Differential Diagnosis in Neurology

2.8. Unusual Seizures and Concomitant Medical Conditions

Lateralizing Signs in Partial Seizures

The percentage of identifying focal seizure foci with the following lateralizing signs:

• Version – 94%
• Dystonic posture – 93%
• Ictal speech deficit – 83%
• Automatism with preserved responsiveness (right hemisphere)
• Ictal vomiting – right temporal lobe
• Early head turning – 89% (to the ipsilateral hemisphere)
• Dystonic limb posturing – 88%
• Blinking (wink-like rather than clonic); more common in left temporal lobe than from the right temporal lobe
• Ipsilateral seizure focus:
  • Unilateral automatism
  • Early head turning
• Motor events contralateral to the seizure focus:
  • Bilateral automatisms interrupted by dystonic trunk posturing (contralateral) to the seizure focus
• Blinking representation (parietal 7a)
  • Blinking in one eye
    • Focus is ipsilateral (occipital lobe)
  • Bilateral blinking
    • Focus is in the posterior parietal area 7a
• Post ictal dystonia, dystonic posturing: ictal speech, upper extremity automatisms
  • May be seen from either temporal lobe
• Forced sustained head deviation, dystonic arm posture, jaw and mouth deviation
  • Occur contralateral to frontal seizure focus
  • Unilateral automatism of the upper extremity (ipsilateral focus)
  • Post ictal dysnomia (speech dominant hemisphere)
  • Ictal dysnomia (not reliable)

Cardiac Arrhythmias that Occur During Complex Partial Seizures:

• Supraventricular tachycardia
• Sinus tachycardia
• Sinus bradycardia
• Sinus arrest
• AV block
• Asystole
• Reduced heart rate variability

General features of cardiac arrhythmias during seizures

• Seizure induced arrhythmia is a cause of death in epilepsy patients
• Ictal tachyarrhythmias are more common than bradyarrhythmias
• Bradyarrhythmias occur with both the left or right temporal lobe seizures
• Intraoperative stimulation of the insular cortex
  • Tachyarrhythmias and a pressor response right anterior insular cortex
  • Bradycardia and depressor response: left anterior insular cortex
• Sinus arrest with asystole: left temporal cortex
• Ictal bradycardia: increased parasympathetic out flow through the vagus
• Stimulation of the amygdala causes bradycardia
• Insular projections
  • Lateral hypothalamus
  • Amygdala
• Simulation of the orbital frontal cortex and cingulate gyrus cause brady and tachyarrhythmias

Photosensitive Temporal Lobe Epilepsy

• True temporal lobe epilepsy can be photosensitive
• General photosensitive epilepsy
  • AD trait
  • Age dependent penetrance
  • Wave length dependent

Unusual Seizures

Gelastic Seizures

• Ictal laughter (gelastic seizure)
• Hypothalamic hamartoma is the usual cause:
  • Seizures begin in infancy or childhood
  • Intellectual decline
  • Precocious puberty
  • Behavioral problems
    • Aggressive
    • Disinhibited
    • Autistic features
    • Hyperactive
  • Diabetes insipidus and pan hypopituitarism following resection
  • Symptomatic (ictal laughter) or secondary generalized seizures
  • Laughter:
    • Unmodulated
    • Not associated with mirth
    • Machine gun quality
    • Sudden onset
    • Inappropriate
    • Gelastic attacks may occur when the hypothalamus or adjacent structures are displaced; nodules attached to the tuber cinereum or mamillary bodies have been seen
    • Drop attack
      • Preceded by brief gelastic episode or clonic seizure
  • EEG slow spike and wave may occur in first decade; tonic and atonic GTCS
  • Poor response to anticonvulsants
  • Atonic
  • High incidence of drop attacks
  • Epileptic activity from the hamartoma itself

Dachrymistic Seizures

• Continual crying
• Unmodulated (monotonic)
• Inappropriate
• May have associated tears
• Bilateral temporal lobe disease

Differential Diagnosis: Inappropriate Laughter or Crying

• Bilateral corticormedial lesions (internal capsule)
• Pontine lesions
• Bilateral cortical (insular cortex) lesions

Catamenial Epilepsy

• Usually occurs at midcycle (10–14 days)
• Estrogen is excitatory to cortical neurons and progesterone is inhibitory
• Water retention

Focal Akinetic Seizure

• Focal paresis precedes convulsive activity in the affected part
• Focal paresis may affect one part of the body; convulsive activity may occur in that part
• Somatosensory sensations may occur before or at the onset of the focal paresis in the same body region
• Structural lesions have been documented in central parietal regions

Epileptic Negative Myoclonus

• Action-activated motor activity (jerks) limited to one arm or leg
• Rarely may be multifocal
• Patients may demonstrate motor neglect of the affected part
• Most patients have history of seizures
• Paroxysmal epileptic activity in areas of the sensorimotor cortex

Epilepsy in the Elderly

• Incidence of new epilepsy patients greater than 60 years of age
  • 77/100,000 persons
• Clinical features:
  • Altered mental status
  • Episodes of unresponsiveness
  • Blackouts
• Frontal and parietal lobe involvement
  • Dizziness is the most common symptom
• Younger patients
  • Post ictal confusion lasts 5–10 minutes
• Elderly patients
  • Postictal confusion may last days

Ictal Paralysis that Resembles Todd's Paralysis

• Clinical features:
  • EEG during Todd's paralysis is normal or demonstrates slow waves
  • Ictal paralysis:
    • Generalized (ictal or epileptic negative myoclonus is followed by epileptic drop attacks)
    • Focal motor seizures can be followed by an inhibitory atonic seizure
      • Seizure starts in the motor area and spreads to suppressor strip (premotor area 6)
      • Focal paralysis is seen

SUDEP (sudden unexplained death in epileptic patients)

• Insular cortex
• Multiple drugs
• Severity of the seizures
• GTCS
• 40% of patients have ST depression on EKG
• Increased heart rate

Seizures During Pregnancy

• Occurrence:
  • Seizure frequency increased in 24% of women during pregnancy
  • Most frequent at the end of the first trimester and beginning of the second
  • Increased seizure activity is not dependent on:
    • Seizure type
    • Seizure frequency prior to pregnancy
    • Sex of the fetus
  • Increased seizure activity dependent on:
    • Distribution, protein binding, metabolic rate, and renal excretion of anticonvulsants
    • Clearance returns to baseline at approximately three months post partum
    • Clearance change evident in the first trimester and is maximum at term
• Intestinal Absorption
  • Clearance of anticonvulsants (increased) due to changes in GI absorption and blood volume
  • Gastric emptying and intestinal motility slowed during pregnancy
  • Increased gastric pH and buffering capacity
  • Malabsorption from the baby is not significant in the change of drug clearance
• Hepatic Metabolism:
  • Progesterone stimulates hepatic activity
• Protein binding:
  • Albumin levels decline during pregnancy, which decreases protein binding of the drug; lower albumin level results in proportional reduction of protein binding. This mechanism is most significant in highly bound drugs. An increase in the free fraction of the drug may change very little. Measurement of the free fraction is the best method of monitoring effective drug concentrations.
• Volume of distribution:
  • Body weight increases
  • Intravascular volume increases
  • Volume into which the drug is distributed increases during pregnancy which tends to lower plasma levels
• Urinary excretion:
  • Renal blood flow increases during pregnancy
  • Unbound drugs (lowest protein binding) may have increased excretion
• Hormone variability:
  • Estrogen increases cortical excitability
  • Progesterone suppress epileptic discharges
  • Estriol, estradiol and progesterone increase during pregnancy
  • Ratio of estrogen to progesterone is greatest between weeks 6 to 16, the time seizures increase in frequency

Epilepsy and Reproductive and Endocrine Dysfunction

• 50% of women with TLE
  • Sexual dysfunction
  • Hormonal abnormality
  • 14–20% have amenorrhea
  • Fertility reduced 30%
• Men with TLE
  • Approximately 50–70% sexual dysfunction
• Associated medical and hormonal conditions reported in TLE
  • Hypogonadotropic and hypergonadotropic hypogonadism
  • Functional hyperprolactinemia
  • Polycystic ovary disease
  • Anovulatory cycles

Issues in the Use of Generic Preparations as a Cause of Loss of Seizure Control

• Narrow therapeutic window (carbamazepine)
• Differences in bioavailability between manufactured forms result in variations in serum concentrations:
  • FDA criteria for bioequivalence allow for a +20% difference in bioavailability between generic and brand-name products
  • US plus criteria specify that capsule content be within +% (93–107%) of the stated content of the preparation
  • Bioequivalence studies are performed in healthy adult volunteers; this population does not conform to many patients