Neurology_Adams

Neurology_Adams. This rare disorder, named after Refsum who made the first clinical observations, is inherited as an autosomal recessive trait and has its onset in late childhood, adolescence, or early adult life. It is slowly progressive but may be punctuated by acute or subacute worsening. Clinical diagnosis is based on a combination of clinical manifestations—retinitis pigmentosa, ataxia, and chronic polyneuropathy—coupled with the metabolic marker of the disease, an increase in blood phytanic acid. Phytanic acid accumulates because of a deficiency of the peroxisomal enzyme, phytanoyl-coenzyme A (CoA) hydroxylase. The deficiency is caused by mutations in 1 of 2 disparate genes. Cardiomyopathy and neurogenic deafness are present in most patients, and pupillary abnormalities, cataracts, and ichthyotic skin changes (particularly on the shins) are added features in some. Anosmia and night-blindness (nyctalopia) with constriction of the visual fields may precede the neuropathy by many years. The


Neurology_Adams

Neurology_Adams. skin changes (particularly on the shins) are added features in some. Anosmia and night-blindness (nyctalopia) with constriction of the visual fields may precede the neuropathy by many years. The polyneuropathy is sensorimotor, distal, and symmetrical in distribution, affecting the legs more than the arms. All forms of sensation are reduced, often deep sensation more so than pain and thermal sense, and tendon reflexes are lost. The CSF protein is increased, sometimes markedly. Usually, the polyneuropathy develops gradually, although in some patients it has a subacute onset or, after being established for some time, a tendency to worsen fairly abruptly.


Neurology_Adams

Neurology_Adams. Although the nerves may not be palpably enlarged, “hypertrophic” changes with onion-bulb formation are invariable pathologic features. The metabolic defect has been discovered to be in the utilization of dietary phytol; a failure of oxidation of phytanic acid—a branched-chain tetramethylated 16-carbon fatty acid—that accumulates in the absence of activity of the enzyme phytanoyl-CoA-hydroxylase. The relation between the increased phytanic acid and the polyneuropathy is uncertain. Clinical diagnosis is confirmed by the finding of increased phytanic acid in the blood of a patient with a chronic, mainly sensory neuropathy; the normal level is less than 0.3 mg/dL but in patients with this disease, it constitutes 5 to 30 percent of the total fatty acids of the serum lipids. Urinary phytanic acid concentration is also raised. Genetic testing reveals the mutation, which is in PHYH in 90 percent of cases and in PEX7 in the others.


Neurology_Adams

Neurology_Adams. Treatment Diets low in phytol may be beneficial but this is difficult to judge, because after an acute attack there is sometimes a natural remission. The claimed effects of plasma exchange have also been difficult to interpret. In some patients there is a very slow progression of the disease, and in others, a more rapid progression with death from cardiac complications.


Neurology_Adams

Neurology_Adams. Like the cases of mitochondrial disease with neuropathy reported by Tuck and McLeod, we have observed several in which the clinical picture was almost identical to that of Refsum disease, but elevations in phytanic acid were not present. Mild ichthyosis, sensorineural deafness, ataxia of mixed tabetic-cerebellar type, areflexia, and retinitis pigmentosa were the main findings, conforming to the NARP syndrome described in Chap. 36. None of our cases had a family history of a similar disorder. Sural nerve biopsy showed loss of large fibers. There was an identifiable mitochondrial disorder in most of the recently studied cases, as described in Chap. 36. It should be remarked that most mutations of mitochondrial DNA cause a myopathy with multisystem disease, but not a neuropathy. The onset of the disease is in childhood or adolescence with slow progression. Abetalipoproteinemia (Bassen-Kornzweig Syndrome, MTTP Mutation) (See Also Chap. 36)


Neurology_Adams

Neurology_Adams. This rare autosomal recessive childhood disorder was described in Chap. 37 with the inherited metabolic disorders of the nervous system and commented upon with neuroacanthocytosis in Chap. 38, although there is no relationship between the 2 processes. It is mentioned here because the brunt of the neurologic disorder falls upon the peripheral nerves. Acanthocytosis of red blood cells is its identifying feature. The earliest neurologic finding is usually diminution or absence of tendon reflexes, detected as early as the second year of life. Later, when the child is first able to cooperate in sensory testing, a loss of vibratory and position sense is found in the legs. Cerebellar signs (ataxia of gait, trunk, and extremities; titubation of the head; and dysarthria), muscle weakness, ophthalmoparesis, Babinski signs, and loss of pain and temperature sense are the other characteristic neurologic abnormalities, in more or less this order of frequency. Developmental delay, usually mild,


Neurology_Adams

Neurology_Adams. Babinski signs, and loss of pain and temperature sense are the other characteristic neurologic abnormalities, in more or less this order of frequency. Developmental delay, usually mild, occurs in some patients. Irregular progression occurs over a few years, and many patients are unable to stand and walk by the time they reach adolescence.


Neurology_Adams

Neurology_Adams. Skeletal abnormalities include pes cavus and kyphoscoliosis, which are secondary to the early onset neuropathy. Constriction of the visual fields and ring scotomata are manifestations of the macular degeneration and retinitis pigmentosa in some cases. Cardiac enlargement and congestive failure are serious late complications. Neuropathologic findings consist of demyelination of peripheral nerves and degeneration of nerve cells in the spinal gray matter and cerebellar cortex. Diagnosis is confirmed by the finding of red blood cell acanthocytes, low serum cholesterol, and β (low-density)-lipoproteins. The disease is caused by defects in a triglyceride transfer protein, as discussed in Chap. 36. A deficiency of vitamin E, as a result of malabsorption, may be a factor, and large doses of the vitamin should be tried as therapy.


Neurology_Adams

Neurology_Adams. A closely related disease, also with familial hypobetalipoproteinemia, was described by van Buchem and coworkers. It, too, is associated with malabsorption syndrome, ill-defined weakness, ataxia, dysesthesia of the legs, and Babinski signs. There is no sensory loss.


Neurology_Adams

Neurology_Adams. This is a rare, familial, small-fiber neuropathy of which we have seen a few cases, inherited as an autosomal recessive trait. It is named for the island off the Virginia coast where the first-described patients resided. The mutation eliminates the function of the adenosine triphosphate (ATP)-cassette transporter protein, ABC1. It results in a deficiency of high-density lipoprotein, extremely low serum cholesterol, and high triglyceride concentrations in the serum. Perhaps on the basis of these abnormalities, the patients are disposed to early and severe atherosclerosis. The presence of enlarged, yellow-orange (cholesterol-laden) tonsils is said to be a frequent manifestation (of course, previous tonsillectomies obviate this sign). About half of the reported cases have had neuropathic symptoms, taking the form of an asymmetrical sensorimotor neuropathy that fluctuates in severity.


Neurology_Adams

Neurology_Adams. The sensory loss is predominantly for pain and temperature and extends over the entire body; at times it is limited to the face and upper extremities, simulating syringomyelia (“pseudosyringomyelia”). Tactile and proprioceptive sensory modalities tend to be preserved. The polyneuropathy may come in attacks—that is to say, it simulates a recurrent process. Muscular weakness, if present, affects either the lower or upper extremities or both, particularly the hand muscles, which may undergo atrophy and show denervation by EMG. In a small number of patients there has been facial diplegia out of proportion to weakness elsewhere. In one of our patients, the pain and temperature loss was restricted to the head, neck, and arms. Tendon reflexes are often lost or diminished. Transient ptosis and diplopia have been reported. Nerve conduction is slowed.


Neurology_Adams

Neurology_Adams. Fat-laden macrophages are present in the bone marrow and elsewhere. No complete pathologic studies are available. There is no known treatment but dietary measures to reduce triglycerides may help, particularly in preventing atherosclerosis but the influence on the neuropathy is uncertain. Fabry Disease (Anderson-Fabry Disease, GLA Mutation) (See Also Chap. 36) The genetic and metabolic aspects of this sex-linked disorder caused by deficiency of alpha-galactosidase A were considered with the inherited metabolic diseases. Here we offer some additional remarks about the painful neuropathic component. It bears commenting that 10 percent of heterozygous women display neuropathic symptoms, but usually of later onset and lesser degree than in males.


Neurology_Adams

Neurology_Adams. The pain, which is usually the initial symptom in childhood and adolescence, often has a burning quality or occurs in brief lancinating jabs, mostly in the fingers and toes, and may be accompanied by paresthesias of the palms and soles. Changes in environmental temperature and exercise may induce pain in “crises,” an identifying feature. These abnormalities are a result of the accumulation of glycolipid (ceramide trihexoside) in peripheral nerves, both perineurally and intraneurally, as well as in cells of the spinal ganglia and the anterior and intermediolateral horns of the spinal cord. Ohnishi and Dyck demonstrated a preferential loss of small myelinated and unmyelinated fibers and small neurons of dorsal root ganglia, and by autonomic changes in other cases. Involvement of the sensory ganglia and the associated degenerative changes in the afferent fibers are thought to be the likely cause of the thermally induced painful sensory phenomena (Kahn 1973).


Neurology_Adams

Neurology_Adams. Later in the illness there is progressive impairment of renal function and cerebral and myocardial infarction. The characteristic dermal feature is the presence of numerous dark red macules and papules (angiokeratomas), up to 2 mm in diameter, over the trunk and limbs, most closely clustered over the thighs and lower trunk and around the umbilicus (angiokeratoma corporis diffusum). The comprehensive review by Brady and Schiffman is recommended. The responsible mutation has been identified in GLA. Treatment Phenytoin, carbamazepine, gabapentin, or amitriptyline may be helpful in alleviating the pain and dysesthesias. As discussed in Chap. 36, enzyme replacement therapy has become available and seems to lead to partial remission of many of the features including the neuropathic ones. Polyneuropathy of Acromegaly and Gigantism


Neurology_Adams

Neurology_Adams. Polyneuropathy of Acromegaly and Gigantism Nerve entrapment, particularly of the median nerve, is a well-known feature of acromegaly. Pickett and colleagues identified carpal tunnel syndrome in 56 percent of acromegalics. Also recognized as a complication of acromegaly, but not because of multiple nerve entrapments, is polyneuropathy characterized by paresthesia, loss of tendon reflexes in the legs, and atrophy of slight degree in the distal leg muscles. Sometimes there are enlarged nerves. In the case reported by Stewart, the enlargement was the result of hypertrophic changes in the endoneurial and perineurial tissues, similar to those that occur in other so-called hypertrophic neuropathies of inflammatory or heredofamilial origin. In cases of extreme gigantism, a more severe polyneuropathy has sometimes been reported, to the point of causing Charcot joints (Daughaday).


Neurology_Adams

Neurology_Adams. Mentioned here is a case we have observed in which a severe and slowly progressive relatively symmetric motor neuropathy occurred in a patient with Pyle disease, a metaphyseal dysplasia that resembles acromegaly. Metachromatic Leukodystrophy (ARSA Mutation, See Also Chap. 36)


Neurology_Adams

Neurology_Adams. In this metabolic disease, the congenital absence of the degradative enzyme sulfatase leads to massive accumulation of sulfatide throughout the central and peripheral nervous systems and to a lesser extent in other organs. The abnormality is transmitted as an autosomal recessive trait. Progressive cerebral deterioration is the most obvious clinical feature, but hyporeflexia, muscular atrophy, and diminished nerve conduction velocity reflect the presence of a neuropathy. Early in the course of the illness, the weakness, hypotonia, and areflexia may suggest Werdnig-Hoffmann disease; in older children there may be a complaint of paresthesias and demonstrable sensory loss. Bifacial weakness has been reported but must be rare. Sensory and motor conduction velocities are greatly slowed similarly in all nerves. Metachromatically staining granules accumulate in the cytoplasm of Schwann cells in nerves as well as in the cerebral white matter. There is loss of peripheral myelinated fibers. The


Neurology_Adams

Neurology_Adams. in all nerves. Metachromatically staining granules accumulate in the cytoplasm of Schwann cells in nerves as well as in the cerebral white matter. There is loss of peripheral myelinated fibers. The measurement of arylsulfatase A activity in peripheral leukocytes or urine and biopsies of sural nerves are used to establish the diagnosis, even early in the course of the illness.


Neurology_Adams

Neurology_Adams. Inherited (Familial Amyloidosis, TTR Amyloidosis) Amyloid Neuropathies (See Table 43-6)


Neurology_Adams

Neurology_Adams. As noted earlier in the discussion of acquired (primary) amyloidosis, amyloid is a descriptive term for any of the proteins that are deposited in filamentous beta-pleated sheets; it can be derived from a number of precursor protein sources. Peripheral neuropathy is a common and often the most prominent manifestation of amyloidosis. The polyneuropathies are of 2 main types—those associated with familial amyloidosis (referred to as FA) and the other associated with primary (nonfamilial) systemic deposition of amyloid (termed AL), which is derived from a circulating monoclonal protein. The acquired type has been discussed earlier. The most notable difference between these 2 types is the absence of a significant amount of paraprotein in the inherited forms (see further on). The amyloidosis that is secondary to chronic infectious or inflammatory disease, referred to as AA, is an increasingly rare condition and, in any case, does not affect the nerves.


Neurology_Adams

Neurology_Adams. In the following described most common familial amyloidoses, the amyloid is derived from an inherited abnormality of serum protein transthyretin (TTR, formerly called “prealbumin”). Several different amino acid substitutions have been identified in each type of amyloidosis. In the originally described Andrade type, methionine replaces valine at amino acid 30; therefore this has been referred to as transthyretin amyloidosis and as the TTR met 30 type. However, there are over 100 variants in the transthyretin gene that can give rise to amyloidosis.


Neurology_Adams

Neurology_Adams. The familial amyloid polyneuropathies comprise several distinct groups, as enumerated in Table 43-6. The pattern of inheritance in all types is autosomal dominant; males and females are affected with equal frequency. Although a descriptive classification based on the ethnic or geographic origin of affected families is still in use and is retained in the narrative categorization below, it is now possible to categorize the diseases according to their genetic causes and the corresponding chemical structure of the amyloid protein that is deposited in tissue. The recent cloning of many of the amyloid protein genes has made possible not only the detection of the common transthyretin mutation but also DNA tests for some of the other types of familial amyloidoses. Lachmann and colleagues (2002 and 2007) emphasize the high frequency of genetic defects in amyloid precursor proteins and the finding in one-quarter of cases of a low-level monoclonal gammopathy. Characteristic of all the amyloid


Neurology_Adams

Neurology_Adams. and 2007) emphasize the high frequency of genetic defects in amyloid precursor proteins and the finding in one-quarter of cases of a low-level monoclonal gammopathy. Characteristic of all the amyloid polyneuropathies is the preferential involvement of small-diameter sensory and autonomic nerves and deposition of amyloid in various organs. Sensory loss, therefore, dominates the picture and pain and autonomic changes are prominent in most varieties of the disease.


Neurology_Adams

Neurology_Adams. The following are the main recognized types of familial amyloid neuropathies. 1. The Portuguese (Andrade) type. Andrade, in 1939, recognized that a chronic familial illness known as “foot disease” among the inhabitants of Oporto, Portugal, was a special type of amyloid polyneuropathy. He was not the first to have seen amyloid in degenerating nerve but deserves credit for identifying the disease as one of the heredofamilial polyneuropathies. By 1969 he had studied 148 sibships, comprising 623 individuals, among whom there were 249 with polyneuropathy. Descendants of this family have been traced to Africa, France, and Brazil. Other foci of the disease have been reported in Japan (Araki et al; Ikeda et al), the United States (Kantarjian and DeJong), Germany (Delank et al), Poland, Greece, Sweden, and northwest Ireland (Staunton et al). As far as one can tell, these are separate, unrelated probands in different ethnic groups.


Neurology_Adams

Neurology_Adams. The age of onset of this form of familial amyloid polyneuropathy is between 25 and 35 years. The disease progresses slowly and terminates fatally in 10 to 15 or more years. The initial symptoms are usually numbness, paresthesias, and sometimes pain in the feet and lower legs. Weakness is minimal, and the tendon reflexes, although diminished, may be retained early in the course of the illness. Pain and thermal sense are reduced more than tactile, vibratory, and position sense (a “pseudosyringomyelic”) pattern. Autonomic involvement is another important characteristic—loss of pupillary light reflexes and miosis, anhidrosis, vasomotor paralysis with orthostatic hypotension, alternating diarrhea and constipation, and erectile dysfunction. These autonomic changes tend to be more extensive than the sensory ones. Difficulty in walking also develops and has its basis in a combination of faulty position sense and mild muscle weakness. Later, tendon reflexes are abolished and the legs become


Neurology_Adams

Neurology_Adams. the sensory ones. Difficulty in walking also develops and has its basis in a combination of faulty position sense and mild muscle weakness. Later, tendon reflexes are abolished and the legs become thin. The nerves are not enlarged. Cranial nerve involvement (facial weakness and numbness, loss of taste) is a late manifestation and occurs in only a few cases.


Neurology_Adams

Neurology_Adams. The clinical details vary somewhat from case to case, even within a family. Cardiac enlargement and irregularities in cardiac rhythm as a result of bundle-branch or atrioventricular (AV) block occur early in some and late in others. A few patients have had severe amyloid cardiomyopathy from the onset (Ikeda et al). Weight loss may be pronounced owing to anorexia and disordered bowel function and the later development of a malabsorption syndrome. The liver may become enlarged (as it may in the acquired form). Vitreous opacities (veils, specks, and strands) may progress to blindness but this has been rare; in a few, there has been an impairment of hearing. Involvement of the CNS—manifest as behavioral abnormalities, cerebellar ataxia, and bilateral corticospinal signs—has also been reported in a few cases but their nature and pathologic basis is controversial (Ikeda et al). A nephrotic syndrome and uremia terminate life in some patients. The CSF may be normal or the protein content may


Neurology_Adams

Neurology_Adams. in a few cases but their nature and pathologic basis is controversial (Ikeda et al). A nephrotic syndrome and uremia terminate life in some patients. The CSF may be normal or the protein content may be increased (50 to 200 mg/dL); the blood is normal except for anemia caused by amyloidosis of the bone marrow. This is probably the most common transthyretin mutation–derived amyloidosis.


Neurology_Adams

Neurology_Adams. 2. Familial amyloidosis with carpal tunnel syndrome (Swiss type). Falls and coworkers, in 1955, and later Rukavina and associates described a large group of patients of Swiss stock living in Indiana who developed, in their fourth and fifth decades, a syndrome of acroparesthesias in the hands as a result of deposition of amyloid in the connective tissues and beneath the carpal ligaments. Similar kindreds of German descent were recognized in Maryland. There were sensory loss and atrophic muscle weakness in the distribution of the median nerves, which were compressed. Section of the carpal ligaments relieved the symptoms. In some of the patients, other nerves of the arms were said to have become involved later. Vitreous deposits have been observed frequently in this form of the disease. As with the Portuguese type, an abnormal transthyretin is the basis of the deposition of amyloid.


Neurology_Adams

Neurology_Adams. 3. Iowa type. In 1969, van Allen described an Iowa kindred with onset, in their thirties, of a fairly severe sensorimotor neuropathy, involving the legs and then the arms. There was amyloid deposition in the testes, adrenal glands, and kidneys (the usual cause of death), as well as a high incidence of peptic ulcer disease. The amyloid in this disease is derived from a mutated apolipoprotein A1, in which there is an amino acid substitution.


Neurology_Adams

Neurology_Adams. 4. Cranial neuropathy with corneal lattice dystrophy and facial palsies. This unusual form of amyloid neuropathy was first described in three Finnish families by Meretoja, hence the label “Finnish type.” Subsequently, it was reported from several different parts of the world in families of non-Finnish heritage. The disease usually begins in the third decade with lattice corneal dystrophy. Vitreous opacities are not observed, and visual acuity is little affected. Peripheral neuropathy may not be evident until the fifth decade, at which time the facial nerves, particularly their upper branches, become affected. The nerves of the limbs are involved even later and to a much lesser extent than in other amyloid neuropathies. In advanced cases there is a distinctive appearance of excessive skin folds about the face, facial diparesis, dysarthria, spasticity, and dense loss of posterior column function. At postmortem examination, deposits of amyloid are found in virtually every organ, mainly


Neurology_Adams

Neurology_Adams. folds about the face, facial diparesis, dysarthria, spasticity, and dense loss of posterior column function. At postmortem examination, deposits of amyloid are found in virtually every organ, mainly in the kidneys and blood vessels and in the perineurium of affected nerves.


Neurology_Adams

Neurology_Adams. The amyloid fibrils are derived from the protein gelsolin. The latter is normally an actin-binding protein, but it is also an important constituent of basement membranes, which may explain the deposition of amyloid in the cornea and skin.


Neurology_Adams

Neurology_Adams. Diagnosis of familial amyloid neuropathy When the characteristic painful small-fiber type of sensory disturbance and autonomic changes are coupled with a family history of the same constellation, the diagnosis is not difficult. As noted in the earlier section on the acquired paraproteinemic neuropathy, the presence of a monoclonal (rarely polyclonal) immunoglobulin in the blood is found in only a limited number of patients with familial amyloid cases and it is usually just above the upper limit of normal for the immunoglobulin subclass. Otherwise the two types of amyloid diseases, FA and AL, are quite similar and, indeed, approximately 10 percent of cases considered by history and examination to be acquired will be found to have the genetic disorder (Lachmann et al 2002). The situation has been clarified by the availability of gene sequencing to detect mutations in transthyretin that are related to amyloidosis.


Neurology_Adams

Neurology_Adams. Pathologic findings Amyloid deposits are demonstrable in the walls of blood vessels, the interstitial (endoneurial) tissues of the peripheral somatic and autonomic nerves, and in the spinal and autonomic ganglia and roots. There is a loss of nerve fibers, the unmyelinated and small myelinated fibers being more depleted than the large myelinated ones. The anterior horn and sympathetic ganglion cells are swollen and chromatolyzed because of involvement of their axons, and the posterior columns of the spinal cord degenerate, also on a secondary basis.


Neurology_Adams

Neurology_Adams. The pathogenesis of the fiber loss in familial amyloidosis, as in the acquired type, is not fully understood. On the basis of their findings in a sporadic case of amyloid polyneuropathy with diabetes mellitus, Kernohan and Woltman suggested that amyloid deposits in the walls of the small arteries and arterioles interfered with the blood supply in the nerves and that amyloid neuropathy is essentially an ischemic process. In other cases, however, the vascular changes are relatively slight and the degeneration of the nerve fibers appears to be related to their compression and distortion by the endoneurial deposits of amyloid or, alternatively, there may be a direct toxic effect of the embedded amyloid. Amyloid also deposits in the tongue, gums, heart, gastrointestinal tract, kidneys, and many other organs, where it may act as a tissue toxin or has a mechanically disrupting effect on cells.


Neurology_Adams

Neurology_Adams. Treatment Two novel approaches, a small molecule, tafamidis, that prevents the aggregation of amyloid fibrils by stabilizing it in a tetrameric form (Coelho et al, 2012) and interfering RNA therapy (RNAi) that reduces the production of mutant amyloid (Coelho et al, 2013) are both promising. Both have shown promise in halting or reversing familial amyloidosis (Adams et al 2018 and Benson et al). Beneficial effects have been shown in some aspects of the neuropathy but it is not clear if these are sustained. Liver transplantation has proved curative of some of the familial amyloid polyneuropathies, but obviously it has no role in the acquired forms. According to Herlenius and colleagues, more than 500 patients at the time of their writing had received liver transplants with a 77 percent rate of survival, equivalent to liver transplantation for other diseases. Problems in Diagnosis of the Chronic Polyneuropathies


Neurology_Adams

Neurology_Adams. Problems in Diagnosis of the Chronic Polyneuropathies This is the group of peripheral nerve diseases that has given the present authors the most difficulty. The cause of acute and many of the subacute and relapsing forms of nerve disease usually can be established by widely available clinical and laboratory methods. It is the early and late chronic polyneuropathies that continue to baffle the neurologist and general physician, despite the value of EMG and nerve conduction studies and the respectable advances that have been made in the field of genetic testing. Diagnosis of Early Chronic Polyneuropathy


Neurology_Adams

Neurology_Adams. A sensorimotor paralysis, which evolves over several weeks (subacutely) or more slowly, over many months or a year or two, and involves legs more than arms and distal parts more than proximal should lead to a search for diabetes, occult neoplasia (carcinoma, lymphoma, multiple myeloma, or plasmacytoma), HIV, paraproteinemia (including amyloid neuropathy), systemic autoimmune disease, and CIDP. In our experience, the subacute and chronically evolving demyelinating neuropathies (over months) that have slowed motor conduction velocities, conduction block, and relatively normal needle EMG studies generally turn out to be variants of CIDP, some with a paraproteinemia. Marked weakness and reduced muscle action potential amplitudes in the face of minimal denervation, even if present in only a few nerves, also indicate the presence of focal demyelination. Most of the mixed axonal–demyelinating cases in which one eventually arrives at a diagnosis will also be related to an immune


Neurology_Adams

Neurology_Adams. in only a few nerves, also indicate the presence of focal demyelination. Most of the mixed axonal–demyelinating cases in which one eventually arrives at a diagnosis will also be related to an immune (paraproteinemic) or inflammatory (CIDP) process. In exceptional cases, a neoplastic process may remain hidden for as long as 2 or 3 years after the onset of neuropathy. An environmental toxin, endocrine disorder (except for diabetes), or nutritional cause is seldom identified, despite the frequent attribution of obscure polyneuropathies to such causes. Nonetheless, history of exposure to industrial or hobbyist toxins, sociopathy or psychopathy that would lead to toxin ingestion, or foreign travel should be sought and the evaluation should include testing for heavy metals in obscure cases. Unusual causes of nutritional deficiency such as celiac-sprue and other malabsorption syndromes (Whipple disease, Crohn disease, chronic hepatic disease, and particularly intestinal bypass surgery) have


Neurology_Adams

Neurology_Adams. causes of nutritional deficiency such as celiac-sprue and other malabsorption syndromes (Whipple disease, Crohn disease, chronic hepatic disease, and particularly intestinal bypass surgery) have usually been obvious enough when present, so that the experienced clinician rarely overlooks them. Perhaps sprue is able to cause a neuropathy with minimal gastrointestinal symptoms. Vitamin B12 deficiency should be sought in cases of large-fiber neuropathy. A difficult problem is that of an older person with a mild, nonprogressive sensorimotor polyneuropathy in whom there is evidence of mild hypothyroidism, marginally low vitamin B12 and folic acid levels in the blood, a somewhat unbalanced diet, perhaps an excessive alcohol intake, and an abnormal glucose tolerance response. It is easy to propose but hard to prove that any of these factors is relevant. Vitamin replacement should be undertaken nonetheless if no other cause is found.


Neurology_Adams

Neurology_Adams. In the purely or predominantly sensory polyneuropathies not caused by diabetes—some painful, some not, and some with marked ataxia—an association with occult carcinoma, an IgM or other paraproteinemia, primary and familial amyloidosis, or Sjögren syndrome are the primary considerations. The problem of a mild sensory neuropathy in an elderly patient with or without burning feet was discussed earlier. When the symptoms are confined to the feet and legs, hereditary sensory neuropathy must always be considered if the condition is long standing. Intoxications with pyridoxine, metals, and idiosyncratic responses to therapeutic medications account for a few chronic sensory neuropathies. Despite all these considerations, we still regularly encounter patients in whom the cause is not disclosed by any of the available tests. We have watched helplessly as some of these patients were reduced to a bed and wheelchair existence and others suffered from pain until they became dependent on opiates.


Neurology_Adams

Neurology_Adams. Table 43-7 lists the laboratory tests that we have found useful in the investigation of this group of neuropathies, with electrophysiology being most valuable. Diagnosis of Late Chronic Polyneuropathy


Neurology_Adams

Neurology_Adams. The majority of these (evolving over years) prove to be genetic, either inherited or one of the infrequent sporadic mutations that are responsible for the inherited types. The observations of Dyck and coworkers (1981), referred to in the introduction to this chapter, are of interest in this respect. In a series of 205 patients who were referred to the Mayo Clinic with neuropathies of unknown cause, 86 were found to have an inherited form of disease. The proportion is presumably higher now that panels of genetic testing are available. With appropriate genealogic data, the diagnoses of the peroneal muscular atrophy of Charcot-Marie-Tooth disease can usually be made on clinical grounds alone (high arches, distal foreleg atrophy, chronicity, etc.). Sporadic cases are more difficult. Some of the patients who have consulted us in adulthood for an obscure polyneuropathy report having had operations on their feet and toes for these reasons, but the connection to a genetic neuropathy had not


Neurology_Adams

Neurology_Adams. the patients who have consulted us in adulthood for an obscure polyneuropathy report having had operations on their feet and toes for these reasons, but the connection to a genetic neuropathy had not been previously made. Additional hints are frequent sprained ankles and the need to tape the ankles during adolescence in order to run or participate in sports. Dyck and associates (1981) found that direct examinations of the patients’ siblings, children, parents, and other close relatives were often successful in revealing a hereditary basis for the neuropathy. The absence of ankle reflexes or foot deformities in relatives discloses the diagnosis.


Neurology_Adams

Neurology_Adams. DNA testing for the main forms of Charcot-Marie-Tooth disease is available from commercial laboratories and has increased the diagnostic certainty. A comment has already been made regarding the utility of such testing and the small number of mutations that give rise to over one-third of cases of inherited sensorimotor neuropathy. As already alluded to, individuals with a chronic demyelinating neuropathy, pes cavus or hammer toes, and a likely autosomal dominant pattern of inheritance probably have CMT1A and sequencing for PMP22 duplication may be undertaken. If there is male-to-male transmission, CMT1X is likely and the GJB1 gene may be investigated. If both genes lack causative mutations in a demyelinating case, CMT1B is possible, especially if motor nerve conduction velocities are very slow (below 15 m/s), and the MPZ gene is suspect. Whether testing beyond this, which would include the SIMPLE, PMP22, and EGR2 genes that occur in low frequency with CMT1A, is worthwhile depends on


Neurology_Adams

Neurology_Adams. slow (below 15 m/s), and the MPZ gene is suspect. Whether testing beyond this, which would include the SIMPLE, PMP22, and EGR2 genes that occur in low frequency with CMT1A, is worthwhile depends on the clinical circumstances. Some cases of axonal, CMT2, will have one of several very low-frequency mutations that have been delineated. Numerous easily accessible algorithms for genetic testing have been published, similar to the guidance in the article by Saporta and colleagues, that are based on inheritance, nerve conduction velocity, and clinical features and we have not reproduced them here.


Neurology_Adams

Neurology_Adams. Slowly progressive polyneuropathy with features of central nervous system degeneration, particularly cerebellar ataxia, most often has a genetic basis, but a small number are found to be the result of a genetic metabolic disorder such as a leukodystrophy. In contrast, a few young patients have come to our attention in whom a gradually progressive polyneuropathy that evolved over almost a decade turned out to be an acquired chronic inflammatory demyelinating condition rather than the expected genetic type. The absence of a family history of neuropathy and of high arches and heterogeneous slowing of both nerve conduction velocities and reductions in motor amplitudes on the nerve conduction studies provided hints to the acquired nature of the condition. Finally, it should be conceded again that even after the most assiduous clinical and laboratory investigation, a substantial proportion of chronic neuropathies remain unexplained. Diagnosis of Recurrent or Relapsing Polyneuropathy


Neurology_Adams

Neurology_Adams. Several types of neuropathies are particularly prone to recurrence: CIDP, Refsum disease, Tangier disease, and porphyria, the last of which may display attacks that recur spontaneously or are precipitated by the administration of various drugs. Repeated exposure to environmental toxins can do the same. Approximately 2 percent of patients with GBS have one or more relapses, in which the clinical and pathologic changes differ little between episodes. Some instances of mononeuritis multiplex, especially when associated with cryoglobulinemia, are also characterized by remissions and relapses over many years, although the remissions are incomplete. A common cause of relapse is the withdrawal of corticosteroids in CIDP patients who are dependent on these drugs; similarly, lapses in the treatment of paraproteinemic neuropathies cause similar fluctuations in symptoms. Enlargement of nerves may occur with repeated attacks from any of these diseases. It is self-evident that patients who have


Neurology_Adams

Neurology_Adams. of paraproteinemic neuropathies cause similar fluctuations in symptoms. Enlargement of nerves may occur with repeated attacks from any of these diseases. It is self-evident that patients who have recovered from an episode of alcoholic–nutritional or toxic polyneuropathy will develop a recurrence if they again subject themselves to intoxication or nutritional deficiency.


Neurology_Adams

Neurology_Adams. Neuropathic symptoms that fluctuate in relation to environmental factors such as cold (cryoglobulinemia), heat (Fabry and Tangier diseases), or intermittent exposure to heavy metal or other type of poisoning may simulate an inherently relapsing polyneuropathy.


Neurology_Adams

Neurology_Adams. The diagnosis of this group of neuropathies rests on the finding of motor, reflex, and sensory changes confined to the territory of a single nerve; of several individual nerves affected in a random manner (mononeuritis or mononeuropathy multiplex); or of a plexus of nerves or part of a plexus (plexopathy). Certain neuropathies of this type—traceable mainly to polyarteritis nodosa or other vasculitides, leprosy, sarcoid, or diabetes—have already been discussed and are the main causes of the multiple mononeuropathy pattern. In addition to the signs of mononeuropathy multiplex, pain overlying the site of nerve infarction or distally is characteristic. The CSF protein is usually normal or slightly elevated, and in certain of these diseases there is a CSF pleocytosis (e.g., HIV, Lyme disease). Inflammatory neuropathy and the multifocal motor neuropathy caused by antibodies to GM1 also may be considered, because of their clinical similarity, in this group.


Neurology_Adams

Neurology_Adams. In identifying a process as caused by single or multiple mononeuropathies, the reader can refer to Table 43-1, which lists the roots, nerves, and muscles that are involved in particular movements, and to Table 43-4, which gives the main etiologies of mononeuropathy multiplex.


Neurology_Adams

Neurology_Adams. Brachial plexus neuropathies, or brachial plexopathies, comprise an interesting group of neurologic disorders. Most develop without apparent cause and manifest themselves by sensorimotor derangements ascribable to one or more of the cords of the plexus. Some are a result of infiltration by tumor, compression, obscure infections (possibly viral), and the delayed effects of radiotherapy. Of obvious cause are those that result from trauma, in which the arm is hyperabducted or the shoulder violently separated from the neck. Difficult births are an important source of such traction injuries to the plexus, but their nature is also evident. Rarely, the brachial plexus or other peripheral nerves may be damaged at the time of an electrical injury, either from lightning or from a household or industrial source (see “Electrical Injuries” in Chap. 41).


Neurology_Adams

Neurology_Adams. Most common in this category is an idiopathic brachial plexus neuritis of obscure origin, also called Parsonage-Turner syndrome, discussed further on. It stands apart as a special clinical entity, often difficult to distinguish from other types of brachial and axillary pain. Some of these cases, surprisingly, are familial; others occur in small outbreaks, but most are sporadic.


Neurology_Adams

Neurology_Adams. Direct compression of parts of the plexus by adjacent skeletal anomalies (cervical rib, fascial bands, narrowed thoracic outlet) represents another, if somewhat controversial, category of brachial plexus injury. A subcutaneous or intramuscular injection of vaccine or foreign serum was in the past sometimes followed by a brachial plexopathy (due to the aforementioned serum sickness reaction), usually a partial plexopathy. There are also plexus lesions of presumed toxic nature, such as following distal intravenous heroin injection. Granulomatous diseases such as sarcoid and secondary inflammatory processes related to lymphoma may implicate a plexus and an ischemic condition resulting from thrombosis of the subclavian artery or vein (Paget-Schrötter syndrome) is known.


Neurology_Adams

Neurology_Adams. In assessing the type and degree of plexus injury, electrophysiologic testing is of particular importance. Early after a traumatic injury or other acute disease of the plexus, the only electrophysiologic abnormality may be an absence of late responses (F wave). After 7 to 10 days or more, as the process of wallerian degeneration proceeds, sensory potentials are progressively lost and the amplitudes of compound muscle action potentials are variably reduced. Fibrillation potentials, indicative of denervation, then begin to appear in the corresponding muscles. Even later, usually after several weeks, signs of reinnervation can be detected. In more chronic cases, all of these features are evident when the patient is first studied. The pattern of denervated muscles allows a distinction to be made between a plexopathy, radiculopathy, and mononeuritis multiplex based on the known patterns of muscle innervation. If denervation changes are found in the paraspinal muscles, the source of


Neurology_Adams

Neurology_Adams. to be made between a plexopathy, radiculopathy, and mononeuritis multiplex based on the known patterns of muscle innervation. If denervation changes are found in the paraspinal muscles, the source of weakness and pain is in the intraspinal roots, proximal to the plexus. In this case, the sensory potentials are retained. MRI may expose metastatic deposits of the plexus, but small nodular lesions may escape detection and one then defers to the clinical data if the circumstances suggest an infiltrative or compressive lesion.


Neurology_Adams

Neurology_Adams. The anatomic plan of the brachial (and lumbosacral) plexus and their relations to blood vessels and bony structures (Fig. 43-5) and one of many detailed maps of the peripheral nerves should be consulted. We resort to the illustrations of individual nerves and plexuses that are well demonstrated in the monograph published by the Guarantors of Brain.


Neurology_Adams

Neurology_Adams. For orientation, it is enough to remember that the brachial plexus is formed from the anterior and posterior divisions of cervical roots 5, 6, 7, and 8 and thoracic nerve root 1. The fifth and sixth cervical roots merge into the upper trunk, the seventh root forms the middle trunk, and the eighth cervical and first thoracic roots form the lower trunk. Each trunk divides into an anterior and posterior division. The posterior divisions of each trunk unite to form the posterior cord of the plexus. The anterior divisions of the upper and middle trunks unite to form the lateral cord. The anterior division of the lower trunk forms the medial cord. Two important nerves emerge from the upper trunk (dorsal scapular nerve to the rhomboid and levator scapulae muscles, and long thoracic nerve to the anterior serratus). The posterior cord gives rise mainly to the radial nerve. The medial cord gives rise to the ulnar nerve, medial cutaneous nerve to the forearm, and medial cutaneous nerve to the


Neurology_Adams

Neurology_Adams. anterior serratus). The posterior cord gives rise mainly to the radial nerve. The medial cord gives rise to the ulnar nerve, medial cutaneous nerve to the forearm, and medial cutaneous nerve to the upper arm. This cord lies in close relation to the subclavian artery and apex of the lung and is the part of the plexus most susceptible to traction injuries and to compression by tumors that invade the costoclavicular space. The median nerve is formed by the union of parts of the medial and lateral cords.


Neurology_Adams

Neurology_Adams. Lesions of the Entire Brachial Plexus In this case, the entire arm is paralyzed and hangs uselessly at the side; the sensory loss is complete below a line extending from the shoulder diagonally downward and medially to the middle third of the upper arm. Biceps, triceps, radial, and finger reflexes are abolished. The usual cause is vehicular trauma, especially motorcycle injury.


Neurology_Adams

Neurology_Adams. This is a result of injury to the distal fifth and sixth cervical roots, the most common causes of which are forceful separation of the head and shoulder during difficult delivery, pressure on the supraclavicular region during anesthesia, immune reactions to injections of foreign serum or vaccines, and idiopathic brachial plexitis (see later). The muscles affected are the biceps, deltoid, supinator longus, supraspinatus and infraspinatus, and, if the lesion is very proximal, the rhomboids. The arm hangs at the side, internally rotated and extended at the elbow. Movements of the hand and forearm are unaffected. The prognosis for spontaneous recovery is generally good, although this may be incomplete. Injuries of the upper brachial plexus and spinal roots incurred at birth (termed in older literature as Erb-Duchenne palsy) usually persist throughout life.


Neurology_Adams

Neurology_Adams. This is commonly the result of traction on the abducted arm in a fall or during an operation on the axilla, infiltration or compression by tumors extending from the apex of the lung (superior sulcus or Pancoast syndrome), or compression by cervical ribs or bands. Injury may occur during birth, particularly with breech deliveries (termed Dejerine-Klumpke paralysis). There is weakness and wasting of the small muscles of the hand and a characteristic clawhand deformity. Sensory loss is limited to the ulnar border of the hand and the inner forearm; if the first thoracic motor root is involved, there may be an associated paralysis of the cervical sympathetic nerves with a Horner syndrome. Invasion of the lower plexus by tumors is usually painful; postradiation lesions are more likely to cause paresthesias without pain (Lederman and Wilbourn, 1984). Infraclavicular Lesions Involving Cords of the Brachial Plexus (See Fig. 43-5)


Neurology_Adams

Neurology_Adams. Infraclavicular Lesions Involving Cords of the Brachial Plexus (See Fig. 43-5) A lesion of the lateral cord causes weakness of the muscles supplied by the musculocutaneous nerve and the lateral root of the median nerve; it manifests mainly as a weakness of flexion and pronation of the forearm. The intrinsic muscles of the hand innervated by the medial root of the median nerve are spared. A lesion of the medial cord of the plexus causes weakness of muscles supplied by the medial root of the median nerve and the ulnar nerve. The effect is that of a combined median and ulnar nerve palsy. A lesion of the posterior cord results in weakness of the deltoid muscle, extensors of the elbow, wrist, and fingers, and sensory loss on the outer surface of the upper arm.


Neurology_Adams

Neurology_Adams. One group of infraclavicular injuries, often iatrogenic, results from damage to the subclavian or axillary vessels and the formation of pseudoaneurysms or hematomas. Small puncture wounds—as might occur with catheterization of the subclavian vein, anesthetic block of the brachial plexus, or transaxillary arteriography—are likely to produce this type of injury. As mentioned earlier, thrombosis of the vessels of the neurovascular subclavian bundle are a rare cause. Other frequent causes of injury to the cords are dislocation of the head of the humerus, direct axillary trauma (stab wounds), and supraclavicular compression during awkward positioning of the arm in an operation. Any cords of the plexus may be injured or they may be affected in various combinations. This subject is discussed extensively in Chap. 10. Brachial Neuritis, Brachial Plexitis (Neuralgic Amyotrophy, Parsonage-Turner Syndrome)


Neurology_Adams

Neurology_Adams. This subject is discussed extensively in Chap. 10. Brachial Neuritis, Brachial Plexitis (Neuralgic Amyotrophy, Parsonage-Turner Syndrome) This illness develops abruptly in an otherwise healthy individual; it may also complicate an infection, an injection of vaccine or antibiotic, childbirth, surgical procedures of any type, or the use of heroin. Magee and DeJong, in 1960, and Tsairis and coworkers, in 1972, reported large series of cases and amplified a well-known clinical picture. The term neuralgic amyotrophy was applied to this symptom complex by Parsonage and Turner, who wrote extensively on the subject. Their term for the condition is appropriate, as the clinical and EMG findings suggest a lesion of the peripheral nerves of the shoulder girdle and upper arm rather than in the cords of the plexus. Actually, the site of the pathologic changes has not been established. Our patients have nearly all been adults, ranging from 20 to 65 years of age. Males may be more susceptible.


Neurology_Adams

Neurology_Adams. Beginning as an ache or deep burning in and around the shoulder that is typically centered over the deltoid, at the root of the neck or in the axilla, and suspected at first of being only a muscle strain, the pain rapidly becomes very intense and may include a component of burning. The onset can be remarkably abrupt and occasionally awakens the patient from sleep. It is made worse by movements that involve the muscles in the region and the patient searches for a comfortable position. Narcotics are usually required to suppress the pain. After a period of several days there is a rapid development of muscular weakness and thereafter, sensory and reflex impairment. With the development of weakness, the pain begins to subside. In a few cases, the neurologic disorder occurs with little or no antecedent pain. Possibly in some there is pain that is not followed by demonstrable weakness. A small proportion of cases are bilateral at the outset, or the opposite side is affected weeks later but


Neurology_Adams

Neurology_Adams. pain. Possibly in some there is pain that is not followed by demonstrable weakness. A small proportion of cases are bilateral at the outset, or the opposite side is affected weeks later but most cases remain one sided.


Neurology_Adams

Neurology_Adams. Unlike restricted radicular lesions, which almost never cause complete paralysis of a muscle because of overlapping innervations, certain muscles involved in brachial neuritis, such as the serratus anterior, deltoid, biceps, or triceps, may be totally or almost paralyzed, sometimes in isolation (see later). Rarely are all the muscles of the arm involved (4 of 99 cases of Tsairis et al). Most of the neurologic deficits in our patients have been localized around the shoulder and upper arm. Either the biceps or triceps reflex may be abolished. In a few cases there has been an additional median, radial, anterior, or posterior interosseous nerve palsy that can be detected and isolated by EMG to a site distal to the plexus (see later). Affected patients usually have no fever, leukocytosis, or increased sedimentation rate. Occasionally there is a mild pleocytosis (10 to 50 white blood cells/mm3) and slightly increased protein in the CSF, but most cases have a normal formula and sampling of


Neurology_Adams

Neurology_Adams. increased sedimentation rate. Occasionally there is a mild pleocytosis (10 to 50 white blood cells/mm3) and slightly increased protein in the CSF, but most cases have a normal formula and sampling of CSF is not necessary for diagnosis.


Neurology_Adams

Neurology_Adams. Recovery of paralysis and restoration of sensation are usually complete in 6 to 12 weeks, but sometimes not for a year or longer. In approximately 10 percent of cases there is residual weakness and wasting of the affected muscles and a similar number have had a recurrence some time later on the same or the opposite side. A number of our elderly patients with this condition have had little recovery of motor function over 5 years. In a series of 246 cases described by van Alfen and colleagues that may be consulted for descriptions of the many clinical variations of this illness, they found that a considerable proportion had chronic pain and residual weakness. (Their series included idiopathic and hereditary brachial pleoxopathy, of the type addressed in the next section.)


Neurology_Adams

Neurology_Adams. Motor nerve conduction (amplitude reduction) becomes impaired in 7 to 10 days, as described earlier. The lesions are presumably of axonal type, and electrophysiologic features of denervation follow. There are highly restricted forms that affect only one or two nerves of the brachial plexus, as mentioned earlier. The most common of these is probably an isolated palsy of the serratus anterior (long thoracic nerve). The suprascapular, axillary, posterior interosseus, and phrenic nerves are other occasional sites of solitary neuritis. In the case of a unilateral phrenic nerve paralysis, there is mild dyspnea on exertion and one hemidiaphragm is found to be elevated on the chest radiographs. When the process is not progressive and no mediastinal lesion can be detected with extensive imaging, a phrenic palsy can be assumed to fall into this idiopathic category. We have seen a Horner syndrome in association with brachial neuritis but this finding is always of greater concern as a sign an


Neurology_Adams

Neurology_Adams. a phrenic palsy can be assumed to fall into this idiopathic category. We have seen a Horner syndrome in association with brachial neuritis but this finding is always of greater concern as a sign an infiltrating neoplasm or granulomatous process.


Neurology_Adams

Neurology_Adams. We have had experience with patients who had this syndrome following parvovirus B19 infection, as has been cited in the literature. Most cases had been preceded within days by an erythematous rash spreading from the limbs to the trunk and face, somewhat similar to the eruption of fifths disease caused by this virus in children. One of our patients had no premonitory features, but her child had just recovered from fifth disease (parvovirus) by the pediatrician. Some reported patients have had preceding influenza-like symptoms and adenopathy as well. A summary of cases that have appeared in the literature can be found in the paper by Maas and coworkers. Duchowny and colleagues described a patient in whom a typical brachial neuritis occurred as part of a febrile illness that proved to be caused by a CMV infection and the same has been observed (albeit rarely) in patients with HIV. A few outbreaks of brachial neuritis have been recorded and prompted the suggestion that the Coxsackievirus


Neurology_Adams

Neurology_Adams. by a CMV infection and the same has been observed (albeit rarely) in patients with HIV. A few outbreaks of brachial neuritis have been recorded and prompted the suggestion that the Coxsackievirus was the cause. Whether Lyme infection can cause brachial neuritis is unsettled, but we have seen at least one instance that was more of a cervical radiculopathy—there was a pleocytosis in the CSF. The therapeutic use of interleukin-2 and interferon has apparently precipitated a few cases. In the past, when animal antisera were in common use, this entity was frequent; in the modern era it has been seen rarely after injection of tetanus toxoid, typhoid-paratyphoid vaccine, and triple vaccine (pertussis, diphtheria, and tetanus).


Neurology_Adams

Neurology_Adams. Plexitis also occurs as an uncommon idiopathic complication of the postpartum state (Lederman and Wilbourn, 1996). Some of these are repetitive or bilateral and some are familial, but otherwise the plexopathy has no distinguishing features from the idiopathic type. The heredofamilial variety is described later. One must differentiate idiopathic brachial plexitis from the following conditions: (1) spondylosis or ruptured disc with root compression, particularly the C5 and C6 roots, in which paralysis is rarely as severe as it is in plexitis; (2) brachialgia from bursitis, labral tear, or rotator cuff syndrome; (3) polymyalgia rheumatica; (4) entrapment neuropathies, particularly of the subscapular or dorsal scapular nerve; (5) carcinomatous plexopathy; (6) radiation plexopathy; and (7) sarcoid and other granulomatous infiltrations. Dissection of the vertebral artery may rarely simulate the pain and weakness of brachial neuritis (Berroir et al).


Neurology_Adams

Neurology_Adams. Pathologic data are sparse, but Suarez and coworkers (1996) have reported collections of intense mononuclear inflammation in fascicles of the plexus obtained by biopsy. Perivascular lymphocytes were found in the endoneurial space and, less so, in the epineurium. Therapy is purely symptomatic, but we have usually embarked on a course of steroids and, in a few cases, other immunosuppressants, when the illness continued to advance over many weeks. Corticosteroids sometimes have a beneficial effect on pain and have also been successful in some cases of lumbosacral plexitis. Uncontrolled observations by van Eijk and coworkers on the use of prednisolone in 50 patients have suggested that pain relief and motor outcome were better than in untreated patients. Heredofamilial Brachial Plexopathy (Hereditary Neuralgic Amyotrophy, SEPN1 Mutation)


Neurology_Adams

Neurology_Adams. Rarely, an acute and painful recurrent brachial neuropathy occurs in a familial pattern. The inheritance is autosomal dominant and the attacks, occur most commonly in the second and third decades of life. The authors have observed this syndrome in 3 generations of a family, some members having had 5 attacks at ages ranging from 3 to 45 years. We have had experience with the contemporaneous onset of brachial plexitis in an adult brother and sister who shared the same household but had no family history of a similar problem. A shared exposure to viral or environmental agents was suspected. Lower cranial nerve involvement and mononeuropathies in other limbs are conjoined in some instances (see Taylor). Attacks may be spontaneous or precipitated by compression, slight stretching, or minor trauma to the region of the plexus. In one family, attacks have been triggered by events that activate the immune system (fevers, infections, surgical procedures). In several such families, there are


Neurology_Adams

Neurology_Adams. trauma to the region of the plexus. In one family, attacks have been triggered by events that activate the immune system (fevers, infections, surgical procedures). In several such families, there are subtle characteristic facial features including narrowed and horizontally positioned eyes and a long nasal bridge (Modigliani face). Cleft palate and unusual skin folds and creases have been observed in other kindreds (Jeannet et al).


Neurology_Adams

Neurology_Adams. The typical course is usually benign with good recovery of each episode, but residual deficits may accumulate after recurrent attacks. In Dutch families affected by the disease, Alfen and colleagues have pointed out that some patients experience a more chronic and undulating course rather than discrete attacks. Madrid and Bradley examined the sural nerves from two patients with familial recurrent brachial neuropathy. In teased single nerve fibers they found sausage-like segments of thickened myelin and redundant loops of myelin with secondary constriction of the axon. In addition, nerve fibers showed a considerable degree of segmental demyelination and remyelination. They called this aberration of myelin formation “tomaculous” neuropathy (from tomaculum, “sausage”), changes that are now appreciated as valid but relatively nonspecific.


Neurology_Adams

Neurology_Adams. The genetic basis for this is a mutation of SEPN1. Another cause of recurrent brachial palsy, or of derivative syndromes involving nerves in the arms, is HNPP, discussed in the earlier section on inherited neuropathies and due to a deletion in the PMP22 gene (“Hereditary Neuropathy With Pressure Palsies”). As commented there, the gene defect is also on chromosome 17, but it is not the one associated with familial brachial neuritis (see Chance et al). Some confusion has arisen because CMT1A, HNPP, and the familial brachial palsy disease all have chromosome 17 defects. Pressure palsies in HNPP are painless and there is usually an underlying and slowly advancing polyneuropathy. In some families, such as the one reported by Thomas and Ormerod, the distinction between hereditary neuralgic amyotrophy (HNA) and HNPP was unclear as the recurrent brachial plexopathies were painful (consistent with the former), but there was also a painless multifocal sensory neuropathy (consistent with the


Neurology_Adams

Neurology_Adams. (HNA) and HNPP was unclear as the recurrent brachial plexopathies were painful (consistent with the former), but there was also a painless multifocal sensory neuropathy (consistent with the latter).


Neurology_Adams

Neurology_Adams. This is usually a complication of irradiation of the axilla for carcinoma of the breast. Stoll and Andrews studied a group of 117 such patients who were treated with high-voltage, small-field therapy and had received either 6,300 or 5,775 cGy in divided doses. Of those receiving the larger dose, 73 percent developed weakness and sensory loss in the hand and fingers between 4 and 30 months after treatment, most of them after 12 months. In 1 autopsied case, the brachial plexus was ensheathed in dense fibrous tissue; distal to this zone, both myelin and axons had disappeared (wallerian degeneration), presumably as a result of entrapment of nerves in fibrous tissue; possibly a vascular factor was also operative.


Neurology_Adams

Neurology_Adams. Kori and coworkers, who analyzed the brachial plexus lesions in 100 patients with cancer, also found that doses exceeding 6,000 cGy were associated with radiation damage. Usually the upper plexus was involved and was sometimes associated with a painless lymphedema. Myokymic discharges and fasciculations are particularly suggestive of radiation damage. In patients who received lower doses, the development of brachial plexopathy usually indicated tumor infiltration; these lesions affected the lower plexus more than the upper; they were often painful and accompanied by Horner syndrome (see Lederman and Wilbourn, 1984). Rarely, radiation may give rise many years later to a malignant tumor of nerve or the surrounding connective tissue, a sarcoma in 2 cases familiar to us. Herpes Zoster Plexitis, Neuritis, and Ganglionitis (See Chap. 32)


Neurology_Adams

Neurology_Adams. Herpes Zoster Plexitis, Neuritis, and Ganglionitis (See Chap. 32) This organism is perhaps the best defined infectious cause of the above listed syndromes, but its identification is usually obvious on the basis of the skin eruption of shingles. Cases are known in which radicular pain precedes the eruption by many days or in which shingles do not appear, thereby simulating a herniated disc (zoster sine herpete). These conditions are discussed with the other viral infections of the nervous system in Chap. 32.


Neurology_Adams

Neurology_Adams. This nerve is derived from the fifth, sixth, and seventh cervical nerves and supplies the serratus anterior muscle, which fixates the lateral scapula to the chest wall. Paralysis of this muscle results in an inability to raise the arm over the head and winging of the medial border of the scapula when the outstretched arm is pushed forward against resistance. The nerve is injured most commonly by carrying heavy weights on the shoulder or by strapping the shoulder to the operating table. As stated earlier, the neuropathy may be the only affected nerve in a brachial plexus neuropathy of either the inherited or idiopathic variety (Phillips).


Neurology_Adams

Neurology_Adams. This nerve is derived from the fifth (mainly) and sixth cervical nerves and supplies the supraspinatus and infraspinatus muscles. Lesions may be recognized by the presence of atrophy of these muscles and weakness of the first 15 degrees of abduction (supraspinatus) and of external rotation of the arm at the shoulder joint (infraspinatus). The latter muscle is tested by having the patient flex the forearm and then, pinning the elbow to the side, asking him to swing the forearm backward against resistance. This nerve is often involved as a result of a herniated C5-C6 disc (see Chap. 10), or as part of a brachial plexus neuropathy of either the sporadic or inherited type. It may be affected during infectious illnesses and may be injured in gymnasts, or as a result of local pressure from carrying heavy objects on the shoulder (“meatpacker’s neuropathy”). An entrapment syndrome has also been reported; it is characterized by pain and weakness on external rotation of the shoulder joint with


Neurology_Adams

Neurology_Adams. heavy objects on the shoulder (“meatpacker’s neuropathy”). An entrapment syndrome has also been reported; it is characterized by pain and weakness on external rotation of the shoulder joint with atrophy of the infraspinatus muscle (Table 43-8). Decompression of the nerve where it enters the spinoglenoid notch relieves the condition.


Neurology_Adams

Neurology_Adams. This nerve arises from the posterior cord of the brachial plexus (mainly from the C5 root, with a smaller contribution from C6) and supplies the teres minor and deltoid muscles. It may be involved in dislocations of the shoulder joint, fractures of the neck of the humerus, disc protrusion, and brachial neuritis; in other instances, no cause may be apparent. The anatomic diagnosis depends on recognition of paralysis of abduction of the arm (in testing this function, the angle between the side of the chest and the arm must be greater than 15 degrees and less than 90 degrees), wasting of the deltoid muscle, and slight impairment of sensation over the outer aspect of the shoulder.


Neurology_Adams

Neurology_Adams. The origin of this nerve is from the fifth and sixth cervical roots. It is a branch of the lateral cord of the brachial plexus and innervates the biceps brachii, brachialis, and coracobrachialis muscles. Lesions of the nerve result in wasting of these muscles and weakness of flexion of the supinated forearm. Sensation may be impaired along the radial and volar aspects of the forearm (lateral cutaneous nerve). Isolated lesions of this nerve are usually the result of fracture of the humerus.


Neurology_Adams

Neurology_Adams. This nerve is derived from the sixth to eighth (mainly the seventh) cervical roots and is the distal extension of the posterior cord of the brachial plexus. It innervates the triceps, brachioradialis, and supinator muscles, and continues below the elbow as the posterior interosseous nerve, which innervates the extensor muscles of the wrist and fingers, the main abductor of the thumb (the abductor pollicis longus, which is easier to isolate than the median nerve innervated abductor pollicis brevis), and the extensors of the fingers at both joints. A complete proximal radial nerve lesion results in paralysis of extension of the elbow, flexion of the elbow with the forearm midway between pronation and supination (a result of paralysis of the brachioradialis muscle), supination of the forearm, extension of the wrist and fingers, and extension and abduction of the thumb in the plane of the palm. If the lesion is confined to the posterior interosseous nerve, only the extensors of the wrist


Neurology_Adams

Neurology_Adams. extension of the wrist and fingers, and extension and abduction of the thumb in the plane of the palm. If the lesion is confined to the posterior interosseous nerve, only the extensors of the wrist and fingers are affected. Sensation is impaired over the posterior aspects of the forearm and over a small area on the radial aspect of the dorsum of the hand.


Neurology_Adams

Neurology_Adams. The radial nerve may be compressed in the axilla (“crutch” palsy), but more frequently at a lower point, where the nerve winds around the humerus (see Table 43-8); pressure palsies incurred during an alcoholic stupor and fractures of the humerus commonly injure the nerve at the site of injury. It is susceptible to lead intoxication and is frequently involved as part of brachial neuritis and mononeuritis multiplex.


Neurology_Adams

Neurology_Adams. This nerve originates from the fifth cervical to the first thoracic roots but mainly from the sixth cervical root and is formed by the union of the medial and lateral cords of the brachial plexus. It innervates the pronators of the forearm, long finger flexors, and abductor and opponens muscles of the thumb and is a sensory nerve to the palmar aspect of the hand. Complete interruption of the median nerve results in inability to pronate the forearm or flex the hand in a radial direction, paralysis of flexion of the index finger and terminal phalanx of the thumb, weakness of flexion of the remaining fingers, weakness of opposition and abduction of the thumb in the plane at a right angle to the palm (abductor and flexor pollicis brevis), and sensory impairment over the radial two-thirds of the palm and dorsum of the distal phalanges of the index and third fingers. The nerve may be injured in the axilla by dislocation of the shoulder and in any part of its course by stab, gunshot, or


Neurology_Adams

Neurology_Adams. of the palm and dorsum of the distal phalanges of the index and third fingers. The nerve may be injured in the axilla by dislocation of the shoulder and in any part of its course by stab, gunshot, or other types of wounds, and like the radial nerve, is often a component of the mononeuritis multiplex syndrome. Incomplete lesions of the median nerve between the axilla and wrist may result in causalgia (see further on).


Neurology_Adams

Neurology_Adams. Carpal tunnel syndrome (See also Chap. 10.) Compression of the median nerve at the wrist (carpal tunnel syndrome) is the most common disorder affecting the median nerve and the most frequent nerve entrapment syndrome. The problem arises usually as a result of excessive use of the hands and occupational microtrauma. Infiltration of the transverse carpal ligament with amyloid (as occurs in multiple myeloma and amyloidosis) or thickening of connective tissue in rheumatoid arthritis, acromegaly, mucopolysaccharidosis, and hypothyroidism are less commonly identified causes. It is also common for the condition to make its appearance during pregnancy. In elderly individuals, the cause of the carpal tunnel syndrome is often not apparent. According to Kremer and colleagues, it was McArdle, in 1949, who first suggested that the cause of this syndrome was compression of the median nerve at the wrist and that the symptoms would be relieved by division of the flexor retinaculum forming the ventral


Neurology_Adams

Neurology_Adams. who first suggested that the cause of this syndrome was compression of the median nerve at the wrist and that the symptoms would be relieved by division of the flexor retinaculum forming the ventral wall of the carpal tunnel. Dysesthesias and pain in the fingers, referred to for many years as “acroparesthesia” came to be recognized as a syndrome of median nerve compression only in the early 1950s.


Neurology_Adams

Neurology_Adams. The syndrome is essentially a sensory one; the loss or impairment of superficial sensation affects the palmar aspect of the thumb and the index and middle fingers (especially the index finger) and may or may not split the ring finger (splitting does not occur with a plexus or root lesion). The paresthesias are characteristically worse during the night. As pointed out in Chap. 10, the pain in carpal tunnel syndrome may radiate into the forearm and even into the region of the biceps and rarely, to the shoulder. Weakness and atrophy of the abductor pollicis brevis and other median-innervated muscles occur in only advanced cases of compression. Electrophysiologic testing confirms the diagnosis by demonstrating prolonged sensory conduction across the wrist and explains cases in which operation has failed (see the review by Stevens).


Neurology_Adams

Neurology_Adams. Several provocative tests are useful. The Phalen maneuver consists of hyperflexion of the wrist for 30 to 60 s—usually performed by opposing the outer surfaces of the hands with the wrists flexed. The Tinel sign is elicited by lightly tapping the volar aspect of the wrist at the transverse carpal ligament (distal to the first wrist crease). Both of these tests are meant to elicit pain or paresthesias over the digits innervated by the median nerve. The sensitivity of these tests is close to 50 percent, but their specificity is considerably higher. Other tests involving prolonged pressure over the median nerve have been devised, but they are of uncertain value, for example, Durken’s test of the Phalen maneuver combined with digital compression of the nerve.


Neurology_Adams

Neurology_Adams. Treatment Surgical division of the carpal ligament with decompression of the nerve is curative but is required only in severe and protracted cases. Splinting of the wrist to limit flexion almost always relieves the discomfort but denies the patient the full use of the hand for some time. It is a useful temporizing measure for a few weeks, as is the injection of hydrocortisone into the carpal tunnel. Studies of oral corticosteroids give conflicting results. Treatment of an underlying condition such as arthritis, hypothyroidism and possibly diabetes, is often helpful. Some patients have benefited, paradoxically, from the stopping of corticosteroids or estrogen. Also, some practitioners favor the use of nonsteroid anti-inflammatory medication, but we have been generally unimpressed with the results. Most often, splinting and local steroid injections are very satisfactory in the short term, especially if the symptoms are of recent onset.


Neurology_Adams

Neurology_Adams. Another less common site of compression of the median nerve is at the elbow, where the nerve passes between the two heads of the pronator teres, or just above that point behind the bicipital aponeurosis. It gives rise to the “pronator syndrome,” in which forceful pronation of the forearm produces an aching pain (see Table 43-8). There is weakness of the abductor pollicis brevis and opponens muscles and numbness of the first three digits and palm.


Neurology_Adams

Neurology_Adams. This nerve is derived from the eighth cervical and first thoracic roots. It innervates the ulnar flexor of the wrist, the ulnar half of the deep finger flexors, the adductors and abductors of the fingers, the adductor of the thumb, the third and fourth lumbricals, and muscles of the hypothenar eminence. Complete ulnar paralysis is manifest by a characteristic clawhand deformity; wasting of the small hand muscles results in hyperextension of the fingers at the metacarpophalangeal joints and flexion at the interphalangeal joints. The flexion deformity is most pronounced in the fourth and fifth fingers, as the lumbrical muscles of the second and third fingers, supplied by the median nerve, counteract the deformity. Sensory loss occurs over the fifth finger, the ulnar aspect of the fourth finger, and the ulnar border of the palm.


Neurology_Adams

Neurology_Adams. The ulnar nerve is vulnerable to pressure in the axilla from the use of crutches, but it is most commonly injured at the elbow by fracture or dislocation involving the joint. Delayed (“tardive”) ulnar palsy may occur many months or years after an injury to the elbow that had resulted in a cubitus valgus deformity of the joint. Because of the deformity, the nerve is stretched in its groove over the ulnar condyle and its superficial location renders it vulnerable to compression. A shallow ulnar groove, quite apart from abnormalities of the elbow joint, may expose the nerve to compressive injury from more innocuous situations such as prolonged resting of the arm on the side of a chair or even excessive flexion of the elbow. Anterior transposition of the ulnar nerve is a simple and effective form of treatment for these types of ulnar palsies. Compression of the nerve may occur just distal to the medial epicondyle, where it runs beneath the aponeurosis of the flexor carpi ulnaris (cubital


Neurology_Adams

Neurology_Adams. form of treatment for these types of ulnar palsies. Compression of the nerve may occur just distal to the medial epicondyle, where it runs beneath the aponeurosis of the flexor carpi ulnaris (cubital tunnel). Flexion at the elbow causes a narrowing of the tunnel and constriction of the nerve. This type of ulnar palsy is treated by incising the aponeurotic arch between the olecranon and medial epicondyle. Yet another site of ulnar nerve compression is in the ulnar tunnel at the wrist. Prolonged pressure on the ulnar part of the palm may result in damage to the deep palmar branch of the ulnar nerve, causing weakness of small hand muscles but no sensory loss. This site is most often implicated in patients who hold tools or implements tightly in the hand for long periods (we have seen it in machinists and professional cake decorators). The lesion is localizable by nerve conduction studies.


Neurology_Adams

Neurology_Adams. A syndrome of burning pain (causalgia) and associated symptoms (causalgia) may follow incomplete lesions of the ulnar nerve (or other major nerves of the limbs) and is described further on. The twelfth thoracic, first to fifth lumbar, and first, second, and third sacral spinal nerve roots compose the lumbosacral plexuses and innervate the muscles of the lower extremities (Fig. 43-6 and Table 43-1). The following are the common plexus and crural nerve palsies.


Neurology_Adams

Neurology_Adams. Extending as it does from the upper lumbar area to the lower sacrum and passing near several lower abdominal and pelvic organs, this plexus is subject to a number of special injuries and diseases. The cause may be difficult to ascertain because the primary disease is often not within reach of the palpating fingers, either from the abdominal side or through the anus and vagina; even refined radiologic techniques may not reveal it. Diagnosis involves exclusion of spinal root (cauda equina) lesions by EMG, examination of CSF if root disease is likely, and MRI of the plexus. The clinical findings help to focus studies on the appropriate part of the lumbosacral plexus.


Neurology_Adams

Neurology_Adams. The main effects of upper lumbar plexus lesions are weakness of flexion and adduction of the thigh and extension of the leg, with sensory loss over the anterior thigh and leg; these effects must be distinguished from the symptoms and signs of femoral neuropathy (see later). Lower plexus lesions weaken the posterior thigh, leg, and foot muscles and abolish sensation over the first and second sacral segments (sometimes the lower sacral segments also). Lesions of the entire plexus, which occur infrequently, cause weakness or paralysis of all leg muscles with atrophy, areflexia, and anesthesia from the toes to the perianal region and autonomic loss with warm, dry skin.


Neurology_Adams

Neurology_Adams. The types of lesions that involve the lumbosacral plexus are rather different from those affecting the brachial plexus. Cancer, diabetes, and an idiopathic variety have dominated our material. Trauma is a rarity except with massive pelvic, spinal, and abdominal injuries because the plexus is so well protected. Occasionally, a pelvic fracture will damage the sciatic nerve as it issues from the plexus. In contrast, some part of the plexus may be damaged during surgical procedures on abdominal and pelvic organs, often for reasons that may not be entirely clear. For example, hysterectomy has on a number of occasions led to neurologic consultation in our hospitals because of numbness and weakness of the anterior thigh. Either the cords of the upper part of the plexus or the femoral nerve were compressed by retraction against the psoas muscle, or in vaginal hysterectomy (when thighs are flexed, abducted, and externally rotated) the femoral nerve was compressed against the inguinal ligament.


Neurology_Adams

Neurology_Adams. by retraction against the psoas muscle, or in vaginal hysterectomy (when thighs are flexed, abducted, and externally rotated) the femoral nerve was compressed against the inguinal ligament. A similar injury may be associated with vaginal delivery (see further on). Lumbar sympathectomy has also been associated with upper plexus lesions, of which the most disabling sequelae are burning pain and hypersensitivity of the anterior thigh. Appendectomy, pelvic explorations, and hernial repair may injure branches of the upper plexus (ilioinguinal, iliohypogastric, and genitofemoral nerves), with severe pain and slight sensory loss in the distribution of one of these nerves. The pain may last for months or a year or more.


Neurology_Adams

Neurology_Adams. The lumbar plexus may be compressed by an aortic atherosclerotic aneurysm. Usually there is pain that radiates to the hip, the anterior thigh, and occasionally the flank. Slight weakness in hip flexion and altered sensation over the anterior thigh are found on examination. Plexus involvement with tumors is commonplace and presents special difficulties in diagnosis. Carcinoma of either the cervix or prostate may seed along the perineurial lymphatics and cause pain in the groin, thigh, knee, or back without much in the way of sensory, motor, or reflex loss. The pain is more often unilateral than bilateral. The CSF and spinal canal (by MRI) are normal. Testicular, uterine, ovarian, and colonic tumors or retroperitoneal lymphomas, by extending along the paravertebral gutter, implicate various parts of the lumbosacral plexus. Instances of endometriosis that involve the plexus have also been reported, in which case pain fluctuates in parallel with the menstrual cycle (a similar condition


Neurology_Adams

Neurology_Adams. parts of the lumbosacral plexus. Instances of endometriosis that involve the plexus have also been reported, in which case pain fluctuates in parallel with the menstrual cycle (a similar condition exists that implicates only the sciatic nerve). The neurologic symptoms are projected at a distance in the leg and may or may not be confined to the territory of any one nerve. Pelvic and rectal examinations may be negative, and CT scanning and MRI may be necessary to show such lesions. If all these examinations are negative, exploratory laparotomy may have to be undertaken.


Neurology_Adams

Neurology_Adams. In cancer patients, it is sometimes difficult to distinguish the effects of radiation on the lumbosacral plexus from those of metastatic tumor, as is the case in relation to the brachial plexus. Again, the earliest symptom in metastatic lumbosacral plexopathy is usually pain, whereas in radiation plexopathy it is weakness (Thomas et al). Plexopathy from metastatic tumor is usually unilateral and detectable by CT scanning; radiation plexopathy is as often bilateral and changes are not evident in CT or MRI scans. Fasciculations and myokymia are more likely to be seen in patients with radiation plexopathy, which seemingly occurs more frequently in patients with diabetic neuropathy. Sarcoidosis is another cause and may be responsive to corticosteroids.


Neurology_Adams

Neurology_Adams. Reference has already been made to femoral nerve injury during parturition, but other puerperal complications are also observed. Back pain in the latter part of pregnancy is, of course, common, but there are instances in which the patient complains of severe pain in the back of one or both thighs during labor and after delivery has numbness and weakness of the leg muscles with diminished ankle jerks. Parturitional lumbosacral plexus injuries occur with a frequency of 1 per 2,000 deliveries. This injury is usually unilateral and is manifest by pain in the thigh and leg and symptoms and signs of involvement of the superior gluteal and sciatic nerves (Feasby et al). The attribution of these symptoms to pressure of the fetal head on the sacral plexus(es) is conjectural. A limited plexopathy, occurring after difficult vaginal delivery, mainly impairs sensation in the perineum and sphincteric function (Ismael et al). The perineal muscles may show signs of denervation. Protrusion of an


Neurology_Adams

Neurology_Adams. occurring after difficult vaginal delivery, mainly impairs sensation in the perineum and sphincteric function (Ismael et al). The perineal muscles may show signs of denervation. Protrusion of an intervertebral disc may also occur during delivery and simulate plexus injury.


Neurology_Adams

Neurology_Adams. Idiopathic lumbosacral plexitis In addition to the diabetic type detailed earlier in the chapter, an idiopathic neuralgic amyotrophy or lumbosacral plexitis, analogous to the brachial variety, has been observed. Bradley and coworkers have recorded such cases and their paper can be referred to for the clinical details. After causing widespread unilateral or bilateral sensory, motor, and reflex changes in a leg, lumbosacral plexitis may leave the patient with dysesthesias as troublesome as those that follow herpes zoster (which also may occur at this level). Loss of sweating and warmth of the feet indicate interruption of autonomic fibers by lesions in peripheral nerves rather than in roots. The sedimentation rate may be elevated. Dyck and colleagues (2000) inferred an autoimmune basis from biopsy material and immunosuppressant drugs were possibly beneficial in 4 of 6 cases reported by Bradley and coworkers. The outcome is variable with complete recovery being uncommon.


Neurology_Adams

Neurology_Adams. Diabetic amyotrophy caused by involvement of the lumbar plexus and roots was discussed in an earlier section (“Diabetic Multiple Mononeuropathies and Radiculoplexus Neuropathy”). Lateral Cutaneous Nerve of the Thigh (Meralgia Paresthetica) This sensory nerve originates from the second and third lumbar roots and supplies the anterolateral aspect of the thigh from the level of the inguinal ligament almost to the knee. The nerve penetrates the psoas muscle, crosses the iliacus, and passes into the thigh by coursing between the attachments of the lateral part of the inguinal ligament to just anterior to the anterior superior iliac spine. Compression (entrapment) may occur at the point where it passes between the two prongs of attachment of the inguinal ligament.


Neurology_Adams

Neurology_Adams. Compression of the nerve results in uncomfortable paresthesias and sensory impairment in its cutaneous distribution, a common condition known as meralgia paresthetica (meros, “thigh”). Usually numbness and mild sensitivity of the skin are the only symptoms, but occasionally there is a persistent distressing burning pain. Perception of touch and pinprick are reduced in the territory of the nerve; there is no weakness of the quadriceps or diminution of the knee jerk. The symptoms are characteristically worsened in certain positions and after prolonged standing or walking. Occasionally, for an obese person, sitting is the most uncomfortable position. Obesity, pregnancy, and diabetes mellitus may be contributory factors. Most often the neuropathy is unilateral, but Ecker and Woltman found 20 percent of their patients to have bilateral symptoms.


Neurology_Adams

Neurology_Adams. Most of our patients with meralgia paresthetica request no treatment once they learn of its benign character. Weight loss and adjustment of restrictive clothing or correction of habitual postures that might compress the nerve are sometimes helpful. A few with the most painful symptoms have demanded a neurectomy or section of the nerve, but it is always wise to perform a lidocaine block first, so that the patient can decide whether the persistent numbness is preferable. In one specimen of nerve obtained at operation, we found a discrete traumatic neuroma. Corticosteroid injections at the point of entrapment may have helped in a few cases, but this has not been studied in a systematic way.


Neurology_Adams

Neurology_Adams. This nerve arises from the third and fourth and to a lesser extent the second lumbar roots. It supplies the adductors of the thigh and contributes to the innervation of the internal and external rotators. The adductors have the added function of contributing to flexing the hip. The nerve may be injured by the fetal head or forceps during the course of a difficult labor or compressed by an obturator hernia. Rarely, it is affected with diabetes, polyarteritis nodosa, and osteitis pubis and by retroperitoneal spread of carcinoma of the cervix, uterus, and other tumors (Rogers et al).


Neurology_Adams

Neurology_Adams. This nerve is formed from the second, third, and fourth lumbar roots. Within the pelvis it passes along the lateral border of the psoas muscle and enters the thigh beneath the Poupart ligament, lateral to the femoral artery. Branches arising within the pelvis supply the iliacus and psoas muscles. Just below the Poupart ligament the nerve splits into anterior and posterior divisions. The former supplies the pectineus and sartorius muscles and carries sensation from the anteromedial surface of the thigh; the posterior division provides the motor innervation to the quadriceps and the cutaneous innervation to the medial side of the leg from the knee to the internal malleolus. The distinction between femoral neuropathy and a third lumbar root lesion is made by detecting weakness of the hip adductor (innervated by the obturator nerve) in the case of the root lesion.


Neurology_Adams

Neurology_Adams. Following injury to the femoral nerve, there is weakness of extension at the knee, wasting of the quadriceps muscle, and failure of fixation of the knee. The knee jerk is abolished. If the nerve is injured proximal to the origin of the branches to the iliacus and psoas muscles, there is additionally weakness of hip flexion.


Neurology_Adams

Neurology_Adams. The most common cause of femoral neuropathy is diabetes. The nerve may also be involved by pelvic tumors. Not uncommon is injury to the nerve during pelvic operations. Usually this is the result of improper placement of retractors, which may compress the nerve directly or indirectly by undue pressure on the psoas muscle. Bleeding into the iliacus muscle or the retroperitoneum, observed in patients receiving anticoagulants and in hemophilia patients, is a relatively common cause of isolated femoral neuropathy (Goodfellow et al). The presenting symptom of iliacus hematoma is pain in the groin spreading to the lumbar region or thigh, in response to which the patient assumes a characteristic posture of flexion and lateral rotation of the hip. A palpable mass in the iliac fossa and the signs of femoral nerve compression (quadriceps weakness and loss of knee jerk) follow in a day or two. Infarction of the nerve may occur in the course of diabetes mellitus and polyarteritis nodosa. Not


Neurology_Adams

Neurology_Adams. of femoral nerve compression (quadriceps weakness and loss of knee jerk) follow in a day or two. Infarction of the nerve may occur in the course of diabetes mellitus and polyarteritis nodosa. Not infrequently acute femoral neuropathy is of indeterminate cause.


Neurology_Adams

Sciatic Nerve (See Also Chap. 10)

Neurology_Adams. Sciatic Nerve (See Also Chap. 10)


Neurology_Adams

Neurology_Adams. This nerve is derived from the fourth and fifth lumbar and first and second sacral roots, for which reason a ruptured disc at any of these levels may simulate sciatic neuropathy (sciatica). The sciatic nerve supplies motor innervation to the hamstring muscles and all the muscles below the knee through its two divisions, the tibial and peroneal nerves (see later); the sciatic nerve conveys sensory impulses from the posterior aspect of the thigh, the posterior and lateral aspects of the leg, and the entire sole. In complete sciatic paralysis, the knee cannot be flexed and all muscles below the knee are paralyzed. Weakness of gluteal muscles and pain in the buttock and posterior thigh point to nerve involvement in the pelvis. Lesions beyond the sciatic notch spare the gluteal muscles but not the hamstrings. Partial compressive lesions are more common and tend to involve peroneal-innervated muscles more than tibial ones, giving the impression of a peroneal palsy.


Neurology_Adams

Neurology_Adams. Rupture of one of the lower lumbar intervertebral discs is the most common cause of sciatica, although it does, of course, not directly involve the sciatic nerve. The associated motor and sensory findings allow localization of the root compression (L4-L5 disc compressing L5 root: pain in posterolateral thigh and leg with numbness over the inner foot and weakness of dorsiflexion of the foot and toes; L5-S1 disc compressing S1 root: pain in posterior thigh and leg, numbness of lateral foot, weakness of foot plantar flexion and loss of ankle jerk), as discussed in Chap. 10.


Neurology_Adams

Neurology_Adams. The sciatic nerve is commonly injured by fractures of the pelvis or femur, fracture/dislocation of the hip, gunshot wounds of the buttock and thigh, and the injection of toxic substances into the lower gluteal region. Total hip arthroplasty is another cause. Tumors of the pelvis (sarcomas, lipomas) or gluteal region may compress the nerve. Sitting for a long period with legs flexed and abducted (lotus position) under the influence of narcotics or barbiturates or lying flat on a hard surface in a sustained stupor may severely injure one or both sciatic nerves or branches thereof. The nerve may be involved by neurofibromas and infections and by ischemic necrosis in diabetes mellitus and polyarteritis nodosa. Cryptogenic forms of sciatica occur and in a referral practice are more frequent than those of identifiable cause. Partial lesions of the sciatic nerve occasionally result in causalgia (see further on).


Neurology_Adams

Neurology_Adams. The common Morton neuroma, typically between the third and fourth metatarsals, causes interdigital or intermetatarsal pain and can be detected by MRI. It is subject to surgical section. Also mentioned here is a distressingly painful compression of the plantar branches of the sciatic nerve.


Neurology_Adams

Neurology_Adams. Just above the popliteal fossa the sciatic nerve divides into the tibial nerve (medial, or internal, popliteal nerve) and the common peroneal nerve (lateral, or external, popliteal nerve). The latter swings around the head of the fibula to the anterior aspect of the leg, giving off the superficial peroneal nerve that provides musculocutaneous branches (to the peroneal muscles) and to the deep peroneal nerve (formerly called anterior tibial nerve). Branches of the latter supply the dorsiflexors of the foot and toes (anterior tibialis, extensor digitorum longus and brevis, and extensor hallucis longus muscles) and carry sensory fibers from the dorsum of the foot and lateral aspect of the lower half of the leg. There was weakness of dorsiflexion of the foot (foot-drop) in all of the 116 cases of common peroneal neuropathy reported by Katirji and Wilbourn, and numbness of the dorsum of the foot was present in most cases. Weakness of eversion of the foot is usually demonstrable; because


Neurology_Adams

Neurology_Adams. of common peroneal neuropathy reported by Katirji and Wilbourn, and numbness of the dorsum of the foot was present in most cases. Weakness of eversion of the foot is usually demonstrable; because inversion is a function of the L5 root and the tibial nerve, it is spared in peroneal palsy, thereby allowing a distinction between foot-drop at the two sites. (Foot eversion should be tested with the ankle passively dorsiflexed.) Pain is variable.


Neurology_Adams

Neurology_Adams. Pressure during an operation or sleep or from tight plaster casts, obstetric stirrups, habitual and prolonged crossing of the legs while seated, and tight knee boots are the most frequent causes of injury to the common peroneal nerve. The point of compression of the nerve is where it passes over the head of the fibula. Emaciation in patients with cancer or AIDS increases the incidence of these types of compressive injuries. The nerve may also be affected in diabetic neuropathy and injured by fractures of the upper end of the fibula. A Baker cyst, which consists of inflamed synovium extending into the retropopliteal space, may compress the nerve, and it may be damaged by muscle swelling or small hematomas behind the knee in asthenic athletes. The prognosis is generally good in cases of partial paralysis.


Neurology_Adams

Neurology_Adams. This, the other of the two divisions of the sciatic nerve (it divides in the popliteal fossa), supplies all of the calf muscles—that is, the plantar flexors and invertors of the foot and toes—after which it continues as the posterior tibial nerve. This nerve passes through the tarsal tunnel, an osseofibrous channel that runs along the medial aspect of the calcaneus and is roofed by the flexor retinaculum. The tunnel also contains the tendons of the tibialis posterior, flexor digitorum longus, and flexor hallucis longus muscles and the vessels to the foot. The posterior tibial nerve terminates under the flexor retinaculum and divides into medial and lateral plantar nerves (supplying the small muscles of the foot). Complete interruption of the tibial nerve results in a calcaneovalgus deformity of the foot, which can no longer be plantar-flexed and inverted. There is loss of sensation over the plantar aspect of the foot.