# Clinical Cases: Autonomic Nervous System ## Case 1: Horner Syndrome ### Patient Presentation **Demographics:** 45-year-old male **Chief Complaint:** Drooping of right eyelid and decreased sweating on right side of face for 2 weeks **History of Present Illness:** A 45-year-old man noticed his wife pointing out that his right eyelid appeared droopy, and his right pupil looked smaller than the left. He had also noticed decreased sweating on the right side of his face during exercise. Over the past month, he has experienced right-sided neck pain and right arm pain radiating to the medial forearm and hand. He has a 30-pack-year smoking history. He denies headache, visual changes, or weakness. **Physical Examination:** - Vital signs: BP 138/82, HR 76, RR 14 - General: Well-appearing male - HEENT: Right pupil 2 mm, left pupil 4 mm; anisocoria more pronounced in dim lighting; right ptosis (1-2 mm); right-sided facial anhidrosis - Neurological: - Cranial nerves: Ptosis and miosis on right; extraocular movements full; remainder normal - Motor: Normal strength except 4/5 right hand intrinsics - Sensory: Decreased sensation medial right forearm and 4th-5th digits (C8-T1 distribution) - Reflexes: Absent right biceps and brachioradialis **Workup:** - **Pharmacological testing:** Cocaine 4% drops fail to dilate right pupil (confirms Horner syndrome); apraclonidine reverses anisocoria - **Chest X-ray:** Apical mass in right upper lobe with rib destruction - **CT chest with contrast:** 4.5 cm Pancoast tumor (superior sulcus tumor) invading the right brachial plexus and stellate ganglion - **Biopsy:** Non-small cell lung carcinoma **Diagnosis:** Right Horner syndrome secondary to Pancoast tumor (superior sulcus tumor) **Treatment:** - Oncology referral for staging and treatment of lung cancer - Combined chemoradiation followed by surgical resection consideration - Pain management for brachial plexopathy - Horner syndrome is permanent due to destruction of sympathetic chain **Clinical Pearl:** Horner syndrome results from disruption of the oculosympathetic pathway at any of three levels: first-order (hypothalamus to ciliospinal center at C8-T2), second-order (ciliospinal center through stellate ganglion to superior cervical ganglion), or third-order (along internal carotid to orbit). The classic triad is ptosis (paralysis of Muller's muscle), miosis (unopposed parasympathetic pupillary constriction), and anhidrosis (loss of facial sweating in central or preganglionic lesions). A Pancoast tumor affecting the stellate ganglion causes second-order Horner syndrome, often with ipsilateral brachial plexopathy (C8-T1). --- ## Case 2: Orthostatic Hypotension - Autonomic Failure ### Patient Presentation **Demographics:** 72-year-old male **Chief Complaint:** Recurrent lightheadedness and falls when standing **History of Present Illness:** A 72-year-old man with Parkinson's disease diagnosed 8 years ago presents with worsening lightheadedness upon standing, particularly in the morning and after meals. He has fallen three times in the past month when rising from a seated position. He describes near-syncope with graying of vision and weakness in his legs when standing for more than a few minutes. He also reports constipation, urinary hesitancy, and erectile dysfunction that have worsened over the past two years. His Parkinson's disease is treated with carbidopa-levodopa. **Physical Examination:** - Vital signs (supine, after 5 minutes rest): BP 148/88, HR 72 - Vital signs (standing at 1 minute): BP 102/64, HR 76 (inadequate heart rate compensation) - Vital signs (standing at 3 minutes): BP 88/52, HR 78, patient symptomatic - General: Masked facies, resting tremor, bradykinesia - Cardiovascular: Regular rhythm, no murmurs - Neurological: Findings consistent with Parkinson's disease; no focal deficits **Workup:** - **Orthostatic vital signs:** Sustained systolic BP drop >30 mmHg without adequate heart rate increase (neurogenic orthostatic hypotension) - **Autonomic reflex testing:** Reduced heart rate variability with deep breathing; abnormal Valsalva ratio; absent blood pressure overshoot in phase IV of Valsalva - **Plasma norepinephrine levels:** Low in supine position, fail to rise appropriately with standing - **Cardiac MIBG scan:** Reduced cardiac uptake (postganglionic sympathetic denervation) **Diagnosis:** Neurogenic orthostatic hypotension in Parkinson's disease with autonomic failure **Treatment:** - Non-pharmacological measures: Rise slowly from lying/sitting; compression stockings (waist-high); increased salt and fluid intake (2-3 L water, 10g salt daily); elevation of head of bed 10-20 degrees; small frequent meals; avoid alcohol and large carbohydrate loads - Midodrine 5 mg three times daily (alpha-1 agonist, titrated based on response) - Fludrocortisone 0.1 mg daily (volume expansion) - Droxidopa added for persistent symptoms - Review of Parkinson's medications (carbidopa-levodopa may worsen orthostatic hypotension) **Clinical Pearl:** Neurogenic orthostatic hypotension results from failure of the sympathetic nervous system to appropriately vasoconstrict in response to standing, which normally maintains cerebral perfusion despite gravity-induced blood pooling in the lower extremities. In Parkinson's disease and related synucleinopathies (especially multiple system atrophy), degeneration of sympathetic neurons leads to autonomic failure. The key distinguishing feature from non-neurogenic causes is inadequate compensatory tachycardia (heart rate increase <15 bpm) because the baroreflex arc is impaired. --- ## Case 3: Pheochromocytoma - Catecholamine Excess ### Patient Presentation **Demographics:** 38-year-old female **Chief Complaint:** Episodes of severe headache, palpitations, and sweating **History of Present Illness:** A 38-year-old woman presents with a 6-month history of intermittent episodes characterized by severe throbbing headache, pounding heartbeat, and profuse sweating. Episodes occur 2-3 times per week, last 20-30 minutes, and are accompanied by intense anxiety and pallor. She has noted progressively worsening hypertension, with recent readings at home reaching 200/120 mmHg during episodes. Between episodes, her blood pressure is elevated but more modest (150/95 mmHg). She has lost 10 pounds despite normal appetite. Family history is significant for a father who died suddenly at age 42 and a brother with thyroid cancer. **Physical Examination:** - Vital signs (during episode): BP 210/125, HR 124, RR 20, T 37.4C - Vital signs (baseline): BP 158/98, HR 88 - General: Diaphoretic, anxious, pale during episode - Cardiovascular: Tachycardic, regular rhythm, no murmurs - Abdominal: Palpation of left upper quadrant precipitates hypertensive episode (suggestive of tumor manipulation) **Workup:** - **Plasma free metanephrines:** Markedly elevated (metanephrine 856 pg/mL, normal <57; normetanephrine 1243 pg/mL, normal <148) - **24-hour urine catecholamines and metanephrines:** Elevated - **CT abdomen with contrast:** 4 cm left adrenal mass with heterogeneous enhancement - **MIBG scan:** Avid uptake in left adrenal gland, no metastatic disease - **Genetic testing:** RET proto-oncogene mutation positive (MEN2A) - **Serum calcitonin:** Elevated (medullary thyroid cancer screening) **Diagnosis:** Pheochromocytoma in the setting of Multiple Endocrine Neoplasia type 2A (MEN2A) **Treatment:** - Alpha-blockade with phenoxybenzamine initiated 2 weeks before surgery (non-competitive alpha antagonist; titrated to postural hypotension) - Beta-blockade added AFTER adequate alpha-blockade (to avoid unopposed alpha stimulation) - High-sodium diet and fluids to expand contracted intravascular volume - Laparoscopic adrenalectomy after adequate preparation - Screening for medullary thyroid carcinoma and hyperparathyroidism (MEN2A components) - Genetic counseling and family screening **Clinical Pearl:** Pheochromocytoma is a catecholamine-secreting tumor of chromaffin cells, most commonly arising in the adrenal medulla. The episodic nature of symptoms reflects intermittent catecholamine release. The classic triad is headache, diaphoresis, and palpitations. Alpha-blockade must precede beta-blockade to prevent unopposed alpha-mediated vasoconstriction during catecholamine surges. The "10% rule" historically stated 10% are bilateral, 10% extra-adrenal, 10% malignant, and 10% familial, but genetic testing reveals hereditary syndromes in up to 40% of cases. --- ## Clinical Image ![Horner syndrome clinical photograph](case_01_image.jpg) **Image Description:** Clinical photograph demonstrating unilateral Horner syndrome with ptosis (drooping eyelid), miosis (constricted pupil), and apparent enophthalmos on the affected side compared to the normal contralateral eye. **Attribution:** Image from Wikimedia Commons (https://commons.wikimedia.org/), Creative Commons Attribution-ShareAlike license.