Iatrogenic seizures can occur due to several factors including medication initiation and withdrawal, surgical therapy, medical procedures, and diagnostic tests. Certain medications like aminophylline, phenothiazines, lithium, and meperidine are associated with iatrogenic seizures, especially in patients with risk factors like a history of seizures. Seizures can also occur when withdrawing from antiepileptic drugs or other medications like baclofen that have been used long-term. Some medical procedures linked to iatrogenic seizures include surgery, myelography, labor and delivery complications, intrathecal treatments, and electroconvulsive therapy. Physicians should exercise caution when administering seizure-linked medications or treatments to vulnerable patient groups.

1. Iatrogenic Seizures
May 19, 2015

2. EPIDEMIOLOGY
• Stambouly and Pollack study:
- 4.6% of admissions to a pediatric intensive care unit over a 6-month period were for iatrogenic illness
- 12.6%were hospitalized because of iatrogenic disease in an lt intensive care unit
- None of these patients had been treated for iatrogenic seizures
• Wijdicks and Sharbrough study:
- N=55(0.2% of all intensive care unit admissions) associated with surgical trauma
- Iatrogenic drug withdrawal (morphine, propoxy-phene, midazolam, meperidine) accounted for seizures
in 18 (33%)
- postoperative iatrogenic fluid loading in 8(15%)
- iatrogenic drug toxicity in another 8 (15% )
• Messing and colleagues study:
- N=3155
- 18 (0.6%) patients who had had seizures as a result of taking medications as prescribed
- 27(0.8%) had seizures associated with drug overdoses than as a result of an iatrogenic cause

3. DRUG-INDUCED SEIZURES

4. Respiratory Agents
Aminophylline and
Theophylline
• The most common seizure types were
generalized (33%), partial with
secondary generalization (30%), and
29% had status epilepticus
• Serum conc greater than 21 mg/L
• Seizures associated with theophylline
are generally benign
• Complications:
- Refractory seizure
- Memory dysfunction
- death
Terbutaline
• Focal motor seizure with secondary
generalization in a 7-year old girl on
terbutaline 1 mg/kg/day in three
divided doses (7.5-mg dose )
• EEG after 1 month showed
epileptiform abnormalities over the
right frontotemporal area

5. Psychotropic Medications
• Phenothiazine, chlorpromazine (phenothiazine-derivative), tricyclic antidepressants,
clozapine, lithium
• Characteristic of seizures is tonic-clonic generalized
• EEG may show multifocal spike and waves
• Risk Factors: previous or family history of epilepsy, barbiturate withdrawal, previous
ECT, cerebrovascular disease, being first-born, history of postnatal brain damage
• Onset: within a few days after initiation of therapy or after sudden dosage increases
- Clozapine: High dosages (>600 mg/day) were four times more likely than low
dosages (<300 mg/day) to be associated with seizures
- Lithuim toxicity: often develops insidiously, wherein the patient's lithium
concentration was documented 6 hours before the seizure, was 1.9 mEq/

6. Analgesics
• Pentazocine; meperidine
• Characteristic of seizures is generalized tonic-clonic, grand
mal seizures, and status epilepticus in case of pentazocine
poisoning
• Risk factors: history of epilepsy, and stroke and is further
increased in the setting of renal dysfunction

7. Anesthetic Agents
• Lidocaine (at 6-8 mg/kg), fentanyl, and inhalation anesthetics such as
enflurane and isoflurane
• Characteristic of seizures is generalized tonic-clonic
- Duration averaged 105 seconds, postictal period averaged 37 minutes

8. Anti-infectives and Immunosuppressants
Drugs Dosage associated to cause
seizure
Characteristic of seizure
isoniazid (INH) 100 to 150 mg IV to rats generalized seizures ; less fatal when given with
pyridoxine IV
nalidixic acid I gram four times daily for the
treatment of urinary frequency
and dysuria
generalized convulsions 2 days after intake
chlorambucil 5mg/day for chronic lymphatic
leukemia
focal motor seizures 3 weeks after starting
metronidazole 750 mg three times daily as a
radiation sensitizer for the
treatment of metastatic cancer
generalized seizure
cyclosporine 25 mg/day twice daily given to
bone marrow post-transplant
patients
- Generalized convulsions had occurred
- cyclosporine-related seizures in bone marrow
transplant recipients were associated with
hypomagnesemia

9. SEIZURES ASSOCIATED WITH
MEDICATIONWITHDRAWAL

10. Antiepileptic Drugs
• Three phases of the AED withdrawal period:
• 1.) the period of constant therapeutic AED concentrations
• 2.)the period of falling AED concentrations
• 3.) the period of absent or subtherapeutic AED concentrations
• Phenytoin; carbamazepine
• Drug –drug interactions increasing the chance of breakthrough
seizures for hepatically metabolized AEDs (phenytoin, carbamazepine,
or primidone)
• E.g. phenytoin and ticlopidine

11. Non-Antiepileptic Drugs
• Typical withdrawal seizures
• Associated with long-term therapy with sedatives or mild tranquilizers
• Long-term use Baclofen
- status epilepticus
- grand mal seizures
- complex partial seizure

12. SEIZURES ASSOCIATED WITH MEDICAL
PROCEDURES

13. Surgery
• Generalized seizures
• Severe hyponatremia associated with inappropriate secretion of
antidiuretic hormone
• Higher risk for malignancies, history of epilepsy, craniotomy
procedures
• Neurologic procedures with high likelihood for post-operative
seizures:
- Glioma biopsies
- Ventricular shunting
- Tumor excisions
- Aneursymal repairs (middle cerebral artery)
• Cardiac transplantation

14. Myelography
• Seizures can occur with the inadvertent use of ionic contrast media for
myelography
• Case of status epilepticus after receiving 9 mL of ionic contrast medium,
diatriazoate sodium, intrathecally during lumbar myelography
• Ascending tonic-clonic seizure syndrome
o within 6 hours of undergoing myelography, have painful tonic-clonic muscle contractions that
ascend from the lower extremities to the trunk and upper limbs in association with loss of
consciousness
o Treatment: removal of contrast material from the spinal canal as the head and trunk are elevated
as well as supportive management of seizures, rhabdomyolysis, and metabolic abnormalities

15. Labor and Delivery
• Seizures owing to hyponatremia associated with oxytocin-augmented
labor
- Anti-diuretic effect of oxytocin
• Accidental injection of mepivacaine into fetuses during attempts to
induce caudal analgesia in women who were undergoing active labor
- infants had bilateral clonic seizures that began in the first few minutes of life
- pinprick lesions over the infant’s scalp

16. Intrathecal Treatment
• Kofler et.al--
• Three patients who had experienced seizures with clinical and EEG findings
after being given intrathecal baclofen for the treatment of spasticity, including
two patients who had had seizures after a test bolus injection
• All patients had had a history of traumatic brain injury

17. Electroconvulsive Therapy
• ECT ss an established treatment for severe endogenous depression
• Incidence of ECT-induced seizures was 114 per 100,000
• Associated to increased the risk of cerebral hypoxia

18. SUMMARY
• Iatrogenic seizures except those deliberately induced by withdrawing AEDs from patients with
epilepsy who are undergoing surgical evaluation are infrequent and potentially avoidable
complications of medication initiation and withdrawal, surgical therapy, medical procedures, and
diagnostic tests
• Physicians should exercise caution in administering medications associated with iatrogenic
seizures to patients with a previous history of seizures, underlying brain diseases, neurologic or
neuropsychiatric disorders, or positive family histories of epilepsy
• The evaluation of new-onset seizures should prompt a search not only for the usual risk factors,
such as cortical lesions or metabolic derangements, but also the possibility of an iatrogenic causes

19. END. Thank You!

20. References
• Schachter SC. Iatrogenic seizures. Neurol Clin. 1998 Feb;16(1):157-70.
doi: 10.1016/s0733-8619(05)70372-8. PMID: 9421546.