A binary digital communication system employs the signals of a febrile


This application is a divisional of U. The present invention is related to U. The present invention relates generally to characterizing a patient's propensity for a future neurological even and communicating with the patient. More specifically, the present invention relates to characterizing a propensity for a future seizure and when it is determined that the patient has a high or elevated propensity for a seizure, providing a communication to the patient that is indicative of an appropriate action for responding to the patient's elevated propensity for the seizure.

Optionally, such information may be incorporated into an interactive communication protocol in a binary digital communication system employs the signals of a febrile to convey appropriate communications, such as instructions or recommendations to the patient and receive historical and real-time patient status information and acknowledgements associated with the management of the patient's care.

Epilepsy is a disorder of the brain characterized by chronic, recurring seizures. Seizures are a result of uncontrolled discharges of electrical activity in the brain. A seizure typically manifests as sudden, involuntary, disruptive, and often destructive sensory, motor, and cognitive phenomena. Seizures are frequently associated with physical harm to the body e.

A typical seizure, for example, might begin as spontaneous shaking of an arm or leg and progress over seconds or minutes to rhythmic movement of the entire body, loss of consciousness, and voiding of urine or stool.

A single seizure most often does not cause significant morbidity or mortality, but severe or recurring seizures epilepsy results in major medical, social, and economic consequences. Epilepsy is most often diagnosed in children and young adults, making the long-term medical and societal burden severe for this population of patients. People with uncontrolled epilepsy are often significantly limited in their ability to work in many industries and cannot legally drive an automobile.

An uncommon, but potentially lethal form of seizure is called status epilepticus, in which a seizure continues for more than 30 minutes.

This continuous seizure activity may lead to permanent brain damage, and can be lethal if untreated. While the exact cause of epilepsy is uncertain, epilepsy can result from head trauma such as from a car accident or a fallinfection such as meningitisor from neoplastic, vascular or developmental abnormalities of the brain. Most epilepsy, especially most forms that are resistant to treatment i. In order to assess possible causes and to guide treatment, epileptologists both neurologists and neurosurgeons typically evaluate people with seizures with brain wave electrical analysis e.

While there is no known cure for epilepsy, chronic usage of anticonvulsant and antiepileptic medications can control seizures in most people. The anticonvulsant and antiepileptic medications do not actually correct the underlying conditions that cause seizures. Instead, the anticonvulsant and antiepileptic medications manage the patient's epilepsy by reducing the frequency of seizures.

There are a variety of classes of antiepileptic drugs AEDseach acting by a distinct mechanism or set of mechanisms. For most cases of epilepsy, the disease is chronic and requires chronic medications for treatment.

AEDs generally suppress neural activity by a variety of mechanisms, including altering the activity of cell membrane ion channels and the propensity of action potentials or bursts of action potentials to be generated. These desired therapeutic effects are often accompanied by the undesired side effect of sedation.

Some of the fast acting AEDs, such as benzodiazepine, are also primarily used as sedatives. While chronic usage of AEDs has proven to be effective for a majority of patients suffering from epilepsy, the persistent side effects can cause a significant impairment to a patient's quality of life. This creates a scenario in which overpatients in the United A binary digital communication system employs the signals of a febrile alone have uncontrolled epilepsy. If a patient is refractory to treatment with chronic usage of medications, surgical treatment options may be considered.

If no focus is identifiable, or there are multiple foci, or the foci are in surgically inaccessible regions or involve eloquent cortex, then surgery is less likely to be successful or may not be indicated. Surgery is effective in more than half of the cases in which it is indicated, but it is not without risk, and it is irreversible. Because of the inherent surgical risks and the potentially significant neurological sequelae from resective procedures, many patients or their parents decline this therapeutic modality.

Some non-resective functional procedures, such as corpus callosotomy and subpial transection, sever white matter pathways without removing tissue. The objective of these surgical procedures is to interrupt pathways that mediate spread of seizure activity. These functional disconnection procedures can also be quite invasive and may be less effective than resection. This is a reversible procedure which introduces an electronic device which employs a pulse generator and an electrode to alter neural activity.

The vagus nerve is a major nerve pathway that emanates from the brainstem and passes through the neck to control visceral function in the thorax and abdomen.

VNS uses intermittent stimulation of the vagus nerve in the neck in an attempt to reduce the frequency and intensity of seizures. See Fisher et al. Another recent alternative electrical stimulation therapy for the treatment of epilepsy is deep brain stimulation DBS. Open-loop deep brain stimulation has been attempted at several anatomical target sites, including the anterior nucleus of the thalamus, the centromedian nucleus of the thalamus, and the hippocampus.

The results have shown some potential to reduce seizure frequency, but the efficacy leaves much room for improvement. There have also been a number of attempts described in the patent literature regarding the use of predictive algorithms that purportedly can predict the onset of a seizure.

When the predictive algorithm predicts the onset of a seizure, some type of warning is provided to the patient regarding the oncoming seizure.

For example, see U. While conventional treatments for epilepsy have had some success, improvements are still needed. The present invention provides improved systems and methods for monitoring, managing, and treating neurological disorders and communicating with a patient regarding an appropriate action. The systems and methods of the present invention are configured to characterize a patient's propensity for a a binary digital communication system employs the signals of a febrile neurological event, such as an epileptic seizure.

In one embodiment, a patient's propensity for a seizure can be estimated or derived from a neural state which can be characterized as a point along a single or multi-variable state space continuum. The methods and systems of the present invention may also have the capability to use feedback from the patient as an additional metric for characterizing the patient's propensity for a seizure.

For example, in some embodiments, the system may allow the patient to affirm that the AED was taken, indicate that they didn't take the AED, indicate that they are feeling an aura or are experiencing a prodrome or other symptoms that precede a seizure, indicate that they had a seizure, indicate that they are going to sleep or waking up, engaging in an activity that is known to the patient to interfere with their state, or the like.

The present invention has broad therapeutic and diagnostic applications, including the control of neural state to reduce the patient's propensity for future neurological symptoms, as well as to the prediction of future neurological symptoms. In one embodiment, the patient's characterized neural state and other characterized patient parameters are compared to baseline values, and the comparison is used to determine that patient's propensity for a future seizure.

The results of the calculations and comparisons may then be input into a treatment algorithm, such as a fixed or configurable state machine that implements an interactive communication protocol to determine and convey appropriate communications e. Depending on the level of the patient's propensity for a seizure, the communication provided to the patient may take a variety of different forms.

Some embodiments will provide a recommendation or instruction to take an acute dosage of a specified pharmacological agent e. However, the instructions or recommendations may suggest adjusting the timing or dosage of a chronically prescribed pharmacological agent, performing a specific action such as assuming a safe posture or position, activating an implanted drug dispenser, manually activating a neuromodulation treatment such as vagus nerve stimulation VNSdeep brain stimulation DBScortical stimulation, or the like.

In preferred embodiments, the instructions or recommendations provided by the systems and methods of the present invention will be reflective of, or a function of, the patient's propensity for the seizure. For example, if the propensity for a seizure indicates a time horizon, parameters of the therapy recommendation such as dosage will typically be inversely related to the time horizon.

Thus, a higher dosage of medication will a binary digital communication system employs the signals of a febrile be recommended for a short time horizon than for a long time horizon. If the propensity for a seizure is indicative of a likelihood or probability for the seizure, the parameters of the therapy recommendation will likely be directly related to the likelihood or probability. Thus, for a high likelihood a binary digital communication system employs the signals of a febrile high probability of a seizure, a higher dosage of a medication will be recommended than for a low likelihood or low probability of the seizure.

In one specific embodiment, the present invention provides a system that comprises a predictive algorithm that is configured to be used in conjunction with acute dosages of a pharmacological agent, including an AED, such as the rapid onset benzodiazepines. Other antiepileptic drugs or sedatives may be used as well. The predictive algorithm may be used to characterize the patient's propensity for a future seizure. If the predictive algorithm determines that the patient is at an increased or elevated propensity for a future seizure or otherwise predicts the onset of the future seizure, the system may provide an output that recommends or instructs the patient to take an acute dosage of a pharmacological agent such as an AED to prevent the occurrence of the seizure or reduce the magnitude or duration of the seizure.

There are many drug classes that comprise the set of antiepileptic drugs AEDsand many different mechanisms of action are represented. For example, some medications are believed to increase the seizure threshold, thereby making the brain less likely to initiate a seizure. Other medications retard the spread of neural bursting activity and tend to prevent the propagation or spread of seizure activity.

Unlike conventional anti-epileptic drug treatments, which provide for a chronic regimen of pharmacological agents, a binary digital communication system employs the signals of a febrile present invention is able to manage seizures acutely while substantially optimizing the intake of the pharmacological agent by instructing the patient to take a pharmacological agent only when it is determined that a pharmacological agent is necessary.

Furthermore, with this new paradigm of seizure prevention, the present invention provides a new indication for pharmacotherapy. This new indication is served by several existing medications, including AEDs, given at doses which are sub-therapeutic to their previously known indications, such as acute AED administration for seizure termination or status epilepticus. Since this new indication is served by a new and much lower dosing regimen and consequently a new therapeutic window, the present invention is able to provide a correspondingly new and substantially reduced side effect profile.

For example, the present invention allows the use of dosages that are lower than FDA-approved dosages for the a binary digital communication system employs the signals of a febrile anti-epileptic agents. But as can be appreciated, if the measured signals indicate a high propensity for a seizure, the methods and systems of the present invention may recommend taking an FDA or a higher than FDA approved dose of the AED to prevent the predicted seizure.

Such a paradigm has valuable application for patients in which side effects of AEDs are problematic, particular sedation in general and teratogenicity in pregnant women or risk of teratogenicity in all women of child bearing age. By analogy, acetylsalycilic acid ASA or aspirin has a variety of distinct indications which are treated by distinctly different dosing regimens of the same chemical compound. For example, when given at an 81 mg dosage, the anti-platelet therapeutic effect is effective as a preventative agent against cardiovascular disease.

When given at a mg dosage, the analgesic and antipyretic effects is efficacious in pain and fever control. At higher dosages of 1 to 2 grams, the anti-inflammatory effect is efficacious against rheumatoid arthritis. This exemplifies the distinctly different mechanisms of action and indications for the same chemical compound when administered at different dosages with consequent different plasma levels and different therapeutic windows and side effect profiles. The present invention in which acute pharmacotherapy is provided for seizure prevention similarly represents a new indication with a new dosing regimen, a new therapeutic window and a new side effect profile.

In another specific embodiment, the present invention provides a system that comprises a predictive algorithm that may be used to modify or alter the scheduling and dosing of a chronically prescribed pharmacological agent, such as an AED, to optimize or custom tailor the dosing to a particular patient a binary digital communication system employs the signals of a febrile a particular point in time.

This allows for 1 improved efficacy for individual patients, since there is variation of therapeutic needs among patients, and 2 improved response to variation in therapeutic needs for a given patient with time, resulting form normal physiological variations as well as from external and environmental influences, such as stress, sleep deprivation, the presence of flashing lights, alcohol intake and withdrawal, menstrual cycle, and the like The predictive algorithm may be used to characterize the patient's a binary digital communication system employs the signals of a febrile for the future seizure, typically by monitoring the patient's neural state.

If the predictive algorithm determines that the patient is at an increased propensity for an epileptic seizure or otherwise predicts the onset of a seizure, the system may provide an output that indicates or otherwise recommends or instructs the patient to take an accelerated or increased dosage of a chronically prescribed pharmacological agent. Consequently, the present invention may be able to provide a lower chronic plasma level of the AED and modulate the intake of the prescribed agent in order to decrease side effects and maximize benefit of the AED.

In a further embodiment, the present invention provides a method of preventing a predicted epileptic seizure. The method comprises administering an effective amount of an anti-epileptic drug to a patient in need thereof. Some of the more rapid onset of AEDs can terminate seizures in as short a time period as 30 seconds. For example, intranasal midazolam can terminate a seizure in 30 seconds, while intramuscular and IV diazepam may terminate a seizure between about 1 minute and 2 minutes.

While the particular anti-epileptic drug that is administered to the patient will be customized to the specific patient, some preferred anti-epileptic drugs include buccal midazolam, intranasal midazolam, intramuscular midazolam, rectal diazepam, a binary digital communication system employs the signals of a febrile diazepam, intravenous lorazepam, and the like.

While the following discussion focuses on characterizing the patient's propensity for a seizure and managing and treating the epileptic seizures through providing recommendations or instructions to the patient to take an action e. For example, the present invention may also be applicable to management of Parkinson's disease, essential tremor, Alzheimer's disease, migraine headaches, depression, or the like.

As can be appreciated, the features extracted from a binary digital communication system employs the signals of a febrile signals and used by the predictive algorithm will be specific to the underlying disorder that is being managed. While certain features may be relevant to epilepsy, such features may or may not be relevant to the neural state measurement for other disorders.

For a further understanding of the nature and advantages of the present invention, reference should be made to the following description taken in conjunction with the accompanying drawings.

All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:.

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