Natural Ways to Treat Panic Attack

Panic Away Program

Psychologists agree that when a person has anxiety of a certain situation, he may suffer from a panic attack. This person then fears that specific location or event. When he find himself in a similar situation, he fears the onset of an attack and essentially cause himself to have an anxiety attack in the process. The One Move method teaches you how to conquer these fears and end this vicious cycle. The author is a natural at keeping the readers engaged presenting the information in a simple to follow format. He adequately explains himself when he uses a slightly difficult term in his eBook. His technique is unraveled in a natural and logical progression making best use of real life stories to drive home his important points. Once you study the one move technique, you will able to foresee the panic attacks symptoms and conquer it before the panic attack strikes you. It is proven program that worked for many satisfied people worldwide. The book provides real-life situations that are specific: when you suffer from the panic attacks and anxiety in a car, school or home. Read more...

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Benzodiazepine Receptors And Membrane Excitability

In the 1970s use of radioactively labeled benzodiazepine derivatives allowed the detection of specific nanomolar benzodiazepine receptor sites in brain membrane (15-17). These sites have a very high affinity for the benzodiaz-epines, binding in low (nanomolar) concentration ranges. Binding to these receptors is reversible, saturable, and stereospecific. Nanomolar benzodiazepine receptors have now been identified in human brain, where they are widely distributed. The specific membrane protein that accounts for the majority of nanomolar benzodiaz-epine binding has a molecular weight of approximately 50,000 daltons and has been purified from animal and human brain (18). High-affinity benzodiazepine binding has also been observed in peripheral, nonneuronal tissue (19). A different class of benzodiazepine receptor molecules causes this binding, because both the potency and the tissue distribution of this binding are different from that at the central-type receptor. This second class of...

Hyperventilation Syncope

Hyperventilation in any human induces various organic symptoms which may in certain individuals stimulate further hyperventilation and exacerbation of the original symptoms. A degree of panic may be so engendered. Hyperventilation in the clinic may reproduce the concerning symptoms. Hyperventilation may trigger both epileptic and nonepileptic absences.18 Individuals with Rett syndrome may have hyperventilation, apnea, complex behavioral stereotypies, and epileptic seizures, which may lead to diagnostic and therapeutic difficulties.

Depression and anxiety

Conventional mood disorders are encountered in many patients with epilepsy, and these include anxiety, depression, dysthymia and panic disorders. Intermittent affective-somatoform symptoms are frequently present in chronic epilepsy and include irritability, depressive moods, anergia, insomnia, atypical pains, anxiety, phobic fears and euphoric moods. Some are present continually but others show marked variation in relation to seizure activity. Prodromal and peri-ictal dysphoria are common. Both depression and anxiety in epilepsy respond to conventional antidepressant drugs. Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) are routinely given. Fluoxetine is a widely prescribed drug, although it is a powerful CYP3A4 inhibitor and can interact with carbamazepine and other antiepileptics. Other SSRIs commonly used in patients with epilepsy include paroxe-tine and citalopram. Paroxetine does not interact with common antiepileptic drugs. Citalopram may be...

Experimental models of anxiety

In a fMRI activation study in normal volunteers it has been demonstrated that the amygdala is involved in conditioning and extinction of fear responses in a fashion similar to that previously observed in experimental animals (LaBar et al., 1998). There is evidence from studies in normal volunteers that abnormal patterns of limbic activity may result in symptoms resembling both features of temporal lobe complex partial seizures and features of panic attacks. In one study, intravenous injections of procaine resulted in a range of subjective experiences including emotional, somatic and visceral experiences often similar to those experienced in the auras of temporal lobe epilepsy as well as resulting in the development of panic attacks in four out of ten subjects. These experiences also included euphoria, anxiety, depression, fear and derealization. Positron emission tomography (PET) scanning of the subjects during this experiment revealed that all these experiences, described as...

Epidemiology Of Depression And Anxiety In Epilepsy

Like depression, symptoms of anxiety can be exacerbated by seizure activity (peri-ictal, ictal, postictal) and can appear separately or, in other words, interic-tally. Historically, anxiety and epilepsy have been viewed as highly interconnected. Temkin (1971) documented that even in the 1800s it was believed fright could cause epilepsy. Also similar to depression, methodological issues exist when determining the prevalence and incidence of anxiety disorders. Throughout the literature, hospital- or community-based samples are utilized, making it difficult to make generalizations across studies uniform methods are frequently not used to assess or measure symptoms of anxiety (symptom checklist vs. interviews), and control groups are frequently omitted (Scicutella, 2001). In light of these limitations, rates for anxiety disorders are reportedly elevated among individuals with epilepsy and range from 5 to 25 (see Table 7.2). A brief summary of three of these studies follows. Silberman et...

Depression And Anxiety In Epilepsy What Do We Know

Several recent population-based studies have reported elevated symptoms of depression and anxiety among adults and children with epilepsy (Davies et al. 2003 Strine et al. 2005 Tellez-Zenteno et al. 2005 Kobau et al. 2006). However, in the epilepsy literature the co-occurrence of depression and anxiety has received limited attention. Depression and anxiety disorders are frequently reported in over arching categories (e.g., internalizing disorder, neurosis) with no ability to distinguish the individual prevalence rates of each disorder (Jacoby et al. 1996 Davies et al. 2003 Strine et al. 2003), or depression and anxiety are reported as distinct disorders with no acknowledgement of co-occurrence (Ring et al. 1998 Glosser et al. 2000) . Recently, in the 2004 HealthStyles Survey, a large population-based mail survey, Kobau et al. (2006) found 16.7 (OR 3.2 95 CI 1.4-7.4) of individuals with active epilepsy reported both depression and anxiety during the past year. In a multicenter study,...

Common Symptomatology In Depression And Anxiety

Depression and anxiety disorders have overlapping symptomatology. As defined by the DSM-IV-TR (American Psychiatric Association, 2000), major depression and generalized anxiety disorder share four diagnostic symptoms, which include sleep disturbance, difficulty concentrating, restlessness and fatigue. In the DSM-III all anxiety disorders (i.e., social phobia, panic disorder, etc.) were required to occur independently of and symptoms were to be present separate from a depressive episode. However, in the DSM-IIIR (American Psychiatric Association, 1987) this hierarchy was eliminated for all anxiety disorders except generalized anxiety disorder (Zimmerman and Chelminski, 2003). The diagnostic criteria for generalized anxiety disorder states that criteria must be reached independently and outside the presence of a depressive disorder, and this exception is likely related to the fact that both disorders have overlapping symptoms (Zimmermann and Chelminski, 2003 DSM-IV-TR, 2000)....

Interictal Anxiety Disorders

As stated above, anxiety disorders are a common co-morbidity in PWE. Panic disorder (PD) and generalized anxiety disorder (GAD) are the most frequent types of anxiety disorders identified in PWE 1 . The DSM-IV classification of anxiety disorders lists six other types agoraphobia without panic disorder, obsessive compulsive disorder (OCD), social phobia, specific phobia, post-traumatic stress disorder and acute stress disorder. These may also be identified in PWE, but with a much lower frequency. In addition, PWE may often exhibit symptoms of anxiety that fail to meet any DSM-IV diagnostic criteria for a categorical anxiety disorder. As stated above, PD and GAD are commonly associated with depressive disorders and their presence conveys an increased suicidal risk. Thus, when the primary complaint is that of an anxiety disorder, clinicians must carefully investigate the presence of depressive symptoms or episodes. GAD consists of constant uncontrollable worry on a daily basis of at...

Pharmacotherapy Of Anxiety Disorders In

Whether or not the anxiety disorders' response to pharmacotherapy differs between patients with and without epilepsy is yet to be established. To date, the pharmacological treatment of anxiety disorders in PWE is based on the same principles followed in the management of primary anxiety disorders and thus remains empirical. Pharmacological treatment of anxiety disorders depends on the specific type of disorder. Four classes of drugs are typically used (i) anti-depressant drugs (ii) benzodiazepines (iii) AEDs and (iv) buspirone. In the next section, we will discuss the use of these drugs in the treatment of GAD, PD, social phobia and OCD. As shown in Table 15.2, several of the SSRIs have shown efficacy in GAD and PD all SSRIs have also shown efficacy in OCD, but in contrast to the treatment of GAD and PD, a therapeutic effect may not be noticed for 6-12 weeks. However, a cautionary note is in order patients with PD may be extremely sensitive to adverse events of psychotropic drugs....

Common Pathogenic Mechanisms In Depression Anxiety And Epilepsy

There are common pathogenic mechanisms shared by depression, anxiety, and epilepsy. Serotonin (5HT), NE, dopamine, GABA, and glutamate are likely involved in the expression of all three disorders (Jobe et al., 1999 , Ressler and Nemeroff 2000). In depression and anxiety, changes in the noradrenergic and serotoner-gic systems are implicated as playing a significant role in the expression of these disorders. There appears to be increased noradrenergic activity, contrasting with decreased activity in the serotonergic systems. Pharmacological treatments attempt to modulate this activity. Depending on which medication is introduced, there is a combination of increased or decreased release of the serotonin or NE along with an increase or decrease in receptor activity (Stahl, 1997 ) Ressler and Nemeroff, 2000). It is suggested that selective serotonin reuptake inhibitors (SSRIs) reduce noradrenergic transmission and increase serotonergic transmission (Ressler and Nemeroff, 2000) . If there...

Neuroanatomic Imaging Studies In Depression And Anxiety

In anxiety, fMRI studies revealed increased activation in the amygdala (Rauch et al, 2000) . Studies using emission tomography blood flow showed increased glucose metabolism in the orbitofrontal cortex, anterior cingulate cortex, caudate nucleus, and thalamus in obsessive compulsive disorder (Rauch et al, 2001). Utilizing PET and SPECT in neurochemical studies, it has been demonstrated there is a decrease in benzodiazepine receptors throughout the brain, particularly in the hippocampus and precuneus in those with a panic disorder or generalized anxiety disorder (Malizia et al, 1998). Additionally, magnetic resonance spectroscopy (MRS) studies have revealed decreased GABA levels in panic disorder (Goddard et al., 2001). There is evidence of brain changes occurring in the circuit in both anxiety and depression. These structures include frontal cortex, hippocampus, thalamus, amygdala, putamen, caudate, and basal ganglia (Sheline, 2003) . A complete correspondence between structural...

Precautions needed with parenteral benzodiazepines

Although benzodiazepines are the drugs of first choice for emergency therapy, they do carry a risk of respiratory depression, hypotension and cardio-respiratory collapse. In a well-controlled study in anaesthetic practice, for example, diazepam 10 mg was given intravenously to 15 patients and resulted in a drop in blood pressure of 10 mmHg or more in eight patients, a mean 28 decrease in ventilation, and a 23 decrease in tidal volume. The effects on cardiorespiratory function are as great (or even greater) with midazolam or lorazepam. In the occasional patient, the cardio-respiratory effects can be extremely severe, and for this reason it is essential that no patient given parenteral benzodiazepine should be left unattended. After parenteral benzodiazepine administration (buccally, intra-nasally, rectally, IM or IV) pulse, respiration, blood pressure, and (where possible) oxygen saturation should be frequently monitored, until the patient has recovered full consciousness....

Pharmacologic And Psychotherapeutic Treatments For Depression And Anxiety

Has a chronic condition and is depressed there was a poorer prognosis and even increased morbidity and mortality than from the medical diagnosis alone. Additively, co-occurring depression and anxiety is related to poorer prognosis, increased suicide risk, decreased treatment response, and increased functional impairments (Brown et al.) 1996) Sherbourne and Wells., 1997 ) Regier et al.) 1998) Kessler et al.) 1999a) Kessler et al.) 2005a, b) . Generalized anxiety disorder and major depression have been demonstrated to negatively impact quality of life more so than depression alone (Mittal et al.) 2006). Treatment of depression and anxiety will improve quality of life, reduce suicidality, and decrease functional impairments. Leaving depression and anxiety untreated only leads to poorer outcomes and prognosis. In the epilepsy literature, a large knowledge gap exists in understanding the efficacy of pharmacologic and psychological treatments for both depression and anxiety. Notably, Kanner...

Affective disorders and anxiety

Symptoms of anxiety are very common in epilepsy patients, but their classification covers many problems of differentiation between fear of seizures, fear as a symptom of seizures, avoidant behaviours due to stigmatization, fear as a symptom of depression, and others. Accordingly, preoperative estimations of anxiety disorders in candidates for surgery vary between 10 (Manchanda et al., 1996) and 44 (Bladin, 1992). More than 2 years after surgery Koch-Weser et al. (1988) even found higher rates of anxiety than before surgery. Ring et al. (1998) reported a frequency of 42 of early postoperative symptoms of anxiety which had already diminished after 3 months. In the early weeks after surgery, an exact differentiation between the woven symptoms of irritability, anxiety, and mood fluctuation is not easy and might even be impossible. This time period deserves to be better evaluated from the psychopathological perspective.

Anxiety And Depression In The General Population

The general psychiatric literature provides additional insight and findings related to the discussion of depression, anxiety and the co-occurrence of the two disorders. As clinicians and researchers in epilepsy, we can utilize the knowledge gleaned from the general population about depression and anxiety in order to gain an understanding of the similarities and differences in the presentation of these disorders in epilepsy. Based on the National Comorbidity Survey-Replication in the United States, lifetime prevalence rates for depressive disorders is 20.8 with major depression being the most prevalent (16.6 ), and lifetime anxiety disorders identified in 28.8 with specific phobia (12.5 ) and social phobia (12.1 ) as the most commonly occurring anxiety disorders (Kessler et al., 2005a, b). Additionally, the European Study of the Epidemiology of Mental Disorders (ESEMeD) project included representative samples from six European countries (Belgium, France, Germany, Italy, The...


The benzodiazepines are widely used as antiepileptic drugs, as well as for anxiolytic, hypnotic and antispastic indications. The main role in epilepsy for diazepam, lorazepam and midazolam is as acute therapy for status epilepticus, acute seizures and in febrile convulsions, and this is covered on pp. 211-13, 218-21. In chronic epilepsy, in addition to clobazam (pp. 123-6) and clonazepam (pp. 127-9), three other benzodiazepines diazepam, clorazepate and nitrazepam still have a minor role. The benzodiazepines all bind to the GABA-A receptors and exert their antiepileptic action by enhancing inhibitory neurotransmission. Differences between the drugs relate to their differential binding at the receptor and their pharma-cokinetic properties. The similarities between the drugs are greater than the differences (Figure 3.12).


Clonazepam is an alternative to diazepam in stage of early status epilepticus, and there is little to choose between the two drugs. It has a similar onset of action, and a longer duration of action (half-life, 22-33 hours), and may have a lower incidence of late relapse. There is wide experience with the drug in adults and children, although not in neonates, and the drug has proven efficacy in tonic-clonic, partial, and absence status. Clonazepam accumulates on prolonged infusion, with the resulting risk of respiratory arrest, hypotension and sedation a side-effect profile very similar to that of diazepam (see below). The drug has a negative inotropic action, and as with diazepam thrombophlebitis may occur. There is also a danger of sudden collapse if the recommended rate of injection is exceeded. A continuous infusion of clonazepam is not now recommended because of the dangers of accumulation, and respiratory and cardiovascular collapse.


Nitrazepam is a benzodiazepine derivative with a nitro group at the 7 position of the benzodiazepine ring. Oral bioavailability is about 78 . Peak concentrations are reached in about 1.5 hours. Nitrazepam is 85-88 protein bound. The volume of distribution is 2.4 l kg, and is higher in the elderly. The plasma half-life is about 27 hours, but the drug is rapidly taken up into the CSF and brain tissue and the CSF elimination half-life is 68 hours. Nitrazepam is metabolized in the liver by nitro-reduction to the Like most benzodiazepines, nitrazepam can produce sedation, disorientation, sleep disturbance, nightmares, confusion, drowsiness and ataxia. Hypotonia, weakness, hypersalivation, drooling, and impaired swallowing and aspiration seem to particularly common with nitrazepam, particularly in young children. Confusion and pseudodementia can occur in the elderly. Withdrawal symptoms include delirium, mood and behavioural change, insomnia, involuntary movements, paraesthesia and...

Panic Attacks

A growing sensation of anxiety, fear of something vague, tachycardia, and effortful breathing that occurs during panic attacks may lead to loss of consciousness. In these episodes, some patients may have a parasympathetic syncope and others may hyperventilate and faint. Irrespective of the final mechanism, panic attacks are always associated with an initial sensation of anxiety. As with most neuropsychiatric conditions, panic attacks result from an interaction of genetic predisposition with environmental determinants of anxiety states.


The lifetime prevalence of anxiety disorder in the general population in large epidemiological studies ranges from 1.9 to 5.1 (Weissman and Merikangas, 1986 Wittchen et al. 1994 Hunt et al. 2002 Wittchen, 2002 Wober-Bingol et al. 2004 Lieb et al. 2005). The prevalence of anxiety disorders in people with epilepsy in general population studies using ICD and DSM-IV case ascertainment ranges from 11 to 15 . Gaitatzis et al. (2004b) obtained a point prevalence of 11.1 in the National Practice Study, using ICD coded data. Tellez-Zenteno et al. (2005) reported a lifetime prevalence of 12.8 in a Canadian general population study using structured psychiatric interviews (Composite International Diagnostic Interview (CIDI)). Edeh reported a point prevalence of 15 in a register of patients with epilepsy from general practitioners in the United Kingdom. Strine et al. (2005) reported a point prevalence of 14.4 from a health survey where anxiety was ascertained with the Kessler 6 scale. On the other...

Panic disorder

In both the ICD-10 and DSM-IV diagnostic classifications PD is considered as an anxiety disorder. Although these classificatory systems do not represent the last word in mechanistic understanding of behavioural disorders, it is clear from the inclusion of PD within the anxiety disorder neurotic disorder grouping that the general view is that PD has a psychological rather than a biological aetiology. However, whilst it is clear that the core subjective experience of PD is one of extreme fear, this does not in itself prove that the disorder is simply an extreme end of a continuum that starts with mild anxiety. Panic attacks may (in common with epileptic seizures) be described as paroxysmal events. They are discrete periods of intense fear or emotional discomfort, accompanied by a range of somatic symptoms including palpitations, trembling, a feeling of shortness of breath (which may be associated with hyperventilation), sweating, feelings of choking and psychological symptoms including...

Anxiety Disorders

Anxiety, phobias, and fear are common associations with the diagnosis of epilepsy, paroxysmal fear or anxiety being the most commonly reported aura (30 ) in temporal lobe epilepsy (TLE). Because anxiety is a normal emotion and some anticipatory anxiety may be expected in people with a paroxysmal disorder that is not completely controlled, attention is not always given to anxiety disorders in the clinic setting. A disorder requires that impairment of social, occupational, and other areas of functioning occurs as a result of the anxiety.9 Generalized anxiety disorders, panic disorder, phobias, and obsessive-compulsive disorder are conditions that exist in the general population, but may be amplified in people who also have epilepsy, particularly seizures arising from the temporal lobe.11 A comparison of patients with partial epilepsy (106 with TLE and 44 with frontal lobe epilepsy), idiopathic generalized epilepsy (70 patients), and controls demonstrated that there was a significant...

Treatment and outcome

The most effective treatment has been a combination of valproate (35 mg kg per day), clonazepam (0.25 mg kg per day) and benzhexol (3 mg kg per day). Piracetam (up to a maximum dose of 600 mg kg per day) was very effective in controlling this patient's non-epileptic myoclonus when he was 7-9 years of age. Lamotrigine was thought to have exacerbated his epileptic and non-epileptic myoclonus.

Typical absence seizures petit mal seizures

Absences may be precipitated by fatigue, drowsiness, relaxation, photic stimulation or hyperventilation. Typical absence seizures develop in childhood or adolescence and are encountered almost exclusively in the syndrome of idiopathic generalized epilepsy (see pp. 17-19). Variations from this typical form include the myoclonic absence, absence with perioral myoclonia or with eyelid myoclonia. Whether or not these are distinct entities is controversial (see pp. 17-18). The EEG during a typical absence has a very striking pattern. A regular, symmetric and synchronous 3 Hz spike-wave paroxysm is the classic form, although in longer attacks and in older patients the paroxysms may not be entirely regular and frequencies vary between 2 and 4 Hz. The inter-ictal EEG has normal background activity and there may be intermittent short-lived bursts of spike-wave. These spike-wave paroxysms can frequently be induced by hyperventilation and less commonly by photic stimulation.

Biochemistry and Molecular Biology

The ionic (chloride) environment inside the neurons is GABA-mediated tonic inhibition (81). It has been demonstrated that the spillover of GABA outside the synaptic cleft acts on extrasynaptic GABAA receptors. Addition of bicuculline would block these receptors as well as the chloride currents they control. This tonic inhibition, which may be age-specific, presets excitability of the neuronal plasma membrane and modulates the gain of the transmission (82). These extrasynaptic receptors exhibit a high affinity for GABA (hence low ambient concentrations of GABA are sufficient), and do not inactivate rapidly, thus producing a tonic form of inhibition (83). Unlike the syn-aptic (phasic) receptors, they do not bind benzodiazepines (84, 85). Recent studies indicate that during this excitatory GABA developmental period, tonic and phasic GABA activation in immature neurons may play a critical role in their synaptic integration, which is activity dependent. This process takes place in both the...

Who Has A Psychiatric Disorder

This is difficult to apply to large populations, and it is more often used in studies of selected populations. A commonly used method, attractive for its simplicity, relies on self-reported symptoms (Kobau et al.) 2006) obtained through validated screening questionnaires, for example the Beck Depression Inventory (Grabowska-Grzyb et al.) 2006) , the Hospital Anxiety and Depression Scale (HADS) (Mensah et al., 2006) and others (Strine et al., 2005) . These methods are less accurate, often overestimate the prevalence of psychiatric conditions, and should be explicitly considered as measures of symptom endorsement only. Not all psychiatric symptoms necessarily represent psychiatric disorders. The concept of a disorder requires symptoms to be present, but also imposes additional requirements such as persistence, and associated distress and dysfunction. Some studies have used non-standardized interviews to identify psychiatric disorders. This lack of...

Pharmacokinetic properties of the antiepileptic drugs

Renal elimination Gabapentin Pregabalin Vigabatrin Metabolic elimination Carbamazepine Clobazam Clonazepam Diazepam Lamotrigine Lorazepam Phenytoin Tiagabine Valproic acid Metabolic and renal elimination Ethosuximide Felbamate Levetiracetam Oxcarbazepine Phenobarbital Topiramate Zonisamide

Seizures in Male Rats

Muscimol GABAa receptor agonist on both low- and high-affinity receptors. Bicuculline GABAa receptor antagonist on low-affinity receptors. ZAPA GABAa receptor agonist on low-affinity receptors. Zolpidem agonist of benzodiazepine I binding site of GABAa receptor. 7-vinyl GABA irreversible inhibitor of the GABA degradation enzyme, GABA-transaminase. Based on data in (165, 166, 169, 170).

What did I learn from this case

A number of features demonstrated in this case were not helpful in distinguishing non-epileptic seizure from EPC. For example, the arrhythmic movements did not prove their functional nature, since EPC movements are often arrhythmic.2 The failure to demonstrate episodes during sleep does not exclude EPC since it can diminish or stop during sleep.2 A previous psychiatric history was also not helpful since psychiatric disturbances, including depression23-26 and anxiety,27,28 are common in epilepsy.29 Finally, the failure of these episodes to respond to antiepileptic drugs did not exclude EPC, since the response to antiepileptic drugs, including intravenous benzodiazepines, is often poor in EPC.2

General Prevalence Of Psychiatric Disorders

and anxiety anxiety PE, patients with epilepsy PWE, patients without epilepsy GP, general practitioners PBS, population-based study NCOE, non-controlled, only patients with epilepsy NS, not stated NE, not examined. aPoint prevalence bPrevalence during a follow-up of 35 years cLifetime prevalence d12-month prevalence eCombined anxiety and depression symptoms.

Attention Deficit Hyperactivity Disorder ADHD

The inattention and vacant look seen in any child, particularly in children with ADHD, can be misinterpreted as absence seizures. However, absence seizures are almost always characterized by brief episodes of disconnection with sudden onset and termination, usually occurring many times a day. In contrast, the distractability associated with ADHD depends on whether the child is motivated by ongoing activities. Hyperventilation should precipitate an absence attack and make the diagnosis obvious.

Medications and the diet

Common reason for starting the ketogenic diet following seizure reduction is medication reduction . Although our center (John M . Freeman Pediatric Epilepsy Center at the Johns Hopkins Hospital) generally discourages making two changes at once by immediately reducing medications, evidence would suggest it is safe to do so if parents request and physicians believe it is prudent Phenobarbital and clonazepam have been associated with a slightly higher risk of increased seizures during their withdrawal in children on the diet

Investigation of Blackouts

Therefore an EEG must only be interpreted in the correct clinical context a full description of the attacks is essential to the EEG reporter. A routine baseline, interictal EEG lasts 20-30 minutes and involves recording during wakefulness (including a period of hyperventilation and of photic stimulation). Video recording of the procedure is helpful, because it provides a visual record of any events. Recording soon after the last seizure can increase the EEG yield further, as can repeating the awake recording, recording during sleep following prior sleep deprivation, or making more prolonged recordings over days.

Current Possibilities

The greater availability of models of healthy neuronal systems will also benefit research into the underlying causes of neurological diseases. As models become more biologically realistic, have been open to scrutiny by a wide range of neuroscientists and have been shown in a wider range of scenarios to reproduce aspects of cellular behavior, their usefulness for exploratory research increases. This is the hallmark of a good model that it can make experimentally testable predictions, which are not directly linked to the underlying assumptions used when building the model. For example, the effects on a normally behaving cell of deletion of a channel can be quickly checked by copying and altering the cell model in neuroConstruct and comparing the new cell behavior to experimental data from the cell in the presence of the appropriate blocker. This cell can be switched into the network model and the effect on the overall behavior examined. Also, changes in the network topology, e.g....

Current Limitations And Future Directions

NeuroConstruct can be used to study the effect of pharmacological interventions on network behavior if the effect of a drug on single cell behavior is well characterized phenomenologically, such as the effect of benzodiazepines on GABAa receptor physiology. Such effects can be implemented in a network model by using a phenomenological approach, for example by representing the effect of benzodiazepines as slowed decay of GABAA receptor-mediated synaptic conductances, possibly with an increase in their peak amplitude. However, the mechanistic effect of drugs on the receptor kinetics is currently beyond the scope of neuroConstruct. Moreover, it is not yet possible to model the multitude of complex intracellular processes affecting cytoplasmic calcium dynamics, such as calcium induced calcium release or calcium and buffer diffusion in the presence of obstacles like endoplasmic reticulum (ER) cisternae or mitochondria. In the future, the integration of detailed biochemical models will be...

Drugs Effective against Seizures at All Ages

Carbamazepine as well as AEDs that enhance GABAA-mediated inhibition, such as phenobarbital and ben-zodiazepines (i.e., clonazepam and midazolam) are approximately equipotent in both young and adult rats in several seizure models (316, 321-324). However, in PN12 rats in pentylenetetrazol-induced seizures, phenobarbital and carbamazepine can suppress tonic-clonic seizures and at the same time increase the incidence of clonic seizures (322, 323). This suggests that these drugs may have differential effects on various seizure types within a single model. Acute administration of phenobarbital prior to kainic acid inhibits clonic seizures in both PN12 and adult rats (321). However, chronic daily administration of phenobarbital after the kainic acid challenge may have more detrimental effects on memory, learning, and activity level than kainic acid-induced seizures per se (325).

Organic acidurias and aminoacidurias

Lactic acidosis is present in blood and urine in Leigh's syndrome. This is usually due to X-linked or autosomal recessive nuclear gene mutations of one of the mitochon-drial respiratory chain complex I or IV enzymes or pyruvate dehydrogenase (X-linked PDHA1 gene). About 30 are due to mutations in mitochondrial DNA, which have been identified in at least 11 mitochondrial genes. The diagnostic features are a subacute encephalopathy, seizures (myoclonic or tonic-clonic), and progressive dementia with cerebellar and brainstem signs. Motor abnormalities include hypotonia, spasticity, ataxia, involuntary movements and bulbar problems. Vomiting, hyperventilation and abnormalities of thermoregulation are common. Optic atrophy, pigmentary retinopathy, deafness and cardiomyopathy are sometimes present. On imaging, basal ganglia lucencies are highly characteristic, and proton magnetic resonance spectro

Classification of Epilepsy Syndromes

Evaluation General medical and neurologic examinations were normal. Two EEGs during wakefulness and sleep showed normal background activity and sharp waves over the centrotemporal regions, which increased markedly during sleep. Photic stimulation was not available at the EEG lab, and the boy did not cooperate with voluntary hyperventilation. A CT scan was normal, and the parents were informed that an MRI was needed despite the fact that they would need to pay for the exam. The latter was also normal. Treatment Oxcarbamazepine was slowly discontinued, and ethosuximide begun, up to a dosage of 750 mg day. Outcome Seizures were completely controlled, although interictal centrotemporal sharp waves persisted on the EEG. Comment This boy had a form of idiopathic generalized epilepsy, most likely juvenile absence epilepsy. A combination of facts led to misdiagnosis of both the epileptic seizures and the epileptic syndrome, and therefore, to inadequate seizure control and increased costs of...

Surgical Risk Complications And Benefits

Potential surgical complications include infection, cerebral haemorrhage, subdural haematoma and neurological deficits. There is also evidence that epilepsy surgery can precipitate psychiatric disturbances and worsen anxiety and depression in some patients 77 . However, other contradictory findings have documented a post-operative improvement in depression, suggesting that more research in this area is needed 42 . One large literature review was performed by the Quality Standards Subcommittee of the American Academy of Neurology in 2003 77 , and assessed the overall outcome of epilepsy surgery. Surgical complications were tallied in a total of 556 patients from seven centres. A total of 6 of patients experienced neurological deficits (3 transient and 3 permanent) 77 . Postoperative infections were documented in 5 of patients, and hydrocephalus was described in three cases of large resections. A separate series of three papers which included 219 patients discussed post-operative...

The GABAChloride Channel Complex Regulates Seizure Discharge

The chloride channel is surrounded by a GABA receptor, a nanomolar central benzodiazepine receptor, and a receptor site that binds picrotoxin and related con-vulsants as well as barbiturates and related depressants. This channel and its properties, related to the benzodi-azepines, GABA, and convulsant and barbiturate molecules, have been characterized in detail (26). Picrotoxin binds to the proposed site and modulates benzodiaz-epine and GABA receptor binding in a way that inhibits chloride channel permeability, therefore making the cell more excitable. Barbiturate binding potentiates benzodi-azepine receptor binding and thus indirectly potentiates the GABA effect on opening the chloride channel and enhancing neuronal inhibition. This complex interaction between GABA, benzodiazepines, picrotoxin and related convulsants, and the barbiturates and related depressants is a prime example of how pharmacologic agents modulate the function of ion channels through specific receptor binding....

Utility Of Cns Cell Cultures As A Model To Help Understand The Pathophysiology Of Epilepsy And The Mechanisms Of Action

From both biochemical (e.g., receptor binding) studies on processed brain tissue and from studies at the cellular level in cell culture, the GABAa receptor was recognized as a GABA receptor complex (GRC). Studies utilizing cell cultures first described the allosteric modulation of the GRC by benzodiazepines (Choi et al., 1977), a group of drugs used extensively to treat status epilepticus and other forms of seizures but whose mechanism of action had been unknown. Similar studies demonstrated that barbiturates, another class of antiepileptic drug, could allosterically modulate the GRC at a different site (Macdonald and Barker, 1977, 1978 Macdonald and McLean, 1982). Further, unlike the benzo-diazepines, barbiturates at high concentrations could directly activate the GRC. Studies of membrane patches removed from cultured neurons also demonstrated how these drugs worked at the single channel level (Macdonald et al., 1988). Other work focused on a number of new AEDs that were developed...

Calcium Channels and Neuronal Excitability

In conceptualizing the role of calcium in neuronal excitability and anticonvulsant drug action, one must consider both voltage-regulated and excitatory amino acid-modulated calcium channels. The regulation of calcium channels, like the regulation of the chloride channel, by the benzodiazepines, barbiturates, and convulsant drugs may play an important role in modifying neuronal excitability.

Mechanisms of Action of Antiepileptic Drugs

Several of our more commonly employed AEDs work as allosteric modulators of the GABA receptor complex (GRC), mechanisms first elucidated by studies of cell cultures. Benzodiazepines enhance the affinity of GABA at the receptor and allow enhanced channel openings (Macdonald et al., 1986) barbiturates prolong channel openings and can produce channel openings even in the absence of GABA (Macdonald et al., 1988). Topirimate also appears to enhance GABA-mediated inhibition (White et al., 1997, 2000).

Circuit Behavior and Ictogenesis Do Cell Cultures Exhibit Seizurelike Phenomena

DeLorenzo's group has carried out a number of experiments to support their view that this model simulates focal epileptogenesis, dependent on aberrant activation of NMDA receptors. They showed that blockade of the NMDA receptors during the low-Mg treatment of these cultures prevents the development of hyperexcitability (as evidenced by SREDs) (DeLorenzo et al., 1998). Prolonged direct activation of the NMDA receptors, using the physiologic agonist glutamate instead of low magnesium, resulted in a similar long-term hyperexcitability and disruption of calcium homeostasis, likely through alteration in calcium calmodulin kinase II activity (Sun et al., 2001). These alterations in calcium homeostasis may also lead to increased GABAA receptor endocytosis or altered GABAA receptor composition. Low-magnesium-treated cells exhibit a lower current density for a given concentration of GABA and show a lower sensitivity to the benzodiazepine, clonazepam. Blocking clathrin-mediated endocytosis in...

Treatment after diagnosis

There is no consensus on the treatment for benign familial neonatal seizures No currently approved medications have been studied for this condition Phenobarbital, 20 mg kg loading dose, followed by 3-10 mg kg day daily dosing, would be considered first line A level between 20 and 40 mcg mL should be targeted If frequent seizures occur and do not respond to the phenobarbital, benzodiazepines or phe-nytoin should be used The question of whether or not BFNS should be treated has been raised Because the diagnosis is often uncertain until the child has outgrown the syndrome and developed normally, our view is that treatment to stop recurrent seizures is warranted

Conclusions And Implications For Therapeutics

Although the first identification of a channel gene mutation in epilepsy occurred only in 1994, many such mutations have now been identified in 15 different channel subunits and channel-associated proteins. What do these efforts reveal about the causes of epilepsy and potential for novel treatments One remarkable result is that many of the mutations have been found in subunits of voltage-dependent Na+ channels and GABA receptors, important targets of the majority of currently approved drugs, all developed through in vivo pharmacologic screening. Many (but not all) Na+ channel mutations in GEFS + , for example, result in increased Na+ channel activity by contrast, such drugs as phenytoin, carbamazepine, and lamotrigine act by blocking Na+ channel activity. Similarly, in autosomal dominant JME and some cases of GEFS + , mutations in GABA receptor subunits that reduce activity are implicated, whereas benzodiazepines and barbiturates potentiate GABA receptor activity. This is satisfying,...

Social and psychological aspects of aggression in epilepsy

For example, we were able to demonstrate a close link between episodic dyscon-trol, reduced IQ, depression and anxiety. Even though disentangling the complex interaction between these different psychobiological elements is very difficult, it nevertheless may suggest a possible way of treatment, irrespective of which of these elements is the most important one from an aetiological point of view.

Emergent Or Urgent Evaluation Of A Child With A First Unprovoked Seizure

Anxiety following a child's first unprovoked seizure often leads to extensive diagnostic testing in the emergency department, even if the child has returned to baseline. Usually, few diagnostic tests are needed following a first unprovoked seizure. A practice parameter from the American Academy of Neurology and the Child Neurology Society addresses these situations 2 . In the emergency department, a toxicology screen is reasonable. Measuring electrolytes and glucose levels is not required if the seizure has stopped and the child has returned to baseline and is not dehydrated. Except in selected cases, neuroimaging is not helpful in the emergency department 3, 4 . A hospital-based study in Boston made the following recommendations, based on 500 children presenting to the emergency department with a first-time seizure emergent imaging with head computed tomography (CT) scan should be undertaken in children with a known bleeding or clotting disorder, a known history of malignancy, human...

Treatment Of Symptomatic Generalized Epilepsy Lennox Gastaut Syndrome LGS

Other AEDs often used in treatment of LGS, without data from controlled trials, include VPA, vigabatrin (VGB), ZNS, PB, benzodiazepines and adrenocorticotropic hormone (ACTH) or prednisolone. Additional options include the ketogenic diet, vagus nerve stimulator or corpus callosotomy.

Startleinduced epilepsy

Or shows rather non-specific changes. A susceptibility to startle is more common in late childhood and adolescence and may resolve as the patient get older. The most common stimulus is a loud noise, but touch, sudden movement or fright can also precipitate attacks. Startle-induced epilepsy must be differentiated from hyperekplexia, which has a very similar clinical form, but which is not a form of epilepsy. Treatment can be difficult although carbamazepine and the benzodiazepine drugs have been said at an anecdotal level to be most likely to control the attacks.

Examination And Investigations

The seizures remained very active for 2 weeks despite clonazepam followed by intravenous phenytoin, together with high doses of oral antiepileptic drugs in combination (valproate, phenytoin, vigabatrin, and clonazepam). Over the next 2 weeks the seizures disappeared, as shown by EEG monitoring. A brain MRI at day 11 of admission showed a swollen and T2-hypertintense left amygdalo-hippocampal complex with an unchanged right hippocampus (Figure 28.1). Despite the resolution of the status epilepticus, the amnestic and behavioral symptoms regressed slightly and partially during the 2 months of hospitalization. A series of brain MRIs showed at day 42 of arrival, decreased swelling on the left side 3 months later, disappearance of swelling and evolution into a notable hippocampal atrophy on the left side and an increase of right hip-pocampal atrophy (Figure 28.2). The latest MRI (November 1998) confirmed bilateral hippocampal atrophy.

Psychosocial morbidity of epilepsy

The diagnosis of epilepsy also carries psychosocial morbidity. In all large studies, a high proportion of patients with epilepsy had difficulty accepting the diagnosis, significant fears about the risks of future seizures, anxiety about the effect of stigma and the effects on employment, self-esteem, relationships, schooling and leisure activities. Patients with epilepsy carry higher rates of anxiety and depression, social isolation and unmarried status, and are more likely to be unemployed or registered as permanently sick (these aspects are covered in subsequent sections). The psychosocial morbidity of epilepsy can be greatly ameliorated if seizures are brought under control.

Psychological Treatment Of Epilepsy

Anxiety or stress may precipitate seizures, possibly through hyperventilation.149 Treatments aimed at reducing anxiety may reduce seizure frequency150 154 and are free of significant side effects. Psychological symptoms associated with epilepsy may merit treatment in their own right.155

Cognitive sideeffects

All AEDs have the potential for causing cognitive impairment, and some have been identified more often than others 29, 30 . Ascertaining that a certain drug is actually causing cognitive problems in a given child may at times be easy because of an obvious temporal relationship with the introduction of the drug, but it is more often quite difficult. The reason is that cognitive impairment is common in children with epilepsy. Those with treatment-resistant epilepsy are particularly vulnerable because they are more likely to take a greater number of drugs for longer periods of time. The causes are multiple and they include the underlying brain pathology, the epilepsy itself, ongoing electrographic epileptiform activity and psychosocial problems, in addition to drug effect. Therefore, it may at times be virtually impossible to separate the various causes of the cognitive problems that a patient is experiencing at a given time, and the literature on this issue is often ambiguous or...

Evidence For Thalamic Participation In Seizures

The two main thalamic cell types involved in generating oscillations are the thalamocortical (TC) cells, also called relay cells, and the inhibitory neurons of the thalamic reticular (RE) nucleus. In some area of the thalamus and in some species, RE cells provide the sole source of inhibition to relay cells. The connections from RE to TC cells contain both GABAa and GABAb receptors, and there is evidence that GABAb receptors are critical to generate hypersynchronized oscillations. In particular, clonazepam, a known anti-absence drug (GABAa antagonist), was shown indirectly to diminish GABAb-mediated inhibitory postsynaptic potentials (IPSPs) in TC cells, reducing their tendency to burst in synchrony (Huguenard and Prince, 1994a Gibbs et al., 1996). The action of clonazepam appears to reinforce GABAa receptors within the RE nucleus (Huguenard and Prince, 1994a Hosford et al., 1997). Indeed, there is a diminished frequency of seizures following reinforcement of GABAa receptors in the RE...

Diagnostic approach

Opinions regarding efficacious medications vary, and no single agent stands out Treatment with valproic acid along with a benzodiazepine is commonly initially advocated Stiripentol, vigabatrin, and topiramate have demonstrated some efficacy in limited trials or reports . Some authors prefer clonazepam to clobazam . Newer trials with much older agents such as potassium bromide have shown promise against convulsive episodes Other drugs such as carbamazepine and lamotrigine can aggravate seizures The ketogenic diet may help some patients Immunomodulation with

Choice of drug for typical absence seizures

Typical absence seizures ('petit mal' seizures) occur only in the syndrome of idiopathic generalized epilepsy. The traditional first-line treatment is with either ethosux-imide or valproate. For many years ethosuximide has been standard drug therapy and it is highly effective and in general well tolerated. However, it is relatively ineffective in controlling generalized tonic-clonic seizures, which often co-exist with absence seizures, and has a number of troublesome adverse effects (p. 131). It has therefore been largely superseded by valproate as first-line therapy in drug-naive patients. However, it still has a role, particularly in children where there is anxiety about the idiosyncratic effects of valproate. Valproate or ethosuximide can be expected to fully control absence seizures in over 90 of patients on initial therapy. Dosage should be titrated against response. In patients in whom valproate is inappropriate, alternatives include phenobarbital and the benzodiazepine drugs....

Management Of Status Epilepticus

Recommendations for treatment are based on two large prospective, randomised trials of the management of status epilepticus173,174 and on small or uncontrolled studies, physiological principles and pharmacokinetic considerations.167,175-180 Intravenous lorazepam and diazepam are both effective and safe in controlling tonic-clonic status epilepticus, when administered by paramedics, prior to transport to hospital, with a trend in favour of lorazepam.173 Intravenous lorazepam, phenobarbital and diazepam plus phenytoin are all effective initial treatments on hospital admission, with a trend again in favour of lorazepam, which is significantly more effective than phenytoin alone.174 Lorazepam has the advantage over diazepam of a much longer duration of action, but its use in the community is limited by the need for refrigerated storage. There should be a high level of awareness of the risk of respiratory depression. Additional maintenance treatment is required following initial use of...

Case presentation

A developmentally normal, 30-month-old boy began having gelastic (i e , associated with mirth) seizures at the age of four months His past history was significant only for a Nissen fundoplication, which may have been performed for presumptive gastroesophageal reflux disease (GERD) or, more likely, gelastic seizures mistaken for GERD The seizures were stereotyped and characterized by sucking and laughing Often, the patient would ask for a drink during the seizure and would drink ferociously if not restrained At times, the patient would also become violent The seizures were brief and averaged 30 seconds in duration (range 10-90 seconds) with only occasional, minimal postictal lethargy He was subsequently diagnosed with a hypothalamic ham-artoma (HH) on brain MRI scanning Seizure frequency had been variable initially, but gradually evolved to an average of every 5 minutes, constituting status gelasticus . The seizures would persist through sleep and awaken the patient throughout the...

Subsequent Seizures Seizure Exacerbations in Established Epilepsy

Prescription of an oral benzodiazepine such as clobazam after the second seizure of the cluster can be helpful. If the person always has clusters of seizures, then the oral benzodiazepine may be given after the first seizure (of the anticipated cluster). If giving a single dose is not effective, it may be worth considering giving the oral benzodiazepine over the expected period of the cluster. This reduces the number of seizures in at least some people. In others it appears only to delay the cluster. In this context it is worth mentioning that some females have seizure exacerbations around the time of their menstrual period.7,8 If this pattern is well established, giving an oral benzodiazepine such as clobazam for a few days at the right time in the menstrual cycle may greatly decrease the number of seizures or may even eliminate them altogether.

Activation Procedures

Activation procedures, hyperventilation, intermittent photic stimulation and sleep enhance the epileptiform abnormalities and also help to identify seizure precipitating factors. Absence seizures have a special tendency to get precipitated during hyperventilation. The photoparoxysmal response, defined as the occurrence of generalized spike, spike-wave or polyspike wave discharges consistently elicited by intermittent photic stimulation,49 has a high correlation with primary generalized epilepsy.13,50 A proportion of patients with photosensitivity may exhibit a similar EEG response to geometric patterns.13,50 There are some racial differences in the reported prevalence of photoparoxysmal response. In White subjects with epilepsy it varied between 4 to 6 .49-51 A lower prevalence was reported in the African and Asian population with epilepsy, 0.4 to 1.6 .52-54 However, in a recent study from south India, the prevalence was similar to the studies among Whites, 3.5 .55 The wide variations...

Pharmacological treatment

Another significant milestone in AED development was the introduction of phenytoin, the first non-sedating AED, in the 1930s as a result of systematic screening of compounds using novel animal models. A number of other AEDs have become available in the ensuing years, including carbamazepine, ethosuximide, primidone, valproic acid and some benzodiazepines. These agents are generally regarded as old or established AEDs. After a hiatus of nearly 20 years, there has been accelerated development of newer AEDs, with 10 compounds having been licensed globally since the late 1980s. These are in chronological order, vigabatrin, zonisamide, oxcarbazepine, lamotrigine, felbamate, gabapentin, topiramate, tiagabine, levetiracetam and pregabalin. Although none of the modern AEDs has demonstrated superior efficacy to the established agents, they may be the preferred option for some patients as they are generally better tolerated and produce fewer drug inter

What Possible Strategies Exist For The Improvement Of Psychiatric Care For Patients With Refractory Epilepsy

At each level of the spectrum of training there are possible improvements that could focus treatment on both abolishing seizures and treating the comorbidities that would facilitate the best overall health. At the resident level, clearly more didactic sessions, interdisciplinary interactions at conferences and in clinics and more exposure to the outpatient management of mood disorders, anxiety, psychosis and ADHD would be helpful in the training of a neurologist. Specifically, more emphasis on the frontal lobe-related and affective portions of the mental status examination would be helpful, and neurobehavioral rounds in an outpatient or inpatient setting can serve to better integrate the disciplines (Matthews et al., 1998) . The current moment seems an excellent time to develop a curriculum for our residents in psychiatry the residents just starting mandatory rotations and their psychiatry mentors seem ideally positioned to comment on what that experience should entail. What rotations...

Treatment of Convulsive Status Epilepticus

Convulsive status epilepticus may be defined as a tonic-clonic (or clonic) seizure lasting longer than 20 minutes or repeated tonic-clonic (or clonic) seizures without recovery of consciousness. The term convulsive status epilepticus has now become quite widely adopted. However, I am of the opinion that this terminology has serious shortcomings because it is too narrow. If a patient continues to convulse for 20 minutes or longer, this is clearly a medical emergency, but if a patient is unconscious as a result of seizure activity of any type, for 20 minutes or longer, this constitutes a medical emergency. Rarely, tonic status epilepticus may occur with no clonic phase. I have seen this in one of my patients the condition failed to respond to intravenous benzodiazepines, but it eventually responded to intravenous clormethiazole with a rapid return to consciousness. Some patients also seem to have prolonged atonic states in association with seizures. Whether these are ictal or postictal...

Emergency Treatment of Status Epilepticus in Hospital

The principles underlying the in-hospital treatment of status epilepticus in people with or without ID are no different. However, as already discussed, status epilepticus appears to be more common and more difficult to treat in people with ID. It is worth repeating the point that has already been made about the importance of treating promptly, not only because it decreases the probability of brain damage but also because the status epilepticus seems to be much more responsive to treatment if the latter is given early. Prompt treatment can avoid the more difficult-to-treat established status epilepticus. If prompt out-of-hospital treatment is given by the parent or caregiver, hospital treatment may be avoided altogether. However, if treatment in the emergency room, general ward, or intensive care unit is required, there are well-established protocols that can be followed.19,35-37 These generally recommend that if treatment with full doses of a benzodiazepine such as diazepam,...

Major malformations associated with antiepileptic drugs

The most common major malformations associated with traditional antiepileptic drug therapy (phenytoin, phenobarbital, primidone, benzodiazepine, valproate, carbama-zepine) are cleft palate and cleft lip, cardiac malformations, neural-tube defects, hypospadias and skeletal abnormalities. Unfortunately, because most studies have been of women on multiple drug therapy, the risks of individual drugs are not fully established. It is not clear whether or not the benzodiazepines have any teratogenic potential, although there are case reports of facial clefts, and cardiac and skeletal abnormalities.

Treatment strategy

Treatment with conventional seizure medications may reduce seizures initially, but will seldom produce complete remission as the disease progresses Those medications that are usually used for myoclonic seizures generally are more efficacious valproic acid, lamotrigine, zonisamide, levetiracetam, and benzodiazepines However, medication efficacy tends to be patient specific, and no prospective studies have been performed In a small study of five patients with mitochondrial disease due to respiratory chain dysfunction, vagus nerve stimulation did not produce reduction in myoclonic seizure frequency This suggests that placement of the vagus nerve stimulator device be undertaken with caution

Paradoxical Worsening of Seizures

In some instances a patient's seizure control may deteriorate on treatment. There may be a number of reasons for this. An irregular intake of medication in patients who have difficulty with the particular preparation, forget medication, or who are reluctant to comply with therapy may precipitate withdrawal seizures. Alternatively, an individual who has taken too much medication and becomes toxic may also present with seizures. Tolerance is associated with a number of anticonvulsants, in particular benzodiazepines, resulting in a progressive increase in frequency and severity of seizures. In other cases, the side effects of a drug can have direct consequences on seizure frequency. For example, increased somnolence may lead to an increase in seizure activity in a patient who experiences sleep-related seizures.

Sexual Dysfunction In Women With Epilepsy

Women with epilepsy reported inadequate orgasmic satisfaction significantly more than controls in a report by Duncan et al. in their study of 195 women with epilepsy from a hospital-based clinic 86 . In another study of self-reported sexual functioning and sexual arousability in 116 women with epilepsy, anorgasmia was also reported by one-third of 17 women with primary generalized epilepsy and 18 of 99 women with localization-related epilepsy. Compared with historical controls, this group of women did not have reduced sexual experience, but reported less sexual arousability and more sexual anxiety 87 .

Disorders of sexual function

Hyposexuality has been long recognized as a feature of epilepsy in both men and women. Between 30 and 60 of men with epilepsy have reported lack of desire and impotence, and in one study 21 of men with chronic epilepsy had not experienced sexual intercourse. Among women, self reports of dyspareunia, vaginismus and arousal insufficiency are common, and also dissatisfaction with sexual experience. There are a number of potential mechanisms. Clearly the psychosocial difficulties encountered by people with epilepsy could play a part, including stigmatization, lack of self-esteem, restricted life styles, parental over-protection, and depression and anxiety. Biological changes including altered levels of sex hormones (especially free levels) are found in epilepsy, owing to the seizures and to the drug therapy these too could contribute to sexual difficulties. Seizures involving limbic structures too might be expected to alter sexual behaviour, and there is evidence (albeit inconclusive)...

Acute psychotic or depressive states induced by antiepileptic drugs

Many of the drugs can also cause mild psychiatric symptoms, particularly feelings of depression, anxiety or irritation. Levetiracetam seems particularly to cause irritability and dysphoria (a 'short fuse') in a small number of patients, and vigabatrin and tiagabine can cause significant agitation. Barbiturate and benzodiazepine drugs can also cause agitation

General Description Of Model

Generalized absence seizures are defined as a paroxysmal loss of consciousness of abrupt and sudden onset and offset that is associated with bursts of bilaterally synchronous three cycles per second or 3 Hz spike-wave discharge (SWD) recorded on the electroencephalogram (EEG). There is no aura or postictal state. This particular type of seizure usually occurs in children between the ages of 4 years and adolescence, although they can occur at either ends of that age spectrum (Snead, 1995 Snead et al., 1999). Generalized absence seizures are pharmacologically unique, responding only to ethosuximide, trimethadione, valproic acid, or benzodiazepines and being resistant to or worsened by phenytoin, barbiturates, or carbamazepine (Snead et al., 1999) (Table 1).

Psychiatric disturbance and personality change after epilepsy surgery

Epilepsy surgery carries a risk of precipitating psychiatric disturbance. The most common problems are mood swings, anxiety and depression. These are seen in 20-30 of people who undergo surgery for epilepsy. Although distressing, these are generally mild and remit within weeks or months, although some people may need antidepressant medication or counselling. More severe psychiatric breakdown may also occur. In a recent study of subjects who had undergone epilepsy surgery in London, about 10 of patients undergoing temporal lobectomy suffered a depressive or psychotic episode after surgery of a severity that required hospitalization, and many more needed consultation and treatment. Compounding these problems is the fact that no pre-operative risk-factors have been identified that reliably predict postoperative psychiatric disturbance. The lack of pre-operative psychopathology does not seem to protect against postoperative anxiety or depression. There is also no clear relationship...

Pediatric Epileptic Syndromes

EEGs are rarely normal in untreated children with childhood absence epilepsy (formerly referred to as petit mal epilepsy), and hyperventilation is particularly effective in provoking the characteristic EEG abnormality. In fact, repeated normal EEGs in a child with lapse attacks argue strongly against a diagnosis of childhood absence epilepsy. Each absence seizure is accompanied by generalized, symmetric, stereotyped 3- to 4-Hz spike-wave activity (Figure 12-7A). Background activity is otherwise normal or near normal. Sleep produces striking effects on appearance of the epileptiform activity (Figure 12-7B). Classic features are lost, and instead epileptiform bursts are fragmented, are of shorter duration, and contain more single spikes and multiple spikes.

Epilepsy in Pregnancy

The physiological changes that occur during pregnancy result in altered distribution and elimination of AEDs. This may interfere with seizure control, particularly in women who were already poorly controlled before conception. Increased plasma estrogens, water and sodium retention, vomiting, poor compliance with AEDs, anxiety, and sleep irregularities are some of the factors that may affect seizure frequency during pregnancy. Sexually active women who do not wish to become pregnant should know that many enzyme-inducing AEDs (carbamazepine, oxcarbazepine, phenytoin, primidone, and phenobarbital) can decrease the efficacy of oral contraceptives taken by women with epilepsy. This problem can partially be overcome by taking a contraceptive pill with higher estrogen content. Barrier methods are particularly useful adjuncts to oral contraception. Benzodiazepines, gabapentin, lam-otrigine, levetiracetam, tiagabine, and val-proate do not influence the efficacy of oral contraceptives.

Absence Seizures In An Adult

General and neurological examinations were normal. The patient appeared to be of above-average intelligence. An EEG demonstrated hyperventilation-induced three-per-second spike-wave discharges with a generalized distribution and a bifrontal voltage maximum. One of these discharges lasted 14 seconds and was

Dissociation as an alteration in consciousness

A second usage of the dissociation concept refers to an altered state of consciousness characterized specifically by a disengagement from the self or the environment (Cardena, 1994). As Cardena has pointed out, this sense of the dissociation concept should not be applied to everyday phenomena, such as daydreaming and other states of distraction, where engagement with the environment is less than complete. Rather, it should be reserved specifically for states that are regarded by the experiencing individual as qualitatively different to their normal state of awareness. Although a number of different phenomena fall within the bounds of this definition (e.g. 'trance' and 'possession' states), probably the most commonly reported are depersonalization and derealization. In depersonalization, the individual experiences a profound feeling of detachment from their thoughts, perceptions, actions and emotions, often characterized by a sense of numbness or disembodiment. In derealization, the...

Dissociation as a defence mechanism

Finally, dissociation has been described as a defence mechanism that protects the individual from potentially overwhelming pain or anxiety. In many respects, this account of dissociation is indistinguishable from the Freudian concept of repression (Erdelyi, 1985). This sense of the dissociation concept is typically used to

Mental Health of Adults with Epilepsy

Summary Mental Health of Adults With Epilepsy, a chapter in Epilepsy Patient and Family Guide, discusses the mental and behavioral aspects of epilepsy in adult patients. Behavioral disturbances in people with epilepsy may be unrelated to epilepsy, or related to the person's emotional reactions to having epilepsy, the effect of medications, or epilepsy. The chapter discusses (1) personality and epilepsy, (2) depression in epilepsy and in the general population, (3) causes of depression in people with epilepsy, (4) treating depression, (5) anxiety disorders in patients with epilepsy and in the general population, (6)

The relationship of antiepileptic drugs AEDs to depression

The AEDs most associated with this effect seem to be those which act at the benzodiazepine GABA receptor complex, and include tiagabine, topiramate and vigabatrin. Since in psychiatric practice it is known that benzodiazepines and other y-aminobutyric acid (GABA) agonists are associated clinically with depression, and that abnormalities of cerebrospinal fluid (CSF) GABA have been reported in patients with depression (Trimble, 1996) , the link between sudden cessation of seizures, GABAergic agents and the onset of depression seems reasonably secure. Further, these studies have revealed that patients with epilepsy and a prior history of an affective disorder are the more likely to develop depression in these circumstances.

Clinical use in epilepsy

Pregabalin has recently been licensed in Europe, the USA and 40 additional countries, as adjunctive therapy in partial-onset epilepsy in adults, and its place in routine therapy has not yet been fully ascertained. However, the results from the clinical trials are encouraging, and prega-balin appears to be effective. The lack of interactions and its excellent pharmacokinetic properties make pregabalin an easy drug to use. It has no drug interactions and no interactions with the combined oral contraceptive pill. There is not enough experience to recommend use in preganancy, but in animal experimentation, no teratogenic effects were observed. Pregabalin has a reasonable side-effect profile, and the frequency of adverse effects may be reduced by slow titration. No life-threatening or serious idiosyncratic effects have been recorded. In addition to its effects in epilepsy, pregabalin shows a marked analgesic effect, especially against neuropathic pain and the drug is now widely licensed...

Symptomatic Focal Epilepsies

Ideal situation Carbamazepine is generally the drug of choice for symptomatic focal epilepsies in the industrialized world, and the extended release form is preferred because twice-a-day dosing is possible. Although phenytoin is as effective and can be given once a day, it is less often prescribed because of the cosmetic side effects and saturation kinetics. Oxcarbazepine is similar to carbamazepine and is being increasingly used as a first-line drug. Other drugs that are commonly tried if the first-choice drug fails, in no particular order, include valproate, lamotrigine, topiramate, levetiracetam, and zonisamide. Because efficacies are similar, decisions are based more on side effect profiles and dosage regimens acceptable to each individual patient. Tiagabine is less commonly used, and drugs that are sedating, such as phenobarbital, primidone, and the benzodiazepines, are usually avoided. Felbamate and vigabatrin are extremely effective antiepileptic drugs with serious toxicity, so...

Is There An Epilepsyspecific Affective Syndrome

The comorbidity between mood and anxiety disorders could be a potential example of such a peculiarity (see Chapter 16). Comorbid anxiety symptoms have been identified in 73 of patients with epilepsy and depression (Robertson et al., 1987 , Jones et al., 2005a). However, it is still unknown whether this is an association identical to that described in primary mood disorders or a comorbidity typical of chronic illnesses (where anxiety is present, with irritability and generalized turmoil), or if it is distinctive only of epilepsy and interlinked with the underlying brain pathology. The recognition of comorbid anxiety symptoms is very important clinically, since they may worsen the quality of life of depressed patients and significantly increase the risk of suicide (Kanner, 2006).

Idiopathic Generalized Epilepsies

Ideal situation Valproate is commonly preferred as the drug of choice for patients with primary generalized epilepsies that do, or can, manifest with multiple seizure types, because it is effective against generalized tonic-clonic seizures, absences, and myoclonic jerks. Other wide-spectrum antiepileptic drugs that can be used to control all seizure types with a single medication include lamotrigine, levetiracetam, zon-isamide, and topiramate. When these drugs fail, polytherapy is necessary for patients who have generalized tonic-clonic seizures and either absences or myoclonic jerks. Absences can be treated with ethosuximide, and myoclonic jerks with clonazepam and, rarely, primidone. Care must be taken when combining medications to avoid pharmacoki-netic and pharmacodynamic interactions that increase the likelihood of adverse events.

Other Benefits of VNS Therapy

Beneficial clinical effects beyond changes in seizure frequency have been observed. Malow and colleagues84 found that in 16 patients treatment with low stimulus intensities improved daytime sleepiness and promoted alertness. The use of VNS Therapy to reduce morbid obesity,85 86 improve memory,87 improve treatment-resistant depression 8 and to elevate mood59-91 have been reported. Pilot studies investigating the role of VNS Therapy for Alzheimer's disease, obsessive-compulsive disorder, migraine headaches, and anxiety disorders are underway.

Symptomatic Generalized Epilepsies

Sary, and often seizures cannot be completely controlled. Drop attacks are particularly refractory to pharmacotherapy, although fel-bamate, lamotrigine, topiramate, and zon-isamide may be of some benefit. Because these patients are almost always intellectually compromised, drugs that further impair cognitive function, like the barbiturates and benzodiazepines, should be avoided.

Psychiatric side effects of new antiepileptic drugs

Insomnia, which may be associated with irritability, anxiety or even hypomania, is the only significant psychiatric side effect, occurring in 6 of patients treated with lamotrigine in monotherapy, compared to 2 in patients treated with carba-mazepine and 3 in patients treated with phenytoin (Brodie et al., 1995). Ketter et al. (1999) have specifically investigated psychotropic effects of felba-mate. They concluded from their study of 30 refractory epilepsy patients that the stimulating effects of felbamate may be beneficial or negative depending on preexisting psychopathology. Patients with baseline insomnia or anxiety experienced a deterioration in their psychic state, while other children improved.

Epilepsy in Children A Primary Care Perspective

Summary Epilepsy in Children A Primary Care Perspective, a videotape, reviews the diagnosis and management of childhood seizures. Most childhood seizures can be successfully controlled the keys are accurate diagnosis and administration of the most appropriate anticonvulsant medication. A seizure is a symptom of an underlying neurological disorder, which may be epilepsy or an epileptic syndrome. Syndromes are defined by the clinical event, electroencephalography (EEG) characteristics, age at onset, evolution and prognosis, family history, clinical history, and physical findings. Many conditions mimic epilepsy in children, including breath holding, pallid infantile syncope, night terrors, sleep walking, syncope, cardiac arrhythmia, and movement disorders. Once the physician has established that a seizure has occurred, it is important to take a clinical history, especially a detailed description of the event. Diagnosis is based on clinical, not EEG, data, but EEG's may suggest a seizure...

Transient global amnesia

They are doing or where they are going. Although they have little awareness of their current circumstances they typically retain personal information. The episodes can last up to hours, after which small islands of memory start to return of what went on during the amnestic period. However, some never recover any memory for the time that was involved. As a result these episodes typically cause great anxiety to those around them.

Seizures Related To Withdrawal Of Other Central Nervous System Depressants

Drugs that increase GABAA-mediated inhibition (e.g., benzodiazepines, barbiturates) are commonly prescribed for their anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant properties. Prolonged administration of ben-zodiazepines and barbiturates can result in tolerance and physical dependence. The spectrum of behavioral signs and symptoms that occur following withdrawal from barbiturates and benzodiazepines including hyperexcitability, tremors, and seizures is similar to that occurring following alcohol withdrawal (Busto et al., 1986 Hillbom et al., 2003). In addition, genetic characteristics that influence susceptibility to alcohol withdrawal also affect susceptibility to barbiturate and benzodiazepine withdrawal (Metten and Crabbe, 1994, 1999). Furthermore, there is cross-tolerance among benzodiazepines, ethanol, and barbiturates, and ben-

Differential diagnosisdiagnostic approach

There may be subtle movements associated with electrographic seizure In children, there are several types of NCSE NCSE after CSE, with generalized epilepsies (absence SE), with focal epilepsies (complex partial SE), and with the entity referred to as autonomic epilepsy CSE itself is easily recognized, and typically does not require EEG confirmation for diagnosis . However, in patients with CSE in whom convulsive movements are successfully treated with benzodiazepines, persistence of altered awareness raises the question of NCSE This occurs infrequently after the treatment of SE and requires EEG confirmation NCSE occurred in 14 of adults in whom CSE was controlled, whereas the percentage was higher in a small pediatric series (26 ) .

Approach To Newonset Seizures In The Hospital

Implemented, care-givers should ensure the patient is in a safe position to prevent injury and or aspiration. Part of assessment of circulation is obtaining intravenous access and obtaining blood for laboratory studies. In addition to bedside glucose testing, and electrolytes including calcium, laboratory tests should be chosen based on what is known about the patient's other medical conditions, including tests of renal and hepatic function. Part of the initial assessment includes a focused review of the patient's history, including recent neurological and systemic complaints, medications (especially those recently introduced), and drug and alcohol use. A proposed timetable and treatment protocol for acute seizures in the hospitalized patient are outlined in Table 12.1. Treatment should be first directed towards all potentially correctable underlying causes, as delineated in Tables 12.2 and 12.3. Most seizures cease spontaneously within 5 minutes, requiring no immediate intervention....

Unprovoked Seizure Clusters

Patients who have unprovoked status epilepticus or a seizure cluster as their first seizure may have a lower threshold for deciding to begin chronic AEDs. In cryptogenic or idiopathic epilepsy, initial presentation with status epilepticus was not associated with increased risk of subsequent seizures 73 though there may be a greater risk that recurrence will be in the form of another prolonged seizure or cluster (personal communication, W. A. Hauser, 2007). Among remote symptomatic seizure patients, having status epilepticus or post-ictal Todd's paresis increased the risk for recurrence 68 . In patients with status epilepticus or multiple seizures (two or more within 24 h), recurrence risk was 37 at 1 year, 56 at 3 years and 56 at 5 years, compared with 21 , 34 and 43 at 1, 3 and 5 years for those presenting with single seizures. These patients who present with prolonged seizures or clusters should be offered agents for abortive treatment if they have a means of administering it during...

Dependence Of Paroxysms Duration On Model Parameters

For the analysis of the dependence of the model's behavior on parameters, we selected six out of 65 model parameters. We selected the parameters that are either assumed to play a role in the pathophysiology of absence seizures in animals and humans, or are assumed to be targets of antiepileptic drugs, or are associated with seizure activation methods (sleep, hyperventilation). We varied one parameter at a time while all others were kept constant. For each parameter setting we simulated 24 hours of activity and created duration histograms from detected paroxysmal and normal epochs. The histograms were fitted with exponential distributions and the distributions' means were calculated. Each parameter (except cholinergic modulation) was manipulated such that the system's behavior varied from at least one paroxysmal event during 24 hours of activity to a state of continuous paroxysmal activity. The influence of a cholinergic neuromodulatory input originating from the brainstem...

Alcohol and Sedative Drug Withdrawal

Seizures can occur upon sudden alcohol and sedative drug withdrawal, particularly when these drugs have been used for prolonged periods. Although this is much more common in people with epilepsy, seizures in this context can also occur in people without epilepsy. When planned in advance, the period of alcohol withdrawal should be accompanied by the temporary administration of benzodiazepines, which will control not only the anxiety state induced by alcohol discontinuation, but will also increase seizure threshold. The approach to the safe discontinuation of sedative drugs is different, and requires decrease of dosages over a long period of time. In people with epilepsy, rapid withdrawal of barbiturates or benzodizepines are well known seizure precipitants, and the discontinuation of these drugs should be done over weeks or months. When epilepsy is more severe, there is a definite risk of an increase in seizures even with slow discontinuation of barbiturates, and thus small dosages of...

Description Of The Model

In all electrophysiologic studies, agar-embedded zebrafish (7DPF) were exposed to 15mM PTZ until a stable level of baseline bursting was established (40-65 minutes interictal + ictal activity). Next AEDs previously demonstrated to suppress (or abolish) PTZ-induced seizure in rodents were tested e.g., benzodiazepines (clonazepam and diazepam) or valproic acid (Figure 4). Both these agents suppressed PTZ-induced epileptiform discharge in a concentration-dependent manner. Reduction of ictal burst discharge amplitude and frequency could be observed within 30 to 45 minutes of drug exposure. Unlike in vitro slice studies, it was not possible to remove or wash the compounds efficiently from our in vivo preparation thus recovery experiments were not performed. In separate control studies, we also tested AEDs previously shown to have little (or no) effect on PTZ-induced seizures in rodents (e.g., carbamazepine, phenobarbital, ethosuximide, phenytoin). As expected, these AEDs did not...

Time Distributions Of Paroxysmal Events

The critical dependence of paroxysmal activity on the slope of the sigmoid transfer function of cortical interneurons does not have a straightforward interpretation. We may state that an increase of the slope of the sigmoid transfer function is directly related to narrowing the distribution of firing thresholds in a population and thus it represents an increased synchrony in that population. We hypothesize that the slope parameter may mimic the strength of gap-junctional connections within a population of interneurons. Therefore, it may be of interest to note that (a) it was proposed by Velazquez and Carlen (2000) that hyperventilation, which reduces blood CO2 levels and causes alkalosis, may rapidly enhance gap-junctional communication and neural synchrony and (b) anatomical data indicate that gap junctions in the neocortex are specifically formed among inhibitory cells (Galarreta and Hestrin, 2001). In the light of these two statements, our modeling results showing that an increase...

The Acutely Unwell Or Periprocedural Patient

Benzodiazepines are often used perioperatively and may prevent acute seizures, but care must be taken when weaning off these agents to avoid withdrawal seizures. Some analgesics such as the opiates - pethidine (meperidine) in particular - are associated with seizures, and should be avoided, where possible, post-operatively. Benzodiazepines are usually used for acute seizure management rather than for chronic epilepsy treatment, but are available in many different forms which may be useful for patients who are acutely unwell. Lorazepam may be given intravenously or sublingually. Rectal diazepam is well absorbed, and is also available intravenously. Midazolam can be given into the buccal cavity or intranasally.

Vocabulary Builder

Benzodiazepines A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any H-isomer. nih Lorazepam An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. nih

Diagnostic Evaluation And Differential Diagnosis

Benzodiazepines, specifically clonazepam, nitraz-epam, and clobazam, are also first-line AED therapy options (38, 61, 62). All are considered effective against seizures associated with LGS, but side effects and the development of tolerance limit their usefulness over time (38). Side effects of clonazepam include hyperactivity, sedation, drooling, and incoordination, which can significantly affect the quality of life for patients with LGS (38). The efficacy and tolerability profile of nitrazepam is similar to that of clonazepam (38). Clobazam is considered the least sedating benzodiazepine, with the longest time to the development of tolerance (62). Some recommendations to slow the development of tolerance include dosing on an every-other-day schedule or alternate two different benzodiazepines on an alternate-day basis (63, 64). Unfortunately, not all benzodiazepines are beneficial intravenous diazepam and lorazepam have been reported to induce tonic status epilepticus in some patients...

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