Background and Aims:

Sleep changes are reported since early stages of HD and sleep disturbances represent a prominent feature of the advanced disease. The aims our study were: to evaluate sleep-related motor activity, EEG functional connectivity in the sensory-motor network, and autonomic modulation in HD patients.

Methods:

Thirty HD patients, 16 women and 14 men (mean age 57.3±12.2) and 30 matched healthy controls (mean age 56.5±11.8 y) were enrolled. Subjective evaluation of sleep quality and daytime sleepiness was performed. All patients underwent full-night attended video-polysomnography. HRV analysis was conducted on EKG traces obtained during polysomnographic recording. EEG connectivity analysis was performed in a subset of patients by means of exact Low-Resolution Electric Tomography.

Results:

HD patients, compared to controls, showed shorter sleep duration, reduced sleep efficiency, and increased arousals and awakenings. Periodic limb movements during wake and sleep were observed in all patients, but no episode of RBD was observed. During wake and NREM sleep HD patients had higher heart rate than controls, but not during REM sleep. HD patients showed increased lagged phase synchronization among sensory-motor areas (Brodmann areas 1,2,3,4,6,8) during wake and sleep.

Conclusions:

HD patients showed a severe sleep disruption with an overall increase of motor activity, often triggered by periodic limb movements. HRV analysis confirmed the involvement of autonomic nervous system in HD, with a peculiar modulation in sleep. The findings of EEG connectivity may reflect an abnormal function of motor areas or, alternatively, the effort to counterbalance the pathological motor output.

Background and Aims:

Early non-invasive and reliable biomarkers are among the major unmet needs in Parkinson’s disease (PD), in order to monitor therapy response and disease progression. Technology-based objective measures of motor performances could allow a deeper phenotyping of early stage motor changes which could be useful to identify frailer PD patients. Our aim is to identify early prognostic biomarkers in newly diagnosed PD patients and objectively quantify therapy-response.

Methods:

40 de novo PD patients underwent baseline clinical and technology-based kinematic assessments performing seven motor tasks from MDS-UPDRS part III to assess tremor, bradykinesia, gait and postural stability (T0). A follow-up visit after 6 months (T1) and a clinical and kinematic assessment after 12 months (T2) where scheduled. A clinical follow-up was provided between 30 and 36 months after the diagnosis (T3).

We performed an ANOVA for repeated measures to compare patients’ kinematic features at baseline and at T2 to assess therapy response. Pearson correlation test was run between baseline kinematic features and UPDRS III score variation between T0 and T3, to select candidate kinematic prognostic biomarkers. Then, a multiple linear regression model was created to predict the long-term motor outcome using T0 kinematic measures.

Results:

All motor tasks significantly improved after the initiation of a dopamine replacement therapy. A significant correlation was found between UPDRS scores variation and some baseline bradykinesia and gait features. A linear regression models including five baseline kinematic features could significantly predict the motor outcome(p=0.000127).

Conclusions:

Technology-based objective measures represent possible early and reproducible therapy-response and prognostic biomarkers.

Background and Aims:

Late onset Huntington’s disease (LoHD) occurring in tardive adulthood (≥ 60 years) is recently gaining attention. We examined LoHD patients’ clinical, cognitive and behavioral data over 2 years to investigate disease progression.

Methods:

We included 220 European LoHD patients from ENROLL-HD database with 2 annual follow-ups :T0 [baseline]; T1 [375±61.01 days]; T2 [746.39±74.8 days]. Repeated measures ANOVAs were performed to monitor changes over time.

Results:

Patients were 51.8% males and 48.2% females, with mean age at enrollment of 70.00±5.00 years, with mean disease duration of 6.34±3.89 years. Mean CAG in pathological allele was 40.75±1.29. Proportion of LoHD patients without a positive family history was 18%. Body Mass index (BMI) remained stable at T1 and T2. UHDRS Total Motor Score significantly worsened at T2 (p=0.008) and UHDRS Total Functional Capacity reduced by 0.80 point at T1 (p=0.051) and 1.41 at T2 (p<0.001). No significant changes over 2 years in Problem Behaviors Assessment–Short composite scores evaluating depression, irritability/aggressivity, psychosis, apathy.

No significant cognitive changes over two years were observed on MMSE, Phonological Fluency, Symbol Digit Modalities Test, Trail Making Test A&B and Stroop Interference Test. Lower scores were detected at T2 on Stroop Color Naming (p=0.034), Stroop Word Reading (p=0.017) and Categorical Fluency (p=0.033).

Conclusions:

LoHD evolution over 2 years is characterized by significant reduction in daily functionality and motor worsening, whereas psychiatric status remained stable. In cognitive performance significant changes were reported in tasks involving psychomotor speed in spoken context, that can be attentioned as potential markers of disease progression in LoHD phenotype.

Background and Aims:

Background: Parkinson's Disease (PD) patients suffer from a wide range of motor symptoms and PD motor subtypes, including tremor‐dominant (TD) and non‐tremor dominant (nTD) (characterized by postural instability and gait difficulty and known as PIDG) have been described. Heterogeneity have been observed in non-motor symptoms of PD patients, but reports on this topic are conflicting.

Aim: We aimed to investigate autonomic dysfunction in PD motor subtypes by scales for outcomes in PD-autonomic symptoms (SCOPA-AUT).

Methods:

Methods: 46 Non demented PD patients (28 men and 18 women; mean patient’s age 65.1± 9.5; 46% in Hoehn–Yahr stage 1, mean disease duration 3.8 years) were grouped into TD, indeterminant, and PIGD subtypes. Motor and non-motor parameters were analysed at baseline and after 4 years of follow up periods.

Results:

Results: Among our cohort, 22 patients were classified as TD, 5 patients as indeterminant type and 19 patients as PIGD type. At follow-up, 25 patients were classified as PIGD type, 5 as indeterminant type, 16 as TD. At baseline SCOPA-AUT score was higher in PIGD than the subtypes of tremor dominant and intermediate (p 0,007). Taking in to account transition of PD patients in different subtypes, at follow-up, SCOPA-AUT has been observed significantly higher in the PIGD group compared (p 0.05) to the other subtypes.

Conclusions:

Conclusion: Our results support that autonomic dysfunction is more severe in the PIGD than other subtypes .

Background and Aims:

Ma2 antibody-associated encephalitis are nearly always associated with tumors, especially testicular germ cell.

Methods:

This is a case-report of a 30-year-old man suffering from anti-Ma2 limbic encephalitis following testicular teratoma.

Results:

The patient presented high frequency brief episodes of horripilation, cold feelings and tachycardia, associated with insomnia and behavioral change (irritability, anxiety). Testicular post-pubertal teratoma (pT1a) was found and surgically treated. Follow-up was negative for cancer recurrence. Few months later, he presented four sleep-related hypermotor seizures, with right shoulder dislocation. Anti-Ma2 antibodies were found in the cerebrospinal fluid (CSF) and serum. Brain MRI and FDG-PET suggested the presence of limbic encephalitis. Video-EEG monitoring showed left fronto-temporal epileptic abnormalities. Neuropsychological assessment was normal. High dose intravenous steroids and immunoglobulin (IVIg) were promptly started, along with antiseizures treatment (carbamazepine and perampanel). The patients underwent six IVIg sessions on a monthly basis, with a slow tapering of oral steroid. Sleep-related seizures were progressively reduced in frequency during the treatment period. However, each attempt of faster steroid tapering determined seizure recurrence. At the six-months follow-up, the patient was seizure-free, no structural or functional MRI lesions have been shown, the CSF was normal, and he was still, slowly tapering oral steroid treatment.

Conclusions:

Anti-Ma2 associated encephalitis are usually more responsive to oncological and immunological therapy than other paraneoplastic encephalitis. However, aggressive immuno-modulating treatment is not always performed in such patients.

This case confirms that immune-modulating treatments is effective in Anti-Ma2 encephalitis and, if promptly started, it may prevent sequelae such as mesial temporal lobe atrophy.

Background and Aims:

Adenosine A2A receptors are highly expressed in caudate-putamen, and external globus pallidus (GPe), but in trace in internal globus pallidus/entopeduncular nucleus. A2A upregulation in striatal-pallidal pathway is associated with levodopa dyskinesias in Parkinson's disease. Instead, A2A downregulation has been reported in striatum of Huntington Disease.

We investigated distribution of A2A receptors in basal ganglia of Tor1a+/− knock-out mouse model DYT1 primary dystonia.

Methods:

Western blotting and immunofluorescence for A2A receptors were used

Results:

In control Tor1a+/+, Western blotting detected specific A2A 45 kDa band, very intense in the striatum and GPe, but light in entopeduncular nucleus; accordingly, immunofluorescence showed A2A roundish aggregates, 0.3–0.4 μm in diameter, very numerous in neuropil of striatum and GPe, but sparse in entopeduncular nucleus. In experimental Tor1a+/−, A2A Western blotting expression and immunofluorescence aggregates appeared increased in striatum and GPe, but reduced in entopeduncular nucleus. Moreover, in Tor1a+/− A2A aggregates appeared increased in number on ChAT positive cholinergic interneurons compared to Tor1a+/+. Finally, in Tor1a+/−, an increased cAMP signal was detected in the striatum, while significant levels of A2A mRNA were neo-expressed in the GPe.

Conclusions:

Such changes of A2A receptor pathway appear to be specific, differentiating DYT1 dystonia from other forms of movement disorders. Our results suggest that increased A2A receptors in striatal-pallidal indirect pathway may play prominent role in physiopathology of dystonia. However, opposite changes of A2A receptors’ expression in the striatal-pallidal complex and entopeduncular nucleus suggest that pathophysiology of dystonia is critically dependent on a composite functional imbalance of indirect over direct pathway in basal ganglia.