Neurology Case Conference Subsection D2 Rivera. Rivere. Robosa. Rodas

Neurology Case Conference Subsection D2 Rivera. Rivere. Robosa. Rodas
Neurology Case Conference Subsection D2 Rivera. Rivere. Robosa. Rodas. Rodriguez. Rogelio. Roque. Ruanto. Sabalvaro. Salac. Salazar, J. Salazar, R. Salcedo. Saldana. Sales. Salonga. San Diego. San Pedro. Sanez. Sanidad. Santos, E. Santos, J.

CASE 2.1

Case 2.1 A 10 year-old girl was brought by her mother for a consult because of poor academic performance. School teachers often observed her to be absent minded described as recurrent but brief periods of blank staring and inattention. This was accompanied by eye blinking, reflex scratching of her head, lip smacking and chewing movements which all lasts for a few seconds. These would occur many times a day and after each attack, the patient would resume his usual activity.

Missing Data First episode or onset of symptoms
Presence or absence of fever, loose bowel movement, vomiting Previous school performance Family History

Steps in the Diagnosis of Neurologic Disease
Anatomic diagnosis By History Interpretation of symptoms and signs in terms of physiology and anatomy Syndromic formulation and localization of the lesion Mode of onset and course Elicitation of clinical facts Other medical data By neurologic examination Appropriate lab tests 1. The symptoms and signs are secured by history and physical examination. 2. The symptoms and physical signs considered relevant to the problem at hand are interpreted in terms of physiology and anatomy that is, one identifies the disorder(s) of function and the anatomic structure(s) that are implicated. 3. These analyses permit the physician to localize the disease process, i.e., to name the part or parts of the nervous system involved. This step is called anatomic, or topographic, diagnosis. Often one recognizes a characteristic clustering of symptoms and signs, constituting a syndrome of anatomic, physiologic, or temporal type. The formulation of symptoms and signs in syndromic terms is particularly helpful in ascertaining the locus and nature of the disease. This step is called syndromic diagnosis and is often conducted in parallel with anatomic diagnosis. 4. From the anatomic diagnosis and other medical data particularly the mode and speed of onset, evolution, and course of the illness, the involvement of nonneurologic organ systems, the relevant past and family histories, and the laboratory findings one deduces the pathologic diagnosis and, when the mechanism and causation of the disease can be determined, the etiologic diagnosis. This may include the rapidly increasing number of molecular and genetic etiologies if they have been worked out for a particular process. 5. Finally, the physician should assess the degree of disability and determine whether it is temporary or permanent (functional diagnosis); this is important in managing the patient's illness and judging the potential for restoration of function I II III Anatomic Diagnosis IV Pathologic Diagnosis Reference: Adams and Victor’s Principles of Neurology, 8th Edition.

CLINICAL TYPE LOCALIZATION
Table 16-2 Common seizure patterns CLINICAL TYPE LOCALIZATION Somatic motor Jacksonian (focal motor) Prerolandic gyrus Masticatory, salivation, speech arrest Amygdaloid nuclei, opercular Simple contraversive Frontal Head and eye turning associated with arm movement or athetoid-dystonic postures Supplementary motor cortex Somatic and special sensory (auras) Somatosensory Contralateral postrolandic Unformed images, lights, patterns Occipital Auditory Heschl's gyri Vertiginous Superior temporal Olfactory Mesial temporal Gustatory Insula Visceral: autonomic Insular-orbital-frontal cortex Complex partial seizures Formed hallucinations Temporal neocortex or amygdaloid-hippocampal complex Illusions Dyscognitive experiences (deja vu, dreamy states, depersonalization) Affective states (fear, depression, or elation) Temporal Automatism (ictal and postictal) Temporal and frontal Absence Frontal cortex, amygdaloid-hippocampal complex, reticular-cortical system Bilateral epileptic myoclonus Reticulocortical, frontocentral SOURCE: Modified by permission from Penfield and Jasper. Reference: Adams and Victor’s Principles of Neurology, 8th Edition.

Salient Features 10 year old girl Poor academic performance
Absent minded Recurrent, brief periods of blank staring and inattention Accompanied by eye blinking, reflex scratching of her head, lip smacking and chewing movements Occurs many times a day

Differential Diagnosis
(<1month) Neonates (>1 month-<12yrs.) Infants and Children 12-18yrs. Adolescents Young Adults 18-35yrs.

Table 16-4 Causes of recurrent seizures in different age groups
AGE OF ONSET PROBABLE CAUSEa Neonatal Congenital maldevelopment, birth injury, anoxia, metabolic disorders (hypocalcemia, hypoglycemia, vitamin B6 deficiency, biotinidase deficiency, phenylketonuria, and others) Infancy (1-6 months) As above; infantile spasms; West syndrome Early childhood (6 months-3 years) Infantile spasms, febrile convulsions, birth injury and anoxia, infections, trauma, metabolic disorders, cortical dysgenesis, accidental drug poisoning Childhood (3-10 years) Perinatal anoxia, injury at birth or later, infections, thrombosis of cerebral arteries or veins, metabolic disorders, cortical malformations, Lennox-Gastaut syndrome, idiopathic, probably inherited, epilepsy (Rolandic epilepsy) Adolescence (10-18 years) Idiopathic epilepsy, including genetically transmitted types, juvenile myoclonic epilepsy, trauma, drugs Early adulthood (18-25 years) Idiopathic epilepsy, trauma, neoplasm, withdrawal from alcohol or other sedative drugs Middle age (35-60 years) Trauma, neoplasm, vascular disease, alcohol or other drug withdrawal Late life (over 60 years) Vascular disease (usually postinfarction), tumor, abscess, degenerative disease, trauma a Meningitis or encephalitis and their complications may be a cause of seizures at any age. This is true also of severe metabolic disturbances. In tropical and subtropical countries, parasitic infection of the CNS is a common cause. Reference: Adams and Victor’s Principles of Neurology, 8th Edition.

Distribution of the main causes of seizures at different ages
Distribution of the main causes of seizures at different ages. Evident is the prevalence of congenital causes in childhood and the emergence of cerebrovascular disease in older patients. Reference: Adams and Victor’s Principles of Neurology, 8th Edition.

Probable Cause Type Infants and Children (>1 month-<12yrs.) Febrile seizure Genetic disorders (metanolic, degenerative, primary epilepsy syndromes) CNS infection Developmental disorders Trauma Idiopathic Complex partial seizures Generalized Seizures: Atonic Seizures Absence (petit mal) Epilepsy Syndromes JME Lennox-Gastaut MTLE

Complex Partial Atonic JME Lennox-Gastaut MTLE Absence (petit-mal)
TYPES Complex Partial Ictal phase: sudden behavioral arrest or motionless stare Automatisms: Chewing, lip smacking, swallowing, “picking” movements of hands Seconds – an hour Impaired recollection or motionless stare Atonic Briefly impaired consciousness Quick head drop or nodding movement 1 to 2 seconds No post-ictal confusion JME Bilateral myoclonic seizures;single or repetetive Consciousness is preserved Myoclonic seizures frequent in the morning Provoked by sleep deprivation One-third have absence seizures Lennox-Gastaut Multiple seizure types Impaired cognitive function Associated with CNS disease, devt. Abnormalities, perinatal hypoxia/ischemia, trauma, infection Impaired cognitive syndrome MTLE Aura Behavioral arrest/stare Complex automatisms Unilateral posturing Postictal disorientation, memory loss dysphasia Absence (petit-mal) Sudden, brief lapses of consciousness, “daydreaming” No loss of postural control Rapid blinking, chewing movements. Can occur hundred times a day Lasts for seconds No postictal confusion Decline in school performance

Clinical Impression: Absence Seizure

Absence Seizure A type of generalized seizure, lasting for several seconds to minutes and may occur several times a day. Children with idiopathic generalized epilepsies may present with a history of staring spells, but infrequent absence seizures may not be diagnosed until a generalized tonic-clonic seizure has occurred. Reference: Segan, S. (2009). Absence Seizures. American Academy of Neurology and American Epilepsy Society.

Absence Seizure Other symptoms, such as behavioral problems may be the presenting complaint. Although the brief attacks are unrecognized, the lapses of awareness interfere with attention. Decline in school performance may be an indication of the onset or breakthrough of absence seizures. In symptomatic generalized epilepsies, atypical absence seizures often occur in the setting of developmental delay or mental retardation. Reference: Segan, S. (2009). Absence Seizures. American Academy of Neurology and American Epilepsy Society.

Absence Seizure On clinical examination, typical absence seizures appear as: Brief staring spells Patients have no warning phase, and if engaged in gross motor activity, such as walking, they may stop and stand motionless or they may continue to walk. Unresponsive during the seizure Children have no memory of what happened during the attack; they are generally unaware that a seizure has occurred. Reference: Segan, S. (2009). Absence Seizures. American Academy of Neurology and American Epilepsy Society.

Pathophysiology The pathophysiology of absence seizures is not fully understood. Abnormal oscillatory rhythms are believed to develop in thalamocortical pathways. This involves GABA-B–mediated inhibition alternating with glutamate-mediated excitation. GABA-B inhibition appears to be altered in absence seizures. Enhanced burst firing in selected corticothalamic networks may increase GABA-B receptor activation in the thalamus, leading to generalized spike-wave activity. Reference: Segan, S. (2009). Absence Seizures. American Academy of Neurology and American Epilepsy Society.

Absence Seizure vs Complex Partial Seizure
An absence seizures can sometimes be confused with a complex partial seizure but each type has its own distinctive features: Absence seizures : Never preceded by an aura Are of briefer duration – seconds rather than minutes Begin frequently and end abruptly The absence attack is always associated with the strikingly typical EEG abnormality of spike and slow wave discharges, usually at a frequency of 3Hz which occur can occur interictally and ictally and are often provoked by hyperventilation.

Variants of Absence or Petit-Mal Seizure
Atypical Petit Mal Long runs of slow spike-and-wave activity, usually with no apparent loss of consciousness External stimuli such as asking the patient to answer a question or to count will interrupt the run of abnormal EEG activity.

Variants of Absence or Petit-Mal Seizure
Lennox-Gastaut Syndrome Onset between 2-6years old Characterized by atonic, or astatic, seizures (i.e., falling attacks), often succeeded by various combinations of minor motor, tonic-clonic, and partial seizures and by progressive intellectual impairment. With a distinctive, slow (1- to 2-Hz) spike-and-wave EEG pattern. Triad of West Syndrome: Infantile spasms, a characteristic EEG picture (3-Hz hypsarrhythmia), and an arrest in mental development

Absence Seizures

Absence Seizures In childhood absence epilepsy, seizures are frequent and brief, lasting just a few seconds (pyknoleptic). Some children can have many such seizures per day. In other epilepsies, particularly those with an older age of onset, the seizures can last several seconds to minutes and may occur only a few times a day (nonpyknoleptic or spanioleptic absence seizures).

The etiology of idiopathic epilepsies with age- related onset is genetic. About 15-40% of patients with these epilepsies have a family history of epilepsy; overall concordance in monozygotic twins is 74% with a 100% concordance during the peak age of phenotypic expression. Family members may have other forms of idiopathic or genetic epilepsy (eg, febrile convulsions, generalized tonic- clonic seizures.

Typical Absence Seizures
Sudden onset of impaired movements Staring episodes or "absence spells" Accompanied by other motor, behavioral or autonomic phenomena May interfere with school function and learning Reference: Pediatric Epilepsy: Diagnosis and Therapy: John M. Pellock,Blaise F. D. Bourgeois

Atypical Absence Seizure
Less abrupt onset and cessation More pronounced changes in tone and longer duration Usually begins before 5 years of age Associated with other generalized seizure types and mental retardation Reference: Pediatric Epilepsy: Diagnosis and Therapy: John M. Pellock,Blaise F. D. Bourgeois

Diagnostic Work-up

Electroencephalography (EEG)
The only diagnostic test for absence seizures Ambulatory EEG monitoring over 24 hours may be useful to quantitate the number of seizures per day and their most likely times of occurrence.

EEG: Typical Absence Findings in typical absence seizures include the following: Background activity is normal. In syndromes with frequent absence seizures, such as childhood absence epilepsy, a routine awake recording is often pathognomonic. In syndromes with less frequent absence seizures (juvenile absence epilepsy or juvenile myoclonic epilepsy), an awake recording may be normal; a sleep or sleep- deprived recording may be needed. Typical absence seizures have generalized 3-Hz spike- and-wave complexes.

EEG: Typical Absence The spike frequency is often faster at the onset, with a slight deceleration at the end. They can range from Hz, with the faster frequencies seen in syndromes with older age of onset.

EEG: Typical Absence The onset and ending of these seizures are abrupt; no postictal EEG slowing is noted. Hyperventilation often provokes these seizures and should be a routine part of all EEGs in children. EEG video monitoring demonstrates that clinical seizure manifestations may lag behind the start of ictal EEG activity; bursts lasting less than 3 seconds are usually clinically silent. During the absence seizure, rhythmic eye blinks and mild clonic jerks may be present. As a seizure progresses, automatisms may be seen. Clinical and EEG features may vary considerably in different children.

EEG: Atypical Absence Findings in atypical absence seizures include the following: Background activity is often abnormal, reflecting the diffuse or multifocal underlying encephalopathy of symptomatic generalized epilepsy. Seizures are characterized by slow spike-and-wave paroxysms, classically 2.5 Hz.

EEG: Atypical Absence

EEG: Atypical Absence The onset may be difficult to discern, and postictal EEG slowing may be noted. The clinical correlation of generalized spike-and-wave complexes with clinical seizures is not as clear-cut as in typical absence seizures. EEG-video monitoring can show a more varied alteration of consciousness than in typical absence seizures. If the patient has underlying mental retardation, discerning changes in mental status also may be more difficult in atypical absence. Changes in postural tone, most noticeably head nods, are common.

Clinical and EEG Findings in Typical and Atypical Absence Seizures

Laboratory Studies Laboratory tests for:
Metabolic abnormalities Toxic or drug ingestion Blood levels of electrolytes, glucose, calcium, magnesium Hepatic or renal disease If a clear history of the episodic nature of the attacks is obtained, then the EEG can be diagnostic and laboratory tests may not be necessary.

Imaging Studies Neuroimaging is not indicated if the typical clinical pattern is present. Neuroimaging findings are normal in idiopathic epilepsies by definition. Often ordered if a child presents with a generalized tonic-clonic seizure, to rule out significant structural causes of seizures. If imaging is performed, MRI is preferred to CT scanning. MRI is more sensitive for certain anatomic abnormalities.

Treatment

Treatment DEPENDS on the underlying cause Metabolic : correction
Structural abnormality: seizure control + consider surgery Tumor Vascular Idiopathic : seizure control

Treatment Diagnosis and Classification of seizure disorder
Choose Anti-epileptic drug of choice Main Goal: Adequate seizure control Monitoring of response (seizure-free) and side effects Therapeutic Monitoring Drug Interactions

Principles of Treatment
Individualized treatment Selection of specific drug for initial therapy is based on specific clinical seizure type. Monotherapy is preferred. Dose is increased gradually. Enough time for steady state to be reached must be allowed. Prompt substitution when serious adverse reaction develops. If poor seizure control-gradually withdraw first drug while replacing with second drug of choice for seizure type (should not be stopped abruptly). Treatment failures may be due to poor compliance or misdiagnosis. Continue treatment to achieve minimum seizure-free period of 3-5 years. References: Katzung Basic and Clinical Pharmacology, 9th ed. The Treatment of Epilepsy, 3rd ed.

Absence Seizures Ethosuximide is the drug of choice for typical absence seizure Valproic Acid is the drug of choice for atypical absence seizure. Used only when treatment tolerance or failure appear with Ethosuximide Wide spectrum AED

Anti Epileptic Drug Glutamate Antagonist GABA agonist
Na channel blocker Ca channel blocker Phenobarbital * Phenytoin Carbamazepine Valproic Acid Gabapentin Topiramate Oxcarbazepine Ethosuximide Lamotrigine

Ethosuximide Primary indication: First-line or adjunctive therapy of generalized absence seizures Mechanisms of action: Inhibition of neuronal T-type calcium channels in the thalamus (Type III AED) Usual preparations: Capsules: 250 mg; syrup: 250 mg/5 mL Usual dosages: Initial: 250 mg (adults); 10–15 mg/kg/day (children) Maintenance: 750–1500 mg/day (adults); 15–40 mg/kg/day (children) Dosing frequency: 2–3 times/day Significant drug interactions: Ethosuximide levels are reduced by co-medication with carbamazepine, phenytoin, phenobarbital and rifampicin. Valproic acid may exert synergistic effects with ethosuximide in patients refractory to either drug given alone, and may have variable and inconsistent effects on ethosuximide levels. Serum valproic acid levels may be decreased by ethosuximide. Ethosuximide levels are increased by isoniazid. 2 ethyl 2 methylsuccinamide References: Katzung Basic and Clinical Pharmacology, 9th ed. The Treatment of Epilepsy, 3rd ed.

Ethosuximide Serum level monitoring: usually optimized based on clinical and EEG response. Main advantages: Well-established treatment for absence epilepsy without the risk of hepatic toxicity carried by valproic acid Main disadvantages: Adverse effects common. Unlike valproic acid, ethosuximide does not protect against generalized tonic– clonic seizures Common/important adverse effects: Gastrointestinal symptoms, drowsiness, ataxia, diplopia, headache, dizziness, hiccoughs, sedation, behavioural disturbances, acute psychotic reactions, extrapyramidal symptoms, blood dyscrasias, rash, lupus-like syndrome, other severe idiosyncratic reactions. References: Katzung Basic and Clinical Pharmacology, 9th ed. The Treatment of Epilepsy, 3rd ed.

Valproic Acid Primary indications: First line for atypical absence seizures. First-line therapy of idiopathic generalized epilepsies. First-line or adjunctive therapy of cryptogenic or symptomatic generalized epilepsies. Valuable but not generally first-line therapy for partialseizures Mechanisms of action: Increases brain GABA activity by increasing activity of glutamic acid decarboxylase, inhibition of GABA transaminase, inhibition of succinic semialdehyde dehydrogenase Usual dosages: Initial: 400–500 mg/day (adults); 15 mg/kg/day (children) Maintenance: 500–2500 mg/day (adults); 20–40 mg/day (children under 20 kg); 20–30 mg/kg/day (children over 20 kg) Dosing frequency: 2-3 times a day Serum level monitoring: Dosage usually can be adjusted on the basis of clinical response, but monitoring serum valproic acid levels may be useful in selected cases. Branched chain fatty acid structure Lacks the nitrogen or aromatic moiety present in other AEDs Antiepileptic activity greatest for carbon chain length of 5-8 atoms Increasing to 9 atoms imparts sedative effects References: Katzung Basic and Clinical Pharmacology, 9th ed. The Treatment of Epilepsy, 3rd ed.

Valproic Acid Significant drug interactions : Enzyme-inducing drugs and imipenem antibiotics reduce serum valproic acid levels. Felbamate, stiripentol, isoniazid and other drugs may increase valproic acid levels. Valproic acid inhibits the metabolism of a number of drugs, most notably phenobarbital, lamotrigine and rufinamide. Valproic acid displaces phenytoin from plasma protein binding sites and may inhibit phenytoin metabolism at the same time Common/important adverse effects: Tremor, sedation, asthenia, encephalopathy, extrapyramidal symptoms, nausea, vomiting, hyperammonemia, weight gain, polycystic ovary syndrome, hair loss, platelet and coagulation disorders, liver toxicity, pancreatitis, teratogenic effects (including spina bifida) Main advantages: Unsurpassed efficacy in most generalized epilepsy syndromes. Broad spectrum efficacy in different seizure types Main disadvantages: Weight gain, severe liver toxicity (particularly in children), teratogenicity References: Katzung Basic and Clinical Pharmacology, 9th ed. The Treatment of Epilepsy, 3rd ed.

Other Modalities Surgical Management
Surgical excision of epileptic foci in simple and complex partial epilepsies that have not responded to intensive and prolonged medical therapy may be beneficial for some. Regulation of Physical and Mental Activity Precipitating factors need to be modified and stressed to the patient. Moderate amount of physical exercise can also be advised. Psychosocial difficulties need to be identified and addressed early. Reference: The Treatment of Epilepsy, 3rd ed.

Other Modalities Ketogenic Diet Vagal Nerve Stimulation
biochemical alteration both in the blood and in the brain possible GABA-mimetic effects of ketosis given the structural similarities of GABA, -hydroybutyrate and acetoacetate Vagal Nerve Stimulation vagal stimulation produces its effects are unclear and it is done through attachment of electrodes to the vagus nerve at the left carotid bifurcation Reference: The Treatment of Epilepsy, 3rd ed.

Management American Academy of Neurology Guidelines on CESSATION OF TREATMENT Stopping the treatment may be considered when: The patient has been seizure-free for 2 to 5 years. The patient has a single type of seizure. The patient has no abnormalities on neurologic examination and has a normal IQ. The patient’s electroencephalogram (EEG) has become normal.

Case 2.2

CASE 2.2 A 17 year-old male had an excellent antiepileptic drug control of his generalized tonic-clonic seizures for the past 3 years. Work up done showed an abnormal EEG patterns consistent with generalized type of seizures and a normal cranial CT scan.

Missing Data Initial presentation of the patient when diagnosis was established Family history History of trauma, loss of consciousness, severe headache Precipitating factors Fever, stress, fatigue, sleep deprivation, drug abuse, alcohol Prodromal symptoms Mood changes, sleep disturbances, lightheadedness, anxiety, irritability, difficulty concentrating Compliance to anti-epileptic medications Frequency, duration and presentation of the patient during the recent attack Lacking detailed history of the HPI

Salient Features 17 year-old Male
3 year history of generalized tonic-clonic seizures- controlled Abnormal EEG patterns consistent with generalized type of seizures Normal cranial CT scan

Clinical Impression: Generalized Tonic Clonic Seizures, controlled

Generalized Seizures Generalized tonic clonic Myoclonic
Paroxysmal discharges occurring in both hemispheres Convulsive Generalized tonic clonic Nonconvulsive Myoclonic Tonic or Atonic Absence Reference: Rohkamm, Color Atlas of Neurology © 2004 Thieme

Generalized Seizures CAUSES Genetic Acquired Predisposition
Hereditary diseases associated with epilepsies: Tuberous sclerosis, Sturge–Weber syndrome Mitochondrial encephalopathies Sphingolipidoses Acquired Focal – possibly with secondary generalization Bilateral Diffuse – primary generalized epilepsies The causes include developmental disorders, pyridoxine deficiency, hippocampal sclerosis, brain tumors, head trauma, cerebrovascular disturbances, alcohol, drug abuse, medications, and CNS infections. Causes Reference: Rohkamm, Color Atlas of Neurology © 2004 Thieme

Feature Tonic-clonic Seizure Absence Seizure Myoclonic Seizure
Consciousness Impaired Unaffected Duration 1–3 minutes A few (≤30) seconds 1–5 seconds Symptoms and signs Initial cry (occasionally); falls (loss of muscle tone); respiratory arrest; cyanosis; tonic, then clonic seizures; muscle relaxation followed by deep sleep. Tongue biting, urinary and fecal incontinence Brief absence, vacant gaze and blinking followed by immediate return of mental clarity; automatisms (lip smacking, chewing, fiddling, fumbling) may occur Sudden, bilaterally synchronous jerks in arms and legs; often occur in series Age group Any age Children and adolescents Children and adolescents Ictal EEG Often obscured by muscle artifacts Bilateral regular 3 (2–4) Hz spike waves Polyspike waves, spike waves, or sharp and slow waves Hindi ko cnma ung atonic seizures kc ang age grup nya is infants and children, eh 17y/o ung px ntin.. Reference: Rohkamm, Color Atlas of Neurology © 2004 Thieme

Generalized Tonic-Clonic Seizure
A seizure involving the entire body. It is also called a grand mal seizure. Usually involves muscle rigidity, violent muscle contractions, and loss of consciousness They may occur in people of any age, as a single episode, or as part of a repeated, chronic condition (epilepsy). Internationally, as in the United States, only a small proportion of seizures are generalized tonic-clonic seizures (20-25%). Generalized tonic-clonic seizures are the type of seizure that most people associate with the term "seizure," convulsion, or epilepsy.

Pathophysiology Thought to be initiated by 3 different mechanisms: Abnormal response of hyperexcitable cortex to initially normal thalamic input Primary subcortical trigger Abnormal cortical innervation from subcortical structures A seizure results from a paroxysmal high-voltage electrical discharge of susceptible neurons within an epileptogenic focus. These neurons are known to be hyperexcitable and, for unknown reasons, remain in a state of partial depolarization. Generalized tonic-clonic seizures are the type of seizure that most people associate with the term "seizure," convulsion, or epilepsy.

Pathophysiology GABA-ergic and hyperpolarized neurons surrounding the epileptogenic focus inhibit the epileptogenic neurons. At times, when the epileptogenic neurons overcome the surrounding inhibitory influence, the seizure discharge spreads to neighboring cortical structures and then to subcortical and brainstem structures. Generalized tonic-clonic seizures are the type of seizure that most people associate with the term "seizure," convulsion, or epilepsy.

Pathophysiology Brainstem structures involved: Lateral geniculate body – produces a generalized tonic-clonic seizure when kindled in the cat Ascending pathways through the mamillary bodies and anterior thalamus Substantia nigra – includes a nigrotectal GABA-ergic projection and locus ceruleus Phases: Tonic, Clonic, Post-ictal Tonic Phase - spread of excitability to subcortical, thalamic, brainstem, and spinal cord structures Clonic phase – discontinuous bursts of electrical activity brought about by the interruption of the tonic phase by an inhibitory impulse which starts from the thalamus Generalized tonic-clonic seizures are the type of seizure that most people associate with the term "seizure," convulsion, or epilepsy.

Tonic & Clonic Phases Loss of consciousness or fainting – 30 sec to 5 mins. General muscle contraction and rigidity (tonic phase) – sec. Violent rhythmic muscle contraction and relaxation (clonic phase) – 1-2 mins. Biting the cheek/tongue, clenched teeth/jaw Incontinence Stopped breathing or difficulty breathing during seizure Cyanosis Post-ictal Phase Normal breathing Sleepiness – 1 hr or longer Loss of memory (amnesia) regarding events surrounding the seizure episode Headache Drowsiness Confusion, temporary and mild Weakness for up to hours following seizure (Todd's paralysis)

Initial Diagnostic Evaluation
CBC Blood chemistries Liver and thyroid function tests EEG Imaging study of the brain, preferably MRI Video/EEG or prolonged EEG monitoring Other forms: cardiac stress tests, Holter monitor, tilt- table testing, sleep studies CT scanning may only be feasible in an emergency or for very young children. Other forms are sometimes indicated in order to exclude some of the nonepileptic disorders.

EEG Initial Phase Clonic Phase Post-ictal Phase
Movement artifacts obscure the EEG tracing. (+) repetitive spikes or spike-wave discharges lasting a few seconds, followed by an approximately 10-s period of 10-Hz spikes. Clonic Phase Spikes become mixed with slow waves Then, EEG slowly assumes a polyspike-and-wave pattern. Post-ictal Phase Nearly flat for a variable time Brain waves then gradually resume their pre-seizure pattern.

Treatment

Choices of Antiepileptic Drugs by Type of Adult Seizure Disorders
SEIZURE TYPE INITIAL CHOICE SECOND LINE Tonic-clonic Carbamazepine, valproate, phenytoin Lamotrigine, oxcarbazepine Myoclonic Valproate Topiramate, levetiracetam, zonisamide Partial Carbamazepine, phenytoin Valproate, lamotrigine, oxcarbazepine, levetiracetam Absence Ethosuximide, lamotrigine Unclassifiable Lamotrigine Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

General Principles of Treatment
The use of antiepileptic drugs is the most important factor of treatment. Establish the diagnosis and rule out underlying pathology. Classify seizure type, using EEG and clinical criteria. Because of the long half-lives of phenytoin, phenobarbital, and ethosuximide, these drugs need be taken only once daily. Valproate and carbamazepine have shorter half-lives, and their administration should be spaced during the day. In approximately 70 percent of all the patients with epilepsy, the seizures are controlled completely or almost completely by medications; in additional 2o to 25 percent, the attacks are significantly reduced in number and severity. Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

Serum-protein binding characteristics of antiepileptic drugs and the interactions among these drugs and between antiepileptic and other drugs should be considered. Initially, only one drug should be used and the dosage increased until sustained therapeutic levels have been attained. If the first drug does not control seizures, a different one should be tried, but frequent shifting of drugs is not advisable. In changing medication, the dosage of the new drug should be increased gradually to an optimum level while the dosage of the old drug is gradually decreased; the sudden withdrawal of a drug may lead to an increase in seizure frequency or status epilepticus. Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

Phenytoin, carbamazepine, and valproate are representative of antiepileptic drugs and are more or less equally effective in the treatment of both generalized and partial seizures. Phenytoin and carbamazepine act by blocking sodium channels, thus preventing abnormal neuronal firing and seizure spread. Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

Phenytoin Pediatric Dosage: 4-7 mg/kg Adult Dosage: 300-400 mg/day
Oral, IM or IV Idiosyncratic phenytoin hypersensitivity: rash, fever, lymphadenopathy, eosinophilia and other blood dyscrasias, and polyarteritis Overdose: ataxia, diplopia, stupor, hirsutism, hypertrophy of gums, coarsening of facial features Chronic use may be associated with peripheral neuropathy, some form of cerebellar degeneration. Phenytoin should not be used with: disulfiram, chloramphenicol, sulfamethizole, phenylbutazone, or cyclosphosphamide Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

Carbamazepine Pediatric Dosage: 20-30 mg/kg
Adult Dosage: mg/day This drug causes same effects with phenytoin, but to a slightly lesser degree. Mild leukopenia is common; pancytopenia, hyponatremia, diabetes insipidus are rare. Oxcarbazepine, a more recently introduced analogue or carbamazepine, has fewer side effects, especially marrow toxicity. Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

Valproate Pediatric Dosage: 30-60 mg/kg Adult Dosage: 1000-3000 mg/day
All preparations are hepatotoxic. There has been evidence of weight gain during the first months of therapy with valproate. Menstrual irregularities and PCOS may appear in young women taking the drug. Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

Phenobarbital Pediatric Dosage: 3-5 mg/kg Adult Dosage: 90-200 mg/day
Still highly effective, but has many toxic effects: drowsiness, mental dullness, nystagmus, staggering Phenobarbital and primidone may provoke behavioral problems in retarded children. It is still used to advantage as an adjunctive anticonvulsant and as a primary therapy in infantile seizures. Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

Lamotrigine Pediatric Dosage: 0.5 mg/kg Adult Dosage: 300-500 mg/day
Lamotrigine closely resembles phenytoin in its antiseizure activity but has different features relating to toxicity. It selectively blocks the slow sodium channels, thereby preventing the release of the excitatory neurotransmitters glutamate and aspartate. It is effective as a first-line and adjunctive drug for generalized and focal seizures. It does not provoke weight gain and ovarian problems. Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

Discontinuation of Anticonvulsants
Withdrawal of anticonvulsant drugs may be undertaken in patients who have been free of seizures for a prolonged period. If the EEG tracing is abnormal by way of showing paroxysmal activity, it is generally better to continue treatment. Callaghan et al. In patients who had been seizure-free during 2 years of treatment with a single drug, 1/3 relapsed after discontinuation of the drug. This relapse rate was much the same in adults and children and whether the drug was reduced over a period of weeks or months. Relapse rate was lower in patients with absence and generalized onset seizures than in patients with complex partial seizures and secondary generalization. Ang pagkagets ko dito eh sa case, pwede ng babaan ung dose kasi ganun din naman ung risk Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

Discontinuation of Anticonvulsants
Specchio et al. After 2 years on a single anticonvulsant during which no seizures had occurred, the rate of relapse was 40% 2.5 years later and 50% at 5 years after discontinuation. This compared to a seizure recurrence rate of 20% for patients remaining on medication. A longer seizure-free period is associated with a lesser rate of relapse. Dito naman, 20% vs 40% yung risk of relapse. So I guess depende sa doc un. Pwede ng babaan ung dose or idiscontinue na kasi matagal ung seizure-free period nung px. Reference: Adams and Victor’s Principles of Neurology, 9th Edition.

Prognosis With treatment, seizures are eliminated in one-third of patients with epileptic seizures, and frequency of seizures is reduced by > 50% in another one-third. About 60% of patients whose seizures are well- controlled by drugs can eventually stop the drugs and remain seizure-free. Sudden unexplained death in epilepsy (SUDEP) is a rare complication of unknown cause. Good prognosis for the case Reference:

Case 2.3

CASE 2.3 An 11 month-old male infant was rushed to the hospital because of first-onset and single episode of generalized seizure. The infant was noted to be coughing with nasal catarrh for the last 5 days. Hours before the seizure episode, his temperature was taken to be 38.9C. Perinatal and postnatal histories were unremarkable. The father admitted to be having the same episodes when he was still around 5 years old during the height of his fever. Neurological examination was normal.

Salient Features 11 months old Male Recent URI
Spike in body temp 38.9 °C (+)Family history Normal Neuro Exam

Missing Data Duration of the seizure episode
If there are other accompanying symptoms such as vomiting, loss of consciousness, urinating or soiling himself. Recent vaccination (DTP or MMR)

Clinical Impression: Febrile Seizure

DIFFERENTIAL DIAGNOSIS
Meningitis Encephalitis Epilepsy

MENINGITIS An inflammation of the membranes (meninges) and cerebrospinal fluid surrounding the brain and spinal cord, usually due to the spread of an infection. The swelling associated with meningitis often triggers the "hallmark" symptoms of this condition, including headache, fever and a stiff neck. Meningitis is an infection and inflammation of the fluid and three membranes (meninges) protecting your brain and spinal cord. The tough outer membrane is called the dura mater, and the delicate inner layer is the pia mater. The middle layer is the arachnoid, a web-like structure filled with fluid that cushions the brain.

MENINGITIS Most cases of meningitis are caused by a viral infection, but bacterial and fungal infections also can lead to meningitis. Bacterial infections are the most damaging, identifying the source of the infection is an important part of developing a treatment plan. Depending on the cause of the infection, meningitis can resolve on its own in a couple of weeks — or it can be a life-threatening emergency.

Acute Bacterial Meningitis
Usually occurs when bacteria enter the bloodstream and migrate to the brain and spinal cord. Can directly invade the meninges, as a result of an ear or sinus infection or a skull fracture.

Streptococcus pneumoniae Most common cause of bacterial meningitis in infants and young children in the United States. Neisseria meningitidis Another leading cause of bacterial meningitis. It commonly occurs when bacteria from an upper respiratory infection enter your bloodstream. Highly contagious and may cause local epidemics in college dormitories and boarding schools and on military bases.

Haemophilus influenzae Before the 1990s, Haemophilus influenzae type b (Hib) bacterium was the leading cause of bacterial meningitis. Hib vaccines —routine childhood immunization Greatly reduced the number of cases of this type of meningitis It tends to follow an upper respiratory infection, ear infection (otitis media) or sinusitis. Listeria monocytogenes These bacteria can be found almost anywhere — in soil, in dust and in foods that have become contaminated Soft cheeses, hot dogs and luncheon meats Most healthy people exposed to listeria don't become ill Pregnant women, newborns and older adults tend to be more susceptible. Listeria can cross the placental barrier, and infections in late pregnancy may cause a baby to be stillborn or die shortly after birth.

MENINGITIS Viral meningitis Chronic meningitis
Usually mild and often clears on its own within two weeks A group of common viruses known as enteroviruses are responsible for about 90 percent of viral meningitis in the United States Most common signs and symptoms: Rash, sore throat, joint aches and headache “Worst headache I've ever had” Chronic meningitis Ongoing (chronic) forms of meningitis occur when slow-growing organisms invade the membranes and fluid surrounding the brain Although acute meningitis strikes suddenly, chronic meningitis develops over four weeks or more Signs and symptoms: Headaches, fever, vomiting and mental cloudiness Rare

MENINGITIS Fungal meningitis Other Causes Relatively uncommon
Cryptococcal meningitis Fungal form of the disease that affects people with immune deficiencies, such as AIDS Life-threatening if not treated with an antifungal medication Other Causes Meningitis can also result from noninfectious causes, such as drug allergies, some types of cancer and inflammatory diseases such as lupus.

Reference: Harrison’s Principles of Internal Medicine, 17th Edition.

MENINGITIS CASE II month old male infant
First onset and single episode of generalized seizure coughing with nasal catarrh for the last 5 days T = 38.9C Perinatal and postnatal histories were unremarkable The father admitted to be having the same episodes when he was still around 5 years old during the height of his fever Neurological examination was normal MENINGITIS History of infection Classic triad of fever, headache, and nuchal rigidity (+) Kernig's sign and Brudzinski's sign Decreased level of consciousness occurs in >75% of patients and can vary from lethargy to coma Nausea, vomiting, and photophobia are also common complaints Seizures Raised ICP Reduced level of consciousness, papilledema, dilated poorly reactive pupils Seizures occur as part of the initial presentation of bacterial meningitis or during the course of the illness in 20–40% of patients Focal seizures are usually due to focal arterial ischemia or infarction, cortical venous thrombosis with hemorrhage, or focal edema. Generalized seizure activity and status epilepticus may be due to hyponatremia, cerebral anoxia, or, less commonly, the toxic effects of antimicrobial agents such as high-dose penicillin Raised ICP is an expected complication of bacterial meningitis and the major cause of obtundation and coma in this disease of increased ICP include a deteriorating or reduced level of consciousness, papilledema, dilated poorly reactive pupils, sixth nerve palsies, decerebrate posturing, and the Cushing reflex (bradycardia, hypertension, and irregular respirations). The most disastrous complication of increased ICP is cerebral herniation

ENCEPHALITIS “Inflammation of the brain," it usually refers to brain inflammation resulting from a viral infection. Primary encephalitis Involves direct viral infection of the brain and spinal cord Secondary encephalitis A viral infection first occurs elsewhere in the body and then travels to the brain In contrast to viral meningitis, where the infectious process and associated inflammatory response are limited largely to the meninges, in encephalitis the brain parenchyma is also involved.

ENCEPHALITIS It can be caused by: Bacterial infection
Spreads directly to the brain (primary encephalitis) Bacterial meningitis A complication of a current infectious disease Syphilis (secondary encephalitis) Parasitic or protozoal infestations Can also cause encephalitis in people with compromised immune systems Such as toxoplasmosis, malaria, or primary amoebic meningoencephalitis Lyme disease and/or Bartonella henselae may also cause encephalitis

ENCEPHALITIS CASE II month old male infant
First onset and single episode of generalized seizure Coughing with nasal catarrh for the last 5 days T = 38.9C Perinatal and postnatal histories were unremarkable The father admitted to be having the same episodes when he was still around 5 years old during the height of his fever Neurological examination was normal. ENCEPHALITIS History of infection Fever, headache and nuchal rigidity (+) Kernig’s and Brudzinski’s sign Photophobia and seizures Altered level of consciousness Evidence of either focal or diffuse neurologic signs and symptoms Focal findings are aphasia, ataxia, upper or lower motor neuron patterns of weakness, involuntary movements and cranial nerve deficits Hallucinations, agitation, personality change, behavioral disorders, and, at times, a frankly psychotic state Focal findings are aphasia, ataxia, upper or lower motor neuron patterns of weakness, involuntary movements (e.g., myoclonic jerks, tremor), and cranial nerve deficits (e.g., ocular palsies, facial weakness) Involvement of the hypothalamic-pituitary axis may result in temperature dysregulation, diabetes insipidus, or the development of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

EPILEPSY Classified as a disorder of at least two unprovoked recurrent seizures. More common in young and old, plateau at 2nd – 4th decades of life In children (0-14 years old) congenital> trauma=infection>CVA=tumor

EPILEPSY Genetic Predispostion
The direct result of a known or presumed genetic defect in which seizures are the core symptom of the disorder. Examples include childhood absence epilepsy, autosomal dominant nocturnal frontal lobe epilepsy, and Dravet syndrome.

EPILEPSY Epileptic Seizures
No sexual predisposition, may occur at any age. Loss of consciousness is common. Onset is usually abrupt and may have a short aura. Vocalization is present during automatism.

Dravet’s Syndrome Severe myoclonic epilepsy of infancy (SMEI)
Generalized epilepsy syndrome Onset is in the first year of life. Peaks at about 5 months of age with febrile hemiclonic or generalized status epilepticus. Boys are twice as often affected as girls. Prognosis is poor.

Most cases are sporadic.
Family history of epilepsy and febrile convulsions is present in around 25 percent of the cases. Known causative genes are the sodium channel α subunit genes SCN1A and SCN2A, an associated β subunit SCN1B, and a GABAA receptor γ subunit gene, GABRG2.

Pathophysiology Seizure Generation Hyperexcitable state Cellular Level
Na+ channels Increase Influx of Na+ Increase intracellular Na+ and water Increase Tissue excitability Cations Ca2+ channels K+ channels Decrease intracellular K+ Cell hyperexcitability Firing of thalamic and cortical neurons Synaptic Level GABA Decreased Glutamate Increased Hyperexcitable state

CASE DRAVET’S SYNDROME
II month old male infant First onset and single episode of generalized seizure Coughing with nasal catarrh for the last 5 days T = 38.9C Perinatal and postnatal histories were unremarkable. The father admitted to be having the same episodes when he was still around 5 years old during the height of his fever. Neurological examination was normal. DRAVET’S SYNDROME Onset is in the 1st year of life. Peaks at about 5 months of age with febrile hemiclonic or generalized status epilepticus Boys are twice as often affected as girls. (+)Family History

Febrile Seizures

Febrile Seizure Most common type of seizure that occurs during childhood that is associated with a febrile illness not caused by an infection of the central nervous system (CNS), without previous neonatal seizures or a previous unprovoked seizure, and not meeting the criteria for other acute symptomatic seizures (International League Against Epilepsy). Rare before 9 months and after 5 years of age The peak age of onset is months. A strong family history of febrile convulsions in siblings and parents suggests a genetic predisposition. In a child with febrile seizure, the risk of febrile seizure is 10% for the sibling and almost 50% for the sibling if a parent has febrile seizures as well. References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com

Febrile Seizure Febrile seizures are not associated with reduction in later intellectual performance, and most children with febrile seizures have only a slightly greater risk of later epilepsy than the general population. Usually it takes the form of a single, generalized motor seizure occurring as the temperature rises or reaches its peak. Seldom does the seizure last longer than a few minutes. By the time an EEG can be obtained, there is usually no abnormality. Recovery is complete. References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com

Risk Factors Family history of febrile seizures High temperature
Parental report of developmental delay Neonatal discharge at an age greater than 28 days (suggesting perinatal illness requiring hospitalization) Daycare attendance Presence of 2 of these risk factors increases the probability of a first febrile seizure to about 30%. Maternal alcohol intake and smoking during pregnancy has a 2-fold increased risk. References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com

Types of Febrile Seizure
Simple Associated with a core temperature that increases rapidly to ≥39°C. It is initially generalized and tonic-clonic in nature. Lasts a few seconds and rarely <15 mins. Followed by a brief postictal period of drowsiness. Occurs only once in 24 hrs. Complex Duration is >15 mins. Focal seizure activity or focal findings are present during the postictal period. Repeated convulsions occur within 24 hrs. References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com

Recurrent Seizures Approximately 30–50% of children have recurrent seizures with later episodes of fever and a small minority has numerous recurrent febrile seizures. Risk factors for recurrent febrile seizures include the following: Young age at time of first febrile seizure <12 mos. Relatively low fever at time of first seizure Family history of a febrile seizure in a first-degree relative Brief duration between fever onset and initial seizure Multiple initial febrile seizures during same episode Patients with all 4 risk factors have greater than 70% chance of recurrence. Patients with no risk factors have less than a 20% chance of recurrence. References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com

Pathophysiology Febrile seizures occur in young children at a time in their development when the seizure threshold is low. This is a time when young children are susceptible to frequent childhood infections such as upper respiratory infection, otitis media, viral syndrome, and they respond with comparably higher temperatures. Animal studies suggest a possible role of endogenous pyrogens, such as interleukin 1beta, that, by increasing neuronal excitability, may link fever and seizure activity. Preliminary studies in children appear to support the hypothesis. Figure 1. The sequence of events leading to seizures after fever in rat pups. An increase in the respiratory rate produced by hyperthermia enhances elimination of CO2, resulting in brain alkalosis. Neurons in the cortex and the hippocampus are hyperexcited by alkalosis, and this leads to convulsions and epileptiform electrographic discharges, recorded in the cortex. The inspiration of ambient CO2, which generates acidosis, prevents brain alkalosis and thus the seizures. References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com

Febrile Seizures History
The type of seizure (generalized or focal) and its duration should be described to help differentiate between simple and complex febrile seizures. Focus on the history of fever, duration of fever, and potential exposures to illness. A history of the cause of fever (eg, viral illnesses, gastroenteritis) should be elucidated. Recent antibiotic use is particularly important because partially treated meningitis must be considered. A history of seizures, neurologic problems, developmental delay, or other potential causes of seizure (eg, trauma, ingestion) should be sought.

Febrile Seizures Physical Examination
The underlying cause for the fever should be sought. A careful physical examination often reveals otitis media, pharyngitis, or a viral exanthem. Serial evaluations of the patient's neurologic status are essential. Check for meningeal signs as well as for signs of trauma or toxic ingestion.

FEBRILE SEIZURES CASE II month old male infant
First onset and single episode of generalized seizure Coughing with nasal catarrh for the last 5 days T = 38.9C Perinatal and postnatal histories were unremarkable. The father admitted to be having the same episodes when he was still around 5 years old during the height of his fever. Neurological examination was normal. FEBRILE SEIZURES History of infection Ages of 3 months and 5 years Twice more common in boys than girls Fever and seizures

Management

Diagnostics To determine the cause of the fever
To rule out meningitis or encephalitis

Lumbar Puncture with CSF examination
Cerebrospinal fluid (CSF) is essential in confirming the diagnosis of meningitis, encephalitis, and subarachnoid hemorrhage.

Lumbar Puncture with CSF Examination
Contraindications: Elevated ICP owing to a suspected mass lesion of the brain or spinal cord Symptoms and signs of pending cerebral herniation in a child with probable meningitis Critical illness Skin infection at the site of the LP Thrombocytopenia

Lumbar Puncture with CSF examination
WBC Protein Sugar Others Normal 0-5 lymphocyte 15-45 50-75 >50% of blood sugar Clear Acute bacterial High neutrophil → (after 5 days) lymphocytes High Low Turbid Viral N or slight increase TB lymphocytes Low <40 Xanthochromic

EEG Not recommended after an initial simple febrile seizure in children with a normal neurologic examination. Typically does not identify specific abnormalities or help predict recurrent seizures. Consideration of EEG if febrile seizures are complex or recurrent. Reference:

Treatment

Treatment for Nasal Catarrh
Pseudoephedrine/Dextromethorphan can be given for the cough and decongesting the airways of the infant. It works by constricting blood vessels and reducing swelling in the nasal passages, which helps you to breathe more easily. The cough suppressant works in the brain to help decrease the cough reflex. However, you should not use decongestants for more than 5-7 days at a time. This is because they can only provide short-term relief for catarrh, and using them for any longer can make your symptoms worse.

Medical Treatment Treatment of infants with seizures is different than treatment for adults. Unless a specific cause is found, most infant with first-time seizures will not be placed on medications.

Medical Treatment Phenobarbital
- Enhances the inhibitory actions of gamma- aminobutyric acid (GABA) on neurons. - Decreases the occurrence of subsequent febrile seizures. - Oral Dosage (as recommended by the American Academy of Pediatrics): 1 to 3 mg/kg.

Medical Treatment Benzodiazepine Centrally acting muscle relaxant.
Gel, rectal 2.5 mg (pediatric) Anticonvulsant properties may be in part or entirely due to binding to voltage-dependent sodium channels. It can reduce the risk of subsequent febrile seizures. Because it is given intermittently, this therapy probably has the fewest adverse effects. If preventing subsequent febrile seizures is essential, this would be the treatment of choice.

Medical Treatment Paracetamol (Acetaminophen)
- Inhibits prostaglandins in CNS, but lacks anti- inflammatory effects in periphery; reduces fever through direct action on hypothalamic heat-regulating center. -15 mg/kg; taken once every 4 hours, up to 4 times per day if needed

Prevention

Prevention Most seizures cannot be prevented.
There are some exceptions, but these are very difficult to control, such as head trauma and infections during pregnancy. Children who are known to have febrile seizures should have their fevers well controlled when sick.

Prevention The best way to prevent fevers is to reduce the infant's exposure to infectious diseases. Hand-washing is the single most important prevention measure for people of all ages.

Prevention If another seizure ensues:
The initial efforts should be directed first at protecting the infant from additionally injuring himself. Lie down the infant. Remove glasses or other harmful objects in the area. Do not try to put anything in mouth. In doing so, it may injure the infant. Immediately check if the infant is breathing. Call a doctor or proceed to the nearest hospital.

Case 2.4

Case 2.4 A 30 year-old female patient has been maintained on phenytoin 100 mg TID for the past 5 years with good control of her idiopathic generalized seizure. She is 3 months pregnant when she visited your clinic.

Missing Data (+) / (-) Frequency and Severity Associated with:
Subtherapeutic anticonvulsant levels Nausea and vomiting leads to missed doses. Expanded intravascular volume lowers serum drug levels. Hepatic, plasma and placental enzymes increase drug metabolism. Increased glomerular filtration hastens drug clearance.

Missing Data (+) / (-) Frequency and Severity Associated with:
Lower seizure threshold “Exhaustion from sleep deprivation”

Missing Data (+) / (-) Diabetes (+) / (-) Hypertension
(+) / (-) Intake of folic acid

Salient Features 3o year old female 1st trimester of pregnancy
Phenytoin 100mg TID for the past 5 years

Clinical Impression: Idiopathic Generalized Seizure Disorder

Generalized Tonic Clonic Seizure
Prodromal symptoms Occurring hours or days before a seizure. Mood changes, sleep disturbances, lightheadedness, anxiety, irritability, difficulty concentrating and, rarely, an ecstatic feeling, abdominal pain, facial pallor, or headache. Most patients lose consciousness without any premonitory symptoms. Patients with generalized tonic-clonic seizures do not have auras. An aura represents a simple partial seizure.

The patient may have completely nonfocal findings on neurologic examination when not having seizures. Seizures typically are divided into tonic, clonic, and postictal phases. Tonic phase The tonic phase begins with flexion of the trunk and elevation and abduction of the elbows. Subsequent extension of the back and neck is followed by extension of arms and legs. This can be accompanied by apnea, which is secondary to laryngeal spasm.

Autonomic signs are common during this phase and include increase in pulse rate and blood pressure, profuse sweating, and tracheobronchial hypersecretion. Although urinary bladder pressure rises, voiding does not occur because of sphincter muscle contraction. This stage lasts for seconds.

Clonic phase The tonic stage gives way to clonic convulsive movements, in which the tonic muscles relax intermittently, lasting for a variable period of time. A generalized tremor occurs at a rate of 8 tremors per second, which may slow down to about 4 tremors per second. Each spasm is accompanied by pupillary contraction and dilation. Some patients may have tongue or cheek bites. The atonic periods gradually become longer until the last spasm. Voiding may occur at the end of the clonic phase as sphincter muscles relax. The atonic period lasts about 30 seconds. The patient continues to be apneic during this phase. The convulsion, including tonic and clonic phases, lasts for 1-2 minutes.

Postictal state A variable period of unconsciousness during which the patient becomes quiet and breathing resumes. The patient gradually awakens, often after a period of stupor or sleep, and often is confused, with some automatic behavior. Headache and muscular pain are common. The patient does not recall the seizure itself.

Most generalized epilepsies are idiopathic, but a definite genetic locus has been found for some of these generalized types of epilepsy.

History Unusual sensations suggesting an aura Seizure manifestations
SUBTYPE MANIFESTATIONS Absence seizure Brief staring spells with arrest of activity, often w/ eye fluttering, which just last a few seconds Myoclonic seizure Very brief isolated body jerks that tend to occur in the morning Generalized tonic-clonic seizure Convulsions of the whole body lasting 1-2 minutes

History Ask about the first and any subsequent seizures. Duration
Frequency Sequential evolution Longest & shortest interval between seizures Aura Postictal state Precipitating factors

History Risk factors Rare triggers Sleep deprivation
Prior head trauma or CNS infection Drug use or withdrawal Alcohol withdrawal Non-adherence to anticonvulsants Family history of seizures or neurologic disorders Rare triggers Repetitive sounds Flashing lights Touching certain parts of the body Sleep deprivation Can lower the seizure threshold

Physical Examination A bitten tongue, incontinence (eg., urine or feces in clothing), or, in patients who have lost consciousness, prolonged confusion, suggest seizure. Physical examination rarely indicates the cause when seizures are idiopathic but may provide clues when seizures are symptomatic.

Intellectual functions, neurologic exam and imaging (MRI) are normal.
They are genetic and not caused by any brain physical abnormality. This means that the brain is anatomically normal. They basically represent a genetic low threshold (or high susceptibility) for seizures. People with IGE have normal intelligence, normal neurological examination, and normal MRIs.

Diagnostic evaluation must determine whether the event was a seizure vs. pseudoseizure or syncope.

EEG The only definitive test to confirm the diagnosis.
Represents a recurrent, sudden, excessive discharge of cortical neurons. When abnormal, it’s very characteristic: Interictal symmetric bursts of 4- to 7-Hz epileptiform activity Interictal spike-and-wave abnormalities without any clinical seizure activity Electroencephalography (EEG) is the recording of electrical activity along the scalp produced by the firing of neurons within the brain.[1] In clinical contexts, EEG refers to the recording of the brain's spontaneous electrical activity over a short period of time, usually 20–40 minutes, as recorded from multiple electrodes placed on the scalp. In neurology, the main diagnostic application of EEG is in the case of epilepsy, as epileptic activity can create clear abnormalities on a standard EEG study.[2] A secondary clinical use of EEG is in the diagnosis of coma, encephalopathies, and brain death.

EEG of the Subtypes of Generalized Seizure
EEG CHANGES Absence seizure Very characteristic pattern wave complexes Myoclonic seizure Bilateral polyspike and wave abnormality at a rate of 4- to 6-Hz Generalized tonic-clonic seizure Can show either of the above patterns or generalized spikes

Seizure and Pregnancy

Seizure and Pregnancy A woman with a seizure disorder can carry a pregnancy safely. Seizures can harm the developing fetus by reducing the blood supply to the placenta. For most pregnant women who have epilepsy, seizures remain the same. For a few, seizures become less frequent. For others — particularly women who have poorly controlled epilepsy — pregnancy increases the number of seizures.

Complications Severe morning sickness Anemia
Vaginal bleeding during and after pregnancy Abruptio placenta Pre-eclampsia Premature baby LBW baby Higher risk of complications

Complications The occurrence of seizures in the first trimester poses the greatest risk of congenital malformation and developmental delay in the offspring. For babies whose mothers take seizure medication, the risk of birth defects is 4 to 8 percent — compared with 2 to 3 percent for all babies. Higher risk of complications

An antifolate effect on blood and interference with vitamin K metabolism have been reported, for which reason pregnant women taking phenytoin should be given vitamin K before delivery and the newborn infant should receive vitamin K as well to prevent bleeding. Higher risk of complications

The obstetrician and neurologist should work together prior to conception and throughout the pregnancy to closely monitor seizures and contributing factors (eg., sleep deprivation and medication compliance). Higher risk of complications

AEDs & Pregnancy

Phenytoin Fetal hydantoin syndrome
craniofacial anomalies, distal digital hypoplasia, epicanthal folds, hypertelorism, low-set ears, and developmental delay Mothers who received phenytoin monotherapy during pregnancy demonstrated slightly delayed locomotor development. Higher risk of complications

Phenobarbital Fetal hydantoin syndrome and fetal alcohol syndrome
Higher risk of complications

Valproic Acid Syndrome of specific craniofacial abnormalities and long, thin digits with hyperconvex nails Neural tube defects Higher risk of complications

Carbamazepine Craniofacial abnormalities and hypoplastic nails
Neural tube defects and cardiac abnormalities Higher risk of complications

Trimethadione Epicanthal folds, low-set ears, microcephaly, short stature, and irregular teeth Rarely used in the treatment of epilepsy and should certainly be discontinued during pregnancy Higher risk of complications

Prevention and Treatment

Phenytoin: Fetal Hydantoin Syndrome
A 30 year-old female patient has been maintained on phenytoin 100 mg TID for the past 5 years with good control of her idiopathic generalized seizure. She is 3 months pregnant when she visited your clinic. Fetal Hydantoin Syndrome is typically characterized by altered growth, unusual facial features, underdeveloped fingers and toes, and mental deficiencies. The child with Fetal Hydantoin Syndrome may be small at birth, with increased hair on the body and face, and with poorly developed fingernails and toenails. He or she may have poor muscle tone and may be developmentally delayed. Other factors, such as decreased folic acid levels in the mother, may add to the likelihood that the child will exhibit features of the syndrome. Fetal Dilantin Syndrome, Fetal Effects of Mephenytoin, Fetal Hydantoin Effects, Fetal Effects of Hydantoin Anticonvulsants, Fetal Effects of Dilantin, Fetal Effects of Mesantoin and Fetal Effects of Phenytoin are the most commonly used terms to refer to the various forms of impact, resulting from exposure to Dilantin during pregnancy. The most consistent facial features found in affected infants have been a flat bridge of the nose, and eyes that are down-slanted, widely spaced, and crossed (strabismus). An underdeveloped vertical groove in the center of the upper lip (philtrum), cleft lip and/or palate, drooping eyelids (ptosis), and mild webbing of the neck have also been reported. Read more at Suite101: Fetal Hydantoin Syndrome (FHS): Neonatal Effects of Phenytoin (Dilantin) use During Pregnancy | Suite101.com

Because exposure to multiple antiepileptic drugs (AEDs) seems to be more teratogenic than monotherapy, patients are advised to switch to a single AED prior to conception and taper to the lowest possible dose.

Supplemental folate has been shown to decrease neural tube defects in patients without epilepsy and decrease other congenital anomalies in women with epilepsy. 4 mg of folic acid should be taken daily starting two to three months prior to pregnancy and be continued through the first trimester.

A fetal echocardiogram should be performed at 19 to 20 weeks’ gestation with careful attention to cardiac anomalies. Because of the increased risk neural tube defects, a maternal serum AFP and acetylcholinesterase screening test should be offered.

Preconceptual Management of Women With Epilepsy
Attempt to decrease pharmacotherapy to monotherapy. Taper dosages of AEDs to the lowest possible dose. In women who have not had a seizure for 2-5 years, attempt complete withdrawal of pharmacotherapy. Establish the level of total and free AEDs necessary for achieving good clinical control. Consider preconceptual genetic counseling. Supplement the diet with folate at 4 mg/d.

Management of Women With Epilepsy During Pregnancy
Check total and free levels of AEDs monthly. Consider early genetic counseling. Check maternal MSAFP levels and perform a level II fetal survey and ultrasonography at weeks' gestation. Consider amniocentesis for alpha-fetoprotein and acetylcholinesterase.

Gabapentin, lamotrigine, felbamate, topiramate, and oxcarbazepine
These newer anticonvulsants have not been studied extensively in pregnancy, though the use of pregnancy registries for AEDs are providing larger sample sizes. The benefits and risks between congenital anomalies and seizure control needs to be considered when preparing the women with epilepsy for pregnancy. The new anticonvulsants generally have a better pharmokinetic profile and are not metabolized to known teratogens. All of these anticonvulsants are considered US Food and Drug Administration pregnancy category C. Of note, they are still known to both cross the placenta and into breast milk. Several studies of in utero exposure reported either case reports of anomalies or no effects on the fetus. None of the existing studies revealed a rate of congenital malformations greater than that for a woman with epilepsy who is not taking AEDs. However, a large randomized trial did demonstrate that valproate leads to better seizure control than several of these newer AEDs.12 Thus,

Thank you.

Neurology Case Conference Subsection D2 Rivera. Rivere. Robosa. Rodas

Similar presentations

Presentation on theme: "Neurology Case Conference Subsection D2 Rivera. Rivere. Robosa. Rodas"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Neurology Case Conference Subsection D2 Rivera. Rivere. Robosa. Rodas

Similar presentations

Presentation on theme: "Neurology Case Conference Subsection D2 Rivera. Rivere. Robosa. Rodas"— Presentation transcript:

Similar presentations

About project

Feedback