Sexual dysfunction in men with young onset Parkinson's disease.

Sexual dysfunction (SD) is a common, yet under-reported non-motor symptom of PD. Common sexual symptoms among male PD patients include erectile dysfunction, premature ejaculation, and decreased sexual desire. Few research papers have examined sexual dysfunction in PD, especially in YOPD male patients, and there is no Indian research study on sexual dysfunction in YOPD. In this study, we determined the frequency of sexual dysfunction in men with YOPD, and its correlation with other motor and NMS. This prospective cross-sectional study was conducted on YOPD males who presented to the Department of Neurology, NIMHANS, Bangalore, India, from May 2021 to April 2023. The diagnosis of YOPD was made based on MDS criteria for IPD 2015. Sexual functions were evaluated by ASEX, PEDT, QUIP-RS, and sex hormone assay. The patients also underwent other motor and non-motor assessments. Statistical analysis was done using SPSS version 22.0. The study was funded by the PDMD fund. This study included 62 male YOPD patients. The mean age of cases was 44.74 ± 8.54 years. The mean duration of symptoms was 8.45 ± 6.23 years. 43.5% of the cases of PD were Akinetic rigid type. By ASEX Score grading, 46.8% of the cases had erectile dysfunction and 71% of the cases of YOPD had premature ejaculation by PEDT Score grading. 9.7% of the cases had hypersexuality by QUIP-RS. Duration of YOPD was a better predictor of Erectile Dysfunction and premature ejaculation when compared with other variables. SD was related to anxiety and depression and it had a negative impact on the patient's health-related quality of life (HR-QoL). SD should be investigated and treated as an integral part of the neurological assessment in YOPD.

Morphometric alterations of the mesocorticolimbic network in Parkinson's disease with impulse control disorders.

Impulse control disorders (ICDs) are a group of non-motor symptoms of Parkinson disease (PD) leading to significant psychosocial detrimental outcome. The mesocorticolimbic network plays a distinctive role in reward learning and executive decision making and has been suggested to be involved in ICDs in PD. To study morphometric changes of the mesocorticolimbic network in PD with ICD. A total of 18 patients of PD with ICD (PD + ICD), 19 patients of PD without ICD (PD - ICD) and 19 healthy controls (HC) were included in the study. ICDs were diagnosed using Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS). MRI was done using a 3T scanner and assessment of cortical thickness and subcortical volumes were done using FreeSurfer. Brain regions known to be part of the mesocorticolimbic network were extracted and included for statistical analysis. There was no difference between PD + ICD and PD - ICD with regard to duration of illness or total dopaminergic medication. In comparison to HC, patients with PD + ICD demonstrated atrophy of the left frontal pole, and this atrophy neared significance in comparison to PD - ICD. The QUIP-RS had a negative correlation with left caudate volume in PD + ICD. The PD + ICD group showed distinct morphometric changes in regions involved in the mesocorticolimbic system which may contribute to the presence of ICD.

Impact of Non-Motor Symptoms on Quality of Life in Patients with Early-Onset Parkinson's Disease.

BACKGROUND: Early-onset Parkinson's disease (EOPD) refers to patients with Parkinson's disease (PD) whose age at disease onset is less than 50 years. Literature on the non-motor symptoms (NMS) in these patients is very limited in the Indian context. We aimed to study the NMS in patients with EOPD and its impact on the quality of life (QoL). METHODS: We included 124 patients with EOPD with a mean age at disease onset between 21 and 45 years and 60 healthy controls (HC). NMS were assessed using validated scales, and the QoL domains were evaluated using the PD QoL-39 scale (PDQ-39). RESULTS: The mean age at disease onset in EOPD patients was 37.33 ± 6.36 years. Majority of the patients were male (66.12%). The average disease duration was 6.62 ± 5.3 years. EOPD patients exhibited a significantly higher number of NMS per patient (7.97 ± 4.69) compared to HC (1.3 ± 1.39; p < 0.001). The most common NMS reported were urinary dysfunction, body pain, poor sleep quality, constipation, anxiety, depression, cognitive impairment, and REM sleep behavior disorder. The total NMS burden correlated with the QoL measures. Distinctive patterns of QoL subdomain involvement were identified, with sleep/fatigue, mood/cognition, and urinary dysfunction independently influencing QoL metrics. CONCLUSIONS: Our study provides valuable insights into the NMS profile and its impact on QoL in patients with EOPD, addressing an important knowledge gap in the Indian context. By understanding the specific NMS and their influence on QoL, healthcare professionals can develop targeted interventions to address these symptoms and improve the overall QoL.

Yoga as an Add-on Therapy in Parkinson's Disease: A Single Group Open-label Trial.

OBJECTIVE: We aimed to evaluate the effect of yoga on motor and non-motor symptoms and cortical excitability in patients with Parkinson's disease (PD). METHODS: We prospectively evaluated 17 patients with PD at baseline, after one month of conventional care, and after one month of supervised yoga sessions. The motor and non-motor symptoms were evaluated using the Unified Parkinson's disease Rating Scale (motor part III), Hoehn and Yahr stage, Montreal Cognitive Assessment, Hamilton depression rating scale, Hamilton anxiety rating scale, non-motor symptoms questionnaire and World Health Organization quality of life questionnaire. Transcranial magnetic stimulation was used to record resting motor threshold, central motor conduction time, ipsilateral silent period (iSP), contralateral silent period (cSP), short interval intracortical inhibition (SICI), and intracortical facilitation. RESULTS: The mean age of the patients was 55.5 ± 10.8 years, with a mean duration of illness of 4.0 ± 2.5 years. The postural stability of the patients significantly improved following yoga (0.59 ± 0.5 to 0.18 ± 0.4, p = 0.039). There was a significant reduction in the cSP from baseline (138.07 ± 27.5 ms) to 4 weeks of yoga therapy (116.94 ± 18.2 ms, p = 0.004). In addition, a significant reduction in SICI was observed after four weeks of yoga therapy (0.22 ± 0.10) to (0.46 ± 0.23), p = 0.004). CONCLUSION: Yoga intervention can significantly improve postural stability in patients with PD. A significant reduction of cSP and SICI suggests a reduction in GABAergic neurotransmission following yoga therapy that may underlie the improvement observed in postural stability. CLINICALTRIALSGOV IDENTIFIER: CTRI/2019/02/017564.

Ventrolateral medullary compression by vascular contact in primary hemifacial spasm: a radiological analysis.

BACKGROUND: The neurovascular conflict (NVC) causing hemifacial spasm (HFS) can also cause compression of ventrolateral medulla (VLM) which contains the central sympathetic neurons. VLM compression has been associated with hypertension. Whether the VLM compression in HFS patients is associated with hypertension is not clear. OBJECTIVE: To determine the frequency, severity of VLM compression and its association with hypertension in HFS patients. METHODS: A cross-sectional, hospital-based, case control study and recruited 120 study subjects (50 cases of primary HFS, 30 hypertensive and 40 normotensive age-, sex- matched controls). The VLM compression was assessed in magnetic resonance imaging Constructive Interference in Steady State (CISS) 3D sequences. RESULTS: Hypertension was present in 30 cases (60%). Six patients with HFS (20%) were detected to be hypertensive after the onset of HFS. VLM compression was seen in 24 cases (48%), 7 hypertensive controls (23.3%) and 5 normotensive controls (10%) (p = 0.03). Twenty-four patients with hypertension had VLM compression and remaining 6 patients with hypertension did not have VLM compression (80% vs 20%; p = 0.02). Normotensive patients did not have VLM compression. Vertebral artery was the most common artery causing VLM compression (22 patients; 7 hypertensive and 5 normotensive controls). CONCLUSION: VLM compression is more common in HFS patients as compared to hypertensive and normotensive controls. It is more common in hypertensive HFS patients in comparison with normotensive HFS patients. Microvascular decompression is an option in hypertensive HFS patients with VLM compression if the hypertension is medically refractory.

Deep brain stimulation in pediatric dystonia: calls for therapeutic realism over nihilism.

PURPOSE: Pediatric dystonia (PD) has a significant negative impact on the growth and development of the child. This study was done retrospectively to analyze functional outcomes in pediatric patients with dystonia who underwent deep brain stimulation. METHODS: In this retrospective analytical study, all the patients of age less than 18 years undergoing deep brain stimulation (DBS) for dystonia between 2012 and 2020 in a single center were analyzed and their functional outcomes were measured by the Burke-Fahn-Marsden-dystonia-rating-scale (BFMDRS). RESULTS: A total of 10 pediatric patients were included with a mean age of onset, duration of disease, and age at surgery being 5.75 years, 7.36 years, and 13.11 years, respectively, with a mean follow-up of 23.22 months. The mean pre-DBS motor score was 75.44 ± 23.53 which improved significantly at 6-month and 12-month follow-up to 57.27 (p value 0.004) and 50.38 (p value < 0.001), respectively. Limbs sub-scores improved significantly at both the scheduled intervals. There was a significant improvement in disability at 1-year follow-up with significant improvement in feeding, dressing, and walking components. There was a 27.34% and 36.64% improvement in dystonia with a 17.37% and 28.86% reduction in disability at 6 months and 12 months, respectively. There was a positive correlation between the absolute reduction of the motor score and improvement in disability of the patients at 6 months (rho = 0.865, p value 0.003). CONCLUSIONS: DBS in PD has an enormous role in reducing disease burden and achieving a sustainable therapeutic goal.

Novel CWF19L1 mutations in patients with spinocerebellar ataxia, autosomal recessive 17.

Spinocerebellar ataxia, autosomal recessive-17 (SCAR17) is a rare hereditary ataxia characterized by ataxic gait, cerebellar signs and occasionally accompanied by intellectual disability and seizures. Pathogenic mutations in the CWF19L1 gene that code for CWF19 like cell cycle control factor 1 cause SCAR17. We report here two unrelated families with the clinical characteristics of global developmental delay, cerebellar ataxia, pyramidal signs, and seizures. Cerebellar atrophy, and T2/FLAIR hypointense transverse pontine stripes were observed in brain imaging. Exome sequencing identified novel homozygous mutations including a splice acceptor site variant c.1375-2 A > G on intron 12 in a male patient and a single nucleotide variant c.452 T > G on exon 5 resulting in a missense variant p.Ile151Ser in the female patient from two unrelated families, respectively. Sanger sequencing confirmed the segregation of these variants in the family members with autosomal recessive inheritance. Transcript analysis of the splice site variant revealed activation of a novel cryptic splice acceptor site on exon 13 resulting in an alternative transcription with a loss of nine nucleotides on exon 13. Translation of this transcript predicted an in-frame deletion of three amino acids p.(459_461del). We also observed a novel exon 13 skipping which results in premature termination of the protein product. Our study expands the phenotype, radiological features, and genotypes known in SCAR17.

Prevalence and Correlates of Psychiatric Comorbidity and Multimorbidity in Parkinson's Disease and Atypical Parkinsonian Syndromes.

PURPOSE: Psychiatric comorbidity in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) has been consistently associated with poor outcomes. However, the co-occurrence of multiple psychiatric disorders has been sparsely studied. This study examines the prevalence, patterns, and correlates of psychiatric comorbidity and multimorbidity among in-patients hospitalised with PD/APS. METHODS: Patients (N-110 [PD-71, APS-39]) underwent a single cross-sectional assessment. Psychiatric comorbidity was examined using the Mini International Neuropsychiatric Interview. Other domains assessed include sleep disorders, quality of life, and caregiver burden. STATISTICAL ANALYSIS: In addition to descriptive statistics, multinomial logistic regression was used to examine the effect of sociodemographic and clinical factors on comorbidities. RESULTS: The prevalence of psychiatric comorbidity in patients with PD and APS was 77.00% and 71.79%, with approximately half of those having co-occurrence of multiple psychiatric disorders. In both disorders, depression was the most common, followed by anxiety disorder. The two commonest patterns of multimorbidity reported in PD were the combination of depression and anxiety disorder, followed by the combination of psychosis, depression, and anxiety, with the order being reversed in APS. When compared to those without, those with single psychiatric comorbidity had higher odds of having REM sleep behaviour disorder and caregiver stress. Those with multiple psychiatric comorbidities had higher odds of being female, higher UPDRS part-1 scores, REM sleep behaviour disorder, poor sleep quality, and caregiver stress. CONCLUSION: Psychiatric illness is highly comorbid among patients with PD/APS, with most having multiple co-occurring psychiatric illnesses. Clinicians must be aware to ensure early detection and intervention.

Long Latency Reflexes in Clinical Neurology: A Systematic Review.

BACKGROUND: Long latency reflexes (LLRs) are impaired in a wide array of clinical conditions. We aimed to illustrate the clinical applications and recent advances of LLR in various neurological disorders from a systematic review of published literature. METHODS: We reviewed the literature using appropriately chosen MeSH terms on the database platforms of MEDLINE, Web of Sciences, and Google Scholar for all the articles from 1st January 1975 to 2nd February 2021 using the search terms "long loop reflex", "long latency reflex" and "C-reflex". The included articles were analyzed and reported using synthesis without meta-analysis (SWiM) guidelines. RESULTS: Based on our selection criteria, 40 articles were selected for the systematic review. The various diseases included parkinsonian syndromes (11 studies, 217 patients), Huntington's disease (10 studies, 209 patients), myoclonus of varied etiologies (13 studies, 127 patients) including progressive myoclonic epilepsy (5 studies, 63 patients) and multiple sclerosis (6 studies, 200 patients). Patients with parkinsonian syndromes showed large amplitude LLR II response. Enlarged LLR II was also found in myoclonus of various etiologies. LLR II response was delayed or absent in Huntington's disease. Delayed LLR II response was present in multiple sclerosis. Among the other diseases, LLR response varied according to the location of cerebellar lesions while the results were equivocal in patients with essential tremor. CONCLUSIONS: Abnormal LLR is observed in many neurological disorders. However, larger systematic studies are required in many neurological disorders in order to establish its role in diagnosis and management.

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.

A splice altering variant in NDRG1 gene causes Charcot-Marie-Tooth disease, type 4D.

Charcot-Marie-Tooth disease, type 4D (CMT4D) is a progressive, autosomal recessive form of CMT, characterized by distal muscle weakness and atrophy, foot deformities, severe motor sensory neuropathy, and sensorineural hearing impairment. Mutations in NDRG1 gene cause neuropathy in humans, dogs, and rodents. Here, we describe clinical and genetic features of a 17-year-old male with wasting of hand muscle and foot and severe motor neuropathy. Whole exome sequencing was carried out on the patient and his unaffected parents. We identified a novel deletion of nine nucleotides (c.537 + 2_537 + 10del) on the splice donor site of intron 8 in NDRG1 gene. The Sanger sequencing confirmed the segregation of this mutation in autosomal recessive inheritance. Furthermore, transcript analysis confirmed a splice defect and reveals using of an alternate cryptic splice donor site on the downstream intronic region. It resulted in an insertion of 42 nucleotides to exon 8 of NDRG1. Translation of the resulting transcript sequence revealed an insertion of 14 amino acids in-frame to the existing NDRG1 protein. This insertion is predicted to disrupt an alpha helix which is involved in protein-protein interactions in homologous proteins. Our study expands the clinical and genetic spectrum of CMT4D. The splice defect we found in this patient reveals a novel splice isoform of NDRG1 as the potential cause for the neuropathy observed in this patient.

Effect of Lumbar Drainage on Cortical Excitability in Normal Pressure Hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the clinical triad of gait disturbance, urinary incontinence, and memory impairment with normal cerebrospinal fluid (CSF) pressure. Transcranial magnetic stimulation (TMS) has been used to assess the corticospinal motor pathways in patients with iNPH with conflicting results. METHODS: Our study included 11 patients with iNPH and 13 healthy controls. All the subjects underwent TMS and resting motor threshold (RMT), central motor conduction time (CMCT), short-interval intracortical inhibition (SICI), intracortical facilitation, and silent period (SP) were recorded in the upper limb. Besides, RMT and CMCT in lower limb were also recorded. Cognitive assessments were done using mini-mental status examination, Montreal cognitive assessment (MoCA), and Addenbrooke's cognitive evaluation III (ACE III). Same parameters were recorded 24 h of CSF (lumbar puncture, LP) drainage. RESULTS: Mean age of the iNPH patients was 69.00 ± 6.71 years with age at onset being 66.64 ± 7.10 years. Duration of disease was 1.80 ± 1.25 years. A significant difference was noted in CMCT for the lower limb (CMCT-LL), SICI, and ipsilateral SP between pre-LP NPH and controls. Also, there was a significant difference in MoCA and ACE III between pre-LP NPH and controls. A significant reduction was observed in lower limb RMT between pre- and post-LP NPH patients. Post LP, there was a reduction in the lower limb CMCT and improvement in SICI. CONCLUSION: A significant prolongation of CMCT-LL was observed in NPH patients. Lumbar CSF drainage in them resulted in a significant reduction in lower limb RMT thereby suggesting an increase in cortical excitability.

Pediatric Functional Movement Disorders: Experience from a Tertiary Care Centre.

OBJECTIVES: Functional movement disorders (FMDs) pose significant diagnostic and management challenges. We aimed to study the socioeconomic and cultural factors, underlying psychopathology and the phenomenology of FMDs in children. METHODS: The study is a retrospective chart review of 39 children (16 girls and 23 boys) who attended our neurology OPD and the movement disorders clinic at the National Institute of Mental Health and Neurosciences (NIMHANS) between January 2011 and May 2020. The diagnosis of FMD was based on Fahn and Williams criteria and the patients were either diagnosed as "documented" or "clinically established". All the relevant demographic data including the ethnicity, socioeconomic and cultural background, examination findings, electrophysiological, and other investigations were retrieved from the medical records. RESULTS: The mean age at onset was 12.69 ± 3.13 years. Majority of the children were from urban regions (56.41%) and belonging to low socioeconomic status (46.15%). Thirty (76.92%) were found to have a precipitating factor. Myoclonus was the most common phenomenology observed in these patients (30.76%), followed by tremor (20.51%), dystonia (17.94%), and gait abnormality (7.69%). Chorea (5.12%) and tics (2.56%) were uncommon. Tremor (37.5%) and dystonia (18.75%) were more common in girls, whereas myoclonus (39.13%) was more common in boys. CONCLUSIONS: The symptoms of FMD have great impact on the mental health, social, and academic functioning of children. It is important to identify the precipitating factors and associated psychiatric comorbidities in these children as prompt alleviation of these factors by engaging parents and the child psychiatrist will yield better outcomes.

Comparison of effectiveness of trihexyphenidyl and levodopa on motor symptoms in Parkinson's disease.

Despite anti-cholinergics being the oldest type of medication used for the treatment of Parkinson's disease (PD), the mechanism of action and exact benefit is unclear. This study compared the effectiveness of trihexyphenidyl (THP) and levodopa (LD) on motor symptoms in patients with PD. Patients with PD who are currently taking or had taken THP were recruited. UPDRS-III was done following overnight medication OFF state and 30 min, 60 min, 90 min, and 120 min after THP (4 mg). After a forty-eight-hour interval, UPDRS-III was assessed one hour after Levodopa/carbidopa (200/50 mg) in an overnight OFF state. Twenty patients with a mean age of 57.9 ± 7.8 years and mean duration of illness of 5.1 ± 3.6 years were recruited. UPDRS-III score reduction (%) with THP was maximum in the tremor sub-score (53.8 ± 22.8) and was significantly better compared to improvement in total-UPDRS-III (27.0 ± 14.7), bradykinesia-UPDRS-III (22.2 ± 27.2), rigidity-UPDRS-III (29.5 ± 28.0) and axial-UPDRS-III (8.1 ± 13.3) sub-score. In comparison, respective LD improvement was 67.1 ± 22.9 (tremor-UPDRS-III), 61.3 ± 14.4 (total-UPDRS-III), 67.9 ± 32.1 (bradykinesia-UPDRS-III), 65.3 ± 25.5 (rigidity-UPDRS-III) and 50.7 ± 16.0 (axial-UPDRS-III). Improvement (%) in tre-UPDRS-III post-THP was comparable to that of post-LD (53.8 ± 22.8 vs. 67.1 ± 22.9, p = 0.057). Those with same or better tremor response with THP had significantly milder baseline tremor severity than those who had better response with LD (tre-UPDRS-III-OFF, 10.0 ± 2.8 vs. 5.8 ± 4.0, p = 0.013). Both THP and LD showed significant improvement in UPDRS-III. With THP, the maximum degree of improvement was in the tremor sub-score and not significantly different to that obtained by LD. Those with better tremor response on THP had milder tremor severity.

Psychiatric morbidity and poor follow-up underlie suboptimal functional and survival outcomes in Huntington's disease.

BACKGROUND: Huntington's disease (HD), an inherited, often late-onset, neurodegenerative disorder, is considered to be a rare, orphan disease. Research into its genetic correlates and services for those affected are inadequate in most low-middle income countries, including India. The apparent 'incurability' often deters symptomatic and rehabilitative care, resulting in poor quality of life and sub-optimal outcomes. There are no studies assessing disease burden and outcomes from India. METHODS: We attempted to evaluate individuals diagnosed to have HD at our tertiary-care center between 2013 and 2016 for clinical symptoms, functionality, mortality, follow up status through a structured interview, clinical data from medical records and UHDRS-TFC scoring. RESULTS: Of the 144 patients, 25% were untraceable, and another 17 (11.8%) had already died. Mean age at death and duration of illness at the time of death, were 53 years and 7 years respectively, perhaps due to suicides and other comorbidities at an early age. The patients who could be contacted (n = 81) were assessed for morbidity and total functional capacity (TFC). Mean CAG repeat length and TFC score were 44.2 and 7.5 respectively. Most individuals (66%) were in TFC stage I and II and could perhaps benefit from several interventions. The TFC score correlated inversely with duration of illness (p < 0.0001). The majority were being taken care of at home, irrespective of the physical and mental disability. There was a high prevalence of psychiatric morbidity (91%) including suicidal tendency (22%). Three of the 17 who died had committed suicide, and several other families reported suicidal history in other family members. Only about half the patients (57%) maintained a regular clinical follow-up. CONCLUSIONS: This study demonstrates the poor follow-up rates, significant suicidality and other psychiatric symptoms, sub-optimal survival durations and functional outcomes highlighting the need for holistic care for the majority who appear to be amenable to interventions.

Non-motor symptoms in patients with autosomal dominant spinocerebellar ataxia.

OBJECTIVE: The non-motor manifestations of motor predominant disorders have been an area of active interest in recent times. The objective of the study was to determine the prevalence of non-motor symptoms in patients with genetically confirmed spinocerebellar ataxia (SCA). MATERIALS AND METHODS: Forty-one patients of SCA and 48 age-, gender-, and education-matched controls were included. The severity of ataxia was evaluated using the International Cooperative Ataxia Rating Scale (ICARS) and cognitive impairment using a neuropsychological battery. Non-motor features were assessed using standardized scales (HAM-A, HAM-D, Modified Fatigue Severity Scale, RLS questionnaire, ESS, PSQI, WHOQOL, RBDSQ, and BPI). The data were compared with controls and correlated with the severity of ataxia. RESULTS: There were 17 SCA1, 14 SCA2, and 10 SCA3 patients. The mean age of presentation was 35.7 ± 7.9 years for SCA1, 31.1 ± 7.9 years for SCA2, and 30.5 ± 9.5 years for SCA3 patients. The neuropsychological evaluation showed severe impairment of attention, executive functions, visuospatial function, motor speed, response speed, and memory. The severity of ataxia was more for SCA2 patients (ICARS of 39.5 ± 24.4). Ataxia severity was correlated with MMSE, fatigue scale, depression scale, and REM sleep behavior disorder in SCA1 individuals and global cognition, fatigue, anxiety, and depression scales, and RLS in SCA3 patients. All patients reported quality of life as dissatisfied. These patients also had sleep disturbances in the form of RBD, RLS, and EDS. CONCLUSIONS: In addition to the motor symptoms, patients with SCA have several non-motor symptoms that impair the quality of life.

Abnormalities of white and grey matter in early multiple system atrophy: comparison of parkinsonian and cerebellar variants.

OBJECTIVE: Multiple system atrophy (MSA) is a neurodegenerative disorder with progressive motor and autonomic dysfunction. There is a paucity of information on the early neurostructural changes in MSA, especially its subtypes, MSA-P (patients with predominant parkinsonism) and MSA-C (patients with predominant cerebellar signs). This study investigates the abnormalities of grey matter (GM) and white matter (WM) in early MSA and its subtypes using multi-modal voxel-based analysis. MATERIALS AND METHODS: Twenty-six patients with MSA with duration of symptoms ≤ 2.5 years (mean duration: 1.6 ±0.9 years) were assessed clinically and with 3T MRI. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to identify the structural changes in MSA and its subtypes. The GM changes and diffusion parameters of WM tracts were correlated with the clinical scores. The results were compared with MRI of 25 age- and gender-matched healthy controls. RESULTS: The early structural changes in MSA included GM loss of the cerebellum and subcallosal gyrus with widespread involvement of supratentorial and infratentorial WM fibres. In MSA-C, GM loss was limited to the cerebellum with WM changes predominantly affecting the infratentorial WM and association tracts. In contrast, MSA-P did not demonstrate any GM loss and the WM involvement was mainly supratentorial. There was no significant correlation between structural changes and clinical severity score. CONCLUSION: In early MSA, WM microstructure was more affected than GM. These changes were greater in MSA-C than in MSA-P, suggesting variable deterioration in the subtypes of MSA. KEY POINTS: • Structural changes in early multiple system atrophy were evaluated using multi-modal neuroimaging. • White matter was more affected than grey matter in early MSA. • Clinical variables did not correlate with early structural changes.

Neuronal Intranuclear Inclusion Disease: A Rare Etiology for Rapidly Progressive Dementia.

INTRODUCTION: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder pathologically characterized by localized neuronal loss, and presence of eosinophilic intranuclear inclusions in neurons and glial cells. CASE REPORT: A 50-year-old man presented with rapidly progressive dementia, behavioral changes, gait disturbances, and incontinence of 3 months duration. His brain magnetic resonance imaging showed diffuse T2/FLAIR hyperintensity of basal ganglia, thalami, cerebral peduncles, ventral pons, and supratentorial white matter with a frontal predominance. Hyperintensity was noted along the corticosubcortical junction on diffusion-weighted images. NIID was suspected and the patient underwent triple biopsy of the sural nerve with adjacent skin and biceps biopsy. Biopsy revealed ubiquitin-positive intranuclear inclusions surrounding the myofibers, and vascular smooth muscles suggestive of NIID. CONCLUSIONS: NIID is a rare neurodegenerative disorder usually diagnosed postmortem. The rectal and skin biopsy had proved helpful in antemortem diagnosis. We have increased the diagnostic armamentarium by showing the presence of intranuclear inclusions in smooth muscle cells of the muscle. Hence, a high degree of suspicion, magnetic resonance imaging features, with nerve/muscle/skin biopsy can help in diagnosis of NIID.