20.1 Clinical History – Main Complaint

A 70-year-old man was referred because his balance had deteriorated in recent months. While he had only occasionally fallen over the previous 3 years, he now described a strong and consistent tendency to fall backward. He planned to retire as soon as possible partly because of this issue, but also because his productivity at work had decreased. His wife noted that he had been uncharacteristically impatient at home, but denied any memory difficulties.

20.2 General History

At the time of the initial evaluation, the patient was still employed and worked for a charity. He lived with his wife. He had never smoked or used recreational drugs. He drank one to two glasses of wine per day, three to four times a week. He had been diagnosed with hypertension and dyslipidemia for which he was treated with angiotensin conversion enzyme (ACE) and HMG-CoA reductase inhibitors, respectively. He had no urinary symptoms and denied erectile dysfunction.

20.3 Family History

The patient’s father passed away at the age of 63 from a myocardial infarction. His mother died at the age of 88 with a diagnosis of Alzheimer’s disease. She was also known for hypertension and dyslipidemia.

The patient had one sister who was 66 years old and in good health. He had one brother who suffered from bipolar disorder and committed suicide at the age of 35. He had one child, a 40-year-old son, who was in good health.

20.4 General Examination

The patient offered good cooperation but was somewhat apathetic. General examination including vital signs was normal. There was no orthostatic hypotension.

Neurological examination was characterized by poverty of movement and speech. There was striking hypomimia with a significant reduction in blinking. There was mild symmetrical lid retraction. Horizontal saccadic intrusions were observed upon visual fixation. Ocular smooth pursuit was complete, but horizontal pursuit was mildly saccadic and vertical pursuit was slow. Vertical pursuit was improved by the vestibular ocular reflex (VOR). There was no nystagmus. Voluntary vertical ocular saccades were impossible to obtain. Rigidity was prominent in the neck, while it was only seen with reinforcement in the limbs. There was no tremor at rest or during action. Strength was normal. Reflexes were normal and symmetrical. Sensory and cerebellar examinations were also normal. Gait was not wide-based, but the patient was very unstable upon turning and there was no postural response on the pull-test.

Montreal Cognitive Assessment (MoCA) score was 26/30. Executive function was affected as evidenced by multiple errors in Trail Making Test-B and reduced verbal fluency. The patient also had a tendency to persevere on the go-no-go test and was unable to copy a cube. Memory and orientation were not affected. There was no aphasia nor apraxia. When asked to clap his hands three times, the patient clapped six times.

20.5 Special Studies

Routine biochemical and hematological tests were normal.

Magnetic resonance imaging (MRI) of the brain showed mild leukoencephalopathy, proportional to what is observed in the patient’s age group. A [¹⁸F]-fluoro-deoxyglucose (FDG) positron emission tomography (PET) revealed global cerebral hypometabolism with a relative predominance in the frontal lobes.

20.6 Diagnosis

The initial diagnosis was based upon clinical presentation. The combination of postural instability, apathy, marked axial rigidity, and severe abnormalities of vertical ocular saccades strongly suggested progressive supranuclear palsy (PSP). The axial rigidity was not in favor of late-onset Niemann-Pick type C disease. Central nervous system Whipple disease was considered unlikely because the patient did not have systemic symptoms such as arthralgia or weight loss. The absence of autonomic or cerebellar dysfunction along with early cognitive problems did not support a diagnosis of multiple system atrophy (MSA). The lack of asymmetry and apraxia was not suggestive of corticobasal degeneration (CBD). Dementia with Lewy bodies (DLB) was also unlikely given the absence of fluctuations and visual hallucinations.

20.7 Follow-Up

The patient did not respond to 600 mg of levodopa per day. Side effects prevented us from increasing the dosage further. We were thus unable to push the drug trial to 1,500 mg/day. Over the next 2 years, his balance deteriorated quickly and he became wheelchair-bound. Over the following 3 years, speech became unintelligible and he became dependent for most activities of daily living. By then, dysphagia was a significant problem and he was admitted twice for aspiration pneumonia. A dietician and a speech therapist suggested a percutaneous gastrostomy to reduce the risk of aspiration, but this was declined by the family. A year later, he succumbed to another episode of pneumonia. On histology, the substantia nigra showed significant neuronal loss, as well as gliosis. Tau-positive inclusions were observed in neurons (globose neurofibrillary tangles), astrocytes (tufted astrocytes), and oligodendrocytes (coiled bodies). The neuropathologist confirmed the diagnosis of PSP.