eMedicine Specialties > Psychiatry > Adult

Huntington Disease Dementia: Differential Diagnoses & Workup

Author: Idan Sharon, MD, Consulting Staff, Departments of Neurology and Psychiatry, Cornell New York Methodist Hospital; Private Practice
Coauthor(s): Tulay Ersan, MD, Chief of Geriatrics, Department of Internal Medicine, Division of Geriatrics, Monmouth Medical Center; Roni Sharon, University of Michigan
Contributor Information and Disclosures

Updated: Aug 20, 2007

Differential Diagnoses

Alzheimer Disease
Parkinson Disease Dementia
Tourette Syndrome
Wilson Disease

Other Problems to Be Considered

The differential diagnosis of HD depends on the presenting symptoms and family history. The dementia of patients with HD, although characteristic, is not unique. Many conditions must be considered when diagnosing Huntington dementia, as follows:

Genetic disorders

Genetic disorders to consider in the differential of an adult patient who has cognitive impairment with chorea include dentatorubropallidoluysian and neuroacanthocytosis. Dentatorubropallidoluysian is rare in the United States; however, it may be considered in patients of Japanese descent. Patients with neuroacanthocytosis also may present with dementia and chorea, yet the acanthocyte hallmark pathology helps differentiate this disease.

Other genetic conditions that may be considered include Wilson disease, hereditary ataxias, benign hereditary ataxia, and mitochondrial disorders.

Gilles de la Tourette syndrome

Gilles de la Tourette syndrome is most often transmitted in an autosomal dominant pattern, but such patients have an earlier onset, show motor ticks rather than chorea, and lack the behavioral and mental changes.

Chorea

Senile chorea is a rare disorder beginning in persons older than 60 years. The abnormal movements are usually less prominent than in patients with HD, and no comparable degree of dementia develops.

A reversible adult chorea can also develop in association with lupus erythematosus or thyrotoxicosis. Reversible adult chorea has an abrupt onset and gradually disappears within weeks or months. Also, disorders that may mimic HD (eg, schizophrenia, benign familial chorea, inherited ataxias, neural acanthocytosis, familial Alzheimer disease [AD]) do not show the CAG expansion in the HD gene.

Other conditions associated with dementia

When classifying degenerative dementias, 2 major profiles may be considered. The subcortical type primarily affects attention, judgment, and behavior. This dementia pattern resembles such pathologies as HD, Parkinson disease (PD), supranuclear palsy, and dementia of the frontal lobe. Cortical dementias (eg, AD) involve the gray matter cortex and manifest with early-onset memory losses and language disturbances. Patients with subcortical dementias (eg, HD, PD, subcortical vascular dementias) have more motor symptoms than those with temporoparietal or frontal dementias. Unfortunately, clinical characteristics of cortical and subcortical dementias show a subtle overlap, which complicates a distinct diagnosis.

Patients with AD and HD can be differentiated on the basis of specific neurocognitive deficits that are independent of severity. Using the Mattis Dementia Rating Scale, at all levels of severity, patients with HD are found to be more impaired on initiation and perseveration but less impaired on memory. At moderate and severe levels of dementia, patients with HD are more impaired in constructional praxis than patients with AD. These differences relate to the cortical involvement of AD versus the subcortical involvement of HD.

Patients with HD perform better than patients with AD on the immediate and delayed trials of logical memory and on the delayed trial of visual reproduction, but only at the mild stage. Patients with HD have better retention of a word list than patients with AD relative to age- and education-matched control groups. While patients with AD do poorly on the Mini-Mental State Examination, patients with HD may do as well as controls. In particular, patients with AD are impaired in learning or encoding and retention. Patients with HD show better retention and fewer tendencies toward cued intrusions. While patients with AD show deficient word storage, they tend to show particular difficulty with word retrieval in the face of relatively better word storage.

When patients with HD and patients with PD are compared, patients with HD are more impaired than patients with PD in immediate free recall and they do not exhibit the expected learning curve across trials. Patients with HD tend to exhibit a strong recency effect (ie, recalling more items from the end of the stimulus list than from the middle or beginning). Patients with PD make slightly fewer so-called errors of perseveration (ie, repetition), which is significantly fewer than the patients with HD. Patients with HD demonstrate significantly more improvement on recognition testing.

Pick disease

Pick disease affects the frontal and temporal lobes and also features more frontal or cortical signs. Clinically, it resembles HD; however, the age of onset is usually later in life and with a different underlying pathology. Early manifestations show personality and behavior changes with progressive involvement of memory and intellectual facets.

Workup

Laboratory Studies

• DNA repeat expansion
  • This study forms the basis of a diagnostic blood test for the HD gene. Direct gene testing via polymerase chain reaction can identify the HD gene and carrier states.
  • In addition to being a sensitive indicator of the inheritance of HD, CAG expansion is also highly specific because it is not observed in other neuropsychiatric disorders with which HD frequently is confused.
• Dopamine homovanillic acid
  • In 1986, Stahl et al measured the dopamine metabolite homovanillic acid (HVA) in cerebrospinal fluid (CSF) before and after probenecid administration in healthy controls and in patients with HD. Baseline CSF-HVA concentrations correlated positively with age in healthy control subjects. Baseline CSF-HVA concentrations were reduced in patients with HD, and the degree of this reduction correlated with the severity of dementia and with the duration of the disease.
  • In 1995, a study conducted in Spain also showed that the mean levels of HVA in the CSF of patients with HD were reduced significantly compared with those from healthy controls, patients with dystonia, individuals with other neurologic diseases, and even patients with untreated PD. The clinical relevance and practicality of these findings need further research. Data suggest reduced dopamine neurotransmission in persons with HD, and this may account for the bradykinesia observed in these patients.

Imaging Studies

• Computed tomography or magnetic resonance imaging
  • In fully developed cases, these studies show cerebral atrophy, especially of the caudate and putamen, to a degree that is almost specific to the disease.
  • In patients with mild-to-moderate HD, subcortical atrophy observed on an MRI is significantly correlated with specific cognitive deficits and demonstrates that cortical atrophy has an important association with the cognitive deficits in patients with HD.
  • Radiographically, caudate atrophy leads to the typical dilation of the frontal horns of the lateral ventricles; however, the sensitivity of a CT scan is insufficient to justify its role in the investigation of patients with suspected HD, unless genetic test findings and other diagnoses need to be excluded.
• Single-photon emission computed tomography scanning
  • Studies using single-photon emission computed tomography scans show a decrease in glucose metabolism and cerebral blood flow in the caudate nucleus greater than that of the putamen.
  • Additionally, position emission tomography scanning shows decreased D1 and D2 dopamine receptor binding sites in patients with HD. This study may provide a means to track early signs of decline in individuals with the HD gene mutation prior to clinical onset.

Other Tests

• Wechsler Memory Scale-Revised
  • Verbal and visual delayed recall on the logical memory and visual reproduction subtests of the Wechsler Memory Scale-Revised test are the 2 most sensitive neuropsychological tasks for indexing cognitive dysfunction in patients with HD.
  • Contrary to the poor performance of patients with AD on both recall and recognition measures, the pattern of results suggests that patients with HD have only mild-to-moderate memory impairment that results from a retrieval deficit due to frontal-striatal dysfunction.
• Wisconsin Card Sorting Test: Performance on the Wisconsin Card Sorting Test has shown to be able to discriminate approximately 82% of patients with HD from healthy controls. In keeping with the clinical and neuropathological features of HD, this pattern is consistent with the widespread cognitive alterations expected from frontal-subcortical circuit dysfunction.
• Trail-Making Test parts A and B versus Stroop tests: Results from tests of attention (eg, Trail-Making Test parts A and B) show moderate impairment in patients with HD. Performance on the Stroop test is more sensitive than the Trail-Making Test to attention and/or concentration deficit in patients with HD.
• In summary, patients with HD are most deficient on tests of delayed recall, followed by performance on measures of memory acquisition, cognitive flexibility and abstraction, manual dexterity, attention and/or concentration, performance skills, and verbal skills.

Histologic Findings

The disease predominantly strikes the striatum. Gliosis and neuronal loss occur, especially of medium-sized spiny neurons in the caudate and putamen. Relative sparing of large, cholinergic, aspiny neurons occurs.

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