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Arteritic Angiopathic Neuropathies Approximately half of all cases of mononeuropathy multiplex can be traced to a systemic vasculitis of the vasa nervorum These are the classic causes of mononeuritis mulitplex Included in this category are polyarteritis nodosa, the Churg-Strauss syndrome (allergic bronchial asthma and eosinophilia), rheumatoid arthritis, lupus erythematosus, scleroderma, cryoglobulinemia, Wegener granulomatosis, and the aforementioned idiopathic variety of vasculitis that is con ned to the cranial peripheral nerves and has no systemic manifestations A small-vessel arteritis is also the putative mechanism in the multiple mononeuropathies that complicate Lyme disease and AIDS In Said s series of 200 cases of vasculitis affecting the peripheral nerves, 36 percent were due to polyarteritis nodosa, 21 percent to rheumatoid arthritis, and 4 percent to other connective tissue diseases; in 35 percent there were no signs of vasculitis beyond the peripheral nerves Elevation of the sedimentation rate and other serologic abnormalities are typical features of this entire group This subject has been reviewed by Chalk et al; Dyck and Said; and by Kissell Polyarteritis Nodosa Perhaps 75 percent of cases of polyarteritis nodosa show involvement of the small nutrient arteries of peripheral nerves (autopsy gures), but a symptomatic form of neuropathy develops in only about half this number Involvement of the peripheral nerves may be the principal or rst clue to the diagnosis of the underlying disease when, up to that time, the main components of the clinical picture abdominal pain, hematuria, fever, eosinophilia, hypertension, vague limb pains, and asthma had not fully declared themselves or had been misinterpreted Although characteristically a disease of multiple discrete mononeuropathies, the syndrome associated with polyarteritis nodosa may appear to be diffuse and more or less symmetrical as a result of the cumulation of many small nerve infarctions, ie, it can simulate a polyneuropathy In these cases, careful clinical and electrophysiologic examinations disclose elements of mononeuritis that have been engrafted on an otherwise ostensibly generalized process For example, an asymmetrical foot or wrist drop, or a disproportionate affection of one nerve in a limb, such as ulnar palsy with relative sparing of function of the adjacent median nerve, are clues More often it takes form throughout its course of a mononeuropathy multiplex, ie, a random infarction of two or more individual nerves The onset is usually abrupt, with symptoms of pain or numbness at a focal site along a nerve or in the distal distribution of an affected nerve, followed in hours or days by motor or sensory loss in the distribution of that nerve, and then by involvement in a saltatory fashion of other peripheral nerves Both the spinal and cranial nerves may be affected but far less often than the nerves in the limbs No two cases are identical The CSF is usually normal Nerve biopsy, usually taken from the sural nerve, will usually show the necrotizing arteritis in medium sized vessels ( brinoid necrosis of all three coats of the vessel walls), usually with numerous in ltrating eosinophils and with occlusion of vessels Muscle biopsy may also show perivascular in ammation and necrosis but the diagnostic yield is less than for biopsy of an affected nerve On the basis of the smaller size of affected vessels and the presence of perinuclear antinuclear cytoplasmic autoantibodies (p-ANCA), Lhote et al have differentiated a microscopic polyarteritis an entity with which we have had little experience Rapidly progressive glomerulonephritis and lung hemorrhage are the additional features of the latter disease, neuropathy occurring somewhat less frequently than in typical polyarteritis.

Table 46-4 Causes of mononeuritis multiplex Common Polyarteritis nodosaa Isolated vasculitis of peripheral nervesa Wegener granulomatosisa Diabetes Hereditary liability to preserve palsies Cryoglobulinemiaa Sarcoidosis Lyme disease HIVa Rare Sarcoidosis Paraneoplastic Amyloidosis Leprosy Systemic lupusa Rheumatoid arthritisa Leukemia-lymphoma in ltration Intravascular lymphoma Sjogren syndrome

23-2 Simplified cross-sectional drawing of a P-channel JFET (at A) and its schematic symbol (at B)

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A large number of viruses are able to affect the nervous system Among the enteroviruses alone, nearly 70 distinct serologic types have been associated with CNS disease, and additional types from this family of viruses and others are still being discovered There is no need, however, to consider these viruses individually, since there are only a limited number of ways in which they express themselves clinically Seven syndromes occur with regularity and should be familiar to neurologists: (1) acute aseptic ( lymphocytic ) meningitis; (2) chronic meningitis; (3) acute encephalitis or meningoencephalitis, which may be generalized or focal; (4) herpes zoster ganglionitis; (5) chronic invasion of nervous tissue by retroviruses, ie, the AIDS syndrome and tropical spastic paraparesis (TSP); (6) acute anterior poliomyelitis; and (7) chronic viral infections ( slow infections ) The last group is presently distinguished from infections with the unique prion agents, which are discussed later in the chapter

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cultures were negative The term is now applied to a symptom complex that is produced by any one of numerous infective agents, the majority of which are viral (but a few of which are bacterial mycoplasma, Q fever, other rickettsial infections, etc) Since aseptic meningitis is rarely fatal, the precise pathologic changes are uncertain but are presumably limited to the meninges Conceivably, there may be some minor changes in the brain itself, but these are of insuf cient severity to cause neurologic symptoms and signs or to alter the results of computed tomography (CT) or magnetic resonance imaging (MRI) In outline, the clinical syndrome of aseptic meningitis consists of fever, headache, signs of meningeal irritation, and a predominantly lymphocytic pleocytosis with normal cerebrospinal uid (CSF) glucose Usually the onset is acute and the temperature is elevated, from 38 to 40 C (1004 to 104 F) Headache, perhaps more severe than that associated with other febrile states, is the most frequent symptom A variable degree of lethargy, irritability, and drowsiness may occur; confusion, stupor, and coma mark the case as an encephalitis rather than a meningitis Photophobia and pain on movement of the eyes are common additional complaints Stiffness of the neck and spine on forward bending attests to the presence of meningeal irritation (meningismus), but at rst it may be so slight as to pass unnoticed Here the Kernig and Brudzinski signs help very little, for they are often absent in the presence of manifest viral meningitis When there are accompanying neurologic signs, they too tend to be mild or eeting: paresthesias in an extremity, isolated strabismus and diplopia, a slight inequality of re exes, or wavering Babinski signs Other symptoms and signs are infrequent and depend mainly on the systemic effects of the invading virus; these include sore throat, nausea and vomiting, vague weakness, pain in the back and neck, conjunctivitis, cough, diarrhea, vomiting, rash, adenopathy, etc The childhood exanthems associated with meningitis and encephalitis (varicella, rubella, mumps) produce well-known eruptions and other characteristic signs An erythematous papulomacular, nonpruritic rash, con ned to the head and neck or generalized, may also be a prominent feature (particularly in children) of certain echoviruses and Coxsackie viruses An enanthem (herpangina), taking the form of a vesiculoulcerative eruption of the buccal mucosa, may also occur with these viral infections The CSF ndings consist of a pleocytosis (mainly mononuclear except in the rst days of the illness, when more than half the cells may be neutrophils), and a small and variable increase in protein In milder cases, in the rst hours or day of the illness, there may be no abnormalities of the spinal uid, and the patient may erroneously be thought to have migraine or a headache induced by a systemic infectious illness Micro-organisms cannot be demonstrated by conventional smear or bacterial culture As a rule, the glucose content of the CSF is normal; this is important because a low glucose concentration in conjunction with a lymphocytic or mononuclear pleocytosis usually signi es tuberculous or fungal meningitis or certain noninfectious disorders such as carcinomatous or lymphomatous invasion, or sarcoid of the meninges Infrequently, a mild depression of the CSF glucose (never below 25 mg/dL) has been reported with the meningitis caused by mumps, HSV-2, lymphocytic choriomeningitis, or VZV.

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