Peripheral neuropathy in chronic venous insufficiency

Chronic venous insufficiency (CVI) of the lower legs may cause tissue damage, but involvement of peripheral nerves is uncertain. We examined 30 patients with CVI and 20 healthy controls using motor and sensory nerve conduction studies, vibration testing and thermotesting, quantitative sudomotor axon-reflex test, and laser Doppler flowmetry. Subjects with possible confounding factors for peripheral neuropathies were excluded. Prolongation of distal motor latency of the peroneal nerve (median, 5.4 versus 4.5 ms; P = 0.02), increased limits for warm (9.60 degrees C versus 5.20 degrees C; P = 0.016) and cold detection (3.45 degrees C versus 1.55 degrees C; P = 0.016) and reduced vibration sense (2.8925 versus 1.1075; P < 0.008) were found. The results demonstrate a disturbance of A-alpha fibers, A-beta fibers, A-delta fibers, and thermoafferent-C fibers, possibly induced by ischemia due to venous microangiopathy and increased endoneurial pressure. Analogous to neuropathic ulcers in diabetes, the CVI-associated neuropathy may also be a cofactor in the development of venous ulcers.     

Peripheral neuropathy after chronic endoneurial ischemia

We have developed a method for producing chronic regional nerve ischemia in rats by creating proximal limb arteriovenous shunts. This procedure results in a 50 to 75% reduction in endoneurial blood flow within the distal sciatic nerve as measured by the iodoantipyrine method. Nerve conduction velocities in sciatic nerves ipsilateral to the shunt fell by 25 to 30% within 2 weeks after creation of the shunt and did not recover for up to 10 months after the procedure. Morphological studies of the ischemic nerves showed structural abnormalities at nodes of Ranvier and mild axonal atrophy. Neither segmental demyelination nor axonal degeneration were evident. These results indicate that reduced endoneurial blood flow, insufficient to cause infarction, may result in measurable functional and morphological abnormalities in peripheral nerves.     

Peripheral neuropathy

Poster Session 5

Peripheral neuropathy     

Neurophysiological changes in COPD patients with chronic respiratory insufficiency

Chronic hypoxemia is known to cause peripheral neuropathy (PNP) in chronic obstructive pulmonary disease (COPD) patients. We aimed to know how often PNP is encountered in such patients and the changes in the central nervous system (CNS) if any. We enrolled 32 patients (30 M, 2 F; mean age +/- SD: 61.5 +/- 8.8 years) with COPD into the study. PaO2 > or = 55 mmHg was considered as the cut-off value designating tissue hypoxia. According to this cut-off value the subjects were divided into two groups: Group I, n: 19, PaO2 < 55 mmHg and Group II, n: 13, PaO2 > or = 55 mmHg. All subjects were evaluated with motor and sensory nerve conduction studies (MNCV and SNCV, respectively), electromyography, visual and brainstem evoked potentials (VER and BAER, respectively). We detected PNP in 93.8% of the study subjects. Distal latency of sural nerve correlated significantly with cigarette consumption and reduction in PEFR. SNCV of median nerve was reduced as PaCO2 was elevated and pH was lowered. BAER wave III latency showed significant inverse correlation with PEFR, FEF25 and FEF25-75. Interpeak latency (IPL) of BAER I-III was also significantly and inversely correlated with FEV1/FVC and FEF25-75. IPL of BAER III-V too showed significant correlations with PaCO2, HCO3- and pH of the arterial blood. As BAER III and IPLs of it represent the pontomedullary portion of the brain, cigarette smoking and airways obstruction may not only cause peripheral neuropathy but also a delay in evoked responses of the brain stem by inducing chronic hypercapnia and respiratory acidosis in patients with COPD.     

Peripheral neuropathy associated with chronic natural killer cell lymphocytosis

We report a patient with steroid-responsive peripheral neuropathy which developed with chronic natural killer cell lymphocytosis (CNKL). A 70-year-old female with a 2-week history of progressive motor and sensory neuropathy showed a marked increase of natural killer (NK) cells in the blood, and was diagnosed as having CNKL. Nerve conduction studies (NCS) revealed a mixed axonal and demyelinating neuropathy. A sural nerve biopsy revealed infiltration of NK cells into the nerve fascicles, and demyelinating changes with axonal degeneration. The infiltrating NK cells were adjacent to myelinated fibers, showing damage of Schwann cell membrane. Treatment with oral prednisolone resulted in rapid improvement of the sensory disturbance and weakness with a significant decrease of NK cells in the blood and disappearance of the conduction blocks in NCS. This is the first case of CNKL associated neuropathy in which infiltration of NK cells was demonstrated in the nerve fascicles. Our observations suggest that the infiltrating NK cells may directly damage myelin and Schwann cells, thus causing demyelination.     

Neuropathies and chronic respiratory insufficiency: electrophysiologic study

In order to determine the frequency and the characteristics of neuropathies in chronic respiratory insufficiency, a systematic study of 43 patients affected by a chronic obstructive pulmonary disease was performed. In addition to neurological and electrophysiological examinations (including 6 nerve conduction studies on median, ulnar and peroneal nerves and EMG of 4 to 8 muscles), nerve and muscle biopsies (of the superficial peroneal nerve and lateral peroneus brevis muscle) were performed in 13 cases. Polyneuropathies were found in 74% patients: but mild in 39%, severe in 35%. Most were subclinical or poorly symptomatic. We determined the importance and distribution of abnormalities on the different nerves. From this we established that neuropathies are mixed but predominantly of the axonal type. Axonal degeneration and demyelination were confirmed by nerve biopsy; muscles presented neurogenic atrophy. Statistical analysis showed that the duration of hypoxemia was related to neuropathy. The pathogeny of these neuropathies is discussed.     

Acute neuropathy with tetraparesis and respiratory insufficiency in cases of acute intermittent porphyria

Acute intermittent porphyria is a hereditary disorder resulting from a partial deficiency of the third enzyme in the haeme biosynthetic pathway. Symptoms are due to metabolic effects on the peripheral autonomic and sensomotoric, as well as the central nervous system. We report on the case of a life-threatening acute crisis with tetraplegia and respiratory insufficiency.     

Peripheral neuropathy in scleroderma

Because patients with scleroderma report neuropathic symptoms including numbness, paresthesias, and dysesthesias, we assessed peripheral nerve function in such patients. Fourteen scleroderma patients underwent complete neurologic examination, nerve conduction studies (NCS) and quantitative sensory testing (QST). Neurologic examination revealed reduced vibration (7) or pinprick (4) sensation in the upper or lower extremities, focal atrophy or proximal weakness (2), and decreased deep tendon reflexes (2). NCS showed reduced sensory nerve action potentials (1) and carpal tunnel syndrome (1). QST of the upper and lower extremity revealed increased cold or vibration detection thresholds in 8 of 14 patients. Our findings suggest that peripheral neuropathy occurs in patients with scleroderma at a higher frequency than previously appreciated. These findings cannot be ascribed to compression neuropathies, but rather involve large and small fibers in a non-length-dependent fashion. Larger, prospective studies using the more sensitive QST as well as pathologic studies of nerve, including cutaneous innervation, are needed to further assess the characteristics and etiology of the neuropathy.     

Peripheral neuropathy in CADASIL

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary cerebral microangiopathy associated with mutations in the Notch 3 gene. The clinical phenotype is characterized by cerebral impairment even though typical microvascular changes are diffuse. Objective To assess peripheral neuropathy in patients with CADASIL. Patients and Methods We enrolled eleven CADASIL patients with variable phenotype including clinical signs of peripheral nerve involvement. In all patients electromyography and nerve conduction velocities were performed. Peripheral nerve biopsy was performed in three cases. Results We found sensory motor neuropathy in 7/11 patients. Nerve biopsy revealed axonal and demyelinated findings. Conclusion Our findings suggest that peripheral neuropathy may be part of the CADASIL phenotype.     

Peripheral neuropathy in abetalipoproteinemia

We studied the peripheral neuropathy of three sisters with abetalipoproteinemia. Clinically, a sensory neuropathy progressively increased in severity. There was a diminution in the amplitude of sensory action potentials and a slight-to-moderate slowing in maximum sensory conduction velocity, initially most marked in distal portions of the nerves. Motor conduction was normal, although EMG indicated subclinical signs of partial chronic denervation. The sural nerves showed a decreased number of large fibers (greater than 7 micron); in the patient with the neuropathy of shortest duration, small fibers and clusters of regenerating fibers indicated regeneration. In the two patients with advanced neuropathy, one-half the segments of teased fibers showed paranodal demyelination. Also, unmyelinated fibers showed evidence of regeneration.     

Evidence of motor neuron involvement in chronic respiratory insufficiency.

Nineteen patients with chronic respiratory insufficiency, mean age 61.4 +/- 12.2, have been investigated with pulmonary function tests, clinical neurological examination and neurophysiological methods including motor and sensory conduction studies and needle electromyography. None of them had conditions known to affect the peripheral nervous system such as diabetes, alcoholism, or uraemia. The motor and sensory conduction studies showed only a reduced mean amplitude of the ulnar nerve SAP and of the compound muscle action potential of the APB and EDB muscles. The EMG was abnormal in 94.7% of the cases and showed an increased percentage of polyphasic potentials and a reduced recruitment pattern of motor units firing at high frequency. The data seem to support the hypothesis of an involvement of motor neurons in this condition although the evidence for a neuropathy is lacking.     

Peripheral neuropathy, cerebral atrophy, and intellectual impairment in chronic alcoholics

Peripheral neuropathy, cerebral atrophy, and intellectual impairment was investigated in 46 males with alcoholic nervous system damage. An overall correlation was found between peripheral neuropathy and cerebral atrophy and between several of the individual neurophysiological and neuroradiological variables examined. There was also a correlation between cerebral atrophy and intellectual impairment. The findings support the view that alcohol in itself is toxic to central and peripheral nervous tissues, although a dose-response dependence could not be established.     

Peripheral neuropathy in mitochondrial disease

Clinical, electrophysiological, histological and biochemical studies of two patients with mitochondrial disease revealed a moderately advanced axonal neuropathy with mitochondrial paracrystalline inclusions in Schwann cells, fibroblasts and muscle fibers. In addition there was a myopathy, and the activity of muscle cytochrome c oxidase was diminished by more than 50%. There were electrophysiological signs of myopathy, neuropathy and failure of excitation-contraction coupling in both patients. The partial enzyme deficiency raises some questions as to its pathogenetic role in these neuromyopathies.     

Peripheral neuropathy in cerebrotendinous xanthomatosis

We performed a sural nerve biopsy in a patient with cerebrotendinous xanthomatosis (CTX) because of electrophysiologic evidence of peripheral neuropathy. The sections showed a striking loss of myelinated axons, the distribution of which suggested a compressive and/or ischemic process. Biochemical analysis disclosed large amounts of cholestanol, a cholesterol derivative that characteristically accumulates in CTX. However, the biochemical abnormality was not associated with any obvious structural alterations in the myelin lamellae or with abnormal storage material in Schwann's cells.