Bevezetés: A cerebelláris kognitív-affektív szindróma olyan tünetegyüttest jelent, amely a motoros és végrehajtó funkciók zavarán túl a memória, a váltás-gátlás, a konceptualizálás és az érzelem és viselkedés szabályozásában is megnyilvánulhat. A szindróma felmérésére dedikált magyar nyelvű mérőeszköz eddig nem állt a hazai szakemberek rendelkezésére. Célkitűzés: A kutatás célja volt a Cerebelláris Kognitív-Affektív Szindróma Skála (CCAS-H) magyar mintán történő validációja, diagnosztikus érvényességének felmérése, valamint a teszt közzététele a szakemberek számára. Módszer: Multicentrikus kutatási elrendezésben, hat kórházi osztállyal való együttműködés keretében cerebelláris érintettségű páciensekkel és kontrollszemélyekkel történtek tesztfelvételek 2021. 07. 12. és 2023. 12. 31. között. A statisztikai elemzések során normalitástesztelést, leíró statisztikát, átlagok tesztelését, korrelációszámításokat, valamint ROC-elemzést végeztünk, Cronbach-alfa-értékeket, Cohen-féle kappát határoztunk meg. A normalitás sérülése esetén robusztus próbákat választottunk. Eredmények: 54 cerebelláris és 40 kontrollszeméllyel történt tesztfelvétel, amelyekből különböző alcsoportokat képeztünk. Mintánkban az életkor (r = –0,581***, df = 87, p<0,001) és az iskolázottság (r = 0,360***, df = 87, p<0,001) szignifikáns együttjárást mutatott az összpontszámokkal. A CCAS-H megfelelő belső konzisztenciájú (α = 0,771), teszt-reteszt vizsgálat alapján stabil (r = 0,793***, df =13, p<0,001), és megítélők közti 88,2%-os egyetértést mutatott (𝜅 = 0,779, z = 4,79, p<0,001). A fals pozitív esetek csökkentése érdekében a szindrómát előre jelző vágópontokat megemeltük, így 5 hibapontnál felmerül (szenzitivitás: 100%, specificitás: 43,48%), 6 hibapontnál valószínű (szenzitivitás: 90,91%, specificitás: 62,32%), 7 hibapontnál határozott (szenzitivitás: 81,82%, specificitás: 73,91%) a szindróma előfordulásának valószínűsége (AUC: 0,836). Megbeszélés: Az elemzések a nemzetközi ajánlásoknak megfelelően készültek. Az eredeti és más validált változatokhoz képest a magyar verzió nagyobb belső konzisztenciát mutatott. A skála stabil és megbízhatóan alkalmazható, emellett ismertetjük a teszt adta újabb kutatási kérdéseket. Következtetés: Az újonnan validált skála alkalmas mérőeszköz a szindróma mérésére. Tanulmányunkkal elérhetővé tettük a CCAS-H-t a magyar szakemberek számára. Orv Hetil. 2024; 165(20): 785–798.

Neurological symptoms following cerebellar stroke can range from motor to cognitive-affective impairments. Topographic imaging studies from patients with lesions confined to the cerebellum have shown evidence linking anterior cerebellar lobules with motor function and posterior lobules with cognitive function. Damage to the cerebellum can disrupt functional connectivity in cerebellar stroke patients, as it is highly interconnected with forebrain motor and cognitive areas. The hippocampus plays a key role in memory acquisition, a cognitive domain that is negatively impacted by posterior cerebellar stroke, and there is increasing evidence that the cerebellum can affect hippocampal function in health and disease. To study these topographical dissociations, we developed a mouse photo-thrombosis model to produce unilateral strokes in anterior (lobules III-V) or posterior (lobules VI-VIII) cerebellar cortex to examine hippocampal plasticity and behavior. Histological and MRI data demonstrate reproducible injury that is confined to the targeted lobules. We then measured hippocampal long-term potentiation (LTP) ex-vivo with extracellular field recording experiments in acute brain slices obtained from mice 7 days post-cerebellar stroke. Interestingly, we found that a unilateral posterior stroke resulted in a contralateral hippocampal impairment, matching the cerebellothalamic pathway trajectory, while LTP was intact in both hippocampi of mice with anterior strokes. We also assessed motor coordination and memory function at 7 days post-stroke using a balance beam, contextual and delay fear conditioning (CFC and DFC), and novel object recognition (NOR) tasks. Mice with anterior strokes showed lack of coordination evaluated as an increased number of missteps, while mice with posterior strokes did not. Mice with anterior or posterior cerebellar strokes demonstrated similar freezing behavior to shams in CFC and DFC, while only posterior stroke mice displayed a reduced discrimination index in the NOR task. These data suggest that a unilateral LTP impairment observed in mice with posterior strokes produces a mild memory impairment. Our results demonstrate that our model recapitulates aspects of clinical lesion-symptom mapping, with anterior cerebellar strokes producing impaired motor coordination and posterior cerebellar strokes producing an object-recognition memory impairment. Further studies are warranted to interrogate other motor and cognitive-affective behaviors and brain region specific alterations following focal cerebellar stroke. The novel model presented herein will allow for future preclinical translational studies to improve neurological deficits after cerebellar stroke.

Many patients with spinocerebellar ataxia (SCA) suffer from diverse neuropsychiatric issues, including memory impairments, apathy, depression, or anxiety. These neuropsychiatric aspects contribute per se to the reduced quality of life and worse prognosis. However, the extent to which SCA-related neuropathology directly contributes to these issues remains largely unclear. Behavioral profiling of various SCA mouse models can bring new insight into this question. This paper aims to synthesize recent findings from behavioral studies of SCA patients and mouse models. The role of SCA neuropathology for shaping psychiatric-like impairments may be exemplified in mouse models of SCA1. These mice evince robust cognitive impairments which are shaped by both the cerebellar as well as out-of-cerebellar pathology. Although emotional-related alternations are also present, they seem to be less robust and more affected by the specific distribution and character of the neuropathology. For example, cerebellar-specific pathology seems to provoke behavioral disinhibition, leading to seemingly decreased anxiety, whereas complex SCA1 neuropathology induces anxiety-like phenotype. In SCA1 mice with complex neuropathology, some of the psychiatric-like impairments are present even before marked cerebellar degeneration and ataxia and correlate with hippocampal atrophy. Similarly, complete or partial deletion of the implicated gene (Atxn1) leads to cognitive dysfunction and anxiety-like behavior, respectively, without apparent ataxia and cerebellar degeneration. Altogether, these findings collectively suggest that the neuropsychiatric issues have a biological basis partially independent of the cerebellum. As some neuropsychiatric issues may stem from weakening the function of the implicated gene, therapeutic reduction of its expression by molecular approaches may not necessarily mitigate the neuropsychiatric issues.

Dentatorubral-pallidoluysian atrophy is a hereditary neurodegenerative disease prevalently reported in Japan but rare in Caucasians. The objective of this study was to reconstruct the pedigree of Italian dentatorubral-pallidoluysian atrophy familial cases describing their clinical features.
We investigated 6 apparently unrelated dentatorubral-pallidoluysian atrophy families comprising a total of 51 affected individuals: 13 patients were clinically examined, and for 38 patients clinical data were collected from clinical sources. The dentatorubral-pallidoluysian atrophy diagnosis was genetically confirmed in 18 patients. Genealogical data from historical archives were analyzed.
All 6 families were unified in a large pedigree deriving from a founder couple originating from Monte San Giuliano (Italy) in the late 1500s, with 51 affected subjects over the last 4 generations. Wide phenotypical variability in age at onset and clinical features was confirmed. Epilepsy was more frequent in juvenile cases than in late adults, with cognitive/psychiatric and motor disorders observed regardless of age at onset.
We have described the largest Caucasian dentatorubral-pallidoluysian atrophy pedigree from a single founder couple. The introduction of the dentatorubral-pallidoluysian atrophy gene in Italy could have arisen as a result of trade relationships between the Spanish or Portuguese and the Japanese in the 1500s. © 2019 International Parkinson and Movement Disorder Society.