Late-Onset Huntington’s Disease Masquerading as Normal Pressure Hydrocephalus

A 71-year-old man with medical history significant for benign prostatic hypertrophy and normal pressure hydrocephalus presented to the emergency room with behavioral changes. He had no known past psychiatric history and no history of substance use beyond tobacco. He was highly educated and had been functioning well as an investment banker when he began experiencing mild memory difficulty 1 year ago. This symptom prompted an outpatient visit to neurology, resulting in an MRI and a subsequent suggested diagnosis of normal pressure hydrocephalus, though without confirmation by lumbar puncture. Gradually over the next year, the patient’s personality and behavior changed. He began to have temper outbursts and to excessively insult his wife of 12 years. He abruptly quit his job, became more religious and he gave away large sums of money to charities, attempting to liquidate all of his assets. He became increasingly paranoid, and thought that there were strange people in his house that he could never see. He began to accuse his wife of having relations with other men and threatened to burn down their house. From the emergency room, he was admitted to the neurology service with subsequent consultation to psychiatry.

Upon presentation, his physical exam was remarkable only for wide-based gait. His thought process was both tangential and circumstantial with perseveration on several delusional ideas. There was no evidence of suicidal or homicidal ideation. At night he would become agitated, repeatedly attempted to leave the hospital, and was mildly combative. Review of systems was positive for increased urinary frequency that resolved with antibiotics following a positive urine culture. Mini-Mental State Examination (MMSE) score at presentation was 29/30, but more comprehensive neuropsychological testing revealed poor performance on tasks of memory, visual-spatial construction, and executive functioning with an overall reduced processing speed significant in a man of such previous high functioning. A CT and MRI showed enlarged temporal horns of the lateral ventricles suggestive of normal pressure hydrocephalus, however without the associated white matter changes around the ventricles. There was no evidence of ischemic injury or parenchymal atrophy. All laboratory values were within normal limits and a lumbar puncture to reevaluate normal pressure hydrocephalus showed a normal opening pressure of 45 mm H ₂ O with normal protein, glucose, and cell count. There was no improvement of gait symptoms following the lumbar puncture. Family history revealed a sister in her late 60s who had recently been diagnosed with Huntington’s disease, and a genetic test for Huntington’s disease was performed.

Risperdol, 1 mg b.i.d., brought significant resolution of the psychosis and agitation and subjective improvement of his gait. After discharge, the genetic test for Huntington’s returned positive with 40 CAG repeats on one allele.

Huntington’s disease is an autosomal dominant neurodegenerative disorder with a variety of presenting symptoms and ages of onset. Although the average age of onset is between 40 and 50 years old, 25% of patients experience their initial symptom development after the age of 50, and patients have been diagnosed as late as 80 years old. One study found that the disease progressed more slowly in older patients. 1 Given the anticipatory effect of the mutation, elderly patients with late-onset disease have many fewer repeats than patients in their 40s, which perhaps accounts for the milder symptoms.

It is not uncommon for cognitive or psychiatric symptoms to be the initial presenting sign of Huntington’s disease. Huntington’s disease patients tend to have difficulties with visuospatial tasks, and often present with impairments in planning and judgment with increasingly impulsive behavior. Patients may become apathetic, irritable, and even violent with accompanying emotional lability and decreased concentration leading to subsequent intellectual decline. Psychotic symptoms like those in this patient are present in 3%–11% of cases and include isolated delusional states, auditory hallucinations and paranoia. 2

After establishing the diagnosis of Huntington’s disease with genetic analysis, the MRI images for this patient were reevaluated. They were again read as showing only ventricular enlargement evocative of normal pressure hydrocephalus, without evidence of the surrounding caudate atrophy associated with Huntington’s disease. Could both diagnoses be present? A review of the literature revealed two case reports of patients diagnosed with Huntington’s disease by motor symptoms and family history, who then developed ventricular enlargement accompanied by cognitive symptoms that suggested to the authors an additional diagnosis of normal pressure hydrocephalus. 3 Lumbar punctures revealed normal opening CSF pressure and shunts placed in these patients improved their cognitive symptoms but did not affect their chorea. This finding prompted the authors to speculate a process by which the cortical changes in Huntington’s disease contributed to the development of normal pressure hydrocephalus. Nonetheless, despite the suggestive imaging, the genetic diagnosis of Huntington’s disease in this patient indicates a convincing single diagnosis whose symptoms were, unlike the earlier case reports, unchanged after a lumbar puncture. It is unlikely that he possesses both diagnoses.

A retrospective look at this patient’s case suggests that this patient’s behavior and cognitive decline are consistent with the diagnosis of Huntington’s disease. It is crucial to consider Huntington’s disease as a diagnosis in elderly patients exhibiting cognitive decline with prominent psychiatric symptoms even in the presence of imaging studies that suggest normal pressure hydrocephalus. These elderly patients may be the first in their family to exhibit symptoms of Huntington’s disease.