Search

We report an individual with rapidly progressive motor neuron disease (MND), phenotypically compatible with amyotrophic lateral sclerosis (ALS). The patient described in this case report proved positive for human immunodeficiency virus (HIV) and was initiated on antiretroviral therapy (ART). Following ART he clinically stabilised over 10 years and deteriorated again due to noncompliance or ART resistance. HIV infection can give rise to an MND mimic, HIV-ALS. The improvement in response to ART supports the notion that HIV-ALS is a treatable entity also in Africa. This is the first case report of a patient with HIV-ALS and long term follow up in Sub-Saharan Africa. The report raises the suggestion that an additional (retro)virus can play a role in the aetiology of ALS.

INTRODUCTION Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that affects both upper and lower motor neurons and is fatal in its course. This evidence-based position paper represents the official position of the UEMS PRM Section. The aim of the paper is to define the role of the physical and rehabilitation medicine (PRM) physician and PRM professional practice for people with ALS. EVIDENCE ACQUISITION A systematic review of the literature and a consensus procedure by means of a Delphi process have been performed involving the delegates of all European countries represented in the UEMS PRM Section. EVIDENCE SYNTHESIS The systematic literature review is reported together with thirty-two recommendations resulting from the Delphi procedure. CONCLUSIONS The responsibility of the PRM physician is functional assessment of persons with ALS and delivering the optimal and most effective PRM program of care. The rehabilitation program of patients with ALS should be delivered and monitored by the multiprofessional team, with the PRM physician as principal coordinator.

une system play a complex role, either protective or toxic, in ALS pathogenesis [1–3]. In particular, compelling evidence indicate that increased blood level of natural killer (NK) and NK-T cells may contribute to the disease development and progression [2,3]. Here, we report on a patient with an aggressive Motor Neuron Disease (MND) associated with NK/NK-T cells leukaemia. 1. Case report A 79-year-old man presented with several months-history of a progressive atrophy and weakness of the upper limbs, which quickly spread to the lower limbs. Onset was subtle and apparently occurred in the month of July (the specific date is not shown for privacy), when the patient noticed a mild weakness in the proximal muscles of the right arm. From July through August, the patient's global functioning was however roughly normal. However, between September and early October the patient experienced a rapid worsening, with a severe weakness of the shoulder girdle, of the right arm and in both legs. He was referred to our ALS Center for evaluation. The neurological examination documented marked muscle atrophy of the shoulder girdle, the right arm and both lower limbs, with bilateral foot drop. Deep tendon reflexes were absent, with the exception of the left arm. Bulbar functions were normal. Needle EMG showed widespread polyphasic MUP and fibrillation potentials, with normal sensory and motor conduction velocities and no conduction blocks. Sensory and motor nerves amplitudes in the upper limbs were within the normal range. A brain and cervical MRI was within normal range. Extensive biochemical and immunological work-up, including CSF, blood cell count, a large antibody battery which included antibodies to anti-Hu, anti-Ri, anti-Yo, and anti-gangliosides were negative. Serum creatine phosphokinase level was mildly increased. A diagnosis of a very rapidly progressing lower motor neuron disease (MND) was made, with an ALSFRS-R score of 18/ 48 and a ΔFS [4] of 10 (Fig. 1A). Although the clinical features of the patient did not fit with a formal diagnosis of ALS, a genetic testing for the major ALS related genes (C9orf72, FUS, TARDBP, SOD1, and Angiogenin) was performed, which gave negative results. In the middle of November 2016, a follow-up blood test showed a marked increase of WBC (i.e., 76,050/μL), with a high prevalence of lymphocytes. He was then admitted to the Hematology Unit in our Hospital. Blood cytofluorimetric analysis and a bone marrow biopsy showed a marked infiltration by immature NK and NK-T cells (Fig. 1B). A new CSF analysis was performed, which showed increased proteins and 360/μL WBC, of which about 70% were NK/NK-T cells. A diagnosis of NK/NK-T cell leukaemia was made. A systemic chemotherapy according to Hyper-CVAD schema was started (i.e., High Dose Dexamethasone; Hyperfractionated Cyclophosphamide; Oncovine and Doxorubicine), along with repeated intrathecal injections with Methotrexate, Ara-C and Dexamethasone. In the following weeks, the patient showed a transient improvement in muscle strength and function; a ALSFRS-R evaluation, made in December 2016, gave a score of 27/48, with a ΔFS dropping to 4.2 (Fig. 1A). Unfortunately, the general health status deteriorated over time, and in late December, the patient was referred to a Hospice, where a few weeks later he peacefully passed away. 2. Discussion We have described an aggressive lower MND, which might be paraneoplastic, associated with an NK-T leukaemia. A paraneoplastic association between either lower MND and lymphoma or the upper predominant MND and breast cancer has been reported [5–7]. The presence of a high number of NK/NK-T cells in the CSF indicates a meningeal metastasis from the acute leukaemia. These cells are most probably involved in the lower motor neuron degeneration in our patient. The clinical diagnosis of MND in this case is supported by several lines of evidence: a) the onset of atrophy and weakness occurred in the shoulder girdle, involving first the right shoulder with a rapid progression to the left shoulder, and then with a proximal-to-distal spreading to the right arm and then to the lower limbs. This pattern of spreading is consistent with a primarily MND involvement, rather than a poly/multi-neuropathy; b) the EMG/ENG pattern was also consistent with a lower motor neuron disease, as neither abnormal sensory/motor amplitudes (recorded in the upper limbs) nor conduction velocities/ blocks (recorded in both the upper and lower limbs) could be detected. It cannot, however, be excluded a contemporary involvement of the motor neurons cell bodies and the proximal section of the axons (i.e. the motor roots).

Human Genomics Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that affects nerve cells in the brain and the spinal cord. It has proven difficult to identify the early stages of disease and where it spreads within the body. Maniatis et al. used RNA sequencing to define transcriptomic changes over the course of disease in different regions of the spinal cord of a mouse ALS model and a postmortem human ALS spinal cord. From changes in gene expression, they identified disease-associated pathways and established the key steps in motor neuron degeneration observed in ALS. Science , this issue p. [89][1] [1]: /lookup/volpage/364/89?iss=6435

Spinal muscular atrophy (SMA) is a progressive motor neuron disease, which is one of the most common forms of inheritable infant death in the world. SMA results from reduced levels of SMN protein. Various models systems used in SMA research are available and it is possible to assess their strengths and weaknesses. Although each of these models has its limitations, they must be used together so as to effectively and efficiently identify potential SMA therapeutics.

International audience; We report the third case of amyotrophic lateral sclerosis related to p.E121G Superoxide dismutase-1 (SOD1) mutation. Besides a sporadic presentation and a slow progressive course, as described in the 2 previously cases, our patient presented with prominent sensory and cerebellar signs. This case report strengthens that p.E121G should be considered as a causal mutation. Slowly upper and lower motor neuron degeneration, even with non-motor clinical features, should prompt a sequencing of SOD1.

The present report deals with the clinical phenomenology of three members (brothers) of one family with McLeod syndrome (MLS). In two, the clinical pictures were of choreiform disorders with amyotrophy, which were found to be neurogenic in origin by detailed electrophysiological study. The index case had peripheral acanthocytosis; immunohematological and molecular genetic studies confirmed diagnosis of MLS. However, one brother only had a slowly progressive motor neuron disease like picture but no abnormal movement disorder. He had peripheral acanthocytes as well. The inheritance seems to be X-linked recessive in nature. The affected family members exhibited much phenotypic heterogeneity. This appears to be the first report of MLS from India.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive motor neuron disease that poses a myriad of clinical problems. Patients with ALS are best treated in a multidisciplinary setting involving physicians, clinical nursing specialists, and physical, occupational, speech, and respiratory therapists, as well as psychologists and social workers. Palliative and rehabilitative strategies may ease suffering, while new treatments provide hope for effective treatment of this disease.

Objective The clinical and epidemiological profile of sporadic amyotrophic lateral sclerosis (ALS), a chronic, degenerative, progressive motor neuron disease of unknown etiology, was described and evaluated in the city of Rio de Janeiro. Method Patients with a diagnosis definite of ALS according to the revised criteria of the El Escorial World Federation of Neurology were included in this retrospective, descriptive study (n = 227). Demographic data, clinical variables, mortality and survival of these patients were assessed. Results Of the 227 included cases, 143 (63%) were male and 84 (37%) were female, resulting in a male/female ratio of 1.7:1. Mean age at onset of the disease was 53.6 ± 12.1 years, overall median survival time was 49 months (95%CI: 42.4–55.5) and the majority of patients (71.4%) were white, black patients 15.9% and mulattos 12.8%. The most common forms of the disease were classic and bulbar ALS. Conclusion Taking classic and bulbar ALS together, the disease was more common in white, male patients of 50 to 70 years of age. When analyzed separately, the bulbar form was more common in women and in older patients. Survival of patients with bulbar ALS was shorter compared to that of patients with classic ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that is currently untreatable. Many compounds have been tested in laboratory-based models and in patients with ALS, but so far only one drug, riluzole, has shown efficacy, yet it only slightly slows disease progression. Several new insights into the causes of motor neuron death have led to the identification of some important novel targets for intervention. At no time have studies involved such a wide range of innovations and such advanced technologies. Many promising studies are underway to test potential targets that will hopefully translate into meaningful therapeutics for patients with ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease. Methods of dental treatment of a young male patient with ALS are presented. This case is unusual in several respects: the early age of onset, the long survival time, and the period of time in which the case was followed in our dental clinic. Aspects of ALS which are of concern to dentistry, as related to clinical care and strategies for effective oral health delivery, are presented.

A patient in perfect health prior to electrical shock developed an ALS-like syndrome after the shock. Onset of the disease occurred in the limb through which the shock entered, and subsequently followed a course well-described in previous case reports. Possible mechanisms of disease are discussed.

The autosomal dominant ataxias are a heterogenous group of disorders. Almost 30 different genetic loci have been identified. Spinocerebellar ataxia type 2 (SCA2) is one of many autosomal dominant cerebellar ataxias. Electrophysiologic studies in SCA2 have shown mainly a sensory neuropathy or neuronopathy. To determine if electrophysiologic testing reveals concomitant or isolated involvement of motor nerves in SCA2 we reviewed historic and electrophysiologic data on all cases of genetically confirmed SCA2 who underwent nerve conduction studies and needle electromyographic during initial evaluation at our institution. We performed electrophysiologic studies in six genetically confirmed, unrelated, cases of SCA2 and discovered that in three patients, there were findings consistent with motor neuronopathy or neuropathy without sensory involvement. One patient had normal results and only one had a pure sensory neuropathy or neuronopathy. The sixth patients had mixed sensorimotor neuropathy. This is the first study that demonstrates isolated involvement of motor neurons and/or axons occur in SCA2. Therefore, electrophysiologic findings in SCA2 are not limited to mainly a sensory neuropathy but are varied and can even mimic slowly progressive motor neuron disease.

Exogenous toxins and chronic hypoxia have been implicated in the etiopathogenesis of a variety of neurological disorders, but it is not always possible to establish a cause-effect relationships. We describe a patient who presented with an unusual gait disorder and progressive motor neuron disease after residing for 2 years within Biosphere 2, a scientifically engineered dome, tightly sealed to allow miniscule exchange of air between its atmosphere and the earth's atmosphere. We postulate that this unusual syndrome resulted from chronic hypoxia possibly coupled with carbon monoxide and nitrous oxide exposure.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that mainly causes degeneration of the upper and lower motor neurons, ultimately leading to paralysis and death within three to five years after first symptoms. The pathological mechanisms leading to ALS are still not completely understood. Several biomarker candidates have been proposed in cerebrospinal fluid (CSF). However, none of these has successfully translated into clinical routine. Part of the reason for this failure to translate may relate to differences across laboratories. For this reason, several of the most commonly used ALS biomarker candidates were evaluated on clinically well-defined ALS samples from six European centres in a multicentre sample-collection approach with centralized sample processing. Results showed that phosphorylated neurofilament heavy chain differentiated between ALS and control cases in all centres. We therefore propose that measurement of phosphorylated neurofilaments in CSF is the most promising candidate for translation into the clinical setting and might serve as a benchmark for other biomarker candidates.

A patient is described who was microcephalic at birth. After attaining early motor milestones, she developed progressive lower motor neuron dysfunction of the limb and bulbar musculature, combined with dystonia and an action tremor. The pathology and possible pathogenesis are discussed.