors of the toes to dorsiflex the proximal phalanges and the long flexors to shorten the foot, heighten the arch, and flex the distal phalanges. The result is the claw foot—le pied en griffe—or pes cavus (high arches) when the process is less severe. These changes in the structure of the foot are valuable diagnostic indicators that a


Neurology_Adams

Neurology_Adams. The result is the claw foot—le pied en griffe—or pes cavus (high arches) when the process is less severe. These changes in the structure of the foot are valuable diagnostic indicators that a neuromuscular disease originated in early childhood or during intrauterine development. A congenital claw hand has a similar implication. Unequal weakening of the paravertebral muscles on the 2 sides of the spine during early development leads to kyphoscoliosis.


Neurology_Adams

Neurology_Adams. Denervation atrophy of muscle can be considered the main trophic disturbance resulting from interruption of the motor nerves. However, there are numerous other changes. Analgesia of distal limb parts makes them susceptible to burns, pressure sores, and other forms of injury that are easily infected and heal poorly. In an anesthetic and immobile limb, the skin becomes tight and shiny, the nails curved and ridged, and the subcutaneous tissue thickened (“trophic changes”). Hair growth is diminished in denervated areas. If the autonomic fibers are also interrupted, the limb becomes warm and pink. Repeated injuries and chronic subcutaneous and osteomyelitic infections result in a painless loss of digits and the formation of plantar ulcers (mal perforant du pied). These are prominent features of the recessive form of hereditary sensory neuropathy and we have observed them in dominant forms as well. In tabes dorsalis and syringomyelia as well as certain familial and other chronic


Neurology_Adams

Neurology_Adams. features of the recessive form of hereditary sensory neuropathy and we have observed them in dominant forms as well. In tabes dorsalis and syringomyelia as well as certain familial and other chronic polyneuropathies, analgesic joints, when chronically traumatized, may first become deformed and then actually disintegrate in a process called Charcot arthropathy (“Charcot joint”).


Neurology_Adams

Neurology_Adams. Apart from analgesia, a critical factor in these trophic changes may be aberrant neural regulation of the distal vasculature, which interferes with normal tissue responses to trauma and infection. Ali and colleagues have related the ulcer formation to loss of C fibers, which mediate both pain and autonomic reflexes. However, paralyzed limbs, even in hysteria, if left dependent, are often cold, swollen, and pale or blue. These are probably secondary effects of immobilization, as pointed out long ago by Lewis and Pickering. Erythema and edema, burning pain, and cold sensations surely can be evoked by peripheral nerve irritation, particularly of C and A-δ fibers as discussed in Chap. 7.


Neurology_Adams

Neurology_Adams. Anhidrosis and orthostatic hypotension, two of the most frequent manifestations of autonomic failure, predominate in certain types of polyneuropathies. They occur frequently in amyloidosis and in other small-fiber polyneuropathies, especially diabetic, and in several congenital types. These are also the main features of an acute autonomic polyneuropathy called pandysautonomia (Young et al; Adams et al; Low et al) and can be prominent in some cases of GBS. The neuropathic dysautonomic conditions are described in detail in Chap. 25 and later in this chapter.


Neurology_Adams

Neurology_Adams. Other manifestations of autonomic paralysis are small or medium-sized unreactive pupils that are unusually sensitive to certain drugs (see Chap. 13); lack of sweat, tears, and saliva; erectile dysfunction; weak bowel and bladder sphincters with urinary retention or overflow incontinence; and weakness and dilation of the esophagus and colon. As a result of vagal and other parasympathetic dysfunction, the normal variability of heart rate with respiration (sinus arrhythmia) is lost and there may be paralytic ileus or dyscoordinated peristalsis, as well as achlorhydria and hyponatremia. Some of these abnormalities are found in diabetic and amyloid polyneuropathy. They correspond to degeneration of small unmyelinated autonomic fibers in the peripheral nerves.


Neurology_Adams

Neurology_Adams. In any neuropathy involving sensory nerves, there is loss of autonomic function in the same zones as sensory loss. This is not true of radicular diseases because the autonomic fibers join the spinal nerves from the sympathetic chain and parasympathetic ganglia more distally. Changes in sweating and cutaneous blood flow may be demonstrated by a number of special tests described in Chap. 25. Fasciculations, Cramps, and Spasms (See Also Chap. 46)


Neurology_Adams

Neurology_Adams. Fasciculations, Cramps, and Spasms (See Also Chap. 46) Fasciculations and cramps are not prominent features in most polyneuropathies and in this respect there is a difference from diseases of the anterior horn cells where they are important features. There are exceptions, however. Chronic spinal motor root compression leads to fasciculations or painful spasms in the innervated muscles. Occasionally one observes a state of mild motor polyneuropathy that, upon recovery, leaves the muscles in a state variably referred to as myokymia, continuous muscular activity, and neuromyotonia as discussed in Chap. 46. The affected muscles ripple and quiver and occasionally cramp. Use of the muscles increases this activity and there is a reduction in their contractile efficiency, which the patient senses as a stiffness and heaviness. In some instances this apparently constitutes the entire neuropathic syndrome and may be relieved by carbamazepine or phenytoin.


Neurology_Adams

Neurology_Adams. Other closely related phenomena are spasms or involuntary movements of the toes and feet. The latter, when the sole manifestation of disease, was referred to by


Neurology_Adams

Neurology_Adams. Spillane and colleagues as the syndrome of painful legs and moving toes. It has been attributed by Nathan to ectopic discharges in sensory roots, ganglia, or nerves, evoking both pain and organized movements. This is but one of many causes of the nocturnal restless leg syndrome, but it does not explain the more common type of idiopathic restless leg nocturnal syndrome described in Chap. 18. Other possible mechanisms for cramps and spasms are ephaptic cross-transmission between adjacent axons denuded of myelin, segmental hyperactivity from deafferentation, and neuronal sprouting during reinnervation. Infrequently, the muscle activity induces odd postures or slow writhing movements that Jankovic and van der Linden have likened to dystonia. The pathophysiology of these asynchronous activities of motor neurons is not known. Stimulation of a motor nerve in these cases, instead of causing a brief burst of action potentials in the muscle, results in a prolonged or dispersed series of


Neurology_Adams

Neurology_Adams. of motor neurons is not known. Stimulation of a motor nerve in these cases, instead of causing a brief burst of action potentials in the muscle, results in a prolonged or dispersed series of potentials lasting several hundred milliseconds. Evidently, branched axons involved in collateral innervation have unstable polarization that may last for years.


Neurology_Adams

Neurology_Adams. The clinician is faced initially with several problems that can be solved sequentially when dealing with this group of diseases: (1) establishing the existence of disease of the peripheral nervous system and differentiating it from a process of the central nervous system, neuromuscular junction or the muscles; (2) distinguishing by clinical examination which of the main topographic syndromes is being displayed; (3) determining by examination and nerve conduction studies if the problem is predominantly motor or sensory or autonomic in nature or is of mixed type and whether the myelin sheath, the axon, or cell body (motor or sensory neurons) is the target of disease; and (4) assessing if the neuropathy is acquired or hereditary in nature. When taken together, these features limit the likely etiologic diagnoses from a vast list of possibilities. Topographic and Clinical Patterns of Neuropathy (Table 43-1)


Neurology_Adams

Neurology_Adams. Topographic and Clinical Patterns of Neuropathy (Table 43-1) At the outset it must be determined whether the neurologic findings correspond to one of the following syndromic patterns: 1. Polyneuropathy 2. Radiculopathy or polyradiculopathy 3. Neuronopathy—motor or sensory 4. Mononeuropathy 5. Multiple mononeuropathies (mononeuropathy multiplex) 6. Plexopathy (involvement of multiple nerves in a plexus) A discussion of these patterns is given in Chap. 8, but the main facts are repeated here. In polyneuropathy, a generalized process affecting the peripheral nerves, weakness is relatively symmetrical from the beginning and progresses bilaterally; reflexes are lost in affected parts but particularly at the ankles; sensory complaints and loss of sensation are most pronounced distally, and in the feet before the hands in most cases.


Neurology_Adams

Neurology_Adams. Polyradiculopathy, a disease of multiple spinal roots, differs from polyneuropathy in that the neurologic signs are asymmetrical, with an erratic distribution that may, for example, be proximal in one limb and distal in another. Weakness and zones of sensory loss correspond to involvement of one or more spinal or cranial roots. Pain in the sensory distribution of the roots is a common feature. The common single radiculopathy, most often the result of root compression by disease of the spinal column, is identified by pain, sensory, motor, and reflex change solely in the distribution of one nerve root. The distinction from mononeuropathy (see later) is not always apparent and one must resort to a reference or to memorized knowledge of the motor and sensory innervation patterns of roots and nerves as given in Figs. 8-1, 8-2, and 8-3 and on the overleafs. Most helpful is the limitation of sensory loss to one of the dermatomes, but it so happens that there is overlap between adjacent


Neurology_Adams

Neurology_Adams. and nerves as given in Figs. 8-1, 8-2, and 8-3 and on the overleafs. Most helpful is the limitation of sensory loss to one of the dermatomes, but it so happens that there is overlap between adjacent dermatomes and such a pattern is not easily discerned.


Neurology_Adams

Neurology_Adams. Mononeuropathy is the most circumscribed form of peripheral nerve disease. It is reflected by weakness and sensory loss in the territory of a single peripheral nerve. Specific features serve to differentiate mononeuropathy from a radiculopathy—for example, weakness in dorsiflexion and eversion of the foot is referable either to the peroneal nerve or to the L5 nerve root; however, if there is weakness of inversion of the foot, innervated by the tibial nerve, the fault must be with the L5 root, not with the peroneal nerve. Conversely, if inversion is spared in a foot drop, the lesion is in the peroneal nerve. The distribution of sensory loss also aids in distinguishing the two processes; for example, in the aforementioned case the region of sensory change corresponding to the L5 root extends almost up to the knee on the anterior surface of the foreleg whereas it ends a limited distance above the ankle in the case of a peroneal nerve lesion (see the sensory maps in Figs. 8-1, 8-2, and


Neurology_Adams

Neurology_Adams. almost up to the knee on the anterior surface of the foreleg whereas it ends a limited distance above the ankle in the case of a peroneal nerve lesion (see the sensory maps in Figs. 8-1, 8-2, and 8-3).


Neurology_Adams

Neurology_Adams. At times, particularly in advanced stages, the accumulation of multiple mononeuropathies, termed mononeuropathy multiplex, may be difficult to differentiate from polyneuropathy as discussed further on. Plexopathies (brachial or lumbosacral) create the most confusing patterns of motor and sensory involvement; only one limb is affected, but the motor, sensory, and reflex loss does not conform to a pattern of several adjacent nerve roots or nerves. Knowledge of the innervation of the involved muscles at the level of the plexus usually clarifies the situation.


Neurology_Adams

Neurology_Adams. In sensory neuronopathy, the ganglion cells rather than the peripheral sensory nerves are predominantly affected. This gives rise to symptoms and signs of sensory loss in both a proximal and distal distribution, including the scalp, thorax, abdomen, and buttocks as well as the extremities; sensory ataxia is a common accompaniment. There is no weakness, but movements may be awkward as a result of a sensory ataxia. Motor neuronopathy is essentially the obverse condition, a disorder of the anterior horn causing weakness, fasciculations, and atrophy in a widespread distribution and, therefore, not properly included as a process of the peripheral nerves. The apparent complexity of peripheral nerve disease is greatly simplified by recognizing that, of the multitude of diseases, each manifests itself by one or another of above-described topographic and sensory-motor patterns for which reason the pattern of neuropathy sets limits on the etiologic possibilities.


Neurology_Adams

Neurology_Adams. In the analysis of a polyneuropathy, it is of further value to determine whether the process is predominantly motor with less sensory involvement or the converse, or purely sensory, motor, or mainly autonomic. The time course of the disease also informs diagnosis. An acute onset (i.e., rapid evolution) is nearly always an inflammatory, immunologic, toxic, or vascular polyneuropathy. The other extreme, a polyneuropathy evolving over many years, is indicative of a hereditary or, rarely, a metabolic disease. Most of the toxic, nutritional, and systemic diseases of nerve develop subacutely over several weeks and months. In addition to the patient’s report of the progress of symptoms, signs such as muscle atrophy signify a process of relatively long duration, at least several months.


Neurology_Adams

Neurology_Adams. The etiologic diagnosis of polyneuropathy is next guided by deducing whether the myelin sheath or the axon is primarily involved (i.e., demyelinating or axonal neuropathy). The neurologic examination alone may be sufficient to make this distinction, but greater precision is attained from nerve conduction studies and needle examination of muscles (EMG). The latter test also helps separate primary disorders of muscle (myopathies) and neurogenic denervation of muscle or neuromuscular block (myasthenia). The electrical examinations of nerve and muscle described in Chap. 2 greatly reduce the number of possible diagnoses. These EMG and nerve conduction abnormalities may be so characteristic as to virtually define a neuropathy, for example, chronic demyelinative motor neuropathy with multifocal conduction block.


Neurology_Adams

Neurology_Adams. Other useful laboratory procedures are (1) biochemical tests to identify metabolic, nutritional, or toxic states; (2) CSF examination (increase in protein and in cells that indicate radicular or meningeal involvement); (3) nerve, and occasionally accompanying muscle biopsy (the latter aids in the diagnosis of vasculitic causes of neuropathy); (4) measurement of immunoglobulins and antineural antibodies that relate to immune-mediated neuropathies; and (5) genetic testing for several of the inherited neuropathies. These are discussed in the context of each of the main diseases of nerve and in the later parts of Chap. 2.


Neurology_Adams

Neurology_Adams. Chap. 2. Once having established that the patient has a disease of the peripheral nerves and having ascertained its clinical and electrophysiologic pattern and time course, one is usually able to determine its cause. This is accomplished most readily by allocating the case in question to one of the categories listed in Table 43-2, which classifies the peripheral nerve diseases syndromically according to their mode of evolution and clinical presentation. Our use of the terms acute, subacute, and chronic neuropathy must be explained. By acute, we mean evolution in terms of days, and by subacute, evolution in terms of weeks. Chronic is divided into two groups: one in which the neuropathy has progressed for a period of several months to a few years and another in which progression is over many years, most of which prove to have a genetic cause. It can be restated that these temporal properties are, with the topographic pattern, the main determinants in the categorization of neuropathy.


Neurology_Adams

Neurology_Adams. Diseases of the peripheral nerves are considered in a more comprehensive fashion in the two-volume Peripheral Neuropathy, edited by Dyck and colleagues and in the text by Amato and Russell cited in the references. Also recommended are more concise monographs by Schaumburg and associates and by Asbury and Thomas, and the atlas on the pathology of peripheral nerve by King. A number of differences separate the polyneuropathies in this category: (1) acute inflammatory demyelinating or axonal polyneuropathy (GBS), (2) vasculitic polyneuropathies, (3) porphyria, (4) certain toxic polyneuropathies, and (5) acute sensory and autonomic polyneuropathies. Of these various acute polyneuropathic diseases, the Guillain-Barré demyelinative syndrome, because of its frequency and gravity, is most demanding of the physician’s attention. Guillain-Barré Syndrome (Landry-Guillain-Barré-Strohl Syndrome, Acute Inflammatory Demyelinating Polyneuropathy, AIDP)