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Neuropsychiatric Manifestations of Wilson Disease: Correlation with MRI and Glutamate Excitotoxicity

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Abstract

This study aims to identify neuropsychiatric manifestations in neurological Wilson disease (NWD), and their correlation with MRI changes and glutamate excitotoxicity. Forty-three consecutive patients with NWD from a tertiary care teaching hospital were evaluated prospectively who fulfilled the inclusion criteria. The neuropsychiatric evaluation was done using Neuropsychiatric Inventory (NPI) battery that assesses 12 domains including delusion, hallucination, agitation/aggression, dysphoria/depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, appetite change, and abnormal nighttime behavior. Cranial MRI was done using a 3 T machine, and locations of signal changes were noted including the total number of MRI lesions. Serum glutamate level was measured by a fluorescence microplate reader. Abnormal NPI in various domains and total NPI scores were correlated with MRI lesions, serum and urinary copper, and glutamate level. The median age of the patients was 16 years. Forty-one (48.8%) patients had cognitive impairment and 37 (86%) had movement disorder. Neurobehavioral abnormality was detected in all—commonest being agitation (90.7%) followed by appetite change (81.4%), elation (74.4%), irritability (69.8%), anxiety (67.4%), depression (65.1%), apathy (44.2%), night time abnormal behavior (32.6%), aberrant motor behavior (20.9%), delusions (16.3%), and hallucination (18.6%). The thalamic lesion was associated with depression, globus pallidus with depression and anxiety, caudate with anxiety and agitation, brainstem with irritability, and frontal cortex with apathy. Serum glutamate level was higher in NWD. NPI sum score correlated with MRI load and glutamate level. Varying severity of neurobehavioral abnormalities are common in the patients with NWD and correlate with the location of MRI lesion and glutamate level.

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Data Availability

The data supporting the results of this investigation are available from the corresponding author upon request.

Abbreviations

ADL:

Activity of daily living

BFM:

Burke-Fahn-Marsden

CNS:

Central nervous system

Cu:

Copper

MRI:

Magnetic resonance imaging

MMSE:

Mini-Mental State Examination

NPI:

Neuropsychiatric Inventory

NMDA:

N-methyl-D-aspartate

WD:

Wilson disease

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Acknowledgements

We acknowledge Professor S Kumar, Department of Radiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences for the evaluation of MRI.

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Authors and Affiliations

  1. Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India

    Jayantee Kalita & Usha K. Misra

  2. Department of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea

    Vijay Kumar

  3. Department of Neurology, Sawai Man Singh Medical College, Jaipur, 302004, India

    Vasudev Parashar

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  1. Jayantee Kalita
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  4. Usha K. Misra
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Contributions

Conceptualization: [J. Kalita]; Methodology: [J. Kalita]; Formal analysis and investigation: [J. Kalita, V. Kumar, V. Parashar]; Writing — original draft preparation: [J. Kalita]; Writing — review and editing: [J. Kalita, V. Kumar,]; Funding acquisition: [J. Kalita]; Resources: [J. Kalita, U. K. Misra]; Supervision: [J. Kalita, U. K. Misra].

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Correspondence to Jayantee Kalita.

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Kalita, J., Kumar, V., Parashar, V. et al. Neuropsychiatric Manifestations of Wilson Disease: Correlation with MRI and Glutamate Excitotoxicity. Mol Neurobiol 58, 6020–6031 (2021). https://doi.org/10.1007/s12035-021-02525-4

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