Autonomic peripheral neuropathy

Most generalized peripheral polyneuropathies are accompanied by clinical or subclinical autonomic dysfunction. There is a group of peripheral neuropathies in which the small or unmyelinated fibers are selectively targeted. In these neuropathies, autonomic dysfunction is the most prominent manifestation. The features associated with an autonomic neuropathy include impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic function.     

Autonomic neuropathy in mixed cryoglobulinemia

A retrospective, cross-sectional study was performed on a series of HCV-related mixed cryoglobulinemia (HCV-MC) patients to assess autonomic neuropathy (AN) and its relation to peripheral neuropathy (PN). Thirty consecutive patients affected by HCV-MC underwent clinical, neurological and electrodiagnostic examinations. Autonomic nervous system (ANS) involvement was assessed by functional cardiovascular tests and sympathetic skin response (SSR) evaluation. Sural nerve biopsy was performed in 10 patients with PN. All patients received steroids, 15 also received recombinant interferon-α2b (RIfn-α2b). PN occurred in 27 patients (90.0%) and AN in 4 (13.3 %) all with signs of PN. SSR was the autonomic test more frequently altered. Biopsy disclosed axonal degeneration more evident in the 4 patients with AN. Three out of 4 patients with AN received steroids and rIFN-α2b and 1 steroids alone. In our study on HCV-MC, it was concluded that AN can occur also without dysautonomic symptoms, SSR appears to be one of the optional tests to use together with dysautonomic tests to identify AN and finally PN and AN do not seem to be positively influenced by addition of rIFN-α2b to steroid treatment. Received in revised form: 4 April 2006     

Treatment of painful neuropathy

PURPOSE OF REVIEW: With the aging of the population, treatment of painful neuropathies is becoming more and more important for neurological practice. This short review highlights recent findings and current problems. RECENT FINDINGS: In addition to tricyclic antidepressants and gabapentin, the reliability of which is established, some drugs have more recently been demonstrated to be efficacious: major and minor opioids, pregabalin, and serotonin-noradrenaline-reuptake inhibitors. In contrast, some other drugs have yielded disappointing results: memantine, mexiletine, topiramate, and - very recently - lamotrigine. Three main questions are currently being debated. Notwithstanding their proven efficacy, should opioids be used in chronic noncancer pain? In which patients should serotonin-noradrenaline-reuptake inhibitors be preferred to tricyclic antidepressants? What is the difference between pregabalin and gabapentin? The whole field suffers from important limitations that make evidence-based medical data hard to translate in clinical practice: most clinical trials were and still are focused on two conditions only (diabetic neuropathy and postherpetic neuralgia) and studies on polytherapy are insufficient. SUMMARY: A large variety of drugs are being tried in the treatment of painful neuropathy. Neurologists now have a wide choice. Recent publications can help in choosing the best treatment course.     

Chemotherapy-evoked painful peripheral neuropathy

Vincristine and paclitaxel, two of the most effective drugs in the battle against cancer, produce a dose-limiting neurotoxicity that sometimes presents as a painful peripheral neuropathy. For the first time, investigators have been able to produce these chemotherapy-evoked painful peripheral neuropathies in the laboratory rat. These new models have already begun to elucidate the causes of the neuropathic pain associated with these antineoplastic drugs, which will now make it possible to search for effective ways to prevent and treat it.     

Alcohol-induced stress in painful alcoholic neuropathy

Chronic alcohol consumption induces a painful small-fiber peripheral neuropathy, the severity of which increases during alcohol withdrawal. Chronic alcohol consumption also produces a sustained increase in stress hormones, epinephrine and corticosterone, that is exacerbated during alcohol withdrawal. We report that adrenal medullectomy and administration of a glucocorticoid receptor antagonist, mifepristone (RU 38486), both prevented and reversed a model of painful peripheral neuropathy in alcohol binge-drinking rats. Chronic administration of stress levels of epinephrine to rats that had undergone adrenal medullectomy and were being fed the alcohol diet reconstituted this phenotype. Intrathecal administration of oligodeoxynucleotides antisense to the β₂-adrenergic- or glucocorticoid-receptor also prevented and reversed the pro-nociceptive effects of ethanol. Our results suggest a convergence of the effects of mediators of the hypothalamic-pituitary- and sympathoadrenal-stress axes on sensory neurons in the induction and maintenance of alcohol-induced painful peripheral neuropathy.     

Treatment options in painful diabetic neuropathy

Diabetic neuropathy is common in patients with diabetes mellitus, and 7.5% of diabetics experience pain from diabetic neuropathy. Complications of diabetes mellitus are more common where control of the disease is not optimal. By improving the control of the disease, both the neuropathy and the pain it can produce may be improved. The pain of diabetic neuropathy can frequently be controlled using analgesics, antidepressants, anticonvulsants, topical capsaicin, and neuromodulation, either alone or in any combination.     

Gabapentin in acute painful diabetic neuropathy

Sir, Acute painful diabetic neuropathy (APDN) is an uncommon syndrome originally recognized by Ellenberg (1974) and termed ‘diabetic neuropathic cachexia’. It has been described in diabetic patients and also in females with diabetes and anorexia nervosa (Steele et al., 1987). Its clinical features consist in an unremitting burning pain in the lower limbs, which is more troublesome at night (Thomas and Griffin, 1995). We present the case of a woman with APDN who improved and became asymptomatic with low doses of gabapentin.     

Acute painful neuropathy in thallium poisoning

Dysesthesia, allodynia, distal muscle weakness, and sensory impairment were noted in two patients with acute thallium intoxication. Two months later, nerve conduction studies showed an axonal degeneration. Sural nerve biopsy disclosed a decreased fiber density in the large myelinated fibers. Quantitative sensory testing also revealed an impairment of pinprick, temperature, and touch sensations. Cutaneous nerve biopsy confirmed a loss of epidermal nerves indicating an involvement of the small sensory nerves.     

Autonomic neuropathy in familial amyloidotic polyneuropathy

Familial amyloidotic polyneuropathy (FAP) is characterized by both sensimotor and autonomic dysfunction. Autonomic disturbance involving the gastrointestinal tract, the urinary bladder, the cardiac conduction system, and the peripheral circulation has been described. In this study simple, non-invasive tests of autonomic function based on heart rate variability were applied to 12 patients with FAP and 12 healthy volunteers. The heart rate variation during normal breathing, deep breathing and during tilt from recumbent to standing position was measured. All tests showed significantly less heart rate variation in patients than in controls and the heart rate variation decreased with increasing severity of neurological disability, but the small number of patients in our study does not allow any further comparison between subgroups. Our study thus indicates impaired cardiovascular autonomic function in patients with FAP and we believe that these findings might also be of importance in other forms of systemic amyloidosis.     

Autonomic dysfunction in diphtheritic neuropathy.

Sympathetic and parasympathetic function and somatic nerve conduction were assessed in ten patients with diphtheritic neuropathy and 28 controls. None of the patients had postural hypotension. The Valsalva ratio was abnormal in two patients who also had myocarditis, but it was normal in five cases. Cardiac vagal dysfunction was found in five patients. One case showed cardiac parasympathetic denervation despite normal conduction velocity in the limbs.     

Autonomic neuropathy: the diagnosis

ABSTRACT- The diagnosis of autonomic neuropathy is often difficult to establish, since clinical symptoms generally appear late in the course of the disease, and may be non-specific. A number of recently developed quantifiable and reproducible autonomic nerve function tests are reviewed, with emphasis on the physiological basis of the tests and on practical applicability. Finally, diagnostic criteria, based on autonomic nerve function tests, are suggested.     

Paraneoplastic painful ulnar neuropathy.

A 58-year-old woman developed painful, bilateral ulnar neuropathy in conjunction with small cell lung carcinoma and high serum titer of anti-Hu antibody. An incidental stage I plasma cell dyscrasia, with immunoglobulin G kappa monoclonal protein, was also present. Electropysiological assessment excluded a generalized neuropathy, and nerve biopsy showed marked loss of myelinated and small unmyelinated fibers, without inflammatory changes or amyloid deposition. High titers of circulating anti-Hu antibody can be associated with symptoms resembling a paraneoplastic mononeuropathy.     

Autonomic neuropathy and coeliac disease

Coeliac disease is associated with numerous neurological manifestations including cerebellar ataxia, myelopathy, myopathy, and peripheral neuropathy. This report describes four patients who presented subacutely with presyncope and postural nausea. All four patients had biopsy proven coeliac disease with dysautonomia present on autonomic evaluation. These four patients comprised 2.4% of patients referred for autonomic testing in one year. Thus the frequency of coeliac disease is similar to that reported in idiopathic peripheral neuropathy.     

Autonomic impairment in amyotrophic lateral sclerosis

PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss of motor neurones, but it is increasingly recognized to be a more disseminated disease. The autonomic nervous system may also be involved. Here we review the literature with specific emphasis on autonomic functions in ALS. RECENT STUDIES: Ample evidence exists for subclinical dysfunction of cardiovascular, sudomotor, gastrointestinal, salivary and lacrimal regulation, even in early ALS cases. Autonomic disturbances may lead to circulatory collapse or sudden death in respirator dependent patients. Several studies suggest the existence of sympathetic hyperactivity in ALS. We discuss some possible pathophysiological mechanisms of the subtle abnormalities and some clinical and treatment implications. SUMMARY: The wide range of autonomic involvement, together with results suggesting cognitive and extrapyramidal dysfunction, supports the view that ALS is a multisystem degenerative disease.     

Etanercept reduces hyperalgesia in experimental painful neuropathy

Etanercept, a recombinant tumor necrosis factor receptor (p75)-Fc fusion protein competitively inhibits tumor necrosis factor-alpha (TNF). Etanercept has been successfully used in patients with rheumatoid arthritis, where it reduces pain and inflammation. Because locally produced proinflammatory cytokines play a role in pain after nerve injury, we investigated whether etanercept can reduce pain and hyperalgesia in an animal model of painful neuropathy, the chronic constriction injury of the sciatic nerve. C57BL/6 mice received etanercept or sham treatment by local near-nerve injection to the injured nerve or by systemic application. Treatment with etanercept reduced thermal hyperalgesia and mechanical allodynia significantly in both modes of application. The effect of etanercept was present in animals that were treated from the time of surgery and in those that were treated from day 6, when hyperalgesia was already present. These results suggest the potential of etanercept as a treatment option for patients with neuropathic pain.     

Autonomic neuropathy in the streptozotocin diabetic rat

An ultrastructural study of the sympathetic ganglia, dorsal sympathetic chain, and Auerbach's plexus is described in the streptozotocin diabetic rat. The observations cover the first six weeks following induction of diabetes. Degenerative changes began to appear in the axonal plasma membranes and axoplasm of unmyelinated fibers at 24 hours and were widespread by two weeks. Axonal sprouting and regenerating axons began to appear and increase in number through the 6th week. Chromatolysis in ganglion cells in sympathetic ganglia became apparent by two weeks as did degenerative changes in axons of Auerbach's plexus. This somewhat later appearance of changes in ganglion cells and Auerbach's plexus suggested the primary changes occurred in the postganglionic fibers. The cycle of change from degeneration to regeneration in the areas examined suggests either a possible toxic effect of streptozotocin or a combination of metabolic disturbances as a cause of this neuropathy.