Tuberous sclerosis complex-associated neuropsychiatric disorder (TAND) in a low-resource setting – From seizure to psychosis: A case report

Abstract

Introduction

Tuberous sclerosis complex (TSC) patients commonly present with neuropsychiatric symptoms – grouped as TSC-associated neuropsychiatric disorder (TAND) - incorporating Autism Spectrum Disorder (ASD) symptoms, intellectual and learning disabilities, psychiatric and behavioral problems. A structured symptomatic assessment known as the TAND-checklist can be useful in reviewing these symptoms systematically and comprehensively.

Case summary

A 21-year-old woman presented with delusions of reference, auditory hallucinations, irritability, restlessness, aggressive behavior, new-onset tremors and rigidity in both upper limbs, and refusal of food and medication intake for 1 week. She has a history of several seizure episodes since 3 years of age which was controlled on oral sodium valproate, carbamazepine, and clobazam. MRI revealed tubers in frontal and insular cortex.Ultrasound of the abdomen showed bilateral renal angiomyolipomas. She was diagnosed with TSC with psychotic symptoms.

Discussion

TSC2 mutations usually present early with epileptic spasms (ES), complex epilepsies, intellectual and cognitive deficits, cardiac rhabdomyomas, and sub-ependymal giant-cell astrocytomas (SEGAs) with high tuber-to-brain proportions (TBP). There is also a remarkable symptom overlap between autism spectrum disorder (ASD) and TSC with behavioral/psychiatric disorders. Social and behavioral problems seen in our patient may be a manifestation of either TSC, ASD, or both. Cost-effectiveness and pragmatism must be considered for TAND-patients in low-resource settings. While it may be theoretically valid to seek genetic testing, TBP-measurement, and mTOR-inhibitor therapy to address TAND-symptoms, they are impractical when compared to TAND-checklist during follow-up.

Highlights

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  Tuberous sclerosis complex (TSC) patients commonly present with neuropsychiatric symptoms – grouped as TSC-associated neuropsychiatric disorder (TAND) - incorporating Autism Spectrum Disorder (ASD) symptoms, intellectual and learning disabilities, psychiatric and behavioral problems.

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  Cost-effectiveness and pragmatism must be considered for TAND-patients in low-resource settings. TAND-checklist can be useful in reviewing TAND symptoms systematically and comprehensively.

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  Tuber-to-brain proportion (TBP) from imaging studies also help predict cognitive and neuropsychiatric disorders better than only radiologically summing up the number of tubers at a certain age; and TBP is inversely related to age at seizure onset, and cognitive index.