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.

A 24-year-old man comes to the physician due to excessive daytime sleepiness. The patient is a college student whose symptoms started around age 12, when he began needing more sleep than his peers to feel refreshed. Two years later, he started having daily episodes of sudden weakness, consistently triggered by laughter or crying, in which his head would nod or his knees would buckle for about 30 seconds. The patient also describes times when he was unable to move for several minutes after awakening from sleep. He mentions nightly dreams that seem very real, often featuring activities that he had been engaged in during the preceding day.

Educational objective: Hypocretin-1 {orexin-A) and hypocretin-2 (orexin-B) are neuropeptides produced in the lateral hypothalamus that promote wakefulness and inhibit REM sleep-related phenomena. Most patients who have narcolepsy with cataplexy have undetectable levels of hypocretin-1 in their cerebrospinal fluid.

A 36-year-old woman is evaluated for several months of tingling and numbness of the right hand and fingers that has progressed to dull, aching pain. The symptoms initially were intermittent but have become persistent, with the pain worsening overnight. The patient works as an office secretary and has had difficulty typing and holding the phone due to hand weakness. On examination, she has weakness of thumb opposition and atrophy of the thenar eminence. The patient attempted treatment with conservative measures but had no significant improvement and has now been referred for surgery.

Educational objective: The carpal tunnel is formed by the carpal bones and the transverse carpal ligament (flexor retinaculum). Carpal tunnel syndrome results from compression of the median nerve as it passes through the carpal tunnel with 9 flexor tendons. Longitudinal incision of the transverse carpal ligament can decrease pressure within the carpal tunnel, improving patients' symptoms.

A 65-year-old man is brought to the emergency department due to acute onset of a severe headache and dizziness. He describes it as a throbbing that localizes to the back of his head, with associated vertigo and mild nausea. The patient has a past medical history of type 2 diabetes mellitus, hypertension, chronic obstructive pulmonary disease, and a recent diagnosis of lung adenocarcinoma. He has smoked 1-2 packs of cigarettes daily for the past 30 years. His temperature is 36. 7 C (98 F), blood pressure is 170/96 mm Hg, pulse is 80/min, and respirations are 14/min. Noncontrast head CT reveals an acute hemorrhage in the cerebellar vermis without mass effect or midline shift.

Educational objective: Acute lesions to the cerebellar vermis typically cause truncal and gait ataxia due to impaired modulation of the medial-descending motor systems. Involvement of the lower vermis and the flocculonodular lobe also causes vertigo/nystagmus due to dysregulation of the vestibular nuclear complex.

A 45-year-old woman is evaluated for numbness and painful tingling of the right hand. The symptoms began 2 months ago and are especially prominent after she plays tennis. On examination, there is diminished sensation in the lateral palm, thenar eminence, and palmar aspect of the first 3Y:z digits of the right hand.