AWARD PAPER SESSION
Year : 2019 | Volume
: 22 | Issue : 5 | Page : 33--44
|How to cite this article:|
. Abstracts.Ann Indian Acad Neurol 2019;22:33-44
|How to cite this URL:|
. Abstracts. Ann Indian Acad Neurol [serial online] 2019 [cited 2020 Jul 10 ];22:33-44
Available from: http://www.annalsofian.org/text.asp?2019/22/5/33/267230
Sunday, October 06, 2019, 08:30AM-09:30AM, Hall A
Award Paper Session 01: Neurology
AWP/N1/229: Use of transcranial Doppler for monitoring and evaluation of idiopathic intracranial hypertension
Dhananjay Gupta, Pradeep R, Mehta A, Javali M, Srinivasa R, Acharya P
Department of Neurology, Ramaiah Medical College, Bengaluru, Karnataka, India.
Introduction: Idiopathic Intracranial Hypertension (IIH), is a disorder of unknown cause, presenting with signs and symptoms of raised intracranial pressure (ICP), in absence of underlying structural or other identifiable causes. Repeated measurement of ICP is essential for diagnosis and monitoring response to therapy. As such, repeated lumbar punctures (LP) prove to be uncomfortable for the patient as well as the physician. To overcome this, non-invasive methods such as transcranial Doppler (TCD) are being evaluated as indirect measure of ICP. A significant correlation between ICP and the TCD derived pulsatility index (PI) values has been shown in various neuro-critical care patients, including those with head trauma, sub-arachnoid haemorrhage, acute bacterial and tubercular meningitis. Similar studies in patients of IIH are limited and have shown contrasting results. Methodology: Fifteen consecutive patients, suspected to have IIH, based on clinical findings (headache, vomiting, abducens palsy and papilledema) were enrolled for the study. All these patients underwent neuroimaging (with computed tomography, CT or magnetic resonance imaging, MRI) to exclude any underlying structural cause or cerebral venous sinus thrombosis. A TCD and lumbar puncture were done and CSF opening pressure estimated. 3 patients had normal pressures and were omitted from the study. Twelve remaining patients with elevated pressures, >250 mmH2O and a normal CSF analysis were enrolled in the study. All patients with elevated CSF pressures had therapeutic CSF drainage. We compared the pre-and post-CSF withdrawal TCD derived mean blood flow (MBF), peak systolic flow (PSV) and PI values of the right and left middle cerebral (MCA), posterior cerebral (PCA) and basilar arteries (BA). Results: 9 male and 3 female patients were enrolled in the study. The mean age was 30.13 years with mean CSF opening pressure of 32.57 ± 7.27 mmH2O. The pre-LP MBF (RMCA), PSV (RMCA) and PI (RMCA) values were 59.7 ± 11.9, 98.3 ± 20.3 cm/sec and 0.96 ± 0.09 respectively. The values of pre-LP MBF (LMCA (, PSV (LMCA) and PI (LMCA) values were 61.6 ± 22.2, 94.8 ± 25.7 cm/sec and 0.88 ± 0.17. In both left and right MCA, the mean and peak blood flow velocities showed significant reduction after therapeutic CSF drainage (p<0.05). The mean and peak blood flow velocities and the PI values for BA and PCA were comparable and did not show significant reduction after CSF drainage. Discussion: A significant reduction in TCD values of right and left MCA can help in non-invasive monitoring of ICP in patients with IIH. A combination of ophthalmological examination and TCD can significantly reduce patient discomfort due to repeated invasive lumbar punctures. Limitations: The study is limited by a small sample size. 3 patients had very high CSF pressures (>400 mmH2O) with corresponding high blood flow velocities, which might have skewed the data. Future Scopes: A similar study with follow up after 1 and 6 months of CSF drainage would help in conclusively establishing the role of TCD derived blood flow velocities as an indicator for ICP.
AWP/N2/426: Optimising investigations for the enlargements of lower motor neuron: A study of 140 patients
Amit Chaudhari, Khadilkar S, Deshmukh N, Shah N, Jaggi S, Shah S, Mansukhani K, Patil S, Patel B, Shetty V
Department of Neurology, Bombay Hospital Institute of Medical Sciences, Mumbai, Maharashtra, India.
Background: A wide variety of neurological diseases result in the enlargement of nerves, roots and plexii. Clinical examination detects distal nerve enlargements and points to diagnosis of conditions like leprosy, inherited and acquired neuropathies. Contemporary electrophysiology and MRI Neurography (MRN) can evaluate the proximal segments as well. Comprehensive information on this aspect of the enlargements of the lower motor neuron is sparse. This prompted us to undertake this study. Materials and Methods: This retrospective study was performed at a tertiary care centre from January 2010 to June 2018. Patients having clinical and/or radiological enlargements of the lower motor neuron were included. Data on pertinent clinical and laboratory work up, electrophysiology, MRN and biopsy studies performed, was obtained from the patient records and was analysed. Detailed nerve conduction studies for sensory and motor parameters performed on an 8 channel Neurosoft electromyography equipment were documented. F waves, H reflexes and proximal conductions were recorded. Data of MRN which was performed on 3T Philips Achieva machine, acquiring T1and T2 weighted images in axial and sagittal planes, STIR (Short T1 inversion recovery) images in axial and coronal planes, diffusion-weighted imaging with background signal suppression (DWIBS) with coronal reconstruction, contrast enhanced T1 fat saturated axial, sagittal and coronal images were recorded. Results and Conclusions: This is the first comprehensive evaluation of the subject comprising of a large series of 140 patients. While a variety of conditions were documented, the main categories were leprosy (43) and immune neuropathies (37), nerve infiltrations (18), inherited neuropathies (12) and diabetic radiculopathies (11). Seven patients had the isolated proximal form of immune radiculopathy (Chronic immune sensorimotor polyradiculopathy, CISMP) and 7 others had non entrapment mono neuropathies (5 sciatic, 1 radial and 1 ulnar). Electrophysiology contributed to the proximal localization and characterized the demyelinating or axonal nature of the diseases; separated motor diseases like MMN from others and helped the localization of neuropathies. MRN was most useful to evaluate proximal conditions such as CISMP and sciatic neuropathies. MRN also helped characterization of nerve tumors. Utility of clinical examination. Documenting the thickening of distal nerves e.g. Leprosy, Utility of electrophysiology, CISMP: In patients with sensory ataxia, areflexia and weakness, when the distal segments were normal, study of the proximal segments with F wave and H reflex and SSEP studies assumes importance. In clinical mononeuropathies, A. Localization of mononeuropathies, B. Confirmed presence or absence of other nerve involvements, C. Gave information on conduction blocks and dispersion. Confirmed demyelinating nature in cases of CIDP. Helped differentiate between dysmyelinating and acquired demyelinating neuropathies. Utility of the MR Neurography: For confirmation of lumbosacral plexus or proximal root involvement, Details of localization, extent of involvement of neuropathies, to rule out entrapment and to determine the site of biopsy, Details of nerve tumors, Differentiating MMN from ALS, As an adjunct tool in evaluation of demyelinating and dysmyelinating neuropathies. Limitations and Further Scope: Unclassified mononeuropathies need a long term study. MRN could be used for follow ups.
AWP/N3/96: Frontal subcortical contribution to memory dysfunction in vascular cognitive impairment subtypes - A comparative study from a tertiary centre in Kolkata
Ashwani Bhat, Biswas A, Das G, Mukherjee A
Depatment of Neurology, Bangur Institute of Neurosciences, Kolkata, West Bengal, India.
Introduction: Vascular Dementia (VaD) is the second leading cause of dementia worldwide, superseded only by Alzheimer's disease. Its heterogenous pathology and clinical profile along with its potentially preventable nature make it a unique entity. The cerebral Small vessel disease is known particularly for its subcortical nature of memory impairment which is due to the disruption of frontal subcortical circuitry. This along with the course and natural history can be helpful in distinguishing between the various VaD subtypes as well as differentiating it from other dementias. Aims and Objectives: 1) To study and compare the memory dysfunction in various sub types of Vascular dementia namely small vessel and large vessel dementia respectively. 2) To study the contribution of frontal lobe and frontal subcortical circuitry dysfunction to the memory impairment. Materials and Methods: 76 patients of diagnosed Vascular Dementia were recruited at xxx. The patients were then classified as small vessel VaD and large vessel VaD accordingly. The memory function was tested using Word list memory task in Kolkata cognitive battery (KCB) for verbal memory and other standard tests while the tests from frontal assessment battery and KCB were used to test the frontal lobe and its connections. Results: Among 76 patients of VaD, small vessel VaD was identified in 48 (63.2%) cases and large vessel VaD in 28 (36.8%) cases. Hypertension, smoking and type 2 diabetes were the most prevalent risk factors. The prevalence of memory dysfunction was 36.84% (n=28) in the total sample. The prevalence of memory dysfunction was 37.5% (n=18) in small vessel disease and 35.7 % (n=10) in large vessel disease. Executive dysfunction was present in 68.8% (n=33) cases of small vessel disease and 28.65% (n=8) cases of large vessel disease (p<0.05). The nature of memory impairment in small vessel disease was predominantly subcortical when compared to large vessel disease (p<0.05). The memory impairment in small vessel disease was predominantly recent and episodic while in large vessel disease recent as well as remote memory was impaired. In small vessel disease executive dysfunction was present in 100 % of cases with memory impairment (p<0.05). Conclusion: The above findings suggest that the nature of memory impairment is different in both VaD subtypes In small vessel disease the memory impairment is subcortical in nature in and this can be attributed to concomitant executive dysfunction and disruption of frontal subcortical circuits. Thus small vessel disease can be distinguished from other cortical predominant dementias by the above mentioned features. Limitations: The limitations in our study was lack of a functional imaging study and lack of histopathological examination to support our results. Further Scope: Functional imaging can be used to further corroborate our findings. We intend to follow up our subjects to study the natural course and response to therapy as well as risk factor control since small vessel dementia is preventable at earlier stages. Increasing the sample size and adding another group from degenerative dementias will be of help.
AWP/N4/393: Spectrum and clinical profile of acute optic neuropathy patients in a tertiary care hospital in North India: A prospective observational study
Karthik Vinay Mahesh, Lal V, Goyal M, Singh P, Singh R, Takkar A
Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Introduction: Acute optic Neuropathy refers to any dysfunction of the optic nerve that causes impairment of function within 4 weeks. The etiologies are myriad and exhausting. In this study we have attempted to classify and define the clinical picture of individual etiologies and their respective investigational profile. Methods: It was an prospective observational study, we recruited consecutive patients of acute optic neuropathy presenting to our Neurology/neurophthalmology/ophthalmology clinic over a span of 1 year. their clinical and investigational profile including Neuroimaging, OCT-RFNL, Visual Acuity and Visual Fields were noted and followed up over a period of 6 months. Results: A total of 139 patients fullfing the criteria were recruited. Demyelinating Optic Neuropathy was the most common diagnosis 44.53% (n=61), followed by ischemic optic neuropathies 23.36% (n=32), undetermined etiology at 10.2 %(n=14). Demyelinating optic neuropathies were common in females (M:F = 1:4.1). disease was bilateral in 30.7% (n=43) commonly seen in Toxic Optic Neuropathy and Fulminant Intracranial Hypertension. RFNL thickness was lowest in demyelinating optic neuropathies and was maximum in fulminant intracranial hypertension. T2 hyperintense optic nerves were the most common MRI findings seen mostly in demyelination whereas ischemic optic neuropathy had relatively normal MRI. Good visual outcome defined as Visual acuity of (6/12 or better or > 2 scale improvement in the range of vision was seen in 24.8% (n=34), best outcomes were seen in Fulminant IIH (54.5%) followed by Demyelinating optic neuropathy (36%). Conclusion: Our study is large prospective study of all acute optic Neuropathies presenting to a neurologist, We have tried to categorise the clinical and investigational profile of acute optic neuropathies to better understand, avoid misdiagnosis and improve therapy in acute optic neuropathies.
AWP/N5/240: A study of inflammatory optic neuropathies from a tertiary care center in India
Prachi Barvalia, Jagiasi K, Ojha P, Soni G, Khadilkar S, Singh R, Singh R
Department of Neurology, Grant Medical College and Sir JJ Group of hospitals, Mumbai, Maharashtra, India.
Introduction and Background: Inflammatory optic neuropathies are immune mediated optic nerve disorders presenting with acute onset vision loss, pain and variable recovery. It comprises of,-optic neuritis (non-systemic-most common-Idiopathic, MS associated, NMO, MOG, ADEM) and of,-systemic inflammatory disorders such as-SLE, Sjogren's, Sarcoid, Wegeners. It is important to study the various aetiologies as treatment and prognosis differ. Indian etiological spectrum is different from western world. Materials and Methods: We studied clinical profiles, investigations, treatment & outcomes of 58 patients with optic neuritis admitted in our hospital from January 2016 to June 2019. Results: Out of 58 patients & 85 eyes studied, 31 (54%) had unilateral and 27 (46%) had bilateral optic neuritis. Male: Female ratio-:0.9:1. Age group-:12-87 yrs. Mean age 37.8 yrs. Painful vision loss: 72%. Varied from mild blurring to no light perception. Out of 58 cases-26 (45%) Idiopathic, 16 (26%) NMO, 4 (7%) MOG (7%), 4 (7%) MS, 1 case each-Idiopathic Hypertrophic pachymeningitis (HPM), IgG4 HPM, TB HPM, Neurosarcoid, CRION, Wegeners, Sjogren's, GQ1b. 21 (36 %)-recurrent attacks. 75% of total MOG and 50% of total NMO cases had recurrent attacks whereas only 23% idiopathic cases relapsed. 20 %-had myelitis. 83 % NMO, rest-Sjogren's & MS. Imaging-All idiopathic & 75% MOG: normal MRI brain or only optic nerve involvement. 25% MOG: extensive subcortical hyperintensities, midbrain, crus cerebri involvement and swollen optic nerve, more anterior & sparing chiasma. NMO: long segment optic nerve, chiasmal involvement & patchy enhancement. 10/16 cases: long segment myelitis, brain lesions-50 % NMO. Medulla, pons, MCP, thalamus, putamen, subcortical white matter-parietal, frontal, occipital, peri trigonal, most commonly involved. Sjogren's: aseptic meningitis, short segment myelitis, nodular leptomeningeal enhancement. Neurosarcoid: intense diffuse persistent optic nerve enhancement, hypertrophic pachymeningitis. Therapy-IV MPS given to all. 8 plasma exchange and 2 IVIG. 68 % received secondary immunosuppression. Azathioprine-most common, f/b rituximab, mycophenolate, cyclophosphamide, methotrexate, interferon. Outcomes-50% completely improved-75 % MOG, 45 % idiopathic, 25% NMO. No improvement:14%. 4 – NMO, 2-idiopathic, 1-Wegeners, 1-MOG. They presented late (>1month after the attack) 3 cases: lost to follow up. Conclusions: Inflammatory optic neuropathies comprise many disorders and etiological classification is of utmost importance as therapeutic goals and outcomes differ. NMO is most common in Indian perspective as against MS in western countries. MOG (75%) presents-bilateral optic neuritis. NMO has severe vision loss with poor recovery. Imaging can help determine Etiology. Diseases like NMO, MS, need to be aggressively managed whereas most MOG cases have excellent response to steroids. Long term immunosuppression needed in secondary inflammatory disorders. Idiopathic optic neuritis is a diagnosis of exclusion. Limitations: Serological tests could not be done in all patients due to financial constraints, few patients were lost to follow up. Further Scopes: To increase the duration of follow up and see how many idiopathic patients progress to MS, NMO Or MOG. Increase the number of cases and do a collaboration with other Indian institutes to understand better, the etiological spectrum from an Indian perspective.
AWP/N6/340: MeCP2 and fragile X negative autistic spectrum disorders in South Indian Tamilians commonly associated with non-specific brain imaging anomalies
Mohan Rao, Narayan SK, Kandasamy P, Mahadevan S, Nagarajan K
Department of Neurology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Background and Objectives: Autism is one of the most common neurodevelopmental disorder affecting around 0.9 in 1000 children. Aetiology of Autism spectrum disorder (ASD) is multifactorial but genetics is thought to play a major role. We examined for brain imaging anomalies and genetic profile in South Indian Tamilian ASD children and explored for any association of MRI Brain and gene mutations with the severity of autism. Materials and Methods: Children from child Guidance clinic of a quaternary referral institute full filling DSM IV Diagnostic criteria were recruited over a period of 2 years. Using a Seamen 1.5 T MRI, brain imaging was done with FLAIR, FA 150 and T1 inversion recovery sequences. DNA was analysed for the genetic mutations of Exon 2, 3 and 4 of the MeCP2 gene and also for FMR mutations. Childrens with autism spectrum disorder were included and children with deafness, visual impairment and other syndromic children were excluded. Data was analysed with SPSS version 19. Results: Of 350 screened children, 58 ASD were identified and among them, Male: female= 3.8, mean age at diagnosis 3.6. 36.2% had seizures disorders, most commonly GTCS, two had cardiac septal defects. Mean CARS score was 35.8. Comorbidities were feeding problems in 10.3%, scholastic problems in 89.7%, sleeping problems in 39.7% and hearing impairment in 6.9%. around 43% were mild autistic, 19% were moderate and 38% were severe. We anomalies noted were hippocampal atrophy, inversion or altered signals in 29 (75%) out of 39 children, but no macrocephaly or lobar hyperplasia. There was no much differences between right and left as ASD is a neurodevelopmental disorder with language disorder. 14% of the children had corpus callosum changes, 12% had temporal lobar changes and 8% had cerebellum and vermian hypoplasia. We did not find any changes in the basal ganglia or thalamic brain regions. Other nonspecific changes were HIE and Periventricular leukomalacia. Severity of the autism was not associated with comorbidities or with MR anomalies. Genetic analysis ruled out Fragile X (FMR) and MeCP2 gene mutations. Conclusions: Psychomotor comorbidities and non-specific brain imaging anomalies were common in South Indian Tamilian children, negative for common MeCP2 and FMR mutations. We also found that either the duration or severity of the autism did not correlate with the severity of MRI changes with the dichotomised MRI results. Limitations: 1. Volumetric analysis of the brain was not done, 2. Genetic studies were restricted to MeCP2 and FMR. MeCP2 is most commonly related with Rett syndrome. Further Scope: Genetic studies and volumetric analysis of the brain in ASD children in future studies will be useful to study more details on autism spectrum disorder in Tamilian children.
Sunday, October 06, 2019, 08:30-09:30, Hall B
Award Paper Session 02: Movement Disorders
AWP/MD1/297: Intravenous immunoglobulin in sydenham chorea
Department of Neurology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Introduction: Sydenham chorea is an autoimmune neurological disorder representing a common form of childhood chorea. The use of symptomatic treatment in Sydenham chorea include neuroleptics (haloperidol, risperidone, olanzapine, and pimozide) and anticonvulsants (valproate, and carbamazepine). As it is known that Sydenham chorea is an autoimmune disorder; immunomodulator treatments like corticosteroids have been tried with good results. The use of other immunomodulators such as intravenous immunoglobulin (IVIG) and plasmapheresis in Sydenham chorea is a topic of emerging interest. Aims: To study the beneficial effects of IVIG in Sydenham chorea patients with severe symptoms. Materials and Methods: Sydenham chorea patients who presented in movement disorder clinic and emergency between, January 2018 to June 2019 were recruited. All Sydenham chorea patient with severe chorea (as assessed by Walker, Wilmshurst, Wendy Clinical Rating Scale) were given IVIG (2gm/kg) over 5 days. Patients were followed up at the end of therapy, at one month and 3 month follow-up. Results: Out of 18 cases of Sydenham chorea, three cases had severe chorea. Two cases were newly diagnosed and one case presented with relapse. They had severe chorea and behavioral problems. They responded well to IVIG. The score was reduced in all three cases at the end of therapy. Follow up of all cases showed no relapse of symptoms. Conclusions: Considering an early and good outcome with minimal side effect profile compared to other treatment modalities, IVIG should be considered as an early option for primary treatment modality in cases of severe Sydenham chorea.
AWP/MD2/427: Is there a difference in autonomic dysfunction between multiple system atrophy subtypes?
Divyani Garg, Srivastava AK, Jaryal AK, Rajan R, Singh A, Pandit AK, Vibha D, Shukla G, Garg A, Pandey RM, Prasad K
Department of Neurology, Lady Hardinge Medical College, New Delhi, India.
Introduction and Background: Autonomic dysfunction is a core feature of diagnosis in Multiple System Atrophy (MSA). Early autonomic dysfunction may also be associated with poorer prognosis. Data is limited on differences in autonomic dysfunction between the two subtypes of MSA, MSA-C and MSA-P. We assessed autonomic dysfunction in MSA subtypes and Parkinson's disease (PD) and contrasted it with healthy controls. Materials and Methods: We conducted an observational cross-sectional study in North India. Patients with probable MSA (as per Gilman's consensus criteria) and PD (as per the UK Brain Bank criteria) were enrolled. A validated, self-administered questionnaire (SCOPA-AUT) was used for autonomic symptom screening. Cardiovascular autonomic testing included deep breathing tests (change in heart rate and E: I ratio), Valsalva ratio, diastolic blood pressure (BP) rise (hand-grip and cold pressor test) and postural tests (change in systolic BP and 30: 15 ratio). Disease severity was assessed by Unified MSA Rating Scale (UMSARS), Hoehn and Yahr stage and Unified Parkinson's Disease Rating scale part III (UPDRS III). Results: MSA-P (48 subjects; age 63.6 ± 9.7 years; UMSARS 45.0± 16.5), MSA-C (52 subjects; age 58.0 ± 8.1 years; UMSARS 44.0± 12.8), IPD (50 subjects; age 57.6±6.7 years) and healthy controls (50 subjects; 58.0±8.0 years) were enrolled. MSA patients were more symptomatic in gastrointestinal, urinary, cardiovascular and sexual domains than controls and in gastrointestinal, urinary and cardiovascular domains as compared to PD. The two MSA subtypes did not differ in autonomic function. Heart rate change (standing and deep breathing) and diastolic BP rise on cold pressor test were worse in MSA versus PD patients. Conclusions: We did not find any differences in autonomic dysfunction symptomatology or cardiovascular autonomic function tests between MSA-P and MSA-C patients. Symptoms of autonomic disturbance were significantly more prominent in MSA patients compared to PD patients. Orthostatic blood pressure fall in our series was lower compared to other series and requires further studies. There were minor but significant differences in cardiovascular, urinary and gastrointestinal complaints and heart rate changes in autonomic testing compared to patients with Parkinson's disease. There appeared to be no correlation between severity of autonomic symptoms and motor severity or duration of disease in patients with MSA and PD. Limitations: The diagnosis of MSA and PD both was based on clinical criteria and none of these cases had pathologic confirmation. We also restricted the objective autonomic function testing to the cardiovascular domain. Other domains of autonomic function including sudomotor testing (thermoregulatory sweat test, quantitative sudomotor axon reflex test distribution, sympathetic skin response) and pupillography were not performed. We used SCOPA-Aut which, while validated for MSA, is not as detailed as some other clinical autonomic scales hence, some symptom data may have been missed. Further Scopes: This is the largest study in literature so far on this subject. However, further detailed symptomatology screening as well as autonomic testing of gastrointestinal, thermoregulatory, pupillomotor domains etc. will shed further light on this topic.
AWP/MD3/60: Social cognition in PD-emotion recognition in comparison to normal Indian population
Meenakshisundaram S, Ranganathan LN, Samivel B, Shanmugasundaran N
Department of Neurology, Madras Institute of Neurology Madras Medical College, Chennai, Tamil Nadu, India.
Introduction and Background: Social cognition refers to the ability to correctly recognise emotions and respond appropriately to the situation. Classically social cognition is impaired in children with autism. However, recent studies have shown that social cognition may be impaired in many degenerative neurological diseases of adulthood. Aim: 1. To obtain the normative data for a test of facial emotion recognition across a pan-Indian population. 2. To study the social cognition in patients with PD and compare it with normal controls. Materials and Methods: 75 patients with PD and 1792 controls across different ages and educational levels in India were evaluated using a Faces Test for ability to recognise emotions in facial expressions. It was a self administered questionnaire with 20 questions and 2 choices for each question. The first 10 were basic emotions and the latter 10 were complex emotions. The test was self administered to the controls and administered by a single interviewer to the patients to eliminate inter-observer bias. The data was collated and the results were compared. Results: 1. This data was analysed and showed that age had a significant effect on the mean scores, with the scores decreasing with age. Females were found to have higher mean scores than males. Education had a significant effect, with higher education leading to higher scores. On average, people tended to score lower in recognising complex emotions compared to basic emotions. 2. Patients with PD were found to have significantly lower scores for both basic and complex emotions, when compared to healthy controls. The Gender-based difference in scores was absent in patients with PD. The stage and duration of disease did not have an effect on the score. Education level had an effect on the score in patients with PD while age did not have an effect. Patients with PD performed significantly worse on recognition of complex emotion compared to basic emotion. Conclusion: 1. This data may be used to formulate normal values for comparison with various disease states, in which testing of social cognition may be needed. 2. Impaired social cognition is a definite non-motor symptom of PD and could offer an alternative explanation regarding the mechanism of hypomimia in PD. The degree of involvement does not parallel the progression of motor symptoms of PD. 3. This lack of emotion recognition may interfere with the interpersonal relationships and adversely affect quality of life. For the clinician, this symptom could lead to misunderstanding with the patients and impair establishment of the doctor-patient rapport. Limitations: 1. The facial emotion recognition aspect of social cognition was tested in the controls and patients. However the other aspects of social cognition such as prosody recognition, appropriate response, etc., were not tested. 2. Further research is necessary to clearly define the clinical implications of these findings. Future Scope: 1. Functional imaging while assessing social cognition might help to recognise the site of pathology.2. Development of normative data for the other aspects of social cognition in the Indian population.
AWP/MD4/468: Motor response inhibition: A potential tool to determine optimum STN-DBS parameters
Supriyo Choudhury, Basu P, Roy A, Kumar H
Department of Neurology, Institute of Neurosciences, Kolkata, West Bengal, India.
Introduction and Background: Deep brain stimulation (DBS) of subthalamic nucleus (STN) is increasingly used in the treatment of Parkinson's disease (PD), across the globe. The effectiveness of the DBS treatment depends to a large extent on periodic programming of the device. The optimum setting of DBS parameters is determined by clinical assessments of the motor score. The hyper-direct pathway connecting the frontal cortex and STN is strongly implicated in the control of motor response inhibition. We therefore hypothesize, that optimal STN DBS will tend to normalize the SSRT in PD patients by activating this pathway. Aims: To explore the possibility of using an automated bed side test of motor response inhibition-Stop Signal Reaction Time (SSRT) while optimizing DBS parameters. Materials and Methods: We developed a stand-alone battery-operated box with one green, one red LEDs and a press-button on it. The patients were instructed to release the button as soon as the green LED flashed. Randomly, in some trials (45 out of total 180 trials) the red LED flashed just after the green LED. In those trials the patients were instructed to inhibit the activity of releasing the button. These responses can be statistically analysed to obtain an objective statistical measure-Stop Signal Reaction Time (SSRT) indicating the efficiency of response inhibition. We assessed the SSRT and UPDRS III in three situations. Initially, when the patient came to the clinic complaining of motor slowness or deteriorated tremor in existing DBS setting, after turning off the DBS and after optimizing the DBS programming. Results: We included 7 consecutive Parkinson's patients with STN-DBS leads in situ. The baseline average UPDRS III and SSRT was 26 ms (SD 12 ms) and 331 ms (SD 71 ms) respectively. We observed an increase in the UPDRS III (37, SD 17) and significant (p 0.018) prolongation of the SSRT (412 ms, SD 92 ms), after turning off the DBS. The UPDRS III reduced (11, SD 8) and SSRT shortened (285 ms, SD 45 ms) significantly (p 0.018) from baseline after optimizing the DBS settings. The percentage of patients showing improvement in UPDRS following optimisation of DBS programme had shown a perfect agreement with percentage of patient demonstarted improvement in SSRT. Conclusion: SSRT could be developed as a simple, objective and quantitative bedside tool for optimizing DBS parameters. Such an approach could be implemented with minimal training. Limitations: In this stage, the major limitation of the study is its limited sample size and collection of data from a single centre. Future multi-centric study with a large sample size will overcome these limitations. Further Scope: A mobile application will be developed to estimate the SSRT in near future. This will make the process of patient assessment much simpler and user friendly.
Sunday, October 06, 2019, 08:30AM-09:30AM, Hall C
Award Paper Session 03: Stroke
AWP/S1/135: Predictors of post-thrombolysis outcome and post-thrombolysis hemorrhage following intravenous thrombolysis with alteplase for ischemic stroke
Das S, Mondal GP, Bhattacharya R, Ghosh KC, Pattem HK
Department of Neurology, Calcutta National Medical College, Culcutta, West Bengal, India.
Introduction: Multiple trials have demonstrated the role of alteplase in reducing the growth of the infarct and significantly increasing reperfusion and recanalization of the occluded artery. However, post-thrombolysis hemorrhage is a dreaded complication. Biomarkers to identify patients at risk of severe disease and having a higher chance of post-thrombolysis hemorrhage would be valuable in guiding treatment and prognosis. Few studies have systematically evaluated the multimodal factors (demographic, clinical, radiological and biomarkers) in unselected consecutive ischemic stroke patients. Aims: To evaluate the post-thrombolysis improvement of the neurologic deficit on NIHSS and to identify the independent risk factors for poor outcome and post-thrombolysis hemorrhage. The secondary aim was to evaluate the role of biomarker (serum fibrinogen) to predict the unfavorable outcome and the chance of post-thrombolysis hemorrhage. Methods: All patients with ischemic stroke admitted to the Neurology Department between 1st May 2018 to 30th April 2019 were included in this study. Stroke severity was evaluated using the NIHSS. Furthermore, strokes were classified according to the Bamford criteria. Patients being admitted within 4.5 hours of the onset of symptoms were thrombolysed with alteplase. For each patient, a history taking, systemic examination, a noncontrast CT, routine hematological and biochemical tests, vasculitis and cardiological profiles were done. We evaluated the serum fibrinogen level at admission and 24 hours later. The degrees of disability were assessed on an outpatient basis using the modified Rankin scale. Results: 180 patients were admitted during the study period. We thrombolysed 60 patients (24 had mild, 20 had moderate and 16 had a severe stroke). 46 patients had mRS score<2, 14 had mRS score≥2. 4 patients expired. 8 patients developed intracerebral hemorrhage, among whom 3 patients expired. Higher BMI and age, diabetes, previous TIA, CHADS2 score≥2, and occurrences of total anterior circulation stroke (TACS) independently affected stroke severity. Previous TIA, low ejection fraction, CHADS2 score≥2, and occurrence of TACS predicted mRS score≥2. Atrial fibrillation, previous TIA, and CHADS2>2 predicted mortality. CHADS2>2, atrial fibrillation, the occurrence of TACS, lower ASPECT and higher SEDAN score, previous antiplatelet therapy, and anticoagulant therapy predicted the occurrence of post-thrombolysis hemorrhage. High mean arterial blood pressure (MABP) and capillary blood glucose (CBG) at admission were significant predictors of stroke severity, unfavorable outcome, mortality and the higher chance of post-thrombolysis hemorrhage. Thrombolysis significantly reduced the incidence of disability but did not significantly reduce death. Fibrinogen levels were significantly higher among those with severe stroke and post-thrombolysis hemorrhage. The performance of thrombolysis within 3 hours or between 3-4.5 hours after symptom onset did not affect morbidity, mortality or the occurrence of post-thrombolysis hemorrhage. Conclusion: The occurrence of TACS, CHADS2>2, cardioembolic stroke and higher MABP and CBG at admission emerged as the common risk factors for mRS score≥2 and post-thrombolysis hemorrhage. Fibrinogen level>450 mg/dL is a useful biomarker for predicting the higher chance of post-thrombolysis hemorrhage.
AWP/S2/171: Predictors of functional recovery of upper limb following acute ischemic stroke
Karnati Mrudula, Reddy ES, Chawda KM
Department of Neurology, Kamineni Hospitals, Hyderabad, Telangana, India.
Introduction: Stroke is the third most common cause of long-term adult disability (WHO 2004). It is estimated that 25% to 74% of stroke survivors worldwide require some or full assistance for ADL after stroke. The recovery of motor function, particularly of the upper limb determines the ability to independently undertake activities of daily living (Veerbeek et al., 2011). Being able to predict it using clinical scales and neuroimaging techniques may facilitate the use of effective targeted rehabilitation strategies & manage patient expectations. Hence this prospective observational study to predict the potential recovery of upper limb & functional independence at 3 mon. Aims and Ojectives: To analyse multivariables to determine & predict the functional recovery of upper limb after acute ischemic stroke. Clinically using Shoulder Abduction and Finger Extension (SAFE) score & Action Research Arm Test (ARAT) Score Radiologically using MRI – Diffusion tensor imaging & Fractional Anisotropy (FA) measurement. Materials and Methods: Study Site: Kamineni hospitals, Hyderabad. Inclusion Criteria: Patients with acute ischemic stroke within 3 days of onset Patients aged > 18 yrs. Exclusion Criteria: Patients with prior h/o Stroke/seizures. MRI contraindicated patients, pregnant patients. Patients with bilateral or posterior circulation strokes or cardioembolic strokes. Study Design: Prospective observational study. Sample Size: 51. Time Frame: Nov 2016 to March 2018. All the recruited 51 patients were assessed clinically using SAFE score, NIHS score initially and followed up with ARAT score. All the patients have undergone conventional neuroimaging using 1.5 Tesla Seimens. 40 patients were cooperative for diffusion tensor imaging & FA analysis. Results: Based on 3rd month post stroke ARAT score (ARAT III), they are grouped into good (ARAT = 34-57) & poor recovery (ARAT = 0-33). In our study, 39 (76.5%) patients out of 51 had normal to near normal recovery. Out of 39, 26 patients aged <=60 yrs had good recovery. There is a significant association (p=0.01) between age and upper limb recovery post stroke. Initial Mean average MRC power of good recovery group is 2.32. Mean SAFE (0-10) score for good recovery group is 4.74. Mean NIHS upper limb motor subset score (0-4) for good recovery is 2.02. In our study there is a significant positive coorelation between SAFE score and ARAT III score (r=0.458, p=0.01). In our study there is a significant negative correlation between fractional anisotropy asymmetry index and ARAT III score (r=-0.319, p=0.045). Conclusions: This is the first Indian study of similar prototype to predict the functional recovery of upper limb following acute ischemic stroke using clinical assessment scales (SAFE and ARAT scores), and DTI imaging and FA Asymmetry Index analysis. More FA asymmetry index of posterior limb of internal capsule (PLIC) suggest more structural asymmetry of PLIC and poor recovery. Out of clinical and neuroimaging scales, clinical assessment scales have high significant predictive value of recovery. Thus with initial simple clinical assessment scales most of the recovery can be predicted.
AWP/S3/221: Lower dose of oral, direct thrombin inhibitor, a novel therapy in cerebral venous sinus thrombosis - A case series study
Manorenj S, Manorenj S, Jawalkar S, Naaz B, Kumar A, Bilal MSU
Department of Neurology, Princess Esra Hospital, Deccan College of Medical Sciences, Hyderabad, Telangana, India.
Introduction and Background: Cerebral venous sinus thrombosis (CVT) is a medical emergency and accounts for 0.5% of all strokes. Published guidelines recommend usage of heparin followed by longer term oral Vitamin K antagonists. There is little knowledge about the role of newer oral anticoagulants (NOAC) like Dabigatran in CVT. Dabigatran is a reversible direct thrombin inhibitor with fastest mode of action and propitious safety profile. Presently Dabigatran is approved by the FDA for use in cardio-embolic stroke in non valvular atrial fibrillations and leg venous thrombosis. The dosage recommended in these conditions are 150 mg of Dabigatran twice a day. The FDA decision not to approve dabigatran 110 mg was based on the conclusion that dabigatran 150 mg was superior to dabigatran 110 mg for all patients. The 110 mg dose is recommended in patients at high-risk of bleeding. Data on the usage, dosage and efficacy of Dabigatran in CVT is negligible. Aim and Objective: Here we reviewed a case series of twenty patients with CVT started with 110 mg of Dabigatran twice daily in our centre. Materials and Methods: A clinical diagnosis of CVT was made after history and examination, and a MRI brain and MR venogram were performed to demonstrate thrombosis of relevant cortical venous sinuses. Study was conducted for a period of one year from January 2018 onwards. Informed consent was taken among patients diagnosed with CVT and were asked to report immediately if there was an external bleeding tendency or worsening headache or deficit. Patients were started on heparin initially followed by long term dabigatran 110 mg twice a day. Follow up of these patients were done at 2 weeks, 2 months and at 6 months. Information was collected using a proforma. Patient's improvement was determined in terms of reduction of headache and recanalization of venous sinus. Results: 35 patients were diagnosed to have CVT, out of which 21 patients gave consent for starting heparin followed by Dabigatran 110 mg twice daily. Out of 21 cases 1 patient expired during initial stay at hospital. Hence 20 patients were included in the study comprising 11 females and 9 males with ages ranging from 26 to 50 years. Repeat MRI brain with venogram at 6 months was done in 12 patients. Seizure with headache was the most common presentation occurring in 16 patients (80%), out of which, 2 patients were in status epilepticus. Isolated headache occurred in 3 patients and hemiparesis was observed in 1 patient. Single sinus thrombosis was observed in 8 patients (40%) while 12 patients had multiple sinus thrombosis. Complete resolution of symptoms occurred in all the patients (100%). Majority of the patients did not report any external bleeding tendency, while 3 patients reported Menorrhagia. Complete recanalization was observed in 11 patients (91.6%). Conclusion: Our case series demonstrates, lower dose of oral Dabigatran appears to be effective and safe in the treatment of cortical venous sinus thrombosis. However large scale randomized controlled trials will be required to confirm its efficacy as a therapeutic modality.
AWP/S4/358: Vessel wall imaging of stroke in young patients: A case series of 18 patients
Shivaram Rao Komandla, Tandra SR, Arora AJ, Dara S, Murthy N, Jabeen SA, Rani YJ, Meena AK, Borgohain R
Department of Neurology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India.
Introduction: Causes of stroke vary widely in young patients with stroke compared with older patients. High resolution contrast enhanced vessel wall magnetic resonance imaging (VW-MRI) is an emerging method of differentiating among intracranial causes of stroke such as intracranial atherosclerosis, CNS vasculitis and reversible cerebral vasoconstriction syndrome. DSA, MRA and CTA can tell only about lumen but cannot characterize the vessel wall. Methodology: Aim of Study: To examine the incidence and patterns of abnormalities in intracranial vessel wall of patients with young stroke. Design of Study: Case series and descriptive analysis. Inclusion criteria– All patients in age group of 18-45 years of age with ischemic stroke who underwent intracranial vessel wall imaging for evaluation of stroke and suspected vasculitis of all ages were included in the study. Exclusion criteria – Cardio embolic stroke Extracranial vascular occlusion. Results: Total of 18 cases of young stroke patients were studied. Of these 9 were male patients and 9 were female patients. The median age of the patients in the study is 29.5 years. 14 patients had anterior circulation strokes and 4 had posterior circulation strokes. 5 patients had NIHSS score of more than 5. 2 patients had significant homocysteine elevation. Mean duration from the time of stroke to MRI scan performed was 14 days. Concentric enhancement was seen in 4 patients, eccentric enhancement seen in 10 patients and no enhancement was seen in 3 patient. Grade 1 enhancement was seen in 4 patients, grade 2 enhancement was seen in 9 patients and no enhancement in 5 patients. Thrombus in the vessel was seen in 10 patients. Limitations: Retrospective study All patients with vasculitis received steroids or on long term immunosuppression by the time of study. Future Scope: Vessel wall imaging helps in identifying the etiology of the cause of stroke in young patients and helps in management of patients.
AWP/S5/283: Thrombaspiration versus thrombolysis in acute ischemic stroke: A prospective observational study from a rural tertiary care centre from South India
Ahamed Subir, Ghafoor F, Krishnadas NC, Rafeeque M
Department of Neurology, MES Medical College, Malappuram, Kerala, India.
Introduction and Background: Increasing stroke burden among rural Indians warrants timely treatment with newer modalities. This study is first of its kind to be reported from a rural tertiary care centre comparing clinico-epidemiological as well as in-hospital parameters and outcomes with I. V thrombolysis, thrombolysis and dual antiplatelet therapy (DAPT) in acute ischemic stroke. Materials and Methods: Prospective observational study enrolled 106 participants who underwent thrombolysis (n=47) [alteplase (n=28) and tenecteplase (n=19)], thromboaspiration (n=10) and DAPT (n=49) presenting with stroke within 6 hours of symptom onset. Age ≤ 18 years intracranial hemorrhage, wake up stroke, seizures at stroke onset and TIAs were excluded. Data was collected in case record forms and included history, physical examination, imaging findings, NIHSS (baseline, 1, 24 hrs&7 days) and modified rankin scale (mRS) at 1&3 months and were analysed using R™. Normality distribution was assessed using Shapiro-Wilk test and the tests of significance were 't' test, one-way ANOVA, repeated measures ANOVA, Mann Whitney U test, Kruskall Wallis test, Friedman test, Wilcoxon signed rank test and Chi square test and p. Results: Between treatment groups participants who underwent thromboaspiration had lower age, higher proportion had aphasia (p=0.02), dyslipidemia (p=0.004) and higher NIHSS (p=0.01) at baseline. Participants who underwent thrombolysis had higher systolic (p=0.01) and diastolic BP (p=0.01) at baseline. Participants who underwent thrombolysis had significantly lower NIHSS at 1 hour (p<0.001), 24 hours (p=0.01) and at 7 days (p=0.005) compared to baseline. Participants who received alteplase had significantly lower NIHSS at 1 hour (p<0.001) and who received tenecteplase had significantly lower NIHSS at 1 hour (p=0.008), 24 hours (p=0.01) and 7 days (p=0.009) compared to baseline. Significantly higher reduction in NIHSS was observed with thromboaspiration (p=0.02) compared to other groups. Significantly lower mRS at 3 months was observed for all treatment groups including both rt-PA and higher reduction in mRS was observed with thrombolysis (p=0.03). Between alteplase and tenecteplase, no significant difference in reduction in NIHSS and mRS was observed. But symptomatic intracranial hemorrhage (sICH) was less with tenecteplase. 10% (n=1) and 8.5% (n=4) in participants who underwent thromboaspiration and thrombolysis respectively had sICH. 10.7% (n=3) and 5.3% (n=1%) participants who received alteplase and tenecteplase had sICH respectively. Conclusions: Endovascular thromboaspiration and thrombolysis using alteplase and tenecteplase were effective than DAPT. Tenecteplase had the least risk of sICH compared to other effective treatment options and makes it a preferred thrombolytic because of faster bridging time along with its other advantages especially in centers with endovascular procedures. Limitations: Small sample size and lack of randomization are the major limitations of the study. Future Scope: Larger randomized trials on comparison of efficacy and safety is required to evaluate the efficacy of treatment options in acute ischemic stroke.
AWP/S6/367: Comparative evaluation of stroke in nondiabetic, prediabetic and diabetic Indian patients
Neetu Ramrakhiani, Kurupathy S, Dubey R, Jain N
Department of Neurology, Fortis Hospital, Jaipur, Rajasthan, India.
Aim: Comparison of stroke risk and outcome between non diabetic, pre-diabetic and diabetic population. Methods: This prospective study was conducted in Department of Neurology at XXX. Inclusion criteria included patients more than 18 years of age presenting with acute ischemic stroke with onset in less than/equal to 2 weeks willing to give informed consent. Patients less than 18 years, patients with intracranial bleed or venous sinus thrombosis were excluded from this study. History of diabetes, intake of oral hypoglycemic agents, insulin, blood sugar on admission, HBA1C were recorded. Patients were divided into categories of non diabetic, prediabetic and diabetic on basis of history and HBA1C values as per ADA 2019 guidelines. mRS was recorded at admission and 3 months. Demographic data, vessel anatomy and subtyping of stroke was done through TOAST classification. Results: Study population consisted of 365 patients with acute ischemic stroke. 135 (36.98%) patients were non diabetic, 95 (26.02%) were prediabetic and 135 (36.98%) patients were found to be diabetic. 20 patients (5.4%) were found to be newly diagnosed diabetics as per HBA1C criteria. None of the prediabetic patients were aware of their metabolic status. The mean age of patients was 59.13 years. Commonest stroke was large artery atherosclerosis in 137 (37.5%). More small vessel occlusion was seen in diabetic compared to non diabetic subgroup which was statistically significant. No such difference was found between prediabetic and diabetic subgroup. Patients were divided into ACA, MCA. PCA, AICA, PICA and SCA territory infarcts without clear predilection for either sub groups. Thrombolysis was performed in 31 patients (8.49%), no clear difference in outcome in three subgroups was noticed. A longer duration of hospital stay was observed in diabetic subjects compared to non diabetic population. However no such difference was found in the prediabetic group compared to non diabetic subgroup. No statistically significant difference was seen in post stroke events. What is known-1 the prevalence of prediabetes in previously nondiabetic patients with a recent ischemic stroke or TIA is on average 37% (range 29-53%) within 3 months of event. However only two studies used HBA1C as criteria. 2 There is lack of consensus about impact of prediabetes on stroke outcome with some studies reporting an adverse outcome and others reporting no impact. What our study adds-1 Study adds Indian data collected in a prospective manner in patients with ischemic stroke and detected prediabetes in 26 % of patients and newly detected diabetes in 5% presenting with ischemic stroke. 2 Study was positive for longer duration of hospital stay in patients with ischemic stroke. However same effect was not seen in prediabetic patients. 3 There was statistically significant worsening 3 month outcome calculated by mRS score across increasing range of diabetic control on admission recorded by HBA1C which was statistically significant. Limitations: Short follow up of 3 months. Furthur Scope: Studies with larger number of patients required to assess the impact of prediabetes on stroke outcome.
AWP/S7/455: A study of vascular imaging of intracranial vessels in ischemic stroke patients
Abhas Kumar, Renjen PN, Chaudhari D, Ahmad K, Mishra A
Department of Neurosciences, Indraprastha Apollo Hospital, New Delhi, India.
Introduction: Stroke is defined as the acute onset of focal neurological deficit of the central nervous system by a vascular cause. Factors reported to be associated with stroke severity include the location of the stenosis, plaque morphology, arterial calcification and the presence of collateral circulation. Aims: 1. To study the characteristics of atheromatous plaques in ischemic stroke patients. 2. To study the correlation between characteristics of atheromatous plaques and NIHSS score in ischemic stroke patients at the time of presentation. Materials and Methods: The present study was a cross-sectional hospital based study conducted in the Department of Neurosciences at Indraprastha Apollo Hospital, New Delhi, India. A total of 83 acute ischemic stroke patients were enrolled from August, 2017 to December, 2018, as per the inclusion and exclusion criteria. Patients were evaluated for severity of stroke by NIHSS score, risk factors of stroke and were subjected to HR-MRI/Vessel wall imaging (Black Blood imaging) apart from regular neuroimaging modalities including MRI/CT Brain. Atheromatous plaques were classified based on the dominant morphological plaque characteristics involving the symptomatic ICA in Calcified, FCR (Fibrous Capsular Rupture), IPH (Intra-Plaque Hemorrhage), LRNC (Lipid Rich Necrotic Core). Results: The present study included 83 patients (males-59%; females-41%) with mean age of females being 52.8 ± 11.6 years and of males being 54.5 ± 11 years. In the study population 29% had Calcified morphology whereas 11% had FCR, 22% had IPH and 39% had LRNC. The mean NIHSS score for Calcified plaques was 6 ± 3.3, for FCR plaques was 6.6 ± 1.8, for IPH plaques was 12.7 ± 3.7 and for LRNC plaques it was 8.8 ± 3.7. All these values were statistically significant (P-Value < 0.001). The mean NIHSS score being maximum in IPH plaque group of patients followed by LRNC. The mean ICA stenosis (%) for Calcified plaques was 46 ± 22.5 which was statistically significant (P-Value < 0.001). The mean ICA stenosis (%) being maximum in IPH plaque group of patients followed by LRNC. Correlation between NIHSS and Lumen area revealed statistically significant P-value (<0.001) with Pearson's correlation co-efficient being-0.666, suggesting a negative correlation. Conclusions: Compared to measuring luminal stenosis alone, more high-risk plaques can be identified by direct MR vessel wall imaging. In addition, carotid atherosclerotic plaque characteristics are significantly associated with severity of ischemic stroke, even after adjustment for traditional risk factors or carotid luminal stenosis. Non-invasively characterizing carotid atherosclerotic plaque by MR vessel wall imaging may be useful to better select proper treatment options of stroke subjects. CT scan is a better modality to confirm the calcified plaques as compared to HR-MRI.
Sunday, October 06, 2019, 08:30AM-09:30AM, Hall D
Award Paper Session 04: Neurogenetics & Epilepsy
AWP/NG1/370: Targeted next generation sequencing could be a first step diagnostic tool in duchenne and becker muscular dystrophies
Kiran Polavarapu, Gunasekharan S, Saroja M, Vengalil S, Nashi S, Kumar VP, Sekar D, Mahajan N, Keerthipriya M, Debnath M, Rao S, Nalini A
Departments of Neurology and Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.
Introduction: Dystrophin is the largest human gene with a complex mutational spectrum. Current genetic diagnosis of Duchenne (DMD) and Becker (BMD) muscular dystrophies usually requires two or more steps involving testing for Copy number variations (CNVs) with Multiplex ligation-dependent probe amplification (MLPA) followed by either direct sequencing for Single nucleotide variations (SNVs) and small Insertion/Deletions (INDELs) or muscle biopsy showing dystrophin loss. The present study aims at establishing a first line comprehensive diagnostic tool using targeted Next Generation Sequencing (NGS) technique to perform detailed mutational analysis of DMD/BMD patients. Methodology: Clinically suspected DMD/BMD patients with high serum Creatine kinase (CK) were recruited after MLPA results and divided into two groups: MLPA negative and MLPA positive. Custom probe design for DMD gene was created using Agilent's Sure Design TM tool with a total capture size of 2.077Mbp to cover entire gene (exons, introns and promoter regions) at least twice. After obtaining informed consent/assent, DNA extracted from blood was used to prepare libraries and sequenced on NextSeqTM (Illumina). Results: The sample size included was 163, of which, 158 were clinically diagnosed as DMD, while 5 had milder BMD phenotype. MLPA positive cases were 63 (Deletions: 56, Duplications: 7). Out of 100 MLPA negative cases, 67 underwent muscle biopsy (Absent dystrophin: 35 (53.7%), revertant fibres: 28 (41.8%), partial loss of dystrophin: 3 (4.5%)). NGS detected putative disease-causing DMD mutations in 156/163 cases (95.7%). All the CNVs and accurate intronic breakpoints in 63 patients were detected in concordance with MLPA results. NGS detected 89 unique small mutations (SNVs and INDELs) in 93/100 MLPA negative patients (93%), while no mutations were identified in 7 biopsy confirmed cases of DMD. Most of the small mutations (96.6%) identified are private mutations with 52.3% (46) being novel. Nonsense mutations were most common (54%) followed by frameshift mutations due to INDELs (20%) and splice mutations (17%). Missense mutation and deep intronic insertion were identified in one case each. Small mutations occurred in in-frame skippable exons in 41/93 (44%) patients (DMD: 38, BMD: 3). Revertant fibres are found to be significantly more common (p = 0.00004) in small mutations affecting in-frame skippable exons suggesting a complex role of beneficial exon skipping and somatic mosaicism. Conclusions: This study achieved >95% of overall mutation detection rate in Dystrophinopathy patients using targeted NGS as a first line diagnostic method. Our findings preclude undertaking the lengthy diagnostic algorithm of MLPA followed by direct sequencing and essentially eliminates the need of invasive muscle biopsy for DMD/BMD diagnosis except in 3-5% of suspected dystrophinopathies. Limitations: Lack of adequate control read data reduced the accuracy of detecting duplicated exons, resulting in false positive and negative ratios in some of the exons. Further Scope: This NGS based mutational study on a large cohort serves as a primer to develop a comprehensive mutational database of DMD mutations in India and identification of ideal candidates for emerging mutation-based therapies like exon skipping and nonsense read-through clinical trials.
AWP/NG2/430: Genetic profile of spino-muscular atrophy and its clinical correlation in a tertiary care centre: A study from Eastern India
Debasish Panigrahy, Panigrahy D, Mallick AK, Mohanty G, Mishra S, Nayak SD
Department of Neurology, Srirama Chandra Bhanja Medical College and Hospital, Cuttack, Odisha, India.
Background: Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by progressive degeneration of alpha motor neurons, leading to muscle atrophy, paralysis, and even death. The gene for SMA, survival motor neuron (SMN1) has been mapped on the 5q11.2-13.3 region and there are two copies of SMN gene: SMN1 and SMN2. Objective of this study was to estimate common genetic mutation of spino-muscular atrophy in our population and to document the clinical characteristics of SMA. Materials and Methodology: Prospective clinical study from January 2016 to December 2018 in the outpatient department of neurology. All cases with clinical characteristics of SMA along with positive electro diagnostic parameters and positive genetic mutation were included in the study. The clinical parameters were documented in a format. Statistical analysis was done using SPSS version 20.0. Results: Total patients included in the study were 25. Male: female ratio was 16:9. Most of the patients were having SMA-1 (Werdnig Hoffman) (40%). Deletion of exon 7 and exon 8 in SMN1 gene is the commonest deletion. The history of delayed development and undiagnosed early ambulatory difficulty was observed in 21 patients. Hypotonia was most common presentation. Fasciculation was grossly seen in SMA-3 and SMA 4 subtypes. In one family 4 generation people were involved. Conclusion: SMA is not an uncommon neurodegenerative disorder in eastern India and SMA type I was the most common type. SMN1 gene deletion was the most common genetic deletion found in this study. This study highlights the need for implementation of prenatal diagnosis in families with history of consanguinity or history of SMA in any generation. Limitation: It is an ongoing study. Small numbers of patients were included. We could not include different pediatric neurology centres for exact incidence estimation in eastern India. Further Scope: Genetic profile of SMA will help to know the variation of mutation in this area. Wide variation will open different scopes to prognosticate and will help in genetic counseling.
AWP/NG3/462: Parkin mutation in early and familial onset Parkinson disease patients
Laxmikant Tomar, Pandey S, Thelma BK, Kumar S, Dinesh S
Department of Neurology, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India.
Introduction and Background: Parkin is a protein, which is encoded by the PARK2 (PRKN) gene. It is commonly encountered in early onset Parkinson disease (PD) and is the commonest cause of genetic PD. Materials and Methods: To identify Parkin mutations in patients with early onset PD patients with (FEOPD; ≤50 years at onset) or without family history (EOPD; ≤50 years at onset) and late onset familial patients (FLOPD; >50 years at onset) and to do their genotype phenotype correlations. The study was conducted at xxx. The diagnosis of PD was made based on “UK Parkinson's disease society brain bank clinical diagnostic criteria”. Blood samples of 97 patients including 52 EOPD and 45 familial PD (FEOPD: 23; FLOPD: 22) were tested for all 12 exons of the Parkin gene by polymerase chain reaction (PCR)-Sanger sequencing. Further PRKN dosage and variants in known PD genes were screened by Quantitative PCR and whole exome sequencing (WES) was performed in the subset of samples. Results: A total of 25.77% (n=25) patients (EOPD: 12, FEOPD: 6, and FLOPD: 7) showed Parkin mutations. Of these 25 patients with Parkin mutation, two patients manifested as homozygous variants; while three patients were possibly compound heterozygous/bi-allelic and remaining 20 (80%) patients were with heterozygous variants. About 32% of the observed variants were found in exon 2, including a novel truncating variant i.e. (Arg 33 Ter) in a homozygous state, which is first time reported in our EOPD cohort. WES was performed in five PD subjects with homozygous variants (n=2) or likely possibly compound heterozygous PRKN variants (n=3). We found no gene variant in any known PD genes in individuals with homozygous PRKN variants, while three patients with likely possibly compound heterozygous variants had single base substitutions in VPS13C, suggesting a digenic contribution. Majority (7/12; 58.33%) of the cases were of akinetic-rigid type in EOPD group and levodopa induced dyskinesia was only seen in EOPD groups. Our study also revealed new phenotypes like: 1) Lingual dystonia (n=2) prior to levodopa treatment including one with homozygous and one with possibly compound heterozygous mutation, 2) hyperhidrosis (n=1) before the onset of motor symptoms harbouring a homozygous truncating variant Arg33Ter, 3) Mirror movement (n=2) including one with involvement of the lips with possibly compound heterozygous variants. Conclusion: This study indicate that parkin gene mutation represents a frequent cause of early-onset and familial parkinsonism in North India population. Atypical features like lingual dystonia, hyperhidrosis and mirror movements added a new phenotype in the literature. Limitations: Firstly, our study mainly focused on PRKN variants, despite the well-documented genetic heterogeneity in PD. Secondly, it is a single centric study. Future Scopes: This study revealed ~80% of the PRKN variants that harbours a heterozygous mutation making the utility of the cohort for further identification of known or additional novel genetic risk factors conferring PD gene. Disclosures: This study was funded by department of biotechnology, government of India and part by JC Bose fellowship. A poster was presented during IPMDS conference 2019 using this data.
AWP/E1/238: Disability adjusted life years as measure of burden of epilepsy in persons who undergo seizure monitoring
Mohan V Sumedha Maturu, Thomas SV, Sarma SP
Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
Introduction: Epilepsy prevalence reported in various Indian studies is 3.0-11.9/1000. For the population of 1.3 billion in India, there is only 1 estimate of DALY of Epilepsy (Kolkata) till now. Aim: To estimate DALY of epilepsy using WHO recommended protocols in People with Epilepsy (PWE) residing in Kerala. Methods: This is Retrospective-Prospective study. All PWE residing in Kerala, admitted to Epilepsy Monitoring Unit (EMU) of tertiary epilepsy centre between 01/01/2005-31/12/2015 were enrolled. Demographic and clinical characteristics including seizure burden at time of admission and last follow up were abstracted from medical records. Those who had last visit before 31/12/2016 were contacted through mail to enquire about their latest status and seizure burden. Those who did not respond to mail were treated as “Lost to follow up.” Those to responded to mail and/or attended clinic after 31/12/2016 were treated as “Survivors.” Those reply mails that communicated the demise of person were used to identify the “deaths” during study period. The study sample was derived as 10% of survivors (Identified by age and sex stratified computer assisted random allocation) and all deaths. Prevalence based YLD was calculated as per recent WHO methods. Disability weight and Standard Loss function were extrapolated from WHO-DALY methods 2018. DALY was calculated by adding YLL and YLD. Results: 3506 PWE were enrolled. There were 45 (1.3%) deaths, 1491 (42.5%) had lost to follow up, 1970 (56.2%) were survivors of which 1448 had attended clinic while the rest 522 communicated via mail. For the analysis of DALY, the study sample included 204 (10.3%) survivors along with 45 (100%) deceased. 137 (55%) were males and 112 (45%) were females. 146 (58.6%) had epilepsy onset at age ≤20 yrs, 79 (31.7%) had onset between 21-40 yrs and 24 (9.6%) had onset >40 yrs. Mean DALY was found to be 512.48. Males were found to have higher DALY (578.40) as compared to females (429.87). People with younger age of onset ≤20 yrs had higher DALY (1173.36) as compared to middle age 21-40 yrs (284.08) or older age >40 yrs (79.11). Despite most of the enrolled PWE had refractory epilepsy, we have observed that DALY of epilepsy between 2005-15 in Kerala (512.48) was lower as compared to DALY reported between 2003-08 from Kolkata (846.96). This may be due to fact that most of PWE went into remission at their last visit as result of adequate AED optimization, timely planning of epilepsy surgeries. Conclusion: This is first study in India to determine the DALY of epilepsy using GBD2016. The results of this study indicate that epilepsy burden could be reduced with adequate management. Age, sex based variations in DALY should be taken into consideration when planning National policies of Epilepsy care. Limitations: While interpreting this data, it is to be kept in mind that this study was conducted in tertiary epilepsy centre. Further Scopes: Our study forms the basis for undertaking similar studies from different parts of India.
AWP/E2/422: EEG patterns in focal cortical dysplasia and refractory epilepsy-correlation with imaging and post surgical outcomes
Anuja Patil, Jayalakshmi S, Babu S
Department of Neurology, Krishna Institute of Medical Sciences, Secunderabad, Telangana, India.
Introduction: Focal cortical dysplasia (FCD) is the most common malformation of cortical development (MCD), leading predominantly to focal epilepsies that are medically refractory and requires surgery in a majority. In many cases, the FCDs are both intrinsically epileptogenic and the epileptogenic zone (EZ) extends well beyond the structural lesion. Precise characterisation of this EZ with multimodal evaluation is crucial for surgical success. Objective: To characterize the clinical, imaging and EEG patterns of type-1 and type-2 FCDwith refractory epilepsy and determine predictors of surgical outcome. Methods: Retrospective analysis of data of 188 consecutive patients operated for drug resistant epilepsy and a diagnosis of FCD with at least two years post-surgery follow-up was done. The clinical features, MRI, interictal and ictal EEG patterns were studied for all patients. Inter-ictal PET and ictal SPECT were studied in some cases with normal or subtle MRI findings. these parameters weere compared among patients with postsuregery seizure remission (ILAE class I) versus those with persistent seizures (class II to VI). Results: Average age of patients was 17.31±11.26 (2 – 64) years with 92 (48.9%) women. Mean age at surgery was 17±11.26 years (2-64 years). About 47 (25%) patients had history of delayed development while at the time of presentation 106 (56.4%) had daily multiple seizures for a period of at least 6 months. Interictal EEG showed regional pattern in 66% of FCD2 patients (p=0.04), while generalised interictal discharges were commonly associated with persistent seizures after surgery (p=0.016). Ictal beta rhythm was significantly associated with FCD2 (p=0.05). Generalised ictal onset was significantly seen in patients with persistent seizures after surgery (p=0.48). MRI showed clear cut FCD in 72.3% patients. Inter-ictal FDG-PET showed focal hypo/hypermetabolism in 76.6%; Ictal SPECT showed focal hyperperfusion was noted in 70.3%. At last follow-up 66.0% were seizure free. Patients with FCD type-1 had earlier age at onset (p=0.029) of epilepsy and had multiple seizure patterns (0.034). Patients with FCD type-2 commonly reported aura (p=0.019) and had clear-cut lesion on MRI (p=0.021) and high seizure freedom (p=0.004). Patients with FCD type-1 more often had normal MRI, and were detected on PET-MRI fusion study, underwent multilobar resections and had higher rate of acute postoperative seizures, while complete resection was more frequent in type-2 FCD. Conclusion: FCD type-1 was associated with early onset of seizures with multiple seizure types in the same patient, subtle MRI, multi-lobar location hence multi-lobar resection and poor surgical outcome while type-2 FCD was associated with clear-cut MRI lesion, regional inter-ictal discharges, ictal beta at onset with complete resection at surgery hence more favorable post-surgical outcome.
AWP/E3/188: Do women with epilepsy benefit from epilepsy specific pre-conception care
Jitupam Baishya, Thomas S, Reshma AS, Jose M, Sarma S
Department of Neurology, Post Graduate Institute for Medical Education and Research, Chandigarh, India.
Introduction and Background: Risk of anti-epileptic drug (AED) associated fetal malformation and strategies to minimize this risk are major concerns for WWE and their care providers. Preconception care (PCC) is the process of planning and preparing for pregnancy through appropriate physical, mental, and emotional health interventions in order to reduce adverse pregnancy outcome and improve the health of the mother and child. To our knowledge no studies have examined systematically the benefit of PCC in pregnancy outcome and seizure outcome of WWE in pregnancy period. The objective of this analysis is to assess how PCC influenced the maternal and fetal outcome of pregnancy in WWE. Materials and Methods: All primigravida in the Kerala registry of epilepsy and pregnancy (KREP) with the final outcome of pregnancy known who were enrolled prospectively in pre-conception stage (PCC group) or first trimester of pregnancy (PRG group) were included. Multigravidae were excluded from this analysis as they would have received counselling, precautionary advices and care related to epilepsy and pregnancy during previous pregnancies. We compared the PCC and PRG groups for outcome measures: AED and folic acid usage during pregnancy, seizure relapse during pregnancy, fetal loss and incidence of MCM in the baby. Statistical Analysis: Quantitative data were summarized with mean and standard deviation. Categorical variables were described as percentages. Statistical significance of differences were ascertained by t- test for quantitative variables, and by chi-square tests/Fisher's exact tests for categorical variables considering p≤.05 as significant. Results: There were 320 (30.4%) in PCC group and 732 in PRG group. Both groups were comparable for epilepsy classification, maternal birth defects and family history of epilepsy but the PCC group had significantly higher education (48.9%, p=.027) and employment (22.1%, p<.001). They had higher usage of folate in pre-pregnancy month (87.5%, p<.001) and first trimester (96.3%, p<.001) than PRG group. Fewer women in the PCC group were off AEDs in first trimester (5% vs 9.3%, p=.018). Within monotherapy group, use of levetiracetam (10.8%, p=.017), valproate (34%, p=.002) in PCC group and carbamazepine (39.1%, p=.04), phenobarbitone (13.3%, p=.001) in PRG group was significantly high. More women in this group were seizure free during pregnancy (62.8%, p=.005) than PRG group. Early fetal loss was better captured in PCC (90.6%, p=.025) than in the PRG. There was no difference in malformation rate between PCC (7.2%) and PRG groups (6.1%, p=.3). Conclusion: PCC reduced the risk of seizures during pregnancy and improved the periconceptional use of folate but did not influence the fetal malformation risk. The association of seizure freedom and pre-pregnancy folic acid usage with PCC highlights the public health role of PCC in WWE. Limitations: As data for the registry is provided by the participants on scheduled visits, recall bias should be kept in mind while analysing the dataset.