The natural history of ALS: Baseline characteristics from a multicenter clinical cohort.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare disease with urgent need for improved treatment. Despite the acceleration of research in recent years, there is a need to understand the full natural history of the disease. As only 40% of people living with ALS are eligible for typical clinical trials, clinical trial datasets may not generalize to the full ALS population. While biomarker and cohort studies have more generous inclusion criteria, these too may not represent the full range of phenotypes, particularly if the burden for participation is high. To permit a complete understanding of the heterogeneity of ALS, comprehensive data on the full range of people with ALS is needed. METHODS: The ALS Natural History Consortium (ALS NHC) consists of nine ALS clinics and was created to build a comprehensive dataset reflective of the ALS population. At each clinic, most patients are asked to participate and about 95% do. After obtaining consent, a minimum dataset is abstracted from each participant's electronic health record. Participant burden is therefore minimal. RESULTS: Data on 1925 ALS patients were submitted as of 9 December 2022. ALS NHC participants were more heterogeneous relative to anonymized clinical trial data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. The ALS NHC includes ALS patients of older age of onset and a broader distribution of El Escorial categories, than the PRO-ACT database. CONCLUSIONS: ALS NHC participants had a higher diversity of diagnostic and demographic data compared to ALS clinical trial participants.Key MessagesWhat is already known on this topic: Current knowledge of the natural history of ALS derives largely from regional and national registries that have broad representation of the population of people living with ALS but do not always collect covariates and clinical outcomes. Clinical studies with rich datasets of participant characteristics and validated clinical outcomes have stricter inclusion and exclusion criteria that may not be generalizable to the full ALS population.What this study adds: To bridge this gap, we collected baseline characteristics for a sample of the population of people living with ALS seen at a consortium of ALS clinics that collect extensive, pre-specified participant-level data, including validated outcome measures.How this study might affect research, practice, or policy: A clinic-based longitudinal dataset can improve our understanding of the natural history of ALS and can be used to inform the design and analysis of clinical trials and health economics studies, to help the prediction of clinical course, to find matched controls for open label extension trials and expanded access protocols, and to document real-world evidence of the impact of novel treatments and changes in care practice.

The NEALS primary lateral sclerosis registry.

BACKGROUND AND OBJECTIVE: Primary lateral sclerosis (PLS) is a neurodegenerative disease characterized by progressive upper motor neuron dysfunction. Because PLS patients represent only 1 to 4% of patients with adult motor neuron diseases, there is limited information about the disease's natural history. The objective of this study was to establish a large multicenter retrospective longitudinal registry of PLS patients seen at Northeast ALS Consortium (NEALS) sites to better characterize the natural progression of PLS. Methods: Clinical characteristics, electrophysiological findings, laboratory values, disease-related symptoms, and medications for symptom management were collected from PLS patients seen between 2000 and 2015. Results: The NEALS registry included data from 250 PLS patients. Median follow-up time was 3 years. The mean rate of functional decline measured by ALSFRS-R total score was -1.6 points/year (SE:0.24, n = 124); the mean annual decline in vital capacity was -3%/year (SE:0.55, n = 126). During the observational period, 18 patients died, 17 patients had a feeding tube placed and 7 required permanent assistive ventilation. Conclusions: The NEALS PLS Registry represents the largest available aggregation of longitudinal clinical data from PLS patients and provides a description of expected natural disease progression. Data from the registry will be available to the PLS community and can be leveraged to plan future clinical trials in this rare disease.

Value of terminal latency index and sensory electrophysiology in idiopathic and diabetic chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVES: To evaluate sensory electrophysiology, terminal latency index (TLI), and treatment response in idiopathic and diabetic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We performed a retrospective review of 147 patients with CIDP who underwent electrodiagnostic evaluation (January 2000-December 2015). Eighty-nine patients fulfilled electrophysiological criteria described by the Ad hoc Subcommittee of the American Academy of Neurology and Albers et al. Fifty-eight patients were divided into idiopathic (N = 40) and diabetic (N = 18) groups. These groups were compared for age, sex, cerebrospinal fluid protein, response to treatment, sensory response abnormalities, and TLI measurements using chi-square tests for binary and categorical variables and using t-tests and mixed-effects models for continuous variables. RESULTS: The difference in abnormal rates of sensory responses was significant for the sural nerve, with the idiopathic group having a lower rate than the diabetic group (80% vs. 100%, p < 0.001). No group differences in the TLI measurements were significant. CONCLUSIONS: Sural sensory responses may have some value in differentiating idiopathic CIDP from diabetic CIDP. Larger prospective studies are needed to confirm our findings. SIGNIFICANCE: Our study suggests that abnormal sural sensory potentials may have some significance in differentiating idiopathic CIDP from diabetic CIDP.

Atypical Presentation of Glioblastoma Multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is a highly malignant glial tumour classified by the World Health Organization (WHO) as a stage IV astrocytoma. It varies in shape and size and can be cystic, vascular and necrotic. It often appears as a ring-enhancing lesion on magnetic resonance imaging (MRI). The most common symptoms of GBM, such as headache, vomiting and seizures, are due to increased intracranial pressure. The objective of this case report is to describe an atypical presentation of GBM. CASE REPORT: A 53-year-old woman of Italian origin presented with a 2-week history of lack of coordination in her hands and some difficulty in speech. Electromyography for assessment of her arms and cranial bulbar function was normal. However, 2 days later, the patient presented to the emergency department with progressive weakness in her left arm and leg as well as difficulty in speech. Mild left facial asymmetry was noted. A brain MRI revealed a right frontal mass. Stereotactic surgical resection was performed 2 days later, and biopsy confirmed the diagnosis of GBM. Although headache and other features of raised intracranial pressure are the most common initial symptoms of GBM, any atypical neurological or psychiatric presentation in an adult patient should raise suspicion for this tumour. CONCLUSION: Careful analysis of an adult with atypical signs and symptoms along with thorough review of radiological tests will facilitate early diagnosis of dangerous tumours such as GBM. LEARNING POINT: An adult patient with symptoms that do not conform to a neurological condition should be investigated for a brain tumour.Careful history taking and examination are essential for reaching the correct diagnosis as soon as possible.Meticulous review of radiological images in order to detect subtle changes in brain anatomy is essential.

Multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is a rare disorder in which the symptoms are caused by persistent conduction block lesions. The mononeuropathy multiplex progresses over time with increasing axonal loss. The cause of the conduction blocks and axonal loss are not completely understood but immune mechanisms are involved and response to intravenous immunoglobulin has been established. The importance of MMN goes beyond its clinical incidence as the increasing understanding of the pathogenesis of this disorder has implications for other peripheral nerve diseases and for our knowledge of peripheral nerve biology.

Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy, which has various clinical presentations and both axonal and demyelinating forms. The original description of "ascending paralysis" encompasses the most common varieties: the primary demyelinating form, acute inflammatory demyelinating polyneuropathy (AIDP), and some of the axonal forms, acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN). However, there are now well-documented acute "monophasic" polyneuropathies that have a different clinical phenomenology than that described originally by Guillain, Barré, and Strohl: Miller Fisher syndrome, pure sensory neuropathy/neuronopathy, pandysautonomia, and oropharyngeal variant. Here the authors review both typical GBS (AIDP, AMAN, and AMSAN), and variant syndromes with a focus on clinical and diagnostic features, pathologic findings, pathogenesis, and treatment.