Rehabilitation of Lower Limb Motor Dysfunction and Neurogenic Bladder After Low-Dose Chlorfenapyr Poisoning With Delayed Rhabdomyolysis: A Case Report

Introduction

Chlorfenapyr, an arylpyrrole insecticide widely used for insect control, is classified as a moderately hazardous pesticide [1,2]. It poses a threat to human health and is degraded in vivo into multiple compounds, among which tralopyril is the most toxic [2]. Chlorfenapyr poisoning is a severe intoxication resulting from ingestion, inhalation, or dermal exposure to chlorfenapyr-containing pesticides, with a mortality rate of 75% to 84% [2–4]. Its toxicity primarily involves the disruption of mitochondrial oxidative phosphorylation and inhibition of adenosine triphosphate (ATP) production, leading to mitochondria-mediated programmed cell death and DNA damage [2]. High-energy-dependent organs, such as the nervous, cardiovascular, and musculoskeletal systems, are particularly vulnerable [2,4,5]. Due to the lack of effective antidotes, surviving patients are rare [6,7], and even fewer reports describe rehabilitation for chlorfenapyr-induced dysfunction.

Among the limited number of surviving patients reported, 1 experienced sequelae such as lower limb weakness progressing to paralysis and urinary dysfunction [6]. Subsequent follow-up demonstrated no improvement in paraplegic symptoms, and urinary function was not further monitored [6]. Recent case reports have demonstrated that central nervous system injury resulting from chlorfenapyr poisoning manifests as leukoencephalopathy on magnetic resonance imaging (MRI); additional spinal abnormalities include spinal cord edema and demyelination [4,6,8]. Although leukoencephalopathy is reportedly reversible [6], it remains unclear whether spinal cord lesions can also resolve or whether the associated functional impairments can recover.

Given the high mortality rate of chlorfenapyr poisoning and limited research concerning the prognosis of surviving patients, we present a case of chlorfenapyr poisoning with persistent bilateral lower limb weakness and neurogenic bladder. Our patient demonstrated substantial improvements in brain and spinal cord imaging and functional outcomes after comprehensive rehabilitation.

Case Report

A 55-year-old man was admitted to the Rehabilitation Department of our hospital with prominent bilateral lower limb dyskinesia and urinary dysfunction. These symptoms had begun 2 months before admission and were accompanied by fever, chest tightness, profuse sweating above the waist, and paresthesia in the lower limbs. Twelve days after symptom onset, he presented to a local hospital, where initial laboratory results showed no obvious abnormalities, leaving the etiology undetermined. Two days later (2 weeks after symptom onset), he was transferred to the emergency department of a tertiary hospital. On admission, he was alert, with temperature 36.5°C, pulse 84 beats/min, respiratory rate 20 breaths/min, and blood pressure 121/74 mmHg. He had lower limb weakness and diminished touch and pain sensation below T12. Immediate laboratory tests revealed a considerably elevated creatine kinase level (5725.7 U/L) and a normal serum creatinine level (90.3 μmol/L). Urinalysis revealed protein and occult blood, with urinary red and white blood cell counts of 64/μL and 194/μL, respectively. Blood urea nitrogen results were unavailable. He was medically healthy without a history of hypertension, diabetes mellitus, or cardiovascular disease.

Given his occupational history of more than 3 years in a chemical factory, including 2 months of exposure in a chlorfenapyr production workshop shortly before symptom onset, blood toxicant testing was performed. The results showed a chlorfenapyr concentration of 659 ng/mL and tralopyril concentration of 7.1 μg/mL. Brain MRI (approximately 2 weeks after onset) demonstrated diffuse bilaterally symmetrical leukoencephalopathy involving the cerebral hemispheres, corpus callosum, internal and external capsules, midbrain, pons, cerebellar peduncles, and medulla oblongata, with high signals on diffusion-weighted imaging (Figure 1(A1, A2)). During spinal MRI, T2-weighted imaging (T2WI) showed abnormal hyperintensities in the lateral thoracic spinal cord with cord swelling, particularly at segments T9 and T10 (Figure 1(B1, B2)). After hemoperfusion, plasma exchange, and steroid pulse therapy, chlorfenapyr was no longer detected in the blood, and the tralopyril concentration decreased to 95 ng/mL. The patient was subsequently transferred to the rehabilitation medicine department, where he continued pharmacologic therapy and underwent comprehensive rehabilitation, including exercise therapy, occupational therapy, acupuncture, and repetitive transcranial magnetic stimulation.

The patient’s initial assessment revealed an inability to stand, with lower limb muscle strength graded as IV according to Manual Muscle Testing, indicating movement against gravity and moderate resistance. The patient also presented with paresthesia, an indwelling catheter, and drug-assisted defecation. He could respond appropriately to external perturbations (eg, gentle pushes) without losing postural control while sitting and could maintain a standing posture independently without external support. He had a Berg Balance Scale score of 11, indicating severe balance impairment and a high risk of falls, and a Modified Barthel Index score of 32, suggesting moderate dependence. On admission, brain MRI (approximately 8 weeks after onset) showed no clinically significant abnormal signals on T2WI (Figure 1(A3, A4)). The abnormal signals and cord swelling previously observed on T2WI at segments T9 and T10 had resolved (Figure 1(B3, B4)). Based on these findings, a comprehensive treatment plan was implemented. For nerve recovery, oral mecobalamin (0.5 mg, 3 times daily) and vitamin B1 (10 mg, 3 times daily) were administered. Sensory abnormalities were treated with pregabalin. Lower limb motor dysfunction was addressed through resistance, balance, and suspension training to enhance muscle strength, along with robotics-assisted gait training and treadmill training to improve walking ability. Neurogenic bladder management included pelvic floor electrical stimulation and repetitive peripheral magnetic stimulation (rPMS) targeting the third sacral nerve. Bowel dysfunction was managed with oral lactulose (10 mL, 3 times daily) and glycerin enema (per rectal insertion, as needed) for evacuation. To prevent catheter-associated urinary tract infections, timed clamping of the urinary catheter was initiated for bladder training, followed by a transition to clean intermittent catheterization, supported by a hydration plan and bladder diary education.

After 1 month of systematic rehabilitation, the patient was able to ambulate independently; his lower limb muscle strength, Berg Balance Scale score, and Modified Barthel Index score increased to grade V, 46, and 84, respectively. However, residual issues were noted, including abnormal gait (ie, a Trendelenburg gait), limited improvement in paresthesia, involuntary lower limb twitching possibly due to muscle spasticity, urine volumes exceeding 400 mL during intermittent catheterization, and excessive sweating likely related to autonomic dysregulation. To identify the underlying causes of these symptoms, urodynamic testing was conducted, revealing a low-pressure, high-capacity bladder with detrusor overactivity during the storage phase and detrusor underactivity during the voiding phase (Table 1). Dynamic electrocardiography showed a low-frequency/high-frequency ratio of 4.37, indicating sympathetic nervous system (SNS) overactivation. Based on these findings, the intervention plan was adjusted. Gait training focused on strengthening the core muscle group. Pharmacologic adjustments included solifenacin succinate (5 mg orally at bedtime) to suppress bladder overactivity, baclofen (5 mg orally 3 times daily) to reduce muscle spasticity, and gabapentin (100 mg orally 3 times daily) to improve sensory abnormalities and inhibit sympathetic overactivation.

One month later (ie, after 2 months of systematic rehabilitation), the patient demonstrated substantial improvement in ambulation and gait; his Berg Balance Scale and Modified Barthel Index scores further increased to 56 and 98, respectively. Urinary function also showed considerable improvement, as indicated by a decreased number of catheterizations, reduced single-catheterization volume in Period 3 compared with Period 1, and increased spontaneous urination volume in Period 3 compared with Period 2 (each period comprised 14 days after catheter removal; Table 2). However, symptoms of lower limb paresthesia and excessive sweating remained unresolved. During telephone follow-up 2 weeks after discharge, the patient described his experience as follows: “I feel stable without any new symptoms. I’m satisfied with the treatment and grateful for the care I received.”

Discussion

Early symptoms of chlorfenapyr poisoning commonly include nausea, vomiting, fever, and sweating [2,9]. Laboratory examination shows elevated aminotransferase and myocardial enzyme levels, and MRI reveals white matter and spinal cord lesions. Based on characteristic poisoning symptoms, exposure history, and positive test results for chlorfenapyr and its metabolites, a diagnosis of chlorfenapyr poisoning was confirmed in our patient. Compared with cases involving ingestion [3,4,6,7], this patient may have been poisoned through dermal contact or inhalation, resulting in relatively low toxicity and slower disease progression. These factors, combined with timely medical intervention, contributed to the patient’s survival and favorable prognosis. Intriguingly, the patient’s blood creatine kinase level was not elevated during initial presentation, suggesting that rhabdomyolysis had not occurred early in the disease course. Subsequent events, such as vigorous exercise or even routine physical activity, may have contributed to creatine kinase elevation and the onset of rhabdomyolysis. Considering that chlorfenapyr poisoning leads to cellular energy depletion, this mechanism might also explain the delayed clinical deterioration.

Chlorfenapyr-induced dyskinesia may result from direct muscle toxicity or neurological injury affecting motor conduction pathways [2]. The corticospinal tract is essential for voluntary muscle movement. Brain MRI showed corticospinal tract involvement in our patient, whereas spinal MRI revealed damage to the spinal horn (T8-L1), which contains descending corticospinal tract fibers. These neuroimaging findings could explain the patient’s lower limb motor dysfunction. The prognosis of motor dysfunction remains unclear. In 1 reported case, ingestion caused lower limb weakness, paralysis, and death within 10 days of exposure [8]. Another patient immediately spat out chlorfenapyr without swallowing; they survived but remained paralyzed during follow-up [6]. In the present case, the patient’s lower limb motor dysfunction and abnormal gait were treated through conventional (eg, resistance, balance, and suspension training) and advanced (eg, robotics-assisted gait training) methods. Advanced rehabilitation techniques, such as exoskeleton systems [10] and weight support feedback canes [11], have been shown to improve lower limb muscle activity and gait performance in patients with chronic stroke, providing insight into alternative strategies for enhancing motor recovery.

Chlorfenapyr poisoning–associated neurogenic bladder may involve damage to a neural network distributed across both subcortical and cortical regions [12,13]. The SNS originates from T10 to L2 and regulates bladder function through the hypogastric nerve. α1-Receptors mediate bladder neck contraction, whereas β3-receptors inhibit detrusor activity. Micturition requires the brain to disinhibit the pontine micturition center, thereby suppressing the SNS and triggering urination [14,15]. Early MRI of our patient revealed lesions in the brain, pons, and T9 to T10 spinal cord, causing urinary retention due to bladder neck laxity, as well as voiding initiation difficulty. Follow-up MRI indicated reversibility of both white matter and spinal cord lesions. Previous reports concerning chlorfenapyr poisoning have suggested reversibility of white matter disease, whereas residual spinal cord atrophy persisted at follow-up [6,16]. However, the mechanisms underlying spinal cord and brain recovery remain unclear.

After catheter removal, urodynamic examination revealed detrusor overactivity during the storage phase and detrusor underactivity during the voiding phase, requiring abdominal pressure for urination. The voiding diary from Period 1 showed excessive single voided volumes, predisposing the bladder to overdistension and increasing the risk of urinary tract infection and renal damage. To address these issues, solifenacin succinate was administered to selectively block M3 receptors in the bladder, thereby alleviating detrusor overactivity. Consequently, compared with Period 1, the voiding diary from Period 2 indicated a lower mean daily voluntary voided volume, higher catheterization frequency, and reduced mean voided volume per catheterization, thereby lowering the risk of overactive bladder (Table 2). After intensive education focused on voiding and hydration planning [17], the patient showed increased mean daily voluntary voided volume and decreased mean daily catheterization volume and frequency during Period 3, indicating improved voluntary voiding safety (Table 2). Additionally, non-invasive modalities such as pelvic floor electrical stimulation and rPMS were utilized. rPMS is a neuromodulation technique targeting peripheral nerves or skeletal muscles to enhance neuroplasticity; it has been widely used to treat dysfunction caused by neurological injury [18]. Current studies indicate that repetitive transsacral magnetic stimulation significantly improves neurogenic bladder and bowel dysfunction [19,20]. These multimodal interventions successfully restored low-pressure voluntary voiding capacity in our patient, demonstrating the effectiveness of this comprehensive approach in addressing urinary dysfunction associated with chlorfenapyr exposure.

Another notable symptom in the present case was excessive sweating, likely due to heat production from muscle spasms and overexcitation of the SNS. Frequent involuntary twitching of the lower limbs suggested the presence of muscle spasms. Furthermore, ambulatory electrocardiography indicated sympathetic excitation, as evidenced by increased heart rate variability [21]. Spinal MRI revealed damage to the lateral cord, implying impaired spinal autonomic function and disruption of communication pathways between primary and higher central structures. To address these potential etiologies, baclofen and diazepam were administered to alleviate muscle spasms and paroxysmal sympathetic hyperactivity; gabapentin was utilized to relieve lower limb sensory abnormalities and potential sympathetic excitation. Gabapentin, which binds to voltage-gated calcium channels, is widely used to manage pain and abnormal sensations; it is suspected to reduce sympathetic excitability [22]. Additionally, current literature suggests that stimulation of the vagus nerve can enhance parasympathetic activity, reduce the low-frequency/high-frequency ratio, and provide therapeutic benefits for disorders associated with sympathetic hyperactivity [23]. Therefore, rPMS targeting the vagus nerve was administered in the present case to modulate autonomic balance and inhibit SNS hyperactivity. However, no clinically significant improvements in sweating or paresthesia were observed. This finding suggests a limitation in the efficacy of rPMS for autonomic modulation in cases of chlorfenapyr poisoning and underscores the need for future studies to identify more effective therapeutic strategies.

Conclusions

This report describes a rare case of chlorfenapyr poisoning characterized by lower limb motor dysfunction, neurogenic bladder, and white matter and spinal cord lesions. Despite the severity of neurological involvement, the patient achieved substantial functional and radiological improvement after comprehensive rehabilitation, underscoring the importance of early and multidisciplinary intervention. However, the incomplete resolution of hyperhidrosis and lower limb dysesthesia suggests the need for future studies to clarify underlying mechanisms and optimize treatment strategies.