Correlation of CT perfusion with MRI brain in symptomatic carotid artery stenosis.

Background: Cerebral white matter disease and large vessel cerebral steno-occlusive are both associated with high incidence of strokes and mortality. There is a lack of literature correlating the cerebral perfusion downstream of a stenotic lesion with white matter changes in the cerebral hemispheres. The aim of this study was to correlate the white matter changes in magnetic resonance imaging (MRI) with computed tomography (CT) perfusion parameters in patients with symptomatic carotid stenosis. Methods: A total of 50 patients with symptomatic carotid stenosis underwent MRI brain and CT Perfusion. Percentage differences in cerebral blood flow (CBF) and mean transit time (MTT) were correlated with symmetric and asymmetric small vessel ischemic disease (SVID) on MRI. Receiver operating characteristic (ROC) curve analysis was performed to determine sensitivity and specificity for different values of percentage CBF and MTT difference. Results: A total of 17 patients with symmetrical SVID had a mean CBF difference of 6.58 (SD of 3.17) and mean MTT difference of 11.61 (SD of 4.32). 33 patients with asymmetrical SVID had a mean CBF difference of 34.73 (SD of 6.87) and mean MTT difference of 44.63 (SD of 9.12). ROC curve analysis showed percentage CBF and MTT differences of 12.5% and 26.5% respectively to be associated with 100% specificity and sensitivity. Conclusion: In patients with symptomatic carotid stenosis, CT perfusion parameters correlate with MRI features of SVID.

Vogt-Koyanagi-Harada Syndrome - A Neurologist's Perspective.

Vogt-Koyanagi-Harada (VKH) syndrome is an immune-mediated granulomatous disease which affects melanin-rich organs like eyes, skin, nervous system, and ears. Neurological and auditory manifestations usually precede the involvement of other sites. Patients may manifest with "complete" or "incomplete" syndrome. We report two patients who presented with acute headache and impaired vision. Fundus examination revealed optic disc hyperemia and exudative retinal detachment which provided a clue for the diagnosis at the bedside. Fundus fluorescein angiogram (FFA) revealed abnormal dye leakage, whereas B scan showed choroid thickening. Cerebrospinal fluid (CSF) pleocytosis contrasted with unremarkable brain magnetic resonance imaging and lack of meningeal signs. Melanophagocytosis was evidenced by melanin-laden macrophages in CSF and skin biopsy. This finding is specific for VKH syndrome and helps to clinch the diagnosis even when the complete syndrome is not present cross-sectionally. VKH syndrome should be suspected in patients with aseptic meningitis if tests for common infectious and immune-mediated diseases are negative.

A Study on the Distinctive Clinical Profile and Thrombophilia in Pediatric Cerebral Venous Sinus Thrombosis.

Aim: The objective of the study was to systematically bring out the clinical presentations, neuro-imaging features, treatment given, and long-term outcomes of children with cerebral venous sinus thrombosis (CVST). Materials and Methods: Data were obtained by retrospective analysis of electronic records spanning 13 years, of children (<18 years) with a confirmed diagnosis of CVST based on magnetic resonance imaging of the brain and managed at a tertiary care children's hospital in the UK. Results: Seventeen patients with pediatric CVST were identified over a 13-year study period, highlighting the uncommon prevalence of this entity. This study comprised 10 males and seven females. The age range at presentation was between 2 days and 17 years with a median age of 5.5 years. Headache was the commonest presenting symptom in 10 of 17 children and focal neurological signs were seen in 11 of 17 patients. Among risk factors, six patients had an antecedent infection of the ear/mastoid, three children had acute leukemia, and two patients had central venous catheters. Para-infectious CVST (seven of 17 patients) responded well to appropriate antibiotic therapy. Thrombophilia screens were available in 10 of 17 patients with noninfectious CVST and returned abnormal in four patients (two with Factor V Leiden mutations and one each with deficiency of protein C and anti-thrombin III). Anticoagulants were used in only six of 17 cases and were generally well tolerated. Follow-up data revealed, 11 of 17 patients had a complete recovery and four of 17 patients had residual neurological deficits. Two children died in the entire cohort. Conclusion: Pediatric CVST is uncommon and has a different spectrum from adults, with unique clinical triggers and thrombophilic states. Management varies significantly among clinicians, due to the paucity of trial evidence and also due to the heterogeneity of this condition in children.

Multicentric clinical and epidemiological comparison of neuromyelitis optica spectrum disorder with multiple sclerosis from India.

BACKGROUND: In India, Neuromyelitis optica spectrum disorders (NMOSD) can often be misdiagnosed as multiple sclerosis (MS) leading to wrong or delayed treatment. Although diagnostic criteria exist it is important to flag certain highlights in the phenotype by direct comparison which will prompt investigation in the right direction. The aim was to identify distinguishing features, especially differences in disability status and frequency of the optico-spinal syndrome. METHODS: This study was designed as a multicentric, hospital based, ambispective, observational study of patients with primary demyelination due to either NMOSD or MS. Various variables were collected using a data extraction proforma and were compared using statistical means. RESULTS: A total of 212 patients, 166 (78.3%) with MS and 46 (21.7%) with NMOSD, were included from six different cities across India. The male to female ratio was 1:1.3 in MS group and 1:2.3 in NMOSD group. Significant differences on logistic regression included: patients with NMOSD were more disabled despite having a shorter duration of illness with a high progression index (EDSS/ duration of disease in years) of 5.99 vs 0.74 respectively (p = 0.02); in subset of relapsing patients relapsing optico-spinal syndrome (optic neuritis with myelitis) was more common in NMOSD (39.1% vs 0.8%); presence of at least one T2 lesion in the last available MRI brain (78.6% vs 39.1%) and presence of at least one gadolinium enhancing lesion in brain MRI documented during course of illness (30.2% vs 8.7%) was more in MS patients. If the patient with demyelination had a progression index of ≥ 0.39, the Likelihood Ratio (LR) of having NMOSD was 1.32 (95% CI 1.06-1.64), the sensitivity was 0.74 and specificity 0.44. Other notable variables significant on univariate but not on multivariate analysis were: other autoimmune diseases were present more in the NMOSD group (13% vs 2.4%); proportion of patients who had only school education (up to class 12) but not higher were more in NMOSD (67.4% vs 38.5%); the most common clinical presentation in MS patients was either a brainstem or cerebral syndrome (41% vs 21.8%) while it was isolated myelitis in NMOSD patients (37% vs 19.3%). Other findings included: optic neuritis as a presenting feature was common and present in similar proportions in both the groups (around 37%); 50% (23/46) of NMOSD and around 30% (50/166) of MS patients had a single clinical episode during the course of their illness and in the relapsing patients, mean no of relapses (around 2.7) and ARR (MS 0.38, NMOSD 0.54) were similar. Secondary progressive MS was diagnosed in 4.8% (8/166) and primary progressive MS was diagnosed in 3.7% (6/166). CONCLUSION: Index of suspicion for NMOSD should be high in a patient if: the course is relatively short; disability is out of proportion and progression index is ≥0.39 or the patient has had recurrent optico-spinal relapses. It is important to distinguish early in the course NMOSD from MS as timely specific treatment may prevent future disability.

A Study of the Clinical Profile, Radiologic Features, and Therapeutic Outcomes in Neurosarcoidosis from Two Tertiary Care Centers in Southern India.

BACKGROUND: Sarcoidosis is an inflammatory granulomatous disease affecting multiple organ systems. Neurological manifestations are rare and seen in approximately 5% cases of sarcoidosis. They may commonly precede the diagnosis of sarcoidosis. Since there is paucity of Indian literature on this subject, we decided to review the clinical and radiological profile, laboratory abnormalities, treatment and long-term outcomes in our patients with neurosarcoidosis (NS). METHODS: The study was done by retrospective review of medical records for all cases diagnosed as NS during the period Jan 2014-Jan 2018. These cases were classified as definite, probable, and possible NS, on the basis of established diagnostic parameters (Zajicek criteria). The follow-up record in these cases ranged from 6 months to 3 years, with special emphasis on monitoring the response to treatment and long-term disability. RESULTS: The cases showed varied clinical abnormalities and imaging findings. Cranial neuropathies and myelopathy were the most common clinical presentations. Optic neuritis was most common cranial neuropathy, followed by facial nerve palsy and lower cranial nerve palsies. Most common magnetic resonance imaging findings were T2 hyperintense parenchymal lesions and meningeal enhancement. There was strong correlation between baseline clinico radiological parameters and long-term outcomes, as evidenced by relatively poor prognosis seen in cases with bilateral optic neuritis, myelopathy and imaging evidence of hydrocephalus, or leptomeningitis. CONCLUSION: The diagnosis of NS requires a high degree of suspicion, coupled with exclusion of alternate diagnosis. It commonly precedes the onset of systemic sarcoidosis. Central nervous system involvement in sarcoidosis is associated with poor clinical outcomes.

Recurrent Encephalopathy with Transverse Myelitis: An Uncommon Presentation of Neurobrucellosis.

Brucellosis (malta fever) is a zoonotic infection caused by a gram-negative coccobacillus which is a facultative intracellular pathogen. It causes a chronic granulomatous infection, similar in histology to tuberculosis. Brucellosis remains a diagnostic dilemma due to misleading, nonspecific manifestations and increasing trend of unusual presentations. In brucellosis, the nervous system involvement occurs in only 5 to 7% of untreated patients, and it may manifest with encephalitis, meningoencephalitis, radiculitis, and peripheral and cranial neuropathies. Transverse myelitis is an unusual occurrence. Here, the authors are reporting an unusual case of neurobrucellosis in an elderly male patient who visited multiple hospitals with recurring febrile encephalopathy and paraparesis. The diagnosis was suspected by his occupational history of working as an abattoir worker and was confirmed by the presence of high titers of Brucella immunoglobulin (Ig) M and IgG antibodies in the serum. The patient was managed with injection gentamicin for 2 weeks along with oral course of doxycycline and rifampicin for 6 weeks. He made a good clinical recovery and went back to work with mild residual deficits.

A Study on the Clinical and Angiographic Spectrum of Spontaneous Extracranial Dissections in the Cerebral Vasculature.

AIM: To prospectively study the clinical profile, angiographic features, and functional outcomes, in consecutive cases of extracranial dissection seen at two tertiary stroke care centers in South India. MATERIALS AND METHODS: In this observational study, spanning 4 years (December 12-December 16), a total of 442 patients presented with an acute ischemic stroke/transient ischemic attack (TIA) at our study centers. 14/546 (3.2%) of these patients had magnetic resonance angiography (MRA)/computed tomography angiography (CTA) evidence of extracranial dissections. All cases underwent detailed clinical evaluation on arrival, and data were recorded on a predesigned stroke pro forma. Contrast MRA was done on arrival in all cases as part of a standard stroke protocol, and CTA was done only if MRA was inconclusive. The pattern of the vessel involved and morphology of vessel dissection was analyzed as per a standard radiology protocol. All the cases were managed with short-term anticoagulation using low-molecular-weight heparin followed by oral anticoagulants for 3-6 months. All cases were followed up for 1-2 years and the functional outcomes were recorded using the modified Rankin Scale (mRS). RESULTS: There were 11 males and 3 females in the study, and the mean age was 45.1 years (range = 27-65 years). Focal neurological symptoms occurred in all these patients (10 patients had a stroke, and 4 had TIA). Nearly 64.2% of these (9/14) were stroke in young (age <45 years). The internal carotid artery was the most common vessel involved in 85.7% (12/14) cases. Of the ten patients with completed stroke, a good functional outcome (mRS 1-2) was seen in 8/10 (80%). Digital subtraction angiography and revascularization procedures were needed only in a minority of cases 3/14 (21%).\. CONCLUSION: This hospital-based study highlights the importance of suspecting arterial dissections in young strokes of unexplained etiology, and offering optimum anticoagulant therapy in the acute phase, to achieve good long-term outcomes.

Randomized trial to assess safety and clinical efficacy of intensive blood pressure reduction in acute spontaneous intracerebral haemorrhage.

BACKGROUND: Haematoma expansion due to raised blood pressure in spontaneous intracerebral haemorrhage may determine outcome. The aim of this study was to determine safety and efficacy of lowering blood pressure in acute spontaneous intracerebral haemorrhage. METHODS: This open label, multicentric trial randomized patients ≥18 years with spontaneous intracerebral haemorrhage with no secondary cause within 72 h of onset to tight BP control arm where treatment was initiated if mean arterial pressure (MAP) was ≥115 mm of Hg and conventional BP control arm where treatment was initiated if MAP was ≥130 mm of Hg. The MAP was maintained in the respective arm for another 72 h after which both arms had MAP below 115 mm of Hg. Primary outcome was modified Rankin Scale at 90 days. RESULTS: 118 patients, 59 in each arm were included. Follow up was available for all. Baseline characteristics were similar. At 90 days there was no significant difference between median mRS between the two arms. Odds Ratio for "poor outcome" (mRS 3-6) in the tight control arm (safety of the intervention) against "good outcome" (mRS 0-2) was not significant (OR 0.70 [95% CI 0.34-1.47] p = 0.35). Efficacy of the intervention in the form of Odds Ratio for "good outcome" in the tight control arm was not significant (OR 1.43 [95% CI 0.68-2.99], p = 0.35). CONCLUSION: In patients with spontaneous intracerebral haemorrhage who present within 72 h of the onset of symptoms, MAP can be safely lowered if it crosses 115 mm of Hg but it does not improve clinical outcome.

A genetic study of Factor V Leiden (G1691A) mutation in young ischemic strokes with large vessel disease in a South Indian population.

Factor V Leiden (FVL) has been, by far, the most investigated gene mutation, with 26 studies to date, on its role in arterial strokes. Overall, a meta-analysis of all these studies taken together showed that carriers of the Factor V Leiden allele were 1.33times more likely to develop arterial strokes when compared to controls. We subjected a highly select subset of young strokes, with large vessel infarcts, to genetic analysis for FVL mutation and compared them with matched healthy controls to look for a statistically significant association. In this prospective study, 6/120 cases (5%) and 2/120 controls (1.6%) were positive for heterozygous FVL (G1691A) mutation. The higher prevalence of FVL mutation in cases (5%) compared to controls (1.6%) did not show statistical significance with a Pearson's Chi square P value of 0.15. The Odds Ratio (OR) for risk of large vessel disease in FVL positive cases was 3.10 (95% CI of 0.61-15.7). FVL mutation (G1691A) in young Indian subjects with ischemic strokes does not seem to be significantly associated with large vessel disease.

Recurrent Longitudinally Extensive Myelitis and Aquaporin-4 Seronegativity - The Expanding Spectrum of Neuromyelitis Optica.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a recently proposed unifying term for Neuromyelitis Optica (NMO), also known as Devic's disease and related syndromes. It is a relapsing inflammatory demyelinating disease that most commonly affects optic nerves and the spinal cord, leading to sudden vision loss or weakness in one or both eyes, and loss of sensation and bladder function. Though inflammation may also involve the brain, the lesions seen in NMO are different from Multiple Sclerosis (MS) which has a similar clinical course. Attacks of NMOSD tend to be more severe and often different in nature from MS. MS and NMOSD are often confused but require a different course of treatment for optimal results. Here, we describe a patient who had clinical features suggestive of NMO but showed seronegativity for anti-aquaporin antibodies, done twice. Initially he was managed on the lines of MS but showed a deteriorating clinical course on initiation of treatment with interferons. Later, his diagnosis was revised to seronegative NMO and he was started on immunosuppressive therapy with azathioprine to which he showed optimal response and achieved disease stabilization.

ANCA Associated Mononeuritis Multiplex with Overlap in Vasculitic Syndromes.

Mononeuritis multiplex is a common manifestation of many illnesses which includes Hansen's disease and certain types of systemic vasculitis. The Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (AAV) is a group of rare diseases which show typical characteristic inflammatory cell infiltration and blood vessel wall necrosis. AAV syndromes include Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA). We describe a patient who presented with mononeuritis multiplex and had features of overlap between EGPA and MPA. The patient was treated with standard regimen of steroids and pulsed cyclophosphamide and she achieved excellent clinical remission.

Plasma factor VIII in non-puerperal cerebral venous thrombosis: a prospective case-control study.

Elevated plasma factor VIII (FVIII) is increasingly recognized as an independent risk factor for thrombotic diseases. Our aim was to evaluate the association of increased plasma FVIII with cerebral venous thrombosis (CVT). Forty eight patients with non-puerperal, aseptic CVT were recruited for the study along with 50 age- and gender-matched, healthy controls. Blood samples were collected 3 months after the thrombotic event in patients. Plasma FVIII and fibrinogen levels were measured by a functional clot-based assay. Mean plasma FVIII was significantly higher in patients when compared to controls (235.40 ± 94.5 vs.121.2 ± 28.3IU/dl, p<0.001). Absence of significant elevation of fibrinogen suggested that the increase in FVIII was not due to an acute phase reaction. Elevated FVIII (>170 IU/dl) was associated with >18-fold increase in the risk for non-puerperal CVT (adjusted OR: 18.754, 95% CI 10.2-203.0, p<0.001). Non-O blood groups were more prevalent in CVT patients. Mean FVIII levels were higher in subjects with non-O blood group as compared to those with O blood group (155.16 ± 46.05 vs. 129.09 ± 40.06 IU/dl, p<0.001). Multivariate analysis with logistic regression showed that only elevated FVIII, and not blood group, was significantly associated with CVT. Our study demonstrates that elevated FVIII is an independent risk factor for non-puerperal CVT in an Indian population.

Isolated protein S deficiency presenting as catastrophic systemic arterial and subsequently venous thrombosis.

Isolated protein S deficiency is an inherited condition having proven association with venous thromboembolism. There is controversy regarding clear association between protein S deficiency and arterial thrombosis. It is therefore necessary to bring focus to this uncommon clinical condition and highlight the probable association with arterial thrombosis facilitating timely diagnosis of this condition. We describe a 48-year-old male with stroke and pulmonary thromboembolism with chronic deep vein thrombosis secondary to isolated protein S deficiency, managed with thrombolysis and long-term anticoagulation.