Enfermedades neuromusculares catastrófi cas

Neurologists should anticipate and recognize the onset of respiratory failure in patients with neuromuscular diseases. Symptoms vary according to the speed of onset of respiratory muscle weakness. Catastrophic situations usually occur in three clinical scenarios: 1) incorrect management of acute respiratory failure of neuromuscular origin, autonomic dysfunction or during general anaesthesia of patients with neuromuscular diseases ; 2) incorrect prognosis and treatment due to the lack of a correct diagnosis. This situation is more common in ventilated patients with associated muscular weakness, acute neuropathies or motor neuron disease, and 3) inappropriate medical intervention in patients with neuromuscular disease with a definitive diagnosis but longstanding disease (amyotrophic lateral sclerosis, spinal muscular atrophy, myotonic dystrophy and other muscular dystrophies).     

Late onset Pompe disease: clinical and neurophysiological spectrum of 38 patients including long-term follow-up in 18 patients

To describe the clinical and neurophysiological spectrum and prognosis in a large cohort of biochemically and genetically proven late onset Pompe patients. Thirty-eight diagnosed with late onset Pompe disease at our neuromuscular department during 1985 and 2006 are described in detail. The mean delay from onset of symptoms or first medical consultation until diagnosis was 10.4 and 7.1 years, respectively. A different diagnosis was suggested in 11 of 38 patients. Ten patients underwent repeated muscle biopsies before diagnosis of Pompe disease was established. Limb girdle weakness was the most frequent presenting sign. Six patients complained of myalgia. Wolf-Parkinson-White syndrome was found in 3 of 38 patients. Respiratory failure preceded the onset of overt limb muscle weakness in three patients. The course of the patients was progressive in all, but there was a wide variety of progression, which did not correlate with the age of disease onset. In 71% of the patients, neurophysiological investigations revealed a myopathic EMG pattern, half of the patients had spontaneous activity including complex repetitive discharges. A normal EMG was found in 9% of the patients. Nerve conduction studies were normal in all. Pompe disease should be taken into consideration in patients with unexplained limb girdle muscular weakness with respiratory failure. Cardiac manifestations may not be restricted to infantile Pompe disease.     

Neuromuscular disease and respiratory failure

Neurologists should be able to anticipate and recognise the onset of respiratory failure in patients with neuromuscular disorders. Symptoms will differ depending on the speed of onset of the respiratory muscle weakness. Careful monitoring of respiratory function is particularly important in acute disorders such as Guillain-Barré syndrome. Patients with an unrecognised neuromuscular disorder may occasionally present with respiratory failure. Important investigations include vital capacity, mouth pressures, arterial blood gases, chest x ray and sometimes overnight respiratory monitoring. Patients with Guillain-Barré and other acute conditions may require short-term ventilatory support in the intensive care unit. Patients with some chronic disorders, such as motor neuron disease and Duchenne dystrophy, can be successfully treated with non-invasive ventilation, usually in collaboration with a respiratory physician. New-onset weakness of limb and respiratory muscles in the intensive care unit is usually due to critical illness myopathy or critical illness polyneuropathy, and treatment is supportive.     

Ventilatory support in facioscapulohumeral muscular dystrophy

Respiratory insufficiency due to respiratory muscle weakness is a common complication of many neuromuscular diseases. The prevalence of respiratory failure in facioscapulohumeral muscular dystrophy (FSHD) is unknown. The authors identified 10 FSHD patients on nocturnal ventilatory support at home, representing approximately 1% of the Dutch FSHD population. Severe muscle disease, wheelchair dependency, and kyphoscoliosis appeared to be risk factors for respiratory failure.     

Intermittent negative pressure ventilation in the treatment of respiratory failure in progressive neuromuscular disease

Five men with degenerative neuromuscular diseases (three with amyotrophic lateral sclerosis [ALS] and two with Duchenne's muscular dystrophy [DMD]) who had respiratory failure were treated with intermittent negative pressure ventilation (NPV). One patient with ALS in severe acute respiratory failure was successfully treated with NPV alone. This patient and two other ALS patients in chronic respiratory failure with PaCO2 elevation stabilized or improved their vital capacity (VC) and lowered their PaCO2 after 5 to 11 weeks of therapy. Finally, intermittent NPV was used to replace 24-hour positive pressure ventilation in two patients with DMD. It is concluded that intermittent NPV may stabilize or temporarily improve the respiratory status in patients with progressive neuromuscular diseases.     

Selenoprotein N muscular dystrophy: differential diagnosis for early-onset limited mobility of the spine

Early spinal rigidity is a nonspecific feature reported in diseases such as neuromuscular and central movement disorders. We present a male patient with rigid spine muscular dystrophy caused by newly identified compound heterozygote mutations of the selenoprotein N gene and discuss this disease as a possible differential diagnosis for early-onset reduced spine mobility. Rigid spine muscular dystrophy is a rare myopathy presenting in childhood with a typical combination of stable or slowly progressive mild to moderate muscle weakness, limitation in flexion of the spine, and progressive restrictive ventilatory disorder. The clinical features of our patient include early-onset rigidity of his spine, scoliosis, mild muscular weakness predominantly of neck and trunk flexors, and restrictive ventilatory disorder. Biopsy of the biceps muscle revealed nonspecific myopathic changes, and molecular analysis confirmed the diagnosis of rigid spine muscular dystrophy. Thus, neuromuscular diseases such as muscular dystrophy must be considered in all patients presenting with early spinal rigidity, and genetic determination is a possible way to determine the diagnosis.     

Mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13

Distal spinal muscular atrophy is a heterogeneous group of neuromuscular disorders caused by progressive anterior horn cell degeneration and characterized by progressive motor weakness and muscular atrophy, predominantly in the distal parts of the limbs. Here we report on chronic autosomal recessive distal spinal muscular atrophy in a large, inbred family with onset at various ages. Because this condition had some of the same clinical features as spinal muscular atrophy with respiratory distress, we tested the disease gene for linkage to chromosome 11q and mapped the disease locus to chromosome 11q13 in the genetic interval that included the spinal muscular atrophy with respiratory distress gene (D11S1889-D11S1321, Z(max) = 4.59 at theta = 0 at locus D11S4136). The sequencing of IGHMBP2, the human homologue of the mouse neuromuscular degeneration gene (nmd) that accounts for spinal muscular atrophy with respiratory distress, failed to detect any mutation in our chronic distal spinal muscular atrophy patients, suggesting that spinal muscular atrophy with respiratory distress and chronic distal spinal muscular atrophy are caused by distinct genes located in the same chromosomal region. In addition, the high intrafamilial variability in age at onset raises the question of whether nonallelic modifying genes could be involved in chronic distal spinal muscular atrophy.     

Muscle diseases with prominent joint contractures: Main entities and diagnostic strategy

Muscle diseases may have various clinical manifestations including muscle weakness, atrophy or hypertrophy and joint contractures. A spectrum of non-muscular manifestations (cardiac, respiratory, cutaneous, central and peripheral nervous system…) may be associated. Few of these features are specific. Limb joint contractures or spine rigidity, when prevailing over muscle weakness in ambulant patients, are of high diagnostic value for diagnosis orientation. Within this context, among several disorders, four groups of diseases should systematically come to mind including the collagen VI-related myopathies, the Emery–Dreifuss muscular dystrophies, the SEPN1 and FHL1 related myopathies. More rarely other genetic or acquired myopathies may present with marked contractures. Diagnostic work-up should include a comprehensive assessment including family history, neurological, cardiologic and respiratory evaluations. Paraclinical investigations should minimally include muscle imaging and electromyography. Muscle and skin biopsies as well as protein and molecular analyses usually help to reach a precise diagnosis. We will first describe the main muscle and neuromuscular junction diseases where contractures are typically a prominent symptom of high diagnostic value for diagnosis orientation. In the following chapters, we will present clues for the diagnostic strategy and the main measures to be taken when, at the end of the diagnostic work-up, no definite muscular disease has been identified.     

Post-polio syndrome. A case report

Certain acute anterior poliomyelitis survivors express complaints of abnormal fatigue, weakness and muscular atrophy many years after acute onset. These are basic clinical symptoms of so-called post-polio syndrome (PPS). PPS is characterized by a relatively slow, but progressive pathological muscular process, in some cases leading to functional impairment of daily living and professional activity. Breathing, speaking and swallowing impairment are common but not severe medical problems of post-polio patients. Diagnosis is usually based on a typical medical history, electromyographic investigation and exclusion of other diseases presenting similar features. We report a case of PPS in a 49-year-old woman diagnosed in the Neurological Department in Zabrze. Thirty six years after acute anterior poliomyelitis with partial recovery, new symptoms of fatigue, muscular atrophy, exertional dyspnea, walking impairment and joint pain developed. Electromyography revealed features of coexisting spinal denervation and reinnervation in tested muscles. The differential diagnosis excluded other neuromuscular diseases. The patient fulfilled clinical and electromyographic criteria of PPS.     

Neuromuscular disease: health care accessibility in the Nord-Pas-de- Calais region

A survey was conducted to estimate accessibility to current diagnostic techniques for patients with neuromuscular disease living in the Nord-Pas-de-Calais. In association with the "Association fran?aise contre les myopathies", we invited 200 adults with neuromuscular disease to fill out a questionnaire concerning diagnosis of their neuromuscular disease and medical and paramedical follow-up. Each subject answered the questionnaire anonymously providing data on sociodemographic items, diagnosis and medical and paramedical follow-up. The results showed a lack of follow-up for lung disease whereas respiratory failure is known as a frequent complication of neuromuscular disease. Genetic counselling was not suggested often enough. A large proportion (80 p. 100) of the patients had had physiotherapy. Whereas cardiomyopathy and orthopedic buckling with subsequent decreased autonomy are observed in 90 p. 100 of patients with Duchenne muscular dystrophy, only 42 p. 100 of the patients with this disease were followed by a cardiologist and a physical therapists. We suggest more cooperation between specialists in order to improve medical care for patients with neuromuscular diseases.     

Neuromuscular disorders and acute respiratory failure: diagnosis and management

Respiratory failure could result from a cardiopulmonary or a primary neurological disease. The latter could happen as a result of involvement of the central nervous system or a neuromuscular disease. Different neuromuscular diseases could result in respiratory failure by causing significant weakness of the respiratory and upper airways muscles. When confronted with a patient who presents with respiratory failure, the first task of the clinician is to secure the airways and stabilize the hemodynamic condition. The next step is the diagnostic approach and potentially a disease specific treatment, which is the focus of this review.     

Warning signs of imminent respiratory failure in neurological patients

Critically ill neurological patients often need ventilatory assistance. After acute central nervous system insults, the inability to protect the airway and impaired central respiratory drive can only be managed with endotracheal intubation and mechanical ventilation. In patients with acute or worsening neuromuscular disorders, diaphragmatic failure and pronounced bulbar weakness may necessitate intubation to assist in the work of breathing or to prevent upper airway obstruction. Simple respiratory function tests performed at the bedside should be used to monitor patients with progressive neuromuscular respiratory insufficiency. Noninvasive positive pressure ventilation plays an important role in the management of respiratory failure in patients with neuromuscular respiratory failure, and its indications may be expanded in the future.     

Challenges and opportunities in clinical trials for spinal muscular atrophy

Spinal muscular atrophy (SMA) is the most common fatal neuromuscular disease of infancy. SMA type I is the most severe and mortality is usually due to respiratory failure. In type II the disability is of later onset and less severe, and prognosis has improved primarily due to supportive care. Type III is the mildest form with onset usually of weakness in adolescence or young adulthood. SMA is an autosomal recessive disorder with deletions or mutations of the gene at the 5 q11 locus. There is no specific prevention or treatment, but current progress toward potential therapies has been substantial and several candidates including histone deacetylase (HDAC) inhibitors are under consideration for further evaluation. The authors sought to address the challenges and opportunities for testing new therapies for SMA.     

Idiopathic adult‐onset nemaline myopathy presenting with isolated respiratory failure

Idiopathic adult‐onset nemaline myopathy is a rare condition of unknown etiology that usually presents with proximal weakness. This case study reports a 60‐year‐old woman who presented with isolated type 2 respiratory failure secondary to bilateral hemidiaphragm weakness. A left vastus medialis muscle biopsy examined under light microscopy revealed appearances typical of nemaline myopathy. Electron microscopy confirmed the presence of nemaline rods in most muscle fibers, thus establishing idiopathic adult‐onset nemaline myopathy as the cause of her respiratory failure. Our patient's presentation highlights the importance of considering neuromuscular weakness as a cause of respiratory failure. Unless appropriate tests are performed—including a muscle biopsy, if indicated—specific neuromuscular diseases are easily missed. This can lead to inappropriate counseling and treatment. Muscle Nerve 39: 406–408, 2009     

Management of the respiratory complications of neuromuscular diseases in the pediatric intensive care unit

Pediatric neuromuscular diseases such as Duchenne muscular dystrophy and spinal muscular atrophy cause pulmonary compromise. In severely affected patients, upper respiratory tract infections exacerbate lower respiratory tract secretion retention, with the potential for pneumonia, pulmonary atelectasis, and respiratory failure. In the pediatric intensive care unit, effective treatment includes noninvasive positive pressure ventilation and manual and mechanical mucus clearance techniques. A practical approach to commonly encountered respiratory complications in pediatric neuromuscular diseases is presented in this review.     

Treatment of Type I Spinal Muscular Atrophy With Noninvasive Ventilation and Gastrostomy Feeding

Type I spinal muscular atrophy (SMA) is a rapidly progressive, degenerative neuromuscular disease of infancy. In severe SMA, weakness, hypotonia, and bulbar involvement lead to progressive respiratory insufficiency and swallowing dysfunction, which are frequently complicated by aspirations. There are few studies reported in the literature that address the respiratory management of type I SMA. This article reports the results of treating four patients with infantile SMA with noninvasive positive pressure ventilation and gastrostomy feeding. All patients had gastroesophageal reflux disease, which was managed medically. Despite these therapies, survival was only 1 to 3.5 months after presenting with severe aspirations. The treatment strategy, which can be effective in less rapidly progressive neuromuscular diseases, did not alter the very poor prognosis of type I SMA. The treatment options are reviewed, and a strategy designed to optimize quality of life for infants with this fatal disease is presented.     

Familial facioscapulohumeral muscular dystrophy: phenotypic diversity and genetic abnormality

We report two cases showing facioscapulohumeral muscular dystrophy (FSHD) with phenotypic diversity but the same genetic abnormality detected by a p13E-11 probe. The proband, a 26-year-old woman, showed an early onset, tortuosity of retinal arterioles and respiratory failure. The 53-year-old mother of the proband had limb-girdle (L-G) type muscular weakness with very mild facial involvement. Muscle biopsy showed perivascular cell infiltration in both patients. These cases suggest that the phenotypic diversity ranges from L-G type weakness to severe respiratory failure in FSHD family.     

Progressive muscular atrophy: clinical and laboratory study in eleven patients

Progressive muscular atrophy (PMA), an infrequent type of motor neuron disease (MND), is a predominantly lower motor neuron degeneration, causing muscle wasting and weakness with loss of weight and fasciculations. The diagnosis is based on rigid criteria, considering clinical aspects and eletroneuromyography findings. Blood tests and radiological investigation are necessary to look for other diagnosis mimicking PMA. We herein present 11 patients with PMA (5.9% of all our MND patients), 9 men and 2 women, which onset of symptoms occurred mainly under de age of 50, with a mean of 45.5 years. Cramp was the most frequent symptom preceding muscular weakness. Muscle pain, fatigue and fasciculations were also cited as starting symptoms. Asymmetric weakness of the arms was the most frequent pattern of onset of the disease. Bulbar muscular weakness developed in all patients during the course of the disease. Predisposing factors and distinctive clinical outcome was not observed in any of the patients. Ophthalmoparesis and sphincter dysfunction were seen in two patients who had a prolonged time in artificial respiratory assistance. Immunosuppressive therapy was ineffective in all patients. Progressive course was seen in all cases and the mean survival time was 44 months.     

Mitochondrial respiratory chain dysfunction in various neuromuscular diseases.

The mitochondrial respiratory chain function and the occurrence of mitochondrial respiratory chain dysfunction were determined in various neuromuscular diseases. The mitochondrial complexes I-V and citrate synthase in the skeletal muscle taken from 75 orthopaedic surgical patients excluding neuromuscular diseases (control subjects) and 26 patients with various neuromuscular diseases (7 patients with Duchenne muscular dystrophy, 3 patients with spinal muscular atrophy, 6 patients with mitochondrial diseases, 7 patients with type II fibre atrophy and 3 patients with neuropathy) were assayed. Of 26 patients, results of analysis of 3 patients (1 Duchenne muscular dystrophy, 1 spinal muscular atrophy and 1 type II fibre atrophy) were excluded because the citrate synthase activities in their muscle homogenate were less than third percentile of the normal controls. As compared to the control subjects by using Student's t-test, all studied groups of patients had significantly lower activities of more than one or two mitochondrial complexes (p<0.05). However, a significantly higher activity of mitochondrial complex I was observed in patients with mitochondrial diseases (p<0.05). These findings will require further study to elucidate the pathogenesis and role of secondary mitochondrial respiratory chain dysfunction in such neuromuscular diseases.     

Chronic respiratory failure in limb-girdle muscular dystrophy: Successful long-term therapy with nasal bilevel positive airway pressure

Chronic respiratory failure is a major factor contributing to mortality in progressive neuromuscular disorders. Among the muscular dystrophies, respiratory failure most commonly occurs with Duchenne dystrophy, while in Becker, limb-girdle, and facioscapulo-humeral dystrophies, respiratory failure is infrequent and generally occurs in the more severe cases that have progressed to a nonambulatory, advanced functional stage. We report two brothers with a myopathic disease in which the distribution of weakness, initial clinical course, heredity, and muscle pathology most closely resembled a limb-girdle type of dystrophy. Both brothers, however, presented with chronic alveolar hypoventilation and respiratory failure when their locomotor disabilities were still mild. Respiratory failure was reversed, and satisfactory ventilation has been maintained for more than a year using a type of non-invasive intermittent positive pressure ventilation, with a bilevel positive airway pressure device (Bi-PAP), administered through a nasal mask during sleeping hours. These cases demonstrate an unusual presentation of limb-girdle dystrophy, and document that nocturnal, nasal administration of continuous airway pressure using the Bi-PAP device may be sufficient to maintain adequate long-term ventilation in some patients with neuromuscular causes of respiratory failure, and thus significantly improve quality of life and delay the need for more complex or invasive forms of assisted ventilation.