ANO10-Related Spinocerebellar Ataxia: MDSGene Systematic Literature Review and a Romani Case Series.

BACKGROUND: Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX-ANO10). METHODS: Following the MDSGene protocol, we systematically investigated genotype-phenotype relationships in ATX-ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients. RESULTS: Most patients (>80%) had loss-of-function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14-year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX-ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX-ANO10 diagnosis. CONCLUSIONS: The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease-modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

What was first and what is next in selecting device-aided therapy in Parkinson's disease? Balancing evidence and experience.

Parkinson's disease (PD) progresses with motor fluctuations emerging several years after treatment initiation. Initially managed with oral medications, these fluctuations may later necessitate device-aided therapy (DATs). Globally, various DATs options are available, including continuous subcutaneous apomorphine infusion, deep brain stimulation, levodopa-carbidopa intestinal gel, levodopa-entacapone-carbidopa intestinal gel, and subcutaneous foslevodopa/foscarbidopa infusion, each with its complexities. Hence, matching complex patients with suitable therapy is critical. This review offers practical insights for physicians managing complex PD cases. Balancing evidence and experience is vital to select the most suitable DATs, considering factors like disease stage and patient preferences. Comparative analysis of DATs benefits and risks provides essential insights for clinicians and patients. Treatment sequences vary based on availability, patient needs, and disease progression. Less invasive options like apomorphine are often preferred initially, followed by other DATs if needed. Patient selection requires comprehensive evaluations, including motor function and cognitive status. Follow-up care involves symptom monitoring and adjusting medications. Customized treatment plans are essential for optimizing PD management with DATs.

Longitudinal White Matter Damage Evolution in Parkinson's Disease.

BACKGROUND: White matter hyperintensities (WMHs) have a role in cognitive impairment in normal brain aging, while the effect on Parkinson's disease (PD) progression is still controversial. OBJECTIVE: To investigate the longitudinal evolution of micro- and macrostructural damage of cerebral white matter (WM) and its relationship with the clinical picture in PD. METHODS: A total of 154 PD patients underwent clinical, cognitive, and magnetic resonance imaging (MRI) assessment once a year for up to 4 years. Sixty healthy controls underwent the same protocol at baseline. WMHs were identified and total WMH volume was measured. WMHs were also used as exclusion masks to define normal-appearing white matter (NAWM). Using tract-based spatial statistics, diffusion tensor (DT) MRI metrics of whole-brain WM and NAWM were obtained. Linear mixed-effects models defined the longitudinal evolution and association between variables. WM alterations were tested as risk factors of disease progression using linear regression and Cox proportional hazards models. RESULTS: At baseline, PD patients showed alterations of all DT MRI measures compared to controls. Longitudinally, DT MRI measures did not vary significantly and no association with clinical variables was found. WMH volume changed over time and was associated with impairment in global cognition, executive functions, and language. Baseline WMH volume was a moderate risk factor for progression to mild cognitive impairment. CONCLUSIONS: Our study suggests an association between WMHs and cognitive deterioration in PD, whereas WM microstructural damage is a negligible contributor to clinical deterioration. WMHs assessed by MRI can provide an important tool for monitoring the development of cognitive impairment in PD patients. © 2021 International Parkinson and Movement Disorder Society.

Adherence to Medication among Parkinson's Disease Patients Using the Adherence to Refills and Medications Scale.

Objectives: Adherence to medication is an important factor that can influence Parkinson's disease (PD) control. We aimed to explore patients' adherence to antiparkinsonian medication and determine factors that might affect adherence to medications among PD patients. Methods: A cross-sectional, exploratory survey of PD patients treated with at least one antiparkinsonian drug and with a total score of MoCA (Montreal Cognitive Assessment) ≥26 was conducted. The final sample included 112 PD patients. A patient's adherence was assessed through ARMS (Adherence to Refills and Medications Scale). ARMS scores higher than 12 were assumed lower adherence. In addition, each patient underwent neurological examination, assessment of depression, anxiety, and evaluation of the presence of PD nonmotor symptoms. Results: The mean ARDS value in our cohort was 14.9 ± 2.5. Most PD patients (74.1%) reported lower adherence to their medication. Participants in the lower adherence group were younger at PD onset, had significantly higher UPDRS (Unified PD Rating Scale) scores, as well as UPDRS III and UPDRS IV subscores, HARS (Hamilton Anxiety Rating Scale), and NMSQuest (Non-Motor Symptoms Questionnaire for PD) scores compared to the fully adherent group (p=0.013, p=0.017, p=0.041, p=0.043, and p=0.023, respectively). Among nonmotor PD symptoms, the presence of cardiovascular, apathy/attention-deficit/memory disorders, hallucinations/delusions, and problems regarding changes in weight, diplopia, or sweating were associated with lower adherence. Multivariate regression analysis revealed depression as the strongest independent predictor of lower adherence. Conclusion: Depressed PD patients compared to PD patients without clinical depression had a three times higher risk for lower adherence to pharmacotherapy. Recognition and adequate treatment of depression might result in improved adherence.

Brain Structural Changes in Focal Dystonia-What About Task Specificity? A Multimodal MRI Study.

BACKGROUND: The neural basis of task specificity in dystonia is still poorly understood. This study investigated gray and white matter (WM) brain alterations in patients with task-specific dystonia (TSD) and non-task-specific dystonia (NTSD). METHODS: Thirty-six patients with TSD (spasmodic dysphonia, writer's cramp), 61 patients with NTSD (blepharospasm, cervical dystonia), and 83 healthy controls underwent 3D T1-weighted and diffusion tensor magnetic resonance imaging (MRI). Whole brain cortical thickness and voxel-based morphometry; volumes of basal ganglia, thalamus, nucleus accumbens, amygdala, and hippocampus; and WM damage were assessed. Analysis of variance models were used to compare MRI measures between groups, adjusting for age and botulinum toxin (BoNT) treatment. RESULTS: The comparison between focal dystonia patients showed cortical thickness and gray matter (GM) volume differences (ie, decreased in NTSD, increased in TSD) in frontal, parietal, temporal, and occipital cortical regions; basal ganglia; thalamus; hippocampus; and amygdala. Cerebellar atrophy was found in NTSD patients relative to controls. WM damage was more severe and widespread in task-specific relative to NTSD patients. TSD patients receiving BoNT, relative to nontreated patients, had cortical thickening and increased GM volume in frontoparietal, temporal, and occipital regions. NTSD patients experiencing pain showed cortical thickening of areas involved in pain-inhibitory mechanisms. CONCLUSIONS: TSD and NTSD are characterized by opposite alterations of the main cortical and subcortical sensorimotor and cognitive-controlling brain structures, suggesting the possible presence of different pathophysiological and/or compensatory mechanisms underlying the complexity of the two clinical phenotypes of focal dystonia. © 2020 International Parkinson and Movement Disorder Society.

Are there two different forms of functional dystonia? A multimodal brain structural MRI study.

This study assessed brain structural alterations in two diverse clinical forms of functional (psychogenic) dystonia (FD) - the typical fixed dystonia (FixFD) phenotype and the "mobile" dystonia (MobFD) phenotype, which has been recently described in one study. Forty-four FD patients (13 FixFD and 31 MobFD) and 43 healthy controls were recruited. All subjects underwent 3D T1-weighted and diffusion tensor (DT) magnetic resonance imaging (MRI). Cortical thickness, volumes of gray matter (GM) structures, and white matter (WM) tract integrity were assessed. Normal cortical thickness in both FD patient groups compared with age-matched healthy controls were found. When compared with FixFD, MobFD patients showed cortical thinning of the left orbitofrontal cortex, and medial and lateral parietal and cingulate regions bilaterally. Additionally, compared with controls, MobFD patients showed reduced volumes of the left nucleus accumbens, putamen, thalamus, and bilateral caudate nuclei, whereas MobFD patients compared with FixFD demonstrated atrophy of the right hippocampus and globus pallidus. Compared with both controls and MobFD cases, FixFD patients showed a severe disruption of WM architecture along the corpus callous, corticospinal tract, anterior thalamic radiations, and major long-range tracts bilaterally. This study showed different MRI patterns in two variants of FD. MobFD had alterations in GM structures crucial for sensorimotor processing, emotional, and cognitive control. On the other hand, FixFD patients were characterized by a global WM disconnection affecting main sensorimotor and emotional control circuits. These findings may have important implications in understanding the neural substrates underlying different phenotypic FD expression levels.

The Profile and Evolution of Neuropsychiatric Symptoms in Multiple System Atrophy: Self- and Caregiver Report.

OBJECTIVE: Recent research shows that patients with multiple system atrophy (MSA) have significant cognitive and neuropsychiatric comorbidities that can color the clinical presentation of the disease and affect their quality of life. The aims of this study were to determine the neuropsychiatric profile in a cohort of patients with the parkinsonian type of MSA (MSA-P) and their dynamic changes over a 1-year follow-up period and to compare rates of neuropsychiatric symptoms (NPSs) reported by caregivers and the patients themselves. METHODS: Forty-seven patients were assessed at baseline; of these, 25 were assessed again after 1 year. NPS assessment tools included the Neuropsychiatric Inventory (NPI), the Beck Depression Inventory, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Apathy Evaluation Scale. RESULTS: The prevalence of NPSs in patients with MSA-P was very high, with depression, sleep disturbances, apathy, and anxiety being the most frequently occurring features. The evolution of NPSs was found to be independent of motor, autonomic, and cognitive symptoms. None of the scales measuring NPSs, including the NPI, were capable of detecting changes over the 1-year follow-up period. Although the overall prevalence of depression, apathy, and anxiety obtained from caregivers and the patients themselves was similar, reports from these two sources cannot be considered interchangeable. CONCLUSIONS: The progression of neuropsychiatric symptoms was not a subject of rapid change in MSA-P, in contrast to the observed motor, autonomic, and cognitive deterioration. These findings suggest the need to investigate the utility of available instruments in capturing the evolution of NPSs in MSA over time.

Psychological Effects of "Double Crisis" (COVID-19 Pandemic and Earthquakes) on Croatian Medical Students.

INTRODUCTION: In 2020. the COVID-19 pandemic presented an additional source of stress and anxiety not just to the general population but also to medical students who are, even under normal circumstances, constantly under pressure due to demanding student duties. In addition, they experienced a series of devastating earthquakes in and around the Zagreb region which altogether could have had compromised their psychological well-being. The aim of this review was to evaluate the psychological effects of these two natural disasters on the mental health of Croatian medical students. RESULTS: According to standardized questionnaires for depression and anxiety evaluation, 75.3% of students were anxious and 65.2% were depressive during the "double crisis". No significant difference of these two outcomes was observed regarding genders, but it was found that first year students had a significantly higher anxiety score than older ones. CONCLUSION: In such stressful situations, we should emphasize the importance of mental health not just of healthcare workers, but also of medical students in order to prevent serious psychological consequences and to alleviate the negative effects on students' motivation and their educational process.

Breakdown of the affective-cognitive network in functional dystonia.

Previous studies suggested that brain regions subtending affective-cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective-cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS-fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]). FC of brain regions of interest, known to be involved in affective-cognitive processes, and independent component analysis of RS-fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective-cognitive seeds of interest and the fronto-subcortical and limbic circuits; enhanced FC between the right affective-cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective-cognitive seeds of interest and the sensorimotor and high-order function ("cognitive") areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective-cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.

Tracking Cortical Changes Throughout Cognitive Decline in Parkinson's Disease.

BACKGROUND: The objectives of this study were to investigate progressive cortical thinning and volume loss in Parkinson's disease (PD) patients with different longitudinal patterns of cognitive decline: with stable normal cognition, with stable mild cognitive impairment, with conversion to mild cognitive impairment, and with conversion to dementia. METHODS: We recruited 112 patients (37 Parkinson's disease with stable normal cognition, 20 Parkinson's disease with stable mild cognitive impairment, 36 Parkinson's disease with conversion to mild cognitive impairment, 19 Parkinson's disease with conversion to dementia) and 38 healthy controls. All patients underwent at least 2 visits within 4 years including clinical/cognitive assessments and structural MRI (total visits, 393). Baseline cortical thickness and gray matter volumetry were compared between groups. In PD, gray matter changes over time were investigated and compared between groups. RESULTS: At baseline, compared with Parkinson's disease with stable normal cognition cases, Parkinson's disease with conversion to mild cognitive impairment patients showed cortical atrophy of the parietal and occipital lobes, similar to Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia patients. The latter groups (ie, patients with cognitive impairment from the study entry) showed additional involvement of the frontotemporal cortices. No baseline volumetric differences among groups were detected. The longitudinal analysis (group-by-time interaction) showed that, versus the other patient groups, Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia cases accumulated the least cortical damage, with Parkinson's disease with conversion to dementia showing unique progression of right thalamic and hippocampal volume loss; Parkinson's disease with conversion to mild cognitive impairment patients showing specific cortical thinning accumulation in the medial and superior frontal gyri, inferior temporal, precuneus, posterior cingulum, and supramarginal gyri bilaterally; and Parkinson's disease with stable normal cognition patients showing cortical thinning progression, mainly in the occipital and parietal regions bilaterally. CONCLUSIONS: Cortical thinning progression is more prominent in the initial stages of PD cognitive decline. The involvement of frontotemporoparietal regions, the hippocampus, and the thalamus is associated with conversion to a more severe stage of cognitive impairment. In PD, gray matter alterations of critical brain regions may be an MRI signature for the identification of patients at risk of developing dementia. © 2020 International Parkinson and Movement Disorder Society.

Tracking brain damage in progressive supranuclear palsy: a longitudinal MRI study.

OBJECTIVES: In this prospective, longitudinal, multiparametric MRI study, we investigated clinical as well as brain grey matter and white matter (WM) regional changes in patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). METHODS: Twenty-one patients with PSP-RS were evaluated at baseline relative to 36 healthy controls and after a mean follow-up of 1.4 years with clinical rating scales, neuropsychological tests and MRI scans. RESULTS: Relative to controls, patients with PSP-RS showed at baseline a typical pattern of brain damage, including midbrain atrophy, frontal cortical thinning and widespread WM involvement of the main infratentorial and supratentorial tracts that exceeded cortical damage. Longitudinal study showed that PSP-RS exhibited no further changes in cortical thinning, which remained relatively focal, while midbrain atrophy and WM damage significantly progressed. Corpus callosum and frontal WM tract changes correlated with the progression of both disease severity and behavioural dysfunction. CONCLUSIONS: This study demonstrated the feasibility of carrying out longitudinal diffusion tensor MRI in patients with PSP-RS and its sensitivity to identifying the progression of pathology. Longitudinal midbrain volume loss and WM changes are associated with PSP disease course.

Use of the Neuropsychiatric Inventory to Characterize the Course of Neuropsychiatric Symptoms in Progressive Supranuclear Palsy.

The aim of this study was to determine the neuropsychiatric profile in a cohort of progressive supranucelar palsy (PSP) patients and their dynamic changes over a follow-up period of 1 year. A total of 59 patients were assessed at baseline, while 25 of them were accessible after 1 year of the follow-up. The most common symptoms were apathy and depression, which were also found to be, among other variables, the independent determinants of increased Neuropsychiatric Inventory (NPI) total score. Moreover, apathy deteriorated most profoundly over the follow-up period. The NPI seemed to be a sensitive measure of behavioral changes in PSP.

LAPAROSCOPIC APPENDECTOMY DOES NOT INCREASE THE RATE OF NEGATIVE APPENDECTOMY along with a lower rate of perforated appendicitis - RESULTS IN 1899 PATIENTS at Zagreb UHC.

- Laparoscopic appendectomy is the method of choice of many professional societies owing to its many advantages. The question arises whether surgeons urge more easily to laparoscopic exploration due to its less invasiveness, faster recovery and adequate exploration of the entire abdominal cavity than to observation in unequivocal cases. This retrospective analysis (2009-2016) included 1899 patients undergoing laparoscopic (lap) or gridiron intra-abdominal approach treated at Zagreb University Hospital Centre. The analysis included total negative appendectomy, negative-negative appendectomy (normal appendix and no other pathology found), and negative-positive appendectomy (normal appendix but another pathology found) in children (≤16 years) and adults. There was no statistically significant difference in the rates of negative appendectomy (children) - lap vs. open (p=0.24); negative appendectomy (adults) - lap vs. open (p=0.15); negative-negative appendectomy (children) - lap vs. open (p=0.36); negative-negative appendectomy (adults) - lap vs. open (p=0.21); negative-positive appendectomy (children) - lap vs. open (p=0.53); negative-positive appendectomy (adults) - lap vs. open (p=0.56); and laparoscopy group negative appendectomy in children vs. adults (p=0.56). There was a statistically significantly higher perforation rate with the open approach in total (p<0.0001), in children (p<0.0001) and in adults (p=0.02). There was no statistically significant difference between adults and children in the perforation rate with laparoscopic approach (p=0.24) and perforation rate with open approach (p=0.29). Results confirmed that there was no statistically significant difference in the rate of negative appendectomy in all subgroups. It is concluded that laparoscopic appendectomy should be offered as the method of choice in any patient population with suspicion of acute appendicitis.

Brain Calcification and Movement Disorders.

Brain calcifications may be an incidental finding on neuroimaging in normal, particularly older individuals, but can also indicate numerous hereditary and nonhereditary syndromes, and metabolic, environmental, infectious, autoimmune, mitochondrial, traumatic, or toxic disorders. Bilateral calcifications most commonly affecting the basal ganglia may often be found in idiopathic cases, and a new term, primary familial brain calcification (PFBC), has been proposed that recognizes the genetic causes of the disorder and that calcifications occurred well beyond the basal ganglia. PFBC, usually inherited in an autosomal dominant fashion, is both an intrafamilial and an interfamilial heterogeneous disorder, clinically characterized by an insidious and progressive development of movement disorders, cognitive decline, and psychiatric symptoms, but also cerebellar ataxia, pyramidal signs, and sometimes isolated seizures and headaches/migraines. Heterozygous mutations in four genes (SLC20A2, PDGFRB, PDGFB, XPR1) have recently proved to be the causes of the autosomal dominant forms of PFBC, also suggesting disrupted phosphate homeostasis as "an underlying and converging" pathophysiological mechanism. However, to date, it is not possible to anticipate with acceptable certainty any of known genetic causes of PFBC on the basis of the type, severity, pattern of distribution, or combination of movement disorders (mainly parkinsonism, with or without tremor, but also dystonia, chorea, paroxysmal kinesigenic dyskinesia, orofacial dyskinesia, and gait and speech disorders).

Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H2O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased TBARS levels in the plasma, sphincters and brain tissues. These effects were all counteracted by BPC 157 administration. In conclusion, we revealed that BPC 157 counteracts the anti-emetic neuroleptic class side effect of decreased pressure in sphincters and the dopamine/NO-system/BPC 157 relationship.

Mini-review of the geotechnical parameters of municipal solid waste: Mechanical and biological pre-treated versus raw untreated waste.

The most viable option for biostabilisation of old sanitary landfills, filled with raw municipal solid waste, is the so-called bioreactor landfill. Even today, bioreactor landfills are viable options in many economically developing countries. However, in order to reduce the biodegradable component of landfilled waste, mechanical and biological treatment has become a widely accepted waste treatment technology, especially in more prosperous countries. Given that mechanical and biological treatment alters the geotechnical properties of raw waste material, the design of sanitary landfills which accepts mechanically and biologically treated waste, should be carried out with a distinct set of geotechnical parameters. However, under the assumption that 'waste is waste', some design engineers might be tempted to use geotechnical parameters of untreated raw municipal solid waste and mechanical and biological pre-treated municipal solid waste interchangeably. Therefore, to provide guidelines for use and to provide an aggregated source of this information, this mini-review provides comparisons of geotechnical parameters of mechanical and biological pre-treated waste and raw untreated waste at various decomposition stages. This comparison reveals reasonable correlations between the hydraulic conductivity values of untreated and mechanical and biological pre-treated municipal solid waste. It is recognised that particle size might have a significant influence on the hydraulic conductivity of both municipal solid waste types. However, the compression ratios and shear strengths of untreated and pre-treated municipal solid waste do not show such strong correlations. Furthermore, another emerging topic that requires appropriate attention is the recovery of resources that are embedded in old landfills. Therefore, the presented results provide a valuable tool for engineers designing landfills for mechanical and biological pre-treated waste or bioreactor landfills for untreated raw waste as well as planning landfill mining projects.

A Synchronous Occurrence of Hepatocellular Carcinoma and Echinoccocal Liver Cyst - Can Parasite Promote Carcinogenesis? Literature Review and Classification Proposal.

Concomitant presence of hydatid cyst and hepatocellular carcinoma is a very rare clinical scenario especially in a previously non-diseased liver. Including our case here reported, there are 12 cases of synchronous HCC and hydatid cyst found in the scientific literature and 3 of them were found in a patient with non-diseased liver. We provide detailed review of all reported cases with additional highlights on etiology, pathogenesis, diagnosis, treatment and outcomes of both HCC and echinococcal disease. Although there is a small number of patients, possible relation between these 2 liver lesions should be investigated and standardized classification should be established. This will help us to understand the nature of HCC carcinogenesis, identify diagnostic features of liver lesions and choose the most appropriate type of treatment.

Minimal change multiple system atrophy: an aggressive variant?

BACKGROUND: Glial cytoplasmic inclusions containing α-synuclein are the pathological hallmark of multiple system atrophy (MSA). Minimal change (MC-MSA) is an unusual MSA subtype with neuronal loss largely restricted to the substantia nigra and locus coeruleus. METHODS: Immunohistochemistry on selected brain regions and semiquantitative assessment were performed on six MC-MSA and eight MSA control cases. RESULTS: More neuronal cytoplasmic inclusions were seen in the caudate and substantia nigra in MC-MSA than in MSA controls (P = 0.002), without any statistical difference in glial cytoplasmic inclusion load in any region. Severe glial cytoplasmic inclusion load was found in the ventrolateral medulla (P = 1.0) and nucleus raphe obscurus (P = 0.4) in both groups. When compared with MSA controls, the three MC-MSA cases who had died of sudden unexpected death had an earlier age of onset (mean: 38 vs. 57.6 y, P = 0.02), a numerically shorter disease duration (mean: 5.3 vs. 8 y, P = 0.2) and a more rapid clinical progression with most of the clinical milestones reached within 3 y of presentation, suggesting an aggressive variant of MSA. Another three MC-MSA cases, who had died of unrelated concurrent diseases, had an age of onset (mean: 57.7 y) and temporal course similar to controls, had less severe neuronal loss and gliosis in the medial and dorsolateral substantia nigra subregions (P < 0.05) than in MSA controls, and could be considered as a unique group with interrupted pathological progression. Significant respiratory dysfunction and early orthostatic hypotension were observed in all MC-MSA cases. CONCLUSIONS: Our findings could suggest that α-synuclein-associated oligodendroglial pathology may lead to neuronal dysfunction sufficient to cause clinical symptoms before overt neuronal loss in MSA. © 2015 International Parkinson and Movement Disorder Society.