Epilepsy, commonly known as “goat’s horn” or “sheep’s epilepsy”, is a chronic disease in which sudden abnormal discharges of neurons in the brain cause transient brain dysfunction. According to the latest epidemiological data in China, the overall prevalence of epilepsy in China is 7.0‰, the annual incidence rate is 28.8/100,000, and the prevalence of active epilepsy with seizures within one year is 4.6‰. It is estimated that there are about 9 million epilepsy patients in China, of which 5-6 million are active epilepsy patients, while about 400,000 new epilepsy patients are added every year. Epilepsy has become the second most common disease after headache in neurology in China.
I. Diagnostic principles of epilepsy
The diagnosis of epilepsy can be divided into five steps.
(a) Determining whether a seizure event is a seizure
The identification involving seizure events includes the identification of induced seizures and non-induced seizures. Traditionally, epilepsy is diagnosed when there are two clinical occurrences (at least 24 hours apart) of nonprovoked seizures.
(ii) Determining the type of seizure
Determine according to the ILAE seizure classification.
(iii) Determine the type of epilepsy and epilepsy syndrome
Determine according to the ILAE classification system for epilepsy and epilepsy syndromes. It should be noted that some cases cannot be classified as a specific epilepsy syndrome.
(iv) Determine the etiology
(v) Determine disability and co-morbidities
(ii) Diagnostic methods of epilepsy
(i) Medical history information
A complete history is the most important part of the diagnosis of epilepsy. It should include: history of present illness (with emphasis on seizure history), birth history, past history, family history, psychosocial impact of the disease, etc.
Current medical history
1. age of first seizure
2. pre-episode state or contributing factors (awakening, wakefulness, sleep, alcohol consumption, little sleep, excessive fatigue, psychological stress, mental stimulation, fever, posture, exercise, prodromal symptoms and relationship to menstruation, etc.)
Signs/symptoms at the beginning of the attack (aura, motor manifestations, etc.)
Seizure performance (eye opening, eye closing, posture, muscle tone, motor symptoms, vegetative symptoms, automatism, state of consciousness, tongue bite, urinary incontinence, etc.) Seizure evolution
3.Seizure duration
4. Post-ictal performance (wakefulness, irritability, drowsiness, hazy state, Todd’s palsy, aphasia, amnesia, headache, muscle aches, etc.)
5. Frequency and severity of seizures (including history of persistent state) EEG examination
6. Other ancillary tests (blood pressure, blood glucose, electrolytes, electrocardiogram, head imaging, etc.)
7. Other seizure forms (if any, ask for seizure details according to the above points)
8. Use of antiepileptic drugs (type, dose, duration, efficacy, side effects, compliance, etc.)
9. Interictal status (psychiatric symptoms, memory, anxiety, depression, etc.)
10. Psychomotor development after the onset of seizures
Past history and family history
1. Perinatal history (preterm birth, obstructed labor, hypoxic asphyxia, birth injury, intracranial hemorrhage, etc.)
2, history of other diseases of the central nervous system (infection, trauma, stroke, genetic metabolic diseases, etc.)
3.History of growth and development (psychomotor retardation, regression)
4, history of neonatal convulsions and febrile convulsions (simple and complex)
5.Family history (epilepsy, febrile convulsions, migraine, sleep disorders, genetic metabolic disorders, etc.)
6, the impact of the disease (difficulties in school, unemployment, inability to drive, being overprotected, restricted activities, psychological stress, etc.).
(II) Physical examination
Whole body examination: the focus should be on the nervous system, including: state of consciousness, mental status, focal signs (hemiplegia/hemianopia, etc.), various reflexes and pathological signs, etc. Attention should be paid to the shape and size of the head, external appearance, physical deformities and screening for certain neurocutaneous syndromes. Physical examination is initially suggestive of a diagnosis of the etiology of epilepsy. Some physical signs may suggest adverse reactions to antiepileptic drugs.
(iii) Ancillary tests
1. Electroencephalography (EEG): The most essential feature of seizures is abnormal over-discharge of brain neurons, and EEG is the most intuitive and convenient examination method that can reflect the EEG activity, and is the most important auxiliary means to diagnose seizures, determine the type of seizures and epilepsy, and is a routine examination for epileptic patients. Of course, the limitations of EEG (especially scalp EEG) examination must also be fully understood in clinical application, and the monitoring time can be extended or examined several times if necessary.
2. Neuroimaging: Magnetic resonance imaging (MRI) is of high value in detecting structural abnormalities in the brain.
If available, routine cranial MRI is recommended. CT examination of the head has advantages over MRI in showing calcific or hemorrhagic lesions. In some cases, imaging may be omitted when the diagnosis of a typical idiopathic epilepsy syndrome (e.g., benign partial epilepsy in children) has been clinically confirmed. Other imaging tests, such as functional magnetic resonance (fMRI), magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT), and positron emission tomography (PET), are not routinely performed in patients with epilepsy. It should be noted that a positive imaging result does not mean that there is an inevitable causal relationship between the lesion and the seizure.
3. Others: Selective examinations should be performed according to the patient’s specific situation.
(1) Blood tests: including routine blood tests, blood glucose, electrolytes, liver and kidney function, blood gas, pyruvate and lactate, etc., can help to find the cause of the disease. Regular examination of blood routine and liver and kidney function and other indicators can also assist in monitoring the adverse reactions of drugs. Toxic screening should be performed when toxicity is clinically suspected. Those already taking antiepileptic drugs may be monitored for drug concentrations as appropriate.
(2) Urinalysis: including urinary routine and screening for genetic metabolic disorders.
(3) Cerebrospinal fluid examination: mainly to exclude intracranial infectious diseases, and also helpful in the diagnosis of certain genetic metabolic disorders.
(4) Electrocardiogram: For patients with suspected epilepsy or newly diagnosed epilepsy, routine electrocardiogram is mostly advocated. This helps to detect certain cardiogenic seizures that are easily misdiagnosed as epileptic seizures (e.g. syncopal seizures due to cardiac arrhythmias) and also allows early detection of certain cardiac arrhythmias (e.g. long QT syndrome, Brugada syndrome and conduction block), thus avoiding possible serious consequences from the use of certain antiepileptic drugs.
(5) Genetic testing: It has now become one of the important complementary diagnostic tools. Previously, using one-generation sequencing technology, known epileptogenic genes could be detected one by one, which was only applicable to a certain epilepsy syndrome with high clinical suspicion, such as Dravet syndrome. With the development of high-throughput second-generation sequencing technology and array-based ComparativeGenomic Hybridization (aCGH) for epilepsy research, more and more epilepsy-causing genes have been identified. This method is a rapid, efficient and relatively inexpensive clinical genetic diagnostic technique that can provide us with basic genetic information of epileptic patients. aCGH technology can efficiently detect all known epilepsy-associated pathogenic genes at once and has been successfully applied to the etiological diagnosis of epileptic encephalopathy. The aCGH technique can efficiently detect pathogenic copy number alterations (CNV) associated with epilepsy in patients. Currently, genetic testing is not used as a routine etiologic screening tool and is usually performed when there is already a high clinical suspicion of a disorder.
Considerations in the diagnosis of epilepsy
I. Distinguish between induced and uninduced seizures
Not all seizures have to be diagnosed as epilepsy. By definition, a patient’s seizures must be nonprovoked seizures for a diagnosis of epilepsy to be made, while evoked seizures are usually not considered for a diagnosis of epilepsy even if they are recurrent. The misdiagnosis of recurrent acute symptomatic seizures as “symptomatic epilepsy” inevitably leads to overdiagnosis and treatment, as well as to unreliable epidemiological findings in epilepsy. Conditions in which seizures are present but not usually diagnosed as epilepsy include: benign neonatal seizures, febrile convulsions, alcohol or drug withdrawal seizures, and seizures that occur during the acute phase of a central nervous system or systemic disease. Recurrent reflex seizures can be diagnosed as epilepsy according to the 2014 ILAE Clinical Utility Definition of Epilepsy, even if each seizure appears to be “triggered.
The role of history and ancillary tests in the diagnosis of epilepsy
The medical history is the most important basis for the diagnosis of epilepsy, which is largely a clinical diagnosis. By definition, epilepsy can be diagnosed when there are two clinical occurrences of non-induced seizures, and drug therapy can usually be considered. In most cases, a detailed history, especially a seizure history, is sufficient to determine whether the seizure symptoms are epileptic, or even to make a preliminary diagnosis of seizure type and type of epilepsy (syndrome), with later EEG and imaging often serving as a means to further verify or clarify the prior diagnosis. An abnormal EEG does not necessarily lead to a diagnosis of epilepsy, and a normal EEG does not exclude epilepsy. Patients who have had several typical grand mal seizures in a short period of time, but fail to diagnose epilepsy and delay treatment because of a normal EEG should be avoided.
III. Obtaining a complete seizure history
Inadequate history taking is the most common cause of misdiagnosis of epilepsy. Seizures are often short-lived and it is unlikely that the physician will witness a seizure, so a detailed and organized history taking is especially important. The patient should be advised to attend the clinic with a witness to the seizure in order to obtain a complete history. When the patient’s description is unclear at the time of the visit, it is necessary for the physician to interview the seizure witness by telephone. If possible, it is recommended that the patient or family member videotape the seizure with a cell phone or home video camera for the physician to analyze during the visit. Also, in cases where the patient or witness is unclear, it is good to have them watch a variety of videos of typical seizures, which often allows them to find the seizure that most closely resembles the patient’s presentation. If it is difficult to obtain a reliable history, explain the importance of the history to the patient so that he or she can be observed in the event of another seizure and provided at a follow-up visit.
Avoid missing “minor seizures”
Complete information on the type of seizure is important for the diagnosis of the type of epilepsy (syndrome). When taking a history, it is important to focus on both obvious seizures (e.g., grand mal seizures) and certain “minor seizures” that are often overlooked or not actively reported by patients or witnesses of seizures, such as aura seizures, myoclonic seizures, and focal seizures with minimal impairment of consciousness. For example, in an adolescent patient who complains of several primary grand mal seizures and has a normal past history, if the history asks for “shaking” of the limbs after waking up in the morning, which is often overlooked by the patient, the clinical consideration is “juvenile myoclonic epilepsy”, otherwise Otherwise, it may be considered as “generalized epilepsy with grand mal seizures only”.
V. Application of long-range video-EEG monitoring
By definition, the “gold standard” for the diagnosis of seizures is to establish a “causal relationship” between abnormal EEG activity and clinical manifestations during seizures. Of course, it is neither practical nor necessary to perform long-range monitoring in all patients. In those cases where the nature of the seizure is not clear from a detailed history, long-range video-EEG monitoring can be performed to clarify the diagnosis. In addition, the above-mentioned “gold standard” should also be used to diagnose cases such as “abdominal epilepsy”, “headache epilepsy”, and “epilepsy with xxx as the only seizure manifestation” in China. The “gold standard” should be measured and tested. Of course, the limitations and shortcomings of long-range video-EEG monitoring should also be understood in practice.
Identifying “pseudo” drug-refractory epilepsy
Before diagnosing drug-refractory epilepsy, care should be taken to rule out “pseudophakic” drug-refractory epilepsy. The following should be considered: (1) non-epileptic seizures; (2) misclassification of seizures (e.g., misdiagnosis of aphasic seizures as complex partial seizures); (3) inappropriate drug selection for seizure type (e.g., carbamazepine to control aphasic seizures); (4) inadequate drug dosage or inappropriate drug administration; (5) poor patient compliance with medication; (6) controllable triggers that aggravate seizures (e.g., excessive alcohol consumption, lack of sleep, etc.); (6) drug-refractory seizures. lack of sleep, etc.); and (7) other etiologies that can lead to epilepsy refractory to treatment (e.g., vitamin B6 dependence, glucose transporter I deficiency, etc.). In addition, some patients with epilepsy may have both seizures and non-epileptic seizures, which should be differentiated and the diagnosis should be clarified by performing long-range video-EEG monitoring if necessary. Avoid increasing the dose of medication or changing medication frequently to control “intractable epilepsy” because the seizure symptoms are mistaken for seizures.
The relationship between diagnosis and treatment of epilepsy
Although the diagnosis and treatment of epilepsy are closely related, they are not necessarily linked. The diagnosis of epilepsy does not always require treatment. For example, patients with benign partial epilepsy in children with sparse seizures or epilepsy with mild seizures (e.g., aura-only seizures) may choose not to treat them. The decision to treat a patient with epilepsy depends on a variety of factors, including the patient’s wishes and the individualized benefit-risk ratio of taking/not taking medication. On the other hand, initiation of treatment may be considered without a diagnosis of epilepsy. For example, in patients with recurrent seizures presenting in the acute phase of encephalitis, medication is usually administered clinically despite the absence of a diagnosis of epilepsy.