Background: Elevated levels of prokineticin-2 (PK2), regarded as a protein involved in modulating immune/inflammatory responses, have been detected in the substantia nigra, serum, and olfactory neurons of Parkinson's disease (PD) patients. Of note, emerging evidence suggests that gut alterations, including dysbiosis and enteric inflammation, play a role in PD via the gut-brain axis. Objectives: Our goal was to investigate the expression of PK2 in colonic biopsies of PD patients. Methods: Mucosal biopsies from the descending colon were obtained in 11 PD patients and five asymptomatic subjects. Biopsy samples were processed for PK2 immunofluorescence and western blot. Results: We revealed an increased PK2 expression in colonic mucosa from PD patients in the early stages compared to controls. In addition, we found that PK2 was expressed by activated enteric glial cells and macrophages. Conclusions: PK2 is highly expressed within neurogenic/inflammatory cells of colonic mucosa from early PD patients, suggesting a potential role of PK2 in gut inflammation, especially in the early stages of PD. (c) 2024 International Parkinson and Movement Disorder Society.

Myoclonus-dystonia (MD) is a syndrome characterized by subcortical myoclonus and milder dystonia. The main causative gene is the epsilon sarcoglycan gene (SGCE), but other genes may be involved. Response to medications is variable, with poor tolerability limiting their use. We present the case of a patient with severe myoclonic jerks and mild dystonia since childhood. At first neurological visit at the age of 46 years old, she presented brief myoclonic jerks predominating in the upper limbs and neck, mild at rest and elicited by action, posture and tactile stimulus. Myoclonus was accompanied by mild neck and right arm dystonia. Neurophysiological tests suggested subcortical origin of myoclonus, brain MRI was unremarkable. Myoclonus-dystonia was diagnosed, and genetic testing identified a novel mutation in SGCE gene (c.907delC) in heterozygosis. Over time she assumed a large variety of anti-epileptics without beneficial effect on myoclonus and low tolerability. Add-on treatment with Perampanel was started, with a beneficial effect. No adverse events were reported. Perampanel is the first selective non-competitive AMPA receptor antagonist approved in add-on for focal and generalized tonic–clonic seizures. To our knowledge, this is the first trial of Perampanel in MD. We presented the case of a patient with MD due to SGCE mutation who was treated with Perampanel with beneficial effects. We propose Perampanel as a novel treatment for myoclonus in MD.

BackgroundTo date, a few studies have systematically investigated differences in the clinical spectrum between acquired and idiopathic dystonias. ObjectivesTo compare demographic data and clinical features in patients with adult-onset acquired and idiopathic dystonias. MethodsPatients were identified from among those included in the Italian Dystonia Registry, a multicenter Italian dataset of patients with adult-onset dystonia. Study population included 116 patients with adult-onset acquired dystonia and 651 patients with isolated adult-onset idiopathic dystonia. ResultsComparison of acquired and idiopathic dystonia revealed differences in the body distribution of dystonia, with oromandibular dystonia, limb and trunk dystonia being more frequent in patients with acquired dystonia. The acquired dystonia group was also characterized by lower age at dystonia onset, greater tendency to spread, lower frequency of head tremor, sensory trick and eye symptoms, and similar frequency of neck pain associated with CD and family history of dystonia/tremor. ConclusionsThe clinical phenomenology of dystonia may differ between acquired and idiopathic dystonia, particularly with regard to the body localization of dystonia and the tendency to spread. This dissimilarity raises the possibility of pathophysiological differences between etiologic categories.

Background Spastic Paraplegia type 7 (SPG7) is one of the most common autosomal recessive Hereditary Spastic Paraplegias (HSP); Spastic Paraplegias (SPGs) can present as hereditary ataxias. However, ataxia is frequently the symptom of presentation of many other hereditary/sporadic disorders, such as Multiple system atrophy type C (MSA-C), an α-synuclein sporadic neurodegenerative disorder, in which cerebellar ataxia is one of the main clinical features. Dopamine Transporter imaging (DAT-SCAN), associated with clinical features, can be a helpful tool in order to distinguish MSA-C from other causes of ataxia. Case-presentation We present the case of a 70-year-old man with gait difficulties over a period of 3 years and frequent backward/lateral falls. He also reported urinary urge incontinence, but no symptoms that are compatible with orthostatic hypotension. On neurological examination he showed ataxic gait, spasticity in the left lower limb and trunk and limb ataxia, especially on the left side. Mild hypokinesia was found in all 4 limbs, especially in the left foot. MRI revealed atrophy of the cerebellar hemispheres and vermis. DAT-SCAN imaging revealed bilateral nigro-striatal degeneration, which was compatible with a diagnosis of possible MSA-C. Considering the atypical disease course (the patient walked without any support after 3 years), we carried out a genetic investigation for Ataxia, and a mutation in SPG7 was found. Conclusions DAT-SCAN imaging, evaluated together with the clinical findings, can be useful for differentiating MSA from other possible causes of adult-onset Ataxia. Indeed, patients with MSA-C generally show a decreased uptake of dopamine transporters in DAT-SCAN imaging. Ours is the first case reported in the literature of a patient with SPG7 mutation with nigrostriatal degeneration and a clinical presentation of a possible MSA-C. Performing genetic investigations in patients with an atypical disease course is important to avoid MSA-mimicries. Identifying the correct diagnosis is important not only for prognostic reasons, but also for possible future genetic therapies.

Theory of mind (ToM) is the ability to attribute mental states to one self and others and to understand that others have beliefs different from one's own. Different subcomponents of ToM have also been identified: cognitive and affective. Cognitive ToM refers to the capacity to infer others' beliefs and intentions, while affective ToM implies the ability to appreciate others' emotional states. The aim of this study was to explore ToM in drug-naïve Parkinson's disease (PD) patients and to investigate the effects of chronic dopaminergic therapy on different subcomponents of ToM during a 3 months and 1 year of follow-up. We examined 16 PD patients in three conditions: before (un-medicated) and after dopaminergic therapy (medicated 3 months: T1 and medicated 1 year: T2). We also compared our PD's ToM abilities with 11 healthy individuals. ToM was explored with 5 different tasks: Faux Pas Test, Picture Sequencing Task Capture Story, Emotion Attribution Task, Strange Stories Task, and Karolinska Directed Emotional Faces. Our study confirms that PD patients present deficits in cognitive components of ToM and preserved performances in the affective ones in early stages of disease. We also find a significant effect of dopaminergic therapy on ToM already after 3 months with a good persistency after 1 year of treatment.

Palermo, Giovanni MD; Mazzucchi, Sonia MD; Unti, Elisa MD; Bonuccelli, Ubaldo MD; Ceravolo, Roberto MDAuthor Information

Abstract Background Dystonia is a key symptom in corticobasal syndrome (CBS), and upper limb dystonia is the most common phenotype. Dystonia‐associated pain is frequently reported and can be disabling, with poor benefit from oral treatments. Aims of the Study To investigate the role of botulinum toxin A (BoTNA) in the treatment of dystonia and associated pain in CBS. Methods Ten consecutive patients with a clinical diagnosis of probable CBS and dystonia with/without associated pain were treated with BoTNA every 3 months. Treatment efficacy was assessed during the first follow‐up visit, three months after the first injection, by means of caregiver impression (CI), evaluation of muscle tone with the Ashworth scale (AS), severity of pain measured with the visual analog scale (VAS). Results Nine subjects underwent at least three treatments, four patients discontinued for progressive reduction in efficacy or disease progression, five patients are ongoing with good response, and one completed the 10th treatment. No local or systemic side effects were reported, and levodopa equivalent daily dose remained unchanged in most cases during the observational period. Significant improvement of AS was recorded (from 2.9 ± 0.7 to 2.0 ± 0.5, p = 0.003). CI ranged from mild to moderate benefit. All patients reported efficacy on pain, with a significant reduction of VAS score (from 7.7 ± 1.7 to 1.7 ± 0.7 in the Pain group, p = 0.016). Conclusions Our study confirms safety, efficacy, and tolerability of BoTNA in the treatment of dystonia associated with CBS. Local treatment should be considered as a valid alternative to oral treatment modulation mainly in the presence of associated pain.

Deficits in social-cognition processing have been identified during early stages of Huntington Disease (HD), attracting interest on their relevance as possible predictors of  neurodegenerative progression. Since the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) and the serotonin (5-HT) transporter (SERT) are known to modulate human adaptive behavior, we appraised these two proteins in mild-HD using blood platelets, with the aim at finding relationships with cognitive/psychosocial skills. Thirteen gene positive and symptomatic patients (9M/4W, HD-stage II, age> 40y) together 11 gender/age matched controls without a concurrent diagnosis of psychiatric disorders, underwent a blood test to determine BDNF storage and membrane-bound SERT in platelets by an ELISA immune-enzyme dosage and [3H]-paroxetine ([3H]-PAR) binding, respectively. Enrolled subjects were concurrently evaluated through a battery of socio-cognitive tests and emotion recognition questionnaires.Results showed greater intra-platelet BDNF (~ +20-22%) in patients versus controls, whereas equilibrium [3H]-PAR binding parameters, maximum density (Bmax) and dissociation constant (KD), did not appreciably vary in the two comparison groups. Cognitive/emotion abilities were found significantly reduced in patients. Additionally, platelet BDNF was unrelated to psycho-cognitive scores, but positively correlated with the illness duration. As well, SERT Bmax was unconnected to HD signs or socio-cognitive scores, whilst KDs negatively correlated with scores for angry voice recognition in both controls and patients. This pilot study suggests that platelet BDNF and SERT do not specifically underlie psychosocial deficits in stage II-HD, while higher BDNF storage in delayed mild symptoms, would derive from compensatory mechanisms. Supplementary investigations are warranted, by also comparing patients in other illness's phases.

BACKGROUND:Parkinson's Disease (PD) is characterized by progressive and disabling symptoms. An impaired oxidative metabolism efficiency was supposed to be involved in the systemic impairment. Rehabilitative treatment represents a valid tool in promoting skeletal muscle's adaptations, even if no solid studies on muscle metabolic features are still available. OBJECTIVE:To evaluate the efficiency of skeletal muscle oxidative metabolism in PD patients in comparison with age-matched controls and test the role of an intensive aerobic treatment on muscle oxidative metabolism and its clinical effects. METHODS:60 PD patients and 32 age-matched healthy controls participated. Haematic lactate values were detected during and after a submaximal incremental exercise on treadmill. The number of steps completed during the exercise was recorded. From these patients 10 underwent to an intensive aerobic treatment on treadmill (4 sessions/week for 4 weeks). Haematic lactate values and functional scales were recorded before (T0) and after (T1) treatment. RESULTS:At rest no significant difference in hematic lactate values between PD and control subjects was found. Lactate blood levels were significantly higher (p < 0,001) after the aerobic exercise test in PD patients compared to controls. These values remained higher at any time during recovery period (p < 0,001). No significant relationship between lactate values and the number of completed steps was found. After the rehabilitation treatment haematic value of lactate showed a significant reduction (p < 0,05) at 0, 5 and 10 minutes of recovery period with a normalization of value at 30'. All functional scales showed an improvement trend at T1, in particular Berg Balance Scale and 6 Meter Walking Test showed a significant reduction (p < 0,001 and p < 0,05 respectively). CONCLUSION:Our data clearly show an impaired muscle oxidative efficiency in PD subjects. The intensive rehabilitation program on treadmill showed a beneficial effect on muscle oxidative metabolism, endurance and balance, confirming the focal role of rehabilitation in PD patients.

This study is aimed at relating social cognition in Huntington’s Disease (HD) to plasma levels of the social hormone oxytocin (OT). Indeed, HD patients commonly display reduced social skills and OT is involved in bonding behavior and improved recognition of facial emotions. Twelve mild-symptomatic HD patients (stage II Shoulson & Fahn) and 11 gender/age matched controls (healthy controls, HC), without concurrent psychiatric disorders, were investigated at baseline (T0) for OT plasma levels and social cognition through an extensive battery of neuropsychological tests. Social cognition was also re-examined after two years (T1) in 8 of the 12 patients. Results showed a trend for reduced T0-OT levels in HD vs. HC, mean ± stardard deviation: 6.5 ± 2.4 vs. 9.9 ± 7.2 pg/mL, without reaching statistical significance. At T0, patients showed significantly lower performances than controls at the “Faux-Pas” and “Strange Stories” tests (p < 0.05; p < 0.01); a reduced perception of visual emotions (p < 0.01) and verbal stimuli (p < 0.01) was also reported, involving anger, fear, and sadness (p < 0.05; p < 0.01). Additionally, in the HD population, OT concentrations positively correlated with T1-performances at Neutral\Faux-Pas test (p < 0.05), whereas the cognitive Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) scores positively correlated with psychosocial perception at the “Strange Stories” and Karolinska Directed Emotional Faces (KDEF) tests (p < 0.05). This study, despite its limitations, supports correlations between OT and HD social cognition, suggesting a possible therapeutic use of this hormone. More subjects and additional body tissues/fluids, such as cerebrospinal fluid, should be investigated to confirm this hypothesis.

This is an observational cross-sectional study evaluating gait dynamics in patients with Parkinson's Disease (PD) and severe postural deformities, PD without axial deviations and healthy subjects. Ten PS individuals with Pisa syndrome (PS) and nine subjects with Camptocormia (CC) performed 3-D Gait Analysis and were evaluated with walking and balance scales. Correlations with clinical and functional scales were investigated. Spatio-temporal and kinematic data were compared to ten PD subjects without postural deformities (PP) and ten healthy matched individuals (CG). Data obtained showed decreased walking velocity, stride and step length in PP, PS and CC groups compared to controls. The correlation analysis showed that stride and step length were associated with reduced functional abilities and disease severity in PS and CC groups. Kinematic data revealed marked reduction in range of movements (ROMs) at all lower-extremity joints in PS group. While, in CC group the main differences were pronounced in hip and knee joints. PS and CC groups presented a more pronounced reduction in hip articular excursion compared to PP subjects, revealing an increased hip flexion pattern during gait cycle. Moreover, the increased hip and knee flexion pattern adversely affected functional performance during walking tests. Results obtained provide evidence that step length, along with stride length, can be proposed as simple and clear indicators of disease severity and reduced functional abilities. The reduction of ROMs at hip joint represented an important mechanism contributing to decreased walking velocity, balance impairment and reduced gait performance in PD patients with postural deformities.

BACKGROUND:Pisa syndrome (PS) represents an important source of disability in Parkinson's disease (PD). Currently no consensus has been reached on its definition or diagnostic criteria, and therapeutic approaches are unspecific and often futile. Recently the role of abdominal muscles, and in particular of the external oblique (EO), in the pathogenesis of PS was hypothesized.OBJECTIVES:To evaluate the role of EO and propose a combined therapeutic approach in the management of PS.METHODS:Ten PD patients with PS underwent a combined protocol based on repeated lidocaine injection in EO and rehabilitation program.RESULTS:Our data confirm the primary role of EO muscles in PS pathogenesis and showed an improvement in truncal flexion and balance with a positive impact on patients' quality of life after treatment.CONCLUSIONS:These data highlight the need for accurate characterization of PS focusing on the role of abdominal muscles and the need for a specific rehabilitation protocol for PS management.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy. The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

Background The role of Oxytocin (OT) as social hormone is supported by the improvement of recognition of the expression of the faces after administration of intranasal OT. Impaired social behaviour, partly related to altered perception of emotions, is commonly reported in Huntington’s disease (HD). Aims To evaluate OT plasma level as possible predictor of social cognition performances in a population of symptomatic HD patients. Methods 12 patients with symptomatic HD (stage II S&F) without cognitive impairment were evaluated at the baseline and after 2 years follow up (8 pt) for social cognition through an extensive battery of neuropsychological tests (Faux Pas test, Bush vignettes test, emotion recognition from both faces expression and verbal stimuli, Strange stories test). Plasma OT levels at the baseline were analysed in the whole cohort of subjects and the relationship between the levels of OT and social cognition at the baseline and at the follow up was analysed. OT plasma levels were also compared to that of a population of healthy controls matched for age. Results OT levels did not differ in the two populations, however with a trend for lower values in HD group (average 9.9 ± 7.2 controls, 6.5 ± 2.4 HD). At the baseline OT blood levels did show any significative correlation with social cognition and cognitive tests. The follow up analysis showed that higher OT levels correlated with better performances at the Neutral\Faux Pas score (p < 0.05) and with higher ability of recognising happiness from verbal stimuli (p < 0.05). Conclusions Even though not statistically significant patients showed lower OT circulating levels compared to controls; moreover the follow-up analysis pointed out a possible role of OT in predicting the progression of social cognition in HD. The present data, limited by the sample size and by the biological tissue studied, need to be confirmed in a larger population analysis even by correlating with cerebrospinal fluid measurement.

Parkinsons disease (PD) is the second most neurodegenerative disease, which results in gradual loss of movements. To diagnose PD in a clinical setting, clinicians generally use clinical manifestations like motor and non-motor symptoms and rate the severity based on unified Parkinsons disease rating scale (UPDRS). Such clinical assessment largely depends on the expertise and experience of the clinicians and it is subjective leading to variation in assessment between clinicians. As the gait of people with Parkinson’s generally differs from gait of healthy age-matched adults, the assessment of gait abnormalities can lead to not only the diagnosis of PD but also the rating of severity level based on motor symptoms. Hence, in this paper, a data-driven gait classification framework using the supervised machine learning algorithms is presented. Using the publicly available gait datasets acquired using vertical ground reaction force (VGRF) sensors, we present a correlation based feature extraction technique for improved stage classification of PD. Significant biomarkers from spatiotemporal gait features are obtained based on the correlation, and the normal distribution of the gait dataset is assessed using the Shapiro–Wilk test. Subsequently, four supervised machine learning algorithms, namely, K-nearest neighbours (KNN), Naive Bayes (NB), Ensemble classifier (EC) and Support vector machine (SVM) are used to rate the severity level of PD according to the Hoehn and Yahr (H&Y) scale. The performance of the classifiers, assessed using the confusion matrix and parallel coordinate plots, highlights that SVM can result in a classification accuracy of 98.4%. Moreover, with minimal gait feature set acquired based on the rank correlation, the proposed approach outperforms several other state-of-the-art methods that have used the same dataset for PD stage classification.

Background Impaired social behaviour, partly related to altered perception of emotions, is commonly reported in Huntington’s disease (HD). Aims To evaluate social cognition in symptomatic HD patients and its possible predictors. Methods 12 HD patients (stage II S&F, CAG 40.5 ± 2.5) and 9 healthy controls, matched for age and educational level, performed neuropsychological (Montreal Cognitive assessment- MoCa; Mini Mental State Assessment- MMSE; Frontal Assessment Battery- FAB) and social cognition batteries (Faux Pas test, Bush vignettes test, emotion recognition from both faces expression and verbal stimuli, Strange stories test). After 2 years 8 HD patients were re-evaluated through the same tests. Results HD patients, comparing to controls, showed lower performances in social cognition, particularly in Faux pas test and Strange Stories, and in recognising negative emotions from face expression (KDEF scale) and verbal emotions (p < 0.05, p < 0.01), as well as cognitive impairment expressed by MoCa, MMSE and FAB (p < 0.01). MoCa and MMSE showed positive correlation with social cognitive tests. At the follow up there were no significative differences in motor and cognitive scales (baseline: MoCa 18.6 ± 4.7, MMSE 26.5 ± 2.2, UHDRS 35.2 ± 8.2); (Follow-up: MoCa 19.8 ± 5.6, MMSE 25.5 ± 3.4, UHDRS 36 ± 11.2). Statistical analysis revealed a negative correlation between CAG and Bush vignettes Score (p < 0.05). Moreover, patients with higher MoCa scores at the baseline showed better performances in KDEF total score (p < 0.05), in particular disgust (p < 0.05), and at the strange stories test (p < 0.01); whereas MMSE showed positive correlation only with strange stories test (p < 0.05). Conclusions The present study, albeit limited by small sample size, confirms an impairment of social cognition in HD; in addition it suggests CAG expansion and cognitive performances (MoCa and MMSE scores) as possible predictors of social cognition impairment in the course of the disease.

Introduction: The aim of this review is to overview the pharmacological features of neuroleptics experienced in the treatment of Huntington’s disease (HD) symptoms. Despite a large number of case reports, randomized controlled trials (RCT) and drug comparison studies are lacking.Areas covered: After evaluating current guidelines and clinical unmet needs we searched PubMed for the term ‘Huntington’s disease’ cross referenced with the terms ‘Antipsychotic drugs’ ‘Neuroleptic drugs’ and single drug specific names.Expert commentary: In clinical practice antipsychotics represent the first choice in the management of chorea in the presence of psychiatric symptoms, when poor compliance is suspected or when there is an increased risk of adverse events due to tetrabenazine. Antipsychotics are considered valid strategies, with the second generation preferred to reduce extrapyramidal adverse events, however they may cause more metabolic side effects. In the future ‘dopamine stabilizers’, such as pridopidine, could replace antipsychotics modulating dopamine transmission.