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Natural Insomnia Program Summary

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Primary Sleep Disorders In Patients With Epilepsy

The incidence of primary sleep disorders in the epileptic population is unknown. The literature contains mostly retrospective studies in which patients with epilepsy and suspected sleep disorders are included. Consequently, the reported incidence of sleep disorders is likely to be overestimated. Prospective studies are required to determine how these figures compare with those of the general population. In the largest retrospective study, 63 adults with epilepsy were referred for PSG for EDS and suspected OSAS (27), suspected OSAS without EDS (22), spells and EDS or suspected OSAS (10), nocturnal spells (2), or EDS alone (2) (Malow et al., 1997). Multiple sleep latency tests (MSLTs) were performed in 33 cases. Sleep disorders were suspected in 79 of patients. Obstructive sleep apnea syndrome was diagnosed in 71 . The disorder was considered mild in 14, moderate in 21, and severe in 10 patients, including 7 females. Other diagnoses included nocturnal seizures (4), mild OSAS and...

Sleep Complaints And Sleep Hygiene

Patients with epilepsy commonly report sleep disturbances. Using a six item questionnaire, the frequency of sleep disorder symptoms was compared with 30 treated patients having epilepsy and 23 normal adults (Hoeppner et al., 1984). Patients with simple and complex partial seizures had a higher incidence of sleep symptoms than patients with generalized seizures and normal subjects. The most common complaint was frequent nocturnal awakenings. Patients with seizures at least every month had more sleep-related symptoms and nocturnal awakenings than those with yearly seizures or less. As in the general population, poor sleep hygiene is a common cause of daytime sleepiness and insomnia. In a survey of 100 patients with epilepsy, 37 reported poor sleep (Lannon and Vaughn, 1997). These patients had less exercise and more irregular sleep patterns, took more naps, and consumed more caffeine, alcohol, and tobacco within 6 h of bedtime than those without sleep complaints. Environmental barriers...

Sleep Disorders in General

The parasomnias and neurological disorders of sleep, such as narcolepsy, may be confused with epilepsy due to their paroxysmal nature. The difficulty in differentiating epileptic and nonepileptic events is compounded by the fact that paroxysmal nonepileptic sleep events are more common in children with epilepsy or learning disabilities than in the general childhood population (6). Sleep disorders remain a largely neglected and poorly understood area in pediatrics. However, with careful attention to the timing and semeiology of events and the use of video-EEG and nocturnal polysomnography, these conditions can be classified and distinguished from epileptic seizures (see also Chapter 16).

Sleep Disorders

Nocturnally occurring seizures may resist antiepileptic therapy. Both seizure-related sleep disruption and antiepileptic drugs may produce excessive daytime sleep and mental sluggishness. Several nonepileptic parasom-nias share features with epileptic conditions by interrupting sleep. These also lead to daytime fatigue and sleepiness, possibly compounded by unnecessary antiepileptic medication. Sleep deprivation from para-somnias could aggravate a true epileptic tendency. The foregoing considerations require that the investigation and management of possible seizure disorders include a description of such somnogenic events and scrutiny for symptoms of sleep deprivation (see also Chapter 16). Broughton (102) described three phenomena that superficially resemble dyscognitive (formerly known as complex partial) seizures confusional awakenings (CA), sleep terrors (ST), and sleep walking (SW). CA develop from sleep stages 3 or 4 in the early night (103). The EEG consists of diffuse medium...

REM Sleep Disorders

Nightmares and sleep paralysis are the principal REM sleep disorders that may be confused with epilepsy. They are both common. Ten percent to 20 of individuals will have some experience of sleep paralysis. Waking from REM sleep without abolishing the physiological REM atonia that prevents us from acting out our dreams may lead to a frightening experience of paralysis. Nightmares are usually easier to distinguish from epileptic seizures than night terrors, as the child will have a memory of both waking and of the dream, and will then move into normal wakefulness rapidly. Nocturnal epileptic seizures rarely arise out of REM sleep.

Juvenile Myoclonic Epilepsy

In this syndrome, myoclonic and generalized tonic-clonic seizures occur characteristically in the morning in the first one to two hours after awakening. Seizures may also occur on awakening from a nap but are rare at other times during the day (Dinner, 1987). Sleep deprivation and alcohol appear to be an extremely important precipitant for seizures in this syndrome. The characteristic EEG abnormality in juvenile myoclonic epilepsy consists of spike-wave complexes at 4-6 Hz in a generalized distribution, as well as polyspikes. The discharges increase markedly at sleep onset and on awakening but are virtually absent in NREM and REM sleep and while the patient is awake.

Secondgeneration Aeds

Felbamate is a broad-spectrum anti-epileptic drug. It is not considered to be a first-line drug because of its potential for serious idiosyncratic side-effects, including potentially fatal aplastic anaemia (incidence of 1 in 3000) and hepatic failure (incidence of 1 in 10 000) 43 . Recent analyses indicate that aplastic anaemia and liver failure occur almost exclusively within the first year of therapy. During this period, safety monitoring consisting of liver function tests and blood counts is recommended with a frequency of up to twice monthly, despite lack of evidence that early detection of changes will prevent serious health problems, even if the drug is discontinued. Yet, felbamate may still be an important drug in the armamentarium for refractory patients, because it may control seizures when other drugs fail, and tends to be alerting rather than sedating. It has been found to be particularly effective in patients with Lennox-Gastaut syndrome 44 . Felbamate should be started at...

Tonicclonic seizures grand mal seizures

The plantar responses are usually extensor at this time and the tendon jerks are diminished. Confusion is invariable in the postictal phase. The patient often has a severe headache, feels dazed and extremely unwell, and often lapses into deep sleep. On awakening minutes or hours later, there may be no residual symptoms or, more commonly, persisting headache, dysthymia, lethargy, muscle aching and soreness (including stiffness of the jaw).

Epilepsia Partialis Continua Versus Non Epileptic Seizures

The episodes were stereotypic, beginning with numbness of the left hand and arm and a flushed feeling in his face. This was followed by uncontrollable twitching movements of the right hand. The episodes lasted from 10 minutes to 4 hours and occurred an average of four times a week. Lorazepam 2 mg kg intravenously had been administered at another hospital during a prolonged episode but had no effect. All episodes occurred while the patient was awake and there were no precipitants such as sleep deprivation.

Idiopathic Generalized Epilepsies

Idiopathic generalized epilepsies take many forms, but the best-known examples are childhood absence epilepsy and juvenile myoclonic epilepsy (JME). The seizure types of JME comprise morning myoclonus, generalized tonic-clonic seizures on awakening, and sometimes absences and photosensitivity, all more likely following sleep deprivation. The seizures typically begin in the teenage years, but the epilepsy tendency persists lifelong. The EEG shows interictal generalized polyspike-and-wave activity (Figure 2.2). The seizures usually respond well to valproate.

Differential Diagnosis of Epilepsy

The diagnosis of epilepsy is clinical and relies on accurate personal and eye-witnessed accounts, concentrating on the circumstances of episode, the preceding aura, the interictal state, and postictal events. A diagnosis of epilepsy is a life-changing event with potential psychological consequences the diagnosis should be given and relevant treatment begun only when the there is reasonable certainty. On first contact with the patient all the relevant information may not be at hand the passage of time can be an important diagnostic tool in avoiding misdiagnosis. The conditions most commonly mistaken for epileptic seizures are syncope (vasovagal and cardiac), nonepileptic attacks, and sleep disorders. Table 2.1 outlines other conditions to be considered in the differential diagnosis of epilepsy. Sleep disorders

Effect of epilepsy on sleep

Sleep disturbances are well recognized in patients with epilepsy. The changes reported in the literature with regard to the effect of epilepsy on sleep architecture include an increase of sleep onset latency, an increase in the wake time after sleep onset (WASO), increased instability of sleep stages, increased stage 1 and 2 NREM sleep (light sleep), a decrease in sleep spindle density, and a decrease in REM sleep. With regard to the pathophysiology of the sleep disturbances in these patients, one needs to consider the following mechanisms (1) the epilepsy itself may be associated with a sleep disturbance due to a mechanism intrinsic to the disease itself without the effect of the associated seizures, (2) the effect of seizures on sleep, and (3) the effect of antiepileptic drugs (AEDs) on the sleep architecture.

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.

Electrodiagnostic Monitoring

The routine EEG is useful for diagnosing spells, but the interpretation of the EEG must be cautious. Many normal variants, such as asymmetrical vertex waves, wicket spikes, small sharp spikes, 14- and 6-per second positive spikes, and rhythmical temporal theta bursts of drowsiness (formerly called psychomotor variant), can be mistaken for interictal spikes and sharp waves (109 and see Chapter 1). Additionally, a few percent of the normal American population exhibit interictal epileptiform discharges in a baseline EEG (110,111). The combination of an ambiguous history for a seizure and normal variants in the EEG can be an invitation to inappropriate treatment. Conversely, many individuals who have epilepsy lack abnormalities on an interictal EEG (112). Repeat EEGs to a total of about four EEGs may increase the yield (113). Other procedures useful for eliciting abnormalities in the EEG are activating procedures such as sleep deprivation or use of extra scalp (114) or sphenoidal...

Use Of Eec In The Diagnosis And Classification Of Epilepsy

A normal EEG does not exclude a diagnosis of epilepsy. A single routine EEG recording will show definite epileptiform abnormalities in 29-38 of adults who have epilepsy. With repeat recordings this rises to 69-77 .10-28-31 The sensitivity is improved by performing an EEG soon after a seizure, and by recordings with sleep or following sleep deprivation.10-32-33

Introduction Methods and Results

Plexes and sleep spindles, and its transitional drowsy EEG arousal periods. In contrast, REM sleep, with its asynchonous cellular discharge patterns and skeletal motor paralysis, is resistant to propagation of epileptic EEG potentials and to clinical motor accompaniment even though focal IID persists at this time. The contrasting effects of NREM and REM on IIDs and clinically evident seizures are to some extent nonspecific with respect to epileptic syndrome (Shouse et al., 1996), defined by seizure type, etiology, and clinical course (Commission Report, 1989). On the other hand, clinically evident seizures, particularly generalized tonic-clonic or myoclonic convulsions, occur mainly during NREM sleep, mainly during drowsy wakefulness, or randomly in the sleep-wake cycle depending on epileptic syndrome (e.g., Janz, 1962). Interictal discharges are less likely to propagate and to lead to a clinically evident seizure during intact REM sleep than in any other state regardless of epileptic...

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,...

Primary Generalized Epilepsy

The peak in GABA release that occurs during NREM, although promoting IlDs, seems to discourage clinically evident seizures such as generalized myoclonic and tonic-clonic convulsions. The moderate levels of reticular activation, chemical release, and synchronous thalamocortical discharge patterns during drowsiness are conducive to generalized epileptic EEG discharge propagation with clinical accompaniment (e.g., Gloor and Testa, 1974). In contrast to NREM and drowsiness, extreme activation of ascending brain stem afferents, particularly cholinergic cells, occurs during alert waking and REM sleep (e.g., Jones, 1994 Siegel, 1994), abolishes GABA-mediated synchronous thalamocortical discharge oscillations (Steriade, 1994), and is thought to suppress both ictal and interictal events in PGE (e.g., Guberman and Gloor, 1982 Shouse et al, 1989).

Treatment Of Generalized Epilepsy Idiopathic Generalized Epilepsy

Ideally, the goal in treating JME is to eliminate all seizure types. When this is not possible, targeting the most disabling seizure type, while avoiding obvious triggers (sleep deprivation and alcohol) is reasonable. While VPA has traditionally been used as the first-line AED in JME, there are no controlled trials to support this. In fact, no controlled trials have studied any AED as initial monotherapy for patients with JME. There is evidence from case series and open-label trials to support the use of VPA, LTG, LVT, TPM and zonisamide (ZNS) 10 . However, LTG has also been reported to exacerbate myoclonic seizures in JME. Therefore, in a patient for whom the myoclonus is the primary concern, with infrequent convulsions, LTG may not be the AED of choice 10 .

Treatment And Outcome

On presentation in 1996 the patient was receiving valproate 2250 mg day, carbamaze-pine 1800 mg day, and clonazepam 10 mg day. His therapy was slowly changed to oxcar-bazepine 1600mg day and valproate 2000 mg day. He lost 10 kg of excess weight and developed insomnia. He went into absence status epilepticus, vomiting profusely. Doses were changed to oxcarbazepine 1800 mg day and valproate 1500 mg day. In late 1997 he was having absences every few days. His drug regimen was changed to lamotrigine 150 mg day and valproate 1000 mg day.

Derangments of the Sleep Process

The parasomnias and neurological sleep disorders such as narcolepsy may be confused with epilepsy due to their paroxysmal nature. The difficulties in distinguishing epileptic and nonepileptic events is compounded by the fact that paroxysmal nonepileptic sleep events are more common in children with epilepsy or ID than in the general childhood population. Sleep disorders remain a largely neglected and poorly understood area in pediatrics however, with careful attention to the timing and semiology of events and the use of video EEG and nocturnal polysomnography these conditions can be classified and differentiated from epileptic seizures.

Severe Epileptic Encephalopathies

Antiepileptic medications may also have an indirect effect on sleep organization. With antiepileptic medications, a decrease in the number of microarousals associated with seizures may ultimately improve both sleep organization and seizure control. Specific drugs such as phenobarbital may shorten sleep latency, increase the proportion of S2 sleep, decrease the proportion of REM sleep, and decrease the number and duration of arousals. Phenytoin alternatively may shorten sleep latency but has no effect on arousals or REM sleep percentage (Scher, 1996). Most studies, however, have centered on adults few reports have addressed antiepileptic medication effects on sleep in young infants with seizures.

Precipitating factors in early epilepsy

Avoiding factors that precipitate seizures can be very important. The common factors are listed in Table 1.32 (p. 54). Excess alcohol intake (or its abrupt withdrawal) was a predominant factor in 6 of first seizures in one UK series, and accounted for 27 of first seizures in those between the ages of 30 and 39 years. Sleep deprivation may also be a precipitating factor for seizures in susceptible individuals, and is often a contributory factor in those abusing alcohol. Photosensitivity is encountered mainly in adolescents with idiopathic generalized epilepsy, and is described on p. 56.

Examination And Investigations

Physical and neurological examinations were normal. A magnetic resonance imaging scan showed slight frontoparietal parasaggital atrophy. The routine EEG showed increased generalized intermittant rhythmic slowing that was excessive for her age. With sleep deprivation, bilateral polyspike-and-wave complexes were seen, which were intermittently accompanied by bilateral myoclonic jerks of the upper extremities. An EEG of the mother was obtained, which showed increased generalized intermittent rhythmic slowing but no epileptiform potentials, even after sleep deprivation.

Project Title Effects Of Treating Obstructive Sleep Apnea In Epilepsy

Summary (provided by applicant) Epilepsy affects approximately 2.5 million Americans, resulting in substantial disability. Because up to 30 of patients with epilepsy continue to have seizures despite appropriate treatment with antiepileptic medications, additional interventions to improve seizure control are needed. One approach to improving seizure control is to treat coexisting sleep disorders, such as obstructive sleep apnea. Obstructive sleep apnea (OSA) may exacerbate seizures via sleep fragmentation, sleep deprivation, or other pathophysiological processes that have not yet been determined. The investigators recently documented that OSA is common in epilepsy patients with seizures refractory to medical treatment. In addition, preliminary data in the form of retrospective case series by the investigators and others have suggested that treatment of OSA may improve seizure control. However, no prospective studies have been done to verify these findings. Proof that treating OSA is...

Electroencephalographic Findings

The characteristic feature of this disorder obviously occurs during nonrapid eye movement (NREM) sleep. As soon as the patients fall asleep, continuous bilateral and diffuse slow SWs appear, mainly at 1.5-2 Hz, persisting through all the slow sleep stages (Fig. 9.1). This pattern is generally found between the ages of 4 and 14 years and seems to develop 1 or 2 years after the appearance of seizures. Tassinari et al. (1982, 1985, 1992a,b) stressed the importance of the SW index, which was calculated during all night sleep EEG recordings. In the Marseille series, the SW index ranged from 85 to 100 and this parameter was considered an essential feature for the diagnosis of ESES. The same parameter was adopted by Morikawa et al. (1985, 1992), Boel and Caesar (1989), Hirsch Typically the paroxysmal activity becomes less continuous and the SW index is under 25 in rapid eye movement (REM) sleep however, the focal discharges, predominantly frontal in location, may become prominent during REM...

Syndrome of electrical status epilepticus during slow wave sleep ESES

ESES (continuous spike-wave of slow sleep CWES Table 1.22) refers to an epileptic encephalopathy characterized by the presence of generalized 1-3 Hz spike-wave discharges occupying 85 or more of the EEG of non-REM sleep. Of children with epilepsy, 0.5 show this EEG pattern. The condition is diagnosed during childhood (1-14 years) with a peak age of onset between 3 and 5 years. About 30 of children showing this pattern have identifiable brain pathology such as previous meningitis or brain anoxia, hydrocephalus and developmental lesions, and one pair of affected monozygous twins has also been reported. There are no specific clinical signs during sleep. Overt seizures occur in daytime and at night, and can take various forms, both focal and generalized. Episodes of status are common. The EEG pattern usually occurs in children with severe epilepsy and learning difficulty. Furthermore, many children exhibit the symptoms of the Landau-Kleffner syndrome, and some authorities consider the two...

Psychogenic Nonepileptic Events

Magnetic resonance imaging (MRI) studies were normal. An interictal EEG showed right anterior temporal slowing. No interictal epilepti-form discharges occurred during the awake and sleep states, and there were no epileptiform discharges during a recording obtained following a night of sleep deprivation.

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.

With Epilepsy You Never Know

Seven years later she had a second generalized convulsion, which was provoked by sleep deprivation. At that time a neurologist examined her. Physical examination was normal. The EEG showed right posterior focal slowing but no epileptiform discharges. A computed tomography (CT) scan showed a small, contrast-enhancing lesion in the right frontal lobe. After a negative angiography study, the tentative diagnosis of angioma was changed to cerebral cysticercosis, although cerebrospinal fluid titers remained negative. Anticonvulsant treatment with phenytoin and carbamazepine was started but did not prevent occasional generalized seizures, which were consistently provoked by sleep deprivation and jet lag after long flights. Brief absence-like episodes, sometimes with mild automatisms, started at the age of 14 years and continued despite treatment up to maximum tolerated doses with carbamazepine and phenytoin. When she was 16 years old, phenytoin was replaced by valproate because of...

Funny Jerks Run In The Family

Physical and neurological examinations were normal. A magnetic resonance imaging scan showed slight frontoparietal parasaggital atrophy. The routine EEG showed increased generalized intermittant rhythmic slowing that was excessive for her age. With sleep deprivation, bilateral polyspike-and-wave complexes were seen, which were intermittently accompanied by bilateral myoclonic jerks of the upper extremities.

Benign Neonatal Sleep Myoclonus

Repetitive myoclonic jerks occurring during non-REM sleep constitutes a well-described clinical phenomenon. The myoclonic jerks usually begin in the first few weeks of life and resolve by 2 to 3 months. The jerks are typically bilateral and symmetric, involving the arms and legs. However, focality and migration of the myoclonus among different muscle groups has been noted. The EEG and neurologic outcome is normal. The jerking can be significantly repetitive so as to mimic clonic seizures. Helpful features to distinguish these myoclonic jerks from epileptic phenomena include the absence of autonomic activity, no other associated seizure types, myoclonic jerks occurring only at night, and a normal neurologic and developmental examination. In addition, if the child is awakened during an episode of benign neonatal sleep myoclonus, the movements cease. It should be noted that isolated hypnogogic myoclonic jerks can occur in all age groups and is a normal physiologic phenomena (8,9).

Common Clinical Practice

When clear triggering factors such as sleep deprivation, photic stimulation or excessive alcohol intake have been identified, specific measures to avoid them should be adopted by the patient, as in JME 41 . The pharmacological sensitivity is probably the same as in JME, with VPA being the first-line treatment, together with LTG, TPM and possibly LVT. Zonisamide may be another option in the future.

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). Felbamate is at present only used in a minority of patients, particularly with Lennox-Gastaut syndrome, due to its haematologic and hepatic toxicity. According to the manufacturer psychoses are rare, reported as serious adverse events in 0.02 of all patients treated in 1996 (Essex Pharma, personal communication). Felbamate may lead to increased alertness, inducing sleep problems and behavioural problems related to agitation in some patients, again, particularly in children with learning disabilities (McConnell et al., 1996). Ketter et al. (1999) have specifically investigated psychotropic effects of felba-mate. They concluded from their study of 30 refractory epilepsy...

Differential diagnosis

Lennox-Gastaut syndrome (LGS) first appeared in the medical literature in 1969, even though important clinical and EEG features in this subgroup of epileptic patients had been noted as early as 1939. This syndrome comprises a clinical triad consisting of (1) diffusely slow spike-wave discharges (occurring at a frequency of 1 . 5-2 . 5 Hz), (2) psychomotor retardation, and (3) multiple electroclinical seizure types refractory to medical therapy (including generalized tonic, atonic, atypical absence, myoclonic, and tonic-clonic seizures) The hallmark seizure type is the generalized tonic seizure that most often occurs while falling asleep In most cases, LGS manifests between 2-8 years of age, represents 3-10 of all pediatric epilepsies and, in this condition, affects males more frequently than females There are two general subtypes (1) cryptogenic (i . e . , there is no identifiable cause) in approximately

Association With Parkinsonism And Other Extrapyramidal Disorders

Findings from various centers suggest the following characteristics. First, parkinsonism may be quite prevalent in RBD second, RBD may be the initial manifestation of a parkinsonian disorder in a substantial number of RBD cases initially considered to be idiopathic third, a high percentage of parkinsonian patients without sleep complaints may have either subclinical or clinical RBD fourth, Lewy body pathology may be quite prevalent in RBD and fifth, similar findings have been reported in various extra-pyramidal disorders.

The Acutely Unwell Or Periprocedural Patient

Factors which may exacerbate seizures, such as sleep deprivation and alcohol, should be avoided prior to a procedure, and patients undergoing surgery should be advised to take their usual AEDs on the morning of surgery, even if fasting, and should continue their usual doses as soon as it is safe to do so.

Brain Mechanisms in Combined RBDExtrapyramidal Disorders

The retrorubral nucleus is located near the substantia nigra, and appears to be implicated in the linked PD-RBD pathology (Lai and Siegel, 1990). The retrorubral nucleus projects to the caudate and putamen (extrapyramidal motor system) experimental lesions to the retrorubral nucleus in cats releases abnormal motor activity during both sleep and wakefulness, ranging from myoclonic twitches to rhythmic leg movements and locomotion (Lai and Siegel, 1997). In addition, the substantia nigra also is closely connected to the REM-phasic generator circuitry and may play a major role in the genesis of PGO waves, a characteristic REM sleep phasic event (Datta et al, 1991). In regard to MSA, pontine involvement has been revealed by both gross neuropathological examination and histo-chemical studies, as cited by Plazzi et al. (1997). Functional magnetic resonance brain imaging studies and postmortem brain analyses are required to definitively elucidate the underlying neuropathology...

Nocturnal Paroxysmal Motor Phenomena

The nature of paroxysmal motor phenomena occurring during sleep has been a matter of debate for many years. Various sleep disorders associated with motor activity such as sleepwalking (somnambulism), sleep talking, night terrors (pavor nocturnus), periodic limb movement disorder, and rapid eye movement (REM)

Biological Based Therapies

Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and or control illness as well as promote health. Orthomolecular therapies aim to treat disease with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory diseases.

Methods For Analysis Of The Eeg Frequency Analysis

The EEG during sleep, including the various sleep stages is one that represents evolution of activity, albeit much more gradual and prolonged than that seen during seizures. EEG activity during sleep has been analyzed extensively and frequency bands from 0 to 40 Hz have been correlated with phases of sleep and sleep-related events. Each band of EEG frequencies has been analyzed and correlated with both visual analysis and with sleep stages. Furthermore, cortical and thalamocortical circuits involved in the generation of those frequencies have been investigated to determine if EEG signal frequency can be equated with specific cerebral activity and the location of such activity.

Interictal Depressive Episodes

Interictal depressive episodes disorders are the most frequent form of depression and, by the same token, the most frequent psychiatric co-morbidity in PWE, with prevalence rates ranging from 11 to 60 7 . They may mimic major depression, dysthymic, minor depressive and bipolar disorders described in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). In a significant number of patients, however, depression may present with atypical clinical characteristics. In primary depressive disorders, the difference between major depression and dysthymic disorder is based largely on severity, persistence and chronicity. According to DSM-IV criteria, symptoms in both disorders may include combinations of depressed mood, anhedonia, feelings of worthlessness and guilt, decreased ability to concentrate, recurrent thoughts of death and neurovegetative symptoms (i.e. weight loss or gain, insomnia or hypersomnia, psychomotor agitation or retardation and fatigue). The...

Pathophysiology Of Cataplexy

The muscle atonia seen in cataplexy is the result of postsynaptic hyperpolar-ization of the spinal cord motor neurons, with active inhibition of muscle tone (Glen et al., 1978). The spinal cord makes no essential contribution to the muscle atonia of cataplexy or normal REM sleep. Lesions of the ventral quadrant of the spinal cord, especially the ventrolateral funiculus corresponding to the ventrolateral reticulo spinal tract, inhibit muscle atonia. Because there is a strong analogy in man and dog between cataplexy and the muscle atonia seen during normal REM sleep, it may be that similar final pathways are involved. Siegel (1985) has shown in the cat, using transection experiments and cellular unit activity recordings, that pontine and medullary mechanisms are needed to produce muscle atonia. If transection is made at the pontomedullary junction, no muscle atonia is seen, while in midbrain decerebrate cats, complete bilateral inhibition of the antigravity muscles is seen. Therefore,...

Diagnostic approach

As always, the key to the diagnosis lies in the history This young man experienced vigorous myoclonic jerks while completely awake Myoclonic seizures have a propensity to occur in the early morning hours In combination with a generalized tonic-clonic seizure, the most likely diagnosis is JME Typical EEG findings confirm this suspicion, that is, 4-6 Hz spike-wave and polyspike-wave complexes, occurring spontaneously out of an otherwise normal background (see Figure 32 1) In approximately 30 of patients, these discharges are triggered by photic stimulation, and some will appear after provocation by sleep deprivation or drinking caf-feinated beverages During a myoclonic seizure, the myoclonic jerk corresponds to a polyspike-wave discharge In contrast, other myoclonic jerks, for example, when an individual is drifting off to sleep (hypnagogic myoclonic jerk or sleep myoclonus) or when startled, are not accompanied by epileptiform activity. Neuroimaging in a typical case is not required,...

Treatment strategy

Patients with JME have greater than 90 chance of experiencing recurrent seizures Therefore, lifelong treatment with antiepileptic drugs (AEDs) and avoidance of possibly provoking factors (e g , alcohol, illicit drugs, sleep deprivation, and flickering lights) are recommended Therapeutic agents effective against seizures in generalized epilepsies should be used and are usually very effective in controlling seizures Currently, lamotrigine, levetiracetam, topiramate, zonisamide, and valproic acid (VPA in males), are considered first-line treatment . VPA is typically avoided

Rapid Eye Movement Behavior Disorder

RBD is characterized by the emergence of prominent motor activity from sleep, associated with dream content (Schenck and Mahowald, 1990). The motor activity is often violent including punching, kicking, or running from bed with resultant injury to the patient or bed partner. The individual usually is acting out his or her dreams or nightmares. The PSG may demonstrate the presence of augmented electromyographic (EMG) tone during REM sleep. The motor phenomena such as kicking or punching activity, if recorded, occur during the REM state.

Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis a Syndrome

Electroencephalographic studies demonstrate interictal sharp and slow wave activity from the anterior temporal regions. Interictal activity is usually increased during stage 1 sleep and may become bilateral with slow sleep stages. Ictal scalp recordings usually show lateralizing rhythmic theta activity, and with intracranial recordings focal discharges originating in the hippocampus and amygdala are commonly seen.

Video Electroencephalographypolysomnography

As mentioned earlier, paroxysmal events in sleep characterized by prominent motor activity or complex behavior may represent manifestations of epileptic seizures or sleep disorders and on rare occasions psychogenic seizures. Frequently, it may be difficult to make a definitive clinical diagnosis based solely on the history. In this situation, video EEG-PSG may prove extremely valuable in defining the nature of the paroxysmal events. If one of the recurrent episodes is recorded, careful analysis of the clinical semiology may allow one to determine if the event is consistent with epileptic seizure, parasomnia, or psychogenic seizure. However, at times, the exact nature of the episode may prove very difficult to distinguish solely on the basis of the clinical features. Simultaneous recording of the EEG may demonstrate associated ictal epileptiform In the evaluation of these episodes, because of the absence of associated changes in the EEG recording, these episodes were initially thought...

Myoclonus Epilepsy With Ragged Red Fibers

The EEG shows slowly progressive background slowing, paralleling the degree of clinical deterioration. There are generalized spike-and-wave discharges at 2-5 Hz or multiple spike-and-wave discharges. Sporadic occipital spikes and sharp waves may be seen. Prominent photosensitivity may occur. Non-REM sleep is disorganized, and spike-and-wave discharges are diminished (11, 26).

Unexpected Benefit From An Old Antiepileptic Drug

A 30-year-old man had an uneventful previous history, except for moderate head trauma at the age of 3 years. Four years later, he started to have generalized convulsive seizures with abrupt loss of consciousness and some concomitant absence seizures. Most of the convulsions occurred on awakening those few that did not occurred at random. There was no family history of epilepsy or febrile convulsions. At this time, the patient's sleep rhythm was irregular. He was awake late in the evenings and got up late in the mornings. According to his mother, he suffered from sleep deprivation. He was active in youth athletics but was somewhat hyperactive and restless. Antiepileptic drug therapy was initially unsuccessful but, at the age of 10, he was seizure-free.

Cyclic Alternating Pattern Rate

The percentage ratio of CAP time to sleep time is referred to as CAP rate. CAP rate can be measured in NREM sleep (percentage ratio of total CAP time to total NREM sleep time) and in the single NREM stages (percentage ratio of CAP time in a given stage to the total duration of that stage throughout sleep). In human sleep, CAP rate is an index of arousal instability that shows a u-shaped evolution along the life span (teenagers, mean 43.4 young adults, 31.9 middle aged, 37.5 elderly, 55.3 ) (Parrino et al, 1998) and correlates with the subjective appreciation of sleep quality (the higher the CAP rate the poorer the sleep quality) (Terzano et al, 1990 Terzano and Parrino, 1992). When the increases of CAP rate are not accompanied by relevant variations of the sleep stages (macrostructure), it means that the flexibility of the microstructure (CAP) protects the stability of the macrostructure. However, because CAP rate is a dynamic parameter that measures the effort of the cerebral centers...

Mario Giovanni Terzano

Sleep Disorders Center Department of Neurology University of Parma Italy The variations of the arousal level across the 24-h rhythm play an important role in the modulation of epileptic events. The sleep-wake cycle, and particularly the conditions of instability that occur during sleep, affect significantly the appearance of interictal electroencephalography (EEG) discharges and epileptic seizures. This interaction, either in the sense of inhibition or, more frequently, in the direction of activation, relies on the characteristics of the epileptic syndrome (type of attacks, clinical course, and etiology), on the time of the day, and on the structural components of sleep (falling asleep, EEG arousal, nonrapid eye movement (NREM) stages, and rapid eye movement (REM) sleep). In particular, the two neurophysiological states that characterize sleep (NREM and REM) have opposite consequences on interictal abnormalities and on critical manifestations. A pioneering contribution published 60...

Effects Of Seizures On Sleep And Vigilance

Seizures occurring both at night and during the day can affect sleep architecture and produce daytime sleepiness. In a study comparing the effects of generalized and focal seizures on sleep, nocturnal generalized seizures produced a decrease in sleep time and reduced REM sleep percentage, prolongation of REM latency, and more sleep fragmentation (Touchon et al., 1991). Stages 1 and 2 sleep were increased while the percentage of slow-wave sleep (SWS) was unchanged. REM rebound an increase in REM percentage after REM-suppressing situations (i.e., sleep deprivation) was not observed later in a night after a seizure or during seizure-free nights. Focal seizures occurred during REM and nonrapid eye movement (NREM) sleep. When occurring in isolation, focal seizures produced little or no sleep disruption. However, multiple focal seizures in a night produced a significant reduction of REM sleep and duration of REM periods. As compared with control subjects, patients with epilepsy had...

Case presentation

A 10-year-old right-handed male without a significant past medical history was referred for evaluation of possible nocturnal seizures His seizures began at 7 years of age and have occurred almost exclusively during sleep, usually within 2 hours of falling asleep The stereotyped episode involves rocking and bicycling motions, gagging, rolling of the eyes, and profuse sweating lasting approximately 2 minutes These episodes have occurred on average three times per week, but recently have become more frequent He has had two similar episodes that have occurred while awake The patient's previous evaluation included two routine sleep-deprived EEGs and a 1 .5T noncontrast MRI of the brain, all of which were interpreted as normal Other laboratory tests included a complete blood count and comprehensive metabolic profile, which were also normal His physical and neurologic examination is unremarkable, but his family history is significant for a maternal aunt and brother with epileptic seizures...

Association Of Rapid Eye Movement Sleep Behavior Disorder With Specific Human Leukocyte Antigen Haplotypes

Narcolepsy, like RBD, is a prominent disorder of REM sleep dysregulation. Narcolepsy has a very strong association with HLA class II genes, with the DQB 1*0602 (DQwl group) allele being expressed in nearly all cases. Our center performed HLA class II antigen phenotyping in a group of 25 Caucasian males who had RBD but not narcolepsy 84 (n 21) were DQwl Arnulf, I., Bonnet, A.-M., Damier, P., Bejjani, B.-P., Seilhean, D., Derenne, J.-P., and Agid, Y. (2000). Hallucinations, REM sleep, and Parkinson's disease a medical hypothesis. Neurology 55 281-288. Boeve, B. F Silber, M. H Petersen, R. C., Kokmen, E., Parisi, J. E., and Olson, E. J. (1997). REM sleep behavior disorder and degenerative dementia with or without parkinsonism A syndrome predictive of Lewy body disease Neurology 48 A358-A359. Boeve, B. F., Silber, M. H., Ferman, T. J., et al. (1998). REM sleep behavior disorder and degenerative dementia an association likely reflecting Lewy body disease. Neurology 51 363-370. Cox, S.,...

The Problem Of Depression Diagnosis In Epilepsy

To conclude, a definite diagnosis of depression in patients with epilepsy can be difficult because a number of symptoms, which are recognized as diagnostic criteria for a depressive episode by the ICD-10 and DSM-IV, may occur in epilepsy secondary to seizure activity or AED treatment (e.g., loss of energy, insomnia or hypersomnia, increase or decrease in appetite, loss of libido, psychomotor agitation or retardation, diminished ability to think or concentrate). Because these symptoms may be present in patients who are not depressed, physicians need to explore fully the mental status of their patients. Inquiring about anhedonia has been suggested as an excellent predictor of the presence of depression (Kanner, 2006) and the use of self-rating instruments can be revealing. However, one of the most frequent methodological errors in research studies on depression and epilepsy is the sole reliance on screening instruments to diagnose depressive disorders. Firstly, a depressive episode can...

Typical absence status epilepticus petit mal status

This occurs only in patients with idiopathic generalized epilepsy, usually as part of the subcategory childhood absence epilepsy, in which a history of absence status occurs in about 3 -9 . The attacks can recur, and can last for hours or occasionally days. The episodes are typically precipitated by factors such as menstruation, withdrawal of medication, hypoglycaemia, hyperventilation, flashing or bright lights, sleep deprivation, fatigue, stress, or grief. The principle clinical feature is clouding of consciousness. This can vary from slight clouding to profound stupor. At one extreme patients have nothing more than slowed ideation and expression, and deficits in activities requiring sustained attention, sequential organization or spatial structuring amnesia may be slight or even absent. At the other extreme there may be immobility, mutism, simple voluntary actions performed only after repeated requests, long delays in verbal responses, and monosyllabic and hesitant speech....

The Reflex Epilepsies

The term reflex epilepsy is used to describe cases in which seizures are evoked consistently by a specific environmental trigger. In some cases the stimulus can be highly specific and in others less so. The term is not usually applied to patients whose seizures are precipitated by internal influences such as menstruation, nor to situations where the precipitating factors are vague or ill-defined (e.g. fatigue, stress), nor to patients with existing epilepsy where seizures are more likely to occur owing to specific precipitants (e.g. sleep deprivation, alcohol) transitional cases, however, occur in what can be a nosological grey area. The reflex epilepsies are sometimes subdivided into simple and complex types. In the simple forms the seizures are precipitated by simple sensory stimuli (e.g. flashes of light, startle) and in the complex forms by more elaborate stimuli (e.g. specific pieces of music). The complex forms are much more heterogeneous and the syndromes are less well defined...

Pharmacological Manipulations In Cataplexy

The effects of REM sleep-modulating agents and tricyclic antidepressant compounds have been investigated. Compounds with norepinephrine and serotonin reuptake-blocking properties have been shown to suppress cataplexy in man. The most potent were compounds combining norepinephrine and serotonin reuptake-blocking properties with atropinic effect. Drugs such as protriptyline, imipramine, and clomipramine were shown to significantly reduce cataplectic attacks. Atropine i.v. injections reversed cataplectic attacks in humans, and more specific reuptake blockers such as viloxazine, a specific norepinephrine reuptake blocker, and fluoxetine, a serotonin reuptake blocker were shown to suppress cataplexy without inducing the atropinic side affects (e.g., impotence) often seen with tricyclic antidepressants with anticholinergic properties. Earlier studies had also shown that levadopa (L-dopa), a precursor of dopamine, might have an effect on cataplexy. In interpreting these findings, it must be...

Parasomnia Overlap Disorder

Our center has reported on a group of 33 RBD patients with PSG-docu-mented overlapping NREM-REM sleep motor parasomnias consisting of sleepwalking, sleep terrors, and RBD (Schenck et al., 1997b). Mean age was 34 14 years mean age of parasomnia onset was 15 16 years (range 1-66) 70 (n 23) were males. An idiopathic subgroup (n 22) had a significantly earlier mean age of parasomnia onset (9 7 years) than a symptomatic subgroup (n 11) (27 23 years) whose parasomnia began with neurological disorders, n 6 congenital Mobius syndrome, narcolepsy, multiple sclerosis, brain tumor (and treatment), brain trauma, indeterminate disorder (exaggerated startle response atypical cataplexy) nocturnal paroxysmal atrial fibrillation, n 1 posttraumatic stress disorder major depression, n 1 chronic ethanol amphetamine abuse and withdrawal, n 1 or mixed disorders (schizophrenia, brain trauma, substance abuse), n 2. The rate of psychiatric disorders was not elevated group scores on various psychometric tests...

Paul B Pritchard III MD

Normal adults exhibit little change in serum PRL during waking hours, except for brief elevations after naps (2). Multiple nocturnal PRL surges occur which, unlike growth hormone (GH), are not entrained to specific sleep stages (3). Serum PRL returns to daytime values within 90 minutes of waking.

Rhythmic Movement Disorder

Rhythmic movement disorder, characterized by stereotyped repetitive movements of the head and neck, or sometimes the trunk, is also called head-banging, head-rolling, body-rocking, or body-rolling depending on the type of movement. Other terms sometimes employed include jactatio capitis nocturna and rhythmie du sommeil. The movements occur during drowsy wakefulness and stage 1 sleep at a rate of 0.5-2 Hz, rarely during deeper stages of NREM or REM sleep, and may last from a few seconds to as long as half an hour. When head-banging is the principal symptom, patients may repeatedly and forcefully bang their heads into the pillow, headboard, or wall while lying in a prone position. Rolling head or body movements and leg or arm banging may occur instead of or in addition to head-banging. They occur in the majority of infants, but have usually resolved by age 4 (Klackenberg, 1987). In occasional patients, symptoms persist into adolescence or adulthood.

Diagnosing The Specific Type Of

Findings that may be useful in specific diagnosis include vertex spikes as the main epileptiform abnormality in sialidosis, activation of epileptiform abnormalities in non-REM sleep in the sialidoses and the late-infantile and juvenile forms of NCL, photosensitivity to single flashes in late infantile and adult NCL, and absent ERG in late infantile and juvenile NCL (11).

Cyclic Alternating Pattern And Noncyclic Alternating Pattern

CAP is organized in sequences of two or more CAP cycles. Each CAP cycle consists of a phase A and a phase B, each lasting between 2 and 60 s. All CAP sequences begin with a phase A and end with a phase B. In NREM sleep, the phase A patterns are composed of the single or clustered arousal-related phasic events peculiar to the single sleep stages In NREM sleep, the CAP sequences may extend across successive sleep stages and thus the A phases may present different patterns within the same CAP sequence. In REM sleep, due to the lack of EEG synchronization, the A phases consist exclusively of desynchronized patterns (transient activation phases or arousals). Under physiological conditions, the 3-4-min interval between these A phases in REM sleep (Schieber et al., 1971) does not meet the temporal requirements for the scoring of CAP in this sleep stage. The period of sleep between two successive A phases separated by an interval 60 s is scored as NCAP. The EEG criteria for the identification...

Diagnostic Evaluation

Hypersynchronous Delta Activity

VPSG is the preferred laboratory study, particularly for patients with episodes that occur nightly or almost nightly. It is most useful if a typical episode is recorded. An abrupt arousal from slow-wave sleep is a characteristic finding, usually associated with tachycardia. During an episode, regular, rhythmic, hy-persynchronous delta or theta activity may be seen, and high-voltage EEG slow-wave activity may occur just before the arousal that initiates the behaviors (Fig. 12.1). Even if the behaviors do not occur, the study may be helpful. For example, runs of hypersynchronous delta during arousals from slow-wave sleep are more common in persons with arousal disorders than in other individuals (Blatt et ai, 1991). In patients with a history suggestive of sleepwalking or sleep terrors, the occurrence of confusional arousals supports the presence of an arousal disorder. The EEG during a dissociative episode shows a waking pattern while REM sleep behavior disorder is associated with EEG...

Frequency and Provoking Factors

Ance with the intake of antiepileptic drugs. Such noncompliance may be driven by cultural factors (such as the perception by relatives that the patient is taking too much medication, or that the medication will prove harmful in the future), by the inconsistent availability of antiepileptic medications in public pharmacies, and or by inadequate personal resources to access these medications. The temporal relationship between seizure occurrence and missed medication, as well as with other known provoking factors (such as excessive alcohol intake and sleep deprivation) should always be considered.

Role of the interictal and periictal psychopathology in suicide

Kraepelin (1923) precisely described the intermittent dysphoric disorder of patients with epilepsy. Dysphoric episodes present with depressive moods ('very frequently with utter disgust of life and suicidal bent'), irritability, anxiety, headaches, insomnia or at times with euphoric moods. These polysymptomatic dys-phoric episodes occur without external triggers with rapid onset and termination and recur fairly regularly in a uniform manner in the absence of clouding of consciousness. Dysphoric symptoms can be observed as prodromes of an attack or in the aftermath of an attack, but they most commonly appear as phenomena independent of the seizures, with a frequency varying from every few days to every few months. A patient just awakens one day dysphoric, or the dysphoria develops insidiously through the course of a day. As a rule, the dysphoric state lasts from 1 to 2 days but might dissipate after just a few hours. Based on our own observations, we have added anergia and phobic fears...

Acute Symptomatic Seizures

This unsatisfactory term is reserved for seizures that start in close temporal association to a sudden acute precipitant, in people who had not had prior seizures. If the epilepsy can be attributed to a pre-existing non-acute or static cause, it is referred to as remote symptomatic epilepsy, but clearly there is a grey area in which the distinction between acute and remote symptomatic epilepsies is rather arbitrary. The boundary is similarly blurred in some cases of reflex epilepsy or cases in which seizures have acute precipitants such as sleep deprivation or alcohol. Furthermore, if seizures continue after the acute phase, and if the cause remains present (e.g. post-stroke, post-trauma, tumoural, post-infectious epilepsy), seizures that were initially categorized as acute symptomatic are reclassified as remote symptomatic. This makes rather a nonsense of the classification scheme, the utility of which is best reserved for epidemiologically based incidence studies. Even in cases...

The interictal dysphoric disorder

Parietal Lobe

Kraepelin (1923) ) and then Bleuler (1949), were the first authors to describe in epilepsy a pleomorphic pattern of symptoms, including affective symptoms with prominent irritability intermixed with euphoric mood, fear, anxiety as well as anergia, pain and insomnia. Gastaut et al. (1955) confirmed Kraepelin s and Bleulers observations, leading Blumer to coin the term interictal dysphoric disorder (IDD) to refer to this type of depressive disorder in epilepsy (Blumer, 2000). Blumers description of the IDD is particularly intriguing. It is characterized by eight key symptoms grouped in three major categories (Table 5.1) labile depressive symptoms (depressive mood, anergia, pain, insomnia), labile affective symptoms (fear, anxiety), and supposedly specific symptoms (paroxysmal irritability, euphoric moods). Blumer preferred the term dysphoria to more accurately translate the original definition of Kraepelin Verstimmungszustand to stress the periodicity of mood changes of the patients and...

Other Sleeprelated Paroxysmal Events

Paroxysmal nocturnal motor events characterized by complex, often stereotyped dystonic or choreic movements with sudden onset and variable duration often defy precise classification. Over the years, different hypotheses regarding their origin have been advanced, and they have been variably diagnosed as sleep disorder, movement disorder or epilepsy. More recently, evidence has been mounting that many of these motor manifestations indeed represent seizures originating from the frontal lobe, although epileptiform EEG abnormalities are often lacking. Autosomal dominant transmission has been described in several families, and different mutations affecting the alpha 4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4) have been discovered. ICSD International Classification of Sleep Disorders Diagnostic and Coding Manual. (1990). Diagnostic Classification Steering Committee (M. J. Thorpy, Chairman). Rochester, MN American Sleep Disorders Association. Scheffer, I. E., Bhatia,...

Visual stimuli photosensitivity and photosensitive epilepsy

Epilepsy arising in the occipital region. In idiopathic generalized epilepsy, myoclonus, absence and tonic-clonic seizures can be precipitated by photic stimuli, and factors such as sleep deprivation or alcohol intake have additive effects partying can involve all factors, and seizures are common the morning after the night before. Alternating patterns (such as in some video games, or when looking down large escalators) can precipitate seizures in photosensitive patients, as can disco lights or poorly tuned TV screens (which flicker at the mains alternating current frequency of 50 Hz in the UK and Europe, but not in the USA). Other common stimuli include bright light shimmering off moving water, or the flickering of light through trees from a moving vehicle, and the transition from relative darkness into bright light. Most photosensitive patients have non-photically induced seizures also, but photic seizures can be prevented or reduced by wearing glasses with tinted or polarized...

Characteristic Of The Activity Generated By Human Epileptic Neurons

As reported to occur in animal experiments, Mg2+-free epileptiform events recorded in human tissue are readily blocked by NMDA receptor antagonists. Because Mg2+-free-induced epileptiform activity has been considered as a model of therapy-resistant discharges in vitro (Heinemann et al., 1994 Zhang et al., 1995), Mg2+-free-induced discharges have been used to test the efficacy of standard and new antiepileptic drugs in human tissue. These experiments demonstrated that carbamazepine exerts only a moderate antiepileptic action on Mg2+-free-induced epileptiform activity, whereas vigabatrin is highly effective (Musshoff et al., 2000b) retigabine and melatonin also displayed a suppressive action in this model (Fauteck et al., 1995 Straub et al., 2001).

Generalized Epilepsy and Sleep

Relations of Epileptic Seizures to Sleep-Wake Cycle Sleep Pattern of Patients with Generalized Epilepsy Relation of Epileptiform Discharges to the Sleep-Wake Cycle and Sleep Stages in Generalized Epilepsy Sleep Deprivation later recognized that epileptiform discharges occur more frequently during nonrapid eye movement (NREM) sleep than in rapid eye movement (REM) sleep and waking periods (Gibbs and Gibbs, 1947 Gloor et al., 1958 Shouse et al., 1996). Arousals and transition periods between sleep stages were considered to facilitate epileptiform discharges (Terzano et al., 1989 Hal sz, 1991 Gigli et al., 1992). In this chapter, we discuss clinical and electroencephalographic (EEG) relations between generalized epilepsy and sleep and the effects of antiepileptic drugs on the sleep of patients with generalized epilepsy. Langdon-Down and Brain (1929) were the first to subdivide epilepsy patients according to the occurrence of their seizures. They described (1) a diurnal type, that seizure...

Clinical Features Of Rapid Eye Movement Sleep Behavior Disorder

Classification of sleep disorders (ICSD) in 1990. A typical clinical presentation of RBD is as follows (Schenck et al., 1986) A 67-year-old dextral man was referred because of violent behavior during sleep He had slept uneventfully through adolescence in a small room with three brothers. But on his wedding night, his wife was scared with surprise over his sleep talking, groaning, tooth grinding, and minor body movements. This persisted without consequence for 41 years until one night, 4 years before referral, when he experienced the first 'physically moving dream' several hours after sleep onset he found himself out of bed attempting to carry out a dream. This episode signaled the onset of an increasingly frequent and progressively severe sleep disorder he would punch and kick his wife, fall out of bed, stagger about the room, crash into objects, and injure himself his wife began to sleep in another room 2 years before referral. They remain happily married, believing that these...

Disorders That Occur During Sleep

Head Banging and Other Rhythmic Parasomnias. Repetitive episodes of head banging can occur as an infant is falling asleep and may be mistaken for a seizure because, unlike diurnal episodes of stereotyped movements, they Studies indicate sleep-disordered breathing is sometimes associated with attention deficit disorders and learning difficulties that may improve with treatment of the sleep disorder (35). The behavioral parasomnias noted in children that are often mistaken for epileptic activity include sleepwalking (somnambulism), night terrors (pavor nocturnus), and nightmares (36, 37). The violent behaviors in non-REM sleep in older adults that can result in injury to themselves or to others are rarely seen in children (38). Sleepwalking. Sleepwalking usually begins between 5 and 10 years of age and can persist into adult life (39). Approximately 15 of all children sleepwalk at least one time. Repeated episodes are much less frequent involving less than 2 of the population....

Diagnostic Sensitivity

Dystonic Posturing Seizures

An awake standard EEG record will record IEDs in 50 of adults with epilepsy.12 The chance of recording IEDs increases with multiple EEGs and it is 92 with four recordings.19 The yield substantially increases by recording during sleep, more so after overnight sleep deprivation.20,21 Sleep recordings are of special value for ascertaining focal IEDs in partial epilepsies22,23 and establishing the presence of generalized IEDs in patients with idiopathic generalized epilepsy syndromes.12,13 A single wake and sleep EEG provides information supportive of diagnosis and also

Ruling Out Pseudoresistance

Other possible causes of 'pseudoresistance' are related to the patient's lifestyle or behaviour. As with other chronic medical conditions, imperfect adherence to the therapeutic regimen is one of the most common factors resulting in epilepsy treatment failure. Abuse of alcohol and recreational drugs can cause seizures as well as non-compliance to AED treatment. Sleep deprivation and stress are common precipitating factors for seizures. Therefore, social and lifestyle factors should be considered when evaluating the efficacy of pharmacological treatment.

Rem Behavior Disorder

The second sleep disorder that may mimic convulsive epileptic seizures is REM behavior disorder (RBD) (58,59). RBD is characterized by recurrent episodes of vigorous motor activity occurring during REM sleep, movements that often awaken the patient or spouse. The primary presenting complaints are interrupted sleep or injuries during sleep. RBD is more common in older adults, usually beginning after the age of 50. It is two to five times more common in men than in women. It is possible that rare episodes such as these occur in a large percentage of the population. I am familiar with people who have had rare such episodes throughout their adult life. The movements seen in RBD vary from minor movements of an individual extremity to complex behavior, such as laughing, shouting, or throwing one's self from the bed (58,59). Commonly, the movements are related to a dream the patient is having during REM sleep, and the patient is often able to describe the dream. The frequency of episodes...

NonREM Partial Arousal Disorders Arousal Parasomnias Night Terrors

Brief nocturnal arousals are normal in children. They occur typically in stage 4 non-REM sleep, 1 to 2 hours after sleep onset. They vary from normal events such as mumbling, chewing, sitting up, and staring to arousals that can be thought of as abnormal because of the disruption they cause the family. These include calm and agitated sleepwalking, and a spectrum from confusional arousals to night terrors or pavor nocturnus. The child may exhibit automatic behavior, but the events are not truly stereotyped. The affected children may be very agitated and look frightened, as if they do not recognize their parents. They are in an intermediate stage between waking and sleep, so they may respond, but not normally. They look awake and may be partially responsive but in fact are still in deep slow-wave sleep (stage 4). These events typically only occur once a night, especially 1 or 2 hours after falling asleep and nearly always in the first half of sleep. Children have no memory for them....

Cadd And Modeling Anticonvulsant Drugs

Tricyclic Butterfly

(carbamazepine, oxcarbazepine) as well as psychosis (chlorpromazine), schizophrenia, depression (amitriptyline), headache, insomnia and chronic pain. In treating these many disorders, tricyclic drugs demonstrate an ability to bind to a plethora of different (and structurally quite distinct) receptors, including the voltage gated Na+ channel protein as well as multiple types of dopamine receptors, serotonin receptors and acetylcholine receptors.

Douglas R Nordli Jr Timothy A Pedley

___ he electroencephalogram (EEG) is often the single most informative laboratory test in evaluating a children with seizures. At the most rudimentary level, it helps in differentiating epileptic from nonepileptic behavior. Because many conditions, including breathholding spells, movement disorders, syncope, cardiac arrhythmias, sleep disorders, migraine, and various psychiatric syndromes, may mimic epilepsy, EEG findings are often essential in making an accurate diagnosis.

Eeg Seizure Video Patient

Bilateral Seizures

One patient with a clinical picture of mania was treated with haloperidol and lithium until an EEG indicated a diagnosis of photoconvulsive epilepsy. Subsequent treatment with carbamazepine led to long-term remission of her symptoms (116). A 33-year-old woman presented with disinhibited speech, hyperactiv-ity, generalized amnesia, auditory hallucinations (God was talking to her), visual hallucinations, grandiosity, and complete insomnia 1 week after a skiing accident in which she had lost consciousness. The initial EEG showed bursts of spike waves over the left frontotem-poral region. A computed tomography (CT) scan showed a right frontal subdural hematoma. The EEG normalized after treatment with phenobarbital, but symptoms of mania persisted, despite chlorpromazine, until her third session of electroconvulsive therapy (ECT). She completed six sessions of ECT and was free of symptoms for 3 years. She had two additional episodes of mania and complex partial status, each time with a...

Frequent Night Terrors

No benefit had been obtained from benzodiazepines or counseling with a behavioral therapist familiar with sleep disorders. His past medical history was unremarkable. There was some relevant family background a sibling, an aunt and a cousin had suffered from febrile convulsions, the cousin later developing non-febrile seizures. The accompanying ictal EEG showed an arousal pattern out of non-REM sleep and, amidst muscle artifacts, some bilateral frontal low-voltage theta activity. An ictal single-photon emission computed tomography scan demonstrated an area of hyperperfusion within the left frontotemporal lobes. A magnetic resonance imaging scan was normal.

Electroencephalography EEG

A first EEG recorded from patients with epilepsy shows IEDs in only 20-50 .47,48 The yield of EEG can be substantially increased by repeating recordings and activation techniques like hyperventilation, intermittent photic stimulation, and sleep deprivation.49 Hyperventilation is more effective in generalized epilepsies, where it provokes 3 s spike wave activity hyperventilation seems also able to enhance slow spike and wave activity in symptomatic generalized epilepsies, which occur frequently in persons with ID.50 Intermittent photic stimulation can elicit different EEG responses, of which the photoparoxysmal response (generalized paroxysms with spike- polyspike and slow waves) is specifically associated with epilepsy. It is most probably a genetic trait and is particularly seen in young patients with generalized epilepsies.49 Sleep EEG increases the sensitivity of EEG by a substantial amount of 30-70 (including a sampling effect, due to the additional sleep EEG with a longer...

Step Three Mandatory Investigations

The typical admission varies from several days to several weeks, largely dependent on how quickly the patient has several seizures for characterization. The number of seizures required depends on the number of distinct seizure types the patient has and how easily these are localized and lateralized upon review. Patients with unilateral interictal spikes and a single seizure type may require two or three seizures, whereas patients with multi-focal discharges and multiple distinct seizure types may require two or three seizures of each type. In order to facilitate rapid, but safe, capture of seizures, the patient's AEDs are weaned off after admission. Provocation techniques such as sleep deprivation, exercise, photic stimulation and hyperventilation can be employed to further increase the likelihood of capturing seizures. Seizure precautions are enforced in the epilepsy monitoring unit, particularly for patients on reduced or discontinued medications.

Clinical History Screening Questionnaire

Diagnosis of epilepsy is fundamentally a clinical judgment. Clinical history should elicit details of seizure semiology, seizure provoking factors, and seizure frequency in the preceding five years.7 At times there can be discrepancy in the diagnosis of epilepsy when it is based only on a screening questionnaire. In a recent epidemiological survey in Togo of the 9,155 subjects screened by a screening questionnaire, 285 subjects (3.1 ) reported loss of consciousness, 263 (2.9 ) had seizures and 142 (1.5 ) had foaming and urinary incontinence during the seizure 74 (0.8 ) had absence seizures, 68 (0.7 ) had focal symptoms. During case ascertainment of the 304 subjects studied, diagnosis of epilepsy could be established in only 170 pa-tients.8 Documenting seizure provoking factors like sleep deprivation, photic stimulation, and hyperventilation, helps the clinician in the management of people with epilepsy.9

Seizures versus Epilepsy

As described in Chapter 1, not all seizures indicate the presence of epilepsy. Epilepsy is the chronic persistence of a brain dysfunction, which leads to recurrent epileptic seizures. Some individuals may have a single epileptic seizure, while others may have a few recurrent seizures during life, always related to a specific transient provoking factor. These people do not have epilepsy. Examples include generalized seizures in susceptible individuals under conditions of alcohol withdrawal or prolonged sleep deprivation, or excessive use of illegal stimulant drugs such as cocaine or amphetamines. Still others may harbor specific lesions, such as cortical tumors or parasitic cysts, which may clinically present with a few seizures, but whose tendency to further episodes is eliminated by resection or medical treatment of the lesion.

Predictors Of Sleepiness In Epilepsy

The causes of EDS in the epileptic population are multifactorial. AEDs, seizures, and concomitant sleep disorders have been found to affect sleep macroarchitecture and produce daytime sleepiness. Patients with epilepsy have a high incidence of sleep complaints and poor sleep habits. Primary sleep disorders should be suspected in patients with persistent hypersomnia, particularly those on AED monotherapy or with low serum drug concentrations and well-controlled seizures. Treatment of sleep disorders and improved sleep hygiene may lead to better seizure control.

General approach to episodic disturbances

Nature and speed of recovery as well as whether there were any focal or lateralizing signs after the event. There is no substitute for a detailed history of the attack from both the patient and any eyewitnesses, as well as obtaining a detailed account of the circumstances of the event. For instance, what was the patient engaged in the day and evening prior to the event Was there sleep deprivation or other medical problems Was there unusual stress or anxiety 3 Obtaining an eyewitness account is crucial and the telephone is an invaluable device in this regard, particularly now mobile telephones are so widely owned. Dramatic disparity is often noted between the eyewitness's and patient's stories. Whereas the patient may recall a simple fall or brief loss of consciousness, an eyewitness may provide a detailed account of generalized convulsion with postictal confusion, tongue biting and so on. Patients are often amnestic for the circumstances of the event. In other situations they may...

Status Epilepticus in a Heavy Snorer

A 50-year-old railwayman suffered from idiopathic absence seizures until the age of 16 years and had been seizure-free without antiepileptic treatment since then. Hypothyroidism and arterial hypertension were adequately treated. He was a heavy, habitual snorer. His wife witnessed nocturnal apneas and he reported excessive daytime sleepiness (e.g. falling asleep when watching television or when traveling in the train, or in the car as a passenger). One day after lunch he was tired and nervous and shortly thereafter had three generalized tonic clonic seizures in succession, corresponding to tonic clonic status epilepticus. The patient was treated with intravenous benzodi-azepines, phenytoin, and muscle relaxation, followed by intubation. He was transferred to our department. The mean oxygen level during desaturations was 83, and the minimal oxygen desaturation level was 68 . Sleep latency was 21 min, total sleep time was 357 min, rapid eye movement (REM) latency was 123 min, stage...

Temperal Flat Cake Like Structure Found In The Uterus During Pregnancy

A type of seizure that starts with a sudden cry, fall, and or body stiffness followed by jerking movements as the muscles repeatedly tense and then relax. Skin may be bluish. Possible loss of bladder or bowel control as muscles relax. Usually lasts a minute or two, after which normal breathing returns. The person may be confused or tired afterwards, and fall into a deep sleep. Person may complain of sore muscles or bitten tongue upon awakening. Myoclonic jerk. A sudden jerk of the arm or leg that can occur as a particular seizure type in epilepsy. Many people experience something similar when falling asleep, but it is not epilepsy.

Gyratory Seizures Ataxia And Dysarthria In A Young Adult

A 35-year-old woman had suffered her first generalized tonic convulsion at the age of 9 years when she was in bed soon after falling asleep. One month later, she had another generalized tonic convulsion, and treatment with antiepileptic drugs was started. She developed gyratory seizures several times a day.

Periodic Limb Movements Of Sleep

In addition to the nonepileptic conditions previously discussed, two sleep related conditions can occasionally be confused with convulsive epileptic seizures. These are periodic limb movements of sleep (PLMS) and REM sleep behavior disorder (RBD) (see also Chapter 16). PLMS is characterized by recurrent muscle contractions, primarily of the lower extremities, during sleep (50-53). Simultaneous movements of the upper extremities may occur. The movements tend to occur in clusters, each movement occurring approximately 20 to 30 seconds after the preceding movement, and each cluster lasting from minutes to hours. The movements tend to be more prominent in stage I and stage II sleep and tend to occur early in the night. The movements are characterized by extension of the great toe and flexion at the ankle, knee, and hip. Patients may complain of frequent awakenings, insomnia, or daytime sleepiness, all symptoms that are commonly associated with disrupted sleep. As one might expect, spouses...

Infantile sPAsMs AND west sYNDRoME

Adverse effects include sedation, irritability, insomnia and hypotonia leading to withdrawal in 0-6 39 . Of more concern are irreversible concentric visual field defects that occur in up to 43 of patients 52-54 . Whether these effects are dose dependent and cumulative over time or are the result of an idiosyncratic drug reaction is a controversial topic 52, 55, 56 . The evaluation of visual fields is difficult in infants. Although alternative assessment methods that are tolerated by young children have been developed, at present no recommendations can be made with respect to frequency and methods used for evaluation 57, 58, 39 .

Sleep Wake Transition Disorders

Rhythmic movement disorders such as nocturnal head banging (jactatio capitis nocturna), body rocking, and head rolling typically occur in infants and toddlers as they are trying to fall asleep. They can be present in deep sleep and in wakefulness. They are more common in children with ID. They will typically remit by five years of age but may persist into adult life. Management relies on good sleep hygiene and

Electrical Status Epilepticus Of Sleep

Electrical status epilepticus of sleep (ESES) refers to the occurrence of continuous epileptiform activity for at least 85 of slow-wave sleep. This syndrome is also known as epilepsy with continuous spike waves during slow-wave sleep. The syndrome was first described by Patry (1971). The EEG is characterized by generalized spike-wave complexes at 2-2.5 Hz. There is a marked attenuation of the pattern during REM sleep and in the wake EEG. The condition almost always occurs in patients with a prior history of epilepsy. With the onset of ESES, there is an associated decline in cognitive function with improvement once the ESES has resolved (Jayakar and Seshia, 1991). Seizures may manifest as nocturnal focal motor or generalized tonic-clonic seizures, or as atypical absence or myoclonic seizures.

Temporal Lobe Epilepsy

In Billiard's (1982) study of 127 patients, 9.4 had sleep-related complex partial seizures. In a study of 50 patients with sleep-related complex partial seizures, Cadilhac (1982) found that 32 patients had seizures in NREM sleep, 8 in REM sleep, and 10 in both states. However, in a study of 10 patients with a diagnosis of mesial temporal lobe epilepsy, Montplaisier (1985) found that none of these patients had seizures in NREM sleep. In a study of 15 patients with temporal lobe epilepsy, only 7 of the 67 seizures (10.9 ) occurred in sleep (Crespel et al., 1998). All the seizures occurred during stage 2 NREM sleep, except for one seizure that occurred from stage 3-4 NREM sleep. Quigg and colleagues (1998) studied the time of day when seizures occurred in patients with mesial temporal lobe epilepsy and found the majority of seizures happened during the waking hours with a peak incidence at 3 p.m. In terms of the presence of the IEA, most studies of temporal lobe epilepsy have found that...

Lamotrigine

Patients may do well at serum concentrations of 2 mg l, while others may need levels of up to 20 mg l. Common dose-related side-effects of lamotrigine include mild tremor, double vision, headache and insomnia. Rash, including Stevens-Johnson syndrome and toxic epidermal necrolysis, can occur. Risk is increased for children under 16, and is also more common with concomitant valproate use, and in patients who have experienced rash on other AEDs 54 . Rash almost always occurs within the first 8 weeks of therapy. Other hypersensitivity reactions, although much rarer, may be seen, including lymphadenopathy, fever, hepatic or renal failure, disseminated intravascular coagulation and arthritis 55 . Discontinuation of lamotrigine is recommended in the presence of rash or other indication of hypersensitivity, and it is very important to tell patients to call immediately with such symptoms. Rapid discontinuation can prevent a more severe, potentially life-threatening reaction. In the absence of...

West Syndrome

This syndrome describes the triad of infantile spasms, psychomotor retardation, and hypsarhythmia on the EEG (Fig. 1,3A). The infantile spasms tend to occur infrequently during sleep (Kellaway et al., 1979 Gomez and Klass, 1983). Only 2-5 of the spasms occurred during sleep in the Kellaway series. The EEG abnormalities may be increased in NREM sleep and the hypsarhythmia pattern may become more apparent during sleep. Occasionally the hypsarhythmia pattern may be seen only during sleep (Jeavons and Bower, 1961). In some patients, bursts of spike and slow waves alternate with periods of generalized suppression of the EEG activity in a semiperiodic fashion, giving rise to a burst suppression-like pattern (Fig. 1.3B) (Passouant et al., 1975). During REM sleep, there is a marked attenuation or disappearance of the hypsarhythmia pattern (Jeavons and Bower, 1961).

Effect Of Seizures

There is a well-documented effect of nocturnal seizures on sleep. Patients have been studied in terms of their sleep architecture on nights with and without nocturnal seizures, and found to have an increase in WASO, a decrease in REM sleep, and a decrease in sleep efficiency. These effects are found with both focal and generalized seizures (Touchon, 1991). However, in the patients with temporal lobe epilepsy, he found that a significant decrease in REM sleep occurred only in the patients with multiple nocturnal seizures and not if only a single seizure occurred. In the patients with temporal lobe epilepsy, in addition to the effect of nocturnal seizures on REM sleep, a decrease in slow-wave sleep (stages 3 and 4 NREM) has been reported (Sammaritano, 1996 Castro, 1997). In addition, daytime seizures may also have an effect on sleep architecture on nights following seizures. A significant decrease in the percentage of REM sleep as well as a prolongation of the REM latency (time from...

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