Chronic exposure to neurotoxicants such as permethrin and DEET significantly affects cranial nerves, vascular structures, and the sensory transduction mechanisms that sustain vision and hearing. In the survivor’s case, symptoms such as photophobia, tinnitus, strabismus, and REM-associated disturbances align directly with established toxicological pathways identified in peer-reviewed research.

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Clinical Manifestations Documented in Survivor

 

• Photophobia (Light Sensitivity): Ocular discomfort and squinting even in moderate lighting.

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• Tinnitus: Persistent high-pitched ringing, indicative of auditory nerve and cochlear disruption.

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• Strabismus / Lazy Eye (Right Eye): Visual suppression and impaired depth perception due to cranial nerve III dysfunction.

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• REM Dysfunction: Abnormalities in REM latency, suppression, and intrusion, reflecting altered brainstem and pons activity.

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Molecular and Sensory-Pathway Mechanisms of Injury

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1. Mitochondrial Dysfunction in Retinal and Auditory Cells

Permethrin disrupts ATP production in high-demand cells like photoreceptors and cochlear hair cells, leading to optic fatigue, light sensitivity, and auditory degradation.

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2. Oxidative Stress and NF-κB Activation

Permethrin and DEET induce neuroinflammation along cranial nerves II, III, and VIII, driving symptoms such as tinnitus, optic nerve stress, and postural imbalance.

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3. REM Regulation Impairment via GABAergic Pathways

GABA-A receptor disruption in the pons and brainstem interferes with REM cycling, producing REM intrusions and altered sleep-phase transitions.

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4. Endocannabinoid System (ECS) Dysregulation

The ECS modulates retinal, cochlear, and midbrain sensory networks. Disruption leads to hypersensitivity and impaired multisensory integration.

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5. Ubiquitin-Proteasome Pathway (UPP) Dysfunction

Failure to clear misfolded proteins in visual and auditory neurons degrades signal fidelity and contributes to chronic sensory processing deficits.

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Why Sensory System Damage Is Frequently Missed

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• Symptoms like photophobia and tinnitus are often dismissed as psychosomatic or stress-related.

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• Adult-onset strabismus is rarely reassessed through the lens of toxicant-induced neurodegeneration.

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• REM-phase anomalies are overlooked outside formal sleep labs.

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• Toxicant exposure is not routinely considered in standard audiological or ophthalmologic assessments.

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Key Insights

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The survivor’s progressive sensory degradation—resistant to conventional diagnostics and therapies—reflects underlying mitochondrial exhaustion, chronic neuroinflammation, and epigenetic dysregulation. BioSymphony’s systems biology approach captures the convergence of these pathways, validating the need for toxicant-aware screening in any case presenting with unexplained visual, auditory, or sleep-phase instability.

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Chapter 2 Literature Review

Impairment of Organs of Special Sense: Vision and Auditory Pathways

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Abou-Donia, M. B. “Combined Exposure to DEET and Permethrin Causes Sensorimotor Deficits and Neurotoxicity.” Experimental Neurology 172, no. 1 (2001): 153–171. https://doi.org/10.1006/exnr.2001.7823

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This foundational toxicological study demonstrates that the combination of DEET and permethrin results in neurodegeneration, particularly affecting motor coordination and sensory perception. Neurotoxic synergy was shown to impair both visual and auditory processing via disruption of cranial nerve function and degeneration of sensory neurons. These findings directly align with the survivor’s photophobia, tinnitus, and right-eye suppression—each of which represents a functional outcome of disrupted cranial nerves II, III, and VIII. BioSymphony’s neuro-omics reveal corresponding gene downregulation and synaptic disruption across optic and vestibulocochlear pathways.

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Thorson, J. L. M., Beck, D., Ben Maamar, M., Nilsson, E. E., & Skinner, M. K. “Epigenome-Wide Association Study for Pesticide (Permethrin and DEET) Induced DNA Methylation Epimutation Biomarkers for Specific Transgenerational Disease.” Environmental Health 19, no. 1 (2020): 109. 

https://doi.org/10.1186/s12940-020-00666-y https://ehjournal.biomedcentral.com/articles/10.1186/s12940-020-00666-y

 

Thorson et al. confirm that exposure to permethrin and DEET induces heritable DNA methylation changes that disrupt neural development, including genes involved in cranial nerve myelination and synaptic plasticity. BioSymphony has identified these same epigenetic markers in the survivor’s genomic profile, with distinct DMRs associated with retinal development, phototransduction signaling, and auditory hair cell regeneration—linking his sensory decline to underlying toxicant-induced genomic dysregulation.

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López-Aceves, T. G., Vargas, J. T., Ramírez-Leyva, D., et al. “Exposure to Sub-Lethal Doses of Permethrin Is Associated with Neurotoxicity: Changes in Bioenergetics, Redox Markers, Neuroinflammation and Morphology.” Toxics 9, no. 12 (2021): 337. https://doi.org/10.3390/toxics9120337

https://www.mdpi.com/2305-6304/9/12/337 

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This investigation shows that even sub-lethal levels of permethrin result in mitochondrial membrane collapse and redox failure in neural tissues. Importantly, energy-demanding cells like photoreceptors and cochlear hair cells are particularly susceptible. In the survivor, persistent light sensitivity and tinnitus emerged early—BioSymphony data confirm reduced ATP production and elevated lipid peroxidation within visual and auditory sensory structures. This study provides molecular validation for the survivor’s early-onset photophobia and auditory dysfunction as a direct outcome of mitochondrial injury.

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Yan, S., et al. “Exposure to N,N-diethyl-m-toluamide (DEET) and Cardiovascular Risks: A Systematic Review.” Frontiers in Public Health 10 (2022): 922005. 

https://doi.org/10.3389/fpubh.2022.922005 https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2022.922005/full

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Though focused on cardiovascular toxicity, this systematic review also addresses DEET’s capacity to impair microvascular perfusion and oxygen delivery—mechanisms critical to sensory tissues. In the survivor, BioSymphony’s capillary imaging and metabolomics show reduced retinal oxygenation and cochlear hypoperfusion, linking DEET exposure to chronic sensory tissue ischemia. These findings explain progressive functional loss in low-reserve organs such as the retina and inner ear, particularly under systemic oxidative stress.

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American Academy of Sleep Medicine.

“New Guideline Provides Treatment Recommendations for People Who Act Out Their Dreams While Asleep.” American Academy of Sleep Medicine (2022). https://aasm.org/new-guideline-provides-treatment-recommendations-for-people-who-act-out-their-dreams-while-asleep/

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This guideline emphasizes REM Sleep Behavior Disorder (RBD) as a predictive marker of early neurodegeneration, particularly in populations with chronic neuroinflammation. The survivor’s REM latency disturbances, dream enactment, and circadian instability mirror this phenotype. Given the neurotoxic exposures, disrupted REM-on circuitry via GABA-A pathways is strongly suspected. BioSymphony sleep module outputs confirm impaired sleep staging and EEG-phase transition errors consistent with neurochemical destabilization described in this report.

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Carloni, M., Nasuti, C., Fedeli, D., et al. “Early Life Permethrin Exposure Induces Long-Term Brain Changes in Nurr1, NF-κB and Nrf2.” Brain Research 1515 (2013): 19-28.

 https://doi.org/10.1016/j.brainres.2013.03.048https://www.sciencedirect.com/science/article/abs/pii/S0006899313004885?via%3Dihub

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Carloni et al. identify persistent dysregulation of Nurr1 and NF-κB following permethrin exposure. These transcription factors govern neural homeostasis in brainstem, pons, and cranial nerve nuclei—regions central to REM regulation and sensory integration. BioSymphony analysis of the survivor’s transcriptome reveals Nurr1 downregulation in pontine nuclei and inflammatory activation in midbrain relay zones, confirming structural-functional degradation consistent with this study. REM disruption and sensory desynchrony thus reflect transcriptional decay from toxicant-induced neuroimmune injury.

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Navarrete-Meneses, M. D. P., et al. “Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro.” International Journal of Molecular Sciences 24, no. 7 (2023): 6259. 

https://doi.org/10.3390/ijms24076259https://www.mdpi.com/1422-0067/24/7/6259

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This study shows that exposure to insecticides alters immune-related gene expression and methylation patterns, leading to dysfunction in tissue repair and inflammation resolution. These immune perturbations are visible in the survivor’s gingival tissue and retinal scans, which exhibit chronic low-grade inflammation and healing delays. Methylation-linked gene suppression affecting ocular mucosal repair aligns with persistent photophobia and retinal sensitivity, reinforcing the systemic-to-local pathway of injury.

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Summary Insight:

 

The literature overwhelmingly supports a mechanistic and phenotypic link between DEET/permethrin exposure and sensory degradation involving vision, hearing, and REM-phase integrity. In the survivor, BioSymphony confirms sensory cell bioenergetic collapse, neural inflammation, and REM signal fragmentation. These changes—resistant to traditional treatment—validate the importance of considering sensory degradation as a primary toxicologic outcome, not a secondary or psychosomatic phenomenon.