Clinical trials

Background: SARS-CoV-2 is the virus that causes COVID-19. Some people who recover from an acute COVID-19 infection may continue to have symptoms that persist for months or years. These can include neurological symptoms, such as headaches, loss of taste or smell, dizziness, or trouble walking. Pembrolizumab is a drug approved to treat certain cancers. Researchers think this drug might reduce long-term neurologic symptoms after a COVID-19 infection. Objective: To test pembrolizumab in people with ongoing neurologic symptoms of COVID-19. Eligibility: People aged 18 years or older who had COVID-19 at least 6 months ago and have ongoing neurologic symptoms. Design: Participants will have 7 clinic visits in 7 months. Participants will be screened. They will have a physical exam with blood tests. Swabs will be used to collect cells from inside the mouth and nose. They may opt to have an imaging scan. Participants will also have other tests before they are given the study drug. These include eye and skin exams; tests of their memory and thinking; and tests of involuntary body functions, such as heart rate, blood pressure, sweating, and digestion. Their grip strength and walking pace will be measured. They will wear a heart rate monitor for 24 hours. They will wear devices on a wrist and thigh to measure activity for 10 days. Participants will have a lumbar puncture (spinal tap): A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord. Pembrolizumab is given through a needle inserted into a vein. Participants will receive 1 dose of the drug. Participants will have 4 follow-up visits over 6 months. Tests may be repeated during these visits.

Background: Tics are involuntary movements and vocalizations. Some tics are organic: They are related to diagnosed disorders. Sometimes tics have other causes, such as problems with how the brain and body send and receive messages. These are called functional tics. It can be difficult to tell the difference between these 2 types of tics. Doctors need to know more so they can make more accurate diagnoses. Objective: To learn more about the difference between functional and organic tics. Eligibility: Adults aged 18 to 80 years who have a tic that causes involuntary movements. Healthy volunteers with no tics are also needed. Design: Participants will have one 4-hour clinic visit. The visit may be done in 1 or 2 days. Participants will refrain from consuming alcohol or caffeine before the visit. They may have a physical exam. Participants will wear two types of sensors: Electromyography (EMG): Adhesive disks with sensors will be attached to the skin above some muscles. These disks will record electricity in the muscles as the participant moves. Electroencephalography (EEG): Sensors will be placed on the participant s scalp. The sensors may be adhered directly, or the participant may wear an electrode cap. The sensors will detect brain waves. Participants will rest while seated in a chair. Their involuntary tics will be monitored with the EMG and EEG. Then they will be asked to make movements to mimic their tics. Healthy volunteers will also rest; then they will be asked to perform movements that mimic tics. Participants will have their blink reflex tested. EMG sensors will be placed on the muscles near the eyes. Electrical pulses will be used to stimulate blinking. Participants will answer questionnaires about their tics and their health....

Background: Stroke is the fifth leading cause of death in the United States. It is also a leading cause of disability. More than 70% of people who survive strokes have mental impairment or dementia. Medical factors, such as the severity of the stroke, affect whether a person will have mental impairment afterward. But social factors, such as education and ethnicity, seem to play a role as well. Researchers want to learn more about how social and lifestyle factors affect a person s chances of maintaining mental functions after a stroke. Objective: To better understand how social and lifestyle factors affect the risk of mental impairment after a stroke. Eligibility: People aged 18 years and older who had a stroke and a brain scan while they were enrolled in NIH Study 01N0007 (Natural History of Stroke Study). Design: Participants will have 1 study visit, by telephone. The call will last about 45 minutes. Participants will talk about their health since their stroke. They will answer questions about themselves. Topics will include: * Their race * Education * Ethnicity * Employment * Marital status * Residence address * Recent health history * Medical insurance They will have tests of their memory, attention, and language skills. They will repeat numbers and words forward and backward. Researchers will look at the data and imaging scans collected during participant s enrollment in NIH Study 01N0007. This data will include: * The hospital that first saw the participant at the time of their stroke. * The type of imaging that was first used then. * The primary diagnosis at admission. * Other medical details.

Background: \- In deep brain stimulation (DBS), a device called a neurostimulator is placed in the chest. It is attached to wires in parts of the brain that affect movement. DBS might help people with movement disorders like Parkinson s disease (PD), dystonia, and essential tremor (ET). Objective: \- To provide DBS treatment to people with some movement disorders. Eligibility: \- Adults 18 years and older with PD, ET, or certain forms of dystonia. Design: * Participants will be screened with medical history and physical exam. They will have blood and urine tests and: * MRI brain scan. The participant will lie on a table that slides in and out of a metal cylinder with a magnetic field. They will be in the scanner about 60 minutes. They will get earplugs for the loud noises. During part of the MRI, a needle will guide a thin plastic tube into an arm vein and a dye will be injected. * Electrocardiogram. Metal disks or sticky pads will be placed on the chest, arms, and legs. They record heart activity. * Chest X-ray. * Tests of memory, attention, concentration, thinking, and movement. * Eligible participants will have DBS surgery. The surgery and hospital care afterward are NOT part of this protocol. * Study doctors will see participants 3 4 weeks after surgery to turn on the neurostimulator. * Participants will return every month for 3 months, then every 3 months during the first year, and every 6 months during the second year. Each time, participants will be examined and answer questions. DBS placement will be evaluated with MRI. The neurostimulator will be programmed. At two visits, participants will have tests of movements, thinking, and memory.

Background: The way the brain processes rewards and punishments may play a role in some disorders of the nervous system. People with chronic overlapping pain conditions (such as myalgic encephalomyelitis/chronic fatigue syndrome \[ME/CFS\]) may have heightened responses to unpleasant, punishing sensations. Some of these conditions may also cause heightened responses to effort; this is an unpleasant sensation felt during physical and mental exertion. Objective: To learn more about how the brain processes different unpleasant sensations. Eligibility: People aged 18 to 50 years with ME/CFS. Healthy volunteers are also needed. Design: Participants will have 3 visits in 1 to 5 weeks. Visit 1: Participants may have a neurologic exam. They will have a mock magnetic resonance imaging (MRI) scan. They will lie on a bed in a wooden tube while they practice 2 tasks: Thermal pain rating: A device that creates mild to moderate heat will be placed on one leg. Physical effort rating: Participants will squeeze a plastic bar with different levels of force. Visit 2: Participants will have a real MRI scan. They will lie on a table that slides into a large tube. Visit 3: Participants will have another MRI scan. They will repeat the thermal pain and physical effort tasks while in the scanner. Sensors will be placed on 1 arm to measure how the muscles function as they squeeze the bar. Their heart rate will be tested: They will hold their finger against a camera lens for 1 minute. They will do 2 other tasks: 1 requires repeatedly pressing a key on a keyboard, and the other requires squeezing a bar.

Background: \- Inflammation is how the body reacts to infection or injury. Infections or inflammation in the brain and nerves can be serious. There aren t always good tests to detect this. Researchers want to learn more about how diseases affect the brain and nerves to develop better tests and treatments. Objective: \- To learn more about how inflammation and infections hurt the brain and nervous system. Eligibility: \- People at least 2 years old with a diagnosis or suspected diagnosis of nervous system infection or inflammation. Design: * For some participants, a clinician outside of NIH will collect blood, tissue, and other samples. These will be sent to NIH and analyzed. * Other participants will have several visits to NIH. Children may not have all these tests. * Participants will have: * Medical history. * Physical and neurological exam. * Blood and urine samples collected. * Saliva collected. They will chew on a piece of sterile cotton for one minute. * Magnetic resonance imaging (MRI) scan. The scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the cylinder. Participants will get a contrast agent through an intravenous (IV) catheter during the MRI. A needle will be used to guide a thin plastic tube (catheter) into an arm vein. * Lumbar puncture. Skin will be numbed and a needle will be inserted into the space between the bones in the back. Fluid will be removed. * Some participants may have optional study procedures. These may include eye tests, memory and thinking testing, tests with electrodes on the head, or skin biopsy.

Background: Magnetic resonance imaging (MRI), which uses strong magnets to get images of structures inside the body, is a valuable tool in modern medicine. But researchers are always looking for ways to improve this technology. To better understand how to use MRI to diagnose problems, researchers need to collect more data from scans of healthy people. Objective: To get MRI scans of healthy people to improve the measurements doctors can make from the images. Eligibility: People aged 18 years or older in good general health. Design: Participants will be screened. They will have a physical exam focused on their nervous system. They will complete questionnaires. Participants will have at least 1 MRI scan. The target of the scan may be the brain, liver, prostate, breast, or other body part. Before the scan, participants will remove any metallic objects. They will lie on a narrow table that moves into a long, narrow tube. They may have special pads placed around them to help them remain still. Participants will hear loud noises during the scan. They will get earplugs or earmuffs to wear to muffle the sound. They can communicate with the MRI technician and will have an emergency button to squeeze at any time if they want the scan to stop. The scan will take up to 2 hours. Some participants may be asked to perform tasks on a computer screen during the scan. Participants may return for up to 5 scans in 3 months. Some may have as many as 30 MRI visits per year. They may remain in the study for up to 2 years.

Background: Current techniques used to measure the health and function of a person s nerves and muscles are generally effective, but they do have limits. Researchers are looking for ways to improve the ability to observe nerves and muscles and how they function in this natural history protocol. Objective: To study the use of ultrasound (sound waves) to learn more about nerves and muscles. Eligibility: Healthy adults, aged 18 and older, with no history of stroke, nerve or muscular disorders, or spine surgery are also needed. A smaller population of adults aged 18 and older who have a neuromuscular disorder or show symptoms of nerve or muscle disorder will also be evaluated. Design: Participants will be screened with a medical record review. Participants will have up to 5 outpatient clinic visits. Most participants will have 1 or 2 visits. Visits will last for less than 3-4 hours each. During each visit, participants will give a brief medical history and have a physical exam. Participants will have ultrasounds to get pictures and measurements of their nerves and muscles. Gel will be applied to their skin. A probe will be placed on the skin surface. Sound waves sent through the probe will be used to create pictures. Participants may have nerve conduction studies. Wires will be taped to the skin surface near a muscle or nerve in the arm or leg. The nerve will be stimulated with a small electric current that feels like a rubber band flick. The response will be recorded through the wires.

Background: Memory consolidation is the process by which memories become stable, long-term representations in the brain. Consolidation of a motor skill is dependent upon sleep. Some research shows that daytime naps improve people s motor performance and memory retention. Researchers want to find out how daytime naps may contribute to learning and support consolidation of motor skill memories. Objective: To learn the role of memory replay during wakeful rest and sleep (naps) in retaining a newly learned skill. Eligibility: English-speaking adults ages 18 and older with chronic stroke, or healthy, right-handed, English-speaking adults ages 18-35 and 50-80 Design: Participants will be screened with: * medical history * neurological history * medicine review * medical exam * neurological exam. Participants will have a magnetic resonance imaging (MRI) scan of the brain. For this, they will lie down in a scanner. The scanner makes loud noises, so they will wear earplugs. They will fill out an MRI screening form before each MRI. Participants will also have magnetoencephalography (MEG). MEG maps brain activity. It does this by recording the magnetic fields produced by naturally occurring electrical currents in the brain. For MEG, participants will lie down in the MEG room. Their eye movements may be recorded by a video camera. Participants will have behavior testing. They will practice typing random keys. Then they will repeatedly type a custom sequence that they see on a computer screen. Then they will take a 2-hour nap. Then they will type the same sequence again. Participants will have no more than 4 visits at the NIH over 3 months. Visits will last 2-4 hours each.

Objective: This protocol is designed to allow the Surgical Neurology Branch to evaluate and treat the neurosurgical disorders of protocol participants. The participants will receive standard-of-clinical-care evaluation and treatment. The clinical data and samples generated during standard of care treatment will be collected as part of this study. Study Population: Participants 4 years of age and older with neurosurgical-related conditions, who are seeking care from or referred to the Surgical Neurology Branch for evaluation, are eligible for this protocol. Study Design: This is an observational study. Participants will receive standard-of-clinical-care evaluation and treatment for their neurosurgical condition. Clinical evaluation may include laboratory and radiological studies designed to aid in diagnosis or differential diagnosis of the participant s condition or to facilitate treatment. The evaluations may take place in the outpatient clinic areas or in the inpatient units. Some participants will receive standard-of-care medical or surgical treatment for their disorder. Clinical data, tissue samples or body fluids obtained during standard of care treatment, may be used for research. Additional genetic testing may be performed on subjects and their blood relatives if a genetic mechanism underlying the neurological disorder is suspected. Patients in this study may choose to consent to skin biopsies for research purposes, in which case they will sign an additional consent document for this research procedure. Outcome Measures: No additional research outcome measures will be tracked in this study, as this study is collecting data for potential future use. All outcomes will be those of standard clinical evaluation and treatment. A clinical and research database will be kept of patient s diagnosis, progression, and treatment. Clinical database information may be reported or be used in other studies.

This study is designed to learn more about the natural history of inherited neurological disorders and the role of heredity in their development. It will examine the genetics, symptoms, disease progression, treatment, and psychological and behavioral impact of diseases in the following categories: hereditary peripheral neuropathies; hereditary myopathies; muscular dystrophies; hereditary motor neuron disorders; mitochondrial myopathies; hereditary neurocognitive disorders; inherited neurological disorders without known diagnosis; and others. Many of these diseases, which affect the brain, spinal cord, muscles, and nerves, are rare and poorly understood. Children and adults of all ages with various inherited neurological disorders may be eligible for this study. Participants will undergo a detailed medical and family history, and a family tree will be drawn. They will also have a physical and neurological examination that may include blood test and urine tests, an EEG (brain wave recordings), psychological tests, and speech and language and rehabilitation evaluations. A blood sample or skin biopsy may be taken for genetic testing. Depending on the individual patient s symptoms, imaging tests such as X-rays, CT or MRI scans and muscle and nerve testing may also be done. Information from this study may provide a better understanding of the genetic underpinnings of these disorders, contributing to improved diagnosis, treatment, and genetic counseling, and perhaps leading to additional studies in these areas. ...

Studies performed under 89-N-0045 are designed to examine the natural history of multiple sclerosis (MS) using MRI and immunological measures. In addition to studying the natural history of untreated patients, the natural history of patients receiving approved disease-modifying therapies of MS will be examined. In both cohorts of patients levels of disease activity on MRI will be compared with immunological characteristics in order to help identify disease mechanism. Patients with either definite MS (based either on clinical or combined clinical and MRI criteria) or with an initial presentation of neurological dysfunction consistent with MS will be studied longitudinally by MRI. Disease activity on MRI will be assessed using several MRI measures of disease activity including the number of contrast enhancing lesions, the overall burden of disease, brain atrophy and measures to assess axonal damage. Patients will be assessed clinically and correlations between immunological and genetic factors and disease activity as seen clinically or by MRI will be studied. A second cohort of patients starting the use of approved therapy will also be examined. Patients referred to NIH prior to beginning approved therapy will be assessed with a series of three monthly MRIs to determine the level of pretreatment disease activity. After beginning approved therapy under the direction of their private physician, patients will be followed similarly to the natural history cohort. Immunological and genetic findings will be accessed before and during therapy in order to help establish the mechanisms of action of the therapies and to identify mechanisms accounting for either a response or lack of response to therapy. Part of the collected samples willl be cryopreserved to provide respository for further studies focusing on detection of biomarkers indicative of disease state, disease stage or repsonse to therapies. Additionally, a cohort of normal volunteers will be studied. The studies in the normal volunteers will be used to establish the most appropriate imaging sequences for studying normal white matter in MS patients using magnetization transfer (MT) imaging sequences for studying normal white matter in MS patients using magnetization transfer (MT) imaging and to provide normative immunological measures. ...

Background: \- The blood-brain barrier separates the brain from the rest of the body. Epilepsy is a neurological disease that causes seizures. It can affect this barrier. Researchers think a contrast agent called mangafodipir might be better able to show areas of the brain that epilepsy affects. Objective: \- To see if mangafodipir is well tolerated and safe. To see if magnetic resonance imaging (MRI) using either mangafodipir or gadolinium can show areas of blood-brain barrier breakdown in people with epilepsy. Eligibility: * People ages 18-60 who: * Have epilepsy not controlled by drugs * Prior or concurrent enrollment in 18-N-0066 is required Design: * Participants will be screened with: * Medical history * Physical exam * Blood and urine tests * Participants will have up to 6 visits in 1-3 months. One visit is an inpatient stay lasting 2-10 days. Visits may include: * Video-EEG monitoring for participants with epilepsy * An IV catheter put in place: a needle guides a thin plastic tube into an arm vein. * Getting mangafodipir through the IV. * Getting gadolinium through the IV. * Up to 6 MRI scans over a 10-day period: a magnetic field and radio waves take pictures of the brain. Participants lie on a table that slides into a metal cylinder. They are in the cylinder for 45-90 minutes, lying still for up to 10 minutes at a time. The scanner makes loud knocking sounds. Participants will get earplugs. * A final MRI at least 2 weeks after receiving mangafodipir....

The purpose of this study is to learn more about stroke and obtain information that may serve as the basis for future investigations. It will 1) establish a registry of patients with cerebrovascular disease (stroke); 2) characterize the natural history of acute stroke and transient ischemic attacks (TIA)-an interruption of blood flow to the brain that causes stroke symptoms for a short period of time); and 3) evaluate the data to generate ideas for future studies. Patients 18 years of age or older with suspected acute stroke or TIA may be eligible for this study. Subjects will be recruited from patients who present with stroke at the emergency department of Suburban Hospital in Bethesda, Maryland. The study will gather data collected from diagnostic and laboratory tests the patient undergoes as part of standard medical care, including findings of medical and neurological examinations and other tests. In addition, studies will be done for research purposes only to gather data about stroke and TIA. These may include the following: * Blood and urine tests not more than 2 tablespoons of blood will be drawn for various tests. * Electrocardiogram (EKG) (heart tracing)-electrodes placed on the chest wall detect the heartbeat and heart rhythm. * Computed tomography (CT) scan of the head-specialized X-rays are used to obtain images of the brain. * Magnetic resonance imaging (MRI) of the brain-a strong magnetic field and radio waves are used to produce images that provide information about the brain tissue and blood vessels. * Transcranial Doppler (TCD)-sound waves are used to image the arteries of the brain and neck. * Echocardiogram-sound waves are used to image the heart and evaluate heart function. Patients may be asked to return to Suburban Hospital for follow-up testing in 1, 3, and/or 12 months, when some of these tests may be repeated to assess changes over time ...

BTX has been used since the 1980s in support of the research mission of NINDS. Initial studies were focused on expanding the applicability of BTX treatment to movement disorders and exploring new indications. We evaluated the efficacy of an alternative serotype, type F. Under other protocols, we continue to study the physiology of movement disorders and BTX response. The application of BTX therapy to movement disorders requires an understanding of BTX preparation and handling. The treatment must be tailored to the disorder under treatment and to its expression in the individual patient. Users must know the specific techniques of injection, including the use of EMG and ultrasound guidance. This protocol allows us to train physicians in all aspects of the use of BTX. It also provides us with a cohort of patients, receiving a standard method of treatment and with a stable response to BTX injection, for participation in other protocols on movement disorders and on the responses to BTX injection.

Background: Parkinson s disease is a neurologic disorder that affects movement. Its cause is unknown, and it usually begins later in life. Gene changes (PRKN and PINK1) can also cause rare types of Parkinson s disease that start at a young age. Researchers want to conduct a natural history study to learn more about how genes play a role in Parkinson s disease. Objective: To collect data and biological samples from people with different types of Parkinson s disease. Eligibility: People aged 18 to 80 years with either Parkinson s disease or PRKN- and PINK1-linked Parkinson s disease. Healthy volunteers are also needed. Design: Participants will have 6 clinic visits over 5 years. Each visit may take 1 to 3 days. During each visit: Participants will have a physical exam. The exam will be videotaped. They will answer questions about their movement, thinking, mood, and sense of smell. The extent of any symptoms of Parkinson s disease will be evaluated: Participants movements may be assessed with a finger tapping test. They may be asked to scratch and sniff different scented strips to identify odors. They will wear motion sensors on their arms, legs, chest, and back at the clinic. They will wear motion sensor devices on their wrists at home for 1 week. Blood and urine samples will be collected. Other tests are optional: Magnetic resonance imaging (MRI) scan of the brain. Participants will lie on a table that slides into a tube. Lumbar puncture (spinal tap). A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord. Muscle biopsy. A small sample of tissue will be taken from the leg.

Background: Congenital myasthenic syndromes (CMSs) are a group of inherited disorders that affect how the nerves communicate with muscles. These can cause many problems that affect how people can move and use their bodies. Objective: This is a natural history study to learn more about how CMSs affect the body and cause changes over time. Eligibility: People aged 6 months or older with a CMS. The study will focus on DOK7- and COLQ-related CMSs, as well as other forms. Design: Participants will have up to 7 visits in 5 years. At each visit, participants will undergo many tests, including: Physical exam with blood and urine tests. Tests of their heart and lung function. Exams of the eyes, lungs, muscles, and nerves. These will be done with different specialists. Exams of the arms and hands and of body use and movements. These will also be done with specialists. Photos and videos may be taken. Muscle ultrasound. Participants will lie still as a wand is rubbed over their skin. Magnetic resonance imaging (MRI) scans. Participants will lie still on a bed that slides partway into a large tube. A parent or other person may remain in the room, too. The scan will take 60 minutes. Electromyography (EMG). Participants will lie still or may be asked to move around. A machine will measure the electrical activity in their muscles. An activity monitor may be placed on the participant s wrist, ankle, or hip for up to 2 weeks. The monitor is about the size of a wristwatch. A sample of skin may be removed....

Background: SBMA is an inherited chronic disease. It affects males in mid to late adulthood. It causes slowly progressive weakness of muscles and hand tremors. Researchers want to learn more about the effects of SBMA. Objective: To identify measurements that change over time in SBMA, including tests of muscle strength and function, as well as measurements of muscle and fat size. Eligibility: Men over the age of 18 both with and without a history of SBMA. Design: Participants will have a medical history, physical exam, and blood and urine tests. They will have neuromuscular ultrasound. They will have a lumbar puncture to obtain spinal fluid. For this, a needle will be inserted into the spinal canal in the lower back. Participants will have muscle strength and function tests. These tests may include pushing, pulling, rising from a chair and sitting back down, and/or walking. During these tests, they may wear an accelerometer (activity tracker) on their wrist. Participants will get an activity tracker to wear on their wrist for 10 days at home every 3 months. Participants with SBMA will also have lower limb magnetic resonance imaging (MRI) and optional whole-body MRI. They will have lung function tests. They will have speech and swallow tests. They will complete questionnaires. They may have optional body scans to measure bone density and lean body mass. They may have optional muscle biopsies. For biopsies, a needle will be used to take a small piece of muscle from the leg. Participants with SBMA will have 5 study visits over 2 years (every 6 months). Participants without SBMA will have 1 study visit.

Tumors of the pituitary gland comprise up to 20% of all brain tumors. The central location and the small size of the pituitary gland make the management of tumors particularly challenging. Transsphenoidal surgery (TSS) to resect pituitary tumors is highly successful at achieving complete cure for functional pituitary adenomas. It is most successful when such adenomas can be localized by preoperative MRI of the pituitary. However, in some instances, small functional tumors cannot be visualized. In the case of Cushing s disease (CD), such non-visualization may be as high as 50%. The success of transsphenoidal surgery is substantially reduced in patients with negative MRI, as some of the adenomas that cause CD are so small that they are difficult to find during surgical exploration of the pituitary. Surgical success is also diminished when tumors invade the walls of the cavernous sinus. MRI of the pituitary lacks imaging resolution to detect such invasion and so the surgeon cannot perform a complete resection with surgery based on the preoperative MRI. Signal to noise ratio (SNR) is the primary constraint on achieving high quality high resolution MRI images. SNR can be improved by longer scan times or by increasing the field strength of the MRI magnet. SNR is proportional to the square of imaging time, however, long imaging times are not clinically feasible. SNR is linearly proportional to field strength, however, replacing MRI magnets is cost prohibitive. Another strong determinant of SNR is the proximity of the MRI receiver coil to the tissue being imaged. Placement of a coil in close proximity to the structure of interest dramatically increases SNR, often as much as 10-fold. Clinically this is routinely put into practice for superficial body parts, such as the temporomandibular joints, in which small coils are placed directly over the joints to achieve rapid high-resolution imaging. For deep structures, the use of superficial coils is of no benefit. This has led to the development of endocavitary coils, such as the endorectal coil used to image the prostate gland. Such coils are now in routine clinical use here at the NIH and elsewhere. During routine TSS, the surgical approach to the pituitary provides a route for placement of imaging tools, such as handheld ultrasound and Doppler probes in close proximity to the gland. Extending this model to MRI imaging, we realized that an endocavitary surface coil within the sphenoid sinus will allow for a marked improvement in SNR for imaging the sella. To this end, we have developed an endosphenoidal coil (ESC), demonstrated its MRI safety, and performed preliminary studies in cadaver heads to determine that the ESC can be placed through the transsphenoidal approach. Placement of ESC needs no modification in the surgical TSS approach to the pituitary gland. The goal of this protocol is to examine the safety and feasibility of ESC placement and imaging during TSS.

Background: Neurodegenerative disorders can lead to problems in movement or memory. Some can cause abnormal proteins to build up in brain cells. Researchers want to understand whether these diseases have related causes or risk factors. Objective: To test people with movement or thinking and memory problems to see if they are eligible for research studies. Eligibility: People ages 18 and older with a neurodegenerative disorder associated with accumulation of TDP-43 or Tau proteins Design: Participants will have a screening visit. This may take place over 2-3 days. Tests include: Medical history Physical exam Questions about behavior and mood Tests of memory, attention, concentration, and thinking Movement measurement. The speed at which participants can stand up from a chair, tap their finger and foot, and walk a short distance will be measured. Some movements will be videotaped. They will be videotaped while they speak and read a paragraph. Blood tests. This might include genetic testing. Lung and breathing tests MRI. They will lie on a table that slides into a cylinder that takes pictures of the body. Some participants will get a dye through IV. Electromyography. A thin needle will be inserted into the muscles to measure electrical signals. Nerve tests. Small electrodes on the skin record muscle and nerve activity. A small piece of skin may be removed. A skin or blood sample may be taken to create stem cells. Optional lumbar puncture. A needle will be inserted into the space between the bones of the back to collect fluid. If participants are not eligible for current studies, they may be contacted in the future.

Background: An electroencephalogram (EEG) measures the brain s electrical activity. EEG shows that the louder the sound needed to wake a person, the deeper the person s sleep. Researchers are using functional magnetic resonance imaging (fMRI) to study people during sleep so they can view brain activity in 3D. But they still need to correlate fMRI with sound thresholds, like the EEG. Objective: To measure brain activity during sleep using fMRI and EEG. Eligibility: Healthy people ages 18 34 who can sleep on their back for several hours. Design: Participants will be screened online about their sleep and general health. At a screening visit, participants will have: Physical exam Hearing exam MRI scan. A strong magnetic field and radio waves take pictures of the brain. Participants will lie down on a bed that slides into the scanner, which is shaped like a cylinder. Participants will wear an actigraph on their wrist that records their motor activity. Participants will follow a 2-week routine. This includes regular in-to-bed and out-of-bed times and limits on alcohol, caffeine, and nicotine. During the overnight visits, participants will have: Female subjects will have a urine pregnancy test. fMRI. A coil will be placed over the head. Participants will do tasks shown on a computer screen inside the scanner. EEG. Small electrodes on the scalp will record brain waves while sleeping or doing a task in the scanner. Participants will be asked to try to sleep while researchers collect fMRI and EEG data. Participants eyes will be monitored with a video camera. Headphones will deliver sounds to wake them up throughout the night. ...

Objectives: The overall study objective is to compare the sensitivities and specificities of morphometric analysis techniques using structural MRI images based on pre- and postsurgical localization of epileptic foci in patients undergoing presurgical evaluation for medically refractory epilepsy. To carry out these analyses, we aim to establish an age-stratified normative imaging database using healthy volunteers. Additional objectives are to identify abnormal networks in these patients using resting state fMRI/EEG and MEG/EEG, and to use language and memory fMRI tasks to examine the effects of epileptogenic zones and surgery on cognitive function and the networks associated with these functions. Study population: 300 adults and children (age 8 and older) with uncontrolled focal epilepsy, and 200 age-stratified healthy volunteers. Design: A retrospective and prospective natural history study. Research procedures for patients in this study include neuropsychological testing and 1-4 MRI sessions during presurgical evaluation and an additional 1-3 MRI sessions and neuropsychological testing approximately 12 months post-operatively. Research testing (such as research neuropsychological tests or MRI scanning sequences) will be done during a visit for clinical testing whenever possible, likely reducing the number of required visits. Patients will also have optional MEG and 7T structural imaging. Data will also be obtained from patients who have already undergone epilepsy surgery if they had procedures as outlined in the protocol and are willing to share the data. Healthy volunteers will receive a subset of the pre-operative procedures for patients, requiring at least 3 visits. In order to ensure adequate data acquisition, subjects may be re-scanned up to three times for the portions of the study in which they participated, possibly requiring additional visits. Outcome measures: The main outcomes will be establishment of normative values for morphometric analysis methods in age-stratified normal controls, and comparison of the sensitivity and specificity of these measures to pre- and postsurgical localization of the epileptogenic zone. Secondary outcome measures will include determination of the sensitivity and specificity of source localization using MEG/EEG and resting state fMRI/EEG, and to evaluate changes in activation during rest, as well as language and memory fMRI tasks in patients pre- and postsurgically, to examine the effects of epileptogenic zones and surgery on cognitive function and the networks underlying these functions.

Background: \- Deep brain stimulation (DBS) is an approved surgery for certain movement disorders, like Parkinson's disease, that do not respond well to other treatments. DBS uses a battery-powered device called a neurostimulator (like a pacemaker) that is placed under the skin in the chest. It is used to stimulate the areas of the brain that affect movement. Stimulating these areas helps to block the nerve signals that cause abnormal movements. Researchers also want to record the brain function of people with movement disorders during the surgery. Objectives: * To study how DBS surgery affects Parkinson s disease, dystonia, and tremor. * To obtain information on brain and nerve cell function during DBS surgery. Eligibility: \- People at least 18 years of age who have movement disorders, like Parkinson's disease, essential tremor, and dystonia. Design: * Researchers will screen patients with physical and neurological exams to decide whether they can have the surgery. Patients will also have a medical history, blood tests, imaging studies, and other tests. Before the surgery, participants will practice movement and memory tests. * During surgery, the stimulator will be placed to provide the right amount of stimulation for the brain. Patients will perform the movement and memory tests that they practiced earlier. * After surgery, participants will recover in the hospital. They will have a followup visit within 4 weeks to turn on and adjust the stimulator. The stimulator has to be programmed and adjusted over weeks to months to find the best settings. * Participants will return for followup visits at 1, 2, and 3 months after surgery. Researchers will test their movement, memory, and general quality of life. Each visit will last about 2 hours.

Background: SARS-CoV-2 is the virus that causes COVID-19. Some people who recover from COVID-19 have symptoms that last long after the active infection ends. This is called "long COVID." Sometimes, long COVID can affect the nerves and cause problems with sleep, thinking, the senses, and movement. Researchers want to find out whether people with long COVID have retained inactive remnants of SARS-CoV-2 in their bodies. Objective: To collect tissue samples to see if people with long COVID have remnants of SARS-CoV-2 in their bodies. Eligibility: People 18 years or older who have recovered from COVID-19, both with and without neurologic symptoms. Design: Participants will have 2 to 6 inpatient or outpatient visits over 4 months. Each visit will last 4 to 5 days. Participants will be screened to make sure it is safe to collect tissue samples from their body. They will have a physical and dental exam. They will have imaging scans and a test of their heart function. They will complete questionnaires about their health. They will give blood, urine, saliva, and stool samples. Their sense of taste and smell will be tested. Tissue samples will be taken from the digestive tract, lungs, colon, skin, muscle, lymph nodes, nasal passages, and mouth. Participants may be numbed or sedated for some of the procedures. Swabs will be used to collect cells from inside the mouth and nose. Participants will undergo lumbar puncture. A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord. Participants will have follow-up phone calls after each clinic visit.

Background: Most people who are referred to the EMG (Electromyography) Section of the NIH are enrolled into specific active studies. This allows researchers to learn about a range of rare neuromuscular disorders. But study criteria may not give researchers the chance to evaluate a single person or study a common symptom. Therefore, researchers want to assess people with neuromuscular disorders who are not currently enrolled in any NIH studies. They will perform tests on these individuals in the EMG Lab. Then they will create a repository of data that may be used for future research. This will help them learn more about these disorders. Objective: To retain data that is collected as part of participant visits to the NIH. Eligibility: People aged 18 and older who will be visiting the NIH for evaluation of their neuromuscular disorder. Design: Participants will be screened with a medical record review. Participants will have a physical exam. They will be evaluated for their neuromuscular disorder. They may have tests to learn more about how their nerves and muscles work that are called nerve conduction and EMG studies. Their muscles and nerves may be assessed with an ultrasound. Their ability to sweat may be measured. Their heart rate and blood pressure may be taken. Changes to their breathing or changes in their body position may be measured. Participant data will be given a unique numerical identifier that can be used if the data is shared. Data will be stored on a server and in a database. Participants will have 1-2 visits. Each visit will last less than 4 hours. They may be contacted for a follow-up visit.