Faculty Bibliography

Autoimmune autonomic ganglionopathy (AAG) and myasthenia gravis (MG) are both autoimmune channelopathies mediated by antibodies directed against nicotinic acetylcholine receptors. While both diseases target acetylcholine receptors, skeletal muscle and ganglionic receptor subtypes have key immunologic and genetic distinctions, and reports of patients with both AAG and MG are rare. We report a patient with antibody-confirmed AAG and elevated levels of ACh binding antibodies that did not meet clinical or electrodiagnostic criteria for MG. We presume that his skeletal muscle nAChR seropositivity was a false positive, perhaps due to the cross reactivity of the patient's ganglionic nAChR antibodies with skeletal nAChR subtypes

Orthostatic hypotension is defined as a blood pressure fall of > 20 mm Hg systolic and/or 10 mm Hg diastolic within 3 minutes of an upright position. The Movement Disorders Society commissioned a task force to assess existing clinical rating scales addressing symptoms of orthostatic hypotension in Parkinson's disease. Seven neurologists and a clinimetrician assessed each scale's previous use and critiqued its clinimetric properties. A scale was "recommended" if it had been applied to populations of patients with Parkinson's disease, with data on its use in studies beyond the group that developed the scale, and was found to be clinimetrically valid. A scale was considered "suggested" if it had been applied to Parkinson's disease, but only 1 of the other criteria was applied. A scale was "listed" if it met only 1 criterion. Symptoms of orthostatic hypotension are generally assessed in scales on wider autonomic or nonmotor symptoms. Some scales designed to detect orthostatic hypotension-related symptoms provide information on their severity: the AUTonomic SCale for Outcomes in PArkinson's Disease and the COMPosite Autonomic Symptom Scale met criteria for recommended with some limitations; the Novel Non-Motor Symptoms Scale and the Orthostatic Grading Scale were classified as suggested. The Self-completed Non-Motor Symptoms Questionnaire for Parkinson's Disease was classified as suggested as a tool for screening orthostatic symptoms. However, these and the listed scales need further validation and application before they can be recommended for clinical use in patients with Parkinson's disease.

Familial dysautonomia (FD) is an autosomal recessive disorder characterized by autonomic and sensory neuropathy. Owing to pervasive dysfunction, the disease has protean clinical manifestations, affecting the ocular, gastrointestinal, pulmonary, orthopedic, vasomotor, and neurologic systems. The gastrointestinal perturbations, including dysphagia, gastroesophageal dysmotility, gastroesophageal reflux, and vomiting crises, are among the earliest signs. Here, we present the first 3 instances of gastric ulcers in patients with FD and discuss their common presenting features and the special management that was required

Whereas aging affects cognitive and psychomotor processes negatively, the impact of aging on emotional processing is less clear. Using an "old-new" binary decision task, we ascertained the modulation of response latencies after presentation of neutral and emotional pictures in "young" (M = 27.1 years) and "young-old" adults with a mean age below 60 (M = 57.7 years). Stimuli varied on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Young-old adults had significantly longer reaction times. However, young and young-old adults showed the exact same pattern of response time modulation by emotional stimuli: Response latencies were longer for high-arousal than for low-arousal pictures and longer for negative than for positive or neutral stimuli. This result suggests that the specific effects of implicitly processed emotional valence and arousal information on behavioral response time are preserved in young-old adults despite significant age-related psychomotor decline.

OBJECTIVE: Panayiotopoulos syndrome is a benign idiopathic childhood epilepsy characterized by altered autonomic activity at seizure onset. METHODS: Three siblings with Panayiotopoulos syndrome underwent 24-hour EEG recording and head-up tilt testing with continuous blood pressure and RR interval monitoring. Plasma catecholamines and vasopressin were measured while supine, upright, and during a typical seizure. RESULTS: Patient 1, a 12-year-old girl, had a history of involuntary lacrimation, abdominal pain, and recurrent episodes of loss of muscle tone and unresponsiveness followed by somnolence. Her EEG revealed bilateral frontotemporal spikes. Patient 2, a 10-year-old boy, had episodic headaches with pinpoint pupils, skin flushing of the face, trunk, and extremities, purple discoloration of hands and feet, diaphoresis, nausea, and vomiting. Tilt testing triggered a typical seizure after 9minutes; there was a small increase in blood pressure (+5/4mm Hg, systolic/diastolic) and pronounced increases in heart rate (+59bpm) and norepinephrine (+242pg/mL), epinephrine (+175pg/mL), and vasopressin (+22.1pg/mL) plasma concentrations. Serum glucose was elevated (206mg/dL). His EEG revealed right temporal and parietal spikes. Patient 3, an 8-year-old boy, had a history of restless legs at night, enuresis, night terrors, visual hallucinations, cyclic abdominal pain, and nausea. His EEG showed bitemporal spikes. CONCLUSION: Hypertension, tachycardia, and the release of vasopressin suggest activation of the central autonomic network during seizures in familial Panayiotopoulos syndrome. These autonomic and neuroendocrine features may be useful in the diagnosis and may have therapeutic implications

An increased incidence of neoplasia was recently reported in patients with familial dysautonomia. This suggests that, in addition to its role in neuronal development, the IKBKAP gene may also influence DNA repair. Here we report the case of a 28-year-old male with familial dysautonomia who was found to have neoplastic lesions detected post mortem as incidental findings. This case indicates that the prevalence of tumorgenesis within this population may be underestimated.

Background: Patients with familial dysautonomia (FD) fail to increase respiratory drive in response to low oxygen and high CO₂ levels. Many hypoventilate and have frequent apneic events during sleep, a time associated with an increased incidence of sudden death. To assess the need for non-invasive ventilation, patients with FD routinely undergo sleep studies with end-tidal CO₂ monitoring. Because most have severe lung disease, it is not known, however, whether end-tidal CO₂ levels accurately reflect arterial blood CO₂ levels. Methods: We studied 88 patients with FD (mean age 25 +/- 1, 45; females:43 males). We measured the partial pressure of CO₂ in blood obtained from the radial artery at the wrist (ABL80 FLEX, Radiometer, Denmark). End-tidal CO₂ was continuously sampled from a nasal canula (infrared analysis 5200 Ohmeda, USA). The average CO₂ value obtained over 10 full tidal breaths was used. All measurements were obtained during relaxed spontaneous breathing in the supine position. The relationship between end-tidal and arterial CO₂ measurements was examined using Pearson correlations. Results: All patients had a history of at least one aspiration pneumonia. The average partial pressure of oxygen in arterial blood was 87 +/- 2 mmHg. Thirty-one patients (36%) had arterial oxygen levels B80 mmHg. The average partial pressure of CO₂ was 43 +/- 0.4 mmHg (range 34-57 mmHg). Thirty-four patients (39%) had hypercapnia with CO₂ in arterial blood >=45 mmHg. Measurements of end-tidal CO₂ correlated tightly with CO₂ measured in arterial blood (y = 0.88x + 2.23, R² = 0.50, p<0.001). Conclusions: Our results show that in patients with FD, despite severe lung disease, the partial pressure of CO₂ measured in expired air (i.e. end tidal CO₂) accurately reflects the partial pressure ofCO₂ in arterial blood. Monitoring end tidal CO₂ is critically important to determine the potential role of apnea/hypoventilation in sudden death during sleep

Background: Hereditary sensory and autonomic neuropathy type IV (HSAN-IV) is a recessive disease caused by mutations affecting the tyrosine kinase receptor. The disorder affects the development of sensory and sudomotor sympathetic nerve fibers resulting in complete insensitivity to pain and anhidrosis. However, little is known about the cardiovascular autonomic phenotype of the disorder. Methods: We measured blood pressure, heart rate and catecholamines, vasopressin, endothelin and renin activity in plasma while supine and after 10 min of passive upright tilt in 10 patients with typical clinical features of HSAN-IV and diagnostic confirmation with genetic testing (mean age 9 +/- 2 years old, 4 females). Results: In the supine position, blood pressures (104 +/- 5/ 58 +/- 4 mmHg) and heart rates (87 +/- 9 beats/min) were normal. During upright tilt, mean arterial blood pressure changed little (-5 +/- 5 mmHg, p = 0.17) and heart rate increased appropriately (+23 +/- 5 beat/min, p<0.001). In all patients, plasma norepinephrine levels were low or undetectable while in the supine position (31 +/- 3 pg/ml) and failed to increase with upright tilt (4 +/- 5 pg/ml). Plasma renin activity levels increased slightly from 2.0 +/- 0.6 to 3.6 +/- 1.1 pg/ml with head-up tilt (+68 +/- 33 D%, p<0.03). Plasma vasopressin increased little and endothelin levels were essentially unchanged during upright tilt. Conclusions: Patients with HSAN-IV have very low levels of norepinephrine while supine and upright, but do not have orthostatic hypotension. Other vasoactive peptides involved in orthostatic blood pressure maintenance are not increased. These results challenge our current concepts of the role of norepinephrine in the regulation of blood pressure. The mechanism by which patients with HSAN-IV maintain their blood pressure is unknown