Faculty Bibliography

BACKGROUND: Few descriptions of cluster and cluster-like headache made before the 19th century have been reported. CASE DESCRIPTION: We present a previously unreported early description of a probable cluster headache case made by Francisco Suarez de Rivera (1686-c.1751), one of the main physicians of the Spanish Age of Enlightenment, writer of almost 40 textbooks about medicine, surgery, pharmacology, and therapeutics. DISCUSSION: The depiction here reported of a woman with probable cluster headache is possibly one of the earliest known and, to our knowledge, the first in Hispanic literature. We also review other descriptions of cluster and cluster-like headache from the same time period.

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.

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.

The glutamate neurotransmitter system has the potential to transform our knowledge of the pathophysiology of schizophrenia and help us identify potential treatment targets. In this section of the supplement, the dopamine system is first reviewed as it relates to schizophrenia and its treatment with the currently available antipsychotics, followed by a discussion of glutamate receptors and how they, too, can impact on positive, negative, and cognitive symptoms. Symptoms of schizophrenia can be theoretically explained by a hyper-dopaminergic state existing in the mesolimbic pathway and a hypodopaminergic state in the mesocortical pathways; the former results in positive symptoms and the latter leads to negative, cognitive, and affective symptoms. Current FDA-approved pharmacologic options for the treatment of schizophrenia involve dopamine blockade at the dopamine D2 receptor. Although commercially available antipsychotic agents have at least some degree of antagonism at the dopamine D2 receptor, there are some investigational agents that produce an antipsychotic effect in the absence of direct dopamine D2 receptor antagonism. The glutamate-dopamine model of schizophrenia offers new therapeutic targets, including NMDA agonists, glycine transport inhibitors, and metabotropic glutamate receptor agonists.

The Riley-Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10 patients. For comparison we also recorded muscle spindles from 15 healthy subjects and from two patients with hereditary sensory and autonomic neuropathy IV, who have profound sensory disturbances but no ataxia. Tungsten microelectrodes were inserted percutaneously into fascicles of the common peroneal nerve at the fibular head. Intraneural stimulation within muscle fascicles evoked twitches at normal stimulus currents (10-30 microA), and deep pain (which often referred) at high intensities (1 mA). Microneurographic recordings from muscle fascicles revealed a complete absence of spontaneously active muscle spindles in patients with hereditary sensory and autonomic neuropathy III; moreover, responses to passive muscle stretch could not be observed. Conversely, muscle spindles appeared normal in patients with hereditary sensory and autonomic neuropathy IV, with mean firing rates of spontaneously active endings being similar to those recorded from healthy controls. Intraneural stimulation within cutaneous fascicles evoked paraesthesiae in the fascicular innervation territory at normal stimulus intensities, but cutaneous pain was never reported during high-intensity stimulation in any of the patients. Microneurographic recordings from cutaneous fascicles revealed the presence of normal large-diameter cutaneous mechanoreceptors in hereditary sensory and autonomic neuropathy III. Our results suggest that the complete absence of functional muscle spindles in these patients explains their loss of deep tendon reflexes. Moreover, we suggest that their ataxic gait is sensory in origin, due to the loss of functional muscle spindles and hence a compromised sensorimotor control of locomotion

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

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

Background: Visceral sensations are relayed to the brain through a network of afferent nerves. Awareness of these sensations differs among individuals, likely due to different thresholds and CNS processing characteristics. Differences in the conscious awareness of bodily sensations may explain specific cardiovascular phenotypes. Thus, our goal was to evaluate the role, if any, of conscious awareness of body sensations and their relationship with hemodynamic responses to tilt in patients with orthostatic intolerance. Methods: Thirty-two otherwise healthy patients who complained of orthostatic intolerance participated in the study. We assessed perception of body sensations on a self-reported body vigilance scale. We measured blood pressure, heart rate and plasma catecholamine responses to passive upright tilt. Thirteen patients experienced typical vasovagal syncope (i.e., a fall in blood pressure and heart rate) 4; patients had an increase in heart rate >30 beat/min without a fall in blood pressure and were diagnosed as postural tachycardia syndrome; and 15 patients had normal cardiovascular responses to tilt and were classified as having unexplained orthostatic intolerance. Results: Self-reported feelings of shortness of breath (p<0.05), tingling (p<0.01), numbness (p<0.003) and chest discomfort (p<0.01) were correlated positively with supine plasma epinephrine levels and the increase in plasma epinephrine levels with tilt (p<0.02). Higher body vigilance was significantly related with the increase in heart rate during tilt, both at 3 min (p<0.02) and the maximum heart rate recorded (p<0.002). Patients with unexplained orthostatic intolerance scored higher for the time spent 'scanning their body for sensations' compared with patients who had vasovagal syncope during tilt (52 +/- 9 vs. 23 +/- 6%, p<0.02). Conclusion: Increased somatic vigilance is associated with a greater release of epinephrine on standing and faster heart rates. Increased somatic vigilance is associated with the postural tachycardia syndrome and may be the cause of hitherto unexplained orthostatic intolerance

Background: Patients with familial dysautonomia have a selective defect in the afferent neurons of the baroreflex. Failure to sense blood pressure result in the unregulated release of plasma catecholamines and volatile blood pressure. One of the most disabling features of familial dysautonomia are the recurrent attacks of nausea, retching and vomiting triggered by emotional or physiological stressors and associated with hypertension, tachycardia and psychomotor agitation. A pronounced surge in circulating norepinephrine during these crises readily explains the hypertension, but the cause of the nausea and vomiting remains unknown. Methods: Seven patients with familial dysautonomia (mean age 17 +/- 3 years, 4 females) confirmed by genetic testing were studied. We monitored blood pressure and heart rate and measured plasma catecholamines when they were feeling well and during typical vomiting crises triggered by emotionally charged situations. Results: When the patients were feeling well, average supine blood pressure was 124 +/- 7/64 +/- 5 mmHg with a heart rate of 81 +/- 3 beats/min. All patients experienced typical crises when they complained of severe nausea and were retching loudly. Vomiting was prevented by the fundoplication surgery. During crises, all patients were hypertensive (180 +/- 9/116 +/- 4 mmHg) and tachycardic (124 +/- 4 beats/min) but denied feeling palpitations. While supine, plasma norepinephrine levels increased from 130 +/- 42 to 772 +/- 151 pg/ml (p<0.002), plasma epinephrine levels increased from 20 +/- 5 to 63 pg/ml, and plasma dopamine levels increased markedly from 22 +/- 2 to 96 +/- 20 pg/ml. Conclusions: Our finding of high levels of circulating dopamine during crises in patients with familial dysautonomia suggest that the severe nausea and vomiting is due to activation of dopamine receptors in the chemoreceptor trigger zone