Background: Continuous subcutaneous apomorphine infusion (CSAI) is a standard of care treatment in advanced Parkinson's disease (PD) to treat motor fluctuations. However, literature about its long-term data is scarce. Objective: The aim of this study was to report about CSAI tolerance and discontinuation predictors in a large monocentric cohort. Methods: Consecutive PD patients who had CSAI were included. CSAI duration, discontinuation rates at 3, 12, 24, 36, 48, and 60 months, demographic data, MDS-UPDRS motor score, adverse events (AEs), discontinuation reasons and predictive factors were analyzed with logistic regression. Results: A total of 208 patients were included from 1999 to 2023 (51% male; age: 67.4 ± 8.3 years; PD duration: 11.2 ± 5.0 years). In the overall group, CSAI duration was 25.0 ± 32.9 months (median: 13.0, range: 0.1–260.0). Ninety-five patients (45.7%) discontinued CSAI after 12.7 ± 15.3 months (median: 8.0). Main discontinuation causes were switching to deep brain stimulation (44.2%) and low efficacy (15.8%). Sixty% of discontinuations occurred within the first year. CSAI duration was the only significant difference between ongoing CSAI (116) and discontinued patients (35.4 ± 39.7 vs. 11.1 ± 18.4 months; p < 0.001), after excluding 42 CSAI-to-DBS. About 79.8% patients had AEs, mainly hallucinations (41.3%) and nodules (24.0%). The best discontinuation predictors were CSAI duration and baseline off medication MDS-UPDRS motor score. Conclusions: These results may help clinicians better select patients, anticipate and manage AEs, and predict CSAI discontinuation.

Background: Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies. Objective: To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor. Methods: Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported. Results: Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients. All three patients showed optimal control of both tremor and dystonic features at short-term (6 months) and long-term follow-up (up to 6 years). No adverse events occurred. Conclusion: In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution.

Background/Objectives: Cognitive impairment in spinocerebellar ataxia patients has been reported since the early-disease stage. We aimed to assess cognitive differences in SCA1 and SCA2 patients. Methods: We performed neuropsychological (NPS) and neurophysiological (auditory event-related potentials, aERPs) assessments in 16 SCA1 and 18 SCA2 consecutive patients. Furthermore, clinical information (age at onset, disease duration, motor disability) was collected. Results: NPS tests yielded scores in the normal range in both groups but with lower scores in the Frontal Assessment Battery (p < 0.05) and Visual Analogue Test for Anosognosia for motor impairment (p < 0.05) in SCA1, and the Trail Making Test (p < 0.01), Raven’s progressive matrices (p < 0.01), Stroop (p < 0.05), and emotion attribution tests (p < 0.05) in SCA2. aERPs showed lower N100 amplitude (p < 0.01) and prolonged N200 latency (p < 0.01) in SCA1 compared with SCA2. Clinically, SCA2 had more severe motor disability than SCA1 in the Assessment and Rating of Ataxia Scale. Conclusions: SCA2 showed more significant difficulties in attentional, visuospatial, and emotional function, and greater motor impairment. In contrast, SCA1 showed less cognitive flexibility/phasic ability, probably affected by a more severe degree of dysarthria. The same group revealed less neural activity during nonconscious attentional processing (N100-N200 data), suggesting greater involvement of sensory pathways in discriminating auditory stimuli. NFS did not correlate with NPS findings, implying an independent relationship. However, the specific role of the cerebellum and cerebellar symptoms in NPS test results deserves more focus.

Background: Levodopa‐carbidopa intestinal gel infusion (LCIG) is an effective therapy for advanced Parkinson's disease (PD). Opicapone (OPC) is an enzyme inhibitor that enhances the bioavailability of levodopa in the brain. Objectives: This study evaluates the effect of Opicapone addition in PD‐LCIG patients, assessing its impact on motor fluctuations and dyskinesias. Secondly, the study analyses the impact of OPC on non‐motor symptoms, LCIG dosage, and peripheral neuropathy. Methods: In this pilot study, 22 PD patients on LCIG were randomized to receive OPC or not, based on persistent or reemergent fluctuations. The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), Unified Dyskinesia Rating Scale (UDysRS), Montreal Cognitive Assessment (MoCA), electroneurography (ENG), LCIG doses, homocysteine, vitamin B12, and folic acid levels were measured at baseline (T0) and after 12 months (T1). Results: Eleven patients added OPC (addOPC group), while 11 maintained standard treatment (nOPC group). At baseline, both groups had similar disease duration and severity. At T1, the addOPC group showed significant: (i) improvement in motor fluctuations evaluated by the MDS‐UPDRS part IV; (ii) reduction in dyskinesias (UDyRS); (iii) decrease in LCIG infusion rate; (iv) improvement in motor and non‐motor symptoms (MDS‐UPDRS parts I‐III); (v) increase in Vitamin B12. No significant differences were observed in the ENG data, and no serious adverse events occurred. Four addOPC patients (36%) discontinued OPC after 15 ± 2 months, mainly due to hallucinations. Conclusions: OPC addition appeared well tolerated and beneficial in reducing motor fluctuations, dyskinesia, and LCIG dose. Randomized controlled trials are needed to confirm these findings.

The Heidenhain Variant of Creutzfeldt–Jakob disease (CJD) is an uncommon early clinical syndrome of the otherwise regular sporadic CJD, which belongs to the group of prion diseases caused by a transmissible agent, the misfolded form of the prion protein. The most characteristic symptoms of CJD are rapidly progressive cognitive impairment, typical motor manifestations and mental and behavioural changes. Conversely, in the Heidenhain Variant, different kinds of visual disturbances are observed at onset due to microvacuolar spongiform degeneration or, less frequently, confluent spongiform changes in the parieto-occipital area, detectable through brain MRI with hyperintensity in T2-FLAIR or DWI in the same areas. Since this an extremely rare condition with a heterogeneous clinical presentation, it may easily be misdiagnosed with other diseases at the earlier stages. Here, we describe the case of a patient initially diagnosed with posterior reversible encephalopathy syndrome (PRES), presenting with visual disturbances and headache at onset in a context of poorly controlled arterial hypertension. Subsequently, a rapid worsening of cognitive decline, associated with myoclonus and startle reaction led to further investigations, shifting the diagnosis toward a rapidly evolving neurodegenerative form. This hypothesis was also supported by EEG traces, MRI and CSF analysis. Finally, the clinical–instrumental evolution confirmed the diagnosis of Heidenhain Variant of CJD.