Search

Purpose: Non-motor symptoms, such as sleep disturbances, fatigue, neuropsychiatric manifestations, cognitive impairment, and sensory abnormalities, have been widely reported in patients with idiopathic cervical dystonia (ICD). This study aimed to clarify the autonomic nervous system (ANS) involvement in ICD patients, which is still unclear in the literature. Methods: We conducted a pilot case-control study to investigate ANS in twenty ICD patients and twenty age-sex-matched controls. The Composite Autonomic System Scale 31 was used for ANS clinical assessment. The laser Doppler flowmetry quantitative spectral analysis, applied to the skin and recorded from indices, was used to measure at rest, after a parasympathetic activation (six deep breathing) and two sympathetic stimuli (isometric handgrip and mental calculation), the power of high-frequency and low-frequency oscillations, and the low-frequency/high-frequency ratio. Results: ICD patients manifested higher clinical dysautonomic symptoms than controls (p < 0.05). At rest, a lower high-frequency power band was detected among ICD patients than controls, reaching a statistically significant difference in the age group of ≥ 57-year-olds (p < 0.05). In the latter age group, ICD patients showed a lower low-frequency/high-frequency ratio than controls at rest (p < 0.05) and after mental calculation (p < 0.05). Regardless of age, during handgrip, ICD patients showed (i) lower low-frequency/high-frequency ratio (p < 0.05), (ii) similar increase of the low-frequency oscillatory component compared to controls, and (iii) stable high-frequency oscillatory component, which conversely decreased in controls. No differences between the two groups were detected during deep breathing. Conclusion: ICD patients showed ANS dysfunction at clinical and neurophysiological levels, reflecting an abnormal parasympathetic-sympathetic interaction likely related to abnormal neck posture and neurotransmitter alterations. [ABSTRACT FROM AUTHOR]

AFG3-like matrix AAA peptidase subunit 2 gene (AFG3L2, OMIM * 604,581) biallelic mutations lead to autosomal recessive spastic ataxia-5 SPAX5, OMIM # 614,487), a rare hereditary form of ataxia. The clinical spectrum includes early-onset cerebellar ataxia, spasticity, and progressive myoclonic epilepsy (PME). In Italy, the epidemiology of the disease is probably underestimated. The advent of next generation sequencing (NGS) technologies has speeded up the diagnosis of hereditary diseases and increased the percentage of diagnosis of rare disorders, such as the rare hereditary ataxia groups. Here, we describe two patients from two different villages in the province of Ferrara, who manifested a different clinical ataxia-plus history, although carrying the same biallelic mutation in AFG3L2 (p.Met625Ile) identified through NGS analysis. [ABSTRACT FROM AUTHOR]

Understanding the pathophysiology and genetic background of Parkinson's disease (PD) increases the likelihood of developing effective disease-modifying therapeutic strategies. In particular, the discovery of genetic variants causing or increasing the risk for PD has contributed to refining the clinical, biological, and molecular classification of the disease and has offered new insights into sporadic forms. It is even more evident that specific genetic mutations can show different responses to pharmacological and device-aided therapies. To date, several agents acting on multiple PD-causing pathogenic pathways have been tested as disease-modifying strategies, with disappointing results. This may be caused by the recruitment of PD populations whose underlying molecular pathophysiology is heterogeneous. We believe that an effective model of personalized medicine must be prioritized in the near future. Here, we review the current therapeutic options under clinical and preclinical development for PD and discuss the key pending questions and challenges to face for successful clinical trials. Furthermore, we provide some insights into the role of genetics in guiding the decision-making process on symptomatic and device-aided therapies for PD in daily clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Biallelic intronic AAGGG repeat expansion in the replication factor C subunit 1 (RFC1) gene was recently identified in two/third of patients with cerebellar ataxia, sensory neuropathy, and bilateral vestibular areflexia syndrome (CANVAS). The phenotypic spectrum has expanded since (i.e., parkinsonism, motor neuron involvement, cognitive decline); no behavioral symptoms have been reported yet. Case report: We report an Italian family that met the diagnostic criteria for CANVAS, and RFC1-expansion was detected in five of seven. All the affected members presented behavioral-psychiatric symptoms (anxiety, panic attacks, alcohol abuse) before the multisystemic RFC1-expansion manifestation. The disease course was progressive, with ataxia and behavioral-cognitive aspects as the most disabling symptoms. Conclusion: These behavioral-cognitive observations may broaden the RFC1-expansion phenotypic spectrum and highlight the importance of investigating the whole non-motor symptoms in ataxic patients. [ABSTRACT FROM AUTHOR]

Background: Movement disorders affecting the trunk remain a diagnostic challenge even for experienced clinicians. However, despite being common and debilitating, truncal movement disorders are rarely discussed and poorly reviewed in the medical literature. Objectives: To review common movement disorders affecting the trunk and provide an approach for clinicians based on the truncal region involved (shoulder, chest, diaphragm, abdomen, pelvis, and axial disorders). For each disorder, clinical presentation, etiologic differential diagnosis, and "clinical clues" are discussed. Conclusion: This review provides a clinically focused, practical approach to truncal movement disorders, which will be helpful for physicians in everyday practice. [ABSTRACT FROM AUTHOR]

Background: Event-related potentials (ERPs) reflect cognitive processing: negative early components (N100, N200) are involved in the sensory and perceptual processing of a stimulus, whereas late positive component P300 requires conscious attention. Both neuropsychological and affective disorders are present in patients with spinocerebellar ataxia type 1 (SCA1), but the underlying mechanisms need further clarification. Materials and methods: In this pilot study, we assessed cognitive processing by recording auditory ERPs in 16 consecutive SCA1 patients and 16 healthy controls (HC) matched for age and sex. Motor and nonmotor symptoms were evaluated using the Scale for the Assessment and Rating of Ataxia (SARA) and an extensive neuropsychological battery. ERPs were recorded using an oddball paradigm, and peak latency and amplitude of N100, N200, and P300 were measured in the averaged responses to target tones. Results: We found in SCA1 significantly increased latencies of N200 and P300 (p=0.033, p=0.007) and decreased amplitudes of N100 and P300 (p=0.024, p=0.038) compared with HC. Furthermore, P300 latency had the highest AUC in the discrimination of SCA1 in ROC analysis. The expansion of trinucleotide repeats correlated with P300 latency (r=−0.607, p=0.048), whereas both P300 and N100 amplitudes correlated with the severity of motor symptoms (r=−0.692, p=0.003; r=−0.621; p=0.010). Significant correlations between P300 latency and the scores of Emotion Attribution Task (r=−0.633, p=0.027), as well as between N200 latency and the scores of Frontal Assessment Battery and Stroop test (r=−0.520, p=0.047; r=0.538, p=0.039), were observed. Conclusions: This research provides for the first time an extensive characterization of ERPs as useful electrophysiological markers to identify early cognitive dysfunction in SCA1. [ABSTRACT FROM AUTHOR]

Glucocerebrosidase (GCase) is a lysosomal enzyme that catalyzes the breakdown of glucosylceramide in the presence of its activator saposin C (SapC). SapC arises from the proteolytical cleavage of prosaposin (encoded by PSAP gene), which gives rise to four saposins. GCase is targeted to the lysosomes by LIMP-2, encoded by SCARB2 gene. GCase deficiency causes Gaucher Disease (GD), which is mainly due to biallelic pathogenetic variants in the GCase-encoding gene, GBA1. However, impairment of GCase activity can be rarely caused by SapC or LIMP-2 deficiencies. We report a new case of LIMP-2 deficiency and a new case of SapC deficiency (missing all four saposins, PSAP deficiency), and measured common biomarkers of GD and GCase activity. Glucosylsphingosine and chitotriosidase activity in plasma were increased in GCase deficiencies caused by PSAP and GBA1 mutations, whereas SCARB2-linked deficiency showed only Glucosylsphingosine elevation. GCase activity was reduced in fibroblasts and leukocytes: the decrease was sharper in GBA1- and SCARB2-mutant fibroblasts than PSAP-mutant ones; LIMP-2-deficient leukocytes displayed higher residual GCase activity than GBA1-mutant ones. Finally, we demonstrated that GCase mainly undergoes proteasomal degradation in LIMP-2-deficient fibroblasts and lysosomal degradation in PSAP-deficient fibroblasts. Thus, we analyzed the differential biochemical profile of GCase deficiencies due to the ultra-rare PSAP and SCARB2 biallelic pathogenic variants in comparison with the profile observed in GBA1-linked GCase deficiency. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance‐guided focused ultrasound (MRgFUS) thalamotomy is increasingly used to treat drug‐resistant essential tremor (ET). Data on MRgFUS thalamotomy in dystonic tremor (DT) are anecdotal. Objectives: To investigate efficacy, safety, and differences in target coordinates of MRgFUS thalamotomy in DT versus ET. Methods: Ten patients with DT and 35 with ET who consecutively underwent MRgFUS thalamotomy were followed for 12 months. Although in both groups the initial surgical planning coordinates corresponded to the ventralis intermediate (Vim), the final target could be modified intraoperatively based on clinical response. Results: Tremor significantly improved in both groups. The thalamic lesion was significantly more anterior in DT than ET. Considering both ET and DT groups, the more anterior the lesion, the lower the odds ratio for adverse events. Conclusions: MRgFUS thalamotomy is safe and effective in DT and ET. Compared to classical Vim coordinates used for ET, more anterior targeting should be considered for DT. [ABSTRACT FROM AUTHOR]

Background: Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO‐B inhibitors (iMAO‐B) safinamide and rasagiline are still based on empirical approaches. Objectives: To estimate LED of safinamide 50 and 100 mg. Methods: In this multicenter, longitudinal, case–control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N = 130), safinamide 50 mg (N = 144), or rasagiline 1 mg (N = 97) for 9 ± 3 months and a control group of patients never treated with any iMAO‐B (N = 129). Results: Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS‐II scores and Levodopa dose than control subjects. After a mean follow‐up of 8.8‐to‐10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS‐III and OFF‐related UPDRS‐IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO‐B groups. After adjusting for age, disease duration, duration of follow‐up, baseline values and taking change in UPDRS‐III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED. Conclusions: We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings. [ABSTRACT FROM AUTHOR]

Objectives: Levodopa–Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson's disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG. Methods: Out of 512 PD subjects treated with LCIG at 9 Italian PD centers, we selected 25 LE-PD defined as age ≥ 80 years at last follow-up who were available to attend the study visit. Twenty-five PD patients (Control-PD, defined as age < 75 years at last follow-up) matched to LE-PD by disease and LCIG duration served as control group. The following motor and non-motor variables were ascertained: quality of life (PDQ-8), time spent in ON, wearing-off Questionnaire, Unified PD Rating Scale, freezing of gait questionnaire, Parkinson's disease sleep scale-2, Non Motor Symptoms Scale (NMSS), and MOCA. Results: No statistically significant differences were found between LE-PD and Control-PD on PDQ-8 and several motor and non-motor variables. LE-PD had less frequent and milder impulsive–compulsive behaviors and milder dyskinesia. At multivariable regression, worse quality of life was associated with UPDRS-III and NMSS scores but not to age at study visit and age at LICG implant. Rate of adverse effects was similar in both groups. Drop-out rate calculated in the whole PD cohort was comparable between the two groups. Conclusion: Our data provide evidence that valuable LCIG infusion might be achieved in late elderly PD. [ABSTRACT FROM AUTHOR]

The present report describes a case of cutaneous protothecosis caused by Prototheca wickerhamii in a nonimmunocompromised Brazilian female. Dermatological examination revealed a 15-cm diffusely infiltrated eczema-like plaque recovered with many pustule-like lesions on the right forearm. We emphasize the mycological and pathological aspects of this infection that can lead to misdiagnosis. The patient was successfully treated with itraconazole. [ABSTRACT FROM AUTHOR]