Atypical Parkinsonian Disorders Research Articles

Utility of the new Movement Disorder Society clinical diagnostic criteria for Parkinson's disease applied retrospectively in a large cohort study of recent onset cases

ObjectiveTo examine the utility of the new Movement Disorder Society (MDS) diagnostic criteria in a large cohort of Parkinson's disease (PD) patients. MethodsRecently diagnosed (<3.5 years) PD cases fulfilling United Kingdom (UK) brain bank criteria in Tracking Parkinson's, a UK multicenter prospective natural history study were assessed by retrospective application of the MDS criteria. ResultsIn 2000 cases, 1835 (91.7%) met MDS criteria for PD, either clinically established (n = 1261, 63.1%) or clinically probable (n = 574, 28.7%), leaving 165 (8.3%) not fulfilling criteria. Clinically established cases were significantly more likely to have limb rest tremor (89.3%), a good l-dopa response (79.5%), and olfactory loss (71.1%), than clinically probable cases (60.6%, 44.4%, and 34.5% respectively), but differences between probable PD and ‘not PD’ cases were less evident. In cases not fulfilling criteria, the mean MDS UPDRS3 score (25.1, SD 13.2) was significantly higher than in probable PD (22.3, SD 12.7, p = 0.016) but not established PD (22.9, SD 12.0, p = 0.066). The l-dopa equivalent daily dose of 341 mg (SD 261) in non-PD cases was significantly higher than in probable PD (250 mg, SD 214, p < 0.001) and established PD (308 mg, SD 199, p = 0.025). After 30 months' follow-up, 89.5% of clinically established cases at baseline remained as PD (established/probable), and 86.9% of those categorized as clinically probable at baseline remained as PD (established/probable). Cases not fulfilling PD criteria had more severe parkinsonism, in particular relating to postural instability, gait problems, and cognitive impairment. ConclusionOver 90% of cases clinically diagnosed as early PD fulfilled the MDS criteria for PD. Those not fulfilling criteria may have an atypical parkinsonian disorder or secondary parkinsonism that is not correctly identified by the UK Brain Bank criteria, but possibly by the new criteria.

Spotlight on the March 7 issue

#### Notable in Neurology This issue features an article that investigates whether variations in fasting plasma glucose are predictors of diabetic polyneuropathy risk and another that determines the association of lesion location with speech comprehension deficits in chronic aphasia. A featured Views and Reviews paper reports a lack of consensus on the definition of familial amyotrophic lateral sclerosis, and discrepancy in attitudes and practices related to genetic testing in amyotrophic lateral sclerosis. ### Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder![Graphic][1]</img>![Graphic][2]</img> ### Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias![Graphic][3]</img> Blood-based neurofilament light chain (NfL) markers were found in parkinsonian disorders and primary progressive aphasia (PPA), offering a method to distinguish Parkinson disease from atypical parkinsonian disorders, and to differentiate … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif

Evaluation of an optimized [18 F]fluoro-deoxy-glucose positron emission tomography voxel-wise method to early support differential diagnosis in atypical Parkinsonian disorders.

Atypical Parkinsonian disorders (APD) frequently overlap in clinical presentations, making the differential diagnosis challenging in the early stages. The present study aimed to evaluate the accuracy of the [18 F]fluoro-deoxy-glucose positron emission tomography Statistical Parametric Mapping (SPM) optimized procedure in supporting the early and differential diagnosis of APD. Seventy patients with possible APD were retrospectively included from a large clinical cohort. The included patients underwent [18 F]fluoro-deoxy-glucose positron emission tomography within 3 months of the first clinical assessment and a diagnostic follow-up. An optimized SPM voxel-wise procedure was used to produce t-maps of brain hypometabolism in single subjects, which were classified by experts blinded to any clinical information. We compared the accuracy of both the first clinical diagnosis and the SPM t-map classifications with the diagnosis at follow-up as the reference standard. At first diagnosis, 60% of patients were classified as possible APD (progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy) and about 40% as APD with uncertain diagnosis, providing 52% sensitivity, 97% specificity and 86% accuracy with respect to the reference standard. SPM t-map classification showed 98% sensitivity, 99% specificity and 99% accuracy, and a significant agreement with the diagnosis at follow-up (P < 0.001). The SPM t-map classification at entry predicted the second diagnosis at follow-up. This indicates its significantly superior role for an early identification of APD subtypes, particularly in cases of uncertain diagnosis. The use of a metabolic biomarker at entry in the instrumental work-up of APD may shorten the diagnostic time, producing benefits for treatment options and support to the patients.

Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder.

Objective:To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders.Methods:The study included 3 independent prospective cohorts: the Lund (n = 278) and London (n = 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n = 109) of patients with PD, PSP, MSA, or CBS with disease duration ≤3 years. Blood NfL concentration was measured using an ultrasensitive single molecule array (Simoa) method, and the diagnostic accuracy to distinguish PD from APD was investigated.Results:We found strong correlations between blood and CSF concentrations of NfL (ρ ≥ 0.73–0.84, p ≤ 0.001). Blood NfL was increased in patients with MSA, PSP, and CBS (i.e., all APD groups) when compared to patients with PD as well as healthy controls in all cohorts (p < 0.001). Furthermore, in the Lund cohort, blood NfL could accurately distinguish PD from APD (area under the curve [AUC] 0.91) with similar results in both the London cohort (AUC 0.85) and the early disease cohort (AUC 0.81).Conclusions:Quantification of blood NfL concentration can be used to distinguish PD from APD. Blood-based NfL might consequently be included in the diagnostic workup of patients with parkinsonian symptoms in both primary care and specialized clinics.Classification of evidence:This study provides Class III evidence that blood NfL levels discriminate between PD and APD.

Meta‐analysis of dorsolateral nigral hyperintensity on magnetic resonance imaging as a marker for Parkinson's disease

Dorsolateral nigral hyperintensity on iron-sensitive magnetic resonance imaging (MRI) sequences seems to be a typical finding in Parkinson's disease (PD), but most studies have involved small samples and have had heterogeneous control populations. The objective of this study was to perform a meta-analysis on dorsolateral nigral hyperintensity as an imaging marker for PD. The methods included a systematic literature search and a hierarchical summary receiver operating characteristics curve approach. Of the 16 identified studies, 10 were suitable for analysis, including 364 PD and 231 control cases. The meta-analysis showed an overall sensitivity and specificity of the absence of dorsolateral nigral hyperintensity for PD versus controls of 97.7% and 94.6% (3 and 7 Tesla) and of 94.6% and 94.4% (3 Tesla only). Descriptive analysis among the 4 studies including patients with non-PD parkinsonism showed that dorsolateral nigral hyperintensity was absent in 89.4% of cases with atypical parkinsonian disorders (n = 74), but only in 21.7% of cases with non-neurodegenerative parkinsonism (n = 69). Moreover, in 2 of these studies, the absence of dorsolateral nigral hyperintensity predicted ipsilateral dopamine-transporter deficiency with 87.5% sensitivity and 83.6% specificity. Visual assessment of dorsolateral nigral hyperintensity on iron-sensitive MRI sequences provides excellent diagnostic accuracy for PD versus controls. Moreover, its loss appears to be a marker of nigral pathology and holds the potential for the differentiation of neurodegenerative from non-neurodegenerative parkinsonian disorders. © 2017 International Parkinson and Movement Disorder Society.

Review of tremor in Parkinson's disease and atypical parkinsonian disorders

Rest tremor (RT), a cardinal feature of Parkinson's disease (PD) is often accompanied by other types of tremor such as action tremor, which includes postural tremor, kinetic tremor, re-emergent tremor (ReT), and orthostatic tremor (OT). Literature on other tremors of PD, especially ReT and OT, is scarce. Tremor can be present in any of the atypical parkinsonian disorders such as progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. RT can even be the presenting symptom of these disorders. The objective of this review is to provide a comprehensive review of lesser known tremors in PD and to critically look at the prevalence of tremor in atypical Parkinsonian disorders.

The Importance of Connection to Others in QoL in MSA and PSP.

Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are atypical Parkinsonian disorders with extended morbidity and reduced lifespan, known to have marked and early impact upon quality of life (QoL). This study aimed to address the lack of studies in the literature regarding personal perspectives on QoL in MSA and PSP in both patients and carers. Participants took part in qualitative, in-depth interviews in the North East of England, exploring what impacts their QoL and their experiences of living with these complex conditions. Connection to others was found to be a prevailing theme, encompassing difficulty communicating, social isolation, impact on personal relationships, and stigma. This work is helpful in that it emphasises the personal experiences of these patients and carers, which can provide insights into important areas for clinical service planning and best clinical management of individual patients as well as considerations for future research into QoL in these rare disorders.

Sniffing the diagnosis: Olfactory testing in neurodegenerative parkinsonism

ObjectiveTo determine the diagnostic utility of olfactory testing in patients with neurodegenerative parkinsonism. MethodsThe Sniffin' Sticks test battery for assessment of odor identification, discrimination, and threshold was applied to patients with Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) as well as healthy controls (HC). Two different cohorts were analyzed: A PD/healthy control that included PD patients and HC as well as a PD/diseased control cohort for which patients PD, MSA and PSP were recruited. The former cohort was exploited to calculate cut-off values that discriminate PD patients from HC with a sensitivity (sensitivity-weighted cut-off) or specificity (specificity-weighted cut-off) exceeding 95%, respectively. The PD/diseased controls cohort was used to determine the diagnostic accuracy using these cut-off values in discriminating patients with neurodegenerative parkinsonism. ResultsPD patients (n = 67) performed significantly worse in olfactory testing than HC (n = 41) and patients with MSA (n = 23) or PSP (n = 23). There was no significant difference in olfactory function between MSA and PSP patients. Diagnostic performance of the identification subscore was similar to the sum score of the Sniffin’ Sticks test (AUC identification test 0.94, AUC sum score 0.96), while threshold and discrimination subscores were inferior. In patients with parkinsonism, the specificity-weighted cut-off predicted a diagnosis of PD with a sensitivity and specificity of 76.6 and 87.0%, respectively. The discriminative value of this cut-off in separating PD from MSA was 76.7% (sensitivity) and 95.7% (specificity). The corresponding, prevalence-adjusted positive predictive value of olfactory testing exceeded 95%. ConclusionsOur data suggest that assessment of olfactory function, particularly odor identification, can be useful to discriminate PD from atypical parkinsonian disorders, particularly MSA patients.

Parkinsonism

Parkinsonism is a clinical syndrome, which is characterized by bradykinesia, rigidity, rest tremor, and postural instability. Idiopathic Parkinson disease (PD) is the most common cause of this syndrome, though there are several other important etiologies that must be considered. These include the atypical Parkinsonian disorders multiple system atrophy (MSA), dementia with Lewy Bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS); as well as secondary causes of parkinsonism. These various disease entities may be distinguished based on key clinical features, which is critical for the purposes of diagnosis, treatment, and prognosis.

Depressive Symptoms are Frequent in Atypical Parkinsonian Disorders.

To compare the incidence and prevalence of depressive symptoms in atypical parkinsonian (APD) syndromes versus Parkinson disease (PD). In a large retrospective patient cohort we analyzed the incidence and prevalence of depressive symptoms using the Beck Depression Inventory (BDI) and evaluated subjects longitudinally on subsequent visits. For individuals who followed in subsequent visits we calculated incidence rates in person-years as a measure of incidence. We identified 361 patients with APD including Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB), and 2352 PD controls. The mean BDI values were significantly higher in APD (F=14.19, p < 0.001). A significantly higher proportion of APD subjects screened positive for depressive symptoms both at initial and subsequent patient visits (p < 0.001), which appeared to be more severe in the APD subgroups. UPDRS part III and disease duration weakly correlated with depressive symptoms. Our results suggest that the incidence and prevalence of depressive symptoms are higher in APD and appear also to be more severe than in PD. Depressive symptoms in APD are common and affect patients regardless of disease duration or motor severity.

Comparison of the Performances of (18)F-FP-CIT Brain PET/MR and Simultaneous PET/CT: a Preliminary Study.

(18)F-FP-CIT [(18)F-fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane] has been well established and used for the differential diagnosis of atypical parkinsonian disorders. Recently, combined positron emission tomography (PET)/magnetic resonance (MR) was proposed as a viable alternative to PET/computed tomography (CT). The aim of this study was to compare the performances of conventional (18)F-FP-CIT brain PET/CT and simultaneous PET/MR by visual inspection and quantitative analysis. Fifteen consecutive patients clinically suspected of having Parkinson's disease were recruited for the study.(18)F-FP-CIT PET was performed during PET/CT and PET/MR. PET/CT image acquisition was started 90min after intravenous injection of (18)F-FP-CIT and then PET/MR images were acquired. Dopamine transporter (DAT) density in bilateral striatal subregions was assessed visually. Quantitative analyses were performed on bilateral striatal volumes of interest (VOIs) using average standardized uptake values (SUVmeans). Intraclass correlation coefficients (ICCs) and their 95% confidence intervals (CIs) were assessed to compare PET/CT and PET/MR data. Bland-Altman plots were drawn to perform method-comparisons. All subjects showed a preferential decrease in DAT binding in the posterior putamen (PP), with relative sparing of the ventral putamen (VP). Bilateral striatal subregional binding ratio (BR) determined PET/CT and PET/MR demonstrated close interequipment correspondence (BRright caudate - ICC, 0.944; 95% CI, 0.835-0.981, BRleft caudate - ICC, 0.917; 95% CI, 0.753-0.972, BRright putamen - ICC, 0.976; 95% CI, 0.929-0.992 and BRleft putamen - ICC, 0.970; 95% CI, 0.911-0.990, respectively), and Bland-Altman plots showed interequipment agreement between the two modalities. It is known that MR provides more information about anatomical changes associated with brain diseases and to enable the anatomical allocations of subregions than CT, though this was not observed in the present study. Although the subregional BR of simultaneous PET/MR was comparable to that of PET/CT in Parkinson's disease, our isocontouring method could make bias. A future automated method using standard template study or manual segmentation of putamen/caudate based on MR or CT is needed.

α-Synuclein-induced myelination deficit defines a novel interventional target for multiple system atrophy.

Multiple system atrophy (MSA) is a rare atypical parkinsonian disorder characterized by a rapidly progressing clinical course and at present without any efficient therapy. Neuropathologically, myelin loss and neurodegeneration are associated with α-synuclein accumulation in oligodendrocytes, but underlying pathomechanisms are poorly understood. Here, we analyzed the impact of oligodendrocytic α-synuclein on the formation of myelin sheaths to define a potential interventional target for MSA. Post-mortem analyses of MSA patients and controls were performed to quantify myelin and oligodendrocyte numbers. As pre-clinical models, we used transgenic MSA mice, a myelinating stem cell-derived oligodendrocyte-neuron co-culture, and primary oligodendrocytes to determine functional consequences of oligodendrocytic α-synuclein overexpression on myelination. We detected myelin loss accompanied by preserved or even increased numbers of oligodendrocytes in post-mortem MSA brains or transgenic mouse forebrains, respectively, indicating an oligodendrocytic dysfunction in myelin formation. Corroborating this observation, overexpression of α-synuclein in primary and stem cell-derived oligodendrocytes severely impaired myelin formation, defining a novel α-synuclein-linked pathomechanism in MSA. We used the pro-myelinating activity of the muscarinic acetylcholine receptor antagonist benztropine to analyze the reversibility of the myelination deficit. Transcriptome profiling of primary pre-myelinating oligodendrocytes demonstrated that benztropine readjusts myelination-related processes such as cholesterol and membrane biogenesis, being compromised by oligodendrocytic α-synuclein. Additionally, benztropine restored the α-synuclein-induced myelination deficit of stem cell-derived oligodendrocytes. Strikingly, benztropine also ameliorated the myelin deficit in transgenic MSA mice, resulting in a prevention of neuronal cell loss. In conclusion, this study defines the α-synuclein-induced myelination deficit as a novel and crucial pathomechanism in MSA. Importantly, the reversible nature of this oligodendrocytic dysfunction opens a novel avenue for an intervention in MSA.

Postural & striatal deformities in Parkinson`s disease: Are these rare?

Parkinson's disease (PD) is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, Pisa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS) and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.

Imaging pathological tau in atypical parkinsonian disorders.

This review examines the current literature on tau imaging in atypical parkinsonian disorders and other tauopathies. There are a number of tau PET radiotracers that have demonstrated promising preliminary results in atypical parkinsonian disorders, such as progressive supranuclear palsy and corticobasal degeneration. These radiotracers were capable of selectively labeling tau in vitro and in vivo, with high affinity. Other radiotracers tested more extensively in patients with Alzheimer's disease have also been able to successfully image tau deposition. The development of tau radioligands for PET has led to the current testing of these tracers in clinical studies, many of which concentrate on patients with Alzheimer's disease. Atypical parkinsonian disorders such as progressive supranuclear palsy and corticobasal degeneration are now being investigated as well. These disorders can be very difficult to diagnose, because of their clinical overlap with other parkinsonian disorders. Imaging tau using PET could serve as a diagnostic biomarker for these tauopathies and provide a means of assessing treatment that targets tau burden.

Therapeutic advances in multiple system atrophy and progressive supranuclear palsy.

Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these diseases and in the search for biomarkers have paved the way for the first large and well-designed clinical trials aiming at disease modification. Targets of intervention in these trials have included α-synuclein inclusion pathology in the case of MSA and tau-related mechanisms in PSP. Since 2013, four large randomized, placebo-controlled, double-blind disease-modification trials have been completed and published, using rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), or davunetide (PSP). All of these failed to demonstrate signal efficacy with regard to the primary outcome measures. In addition, two randomized, placebo-controlled, double-blind trials have studied the efficacy of droxidopa in the symptomatic treatment of neurogenic orthostatic hypotension, including patients with MSA, with positive results in one trial. This review summarizes the design and the outcomes of these and other smaller trials published since 2013 and attempts to highlight priority areas of future therapeutic research in MSA and PSP. © 2015 International Parkinson and Movement Disorder Society.

Pain in multiple system atrophy and progressive supranuclear palsy compared to Parkinson's disease.

BackgroundPain is a common nonmotor symptom in Parkinson's disease (PD). The pathophysiology of pain in PD is not well understood. Pain characteristics have rarely been studied in atypical parkinsonian disorders such as Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP).Aim of the studyWe aimed to evaluate pain intensity, location, and associated symptoms in atypical parkinsonian disorders compared to PD.MethodsTwenty-one patients with MSA, 16 patients with PSP, and 65 patients with PD were screened for pain using question 1.9 of the MDS-UPDRS. Pain intensity was quantified using the short form McGill Pain Questionnaire (SFMPQ). Pain locations were documented. Motor disability was measured using UPDRS-III. Affective symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS).ResultsPain was significantly more common and more severe in PD and MSA compared to PSP (P < 0.01). Pain locations were similar with limb pain being the most common followed by neck and back pain. Pain intensity correlated with HADS scores but not motor severity.ConclusionsPain is more common and more intense in PD and MSA than PSP. Differences in distribution of neurodegenerative pathologies may underlie these differential pain profiles.

Use of 11C-PE2I PET in differential diagnosis of parkinsonian disorders.

In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and overall brain functional activity are altered to different degrees, causing difficulties in achieving an unambiguous clinical diagnosis. A dual examination using (123)I-FP-CIT ((123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane, or (123)I-ioflupane) SPECT and(18)F-FDG PET provides complementary information on dopamine transporter (DAT) availability and overall brain functional activity, respectively. Parametric images based on a single, dynamic (11)C-PE2I (N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methyl-phenyl)nortropane) scan potentially supply both DAT availability (nondisplaceable binding potential [BPND]) and relative cerebral blood flow (relative delivery [R1]) at voxel level. This study aimed to evaluate the validity of (11)C-PE2I PET against the dual-modality approach using (123)I-FP-CIT SPECT and (18)F-FDG PET. Sixteen patients with parkinsonian disorders had a dual examination with (18)F-FDG PET and (123)I-FP-CIT SPECT following clinical routines and additionally an experimental (11)C-PE2I PET scan. Parametric BPND and R1 images were generated using receptor parametric mapping with the cerebellum as a reference. T1-weighted MR imaging was used for automated definition of volumes of interest (VOI). The DAT VOIs included the basal ganglia, whereas the overall brain functional activity was examined using VOIs across the brain. BPND and R1 values were compared with normalized (123)I-FP-CIT and (18)F-FDG uptake values, respectively, using Pearson correlations and regression analyses. In addition, 2 masked interpreters evaluated the images visually, in both the routine and the experimental datasets, for comparison of patient diagnoses. Parametric (11)C-PE2I BPND and R1 images showed high consistency with (123)I-FP-CIT SPECT and (18)F-FDG PET images. Correlations between (11)C-PE2I BPND and (123)I-FP-CIT uptake ratios were 0.97 and 0.76 in the putamen and caudate nucleus, respectively. Regional (11)C-PE2I R1 values were moderately to highly correlated with normalized (18)F-FDG values (range, 0.61-0.94). Visual assessment of DAT availability showed a high consistency between (11)C-PE2I BPND and (123)I-FP-CIT images, whereas the consistency was somewhat lower for appraisal of overall brain functional activity using (123)I-FP-CIT and (18)F-FDG images. Substantial differences were found between clinical diagnosis and both neuroimaging diagnoses. A single, dynamic (11)C-PE2I PET investigation is a powerful alternative to a dual examination with (123)I-FP-CIT SPECT and (18)F-FDG PET for differential diagnosis of parkinsonian disorders. A large-scale patient study is, however, needed to further investigate distinct pathologic patterns in overall brain functional activity for various parkinsonian disorders.

Differentiating between visual hallucination-free dementia with Lewy bodies and corticobasal syndrome on the basis of neuropsychology and perfusion single-photon emission computed tomography.

IntroductionDementia with Lewy bodies (DLB) and Corticobasal Syndrome (CBS) are atypical parkinsonian disorders with fronto-subcortical and posterior cognitive dysfunction as common features. While visual hallucinations are a good predictor of Lewy body pathology and are rare in CBS, they are not exhibited in all cases of DLB. Given the clinical overlap between these disorders, neuropsychological and imaging markers may aid in distinguishing these entities.MethodsProspectively recruited case–control cohorts of CBS (n =31) and visual hallucination-free DLB (n =30), completed neuropsychological and neuropsychiatric measures as well as brain perfusion single-photon emission computed tomography and structural magnetic resonance imaging (MRI). Perfusion data were available for forty-two controls. Behavioural, perfusion, and cortical volume and thickness measures were compared between the groups to identify features that serve to differentiate them.ResultsThe Lewy body with no hallucinations group performed more poorly on measures of episodic memory compared to the corticobasal group, including the delayed and cued recall portions of the California Verbal Learning Test (F (1, 42) =23.1, P <0.001 and F (1, 42) =14.0, P =0.001 respectively) and the delayed visual reproduction of the Wechsler Memory Scale-Revised (F (1, 36) =9.7, P =0.004). The Lewy body group also demonstrated reduced perfusion in the left occipital pole compared to the corticobasal group (F (1,57) =7.4, P =0.009). At autopsy, the Lewy body cases all demonstrated mixed dementia with Lewy bodies, Alzheimer’s disease and small vessel arteriosclerosis, while the corticobasal cases demonstrated classical corticobasal degeneration in five, dementia with agyrophilic grains + corticobasal degeneration + cerebral amyloid angiopathy in one, Progressive Supranuclear Palsy in two, and Frontotemporal Lobar Degeneration-Ubiquitin/TAR DNA-binding protein 43 proteinopathy in one. MRI measures were not significantly different between the patient groups.ConclusionsReduced perfusion in the left occipital region and worse episodic memory performance may help to distinguish between DLB cases who have never manifested with visual hallucinations and CBS at earlier stages of the disease. Development of reliable neuropsychological and imaging markers that improve diagnostic accuracy will become increasingly important as disease modifying therapies become available.

Clinical movement disorders - a new era.

We are proud to announce the launch of a new open access journal, entitled Journal of Clinical Movement Disorders (JCMD). The aim of the journal is to offer an open access forum for the publication of scientifically rigorous articles focusing on the natural history, etiology, evaluation and treatment of patients with a wide range of movement disorders [1]. We are interested in topics important to the practicing clinician, but especially in articles that explore the ways in which translational approaches are changing the evaluation and treatment of patients with movement disorders in the 21st century. We are particularly pleased to launch JCMD as a fully open access journal. At present, only one journal devoted to movement disorders (Tremor and Other Hyperkinetic Disorders) offers an open access format. We believe that the open access format offers numerous advantages to traditional publication strategies. Articles will be published as soon as they are accepted, markedly decreasing the time for evaluation and distribution. All articles are available online at no cost throughout the world, enabling the widest possible reach for the journal irrespective of a reader’s location or economic resources [2]. Authors will continue to hold copyright for their work, and articles will be archived in PubMed Central. The online format allows articles to be published without constraints on length of text. Further, the format is a perfect vehicle for publication of videos demonstrating salient features in articles, a critical feature of clinical movement disorders. JCMD will publish articles covering the full spectrum of movement disorders including hypokinetic disorders (Parkinson’s disease, atypical parkinsonian disorders such as multiple system atrophy, progressive supranuclear palsy, corticobasal syndrome, dementia with Lewy body disease, frontotemporal dementia, etc.), and usual and unusual hyperkinetic disorders (myoclonus, chorea, tics, tremor, dystonia, stereotypies, paroxysmal movement disorders, etc.). We are interested in both descriptive articles that illustrate phenotype, as well as hypothesis driven articles that explore the etiology, genetics, pharmacology, neuroimaging and treatment options for these patients. Submissions on both adult and pediatric disorders are welcome, and we are particularly interested in novel treatments such as deep brain stimulation. Special features that we plan to integrate into the journal include a clinical phenomenology section, a section devoted to current controversies, and reviews that summarize important findings in the field. All manuscripts submitted to JCMD will be independently reviewed by two experts in the field, by a member of the Editorial Board and by the Editor-in-Chief. We are interested in publishing articles of the highest quality and novelty, but will also consider research that may be of more general interest to readers due to novel clinical or examination features, clinical relevance or unusual phenotype, even if the findings are confirmatory. We believe that clinical movement disorders is unique as a subspecialty area in neurology, in that many are drawn to the field by the complexity and subtlety of the clinical examination, and the way in which 21st century technologies can help illuminate these findings. The Editorial Board of JCMD includes 43 members from 11 different countries [3]. We believe that the broad expertise and international reputations of the Editorial Board attests to their confidence that JCMD will succeed. We hope that you enjoy JCMD, and that you will consider it when deciding where to publish your work. Welcome!

The circulating level of leptin and blood pressure in patients with multiple system atrophy

Patients with multiple system atrophy (MSA) frequently exhibit orthostatic hypotension (OH). Leptin, an adipose-derived hormone, contributes to the sympathetic control of blood pressure (BP), and loss of leptin may cause OH. We aimed to clarify the relationship between leptin and OH in MSA. Serum leptin levels were measured in 36 patients with MSA, 25 patients with other atypical parkinsonian disorders (APDs), including progressive supranuclear palsy-Richardson syndrome and corticobasal syndrome, and 26 control subjects. Blood samples were obtained after fasting for 12h. In MSA patients, baseline BP was measured in the recumbent position after a 3-min rest, and orthostatic changes in BP were evaluated after 0–3min of standing. Serum leptin levels did not differ significantly between MSA patients (5.9±0.8ng/ml), other APD patients (5.2±0.8ng/ml), and controls (6.1±1.3ng/ml; P=0.8). In MSA patients, serum leptin levels correlated significantly with body mass index (P=0.01), but not baseline BPs (systolic BP, P=0.20; diastolic BP, P=0.44) or orthostatic drop in BP (systolic BP, P=0.13; diastolic BP, P=0.58). Our observations indicated that the circulating level of leptin was preserved, and OH occurred independent of the leptin level in MSA patients.