Disorders of the Neuromuscular Junctions

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder affecting the neuromuscular junction and has a strong association with small cell lung carcinoma. Lambert-Eaton myasthenic syndrome affects the voltage-gated calcium channels at the presynaptic membrane. Presentation includes proximal muscle weakness and symptoms of autonomic dysfunction such as dry mouth and sluggish pupillary reflexes. Diagnosis includes nerve conduction studies/electromyography (EMG) and serum detection of antibodies. Management is mainly symptomatic with the use of potassium channel blockers and immunosuppressants. Prognosis is good for nonparaneoplastic LEMS but usually poor for paraneoplastic LEMS secondary to underlying malignancy.

A toxidrome is a group of clinical signs and symptoms associated with a toxic ingestion or exposure. There are 5 traditional toxidromes: anticholinergic, cholinergic, opioid, sympathomimetic, and sedative-hypnotic. Toxidromes often arise from ingestion of overdose amounts, accumulation of medications with resultant elevated serum levels, adverse drug reactions, or interactions between 2 or more medications. Rapid recognition of a toxidrome can help determine the specific poison or class of toxin that was ingested. On presentation of a suspected toxidrome, appropriate airway, breathing, and circulation assessment is initiated. Decontamination is performed, and the patient is stabilized. Diagnosis is accomplished with clinical findings based on medication and exposure history, vital signs, mental status, and physical examination. Testing generally includes toxicology and drug levels, electrolytes, and ECG. Management consists of supportive care and antidote administration if indicated.

Herbicides are chemical substances used to kill or control the growth of unwanted plants. Important herbicides that can affect humans include paraquat, Agent Orange, glyphosate, and organophosphates. Different types of herbicides result in different clinical manifestations and have various toxicity levels. Paraquat ingestion is associated with multiorgan damage within a few hours and is fatal in large amounts. In contrast, glyphosate typically has low toxicity, but if a significant volume is ingested, serious adverse effects occur. Organophosphates, which are broadly used as pesticides, produce a cholinergic toxidrome. Agent Orange, containing 2,3,7,8-tetrachlorodibenzo-p-dioxin, a human carcinogen, carries both short-term (e.g., chloracne, liver toxicity) and long-term (e.g., cancers) complications. Exposure can be dermal or via inhalation or ingestion. In general, early detection is important to prevent serious sequelae. Initial management consists of stabilizing the patient and decontamination. An antidote is given, if available. Treatment of herbicide poisoning revolves around supportive care that depends on the involved organ system.

An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. An increase in the concentration of these substances to toxic levels can occur accidentally or intentionally, resulting in both acute and chronic presentations. Some substances can be detected using specific laboratory tests, whereas the detection of others relies on nonspecific findings. Thus, it is important to recognize substance poisoning by history, individual risk factors, and physical examination. Antidotes along with supportive care and monitoring are part of the management.

Insecticides are chemical substances used to kill or control insects, to improve crop yields, and to prevent diseases. Human exposures to insecticides can be by direct contact, inhalation, or ingestion. Important insecticides that can affect humans include organochlorines (dichlorodiphenyltrichloroethane (DDT)), organophosphates (malathion and parathion), and carbamates (carbaryl, propoxur, aldicarb, and methomyl). Because of DDT's long-term adverse effects on wildlife and the environment, it is now not used in many areas. However, it is still in use in areas with high rates of malaria infection. The chemical produces neurotoxicity and endocrine disruption. Organophosphates and carbamates produce cholinergic effects, given their similar mechanism of action of inhibiting acetylcholinesterase. Organophosphates, though, bind the enzyme irreversibly, while carbamates inhibit the enzyme for < 48 hours. Diagnosis is based on history and clinical findings, with tests available for confirmation. Management involves decontamination, supportive care, and symptom control. For the cholinergic toxidrome, atropine and pralidoxime are given to reverse the effects of cholinergic excess.

Botulism is a rare, neuroparalytic syndrome caused by Clostridium botulinum (C. botulinum). A fatal neurotoxin (botulinum toxin) is released causing varying degrees of muscle paralysis and distinct clinical syndromes. The most common types of botulism are foodborne and infant. Botulism presents with blurred vision, respiratory failure, and symmetric, descending flaccid paralysis. Characterization includes intact sensorium, normal heart rate and blood pressure, absence of fever, and absence of sensory deficits. Diagnosis is made on clinical grounds and can be confirmed by the isolation of bacteria or toxins from stool, wound specimens, or food sources. The approach to managing a case of botulism should include prompt management of respiratory failure, administration of antitoxin, and supportive care for paralysis.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. Myasthenia gravis presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Diagnosis is established based on clinical presentation, detection of antibodies, and electrophysiologic studies. Management is aimed at increasing the activity of acetylcholine at the neuromuscular junction and suppression of antibodies. This disease can be associated with thymomas and thymic hyperplasia, and thymectomy is sometimes indicated. Myasthenia gravis can progress to a life-threatening cholinergic crisis with respiratory failure, but this is preventable with appropriate management. Prognosis is generally good with treatment, and some patients can achieve a long-term remission.