Association Between Frailty and Antiseizure Medication Tolerability in Older Adults With Epilepsy.

BACKGROUND AND OBJECTIVE: Frailty is an important aspect of biological aging, referring to the increased vulnerability of individuals with frailty to physical and psychological stressors. While older adults with epilepsy are an important and distinct clinical group, there are no data on frailty in this population. We hypothesize that frailty will correlate with the seizure frequency and especially the tolerability of antiseizure medications (ASMs) in older adults with epilepsy. METHODS: We recruited individuals aged 60 years or older with active epilepsy from 4 Canadian hospital centers. We reported the seizure frequency in the 3 months preceding the interview, while ASM tolerability was quantified using the Liverpool Adverse Events Profile (LAEP). We applied 3 measures of frailty: grip strength as a measure of physical frailty, 1 self-reported score (Edmonton frail score [EFS]), and 1 scale completed by a healthcare professional (clinical frailty scale [CFS]). We also administered standardized questionnaires measuring levels of anxiety, depression, functional disability, and quality of life and obtained relevant clinical and demographic data. RESULTS: Forty-three women and 43 men aged 60-93 years were recruited, 87% of whom had focal epilepsy, with an average frequency of 3.4 seizures per month. Multiple linear regression and zero-inflated negative binomial regression models showed that EFS and CFS scores were associated with decreased ASM tolerability, each point increase leading to 1.83 (95% CI: 0.67-4.30) and 2.49 (95% CI: 1.27-2.39) point increases on the LAEP scale, respectively. Neither the EFS and CFS scores nor grip strength were significantly associated with seizure frequency. The EFS was moderately correlated with depression, anxiety, quality of life, and functional disability, demonstrating the best construct validity among the 3 tested measures of frailty. DISCUSSION: The EFS was significantly, both statistically and clinically, associated with ASM tolerability. It also showed multiple advantages in performance while assessing for frailty in older adults with epilepsy, when compared with the 2 other measures of frailty that we tested. Future studies must focus on what role the EFS during epilepsy diagnosis may play in ASM selection among older adults with epilepsy.

Art and psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) are episodes of seizure-like symptoms that are not associated with epileptiform discharges on electroencephalogram (EEG). They can be remarkably difficult to distinguish from epileptic seizures: both may involve alterations in mental status and behavior, sensory or perceptual disturbances, as well as simple or complex motor patterns. Pictorial expressions of PNES have always attracted attention from the lay public and medical practitioners alike, by showing the rich variety of semiologies seen in the condition and its differences with epileptic seizures. In this article, we present two new contemporary artistic descriptions by the Canadian artist Iris Hauser about PNES. The depictions highlight key signs seen in PNES such as "eyes closed during events", "the hyperextension of the back and limbs", and the "claw-like finger posturing". We believe that the drawings can provide a valuable educational component in the initial assessment of patients suspected of having PNES as a training tool to identify and refer patients for more advanced testing.

Resolution of ictal bradycardia and asystole following temporal lobectomy: A case report, and review of available cases using pacemakers.

Ictal bradycardia (IB) and ictal asystole (IA) are uncommonly recognized phenomena that increase morbidity in patients with epilepsy by causing syncope and seizure-related falls. These arrhythmias are also suspected to be involved in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). We report a case of a 57-year-old male with left temporal lobe epilepsy who experienced both IB and IA. This patient was initially managed with pacemaker implantation, prior to undergoing left temporal lobectomy. Following surgery, the patient had no ongoing IB or IA on his pacemaker recordings, and his seizure control was greatly improved. His pacemaker was removed approximately one year post-operatively and he continued treatment with anti-seizure drugs (ASDs). A literature review of cases of IB and IA that were managed with pacemakers was performed. Pacemaker implantation appears to be quite effective for reducing seizure-related syncope and falls in the setting of IB/IA. Epilepsy surgery also seems to be an effective treatment option for IB/IA, as many patients are able to have their pacemakers removed post-operatively. Further investigations into the pathophysiology of IB and IA and long-term outcomes using different treatment modalities are clearly needed to help formulate treatment guidelines and, potentially, to reduce the occurrence of SUDEP in these patients.

Forced normalization: A systematic review.

OBJECTIVE: Forced normalization (FN) is an intriguing phenomenon characterized by the emergence of psychiatric disturbances following the establishment of seizure control or reduction in the epileptic activity in a patient with previous uncontrolled epilepsy. We aim to describe the clinical characteristics of the condition. METHODS: We conducted a systematic review on MEDLINE, EMBASE, Cochrane, and Scielo from January 1953 to January 2018. Clinical, electrographic, and imaging data were gathered. We considered all outcomes in children and adults. We performed no meta-analyses due to the limited available data. RESULTS: Of 2606 abstracts identified, 36 fulfilled the FN diagnostic criteria; 193 FN episodes were evaluated and 77 of them were analyzed extensively. Sixty percent of cases were female. Mean age ± standard deviation (SD) was 28.3 ± 14.2 years. The majority of patients had focal (80%) symptomatic (44%) epilepsy. Most patients reported a high ictal frequency (58%) and were on polytherapy (51%). Patients presented psychosis (86.4%), mood disorders (25.8%), and dissociation (4.5%) as the main manifestations. In the psychosis group, persecutory (52.6%) and reference (47.3%) delusions were frequent. FN was provoked by an antiepileptic drug (AED) (48.5%) mainly levetiracetam, epilepsy surgery (31.8%), or vagus nerve stimulation (13.6%). Treatment was homogeneous including anticonvulsant withdrawal (47%) or taper (25%); antipsychotics were initiated in the majority of cases (73%). Psychiatric symptoms were partially controlled in 35%, with complete resolution of symptoms in the remaining 65% of cases. The majority of patients (87%) with AED trigger and withdrawal presented complete resolution of symptoms in comparison to 28.5% of patients triggered by surgery. SIGNIFICANCE: Forced normalization is an entity whose pathophysiology remains uncertain. Antipsychotic drug use does not predict complete resolution of psychiatric symptoms in comparison with AED withdrawal. Although there is a positive response to treatment in patients with FN triggered by drugs, the prognosis is obscure in patients with surgery triggered FN.

Deep Brain Stimulation and Drug-Resistant Epilepsy: A Review of the Literature.

Introduction: Deep brain stimulation is a safe and effective neurointerventional technique for the treatment of movement disorders. Electrical stimulation of subcortical structures may exert a control on seizure generators initiating epileptic activities. The aim of this review is to present the targets of the deep brain stimulation for the treatment of drug-resistant epilepsy. Methods: We performed a structured review of the literature from 1980 to 2018 using Medline and PubMed. Articles assessing the impact of deep brain stimulation on seizure frequency in patients with DRE were selected. Meta-analyses, randomized controlled trials, and observational studies were included. Results: To date, deep brain stimulation of various neural targets has been investigated in animal experiments and humans. This article presents the use of stimulation of the anterior and centromedian nucleus of the thalamus, hippocampus, basal ganglia, cerebellum and hypothalamus. Anterior thalamic stimulation has demonstrated efficacy and there is evidence to recommend it as the target of choice. Conclusion: Deep brain stimulation for seizures may be an option in patients with drug-resistant epilepsy. Anterior thalamic nucleus stimulation could be recommended over other targets.

Forced normalization after turning off vagus nerve stimulation in Lennox-Gastaut syndrome.

Forced normalization is the development of psychiatric symptoms in a patient experiencing remission of seizures. We present a case of Lennox Gastaut syndrome in which forced normalization developed after vagus nerve stimulation was stopped. The patient had drug resistant epilepsy and failed anti-seizure drugs, vagus nerve stimulation, and a partial callosotomy. The patient had multiple types of seizures including drop attacks, absences, and tonic-clonic seizures. He tried vagus nerve stimulation for two years without success. Forced normalization developed after the vagus nerve stimulator was turned off. This is the first case to our knowledge to describe forced normalization after turning off the vagus nerve stimulator.

Epilepsy, Physical Activity and Sports: A Narrative Review.

People with epilepsy (PWE) are less physically active compared with the general population. Explanations include prejudice, overprotection, unawareness, stigma, fear of seizure induction and lack of knowledge of health professionals. At present, there is no consensus on the role of exercise in epilepsy. This paper reviews the current evidence surrounding the risks and benefits associated with physical activity (PA) in this group of patients. In the last decade, several publications indicate significant benefits in physiological and psychological health parameters, including mood and cognition, physical conditioning, social interaction, quality of life, as well as potential prevention of seizure presentation. Moreover, experimental studies suggest that PA provides mechanisms of neuronal protection, related to biochemical and structural changes including release of ß-endorphins and steroids, which may exert an inhibitory effect on the occurrence of abnormal electrical activity. Epileptic discharges can decrease or disappear during exercise, which may translate into reduced seizure recurrence. In some patients, exercise may precipitate seizures. Available evidence suggests that PA should be encouraged in PWE in order to promote wellbeing and quality of life. There is a need for prospective randomized controlled studies that provide stronger clinical evidence before definitive recommendations can be made.

The Montreal procedure: The legacy of the great Wilder Penfield.

Wilder Penfield pioneered the early practice of brain surgery. In binding together the disciplines of neurosurgery, neurology, neuropathology, psychology, and related basic sciences, Penfield transformed our understanding of the field of neuroscience. He brought to the operating room the meticulous techniques of Sherrington, combined with methods of stimulation described by Foerster, which he complemented with expert knowledge of the neurocytology of nervous tissue. While developing surgical treatments for epilepsy, Penfield began to map the brain. He established the "Montreal procedure" for the surgical treatment of epilepsy. His scientific contributions on neurostimulation were transformative in their time and continue to resonate today. This article reviews the life of Wilder Penfield and summarizes key scientific contributions. Specifically, we detail the Montreal procedure. We additionally present a painting by Canadian artist Iris Hauser, which purports to display the hidden treasures of the human mind.

Intracranial investigation of a patient with nodular heterotopia and hippocampal sclerosis: dealing with a dual pathology.

The pre-operative assessment and surgical management of patients with dual pathology is challenging. We describe a patient with drug-resistant focal epilepsy with hippocampal sclerosis and extensive periventricular nodular heterotopia in the same hemisphere. The semiology, scalp EEG, and imaging were divergent, but the presence of focal interictal and ictal epileptic discharges of the putative ictal onset zone resulted in successful localization of the epileptogenic zone. A less aggressive resection was performed based on intracranial EEG recording. The patient has been seizure-free for three years since resection. Electroclinical hypotheses and challenges in defining the epileptogenic network are discussed.

StatNet Electroencephalogram: A Fast and Reliable Option to Diagnose Nonconvulsive Status Epilepticus in Emergency Setting.

BACKGROUND: The StatNet electrode set is a system that can be applied by a non-electroencephalogram (EEG) technologist after minimal training. The primary objectives of this study are to assess the quality and reliability of the StatNet recordings in comparison to the conventional EEG. METHODS: Over 10 months, 19 patients with suspected nonconvulsive status epilepticus were included from university hospital emergency settings. Each patient received a StatNet EEG by a trained epilepsy fellow and a conventional EEG by registered technologists. We compared the studies in a blinded fashion, for the timeframe from EEG order to the setup time, start of acquisition, amount of artifact, and detection of abnormalities. The nonparametric Mann-Whitney two-sample t test was used for comparisons. The kappa score was used to assess reliability. RESULTS: Mean age of patients was 61±16.3 (25-93) years. The inter-observer agreement for detection of abnormal findings was 0.83 for StatNet and 0.75 for conventional EEG. Nonconvulsive status epilepticus was detected in 10% (2/19) in both studies. The delay from the time of EEG requisition to acquisition was shorter in the StatNet (22.4±2.5 minutes) than the conventional EEG (217.7±44.6 minutes; p<0.0001). The setup time was also shorter in the StatNet (9.9±0.8 minutes) compared with the conventional EEG (17.8±0.8 minutes; p<0.0001). There was no difference in the percentage of artifact duration between the two studies (p=0.89). CONCLUSION: This study demonstrates that StatNet EEG is a practical and reliable tool in the emergency setting, which reduces the delay of testing compared with conventional EEG, without significant compromise of study quality.

Tlazolteotl, the Aztec goddess of epilepsy.

Epilepsy has afflicted humanity during most of the extent of documented history. The Aztecs believed that illnesses were punishments that were sent from a furious goddess. In particular, epilepsy was considered in Aztec culture as a "sacred disease", and convulsions were traditionally associated with a deified woman who had died at childbirth. As the goddess Shiva and Apasmâra in ancient India and Saint Valentine in Germany, Tlazolteotl was considered able to bring about and send away epilepsy. We performed a comprehensive review to identify Tlazolteotl depictions and its historical context related with epilepsy. Tlazolteotl is one of the most endearing and complex goddesses of the Mesoamericans. She was the deity of the black fertile and fecund earth that gains its energy from death and in turn feeds life. Associated with purification, expiation, and regeneration, she embodied fertility and turned all garbage, physical and metaphysical, into rich life. This article reviews the most relevant artistic works related with Tlazolteotl. We also present a modern depiction of the Aztec goddess of epilepsy from the Mexican artist Eduardo Urbano Merino, displaying the supernatural view of epilepsy in America.

Epilepsy through the ages: An artistic point of view.

The historical allure of epilepsy transcends academic circles and serves as fascinating critique of the state of the times-its values, judgments, mythos, and people. Immortalized and laid bare in artistic renderings of epilepsy are societal truths, at times both disparately grandiose and grotesque. During the middle ages and Renaissance, the European discourse on epilepsy assumed religious fervor. Epilepsy was considered a demonic machination and its cure an act of divine intercession. A similar theme is found in the artistic depiction of epilepsy from the Inca and Aztec civilizations of that time. After the 19th century drew to a close, the ascendency of empiricism coincided with waning creative interest in epilepsy, with few paintings or pieces to capture insightful perspectives on the illness. In this paper, we review the relationship between art and epilepsy and present two contemporary paintings that convey current western perceptions. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity".

Medicinal marijuana for epilepsy: a case series study.

OBJECTIVE: To describe the social, clinical and use-patterns characteristics of medicinal marijuana use among patients with epilepsy (PWEs). METHODS: Eighteen PWEs with prescriptions for medicinal marijuana from a Canadian adult-epilepsy clinic were included in this study. RESULTS: Eighteen patients had a prescription of medicinal marijuana from a total population of 800 PWEs in our center (2.2%). Mean age of patients was 30±7.4 (19-50) years. Twelve (67%) patients were males. Eleven (61%) patients had drug-resistant epilepsy. Eleven (61%) patients suffered a psychiatric comorbidity and reported the use of illicit substances or heavy alcohol or tobacco consumption. Only two (11%) patients were married; the rest of patients (89%) were single or divorced. The drug use pattern was similar among patients. All patients asked for marijuana permission in the epilepsy clinic. Most (83%) had a previous history of marijuana smoking, with a mean of 6.6±3 (1-15) years. The mean consumption dose was 2.05±1.8 (0.5-8) grams per day. Ten (56%) patients reported withdrawal seizure exacerbation when they stopped the marijuana. Only two patients (11%) reported side effects, and all patients found medicinal marijuana very helpful for seizure control and improvement of mood disorder. CONCLUSIONS: PWEs using medicinal marijuana have a common profile. They are usually young single men with drug-resistant epilepsy and psychiatric comorbidity. Most used marijuana before formal prescription and all believe the drug was effective on their seizure control. Because of the concurrent use of other antiseizure medications, it is complex to estimate the actual effect of marijuana.

Art and epilepsy surgery.

The impact of health and disease has led many artists to depict these themes for thousands of years. Specifically, epilepsy has been the subject of many famous works, likely because of the dramatic and misunderstood nature of the clinical presentation. It often evokes religious and even mythical processes. Epilepsy surgical treatment has revolutionized the care of selected patients and is a relatively recent advance. Epilepsy surgery has been depicted in very few artistic works. The first portrait showing a potential surgical treatment for patients with epilepsy was painted in the 12th century. During the Renaissance, Bosch famously provided artistic commentary on traditional beliefs in "The stone of madness". Several of these works demonstrate a surgeon extracting a stone from a patient's head, at one time believed to be the source of all "folly", including epileptic seizures, psychosis, intellectual disability, depression, and a variety of other illnesses. There are some contemporary art pieces including themes around epilepsy surgery, all of them depicting ancient Inca Empire procedures such as trepanning. This article reviews the most relevant artistic works related with epilepsy surgery and also its historical context at the time the work was produced. We also present a painting from the Mexican artist Eduardo Urbano Merino that represents the patient's journey through refractory epilepsy, investigations, and ultimately recovery. Through this work, the artist intends to communicate hope and reassurance to patients going through this difficult process.

[Temporal epilepsy: clinical, diagnostic and therapeutic aspects]. / Epilepsia temporal: aspectos clinicos, diagnosticos y de tratamiento.

INTRODUCTION: Epilepsy is a common neurological disease with significant public health impact. Temporal lobe epilepsy (TLE) is one of the most frequent and complex epilepsies. AIM: To review the most important aspects of clinical diagnosis, the use of diagnostic tests, and medical and surgical treatment of TLE. DEVELOPMENT: TLE is a well described type of epilepsy. Approximately 40% of patients with TLE develop drug resistant epilepsy. Nowadays, new diagnosis tools have been added for the assessment of patients with TLE that could be candidates for epilepsy surgery. However semiology remains the starting point for the disease understanding and every localizing and lateralizing sign is relevant to understand the potential onset and dissemination of seizures. The combination of tests and semiology is important to decide which cases require intracranial electrodes. The prognosis of epilepsy surgery in TLE is very good and between 60 to 70% of patients rendered seizure free after surgery. CONCLUSIONS: The approach to patients with TLE is complex and requires a multidisciplinary team of trained specialists.

Epilepsia temporal: aspectos clínicos, diagnósticos y de tratamiento / Temporal epilepsy: clinical, diagnostic and therapeutic aspects

Introducción. La epilepsia es una enfermedad neurológica frecuente con gran impacto en la salud pública. La epilepsia del lóbulo temporal (ELT) es una de las causas más prevalentes y complejas. Objetivo. Revisar los aspectos más importantes del diagnóstico clínico, el uso de pruebas diagnósticas, y el tratamiento médico y quirúrgico de la ELT. Desarrollo. La ELT abarca un grupo de síndromes electroclínicos bien descritos; la epilepsia de origen mesial es la más resistente a fármacos y representa un reto para el epileptólogo. En la actualidad, se cuenta con numerosas herramientas diagnósticas novedosas; sin embargo, la semiología continúa siendo el punto de partida para el entendimiento de la enfermedad. Se debe conocer el valor localizador y lateralizador de cada signo y las vías preferenciales de propagación de los focos, de igual manera que se deben reconocer los hallazgos eléctricos propios de la enfermedad y decidir qué casos clínicos requieren electrodos intracraneales, subdurales o profundos. La resonancia magnética es vital en la evaluación prequirúrgica y funciona como un importante factor pronóstico. Otras herramientas imaginológicas continúan siendo complementarias en la actualidad. Conclusiones. El abordaje de pacientes con ELT es un trabajo arduo que debe ser multidisciplinario y requiere un equipo de especialistas entrenado. Es indispensable la presencia de un epileptólogo y un neurocirujano con experiencia en cirugía de epilepsia. Se debe contar, adicionalmente, con neuropsicólogos, radiólogos y psiquiatras(AU)

Introduction. Epilepsy is a common neurological disease with significant public health impact. Temporal lobe epilepsy (TLE) is one of the most frequent and complex epilepsies. Aim. To review the most important aspects of clinical diagnosis, the use of diagnostic tests, and medical and surgical treatment of TLE. Development. TLE is a well described type of epilepsy. Approximately 40% of patients with TLE develop drug resistant epilepsy. Nowadays, new diagnosis tools have been added for the assessment of patients with TLE that could be candidates for epilepsy surgery. However semiology remains the starting point for the disease understanding and every localizing and lateralizing sign is relevant to understand the potential onset and dissemination of seizures. The combination of tests and semiology is important to decide which cases require intracranial electrodes. The prognosis of epilepsy surgery in TLE is very good and between 60 to 70% of patients rendered seizure free after surgery. Conclusions. The approach to patients with TLE is complex and requires a multidisciplinary team of trained specialists(AU)

[Extratemporal epilepsy. Its clinical, diagnostic and therapeutic aspects]. / Epilepsia extratemporal. Aspectos clínicos, diagnósticos y de tratamiento.

INTRODUCTION: Partial seizures of extratemporal origin may present unique challenges in the patient with medically refractory seizures. Extratemporal focal cortical resections may be less effective than anterior temporal lobectomy for intractable epilepsy. DEVELOPMENT: Surgical complications may be increased in individuals with extratemporal epilepsy because eloquent cortex may involved, and larger cortical resections may be needed to significantly reduce epileptogenicity. 30-40% of patients with newly diagnosed epilepsy will develop medically refractory seizure disorders. CONCLUSIONS: The most effective treatment for intractable partial epilepsy is a focal cortical resection with excision of the epileptogenic zone, i.e., area of ictal onset and initial seizure propagation. The preoperative evaluation and surgical strategy in patients with partial epilepsy of extratemporal origin associated with pharmacoresistant seizures is determined by the anatomical localization of the epileptogenic zone and the presence of a lesion-related epilepsy. Prior to surgical treatment patients with extratemporal epilepsy will require a comprehensive preoperative evaluation including routine EEG, long-term EEG monitoring, neuropsychological studies, and magnetic resonance imaging.

[Injuries, accidents and mortality in epilepsy: a review of its prevalence risk factors and prevention]. / Lesiones, accidentes y mortalidad en epilepsia: Una revisión de sus prevalencias, factores de riesgo y prevención.

Currently, there is intense clinical research into various aspects of the medical risks relating to epilepsy, including total and cause-specific mortality, accidents and injuries in patients with epilepsy and mortality related with seizures. Submersion injuries, motor vehicle accidents, burns, and head injuries are among the most feared epilepsy-related injuries. Published risk factors for injuries include the number of antiepileptic drugs, history of generalized seizures, and seizure frequency. In general, studies focusing on populations with more severe forms of epilepsy tend to report substantially higher risks of injuries than those involving less selected populations. On the other hand, studies based in non selected populations of people with epilepsy have not shown an increase frequency of injuries in people with epilepsy compared with the general population. Some studies have shown that patients with epilepsy are more frequently admitted to the hospital following an injury. Possible explanations include are more cautious attitude of clinicians toward injuries occurring in the setting of seizures; hospitalization required because of seizures and not to the injuries themselves; and hospitalization driven by other issues, such as comorbidities, which are highly prevalent in patients with epilepsy. This article reviews information about specific type of injuries such as fractures, burns, concussions, dislocations, etc. Finally this article review in a comprehensive way information of mortality in patients with epilepsy. Aspects of mortality discussed in this review are: epidemiology, causes of mortality, sudden death in epilepsy and prevention measures.

Respiratory and non respiratory oscillations of the skin blood flow: a window to the function of the sympathetic fibers to the skin blood vessels.

OBJECTIVE OF THE STUDY: The skin blood flow (SBF) has been known to oscillate in frequency and amplitude. The nature and type of these oscillations have remained obscure. We studied the oscillations of the SBF in frequency and amplitude with non invasive techniques during normal breathing at rest and compared it to the oscillations during rhythmic paced breathing at 6 cycles per minute. SUBJECTS AND METHODS: Thirty healthy subjects were studied under normothermic conditions. The following variables were recorded: 1) EKG signal; 2) SBF signal given by an infrared photoplethysmograph; 3) respiratory movements (RM). A correlation of the frequency of the respiration, the SBF and the EKG was made. The variability of the amplitudes of the SBF, RR intervals and pulse intervals was analyzed in the time domain and with spectral analysis using Fourier analysis. RESULTS: We found no clear respiratory modulation of the amplitude of the SBF during natural breathing at rest. With default breathing there was a low frequency oscillations (LF 0.04 to 0.15 Hz) modulation of the amplitude of the SBF that was non respiratory in nature. During rhythmic breathing at 0.1 Hz there was a strong modulation at LF of the SBF with a typical waxing and waning appearance, decreasing in amplitude during the tachycardia period and increasing in amplitude during the bradycardia period. CONCLUSIONS: Under normothermic conditions there is a consistent variability of the frequency and amplitude of the SBF with normal and rhythmic breathing. While breathing at rest the modulation of SBF amplitude was clearly seen at LF and non respiratory related. With rhythmic breathing there is a strong modulation of amplitude and frequency at the respiratory frequency.

Respiratory and non respiratory oscillations of the skin blood flow: a window to the function of the sympathetic fibers to the skin blood vessels

OBJECTIVE OF THE STUDY: The skin blood flow (SBF) has been known to oscillate in frequency and amplitude. The nature and type of these oscillations have remained obscure. We studied the oscillations of the SBF in frequency and amplitude with non invasive techniques during normal breathing at rest and compared it to the oscillations during rhythmic paced breathing at 6 cycles per minute. SUBJECTS AND METHODS: Thirty healthy subjects were studied under normothermic conditions. The following variables were recorded: 1) EKG signal; 2) SBF signal given by an infrared photoplethysmograph; 3) respiratory movements (RM). A correlation of the frequency of the respiration, the SBF and the EKG was made. The variability of the amplitudes of the SBF, RR intervals and pulse intervals was analyzed in the time domain and with spectral analysis using Fourier analysis. RESULTS: We found no clear respiratory modulation of the amplitude of the SBF during natural breathing at rest. With default breathing there was a low frequency oscillations (LF 0.04 to 0.15 Hz) modulation of the amplitude of the SBF that was non respiratory in nature. During rhythmic breathing at 0.1 Hz there was a strong modulation at LF of the SBF with a typical waxing and waning appearance, decreasing in amplitude during the tachycardia period and increasing in amplitude during the bradycardia period. CONCLUSIONS: Under normothermic conditions there is a consistent variability of the frequency and amplitude of the SBF with normal and rhythmic breathing. While breathing at rest the modulation of SBF amplitude was clearly seen at LF and non respiratory related. With rhythmic breathing there is a strong modulation of amplitude and frequency at the respiratory frequency.