Neuro Case Challenge: A 35-Year-Old With Angry, Aggressive Outbursts, Memory Loss, and Insomnia  

Niranjan N. Singh, MBBS, MD, DM


October 04, 2022

The optimal management of Huntington disease involves a multidisciplinary approach that includes neurology, nurses, physical therapy, speech-language pathology, and dietitians and other healthcare professionals. The goal is to optimize the quality of life based on the changing need of the patient. These consist of combined pharmacologic and lifestyle changes, including behavioral therapy. Tetrabenazine and the modified version, deutetrabenazine, can be used to treat choreiform movements. A sustained anti-choreic effect is seen at 50-75 mg/day.[9] Side effects include depression and anxiety. Sulpiride, olanzapine, risperidone, and quetiapine are also used to manage chorea; weight gain and sedation are important side effects.

Limited evidence is available regarding the treatment of psychiatric symptoms in Huntington disease. Depression, anxiety, obsessive-compulsive disorder, and irritability may be treated with nonpharmacologic interventions, such as cognitive-behavioral therapy or psychodynamic therapy. Pharmacologic interventions may involve selective serotonin reuptake inhibitors, including citalopram, fluoxetine, paroxetine, sertraline, mirtazapine, and venlafaxine. Neuroleptics can be used to treat psychosis. Methylphenidate, atomoxetine, modafinil, amantadine, bromocriptine, and bupropion have been used to treat apathy. Evidence does not support medications used to help cognitive symptoms. Coping strategies may be useful as an alternative.

Apart from symptomatic treatment, pharmacologic agents have failed to show benefit in clinical trials as disease-modifying agents. The most promising approaches in regard to disease modification are emerging therapies aimed at lowering levels of mHTT by targeting either the DNA or RNA of the mHTT gene.[10] RNA targeting can be achieved using antisense oligonucleotides (ASOs), RNA interference (RNAi), or small-molecule splicing inhibitors. ASOs are currently being tested in humans for the first time. They are delivered intrathecally and catalyze the degradation of HTT mRNA by RNAse H, thereby reducing the production of the mHTT protein. In animal models, this results in as much as an 80% sustained reduction in HTT mRNA levels. Targeting the DNA of mHTT can be achieved using two approaches: zinc finger proteins and the clustered interspaced short palindromic repeats (CRISPR)/Cas9 system. The method was successfully tested in a rodent model of Huntington disease.[11]

The patient in this case was diagnosed with Huntington disease with CAG repeat 78. He was started on tetrabenazine for abnormal movements and citalopram for depression. He opted to apply for federal disability. His children are asymptomatic, and the family decided not to investigate until symptoms develop or they are age 18 years.


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