Sir,
Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disease with an estimated prevalence of 0.40/100,000 in Asia compared to 5.70/100,000 in Europe, North America, and Australia.[1] It is commonly characterized by a triad of motor, cognitive, and behavioral manifestations. Of which, the motor and cognitive symptoms remain the more common ones. The premanifest and prodromal period of HD is often depicted by subtle motor, cognitive, or behavioral signs which later inevitably progress to full-blown illness.[2] Diagnosis of HD with psychosis could be delayed and difficult as the use of antipsychotics can mask the chorea associated with HD.[3] With this background, we present a rare and challenging case of HD with treatment-resistant psychosis discussing the management issues.
A 35-year-old female patient presented with a 5-year continuous illness characterized by increased irritability, delusion of reference, increased religiosity, impaired care of her children, and hallucinatory behavior with no response to adequate trials with olanzapine and quetiapine. Her premorbid personality was depicted by easy irritability, low frustration tolerance, mood swings, and stubbornness. Further exploration revealed neurological manifestations in the form of speech and gait abnormalities for the past 6 months. A family history of similar neurological signs/symptoms was elicited in her father, brother, and paternal uncle. All of whom had expired before the age of 45 years, but none of them had the associated psychiatric symptoms as in the index case. Neurological examination revealed waddling gait and slurring of speech. Mental status examination revealed hallucinatory behavior, irritable affect, and somatic preoccupation.
Neurology referral was taken, and genetic testing for HD was advised. The test revealed positive for HD with 49 cytosine–adenine–guanine nucleotide repeats within the huntingtin gene. A diagnosis of HD with psychosis not otherwise specified with borderline personality traits was made. The Brief Psychiatric Rating Scale (BPRS) at baseline was 46. Due to failed trials of adequate dose and duration with olanzapine and quetiapine, the patient was started on tablet clozapine 12.5 mg and tetrabenazine 25 mg with benzodiazepines. Gradually, clozapine was uptitrated to 175 mg over 3 weeks. Clozapine was well tolerated with no persistent adverse effects. At the end of 6 weeks, the patient showed a significant improvement in domains of irritability, hallucinatory behavior, and suspiciousness and BPRS improved to 32. Her speech and gait disturbances continued to remain, although no worsening was seen. Genetic counseling was provided to the family members.
In the current case of HD with treatment -resistant psychosis, it is difficult to ascertain whether psychosis is secondary to HD or is comorbidity with HD. Schizophrenia-like symptoms have been found to occur anytime during the illness and cases exist where psychotic symptoms have preceded neurological symptoms by 5 years, similar to our case.[2,4]
The case offers several unique learning points. First, the preclinical phase of HD was dominated by psychotic manifestations. This is in contrast to the most common manifestation of mood symptoms, as high as 33%–76%. Psychotic or schizophrenia-like symptoms are seen in 6%–25% of patients with HD, significantly higher than the general population.[2,4] Further, the borderline personality traits were also a significant contributor to the morbidity.
Second, the case was associated with management challenges in the form of treatment-resistant psychosis with failed trials of quetiapine and olanzapine. First-generation antipsychotics were not chosen due to increased propensity to extrapyramidal symptoms. Further, clozapine is known to be effective for both HD (reduces abnormal involuntary movements) and treatment-resistant psychosis.[5] The case demonstrates safety and efficacy of clozapine in HD.
The index case is probably the first of its kind reported from India. The case highlights the importance of careful history taking and timely assessment for HD in patients with a positive family history. Neurologists and psychiatrists alike must be sensitized to have a high degree of suspicion in patients with atypical presentations and psychiatric illness with neurological manifestations.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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