Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological Techniques

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder of the motor neurons, characterized by focal onset of muscle weakness and incessant disease progression. While the presence of concomitant upper and lower motor neuron signs has been recognized as a pathognomonic feature of ALS, the pathogenic importance of upper motor neuron dysfunction has only been recently described. Specifically, transcranial magnetic stimulation (TMS) techniques have established cortical hyperexcitability as an important pathogenic mechanism in ALS, correlating with neurodegeneration and disease spread. Separately, ALS exhibits a heterogeneous clinical phenotype that may lead to misdiagnosis, particularly in the early stages of the disease process. Cortical hyperexcitability was shown to be a robust diagnostic biomarker if ALS, reliably differentiating ALS from neuromuscular mimicking disorders. The present review will provide an overview of key advances in the understanding of ALS pathophysiology and diagnosis, focusing on the importance of cortical hyperexcitability and its relationship to advances in genetic and molecular processes implicated in ALS pathogenesis.

Those eyes don’t lie: a case of osmotic demyelination syndrome in a patient with hepatic encephalopathy

Osmotic demyelination syndrome (ODS), previously known as central pontine myelinolysis, is a rare neurological condition characterized by demyelination of the pons or extrapontine areas including the midbrain, thalamus, basal nuclei, and cerebellum, resulting in upper motor neuron dysfunction and pseudobulbar palsy. We report a case of a 45-year-old woman with a history of alcohol dependence and end stage liver disease complicated by hepatic encephalopathy who developed symptoms suspicious of recurrent hepatic encephalopathy and experienced a generalized seizure during an inpatient stay. After 10 days of treatment with no improvement, it was noted that the patient had locked-in syndrome and that her sodium levels had rapidly risen 2 days prior. This led to a clinical suspicion of ODS, which was confirmed on T2-weighted MRI and subsequently on autopsy. In this clinical vignette, we review the clinical presentation, prognosis, and diagnostic considerations of ODS.

Clinical Signs

In clinical neuromuscular medicine, clinical signs are very important for elucidation of the right diagnosis. There is nothing better than videos to demonstrate these signs and their elicitation and significance. We selected several clinical signs from our video archives for this purpose. Babinski sign is an important clue to upper motor neuron dysfunction. Bell’s phenomenon is a normal response. Facilitation of reflexes is a strong indication of a presynaptic neuromuscular transmission disorder. By definition a sign is a clinical finding as opposed to a symptoms which is what the patient report. Some signs are transient and not captured during clinical examination. The advent of video recording ability to general public facilitate capturing of physical signs in videos.