Peripheral nerve involvement in chronic liver disease. Clinical and electrophysiological study

A clinical and electrophysiological study was carried out on 19 selected patients with chronic liver disease. Clinical signs of peripheral nerve involvement were found in 4 patients (21%); while electrophysiological impairment was present in 11 patients (57.8%). These abnormalities were mostly limited to the sensory and motor fibers of the tibialis posterior nerve. Our data confirm the presence of peripheral nerve involvement in chronic liver disease, and that it may be evidenced by careful electrophysiological examination.

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Sommario Uno studio clinico ed elettrofisiologico è stato condotto su 19 pazienti affetti da malattia epatica cronica, non diabetici, non alcolisti. Segni clinici di neuropatia sono stati riscontrati in 4 pazienti (21%), mentre 11 pazienti (57.8%) presentavano alterazioni elettrofiosologiche per lo più limitate alle fibre motorie e sensitive del nervo tibiale posteriore. I nostri dati confermano un interessamento nervoso periferico in corso di epatopatia cronica che, anche se modesto dal punto di vista clinico, viene evidenziato all'esame elettrodiagnostico.

     

Neuromuscular dysfunction and ultrastructural pathology in children with chronic cholestasis and vitamin E deficiency

The ultrastructural pathology of nerve and muscle and the neurological dysfunction in children with cholestatic liver disease and vitamin E deficiency have not been previously correlated. We studied two children with this syndrome. One child, 11 years of age, had severe hyporeflexia and decreased vibratory sense. Nerve conduction was delayed. The second child, 2 years of age, was neurologically normal. Both children showed ultrastructural evidence of damage to the sural nerve and accumulation of electron-dense deposits in the muscle fibers. Abnormalities of the nerves included disruption of the myelin sheath and separation and degeneration of the inner and outer components of the Schmidt-Lanterman incisure.     

Peripheral nerve involvement in primary systemic AL amyloidosis: a clinical and electrophysiological study

Background: Involvement of visceral organs usually dominates the clinical picture of primary systemic AL amyloidosis, but some patients suffer from serious peripheral neuropathy. The aim of this study is to clinically and electrophysiologically investigate peripheral nerve involvement in AL amyloidosis patients. Patients and methods: We reviewed clinical manifestations, electrophysiological findings including nerve conduction velocities and treatments in 43 consecutive patients. Twenty age‐matched healthy subjects were employed as controls. Results: Fifteen patients (34.9%) showed apparent neuropathic symptoms, which consisted of polyneuropathy in 11 (25.6%), bilateral carpal tunnel syndrome in 4 (9.3%), and autonomic dysfunction in 8 (18.6%). Polyneuropathy in this disease was characterized by symmetrical and sensory‐dominant impairment, early involvement of the lower limbs, loss of all sensations, rarity of motor weakness, and painful paresthesia in the legs predominant at an early stage. Autonomic dysfunction including orthostatic hypotension was frequently associated with polyneuropathy at an advanced stage. On electrophysiological studies, motor conduction velocity and compound muscle action potential of both median and tibial nerves were significantly decreased in the patients with polyneuropathy but also in those without any signs of neuropathy. Only four of 15 patients with neuropathy were able to receive intensive but promising chemotherapy with a large dose of melphalan for plasma cell dyscrasia. Conclusions: Peripheral nerves in primary systemic AL amyloidosis patients seem to be involved more extensively than clinical manifestations might suggest. The clinical picture of polyneuropathy in this disease closely resembles that in transthyretin‐type familial amyloid polyneuropathy patients with a late age at onset, particularly those originating from sporadic kindreds.     

A clinical, electrophysiological, morphological and immunological study of chronic sensory neuropathy with ataxia and paraesthesia

We have observed 9 patients (8 men and 1 woman), 58 to 77 years of age with neuropathy with only sensory symptoms and insidious onset. Five of them (4 men and 1 woman) aged 65 to 77 years, had normal serum electrophoretic profiles, while the others (all men), 58 to 74 years, had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinical data were consistent with a sensory neuropathy affecting predominantly the kinesthetic sense (position and vibration sensation). The electrophysiological data indicated predominant sensory axonal neuropathy. Morphological data confirmed the primary axonal damage. Western immunoblot showed that the IgG from a patient without MGUS reacted with a 55 kD protein of dorsal root ganglion homogenate. Three of four patients with IgM MGUS were serum reactive against chondroitin sulfate C (ChS-C) in double immunodiffusion. After absorption with ChS-C the monoclonal peak completely disappeared from two patients and was decreased in the third patient. Our data indicate that immunological abnormalities are part of the pathogenesis for a subgroup of chronic neuropathy with only sensory symptoms.     

Asymptomatic nerve hypertrophy in lepromatous leprosy: a clinical,electrophysiological and morphological study

Summary In order to learn more about early nerve lesions observed in leprosy, we performed a clinical, electrophysiological and morphological study in seven patients with untreated lepromatous leprosy, palpably enlarged radial cutaneous nerve and preserved sensation in the corresponding territory. The conduction velocity of the cutaneous radial nerve, which was decreased in all patients, did not significantly differ from that of a group of patients with lepromatous leprosy, hypertrophy of the radial cutaneous nerve and sensory loss. In contrast, the sensory action potential was significantly lower in patients with sensory loss, which demonstrates that axon loss is more important than demyelination in producing sensory loss. In all patients nerve enlargement was due to thickening of the epineurium and of the perineurium subsequent to inflammatory infiltrates and proliferation of fibroblasts and perineurial cells. In several fascicles, the inflammatory infiltrates and the infected cells infiltrated endoneurial connective tissue septa and blood vessels.Mycobacteria leprae were abundant in peri neurial cells, fibroblasts, macrophages, Schwarm cells and endothelial cells, and lymphocytic vasculitis present in all cases. The average density of myelinated fibres was 2600 SD 880 fibres/mm² (control: 7700 fibres/mm²), with marked differences between individual fascicles, versus 420 fibres/mm² in patients with nerve hypertrophy and sensory loss (range 0–2080 fibres/mm²). Single fibre preparations showed that segmental demyelination pre dominated in two patients, axonal degeneration in one, while inflammatory infiltrates and proliferation of connective tissue adhering to individual fibres were prominent in the others. Both infection of Schwann cells and secretory products released by mononuclear cells involved in the inflammatory process are likely to play a role in the lesions of nerve fibres observed in early stages of lepromatous leprosy.Presented in part at the Second Meeting of the European Neurological Society, Brighton (UK), June 1990     

Peripheral neuropathy in chronic occupational inorganic lead exposure: a clinical and electrophysiological study.

BACKGROUND AND OBJECTIVES: Traditionally the neuromuscular disorder associated with lead poisoning has been purely motor. This study assessed peripheral nerve function clinically and electrophysiologically in 46 patients with neuropathic features out of a total population of 151 workers with raised blood and/or urinary lead concentrations. RESULTS: Average duration of occupational exposure for the neuropathic group ranged from 8-47 years (mean 21.7). Their mean blood lead concentration (SD) was 63.9 (18.3) microg/dl (normal <40), urinary lead 8.6 (3.3) microg/dl (normal<5.0), urinary coproporphyrins 66.7 (38.4) microg/g creatinine (20-80), urinary aminolaevulinic acid 1.54 (0.39) mg/g creatinine (0.5-2.5). All 46 had distal paraesthesiae, pain, impaired pin prick sensation, diminished or absent ankle jerks, and autonomic vasomotor or sudomotor disturbances. Reduced vibration sensation and postural hypotension were present in all 20 studied. None of these 46 patients had motor abnormalities. Motor conduction velocity and compound muscle action potential amplitudes were normal, with marginally prolonged distal motor latencies. Sensory nerve action potential amplitudes lay at the lower end of the normal range, and the distal sensory latencies were prolonged. No direct correlation was found between the biochemical variables, and the clinical or electrophysiological data. CONCLUSIONS: One additional patient was seen with shorter term exposure to lead fumes with subacute development of colicky abdominal pain, severe limb weakness, and only minor sensory symptoms. Unlike the patients chronically exposed to lead, he had massively raised porphyrins (aminolaevulinic acid 21 mg/g creatinine, coproporphyrins 2102 microg/g creatinine). Patients with unusually long term inorganic lead exposure showed mild sensory and autonomic neuropathic features rather than the motor neuropathy classically attributed to lead toxicity. It is proposed that the traditional motor syndrome associated with subacute lead poisoning is more likely to be a form of lead induced porphyria rather than a direct neurotoxic effect of lead.     

A combined morphological and electrophysiological study of conduction block in peripheral nerve

The reliability of the electrophysiological criterion of conduction block in determining the presence of focal demyelination in a peripheral nerve has been studied in an animal model. Demyelination was produced in the rat tibial nerve by one or two closely spaced microinjections of lysophosphatidylcholine (LPC). Histological and electrophysiological data were obtained on the acute lesion (up to 6 days), and during recovery (up to 11 weeks). Single LPC injections produced a lesion of very variable severity. Double injections more reliably produced a severe lesion with marked conduction block. Slight axonal damage was occasionally seen in nerves showing severe demyelination. The ratio of amplitude of muscle action potentials evoked by stimuli proximal and distal to the sites of nerve injection was calculated to detect the development of conduction block. The post injection ratio was more than 2 standard deviations below the control mean in 86% of nerves showing signs of demyelination. No control saline injected nerves showed such evidence of conduction block. The severity of the electrophysiological abnormality did not prove a reliable indicator of the severity of the histological lesion, however. The possible reasons for this variability are discussed and it is argued that caution should be exercised when interpreting this particular electrophysiological finding in clinical practice.     

Ataxia telangiectasia in Chinese children. A clinical and electrophysiological study

The clinical manifestations, immunological, chromosomal, and multimodal electrophysiological studies of five Chinese patients with ataxia telangiectasia are described. One died of hepatocellular carcinoma not associated with Hepatitis B-antigenaemia. Another died of respiratory failure. Two siblings are free of sinopulmonary infections although they are wheelchair bound. Computed tomography of the brain showed cerebellar atrophy in four cases. Nerve conduction studies showed evidence of axonal neuropathy in all cases with the earliest detection at six years. Electromyography showed mild denervation changes in two cases. Two patients had abnormal somatosensory evoked potentials and one had abnormal visual and brain stem auditory evoked potentials. The level of alpha foetal protein was elevated whereas the serum carcino-embryonic antigen was normal in all patients.     

Peripheral nerve involvement in sarcoidosis: an electrodiagnostic study.

The frequency of peripheral nerve involvement in sarcoidosis is uncertain. To determine how often peripheral nerves are affected in the absence of symptoms, electromyography was performed on 29 sarcoid patients and 29 age-matched controls. Nineteen sarcoid patients, compared to two controls, had abnormally low sensory amplitudes in one or more nerves, and the mean sensory amplitudes for median, ulnar, and sural nerves were lower in the patient than in the controls. Subclinical mononeuropathy multiplex appears to be common in sarcoidosis.     

Age-dependent changes in cat masseter nerve: an electrophysiological and morphological study.

The present study was undertaken to determine the manner in which aging affects the function and structure of the masseter nerve in old cats. Electrophysiological data demonstrated a significant decrease in the conduction velocity of the action potential in old cats compared with that observed in adult cats. Light microscopic analyses revealed an age-dependent decrease in axon diameter. Electron microscopic observations of the masseter nerve in the aged cats revealed a disruption of the myelin sheaths and a pronounced increase in collagen fibers in the endoneurium and perineurium. These morphological changes are discussed and then related to the decrease in conduction velocity which was observed in the electrophysiological portion of this study.     

Subclinical peripheral nerve involvement in AIDS: an electrophysiological and pathological study.

Thirty patients with AIDS without symptoms or signs of peripheral neuropathy were compared electrophysiologically with 23 age and sex matched healthy controls. The patients had a mean reduction in the amplitude of common peroneal compound muscle action potentials of 37% (95% CI 11-70%) and of sural sensory action potentials of 34% (CI 18-49%). Mean conduction velocity of both motor and sensory nerves was reduced by between 1 and 7 m/s, with a prolongation of F waves corrected for height of 5% in the arms and 13% in the legs. The distal motor latencies were unchanged. These changes did not correlate with the duration of AIDS, degree of immunosuppression (CD4 count), Body Mass Index, albumin or vitamin B12 level. Four patients had subclinical mononeuropathies. Sural nerve taken at necropsy from five asymptomatic AIDS patients had evidence of axonal degeneration without inflammation or demyelination. There was a mean reduction in myelinated fibre density of 30.5% (CI 10-51%) compared with eight age matched sudden death controls (p = 0.01). This loss principally affected the larger fibres. The pathological and electrophysiological changes indicate axonal degeneration and are similar to those seen in other chronic disorders and in normal ageing. It is concluded that this axonal degeneration is not specific to HIV.     

Acute ataxic neuropathy: a clinical, electrophysiological and morphological study

Sensory ataxia as the chief manifestation of acute neuropathy is rather rare. Of the 224 cases of acute polyneuropathy seen over 6 years (1984-1990) only 10 patients (M:F 3:7) had disabling ataxia as the presenting feature. Their ages ranged from 14-61 years. Antecedent febrile illness was present in 6 patients and the peak deficit evolved over 2-25 days. Severe ataxia, paresthesia, distal areflexia and predominant joint sense loss were common to all, motor weakness was either absent or insignificant. CSF was acellular and revealed elevated protein in 3 subjects. All patients had electrophysiological evidence of severe sensory neuropathy with mild or no motor neuropathy. Sural nerve biopsy in one patient showed loss of large, as well as small, diameter myelinated fibres, secondary demyelination, but no evidence of inflammation. At follow up marginal to moderate improvement in ataxia was noted in only 5 patients. Absence of ophthalmoplegia and motor weakness, poor prognosis and characteristic electrophysiological and histopathological observations suggest that acute ataxic neuropathy may be a distinct entity.     

Peripheral nerve involvement in Batten-Spielmeyer-Vogt''s disease.

Electromyography and sensory and motor nerve conduction were studied in 23 patients with Batten-Spielmeyer-Vogt's disease ("juvenile amaurotic idiocy", cerebral ceroidlipofuscinosis). A slight to moderate slowing of the sensory conduction velocity was found in the median as well as in the sural nerve, more pronounced in the distal than in the proximal segments. The findings are interpreted as evidence of impaired transmission of the peripheral nerves in Batten-Spielmeyer-Vogt's disease.     

Inclusion body myositis: peripheral nerve involvement. Combined morphological and electrophysiological studies on peripheral nerves

The occurrence of neuropathy in 5 cases of inclusion body myositis (IBM) was studied. The intramuscular nerve branches showed variable ultrastructural changes in all cases. The observed changes were loss of axons, wallerian degeneration and axon terminal atrophy. EMG with concentric needles showed myopathic motor unit potentials in all cases. A reduced interference pattern due to loss of motor units was found in all cases. All but one patient showed fibrillation potentials in several muscle groups. Motor nerve conduction velocities and F-wave latencies were pathological in two of the cases, in which there were motor unit potentials with increased amplitude and duration as evidence of reinnervation. Sural nerve biopsy in one of these cases revealed slight neuropathy of the axonal type. These findings support the concept of peripheral nerve involvement in many cases of IBM.     

Neuropathology of chronic vitamine E deficiency in fatal familial intrahepatic cholestasis

Summary A progressive neuromuscular syndrome developed in a girl suffering from fatal familial intrahepatic cholestasis (Byler disease). The neuromuscular syndrome included muscular wasting of the legs, pes cavus, areflexia, decreased vibratory sensation, cerebellar symptoms, ophthalmoplegia, and visual disturbance with retinitis pigmentosa. The serum vitamin E level was extremely low. Postmortem neuropathologic study revealed the following lesions: (1) Systemic axonopathy involving the peripheral nerves and proximal axons of the dorsal root ganglia and posterior roots as well as the distal axons of the central nervous system (CNS) (2) Neuronal loss in the sensory and oculomotor nuclei of the brain stem, basal ganglia, Clarke's column, posterior horn, and dorsal root ganglia. (3) Neuronal lipofuscinosis. Axonopathy was severer in the more distal axonal segments, although the cuneate fasciculus was more affected than the gracile fasciculus. The severity of neuronal lipofuscinosis was not correlated with that of neuronal disintegration. The electron-dense bodies in the dystrophic swollen axons resembled lipofuscin granules. These neuropathologic lesions were considered to be the sequelae to chronic vitamin E deficiency.     

Peripheral nerve involvement in familial spastic paraplegia.

A sural nerve biopsy specimen was obtained from a 16-year-old girl affected by a clinically uncomplicated form of familial spastic paraplegia. The electron microscopic study evidenced degenerative changes in some large myelinated fibers. Onion bulb formations and clusters of small myelinated fibers were also observed. Quantitative determinations showed a decreased density of the large myelinated fibers and a mild decrease in the percentage of the endoneural area covered by the myelinated fibers. The unmyelinated fibers were uninvolved except for their participation in onion bulb formations.