Peripheral neuropathy associated with angioimmunoblastic lymphadenopathy

A 49-year-old man developed mononeuritis multiplex associated with angioimmunoblastic lymphadenopathy. The biopsy of the sural nerve revealed focal reduction of myelinated fibres and axonal degeneration, as well as perivascular inflammatory infiltrates composed of lymphocytes and plasma cells, exhibiting policlonal immunoglobulin expression, proliferation of blood vessels, thickening of the vessel wall and endothelial hyperplasia. These latter changes are similar to those commonly encountered in the lymph nodes, as well as in other organs, in patients suffering from angioimmunoblastic lymphadenopathy.     

Peripheral neuropathy associated with Crohn's disease

Peripheral neuropathy in Crohn's disease has been described, to date, only with vitamin B12 deficiency or as due to oral metronidazole treatment. We report the association of Crohn's disease and peripheral neuropathy in two patients in whom neither of these pathogenetic factors of nerve damage apply. The CSF of both was normal. Patient 1 has had Crohn's disease for 12 years with predominantly sensory distal neuropathy and recurrent course related to worsening and improvement of the enteritis. Patient 2 had Crohn's disease some years before symptoms of recurrent sensory loss in the feet. Axonal degeneration was the mechanism of nerve damage in both patients.     

Peripheral neuropathy associated with hypereosinophilia.

Three patients with hypereosinophilia showed different forms of peripheral neuropathy: severe polyneuropathy of prevalently sensory type (case 1), mild sensory neuropathy (case 2), acute mononeuropathy of the median nerve with subclinical polyneuropathy (case 3). Hypereosinophilia was probably idiopathic, however the presence of atypical findings suggested transition to vasculitides or collagen disease. Sural nerve biopsy in cases 1 and 2 showed features of axonopathy in both, although of different severity, reflecting the variability of clinical involvement and, probably, heterogeneous pathogenic mechanisms. Peripheral nerve involvement associated with hypereosinophilia may be related to neurotoxicity of eosinophils, or to vascular damage.     

Peripheral neuropathy associated with Castleman's disease

Four patients with polyneuropathy complicating the plasma cell variant of Castleman's disease (angiofollicular lymph node hyperplasia) are described. The neuropathy was predominantly motor and severely disabling. Vasculopathy, papilloedema, organomegaly, endocrinopathy, oedema and paraproteinaemia were variably present in these patients. Sural nerve biopsy showed changes of both demyelination and axonal loss. Capillary proliferation and endothelial hypertrophy in the epineurium and endoneurium, similar to that seen in affected lymph nodes, suggested that a diffuse vasculopathy may contribute to the neuropathy. Serum antibody activity against a variety of neural antigen preparations was not detected in any of the patients. Two untreated patients died. Substantial improvement in the neuropathy occurred in the two patients treated with cyclophosphamide and prednisolone.     

Peripheral neuropathy associated with simvastatin.

Four patients are described who developed sensorimotor neuropathy while being treated with simvastatin and had complete or partial resolution of clinical abnormalities after withdrawal of treatment. In one case onset was within days of commencing treatment, but in two cases symptoms did not develop for two years. The electrophysiological and pathological features of the neuropathy were those of axonal degeneration. Clinical evidence of proximal and distal weakness and muscle fasciculations and persistent abnormalities of sensory conduction after recovery suggest the possibility of toxic damage to anterior horn cells and dorsal root ganglia. Thirty eight other cases with symptoms suggestive of peripheral neuropathy have been reported to the Australian Adverse Drug Reactions Advisory Committee, 22 of whom recovered after cessation of treatment; in five cases there was recurrence after re-exposure to the drug. Simvastatin should be considered among the causes of peripheral neuropathy, and the drug should be withdrawn if patients receiving it develop muscle weakness or sensory disturbances.     

病毒性肝炎伴发周围神经病变

病毒性肝炎可伴发周围神经病变,其中乙型肝炎患者主要表现为以脱髓鞘病变为主的周围神经损害,乙型肝炎病毒感染引起的免疫功能异常为其主要发病机制;而丙型肝炎患者大多伴发轴索性周围神经病,发病机制与冷球蛋白血症和血管炎有关;另外一些患者则由抗病毒药物治疗而诱发周围神经损害。对于肝炎伴发周围神经病的治疗,建议在积极治疗原发病变的基础上,应用免疫调节治疗。     

Peripheral neuropathy associated with eosinophilia-myalgia syndrome

In 1989, the Centers for Disease Control recognized the existence of an epidemic illness characterized by myalgia and eosinophilia in individuals taking preparations containing L-tryptophan. We evaluated 3 patients with eosinophilia-myalgia syndrome who presented with subacute progressive neuropathies. The neuropathies were predominantly motor and maximal in the lower extremities. Two patients were confined to a wheelchair and one was ventilator-dependent and bedridden. Sensory loss predominantly involved small fiber modalities. Electrophysiological studies showed multifocal marked conduction slowing and conduction block indicating segmental demyelination, with associated axonal degeneration that was accentuated distally. Examination of sural nerve biopsy specimens demonstrated axonal degeneration in all 3 patients and perivascular infiltrates in 2. Levels of quinolinic acid, a neurotoxic metabolite of L-tryptophan, were elevated in the cerebrospinal fluid in the 2 patients in whom it was measured. The cause of the neuropathy is unknown but may include immune mechanisms or toxicity of eosinophils, L-tryptophan, its metabolic products, or contaminants within L-tryptophan preparations.     

Peripheral neuropathy associated with disulfiram administration

Very few cases of peripheral neuropathy as a complication of disulfiram therapy have been described. The clinical and electrodiagnostic features of two patients who developed a severe peripheral neuropathy during disulfiram administration are reported. Evidence is presented which suggests that disulfiram causes a dying-back axonal neuropathy.     

Peripheral neuropathy associated with mitochondrial myopathy

Twenty patients with mitochondrial myopathy were investigated for the presence of peripheral neuropathy. There were clinical features of a mild sensorimotor neuropathy in 5 patients (25%) and nerve conduction studies were abnormal in 10 patients (50%). Electrophysiological studies of the whole group showed significant impairment of motor and sensory conduction, compared with controls. Sural nerve biopsy and morphometric studies were performed on 4 patients with clinical neuropathy. There was a reduction in density of myelinated fibers and electron microscope features of axonal degeneration affecting myelinated and unmyelinated fibers. Abnormal mitochondria containing paracrystalline inclusions were seen in the Schwann cell cytoplasm of two nerves.     

Peripheral neuropathy associated with intestinal inflammatory disease

The association of outlying peripheral neuropathy and inflammatory bowel disease is a rare fact leaving aside factors like the deficit of intestinal absorption of vitamins or the neurotoxicity of drugs employed for the treatment of the inflammatory bowel disease. We presented a series of four patients with this association, to whom a retrospective study was carried out. In all cases polineuropathy followed a course parallel to the inflammatory bowel disease, being acute and reversible in two cases. The polyneuropathy could be attributed to a deficit of vitamin B12 in one case and to metronidazole neurotoxicity in the other; in the remaining two cases the polineuropathy was chronic and no etiological factor could be found except for the own activity of the inflammatory bowel disease. We think that the neuropathy can represent a rare extraintestinal manifestation of the illness with a common autoimmune pathogenic mechanism. In one of our cases, the nerve biopsy demonstrated an axonal neuropathy with an alteration of the epineural vessels which showed a healed aspect.     

Peripheral neuropathy associated with erythrophagocytic lymphohistiocytosis.

A 12 year old patient who developed clinical, biochemical and histological features of erythrophagocytic lymphohistiocytosis is described. In contrast to previously reported cases, the prominent neurological feature was a subacute sensorimotor polyneuropathy. Sural nerve biopsy showed a marked reduction of myelinated fibres and severe axonal lesions, absence of histiocyte infiltration and deposits of IgM along the epineurium. In addition to the hypertriglyceridaemia previously described in this condition, an elevation of plasma very long-chain fatty acids and phytanic acid was found which suggests a transient impairment of peroxisomal functions.     

Peripheral neuropathy associated with mycosis fungoides.

A 56 year old man with acute sensory-motor polyneuropathy associated with mycosis fungoides is described. EMG studies showed diffuse signs of muscle denervation. A skin biopsy specimen showed a lymphocyte infiltration in the dermis, composed of mycosis cells characterised by deep invaginations of the nuclear membrane, and small Pautrier's microabscesses in the epidermis. Sural nerve biopsy revealed endoneurial fibrosis, a decreased number of myelinated fibres and acute axonal degeneration.     

Peripheral neuropathy associated with alpha 1-antitrypsin deficiency

Peripheral neuropathy associated with alpha 1-antitrypsin deficiency is an uncommon condition. Several recent studies have investigated the possible roles of serum proteinase inhibitors in inflammatory neuropathies, such as multiple sclerosis, Landry-Guillain-Barré syndrome, and various chronic inflammatory demyelinating peripheral neuropathies. We present a case in which alpha 1-antitrypsin deficiency (proteinase inhibitor ZZ phenotype) was diagnosed in a young white man with clinical signs and symptoms of peripheral neuropathy and a history of Landry-Guillain-Barré syndrome. We wish to emphasize the importance of serum protein electrophoresis in the diagnostic workup of patients presenting with the clinical manifestations of peripheral neuropathy.     

Peripheral neuropathy associated with mitochondrial disease in children

Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease.