The collective evidence to date suggests that environmental exposure to excessive amounts of manganese (Mn) can cause a neurodegenerative condition known as manganism. It is now also relatively clear that Mn is involved in the pathogenesis of Alzheimer's disease and at least some prion diseases. The potential involvement of Mn in a panel of other neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Batten disease has been suggested and investigated, but the results to date are somewhat inconclusive. Herein, previously reported experimental studies investigating the involvement of Mn in the pathogenesis of these conditions are narratively reviewed.

Background and Purpose: Epidemiological studies on the extent of the interaction and/or influence of stroke severity on clinical outcomes are important. The aim of the present study was to investigate the putative (and degree of) impact of initial stroke severity in predicting the overall functional outcome, in-hospital placement, and mortality in acute ischemic stroke (AIS) in comparison with age, admission to the stroke unit and thrombolytic treatment. Materials and Methods: The John Hunter Hospital acute stroke register was used to collect a retrospective cohort of AIS patients being assessed for reperfusion therapy and admitted between January 2006 and December 2013. Univariate and multivariate logistic regression and receiver operating characteristics analyses were used to assess associations with functional outcome, in-hospital placement, and mortality at 90 days. Results: 608 AIS patients with complete datasets were included in the study. On univariate analysis, initial stroke severity showed the strongest independent association to the risk of death within 90 days (Odds ratio (OR) =1.15; P < 0.001; 95% confidence interval (CI) = [1.11, 1.18]); age was a less significant independent influence (OR = 1.02; P = 0.049; 95% CI = [1.00, 1.03]). Multivariate logistic regression analysis demonstrated that initial stroke severity independently predicted the 90 day mortality (OR = 1.16; 95% CI = [1.12, 1.2]; P < 0.0001) and unfavorable outcome (OR = 1.16; 95% CI = [1.13, 1.2]; P < 0.0001). Higher National Institute of Health Stroke Scale at admission was significantly associated with longer in-hospital placement (P < 0.0001). Conclusions: In this acute stroke cohort, initial stroke severity had a major impact on the likelihood of death following an AIS and appears to be the dominant influence on the overall stroke outcome and in-hospital placement.

Aims: We studied the referral practice, reporting standards, and the impact of 123 ioflupane single photon emission computed tomogram dopamine transporters (DAT-SPECT) scans conducted for the diagnosis and clinical management of patients. Settings and Designs: The present study was a retrospective, non-interventional study. Materials and Methods: We assessed the DAT scan referral and the official reports available from the Nuclear Medicine Department of the Mater Misericordiae University Hospital over 1 year (2013). We also assessed the impact of the DAT scan result on the management of patients by analyzing patient records. The European Association of Nuclear Medicine Neuroimaging (EANM) 2010 and the Federal Drug Administration (FDA) 2012 guidelines were taken as the standard against which the quality of our DAT scans reporting was assessed. Statistical Methods: Microsoft Excel 2010 and graphpad software were used for statistical analysis. Results: Twenty five (56.2%) out of a total of 48 DAT scans were performed to confirm early Parkinson's disease, 5 (8.9%) were done to exclude drug-induced parkinsonism, and 8 (14.3%) to distinguish essential tremor from parkinsonism; 2 scans were performed to distinguish Lewy body diseases from Alzheimer's dementia, and 4 indications were outside the recommended guidelines. Twelve out of the 26 (46%) abnormal scans had bilateral abnormalities. Twenty one out of the 25 DAT scans proved the clinical diagnosis of degenerative parkinsonism to be correct. Conclusion: The overall compliance of the DAT imaging with the existing standard guidelines was good. DAT scan can be very useful in clinical practice because it influences the clinical diagnosis and management in 23% of the patients.

Background: 'Wearing off' refers to the phenomenology of movement disorders in Parkinson's disease (PD) that appears early and is much commoner than generally believed. It may be present in the form of either motor symptoms or non-motor symptoms. Aim: To investigate the utility of wearing-off questionnaire (WOQ-19, Italian version) in the outpatient clinical practice to assess the suitability of different combinations of treatment, in various stages of PD. Methods: 73 consecutive patients (58% male and 42% female) suffering from PD were recruited through the Santorso Hospital and San Martino Hospital from September 2012 to March 2014. The patients were asked to indicate whether or not they experienced any of the 19 symptoms listed in the questionnaire during the day; if one or more of these referred symptoms relating to PD improved after taking an additional dose of levodopa; and, if these variations were present routinely. Furthermore, we also evaluated the possible correlation between the presence of motor and non-motor symptoms that were listed in the WOQ 19 with the motor impairment assessed by the Hoehn and Yahr stage (HY) and the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor section, in the whole patient cohort as well as in different subgroups undergoing therapy. Results: Among the 73 patients, 22% were receiving levodopa (a mean daily dose of 300 ± 121.3 mg), 38.3% levodopa and dopamine agonists, 12.3% levodopa/rasagiline, 8.2% levodopa/selegiline, and 19.2% a combination of levodopa/dopamine agonists (DA)/monoamine oxidase inhibitors (MAOI). The most prevalent symptoms were the non-motor symptoms included in the WOQ-19. A significant correlation between the scores obtained on the different motor and non-motor items recorded by the WOQ-19 and the UPDRS motor section and HY scores was found. The therapeutic benefit was especially related to the motor symptoms. Discussion: In clinical practice, this simple and easily administered questionnaire may be useful for the early detection of fluctuations in symptomatology in patients with PD. It will, therefore, help to improve the quality of the global care of patients with PD detected in various stages of the disease.

Background: Headache is common in communities; however, epidemiological research regarding its prevalence is infrequent in India. Aim: We planned to study the prevalence of migraine, its disease burden, and the associated risk factors. Setting and Design: This is an urban community study conducted in Kolkata with a cross-sectional and nested case-control design. Materials and Methods: The criteria to study headache among a representative sample (aged 20–50 years) was based on the International Classification of Headache Disorders-II. Sex- and age-matched controls without headache were evaluated for putative risk factors. The disease burden was measured as disability adjusted life years (DALY). Results: Screening of 2421 individuals revealed that the 1-year prevalence of migraine was 14.12%. Education, environmental exposure, travel, and oral contraceptives determine approximately 75% of the underlying risks. DALY showed maximum burden among women in the age range of between 30 and 34 years. Conclusion: The community-based prevalence of migraine in India is similar to that observed in other countries except Africa. The burden was maximum among women. The risk factors responsible for migraine should be addressed and institution of public health measures are warranted.

Background: Central nervous system (CNS) vasculitis is an uncommon disease, which is a diagnostic and therapeutic challenge for physicians. Large and medium vessel vasculitis is relatively easy to diagnose by angiogram compared to small vessel vasculitis, where angiograms are often normal; imaging features described till date are sensitive but not specific. Purpose: Here, we describe distinct magnetic resonance (MR) imaging features of CNS small vessel vasculitis. Materials and Methods: Five histologically proven small vessel vasculitis cases were retrospectively reviewed from medical records between January 2008 to July 2012. Angiogram (magnetic resonance angiography in all and digital subtraction angiography in three patients) were normal, ruling out associated large and medium vessel vasculitis. The MR imaging findings were analyzed for T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities and blooming on susceptibility weighted imaging (SWI). Results: Five patients (3 males) with a mean age of 34.2 years (range: 18 to 62 years) were included for analysis. Three patients with lymphocytic vasculitis had 43 discrete T2/FLAIR hyperintense lesions in brain parenchyma. All the brain lesions revealed central areas of SWI blooming in linear and/or lace-like pattern, surrounded by FLAIR hyperintensity. Corresponding T1-weighted contrast-enhanced images revealed subtle linear and lace-like enhancement. Coarse granular pattern of SWI blooming was seen in the patient with tuberculous vasculitis and no parenchymal abnormalities were seen in the patient with hypertrophic pachymeningitis. Conclusions: The linear SWI blooming along the course of small cerebral vessels and lace-like enhancement pattern in spin echo post-contrast T1-weighted sequences are suggestive MR imaging features for lymphocytic CNS small vessel vasculitis.

Background: Even after decades of research in the field of gliomas, the overall prognosis is still quite dismal. Several factors have been proposed that affect the outcome and survival length of patients with a glioma. Here, we present a series of 471 patients, who underwent surgical resection of their glioma at a tertiary level neurosurgical centre. Materials and Methods: We noted retrospective data of patients' age, histological tumor grade, and whether or not intraoperative magnetic resonance imaging (MRI) was used, and assessed the survival length of these patients from the day of surgery. Results: The overall survival in our series was approximately 14 months. Predictably, those with age less than 40 years and those with Karnofsky performance score (KPS) ≥80 had longer survival than those with a higher age and KPS <80; those with World Health Organisation (WHO) grade IV lesions had the shortest survival length compared to all the other grades. However, while comparing survival among other tumor grades, we did not find significant difference. Further, use of intraoperative MRI did not offer any statistically significant difference in survival. Conclusion: In addition to the conventional prognostic factors we need more definate ways to accurately predict survival in patients harbouring a glioma. Probably, assessing molecular characteristics of the individual tumors, such as presence of isocitrate dehydrogenase (IDH) mutation versus wild-type IDH, would help us in predicting survival more accurately.

Objective: Among newer neuroprotectant modalities, hypothermia and progesterone have shown a beneficial role in preliminary studies enrolling patients with severe traumatic brain injury (sTBI). The primary objective of this study was to evaluate the efficacy of progesterone with or without prophylactic hypothermia in acute sTBI patients. Materials and Methods: This is a prospective, outcome assessor, statistician blinded, randomized, and placebo-controlled phase II trial of progesterone with or without hypothermia (factorial design). All adult patients (18–65 years) with acute sTBI (Glasgow coma score of 4–8) and presenting to trauma center within 8 h after injury were included in the trial. Computer-generated randomization was done after exclusion; sequentially numbered, opaque, sealed envelope technique was used for allocation concealment. The enrollment duration was from January 2012 to October 2014. The primary endpoint was dichotomized Glasgow outcome score (GOS) [poor recovery = GOS 1–3; good recovery = GOS 4–5], and secondary endpoints were functional independence measure (FIM) score and mortality rate at 6 and 12 months follow-up after recruitment. Results: A total of 107 patients were randomized into four groups (placebo [n = 27], progesterone [n = 26], hypothermia alone [n = 27], and progesterone + hypothermia [n = 27]). The study groups were comparable in baseline parameters except for a higher incidence of decompressive craniectomy in the placebo group (P = 0.001). The analysis of GOS at 6 months revealed statistically significant better outcome in the hypothermia group (82%; P = 0.01) and a weaker evidence for progesterone group (74%; P = 0.07) as compared with the placebo group (44%). However, the outcome benefit was marginal at 1-year follow-up for the hypothermia group (82% vs. 58%, P = 0.17). The adjusted odds ratio of poor recovery at 6 months in the hypothermia group was 0.21 (confidence interval = 0.05–0.84, P = 0.03), as compared with the placebo group. Although mean FIM scores at 6 and 12 months respectively were marginally higher in the hypothermia and progesterone groups compared with the placebo group (P = 0.06 and 0.27), the proportion of functionally independent individuals were similar in all the groups (P = 0.79 and 0.51). The mortality rates were similar in all the groups at 6 and 12 months (P = 0.78 and 0.52 respectively). Conclusions: A strong evidence for prophylactic hypothermia and a weak evidence for progesterone therapy was observed for a better primary outcome at 6 months as compared to the placebo. A similar trend was observed at a 1-year follow-up. Contrary to our hypothesis, prophylactic hypothermia therapy suppressed the beneficial effects of progesterone therapy in sTBI patients. The complex cascades of factors responsible for such interactions are still unknown and need to be further determined.

Background: Patients with acromegaly have 2–3 times the expected mortality rates primarily due to cardiovascular risks. Echocardiographic studies showing improvement of cardiac function following transsphenoidal surgery (TSS) are limited. Materials and Methods: All patients with acromegaly underwent preoperative echocardiography and tissue Doppler (Philips i33, 3D ECHO) for assessment of cardiac indices. In the prospective group of patients, echocardiography was repeated after 6 months of surgery. In the retrospective group of patients, echocardiography was performed for left ventricular diastolic dysfunction and ejection fraction. Biochemical cure was confirmed at least after 6 months by glucose-suppressed plasma growth hormone (GH) concentrations (GH-OGTT) of less than 0.4 ng/ml, random GH of less than 1 ng/ml, and normal age-corrected insulin-like growth factor (IGF-1) values. Results: In the prospective group (38 patients), there was a significant decrease in the left ventricular mass (LVM) and LVM index (LVMI) in patients who were cured as well as in patients with postoperative growth hormone (GH) 1–5 ng/ml. In the prospective group, LVMI completely normalized in 2 and a new-onset deterioration was detected in 1 patient (who was not cured) and improved in 8 others. Left ventricular systolic function was abnormal at baseline in 18 (47.3%) patients, which normalized in 11 (61.1%) patients postoperatively, and in 7 patients, it improved significantly although it did not normalize completely. There was also a significant improvement in the left ventricular ejection fraction (P = 0.01). Post TSS, in patients with GH-OGTT >5 ng/ml, there was no significant decrease in the LVM, LVMI and ejection fraction (EF). In the retrospective group, 62 patients were analyzed for a change in the EF with a mean follow-up of 20.3 months. There was a significant improvement in the left ventricular EF in patients who were cured (P < 0.001). Conclusion: Reduction in growth hormone levels and insulin-like growth factor type 1 can decrease the LVM and LVMI, which directly or indirectly contributes to the improvement in diastolic as well as systolic function and probably mortality.

Objective: To objectively document autonomic dysfunction in the affected arm with traumatic brachial plexus injury (TBPI) using quantitative sudomotor axon reflex test (QSART). Materials and Methods: Patients with TBPI presenting to the neurosurgical outpatient department from August 2013 to November 2014 were included in the study. The QSART was administered to each patient with prior informed consent detailing the procedure. A total of 20 patients with TBPI were included in the study. The age, sex, mode of injury, date of injury, side of injury, and type of injury (pan brachial plexus vs preserved distal function) were recorded. The presence of any pain was also recorded. The injuries were also grouped as preganglionic and postganglionic injuries based on clinical, electroneuromyography (ENMG) and magnetic resonance imaging (MRI) findings. The results of the test for the affected and normal limb were recorded and analyzed with appropriate statistical tests to determine any significant differences. Results: The study included 20 patients, with their age ranging from 15 to 50 years. Out of the 20 patients, one was female and the rest 19 were males. Seven (35%) of the injuries were complete (pan brachial plexus) and 13 (65%) were incomplete (preserved distal function). All patients had preganglionic TBPI. There was no evidence of any statistically significant difference between the affected and normal arm for total sweat volume (P = 0.20) and latency period (P = 0.42). However, the average mean values for the same were lower in the affected arm as compared to the normal. The baseline sweat output (P = 0.010), however, was significantly lower in the affected arm as compared to the normal arm. Conclusion: QSART has demonstrated reduced baseline sweat output in the affected arm in patients with TBPI. This indicates the presence of autonomic dysfunction in the injured arm.

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.

We present an unusual case of primary diffuse craniospinal leptomeningeal gliomatosis (PGDL), who was initially diagnosed on the basis of imaging, laboratory findings, and cranial meningeal biopsy as tuberculous meningitis and showed clinical deterioration while on anti-tuberculous treatment for 2 months. The patient was subsequently correctly diagnosed on diffusion weighted and post-contrast T1-weighted imaging of the craniospinal axis along with whole body imaging. The radiological findings were confirmed on histopathology and immunohistochemistry performed from the previous block as well as biopsy from the nodular mass in the lumbosacral meninges. We conclude that peroperative imaging may help in pinpointing the correct diagnosis and assist in guiding the surgeon to the site of biopsy.

Subacute sclerosing panencephalitis is a late complication of measles infection and develops usually 6 to 15 years after the primary measles infection. Fulminant subacute sclerosing panencephalitis is an infrequently encountered form wherein the disease rapidly progresses to death. A six-year old male child presented with fever, abnormal movements of the left side of body followed by weakness of the left side of the body, and involuntary abnormal movements of right upper and lower limbs. On examination, he was drowsy and was unable to communicate. He had right-sided hemiballismus. He also had left-sided hemiparesis and the left plantar reflex was extensor. Cerebrospinal fluid examination revealed elevated protein and cells. In the serum and cerebrospinal fluid, anti-measles IgG antibodies were found to be positive. No other viral marker was noted in the cerebrospinal fluid. Magnetic resonance imaging of the brain showed extensive damage to the right temporal, parietal, and to a lesser extent, the frontal region as well as subcortical structures of these regions. Electroencephalography revealed generalized slowing of waves. Over a period of the next 3 days, the intensity and frequency of choreiform movements markedly reduced and the patient developed periodic generalized myoclonus, which was predominantly present on the right side. The patient succumbed to his illness and died after one month. Fulminant subacute sclerosing panencephalitis may have unusual clinical manifestations such as hemiballismus. In fulminant subacute sclerosing panencephalitis, neuroimaging may show extensive cortical damage.

Background: The most reliable histological correlate of recurrence risk in meningiomas is increased mitotic activity. Proliferative index with Ki-67 immunostaining is a helpful adjunct to manual counting. However, both show considerable inter-observer variability. A new immunohistochemical method for counting mitotic figures, using antibody against the phosphohistone H3 (PHH3) protein was introduced. Similarly, a computer based automated counting for Ki-67 labelling index (LI) is available. Aims and Objectives: To study the use of these new techniques in the objective assessment of proliferation indices in meningiomas. Materials and Methods: This was a retrospective study of intracranial meningiomas diagnosed during the year 2013.The hematoxylin and eosin (H and E) sections and immunohistochemistry (IHC) with Ki-67 were reviewed by two pathologists. Photomicrographs of the representative areas were subjected to Ki-67 analysis by Immunoratio (IR) software. Mean Ki-67 LI, both manual and by IR were calculated. IHC with PHH3 was performed. PHH3 positive nuclei were counted and mean values calculated. Data analysis was done using SPSS software. Results: A total of 64 intracranial meningiomas were diagnosed. Evaluation on H and E, PHH3, Ki-67 LI (both manual and IR) were done in 32 cases (22 grade I and 10 grade II meningiomas). Statistically significant correlation was seen between the mitotic count in each grade and PHH3 values and also between the grade of the tumor and values of Ki-67 and PHH3. Conclusion: Both the techniques used in the study had advantage over, as well as, correlated well with the existing techniques and hence, can be applied to routine use.

Aim: Surgery for intracranial complex vascular malformations can be quite exigent and involves considerable preoperative planning. Here, we present the advantages of using three-dimensional (3D) printed models as a preoperative investigational modality. Material and Methods: 3D printed models were made from thin-slice computed tomography (CT) angiography scans of 6 patients with arteriovenous malformations over an18-month period from August 2015 to December 2016. The locations of the arteriovenous malformations were in the Sylvian fissure in 1 patient, posterior frontal region in 2 patients, subfrontal region in 1 patient, and parietal region in 2 patients. The CT angiography was performed on a 64-slice CT scanner. Thin-slice axial CT sections were acquired and a volume file was created of the arteriovenous malformation and the required skull bones. The file was then transferred to the 3D printer for creating the model. Results: The model depicted the precise nature of the compactness and location of the nidus in relationship to the skull. It was possible to clearly delineate the course, size, and number of feeding vessels and draining veins. The model made identification of the normal and abnormal vessels easier and assisted in the preparation and conduct of surgery. The model was made to scale and was placed beside the surgeon during the operation. The limitation of current technology was that the exact differentiation of arteries and veins by color coding was not possible. Conclusion: 3D printed models can be helpful in getting information regarding the architecture and character of the arteriovenous malformation. The models are cost-effective and easy to build.

Foraminal stenosis causing nerve root compression and radiculopathy is a relatively common pathology in the lumbar spine. The treatment of choice, when surgery is indicated, is foraminal decompression at the affected level, usually through a conventional midline open foraminotomy. Minimally invasive lateral foraminotomy with partial lateral facetectomy is a potentially effective surgical alternative when such a surgery is warranted. The evaluation of the efficacy and benefits of this approach for treatment of radiculopathy; an assessment of facet integrity; and, a detailed description of the procedure are also provided. Patients with predominantly unilateral lower limb radiculopathy, who had persistent symptoms despite conservative therapy, underwent a minimally invasive lumbar lateral foraminotomy (through tubular retractors) with partial lateral facetectomy. The Oswestry disability index (ODI) and the visual analog scale (VAS) for back and leg pain were evaluated preoperatively, postoperatively, and at the latest follow-up. Facet integrity was evaluated with postoperative computed tomography (CT) scans. Between 2013 and 2014, in the 12 patients who underwent this procedure and were evaluted after a minimum follow up of 1 year, there was significant improvement in the ODI, VAS based back pain, and VAS based leg pain. A minimally invasive, lateral foraminotomy with partial lateral facetectomy is an effective alternative technique for treatment of radiculopathy due to foraminal stenosis in a carefully selected subgroup of patients. A larger study would possibly highlight the effectiveness of this procedure.

The history of the prestigious Department of Neurosurgery, Gobind Ballabh Pant Institute of Medical Education Institute and Research, New Delhi, a leading tertiary care centre, is presented. Its eminent faculty and outstanding patient care attracts patients and students from all over the country.The patients opt for this institution to get a standard of care that may be comparable with the highest standards prevalent; and, the students achieve their goal of getting excellent education in Neurosurgery at par with the best institutes of the world. The department has, therefore, over the years, established its place in the country as a premier training facility and an epitome of medical excellence.