LONG-TERM PSYCHOLOGICAL AND NEUROLOGICAL COMPLICATIONS
OF LINDANE POISONING
Richard C. W. Hall, M.D.
Courtesy Clinical Professor of Psychiatry
University of Florida, Gainesville
Ryan C. W. Hall, B.A.
This report documents a long-term case of severe hexachlorocyclohexane
(lindane) poisoning where, despite prompt medical treatment, the
patient continued to experience neurological and psychiatric symptoms
for 20 months following her poisoning.
The neurophysiology of the organochlorines (as they relate to
many of this patientís symptoms), the proper uses of anticonvulsants
for organochlorine-induced seizures, and other symptoms are discussed.
The following case is of an individual who was acutely intoxicated
with Kwell, an anti-scabies agent, which employs lindane as its
active ingredient. Although her initial symptoms were indicative
of severe lindane poisoning, what makes the case important are
the prolonged and clearly-related neurological and psychological
symptoms that she experienced for 20 months following her initial
In February 1996, a 37-year-old RN contracted scabies from her
daughter. She applied Kwell on February 2, washing it off the
following day as per instructions. Ten days later, she became
reinfected and again used the Kwell for a 24-hour period. Three
days later, she again developed what she believed to be mite bites.
At this time, she smeared a considerable quantity of Kwell over
her upper body, face, breasts, and under her arms and did not
wash it off the following day. Approximately 18 hours after applying
the third dose of Kwell, she developed a series of acute central
nervous system symptoms. She experienced major motor tics, began
shaking uncontrollably, had speech and thought difficulties and
experienced a "strange sensation" that something was
wrong with her. She developed severe burning paresthesias in her
hands and feet, which she also perceived as ice cold. She became
acutely nauseated, experienced repeated episodes of projectile
vomiting, and began a period of myoclonic jerking (affecting both
her arms and legs) that became so severe that she was unable to
stand. She was taken to an emergency room, where she experienced
profound tonic-clonic movements of her extremities, which persisted
after being treated with muscle relaxants. Over several hours,
her initial symptoms began to abate and she was discharged home
on muscle relaxants.
Eight days after the initial episode, she experienced severe
abdominal pain and urethral, bladder, and bowel spasms, which
caused both urinary and fecal incontinence. She returned immediately
to the emergency room. Her urine was strongly positive for myoglobin
and she was believed to have developed an acute rhabdomyolysis.
At this time, there were signs of central nervous system hyperactivity;
deep tendon reflexes were 4+; and the patient complained of auditory
and "visual hallucinations." She underwent a period
of sustained shaking that she was unable to control and complained
of unusual tastes in her mouth, as well as foul odors, which nauseated
her. The tonic-clonic contractions of her upper extremities increased
in severity, being greater on the left than on the right.
Following stabilization of her acute myoglobinuria, the patient
was discharged home on Valium 2.5 mg p.o. t.i.d. She began to
experience both hypnogogic and hypnopompic hallucinations, as
well as nocturnal confusion. Valium helped control her symptoms
but, if she missed a dose of Valium, they returned. She experienced
myoclonic jerking and twitching, unusual tastes, auditory and
visual hallucinations, projectile vomiting, profound diarrhea,
disconnected thoughts, inability to structure her activities,
and began making compulsive automatic gestures. She lost 15 pounds
during the following two weeks, becoming so profoundly weak that
she could not walk. Her paresthesias in both arms and legs worsened
and she began to experience unusual symptoms where her tongue
or face would become numb. She developed a total-body eczematous
rash and giant hives, for which she was successfully treated with
Her severe diarrhea persisted in spite of anti-diarrheal medication.
She reported episodes of soiling herself at night and was constantly
worried that she would lose control of her bladder or bowels.
Several physicians were contacted and there was clear documentation
of vaginal, clitoral, rectal, and bladder spasms of a severe nature.
She continued on Valium, now 30 mg q. d., and the spasms in her
left arm and both legs, as well as her nocturnal leg cramps, improved.
She became less agitated and frightened.
From April 12, 1996, through April 16, 1996, the patient was
admitted to a local hospital under the care of an internist, who
noted the exposure to Kwell. She was treated with higher doses
of oral Valium, intravenous fluids, and oral vitamin B1.
She was seen by a neurologist. An EEG showed 10 Hz posterior alpha
rhythm while awake with low-amplitude beta activity superimposed
anteriorly with an attenuation of background amplitude associated
with drowsiness. She was unable to tolerate photic stimulation.
Throughout the record were periods of higher amplitude 6-7 Hz
sustained activity, bilaterally.
Progression of Symptoms
When seen on May 1, 1996, the patient reported that she had done
well when taking Valium 2 mg p.o. t.i.d. and 5 mg at h.s. When
she tried to cut back on the Valium, she experienced an acute
recurrence of her previous symptoms.
Over the course of the next year, she tried on several occasions
to lower her Valium dose and had a similar return of symptoms.
During this time (July 1996), she was treated for pneumonia with
Ceftin by an infectious disease specialist. The Ceftin exacerbated
her previous symptoms.
When seen on May 23, 1997, her neurologistís diagnosis was "toxic
encephalopathy." The neurologist felt that the visual changes,
which she had experienced (red-green streaking and halo effects),
were caused by an impairment in the occipital lobe, secondary
to lindane poisoning. On this date, she reported that her mood
had stabilized. She had begun to eat well. Taste had returned
to normal. Sexual drive and function had returned to baseline
levels. She continued to have occasional muscular fasciculations
and "mild" conjugate gaze difficulty involving her left
eye. She reported that she was "95% back to normal."
On July 30, 1997, she reported that she had tried to taper and
stop her Valium, but had reexperienced the nausea, scintillating
scotomata, neuromuscular irritability, cramping, and fasciculations.
She reexperienced the turning-in of her left eye and again began
to see some unusual colors, this time with a bluish cast.
She experienced severe headaches, which disappeared when she resumed
When seen on December 1, 1997, she reported that all of her symptoms
had now abated and she was "back to normal." Her Valium
was diminished to 2 mg daily at that time. She continued it for
30 days longer and then discontinued it without any recurrence
Toxicology of Lindane
BHC (hexachlorocyclohexane) is a
widely used insecticide employed to control insect infestations
on livestock, pets, humans and agricultural products. BHC is a
mixture of isomers, of which the α- and γ-isomers are
central nervous system stimulants, while the β- and δ-isomers
are central nervous system
depressants. Of all the isomers, the γ-isomer (lindane) has
the highest acute toxicity in humans.1-4 The
average lethal dose in humans is 125 mg/per kg.3, 4
Lindane-containing lotions and shampoos are available by a variety
of brand names including Gamene, Kwell, Bio-Well, G-Well, GBH,
Kildane, Scabene, and Thionex. The FDAís current recommendations
are that lindane-containing products only be used after patients
have either failed to respond to adequate doses of other treatments
or have been shown to be intolerant of other approved therapies
for scabies and mites. Lindane has been banned in 18 countries
and is severely restricted in 10 others. Reed and Carnick, the
makers of Kwell, stopped marketing its lindane product in 1995;
however, many pharmacies still have Kwell as part of their shelf
inventory. In addition, a variety of generic brands of lindane
Lindane represents a powerful contact and internal poison, which
can be absorbed through skin, inhaled when in vapor form, or consumed
orally. The agent is a cumulative possible carcinogen and mutagen.
It has teratogenic, immunotoxic, and neurotoxic properties.4
Lindane and other organochlorine insecticides have been shown
on repetitive exposure to produce hepatic, neuronal, renal, and
testicular damage, as well as bone marrow disorders, peripheral
paresthesias and neuropathies, muscular weakness, impaired coordination,
aplastic anemia, and agranulocytopenia.3 -15 The substance
damages developing fetuses and may decrease fertility in females.1
Products containing lindane are all carefully labeled
to warn against its use by infants, pregnant women, and nursing
mothers. Patients are warned about reapplication, as deaths have
been reported following several applications.18 Dieting
women and patients with eating disorders are at greater risk for
long-term poisoning. This increased risk of side effects is particularly
evident in patients on a protein-deficient diet.1 The
patient in our report paid careful attention to her weight and
consumed a predominantly vegetarian diet, which may have been
a factor in her prolonged toxicity.
The onset of signs and symptoms following exposure to hexachlorocyclohexane
insecticides and their resulting poisonings vary, depending on
the weight of the individual, their metabolism, serum protein
levels, and the route and degree of exposure, as well as whether
there are single or multiple exposure to the agent which prolong
the extent of the poisoning.19 The time interval between
high dose exposure and the onset of symptoms is generally less
than 12 hours when exposure is gradual, as through skin contact.13,
14,19 The symptoms produced by these agents may last for
weeks to months and patients often experience periodic relapses
despite adequate therapy because of the initial lipid storage
and subsequent redistribution of these chemicals.19
Following partial recovery from an exposure, patients evidence
an increased susceptibility to subsequent re-exposure for approximately
three months.3 -5, 20-22
Table 1 shows the symptoms experienced by our patient throughout
the course of her poisoning.
Classification of Patientís Signs and Symptoms according
to Receptor Site and Type
Headache - M
Muscle fasciculations of striated muscle - L
Confusion - M
Nausea - M
Profound muscle weakness-S
Seizures - M
Diarrhea - L
Persistent moderate muscle weakness - M
Fatigue - L
Abdominal pain w/cramps -L
Muscle spasm and extensor/flexor imbalance - L
Dysarthria - M
Diaphoresis - I
Tachycardia - M
Ataxia - M
Urinary incontinence - L
Anxiety - L
Fecal incontinence - L
Myoclonic jerks - L
Intrusive thoughts - L
| Word-finding difficulty
Memory impairment - L
Peripheral neuropathy w/ paresthesias and weakness of extremities
Incoordination - L
| Scintillating scotomata
| Red/green visual changes
| Musical hallucinations
Hypnopompic and hypnogogic hallucinations - L
Distortion of size of body parts - L
Amblyopia - M
Anorexia - M
I - Immediate S - Short term/days M- Mid term/weeks L - Long
Pathophysiology of Chlorinated Hydrocarbon Poisoning
In the central nervous system, lindane acts as a non-competitive
GABA antagonist. It has been shown that the inhibitory neurotransmitterís
gamma-aminobutyric acid (GABA) and glycine directly cause an increase
in the conductance to Cl- by bonding to ligand-operated ion channel
receptors at the postsynaptic membrane. The opening of these C1-
channels usually leads to a net hyperpolarization of the cell.
The GABA(A) receptor has separate, but allosterically-interacting,
binding sites for GABA, benzodiazepines, barbiturates, anesthetic
steroids, and the convulsant picrotoxin. The GABA(C) receptor
also forms a Cl- channel, but it has been noted that its pharmacology
differs significantly from that of the GABA(A) receptor. Lindane
produces central nervous system disruption through a variety of
mechanisms, the most important being its ability to act
as a non-competitive GABA antagonist interacting with the picrotoxin
site, both in membranes and in intact cultured neurons, thereby
inhibiting the GABA-induced C1-flux following activation of either
the GABA(A) or GABA(C) receptor.23 - 28
Lindane is heterogeneously distributed throughout the brain,
obtaining higher concentrations in white than grey matter, with
its concentration increasing over time. The highest concentrations
of lindane are found in the thalamus, mid-brain, and pons-medulla.
Its affinity for white matter and myelinated structures is related
to its lipophilic properties and behavior.29,30
Rosa, et al., demonstrated that lindane induces significant changes
in the intracellular Ca2+ homeostasis of central neurons and has
a profound effect in the cerebellum. Lindane primarily affects
the dantrolene-sensitive intracellular Ca2+ stores, causing a
release of calcium from these stores and altering the sensitivity
Sunol, et al., demonstrated that the neurotoxic effects of lindane
are predominantly mediated through its non-competitive antagonism
of the GABA(A) receptor. It was noted that following poisoning
and seizure, the concentrations of dopamine and its primary metabolite
(DOPAC) were increased throughout the mesencephalon and the striatum.32
In cases of chronic intoxication, dopamine levels fluctuated.
These fluctuations, following repetitive exposure to lindane,
may account for some of the Parkinsonian-like symptoms our patient
Sanfeliu, et al., demonstrated that repetitive low-level non-convulsant
doses of lindane produced long-term changes in cerebral 2-14C-deoxyglucose
uptake throughout the subcortical structures of the brain, but
particularly in the dorsal cochlear nucleus and the dentate gyrus.
They suggested that these increases in uptake in the subcortical
regions of the brain, mainly related to the limbic system (e.g.,
Ammonís horn, dentate gyrus, septal nuclei, nucleus accumbens,
olfactory cortex) and associated with a diminished uptake in other
regions, (particularly the auditory and motor cortices), are responsible
for the functional alterations (mood, affect, sensations) seen
during the course of long-term lindane poisoning.33
Tilson, et al., noted that certain commonly-used anti-seizure
agents, particularly Dilantin (phenytoin), should be avoided in
cases of lindane poisoning and Valium should be used instead to
control symptoms. They noted that animals pretreated with Dilantin,
which were then exposed to lindane, had their central nervous
system hyperactivity increased rather than lowered by the Dilantin.
This was true for both convulsant and subconvulsant doses of lindane.
Subconvulsant doses produced an enhanced responsiveness to acoustic
stimuli in the animals and increased agitation.34
Studies in animals after exposure to various insecticides, where
convulsions occur, show small pyknotic hippocampal neurons
and vacuolization of neutrophils. These changes are similar to
changes that have been observed in humans dying after status epilepticus.
These lesions occur in the frontal cortex, entorhinal cortex,
amygdala, caudate nucleus, and hippocampus.21 Ischemic
changes are particularly pronounced in the white matter. Early
treatment with benzodiazepines, particularly diazepam, has been
shown to reduce the incidence and extent of these pathological
changes and to speed recovery in surviving animals.21,22
Attia, et al., have shown that chronic lindane poisoning causes
an enhanced nighttime rise in pineal N-acetyltransferase (NAT)
activity and increased central melatonin secretion, as well as
increased serum melatonin levels. Chronic lindane poisoning also
caused a significant reduction in central serotonin (5-HT) and
5-hydroxyindole acetic acid (5-HIAA).35 This change
in central serotonin may well be the factor which mediates the
anxiety and depressive changes seen in our patient, as well as
the disruption of her sleep cycle.
Nedkova-Bratanova, et al., have shown that chronic lindane poisoning,
even at low levels, diminishes dipeptidase activity and disrupts
the activity of the intestinal disaccharidases for up to 90 days
following low-level poisoning. Sucrase is the most effected disaccharidase.
This disruption of the disaccharidases may be responsible for
the persistent diarrhea experienced by our patient.36
A thin, healthy, partial-vegetarian, white female, who was exposed
to three doses of lindane (through the application of Kwell),
developed a severe long-term lindane poisoning. Review of the
literature suggests that her toxicity was so severe because of
the repetitive nature of her exposure and the fact that she was
partly protein restricted when first exposed. She developed profound
central nervous system toxicity, as well as skin and gastrointestinal
changes, that persisted for 20 months. She was treated with high
doses of Valium. It was noted that every time her Valium was diminished
below a critical level, her symptoms tended to recur until she
had adequately cleared the lindane from her system. We believe
this is the longest term of poisoning reported following exposure
to an organochloride insecticide. Her symptoms are well explained
by the physiology of these compounds as described in the literature.
The case is important for it represents the longest persistence
of symptoms clearly associated with poisoning by the potent gamma
isomer of BHC-lindane.
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