'The phenotypic conundrum of Trp748Ser variant in POLG gene: a report of two patients'.

We present two cases of a 23-years and 32-years old female respectively, who presented with recurrent seizures, ataxia, dysarthria, psychomotor slowing. Magnetic resonance imaging (MRI) of the brain in the first patient revealed T2/FLAIR hyperintensity in the bilateral thalamus and cerebellar white matter with diffusion restriction, with no contrast enhancement. In the second patient, magnetic resonance imaging of brain showed FLAIR hyperintensity in precuneus while CSF showed raised HSV IgG titre on first presentation leading to suspicion of infective etiology. The initial differential diagnosis included autoimmune, metabolic and demyelinating causes. However, routine laboratory investigations, cerebrospinal fluid analysis, and autoimmune panel and demyelination workup were inconclusive. Considering the possibility of a genetic-mediated metabolic disorder, genetic testing was carried out leading to the identification of the Trp748Ser variation in POLG gene associated with mitochondrial DNA depletion syndrome. These cases highlight the diagnostic challenges and complexities in identifying rare metabolic encephalopathy, emphasizing the importance of a multidisciplinary approach in such cases.

Quantification and Clinical Correlation of Posterior Cranial Fossa Cerebrospinal Fluid Volume in Primary Hemifacial Spasm Using Magnetic Resonance Imaging.

BACKGROUND AND OBJECTIVE: Primary hemifacial spasm (HFS) is caused by neurovascular conflict (NVC) at the root entry zone of the facial nerve. Whether reduction of posterior cranial fossa (PCF) cerebrospinal fluid (CSF) volume is a risk factor for HFS is not clear. The study aims at the radiologic assessment of PCF CSF volume and its clinical correlation. METHODS: A cross-sectional, hospital-based, case-control study was conducted, in which 50 cases of primary HFS and 50 age- and sex-matched controls were recruited. PCF CSF volume was quantified in 3-T brain magnetic resonance imaging. RESULTS: The mean age at presentation of cases was 50.7 ± 10.7 years (42-69 years) and controls was 52.4 ± 8.7 years (45-68 years). The mean duration of symptoms was 3.5 ± 1.3 years (1.5-8 years). About 52% of patients had grade 2 (mild) severity of HFS. The mean PCF CSF volume of patients was 13,725.1 ± 909.5 mm 3 and controls was 14,458.5 ± 973.5 mm 3 ( P < 0.001). The mean PCF CSF volume of females with HFS was 13,714.8 ± 852.5 mm 3 and female controls was 14,521.8 ± 973.5 mm 3 ( P = 0.006). PCF CSF volume was significantly associated with the presence of HFS ( P = 0.007), the severity of HFS ( P < 0.001), and the presence of NVC ( P = 0.02). CONCLUSION: PCF CSF volume was lesser in HFS patients and was associated with the presence of HFS, the severity of HFS, and the presence of NVC. Females with HFS had smaller PCF CSF volume. Small PCF CSF volume is a risk factor for HFS, particularly in females with HFS.

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.

Association of Insulin-like Growth Factor-1 and Neurofilament Light Chain in Patients with Progressive Supranuclear Palsy.

Background: Progressive supranuclear palsy (PSP) is the most common primary tauopathy. The definite diagnosis of PSP is established by histopathologic changes in the brain. There are no reliable blood-based biomarkers to aid the diagnosis of this fatal disease at an early stage. Also, the precise etiopathology of PSP and its variants is inadequately understood. Objective: Blood-based molecules such as neurofilament light chain (NfL) and insulin-like growth factor-1 (IGF-1) are shown as important markers of neurodegenerative and aging processes, respectively. These two biomarkers have not been analyzed simultaneously in PSP patients. Methods: To address this knowledge gap, 40 PSP patients and equal number of healthy individuals were recruited and serum levels of NfL and IGF-1 were assayed in all the study participants by enzyme-linked immunosorbent assay (ELISA). Motor and nonmotor symptoms were evaluated in PSP patients using various scales/questionnaires. Cardiac autonomic function tests were performed in a subset of patients (n = 27). Results: A significantly high serum level of NfL (P < 0.01) and a reduced level of IGF-1 (P = 0.02) were observed in PSP patients compared to healthy controls. Besides, a negative correlation (r = -0.54, P < 0.01) between NfL and IGF-1 levels was observed in PSP patients. Conclusion: The finding of this study reinforces the important role of blood NfL level as a potential biomarker of PSP. Further, the current study provides novel insights into the reciprocal correlation between NfL and IGF-1 in PSP patients. Combined analysis of blood levels of these two functionally relevant markers might be useful in the prediction and diagnosis of PSP.

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.

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.

Child Neurology: Mucopolysaccharidosis IIID: Evidence From Ultrastructural and Genomic Study.

Mucopolysaccharidosis IIID (MPS IIID/Sanfilippo syndrome D, OMIM # 252940) is an autosomal recessive lysosomal storage disorder (LSD) and the rarest form of the mucopolysaccharidosis (MPS) III subtypes. It is caused by sequence variations in the gene encoding lysosomal enzyme N-acetyl glucosamine-6-sulphatase (GNS). Deficiency of GNS impairs catabolism of glycosaminoglycans causing accumulation of heparan sulphate within lysosomes of various tissues, which is visualized as membranous cytoplasmic bodies (MCBs) on electron microscopy. The recognition of this ultrastructural feature in a muscle biopsy instigated genetic evaluation for LSD in our case resulting in the detection of a novel pathogenic GNS gene variant. The patient also exhibited intellectual disability since childhood, reduced vision due to pigmentary retinopathy, and behavioral abnormalities without other systemic features of MPS. In this study, we report a patient of Indian origin with MPS IIID based on a novel pathogenic variant c.1078 G>T (p.G360C) in the GNS and the presence of MCBs in muscle biopsy, characterized by several novel findings including the occurrence of pigmentary retinopathy, which extends the clinical spectrum of MPS IIID.

Olfactory Bulb Volume, Olfactory Sulcus Depth in Parkinson's Disease, Atypical Parkinsonism.

Background: About 70-90% of Parkinson's disease (PD) patients have olfactory deficits which is considered as pre-motor symptom of PD. Lewy bodies have been demonstrated in the olfactory bulb (OB) in PD. Objective: To assess the OB volume (OBV), olfactory sulcus depth (OSD) in PD and compare with progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and vascular parkinsonism (VP) patients and determine the cut-off volume of OB that will aid in the diagnosis of PD. Methods: This was a cross-sectional, hospital based, single-center study. Forty PD, 20 PSP, 10 MSA, 10 VP patients and 30 controls were recruited. OBV and OSD was assessed using 3-T magnetic resonance imaging (MRI) brain. Olfaction was tested using Indian Smell Identification test (INSIT). Results: The mean total OBV in PD was 113.3 ± 79.2 mm3 and 187.4 ± 65.0 mm3 in controls (P = 0.003) which was significantly lower in PD. The mean total OSD in PD was 19.4 ± 8.1 and 21.1 ± 2.2 mm in controls (P = 0.41) with no difference. The mean total OBV was significantly lower in PD as compared to that of PSP, MSA and VP patients. There was no difference in the OSD among the groups. The total OBV in PD had no association with age at onset, duration of disease, dopaminergic drugs dosage, motor and non-motor symptoms severity but had positive correlation with cognitive scores. Conclusion: OBV is reduced in PD patients as compared to PSP, MSA, VP patients and controls. OBV estimation by MRI adds to the armamentarium in the diagnosis of PD.