Gerontologists urge vigilance in diagnosing increasing cases of seizures

excerpt, spotting a sezure
Seizures occur when electrical signals in the brain fire uncontrollably. Physicians don't know what causes most seizures. But some may be linked to brain injury from head trauma, perhaps from a sports injury or automobile accident; some to infections such as meningitis, AIDS and encephalitis; and some to genetics, as with an inherited form of juvenile epilepsy.

In the elderly, stroke, cardiovascular disease, brain tumors and Alzheimer's disease can cause seizures. In addition, the wear and tear of the "aging process may predispose people to seizures," said Rowan, and the damage caused by seizures may be greater because it takes longer for the elderly to bounce back from an attack.

Neurologists say proper diagnosis is challenging because seniors typically suffer from complex partial seizures. Unlike the severe convulsions of a grand mal seizure, complex partial seizures are characterized by symptoms as subtle as incoherence or odd arm, leg or mouth movements. Some may stagger or wander about aimlessly.

So how can a doctor, much less a relative or friend, tell whether these behaviors are signs of seizures? Rowan said that keeping a detailed record of such incidents may help determine if there's a pattern to the behavior that can indicate seizures, which often manifest themselves in similar ways. Also, electroencephalograms (EEGs) and magnetic resonance imaging (MRI) scans will often detect the residual brain scarring sometimes left behind from prior seizures.

Entire article here.
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This next one actually suggests a cause. The glutamate discussed, is what Namenda works on.

Excitotoxins

Glutamic acid (also called "glutamate") is the chief excitatory neurotransmitter in the human and mammalian brain (1-3). Glutamate neurons make up an extensive network throughout the cortex, hippocampus, striatum, thalamus, hypothalamus, cerebellum, and visual/auditory system (4). As a consequence, glutamate neurotransmission is essential for cognition, memory, movement, and sensation (especially taste, sight, hearing) (3). Glutamate and its biochemical "cousin," aspartic acid or aspartate, are the two most plentiful amino acids in the brain (5). Aspartate is also a major excitatory neurotransmitter and aspartate can activate neurons in place of glutamate (1,2).

Glutamate and aspartate can be synthesized by cells from each other, and glutamate can be made from various other amino acids, as well. (5) Glutamate and aspartate are both common in foods also. Wheat gluten is 43% glutamate, the milk protein casein is 23% glutamate, and gelatin protein is 12% glutamate. (5)

One of the commonest food additives in the developed world is MSG (monosodium glutamate), a flavor enhancer. By 1972 576 million pounds of MSG were added to foods yearly, and MSG use has doubled every decade since 1948 (2). Aspartic acid is one half of the now ubiquitous sweetener aspartame (NutraSweet®), which is the basis of diet desserts, low-calorie drinks, chewing gum, etc. (2,6) Thus, even a superficial look at glutamate/aspartate in brain chemistry, foods, and food additive technology indicates a major role for them in our lives. Without normal glutamate/aspartate neurotransmission, we would be deaf and blind mental and behavioral vegetables. Yet ironically glutamate and aspartate are the two major excitotoxins out of 70 so far discovered (1-3,6). Excitotoxins are biochemical substances (usually amino acids, amino acid analogs, or amino acid derivatives) that can react with specialized neuronal receptors - glutamate receptors - in the brain or spinal cord in such a way as to cause injury or death to a wide variety of neurons (1-3,8-10).

A broad range of chronic neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's chorea, stroke (multi-infarct) dementia, amyotrophic lateral sclerosis and AIDS dementia are now believed to be caused, at least in part, by the excitotoxic action of glutamate/aspartate (1-3,7-10). Even the typical memory loss, confusion, and mild intellectual deterioration that frequently occurs in late middle age/old age may be caused by glutamate/aspartate excitotoxity (2,6). Acute diseases and medical conditions such as stroke brain damage, ischemic (reduced blood flow) brain damage, alcohol withdrawal syndrome, headaches, prolonged epileptic seizures, hypoglycemic brain damage, head trauma brain damage, and hypoxic (low oxygen) /anoxic (no oxygen) brain damage (e.g. from carbon monoxide or cyanide poisoning, near-drowning, etc.) are also believed to be caused, at least in part, by glutamate/aspartate excitotoxicity (1-3, 7-11). Medical research is focusing more and more on ways to combat excitotoxicity. A drug called "memantine" (www.memantine.info)which blocks the main glutamate-excitotoxicity site in neurons - the NMDA glutamate receptor (more on this later) - has been used clinically in Germany with significant success in treating Alzheimer's disease since 1991. (12) Memantine's NMDA glutamate-receptor blocking action has also shown promise in Parkinson's disease, diabetic neuropathic pain, glaucoma, HIV dementia, alcohol dementia, and vascular (stroke or arteriosclerosis - caused dementia (12). (12). (12). (12).

Experimental NMDA - glutamate receptor blockers such as MK-801 (dizocilpine) have also demonstrated the ability to reduce or eliminate brain damage from acute conditions such as stroke, ischemia/hypoxia/anoxia, severe hypoglycemia, spinal cord injury and head trauma (1-3). Yet the few available clinical or experimental excitotoxicity-blocking drugs so far discovered have significant side effect potential - they may block normal, essential glutamate neurotransmission as well as excitotoxicity (1-3,12). Fortunately, a review of the basics of glutamate excitotoxicity reveals a host of preventative nutritional/life extension drug strategies that will minimize or even eliminate the excitotoxic "dark side" of glutamate/aspartate.

EXCITOTOXICITY 101
Glutamate and aspartate are neurotransmitters. Neurotransmitters are the chemicals that allow neurons to communicate with and influence each other. Neurotransmitters serve either to excite neurons into action, or to inhibit them. Neurotransmitters are stored inside neurons in packages called "vesicles." When an electric current "fires" across the surface of a neuron, it causes some of the vesicles to migrate to the synapses and release their neurotransmitter contents into the synaptic gap. The neurotransmitters then diffuse across the gap and "plug in" to receptors on the receiving neuron. When enough receptors are simultaneously activated by neurotransmitters, the neuron will either "fire" an electric current all over its surface membrane, if the, transmitter/receptors are excitatory, or else the neuron will be inhibited from electrically discharging, if the neurotransmitter/receptors are inhibitory. All the neural circuitry of our brains work through this interacting "'relay race" of neurotransmitters inducing electrical activation or inhibition.

Glutamate receptors are excitatory - they literally excite the neurons containing them into electrical and cellular activity. There are 4 main classes of glutamate receptors: the NMDA (N-methyl-D-aspartate) receptor, the quisqualate/AMPA receptor, the kainite receptor, and the AMPA metabotropic receptor. Each of these receptors has a different structure, and has somewhat different effects on the neurons they excite. The NMDA is the most common glutamate receptor in the brain (13). The NMDA, kainite and quisqualate receptors all serve to open ion channels. Looking at the NMDA receptor diagram, the NMDA receptor is the most complex, and had more diverse and potentially devastating effects on receiving neurons than the others. When glutamate or aspartate attaches to the NMDA receptor, it triggers a flow of sodium (Na) and calcium (Ca) ions into the neuron, and an outflow of potassium (K). It is this ion exchange that triggers the neuron to "fire" an electric current across its membrane surface, in turn triggering a neurotransmitter release to whatever other neurons the just-fired neuron synaptically contacts. The kainite and AMPA ion channels primarily permit the exchange of Na and K ions, and generally cause briefer and weaker electric currents than NMDA receptors. Thus, when glutamate/aspartate acts through kainite/AMPA receptors, it is weakly excitatory, but when glutamate/aspartate act through NMDA receptors, they are strongly excitatory. (14) NMDA receptor activation is the basis of long-term potentiation, which in turn is the basis for memory consolidation and long-term memory formation. (14)

Looking at the NMDA receptor diagram it shows that there are receptor sites for chemicals other than glutamate. The zinc site can be occupied by the zinc ion, and this will block the opening of the ion channel. The PCP site can be occupied by the drug PCP ("angel dust"), an animal tranquilizer; ketamine, an anesthetic; MK-801, an experimental NMDA antagonist; or the previously mentioned meantime. When the PCP is occupied, the opening of the ion channel is blocked, even when glutamate occupies its receptor site. (1-3) The mineral magnesium (Mg) can occupy a site near to, or perhaps identical with, the PCP site. Magnesium blocks the NMDA channel in a "voltage dependent manner." This means that as long as the neuron is able to maintain its normal resting electrical potential of -90 millivolts, the magnesium blocks the ion channel even with glutamate in its receptor.

However, if for any reason (e.g. not enough ATP energy to maintain the resting potential) the surface membrane electrical charge of the cell drops to -65 millivolts, allowing the neuron to fire, the magnesium block is overcome, and the channel opens, allowing the sodium and calcium to flood the neuron. (1-3) After the neuron has fired, membrane pumps then pump the excess sodium and calcium back outside the neuron. (15) This is ne

This message has been edited. Last edited by: ces,

Epilepsy
From MayoClinic.com
Special to CNN.com

Overview

Approximately 2 million people in the United States have epilepsy, a chronic disorder of the brain that causes a tendency to have recurrent seizures. Two or more seizures must occur before a person can receive the diagnosis of epilepsy, also known as a seizure disorder. It's not uncommon for children to have a single seizure, and an estimated 5 percent to 10 percent of the population will experience a seizure at some time in their life.

Seizures occur when there's a sudden change in the normal way your brain cells communicate through electrical signals. During a seizure, some brain cells send abnormal signals, which stop other cells from working properly. This abnormality may cause temporary changes in sensation, behavior, movement or consciousness.

The onset of epilepsy is most common during childhood and after age 65, but the condition can occur at any age. Treatments may be able to leave you free of seizures, or at least reduce their frequency and intensity.


Brain & Nervous System

Signs and symptoms

Because abnormal brain cell activity causes seizures, having a seizure can result in the sudden occurrence of any activity that's coordinated by your brain. This can include slight temporary confusion, complete loss of consciousness, a staring spell, muscle spasms, or uncontrollable, jerking movements of the arms and legs. Seizures originating in your brain's temporal lobe can be associated with a sense of deja vu, anxiety and panic, or simply an uneasy sensation in your stomach, which can be followed by loss of consciousness.

Signs and symptoms may vary depending on the type of seizure. Most people with epilepsy experience the same type of seizure, with similar symptoms, each time they have a seizure, but others may experience a wide range of types and symptoms.

Doctors classify seizures as either partial or generalized, based on how the abnormal brain activity begins. When seizures appear to result from abnormal activity in just one part of the brain, they're called partial seizures. When seizures seem to involve most or all of the brain, the seizures are called generalized.

Both classifications are broken up further into smaller, more specific categories:

Partial seizures are separated into simple partial, complex partial and secondary generalized seizures.
Primary generalized seizures are separated into absence (petit mal), myoclonic, atonic and generalized tonic-clonic (grand mal) seizures.
Partial seizures
Some people experience a warning sensation, called an aura, before one of the following types of partial seizure begins:

Simple partial seizures. These seizures begin from a small area in your brain and don't result in loss of consciousness. They may cause uncontrolled shaking of an arm, leg, or any other part of your body; alter emotions; change the way things look, smell, feel, taste, or sound; or cause speech disturbance.
Complex partial seizures. These seizures also begin from a small area of your brain. They alter consciousness and usually cause memory loss (amnesia). They can cause staring and nonpurposeful movements, such as repeated hand rubbing, lip smacking, posturing of your arm, vocalization or swallowing. After the seizure ends, you may be confused or sleep for a few minutes and may be unaware you had the seizure. Temporal lobe seizures are the most common type of complex partial seizures.
Secondary generalized seizures (partial seizures with secondary generalization). These seizures occur when simple or complex seizures spread to involve your entire brain. They may begin as a complex partial seizure with staring and nonpurposeful movements. The seizure then becomes more intense, leading to generalized convulsions characterized by stiffening and shaking of your extremities and your body.
Generalized seizures

Absence (petit mal seizures). These seizures are characterized by staring, subtle body movement and brief lapses of awareness. They're usually brief, and typically no confusion or sleepiness occurs when the seizure is over.
Myoclonic seizures. These seizures usually appear as sudden jerks of your arms and legs. They typically affect only one side of your body, but may affect both sides. Myoclonic seizures may last only a short time — from less than a second for single jerks to a few seconds for repeated jerks.
Atonic seizures. Also known as drop attacks, these seizures cause you to suddenly collapse or fall down. After a few seconds, you regain consciousness and are able to stand and walk.
Generalized tonic-clonic (grand mal seizures). The most intense of all types of seizures, these are characterized by a loss of consciousness, body stiffening and shaking, and sometimes tongue biting or loss of bladder control. After the shaking subsides, a period of confusion or sleepiness usually occurs, lasting for a few minutes to a few hours.


Temporal lobe seizure


Petit mal seizure


Grand mal seizure


Frontal lobe epilepsy

Causes

The onset of epilepsy can often be traced to an accident, disease or medical trauma — such as a stroke — that injures your brain or deprives it of oxygen, often causing a small scar in your brain. In rare occasions, epilepsy may be caused by a tumor in your brain. However, in many cases there's no identifiable cause for the disease.

Epilepsy isn't a mental disease, although mental health can influence the control of seizures in epilepsy. Epilepsy doesn't cause psychiatric problems or mental retardation, but people with epilepsy may also be afflicted with those conditions.



Traumatic brain injury

Risk factors

Research suggests that genetic abnormalities contribute significantly to epilepsy. If you have a family history of the disease, you may be at increased risk.

Head injuries are responsible for many cases of epilepsy. You can reduce your risk by always wearing a seat belt while riding in a car and by wearing a helmet while bicycling, skiing, riding a motorcycle, or engaging in other activities with a high risk of head injury.

Stroke and other diseases that affect your vascular system can lead to brain damage that may trigger epilepsy. You can take a number of steps to reduce your risk of these diseases, including limiting your intake of alcohol, following a healthy diet, managing your weight, exercising regularly and avoiding cigarettes.

Other epilepsy risk factors include:

Alzheimer's disease
Brain infections
Poisoning from exposure to lead, carbon monoxide and other toxins


This article contains many links. One of these links leads to a short page on AD that also contains many links that are AD specific.

Cathy

Seizures

http://www.alz.org/Resources/Advances/Spring2002.pdf
Scroll down to an article entitled: Are seizures common on AD? Why do they occur

http://www.ahaf.org/whatsnew/Ask_Alzheimers.htm#356
I cannot agree with my friend that Alzheimer's seizures are the same as epileptic seizures. Can you enlighten us on the subject? - LM

Epilepsy is a disease in which the patients suffer from so-called attacks or seizures. An epileptic seizure can best be described as a sudden storm in the brain. At later stages of Alzheimer’s disease (AD) epileptic type seizures can occur. About 10 percent to 15 percent of people with AD—who have no prior history of seizures—do develop seizures. They usually occur in the later stages of the disease. Alzheimer's causes abnormal electrical activity in the brain, which can result in a seizure. Seizures in A D are usually considered partial seizures because they affect only certain parts of the brain—not the whole brain.

Doctors are not sure why some people with Alzheimer's have seizures and others don't. No evidence indicates that people with epilepsy, a chronic seizure disorder, have an increased risk of AD.
(sorry, that's all from that site)

Cathy

MedGenMed Neurology & Neurosurgery
The Therapeutic Potential of Melatonin: A Review of the Science
Posted 04/13/2004

10 page article, 2 excerpts

Seizures
The pineal, acting primarily but not exclusively through melatonin, is proposed to be a "tranquilizing organ" that promotes homeostatic equilibrium.[7] Melatonin stabilizes the electrical activity of the central nervous system and causes rapid synchronization of the electroencephalogram.[9] By contrast, pinealectomy predisposes animals to seizures.[9] Recent evidence from experimental work suggests that melatonin provides anticonvulsant activity in various models of epilepsy. In mice, intracerebroventricular administration of melatonin protected against seizures induced by kainate, glutamate, and N-methyl-D-aspartate;[56] however, it was ineffective against pentylenetertrazol-induced seizures, thereby suggesting a potential role in grand mal epilepsy. Similarly, melatonin antagonized the seizure-producing effects of cyanide[57] and ferric chloride.[58] The anticonvulsant effect of melatonin has also been demonstrated in amygdala-kindled rats.[59]

Some of these experimental data have been corroborated by clinical studies in patients with epilepsy. Bazil and colleagues[60] found melatonin levels to be reduced in patients with intractable epilepsy. In a study of 6 children with intractable seizures, administration of 3 mg of oral melatonin 30 minutes before bedtime in addition to the antiepileptic regimen led to clinical improvement in seizure activity in 5 of the children, by parent report.[61] However, because of the paucity of well-controlled studies, melatonin cannot, as yet, be recommended in any form of epilepsy, although it may have some role as an adjuvant therapy for children with intractable seizures.

Summary
Melatonin is a ubiquitous natural neurotransmitter-like compound produced primarily by the pineal gland. This agent is involved in numerous aspects of the biological and physiologic regulation of body functions. The role of endogenous melatonin in circadian rhythm disturbances and sleep disorders is well established. Some studies have shown that melatonin may also be effective in breast cancer, fibrocystic breast diseases, and colon cancer. Melatonin has been shown to modify immunity, the stress response, and certain aspects of the aging process; some studies have demonstrated improvements in sleep disturbances and "sundowning" in patients with Alzheimer's disease. The antioxidant role of melatonin may be of potential use for conditions in which oxidative stress is involved in the pathophysiologic processes. The multiplicity of actions and variety of biological effects of melatonin suggest the potential for a range of clinical and wellness-enhancing uses. This review summarizes the physiology of melatonin and discusses the potential therapeutic uses of melatonin.

Melatonin is a widely occurring neurotransmitter-like compound derived primarily from the pineal gland. It is also produced in a number of other areas, for example the gastrointestinal tract.[1-3] Once labeled as a master hormone, it has been found to be involved in numerous aspects of biological and physiologic regulation.

Synthesis and Physiologic Role in Humans
Melatonin is an indole hormone, widely distributed in both plant and animal sources, such as human milk,[4] bananas, beets, cucumbers, and tomatoes.[5] Chemically, melatonin is N-acetyl-5-methoxytryptamine, a derivative of serotonin, which in turn is derived from tryptophan. Serotonin is first acetylated by N-acetyltransferase (probably the rate-limiting step) and then methylated by hydroxyindole orthomethyltransferase to form melatonin.[6] Melatonin synthesis depends on intact beta-adrenergic receptor function.[7] Norepinephrine activates the N-acetyltransferase and beta-receptor blockers depress melatonin secretion.[8]

The enzymes of melatonin synthesis are activated and depressed, respectively, by darkness and light. Release of melatonin follows a circadian (circa: about; dias: a day) rhythm generated by the suprachiasmatic nuclei in response to daylight alterations.

Through melatonin release, the pineal gland maintains the internal clock governing the natural rhythms of body function. This apparent clock-setting property of melatonin has led to the suggestion that it is a "chronobiotic" substance that alters and potentially normalizes biological rhythms and adjusts the timing of other critical processes and biomolecules (hormones, neurotransmitters, etc) that, in turn, exert numerous peripheral actions.[9]

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Pharmacologic Management of Epilepsy in the Elderly
from Journal of the American Pharmaceutical Association

excerpt
Epidemiology
The incidence of epilepsy, while high in early childhood, declines to a low, constant rate in adults, only to rise again in individuals over 55 years of age.[8,9 ]Several studies have shown a linear increase in the incidence of epilepsy for each decade after age 60.[8-10] Using the Rochester (Minnesota) Epidemiology Project database, for 1935 through 1984, Hauser et al.[8] reported that the incidence rates for epilepsy and unprovoked seizures were highest in patients older than 75 years (139/100,000 patients). The next highest incidence rate was found among infants less than 1 year of age (82/100,000 patients).[8] Similar incidence rates for epilepsy in the elderly have been reported in the United Kingdom[9] and in France.[10]
While the cause of epilepsy cannot be determined in 60% to 80% of children and adolescents, 50% of epilepsy cases in the elderly are attributable to a specific etiology.[11] More than 30% of new-onset epilepsy cases in the elderly may be attributed to cerebrovascular disease, including ischemic and hemorrhagic strokes.[10-12] Early seizures (i.e., those occurring in the first 1 to 2 weeks following stroke) occur in approximately 4% of patients and appear to be related to the severity of the initial stroke.[13 ]Overall, stroke patients have an 11.5% probability of experiencing one or more seizures within 5 years of their initial stroke. Furthermore, patients suffering hemorrhagic stroke are more likely to develop seizures than those suffering ischemic stroke.[14] Alzheimer's disease and non-Alzheimer's dementias have also been implicated in the development of seizures and epilepsy in the elderly.[15,16] An elderly patient's risk of an unprovoked seizure increases 6-fold with a diagnosis of Alzheimer's disease and 8-fold with a diagnosis of non-Alzheimer's dementia.[17] Other identifiable causes of seizures in the elderly include metabolic disturbances, brain tumor, CNS infections, head injury, brain abscess, and alcohol withdrawal.[8,10,11,17,18]

Recent studies have uncovered age-dependent trends in specific seizure types. New-onset generalized epilepsy has been observed in an age-dependent, bimodal pattern with peaks of incidence in both children and the elderly. In contrast, the incidence of partial (localization-related) epilepsy, which includes both simple-partial and complex-partial seizures, remains constant throughout childhood and peaks only in later years.[8,11] Consciousness may be impaired during complex-partial seizures, whereas normal awareness may be preserved during simple-partial seizures. Although the incidences of both generalized and partial epilepsy increase in the elderly, partial epilepsy is more common, with half of new-onset seizures occurring after age 65 classified as complex-partial.[11] The predominance of partial seizures in the elderly is indicative of the increased occurrence of brain lesions and insults (e.g., CNS tumors and cerebrovascular disease). In contrast, patients with Alzheimer's disease can be affected by either generalized or partial-onset seizures, although generalized seizures are more common.[15,16]

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Epidemiology and Drug Treatment of Epilepsy in Elderly People
Faught E.
Drugs Aging 1999 Oct;15(4):255-269
Seizures are extremely common in the elderly, with an annual incidence reaching 100 per 100,000 people aged over 60 years. Most are precipitated by acute symptomatic illnesses such as stroke or systemic disease. Chronic neurological diseases such as Alzheimer's disease may also cause seizures. The aetiology of seizures in many patients is unknown. Seizures may be situational and subside quickly, but the prevalence of chronic seizures--epilepsy--is as high as 1% in the elderly. The majority of seizures are of partial onset, especially complex partial. Complex partial seizures at this age may be very subtle and hard to diagnose. Generalised-onset seizures also occur, perhaps as a result of diffuse changes with aging or degenerative disease or to a combination of genetic and environmental factors. The prognosis for complete seizure control in this population is relatively favourable. Physiological and disease-related changes with aging result in complex pharmacokinetics. Most changes lead to a need for gentler drug treatment with cautious initiation of drugs at lower dosages. Consideration must be given to renal and hepatic function, protein binding and drug interactions. Determinations of free (unbound) drug concentrations are helpful for highly protein bound drugs. The dosages of newer drugs excreted renally must be adjusted based on creatinine clearance. The dosage of most drugs is determined empirically by careful observation of seizure control and adverse effects. Carbamazepine, valproic acid (sodium valproate), gabapentin and lamotrigine have certain theoretical advantages, but comparative trials of anticonvulsants in the elderly are needed. The ideal drug for older patients would be effective, without neurological toxicity, with low protein binding, a nonparticipant in drug interactions and amenable to once daily administration.

Last abstract on the page.
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Epilepsy Diagnosis Often Delayed in Elderly

Three interesting points in this article:

The condition frequently occurred in elderly patients due to underlying atherosclerosis, he told Medscape in an interview. And symptoms can be subtle, such as a clouded sensorium, confusion, or just "tuning out." In some cases, he said, patients were misdiagnosed with Alzheimer's disease.

Only one in five (20.9%) of the 86 patients with complex partial seizures received a correct diagnosis initially.

Among 29 patients with simple partial seizures, a diagnostic delay of close to three months was common.

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Cathy