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Indian Pediatr 2021;58:
71-73 |
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Herbal Medicine-Induced Seizures in Children: Single-Center
Experience Over 18 Months
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Ramya Bandi,1 Rini Lathiya,2
Lokesh Lingappa1 and Ramesh Konanki1*
Departments of 1Neurology and 2Genetics, Rainbow
Children’s Hospital,
Banjara Hills, Hyderabad 500 034, Andhra Pradesh, India.
Email:
[email protected]
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Many common household herbal
preparations may have seizurogenic ingredients. We report 15 children
with seizures following exposure to such compounds: oral ingestion of
liquid preparation in 13, and local application of balm and Eucalyptus
oil ingestion in one each. All children, except one, had generalized
seizures. This study highlights the need to address this history during
evaluation of first seizure, and increase awareness of seizurogenic
potential of such preparations.
Keywords: Adverse effects,
Complementary and alternative medicines, Epilepsy.
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It is common practice in Indian households to treat minor ailments with
herbal preparations. They are considered natural and safe, and are
easily available as over-the-counter medications. The herbal
preparations have ingredients like camphor, eucalyptus oil, menthol and
other aromatic compounds. All these compounds have adverse effects, with
the most serious being their tendency to provoke epileptic seizure. The
objective of the present study was to highlight the seizurogenic
potential of these components and increase awareness among pediatricians.
This is a case record review, with cases having been
evaluated between December, 2018 and June, 2019 at a tertiary care
pediatric center in Southern India. All children (up to 18 years) with
first afebrile (apparently unprovoked) seizure presenting to emergency
room were evaluated and treated as per standard protocol [1]. The
necessary investigations like blood sugar, serum electrolytes,
electroencephalography (EEG) and neuroimaging were done, with extent of
evaluation varying on case-to-case basis, and treating physician’s
discretion. Children with confirmed acute symptomatic seizures (due to
fever, hypoglycemia, electrolyte disturbances, systemic infections) and
those with remote symptomatic etiology were excluded. All the children
in whom no cause could be identified, but had an antecedent exposure to
any of the seizurogenic compounds and/or herbal preparations in any form
(enteral, inhalational or local application) were included. Children
with unprovoked seizures who were evaluated at other medical centers,
but had come for neurological consultation later, were also included if
all the inclusion criteria were met. The details of dose, route of
exposure, time between exposure and seizure onset, type and duration of
seizures were noted.
A total of 15 children (8 girls) met the inclusion
criteria, with median (range) age of 4.8 years (6 months-14 years) – 10
were younger than 5 years (Table I). All children were with
typical development except one child with pre-existing ischemic stroke
and left hemiparesis due to mineralizing angiopathy. There was no past
history or family history of febrile seizures or epilepsy in any of the
subjects. All these herbal medicines were used by the caretakers for
treatment of minor ailments like nose block, cold and cough in young
children, and headache in older kids.
Table I Characteristics of Study Subjects
| No. |
Age (mo)/ |
Amount |
Indication |
Seizure |
Seizure |
Seizure |
Hospitalization |
|
sex |
ingested a |
|
onset (min) |
type |
duration (min) |
(d) |
| 1 |
24/F |
1 mL |
URI |
90 |
GTCS |
2 |
None |
| 2 |
35/M |
1 mL |
URI |
20 |
GTCS |
2 |
1 |
| 3 |
168/M |
1 mL |
Headache, body pain |
60 |
GTCS |
1 |
1 |
| 4 |
31/F |
2 drops+LA |
URI |
30 |
GTCS |
5 |
None |
| 5 |
6/M |
2 drops+LA |
URI |
20 |
GTCS |
5 |
None |
| 6 |
45/F |
4-5 drops |
For general well being |
90 |
GTCS |
0.5 |
None |
| 7 |
36/F |
Topicalc |
URI |
30 |
GTCS |
2 |
None |
| 8 |
21/F |
5 drops |
URI |
15 |
GTCS |
2 |
None |
| 9 |
18/M |
2 mL |
URI |
60 |
GTCS |
4 |
2 |
| 10 |
66/M |
2 drops |
For digestion |
120 |
Focalb |
3 |
1 |
| 11 |
20/M |
3 drops |
URI |
30 |
GTCS |
5 |
None |
| 12 |
79/M |
2 mL |
URI |
120 |
GTCS |
1 |
2 |
| 13 |
36/F |
5 mL |
Accidental ingestion |
15 |
GTCS |
30 |
6 |
| 14 |
118/F |
3 dropsd |
Coryza |
30 |
GTCS |
45 |
4 |
| 15 |
73/F |
2.5 mL |
URI |
15 |
GTCS |
5 |
2 |
| GTCS: Generalized tonic
clonic seizures; LA: Local application, aof liquid preparation
taken orally; bwith behavioral arrest; cMenthol plus balm;
dEucalyptus oil. |
The most commonly used preparation was a liquid
formulation Zinda Tilismath (Karkhana Zinda Tilismath) (13, 86.7%);
menthol plus was locally applied for one child and eucalyptus oil
ingestion in one child. For Zinda tilismath, drinking after dilution
with water was the commonest mode of exposure (n=10), while three
children had local application as well. Its ingredients include
eucalyptus oil, camphor, menthol, thymol and alkanet root as mentioned
in the package insert. One child was exposed to herbal balm with similar
composition. The quantity of the liquid preparation used was 2-5 drops
(6 of 13 children) and 0.5-2.0 mL (6 of 13 children). One child drank 5
mL of preparation.
Of 15 children, 8 were hospitalized. Two children
were admitted for status epilepticus (eucalyptus oil ingestion, 5 mL of
liquid formulation); one child was ventilated for 1 day for poor
respiratory efforts, and one child was admitted for two days in view of
prolonged postictal encephalopathy. Five children were admitted for
unprovoked seizures for one day each. Mean duration of stay was 2.6
days. Later in the study, children were managed on an outpatient basis
if there was unequivocal history of antecedent exposure to one of these
compounds, and other causes of acute symptomatic seizures were ruled
out. History of previous exposure to the herbal medicine was present in
10 children. The median (range) interval between exposure and onset of
seizures was 49 (15-120) minutes. The median (range) seizure duration
was 3 minutes (30 seconds-5 minutes). Investigations like blood sugar,
serum calcium, magnesium, and serum electrolytes were done in all
children to rule out other causes of acute symptomatic seizures, and
were normal. EEG was done in ten children and was normal. Five children
underwent neuroimaging (computerized tomographic scan, 3; magnetic
resonance imaging, 2), which was normal in all. This included two
children with status epilepticus and one child with focal seizures.
During follow-up of 6-12 months, one child had afebrile seizure and one
had febrile seizure after one month and 20 days, respectively; the rest
of the children were normal.
To the best of our knowledge, this is the largest
case series in children till date, highlighting the seizurogenic
potential of herbal medications/compounds. The list of toxic
compounds/drugs that can cause acute symptomatic seizures is exhaustive
and include compounds like industrial chemicals, pesticides and natural
toxins [2]. Among these, natural plant toxins are the main ingredients
of many herbal medicines, and encephalopathy, seizures, hallucinations,
coma and death have been reported [3].
Few animal studies in rats have proven the
seizurogenic effects of camphor and 1,8-cineole, which is an ingredient
of eucalyptus and other essential oils. They have shown that
epileptiform activity is induced by blockade of K+ channels and
upregulation of Ca2+ inward currents [4-6]. The toxic effects of these
compounds are more pronounced in children due to immature brain. Some of
them have dose-related effects and some are idiosyncratic responses.
When multiple compounds are present in a preparation, the complex
interplay of all ingredients can cause toxic effects [7]. In a similar
study by Mathew, et al. [8] on eucalyptus oil inhalation and
seizures, 10 patients (5 children) were studied [8]. The mean duration
for seizure onset and type of seizures were similar to our study.
However, all the patients in that study were evaluated with EEG and
imaging, whereas these were done in only a few of the children in this
study. This was so because during the later part of the study duration,
we could limit our investigations when an unequivocal temporal relation
was found with herbal compound exposure.
In previous case reports of camphor poisoning in 4
children (age range 15-36 months), the interval between exposure and
seizures was 40 minutes to 2 hours, similar to our study [9,10].
Duration of seizures in this study ranged from 2 minutes to 1 hour, with
all requiring admission and observation. Dose was mentioned for only one
child (750 mg). In our study, the amount of preparation taken had no
correlation with either onset of seizures or duration of seizures
(excluding status epilepticus). This is highlighted by the oldest case
(case 14) developing seizure after ingesting 3 drops of herbal
substance. There were no unique clinical, biochemical, imaging or
electrographic findings associated with herbal compound induced seizures
in our cohort.
Seizures occurring in association with minor
infections without fever, and underlying genetic predisposition for
epilepsy could not be ruled out. Two children in our study had seizure
recurrence within a month, and that is less likely to be due to single
exposure to herbal compounds. Long-term, prospective studies should be
done to answer this.
Despite the previous case reports in literature
quoting seizurogenic potential of the herbal compounds, this awareness
is lacking in both clinicians and parents. This was the reason five
children in our study were admitted (and underwent neuroimaging) as
either the history was taken later or exposure was not considered
causative initially.
Ethics clearance: Institute Ethics Committee of
Rainbow Children’s Hospital. No. RCHBH 085/03-2019, dated 24 August,
2018.
Contributors: RB, RL, LL, RK: were involved in
patients’ care and wrote the initial draft. All authors reviewed the
manuscript and approved the final version.
Funding: None; Competing interest: None
stated.
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