Case Files of the New York City Poison Control Center: Paradichlorobenzene-Induced Leukoencephalopathy
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- Hernandez, S.H., Wiener, S.W. & Smith, S.W. J. Med. Toxicol. (2010) 6: 217. doi:10.1007/s13181-010-0053-2
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KeywordsAtaxia Encephalopathy Leukoencephalopathy Moth ball(s) Paradichlorobenzene White matter disease
A 44-year-old man was brought to the emergency department by emergency medical services after he was discovered lying supine on his apartment floor. He was accompanied by his sister, who had decided to visit him after his absence from a family function. Worsening “bizarre” behavior had been noted by family members for 4 weeks, characterized by anorexia, social withdrawal, flat affect, and alogia. Prior to his illness, he was described as functional, independent, gainfully employed, and social.
The patient had mild mental retardation and hypertension. There was no history of diagnosed psychiatric illness, although his family suspected pica. Medications included an unknown antihypertensive with which he was not compliant. He occasionally used marijuana and alcohol, without history of other abused drugs. The patient’s sister reported significant weight loss over several months. There had been no apparent fevers, cough, vomiting, diarrhea, or convulsions. On physical examination, he appeared drowsy, was markedly cachectic, and emanated an atypical aromatic body odor. Initial vital signs were: blood pressure 154/90 mmHg, heart rate 98/min, respiratory rate 20/min, rectal temperature 37.4°C, and room air oxygen saturation 97%. Head, neck, chest, and abdominal examinations were unremarkable. He had dry, scaling, and ichthyotic skin. He was oriented to person and place, but not to time, date, or indication for hospitalization. Limited cranial nerve evaluation was normal. Pain and light-touch sensation were unaffected. Hyperreflexia (without clonus) and cogwheel rigidity were noted in both lower extremities; upper extremities were normal. Plantar reflexes were normal bilaterally. Muscle bulk, tone, and strength were normal. The patient was unable to stand without support and unable to ambulate, apparently due to impaired equilibrioception. He could follow simple one-step commands. He would speak a few words when asked simple questions, and he avoided eye contact.
Serum electrolytes (sodium, potassium, chloride, calcium, and magnesium) and serum glucose were normal. Tests of hepatic and renal function were: AST 53 U/l (0–40 U/l), ALT 25 U/l (10–40 U/l), alkaline phosphatase 88 U/l (35–145 U/l), total bilirubin 6.84 μmol/l (0.4 mg/dl) (0–20.52 μmol/l; 0–1.2 mg/dl), ammonia 31 μmol/l (43.42 μg/dl) (11–35 μmol/l; 15.41–49.02 μg/dl), BUN 11.42 mmol/l (31.99 mg/dl) (2.86–7.85 mmol/l; 8.01–21.99 mg/dl), and creatinine 136.14 μmol/l (1.54 mg/dl) (35.36–106.08 μmol/l; 0.4–1.2 mg/dl). Microcytic anemia was present without evidence of hemolysis; hemoglobin 99.0 g/l (9.9 g/dl) (140–180 g/l; 14.0–18.0 g/dl), hematocrit 34.3% (42.0–52.0%), MCV 65.3 fl (71.4–94.6 fl), RDW 25.9% (11.5–15.1%). Leukocyte count, differential, T cell subpopulations, and platelets were unremarkable. Nonspecific acute-phase reactants were abnormal: erythrocyte sedimentation rate, 47 mm/h (0–15 mm/h), and serum C-reactive protein, 3,981 nmol/l (41.8 mg/l) (95.2–381 nmol/l; 1.0–4.0 mg/l). Tests for syphilis, Lyme disease, and HIV infection were negative, and thyroid studies were within normal limits. Additional serum studies included folate 12.28 nmol/l (5.42 ng/ml) (2.49–45.32 nmol/l; 1.1–20 ng/ml), vitamin B12 735 pmol/l (996 pg/ml) (155–812 pmol/l; 210–1,100 pg/ml), and ceruloplasmin 441.00 mg/l (44.1 mg/dl) (220–610 mg/l; 22.0–61.0 mg/dl). Cerebrospinal fluid (CSF) was acellular with normal protein and glucose. CSF bacterial and viral cultures and cryptococcal antigen were negative, along with CSF evaluation for prion disease. An atypical viral encephalitis panel was negative. Serum ethanol, methanol, and ethylene glycol were 0 mmol/l (0 mg/dl), and urine toxicology was negative for barbiturates, cocaine, methadone, and opioid metabolites. Urine benzodiazepines were detected barely above the reporting threshold at 1.29 μmol/l (371 ng/ml), consistent with ED administration of midazolam to facilitate computed tomography (CT) imaging.
No clinical seizure activity was evident, and two separate electroencephalograms demonstrated only focal slowing in the temporal lobes without epileptogenic discharges. A CT performed the day of admission and a magnetic resonance imaging (MRI) of the brain without contrast performed within a week were without abnormality. However, a later reevaluation of the initial MRI imaging suggested a signal intensity on T2 and fluid-attenuated inversion recovery (FLAIR) images in the subcortical white matter of the anterior temporal lobes.
What Etiologies Should Be Considered in Leukoencephalopathy?
Nontoxicological differential diagnosis of leukoencephalopathy
Amino acid disorders
Autoimmune thyroid disease (acquired)
Dihydropteridine reductase deficiency
Gyrate atrophy of the choroids and retina
Acute disseminated encephalomyelitis
Acute hemorrhagic leukoencephalitis
Maple syrup urine disease
Balo’s concentric sclerosis
Ornithine transcarbamylase deficiency
Marburg variant acute multiple sclerosis
Autoimmune thyroid disease
Osmotic demyelination syndrome
Tumefactive multiple sclerosis
Congenital disorders of glycosylation
Herpes simplex virus (HSV)
Human immunodeficiency virus (HIV)
Human T cell lymphotropic virus (HTLV)
Adult cerebral X-linked ALD
Childhood cerebral X-linked ALD
Female heterozygote form of ALD
Simian vacuolating virus 40
Globoid cell leukodystrophy (Krabbe disease)
Varicella zoster virus (VZV)
Leukodystrophy with neuroaxonal spheroids
Vanishing white matter disease
Vitamin B12 deficiency
Lipid metabolism disorders
Cerebral amyloid angiopathy
Mucopolysaccharidosis types 1 and 2
Niemann–Pick type C
Organic acid disorders
Glutaric aciduria type 1
Sjögren Larsson syndrome
Kearns Sayre syndrome
Metal metabolism disorders
Menke’s kinky hair disease
Molybdenum cofactor deficiency
Although some may manifest in adulthood, heritable disorders affecting white matter are usually evident early in life [5, 6]. Insufficient metabolic substrates to support white matter integrity, including hypoxia, may result in leukoencephalopathy [7-9]. Sudden elevation in mean arterial pressure—seen in eclampsia or severe hypertension—may exceed CNS vascular autoregulatory capability, resulting in vasogenic edema and leukoencephalopathy . This also may occur secondary to other vascular disorders [11, 12]. Trauma, hydrocephalus, and infection may produce leukoencephalopathy [13-15]. Inflammatory demyelinating disorders include prototypic multiple sclerosis and its less common variants [16, 17]. Toxin-induced leukoencephalopathy is rare and considered once clinical evaluation has ruled out infectious, metabolic, genetic, demyelinating, and structural and traumatic etiologies. Specific toxins are investigated upon obtaining a history of pertinent exposure.
What Is “Coasting”?
Coasting is the phenomenon by which toxicity persists and clinical deterioration occurs despite discontinuation of exposure to a toxin. This has been described with many neurotoxins such as thalidomide, hydrocarbon sniffing with tetraethyl lead, n-hexane (and methyl-n-butyl ketone and 2,5-hexanedione), chemotherapeutic agents, antivirals, and pyridoxine [18-23].
What Toxins Induce Leukoencephalopathy?
Xenobiotics associated with leukoencephalopathy
Abused or misused substances
Cytokines and immune modulators
Environmental and occupational toxins
Other immunosuppressive and immune modulating drugs have been reported to precede the onset of leukoencephalopathy. Bevacizumab (antivascular endothelial growth factor A), dexamethasone, tacrolimus, etanercept (TNF antagonist), interleukin 2, and alpha interferon have been implicated in RPLS [43-48]. Immunosuppressive therapy employing cyclosporine A for stem cell transplant, renal transplant, and focal glomerulosclerosis has resulted in leukoencephalopathy including RPLS and fatal leukoencephalopathy . Treatment of chronic anemia with erythropoietin, particularly in end-stage renal failure patients, can cause hypertension associated with posterior leukoencephalopathy . Although some agents like interleukin 2, interferon, and prednisone have been reported to precipitate reversible posterior leukoencephalopathy, they have also been used to treat progressive multifocal leukoencephalopathy with variable success [51, 52].
Several antimicrobials are associated with leukoencephalopathy. Levamisole, as an immunomodulating agent for recurrent aphthous ulcers, as an anthelmintic, and as an adjuvant for chemotherapy, particularly with 5-fluorouracil (5-FU), may induce multifocal inflammatory leukoencephalopathy. Motor weakness, dysphasia or aphasia, cognitive impairment, and gait abnormalities are among the major clinical features. The MRI may reveal diffuse hyperintensity of signal from periventricular white matter on MRI and/or individual demyelinating lesions [53, 54]. Amphotericin B can cause a diffuse noninflammatory leukoencephalopathy that can be fatal. Postmortem brain analysis demonstrated florid astrogliosis, demyelination, and infiltration of the hemispheric white matter by foamy macrophages [55, 56]. Rare cases of linezolid- and acyclovir-induced posterior leukoencephalopathy have also been reported [57, 58]. The use of hexachlorophene-containing soaps to bathe infants was discontinued after dermal absorption resulted in encephalopathy and death, particularly in premature infants. This vacuolar encephalopathy afflicted the white matter, characterized by wide intralamellar spaces or “splitting” of myelin sheaths .
Chronic alcoholism may be associated with significant white matter pathology. The ethanol metabolites acetaldehyde and related products of lipid peroxidation bind directly to tissues and elicit an immune-mediated response, with subsequent white matter damage. Alcoholics deficient in thiamine may develop cerebral lactic acidosis, swelling of astrocytes, oligodendrocytes, myelin fibers, and neuronal dendrites. Similarly, consumption of thiaminase-containing foodstuffs, such as Anaphe venata (African silkworm) larvae, carp, and bracken fern may produce white matter lesions particularly in the paraventricular regions [60, 61]. Children and adolescents with prenatal exposures to ethanol have demonstrated similar white matter changes as seen in adults. Alcoholics with chronic malnutrition and serum electrolyte abnormalities are at risk for osmotic demyelination syndrome, often in association with Wernicke’s encephalopathy and polyneuropathy. Extensive noninflammatory demyelination occurs within the pons, basal ganglia, thalami, and deep cerebral white matter and less commonly in the lateral geniculate bodies and hippocampi. Marchiafava-Bignami disease, a rare complication of chronic alcoholism, is characterized by demyelination and necrosis of the corpus callosum . Patients who survive methanol or ethylene glycol intoxication may have white matter changes ranging from nonenhancing areas of necrosis within peripheral white matter to general cerebellar white matter abnormalities. Similar abnormalities may result from anoxic–ischemic insults or severe metabolic disturbances [63-65].
Although opiates may produce hypoventilation and subsequent hypoxic brain injury resulting in white matter abnormalities, leukoencephalopathy is also reported without preceding respiratory compromise. Methadone abuse has been reported to precede catatonia and extrapyramidal symptoms, with MRI images demonstrating extensive, symmetric signal-intensity abnormalities in deep white matter. These findings have been compared to the more familiar toxic leukoencephalopathy from heroin pyrosylate [66, 67]. In the 1980s, “chasing the dragon,” inhaling the thick white pyrosylate generated by heating heroin base on aluminum foil, was implicated in an unexplained spongiform encephalopathy in the Netherlands. Similar cases were reported in other parts of Europe and the USA [68, 69]. Clinical features included abulia, ataxia, speech abnormalities, spastic paraparesis, and hypotonia with prominent cerebellar and cerebral white matter destruction on MRI [70, 71]. Although initially thought to be related to the inhalation of aluminum fumes, it is likely attributed to some unidentified impurity in the drug supply since reports of leukoencephalopathy have also occurred with intravenous heroin, inhaled oxycodone, and crack cocaine [72, 73].
Others drugs abused via inhalation that induce leukoencephalopathy include aromatic hydrocarbons. Toluene leukoencephalopathy is a well-characterized demyelinating disorder that spares the axons and afflicts central nervous system, producing neurobehavioral deficits. White matter abnormalities on MRI correspond with clinical severity [74, 75]. Paradichlorobenzene is a very rare cause of leukoencephalopathy. Hallucinogens and amphetamines have been implicated as drugs of abuse associated with leukoencephalopathy. Although psilocybin has been implicated in posterior encephalopathy with cortical blindness and subacute multifocal cerebral demyelination after ingestion of “magic mushrooms,” the association remains questionable, as with all drugs of abuse, because of the possibility of simultaneous exposure to other toxins . Although 3,4-methylenedioxymethamphetamine has been associated with iatrogenic injury to the central white matter through overly rapid correction of associated hyponatremia, it has also been associated with neuropsychiatric sequelae. Ongoing research suggests associated primary white matter pathology [77, 78].
Environmental toxins, especially in occupational settings, have produced leukoencephalopathy. After exposure to trimethyl tin from cleaning a tin tank, a 43-year-old man developed acute toxic leukoencephalopathy with dizziness, disorientation, visual hallucination, and agitation. MR images later revealed extensive abnormal signal intensities in white mater . Long-term carbon disulfide exposure may induce encephalopathy, parkinsonism, pyramidal signs, cerebellar ataxia, cognitive impairments, and axonal polyneuropathy with diffuse hyperintense lesions in subcortical white matter, basal ganglia, and brain stem on MRI [80, 81]. Carbon monoxide (CO) poisoning may precipitate neurologic sequelae with bilateral basal ganglion lesions and subcortical and periventricular white matter demyelination on MRI. White matter changes may not necessarily correlate with carboxyhemoglobin concentrations or neurologic sequelae [82, 83]. Nonetheless, leukoencephalopathy is often difficult to attribute solely to CO poisoning when there is concomitant hypoxia.
What Diagnostic Strategy Should Be Pursued in a Suspected Toxin-Induced Leukoencephalopathy?
Diagnosis of a toxin-induced leukoencephalopathy relies heavily upon a history of exposure. Considering the rarity of toxin-induced leukoencephalopathy, organic, metabolic, infectious, genetic, demyelinating, structural, traumatic, or vascular etiologies should be excluded before pursuing more esoteric etiologies. Occupation, recreational activities, medications (prescribed, over the counter, homeopathic, and herbal), and abused/misused xenobiotics should be investigated. The onset and progression should be characterized and presence or absence of coasting noted. A detailed physical exam should characterize the attributes of disease. Particular cranial nerve, gait, reflex, sensory, or motor abnormalities may be typical or distinctive (e.g. facial nerve deficits in ethylene glycol or diethylene glycol exposure). Concomitant disease to other organ systems may also aid the diagnosis, such as renal tubular acidosis with toluene. The anatomic location(s) of central white matter disease and/or sparing may be consistent with a characteristic pattern, such as the predominant posterior lobe pathology in cases of chemotherapy-induced RPLS. When initial imaging is inconclusive for white matter disease, repeat imaging should be considered, as some toxins may have delayed or evolving manifestations. When applicable, concentrations of toxin in biological samples should be obtained to confirm exposure. When concentrations are unavailable or not well correlated with toxicity, the diagnosis may be primarily clinical. Toxin-specific antidotes, if available, should be implemented when indicated, such as chelation therapy for arsenic. In general, removal from the exposure and supportive care are the mainstays of treatment in toxin-induced leukoencephalopathies.
Inability to discern an etiology and progressive clinical decline prompted toxicological considerations. The patient’s history of pica was further explored. The family revealed he would ingest paradichlorobenzene (PDCB)-containing mothballs and inhale mothball vapors. The patient would frequently “smoke” them by heating them with a flame to enhance vapor formation. This practice had been observed for at least 4 months prior to hospitalization.
What Is PDCB?
PDCB is well absorbed via oral, inhaled, and subcutaneous routes. Inhaled PDCB rapidly distributes in human tissues, accumulates in adipose tissue, and is primarily renally eliminated (5–16% eliminated 9–11 h after exposure) [84, 85]. Cytochrome P450 CYP2E1 (along with CYP1A1 and CYP1A2) convert PDCB to its primary hepatic metabolite, 2,5-dichlorphenol (DCP) [86, 87]. Similarly, in other mammals, almost all PDCB is renally eliminated following biotransformation as free DCP or DCP sulfate or glucuronide conjugates . Minor urinary metabolites include 2,5-dichlorohydroxyquinone, 2-(N-acyl-cysteine-S-yl)-1,4-dichlorobenzene, and 2-(N-acyl-cysteine-S-yl)-2,3-dihydro-3-hydroxy-1,3-hydroxy-1,4-dichlorobenzene [40, 89]. Good correlation exists between PDCB in blood and DCP in urine at low, nonoccupational exposure , and urinary DCP is a suitable index for monitoring low-level exposure of PDCB in the general population .
What Toxicity Is Reported from PDCB Exposure in Animal Research?
The International Agency for Research on Cancer has reasonably anticipated PDCB to be a carcinogen (class 2B) . Species-specific biotransformation of PDCB and production of reactive metabolites yield varied hepatotoxic and nephrotoxic profiles. Hepatocarcinogenicity is observed in mice likely due to increased microsomal production of reactive metabolites. In the rat, PDCB interferes with apoptosis to increase cell proliferation and liver weight, although it does not induce hepatocarcinogenesis [86, 93]. Both mice and rats are prone to nephrotoxicity from PDCB exposure. Mice do not develop true renal carcinogenicity in either sex while rats do so exclusively in males [94, 95]. It has been suggested that renal toxicity in rats secondary to PDCB exposure may be an alpha-2μ-globulin-mediated nephropathy [96, 97]. Similar renal pathology has been described in rabbits and guinea pigs [98, 99].
What Human Toxicity Is Reported from PDCB Exposure?
Although a potential for adverse health effects exists, significant clinical toxicity has not been reported from ambient exposure. Industrial workplace exposure may produce skin and mucous membrane toxicity manifesting as dermatitis, eye and nose irritation, and/or respiratory complaints [99, 100]. Long-term exposure risks are unclear. Although overshadowed by hepatic and renal toxicity, animal studies have demonstrated hematological toxicity. Anemias were evident in early reports of PDCB toxicity in humans [95, 98]. A 3-year-old boy ingested PDCB demothing crystals and a 21-year-old postpartum female ingested PDCB toilet-freshener blocks [101, 102]. In both cases, there was complete recovery with removal from PDCB exposure. Another case described aplastic anemia in a 68-year-old woman who was exposed via inhalation to both naphthalene- and PDCB-containing products . Diagnosis was made primarily by history; the 3-year-old had trace amounts of urinary 2,5-dichloroquinol . Similar reports of anemia have been described with inhalational exposure in the mid-twentieth century literature [104-106].
Other toxicities reported in the mid-twentieth century include sporadic hepatic, renal, and pulmonary pathology. PDCB was thought to be the cause of pulmonary granulomatosis in a 53-year-old woman who habitually scattered PDCB crystals on household furniture and carpeting and had unexplained persistent productive cough and dyspnea. Crystals were found within giant cells on her lung biopsy . Four cases of acute cryptogenic fulminant hepatic failure were associated with chronic PDCB exposure . Additionally, a 31-year-old woman who had worked for 2 years selling mothballs and other products containing PDCB developed hepatitis, subsequent portal hypertension, and esophageal varices . Another report described a 69-year-old man with an anaphylactoid reaction, purpura, and subsequent glomerulonephritis after sitting in a chair that had been treated with PDCB flakes . Although PDCB exposure was associated with these outcomes, it remains uncertain if it was the causative agent.
Characterization of reported cases of PDCB-induced neurotoxicity
Age and sex [ref]
Cerebellar and extrapyramidal signs
WM pathology on MRI
Time to recover
44 M (this case)
Ingestion, inhalation: NS
Bizarre behavior → catatonia
Alogia → mutism
5/5 UE and LE strength; UE cogwheel rigidity
Unable to stand wos, unable to walk
↑UE and LE clonus
Scaling skin, hyperpigmented areas
31 F 
Ingestion: ≥ 2 months
Withdrawn, depressed → mental sluggishness → encephalopathy
32 F 
Ingestion, inhalation: 2 years
Cognitive decline → catatonia
Spastic, hypokinetic, dysarthric
Weakness distal > proximal
Ataxia → unable to walk wos
Limb spasticity, bradykinesia
42 F 
Ingestion: ≥ 2 years
Slow, hypophonia, bradyphrenia → mutism
Dystonia, cogwheel rigidity
Ataxia → unable to walk
Bradykinetic → akinetic, torticollis, dystonia
21 F 
Ingestion: 1–2 MB/day
Withdrawn, depressed, A&O → stupor
Nystagmus, ocular bobbing
Some abulia, otherwise normal
Ataxia, wide-based station
UE dysmetria, truncal ataxia, skew deviation
18 F 
Ingestion: 1/2 MB/day (2 months)
No mental sluggishness
Cerebellar and pyramidal signs, all limbs
Inhalation: 10 min/day (4–6 months)
18 F 
Inhalation: 5–10 min/day (a few weeks)
54 F 
Ingestion: 6 years
Dysphoric mood, no psychosis, intact cognition
Weakness, 3/5 UE, 2/5 LE
Inhalation: 10× per day (≥ 35 years)
16 F 
Behavioral abnormalities, encephalopathy
Bl recurrent optic neuritis
Hypotonia → spastic hypertonia
Intention tremor, Bl cerebellar signs, akinesia
25 F 
Inhalation: 6 years
mod Weakness, all limbs; mld Hypotonia proximal
Gait disturbance → unable to stand wos
Could not use chopsticks
19 F 
Ingestion: 4–5 MB/day (1.5–2 years)
PDCB-induced neurotoxicity varies. Variable nystagmus, vision loss, and optic neuritis have occurred [114, 117]. Sensory deficits have not been described. Weakness and hypotonia without predilection for specific muscle groups are observed [111-114, 116, 118]. Symptoms may evolve and include spasticity and cogwheel-like rigidity [113, 117]. Both hyporeflexia and hyperreflexia have been reported [112, 115, 116, 118].
Cerebellar and extrapyramidal signs and symptoms were reported in the majority of cases with limb spasticity, bradykinesia, dysmetria, ataxia, and tremor. Speech is often affected; deficits range from slow, spastic, hypophonic, dysarthric, bradyphrenic, abulic, or hypokinetic speech to complete mutism [111-114, 118]. Gait disturbance is a predominant feature reported in all cases of neurotoxicity from PDCB. The patient may deteriorate to the point of being unable to walk or even stand without support [111-119].
Skin findings are a distinctive feature, which when paired with neurotoxicity should raise suspicion for PDCB as the underlying etiology in an obscure leukoencephalopathy. Scaling, ichthyotic lesions, and/or hyperpigmentated areas are reported [112, 115, 119]. One case reported body odor of mothballs 1 month after hospitalization . Microcytic anemia may be found in cases of PDCB neurotoxicity [111-116, 118]. Ancillary testing is often normal and fails to determine an alternative etiology.
Neuroimaging, specifically MRI, can be especially helpful in supporting the diagnosis. Hyperintense signal in cerebral white matter is typically seen [111-114, 116]. Specific anatomic locations include periventricular white matter, corpus callosum, deep cerebellar nuclei, parieto-occipital region, and internal capsule [113, 114]. There have been reports of PDCB neurotoxicity lacking such abnormalities on MRI; however, development of these findings may be delayed and may become more evident on subsequent imaging [113, 115, 117, 118]. Computerized tomography is usually reported to be normal [111, 113, 114, 116-118]. Electroencephalogram results vary—normal studies, electrographic status epilepticus, activity slowing, diffuse disorganization, and rapid bursts are all described [111, 113-115, 117, 118].
Clinical toxicity is prolonged and patients may demonstrate coasting, remaining ill or further deteriorating before improving despite hospitalization, supportive care, and discontinuing exposure to PDCB [111, 113, 114, 119]. Onset of improvement has been reported to take up to 6 months . Four case reports note as long as 6 to 9 months for complete recovery [111, 113, 115, 118]. Complete resolution is possible if exposure ceases [115, 117-119].
Approximately 1 month into hospitalization, a serum PDCB concentration was obtained. The result (1.2 μg/ml) prompted consultation with a medical toxicologist for assistance in management.
How Are Biological Markers of PDCB Exposure Interpreted?
Urinary DCP is a suitable index for monitoring PDCB exposure . As a result of ambient exposure, DCP is almost universally present in urine without clinical toxicity, occupational exposure, or abuse. In 1,000 US adults adequately sampled from urban and rural residence, races, ethnicities, regions of the country, genders, and ages, 98% had detectable DCP in their urine and 96% had detectable PDCB in their blood without apparent clinical toxicity. Urinary DCP concentrations were 30 μg/l (median), 200 μg/l (mean), 460 μg/l (90th percentile), and 790 μg/l (95th percentile). The median, mean, 90th percentile, and 95th percentile concentrations of PDCB in blood were 0.33, 2.1, 4.8, and 11 μg/l, respectively. The concentrations of PDCB in blood ranged as high as 49 μg/l . In a previous study of 197 otherwise healthy Arkansas children, 96% had detectable urine DCP . Similar environmental exposure has been demonstrated in Germany and Japan [121, 122].
Only two published case reports of neurotoxicity quantitatively confirmed exposure. A serum PDCB concentration of 34 μg/ml was present in a case of leukoencephalopathy following acute-on-chronic exposure . In a second case, following exposure cessation, PDCB plasma concentrations 2 weeks and 1 month later were 0.50 and 0.39 μg/ml . Two other cases of neurotoxicity and one case of hemolytic anemia detected PDCB or its metabolites without quantification [101, 113, 115]. Elimination may be slow following chronic administration due to significant adipose tissue deposition [85, 91]. Coasting is typical, and serum concentrations may be low despite clinical toxicity. Until further data are available, PDCB leukoencephalopathy remains a diagnosis of exclusion, relying on history, clinical signs of neurotoxicity, and MRI findings.
What Treatment Options Are Available for Patients with PDCB-Induced Leukoencephalopathy?
No specific antidote for PDCB-induced leukoencephalopathy exists. Treatment emphasizes removal from exposure and supportive care. Patients may require invasive procedures to sustain life and provide adequate nutrition such as nasogastric or percutaneous enterogastric feeding tubes during the prolonged elimination period. Efforts focus upon preventing infection and other complications of prolonged hospitalization. Physical therapy may ameliorate muscle wasting, as lack of mobility is prominent feature in cases of PDCB-induced leukoencephalopathy. Patients may require transfer to a rehabilitation facility before fully recovering. Finally, psychiatric consultation may be warranted as the toxicity often originates from abuse of PDCB.
Three months after hospitalization, the patient began to develop slight improvement described as increased responsiveness. A noncontrast CT of the brain performed days prior to transfer demonstrated subtle low attenuation in the periventricular white matter. The patient was transferred to a skilled nursing facility for continued care.
This case was presented at the ACMT Medical Toxicology 11th Annual CPC Competition at the 2009 North American Congress of Clinical Toxicology Annual Meeting, San Antonio, TX, USA, September 22, 2009.