The purpose of this reply is to address the comments given by Kelly et al. on our original paper "Unique Brain Network Identification Number for Parkinson's and Healthy Individuals using Structural MRI". We agree to the inadvertent rounding pitfall in our original paper due to the non-inclusion of symbolic math toolbox (MATLAB). We now provide the actual ranges (with decimal values) of the UBNIN values of healthy individuals and those with Parkinson's disease and further observations. Upon further introspection, we propose another variant, called Modified-UBNIN (UBNIN-MT,MN) which is highly weighted on the node with the highest network degree (i.e., connections). The italicized sentences within inverted commas are statements from Kelly et al.'s comment paper.
BACKGROUND: Diffuse intrinsic pontine gliomas are aggressive tumors that carry a poor prognosis with a 2-year survival rate of <10%. The imaging appearance is often pathognomonic, and surgical biopsy is not mandatory to initiate treatment in children. Studies of biopsy samples provide insight into the disease's molecular pathobiology and open prospects for targeted therapy. This study was conducted to determine the diagnostic yield and safety of stereotactic biopsies. METHODS: This is a prospective observational study from a single tertiary health care center. All patients with clinical and radiological features diagnostic of diffuse intrinsic pontine gliomas (DIPGs) who underwent biopsy from July 2018 to June 2023 were included. Biopsies were performed using either stereotactic frame-based, frameless, or endoscopic techniques. RESULTS: A total of 165 patients with DIPGs were evaluated in the study period. The option of biopsy with its associated risks and benefits was offered to all patients. A total of 76 biopsies were performed in 74 patients (40 children and 34 adults, including 2 repeat biopsies). The median age was 15 years. Diffuse midline gliomas, H3K27M altered, was the most common histopathological diagnosis (85% pediatric and 55.9% adults). The diagnostic efficacy of the procedure was 94.7%. The complication rate was 10.8%, with no permanent neurological deficits due to surgery. There was no procedure-related mortality. CONCLUSIONS: Establishing the safety of the procedure could be an important step toward popularizing the concept, which might offer a better understanding of the disease. Brainstem eloquence and a lack of direct benefit to patients are the primary obstacles to brainstem biopsy.
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.
Background: Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra. SPECT imaging using technetium-99m [99mTc] labeled trodat is the choice of imaging to differentiate PD from its other forms like drug-induced PD. Aims and Objectives: The main objective of our study was to prepare in-house sterile formulation of [99mTc]Tc-trodat and use in clinics. Materials and Methods: The labeling of trodat was standardized using glucoheptonate sodium salt (GHA), stannous chloride dihydrate (in 0.05 N HCl), and ethylenediaminetetraacetic acid (Na-EDTA). The preparation was mixed and autoclaved at 15 psi for 15 min. The standardised formulation was stored at 4°C, -20°C and -80°C and labeling with 99mTc was tested for up to 6 days. The radiochemical purity, chemical impurities, and endotoxin levels were tested. The frozen formulation was tested in swiss mice (n = 3) for biodistribution studies at 4 h. Around 18 ± 2 mCi was injected intravenously in each patient (n = 5) and the image was acquired at 4 h post-injection. Results: The radiochemical purity of the preparation was 98.3 ± 1.4% with a retention time of 16.8 ± 1.5 min as compared to 4.0 ± 0.5 min for free 99mTc. Animal distribution showed highest uptake in liver and dual excretion via hepatobiliary and renal system. [99mTc]Tc-trodat imaging was able to differentiate both caudate and putamen. Conclusions: In-house frozen preparation was advantageous, as it has decreased the chance of manual error as compared to daily make up formulations and economical as compared to commercially available kits.
PURPOSE: Subacute sclerosing panencephalitis (SSPE) is a fatal neurological disorder resulting from persistent measles virus infection within the brain. Although neurological manifestations have been well-documented, the impact of SSPE on cardiac autonomic function, assessed through heart rate variability (HRV), remains understudied. METHODS: In this prospective single-center study conducted from January 2022 to March 2023 in Southern India, 30 consecutive SSPE patients and age- and sex-matched controls underwent electrocardiogram recordings for HRV analysis. Various HRV parameters were assessed, including time-domain metrics (SD of normal-to-normal intervals, root mean square of successive differences between normal heartbeats, percentage of successive normal interbeat intervals greater than 50 msec), SD1 and SD2 for Poincaré plot analysis, and frequency-domain metrics (low frequency %, high frequency %, low frequency:high frequency ratio). RESULTS: In the study, SSPE patients exhibited markedly reduced HRV. Specifically, SD of normal-to-normal intervals (P = 0.003), percentage of successive normal interbeat intervals greater than 50 msec (P = 0.03), and SD2 (P = 0.0016) were significantly lower compared with controls. Frequency-domain analysis did not reveal significant distinctions. Correlation analysis demonstrated a negative relationship between percentage of successive normal interbeat intervals greater than 50 msec and SSPE severity (r = -0.37, P = 0.042). Heart rate variability did not significantly differ between SSPE stages or with clinical variables. The interbeat interval range showed a narrower distribution in SSPE subjects. CONCLUSIONS: Our study highlights the clinical relevance of HRV analysis in SSPE and autonomic dysfunction throughout the disease course underscoring its importance in SSPE. This investigation provides valuable insights into cardiac autonomic dysfunction probably because of affliction of the central autonomic networks caused by the disease process and may be a contributing factor to mortality in SSPE.
Background: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by bi-allelic pathogenic variants in CYP27A1 gene that results in the deposition of cholestanol in the eyes, tendons, soft tissues and nervous system leading to cataracts, xanthomas, and various neuropsychiatric manifestations. The aim of our study is to describe the clinical, radiological and genetic profile of patients with CTX. Methods: This is a retrospective chart review of patients with CTX diagnosed based on classical clinical and radiological findings. The available clinical details, and investigations, including imaging, electrophysiological, pathological and genetic data, were documented. Results: Five patients (4 males) were recruited in the study. The median age at presentation was 32 years (range: 21-66 years). Walking difficulty was the most common symptom at presentation. All patients had cataracts, tendon xanthomas, eye movement abnormalities, dysarthria, pyramidal signs, ataxia and gait abnormality. Dystonia was noted in three patients. Palatal tremor and parkinsonism were noted in one patient each. In MRI brain, dentate, and corticospinal tract involvement were the most frequent imaging findings. Bilateral hypertrophic olivary degeneration was noted in one patient and hot cross bun sign in two. Three patients underwent genetic testing and all had pathogenic variants confirming the diagnosis. Discussion: CTX is a rare treatable disorder. Apart from the usual neurological presentation with spastic-ataxia, it can present at a later age with parkinsonism. Typical patterns of imaging findings are helpful in early diagnosis which aids in the treatment to prevent the neurological sequelae of the disease.
Cataract , Cerebellar Ataxia , Parkinsonian Disorders , Xanthomatosis, Cerebrotendinous , Xanthomatosis , Male , Humans , Young Adult , Adult , Middle Aged , Aged , Xanthomatosis, Cerebrotendinous/diagnosis , Cholestanetriol 26-Monooxygenase/genetics , Cholestanetriol 26-Monooxygenase/therapeutic use , Retrospective Studies , Rare Diseases
Tremor dominant Parkinson's disease (TDPD) and essential tremor plus (ETP) syndrome are commonly encountered tremor dominant neurological disorders. Although the basal ganglia thalamocortical (BGTC) and cerebello thalamocortical (CTC) networks are implicated in tremorogenesis, the extent of functional connectivity alterations across disorders is uncertain. This study aims to evaluate functional connectivity of the BGTC and CTC in TDPD and ETP. Resting state functional MRI was acquired for 25 patients with TDPD, ETP and 22 healthy controls (HC). Following pre-processing and denoising, seed-to-voxel based connectivity was carried out at FDR < 0.05 using ROIs belonging to the BGTC and CTC. Fahn-Tolosa-Marin tremor rating scale (FTMRS) was correlated with the average connectivity values at FDR < 0.05. Compared to HC, TDPD showed decreased connectivity between cerebellum and pre, post central gyrus. While, ETP showed decreased connectivity between pallidum and occipital cortex, precuneus, cuneus compared to HC. In comparison to ETP, TDPD showed increased connectivity between precentral gyrus, pallidum, SNc with the default mode network (DMN), and decreased connectivity between cerebellum with superior, middle frontal gyrus was observed. Tremor severity positively correlated with connectivity between SNc and DMN in TDPD, and negatively correlated with pallidal connectivity in ETP. Pattern of BGTC, CTC involvement is differential i.e., higher connectivity of the BGTC nodes in TDPD, and higher connectivity of cerebellar nodes in ETP. The interesting observation of pallidal involvement in ETP suggests the role of BGTC in the pathogenesis of ETP, and indicated similarities in concepts of tremor genesis in TDPD and ETP.
BACKGROUND: Almost one-fifth of patients undergoing surgery for sellar/supra-sellar tumors do not gain a significant improvement in their vision. Various methods have been described to predict prospective visual outcomes in them, although they lack uniformity. OBJECTIVE: The study was conducted to predict visual outcomes following surgery for sellar and supra-sellar tumors compressing the anterior optic pathway based on pre-operative optical coherence tomography (OCT) parameters. METHODS AND MATERIALS: This was a record-based observational descriptive longitudinal study done in a tertiary care center in India. Thirty-seven patients (74 eyes) diagnosed with sellar supra-sellar lesions were included in the study. Patients' ophthalmic evaluations, done pre-operatively and 3 months post-operatively, were reviewed. Spectral-domain OCT and segmentation were done using the automated segmentation technology of Spectralis software. The thickness of the respective layers was measured. RESULTS AND CONCLUSIONS: The mean age of the study population was 42.68 years. Eyes with a pre-operative visual acuity component of VIS (visual impairment score) ≤61, pre-operative ganglion cell layer thickness ≥26.31 um, a pre-operative inner plexiform layer thickness of ≥25.69 um, a pre-operative ganglion cell inner plexiform layer thickness of 52.00 um, pre-operative ganglion cell complex thickness ≥84.47 µm, and a pre-operative inner retinal layer thickness of ≥205.25 µm were more likely to have an improved visual outcome. Eyes with a pre-operative duration of visual symptoms of ≥15 months, VIS ≥126.50, a pre-operative decimal visual acuity of <0.035, a pre-operative visual field index of ≤8%, a pre-operative macular thickness of ≤287.06 um, a pre-operative macular RNFL (retinal nerve fiber layer) thickness ≤66.00 µm, and a pre-operative peri-papillary RNFL thickness ≤64.62 µm were unlikely to have visual improvement.
Skull Base Neoplasms , Tomography, Optical Coherence , Humans , Adult , Longitudinal Studies , Prospective Studies , Retina/diagnostic imaging , Retina/surgery
Background: Amino acid positron emission tomography (PET) imaging plays a significant role in the diagnosis of gliomas and in differentiating tumor recurrence from necrosis. In this study, the authors have evaluated the diagnostic efficacy of [99mTc]Tc-methionine single-photon emission computed tomography-computed tomography (SPECT-CT) in comparison with [11C]methionine PET-magnetic resonance imaging (MRI) in delineating tumors. Methods: Thirty-one (primary: 16 and postoperative: 15) patients of confirmed (either MRI or histopathological proven) glioma underwent both [99mTc]Tc-methionine SPECT-CT and [11C]methionine PET-MRI. A comparative analysis was performed between SPECT, PET, and MR images to calculate the concordance between the modalities and to evaluate the diagnostic efficacy of the [99mTc]Tc-methionine SPECT. Results: [99mTc]Tc-methionine SPECT showed comparable uptake in the tumor lesions in comparison to [11C]methionine PET. A significant and strong positive correlation was observed between the volume of tumor (Vt) in PET and Vt MR (p < 0.004). Likewise, a significant and strong positive correlation was found between Vt SPECT and Vt MR. [99mTc]-methionine has a sensitivity and specificity of 91% and 75%, respectively, compared with 82% and 100% for [11C]methionine in postoperative cases to differentiate the tumor recurrence from necrosis. The sensitivity and specificity of [99mTc]Tc-methionine was 92% and 100%, respectively, compared with 92% and 67% for [11C]methionine in primary tumors. Conclusion: [99mTc]Tc-methionine SPECT-CT is as equally good as [11C]methionine for diagnosing and differentiating it from necrosis especially in high-grade glioma.
The incidence of tubercular tenosynovitis around the foot and ankle is rare even in endemic areas. We present an unusual case involving the isolated tubercular tenosynovitis of the Anterior Tibial tendon, which was successfully managed through a combination of medical treatment and endoscopic intervention. Our patient, a 30-year-old female, sought medical attention due to a gradually worsening painful swelling localized to the anterior aspect of her left ankle. Diagnostic imaging, specifically Magnetic Resonance Imaging (MRI), revealed alterations in signal intensity within the Anterior Tibial tendon. Importantly, the infection had not spread to involve the ankle joint. We performed both diagnostic and therapeutic tenosynovectomy endoscopically and subsequently sent the tissue for histopathological examination. The histopathological findings revealed the presence of histiocytic granulomas containing Langhans' giant cells, which strongly suggested a tuberculosis infection. Consequently, we initiated anti-tubercular chemotherapy as the treatment approach. Our patient exhibited a positive response to the treatment, and after one year, she experienced complete resolution of the disease. This case underscores the importance of maintaining a high level of clinical suspicion for tuberculosis, especially in endemic areas, when encountering unusual presentations. Level of evidence: V.
BACKGROUND: Free water (FW)-corrected diffusion measures are more precise compared to standard diffusion measures. This study comprehensively evaluates FW and corrected diffusion metrics for whole brain white and deep gray matter (WM, GM) structures in patients with Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) and attempts to ascertain the probable patterns of WM abnormalities. METHOD: Diffusion MRI was acquired for subjects with PD (n = 133), MSA (n = 25), PSP (n = 30) and matched healthy controls (HC) (n = 99, n = 24, n = 12). Diffusion metrics of FA, MD, AD, RD were generated and FW, corrected FA maps were calculated using a bi-tensor model. TBSS was carried out at 5000 permutations with significance at p < 0.05. For GM, diffusivity maps were extracted from the basal ganglia, and analyzed at an FDR with p < 0.05. RESULTS: Compared to HC, PD showed focal changes in FW. MSA showed changes in the cerebellum and brainstem, and PSP showed increase in FW involving supratentorial WM and midbrain. All three showed increased substantia nigra FW. MSA, PSP demonstrated increased FW in bilateral putamen. PD showed increased FW in left GP externa, and bilateral thalamus. Compared to HC, MSA had increased FW in bilateral GP interna, and left thalamic. PSP had an additional increase in FW of the right GP externa, right GP interna, and bilateral thalamus. CONCLUSION: The present study demonstrated definitive differences in the patterns of FW alterations between PD and atypical parkinsonian disorders suggesting the possibility of whole brain FW maps being used as markers for diagnosis of these disorders.
Brain , Multiple System Atrophy , Parkinson Disease , Supranuclear Palsy, Progressive , Humans , Parkinson Disease/diagnostic imaging , Male , Female , Aged , Middle Aged , Supranuclear Palsy, Progressive/diagnostic imaging , Multiple System Atrophy/diagnostic imaging , Brain/diagnostic imaging , Brain/pathology , Diffusion Magnetic Resonance Imaging/methods , Parkinsonian Disorders/diagnostic imaging , Water , White Matter/diagnostic imaging , White Matter/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology
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.
Disruptive, Impulse Control, and Conduct Disorders , Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Parkinson Disease/drug therapy , Disruptive, Impulse Control, and Conduct Disorders/diagnostic imaging , Disruptive, Impulse Control, and Conduct Disorders/etiology , Impulsive Behavior , Brain , Atrophy
Objective. Delineating Parkinson's disease (PD) into distinct subtypes is a major challenge. Most studies use clinical symptoms to label PD subtypes while our work uses an imaging-based data-mining approach to subtype PD. Our study comprises two major objectives - firstly, subtyping Parkinson's patients based on grey matter information from structural magnetic resonance imaging scans of human brains; secondly, comparative structural brain connectivity analysis of PD subtypes derived from the former step.Approach. Source-based-morphometry decomposition was performed on 131 Parkinson's patients and 78 healthy controls from PPMI dataset, to derive at components (regions) with significance in disease and high effect size. The loading coefficients of significant components were thresholded for arriving at subtypes. Further, regional grey matter maps of subtype-specific subjects were separately parcellated and employed for construction of subtype-specific association matrices using Pearson correlation. These association matrices were binarized using sparsity threshold and leveraged for structural brain connectivity analysis using network metrics.Main results. Two distinct Parkinson's subtypes (namely A and B) were detected employing loadings of two components satisfying the selection criteria, and a third subtype (AB) was detected, common to these two components. Subtype A subjects were highly weighted in inferior, middle and superior frontal gyri while subtype B subjects in inferior, middle and superior temporal gyri. Network metrics analyses through permutation test revealed significant inter-subtype differences (p < 0.05) in clustering coefficient, local efficiency, participation coefficient and betweenness centrality. Moreover, hubs were obtained using betweenness centrality and mean network degree.Significance. MRI-based data-driven subtypes show frontal and temporal lobes playing a key role in PD. Graph theory-driven brain network analyses could untangle subtype-specific differences in structural brain connections showing differential network architecture. Replication of these initial results in other Parkinson's datasets may be explored in future. Clinical Relevance- Investigating structural brain connections in Parkinson's disease may provide subtype-specific treatment.
Parkinson Disease , Humans , Parkinson Disease/diagnostic imaging , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Gray Matter/diagnostic imaging
Charcot-Marie-Tooth disease 4H(CMT4H) is an autosomal recessive demyelinating form of CMT caused by FGD4/FRABIN mutations. CMT4H is characterized by early onset and slowly progressing motor and sensory deficits in the distal extremities, along with foot deformities. We describe a patient with CMT4H who presented with rapidly progressing flaccid quadriparesis during the postpartum period, which improved significantly with steroid therapy. Magnetic resonance imaging and ultrasonography demonstrated considerable nerve thickening with increased cross-sectional area in the peripheral nerves. A nerve biopsy revealed significant demyelination and myelin outfolding. This is the first report of an Indian patient with a novel homozygous nonsense c.1672C>T (p.Arg558Ter) mutation in the FGD4 gene, expanding the mutational and phenotypic spectrum of this disease.
Charcot-Marie-Tooth Disease , Female , Humans , Charcot-Marie-Tooth Disease/genetics , Charcot-Marie-Tooth Disease/pathology , Microfilament Proteins/genetics , Pedigree , Mutation , Phenotype , Guanine Nucleotide Exchange Factors/genetics
PURPOSE: Study assessed the role of MSI in predicting the post-operative seizure outcome. METHODS: This retrospective study included patients who underwent MEG and epilepsy surgery and had a minimum 6 months of postoperative follow-up. Concordance of MEG cluster with post-surgical resection cavity was classified as follows Class I) Concordant and region-specific, Class II) Concordant and region non-specific, Class III) Concordant lateralization only and Class IV) Discordant lateralization. The relationship between MSI concordance and post-operative seizure outcome was assessed. RESULTS: A total of 183 patients (M: F = 109:74) were included. The mean age at onset of seizures: 8.0 ± 6.4 years. The dipoles were frequent in 123(67.2 %). The primary cluster orientation was regular in 59 (32.2 %) and mixed in 124 (67.8 %) patients. Concordance between MEG and resection cavity: Class I - 124 (67.8 %), class II- 30 (16.4 %), class III- 23 (12.6 %), and class IV- 6 (3.3 %). The post-surgically mean duration of follow-up was 19.52 ± 11.27 months. At 6-month follow-up period, 144 (78.7 %) patients had complete seizure freedom out of which 106 (73.6 %) had class I concordance. Concordance of MEG with resection cavity was associated with a good outcome at 6 months (p = 0.001), 1 year (p = 0.001), 2 years (p = 0.0005) and 5 years (p = 0.04). MEG cluster characteristics had no association with seizure outcome except the strength of the cluster and outcome at 3 years (p = 0.02) follow-up. CONCLUSION: The study supports that the complete resection of the MEG cluster had high chance of seizure-freedom and can be used as a complementary noninvasive presurgical evaluation tool.
Electroencephalography , Magnetoencephalography , Humans , Infant , Child, Preschool , Child , Adolescent , Retrospective Studies , Treatment Outcome , Seizures/diagnosis , Seizures/surgery , Magnetic Resonance Imaging
OBJECTIVE: Symptomatic developmental venous anomalies (DVAs) are rare. Here, we illustrate the varied clinicoradiologic profiles of symptomatic DVAs and contemplate the mechanisms that render these (allegedly) benign entities symptomatic supported by a review of literature. METHODS: Institutional databases were searched to identify cases of symptomatic DVAs. Clinical and imaging (angiographic and cross-sectional) data of 9 cases with 11 neurovascular symptoms consequent to inflow/outflow perturbations and mechanical obstruction that manifested because of the strategic topography of underlying DVAs were analyzed. A review of the existing literature on DVAs in agreement with our case series was performed on publications retrieved from the PubMed database. RESULTS: Symptoms secondary to venous hypertension arising from flow-related perturbations were broadly divided into those arising from restricted outflow and increased inflow. Restricted outflow occurred because of collector vein stenosis (n = 2) and collector vein/DVA thrombosis (n = 3), whereas the latter pathomechanism was initiated by arterialized/transitional DVAs (n = 2). A mechanical/obstructive pathomechanism culminating in moderate supratentorial ventriculomegaly was noted in 1 case. One patient was given a diagnosis of hemorrhage associated with a cavernoma. CONCLUSIONS: Awareness and contextualization of potential flow-related perturbations and mechanical insults that render DVAs symptomatic aid in accurate diagnosis, management, and prognostication.
Cerebral Veins , Hemangioma, Cavernous , Hydrocephalus , Humans , Cross-Sectional Studies , Angiography , Constriction, Pathologic/complications , Cerebral Veins/diagnostic imaging , Magnetic Resonance Imaging
