Residual central nervous system damage due to organoarsenic poisoning

Nakamagoe, Kiyotaka; Fujizuka, Natsu; Koganezawa, Tadachika; Shimizu, Kotone; Takiguchi, Shino; Horaguchi, Takahiro; Ishii, Kazuhiro; Tamaoka, Akira

doi:10.1016/j.ntt.2013.02.007

Cited by 8 publications

(3 citation statements)

References 26 publications

(36 reference statements)

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“…The IPL is known to play an important role in controlling the generation of saccadic eye movements in coordination with the frontal eye field (FEF) in the prefrontal cortex [15,16,21]. Damage to the neural mechanisms controlling saccadic eye movements may lead to the occurrence of a type of square-wave jerks (SWJs) [22][23][24][25] classified as saccadic intrusions that have been reported in conjunction with AD [3,26,27]. However, recent studies have reported that SWJs in AD are greatly affected by age and are of limited pathological significance [3].…”

Section: Introductionmentioning

confidence: 99%

Abnormal Saccadic Intrusions with Alzheimer's Disease in Darkness

Nakamagoe

Yamada

Kawakami

et al. 2019

CAR

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Background: Classified as saccadic intrusions, Square-Wave Jerks (SWJs) have been observed during Visual Fixation (VF) in Alzheimer’s Disease (AD). However, the pathological significance of this phenomenon remains unclear. Objective: The present study analyzed the characteristics of SWJs in patients with AD with their eyes open in the dark without VF. Methods: Fifteen patients with AD and 15 healthy age- and sex-matched controls were investigated and compared. Saccadic intrusions with and without VF were detected as SWJs and measured using an electronystagmogram. Results: No significant difference in the frequency of SWJs was observed between control and AD groups with VF, but significantly more SWJs were observed in the AD group than in the control group in the absence of VF (p<0.01). In the control group, the frequency of SWJs was significantly higher with VF as compared to without VF. Conversely, the frequency in the AD group was significantly higher without VF. Furthermore, a directly proportional relationship was observed between the frequency of SWJs and higher-order function (R>0.55) in the AD group. Conclusion: SWJs without VF may have pathological significance in AD. In healthy individuals, SWJs are generated by VF and suppressed without VF. Conversely, in AD, SWJs are generated rather than suppressed in the absence of VF. These pathognomonic SWJs without VF also appear to be correlated with higher-order dysfunction, reflecting AD-related cortical damage. These findings suggest that pathological SWJs without VF observed in AD derive from cortical damage and may constitute an important marker of a higher-order function.

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Section: Introductionmentioning

confidence: 99%

Abnormal Saccadic Intrusions with Alzheimer's Disease in Darkness

Nakamagoe

Yamada

Kawakami

et al. 2019

CAR

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“…Among arsenic compounds detected in the well water, diphenylarsinic acid (DPAA), a degradation or ingredient product of the above-mentioned emetic weapons, was a major compound. With regard to the neurological symptoms suspected to be caused by organoarsenic exposure, a recent study reported abnormal eye movements (upbeat nystagmus) in the victims of the accident as a residual, persistent, and chronic central nervous system (CNS) damage due to organoarsenic poisoning (Nakamagoe et al , 2013). …”

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confidence: 99%

Developmental Subchronic Exposure to Diphenylarsinic Acid Induced Increased Exploratory Behavior, Impaired Learning Behavior, and Decreased Cerebellar Glutathione Concentration in Rats

Negishi

Matsunaga

Kobayashi

et al. 2013

Toxicological Sciences

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In Japan, people using water from the well contaminated with high-level arsenic developed neurological, mostly cerebellar, symptoms, where diphenylarsinic acid (DPAA) was a major compound. Here, we investigated the adverse effects of developmental exposure to 20mg/l DPAA in drinking water (early period [0–6 weeks of age] and/or late period [7–12]) on behavior and cerebellar development in male rats. In the open field test at 6 weeks of age, early exposure to DPAA significantly increased exploratory behaviors. At 12 weeks of age, late exposure to DPAA similarly increased exploratory behavior independent of the early exposure although a 6-week recovery from DPAA could reverse that change. In the passive avoidance test at 6 weeks of age, early exposure to DPAA significantly decreased the avoidance performance. Even at 12 weeks of age, early exposure to DPAA significantly decreased the test performance, which was independent of the late exposure to DPAA. These results suggest that the DPAA-induced increase in exploratory behavior is transient, whereas the DPAA-induced impairment of passive avoidance is long lasting. At 6 weeks of age, early exposure to DPAA significantly reduced the concentration of cerebellar total glutathione. At 12 weeks of age, late, but not early, exposure to DPAA also significantly reduced the concentration of cerebellar glutathione, which might be a primary cause of oxidative stress. Early exposure to DPAA induced late-onset suppressed expression of NMDAR1 and PSD95 protein at 12 weeks of age, indicating impaired glutamatergic system in the cerebellum of rats developmentally exposed to DPAA.

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“…Upbeat nystagmus occurs in association with various disorders, such as infarction (Hirose et al 1998), multiple sclerosis (Fisher et al 1983), Wernicke's encephalopathy (Abouaf et al 2011), cerebellar vermis tumor (Higashi-Shingai et al 2011), and poisoning (Nakamagoe et al 2013). Though many patients developed primary position upbeat nystagmus due to medullary lesions (Hirose et al 1998), an unaccompanied symptom of upbeat nystagmus is an insufficient regional diagnostic sign.…”

Section: Discussionmentioning

confidence: 99%

Upbeat nystagmus is a useful sign in the regional diagnosis of trigeminal nerve disorder with multiple sclerosis

Nakamagoe

Tozaka

Nohara

et al. 2018

Multiple Sclerosis and Related Disorders

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Trigeminal nerve disorder is an important neurological sign that is often seen with multiple sclerosis (MS). We investigated eye movements in three MS patients with trigeminal disorder due to pontine lesions near the trigeminal root entry zone (REZ). Upbeat nystagmus was observed in all MS patients with trigeminal REZ lesions. We conjecture that trigeminal nerve disorder and upbeat nystagmus appeared due to simultaneous damage to both the trigeminal nerve and the vestibulo-ocular reflex pathway. If upbeat nystagmus appears in MS patients exhibiting a trigeminal nerve disorder, such as trigeminal neuralgia, and paralysis, pontine lesions near the trigeminal REZ should be considered. Upbeat nystagmus can be understood as a useful sign for the clinical regional diagnosis of trigeminal nerve disorder.

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Residual central nervous system damage due to organoarsenic poisoning

Abstract: Detection of abnormal ocular movements may be useful in evaluating residual/persistent/chronic CNS damage due to organoarsenic poisoning.

Cited by 8 publications

References 26 publications

Abnormal Saccadic Intrusions with Alzheimer's Disease in Darkness

Abnormal Saccadic Intrusions with Alzheimer's Disease in Darkness

Developmental Subchronic Exposure to Diphenylarsinic Acid Induced Increased Exploratory Behavior, Impaired Learning Behavior, and Decreased Cerebellar Glutathione Concentration in Rats

Upbeat nystagmus is a useful sign in the regional diagnosis of trigeminal nerve disorder with multiple sclerosis

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