6635 Neuro Week 10 original follow due February 7, 2022 at 10 am

Major or Mild Neurocognitive Disorder Due to Huntington’s Disease

Diagnostic Criteria

1. The criteria are met for major or mild neurocognitive disorder.

2. There is insidious onset and gradual progression.

3. There is clinically established Huntington’s disease, or risk for Huntington’s disease based on family history or genetic testing.

4. The neurocognitive disorder is not attributable to another medical condition and is not better explained by another mental disorder.

Coding note: For major neurocognitive disorder due to Huntington’s disease, with behavioral disturbance, code first 333.4 (G10) Huntington’s disease, followed by 294.11 (F02.81) major neurocognitive disorder due to Huntington’s disease, with behavioral disturbance. For major neurocognitive disorder due to Huntington’s disease, without behavioral disturbance, code first 333.4 (G10) Huntington’s disease, followed by 294.10 (F02.80) major neurocognitive disorder due to Huntington’s disease, without behavioral disturbance.

For mild neurocognitive disorder due to Huntington’s disease, code 331.83 (G31.84). (Note: Do not use the additional code for Huntington’s disease. Behavioral disturbance cannot be coded but should still be indicated in writing.)

Diagnostic Features

Progressive cognitive impairment is a core feature of Huntington’s disease, with early changes in executive function (i.e., processing speed, organization, and planning) rather than learning and memory. Cognitive and associated behavioral changes often precede the emergence of the typical motor abnormalities of bradykinesia (i.e., slowing of voluntary movement) and chorea (i.e., involuntary jerking movements). A diagnosis of definite Huntington’s disease is given in the presence of unequivocal, extrapyramidal motor abnormalities in an individual with either a family history of Huntington’s disease or genetic testing showing a CAG trinucleotide repeat expansion in the HTT gene, located on chromosome 4.

Associated Features Supporting Diagnosis

Depression, irritability, anxiety, obsessive-compulsive symptoms, and apathy are frequently, and psychosis more rarely, associated with Huntington’s disease and often precede the onset of motor symptoms(Duff et al. 2007).

Prevalence

Neurocognitive deficits are an eventual outcome of Huntington’s disease; the worldwide prevalence is estimated to be 2.7 per 100,000. The prevalence of Huntington’s disease in North America, Europe, and Australia is 5.7 per 100,000, with a much lower prevalence of 0.40 per 100,000 in Asia(Pringsheim et al. 2012).

Development and Course

The average age at diagnosis of Huntington’s disease is approximately 40 years, although this varies widely(Foroud et al. 1999). Age at onset is inversely correlated with CAG expansion length(Lee et al. 2012). Juvenile Huntington’s disease (onset before age 20) may present more commonly with bradykinesia, dystonia, and rigidity than with the choreic movements characteristic of the adult-onset disorder. The disease is gradually progressive, with median survival approximately 15 years after motor symptom diagnosis(Roos et al. 1993).

Phenotypic expression of Huntington’s disease varies by presence of motor, cognitive, and psychiatric symptoms. Psychiatric and cognitive abnormalities can predate the motor abnormality by at least 15 years(Duff et al. 2007; Stout et al. 2011). Initial symptoms requiring care often include irritabity, anxiety, or depressed mood. Other behavioral disturbances may include pronounced apathy, disinhibition, impulsivity, and impaired insight, with apathy often becoming more progressive over time(Thompson et al. 2012). Early movement symptoms may involve the appearance of fidgetiness of the extremities as well as mild apraxia (i.e., difficulty with purposeful movements), particularly with fine motor tasks. As the disorder progresses, other motor problems include impaired gait (ataxia) and postural instability. Motor impairment eventually affects speech production (dysarthria) such that the speech becomes very difficult to understand, which may result in significant distress resulting from the communication barrier in the context of comparatively intact cognition. Advanced motor disease severely affects gait with progressive ataxia. Eventually individuals become nonambulatory. End-stage motor disease impairs motor control of eating and swallowing, typically a major contributor to the death of the individual from aspiration pneumonia.

Risk and Prognostic Factors

Genetic and physiological

The genetic basis of Huntington’s disease is a fully penetrant autosomal dominant expansion of the CAG trinucleotide, often called a CAG repeat in the huntingtin gene. A repeat length of 36 or more is invariably associated with Huntington’s disease, with longer repeat lengths associated with early age at onset. A CAG repeat length of 36 or more is invariably associated with Huntington’s disease(Groen et al. 2010).

Diagnostic Markers

Genetic testing is the primary laboratory test for the determination of Huntington’s disease, which is an autosomal dominant disorder with complete penetrance. The trinucleotide CAG is observed to have a repeat expansion in the gene that encodes huntingtin protein on chromosome 4. A diagnosis of Huntington’s disease is not made in the presence of the gene expansion alone, but the diagnosis is made only after symptoms become manifest. Some individuals with a positive family history request genetic testing in a presymptomatic stage. Associated features may also include neuroimaging changes; volume loss in the basal ganglia, particularly the caudate nucleus and putamen, is well known to occur and progresses over the course of illness. Other structural and functional changes have been observed in brain imaging but remain research measures.

Functional Consequences of Major or Mild Neurocognitive Disorder Due to Huntington’s Disease

In the prodromal phase of illness and at early diagnosis, occupational decline is most common, with most individuals reporting some loss of ability to engage in their typical work. The emotional, behavioral, and cognitive aspects of Huntington’s disease, such as disinhibition and personality changes, are highly associated with functional decline(Beglinger et al. 2010). Cognitive deficits that contribute most to functional decline may include speed of processing, initiation, and attention rather than memory impairment(Peavy et al. 2010). Given that Huntington’s disease onset occurs in productive years of life, it may have a very disruptive effect on performance in the work setting as well as social and family life. As the disease progresses, disability from problems such as impaired gait, dysarthria, and impulsive or irritable behaviors may substantially add to the level of impairment and daily care needs, over and above the care needs attributable to the cognitive decline. Severe choreic movements may substantially interfere with provision of care such as bathing, dressing, and toileting.

Differential Diagnosis

Other mental disorders

Early symptoms of Huntington’s disease may include instability of mood, irritability, or compulsive behaviors that may suggest another mental disorder. However, genetic testing or the development of motor symptoms will distinguish the presence of Huntington’s disease.

Other neurocognitive disorders

The early symptoms of Huntington’s disease, particularly symptoms of executive dysfunction and impaired psychomotor speed, may resemble other neurocognitive disorders (NCDs), such as major or mild vascular NCD.

Other movement disorders

Huntington’s disease must also be differentiated from other disorders or conditions associated with chorea, such as Wilson’s disease, drug-induced tardive dyskinesia, Sydenham’s chorea, systemic lupus erythematosus, or senile chorea. Rarely, individuals may present with a course similar to that of Huntington’s disease but without positive genetic testing; this is considered to be a Huntington’s disease phenocopy that results from a variety of potential genetic factors(Wild et al. 2008).

References: Major or Mild Neurocognitive Disorder Due to Huntington’s Disease

• Beglinger LJ , O’Rourke JJ , Wang C , et al: Earliest functional declines in Huntington disease. Psychiatry Res 178(2):414–418, 2010 10.1016/j.psychres.2010.04.030

• Duff K , Paulsen JS , Beglinger LJ , et al: Psychiatric symptoms in Huntington’s disease before diagnosis: the predict-HD study. Biol Psychiatry 62(12):1341–1346, 2007

• Foroud T , Gray J , Ivashina J , Conneally PM : Differences in duration of Huntington’s disease based on age at onset. J Neurol Neurosurg Psychiatry 66(1):52–56, 1999

• Groen JL , de Bie RMA , Foncke EM , et al: Late-onset Huntington disease with intermediate CAG repeats: true or false? J Neurol Neurosurg Psychiatry 81(2):228–230, 2010 10.1136/jnnp.2008.170902

• Lee JM , Ramos EM , Lee JH , et al: CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion. Neurology 78(10):690–695, 2012 10.1212/WNL.0b013e318249f683

• Peavy GM , Jacobson MW , Goldstein JL , et al: Cognitive and functional decline in Huntington’s disease: dementia criteria revisited. Mov Disord 25(9):1163–1169, 2010 10.1002/mds.22953

• Pringsheim T , Wiltshire K , Day L , et al: The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis. Mov Disord 27(9):1083–1091, 2012 10.1002/mds.25075

• Roos RA , Hermans J , Vegter-van der Vlis M , et al: Duration of illness in Huntington’s disease is not related to age at onset. J Neurol Neurosurg Psychiatry 56(1):98–100, 1993

• Stout JC , Paulsen JS , Queller S , et al: Neurocognitive signs in prodromal Huntington disease. Neuropsychology 25(1):1–14, 2011 10.1037/a0020937

• Thompson JC , Harris J , Sollom AC , et al: Longitudinal evaluation of neuropsychiatric symptoms in Huntington’s disease. J Neuropsychiatry Clin Neurosci 24(1):53–60, 2012 10.1176/appi.neuropsych.11030057

• Wild EJ , Mudanohwo EE , Sweeney MG , et al: Huntington’s disease phenocopies are clinically and genetically heterogeneous. Mov Disord 23(5):716–720, 2008 10.1002/mds.21915