Perspectives for Better Neurological Care

 

                    C. Robert Adams, M.D.

                            Board Certified Neurologist

       109 N. 15th St., Ste 14, Norfolk Ne. 68701 Phone: 402-371-0226 Toll Free: 888-516-2398

                                                 3900 Dakota Ave, South Sioux City, NE . 68776

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Dizziness, Seizures, and Spells – Oh My!

Alternative titles: 

“Paroxysmal Occurrences” 

“A Potpourri of Puzzling Neurologic Phenomena from Infants to Grandparents”

 

 

Accuracy in diagnosis leads to better treatment and happier patients.  Using monikers to label someone “epileptic” or “a hyperventilator” can sometimes add grief to an already difficult situation.  Always carefully individualize evaluations to respect the unique character of every patient. 

 

 

I.                   “I’m dizzy.”  There are four major categories of dizziness (syncope, vertigo, ataxia, cognitive).  It should be noted that there can be significant overlap with these different types of dizziness. 

A.    Syncope or diminished cerebral blood flow.

                                                            1.      Simple orthostatic hypotension (low blood pressure while standing up).

                                                            2.      Complicated orthostatic hypotension with iron deficiency, anemia, etc., playing a role. 

                                                            3.      Vasovagal phenomenon (common fainting), which can occur with striking “seizure-like convulsions.” (5% of fainters in a blood donation center have outright tonic-clonic activity as an accompaniment.)

                                                            4.      Breath-holding spells (tantrums), which may or may not be associated with mitigating pulmonary or cardiac disease.

                                                            5.      Pulmonary causes, particularly reactive airways disease (asthma) without significant or obvious wheezing (do not forget pulmonary embolism).

                                                            6.      Cardiac disease of a variety of types including coronary artery disease, congenital valve disease, vascular anomalies, and even intrinsic myocardial conduction defects.

B.     Vertigo or labyrinthine-like dizziness (a sensation of spinning or swaying, sometimes with nausea).

                                                            1.      Middle or inner ear infection, inflammation, or even “just” otitic pressure (extremely common in children and adults).

                                                            2.      Posttraumatic cochlear and labyrinthine dysfunction (such as after a motor vehicle accident).

                                                            3.      Drug-related or toxic vertigo such as a side effect of antibiotics, etc.

                                                            4.      Otosclerosis (ear “rocks”), especially in older patients.

                                                            5.      Structural causes, including cerebellopontine angle tumors (acoustic neuroma) and brainstem tumors.

 

*This is a presentation Dr. Adams has given to a number of audiences of doctors, nurses, and other health care professionals for CME, etc. 


 

 

C.     This leads us in to the third category of actual imbalance, which is or ataxia (difficulty walking and maneuvering with tendency towards falling).  This type of dizziness is associated with a wide-based stance, stumbling, plus obvious impairment of leg and foot function.

                                                            1.      Stroke (ischemic or hemorrhagic).

                                                            2.      Head trauma with or without intracranial bleeding.

                                                            3.      Vascular malformations (cavernous angiomas and aneurysms).

                                                            4.      Hydrocephalus.

                                                            5.      Intracranial tumors.

                                                            6.      Spinal cord tumors or masses causing myelopathy (spinal cord dysfunction), spinal stenosis, or herniated disks in the neck can cause ataxia.

                                                            7.      Lumbosacral radiculopathy (pinched low back nerves) as from herniated disk and arthritis.

7.                                                            8.      Peripheral neuropathy as from diabetes, toxicity from drugs, vitamin deficiency, and others.

D.    Last, vaguely described subjective or “cognitive” dizziness.

                                                            1.      Hyperventilation with panic attacks in the setting of anxiety is always the first to come to mind; however, all the other causes of dizziness should be ruled out first.  Patients with marked anxiety and panic attacks often are afflicted by other types of dizziness as well.  The “hidden” problems may be generating a secondary anxiety disorder.

                                                            2.      Medication or drug effect.

2.                                                            3.      Migrainous encephalopathy (confusional state).

3.                                                            4.      Discrete psychiatric disease.  Children with ADHD (attention deficit hyperactivity disorder) may feel their “mind is full” or overloaded.  A racing or ruminative mind in obsessive-compulsive disorder and bipolar illness can put a child’s brain in such a “buzz” that internal feelings and behavior can be very erratic and suddenly unpredictable. 

4.                                                            5.      Interictal or postictal state with seizures (epilepsy), which leads us in to the next part of our presentation.

 

II.                Seizure disorders (epilepsy) and available treatmentdiagnosis and treatment.

A.    General information.

                                                            1.      A seizure disorder is a paroxysmal involuntary electrical disturbance of brain function.  It may manifest as:

a.       An impairment or loss of consciousness.

b.      Abnormal motor activity.

c.       Behavior abnormalities.

d.      Sensory disturbances.

e.       Autonomic dysfunction.

                                                            2.      Epilepsy is defined as recurrent seizures unrelated to:

a.       Fever,

b.      Obvious acute traumatic cerebral insult, or

c.       Metabolic derangement.


 

 

                                                            3.      The designation “seizure disorder” is sometimes more tactful, kind, and more easily accepted than the label of “epilepsy.”  I try to reassure patients that seizure disorders or epilepsies are a very treatable entity that can be effectively dealt with just as with diabetes or asthma.  A misdiagnosis of epilepsy versus complicated fainting can drastically harm and change an individual’s future.

                                                            4.      Optimism that a normal lifestyle is possible should be balanced with caution of long-term or future issues.  (To obtain or renew a Nebraska driver’s license one has to be seizure free for three months before the application or renewal Regulations and restrictions vary considerably from state to state.)

                                                            5.      Death from seizure activity or epilepsy is extremely rare.  It most often occurs in individuals more handicapped by congenital brain abnormalities or acquired structural disease causing a more resistant electrical cerebral irritability in an already compromised brain.

                                                            6.      More common sequelae of seizures can include risks of head and dental injuries, aspiration pneumonia, stress fractures, and especially psychosocial hindrance in school and at work. 

                                                            7.      Precautions when taking a bath, swimming, operating dangerous machinery, or moving about in precarious or high places is in order if seizures are not yet controlled.

                                                            8.      Depression is common not only due to inherent predisposition in epileptics, but also to effects of medications.  Interictal or postictal state can be difficult to recognize and distinguish from depression or mood swings Head trauma patients with a frontal lobe syndrome can show an odd affect of emotional flatness. 

                                                            9.      Etiology of seizures include:

a.       Head trauma (history of a motor vehicle accident or of an assault).

b.      Stroke (ischemic or hemorrhagic infarction).

c.       Metabolic derangements, particularly hypoglycemia and hyponatremia.

d.      Toxic effects of drugs and chemicals, particularly psychotropics, antidepressants, stimulants, and even some antibiotics.  Aspartame or Nutrasweet can in some circumstances bring out seizures and migraines.

e.       Vascular malformations, particularly arteriovenous malformations, cavernous angiomas, etc., (e.g. Sturge-Weber Syndrome).

f.       Infectious inflammatory processes including meningitis and encephalitis from bacterial or viral causes, etc.  (Focal infections including chronic otitis media can sometimes cause focal inflammatory injury of the brain resulting in a seizure disorder even without history of meningitis.)

g.      Neoplasm or tumors of primary or metastatic character.

h.      Familial hereditary epilepsy and tendencies (without "structural” brain change).

i.        Genetic metabolic disturbances including inherited and mutated variety (tuberous sclerosis and neurofibromatosis).

j.        Idiopathic (no identifiable cause).


 

 

B.     Diagnostic stratification of epilepsies include:

                                                            1.      Etiologic:

a.       Symptomatic epilepsy as due to a brain lesion; for example, traumatic contusion, stroke or tumor.

b.      “Sympathetic” or accessory epilepsy due to extracerebral disturbances as from toxic drug effect, hyponatremia, or fever.  With regards to the latter, benign febrile seizures tend to be “benign,” except when they are not.  In particular, a febrile seizure of focal nature carries a particularly high risk for subsequent focal (partial) and partial complex seizures. 

c.       Essential or idiopathic epilepsy (no structural or metabolic brain abnormalities).

                                                            2.      An elaborate classification of epileptic spells includes:

a.       Simple partial or focal seizures, which begin in one discrete area on one side of the brain. There is minimal or limited impairment of consciousness.

i.        Focal motor.

ii.      Focal sensory.

iii.    Jacksonian with spread.

iv.    Versive or contraversive or “head turning” episodes.

v.      Speech arrest with preserved awareness.

vi.    Sensory symptoms including:

                                                                                                                                     a.      Visual (macropsia, micropsia, altered distance perception, etc.).

                                                                                                                                    b.      Auditory (a noise that is advancing, receding, louder, softer, etc.).

                                                                                                                                     c.      Olfactory (some symptoms can suggest localization of an irritating process or brain injury).

                                                                                                                                    d.      Gustatory.

                                                                                                                                     e.      Autonomic phenomenon (sweating, flushing, etc.).

b.      Complex partial, temporal lobe, or psychomotor seizures.

i.        Simple dulled attentiveness.

ii.      Complex mental phenomenon including déjà vu, jamais vu, and “dreamy states.”

iii.    Sudden forced emotional states such as unexplained instant combativeness.

iv.    Psychosensory phenomenon such as epigastric distress or chest heaviness with emotional feelings that can range from mild anxiety to intense terror.

v.      Sexual phenomenon even organisms can occur with seizures.

c.       Partial seizures secondarily generalized.  Phenomena can include Jacksonian spread and Todd’s or postictal paralysis.  (With the latter, a person may be “paralyzed” on one side for up to several minutes or even several days after a seizure.) 


 

d.      Generalized seizures occur with bilateral brain electrical irritability and instability without obvious focal onset.

i.        Simple absence seizures only with impairment only of consciousness.

ii.      Complex absence seizures include other phenomenon on top of the alteration of consciousness, such as: 

                                                                                                                                     a.      Myoclonic jerks or myoclonus.

                                                                                                                                    b.      Increased in postural tone.

                                                                                                                                     c.      Atonic types with loss of postoral tone.

                                                                                                                                    d.      Automatisms as with lip smacking and blinking.

                                                                                                                                     e.      Autonomic phenomenon including episodes associated with enuresis.  (All bedwetting is not due to delayed physical and social maturity.  Nocturnal seizures may present as bedwetting.) 

 

iii.    Myoclonic epilepsy.  (Not all myoclonic jerks are epileptic.)  Benign nocturnal myoclonic jerks are, of course, common.  Nonspecific myoclonic jerks can occur due to spinal cord disease and other structural injuries to the CNS.)

iv.    Infantile spasms.

                                                                                                                                     a.      The West syndrome is a triad of infantile spasms, mental deterioration, and a characteristic EEG picture of hypsarrhythmia.  This syndrome usually develops between 3 and 12 months of age, and the spasms have usually stopped before age 5, often transitions to other types of seizures.  The presentation is significant in that infantile spasms or “salaam attacks” can be mistaken for colic.  The spasms often occur in clusters in the early morning or upon awakening from a nap with the baby doubling up as if in pain and often crying afterwards.

v.      Clonic seizures.

vi.    Tonic seizures.

vii.  Grand mal or tonic-clonic seizures.

vii. Atonic seizures, particularly episodes that cause “drop attacks.”

ix.  Akinetic seizures or loss of movement, although without loss of muscle tone.

e.       On the other hand, to simplify classification of seizures, one could grossly consider two major types of seizure disorders: 

i.        Generalized seizures tend to cause unresponsiveness and bilateral or non-focal motor phenomenon.  There is no obvious structural cause.

ii.      Focal or partial complex seizures originating on one side of the brain and often suggesting discrete structural or identifiable etiologic injury to that side of the brain. 


 

 

C.     It is often difficult to assess impairment of consciousness in neonates, infants, and very young children.  Neonatology is, of course, a very delicate super specialization.  The clinical presentation of seizures in infants can be very subtle, nonspecific, and non-stereotyped (restlessness, yawning, crying, etc.)

 

D.    Diagnostic workup of a seizure should include:

                                                            1.      Historical clarification of familial predisposition as well as prior injuries or cerebral insults, and in particular, head trauma.  (Genetic disorders such as tuberous sclerosis and neurofibromatosis are common.)

                                                            2.      Metabolic workup,  including at least a complete blood count, chem profile with blood sugar and sodium level, magnesium, T4, TSH, and serum iron studies, with plus a serum ferritin. , aAdding more complex metabolic screens and genetic analysis dependsing upon the suggestive circumstances.  A lead level may be indicated.  A drug screen can be important, particularly to catch elicit drugs as with stimulant abuse or poisoning Screening for infection including blood cultures, urine tests, etc., may also be needed. 

                                                            3.      Brain imaging.

a.       CT scanning with contrast is the “gold standard” for identifying hemorrhage and clarifying traumatic injuries and as a tool to screen for aneurysms and vascular malformations.

b.      Magnetic resonance imaging (MRI) is more sensitive for posterior fossa or brainstem and cerebellar disease and for “subtle lesions” in the temporal areas.  The MRI is helpful in identifying multiple sclerosis and small vessel angiopathy (mini strokes).

c.       Magnetic resonance angiography (MRA) has in many cases replaced the more tedious and dangerous vascular injurious catheterization that was formerly needed for identification of aneurysms and vascular malformations.

d.      Positron emission tomography (PET) is used in evaluating focal metabolic function in different areas of the brain (differentiating malignant brain metastasis from radiation brain injury).

                                                            4.      An EEG or electroencephalogram, which helps in clarifying:

a.       Presence or absence of electrical irritability (a “normal” EEG does not absolutely rule out a seizure disorder).  Recurrent, unexplained stereotyped events may merit an empiric trial on anticonvulsants.  A positive response to treatment, however, does not necessarily confirm a diagnosis of epilepsy.  In particular, migraine phenomenon, panic attacks, and labile psychiatric changes can also respond positively to some of the newer “broad spectrum” anticonvulsants.  Some of the newer agents, for instance lamotrigine, can be very useful psychiatrically as a mood stabilizer (as for bipolar illness).

b.      Assessing frequency of electrical discharge and to help in assessment of the threshold (tendency) for further seizures.

c.       May help to judge the therapeutic benefit to a medication; however, do not chase the brain wave test (treat the paper) just to try to normalize it.  The seizure patient should be treated clinically, hoping to improve but not necessarily normalize the EEG.

d.      Lateralization to one side of the EEG to suggest focal structural disease.

e.       More definitive diagnosis in some cases from the EEG alone (as with familial epilepsies).

f.       Brain mapping can be helpful in localizing a locus of structural disease that might merit surgical intervention.   

                                                            5.      Ancillary tests to clarify manifestations of systemic disease:

a.       Chest x-ray to findsee pneumonia.

b.      An echocardiogram to identify congenital vascular abnormalities and valvular disease in the heart, which could be a source of emboli.

c.       A spinal tap if meningitis is suspected.

 

 

E.     Palliation or treatment of seizure disorders.  I think it would be most edifying usefuto start from the most easy and common sense suggestions and progress to the most drastic and heroic treatments:

                                                            1.      Never forget to counsel with regards:

a.       Avoiding fasting or skipping meals.

b.      Getting regular sleeping hours, particularly not enough sleep but also considering issues of disturbed circadian rhythms and excessive sleeping.

c.       Avoidance of alcohol, particularly alcoholic binges.

d.      Caution with regards to flickering stimuli as from video games.

e.       Do not overestimate or “push” the issue of stress as a reason for the medical problem.  Never forget that all medical problems cause significant stress and anxiety even as apart from pre-existing psychiatric tendencies and conditions.

                                                            2.      Correction of modifiable derangements including:

a.       Infection as from septicemia or meningitis.

b.      Metabolic disturbances, particularly hyponatremia, hypomagnesia, and hypocalcemia.

c.       Removal of toxic provocation as with aminophylline.  (There is almost no reason to use CNS toxic aminophylline any more with the asthma treatments now available.) 

                                                            3.      Drug therapy (to be further discussed). 

                                                            4.      Vagus nerve stimulation. 

                                                            5.      Deep brain stimulation. 

                                                            6.      Ketogenic diet or liquid fat supplement (besides being distasteful, long-term vascular disease is a concern). 

                                                            7.      Brain resection of not only obvious neoplastic processes but also of resistant irritable electrical scar foci. 

 

F.      Drug treatment.

                                                            1.      Common or “class action” side effects are:

a.       Dizziness, including ataxia and vertigo.

b.      Somnolence.

c.       Asthenia (fatigue).

d.      Mental slowing, including problems with word finding.  (This is an important issue in children who are developing their thought patterns and speed of communication.)

e.       Personality change.  (Depression, new onset aggressive tendencies, and even simple loss of enthusiasm.  Suicidal ideation is not common without other psychiatric factors involved.)

f.       Outright psychosis.

f.g.      Headaches.

g.h.      Gastrointestinal tract upset.

h.i.        Rash.

i.        Usually occurs within several days to up to six to eight weeks after exposure but not always.

ii.      Make sure the drug is the culprit.  Do not be fooled by:

                                                                                                                                     a.      Poison ivy.

                                                                                                                                    b.      Bug bites.

                                                                                                                                     c.      Allergies to other substances including foods, skin care products such as lotions and soaps.

                                                                                                                                    d.      Viral and other infections.

                                                                                                                                     e.      Other drugs reactions.

                                                                                                                                     f.      Photosensitivity to sun can occur, although without “true” rash.

iii.    Prominent rash on the trunk probably promotes more suspicion for skin reaction to the anticonvulsant (drug).

iv.    Clarification of an anticonvulsant rash or sensitivity is critical to not “burn bridges” with a therapeutic approach that may be desperately needed in the future.

v.      If an antiepileptic drug (AED) is a suspected cause of a rash, always stop the drug due to possible relentless progression to Stevens-Johnson syndrome or toxic epidermal necrolysis.

i.j.        Interference with the effects of oral contraceptive drugs or other drug levels.

j.k.      Disturbances of weight regulation (changes in appetite or metabolism).

k.l.        Exacerbation or alteration of seizures can occur.  Take the family seriously if they report increased seizures or other new phenomena are associated with the institution of a new the drug.

l.m. Unique side effects more commonly seen with certain drugs.

i.        Blood dyscrasias including aplastic anemia as from felbamate (Felbatol).

ii.      Hepatic failure or dysfunction as from felbamate (Felbatol) and valproic acid (Depakote ER).  It should be clarified that phenytoin (Dilantin) very commonly causes a “reactive” elevation of liver enzymes that can be “followed” and is not necessarily harmful or consequential.  Valproic acid can cause troublesome hyperammonemia even without obvious liver enzyme disturbance.

iii.    Gingival hyperplasia as from phenytoin (Dilantin).

iv.    Nephrolithiasis from topiramate (Topamax) and zonisamide (Zonegran). 

v.      Open-angle glaucoma as from topiramate (Topamax).

vi.    Hyponatremia from carbamazepine (Tegretol, Carbatrol) and to a lesser extent oxcarbazepine (Trileptal).

vii.  Irritability, confusion, and psychosis with levetiracetam (Keppra) and zonisamide (Zonegran).

vii.viii.Teratogenic effects, particularly neural tube defects in the setting of valproic acid or Depakote.  This adverse effect has serious future implications, when considering Depakote in a young girl who may at some point in the future become a prospective mother.

                                                            2.      Concerns in pregnancy:  

a.       Always maintain folic acid supplementation (prenatal vitamins).

b.      Consider diagnostic testing at 14-20 weeks with alpha-fetoprotein levels and structural ultrasound.

c.       With regards to birth defects in animals and in early clinical studies, the newer anticonvulsants seemed to have a favorable profile and most are Class C.  (Possible choices include Keppra, Vimpat, Lamictal, Lyrica, Neurontin, etc.)

d.      Breastfeeding and long term sequelae of drugs given to the baby in breast milk remain uncertain.

                                                            3.      Specific drugs (the order of this list does not suggest importance or efficacy):

a.       Phenobarbital has horrendous psychiatric side effects (avoid if possible).

b.      Phenytoin (Dilantin, Phenytek, and IV Cerebyx)

i.        Very effective in certain seizure types such as focal seizures and secondary generalized tonic-clonic seizures, excluding absence or myoclonic epilepsy.

ii.      Phenytoin is not helpful and can even exacerbate absence or myoclonic epilepsy. 

iii.    It has the advantage of a “therapeutic window,” when tends to be very protective in the range of 10-20.  However, ataxia and lethargy can occur over that level and is a common problem with that drug. 

iv.    It can often be given in a once-daily dosage as compared to most of the other anticonvulsants needing a scheduled multidose regimen.

v.      Always advise parents to vigorously shake Dilantin and other suspensions due to variable bioavailability.

c.       Valproic acid (Depakote).

i.        It is very effective for a variety of seizure types, particularly absence, myoclonic, generalized tonic-clonic convulsions, and helpful but somewhat less useful for strict partial or focal seizures.

ii.      Although very useful, it may not have quite lived up to its original “billing” as the “all purpose anticonvulsant.”

iii.    The extended-release formulation sometimes lessens side effects of limiting nausea.

iv.    Weight gain is often a big issue.

v.      Tremors can occur.

vi.    Liver toxicity with high ammonia or even hepatic failure can occur.

vii.  Never forget the issue of teratogenicity (spinal dysraphism young girls or females that may some day become mothers).

d.      Carbamazepine (Tegretol, Carbatrol).

i.        Useful in focal or partial complex seizures or in secondary generalized seizures, it can exacerbate absence or myoclonic epilepsy. 

ii.      Often the “gold standard” used for controlled comparison in studies of benefit of anticonvulsants. 

iii.    Diplopia, lethargy, and disturbed gait can be quite striking when carbamazepine is initiated.  Slow titrations are important, especially in the elderly.  “Borderline high” blood levels can be associated with _____________ ________________.

iv.    Possible favorable behavioral effects such as decreased anxiety, improved mood, and decreased aggression.

v.      Used as a mood stabilizer for bipolar illness.

vi.    Class D for pregnancy, although teratogenicity is much less than for valproic acid.  This has been the standard pregnancy drug, although Most of the newer agents are all primarily Class C.

vii.  Laboratory abnormalities can include low white blood cell counts (usually of benign character) and hyponatremia of uncertain significance, both of which need monitoring with blood work.

e.       Lamotrigine (Lamictal).

i.        Approved FDA indications include:

                                                                                                                                     a.      Bipolar disorders in patient greater than age 18.

                                                                                                                                    b.      Adjunctive treatment for partial seizures in pediatric patients greater than and equal to 2 years of age.

                                                                                                                                     c.      There is optimism for significant help in other conditions including new-onset typical and atypical absence seizures, generalized tonic-clonic seizures, atonic and myoclonic seizures, and the difficult to treat Lennox-Gastaut syndrome.

ii.      Rash can occur in up to 10% of patients as it does with other drugs, particularly carbamazepine.  The drug should absolutely be stopped if a rash occurs and will probably not be an option in the future. 

iii.    Due to “antigen-loading phenomenon” titration should be slow (especially when added to valproic acid) Depakote greatly increases the half life of lamotrigine.

iv.    With gradual escalation, doses higher than 600-800 mg have been used in seizure patients.

iv.v.      The combination of lamotrigine and valproic acid has been very effective in very difficult, resistant epilepsies, even those who have sometimes failed ablative brain-resection surgery.

f.       Gabapentin (Neurontin).

i.        Efficacy in partial complex and mixed-seizures disorders as with secondary convulsions is comparable to carbamazepine.

ii.      It has a 95-100% renal excretion and no appreciable interactions with other drugs.

iii.    It has an idiosyncrasy of a slower absorption with greater increasing doses due to saturation kinetics.  (Higher doses sometimes do not seem to provide much more added benefit.)

iv.    Success as an antineuralgic agent in palliating intractable pain and in treating migraines.

v.      Elderly patients can be susceptible to its sedative and depressant effects. 

g.      Pregabalin (Lyrica).

i.        It has a renal excretion and limited interactions with other drugs.

ii.      It is effective in partial complex and mixed-type seizures with convulsions.

iii.    Dizziness, mental slowing, and ataxia can occur, particularly in the elderly.

iv.    It is very helpful in treating neuralgic pain and intractable headaches in conditions such as fibromyalgia. 

v.      As opposed to the other anticonvulsants listed, it is a “scheduled” drug as some individuals have used it illicit fashion to “get high.” 

h.      Lacosamide (Vimpat).

i.        It has a broad range of benefits in a variety of seizure disorders.

ii.      It has renal excretion and limited interactions with other drugs.

iii.    It can be helpful in very resistant seizure disorders and in patients who are on multiple anticonvulsants.

i.        Oxcarbazepine (Trileptal).

i.        This is approved as being very effective for partial and mixed seizures in ages 4 and over.  Studies suggest tolerance and possible safety even used in children down to less than one year of age.

ii.      As with carbamazepine, Trileptal has been helpful in treating chronic and intractable pain.

iii.    Hyponatremia can occur as with carbamazepine, but probably less often.

iv.    Better tTolerance and similar efficacy with careful titration also tends to show a positive trend in some patients as compared to carbamazepine.

j.        Levetiracetam (Keppra).

i.        As with Neurontin, a primary renal excretion limits interactions with other drugs.

ii.      Possibly less sleepiness or fatigue than with Neurontin (gabapentin) or Lyrica (pregabalin).

iii.    Minimal systemic adverse effects.

iv.    Dysphoric ideation (sadness) can occasionally (rarely) occur.

iv.v.      Occasional worsening of mood and behavior can be seen even .to the point of drastic pediatric personality change or even agitated psychotic behavior.  (This most commonly occurs in patients with handicaps such as cerebral palsy.)

v.vi.    On the other hand, Iit can tends to cause less cognitive impairment, lethargy, and sleepiness than some other anticonvulsants.

vi.vii.  Starting dose can be a therapeutic dose (250-500 mg p.o. b.i.d. in an average adult).

k.      Topiramate (Topamax).

i.        Besides help in control of partial seizures and generalized tonic-clonic events, benefit in the Lennox-Gastaut syndrome and with infantile spasms has been shown.

ii.      This drug has been extremely helpful in prophylaxis of very intractable migraine .events, even at lower doses such as 25100 mg a day.

iii.    Metabolic acidosis with altered sodium bicarbonate levels can occur, although usually without clinical symptoms.  Hypohidrosis and hyperthermia can rarely occur more often in children.

iv.    Cognitive side effects can include problems with “word finding,” which would be distressing with a developing young mind.

v.      Tolerance tends to be “black or white.” If it induces dysphoria or causes mental slowing, it has to be discontinued.

vi.    Tingling or dysesthesias of the arms and legs can sometimes be a limiting side effect, probably prompting discontinuation of the drug.

vii.  It tends to curve the appetite, although will not necessarily cause weight loss. 

l.        Zonisamide (Zonegran).

i.        It is a sulfonamide with consideration of allergic sensitivity to sulfa.

ii.      Marked lethargy, agitation, and psychiatric presentations can be occasionally seen.

iii.    As with topiramate, cognitive slowing or dullness can occur.

ii.iv.    Possible once-a-day dosage.

v.      It tends to curve the appetite, although will not necessarily cause weight loss.

m.    Tiagabine (Gabitril).

i.        Useful for partial seizures as well as treatment of migraine and neuropathic pain, especially with spasticity.

ii.      Sedation can often be a problem.

ii.iii.    Can be useful as a nighttime hypnotic for insomnia.

n.      Ethosuximide (Zarontin).

i.        It has been extremely helpful in the control of absence seizures.  (In fact, it is the “gold standard.”)

o.      Clonazepam (Klonopin).

i.        An adjunct in the management of “breakthrough” seizures, particularly in the setting of marked anxiety, nervousness, and sporadic myoclonic jerks.

p.      Rectal diazepam (Diastat).

i.        Useful in some pediatric circumstances to stop a cycle of “breakthrough” seizures, preventing a visit to the emergency room.


 

 

q.      Felbamate (Felbatol).

i.        Indicated for partial seizures with or without generalization and Lennox-Gastaut syndrome. 

ii.      Warning risk of potentially fatal aplastic anemia and liver failure requiring blood monitoring. 

r.        Rufinamide (Banzel).

i.        Approved for Lennox-Gastaut syndrome (adults and children over 4 years old).

s.       Vigabatrin (Sabril).

i.        Used in resistant partial complex and secondary generalized seizures and with infantile spasms or West syndrome.  Warning can cause irreversible atrophy of the optic nerve with visual loss or blindness. 

t.        Anticonvulsants in summary:

i.        Narrow spectrum AED’s.

                                                                                                                                     a.      Most useful in focal, partial complex, and seizures secondarily generalizing from a focal source.

1.      Phenytoin (Dilantin).

2.      Carbamazepine (Tegretol).

3.      Oxcarbazepine (Trileptal).

4.      Gabapentin (Neurontin).

5.      Pregabalin (Lyrica).

6.      Levetiracetam (Keppra).

7.      Lacosamide (Vimpat).

ii.      Broad spectrum AED’s.

                                                                                                                                     a.      Effective for generalized seizure types such as absence, tonic, tonic clonic, myoclonic, and atonic.

1.      Ethosuximide (Zarontin, for simple absence seizures only).

2.      Valproic acid (Depakote).

3.      Lamotrigine (Lamictal).

4.      Topiramate (Topamax).

5.      Zonisamide (Zonegran). 

6.      Levetiracetam (Keppra).

7.      Lacosamide (Vimpat).

8.      Felbamate (Felbatol).

iii.    Monitoring drug levels.

                                                                                                                                     a.      As opposed to the monitoring required with phenytoin, valproic acid, and carbamazepine, the “newer” anticonvulsant agents are more empirically administered and often titrated often without need for tedious and obsessive drug-level testing.

iv.    Low risk of cognitive side effects (mental dulling):

                                                                                                                                     a.      Lamotrigine (Lamictal).

                                                                                                                                    b.      Levetiracetam (Keppra).

                                                                                                                                     c.      Lacosamide (Vimpat).


 

                                                                                                                                    d.      Felbamate (Felbatol).

                                                                                                                                     e.      Oxcarbazepine (Trileptal).

v.      Minimal drug interactions:

                                                                                                                                     a.      Gabapentin (Neurontin), renal excretion.

                                                                                                                                    b.      Levetiracetam (Keppra), renal excretion.

                                                                                                                                     c.      Pregabalin (Lyrica), renal excretion.

                                                                                                                                    d.      Lacosamide (Vimpat), renal excretion.

vi.    Helps promote weight loss.

                                                                                                                                     a.      Topiramate (Topamax).

                                                                                                                                    b.      Zonisamide (Zonegran).

                                                                                                                                     c.      Felbamate (Felbatol).

                                                                                                                                    d.      Lamotrigine (Lamictal) tends to be neutral with regards to weight gain.

vii.  With regards to efficacy in partial and mixed seizure disorders with or without convulsions:

                                                                                                                                     a.      Phenytoin is comparable to carbamazepine.  The latter has been the standard with which to compare the new anticonvulsants. 

                                                                                                                                    b.      Lamotrigine is comparable to phenytoin and carbamazepine.

                                                                                                                                     c.      Oxcarbazepine is effective as carbamazepine but possibly less rash, hyponatremia, and adverse CNS side effects, particularly with careful titration. 

                                                                                                                                    d.      Levetiracetam, lacosamide, and zonisamide have been helpful in resistant cases. 

 

 

III.             Enlightening cases.

A.    A 10-year-old “princess” turned “devilish.”

Resolution: A truly angelic straight-A student was turned into an obnoxious biting monster by “innocent” use of Dimetapp by her parents. A switch to a nonsedating sinus medication allowed her to revert back to her normal personality.

 

B.     A 5-month-old girl with spells of “shuddering.”

Resolution:  Multiple EEG studies in an infant with clusters of shuddering spells over a several-week period failed to reveal any answer.  Eventual treatment of urinary tract abnormalities leading to recurrent infection stopped the vasovagal phenomenon (fainting) that was associated with that irritation.

 

C.     A 10-year-old handicapped girl with a history of multiple shunt revisions for hydrocephalus having spells of intermittent jerking with lethargy not responding to triple anticonvulsant therapy.

Resolution: Her antiepileptic drugs were associated with marked sedation and personality change but did not help in decreasing spells of sudden altered consciousness with variable intermittent drop attacks.  After nine months of repeated CT scans and pleadings with the neurosurgeon, another shunt revision was done showing not only blockage but also shunt infection.  The spells and drop attacks were eliminated with much improvement in her personality.  This allowed the tapering and elimination of her anticonvulsants that were causing serious sedative side effects.

 

D.    A 14-year-old female basketball player with paroxysmal exertional dizziness stopping her play.

Resolution: Seizure disorder, cardiac disease, and common teenage girl problems of orthostatic hypotension and iron deficiency were ruled out.  Treatment of “silent” asthma (marked exertional-related reactive airways disease without wheezing) was made with Singulair and beta-adrenergic inhalers. She was then able to achieve her high-athletic potential without spells.

 

E.     A 7-year-old with recurrent salivation and drooling in the setting of persistent and chronic rhinitis and postnasal drip.

Resolution:  Antihistamines and decongestants in multiple trials failed to provide any benefit.  Benign childhood epilepsy or Rolandic epilepsy was present with the presentation of postnasal drip and drooling as focal seizure activity.  After EEG identification, there was complete elimination of episodes with low-dose carbamazepine.

 

F.      A 9-year-old baseball player with sleep onset jerks and twitches.

Resolution: Nocturnal disturbances of jerks and twitches turned out to be focal seizures caused by the glancing blow of a baseball as it slipped out of the young outfielder’s hand, hitting his head one year prior.  Gabapentin (Neurontin) halted the nighttime problems without slowing the cognitive function in this straight-A student.  Levetiracetam (Keppra) had to be added later due to marked seizure activity on his EEG.

 

G.    A 9-year-old boy being considered for diagnosis of Tourette’s syndrome due to tics, twitching, and multiple “restless” behaviors.

Resolution:  Caution should be made in jumping to treatment with antipsychotic tranquilizers for tics.  The following discoveries were made:

                                                            1.      Squinting with facial twitching and grimacing was eliminated by prescription glasses for impaired vision.

                                                            2.      Antihistamine treatment stopped the recurrent throat clearing that was a subject to ridicule for this boy in class. 

                                                            3.      His odd barking cough resolved with treatment of his reactive airways disease with bronchodilators.

                                                            4.      His restlessness with limited ability to sit still was essentially eliminated by treatment of his chronic constipation with his infrequent “once a week bowel movements.” The end result of this was elimination of his distracting behavior with no need for tranquilizers over a three-year followup. 

                                                            5.      The moral of the story is that all tics are not Tourette’s.

 

                                                                                                                                                     Rev.02/14/11


 

 

References:

1.            Epilepsy and Pregnancy:  Minimizing the Risks.  Martha J. Morrell, M.D., Contemporary OB/GYN, Archives January 1, 2004.

2.            Pharmacokinetic Profile of Levetiracetam:  Towards Ideal Characteristics.  P.N. Pat Salos, Pharmacology and Therapeutics, 85(2000) 77-85.

3.            The Treatment of Epilepsy:  Principles and Practice. Editor Elaine Willie, M.D.  Text published by Lea and Fbiger.

4.            Antiepileptic Agents:  CNS News, May 2004.

5.            Antiepileptic Agents:  2002.  John R. Gates, M.D.  Minnesota Epilepsy Group, P.A.  Web site:  www.mnepilepsy.org

6.            Folic Acid Supplementation to Prevent Neural Tube Defects. The Medical Letter, Volume 46 (Issue 1177), March 1, 2004.

7.            Long-Term Safety of Oxcarbazepine in Very Young Children with Partial Epilepsy.  Ralph S. Northam, M.D., Neurology Reviews, June 2004.

8.            The Importance of Monotherapy in Pregnancy.  Paige B. Pennell, M.D. Neurology 60 (supplement 4), June 2003.

9.            Review:  Side Effect Profiles and Behavioral Consequences of Antiepileptic Medications.  John R. Gates, M.D.  Epilepsy and Behavior 1, 153-159 (2000).

10.        How to Minimize Drug Induced Rash in Epilepsy Patients.  Barry Gidal, Pharm.D., et al, Practical Neurology, Page 64.

11.        Efficacy and Tolerability of the New Antiepileptic Drugs I:  Treatment of New Onset Epilepsy.  J. A. French, M.D., et al.  Neurology 62, April 2004.

12.        The Effect of Tiagabine on Spasticity in Children with Intractable Epilepsy:  New Pilot Study.  Kenton R. Holden, M.D., et al.  Pediatric Neurology, Volume 21, Number 4, October 1999.

13.        Efficacy and Tolerability of the New Antiepileptic Drugs II:  Treatment of Refractory Epilepsy.  J. A. French, M.D., et al.  Neurology 62, April 2004.

14.        Electroencephalography:  Basic Principles, Clinical Applications, and Related Fields.  Ernst Neidermeyer, et al.  Published by Urban and Schwartzenberg.

15.        C. Robert Adams, M.D., is a board-certified neurologist who graduated from Kansas University Medical Center and who has been in clinical practice for over 20 years.