Fatal hepatic hemorrhage by peliosis hepatis in X-linked myotubular myopathy: A case report

We report a 5-year-old boy with X-linked myotubular myopathy complicated by peliosis hepatis. At birth, he was affected with marked generalized muscle hypotonia and weakness, which required permanent ventilatory support, and was bedridden for life. He died of acute fatal hepatic hemorrhage after using a mechanical in-exsufflator. Peliosis hepatis, defined as multiple, variable-sized, cystic blood-filled spaces through the liver parenchyma, was confirmed by autopsy. To avoid fatal hepatic hemorrhage by peliosis hepatis, routine hepatic function tests and abdominal imaging tests should be performed for patients with X-linked myotubular myopathy, especially at the time of using artificial respiration.     

The value of artificial respiration for patients with myasthenia gravis (author's transl)]

The value of artificial respiration for the bridging of crises in patients with myasthenia gravis is emphasized on some typical cases. Further use, beyond a life-saving indication, for limited periods is described. Such relative indications may exist, when there is not yet complete respiratory failure but when a worsening of myasthenic weakness or cholinergic intoxication may threaten a respiratory crisis. In order to prevent serious complications, early artificial respiration may be indicated in the following situations: deterioration of cardio-pulmonary complications, important changes in therapy, particularly at the start of immuno-suppressive treatment, following tracheobronchial aspiration, in chronic cholinergic intoxication, following operations under general anesthesia, particularly after thymectomy. The importance of careful psychotherapy of myasthenics threatened by respiratory crises and the well-timed information on the chances, intentions and goals of intensive care including artificial respiration is emphasized.     

Treatment of Guillain-Barré syndrome by plasma exchange

Summary Plasma exchange has been used for therapy in eight patients with the Guillain-Barré syndrome. All patients were severely ill. They became tetraplegic and showed cranial nerve involvement. Five patients received assisted respiration, but the others were also at risk of ventilatory insufficiency. Recovery was abrupt in all cases after the first plasma exchanges. Improvement was more marked when plasmapheresis was done on three successive days with plasma exchanges of 2.0–3.01 each in the initial progressive stage of the disease. A considerable advantage of this therapy is the avoidance of continued artificial respiration and nutrition, which both carry the risk of further complications.Parts of the paper were presented at the International Symposion on Plasma Exchange Therapy, Wiesbaden, April 15/16, 1980 [23]     

Effects of electrical stimulation on intracranial pressure and systemic arterial blood pressure in cats: Part I: Stimulation of brain stem

It has been suggested that brain stem activity is involved in the occurrence of pressure waves. Different sites in the brain stem were activated by electrical stimulation in cats anaesthetized with sodium pentobarbital, to produce an increase in intracranial pressure (ICP) similar to the pressure waves. Then the effect of artificial ventilation on the occurrence of the pressure wave-like response produced under spontaneous respiration was examined since Lundberg’s A-waves appear even in artificial ventilation, and B-waves are effaced during artificial ventilation. This results in a brain stem map of ICP and systemic arterial blood pressure (BP) produced by electrical stimulation during spontaneous respiration. Stimulation of the rostral medullary reticular formation produced a rise in ICP and BP in association with a change in the rhythm of the spontaneous respiration; with artificial ventilation, stimulation produced a rise in BP but ICP kept almost at the same level. However, the rise in ICP that was produced by stimulation of the caudal medullary reticular formation during spontaneous respiration also occurred with a depressor response of BP during controlled ventilation. The pressure wave-like responses could be classified, therefore, into two types. One was the response seen during both spontaneous and controlled ventilation, which we designated the ‘α’ wave. The other was the response seen only during spontaneous ventilation, the ‘β’ wave. These observations suggest that the origins of A- and B-waves may be related to those of ‘α’ and ‘β’ waves, respectively.     

Effects of electrical stimulation on intracranial pressure and systemic arterial blood pressure in cats. Part I: Stimulation of brain stem

It has been suggested that brain stem activity is involved in the occurrence of pressure waves. Different sites in the brain stem were activated by electrical stimulation in cats anaesthetized with sodium pentobarbital, to produce an increase in intracranial pressure (ICP) similar to the pressure waves. Then the effect of artificial ventilation on the occurrence of the pressure wave-like response produced under spontaneous respiration was examined since Lundberg's A-waves appear even in artificial ventilation, and B-waves are effaced during artificial ventilation. This results in a brain stem map of ICP and systemic arterial blood pressure (BP) produced by electrical stimulation during spontaneous respiration. Stimulation of the rostral medullary reticular formation produced a rise in ICP and BP in association with a change in the rhythm of the spontaneous respiration; with artificial ventilation, stimulation produced a rise in BP but ICP kept almost at the same level. However, the rise in ICP that was produced by stimulation of the caudal medullary reticular formation during spontaneous respiration also occurred with a depressor response of BP during controlled ventilation. The pressure wave-like responses could be classified, therefore, into two types. One was the response seen during both spontaneous and controlled ventilation, which we designated the 'alpha' wave. The other was the response seen only during spontaneous ventilation, the 'beta' wave. These observations suggest that the origins of A- and B-waves may be related to those of 'alpha' and 'beta' waves, respectively.     

The usefulness of tracheostomy in Duchenne muscular dystrophy ventilated by a chest respirator]

The respiratory dysfunction in Duchenne muscular dystrophy (DMD) patients increases with age. We have attempted various methods of artificial respiration for them. Recently, a non-invasive positive pressure ventilation (NIPPV) became the first choice of respiration, but the chest respirator (CR) was still one of the choices. In our hospital, DMD patients with tracheostomy wearing a CR were alive for longer period, despite of respiratory dysfunction and complications. We studied 6 DMD patients with CR to evaluate nocturnal hypoxia index (NHI) by examining nocturnal periodic hypoxia, and measured oxygen saturation after 20 mg of clomipramine hydrochloride administration before sleep. Three patients had periodic nocturnal hypoxia which was prevented by the clomipramine administration. Two patients with tracheostomy did not exhibit hypoxia. We speculated that pharyngeal hypotonia during REM sleep induces periodic nocturnal hypoxia, therefore the tracheostomy would prevent hypoxia. Next, we examined the pharyngeal MRI on one DMD patient at the same disease stage who also had night NIPPV. We found that his soft palate and tongue shifted downward, which narrowed his pharynx during REM sleep. Consequently we have concluded that noctunnal periodic hypoxia is mainly caured by obstructive sleep apnea. For DMD patients with CR, the tracheostomy may be effective to prevent hypoxia during sleep.     

Loss and renewal of thick myofilaments in glucocorticoid-treated rat soleus after denervation and reinnervation.

Denervation of rat soleus muscle and simultaneous administration of high doses of corticosteroids for 7 days caused marked muscle fiber atrophy and selective loss of thick myofilaments from many muscle fibers by light and electron microscopy. Myosin heavy chain/actin ratios were greatly reduced on polyacrylamide gel electrophoresis. Nerve crush instead of cut permitted reinnervation after 2 weeks and demonstrated the reversibility of the muscle changes within a week after reinnervation. There was formation of new thick filaments and their reintegration into myofibrils without further breakdown, although large areas of Z-disc streaming appeared. The mechanism of A-band breakdown remains obscure, but it presumably starts with limited proteolysis and continues with disaggregation of myosin molecules. This is consistent with our observation that the muscle fibers retain a relatively good reactivity to antibodies against myosin heavy chain 1 week after denervation and corticosteroid administration. A syndrome recalling these experiments is seen in severely asthmatic patients receiving corticosteroids and pharmacologically paralyzed for mechanical respiration.     

The effect of respiratory muscle endurance training in patients with myasthenia gravis

We tested the effect of a home-based respiratory muscle endurance training in patients with mild to moderate generalized myasthenia gravis (MG) on Besinger score, lung function and respiratory muscle endurance. Ten patients performed respiratory muscle endurance training in form of normocapnic hyperpnea training at 50-60% of their maximal voluntary ventilation over 4-6 weeks. MG score, lung function and respiratory endurance were assessed before and after training period. The training significantly increased respiratory endurance from 8.4+/-0.9 min to 17.1+/-1.3 min (p<0.001) and total ventilatory volume from 555+/-87 L to 1081+/-127 L (p=0.004). About 25% of this gain was lost after 3-5 months of detraining. The remaining 75% gain might result from improved neuromuscular coordination rather than muscular training. MG score and lung function, however, did not change. Patients assessed the training effects on physical fitness and respiration as positive. In conclusion, respiratory muscle endurance training can be useful for MG patients as it is enhancing respiratory muscle endurance.     

Evaluation and management of respiratory muscle dysfunction in ALS

Neuromuscular respiratory failure is the cause of death in the majority of patients with ALS. Respiratory muscle dysfunction impacts on quality of life and survival. Attentive management of respiratory muscle weakness is an important aspect of the management of the ALS patient. The respiratory muscles may be thought of as four functional groups: the inspiratory muscles, the expiratory muscles, the accessory muscles of respiration, and the upper airway muscles. This paper will review the structure and function of the neuromuscular respiratory system, and the evaluation and management of respiratory muscle dysfunction in ALS patients.     

Respiratory function after lesions in medulla oblongata

Abstract

Objectives: To evaluate the correlation of lesions of the brain as visualized in cranial magnetic resonance imaging (MRI) and the ability of spontaneous respiration.

Methods: In a prospective concept, cranial MRI after traumatic brain injury or spontaneous intracerebral hemorrhage was performed in 250 subjects at an early stage. All MRI findings were correlated with respiratory conditions on the day of examination. Sedation was performed only to facilitate toleration of the artificial ventilation, as and when necessary. Spontaneous respiration could hence be registered clinically.

Results: Thirteen subjects (5.2%) had no spontaneous respiration. In these cases, a bilateral lesion of the distal medulla oblongata could be displayed. In four of these cases, no additional injuries of the brainstem were detected. These subjects awoke 2 days after the impact with tetraparesis and apnea. Combined lesions of the medulla oblongata and other brainstem regions were found in nine subjects. All these patients died without awakening. In the absence of a bilateral lesion of the caudal medulla oblongata, spontaneous respiration was always possible. A unilateral lesion of the caudal medulla oblongata was visualized in one patient who had the ability of spontaneous respiration.

Conclusions: This work confirms the presence of autonomous respiratory centers within the caudal medulla oblongata that allows sufficient adequate respiration in coma. Respiration ceases in the presence of a bilateral lesion of this area.     

Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia

Friedreich's ataxia (FA) is the most common form of autosomal recessive spinocerebellar ataxia and is often associated with a cardiomyopathy. The disease is caused by an expanded intronic GAA repeat, which results in deficiency of a mitochondrial protein called frataxin. In the yeast YFH1 knockout model of the disease there is evidence that frataxin deficiency leads to a severe defect of mitochondrial respiration, intramitochondrial iron accumulation, and associated production of oxygen free radicals. Recently, the analysis of FA cardiac and skeletal muscle samples and in vivo phosphorus magnetic resonance spectroscopy (31P-MRS) has confirmed the deficits of respiratory chain complexes in these tissues. The role of oxidative stress in FA is further supported by the accumulation of iron and decreased aconitase activities in cardiac muscle. We used 31P-MRS to evaluate the effect of 6 months of antioxidant treatment (Coenzyme Q10 400 mg/day, vitamin E 2,100 IU/day) on cardiac and calf muscle energy metabolism in 10 FA patients. After only 3 months of treatment, the cardiac phosphocreatine to ATP ratio showed a mean relative increase to 178% (p = 0.03) and the maximum rate of skeletal muscle mitochondrial ATP production increased to 139% (p = 0.01) of their respective baseline values in the FA patients. These improvements, greater in prehypertrophic hearts and in the muscle of patients with longer GAA repeats, were sustained after 6 months of therapy. The neurological and echocardiographic evaluations did not show any consistent benefits of the therapy after 6 months. This study demonstrates partial reversal of a surrogate biochemical marker in FA with antioxidant therapy and supports the evaluation of such therapy as a disease-modifying strategy in this neurodegenerative disorder.     

Peculiar septic responses in traumatic tetraplegic patients

Patients with a high level tetraplegia from a spinal injury have only been able to survive the critical initial period since the development of modern resuscitation techniques including artificial respiration. However, their lives are still threatened by many complications, such as decubitis ulcers, infections and respiratory failure. We describe four young tetraplegic patients who developed an unusual sepsis pattern several years after the injury. The sepsis was accompanied by hypothermia, leukopenia and mental deterioration. This peculiar 'silent' sepsis may also occur in elderly people who are not paralysed. The question arises, therefore, if the chronic spinal cord injured patient may become 'prematurely aged'.     

Effect of exercise on the motor unit

The motoneuron part of this review deals with the changes in recruitment and firing rates of the motor unit types upon changes from a physically inactive life to endurance or strength training. The muscle fibers react to prolonged exercise by adaptation to a higher level of performance. A matter of discussion is the prerequisites for a transformation between the basic muscle fiber types, slow twitch and fast twitch, during voluntary (transsynaptic) activity, which is demonstrated after artificial nerve stimulation. The review includes current knowledge of muscle fiber transformation as an adaptive response to increased usage either by electrical stimulation or by transsynaptic neuronal activity. The metabolic adaptation related to increased endurance is reviewed with special reference to effects on muscle fibers. The increase in strength as a result of high resistance training is mainly the result of increased muscle cross-section. Whether this is solely the result of an increase in size of individual fibers or an increased fiber number is a controversial matter.     

Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice.

The mdx mouse serves as animal model for Duchenne muscular dystrophy. Energy status in muscles of mdx mice is impaired and we have demonstrated recently that the energy precursor creatine exerts beneficial effects on mdx skeletal muscle cells in culture. Here we show that feeding a creatine-enriched diet to new-born mdx mice strongly reduced the first wave of muscle necrosis four weeks after birth. Necrosis of the fast-twitch muscle extensor digitorum longus was inhibited by 63+/-14% (P<0.0001) while necrosis of the slow-twitch soleus muscle was not significantly decreased. In addition, using chemically skinned muscle fibres, we found that mitochondrial respiration capacity was decreased by about 25% in mdx-derived fibres and that long-term creatine-feeding restored respiration to wild-type levels. These results provide evidence that creatine supplementation in mdx mice improves muscle health and may provide a scientific basis for its use as adjuvant therapy in Duchenne muscular dystrophy.     

Mitochondrial respiratory chain function in skeletal muscle of ALS patients

Evidence implicating mitochondrial dysfunction in the central nervous system of patients with sporadic amyotrophic lateral sclerosis (SALS) has recently been accumulating. In contrast, data on mitochondrial function in skeletal muscle in SALS are scarce and controversial. We investigated the in situ properties of muscle mitochondria in patients with early-stage SALS and sedentary (SED) controls using the skinned fiber technique to determine whether respiration of muscle tissue is altered in early-stage SALS in comparison with SED. Musculus vastus lateralis biopsies were obtained from 7 SED group members and 14 patients with early-stage SALS (mean disease duration, 9 months). Muscle fibers were permeabilized with saponine and then skinned and placed in an oxygraphic chamber to measure basal (V(0)) and maximal (V(max)) adenosine diphosphate-stimulated respiration rates and to assess mitochondrial regulation by adenosine diphosphate. Muscle oxidative capacity, evaluated with V(max), was identical in patients in the SALS and SED groups (V(0): SALS, 1.1 +/- 0.1; SED, 0.8 +/- 0.1, micromol 0(2). min(-1). gm(-1)dw and V(max): SALS, 3.1 +/- 0.3; SED, 2.5 +/- 0.3, micromol 0(2). min(-1). gm(-1)dw). This study shows an absence of large mitochondrial damage in skeletal muscle of patients with early-stage SALS, suggesting that mitochondrial dysfunction in the earlier stages of SALS is almost certainly not systemic.     

Tumor necrosis factor and interleukin-6 in critical illness polyneuromyopathy

Critical illness polyneuromyopathy (CIPN) occurs in critically ill patients on artificial respiration. The pathophysiology of this disease is unknown. Because of the strong association with sepsis, the levels of cytokines, TNF and IL-6 were measured several times daily in patients having CIPN and in a control group of critically ill patients without CIPN. The diagnosis of CIPN was made on clinical criteria. Patients with CIPN had no significantly elevated levels of TNF or IL-6 as compared to controls.     

On the pathogenesis of mitochondrial myopathies

Summary The intra-arterial injection of 2–4 dinitrophenol, an uncoupler of oxidative phosphorylation, resulted in the production of ragged red fibers.The ultrastructure of these fibers showed intramitochondrial paracrystalline inclusions, laminar and fingerprint bodies. Antimycin A and oligomycin injection (which inhibit mitochondrial respiration) only caused swelling and disruption of the mitochondria. An increase in muscle lactic acid, decrease in ATP, glycogen and phosphocreatine was observed after the injection of all these agents. This indicates that lactic acidosis has no significant role in the pathogenesis of mitochondrial pathology. It is concluded that mitochondrial changes are a morphological expression of uncopuled but intact mitochondrial respiration.     

Neuromuscular Electrical Stimulation As a Possible Means to Prevent Muscle Tissue Wasting in Artificially Ventilated and Sedated Patients in the Intensive Care Unit: A Pilot Study

Objective: The aim of this study was to explore if electrical stimulation could prevent muscle atrophy. Material and Methods: Patients were hospitalized for postoperative coronary artery bypass graftin, chronic obstructive pulmonary disease, ventilatory failure, or acute cerebro‐vascular accident, and were divided into an intervention group or a control group. The intervention group underwent daily 30 minute training with an intermittent neuromuscular electrical stimulation applied to the right quadriceps muscle. Heart rate, respiration rate, systolic and diastolic blood pressure, and oxygen saturation were monitored before, during, and after electrical stimulation. Circumference of both thighs was measured. Results: The intervention resulted in a significant reduction of muscle atrophy in the stimulated as compared with the non‐stimulated limb (p < 0.05), without making any impact on cardiovascular, respiratory and, hemodynamic characteristics. Conclusions: Muscle atrophy is prevented by intermittent neuromuscular electrical stimulation while this intervention showed no obvious impact on the cardio‐respiratory conditions of the patients.     

A serial muscle biopsy study in a case of congenital fiber-type disproportion associated with progressive respiratory failure

The muscle fiber diameter and distribution were studied in serial muscle biopsy specimens taken at the ages of 21 months and 8 years in a girl with congenital fiber type disproportion. The patient was floppy from birth and showed delayed motor development. Progressive respiratory failure developed from the age of 8, which required artificial respiration during the night. The mean diameters of type 1 fibers at the ages of 21 m and 8 y were 10 mu and 21 mu, and those of type 2 fibers 32 mu and 61 mu, respectively. Whereas most type 1 fibers were hypotrophic in both biopsy specimens, a small number of type 1 fibers (approximately 15%) were normal-sized or hypertrophic, measuring 50 to 90 mu, in the second biopsy specimen, which were thought to have arisen on the maturation of normal-sized or hypertrophic type 1 fibers measuring 15 to 35 mu in the first biopsy specimen. Excessive hypotrophy of type 1 fibers was considered to be responsible for the progressive respiratory failure due to weakness of the diaphragm. The pattern of type 1 fiber evolution from the first to the second biopsy specimen suggested that dysmaturation of spinal motoneurons innervating type 1 muscle fibers would be involved in the pathophysiology of the fiber type disproportion in this case.     

Sympathetic facilitation of hyperalgesia evoked from myofascial tender and trigger points in patients with unilateral shoulder pain.

OBJECTIVE: To provide evidence for the sympathetic-sensory interaction within a trigger point, which may contribute to local and referred pain and sympathetic symptoms in myofascial pain syndrome. METHODS: Pressure pain threshold (PPT) was measured from a trigger point in the painful side, from a tender point in the non-painful side in the infraspinatus muscles, and from a normal control point in the tibialis anterior muscle in 21 patients with unilateral shoulder pain. In addition, pressure threshold for eliciting referred pain (referred pain threshold, PTRP) was determined, then the intensity was measured of local and referred pain evoked by a pressure equal to 1.5 times PRPT, applied at the trigger point, in 11 patients. All measurements were taken during normal respiration and elevated intrathoracic pressure (EITP). RESULTS: PPT was significantly lower at the trigger than tender points during normal respiration (P=0.001). PPT decreased significantly at both the tender and trigger points during EITP compared with normal respiration (P<0.001). Significant decreases in referred pain threshold and increases in local and referred pain intensities were seen during EITP than normal respiration (all, P<0.01). CONCLUSIONS: These results provide evidence of sympathetic facilitation of mechanical sensitization and the local and referred muscle pain. SIGNIFICANCE: Sympathetic hyperactivity needs to be considered during the clinical evaluation and management of myofascial pain syndrome.