Case 3 – A Young Man with Memory and Walking Difficulties

Abstract

A young 41-year-old man with memory problems and walking difficulties.

Case 3 A Young Man with Memory and Walking Difficulties

Monica Shin , Mira Chamoun , Tharick A. Pascoal , Melissa Savard , Jean-Paul Soucy , Marie Christine Guiot , Pedro Rosa-Neto , and Serge Gauthier

3.1 Main Complaint

A young 41-year-old man with memory problems and walking difficulties.

3.2 Clinical History

A young man came for a consultation accompanied by his father. He reported that his problems started at the age of 30 when he noticed fatigue and incapacity to accomplish his tasks at work. He was having difficulties remembering names of his colleagues and committed numerous mistakes as a clerk. When relocated to perform easier tasks at the store, he struggled to follow instructions. The cognitive deficits progressed to the point that he had to quit his job. As he was not able to manage his financial affairs anymore, his father became his caregiver since his wife abandoned him terrified by his progressive cognitive decline. His Montreal Cognitive Assessment (MoCA) declined by 6 points in 4 years. At age 34 years, he experienced difficulties in walking and started using a walker to avoid falls.

3.3 General History

He had thalassemia minor, with no clinical impact. He also used illicit drugs such as ecstasy and marijuana.

3.4 Examination

The physical examination conducted 10 years after the first manifestation of Alzheimer’s disease (AD) was unremarkable. During the mental status exam, he was cooperative, attentive, and responsive, although showing some degree of time and space disorientation. His immediate recall was impaired. He was not capable of spelling backward. He made mistakes on the serial 7s. The figure copy and clock drawing were abnormal. Anterograde memory evoked by a delayed recall showed deficits, which were partially corrected by cueing. His speech was mildly slurred. The verbal fluency was reduced. He scored 20 on the MMSE and 14 on the MoCA.

During the neurological exam, the cranial nerves were normal. The motor exam revealed normal and symmetric strength. The tonus was symmetrically increased. He had hyperreflexia of all four limbs, bilateral plantar response, sustained clonus of both ankles, and showed decreased bilateral hand and foot tapping. Primitive reflexes (glabellar, palmomental, and snout reflexes) were present. Sensory examination was unremarkable. Cerebellar examination was within the limits of normality. His gait was spastic with a narrow base.

3.5 Family History

His mother died in 1981, at the age of 43, as a consequence of Gerstmann-Sträussler-Scheinker disease (GSS). Her brain necropsy revealed congophilic angiopathy, diffuse cortical neuronal loss, neuritic plaques, and status spongiosis of the neuropil, Kuru plaques in the parieto-occipital cortex and the cerebellum. The cholinergic innervation was reduced in the medial frontal cortex.¹ Recent reassessment of the pathological material with current pathology techniques ruled out the presence of the prion protein (PRNP) but revealed cotton wool amyloid formations on the tissue. To the best of their knowledge, there was no other individual affected by a neurodegenerative or psychiatric condition in their family.

3.6 Laboratorial Assessment

Blood tests showed that the plasma ceruloplasmin level was at 272 mg/L (220–480). The screen for HIV-1 and HIV-2 were both negative. A genetic study was negative for PRNP. The neuropsychological testing revealed a significant decline in all spheres of cognition. [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) images showed a marked (~30%; Figure 3.1c and d) deterioration of uptake in multiple cortical areas, including the temporal lobes (both lateral and the hippocampal formations), the parietal lobes and, to a lesser extent, the frontal lobes. The amyloid imaging showed increased accumulation of the tracer with a cortical pattern, involving at a low level the frontal, temporal, and parietal cortices, with a much higher uptake in the occipital regions (~45%; Figure 3.1a and b). There was also significant increased uptake in the striatum, thalamus, brain stem, and cerebellum. Fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) of brain without enhancement showed diffuse cerebral volume loss, including the cerebellum and no signs of white matter or cerebrovascular disease (Figure 3.1e and f). A repeat amyloid imaging conducted 24 months later showed significant uptake of tracer in various brain regions including the striatum. CSF revealed AB_1–42 = 338.25 pg/mL, T-tau = 926.75 and p-tau = 139.3.

Figure 3.1 Representative images of a baseline assessment of amyloid load (a, b) with PET [¹¹C]PIB, [¹⁸F]FDG (c, d), MRI FLAIR images (e, f), and photomicrographs obtained from paraffin sections of formaldehyde-fixed brain tissue stained with hematoxylin-eosin (HE) at 10× (g) and 20× (h). Note the fast rate of increase of PIB load in a 24-month follow-up, the decline in cortical metabolism (blue arrows), ventricular dilation (f; red arrow), and cortical atrophy (f). HE stains reveals round, eosinophilic CWP (*) displacing normal structures in the cortical areas at 10× and 20×.

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