Jose-Alberto Palma

Autonomic disorders predicting Parkinson's disease

It is now well recognized that there is a premotor phase of Parkinsons disease (PD) with hyposmia and REM sleep behavior disorder caused by degeneration of specific CNS neurons. Most patients with PD describe autonomic symptoms at the time of diagnosis suggesting that these features may have potential sensitivity as clinical biomarkers of the premotor phase. The recognition that damage to peripheral autonomic neurons is present in the early stages of PD has led to a search for specific abnormalities in autonomic function that could serve as predictive biomarkers. There is evidence that constipation, urinary and sexual dysfunction and more recently decreased cardiac chronotropic response during exercise, are part of the premotor parkinsonian phenotype. The sensitivity and specificity of these features has yet to be accurately assessed. We briefly review the evidence for autonomic dysfunction as biomarker of premotor PD.

Neural control of the heart: Recent concepts and clinical correlations

Areas distributed throughout the neuraxis, including the anterior insula, anterior cingulate cortex (ACC), amygdala, hypothalamus, periaqueductal gray matter, parabrachial nucleus, and several regions of the medulla, exert a beat-to-beat control on cardiac function. These areas are critically involved in emotional behavior, stress responses, and homeostatic reflexes and exert their influence on heart rate (HR) and cardiac contractility via the sympathetic and parasympathetic nervous systems. Over the past several years, advances in neuroanatomical, neurophysiologic, and functional imaging studies have provided insight into the central and peripheral mechanisms of neural control of cardiac function in humans. Whereas some issues, such as lateralization of this central control, remain unresolved, the adverse cardiac consequences of a wide variety of neurologic disorders emphasize the need to better understand the functional anatomy and neurochemical mechanisms of the neural control of the heart. Important examples are severe arrhythmias and myocardial injury in the setting of neurologic catastrophes and sudden unexplained death in epilepsy. This review will focus on some of the current experimental and clinical information related to these relevant issues for the neurologist.

Sleep loss as risk factor for neurologic disorders: A review

Sleep loss refers to sleep of shorter duration than the average baseline need of seven to eight hours per night. Sleep loss and sleep deprivation have severe effects on human health. In this article, we review the main aspects of sleep loss, taking into account its effects on the central nervous system. The neurocognitive and behavioral effects of sleep loss are well known. However, there is an increasing amount of research pointing to sleep deprivation as a risk factor for neurologic diseases, namely stroke, multiple sclerosis, Alzheimers disease, headache, epilepsy, pain, and somnambulism. Conversely, sleep loss has been reported to be a potential protective factor against Parkinsons disease. The pathophysiology involved in this relationship is multiple, comprising immune, neuroendocrine, autonomic, and vascular mechanisms. It is extremely important to identify the individuals at risk, since recognition and adequate treatment of their sleep problems may reduce the risk of certain neurologic disorders.

Orthostatic hypotension in Parkinson disease: How much you fall or how low you go?

Orthostatic hypotension (OH) is frequent in patients with Parkinsons disease (PD) and can occur with or without symptoms. Pharmacological treatments are effective, but often exacerbate supine hypertension. Guidelines exist for the diagnosis, but not for the treatment of OH. We examined the relationship between blood pressure (BP) and symptoms in a cohort of PD patients with the goal of identifying a hemodynamic target to guide treatment. We measured BP supine and upright (tilt or active standing) and identified the presence or absence of symptomatic OH by using a validated patient‐reported outcome questionnaire in 210 patients with PD. We evaluated the usefulness of the 20/10 and 30/15 mmHg diagnostic criteria (systolic/diastolic) to identify symptomatic OH. Fifty percent of the PD patient cohort met criteria for the 20/10 fall and 30% for the 30/15 BP fall. Among the patients who met either OH criteria, the percentage of those with symptoms was small (33% of those with 20/10 and 44% of those with 30/15 mmHg; 16% and 13%, respectively, overall). Symptomatic OH was associated with an upright mean BP below 75 mmHg. A mean standing BP <75 mmHg had a sensitivity of 97% and a specificity of 98% for detecting symptomatic OH. Although the prevalence of OH in PD is high, not all patients have symptoms of organ hypoperfusion. A mean standing BP below 75 mmHg appears to be a useful benchmark when deciding whether the benefits of initiating pharmacological treatment of OH outweigh the risks of exacerbating supine hypertension.

Droxidopa in neurogenic orthostatic hypotension

Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure (BP) on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy (MSA), pure autonomic failure (PAF), and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise BP by acting at the neurovascular junction to increase vascular tone. This article summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials.

Natural history of pure autonomic failure: A United States prospective cohort

To define the clinical features and biomarkers that predict which patients with pure autonomic failure will develop Parkinson disease, dementia with Lewy bodies, or multiple system atrophy.

Changes in the Heart Rate Variability in Patients with Obstructive Sleep Apnea and Its Response to Acute CPAP Treatment

Introduction Obstructive Sleep Apnea (OSA) is a major risk factor for cardiovascular disease. The goal of this study was to demonstrate whether the use of CPAP produces significant changes in the heart rate or in the heart rate variability of patients with OSA in the first night of treatment and whether gender and obesity play a role in these differences. Methods Single-center transversal study including patients with severe OSA corrected with CPAP. Only patients with total correction after CPAP were included. Patients underwent two sleep studies on consecutive nights: the first night a basal study, and the second with CPAP. We also analyzed the heart rate changes and their relationship with CPAP treatment, sleep stages, sex and body mass index. Twenty-minute segments of the ECG were selected from the sleep periods of REM, no-REM and awake. Heart rate (HR) and heart rate variability (HRV) were studied by comparing the R-R interval in the different conditions. We also compared samples from the basal study and CPAP nights. Results 39 patients (15 females, 24 males) were studied. The mean age was 50.67 years old, the mean AHI was 48.54, and mean body mass index was 33.41 kg/m2 (31.83 males, 35.95 females). Our results showed that HRV (SDNN) decreased after the use of CPAP during the first night of treatment, especially in non-REM sleep. Gender and obesity did not have any influence on our results. Conclusions These findings support that cardiac variability improves as an acute effect, independently of gender or weight, in the first night of CPAP use in severe OSA patients, supporting the idea of continuous use and emphasizing that noncompliance of CPAP treatment should be avoided even if it is just once.

Refractory migraine in a headache clinic population

BackgroundMany migraineurs who seek care in headache clinics are refractory to treatment, despite advances in headache therapies. Epidemiology is poorly characterized, because diagnostic criteria for refractory migraine were not available until recently. We aimed to determine the frequency of refractory migraine in patients attended in the Headache Unit in a tertiary care center, according to recently proposed criteria.MethodsThe study population consisted of a consecutive sample of 370 patients (60.8% females) with a mean age of 43 years (range 14-86) evaluated for the first time in our headache unit over a one-year period (between October 2008 and October 2009). We recorded information on clinical features, previous treatments, Migraine Disability Assessment Score (MIDAS), and final diagnosis.ResultsOverall migraine and tension-type headache were found in 46.4% and 20.5% of patients, respectively. Refractory migraine was found in 5.1% of patients. In refractory migraineurs, the mean MIDAS score was 96, and 36.8% were medication-overusers.ConclusionsRefractory migraine is a relatively common and very disabling condition between the patients attended in a headache unit. The proposed operational criteria may be useful in identifying those patients who require care in headache units, the selection of candidates for combinations of prophylactic drugs or invasive treatments such as neurostimulation, but also to facilitate clinical studies in this patient group.

The Natural History of Pure Autonomic Failure: a U.S. Prospective Cohort

To define the clinical features and biomarkers that predict which patients with pure autonomic failure will develop Parkinson disease, dementia with Lewy bodies, or multiple system atrophy.

Is cardiac function impaired in premotor Parkinson's disease? A retrospective cohort study

The objective of this study was to assess cardiovascular response during cardiac stress testing in neurologically asymptomatic individuals who developed motor features of Parkinsons disease several years after the cardiac stress testing. This was a retrospective cohort study of patients who underwent cardiac stress testing between January 2001 and December 2010. Patients were followed until May 2012 to select those who developed Parkinsons disease. Heart rate and blood pressure both at rest and at peak exercise and heart rate variability at rest were recorded. For each patient who developed Parkinsons disease, 2 matched controls who did not develop Parkinsons disease at the end of the follow‐up period were selected. Patients who were diagnosed with Parkinsons disease the same day of cardiac stress testing also were selected for comparison purposes. After excluding participants who were lost to follow‐up, 2739 patients remained. From this cohort, 18 (11 men) had developed Parkinsons disease 4.27 ± 2.56 years after the cardiac stress test. Thirty‐six matched controls were selected. At peak exercise, the maximum heart rate and the percentage of theoretical maximum heart rate were significantly lower in patients who developed Parkinsons disease after cardiac stress testing compared with controls. The sensitivity of a maximum heart rate ≤ 143 beats per minute to predict a diagnosis of Parkinsons disease after a mean of 4.27 years was 83%, and the specificity was 62%. The results from this exploratory study demonstrate that chronotropic insufficiency may constitute an early sign of Parkinsons disease during the premotor phase, serving as potential risk factor for its diagnosis. Further investigations are needed in larger populations.