Dysimmune neuropathy

Busby M, Donaghy M. Chronic dysimmune neuropathy. A subclassification based upon the clinical features of 102 patients. J Neurol 2003 250(6) 714-724. 

Circulating toxic auto-antibodies can result in type-2 fiber atrophy in dysimmune neuropathies these are dyssdiwannian more often than dysneuronal type (see above). 

In adult-onset rod myopathy, which we now designate as adult-onset rod myopathy syndrome because of its association with a monoclonal gammopathy [93-95], with or without dysschwannian, probably dysimmune, neuropathy [96]. Recently, we have... 

Carefully seek all possibly relevant treatable diseases, and treat any identified correctable causative disorder, e.g. dysimmune neuropathy or primary hyperparathyroidism. 

Pseudo-ALS example fasciculating dysimmune neuropathy. treatable with IVIG, plus unilateral cerebral arteriovenous malformation in the motor area causing hyperreflexic hemiparesis, treated with focal microembolization. The ipsilateraUty was postulated to be due to a vascular steal from the contralateral brain motor area.)... 

Ophthalmoparesis, presumably from mitochondrial myopathy diagnosed by a biceps-muscle biopsy, plus a dysimmune neuropathy associated with elevated CSF protein 120 mg/dL (upper normal is 45 mg/dL), which was treatable with IVIG. One should not assume that all neuromuscular aspects of a mitochondrial myopathy patient are due to an untreatable mitochondrial or nuclear DNA mutation. 

Genetico-diabetoid-2 dysimmune polyneuropathy is our term, which we have been using for 15 years to describe the same clinical and laboratory features in patients as in the above-mentioned "diabetes-2 dysimmune neuropathy," who themselves do not yet have detectable glucose dysmetaboUsm parameters that would be considered indicative of actual diabetes-2, but have a close family history of diabetes-2 [4] (and Engel, unpublished work). In such patients, we have found that their polyneuropathy can be manifest as long as 10 years... 

The excellent improvement of this fever-responsive dysimmune neuropathy patient suggests that perhaps we should always treat dysimmune patients by combining anti-dysimmune and antiviral (or other antimicrobial) drugs, or one drug that does both. This concept is a putative model for future "combined anti-dysimmune plus anti-microbial therapy." And in each dysimmune patient we should always be searching for tracks of a relevant microbe."... 

Vignette 6. Myofibrillar myopathy, plus a treatable dysimmune neuropathy CCIDP)... 

Treatment Because of the sensory abnormalities, dysschwannian nerve conductions, elevated CSF protein, aspects of denervation-reinnervation in the muscle biopsy, and the diabetes-2 in both parents, we considered that our patient probably had coexisting genetico-diahetoid-2 dysimmune neuropathy," a type of chronic immune dysschwannian polyneuropathy (CIDP) (sometimes less precisely called chronic inflammatory demyelinating polyneuropathy, Chapter 2). We therefore treated her using/WG, and she was remarkably benefited her walking ability and endurance greatly improved, she did not require frequent rests, and was able to ascend steps much more easily. 

Also in that theme, we should remember that the cumulatively dramatic, and apparently enduring, benefit of interferon-o2A in a fever-responsive dysimmune neuropathy patient (see Chapter 2) may be due to both the known anti-dysimmune and the known... 

Engel, WK (2011) Remarkable benefit persisting un-diminshed for 8 years after stopping 14 years of Interferon-a2A (Inf-a) treatment for fever-responsive dysimmune neuropathy (FRDN) possibly a combined antidysimmune plus antiviral effect, and thus a puta-... 

The earliest reports of neurological complications of AIDS described distal symmetrical, painful sensory neuropathy occurring in HIV patients (Snider et al. 1983). Dysimmune inflammatory polyneuropathy was subsequently recognized as a complication of AIDS (Lipkin et al. 1985). Progressive polyneuropathy associated with cytomegalovirus (CMV) infection was documented as the first truly opportunistic infection of the peripheral nerve (Eidelberg et al. 1986). 

Vasculitic neuropathy Early Stepwise progression Multiple, asymmetric mononeuropathies, usually painful Dysimmune or vasculitic mechanisms... 

PATIENTS WITH DYSIMMUNE NEUROLOGICAL DISEASES REFRACTORY TO HIGH PROLONGED DOSES OF PREDNISONE PLUS AZATHIOPRENE OR CYCLOPHOSPHAMIDE HAVE SHOWN MODERATE TO DRAMATIC IMPROVEMENT. THESE INCLUDE CHRONIC DYSCHWANNIAN NEUROPATHY DYSNEURONAL ... 

Figure 1.3 (a-c) Established reinnervation, indicated by muscle fiber type-grouping, in three adult males with chronic dysimmune peripheral neuropathy. Darkly-stained type-2 fibers and Ughtly-stained type-1 fibers are type-grouped, in contrast to what normally would be a rather even intermixture of fiber types (not illustrated). The successfully "foreign reirmervated" fibers among the type-grouped type-1 fibers have retained, or re-achieved, their normal diameter. 

In HIV there is often a complex pathogenesis of the muscle atrophy, which histochemically is type-2 fiber atrophy with or without denervation atrophy. It can have five components (a) neuropathic, viz. dysimmune dysschwannian denervation neuropathy early in the course of the disease, and virogenic toxicity causing dysneuronal neuropathy later (b) often cachexia (c) hypomotUity/disuse (d) possible nerve toxicity of anti-HIV dmgs (e) infrequently, myotoxicity from viral products. With HIV, type-2 fiber atrophy in response to a hyponutri-tional/cachectic aspect would be altmistic, but when in response to the other causes it would not be. 

Symptomatically treatable muscle cramps accompanying various disorders, especially neuropathic abnormalities, are often well controlled with clonazepam [8, 9] (see vignette 8 in Chapter 3). Most muscle cramps are neurogenic, a few are myopathic. Cramps can be caused by a neuropathy that might otherwise be mild. If the neuropathy is worse than mild, it might itself be treatable with IVIG or other anti-dysimmune measure (see below). 

Sporadic inclusion-body myositis (s-EBM) plus genetico-diabetoid-2 dysimmune peripheral neuropathy, the latter very treatable with IVIG (see below). 

Engel, WK. (2002) In type-2 diabetes, diabetic neuropathy is usually responsive to intravenous IgG (IVIG) treatment, ergo presumably dysimmune. Acta Myologica 21, A79. 

Engel WK. (1997) Intravenous immunoglobulin (IVIG) - an often-overlooked treatment - produces rapid, remarkable, sustained benefit in "diabetic neuropathy complex", suggesting a dysimmune mechanism. Ann Neurol 42, 414. 

Comment Even though there is no specific treatment for myofibrillar myopathy, this patient greatly benefited from treatment of her coexisting dysimmune motor-sensory neuropathy. This exemplifies the need for carefully seeking treatable aspects in each patient (see Chapter 2). 

Vignette 12. Treatable forms of "diabetic neuropathy" diabetes-2 dysimmune sensory-motor polyneuropathy, and genetico-diabetoid-2 dysimmune polyneuropathy... 

For many years, and even today, any neuropathy occurring in a diabetes-2 patient has, simplisticaUy, incorrectly, and pessimistically often been called "nntreatable diabetic nenropathy." However, our 1993 demonstration of the widely occurring and heqnently gratifyingly treatable diabetes-2 dysimmune polyneuropathy, nsnally associated with elevated CSF protein, has led to onr benefiting many patients dismissed by others. IVIG is especially beneficial... 

Treatment The carcinoma was excised, and radiation and chemotherapy started. (Note certain forms of anticancer chemotherapy can themselves produce a toxic neuropathyr which complicates interpretation of any worsening of the patient s neuropathy.) For the probable dysimmune component of this neuropathy, the patient was also started on TVIG 0.4g/kg/ day, on two nonconsecutive days every week. He showed some improvement, but we do not know which treatment, or treatments, should receive the credit, because some anticancer treatments are also anti-dysimmune. 

Comment This patient has a sensory neuropathy (small- and large-fiber), plus a motor neuropathy. In general, if there is significant worsening over age 40 of a chronic, presumably genetic neuropathic process that had been present from childhood, one should look for a recent additional pathogenesis, such as dysimmune, that might be treatable, as exemplified in this patient. She also exemplifies an excellent... 

Vignette 17. Amyloid neuropathy, dysimmune, due to B-lymphocyte dyscrasia... 

Comment For therapeutic purposes, it is important to distinguish between a focal mechanical neuropathy and a generalized neuropathy, or the coexistence of both. One should consider various peripheral neuropathies (such as potentially treatable dys-immune diabetes-dysimmune and B12 insufficiency neuropathies), because even subtle ones probably can predispose to mechanical neuropathies of the median and ulnar nerves, as well as to cervical and lumbosacral radiculopathies from mechanical "spondylotic" changes. 

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