Articles

Seizure Disorders

Introduction

Epilepsy (also known as seizure disorder) is a neurological condition with symptoms which vary from a momentary lapse of attention to convulsions. Damage to brain cells can disrupt the normally smooth-running pattern of electrical activity in the brain by causing an electrical overload. This can create a seizure, which causes a sudden change in the individual's consciousness and/or change in motor activity. Epilepsy was one of the first brain disorders to be described. It was mentioned in ancient Babylon more than 3,000 years ago. The word epilepsy is derived from the Greek word for "attack." It was once thought that people who had epilepsy were being visited by demons or gods. However in 400 B.C., the early physician Hippocrates suggested that epilepsy was a disorder of the brain.

A seizure disorder includes any condition in which there are repeated episodes of seizures of any type. Epilepsy (idiopathic seizure disorder) is a term used when the seizure disorder has no identifiable cause such as brain disease. A seizure disorder affects about 0.5% of the population, and may affect people of any age. (1) The symptoms, frequency, intensity, and types of seizures vary greatly from person to person. Those whose condition is controlled by medication may not experience seizures at all.

In many cases, the cause of epilepsy is unknown. (2) It can occur as a result of an infection, head injury, brain tumor, hydro-cephalus, toxic reaction to drugs and alcohol, or other conditions which injure the brain and damage brain cells. (3) , (4) Genetic factors may contribute to the development of a seizure disorder, but are not a primary cause. (5) It may also be associated with other neurological conditions such as cerebral palsy. The cause of the seizure correlates to some extent with the onset of age. In some people, seizures may be triggered by hormone changes such as pregnancy or menstruation. They may also be triggered by illness or by sensory stimuli such as lights, sounds, and touch. One study noted that free radicals may also be implicated in epilepsy. Plasma levels of vitamin A, vitamin C and vitamin E were normal in the control population as well as the patients with epilepsy who had been seizure free for one year. The status of these antioxidants in the blood of epileptic patients with active seizures was low compared to the control groups. (6) In many cases, no trigger is found for the seizures.

Some of the more common causes of seizures include: (7)

Idiopathic (no identifiable cause)

    Usually begin between ages 5 to 20 May occur at any age No other neurologic abnormalities present Often a family history of epilepsy or seizures
Congenital defects and perinatal injuries
    Seizures usually begin in infancy or early childhood
Metabolic abnormalities
    May affect any age Diabetes mellitus complications Electrolyte imbalances Kidney failure, uremia (toxic accumulation of wastes) Nutritional deficiencies Phenylketonuria (PKU)-can rarely cause seizures in infants Use of or intoxication from alcohol or drugs Alcohol withdrawal Drug withdrawal
Brain injury
    May affect any age, highest incidence in young adults; Most likely if the brain membranes are damaged; Seizures usually begin within 2 years after the injury Early seizures (within 2 weeks of injury)-do not necessarily indicate that chronic seizures will develop
Tumors and brain lesions that occupy space (i.e. hematomas)
    May affect any age, more common after age 30 Partial (focal) seizures most common initially May progress to generalized tonic-clonic seizures
Disorders affecting the blood vessels (stroke, TIA, etc…) Most common cause of seizures after age 60 Degenerative disorders (senile dementia of Alzheimer type, or similar organic brain syndromes)
    Mainly affecting elderly Infections May affect all ages May be a reversible cause of seizures Brain infections (meningitis, encephalitis) Brain abscess Acute severe infections of any part of the body Chronic infections (such as neurosyphilis) Complications of AIDS or other immune disorders

There may be changes in mental status (such as alertness and awareness) and/or focal neurologic symptoms (localized symptoms of changes in brain function) associated with the seizures. The type of seizure that occurs varies depending on the location and type of the problem causing the seizure and with individual response to the problem.

Seizures may occur in a generalized form (affecting all or most of the brain) or in a partial form. Epilepsy is typically generalized (except in some cases that develop in childhood and have a specific focus). Generalized seizures include variations of generalized tonic-clonic seizures and petit mal seizures. Partial seizures include focal seizures (during which the person remains alert but there are abnormal movements or sensations) and partial complex seizures (during which the abnormal movement or sensation is accompanied by changes in consciousness).

Statistic

National Institute of Neurological Disorders and Stroke, National Institute of Health, 1999.

    About 60 percent of people with epilepsy have partial seizures. 20 percent — about 600,000 people with epilepsy in the United States — have intractable seizures. 400,000 feel they get inadequate relief from available treatments. Approximately one in every 25 children will have at least one febrile seizure, and more than one-third of these children will have additional febrile seizures before they outgrow the tendency to have them. Febrile seizures usually occur in children between the ages of 6 months and 5 years and are particularly common in toddlers. Children rarely develop their first febrile seizure before the age of 6 months or after 3 years of age. The older a child is when the first febrile seizure occurs, the less likely that child is to have more. Between 95 and 98 percent of children who have experienced febrile seizures do not go on to develop epilepsy.

Signs and Symptoms

[span class=alert]The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.[/span]

Epilepsy is characterized by seizures of any type that occur on a chronic, recurrent basis and have no known cause. (8) Nonspecific symptoms and/or signs may occur along with the seizures; including headache, mood changes, changes in energy levels, dizziness, confusion, fainting, and memory loss. An aura, sensations indicating a seizure is imminent, occur in some persons just prior to a generalized seizure.

Types of seizures and their symptoms:

Petit mal seizures:
  • Minimal or no movements (usually, except for "eye blinking")
  • Sudden loss of awareness or conscious activity
  • Recurs many times
  • Occurs most often during childhood
  • Decreased learning
Grand mal seizures (Generalized tonic-clonic):
  • Generalized, violent muscle contractions
  • May affects a major portion of the body
  • Loss of consciousness
  • Breathing stops temporarily, then "sighing"
  • Urinary incontinence
  • Tongue or cheek biting
Single focal seizures:
  • Muscle contractions of a specific body part
  • Abnormal sensations
  • May have nausea, sweating, skin flushing and mydriasis
  • May have other focal (localized) symptoms
Partial complex seizures:
  • Automatism (automatic performance of complex behaviors)
  • Abnormal sensations
  • May have nausea, sweating, skin flushing, and dilated pupils
  • May have other focal (localized) symptoms
  • Recalled or inappropriate emotions
  • Changes in personality or alertness
  • May or may not lose consciousness
  • Olfactory (smell) or gustatory (taste) hallucinations or impairments (if temporal focus)
Status epilepticus:
  • More than 30 minutes of continuous seizure activity or two or more sequential seizures without full recovery of consciousness between seizures.
  • More common in the younger child with the average age of onset being less than 3 years of age
  • Divided into two general types: convulsive and nonconvulsive.

Treatment Options

Conventional

Treatment of epilepsy is aimed at controlling seizures as well as treating their underlying cause if it is known. Oral anticonvulsants prevent or minimize the number of future seizures. Response is individual, and the medication used and dosage may have to be adjusted repeatedly.

Types of seizures and the corresponding medications:

    Petit mal seizures usually respond best to valproic acid or ethosuximide. Clonazepam or other medications may also be used. Grand mal seizures usually respond best to phenytoin, carbamazepine, valproic acid, or phenobarbital. Primidone or other medications may also be used. Focal seizures or partial complex seizures usually respond to phenytoin or carbamazepine. The drug of choice in status epilepticus is lorazepam. (9) Other medications used as antiepileptic drugs (AEDs) include midazolam (VersedTM), clonazepam (ClonopinTM), lorazepan (diazepam) (ValiumTM), felbamate (FelbatolTM), and lamotrigine (LamictalTM). (10) Topiramate (TopamaxTM) is approved as adjunctive treatment in patients with partial-onset seizures; however, there is strong evidence that it has a wide spectrum of efficacy against partial and generalized seizure types. Tiagabine (GabitrilTM) is approved as an adjunctive treatment for partial-onset seizures. Gabapentin (NeurontinTM) is an antiepileptic drug used in the treatment of partial and generalized tonic-clonic seizures. Its antiepileptic mechanism of action is not known at this time. Gabapentin is transported across membranes and has demonstrated effects on voltage-gated ion channels (sodium, calcium), presynaptic mechanisms that can enhance GABAergic inhibition, and ligand-gated ion channels (GABA receptors and glutamate receptors). (11)

Several AEDs may become available in the near future. The list includes zonisamide (ZonegranTM), vigabatrin (SabrilTM), oxcarbazepine (TrileptalTM), and levetiracetam (KepraTM). All appear effective against partial-onset seizures. Zonisamide is reported effective against progressive myoclonus epilepsies, a group of difficult-to-treat symptomatic generalized epilepsies. Oxcarbazepine offers efficacy similar to carbamazepine but has less adverse effects and less interactions. Levetiracetam appears to have a wide spectrum of efficacy and an excellent pharmacokinetic and safety profile.

Once seizures are controlled, therapy should preferably be continued for at least 2 years. Withdrawal of AED therapy can be considered after 2 to 5 years of seizure freedom, depending on the risk of recurrence for the individual patient. Sixty to 75% of patients who are free of seizures for 2 to 4 years on will remain seizure free after AED withdrawal. Factors associated with a greater risk of seizure recurrence include remote symptomatic etiology, presence of a structural lesion, abnormal neurologic examination, abnormal EEG with epileptiform discharges or slow activity, and age at onset in adolescence. Patients with juvenile myoclonic epilepsy have a high seizure recurrence rate and should not be withdrawn from AED therapy. AED withdrawal should be very gradual over several weeks to months. Most recurrences will occur in the first 6 to 12 months after AED discontinuation.

Nutritional Supplementation


Vitamin D

The most commonly prescribed anti-seizure medications, including phenobarbital, phenytoin, and carbamazepine, inhibit the vitamin D metabolism. (12) , (13) In addition to depleting vitamin D levels, this also interferes with the body’s ability to absorb calcium. Interference with vitamin D and calcium metabolism may cause the development of skeletal problems such as rickets, osteomalacia, and osteoporosis. Although these patients are likely to be deficient in calcium, calcium supplementation is not warranted. The correct therapeutic intervention is to provide adequate levels of supplemental vitamin D, which will enable normalization of calcium absorption.


Folic Acid

A study involving 42 adult patients on carbamazepine (CBZ) and 42 healthy controls used the methionine loading test for better assessment of homocysteine metabolism. The results were folic acid metabolism was interfered with by primary anticonvulsant medications. (14) This could increase the risk of birth defects, cervical dysplasia, anemia, cardiovascular disease (from elevated homocysteine), depression, and breast and colorectal cancers. (15) , (16) , (17) , (18) Some studies suggest that the antiepileptic effects of phenytoin is due to its anti-folate action. For this reason, administration of folic acid to patients who are already stabilized on phenytoin therapy should be closely monitored. In some cases, the dosage of phenytoin will need to be increased in order to help prevent seizures. (19)


Magnesium

Prolonged magnesium deficiency can result in neurologic symptoms, including seizure, coma, and death. Neurological disturbances, including hyperexcitability, convulsions, and psychiatric disturbances can occur in individuals with severe magnesium deficiency and these problems can be corrected with appropriate magnesium supplementation. (20) Magnesium deficiency is seldom a cause of epilepsy but in rare cases, magnesium supplementation has been life-saving in patients who were suffering from acute intractable seizures due to magnesium deficiency. (21)

Compared to controls, patients with idiopathic epilepsy were documented to have a decline in serum magnesium during certain periods following seizure activity. The fall was substantially greater in status epilepticus and severe epilepsy compared to mild and moderate epilepsy. Serum magnesium returned to normal more quickly in mild and moderate epilepsy than in other types, indicating that serum magnesium levels have some prognostic value. Individuals who experience a smaller fall in the magnesium levels have less frequent convulsions and vice versa. Serum magnesium levels can be used as a sensitive early diagnostic index of idiopathic epilepsy. (22)

Magnesium compounds are useful in seizures associated with eclampsia during pregnancy. Magnesium sulfate is reportedly the drug of choice for the prevention of recurrent seizures in women with eclampsia, providing better results than either diazepam or phenytoin. Magnesium sulfate has multiple cardiovascular and neurological effects and also alters calcium metabolism. Magnesium sulfate therapy needs to be carefully monitored because there is some risk of toxicity at higher dosage levels. The most serious situation to guard against is a neuromuscular blockade that may result in respiratory arrest. Even though there are some risks, magnesium sulfate remains the drug choice for treating eclamptic patients. However, studies still need to be conducted to determine whether or not magnesium can function as a prophylactic agent in the prevention of eclampsia. (23)


Manganese

Research results determined that blood, and possibly hair manganese levels, were substantially lower in individuals with epilepsy compared to controls. Even though some patients did not exhibit reduced tissue manganese levels, patients with a higher frequency of seizures had the lowest manganese levels, suggesting that lower tissue manganese levels might be associated with higher seizure activity. One of manganese’s functions is to stabilize membrane excitability. Therefore, a deficiency of manganese may cause a destabilization in neurons that increases the likelihood of seizure activity in epileptic individuals. (24)

Another study correlated the fact that manganese levels of patients with epilepsy were significantly lower than the manganese levels in normal individuals. (25)


Taurine

Taurine is a neuroinhibitory amino acid whose role in the treatment of seizure disorders is still not totally clear. Apparently there are several genetic variations that determine how people metabolize taurine. An evaluation of plasma and urinary taurine was carried out in 41 epileptic and 68 control subjects. The plasma concentrations among patients with epilepsy were similar to those of normal controls. However, two or three levels of plasma taurine concentrations, which possibly denote different genetically regulated methods of metabolism, were found in both epileptic and control subjects. Also, three variations of genetically-controlled taurine excretion pathways have been reported. In general, a greater number of epileptic individuals are low excretors (high reabsorbers) of taurine.These findings may help explain why taurine is therapeutically beneficial in some epileptics but not in others. (26)

Taurine’s metabolic role in epilepsy is still not well understood. In a more recent study, it has been suggested that studies on cellular rather than plasma taurine levels may provide a better understanding of this agent’s role in epilepsy. (27) Another study, using newer technology, has reported that epileptic individuals are lower excretors of taurine, compared older studies reporting higher excretion. It is now understood that the equipment used in the older studies produced some contaminants, which resulted in the faulty high taurine excretion values. Because taurine can act as both a neurotransmitter and a modulator of neurotransmission, it is desirable to gain a clear understanding of the role it plays in epilepsy. (28)

Although studies have confirmed that taurine does provide some antiepileptic activity, it does not seem to possess major clinical significance because longer follow-up trials have only yielded moderate results. The fact that taurine does not easily cross the blood-brain barrier may limit the antiepileptic effect of this compound. (29)

However, taurine does effectively reduce seizures in some patients. In one small study, 9 patients were treated with taurine (100 mg/kgm/day) or placebo for two months. With taurine, one patient had nearly complete cessation of seizures, and 2 of 9 patients decreased seizure activity by about 50%. (30)

Herbal Supplementation


Vinpocetine

Vinpocetine is chemically related to, and derived from vincamine, an alkaloid found in the periwinkle plant. Vinpocetine was introduced into clinical practice in Europe more than two decades ago for the treatment of cerebrovascular disorders and related symptoms. (31) , (32) , (33) , (34)

Early experiments with vinpocetine indicated five main pharmacological and biochemical actions: (35) (1) selective enhancement of the brain circulation and oxygen utilization without significant alteration in parameters of systemic circulation, (2) increased tolerance of the brain toward hypoxia and ischemia, (3) anticonvulsant activity, (4) inhibitory effect on phosphodiesterase (PDE) enzyme and (5) improvement of rheological properties of the blood and inhibition of aggregation of thrombocytes. Evidence has been obtained that neuroprotective action vinpocetine is related to the inhibition of operation of voltage dependent neuronal Na(+)-channels, indirect inhibition of some molecular cascades initiated by the rise of intracellular Ca(2+)-levels and, to a lesser extent, inhibition of adenosine reuptake. (36) Vinpocetine has been shown to be selective inhibitor of Ca(2+)-calmodulin dependent cGMP-PDE. (37) It is assumed that this inhibition enhances intracellular a GMP levels in the vascular smooth muscle leading to reduced resistance of cerebral vessels and increase of cerebral flow. This effect might also beneficially contribute to the neuroprotective action. (38) , (39) The antioxidant effect of vinpocetine might contribute to the protective role exerted by the drug in reducing neuronal damage in pathological situations. (40)

Vinpoceptine has anticonvulsant action, possibly linked to its neuronal protective capacity and/or its modulation of several chemical transmitter systems. (41) , (42) In these respects vinpocetine resembles adenosine, thought to be a major endogenous anticonvulsant and cerebral protectant; Vinpocetine happens to be an effective adenosine re-uptake inhibitor. It increases cerebral metabolism and raises ATP levels in nerve cells, perhaps also raising neuronal excitability more directly by modulating cellular enzymatic control systems. (43) , (44)


Gymnema

The leaves of gymnema are thought to increase insulin secretion, and several studies report control of hyperglycemia in moderately diabetic laboratory animals. (45) , (46) A decrease in body weight was also reported. Gymnema reportedly produced blood glucose homeostasis and increased the activity of the enzymes involved in the utilization of glucose by insulin dependent pathways. (47)

Human studies have reported a significant reduction in blood glucose during therapy with gymnema. (48) , (49) A reduction in glycosylated hemoglobin and glycosylated plasma proteins has also been reported, with a reduction in conventional drug dosage. In studies patients with diabetes were able to discontinue conventional drugs and maintain their blood glucose homeostasis with gymnema alone. (50) Researchers suggest that beta cells may be regenerated and/or repaired in Type 2 diabetics on gymnema supplementation. (51) They support their claim by the appearance of increased endogenous insulin levels in the serum of individuals after gymnema supplementation. Other studies report that gymnemic acids suppress the elevation of blood glucose levels by inhibiting glucose uptake in the intestine. (52)

Acupuncture & Acupressure

30 cases of epilepsy were treated with acupuncture. The acupoints selected to receive treatment were: Cheng Jiang (Ren 24), Tan Zhong (Ren 17), Jiu Wei (Ren 15), Zhong Wan (Ren 12), Guan Yuan (Ren 4), Lie Que (L 7), and Zhao Hai (K 6). The manipulation used the reinforcing method after the initial needling sensation was obtained, and retained the needles for 30 minutes. 10 sessions comprised one course of treatment. A comparison group of 30 cases was treated with phenytoin sodium (0.1g a time, 3 times daily) and oryzanol. The results: after 2~3 courses of treatment, of the treatment group, 22 cases greatly improved, 7 cases improved, and 1 case did not respond to the treatment, with a total effective rate of 96.7; of the comparison group, the corresponding numbers were 14, 14, 2, and 93.3% (P

Traditional Chinese Medicine

Seizure Disorders

Extensive information regarding the treatment of this health condition using Traditional Chinese Medicine is available through the link above.

Diet & Lifestyle

A study reported in the October issue of Pediatrics, indicates that there may be a role for high fat diets in treatment protocols for children suffering from severe seizure disorders. Researchers from the Johns Hopkins Medical Center in Baltimore, followed 150 children diagnosed with seizure disorders, 83 of whom were considered in the "difficult to control" category. Children were placed on a Ketogenic diet, a diet that is extremely high in fat and low in carbohydrates, and were followed for three to six years.

At the conclusion of the study period, 107 families responded to report questionnaires initiated by Hopkins neurologists. Of the original patient group of 150, 20 were seizure free, and 21 had a 90% to 99% reduction in frequency of seizures. In regard to medication use, 29 were medication free and 28 had been successful in reducing their daily treatment to a single medication. Researchers state that the results of this study indicate that a Ketogenic diet is successful in controlling difficult to control seizures in children, is well tolerated and often allows a decrease or even discontinuation of medication. (53)

Clinical Lab Assessment

Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.

Chemistry Profile (Blood)

A multifactorial assessment of chemistry profile values can reveal useful information regarding concurrent disorders and possible nutrient imbalances. Acid-base balance (anion gap, calcium, CO2) and electrolyte levels (chloride, potassium, and sodium) would be important information in the assessment of seizure disorders.

Electroencephlogram (EEG)

EEG is most commonly ordered for the diagnosis of epilepsy and to detect other brain abnormalities. There are various abnormalities which can arise on an EEG, some are specific like the sharp waves seen in seizures and some are very non-specific and cannot always be used to clarify a diagnosis. Non specific EEG abnormalities are seen in a range of situations from people who are completely normal to liver disease, dementia, epileptics, coma, and brain tumors.

Electrolytes, Plasma, Serum, or Urine

Elevations in serum sodium precipitate seizures. These values are monitored especially when medications are being used. Edema precipitates seizures. Diuretics are often used. Many diuretics deplete potassium. Low serum potassium (with or without alkalosis) is indication for further renal function study.

Glucose

A decrease in serum glucose precipitates seizures. Blood glucose levels vary in response to food intake, stress, physical exertion, and various disorders. Elevations of serum glucose should lead to confirmatory testing such as fasting insulin, serum phosphorus, magnesium, hemoglobin A1c, and/or fructosamine.

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