Albert Stezin

Three‐dimensional neuromelanin‐sensitive magnetic resonance imaging of the substantia nigra in Parkinson's disease

The aim was to investigate the diagnostic utility of signal intensity measurement of the substantia nigra pars compacta (SNc) using three‐dimensional (3D) neuromelanin‐sensitive magnetic resonance imaging (MRI), for discrimination of patients with Parkinsons disease (PD) from healthy controls.

Implications of secondary unresponsiveness to dopaminergic drugs with preserved response to subthalamic nucleus stimulation in Parkinson's disease

Improvement in motor symptoms with levodopa is one of the hallmark features of Parkinsons disease (PD). The response to levodopa may reduce during the course of the illness. Few studies have also reported reduced response to levodopa in patients with PD several years after deep brain stimulation (DBS) of the subthalamic nucleus (STN) on both the sides. In this study, we report an extreme unresponsiveness to levodopa in the presence of a good response to STN stimulation in a patient 5 years after the DBS proceudre had been carried out. The implications of this phenomenon are also discussed.

Non-ataxic manifestations of Spinocerebellar ataxia-2, their determinants and predictors

INTRODUCTION To evaluate the non-ataxic clinical manifestations in genetically proven Spinocerebellar ataxia 2 (SCA2) and identify their determinants and predictors. METHODS Seventy-three subjects with genetically proven SCA2 were evaluated clinically for the common non-ataxic manifestations. Based on the presence or absence of non-ataxic manifestations, patients were classified into groups and then compared for significant differences in the CAG repeat length, age at onset (AAO), duration of disease, and ataxia rating score. Predictors of non-ataxic symptoms were identified using multivariable binary logistic regression. RESULTS The most common non-ataxic clinical manifestations were peripheral neuropathy, extrapyramidal features, pyramidal signs, cognitive impairment and lower motor neuron signs. The CAG repeat length was inversely related to the AAO of symptoms (r = -0.46, p < .001). Patients with peripheral neuropathy and psychiatric symptoms had earlier AAO. Patients with cognitive impairment and extrapyramidal symptoms had higher CAG repeat length whereas presence of lower motor neuron signs was more common in patients with lower CAG repeat length. CONCLUSION The lower strength of association between CAG repeat length and AAO in our cohort suggests the presence of additional factors underlying the variability in AAO. Both CAG repeat length and AAO were identified as significant determinants and predictors of non-ataxic symptoms.

Shaky and unsteady: Dynamic posturography in essential tremor

BACKGROUND The spectrum of symptoms exhibited by patients with essential tremor (ET) extends far beyond the classical tremor. This study aims to explore and establish the presence of subtle balance abnormalities in ET using dynamic posturography (DP). METHODS DP was performed on 18 patients with ET and 26 controls. Diagnosis of ET was based on the Consensus Statement of the Movement Disorder Society on Tremor. Dynamic stability which included the overall balance index, anterior-posterior index and mediolateral index, and limits of stability were measured. RESULTS Patients with ET had significantly impaired balance indices. Impairment of dynamic stability revealed poor static balance control in all directions. Lower limits of stability scores indicated a smaller range of motion prior to which patients have to shift foot balance. No correlations were observed between age at evaluation, age at onset, duration of illness and the balance indices. CONCLUSIONS Dynamic posturography reveals significant balance impairment in patients with ET which is unrelated to the age at onset, age at evaluation or duration of illness. This finding concurs with pre-existing reports and adds to the growing body evidence of cerebellar involvement in ET.

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

ObjectiveMultiple 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 methodsTwenty-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.ResultsThe 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.ConclusionIn 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.

Clinical utility of visualisation of nigrosome-1 in patients with Parkinson’s disease

AbstractObjectiveTo determine the diagnostic characteristics of poor visualisation of nigrosome-1 as a neuroimaging biomarker in Parkinson’s disease (PD) and to explore the relationship of poor visualisation of nigrosome-1 and clinical asymmetry.MethodsHigh-resolution gradient-echo sequences of 67 patients with PD and 63 healthy controls were reviewed by two radiologists blinded to the clinical details. A three-tier classification system was used to categorise the scans based on the visualisation of nigrosome-1, and inter-rater reliability was calculated at each level of classification. Other diagnostic properties such as sensitivity, specificity and predictive values were calculated. The relationship between poor visualisation of nigrosome-1 and clinical asymmetry was also assessed.ResultsPoor visualisation of nigrosome-1 had high sensitivity (98.5%), specificity (93.6%), positive-predictive value (94.3%), negative-predictive value (98.3%), accuracy (96%) and inter-rater reliability (k = 0.75–0.92). Poorly visualised nigrosome-1 was significantly associated with higher motor asymmetry in the contralateral side in 64.8% of subjects (p = 0.004).ConclusionsPoor visualisation of nigrosome-1 in PD had good diagnostic properties as a neuroimaging biomarker in PD. There was also a significant agreement on clinical asymmetry and poor visualisation of nigrosome-1.Key Points• Nigrosome-1 represents the largest collection of dopaminergic neurons in dorso-lateral substantia nigra. • Loss of nigrosome-1 is being studied as a biomarker in Parkinson’s disease. • Visualisation of nigrosome-1 had good diagnostic properties as a biomarker. • There was a contralateral relationship between nigrosome-1 lateralisation and clinical asymmetry. • We also highlight the potential limitations of nigrosome-1 visualisation as a biomarker.

Orofacial Involuntary Movements in Neurosyphilis: Beyond the Candy Sign

Background Involvement of the central nervous system in patients with syphilis (neurosyphilis) may result in several neuropsychiatric symptoms. Rarely, patients with neurosyphillis may develop movement disorders with different phenomenology. Subtle orofacial dyskinesias have been reported in patients with neurosyphilis, known as the candy sign. Case Report We describe a patient with neurosyphilis who presented with severe orofacial involuntary movements. Discussion Our patient had orofacial movements at presentation and severity of the movements was much higher than the candy sign that has been reported in patients with neurosyphilis. This report contributes towards the ever-expanding clinical spectrum of neurosyphilis.

Experience of pallidal deep brain stimulation in dystonia at a tertiary care centre in India: An initial experience

Introduction: Dystonia is one of the most prevalent forms of movement disorders and is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonia causes significant morbidity with an adverse impact on the quality of life. When dystonia is medically refractory, causing severe pain and impairment in activities of daily living, deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a potential option to reduce disability. Materials and Methods: This is a chart review of patients who underwent DBS for dystonia (from 2009 to 2015) at our tertiary referral centre. A total of ten patients (7 males, 3 females) underwent DBS for non-parkinsonian conditions. The patients were selected after failure of adequate medical management. All the patients had a severe disability with normal cognitive (Mini-Mental State Examination) and psychiatric profile. They also had to have a suitable GPi for DBS based on magnetic resonance imaging. Results: The mean baseline Burke–Fahn–Marsden dystonia movement score of the 10 patients selected for surgery was 60.3 ± 27.3 (ranging from 19 to 104). On repeated-measures analysis of variance, there was significant difference in the different time points (pre-DBS, post-DBS at 3 months, 6 months, and 1 year) F (3, 5) = 7.68, P = 0.026. The data showed that there was a maximum improvement after 1 year of stimulation (pre-DBS vs. 3 months 12.9 ± 1.9 vs 8.8 ± 2.1, P = 0.01; pre-DBS vs. 6 months 12.9 ± 1.9 vs 7.4 ± 1.6, P = 0.04; pre-DBS vs. 1 year, 12.9 ± 1.9 vs. 7 ± 2.4. Conclusion: In medically refractory primary or secondary dystonia patients, bilateral GPi DBS can be considered as an option. Patients with disabling symptoms that significantly deteriorate activities of daily life may consider DBS before these symptoms become fixed.

Impaired frontal lobe functions in patients with Parkinson’s disease and psychosis

INTRODUCTION Patients with Parkinsons disease (PD) may develop several non-motor symptoms (NMS). Psychosis is one of the debilitating NMS of PD. The neurobiology of psychosis is not fully understood. This study aims to compare the frontal lobe functions of PD patients with and without psychosis using the Frontal Assessment Battery (FAB). METHODOLOGY This study included 69 patients with PD; 34 with psychosis (PD-P) and 35 without psychosis (PD-NP). Mini Mental Status Examination (MMSE) was used to screen for cognitive impairment. Unified Parkinsons disease Rating scale part-III (UPDRS-III) was used to measure the severity and Hoehn and Yahr score (H&Y) was used to measure the stage of PD. Frontal lobe functions were assessed by FAB. RESULTS The PD-P and PD-NP groups were comparable for age (58.7±8.4 vs 55.7±8.2, p=0.14), age at onset of symptoms (51.4±8.1 vs 50.0±8.8, p=0.48), gender distribution (men: 88%vs 80%, p=0.51), MMSE (28.2±1.9 vs 28.7±1.2 p=0.12), levodopa equivalent dose/day (736.0±376.3 vs 625.2±332.2, p=0.19), UPDRS-III OFF-score (36.7±8.8 vs 35.4±13.2, p=0.64), UPDRS-III ON-score (13.2±5.4 vs 12.4±6.6, p=0.44) and H&Y stage (2.3±0.3 vs 2.3±0.3, p=0.07). PD-P group had lower total FAB score compared to PD-NP group (13.9±2.2 vs 16.5±1.8, p<0.01). On the FAB, PD-P group had lower scores compared to PD-NP in lexical fluency (FAB-2), programming (FAB-3), sensitivity to interference (FAB-4) and inhibitory control (FAB-5). CONCLUSION Patients with PD-P had significant frontal lobe dysfunction compared to PD-NP. FAB may be a simple and useful bedside tool to assess frontal dysfunction in patients with PD in a busy neurological set up.