John Anthony Morren

Current and prospective disease-modifying therapies for amyotrophic lateral sclerosis.

Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating illness of unclear etiology affecting motor neurons. It causes unremitting muscle paralysis, atrophy and death usually within 3 – 5 years from diagnosis. The human and economic costs for those affected are sobering. To date, tremendous efforts have failed to find a cure. Areas covered: An extensive literature search was undertaken using Medline and the Cochrane Systematic Review and Clinical Trial databases. Riluzole and investigational ALS drugs are discussed. Riluzole is the only approved disease-modifying therapy despite its modest effect on survival. Recent research has produced promising agents aimed at better disease control if not a cure. This review discusses agents targeting neuronal glutamate excitotoxicity, protein misfolding and accumulation, autophagy, apoptosis, mitochondrial dysfunction, free radical oxidative injury, immunomodulation, mutant mRNA counteraction, muscle physiology, neurotrophic factors and stem cell applications. The challenges in ALS drug development are highlighted. Expert opinion: Riluzole should be used for patients with definite, probable, suspected or possible ALS by World Federation of Neurology diagnostic criteria. Systematic monitoring for hepatic dysfunction, neutropenia and other serious adverse effects should be done routinely as outlined. All ALS patients should consider genetic screening and enrollment in ALS trials guided by the data reviewed.

Neck and Back Pain

Acute back and neck pain is a common complaint seen in the emergency department. Chronic pain, lasting more than several months, can be indicative of an underlying back condition such as disk (nucleus pulposus) herniation, spinal stenosis, or cervical spondylosis in cases of neck pain. A comprehensive back or neck pain assessment is required for appropriate treatment. In the trauma patient, acute neck pain necessitates neck immobilization to prevent untoward cervical cord damage.

Where is dihydroergotamine mesylate in the changing landscape of migraine therapy

Importance of the field: Migraine affects approximately 18% of women and 6% of men, and has an immense impact on quality of life and productivity. Advancement in therapeutic options has been slow. For many patients with difficult-to-treat migraine, the appropriate use of dihydroergotamine mesylate (DHE) can result in treatment success and unprecedented patient satisfaction. Areas covered in this review: Migraine treatment guidelines regarding the role of DHE are highlighted. An overview of the market for antimigraine drugs is provided in the context of DHE, since its introduction in 1943, and the novel agents that are likely to be available in the near future. An extensive literature search was undertaken using Medline and the Cochrane Systematic Review and Clinical Trial databases. What the reader will gain: An understanding of which migraine patients are likely to benefit maximally from treatment with DHE in its various forms. Take home message: In the most difficult patient groups – including those with status migrainosus, migraine recurrence, medication-overuse headache, and chronic daily headache – DHE has therapeutic efficacy superior to other agents. The side-effect profile of DHE is more benign than is often perceived and should not be a deterrent for use in well-chosen cases.

Stroke and TIA

Transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. A stroke occurs with progression to acute infarction in this context.

Multiple Sclerosis (Exacerbation)

Approximately 85 % of patients with multiple sclerosis (MS) present with the relapsing-remitting form of the disease. A high frequency of relapses in the first year after diagnosis is associated with poor prognosis. Exacerbations of multiple sclerosis are characterized by episodes of focal neurological disturbance lasting more than 24 h and preceded by a period of clinical stability lasting 30 days or more. Fluctuations in symptoms with fever, heat, or infection may not be considered true exacerbations since in these contexts previous deficits may be simply “unmasked.” For this reason, screening labs should include a CBC and urinalysis to help exclude intercurrent infection. Contrasted brain MRI is useful to assess any new (typically enhancing) lesions which may be responsible for the acute exacerbation. Lumbar puncture and CSF analysis are not necessary if the diagnosis of multiple sclerosis is already established. However, it may show a variable degree of pleocytosis and increased total protein, myelin basic protein, and oligoclonal bands with an elevated IgG synthesis rate and IgG index. Visual evoked potentials remain abnormal years after an episode of optic neuritis. Somatosensory and brainstem auditory evoked potentials are abnormal in at least one-third to one-half of patients with MS.

Stem cell injection-induced glioneuronal lesion of the cauda equina

Commercial stem cell therapy and “stem cell tourism” refer to the for-profit industry that has recently experienced a rise in popularity due to the regenerative potential of pluripotent stem cells. Without regulatory oversight, there is a growing concern for the future of legitimate research into stem cell therapy due to exaggerated claims of potential benefit, which in turn can contribute to research misconduct and loss of scientific credibility.1 Associated morbidities such as stem cell-induced lesions are often not given adequate consideration. We present a case illustrating the development of a proliferative lesion after stem cell therapy with a unique morphologic pathology, illustrating this medical conundrum.

Diagnostic Accuracy of Single Fiber Electromyography for Myasthenia Gravis in Patients Followed Longitudinally

Introduction: The literature lacks data on accuracy of single fiber electromyography (SFEMG) for myasthenia gravis (MG) patients followed longitudinally. Methods: We included patients with a clinical suspicion of MG who received SFEMG and follow-up at our institution between 2003 and 2013. Data collected included demographics, symptom details, clinical deficits, other diagnostic testing results, MG medication regimen, duration on treatment, response to therapy, and ultimate diagnosis after follow-up. When available, information was also extracted from the MG-specific Activities of Daily Living, MG Quality of Life, and European Quality of Life assessments before and after SFEMG. Results: Three hundred forty eight SFEMG patients met inclusion criteria. Myasthenia gravis was ultimately diagnosed in 31% (19% ocular, 12% generalized). A sensitivity of 78% was seen for MG regardless of subtype, 73% for ocular MG, and 85% for generalized MG. A specificity of 91% was obtained for MG of either ocular or generalized subtype. Conclusions: The diagnostic accuracy of SFEMG using this methodology minimizing incorporation bias is more reliable than that usually described in previous studies. There is utility in increasing diagnostic yield when SFEMG results are combined with clinical data and those from other diagnostic tests, particularly serology.

Neurologic Complications in Critically Ill Patients

Neurologic complications of sepsis are related primarily to inflammatory mediators that gain access to both the central and peripheral nervous systems. These mediators have significant effects on oxygen delivery and utilization at the level of the microvasculature endothelium and mitochondria. The resultant inhibition can lead to neurologic dysfunction and death through a variety of mechanisms including ischemia, hypoxia, and decreased axonal transport of nutrients. Both the central and peripheral manifestations of inflammatory mediators have a profound effect on long-term cognition and potential for rehabilitation. The encephalopathy associated with sepsis occurs in many critically ill patients. Although a diagnosis of exclusion, its presence can be detected on examination and EEG monitoring and portends a worse outcome than otherwise. Critical illness neuropathy and myopathy represent a spectrum of diseases that result from either the effects of inflammatory mediators or treatments initiated to treat critically ill patients. The extent of the neuropathy correlates with the duration and severity of the underlying illness. This chapter explores the diagnosis, evaluation, pathogenesis, and treatment strategies for these various entities.

Spinal Cord Compression

Spinal cord compression is a serious neurological emergency and should be evaluated without any delay. The prognosis of spinal cord compression depends on the nature and extent of the original injury as well as the timely assessment and initiation of treatment. Patients who are brought to the hospital already paraplegic may not be able to walk again even after treatment. Therefore, actions should be expedient. Symptoms and signs of acute spinal cord compression include bilateral weakness of the lower extremities, with or without upper extremity involvement. There may be loss of sensation with the presence of a sensory level. Bowel or bladder sphincteric dyscontrol is further indicative.

Seizures and Status Epilepticus

Seizures are caused by abnormal excessive synchronous discharges of cortical neurons which produce a sudden change in neurological function. Seizures may be generalized, focal, or focal onset with secondary generalization.