The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Motor band sign in a Huntington disease phenocopy.

We report a 68-year-old lady who presented with Huntington phenocopy with generalized chorea and was genetically proven to have Spinocerebellar ataxia (SCA)17. MRI Brain demonstrated motor band sign, which is most commonly reported in motor neuron disease. This is the first case of motor band sign with SCA 17 and highlights the widening spectrum of radiological signs in SCA 17.

Primary CNS vasculitis (PCNSV): a cohort study.

Primary CNS Vasculitis (PCNSV) is a rare inflammatory disorder affecting the blood vessels of the central nervous system. Patients present with a combination of headaches, seizures, and focal neurological deficits. There is usually a diagnostic delay. Treatment is based on observational studies and expert opinion. Our objective was to identify clinical, laboratory, neuroimaging, pathologic or management-related associations with 2 year outcome in patients with primary CNS vasculitis. We conducted a cohort study at a single tertiary care referral centre of prospectively (2018-2019) and retrospectively (2010-2018) identified individuals with primary CNS vasculitis (diagnosis was proven by either brain biopsy or cerebral digital subtraction angiography). Clinical, imaging and histopathologic findings, treatment, and functional outcomes were recorded. Univariate and stepwise multiple logistic regression were applied. P-value<0.05 was considered statistically significant. The main outcome measures were documentation of clinical improvement or worsening (defined by mRS scores) and identification of independent predictors of good functional outcome (mRS 0-2) at 2 years. We enrolled eighty-two biopsy and/or angiographically proven PCNSV cases. The median age at presentation was 34 years with a male predilection and a median diagnostic delay of 23 months. Most patients presented with seizures (70.7%). All patients had haemorrhages on MRI. Histologically lymphocytic subtype was the commonest. Corticosteroids with cyclophosphamide was the commonest medication used. The median mRS at follow-up of 2 years was 2 (0-3), and 65.2% of patients achieved a good functional outcome. Myelitis and longer duration of illness before diagnosis were associated with poorer outcomes. The presence of hemorrhages on SWI sequence of MRI might be a sensitive imaging marker. Treatment with steroids and another immunosuppressant probably reduced relapse rates in our cohort. We have described the third largest PCNSV cohort and multi-centre randomised controlled trials are required to study the relative efficacy of various immunosuppressants.Study registration: CTRI/2018/03/012721.

Evaluation of the Impact of Integrated Care and Self-Management After Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder with a myriad of motor and non-motor symptoms. Although deep brain stimulation (DBS) has a dramatic impact in the lives of people with PD, care delivery remains complex. There is a lack of evidence on the implementation and role of integrated care and self-management support in people with PD with chronic DBS. OBJECTIVE: To evaluate care needs, implementation and impact of a pragmatic network for PD care, the Integrated Parkinson Care Network (IPCN). METHODS: This is a subgroup analyses of a 6-month, pre-post design, single-centre, phase 2 study to assess a patient-centred care model based on integrated care, self-management support (IPCN) in PD, focusing on those participants with chronic DBS. RESULTS: We included 22 people with PD and chronic DBS (median time since DBS - 30 months). The mean age was 63.9 (7.6) years and mean disease duration was 15.2 (6.9) years. The top three care priorities were speech (54.5%), mobility (40.9%) and mood (31.8%). After the IPCN program, there was a positive change in the perception of support for chronic care (Patient Assessment of Chronic Illness Case: 0.85; 95% CI: 1.2 to -0.4) and self-management (5As: 0.77; 95% CI: 0.39 -1.15), along with quality of life (PDQ8 : 7.1, 95% CI:1.8 -12.4). CONCLUSION: The IPCN is a care delivery model that addresses specific care needs of people with PD and chronic DBS. The current study showed its feasibility and warrants further evaluation.

Spectrum of Movement Disorders of Late-Onset Niemann-Pick Disease Type C.

Niemann-Pick disease type C (NPC), is a rare lysosomal storage disorder, which has a variable presentation based on the age of onset. We describe five adult/adolescent-onset NPC cases presenting with a range of movement disorders along with vertical supranuclear gaze palsy as part of the clinical presentation. A diagnostic delay of 4-17 years from the symptom onset was found in this case series. A high index of clinical suspicion in adult/adolescent patients presenting with vertical supranuclear gaze palsy along with various movement disorder phenomenology can help in the early diagnosis of NPC.

Clinical Features, Gender Differences, Disease Course, and Outcome in Neuromyelitis Optica Spectrum Disorder.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is an astrocytopathy with a predilection for the optic nerve, spinal cord, and brainstem. In this ambispective study, we evaluate clinical characteristics, responses to therapy, and disability outcomes in patients with NMOSD. METHODS: Patients diagnosed as NMOSD and following up for at least 1 year at a tertiary care center in India were recruited. Patient data were collected ambispectively from January 2012 until December 2018. RESULTS: A total of 106 patients (29M/77F) with NMOSD were evaluated. The mean age of onset was 29 (±11.6) years. About 77 patients (72.64%) were positive for the AQP4 antibody. Age of onset was higher for those presenting with an opticospinal syndrome (34.2 years) as compared to either isolated longitudinally extensive transverse myelitis (LETM) (30 years) or optic neuritis (ON) (25.3 years). The most common syndrome at onset was LETM in 57 patients (53.77%) followed by ON in 31 patients (29.24%). Azathioprine was the most common immunotherapy (83.96%) prescribed followed by rituximab (7.54%) and mycophenolate mofetil (1.88%). There was a significant decrease in the number of relapses post-azathioprine (P < 0.001). Out of 67 patients with ON, 21 (31.34%) had complete recovery while 17 (25.37%) patients had a severe deficit at a 3-month follow-up. Out of 92 patients with a motor deficit, 49 (53.26%) patients had a partial motor deficit at a 6-month follow-up. The severe visual deficit at baseline and female gender predicted poor visual and motor recovery, respectively. CONCLUSION: This is the largest descriptive study on patients with NMOSD from India. Relapse rates were similar irrespective of the clinical presentation, age, gender, and disease course. Treatment with immunosuppressive treatment significantly affected the disease course.

Do Imaging Markers of Cerebral Small Vessel Disease Predict Hematoma Volume and Outcome in Acute Intracerebral Hemorrhage?

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) markers have not been widely studied in relation to hematoma volume and growth in hypertensive intracerebral hemorrhage (ICH). The objectives to assess the relationship of white matter hyperintense lesions (WMHL), microbleeds (MBs), and cortical siderosis (CSS) with hematoma volume, hematoma expansion (HE), and 3 months outcome in patients with hypertensive ICH. METHODS: All consecutive acute hypertensive supratentorial ICH presenting to the emergency were prospectively recruited. Baseline and 24 hours computed tomography (CT) to assess hematoma volume and magnetic resonance imaging (MRI) for CSVD markers were performed in all subjects. WMHL (graded using Fazekas's scale), MBs, and CSS were assessed and compared with baseline variables and outcomes. All the images were assessed by an experienced stroke neurologist/neuroradiologist. RESULTS: One hundred and fifty-seven patients were screened and 60 were included. Mean age was 54.08 ± 11.57 years and 47 (78%) were males. Of 60, 19 (28.1%) had HE, 31 (51.6%) had major bleed (>30 ml), and 28 (47.46%) had poor 3 month outcome (mRS 4-6). On univariate analysis, high grade WMHL was associated with greater HE [odds ratio (OR): 2.65, confidence interval (CI) 1.48-4.72, P = 0.001), greater proportion with volume >30 ml (OR: 7.16, CI: 1.09-47.13, P = 0.001) and poor outcome (OR: 2.1, CI: 0.05-3.27, P = 0.001). MBs were associated with poor outcome (P = 0.029) but not with HE/volume. CSS was related to HE (P = 0.031), a large volume bleed (P = 0.023), and poor outcome (P = 0.021). On multivariate model, only WMHL independently predicted HE (P = 0.034), greater proportion with bleed volume >30 ml (P = 0.041), and poor outcome (P = 0.042). CONCLUSIONS: WMHL in MRI serves as a predictor of hematoma expansion, a large volume bleed, and poor outcome in hypertensive ICH and may be incorporated into existing prediction models.

Clinical and laboratory evidence of Lyme disease in North India, 2016-2019.

BACKGROUND: Lyme disease is endemic to parts of the Americas, Europe and Asia. However, only a handful of sporadic cases have been reported from India. In this study, we systematically evaluated the clinical and epidemiological features of Lyme disease in North India. METHOD: All samples were tested by using the standard two-tiered testing algorithm (STTA). Paired serum and cerebrospinal fluid (CSF) were used for demonstrating Borrelia burgdorferi specific intrathecal IgG antibody synthesis (AI). In addition, a commercial tick-borne bacterial flow chip (TBFC) system and a real-time PCR were also used to detect Borrelia species and Anaplasma phagocytophilum in patients who were positive by STTA. RESULTS: The diagnosis of Lyme disease was confirmed in 18 (7.14%) of the 252 clinically suspected cases by STTA. Neurological involvement was reported in 14 (77.78%) patients, whereas joint and heart involvement was reported in five (27.78%) and three (16.67%) patients, respectively. Lymphocytic pleocytosis (median 37.5 cells/mm3; range 12-175 cells/mm3) in the CSF was seen in 11 of 14 Lyme neuroborreliosis (LNB) patients. Intrathecal production of Borrelia specific IgG antibodies was demonstrated in 9 (64.28%, n = 14) patients, a highly specific finding for neuroborreliosis. Two patients (11.11%) were also found to be co-infected with human granulocytic anaplasmosis. CONCLUSIONS: The results of this study show clinical and laboratory evidence of endemic Lyme disease in North India and thus, highlight the importance for travel medicine practitioners and physicians to evaluate for Lyme disease in patients with compatible symptoms and a history of travel to tick risk areas.

Diagnostic added value of interictal magnetic source imaging in presurgical evaluation of persons with epilepsy: A prospective blinded study.

BACKGROUND AND PURPOSE: In presurgical evaluation for epilepsy surgery, information is sourced from various imaging modalities to accurately localize the epileptogenic zone. Magnetoencephalography (MEG) is a newer noninvasive technique for localization. However, there is limited literature to evaluate if MEG provides additional advantage over the conventional imaging modalities in clinical decision making. The objective of this study was to assess the diagnostic added value of MEG in decision making before epilepsy surgery. METHOD: This was a prospective observational study. Patients underwent 3 h of recording in a MEG scanner, and the resulting localizations were compared with other complimentary investigations. Added value of MEG (considered separately from high-density electroencephalography) was defined as the frequency of cases in which (i) the information provided by magnetic source imaging (MSI) avoided implantation of intracranial electrodes and the patient was directly cleared for surgery, and (ii) MSI indicated additional substrates for implantation of intracranial electrodes. Postoperative seizure freedom was used as the diagnostic reference by which to measure the localizing accuracy of MSI. RESULTS: A total of 102 patients underwent epilepsy surgery. MEG provided nonredundant information, which contributed to deciding the course of surgery in 33% of the patients, and prevented intracranial recordings in 19%. A total of 76% of the patients underwent surgical resection in sublobes concordant with MSI localization, and the diagnostic odds ratio for good (Engel I) outcome in these patients was 2.3 (95% confidence interval 0.68, 7.86; p = 0.183) after long-term follow-up of 36 months. CONCLUSION: Magnetic source imaging yields additional useful information which can significantly alter as well as improve the surgical strategy for persons with epilepsy.

High-Pressure Normocephalus-Raised Intracranial Pressure with False Localizing Signs.

Normal-sized ventricles and absence of papilledema do not rule out shunt failure and raised intracranial pressure (ICP). Raised ICP can present with false localizing signs which may be cranial nerve palsies or extensive polyradiculopathy. Our patient with a history of ventriculoperitoneal (VP) shunt presented with rapidly progressive vision loss without papilledema, as well as multiple cranial nerve palsies and radiculopathy. Imaging did not reveal hydrocephalus, however, cerebrospinal fluid (CSF) manometry revealed high CSF opening pressure. After lumbar thecoperitoneal shunting, vision did not improve, but the rest of cranial nerve palsies and radiculopathy improved. In a patient in whom VP shunt is in situ, headache and vomiting should prompt evaluation for raised ICP though there is no ventriculomegaly of papilledema. Vision can be saved if raised ICP is suspected, CSF opening pressure measured at presentation and prompt surgery is performed.

Therapeutic Update on Huntington's Disease: Symptomatic Treatments and Emerging Disease-Modifying Therapies.

Huntington's disease (HD) is a monogenic neurodegenerative disorder that presents with progressive motor, behavior, and cognitive symptoms leading to early disability and mortality. HD is caused by an expanded CAG repeats in exon 1 of the huntingtin (HTT) gene. The corresponding genetic test allows a clinical, definite diagnosis in life and the identification of a fully penetrant mutation carrier in a premanifest stage. In addition to the development of symptomatic treatments that attempt to address unmet care needs such as apathy, irritability, and cognition, novel therapies that target pathways specific to HD biology are being developed with the intent of slowing disease progression. Among these approaches, HTT protein lowering therapies hold great promise. There are currently active programs using antisense oligonucleotides (ASOs), RNA interference, small-molecule splicing modulators, and zinc-finger protein transcription factor. Except for ASOs and RNA interference approaches, the remaining therapeutic strategies are at a preclinical stage of development. While the current therapeutic landscape in HD may bring an unparalleled change in the lives of people with HD and their families with the first-ever disease-modifying therapy, the evaluation of these therapies requires novel tools that enable a more efficient and expedited discovery and evaluative process. Examples are biomarkers targeting the HTT protein to measure target engagement or disease progression and rating scales more sensitive to the earliest clinical changes. These tools will be instrumental in the next phase of disease-modifying clinical trials in HD likely to target the phenoconversion period of the disease, including the prodromal HD stage.

Effect of yoga as add-on therapy in migraine (CONTAIN): A randomized clinical trial.

OBJECTIVE: To evaluate the effectiveness of yoga as an adjuvant to conventional medical management on clinical outcomes in patients with migraine. METHODS: CONTAIN was a prospective, randomized, open-label superiority trial with blinded endpoint assessment carried out at a single tertiary care academic hospital in New Delhi, India. Patients enrolled were aged 18-50 years with a diagnosis of episodic migraine and were randomized into medical and yoga groups (1:1). Randomization was computer-generated with a variable block size and concealed. A predesigned yoga intervention was given for 3 months. Outcomes were recorded by a blinded assessor. The primary endpoint was a decrease in headache frequency, headache intensity, and Headache Impact Test (HIT)-6 score. Secondary outcomes included change in Migraine Disability Assessment (MIDAS) score, pill count, and proportion of headache free patients. RESULTS: Between April 2017 and August 2018, 160 patients with episodic migraine were randomly assigned to medical and yoga groups. A total of 114 patients completed the trial. Baseline measures were comparable except for a higher mean headache frequency in the yoga group. Compared to medical therapy, the yoga group showed a significant mean delta value reduction in headache frequency (delta difference 3.53 [95% confidence interval 2.52-4.54]; p < 0.0001), headache intensity (1.31 [0.60-2.01]; p = 0.0004), HIT score (8.0 [4.78-11.22]; p < 0.0001), MIDAS score (7.85 [4.98-10.97]; p < 0.0001), and pill count (2.28 [1.06-3.51]; p < 0.0003). CONCLUSION: Yoga as an add-on therapy in migraine is superior to medical therapy alone. It may be useful to integrate a cost-effective and safe intervention like yoga into the management of migraine. CLINICALTRIALSGOV IDENTIFIER: CTRI/2017/03/008041. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with episodic migraine, yoga as adjuvant to medical therapy improves headache frequency, intensity, impact, and disability.

Anti-myelin oligodendrocyte glycoprotein antibody associated disease spectrum - A north Indian tertiary care centre experience and review of literature.

INTRODUCTION: MOG antibody associated disease is a relatively new disorder for which the full clinical spectrum is being described and the literature is evolving. The current study outlines the observations on a cohort of patients diagnosed with this clinical entity. METHODS: This is a retrospective review of prospectively followed up patients with MOG antibody positive neurological illness. Case records of patients following up in neuroimmunology clinic of All India Institute of Medical Sciences(AIIMS), New Delhi from January 2007 to July 2019 were reviewed for MOG antibody positivity and those patients with positive antibody result were included in this study. FINDINGS: A total of 20 patients were tested positive for MOG-IgG antibody. 75% were females. Median (Range) age was 30.5 years (8-58). Median disease duration was 22 months (1-139). Most common symptom at presentation was decrease in vision (unilateral or bilateral) (80%). Most common syndrome at onset was unilateral optic neuritis (ON) (40%) followed by bilateral ON (35%), transverse myelitis (TM)(15%), ON plus TM (5%) and cerebral syndrome (5%). Median number of demyelinating episodes per person was 2.5. Out of 29 affected eyes, 26 had good outcome. Out of 7 patients with motor disability, 5 patients had good outcome. CONCLUSION: MOG antibody associated disease presents predominantly as recurrent ON, but may also present as an opticospinal, cerebral or brainstem syndrome and recurrent myelitis. Many of the patients had relapses, but had good outcomes with treatment.

Validation of ICH and ICH-GS Scores in an Indian Cohort: Impact of Medical and Surgical Management.

OBJECTIVE: Prognostic scores help in predicting mortality and functional outcome post intracerebral hemorrhage (ICH). We aimed to validate the ICH and ICH-GS scores in a cohort of Indian patients with ICH and observe the impact of any surgical intervention on prognostication. METHODS: This was an ambispective observational study of primary ICH cases enrolled between January 2014 and April 2018. Observed mortality on ICH and ICH GS scores for the entire cohort and individually for the medically and surgically managed patients was compared to the published mortality in the original derivation cohorts. RESULTS: 617 patients, (464 retrospective and 153 prospective) of ICH were included. In hospital mortality and 30-day mortality was 28.7% and 28.5% respectively. There was a significant association of increasing mortality with increasing ICH and ICH-GS scores. Area under receiver operating characteristic curve for 30-day mortality was 75.9% and 74.1% for ICH and ICH-GS scores respectively. However, mortality observed at individual scores was significantly less than previously reported. Among the surgically intervened patients (n = 265), both the expected mortality at baseline and discriminative ability of ICH and ICH-GS scores for 30-day mortality was significantly reduced following surgical intervention (ROC in surgically intervened groups: 59.9 (52.6-67.2) and 63(56-70) for ICH and ICH-GS scores respectively). CONCLUSIONS: Although ICH and ICH-GS scores are valid in Indian population, mortality at individual scores is lower than previously reported. Mortality prediction using ICH and ICH GS scores is significantly modified by surgical interventions. Thus, newer prognostic tools which incorporate surgical intervention need to be developed and validated in future.

Progress in Pharmacological and Surgical Management of Tourette Syndrome and Other Chronic Tic Disorders.

BACKGROUND: Tourette syndrome (TS) and other chronic tic disorders are clinically heterogenous and cause physical discomfort, social difficulties, and emotional distress. In addition to tics, TS patients have a variety of behavioral comorbidities, including obsessive-compulsive disorders and attention-deficit hyperactivity disorders. TS treatment is multidisciplinary, involving behavioral therapy, oral medications, and botulinum toxin injections. METHODS: Relevant studies on pharmacological and surgical treatment options for TS and other chronic tic disorders, their limitations and current recommendations were reviewed using the PubMed search till April 2, 2018. Besides, the reference lists of the retrieved publications were manually searched to explore other relevant studies. This review aims to discuss the progress in pharmacological and surgical treatment options for TS and other chronic tic disorders. RESULTS AND CONCLUSIONS: Both typical and atypical antipsychotic agents are mainstays of pharmacological treatment of TS and other chronic tic disorder patients; however, their use is limited by serious side effects considering their potential of dopamine blockade. Because of the phenotypic variability, no medication has proven effective for all persons with TS and other chronic tic disorders. Botulinum toxin has emerged as a good therapeutic option, especially for focal and dystonic tics. But, their uses are limited by lack of sufficient evidence and high cost. Surgical treatment is considered in medically refractory and severely disabled tics patients. Deep brain stimulation has replaced lesional surgeries; however, there is uncertainty regarding the selection of patients and target of stimulation.