Type Of Multiple System Atrophy Research Articles

Wait and see... is it multiple system atrophy type C? A case report

Wait and see... is it multiple system atrophy type C? A case report

Cerebellar blood perfusion is a diagnostic, but not a prognostic, marker for parkinsonian-dominant type multiple system atrophy

IntroductionMultiple system atrophy (MSA) is clinically characterized by various neurological symptoms. According to the diagnostic criteria, MSA is classified into parkinsonian-dominant type (MSA-P) or cerebellar ataxia-dominant type (MSA-C) based on the predominant signs displayed. Recently, N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) single-photon emission computed tomography (SPECT), a radiological examination evaluating brain perfusion, has been successful in detecting cerebellar hypoperfusion in MSA-P patients, demonstrating its utility in the early detection of cerebellar dysfunction. In this study, we further explored whether this cerebellar hypoperfusion impacts the clinical features of MSA-P, whether it is observable in patients without cerebellar symptoms, and, most importantly, whether it influences the prognosis of MSA-P. MethodsWe conducted a retrospective analysis of 88 MSA patients who were admitted to our department for the last fifteen years. Clinical data were collected, and cerebellar perfusion was examined using 123I-IMP SPECT. This analysis includes the application of the three-dimensional stereotactic surface projection (3D-SSP) technique and Z-score. ResultsCerebellar perfusion decreased in MSA-P patients without cerebellar ataxia, compared to healthy individuals (p = 0.0017). The Receiver Operating Characteristic (ROC) curve demonstrated a moderate ability to distinguish MSA-P patients without cerebellar ataxia (MSA-Pp) from healthy controls (AUC = 0.6832). Among MSA-Pp, those exhibiting cerebellar hypoperfusion showed relatively improved neurological prognosis, although the difference was not statistically significant when compared to those with normal cerebellar perfusion. ConclusionAssessing cerebellar perfusion through IMP-SPECT proves valuable in detecting subclinical cerebellar dysfunction in MSA-Pp. Importantly, cerebellar hypoperfusion does not correlate with a poorer neurological prognosis.

Three Hertz postural leg tremor impairs posture maintenance in multiple system atrophy-cerebellar type.

Three-Hz postural leg tremor has recently been identified as highly prevalent in patients with the cerebellar type of multiple system atrophy, but its impact on posture maintenance remains poorly understood. Thirty-seven patients with spinocerebellar ataxia and 58 others with cerebellar type of multiple system atrophy were given Synapsys posturography examinations. Fifty-three healthy controls were also tested. Low, medium, and high-frequency sway were recorded to compute energy values. Frequency shift and postural strategy predominance were evaluated from the postural sway distributions, mainly from the proportions of higher frequency values among the total values. The trajectories of postural sway components were evaluated with the generalized additive mixed model. Distributions of the components and their relationships with falls and tremors were assessed through repeated measures correlation analysis. As the test difficulty increased, the standard controls showed slight increases in the energy values at every frequency. Distributions of the higher frequency (>0.5 Hz) values increased escalatingly with test difficulty, illustrating frequency shifts and hip strategy predominance. Medium and high-frequency values were strongly and positively inter-correlated in normal stances, but this was not observed among the spinocerebellar ataxia or multiple system atrophy patients. Unlike normal stances, the proportion of medium frequency values was negatively related to the total value among the spinocerebellar ataxia and multiple system atrophy patients, implying a failure of frequency shift in response to perturbation. Medium frequency proportions were also inversely correlated with tremors among the multiple system atrophy patients. The observed synchronized changes in medium and high-frequency postural sway indicate that they constitute a complete hip strategy for posture control. The strategy was rigid in those with spinocerebellar ataxia but completely disrupted in those with multiple system atrophy. Three Hertz postural leg tremors destabilize the ankle joints and interfere with postural adjustment among those with multiple system atrophy.

Syndrome of Orthostatic Hypotension with Supine Hypertension: A Therapeutic Dilemma for Cardiologists

Orthostatic hypotension (OH) and supine hypertension (SH) are two cardiovascular symptoms of autonomic failure that frequently coexist in the same patient.
 Clinicians are faced with a dilemma because aggressive orthostatic intolerance treatment can exacerbate supine hypertension, and vice versa for supine hypertension management.
 The objective of our article is to provide a better framework for the clinical evaluation, the right choice of therapeutic options and the improvement of the quality of life of patients with OH-SH syndrome. For these reasons, we report three observations, whose etiologies, clinical presentation, and treatment are different, namely diabetes, multiple system atrophy type C (MSA) and Parkinson's disease.

Improved interpretation of 18F-florzolotau PET in progressive supranuclear palsy using a normalization-free deep-learning classifier

While 18F-florzolotau tau PET is an emerging biomarker for progressive supranuclear palsy (PSP), its interpretation has been hindered by a lack of consensus on visual reading and potential biases in conventional semi-quantitative analysis. As clinical manifestations and regions of elevated 18F-florzolotau binding are highly overlapping in PSP and the Parkinsonian type of multiple system atrophy (MSA-P), developing a reliable discriminative classifier for 18F-florzolotau PET is urgently needed. Herein, we developed a normalization-free deep-learning (NFDL) model for 18F-florzolotau PET, which achieved significantly higher accuracy for both PSP and MSA-P compared to semi-quantitative classifiers. Regions driving the NFDL classifier's decision were consistent with disease-specific topographies. NFDL-guided radiomic features correlated with clinical severity of PSP. This suggests that the NFDL model has the potential for early and accurate differentiation of atypical parkinsonism and that it can be applied in various scenarios due to not requiring subjective interpretation, MR-dependent, and reference-based preprocessing.

Systematic assessment of plasma biomarkers in spinocerebellar ataxia

Background and objectivesPlasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), phosphorylated-tau (p-tau), and β-amyloid (Aβ) have emerged as promising markers in several neurodegenerative disorders, but whether they can be used as biomarkers in spinocerebellar ataxias (SCA) is yet to be determined. This study aimed to identify sensitive plasma markers for SCA and investigate their effectiveness in tracking ataxia severity, cognition, non-motor symptoms, and brain atrophy. MethodsThis observational study recruited consecutive participants from Huashan Hospital and the CABLE study from November 2019. Patients with SCA were genetically diagnosed, grouped according to the ataxia severity, and compared with healthy older individuals and patients with multiple system atrophy type C (MSA-C). Plasma NfL, GFAP, p-tau, and Aβ levels were measured by Simoa in all participants. Analysis of covariance, Spearman correlation, and multivariable regression were used to explore candidate markers in SCA. ResultsA total of 190 participants (60 SCA, 56 MSA-C, and 74 healthy controls) were enrolled. Plasma NfL level increased early in the pre-ataxic stage of SCA (32.23 ± 3.07 vs. 11.41 ± 6.62 pg/mL in controls), was positively associated with the ataxia severity (r = 0.45, P = 0.005) and CAG repeat length (r = 0.51, P = 0.001), varied among the different SCA subtypes (39.57 ± 13.50 pg/mL in SCA3, which was higher than 28.17 ± 8.02 pg/mL in SCA2, 17.08 ± 6.78 pg/mL in SCA8, and 24.44 ± 18.97 pg/mL in rare SCAs; P < 0.05), and was associated with brainstem atrophy. NfL alone (area under the curve [AUC] 0.867) or combined with p-tau181 and Aβ (AUC 0.929), showed excellent performance in discriminating SCA patients from controls. Plasma GFAP distinguished SCA from MSA-C with moderate accuracy (AUC > 0.700) and correlated with cognitive performance and cortical atrophy. Changes in levels of p-tau181 and Aβ were observed in SCA patients compared to controls. They were both correlated with cognition, while Aβ was also associated with non-motor symptoms, such as anxiety and depression. DiscussionPlasma NfL may serve as a sensitive biomarker for SCA, and its level is elevated in the pre-ataxic stage. The different performance of NfL and GFAP indicates differences in the underlying neuropathology of SCA and MSA-C. Moreover, amyloid markers may be useful for detecting memory dysfunction and other non-motor symptoms in SCA.

Phosphorylated α-synuclein in skin Schwann cells: a new biomarker for multiple system atrophy.

Multiple system atrophy (MSA) is characterized by accumulation of phosphorylated α-synuclein (p-syn) as glial cytoplasmic inclusions in the brain and a specific biomarker for this disorder is urgently needed. We aimed at investigating if p-syn can also be detected in skin Remak non-myelinating Schwann cells (RSCs) as Schwann cell cytoplasmic inclusions (SCCi) and may represent a reliable clinical biomarker for MSA. This cross-sectional diagnostic study evaluated skin p-syn in 96 patients: 46 with probable MSA (29 with parkinsonism type MSA and 17 with cerebellar type MSA), 34 with Parkinson's disease (PD) and 16 with dementia with Lewy bodies (DLB). We also included 50 healthy control subjects. Patients were recruited from five different medical centres. P-syn aggregates in skin sections were stained by immunofluorescence, followed by analyses with confocal microscopy and immuno-electron microscopy. All analyses were performed in a blinded fashion. Overall, p-syn aggregates were found in 78% of MSA patients and 100% of patients with PD/DLB, whereas they could not be detected in controls. As for neuronal aggregates 78% of MSA patients were positive for p-syn in somatic neurons, whereas all PD/DLB patients were positive in autonomic neurons. When analysing the presence of p-syn in RSCs, 74% of MSA patients were positive, whereas no such SCCi could be observed in PD/DLB patients. Analyses by immuno-electron microscopy confirmed that SCCi were only found in cases with MSA and thus absent in those with PD/DLB. In conclusion, our findings demonstrate that (i) fibrillar p-syn in RSCs is a pathological hallmark of MSA and may be used as a specific and sensitive disease biomarker; (ii) in Lewy body synucleinopathies (PD/DLB) only neurons contain p-syn deposits; and (iii) the cell-specific deposition of p-syn in the skin thus mirrors that of the brain in many aspects and suggests that non-myelinated glial cells are also involved in the MSA pathogenesis.

Morphological differences between the two major subtypes of multiple system atrophy with cognitive impairment

ObjectiveTo compare the neuropathology between two types of multiple system atrophy - parkinsonism-predominant (MSA-P) and cerebellar ataxia-predominant (MSA-C) with cognitive impairment. Material & methods35 cases of MSA-P (mean age at death 60.5 ± 7.8 years) and 15 cases of MSA-C (mean age at death 61.3 ± 6.8 years), 35.% of which associated with mild to moderate cognitive impairment and one with severe dementia, were examined neuropathologically with semiquantitative evaluation of both α-synuclein and Alzheimer pathologies, including cerebral amyloid angiopathy (CAA) and other co-pathologies. ResultsWhile the mean age at death of both MSA subgroups was similar, the age at onset and duration of disease were slightly higher in the MSA-C group. In line with the classification, the αSyn pathology glial and neuronal inclusions in both the cortex and brainstem were significantly higher in the MSA-P group. With regard to the Alzheimer disease pathology, tau load in cases with mild to moderate cognitive impairment was slightly but not significantly higher in the MSA-P group, one with severe dementia showing fully developed Alzheimer co-pathology, while the amyloid-β (Aβ) load including the CAA was higher in the MSA-C group. The presence of Lewy co-pathology in this series (20%), being similar to that of other MSA cohorts, was more frequent in MSA cases with mild to severe cognitive impairment, but did not differ between the two subgroups and seems not essentially important for MCI in MSA. ConclusionsIn agreement with previous clinical studies that reported more severe cognitive dysfunction in patients with MSA-P, the present neuropathological study showed increased tau pathology in MSA-P and one with severe Alzheimer co-pathology, but only slightly increased amyloid pathology in the MSA-C group. Lewy co-pathology was more frequent in MSA-P cases with cognitive decline. In view of the limited data about the pathobiological basis of cognitive impairment in MSA, further studies to elucidate the differences between the two phenotypes are urgently needed.

The "Hot Cross Bun Sign" in Spinocerebellar Ataxia Types 2 and 7-Case Reports and Review of Literature.

The "hot cross bun" sign is a cruciform hyperintensity is seen on T2 weighted imaging within the pons. The sign is considered to be pathognomic for Multiple system atrophy type C. The clinical and radiological features of Multiple system atrophy type C overlap with the autosomal dominant inherited ataxias. We present a case series of 3 African patients with genetically proven Spinocerebellar Ataxia presenting with the Hot cross bun sign and a scoping review of similar studies. We described the phenotypic and radiological presentation of genetically confirmed SCA-2 in two, and SCA-7 in one patient, with the "hot cross bun" sign. We performed a scoping review on the Hot Cross Bun Sign.A total of 66 articles were retrieved. We describe the diverse aetiologies of the sign and associated phenotypic and radiological features. We review the Spinocerebellar Ataxias described with a Hot cross bun sign and make comparisons to Multiple System Atrophy Type C [Ref. 1,2]. To our knowledge this is the first description of an African cohort presenting with the Hot Cross Bun Sign. We expand the differential diagnosis of the Hot Cross Bun Sign.

Combined functional and structural imaging of brain white matter reveals stage-dependent impairment in multiple system atrophy of cerebellar type

Advances in fMRI of brain white matter (WM) have established the feasibility of understanding how functional signals of WM evolve with brain diseases. By combining functional signals with structural features of WM, the current study characterizes functional and structural impairments of WM in cerebelar type multiple system atrophy, with the goal to derive new mechanistic insights into the pathological progression of this disease. Our analysis of 30 well-diagnosed patients revealed pronounced decreases in functional connectivity in WM bundles of the cerebellum and brainstem, and concomitant local structural alterations that depended on the disease stage. The novel findings implicate a critical time point in the pathological evolution of the disease, which could guide optimal therapeutic interventions. Furthermore, fMRI signals of impaired WM bundles exhibited superior sensitivity in differentiating initial disease development, which demonstrates great potential of using these signals to inform disease management.

Cognitive and Autonomic Dysfunction in Multiple System Atrophy Type P and C: A Comparative Study.

Multiple System Atrophy (MSA) is a rare neurodegenerative disease, clinically defined by a combination of autonomic dysfunction and motor involvement, that may be predominantly extrapyramidal (MSA-P) or cerebellar (MSA-C). Although dementia is generally considered a red flag against the clinical diagnosis of MSA, in the last decade the evidence of cognitive impairment in MSA patients has been growing. Cognitive dysfunction appears to involve mainly, but not exclusively, executive functions, and may have different characteristics and progression in the two subtypes of the disease (i.e., MSA-P and MSA-C). Despite continued efforts, combining in-vivo imaging studies as well as pathological studies, the physiopathological bases of cognitive involvement in MSA are still unclear. In this view, the possible link between cardiovascular autonomic impairment and decreased cognitive performance, extensively investigated in PD, needs to be clarified as well. In the present study, we evaluated a cohort of 20 MSA patients (9 MSA-P, 11 MSA-C) by means of a neuropsychological battery, hemodynamic assessment (heart rate and arterial blood pressure) during rest and active standing and bedside autonomic function tests assessed by heart rate variability (HRV) parameters and sympathetic skin response (SSR) in the same experimental session. Overall, global cognitive functioning, as indicated by the MoCA score, was preserved in most patients. However, short- and long-term memory and attentional and frontal-executive functions were moderately impaired. When comparing MSA-P and MSA-C, the latter obtained lower scores in tests of executive functions and verbal memory. Conversely, no statistically significant difference in cardiovascular autonomic parameters was identified between MSA-P and MSA-C patients. In conclusion, moderate cognitive deficits, involving executive functions and memory, are present in MSA, particularly in MSA-C patients. In addition, our findings do not support the role of dysautonomia as a major driver of cognitive differences between MSA-P and MSA-C.

Positive DAT-SCAN in SPG7: a case report mimicking possible MSA-C

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

Quantitative Evaluation of Cerebellar Function in Multiple System Atrophy with Transcranial Magnetic Stimulation.

Objective evaluation of cerebellar dysfunction in neurodegenerative disorders is often difficult because of other overlapping symptoms. Cerebellar inhibition (CBI) tested by dual-coil transcranial magnetic stimulation (TMS) is anticipated as a promising measure to estimate cerebellar function. Cerebellar TMS inhibits the primary motor cortex (M1), which can be measured as the decrease of motor evoked potential (MEP) elicited by a single-pulse TMS over the M1. This study was conducted to quantify cerebellar dysfunction using CBI in cerebellar type multiple system atrophy (MSA-C) patients. First, CBI was measured using MEP elicited from a hand muscle by stimulating the hand motor area of M1. The amount of CBI was defined as the degree of decrease in the MEP amplitude in the presence of cerebellar stimulation compared with the condition of M1 stimulation alone. Results of the MSA-C patients were compared with those of healthy volunteers. Correlation between amounts of CBI and a clinical scale of ataxia, the International Cooperative Ataxia Scale Rating (ICARS), was assessed. Healthy volunteers showed more inhibition than MSA-C patients. Moreover, ICARS showed that the CBI amount in the patients is correlated with the degree of ataxia significantly. Results suggest that CBI can be a good marker of disease progression in MSA-C patients.

3-Hz Postural Tremor in MSA-C and SCA: Revisiting an Old but Underestimated Cerebellar Sign by Posturography.

The aim of this study is to evaluate the prevalence and electrophysiological features of 3-Hz postural tremor in multiple system atrophy-cerebellar type and spinocerebellar ataxia. A static posturography examination was administered to 37 persons with spinocerebellar ataxia, 58 others with the cerebellar type of multiple system atrophy, and 53 healthy controls. During the sensory organization tests of 5 multiple system atrophy patients, surface electromyograms were recorded from bilateral tibialis anterior and medial gastrocnemius muscles. The patients with multiple system atrophy had, on average, significantly higher scores on the International Cooperative Ataxia Rating Scale and significantly greater prevalence of cross sign. Almost 80% of them fell during the posturography testing compared with two-thirds of the spinocerebellar ataxia patients. Twenty-seven percent of the spinocerebellar ataxia patients and 82.8% of those with multiple system atrophy displayed postural tremor with a frequency of approximately 3Hz. The tremor's frequency tended to be lower in the spinocerebellar ataxia patients. The surface electromyography revealed highly coherent tremor activity at about 3Hz in the patients' bilateral tibialis anterior and alternating firing in the bilateral antagonist muscles. Combining cross sign with a subject's static score of the International Cooperative Ataxia Rating Scale and occurrence of the tremor produced an indicator able to differentiate the two conditions with a sensitivity of 87.9% and a specificity of 89.2%. The area under the receiver operating characteristics curve for the indicator was 0.942. Three-hertz postural tremor is relatively characteristic of cerebellar type of multiple system atrophy and appears at an early stage of the disease. Identification of the tremor by posturography will facilitate its diagnosis.

Lower Urinary tract symptoms in spinocerebellar ataxias

Background: Because urinary dysfunctions are not considered as symptoms of spinocerebellar ataxias (SCAs), there are only a few studies on urinary dysfunctions in SCAs. However, given that a patient with SCAs without a family history might be misdiagnosed as cerebellar type multiple system atrophy (MSA-C) when having urinary dysfunctions, characterization of urinary dysfunctions in SCAs is needed not only to understand SCAs but also to correctly diagnosis patients with ataxia.

Brain MRI of multiple system atrophy of cerebellar type: a prospective study with implications for diagnosis criteria.

The second consensus statement for the diagnosis of multiple system atrophy type cerebellar (MSA-C) includes pons and middle cerebellar peduncle (MCP) atrophy as MRI features. However, other MRI abnormalities such as MCP hyperintensity, hot cross bun sign (HCB), putaminal hypointensity and hyperintense putaminal rim have been described. To evaluate, in patients with sporadic late-onset cerebellar ataxia (SLOCA), the discriminative value of several MRI features for the diagnosis of MSA-C, to follow their evolution during the course of MSA-C, and to search for correlations between these MRI features and clinical signs. Consecutive patients referred for SLOCA underwent comprehensive clinical evaluation and laboratory investigations, brain MRI, DaTscan and a 1-year follow-up. Among 80 patients, 26 had MSA-C, 22 another diagnosis, and 32 no diagnosis at the end of the follow-up. At baseline, MCP hyperintensity and HCB were more frequent in patients finally diagnosed with MSA-C than in other patients with SLOCA (p < 0.0001), and had the highest specificity (98.5%) and positive predictive value (91.7%) for the diagnosis of MSA-C, compared to all other MRI signs. The most relevant MRI sequence regarding HCB sign was the T2-proton density (DP) weighted. All MRI features were more frequent with disease duration. No correlation was found between any MRI feature and neither clinical data, nor dopaminergic neuronal loss (p = 0.5008), except between vermis atrophy and UPDRSIII score. MCP hyperintensity and HCB sign should be added into the list of additional features of possible MSA-C. MRI signal abnormalities suggestive of MSA-C should be searched for in suitable sequence.

Prevalence and clinicoradiological features of spinocerebellar ataxia type 34 in a Japanese ataxia cohort

IntroductionSpinocerebellar ataxia (SCA) type 34, a form of autosomal dominantly inherited ataxia, has recently been associated with mutations in the ELOVL4 gene. However, a genetic study of the prevalence of SCA34 in an ataxia cohort has never been reported. MethodsWe performed a mutation screening of ELOVL4 in a cohort of 153 undiagnosed index ataxia patients, selected after excluding for common SCA types, in a series of 506 Japanese index ataxia patients. ResultsHeterozygous mutation c.698C > T (p.T233M) was detected in an index patient with multisystem neurodegeneration including ataxia and erythrokeratodermia skin lesions, an archetypal skin phenotype in SCA34. The patient's father also presented with ataxia but not skin lesions. Although this mutation has been recently reported in a single English–Canadian patient, the present study confirms its cosegregation with the ataxia phenotype in the Japanese kindred. Brain magnetic resonance imaging (MRI) of the patient and his father revealed marked pontine and cerebellar atrophy as well as the hot cross bun sign, that is common in cerebellar type of multiple system atrophy and was also described in SCA34 patients harboring two other mutations: p.L168F and p.W246G. ConclusionThis represents the first genetic study of the prevalence of SCA34 in an ataxia cohort and demonstrates its low prevalence (0.2%) in ataxia patients. The broad SCA34 clinical spectrum suggests variable multisystem neurodegeneration. Clinicians should be aware of this rare disease entity, particularly if erythrokeratodermia or the hot cross bun sign in MRI are present in undiagnosed degenerative ataxia patients.

Eye movement deficits in X-linked dystonia-parkinsonism are related to striatal degeneration

BackgroundX-linked dystonia-parkinsonism (XDP) is characterized by the unique transition of dystonia to parkinsonism and striatal degeneration. Slowing of saccades on clinical examination has been taken as suggestive of a progressive supranuclear palsy (PSP) phenotype. ObjectivesTo elucidate whether eye movement abnormalities in XDP patients reflect striatonigral impairment or deficits in the brainstem saccade generator as present in PSP. MethodsEye movements of 18 male XDP patients from the Philippines and 16 ethnically and age-matched, healthy control participants were analyzed and the results related to morphometric frontostriatal changes. ResultsThere was moderate saccade hypometria in XDP but velocity of visually guided saccades was normal. XDP patients showed an increased antisaccade error rate which correlated with the reduction of (i) the volume of the pallidum and putamen as well as (ii) the volume and cortical thickness in dorsolateral prefrontal cortex. Amplitude of memory-guided saccades was smaller and latency prolonged. Horizontal smooth pursuit eye movements were impaired. ConclusionsOculomotor abnormalities in XDP resemble those of patients with the Parkinsonian type of multiple system atrophy and - to a lesser degree - Parkinson's disease, but are not compatible with PSP. They indicate striatal impairment and may represent preclinical signs of the parkinsonian stage of XDP. The increasing failure of response inhibition in the antisaccade task with increasing striatal atrophy may indicate an endophenotype for striatal degeneration. Dorsolateral prefrontal degeneration can be inferred from the failure in initiating antisaccades, prolonged latency of memory-guided saccades and the reduction of dorsolateral prefrontal volume and cortical thickness.

Modulation of Cerebellar-Cortical Connections in Multiple System Atrophy Type C by Cerebellar Repetitive Transcranial Magnetic Stimulation

This study aims at modulating the altered cerebellar-cortical interactions in patients with multiple system atrophy-cerebellar subtype (MSA-C) by using cerebellar repetitive transcranial magnetic stimulation (rTMS). We hypothesized that cerebellar modulation by low-frequency rTMS can resolve the abnormal cortical excitability in multiple system atrophy cerebellar subtype. We studied detailed effects of rTMS of the cerebellum on reaction time (RT) and short-latency afferent inhibition (SAI) response in MSA-C group, Alzheimer Disease (AD) group, and a control group of healthy individuals. The RT and SAI responses were measured before and after 1 Hz cerebellar rTMS in all groups. The study was conducted in the neurophysiology laboratory in Hacettepe University Hospital. Our results indicated that motor cortex disinhibition was predominant in patients with AD and MSA-C. In AD and control groups, there were no changes in SAI after rTMS. However, after application of rTMS over the cerebellum in MSA-C patients, the pathological disinhibition and RT results showed an improvement compared to their previous results. Our study highlights that cerebellar rTMS impairs abnormal cerebellar-cortical inhibitory connections in case of MSA-C.

Neuropsychological and clinical heterogeneity of cognitive impairment in patients with multiple system atrophy

ObjectiveWe evaluated neuropsychological tests to compare cognitive impairment between two types of multiple system atrophy: predominant parkinsonism (MSA-P) and predominant cerebellar ataxia (MSA-C). Patients and methodsThis cross-sectional study included 14 patients diagnosed with MSA: four with MSA-C and ten with MSA-P. Presence of motor symptoms was determined by using the Unified Rating MSA Scale (URMSAS). Non-motor symptoms were evaluated by the Short Form Health Survey (SF-36), Scales for Outcomes in Parkinson’s disease Autonomic (SCOPA-AUT), Hospital Anxiety and Depression Scale (HADS), and Beck Depression Inventory (BDI). Neuropsychological tests were used to evaluate general cognition, verbal and visual memory, working memory, constructional ability, visuospatial, language, and executive function. ResultsThe median age of the patients was 62 years, median disease duration was 3.5 years, and median education level was 10 years. The median Mini-Mental State Examination (MMSE) score was 26.5 points, and median Mattis Dementia Rating Scale (MDRS) score was 131.5. We compared the continuous data between the two MSA subtypes and observed that bodily pain reported in the quality of life questionnaire, SF-36, was worse in MSA-P (p<0.05), and attention function evaluated by MDRS was significantly lower in MSA-C than MSA-P (p<0.05). ConclusionOur comparative study of cognitive impairment in MSA-P and MSA-C showed that both groups had impaired executive and visuospatial functions, while the attention deficit was predominant only in MSA-C. These findings support the concept that cognitive deficit originates from striatofrontal dysfunction and cerebellar degeneration. Our study also suggests that cognitive impairment is relevant in MSA, and clinical neurologists should not neglect evaluation of these aspects in their daily clinical practice.