A researcher is investigating a new antiseizure drug that binds to and activates GABA-A receptors in the central nervous system. During the experiment, she isolates a nerve and uses a microelectrode to measure its membrane potential under physiologic conditions. The resting potential of the nerve is found to be - 70 mV.

Educational objective: A drug that binds to and activates GABA-A receptors (or enhances their activity) will increase the conductance of chloride ions, leading to increased passive transport of chloride into the cell interior. This causes the membrane potential to become hyperpolarized (more negative than the resting membrane potential) by approaching or reaching the equilibrium potential for chloride.

A 45-year-old man comes to the office for follow-up. He was diagnosed with focal epilepsy 2 years ago and has been treated with several antiepileptic medications. Over the last 6 months, his seizure frequency has increased despite compliance with medical therapy. Neurologic examination and brain imaging are unremarkable. The patient is started on a new antiepileptic medication that selectively blocks voltagegated calcium channels.

Educational objective: Voltage-gated sodium channels are important for the generation and propagation of action potentials. When the action potential reaches the axon terminal, voltage-gated calcium channels open and allow the influx of calcium, which is essential for the fusion and release of neurotransmitter vesicles into the synaptic cleft.

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A 41-year-old man with trisomy 21 is evaluated in the clinic due to cognitive decline. The patient has a history of moderate intellectual disability, but his higher cognitive functions have become progressively impaired in the past several years. He previously volunteered at a community library but recently lost his position as he could no longer perform his duties. The patient is now completely dependent on a caregiver for assistance with his activities of daily living such as getting dressed, bathing, and using the toilet. The patient keeps wandering in the group home and has become lost on several occasions.

Educational objective: Patients with trisomy 21 (Down syndrome) have 3 copies of the amyloid precursor protein gene located on chromosome 21. This increases amyloid-beta accumulation in the brain, placing these patients at high risk for developing early-onset Alzheimer disease.

A 35-year-old woman, gravida 2 para 1, comes to the office for a routine prenatal visit. Her first child was born with a hydrocele and syndactyly of the first and second toes. The patient has no significant medical problems and takes no medications except for a multivitamin. Examination reveals clear lungs and normal first and second heart sounds. The abdomen is soft and nontender. Uterine size, fetal movements, and fetal cardiac activity are all within appropriate limits. The patient undergoes amniocentesis during the 18th week of pregnancy. Amniotic fluid analysis shows an increased level of acetylcholinesterase.

Educational objective: Neural tube defects most often occur when the neural folds fail to fuse in the region of the anterior or posterior neuropores. Persistent communication between the spinal canal and the amniotic cavity allows leakage of alpha-fetoprotein (AFP) and acetylcholinesterase (AChE) into the amnionic fluid, leading to elevated levels of AFP and AChE that can be detected on amniocentesis.

An 18-year-old previously healthy woman is brought to the emergency department with 2 days of fever, headache, and lethargy. She has also had nausea and several episodes of vomiting. Her temperature is 38.9 C (102 F), blood pressure is 110/60 mm Hg, and pulse is 108/min. On physical examination, the patient is diaphoretic, delirious, and has a petechial rash on the trunk and extremities. Signs of meningeal irritation are present. CT scan of the head reveals no mass lesions. She is scheduled for a lumbar puncture for cerebrospinal fluid analysis.

Educational objective: The optimal location for needle insertion during a lumbar puncture is the L3/L4 or L4/L5 space as this is well below the spinal cord termination site (L 1 in adults). The L4 vertebral body lies on a line drawn between the highest points of the iliac crests.

A 65-year-old woman comes to the office to discuss pain at the posterior chest wall. She was seen 4 months ago for acute shingles involving a right mid-thoracic dermatome. The patient was not treated at that time because she had a delayed presentation and the lesions were already well-crusted and healing. The skin lesions subsequently cleared completely. However, since then, she has had persistent burning and stabbing pain in the same region that has now become severe. She has tried oral acetaminophen without relief. During discussion of treatment options, the patient says she does not want any systemic medications due to concerns about possible side effects. She is started on topical capsaicin cream, and her pain improves markedly over the next several days.

Educational objective: Topical capsaicin causes defunctionalization of afferent pain fibers and depletion of substance P. Initial application results in a burning and stinging sensation, but chronic exposure leads to reduced pain transmission.