Is heart rate variability a valuable method to investigate cardiac autonomic dysfunction in subjects with leukemia? A systematic review to evaluate its importance in clinical practice.

Impaired cardiovascular and autonomic function during treatment and during recovery from leukemia has been indicated. In this context, heart rate variability (HRV) is a non-invasive measure that describes the oscillations of the intervals between consecutive heart beats (RR intervals), influenced by the autonomic nervous system. We intend to review literature showing HRV changes in leukemia subjects. The articles selected in the current review were attained up to March 2018, and the search was limited to articles in English language, published in peer-reviewed journals, with both adult and child age samples. The articles were investigated in the five electronic databases: PubMed, Physiotherapy Evidence Database (PEDro), Cochrane Clinical Trials, Scientific Electronic Library Online (SciELO), and Excerpta Medica dataBASE (EMBASE). Towards the end of the research, 9 studies were included. Subjects undergoing treatment for leukemia have reduced HRV, signifying decreased vagal control of heart rate. The subjects that undertook leukemia treatment and their survivors experienced a reduction in HRV with subsequent recovery, but the recovery time is ill defined. HRV is reduced in leukemia subjects who progress to neuropathy secondary to chemotherapy, accompanied by cardiac dysfunction. We advocate the use of HRV to evaluate autonomic function and decide the treatment to prevent autonomic impairment in leukemia subjects.

Human papillomavirus (HPV) vaccine and autonomic disorders: a position statement from the American Autonomic Society.

INTRODUCTION: Human papillomavirus (HPV) vaccination has been anecdotally connected to the development of dysautonomia, chronic fatigue, complex regional pain syndrome and postural tachycardia syndrome. OBJECTIVES: To critically evaluate a potential connection between HPV vaccination and the above-noted conditions. METHODS: We reviewed the literature containing the biology of the virus, pathophysiology of infection, epidemiology of associated cancers, indications of HPV vaccination, safety surveillance data and published reports linking HPV vaccination to autonomic disorders. RESULTS: At this time, the American Autonomic Society finds that there are no data to support a causal relationship between HPV vaccination and CRPS, chronic fatigue, and postural tachycardia syndrome to other forms of dysautonomia. CONCLUSION: Certain conditions are prevalent in the same populations that are vaccinated with the HPV vaccine (peri-pubertal males and females). This association, however, is an insufficient proof of causality.

Polypharmacy and potentially inappropriate medication use in older patients with multiple myeloma, related to fall risk and autonomous neuropathy.

PURPOSE: Multiple myeloma is a chronic, uncurable hematological cancer with the involvement of multiple organ systems. As a disease affecting older patients, the treatment of multiple myeloma should be based on individual patient characteristics. Polypharmacy is an increasing problem in the care of older patients and in patients with multiple myeloma, polypharmacy is almost inevitable. We aimed to evaluate the applicability of polypharmacy definitions and the relation of polypharmacy with disease outcomes in patients with multiple myeloma. METHODS: Eighty patients older than 65 years and diagnosed with multiple myeloma were retrospectively enrolled. Patient files, prescriptions, evaluations for polypharmacy were determined according to Beers and START/STOPP criteria. Outcomes were recorded from files in terms of fractures, autonomous neuropathy, and renal functions. RESULTS: Polypharmacy with ≥4 drugs was observed in 65 patients while polypharmacy with ≥5 drugs was observed in 51 patients. Autonomous neuropathy, polypharmacy with more than four or five medications, and use of multiple medications in the same category were related with poor ECOG performance status in women, while prolonged use of benzodiazepines and central nervous system (CNS) affecting drugs and inappropriate polypharmacy were more frequent in men with poor ECOG performance status. The majority of patients aged 75-84 years were observed to use inappropriate polypharmacy. Autonomous neuropathy and fall risk were observed to be significantly related with inappropriate polypharmacy. CONCLUSIONS: Drugs affecting balance and perception should be reconsidered in patients with multiple myeloma.

Carfilzomib is an effective upfront treatment in AL amyloidosis patients with peripheral and autonomic neuropathy.

Bortezomib is standard treatment in AL amyloidosis (AL), but is contraindicated in patients with significant neuropathy. Carfilzomib, a second-generation proteosomal inhibitor, results in a lower incidence of neuropathy than bortezomib, but data in AL is scant. We report a cohort of five AL patients treated with upfront carfilzomib. All had cardiac, peripheral and autonomic neuropathy at presentation. All achieved at least a very good partial haematological response. There was no worsening in cardiac function, peripheral or autonomic neuropathy. Carfilzomib is an effective upfront treatment option in AL patients with peripheral and/or autonomic neuropathy (without severe cardiac or renal involvement).

Exposure to antenatal corticosteroids and reduced respiratory sinus arrhythmia in adult survivors of extremely low birth weight.

Purpose/aim: Antenatal corticosteroid (ACS) therapy has dramatically increased survival rates among extremely low birth weight (ELBW) infants. However, the long-term effects of ACS on autonomic nervous system function have not been explored. Using the world's oldest longitudinally followed cohort of ELBW infants we compared respiratory sinus arrhythmia (RSA) among ELBW survivors whose mothers received ACS (ELBW-S), those who did not (ELBW-NS) and normal birth weight (NBW) controls in their 20 and 30 s. Methods: Resting electrocardiogram (ECG) was recorded from ELBW-S (n = 28), ELBW-NS (n = 36), and matched NBW controls (n = 79) at 22-26 and 29-36 years. Resting RSA was compared across groups via analyses of covariance (ANCOVA), adjusting for sex, medication use, postnatal steroid exposure and the presence of chronic health conditions. RSA was also compared across assessments for each group. Results: At 29-36 years, resting RSA in ELBW-S was significantly lower than in NBW controls. RSA in the ELBW-NS group was intermediate between ELBW-S and NBW groups. Although the ELBW-S group also showed nominally reduced RSA compared to NBW controls at the 22-26-year visit, this difference was not statistically significant. Conclusions: ELBW survivors exposed to ACS had lower RSA than NBW controls during their 30 s, suggestive of a decline in parasympathetic input to heart. ELBW survivors who received ACS may be particularly vulnerable to cardiovascular problems in later life.

Prenatal alcohol exposure and autonomic nervous system dysfunction: A review article.

Alcohol is a recognized teratogen that affects various aspects of fetal development. Tissue that is particularly susceptible to its teratogenicity is neuronal tissue. The effect of prenatal alcohol exposure (PAE) on the central nervous system has been extensively studied, yet the knowledge on the influence of PAE on the autonomic nervous system is scarce. The purpose of this article is to review the current state of knowledge about the impact of PAE on the autonomic nervous system. Studies conducted on the PAE animal model have shown that prenatal alcohol exposure is associated with significant alterations in the autonomic nervous system, but the mechanisms and consequences are not yet clearly defined. It was established that PAE causes decreased heart rate variability (HRV) in fetal cardiotocography. Several studies have revealed that later, in infancy and childhood, reduced parasympathetic activity with or without compensating sympathetic activity is observed. This may result in behavioral and attention disorders, as well as an increased predisposition to sudden infant death syndrome. Both animal and human studies indicate that the relationship between PAE and autonomic dysfunction exists, however large, well-designed, prospective studies are needed to con rm the causal relationship and characterize the nature of the observed changes.

Sympathomimetic Toxidromes and Other Pharmacological Causes of Acute Hypertension.

PURPOSE OF REVIEW: Acute drug-induced hypertension, sympathomimetic toxicity, and other hyperadrenergic states can be caused by both xenobiotic toxicity and withdrawal. This manuscript is a selective review of the recent literature regarding pharmacologic causes of hypertensive emergencies and other hyperadrenergic states. RECENT FINDINGS: We will discuss designer stimulants, alpha2 and baclofen agonist withdrawal, and the clinical entity known as posterior reversible encephalopathy syndrome (PRES). Additionally, we examine the controversial "unopposed alpha" phenomenon which may result from use of beta-adrenergic antagonist in the presence of stimulant toxicity. These topics encompass clinical situations and disease entities that are increasingly encountered and are often either unanticipated or under-recognized.

Possible Ameliorative Effect of Ivabradine on the Autonomic and Left Ventricular Dysfunction Induced by Doxorubicin in Male Rats.

Heart failure is a common adverse effect associated with doxorubicin treatment. The aim of this study is to investigate the effect of ivabradine treatment on doxorubicin-induced heart failure in conscious rats. Rats were treated with doxorubicin (2.5 mg/kg/d) or ivabradine (10 mg/kg/d) alone or along with doxorubicin injections. Changes in heart rate variability (HRV), baroreflex sensitivity, left ventricular (LV) function, serum cardiac troponin T, and cardiac histological features were taken as index parameters for the development of heart failure. Ivabradine significantly reduced the elevated heart rate; normalized the parameters of LV function, dP/dtmax and the relaxation time constant (Tau); reduced the elevated serum level of cardiac troponin T; and minimized the cardiac structural abnormalities in doxorubicin-treated rats. Moreover, ivabradine significantly increased the diminished time domain parameters of HRV, SDNN and rMSSD, and decreased the elevated low frequency power and the low frequency/high frequency while having no effect on the reduced high frequency power. Consistently, ivabradine significantly lowered the elevated baroreflex sensitivity measured by sodium nitroprusside. In conclusion, ivabradine ameliorated the LV dysfunction induced by doxorubicin. Moreover, ivabradine increased the overall HRV and restored the autonomic balance by reducing the sympathetic over activation. Therefore, ivabradine may have a possible therapeutic potential against doxorubicin-induced heart failure.

Long-term anabolic steroids in male bodybuilders induce cardiovascular structural and autonomic abnormalities.

OBJECTIVE: The aims of this study were to examine the hypothesis that users of anabolic androgenic steroids (AAS) would have cardiac autonomic disorders and that there is a correlation between sympathetic modulation, high blood pressure (BP) and alterations to cardiac dimensions. METHODS: Forty-five male subjects were enrolled in the study. They were categorized into three groups comprising bodybuilders actively using AAS (AAS users; n = 15), bodybuilders who had never used AAS (nonusers; n = 15) and age-paired healthy sedentary controls (n = 15). Hemodynamic parameters, linear and nonlinear analyses of heart rate variability and electrocardiography and echocardiography analyses were performed at rest. RESULTS: Bodybuilders in the AAS group had a higher mean BP than those in the ASS nonuser group (p < 0.05) and the sedentary controls (p < 0.001). Cardiac sympathetic modulation was higher in AAS users than in AAS nonusers (p < 0.05) and the sedentary controls (p < 0.001), and parasympathetic modulation was lower in AAS users than in nonusers and the sedentary controls (p < 0.05). Shannon entropy was lower in AAS users than in the sedentary (p < 0.05) controls, and the corrected QT interval and QT dispersion were higher in AAS users than in the sedentary controls (p < 0.05). The interventricular septal thickness, left ventricle posterior wall thickness and relative diastolic wall thickness were higher in AAS users than in AAS nonusers and the sedentary controls (p < 0.001). AAS users showed a positive correlation between increased sympathetic modulation and high BP (r = 0.48, p < 0.005), as well as sympathetic modulation and cardiac hypertrophy (r = 0.66, p < 0.001). CONCLUSION: There was a marked cardiac autonomic alteration in AAS users, with a shift toward sympathetic modulation predominance and vagal attenuation. The high BP observed in our group of bodybuilders using AAS was associated with increased sympathetic modulation, and this increased sympathetic modulation was associated with structural alterations in the heart. This association may constitute an important mechanism linking AAS abuse to increased cardiovascular risk.

The impact of paclitaxel and carboplatin chemotherapy on the autonomous nervous system of patients with ovarian cancer.

BACKGROUND: Paclitaxel-based regimens are frequently associated with the development of peripheral neuropathy. The autonomous nervous system (ANS) effects, however, of this chemotherapeutic agent remain unexplored. METHODS: We investigated a group of 31 female patients with ovarian cancer receiving treatment with paclitaxel and carboplatin, as well as a group of 16 healthy age- and gender-matched healthy volunteers. All study participants completed a questionnaire and were assessed neurophysiologically at three time points (baseline, 3-4 months and 6-8 months following the onset of chemotherapy). The evaluation of the ANS included assessment of the adrenergic cardiovascular function (orthostatic hypotension-OH), parasympathetic heart innervation (30/15 ratio) and sympathetic skin response (SSR). RESULTS: At the 3-4 months ANS assessment, 19.2 % of the patients had systolic OH and the same percentage had diastolic OH, but at the 6-8 months evaluation no patient had systolic OH and only 13.8 % had diastolic OH. The values of the 30/15 ratio were significantly reduced at both time points, whereas the SSR was not affected. CONCLUSIONS: Combined paclitaxel and carboplatin chemotherapy is associated with significant effects on the parasympathetic heart innervation and occasionally with effects on the adrenergic cardiovascular reaction. The SSR remained unaffected. Physicians should be alert to the possibility of these treatment-emergent side effects, so as to monitor ANS parameters and introduce treatment modifications accordingly. Our findings however, should be validated in larger cohorts.

Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes.

Treatment-induced neuropathy in diabetes (also referred to as insulin neuritis) is considered a rare iatrogenic small fibre neuropathy caused by an abrupt improvement in glycaemic control in the setting of chronic hyperglycaemia. The prevalence and risk factors of this disorder are not known. In a retrospective review of all individuals referred to a tertiary care diabetic neuropathy clinic over 5 years, we define the proportion of individuals that present with and the risk factors for development of treatment-induced neuropathy in diabetes. Nine hundred and fifty-four individuals were evaluated for a possible diabetic neuropathy. Treatment-induced neuropathy in diabetes was defined as the acute onset of neuropathic pain and/or autonomic dysfunction within 8 weeks of a large improvement in glycaemic control-specified as a decrease in glycosylated haemoglobin A1C (HbA1c) of ≥2% points over 3 months. Detailed structured neurologic examinations, glucose control logs, pain scores, autonomic symptoms and other microvascular complications were measured every 3-6 months for the duration of follow-up. Of 954 patients evaluated for diabetic neuropathy, 104/954 subjects (10.9%) met criteria for treatment-induced neuropathy in diabetes with an acute increase in neuropathic or autonomic symptoms or signs coinciding with a substantial decrease in HbA1c. Individuals with a decrease in HbA1c had a much greater risk of developing a painful or autonomic neuropathy than those individuals with no change in HbA1c (P < 0.001), but also had a higher risk of developing retinopathy (P < 0.001) and microalbuminuria (P < 0.001). There was a strong correlation between the magnitude of decrease in HbA1c, the severity of neuropathic pain (R = 0.84, P < 0.001), the degree of parasympathetic dysfunction (R = -0.52, P < 0.01) and impairment of sympathetic adrenergic function as measured by fall in blood pressure on tilt-table testing (R = -0.63, P < 0.001). With a decrease in HbA1c of 2-3% points over 3 months there was a 20% absolute risk of developing treatment-induced neuropathy in diabetes, with a decrease in HbA1c of >4% points over 3 months the absolute risk of developing treatment-induced neuropathy in diabetes exceeded 80%. Treatment-induced neuropathy of diabetes is an underestimated iatrogenic disorder associated with diffuse microvascular complications. Rapid glycaemic change in patients with uncontrolled diabetes increases the risk of this complication.

Evaluation of the analgesic effect of morphine on models of acute nociceptive pain in rats with a central noradrenergic system lesion.

OBJECTIVES: Stimulation of some noradrenergic system receptors demonstrates a synergistic anti-nociceptive effect with the opioid system at the level of peripheral tissues, spinal cord, and supraspinal structures. Furthermore, opioids stimulate the noradrenergic descending pathways originating from the substantia nigra by presynaptic inhibition of the GABA neuron ends. It is thus important to determine whether a disruption to the adrenergic transmission obtained via DPS-4 administration to neonatal rats impacts the perception of noxious stimuli mediated by 5-HT3-serotonin receptors at the level of spinal cords or higher tiers of the central nervous system. DESIGN & SETTING: The studies were conducted with neonatal and adult rats, males of the Wistar strain in which a central noradrenergic system lesion was induced with DSP-4 on days 1 and 3 of life. Next, the evaluation of the analgesic effect of morphine was performed on 8- to 10-week-old animals using the following models of acute nociceptive pain: the hot plate test and the tail immersion test as models of acute nociceptive pain induced by a thermal stimulus, and the paw withdrawal test as a model of nociceptive pain caused by a mechanical stimulus. RESULTS: Morphine was found to produce a longer-lasting analgesic effect in the tail immersion test in the control group than in rats. Similarly, in the paw withdrawal test, this substance generated a strong analgesic effect (with over 200% of analgesia) in the control group, whereas its action in the rats with DSP-4 lesions was statistically significant. Morphine induced analgesia at about 13-14% in the control rats when examined with the hot plate test. CONCLUSIONS: The disruption to the central noradrenergic system in an early stage of development resulted in a reduction of the analgesic effect of morphine in the models of acute pain in which the mechanisms of supraspinal perception are involved.

Exacerbation of SUNCT and SUNA syndromes during intravenous dihydroergotamine treatment: A case series.

BACKGROUND: The management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and with short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA) remains challenging in view of the limited understanding of their pathophysiological mechanisms. METHODS: An initial observation that patients with both chronic migraine (CM) or cluster headache (CH) and SUNCT/SUNA receiving intravenous dihydroergotamine (IV DHE) had complained of dramatic worsening of the latter led to review of the case notes of patients with CM or CH and co-existent SUNCT/SUNA seen between 2008 and 2013 and who had a trial of IV DHE. RESULTS: Twenty-four patients were identified. IV DHE was ineffective for SUNCT/SUNA in 16 patients, while one patient reported a marginal improvement. Five patients reported dramatic worsening of the SUNCT/SUNA. Moreover, two patients developed new-onset SUNA during their first IV DHE infusion. Out of these seven patients, those requiring repeated courses of IV DHE consistently experienced exacerbations of SUNCT/SUNA which were suppressed with IV lidocaine. CONCLUSIONS: DHE is an ineffective treatment option for SUNCT and SUNA. Physicians who intend to offer IV DHE to CH or CM patients should warn them that IV DHE could exacerbate and possibly even lead to a de novo onset of SUNCT/SUNA. In view of the reported worsening or new onset of SUNCT/SUNA in patients using dopamine agonists for the treatment of pituitary prolactinomas, we speculate that DHE might worsen or induce SUNCT and SUNA, at least in a sub-group of patients, through a perturbation in the dopaminergic system.

Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats.

Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20mg/kg body weight, p.o) and curcumin (100mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin.

Effects of controlled discontinuation of long-term used antipsychotics for behavioural symptoms in individuals with intellectual disability.

BACKGROUND: Antipsychotics are frequently and often long-term used for challenging behaviour in persons with intellectual disability (ID), but the evidence base for this is meagre. As these agents may cause harmful side effects, discontinuation should be considered. Previous studies regarding discontinuation of long-term used antipsychotics mostly were uncontrolled and involved small numbers. The primary objective was to investigate the effects of controlled discontinuation of antipsychotics prescribed for challenging behaviour. Secondary objectives were to compare the results of two discontinuation time schedules, to compare groups of participants who had and had not achieved complete discontinuation, and to identify patient and medication characteristics that might predict the outcomes. Our hypothesis was that discontinuation of antipsychotics used for behavioural symptoms would not lead to worsening in behaviour. METHODS: This was a multi-centre parallel-group study comparing two discontinuation schedules of 14 and 28 weeks. Allocation to the two discontinuation schedules took place in a 1:1 ratio. Antipsychotics were tapered off every 2 or 4 weeks with approximately 12.5% of the initial dosage. Follow-up was 12 weeks after the scheduled complete discontinuation, that is, 26 or 40 weeks after the first dose reduction, respectively. Discontinuation was stopped in case of significant behavioural worsening. Participants were 98 residents with ID of three care providing organisations in the Netherlands, aged 15-66 year, who had used for more than 1 year one or more of the six most frequently prescribed antipsychotics for challenging behaviour. Main outcome measure was the total score of the Aberrant Behaviour Checklist (ABC); also ABC sub-scales were used. RESULTS: Of 98 participants, 43 achieved complete discontinuation; at follow-up 7 had resumed use of antipsychotics. Mean ABC ratings improved significantly for those who achieved complete discontinuation (directly after discontinuation, P < 0.01 and at follow-up, P = 0.03), and at follow-up (P = 0.03) for those who had not achieved complete discontinuation. Similar results were found with respect to most ABC sub-scales, including the 'irritability' sub-scale. There were no significant differences in improvement of ABC ratings between both discontinuation schedules. Higher ratings of extrapyramidal and autonomic symptoms at baseline were associated with less improvement of behavioural symptoms after discontinuation; higher baseline ABC rating predicted higher odds of incomplete discontinuation. CONCLUSIONS: Discontinuation of antipsychotics prescribed for challenging behaviour in patients with ID is associated with improved behavioural functioning. There is no need to taper off in a time frame longer than 14 weeks.

Management of Cholinergic Rebound After Abrupt Withdrawal of Clozapine: A Case Report and Systematic Literature Review.

BACKGROUND: Cholinergic discontinuation symptoms, also known as "cholinergic rebound," from abrupt clozapine discontinuation are characterized by a range of somatic and psychiatric symptoms. OBJECTIVE: The objective of this study was to describe the clinical features and management options for clozapine withdrawal-associated cholinergic rebound syndrome (henceforth referred to as CWCRS) and present an illustrative case report. METHODS: Based on a literature search of the databases PubMed, OVID Medline, and Embase as well as reviewing reference lists of relevant past reviews, we carried out a systematic review of case reports on the management of CWCRS from 1946 to 2023. RESULTS: We identified 10 previously published articles on the clinical management of CWCRS, with a total of 18 patients (6 female, 12 male) with an average age of 43 years (standard deviation 14). Half of the patients had a history of tardive dyskinesia. The mean dose of clozapine before discontinuation was 351 mg/day, with duration of clozapine treatment ranging from 3 weeks to 9 years. Clozapine was the most effective treatment, followed by benztropine. CONCLUSIONS: Given the small number of cases and the nonexperimental nature of the available studies, this review could not provide reliable data to guide management of CWCRS. The findings, however, suggest that clozapine may be more effective than other commonly used treatment options. With the high rates of discontinuation among patients on clozapine, there is a pressing need for further research into the epidemiology, natural history, and management of clozapine withdrawal syndromes.

Liver Cancer with Overlapping Myasthenia Gravis, Myocarditis, Seronegative Autoimmune Autonomic Ganglionopathy, and Myositis Symptoms Induced by Atezolizumab.

An 83-year-old man with hepatocellular carcinoma developed muscle weakness, ptosis, and dyspnea 3 weeks after receiving atezolizumab. Soon after, mechanical ventilation was initiated, which was followed by marked blood pressure spikes. The levels of creatine kinase and troponin-I were significantly elevated, and acetylcholine receptor antibodies were positive. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced myositis, myasthenia gravis (MG), myocarditis, and suspected autoimmune autonomic ganglionopathy (AAG). After immunotherapy, the serum markers and blood pressure normalized, and he was weaned from the ventilator after five months. To our knowledge, this is the first reported case of AAG secondary to ICI-induced myositis, MG, and myocarditis.

Harlequin Syndrome Related to Perioperative Intercostal Blockade: A Case Report.

Harlequin syndrome is a rare syndrome characterized by hemifacial flushing and altered facial sweating, with only a few case reports related to intercostal blockades. We present a case of Harlequin syndrome in a 65-year-old woman after intercostal blockade for video-assisted thoracoscopic lobectomy. One hour postoperatively, the patient became nauseated and presented with flushing of the right half of the face with a clear line of demarcation. Within 3 hours, the flushing disappeared. In this case report, we discuss Harlequin syndrome in relation to intercostal blockade and encourage clinicians to consider this syndrome in the differential diagnosis when encountering similar symptoms.

Headache in three new cases of Harlequin syndrome with accompanying pharmacological comparison with migraine.

BACKGROUND: Harlequin syndrome (HS) is a rare autonomic disorder characterised by unilateral diminished sweating and flushing of the face in response to heat or exercise. Some patients with HS complain of headache. METHODS: We present three new cases to characterise their headache phenotype and pharmacology and review the literature of cases where headache was described. RESULTS Two out of the three patients presented with episodes of unilateral headache associated with exercise: in one case the headache had migrainous features and was contralateral to the side where the flushing occurred, whereas the second patient, who had had migraine attacks in the past, had a brief throbbing headache, with no associated symptoms, ipsilateral to the facial flushing. The third woman had migraine but the attacks were not associated with HS. Pharmacological characterisation suggested the HS and migraine were biologically distinct. HS was not triggered by nitroglycerin and was unaffected by sumatriptan, dihydroergotamine and ergotamine. HS and migraine did not occur together. In the literature, we found six patients with both HS and headache, five of whom had migraine. CONCLUSIONS: These data do not show any correlation between the phenotypic expression of migraine and HS suggesting the syndromes are pathogenetically independent.