Dysregulated Cerebrospinal Fluid Proteome of Spinocerebellar Ataxia Type 2 and its Clinical Implications.

BACKGROUND: Abnormalities in ataxin-2 associated with spinocerebellar ataxia type 2 (SCA2) may lead to widespread disruptions in the proteome. This study was performed to identify dysregulated proteome in SCA2 and to explore its clinical-radiological correlations. METHODS: Cerebrospinal fluid (CSF) samples from 21 genetically confirmed SCA2 were subjected to shotgun proteome analysis using mass spectrometry (MS) and tandem mass tag (TMT)-based multiplexing. Proteins with at least 1.5-fold change in abundance were identified. Their relative abundance was measured using parallel reaction monitoring (PRM) and correlated against disease-related factors. RESULTS: Eleven proteins were significantly upregulated in SCA2. They belonged to the family of cell adhesion molecules and granins. Their fold changes showed significant clinical, genetic, and radiological correlations. CONCLUSIONS: Significant dysregulation of CSF proteome is seen in SCA2. The dysregulated protein may have potential use in clinical evaluation of patients with SCA2. © 2024 International Parkinson and Movement Disorder Society.

Abnormal cortical excitability in patients with spinocerebellar ataxia type 12.

BACKGROUND: Spinocerebellar ataxia type 12 (SCA-12) is an uncommon autosomal dominant cerebellar ataxia characterized by action tremors in the upper limbs, dysarthria, head tremor, and gait ataxia. We aimed to evaluate the motor cortical excitability in patients with SCA-12 using transcranial magnetic stimulation (TMS). METHODS: The study was done in the department of Neurology at the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore. Nine patients with SCA-12 (2 females) and 10 healthy controls (2 females) were included in the study. TMS was performed in all the subjects and various parameters such as resting motor threshold (RMT), central motor conduction time (CMCT) and contralateral silent period (cSP) were recorded. The left motor cortex was stimulated and the recording was done from right first dorsal interossei muscle. The severity of ataxia was assessed using the scale for assessment and rating in ataxia (SARA). RESULTS: The mean age of the patients was 58.11 ± 7.56 years mean age at onset: 51.67 ± 4.18 years. The mean duration of illness was 9.44 ± 4.88 years. The mean SARA score was 13.83 ± 3.60. Patients with SCA-12 had significantly increased RMT (88.80 ± 12.78 %) compared to HC (44.90 ± 9.40 %, p < 0.05). A significantly prolonged CMCT was observed in patients (13.70 ± 2.52 msec) compared to HC (7.31 ± 1.21 msec, p < 0.05). In addition, cSP was significantly increased in SCA-12 patients (144.43 ± 25.79 msec) compared to HC (82.14 ± 28.90 msec, p < 0.05). CONCLUSIONS: Patients with SCA-12 demonstrate a reduced cortical excitability and increased cortical inhibition suggesting an increase in the GABAergic neurotransmission.

Clinical Spectrum, Radiological Correlation and Outcome of Movement Disorders in Wilson's Disease.

Introduction: Movement disorders are the commonest clinical presentation in patients with neurological Wilson's disease (NWD). There are very few studies evaluating the spectrum, severity and their correlation with magnetic resonance imaging (MRI) changes of movement disorders in NWD. Objective: To study the spectrum, topographic distribution, radiological correlate, temporal course and outcome in our cohort of NWD patients. Methods: Retrospective chart review of the NWD patients having movement disorders was performed and analyzed. Results: Sixty-nine patients (males- 47) with NWD were analysed and the mean age at the onset of neurological symptoms was 13.6 ± 6.6 years (median 13 years; range 7-37 years). The first neurological symptom was movement disorder in 55 (79.7%) patients. Tremor (43.6%) and dystonia (41.8%) was the commonest movement disorder as the first neurological symptom. Dystonia (76.8%) was the most common overall movement disorder followed by parkinsonism (52.1%) and tremors (47.8%). Chorea (10.1%), myoclonus (1.4%) and ataxia (1.4%) were the least common movement disorder. Putamen was the most common affected site (95.6%) followed by caudate nucleus (73.9%), thalamus (60.8%), midbrain (59.4%), internal capsule (49.2%), pons (46.3%). Putamen was the most common area of abnormality in dystonia (98%), tremors (85%). Caudate (75%) and putamen (75%) was the most common areas of abnormality in parkinsonism. Favourable outcome was observed in 42 patients (60.8%) following treatment. Conclusion: Dystonia is the most common movement disorder in NWD in isolation or in combination with parkinsonism and tremors. Putamen is the most common radiological site of lesions and more frequently affected in patients with dystonia and tremors. Favourable outcome does occur with appropriate medical and surgical treatment.

Retinal Degeneration in Patients with Wilson's Disease: An OCT Study in Asian Indian Population.

Background: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. We aimed to study the abnormalities in the retinal layers in patients with WD using optical coherence tomography (OCT). Methods: The study is a chart review of 16 patients with WD (six females) who underwent OCT at our hospital during follow-up visits. Spectral-domain OCT was performed in all subjects to assess the thickness of macula and retinal nerve fiber layer (RNFL) and the data was compared with 14 healthy controls (three females). Results: The mean age of the patients was 20.81 ± 7.47 years and controls was 26.86 ± 9.95 years. The mean age at the onset of the illness was 16.25 ± 5.57 years (range 11-28 years) with the mean duration of illness being 4.81 ± 3.31 years at the final follow-up examination. The mean macular thickness was found to be significantly reduced in patients (232.13 ± 19.39) when compared to controls (271.30 ± 17.32 µm; P = 0.01). There was a significant difference in the ganglion cell and inner plexiform (GCIP) layer between the patients (86.83 ± 8.20 µm) and controls (97.72 ± 5.31 µm; P = 0.01). In addition, the outer nuclear layer with the photoreceptor layer (ONL + PRL) thickness was also reduced in WD (93.90 ± 10.23 µm vs. 108.43 ± 10.00 µm; P = 0.01) There was no change in the RNFL thickness, between the two groups (P = 0.53). Conclusions: Abnormalities of the retinal layers were observed in the patients with WD. OCT is a non-invasive tool to identify and quantify the abnormalities of the retinal layers.

Spectrum of Movement Disorders in Niemann-Pick Disease Type C.

Introduction: Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage disorder caused by mutations in the NPC 1 or 2 genes. Movement disorders can occur as the first symptom and as predominant symptom mainly in juvenile-onset. The frequency and heterogeneity of movement disorders in NPC are not well described. We studied the frequency and spectrum of movement disorders in patients with NPC of different age of onset. Methods: Retrospective chart review of patients with NPC diagnosed based on the Suspicion Index tool and demonstration of foamy macrophages/sea-blue histiocytes in bone marrow aspirate. Results: We report 9 cases of NPC with 2 patients of late-infantile, 4 juvenile-onset and 3 of adult-onset. The mean age at onset of symptoms was 11.7 ± 10.4 (range 4-38 years) and the median duration of illness was 4 years. Vertical supranuclear gaze palsy (VSGP) was noted in 8 patients and VSGP with slowing of saccade in 1 patient. Splenomegaly was seen in 5 patients. Movement disorders as the first symptom occurred in 4 patients. Dystonia was the first symptom in 2 patients and cerebellar ataxia in 2 patients. Cerebellar ataxia occurred during the course of illness in 5 patients, dystonia in 6 patients. One patient with late-infantile NPC had stimulus-sensitive myoclonus. Conclusion: Movement disorders are common in NPC and occur as a presenting symptom. Cerebellar ataxia and dystonia are the most common movement disorder in NPC. Vertical supranuclear gaze palsy along with the movement disorders should lead to clinical suspicion of NPC.

Treatable Ataxias: How to Find the Needle in the Haystack?

Treatable ataxias are a group of ataxic disorders with specific treatments. These disorders include genetic and metabolic disorders, immune-mediated ataxic disorders, and ataxic disorders associated with infectious and parainfectious etiology, vascular causes, toxins and chemicals, and endocrinopathies. This review provides a comprehensive overview of different treatable ataxias. The major metabolic and genetic treatable ataxic disorders include ataxia with vitamin E deficiency, abetalipoproteinemia, cerebrotendinous xanthomatosis, Niemann-Pick disease type C, autosomal recessive cerebellar ataxia due to coenzyme Q10 deficiency, glucose transporter type 1 deficiency, and episodic ataxia type 2. The treatment of these disorders includes the replacement of deficient cofactors and vitamins, dietary modifications, and other specific treatments. Treatable ataxias with immune-mediated etiologies include gluten ataxia, anti-glutamic acid decarboxylase antibody-associated ataxia, steroid-responsive encephalopathy associated with autoimmune thyroiditis, Miller-Fisher syndrome, multiple sclerosis, and paraneoplastic cerebellar degeneration. Although dietary modification with a gluten-free diet is adequate in gluten ataxia, other autoimmune ataxias are managed by short-course steroids, plasma exchange, or immunomodulation. For autoimmune ataxias secondary to malignancy, treatment of tumor can reduce ataxic symptoms. Chronic alcohol consumption, antiepileptics, anticancer drugs, exposure to insecticides, heavy metals, and recreational drugs are potentially avoidable and treatable causes of ataxia. Infective and parainfectious causes of cerebellar ataxias include acute cerebellitis, postinfectious ataxia, Whipple's disease, meningoencephalitis, and progressive multifocal leukoencephalopathy. These disorders are treated with steroids and antibiotics. Recognizing treatable disorders is of paramount importance when dealing with ataxias given that early treatment can prevent permanent neurological sequelae.

Rural-urban and gender differences in metabolic syndrome in the aging population from southern India: Two parallel, prospective cohort studies.

Background: Despite the growing evidence of metabolic syndrome as a major risk factor for cardiovascular and cerebrovascular disease, there are limited studies from India on its prevalence, especially in the aging population. We aimed to estimate the prevalence of metabolic syndrome and associated comorbidities in two prospective, aging cohorts from rural and urban India. Methods: In these two parallel, prospective, aging (≥ 45 years) cohorts, the samples included 2171 people from rural India (Srinivaspura Aging, Neuro Senescence and COGnition, SANSCOG cohort; April 23, 2018 to Sept 25, 2021) and 332 people from urban India (Tata Longitudinal Study on Aging, TLSA cohort; July 8, 2015 to Oct 23, 2021). Using cross-sectional data from baseline clinical and biochemical assessments, we calculated metabolic syndrome prevalence using two well established criteria, namely consensus criteria and National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATP III) criteria; further, rural-urban, gender, and age-wise differences were compared. Findings: Proportions of metabolic syndrome were 46.2 and 54.8% as per consensus criteria in rural and urban participants, respectively; corresponding numbers using NCEP-ATP III criteria were 40.3 and 45.1%. Rural-dwelling older adults had a significantly lesser prevalence of all individual metabolic syndrome parameters except impaired triglycerides and high-density lipoprotein levels. Rural women had a significantly higher prevalence of metabolic syndrome than rural men, whereas there was no significant difference among urban participants. We did not observe any consistent age-wise trend when comparing both cohorts. There was high burden of comorbidities among both groups, mostly undiagnosed in rural participants. Interpretation: Roughly one in two older adults had metabolic syndrome, urban significantly more than rural, reaching an alarming 63.1% among urban participants aged 65-74 years. The very high prevalence of undiagnosed co-morbidities among rural adults is extremely concerning, calling for urgent public health measures in this marginalised and health-disparate population. Funding: SANSCOG study is funded through the Centre for Brain Research (CBR), Indian Institute of Science (IISc) by Pratiksha Trust, the philanthropic arm of Mr. Kris Gopalakrishnan. TLSA is funded by Tata Trusts.

Clinical, Radiological, and Genetic Profile of Spinocerebellar Ataxia 12: A Hospital-Based Cohort Analysis.

Introduction: Spinocerebellar ataxia type-12 (SCA12) is a rare form of SCA, most commonly reported from the Indian Agarwal and related families. In this study we describe the clinical, genetic, and radiological characteristics of a sizeable cohort of genetically proven SCA12. Methods: A retrospective chart-review of the genetically confirmed SCA12 patients from our centre. The demographic, clinical, and investigation findings were reviewed. Correlation of expanded repeats length with various demographic and clinical features were studied. Results: A total of 49 patients (34 males, 42 families) were included of which 79.6% belonged to Agarwal community. The mean age at onset and age at presentation were 46.38 ± 11.7 years and 53.16 ± 12.78 years respectively. The most common initial symptom was tremor (73.5%), followed by ataxia (18.4%). At presentation, 95.9% of the patients had tremor with predominant distribution in the bilateral upper limbs (85.7%). At presentation, 73.5% of patients had ataxia and 22.4% had cognitive dysfunction. The mean CAG repeat length in PPP2R2B in the expanded allele was 53.26 ± 6.10 (40-72). The lowest pathogenic expanded repeat sizes in PPP2R2B recorded in our cohort was 40 & 42 repeats from two patients with a consistent clinical phenotype. Another unusual phenotype was the presence of prominent myoclonus. There was no significant correlation between the age at onset of symptoms and the repeat size of CAG repeat. Conclusion: SCA12 is not confined to a single ethnicity. Upper limb tremor and ataxia were the most common presentation. Unusual presentation may cause diagnostic confusion especially when recorded in patients from non-Aggarwal families.

Utility of Clinical Exome Sequencing in Dystonia: A Single-Center Study From India.

OBJECTIVE: With the use of next-generation sequencing in clinical practice, several genetic etiologies of dystonia have been identified. This study aimed to ascertain the utility of clinical exome sequencing (CES) in dystonia and factors suggestive of a genetic etiology. METHODS: This study was a retrospective chart review of patients with dystonia who had undergone CES for the evaluation of dystonia. RESULTS: Forty-eight patients (35 males, 46 families) with dystonia were studied, with a mean age at onset of 16.0 ± 14.1 (1-58) years. A pathogenic/likely pathogenic variant was found in 20 patients (41.7%) among which 14 patients (29.2%) carried a novel variant. CES was more likely to detect a genetic diagnosis in patients with an early age at onset, i.e., ≤ 20 years. CONCLUSION: CES is a useful tool in the diagnostic evaluation of dystonia, with a yield of close to 40%. Patients with an earlier age at onset have a higher likelihood of having dystonia due to a genetic cause than those with a later age at onset.

Fibrinogen and Complement Factor H Are Promising CSF Protein Biomarkers for Parkinson's Disease with Cognitive Impairment─A Proteomics-ELISA-Based Study.

Parkinson's disease (PD) with cognitive impairment (PDCI) is essentially diagnosed through clinical and neuropsychological examinations. There is a need to identify biomarkers to foresee cognitive decline in them. We performed label-free unbiased nontargeted proteomics (Q-TOF LC/MS-MS) on the CSF of non-neurological control; PDCI; PD; and normal pressure hydrocephalus (NPH) patients, followed by targeted ELISA for validation. Of the 281 proteins identified, 42 were differentially altered in PD, PDCI, and NPH. With a certain overlap, 28 proteins were altered in PDCI and 25 proteins were altered in NPH. Five significantly upregulated proteins in PDCI were fibrinogen, gelsolin, complement factor-H, and apolipoproteins A-I and A-IV, whereas carnosine dipeptidase-1, carboxypeptidase-E, dickkopf-3, and secretogranin-3 precursor proteins were downregulated. Those uniquely altered in NPH were the insulin-like growth factor-binding protein, ceruloplasmin, α-1 antitrypsin, VGF nerve growth factor, and neural cell adhesion molecule L1-like protein. The ELISA-derived protein concentrations correlated with neuropsychological scores of certain cognitive domains. In PDCI, the Wisconsin card sorting percentile correlated negatively with fibrinogen. Intraperitoneal injection of native fibrinogen caused motor deficits in C57BL/6J mice as assessed by the pole test. Thus, a battery of proteins such as fibrinogen-α-chain, CFAH, and APOA-I/APOA-IV alongside neuropsychological assessment could be reliable biomarkers to distinguish PDCI and NPH.

Abnormal Intracortical Functions in Parkinson's Disease with Rapid Eye Movement Sleep Behaviour Disorder.

BACKGROUND: Rapid eye movement sleep behaviour disorder (RBD) is considered to be one of the most frequent and important prodromal symptoms of Parkinson's disease (PD). We aimed to study the neurophysiological abnormalities in patients of PD-RBD and PD without RBD (PD-nRBD) using transcranial magnetic stimulation (TMS). METHODS: Twenty patients each of PD-RBD and PD-nRBD were included in the study in addition to 20 age and gender-matched healthy controls. RBD was identified using the RBD screening questionnaire (RBDSQ). All the subjects were evaluated with single and paired-pulse TMS and parameters such as resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were recorded. RESULTS: The mean age of the controls and PD patients with and without RBD was comparable. There were no significant differences in RMT, CMCT and silent period between the two patient groups. SICI was present in all the three groups with significant inhibition noted in PD-RBD group (p < 0.001). ICF was absent in patients of PD-RBD (0.19 ± 0.11) and PD-nRBD (0.7 ± 0.5) when compared to controls (1.88 ± 1.02) with profound impairment in patients with PD-RBD (p < 0.001). The mean MoCA score was found to be significantly different in all the three groups with a worse score in patients with RBD (23.10 ± 2.55; p < 0.001). CONCLUSIONS: PD-RBD patients have significantly greater inhibition and reduced intracortical facilitation suggesting enhanced GABAergic and reduced glutaminergic transmission. These abnormalities may underlie the different pathophysiological process observed in these patients.

Cognitive impairment and its neuroimaging correlates in spinocerebellar ataxia 2.

INTRODUCTION: Cognitive impairment (CI) is reported but is poorly explored in spinocerebellar ataxia 2 (SCA2). This study was undertaken to evaluate and classify cognitive impairment in patients with SCA2 and to identify their grey matter (GM) correlates. METHODS: We evaluated the neurocognitive profile of 35 SCA2 and 30 age-, gender- and education-matched healthy controls using tests for attention, executive functions, learning and memory, language and fluency, and visuomotor constructive ability. Patients were classified into SCA2 with and without CI based on normative data from population and healthy controls. Furthermore, patients with CI were sub-classified based on the number of impaired domains into multi-domain CI (≥3 domains; MDCI) and limited domain CI (≤2 domains; LDCI). The underlying GM changes were identified using voxel based morphometry. RESULTS: The mean age at onset, duration of disease, and ataxia score was 28.7 ± 8.51 years, 66.7 ± 44.1 months, and 16.1 ± 4.9 points, respectively. CI was present in 71.4% of SCA2 subjects (MDCI: 42.7%; LDCI: 28.5%). Patients with CI had significant atrophy of the posterior cerebellum, sensorimotor cortex, and superior frontal gyrus (FWE p-value <0.05). Patients with MDCI had significant GM atrophy of the angular gyrus compared to LDCI (FWE p-value <0.05). CONCLUSION: Patients with CI had significant GM involvement of the posterior cerebellum and frontal lobe, suggestive of impairment in the cerebello-fronto-cortical circuitry.

Morphometric mapping of the macrostructural abnormalities of midsagittal corpus callosum in Wilson's disease.

Background and Purpose: The corpus callosum (CC) consists of topographically arranged white matter (WM) fibers. Previous studies have indicated the CC to be discretely involved in WD. In this study, we strived to characterize the macrostructural properties of the CC using midsagittal cross-sectional area and thickness profile measurements. Materials and Methods: This study was performed using archived magnetic resonance imaging (MRI) scans of 14 patients with WD and 14 age- and gender-matched healthy controls. Using an automated software pipeline for morphometric profiling, the midsagittal CC was segmented into five sub-regions (CC1-5) according to the Hofer-Frahm scheme. The mean thickness and area of different CC segments and their clinical and cognitive correlates were identified. Results: The mean area was significantly different only in CC2 segment (94.2 ± 25.5 vs. 118.6 ± 19.7 mm2, corrected P < 0.05). The mean thickness was significantly different in CC1 (5.06 ± 1.15 vs. 6.93 ± 0.89 mm, corrected P < 0.05), CC2 (3.73 ± 0.96 vs. 4.87 ± 1.01 mm, corrected P < 0.05), and CC3 segments (3.42 ± 0.84 vs. 3.94 ± 0.72 mm, corrected P < 0.05). The age at onset of neurological symptoms and MMSE score was significantly correlated with the morphometric changes of CC1 and CC2 segments. Conclusion: Morphological changes of the CC are discrete in WD. Morphometric loss of CC was associated with an earlier onset of neurological symptoms and cognitive dysfunction in WD.

In vivo microstructural white matter changes in early spinocerebellar ataxia 2.

OBJECTIVE: White matter (WM) integrity of Spinocerebellar ataxia 2 (SCA2) is poorly understood, more so in the early stages of SCA2. In this study, we evaluated the microstructural integrity of the WM tracts with an emphasis on the nature of in vivo pathological involvement in early SCA2. MATERIALS AND METHODS: We evaluated the MRI images of 26 genetically proven SCA2 patients with disease duration <5 years and 24 age- and gender-matched healthy controls using tract-based spatial statistics (TBSS) to identify the WM tract changes and their clinico-genetic correlates (age at onset, duration of disease, ataxia severity and CAG repeat length) using standard methodology. RESULTS: The mean age at onset and duration of disease were 28.7 ± 8.51 years and 3.5 ± 0.69 months, respectively. The mean CAG repeat length was 42.5 ± 4.6, and the ataxia severity score was 16.1 ± 4.9. Altered DTI scalars signifying degeneration was present in the bilateral anterior thalamic radiation (ATR), corticospinal tract (CST), inferior fronto-occipital fasciculus (IFOF), superior and inferior longitudinal fasciculus (SLF and ILF), uncinate fasciculus (UF), cingulum, corpus callosum (CC), forceps major and forceps minor (corrected p < .05). DTI scalars representing demyelination was seen in the superior cerebellar peduncle (SCP) and cerebellar WM. There was a significant correlation of SARA score with axial diffusivity of the bilateral cingulum, ATR, CST, forceps minor, IFOF, ILF, SLF and SCP on the right side (corrected p < .05). CONCLUSION: Extensive WM involvement is present in early SCA2. The DTI scalars indicate degeneration and demyelination and may have clinical implications.

Overview of sleep disturbances and their management in Parkinson plus disorders.

Sleep disturbance is one of the commonly reported non-motor symptoms in patients with Parkinson's disease (PD) as well as in Parkinson plus disorders such as multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). Although there is a wealth of literature on sleep disturbances in PD, the same is not robust on the Parkinson plus disorders. This article aims to comprehensively review the sleep disturbances in Parkinson plus disorders. The literature review was as per the guidelines of the preferred reporting items for systematic reviews and meta-analyses (PRISMA). We searched PubMed and MEDLINE till December 2019 using a combination of words - "Sleep disturbance" with additional search terms such as: "synucleinopathy", "tauopathy", "multiple system atrophy", "dementia with Lewy bodies", "progressive supranuclear palsy", and "corticobasal syndrome". A wide range of sleep disorders that include insomnia, rapid eye movement (REM) sleep behaviour disorder (RBD), periodic limb movement disorder, excessive daytime sleepiness, and sleep apneas, may complicate the course of the Parkinson plus disorders. Pathophysiology of these sleep disorders remains elusive, thus making targeted pharmacotherapy challenging. We describe the cardinal features and the management options of these sleep disorders in the context of Parkinson plus disorders.

The Non-Motor Symptom Profile of Progressive Supranuclear Palsy.

OBJECTIVE: Non-motor symptoms (NMSs) significantly contribute to increased morbidity and poor quality of life in patients with parkinsonian disorders. This study aims to explore the profile of NMSs in patients with progressive supranuclear palsy (PSP) using the validated Non-Motor Symptom Scale (NMSS). METHODS: Seventy-six patients with PSP were evaluated in this study. Motor symptoms and NMSs were evaluated using the PSP Rating Scale (PSPRS), Unified Parkinson's Disease Rating Scale-III, Montreal Cognitive Assessment, Hamilton Depression (HAM-D) and Anxiety Rating Scales, Parkinson's Disease Sleep Scale (PDSS) and NMSS. NMS severity and prevalence were also compared between patients with PSP-Richardson syndrome (PSP-RS) and those with PSP-parkinsonism. RESULTS: All subjects in this cohort reported at least 2 NMSs. The most prevalent NMSs in patients with PSP were in the domains of sleep/fatigue, mood/cognition, and sexual function. The least prevalent NMSs were in the domains of cardiovascular including falls, and perceptual problems/hallucinations. Significant correlations were observed between the NMSS scores and HAM-D, PDSS, PSPRS scores and PSPRS sub-scores. The severity of NMSs was unrelated to the duration of illness. Patients with PSP-RS reported a higher severity of drooling, altered smell/taste, depression and altered interest in sex and a higher prevalence of sexual dysfunction. CONCLUSION: NMSs are commonly observed in patients with PSP, and the domains of sleep, mood and sexual function are most commonly affected. These symptoms contribute significantly to disease morbidity, and clinicians should pay adequate attention to identifying and addressing these symptoms.