Gerstmann–Sträussler–Scheinker (GSS) is a rare autosomal dominant prionopathy. The incidence is 1 to 10 cases per 100 million per year. Onset is usually in the fifth decade, characterized by unsteadiness, followed by myoclonus and dementia, and behavioral abnormalities. We report on a patient with GSS due to PRNP Q217R mutation presenting with parkinsonism and myoclonus.

A 53-year-old man was admitted for confusion in the context of a family history of GSS. He had an 11-year history of progressive motor, cognitive and behavioral changes. He had poor balance, reduced responsiveness and would sometimes leave his apartment door open. Detailed history of the initial symptoms could not be obtained. His earliest documented medical record was dated six months before the current admission. He had presented to the emergency department with a one-month history of worsening confusion and weakness, which was attributed to malnutrition. He presented four months later for generalized weakness and weight loss and was noted to have poor personal hygiene. He was documented to have shuffling gait, cogwheel rigidity, masked facies and bradykinesia that were partially responsive to low-dose levodopa/carbidopa (100/25 mg twice daily). He was eventually brought to a peripheral hospital by ambulance for altered mental status with impaired fine motor coordination and incoherent speech. His medical history was otherwise unremarkable. He had a 10-pack-year smoking history and was an ex-drinker of 40 standard drinks weekly.

Four other family members had confirmed genetic testing for PRNP Q217R mutation: his sister, mother, aunt and cousin (Figure 1). His mother (II-4, Figure 1) first developed progressive gait instability with cognitive concerns at the age of 64 years. She then developed shuffling gait, masked facies and hand tremors two years later. There was no behavioral disturbance. She passed away at the age of 70 years. His aunt (II-2, Figure 1) had symptom onset at the age of 45 years with impaired attention and subsequently behavioral disturbances.^{Reference Woulfe, Kertesz and Frohn1} She was diagnosed with Pick’s disease eight years after onset. She developed Parkinsonian features characterized by right-hand hypokinesis, rigidity and stiff gait. Interestingly, there was no reported ataxia. She died 13 years after disease onset. The patient’s grandfather (I-1, Figure 1) had “abnormal behavior” and parkinsonism and did not undergo genetic testing. His sister (III-5, Figure 1) and cousin (III-1, Figure 1) have been asymptomatic.

Figure 1.

Pedigree of a three-generation family showing transmission of PRNP Q217R mutation-associated GSS. II-2, II-4, III-1, III-4 and III-5 had genetics confirmed Q217R mutation. I-1 had symptoms of “abnormal behavior” and parkinsonism but did not undergo genetic testing and was considered affected by history. GSS, Gerstmann–Sträussler–Scheinker.

On transfer to our neurology unit, the patient was intermittently following one-step commands. Fluency was impaired with neologisms and had trouble following instructions. He had upward gaze palsy, with hypometric saccades and impaired smooth pursuit. There was bradykinesia with alternating pronation and supination and finger tapping. There were postural and stimulus-sensitive myoclonic jerks in bilateral upper and lower limbs (Video 1). He had at least antigravity strength in all four limbs. Reflexes were diffusely brisk, and plantar responses were mute bilaterally. There was no dysmetria on finger-to-nose testing. His Montreal Cognitive Assessment score was 5/30, with impairment to visuospatial/executive function, memory, attention, language, abstraction, delayed recall and orientation.

For investigations, routine blood work, including complete blood count and metabolic panel, was within normal limits. Toxicology was negative. On brain MRI, there was generalized cortical atrophy involving bilateral deep gray nuclei and no diffusion restriction in the basal ganglia (Figure 2A and 2B). Electroencephalogram captured cortical myoclonic jerks in bilateral frontocentral regions (Figure 2C and 2D). His family history prompted genetic testing, which revealed a Q217R mutation in the PRNP gene, consistent with GSS. An autopsy was not performed.

Figure 2.

On MRI, there were no hyperintense signals in the basal ganglia on diffusion-weighted imaging (DWI) (A) or apparent diffusion coefficient (ADC) (B). Bipolar electroencephalogram during hand myoclonus (C) and leg myoclonus (D) showed diffuse slowing with frontocentral spikes time-locked to myoclonus.

Unfortunately, he declined rapidly, received palliative care and died 24 days after admission to hospital.

Herein, we report a case of GSS caused by a PRNP Q217R mutation with prominent parkinsonism and stimulus-sensitive myoclonus. While “confusion” was reported as an early symptom, the limitation of our clinical case is the absence of a reliable and detailed account of his initial presenting symptoms. The Q217R mutation has been reported previously in one Swedish family.^{Reference Hsiao, Dlouhy and Farlow2} The two patients in the Swedish family reported a four-year history of dementia and later developed gait ataxia, dysphagia and confusion. Another case of GSS mimicking frontotemporal dementia with the same Q217R mutation was reported in Canada; this was the aunt of the patient in our case.^{Reference Woulfe, Kertesz and Frohn1} Among family members with genetically confirmed GSS (Figure 1), cognitive and gait concerns were the first presenting symptoms, with parkinsonism and myoclonus presenting as late-stage symptoms. There was no cerebellar ataxia in our patient or reported among family members with the pathological mutation.

Applying the GSS classification set out by Tesar and colleagues for P102L GSS,^{Reference Tesar, Matej and Kukai3} this reported GSS case, with early cognitive changes and confusion and late parkinsonism and stimulus-sensitive myoclonus, fit under the Creutzfeldt–Jakob disease (CJD)-like GSS umbrella. However, because this classification schema was developed based on the presentation of P102L mutation-associated GSS, its generalizability to Q217R mutation-associated GSS is uncertain. This newer classification system replaces the older “typical” versus “atypical” GSS classification system, wherein this patient would fit into “atypical” GSS.

GSS, with P102L being the most common PRNP mutation, is characterized by early gait disturbances with cerebellar ataxia as the defining feature.^{Reference Chen, Kong and Zhang4} Parkinsonism, characterized by gait instability and generalized bradykinesia, can be present in 33% of typical GSS and 65% of CJD-like GSS.^{Reference Chen, Kong and Zhang4} Motor symptoms are usually partially or not responsive to levodopa therapy,^{Reference Ribosa-Nogueé, Pagonabarraga and Gomez-Anson5} though there have been case reports of levodopa-responsive parkinsonism.^{Reference Jiang and Aradi6} Rarely, GSS could mimic progressive supranuclear palsy with vertical gaze palsy, dementia and parkinsonism.^{Reference Rowe, Lewis and Needham7} Myoclonus can be present in 27% of typical GSS and 51.5% of CJD-like GSS.^{Reference Chen, Kong and Zhang4} Both parkinsonism (41% and 6%, respectively) and myoclonus (41% and 15%, respectively) are found more frequently in non-P102L GSS compared to P102L GSS.^{Reference Rodriguez-Porcel, Ciarlariello and Dwivedi8}

In conclusion, we report on a patient with PRNP Q217R GSS presenting with myoclonus and parkinsonism. Early gait and cognitive impairment followed by prominent behavioral disturbance and parkinsonism, without cerebellar ataxia, was a common phenotype in affected family members. One family member had no reports of behavioral disturbances. This case reinforces the wide clinical spectrum of genetic prion diseases, even within related individuals with the same mutation.