A Catamenial Epilepsy During The Reproductive Years
In women with epilepsy during the reproductive years, a correlation has been observed between the cyclic monthly levels of estrogen and progesterone and seizure frequency . Catamenial epilepsy is the term applied when the pattern of seizure occurrence in a woman fluctuates with the menstrual cycle. The reported prevalence of a catamenial epilepsy among women varies due to differing definitions and few formal studies, with reports that it affects between 2070% of women with epilepsy . Work by Herzog et al. has led to a more uniform acceptance of the definition of catamenial epilepsy as a two-fold increase in daily seizure frequency during specific phases of the menstrual cycle .
Schematic diagram of allopregnanolone and its neuroactive steroid binding site on the GABAA-BDZ receptor
Role Of Sex In Epilepsy And Sex
During childhood, seizures and epilepsy syndromes more likely affect boys than girls, although some epilepsies are significantly more common or exclusive in girls than in boys . Sex related differences have been described also in patients with temporal lobe epilepsy, with respect to distinct regional distribution of brain dysfunction during interictal periods, seizure generalization, lateralization, as well as the extent of neuronal damage .
Combination Of Neurosteroids With Tiagabine Or Midazolam
There are data on the pharmacokinetic properties of ALLO and GNX . Plasma and brain levels of ALLO and GNX were determined in naïve mice at various time points following intramuscular dosing . Maximum concentration values for ALLO and GNX were 645 and 550 ng/mL, respectively. Brain levels rose more slowly and peaked at 10 min in both cases, the respective Cmax values being 845 ng/mL for ALLO and 1239 ng/mL for GNX. On the basis of all pharmacokinetic parameters, it was found that the peak brain concentrations and brain exposure for both steroids, was approximately 3-fold the plasma exposure . In the first case, the probable cause is the slightly higher hydrophobicity of GNX than ALLO . In the second case, the authors indicate a higher lipophilicity of GNX as a probable cause . Therefore, GNX initially concentrates in the brain to higher levels, being subsequently redistributed to fat tissue. Maintaining a more flatter distribution in the brain is another factor that may be responsible for the higher effectiveness of ALLO. The common feature of both neurosteroids is that both ALLO and GNX were highly bioavailable, indicating that they were almost completely absorbed following intramuscular injection .
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How Estrogen Levels Impact Migraines
The explanation for why drops and fluctuations in estrogen cause migraines is not completely clear, but there are several possible mechanisms.
Estrogen has a known impact on the action of serotonin, a neurotransmitter that modulates pain and mood. Estrogen also affects blood vessels and blood pressure, and blood vessel alterations are known to play a role in migraines as well.
It is likely that both of these factors, and possibly others, could mediate the estrogen-migraine connection.
Sex Hormones Estrogen And Progesterone Stabilize Brain Cells
The two sex hormones in women that affect brain cells are estrogen and progesterone. When in equal amounts in the body, the hormones balance each other out and the system works in harmony. However, when estrogen is too high, progesterone has dropped too low, or some type of imbalance has occurred, the brain cells will receive different signals. When the cells become over stimulated, a seizure may occur.
Estrogen is the female sex hormone that influences puberty, monthly menstruation, lactation, mood and the aging process. The levels of estrogen decrease with age.
Progesterone is another sex hormone that prepares the uterus to receive and support fertilized eggs. At a normal level, progesterone will keep seizures at bay by stabilizing brain cells.
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Neurosteroids And Catamenial Epilepsy
One of the possible causes of refractory epileptic seizures in women might be disturbances in the levels of progesterone and estrogen. These hormones may affect the electrical excitability of neurons and thus the seizure threshold. It was found that in the case of concentration fluctuations during the menstrual cycle, these hormones contributed to seizure exacerbation, called catamenial epilepsy. It is a dominant a type of drug-refractory epilepsy found in women of reproductive age. The fact that the characteristic feature of catamenial epilepsy is increased frequency of seizures at specific and repetitive times in the menstrual cycle serves as confirmation of how important a role is played here by the hormones .
Progesterone is synthesised in the mitochondrial membranes of body cells, and in the cerebral tissue, in several stages, the first of which is homogenous, while the remaining stages can develop in various ways, which are different in the peripheral and central compartments. There is evidence that in the peripheral compartment, the 5 beta reduction pathway predominates, in turn in the central compartmentthe 5 alpha pathway which is predominant in rats, monkeys, and humans .
Animal studies were conducted in which the progesterone metabolism was blocked by finasteride which resulted in suppressing the anticonvulsant properties of this hormone .
Table 1 Neurosteroidsmechanisms of action and effects on seizure activity.
History And Physical Examination
An eyewitness report of the episode can be very helpful to doctors. An eyewitness can describe exactly what happened, whereas people who have an episode usually cannot. Doctors need to have an accurate description, including the following:
How fast the episode started
Whether it involved abnormal muscle movements , tongue biting, drooling, loss of bladder or bowel control, or muscle stiffening
How long it lasted
How quickly the person recovered
A quick recovery suggests fainting rather than a seizure. Confusion that lasts for many minutes to hours after consciousness is regained suggests a seizure.
Although eyewitnesses may be too frightened during the seizure to remember all details, whatever they can remember can help. If possible, how long a seizure lasts should be timed with a watch or other device. Seizures that last only 1 or 2 minutes can seem to go on forever.
Doctors also need to know what people experienced before the episode: whether they had a premonition or warning that something unusual was about to happen and whether anything, such as certain sounds or flashing lights, seemed to trigger the episode.
Doctors ask people about possible causes of seizures, such as the following:
Which drugs they are taking or have recently stopped
For people who are taking drugs to control seizures, whether they are taking the drugs as directed
Whether they are getting enough sleep
With children, whether they have relatives who also have seizures
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Loss Of Gonadal Hormones And Seizures
A natural menopause is a permanent cessation of ovarian function and occurs in control women without epilepsy between ages 45 and 55. Women with epilepsy have increased risk for premature onset of menopause . Depending on seizure frequency and estimated lifetime number of seizures, the ovarian failure in women with epilepsy occurs as early as around age 40 . The dramatic irregular fluctuations in gonadal hormones during the onset of menopause and their loss at menopause are likely to influence seizure frequency. However, the studies report controversial findings. A study by Harden et al., 1999 showed that women with non-catamenial pattern of seizures during their reproductive age reported worsening of seizure control or no change at menopause, while women with catamenial pattern of epilepsy reported better control of their seizures when reaching the menopause . Similarly, another study describes that about 40% of women with epilepsy reported worsening of their seizures after the menopause, some women had new onset of seizures, while only 18% reported better seizure control after the menopause .
Several studies have shown that addition of sex hormones interferes with levels of some anticonvulsant drugs and vice versa. Thus, special considerations for HRT strategy adjustments are critical in women with epilepsy for full benefits of HRT without the risk of seizure exacerbation .
Hormonal Changes As A Result Of Epileptiform Activity
Both men and women with epilepsy often have altered reproductive function . Steroid hormone levels have been shown to change as a result of seizure activity. Elevations in prolactin and corticosteroids post-seizure are most commonly discussed, attributed to non-specific stress response . Here the focus will be more directed towards less commonly discussed changes in other steroid hormones including the sex hormones.
In patients with epilepsy, it is important to first identify the cause of endocrine dysfunction, whether the anticonvulsant treatment or seizure activity itself are responsible for these alterations . Numerous studies suggest that anticonvulsant treatments may interfere with endocrine function and reproductive health and that the treatment strategy may need adjustments to alleviate these adverse effects .
Effects of repeated seizures on hormonal levels and reproductive system have been observed already during prepubescence, although little has been published on this topic. A significant increase in allopregnanolone serum level was observed in both male and female prepubertal children, independent on the type of epilepsy, during the post-ictal phase but not during the inter-ictal phase .
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How Stress Can Lead To Seizures
A new study finds that one-third of patients admitted to the epilepsy unit are not actually suffering from epileptic seizures: theyre suffering from stress.
As if we werent already stressed out enough about our stress levels, a new study reports that over a third of seizures in patients admitted to the Johns Hopkins in-patient epilepsy unit are actually psychogenic in nature, rather than epileptic. This means that the seizures were actually physical manifestations of emotional stress, and not the result of abnormal electrical activity in the brain, as with epilepsy. The psychogenic seizures in these patients were strongly linked to life stresses or, more specifically, to the methods the people used to cope with their stressors.
The team studied 40 healthy people, 20 people with confirmed epilepsy, and 40 people who had experienced psychogenic non-epileptic seizures . The participants filled out questionnaires to determine which coping style they tended to use, ranging from active coping to denial to religious coping to humor to behavioral or mental disengagement. They also indicated how many of 102 stressful life events theyd been through in the last five years, in the areas of family, legal matters, finances, work, and marriage.
The authors had wagered that the PNES patients would have had more life stressors than controls or epileptic patients, since previous research had suggested the connection.
But this was not what they found.
Recovery And Management Of Seizures In Dogs
Managing seizure disorders in dogs is not always straightforward. Depending on the underlying condition, you can expect follow-up appointments, medication adjustments, and additional treatments and therapies. In cases of idiopathic epilepsy, it can take time for the medication to control your dogs seizures, and in some cases, it may not be possible to control the seizures with medication. Its also important to monitor your dog for any potentially dangerous side effects of medication, like liver and kidney damage.
Seizures caused by an underlying condition often require additional tests, veterinary visits, and medications to manage both the condition and any other side effects and symptoms. The frequency of follow-up visits will be determined by the underlying condition, as will the extent to which you as the owner need to manage the condition.
Monitor the frequency and duration of your dogs seizures by recording the date, time, and duration, as well as recording the seizure when possible will help your veterinarian. Unless your dog is in danger of hurting herself, however, owners should never attempt to touch or hold their dog during a seizure. This can result in unintended injuries like bites, as dogs may not be conscious of their actions or surroundings directly before, during, and after a seizure.
Some causes of seizures can be fatal. In these cases, your veterinarian will discuss your dogs prognosis and help you make any necessary quality-of-life decisions.
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C Other Neuroactive Steroids
Ganaxolone is a neuroactive steroid analog, and is the synthetic 3-methyl derivative of allopregnanolone . It has positive allosteroic modulatory effect at the neurosteroid binding site on the GABAA receptor complex, which is distinct from the benzodiazepine binding site . It has beneficial activity in a broad range of animal models of epilepsy. Ganaxolone also has the advantage that it lacks hormonal activity, and thus can more readily be applied as a therapeutic agent across both genders and all ages than progesterone. Another advantage is that tolerance does not develop to GNX unlike the benzodiazepines, despite working at the same receptor complex.
The findings from a nonrandomized, open-label, pilot study in pediatric and adolescent subjects with refractory epilepsy have been reported . Of the 15 subjects enrolled, 8 completed the trial and 3 continued in the compassionate-use extension period. The responder rate was 25%, and another 13% had a moderate response . Of the 3 that entered the extension phase, one remained seizure-free for over 3.5 years of GNX administration. The medication was tolerated well, with somnolence being the most frequent side effect.
What Are The Symptoms Of A Seizure
Your symptoms depend on the type of seizure. General symptoms or warning signs of a seizure can include:
Breathing problems or stopping breathing
Loss of bowel or bladder control
Falling suddenly for no apparent reason, especially when associated with loss of consciousness
Not responding to noise or words for brief periods
Appearing confused or in a haze
Nodding your head rhythmically, when associated with loss of awareness or loss of consciousness
Periods of rapid eye blinking and staring
During the seizure, your lips may become tinted blue and your breathing may not be normal. After the seizure, you may be sleepy or confused.
The symptoms of a seizure may be like those of other health conditions. Make sure to talk with your healthcare provider for a diagnosis.
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Can Puberty Affect My Epilepsy
The changes in your hormone levels during puberty might cause you to have more seizures. And you might feel more stressed and anxious. There could be a few different reasons for this. Your hormone changes can affect how you feel. Having more seizures than usual can be stressful and can make you feel anxious. And just being a teenager can be pretty stressful in itself.
Are Seizures Dangerous For Dogs
Although a single seizure is not often dangerous, having cluster seizures, multiple seizures in a short period of time, or a seizure that continues for more than a couple of minutes can result in the dogs body temperature rising. This rising of body temperature is called hyperthermia which has its own set of issues and concerns, so be cautious of your dogs temperature elevating.
Status epilepticus, a very serious and life-threatening situation, occurs when a seizure lasts for longer than five minutes. Without the aid of intravenous anticonvulsants to stop the seizure activity, its possible a dog can suffer irreversible brain damage and possibly even death. Receiving treatment from a veterinarian immediately is essential if your dog displays signs of status epilepticus.
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Menstrual Cycles And Periods
Because of the changes in hormone levels that happen throughout the menstrual cycle, one in three women with epilepsy finds that their seizures are affected by their periods.
Some women regularly have their seizures at a particular time during their menstrual cycle. This might be just before or during their period, or at another time, such as ovulation. Women who have their seizures only at these specific times during their menstrual cycle , may have catamenial epilepsy.
Keeping a seizure diary can help to keep track of seizures, to see if there are any patterns to when they happen.
Women with catamenial epilepsy may be prescribed the contraceptive injection Depo Provera. This may reduce seizures for some women as it stops their regular cycle. An extra AED, in addition to their regular AEDs may be prescribed for the week before and during the first few days of their period. If you have catamenial epilepsy, you can discuss options for treatment with your specialist.
Hormones Affect Blood Vessels
Low estrogen levels during menopause directly affect blood pressure and circulation, and a restricted flow of blood and oxygen to the brain can create the loss of equilibrium, which women experience as dizziness. Consequently, by balancing estrogen levels, women might find their circulation improves and, with it, their sense of balance.
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Estrogen Might Sensitize Your Cells
Experts are still studying the role that hormones play in migraine.
But according to a 2018 study, changes in estrogen levels might sensitize certain cells in your body to migraine triggers. This might increase your chances of experiencing migraine symptoms.
The study relied on in vitro and animal models, rather than human research. More research in humans is needed to learn how estrogen and other hormones affect migraine.
Most women of reproductive age go through menstrual cycles. During those cycles, the estrogen levels in your body fluctuate. These changes in estrogen may contribute to the development of migraine symptoms at certain points in your life.
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Relationship Between Epilepsy And The Menstrual Cycle
Catamenial epilepsy is believed to occur secondarily to the neuroactive properties of endogenous steroid hormones and the natural cyclic variation in their serum levels throughout the menstrual cycle.4
Herzog4 distinguished three patterns of catamenial seizure exacerbation, relating to the higher seizure occurrence during the specific phases of the menstrual cycle: the perimenstrual, periovulatory, and inadequate luteal phase patterns.
In ovulatory cycles, the higher ratio of serum estradiol/ progesterone during the premenstrual period has been shown to lead to the clustering of seizures. Probably, the sudden withdrawal of progesterone, analogous to a benzodiazepine withdrawal, could be the cause of the premenstrual rise in seizure frequency, while, during the days preceding ovulation, the rapid and steep rise in serum estradiol concentration is believed to be responsible for the increase of seizures at that time.11 Seizures are least likely to occur during the mid-luteal phase, during which the serum progesterone levels are higher than those of serum estradiol.12,13
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