Nakul Katyal

Shortcomings in the Current Amyotrophic Lateral Sclerosis Trials and Potential Solutions for Improvement

Amyotrophic lateral sclerosis (ALS) is a clinically progressive neurodegenerative syndrome predominantly affecting motor neurons and their associated tracts. Riluzole and edaravone are the only FDA certified drugs for treating ALS. Over the past two decades, almost all clinical trials aiming to develop a successful therapeutic strategy for this disease have failed. Genetic complexity, inadequate animal models, poor clinical trial design, lack of sensitive biomarkers, and diagnostic delays are some of the potential reasons limiting any significant development in ALS clinical trials. In this review, we have outlined the possible reasons for failure of ALS clinical trials, addressed the factors limiting timely diagnosis, and suggested possible solutions for future considerations for each of the shortcomings.

Sleep Disorders in Peripheral Neuropathy

The relationship between sleep apnea and peripheral neuropathy is complex. Neuropathy can cause or worsen sleep apnea while sleep apnea can be an independent risk factor for neuropathy. Both central and peripheral mechanisms operate in neuropathic conditions and can result in both central and obstructive sleep apnea syndromes. Along with sleep apnea, neuropathies can also be associated with hypoventilation, restless legs syndrome, and insomnia. In this chapter, we attempt to go over the sleep issues seen in common neuropathies.

Neuromuscular Respiratory Failure

Respiratory failure can be the result of impairment in the central control of respiration, neuromuscular disorders or due to intrinsic lung problems. In the neuromuscular causes of respiratory failure, several factors like upper airway problems, inspiratory/expiratory muscle weakness, low tidal volumes, etc. can be contributory. Features like rapid shallow breathing, use of accessory muscles of respiration, cough after swallowing, and paradoxical breathing point towards the possibility of impending respiratory failure. For physicians treating neuromuscular disorders, identification of early signs of impending respiratory failure is crucial for better patient outcomes. In this chapter, we review the physiology and pathology of respiration in the setting of neuromuscular disorders along with objective assessment of respiratory failure.

Seizure prophylaxis in the neuroscience intensive care unit

BackgroundSeizures are a considerable complication in critically ill patients. Their incidence is significantly high in neurosciences intensive care unit patients. Seizure prophylaxis with anti-epileptic drugs is a common practice in neurosciences intensive care unit. However, its utility in patients without clinical seizure, with an underlying neurological injury, is somewhat controversial.BodyIn this article, we have reviewed the evidence for seizure prophylaxis in commonly encountered neurological conditions in neurosciences intensive care unit and discussed the possible prognostic role of continuous electroencephalography monitoring in detecting early seizures in critically ill patients.ConclusionBased on the current evidence and guidelines, we have proposed a presumptive protocol for seizure prophylaxis in neurosciences intensive care unit. Patients with severe traumatic brain injury and possible subarachnoid hemorrhage seem to benefit with a short course of anti-epileptic drug. In patients with other neurological illnesses, the use of continuous electroencephalography would make sense rather than indiscriminately administering anti-epileptic drug.

Inadvertent central arterial catheterization: An unusual cause of ischemic stroke

Central venous catheter (CVC) insertion is extensively utilized in Intensive Care Units for evaluation of hemodynamic status, administration of intravenous drugs, and for providing nutritional support in critically ill patients. Unfortunately, CVC use is associated with complications including lung injury, bleeding, infection, and thrombosis. We present a patient with an acute ischemic stroke from an inadvertently placed CVC into the right common carotid artery. A 57-year-old male presented to our institution for left hemiplegia and seizures 2 days after a CVC was placed. He was found to have a right frontal ischemic stroke on computed tomography (CT). CT angiography noted that the catheter was arterial and had a thrombosis around it. He was started on a low-dose heparin infusion. A combination of cardiothoracic surgery and interventional cardiology was required to safely remove the catheter. Central arterial catheterization is an unusual cause for acute ischemic stroke and presents management challenges.

Thromboelastography With Platelet Mapping is Not an Effective Measure of Platelet Inhibition in Patients With Spontaneous Intracerebral Hemorrhage on Antiplatelet Therapy

Thromboelastography with platelet mapping (TEG-PM) is a modality to measure platelet function, especially in patients taking antiplatelet medications. It consists of two components: arachidonic acid (AA), which is sensitive to aspirin, and adenosine diphosphate (ADP), which is sensitive to clopidogrel. In patients with spontaneous intracerebral hemorrhages (sICH), the clinical interpretation of platelet mapping is unclear. The objective of this study was to evaluate TEG-PM in patients with sICH on aspirin and/or clopidogrel who receive platelet transfusions. This study was an IRB-approved, retrospective case-control study over three years at an academic medical center. Adult patients with sICH were included if they had an admission computed tomography head (CTH) and platelet mapping followed by a repeat platelet mapping and CTH post platelet transfusion. A threshold of 50% inhibition was used as the benchmark for both ADP and AA inhibition. Around 248 subjects with sICH were identified, and 107 were excluded for incomplete documentation, leaving 141 for analysis. Of these, nine met our inclusion criteria. No statistical significance was found on the antithrombotic effects of aspirin or clopidogrel on TEG-PM (p=1.00 for both). Sensitivity and specificity of TEG-PM for clopidogrel was 100% and 42.9%, respectively, and 80% and 0%, respectively, for aspirin. Platelet transfusion did not significantly change AA or ADP inhibition (p=1.00). Hemorrhagic expansion on CTH was not associated with a decrease AA or ADP inhibition (p=1.00). TEG-PM is not an effective measure of platelet inhibition in sICH patients who were on antiplatelet medications and is not a reliable measurement following platelet transfusion.

Somatosensory Evoked Potentials as a Tool to Evaluate Brainstem Herniation in the Neuroscience Intensive Care Unit

Somatosensory evoked potentials (SSEPs) are a sensitive, minimally invasive technique used to localize dysfunction of myelinated peripheral and central axons in the nervous system. The utility of SSEPs in acutely assessing central nervous system function in brainstem herniation in the neuroscience intensive care unit (NICU) has not been well established. We discuss a case of an 18-year-old, postpartum female who presented with intermittent headache, diplopia, nausea/vomiting and cachexia following delivery two months prior. Shortly after arrival to the emergency department, she developed flaccid quadriparesis and complete ophthalmoplegia. Computed tomography (CT) of the head showed effacement of the basal cisterns along with 2 cm cerebellar tonsillar herniation into the foramen magnum concerning for intracranial hypotension. Raising the head of bed caused hemodynamic instability necessitating prolonged Trendelenburg positioning. The patient was evaluated with serial SSEPs which initially showed a bilateral low amplitude N20 response and normal N13 response. Subsequent SSEP testing showed increased N20 amplitude which correlated with clinical improvement in the patient. SSEP is a minimally invasive and sensitive method used to assess the integrity of the somatosensory nervous system pathway; SSEPs may be a useful monitoring adjunct to assess the evolution of posterior fossa lesions leading to brainstem compression.

Trans-cranial Doppler as an Ancillary Study Supporting Irreversible Brain Injury in a Post Cardiac Arrest Patient on Extracorporeal Membrane Oxygenation

Obtaining neuroimaging in patients on cardiopulmonary support devices such as extracorporeal membrane oxygenation (ECMO) can be challenging, given the complexities in monitoring, instrumentation, and associated hemodynamic lability. Transcranial Doppler (TCD) is used as an ancillary test for the assessment of cerebral circulatory arrest, but its use in non-pulsatile blood flow in venoarterial (VA) ECMO is not well described. We report the use of TCD in a patient on VA ECMO post-cardiac arrest for evaluation of death by neurological criteria. A 72-year-old female was admitted for elective trans-catheter aortic valve replacement. Her postoperative course was complicated by hemo-pericardium evolving into pulseless electrical activity causing cardiac arrest. She was resuscitated with return of spontaneous circulation and initiated on VA ECMO and intra-aortic balloon pump for cardiogenic shock. Over the next few days, serial evaluations persistently showed a poor neurological examination. She was too unstable to transport for neuroimaging. Evaluation for death by neurological criteria was performed with a clinical examination, apnea testing, and TCD as an ancillary study. TCD showed systolic spikes supporting an impression of cerebral circulatory arrest consistent with an irreversible brain injury.

Multiple Cranial Neuropathies in a Patient with Diffuse Large B-cell Lymphoma: Case Report and Review of Literature

Neuropathies can occur in patients with diffuse large B-cell lymphoma (DLBCL) at any stage of the disease as a presenting symptom or during later stages of illness. A wide spectrum of neurological association is known to occur with DLBCL, ranging from cranial nerve palsies to peripheral neuropathies. Evaluation of cranial and peripheral neuropathies in patients with DLBCL requires meticulous clinical, imaging, and electrodiagnostic testing. A 75-year-old right-handed female with a known history of multiple cranial neuropathies and DLBCL presented with acute dysphagia and upper extremity weakness of one-week duration. On evaluation, she was found to have right vagal nerve palsy. Cerebrospinal fluid (CSF) analysis along with flow cytometry testing showed CD19 and CD20 positive B cells, confirming neoplastic infiltration of CSF. We describe the case and review the literature of the association of cranial nerve palsies with DLBCL.

Internal Carotid Artery Dissection with Lidocaine Nerve Block Injection Trauma: A Rare Case Report

Internal carotid artery dissection (ICAD) accounts for 25% of cerebrovascular accidents in young and middle-aged patients. Dissection occurs when the intimal wall of an artery is damaged as a result of trauma or defect. ICAD development after dental work is a relatively uncommon phenomenon. Our study highlights a rare presentation of ICAD that resulted from a direct lidocaine nerve block injection in a patient undergoing pulpotomy for a right maxillary second premolar tooth. We have described the case and reviewed the literature on this rare but potentially life-threatening phenomenon.