Acary Souza Bulle de Oliveira

Amyotrophic lateral sclerosis: new perpectives and update

Amyotrophic lateral sclerosis (ALS), Charcot’s disease or Lou Gehrig’s disease, is a term used to cover the spetrum of syndromes caracterized by progressive degeneration of motor neurons, a paralytic disorder caused by motor neuron degeneration. Currently, there are approximately 25,000 patients with ALS in the USA, with an average age of onset of 55 years. The incidence and prevalence of ALS are 1-2 and 4-6 per 100,000 each year, respectively, with a lifetime ALS risk of 1/600 to 1/1000. It causes progressive and cumulative physical disabilities, and leads to eventual death due to respiratory muscle failure. ALS is diverse in its presentation, course, and progression. We do not yet fully understand the causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. In this chapter, we will discuss the diagnosis, treatment, and how to cope with impaired function and end of life based on of our experience, guidelines, and clinical trials. Nowadays ALS seems to be a more complex disease than it did two decades – or even one decade – ago, but new insights have been plentiful. Clinical trials should be seen more as experiments on pathogenic mechanisms. A medication or combination of medications that targets more than one pathogenic pathway may slow disease progression in an additive or synergistic fashion.

Botulinum Neurotoxin Type A in Neurology: Update

This paper reviews the current and most neurological (central nervous system, CNS) uses of the botulinum neurotoxin type A. The effect of these toxins at neuromuscular junction lends themselves to neurological diseases of muscle overactivity, particularly abnormalities of muscle control. There are seven serotypes of the toxin, each with a specific activity at the molecular level. Currently, serotypes A (in two preparations) and B are available for clinical purpose, and they have proved to be safe and effective for the treatment of dystonia, spasticity, headache, and other CNS disorders in which muscle hyperactivity gives rise to symptoms. Although initially thought to inhibit acetylcholine release only at the neuromuscular junction, botulinum toxins are now recognized to inhibit acetylcholine release at autonomic cholinergic nerve terminals, as well as peripheral release of neuro-transmitters involved in pain regulation. Its effects are transient and nondestructive, and largely limited to the area in which it is administered. These effects are also graded according to the dose, allowing individualized treatment of patients and disorders. It may also prove to be useful in the control of autonomic dysfunction and sialorrhea. In over 20 years of use in humans, botulinum toxin has accumulated a considerable safety record, and in many cases represents relief for thousands of patients unaided by other therapy.

Hepatitis C virus: a rare manifestation--remitting relapsing central and peripheral demyelination.

The most frequent neurologic manifestations of hepatitis C virus infection include peripheral neuropathy axonal type and central nervous system (CNS) vasculitis. Affected patients usually have cryoglobulinemia and other signs of vasculitis. Demyelinating lesions, both central and peripheral are rarely described. We present a case of simultaneous peripheral nervous system and CNS demyelination that comes in relapsing episodes, with negative cryoglobulins.

MUNIX: Reproducibility and clinical correlations in Amyotrophic Lateral Sclerosis

OBJECTIVE To study the reproducibility, diagnostic yield to detect denervation, and clinical correlations of the Motor Unit Number Index (MUNIX) in subjects with Amyotrophic Lateral Sclerosis (ALS). METHODS MUNIX evaluation was performed in three muscles twice on the same day to assess reproducibility. Cut-off values for the MUNIX were based on data from 51 healthy subjects (controls) to evaluate the sensitivity of the technique to detect denervation in 30 subjects with ALS. RESULTS The method had good reproducibility. The variability was greater in the ALS group. In 23 ALS subjects (77%), low MUNIX values were detected. Most of the muscles with low MUNIX had also low compound muscle action potential (CMAP) and strength, but these parameters were normal in 9% of muscles. According to ROC curve analysis, MUNIX was generally accurate (AUC=0.9504) for discriminating between healthy individuals and subjects with at least one denervated muscle. CONCLUSIONS MUNIX variability was higher in the ALS group. The method showed good diagnostic performance for the detection of denervation in a sample of patients with ALS. SIGNIFICANCE This study demonstrated that in addition to being a quantitative tool MUNIX can detect denervation in subjects with ALS.

Thomsen or Becker myotonia? A novel autosomal recessive nonsense mutation in the CLCN1 gene associated with a mild phenotype

We describe a large Brazilian consanguineous kindred with 3 clinically affected patients with a Thomsen myotonia phenotype. They carry a novel homozygous nonsense mutation in the CLCN1 gene (K248X). None of the 6 heterozygote carriers show any sign of myotonia on clinical evaluation or electromyography. These findings confirm the autosomal recessive inheritance of the novel mutation in this family, as well as the occurrence of phenotypic variability in the autosomal recessive forms of myotonia. Muscle Nerve, 2012

Relação entre degeneração do trato córtico-espinhal através de ressonância magnética e escala funcional (ALSFRS) em pacientes com esclerose lateral amiotrófica

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the corticospinal tract. ALS functional rating scale (ALSFRS) is a questionnaire that quantifies motor deficits, while diffusion tensor imaging (DTI) evaluates the integrity of fibers through the fractional anisotropy (FA). In the present study, seven ALS patients were evaluated by ALSFRS and immediately submitted to DTI, getting FA values in the following regions: cerebral peduncle (PC), internal capsule (CI) and the white matter under the primary motor cortex (M1), secondary motor cortex (M2) and somesthetic cortex (SI). A control group was constituted by twelve healthy individuals. FA values in patients were significantly lower when compared with controls, with a tendency to higher reductions in the right hemisphere and more inferior regions. Interestingly, FA values were reduced in somesthetic area. No correlation was observed between symptoms duration and FA values. Despite the correlation observed between ALSFRS scores and degeneration in PC and CI, our results suggest that this subjective scale is not a good parameter for the evaluation of the structural damage in encephalic portions of the corticospinal tract.

The mutations m.5628T>C and m.8348A>G in single muscle fibers of a patient with chronic progressive external ophthalmoplegia

We identified a double mutation in a patient with chronic progressive external ophthalmoplegia, located in the tRNA(Ala) (m.5628T>C) and tRNA(Lys) (m.8348A>G) genes. Both mutations were previously described separately and considered pathogenic, however the same mutations were also reported as polymorphisms or phenotype modulator. We analyzed the proportion of each mutation in isolated muscle fibers by single fiber-polymerase chain reaction to investigate the contribution of each mutation to mitochondrial deficiency. Our findings demonstrated that the mutations were heteroplasmic in skeletal muscle and both mutations were present in all single muscle fibers. The proportions of the m.5628T>C mutation were not significantly different between normal and cytochrome-c-oxidase (COX) deficient fibers. However, a significant higher proportion of the m.8348A>G mutation was observed in COX deficient fibers. Homoplasmic m.8348A>G was only observed in COX negative fibers. In conclusion, we provide a piece of evidence toward the pathogenicity of the m.8348A>G mutation and suggest that m.5628T>C is probably a neutral polymorphism.

Improving the reproducibility of Motor Unit Index Number (MUNIX)

Introduction: Reproducibility is an important aspect of any method intended to be a marker of disease progression. In this study we investigated approaches for improving motor unit number index (MUNIX) reproducibility. Methods: We used the intraclass correlation coefficient (ICC) and the coefficient of variation (CV) to study reproducibility in healthy subjects. We tested reproducibility between test and retest of a single MUNIX from 3 different muscles (S‐MUNIX) and also of the mean of a set of 3 measurements from these same muscles (M‐MUNIX). Results: M‐MUNIX was more reproducible than S‐MUNIX. The CV showed a greater improvement than the ICC in all 3 muscles. Conclusions: M‐MUNIX may be a valuable approach for following motor unit loss, because it is more replicable than MUNIX. This may be especially relevant in amyotrophic lateral sclerosis patients, in whom MUNIX variability is higher than in healthy individuals. Muscle Nerve, 2016 Muscle Nerve 55: 635–638, 2017

Current issues in the respiratory care of patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a progressive neuromuscular disease, resulting in respiratory muscle weakness, reduced pulmonary volumes, ineffective cough, secretion retention, and respiratory failure. Measures as vital capacity, maximal inspiratory and expiratory pressures, sniff nasal inspiratory pressure, cough peak flow and pulse oximetry are recommended to monitor the respiratory function. The patients should be followed up by a multidisciplinary team, focused in improving the quality of life and deal with the respiratory symptoms. The respiratory care approach includes airway clearance techniques, mechanically assisted cough and noninvasive mechanical ventilation. Vaccination and respiratory pharmacological support are also recommended. To date, there is no enough evidence supporting the inspiratory muscle training and diaphragmatic pacing.

Previous acute polio and post-polio syndrome: recognizing the pathophysiology for the establishment of rehabilitation programs

Previous acute poliomyelitis (PAP) can be defined as an endemic human disease caused by an enterovirus of worldwide distribution, which compromises the anterior horn cells of the spinal cord. Poliovirus has infected and victimized thousands of people all over the world. Only after the development of the inactivated virus vaccine by Jonas Salk, in 1955, and then with the attenuated virus vaccine, by Albert Bruce Sabin, in 1961, we saw a reduction in the number of poliomyelitis cases in the world.¹