Effects of alcohol on bone, muscle and nerve

The acute and chronic effects of alcohol on bone, muscle and peripheral nerves are not well appreciated. Bone complications include traumatic fractures, osteoporosis and osteonecrosis. In muscle, a sustained bout of heavy drinking may cause rhabdomyolysis, while chronic alcohol abuse may produce proximal myopathy. In peripheral nerves, acute alcohol intoxication may lead to pressure neuropathy and chronic abuse may cause peripheral neuropathy.     

Serum carnosinase activities in patients with alcoholic chronic skeletal muscle myopathy

1. Serum carnosinase activity was assayed in a group of alcoholic patients with and without histologically proven atrophy of type II skeletal muscle fibres, and in control subjects. No significant activity was detected in muscle biopsy samples or washed erythrocytes. 2. Serum carnosinase activity was significantly lower in chronic alcoholic patients compared with a group of age-matched controls. Alcoholics with abnormal muscle biopsies had significantly lower enzyme activities than either those patients with normal muscle biopsies or the controls. Serum enzyme activities in patients with normal muscle biopsies were not significantly different from controls. 3. Serum carnosinase activity was inversely correlated with the degree of muscle atrophy as measured by the type II fibre atrophy factor. There was a positive correlation between the enzyme activity and skeletal muscle mass as reflected by the creatinine-height index. Furthermore, the enzyme activity significantly increased, with resolution or improvement in the myopathy, in patients who abstained from alcohol. 4. Kinetic studies showed that the reduced carnosinase activity was due mainly to a decrease in the apparent Vmax. The apparent Km was significantly higher in the myopathic compared with non-myopathic alcoholics. Mixing serum from controls and patients with myopathy gave the expected values, indicating the absence of a serum enzyme inhibitory factor. Acute alcohol loading had no effect on the serum carnosinase activity. 5. The decrease in serum carnosinase activity in alcoholics was not related to the severity of their liver disease. Assays of serum carnosinase in chronic alcoholics, can thus be used as a marker of their associated myopathy.     

Autonomic neuropathy and chronic liver disease

Autonomic neuropathy has been reported in association with alcoholic cirrhosis but there is no information on its occurrence in non-alcoholic liver disease. We have examined autonomic function in 64 patients with biopsy-proven liver disease (22 with alcoholic liver disease and 42 with non-alcoholic liver disease) together with 29 age-matched controls. Forty-five per cent of patients with alcoholic liver disease and 43 per cent with non-alcoholic liver disease showed evidence of parasympathetic damage; 11 per cent of patients with alcoholic liver disease and 12 per cent with non-alcoholic liver disease had sympathetic damage. Forty-five per cent of patients with alcoholic liver disease and 22 per cent with non-alcoholic liver disease had peripheral neuropathy on clinical examination. Sixty-eight per cent of those with peripheral neuropathy also had autonomic neuropathy. This study confirms that autonomic neuropathy is common in alcoholic patients but the fact that it is found with comparable frequency in non-alcoholic liver disease suggests that the neurological defect may be secondary to the disturbed liver function. The implications of these observations with regard to prognosis of chronic liver disease are discussed.     

Glycogen content and activities of key glycolytic enzymes in muscle biopsies from control subjects and patients with chronic alcoholic skeletal myopathy

The capacity for glycolysis in muscle biopsies obtained from long-term heavy alcohol drinking patients has been compared with tissue from control subjects by assay in vitro of the total activities of glycogen phosphorylase, phosphofructokinase and fructose 1,6-bisphosphatase, key regulatory enzymes in the anaerobic glycolytic pathway. Biopsies from 13 of 22 patients had type II fibre atrophy, and the activities of all three enzymes were reduced in these biopsies, when expressed in terms of DNA content, the most striking reduction being in phosphofructokinase activity. The amount of glycogen in the tissue correlated closely with these enzyme activities and was slightly lower in the most atrophic tissue, when expressed in terms of DNA content. The activities of acid and neutral alpha-glucosidases were similar in biopsies from control subjects and patients with various severities of alcohol myopathy. The reduced activities are consistent with a reduced proportion of type II fibre muscle mass in these patients, and suggest that there may be a reduced capacity for glycolysis with resultant reduced lactate production. Whether the changes in enzyme activities are primary to the selective atrophy remains to be established.     

Autonomic Neuropathy and Chronic Liver Disease

Autonomic neuropathy has been reported in association with alcoholiccirrhosis but there is no information on its occurrence in non-alcoholicliver disease. We have examined autonomic function in 64 patientswith biopsy-proven liver disease (22 with alcoholic liver diseaseand 42 with non-alcoholic liver disease) together with 29 age-matchedcontrols. Forty-five per cent of patients with alcoholic liverdisease and 43 per cent with non-alcoholic liver disease showedevidence of parasyrapathetic damage; 11 per cent of patientswith alcoholic liver disease and 12 per cent with non-alcoholicliver disease had sympathetic damage. Forty-five per cent ofpatients with alcoholic liver disease and 22 per cent with non-alcoholicliver disease had peripheral neuropathy on clinical examination.Sixty-eight per cent of those with peripheral neuropathy alsohad autonomic neuropathy. This study confirms that autonomicneuropathy is common in alcoholic patients but the fact thatit is found with comparable frequency in non-alcoholic liverdisease suggests that the neurological defect may be secondaryto the disturbed liver function. The implications of these observationswith regard to prognosis of chronic liver disease are discussed.     

A clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer

The highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma. The clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively. Thirty-five patients had small cell carcinoma and 65 patients non-small cell lung cancer. Clinically, 33 patients had a polymyopathy, of whom 18 had a cachectic myopathy and 15 had a proximal myopathy (two patients had Lambert-Eaton myasthenic syndrome, one presented with dermatomyositis and one had evidence of ectopic ACTH production). Cachexia was more common in non-small cell cancer; proximal myopathy was more common in small cell cancer. Ninety-nine patients had abnormal muscle histology; 74 had type II atrophy, 12 had type I and II atrophy, one had type I atrophy and 12 had necrosis. The majority of patients were affected sub-clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications. Atrophy was not related to the duration of tumour symptoms, ageing, clinical type of myopathy or histological type of lung tumour, and was statistically different from that seen in controls. Qualitatively, the presence of weight loss, muscle wasting and metastatic disease were not factors in the development of atrophy. Similarly, necrosis was not related to the type of lung tumour, the presence of metastases, ageing, weight loss, muscle wasting, duration of tumour symptoms or the clinical form of myopathy. This study demonstrates that lung carcinoma has a direct effect on the motor unit, including atrophy, a necrobiotic myopathy and Lambert-Eaton myasthenic syndrome. Clinical assessment does not accurately assess the 'remote' neuromuscular effects of cancer on the motor unit.     

Myopathy in CRPS-I: Disuse or neurogenic?

The diagnosis Complex Regional Pain Syndrome type I (CRPS‐I) is based on clinical symptoms, including motor symptoms. Histological changes in muscle tissue may be present in the chronic phase of CRPS‐I. Aim of this study was to analyze skeletal muscle tissue from amputated limbs of patients with CRPS‐I, in order to gain more insight in factors that may play a role in changes in muscles in CRPS‐I. These changes may be helpful in clarifying the pathophysiology of CRPS‐I. Fourteen patients with therapy resistant and longstanding CRPS‐I, underwent an amputation of the affected limb. In all patients histological analysis showed extensive changes in muscle tissue, such as fatty degeneration, fibre atrophy and nuclear clumping, which was not related to duration of CRPS‐I prior to amputation. In all muscles affected, both type 1 and type 2 fibre atrophy was found, without selective type 2 fibre atrophy. In four patients, type grouping was observed, indicating a sequence of denervation and reinnervation of muscle tissue. In two patients even large group atrophy was present, suggesting new denervation after reinnervation. Comparison between subgroups in arms and legs showed no difference in the number of changes in muscle tissue. Intrinsic and extrinsic muscles were affected equally. Our findings show that in the chronic phase of CRPS‐I extensive changes can be seen in muscle tissue, not related to duration of CRPS‐I symptoms. Signs of neurogenic myopathy were present in five patients.     

肌电图对手部肌肉萎缩的鉴别诊断价值

目的:探讨肌电图对手部肌肉萎缩的鉴别诊断价值。方法:手部肌肉萎缩患者136例,回顾性分析神经传导、F波和针电极肌电图检测结果。结果:电生理检查显示尺神经单神经病变29例(21.32%),正中神经单神经病变24例(17.65%),尺神经合并正中神经病变17例(12.50%),颈椎病2例(1.47%),臂丛神经损伤2例(1.47%),平山病9例(6.62%),运动神经元病41例(30.15%),肌病7例(5.15%),多发性周围神经病5例(3.68%)。结论:神经电生理检测可以确定手部肌肉萎缩的病变水平和分布。     

Glucocorticosteroid status in chronic alcoholics with and without skeletal muscle myopathy

1. Chronic alcoholism is associated with a selective atrophy of type II skeletal muscle fibres. We studied the glucocorticoid status of chronic alcoholics with and without myopathy to determine if hypercortisolism is responsible for the myopathy. 2. Twenty-four hour urinary cortisol excretion and diurnal serum cortisol measurements were not significantly different in chronic alcoholics, with and without atrophy of type II skeletal muscle fibres. 3. Diurnal serum cortisol variation was normal for both groups of alcoholics studied. None of the patients with myopathy had raised serum cortisol levels. 4. We conclude that chronic alcoholic myopathy is not due to alcohol-related pseudo-Cushing's syndrome.     

Toxic Effects of Ergotamine Used for Migraine

SYNOPSIS
Forty-three patients (6 males and 37 females) who had used ergotamine tartrate 10 mg or more per week continuously over six months were studied. Twenty (47%) of the patients had symptoms and signs compatible with ergotism. This group had not used more ergotamine tartrate than the group, free of symptoms. Of the patients with symptoms, 13 had cardiovascular symptoms and 5 had clinical signs of peripheral neuropathy. Forty-three per cent of the patients examined had a normal electroencephalogram and the remainder relatively slight abnormalities. Eight patients had signs of peripheral neuropathy in their electroneuromyographic examination., The neurophthalmological examinations were all normal. Eighteen of 23 patients examined psychologically and psychiatrically were characterized as neurotic. Concomitant diseases were more often seen in the group with symptoms of ergotism; it is especially notable that all patients with collagen or diabetic disorders belonged to this group.     

Peripheral nerve dysfunction in scleroderma.

Peripheral neuropathy in patients with scleroderma is thought to be rare. We have undertaken a quantitative assessment of peripheral nerve function in 29 patients with either limited cutaneous scleroderma or progressive systemic sclerosis. Tactile thresholds were raised in the fingers in 28 per cent of patients and in the foot in 50 per cent. Two-point discrimination was abnormal in 10 patients, thermal thresholds were abnormal in five and vibration thresholds were abnormal in one. Nerve conduction studies showed abnormalities in six patients, five of whom had clinical signs of a mild peripheral neuropathy: the mean duration of disease in these six patients was 10 years longer than that in the remainder of the patients. There was electrophysiological evidence of a subclinical carpal tunnel syndrome in two patients. The sympathetic skin response was recorded in 16 patients who had not been subjected to sympathectomy for Raynaud's phenomenon, and was abnormal in four. These results indicate that peripheral nerve dysfunction in scleroderma, though mild, is not as uncommon as previously thought. The abnormal cutaneous sensory thresholds may be partly due to altered viscoelastic properties of the skin, but abnormal responses in the lower limbs to tests of tactile sensitivity, the clinical findings and the disturbances of nerve conduction argue in favour of an additional neuropathic process in some patients. Low grade distal nerve trunk ischaemia may be responsible.     

Study of skeletal muscle glycogenolysis and glycolysis in chronic steroid myopathy, non-steroid histochemical type-2 fiber atrophy, and denervation

OBJECTIVE: Muscle biopsies from chronic steroid (glucocorticoid) myopathy, non-steroid histochemical type-2 fiber atrophy, and muscle denervation patients were studied to determine if their glycogen contents, or enzymes involved in glycogenolysis and glycolysis might be related to their fiber atrophy. DESIGN AND METHODS: Fast frozen muscle biopsies from the above patients and from patients later judged by histochemistry to be normal were assayed enzymatically for glycogen content, for enzymes involved in glycogenolysis, and for 6 of the enzymes involved in glycolysis. RESULTS AND CONCLUSION: All three groups of patients had glycogen content, but only the chronic steroid myopathy muscle had statistically less glycogen content than did normal human muscle. All 3 groups had statistically low mean values compared to normal muscles for glycogen phosphorylase activity. This suggests that the biosynthesis and phosphorolysis of glycogen are not involved in muscle fiber atrophy, and glucocorticoid administration does not activate muscle glycogen biosynthesis. Histochemical type-2 fiber atrophy muscles were low compared to normal muscles in three glycogenolysis enzyme activities plus four glycolysis enzyme activities. Muscles from denervation patients were low compared to normal muscles in three glycogenolysis enzyme activities plus five glycolysis enzyme activities. This suggests that muscle denervation may lower the rate of glycolysis enough to fail to provide sufficient pyruvate for mitochondrial ATP biosynthesis, resulting in insufficient protein biosynthesis in both fiber types.     

Skeletal muscle disease in alcoholism

Acute alcoholic myopathy, a syndrome of sudden muscle necrosis, occurs as a result of binge drinking, whereas chronic alcoholic myopathy is a more indolently evolving syndrome of proximal weakness and muscle atrophy that accompanies prolonged alcohol abuse. The characteristic features and management of these disorders are highlighted.     

alpha 1-Antitrypsin phenotypes in cor pulmonale due to chronic obstructive airways disease.

The clinical and radiological features of 23 patients with cor pulmonale due to chronic obstructive airways disease were reviewed. Twenty-two patients had evidence of pulmonary vascular disease and 52 per cent had secondary polycythaemia. Eighteen (78 per cent) had radiological evidence of emphysema. Thirteen of the patients (56.5 per cent) had alpha 1-antitrypsin phenotypes associated with serum deficiency and of these the largest single group was the MZ phenotype (34.8 per cent). No difference was found between the clinical features of patients with the MM phenotype or those associated with alpha 1-antitrypsin deficiency, although radiological emphysema was more common in the latter group (92 per cent compared to 60 per cent).     

The influence of autonomic neuropathy on mortality in insulin-dependent diabetes

Five-year survival was investigated in 506 randomly selected patients with insulin-dependent diabetes mellitus screened for autonomic neuropathy with a series of cardiac autonomic function tests. Of the 484 diabetics traced, 44 (9 per cent) had died. The cumulative 5-year mortality rate was increased more than five-fold in those with autonomic neuropathy: 27 per cent vs. 5 per cent in those with normal autonomic function. Discriminant analysis of survivors and non-survivors showed that autonomic neuropathy was the most important independent predictor of death. Among those who died, autonomic neuropathy was associated with an increased frequency of retinopathy and peripheral neuropathy and a slightly lower frequency of macrovascular disease. Autonomic neuropathy was associated with an increased mortality rate from renal failure, but not from any other causes.     

Clinical approach to the weak patient in the intensive care unit

Motor weakness in a patient in the intensive care unit (ICU) may be related to (1) pre-existing neuromuscular disorder that leads to ICU admission, (2) new-onset or previously undiagnosed neurological disorder, or (3) complications of non-neuromuscular critical illness. Neuromuscular syndromes related to ICU treatment consist of critical illness polyneuropathy, critical illness myopathy, and prolonged neuromuscular blockade, and are now recognized as a frequent cause of newly acquired weakness in ICU patients. Clinical features include quadriparesis, muscle wasting, and difficulty weaning from the ventilator. Evaluation of these patients is based on knowledge of clinical setting and predisposing factors, focused neurological examination, detailed electrophysiological investigation, serum creatine kinase level, other laboratory studies as needed, and histological examination of muscle biopsy. If a central nervous system (brain or spinal cord) lesion is suspected, neuroimaging studies are required. In addition to conventional nerve conduction and needle electromyography, phrenic nerve conduction, diaphragm electromyography, blink reflex, and (recently) the technique of direct muscle stimulation have been employed. Critical illness polyneuropathy is an axonal motor and sensory neuropathy that often follows sepsis and multiorgan failure. Risk factors for critical illness myopathy are corticosteroids and neuromuscular blocking drugs, acute respiratory illness, and organ transplant. Three subtypes (acute necrotizing myopathy, thick myosin filament loss myopathy, and type II fiber atrophy) are recognized. Major differential diagnoses of critical illness related paralysis are incidental Guillain-Barré syndrome and unmasked myasthenia gravis. Rarely, atypical presentation of amyotrophic lateral sclerosis, polymyositis or other myopathies, and precipitation of porphyria or rhabdomyolysis due to drugs used in the ICU have been described. Recently a poliomyelitis-like flaccid paralysis due to West Nile virus infection was reported. A subgroup of patients with myasthenia gravis with muscle-specific tyrosine kinase antibody is noted to present as respiratory crisis. Muscle biopsy in ICU paralysis syndromes may be helpful in arriving at a specific diagnosis or to classify the type of critical illness myopathy. Nerve biopsy is only rarely indicated.     

Autonomic failure and proximal skeletal myopathy in a patient with primary Sj?gren syndrome.

Autonomic failure and proximal skeletal myopathy are rare features of the Sj?gren syndrome (SS). We describe a 51-year-old woman with primary SS who had development of esophageal dysmotility, urinary retention, severe orthostatism, and skeletal myopathy during a 3-month period after the diagnosis of SS. Her symptoms and signs responded well to corticosteroid therapy. Although dysfunction of the peripheral nervous system has a prevalence rate of 20% in patients with SS, most commonly the nerve dysfunction is a sensory deficit, and autonomic neuropathy is less frequent. Autonomic neuropathy due to SS may be underreported. The cause of our patient's myopathy remains undetermined. We speculate that the myopathy was due to either a form of polymyositis or an immune-mediated neuropathy with muscle involvement.     

Acute neuromuscular respiratory failure after ICU discharge

Objective: To describe a syndrome of acute neuromuscular respiratory failure (NM-ARF) caused by ICU-acquired acute myopathy and neuropathy.¶Design: Case series.¶Setting: General Regional University Hospital in Brescia, Italy.¶Patients: Five adult patients with NM-ARF after prolonged ICU stay and successful weaning from the ventilator and ICU discharge.¶Interventions: None.¶Measurements: Clinical signs of NM-ARF, electroneurography and electromyography (ENMG) of peripheral nerves and muscles, and functional assessment of respiratory muscles.¶Results: NM-ARF was diagnosed at the time of (one case), or 1–3 days after, ICU discharge. Limb weakness alarmed the physicians, while the signs of the NM-ARF were initially undetected. In the first observed case the acute respiratory failure was near fatal, and necessitated ICU readmission, while in the other cases 2 weeks of aggressive chest physiotherapy permitted resolution of the respiratory failure. History, clinical course and ENMG indicated the diagnosis of critical illness myopathy and neuropathy (CRIMYNE). Three patients recovered fully, while two had persisting evidence of axonal polyneuropathy several months after the onset.¶Conclusions: Critically ill patients with prolonged ICU stay, sepsis and MOF are at great risk of developing CRIMYNE, which in turn may be responsible for NM-ARF. This latter complication may arise after resolution of the respiratory and cardiac dysfunctions and successful weaning from the ventilator. As NM-ARF may cause unplanned ICU readmission or even unexpected death, strict clinical surveillance and monitoring of respiratory muscle function is recommended after discharge to the general ward of patients with proven NM-ARF. Early intensive chest physiotherapy can resolve the condition.     

Neuromuscular complications of sepsis

Sepsis and multiple organ failure are major problems in medical and surgical intensive care units. Critical illness polyneuropathy occurs in 70% of these patients. Difficulty in weaning from the ventilator is an early sign. Electrophysiological studies are necessary to establish the diagnosis; these studies show an axonal degeneration of peripheral nerve fibres. Recovery occurs in weeks or months, depending upon severity. Muscle biopsy reveals denervation atrophy. Sepsis itself does not induce a neuromuscular transmission defect, but neuromuscular blocking agents may increase the severity of critical illness polyneuropathy. If steroids are used in addition to neuromuscular blocking agents, a severe myopathy may result. Other effects on muscle are cachectic myopathy and panfascicular muscle fibre necrosis. A variety of combinations of these conditions may affect the same patient. Only well-designed prospective studies will determine the true effect of these medications on the neuromuscular system in septic patients.     

Neuromuscular complications of sepsis

Sepsis and multiple organ failure are major problems in medical and surgical intensive care units. Critical illness polyneuropathy occurs in 70% of these patients. Difficulty in weaning from the ventilator is an early sign. Electrophysiological studies are necessary to establish the diagnosis; these studies show an axonal degeneration of peripheral nerve fibres. Recovery occurs in weeks or months, depending upon severity. Muscle biopsy reveals denervation atrophy. Sepsis itself does not induce a neuromuscular transmission defect, but neuromuscular blocking agents may increase the severity of critical illness polyneuropathy. If steroids are used in addition to neuromuscular blocking agents, a severe myopathy may result. Other effects on muscle are cachectic myopathy and panfascicular muscle fibre necrosis. A variety of combinations of these conditions may affect the same patient. Only well-designed prospective studies will determine the true effect of these medications on the neuromuscular system in septic patients.