Gerstmann–Sträussler–Scheinker syndrome (GSS) belongs to the group of prion diseases, which includes Creutzfeldt–Jakob disease (CJD), fatal familial insomnia (FFI), and kuru (35).

GSS is an autosomal dominant disorder caused by a mutation in the prion protein gene (PRNP) located on chromosome 20. Mutation P102L is the most common variant, but different mutations have been identified (such as F198S, Q217R, P105L), with each associated with less typical phenotypes of the disease (12, 13).

Spongiform degeneration is most frequently seen in patients with the P102L mutation (32). All GSS variants share widespread multicentric amyloid plaques, which are an expression of the PrP misfolded protein. A few cases of neurofibrillary tangles (NFT), found coexisting in the neocortex with amyloid plaques, have also been described and could be unique to a variant of GSS, since it is not a feature of iatrogenic or sporadic CJD (21).

GSS is a rare syndrome, with an incidence rate of 1–100 per 10 million and an age of onset ranging from 30 to 60 years. The disease follows a variable course (3.5–9.5 years) and the mean disease duration is 5 years, which is longer than classic CJD (3). The core clinical feature is the progressive cerebellar ataxia, which includes gait unsteadiness, limb ataxia with dysmetria, dysdiadochokinesis, and intention tremor. Other clinical features are pyramidal signs, Parkinsonism, and cognitive decline.

Memory impairment is usually the first indication of cognitive decline, followed by learning difficulties, slowed information processing, and reduced attention span. Cognitive decline and mood disorders seem to appear later in the course of the disease compared to motor impairment, but psychiatric disorders could be presenting symptoms, as reported in the literature (43).

There are no pathognomonic findings in standard instrumental examinations; therefore, diagnosis relies on genetic test results. MRI may show mild cerebellar atrophy and diffuse cortical atrophy, while electroencephalography reveals no specific changes, with only a small percentage of the patients (<35%) showing triphasic periodic complexes (23). There is no effective treatment for GSS and symptomatic treatment provides only partial relief.

To the best of our knowledge, this is the first description of the effects of intensive cognitive-motor rehabilitation training in a patient with GSS.

In January 2023, a 34-year-old woman (S.C.B.) who was diagnosed with GSS (variant Pro102L) in 2020 was admitted to our Neurorehabilitation Unit due to progressive worsening of balance and walking ability.

The first symptoms presented in 2018 with gait instability without falls, early fatigue, and dizziness; a brain MRI scan was performed, which only showed mild bilateral cerebellar hemisphere atrophy, leading to the diagnosis of ataxia of undetermined cause. Her symptoms progressively worsened, and a whole spine MRI scan was conducted in 2019, finding mild dorsal spinal cord hypotrophy (D4–D7) with an associated syringomyelic cavity. Motor (MEP) and somatosensory evoked potentials (SEP) showed central altered conduction abnormalities in both the upper and lower limbs. Brain-stem auditory evoked potentials (BAEPs) were normal. As of 2020, the patient has required a walker to move within her home environment. The brain and spine MRI exams were repeated in 2020, indicating the progression of the known cerebellar hypotrophy and an increase in both the length and width of the syringomyelic cavity, which extended from D4 to D11. Cerebral positron emission tomography (PET) showed cerebellar hypometabolism. Later symptoms included urinary incontinence from a neurogenic bladder (from 2021), initial insomnia and rapid-eye movement sleep behavior disorder (RBD), writing difficulties, and occasional dysphagia to a liquid bolus. Neither a familial history of GSS nor other relevant medical conditions were reported.

Considering the worsening of her symptoms and the wide range of functions affected, a holistic multidisciplinary rehabilitative approach was suggested.

S.C.B. was admitted to attend a 4-week rehabilitation inpatient program in our unit. The weekly schedule consisted of 1 h of face-to-face physiotherapy, 1 h of machine training, 1 h of speech therapy, and 1 h of group occupational therapy treatment, 5 days per week. On the sixth day, the patient had a 1 h activity in the machine room, while the seventh day was dedicated to rest. A total of 4 h per day was planned during the treatment. However, due to the patient's fatigue and attentional burden, the treatment duration was divided into shorter sessions throughout the day, while still achieving the full 4-h total.

Neurological, neuropsychological, physiotherapeutic, occupational, and speech assessments were performed in the first days after hospital admission.

The types of exercises selected were specifically chosen for the patient, without adhering to a specific rehabilitation protocol, due to the complex clinical situation involving both cerebellar symptoms and cognitive decline.

The goals, which were set with the patient, were -

greater autonomy and safety in transfers and ambulation,

At admission, S.C.B. was completely dependent in both ADLs and instrumental activities of daily living (iADLs). The patient entered the rehabilitation ward with her own walker and her wheelchair. She continued to use them throughout the rehabilitation period and, by the end of the hospitalization, no changes were necessary. She returned home with greater autonomy and a better understanding of how to safely use assistive devices and she was able to help her caregivers more during transfers. She was alert, cooperative, well-oriented in herself, partially oriented in space and time, and had dysarthric speech. The neurological examination showed primary position bilateral nystagmus, slow saccades, and bilateral absence of the pharyngeal reflex. Muscle tone was normal and no major deficits in active movements against gravity and resistance were observed, except for a downward drift during left arm extension. Bilateral dysdiadochokinesia and decreased finger dexterity were present, particularly on the right side. Coordination assessment revealed bilateral dysmetria during both finger-to-nose and knee-to-shin maneuvers. Hoffman's and the Babinski signs were evoked in her upper and lower limbs, respectively. Deep tendon patellar and ankle reflexes were weak bilaterally. Superficial sensitivity was normal, while hypopallesthesia and hypobathesthesia were found. The patient was able to stand and move independently with supervision. She presented with a wide walking gait and truncal ataxia with a retropulsion tendency, and therefore required a walker. Pharmacological therapy consisted of oxybutynin 5 mg q.d., gabapentin 100 mg one tablet b.i.d., lorazepam 1 mg one tablet, and cholecalciferol 10,000 UI once a month.

We present the case of a patient with GSS who attended inpatient intensive motor-cognitive rehabilitation training. Several structured rehabilitative approaches have been described and found effective for hereditary ataxias (7, 27, 28), improving mobility function, balance, and ataxia. However, to the best of our knowledge, this is the first description of rehabilitative training and its results in a patient with GSS.

In this patient with GSS, the clinical features, symptom progression, and neuroradiological findings were in line with the literature (40).

In line with the intensive multidisciplinary motor-cognitive rehabilitation treatment approach, the patient was carefully assessed and the intervention was adapted to her needs, despite this treatment not being designed for GSS specifically, as the approach is very adaptable. Since only a few patients with GSS have been referred for intensive rehabilitation treatment, we believe that this case may help clinicians consider intensive multidisciplinary motor-cognitive rehabilitation treatment as a feasible and useful tool for treating these patients.

The neuropsychological assessments painted a picture of the patient’s cognitive difficulties, allowing the therapists to adapt the communication and the way they delivered the training. The team was trained to consider the cognitive ability of the patient and to offer explanations that the patient would understand, thus helping maintain concentration (e.g., splitting one session into two to three shorter ones or frequently giving the patient a break and engaging in simple conversation). Therefore, despite some degree of cognitive dysfunction, the patient was able to perform and participate in the intervention thanks to the care provided by the team. As a result, an improvement was observed in all the intervention areas. Speech therapy was effective on her dysphagia, physiotherapy led to better walking and balance abilities, and occupational therapy allowed the patient to achieve better bimanual coordination and greater control of gestures. Overall, the 4-week intensive motor-cognitive rehabilitation treatment led to a global improvement in autonomy, with a positive impact on ADLs, such as improved self-management (mainly due to better balance, dexterity, and swallowing) within the hospital setting. At the end of the rehabilitation process, all the physiotherapy tests showed a slight improvement despite remaining pathological. This was not unexpected, considering the nature and severity of the pathology, which did not allow for the same outcomes as in less compromised patients. However, the approach focused on physiotherapy treatment, particularly on core postural control, which resulted in an improvement in the safety of postural transition and transfers in the domestic environment. From the occupational therapy point of view, the tests showed maintenance of a significant impairment in upper limb gestures (in gross and fine motor skills), but good improvement in terms of the time needed to finish the requested task. In terms of ADL autonomy progress, the patient went home with better fine motor control, which helped her in writing and small hygiene tasks and, during meal management, cutting and preparing her own food.

We acknowledge that the use of scales originally developed for other movement disorders may be questionable, but, as there are no instruments specifically developed for GSS, and since we used them for test-retest aims, we believe it may be an acceptable solution.

Unfortunately, we did not have the opportunity to perform a follow-up visit, which could have provided insight into the persistence of the improvements achieved, which is clinically important information.

However, it is reasonable to assume that, given this patient improved in many aspects after rehabilitation treatment was started at least 3 years after her diagnosis, an early intervention would be more effective in terms of improvement in quality of life.

We are aware that the generalizability of a single case is poor, but, considering that patients with GSS are rare, and treatment options are scarce, we believe it is important to highlight whatever may help patients to better cope with their symptoms.

In conclusion, since GSS is a relentlessly progressive disease, we believe that being able to obtain sensible results with a rehabilitative treatment is an important step to improve these patients’ quality of life. Furthermore, describing cases such as this increases our knowledge about treatment possibilities that clinicians can propose to patients. There is a lack of studies on the efficacy of rehabilitative training in people with GSS and randomized studies with longitudinal follow-up should be conducted to further explore rehabilitative options and confirm the efficacy of the intervention in this patient population.