Annals of Indian Academy of Neurology
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November-December 2020
Volume 23 | Issue 6
Page Nos. 741-841

Online since Friday, December 18, 2020

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EDITORIAL COMMENTARY  

Diagnostic value of electroencephalogram in Creutzfeldt-Jakob Disease p. 741
Kurupath Radhakrishnan
DOI:10.4103/aian.AIAN_902_20  
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Nusinersen and spinal muscular atrophies: Where are we in 2020? p. 743
Satish V Khadilkar, Rakesh K Singh
DOI:10.4103/aian.AIAN_887_20  
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Editorial comment on erectile dysfunction in migraine p. 745
Sumit Singh
DOI:10.4103/aian.AIAN_1218_20  
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AIAN REVIEW Top

Status epilepticus in neonates and infants p. 747
Rajni Farmania, Divyani Garg, Suvasini Sharma
DOI:10.4103/aian.AIAN_189_20  
Status epilepticus (SE) is a common neurological emergency in childhood associated with high mortality and morbidity. Acute management of seizures along with aggressive evaluation for establishing the underlying cause are crucial determinants of outcome. Neonatal status epilepticus carries the burden of poor neurological outcomes and may lead to global developmental delay as well as persistent seizures. The aetiology and pathophysiological mechanisms of SE in neonates and young infants differ compared to older children and adults. The most common causes of SE in neonates includes hypoxic sequelae, ischemic stroke and intracranial haemorrhage. In infants, febrile status epilepticus and acute symptomatic seizures are more common than remote symptomatic causes. Recent advances in neuroimaging modalities and molecular diagnostic techniques have facilitated better diagnostic precision. There is deplorable lack of evidence evaluating management strategies of SE in this age group. In addition to prompt initiation of antiseizure medications, vitamin supplementation needs to be empirically added. Simultaneously, meticulous evaluation to determine cause must also be conducted. In this review, we discuss challenges and an algorithmic approach to the diagnosis and management of SE in neonates and infants.
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The role of repetitive transcranial magnetic stimulation for enhancing the quality of life in Parkinson's Disease: A systematic review p. 755
Ashima Nehra, Priya S Sharma, Avneesh Narain, Amit Kumar, Swati Bajpai, Roopa Rajan, Nand Kumar, Vinay Goyal, Achal K Srivastava
DOI:10.4103/aian.AIAN_70_20  
Background: Parkinson's disease (PD) is a neurodegenerative disorder which greatly affects patients' quality of life. Despite an exponential increase in PD cases, not much attention has been paid to enhancing their quality of life (QoL). Thus, this systematic review aims to summarize the available literature for the role of repetitive transcranial magnetic stimulation (rTMS) intervention to improve QoL of PD patients. Methods: Literature review was carried out using PubMed, Embase, Web of Science and Scopus databases. The key search words were, “rTMS AND Parkinson AND QoL”, “rTMS AND Parkinson AND Quality of Life”. Cochrane Collaboration software Revman 5.3 was used to assess the quality of studies. Results: Over 707 studies were identified out of which 5 studies were included which consisted of 160 subjects, 89 male and 71 female, with mean age of 65.04 years. PD type varied from idiopathic PD, rigid, akinetic, tremor dominant to mixed type. The overall risk of bias across the studies was low and unclear with high risk of bias in incomplete outcome data domain in one study. Conclusions: The efficacy of rTMS as an adjunct intervention to enhance QoL of PD patients is uncertain due to dire lack of research in this area. The findings of the present review would help researchers conduct a well-defined, randomized, controlled trial by overcoming the present limitations associated with rTMS intervention to improve QoL of PD patients.
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ORIGINAL ARTICLES Top

EEG observations in probable sporadic CJD p. 760
Ravindranadh Chowdary Mundlamurri, Rutul Shah, M Sharath Adiga, Aparijita Chatterjee, Bhargava Gautham, K Raghavendra, A Ajay, Anita Mahadevan, Karthik Kulanthaivelu, Sanjib Sinha
DOI:10.4103/aian.AIAN_672_20  
Introduction: Sporadic Creutzfeldt Jakob Disease, the most common reported prion disease, is a fatal neurodegenerative disease caused by the misfolding of protein PrPC to PrPSC. EEG is the first in vivo test to support the clinical diagnosis of sporadic CJD (sCJD). This study is carried out to describe the comprehensive electroencephalography changes in a cohort of patients with probable sCJD from south India. Methodology: This retrospective observational study is conducted by reviewing case records from 2013–2020. Demographic, clinical, imaging details were noted. Electroencephalogram (EEG) recordings were retrieved and reviewed independently by two qualified epileptologists and the findings were visually analyzed and correlated with clinical and imaging abnormalities. Results: Fifty patients with probable sCJD with the availability of artefact-free EEG were included in the study. The mean age was 59.76 ± 8.17 years and M: F was 31:19. Magnetic resonance imaging (MRI) brain showed abnormality defining CJD in 48/50, i.e., 96%patients. EEG showed specific and or nonspecific abnormalities in 88%. The specific abnormalities, i.e., periodic sharp wave complexes (PSWC), were noted 66%. PSWC were mostly asymmetric (90%) and more frequently seen in the right hemisphere (57.6%). Amplitude maximum in the occipital region was noted in 42.4% and in frontal region in 36.4%. The sensitivity of EEG specific abnormalities to diagnose probable sCJD according to CDC 2018 criteria with positive MRI findings was 68.75%. Conclusion: This study showed that EEG is a relatively inexpensive and sensitive tool and assists in the diagnosis of sCJD. However, it can be normal or show nonspecific abnormalities in the early stages of the disease.
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Efficacy of bacopa monnieri (Brahmi) and Donepezil in Alzheimer's Disease and mild cognitive impairment: A randomized double-blind parallel Phase 2b study p. 767
Sudesh Prabhakar, Venugopalan Y Vishnu, Manish Modi, Manju Mohanty, Anchal Sharma, Bikas Medhi, BR Mittal, Niranjan Khandelwal, Manoj K Goyal, Vivek Lal, Rajesh Singla, Avinash Kansal, Ajit Avasthi
DOI:10.4103/aian.AIAN_610_19  
Objectives: Alzheimer's disease (AD) is the most common cause of dementia worldwide in the older population. There is no disease-modifying therapy available for AD. The current standard of care drug therapy for AD is cholinesterase inhibitors, including donepezil. Bacopa monnieri or brahmi is used in traditional Indian medicine for memory loss. We conducted a phase 2b randomized controlled trial (RCT) to find out the efficacy of brahmi and donepezil in AD and mild cognitive impairment (MCI). Patients and Methods: The study was planned as a 52 week, randomized, double-blind, parallel-group, phase-2 single-center clinical trial comparing the efficacy and safety of Bacopa monnieri (brahmi) 300 mg OD and donepezil 10 mg OD for 12 months in 48 patients with AD and MCI-AD including cognitive and quality of life outcomes. The primary outcome was differences in the change from baseline of the neuropsychological tests [Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) and postgraduate institute (PGI) memory scale] at 12 months between the intervention group (brahmi) and active comparison group (donepezil). Results: The study was terminated after 3 years and 9 months, after recruiting 34 patients, because of slow recruitment and a high dropout rate. Intention to treat analysis after adjusting for baseline confounders showed no difference in the rate of change in ADAS-Cog score from baseline at any time point, including the last follow-up. There was no difference in the rate of change in PGI Memory scale (PGIMS) at 3, 6, and 9 months. In the last follow-up, there was a significant difference in the change in total PGIMS score between brahmi and donepezil, while there was no difference in individual scores of the PGI memory scale. Conclusion: This phase-2 RCT on the efficacy of brahmi vs. donepezil showed no significant difference between them after 1 year of treatment. Larger phase-3 trials, preferably multicentric, are required to find the superiority of brahmi over donepezil.
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Pain assessment in Indian Parkinson's Disease patients using King's Parkinson's Disease pain scale p. 774
Madhuri Behari, Abhilekh Srivastava, Renu Achtani, Neha Nandal, Rupa Bala Dutta
DOI:10.4103/aian.AIAN_449_20  
Background: Pain is a common symptom in Parkinson's disease (PD) patients. Scales to rate pain in PD are marred by several flaws, either not being available in other languages or not specific for PD. Objectives: To assess the frequency of pain among bilingual Indian PD patients using “King's Parkinson's disease pain scale” (KPPS) and to validate it. Methods: We randomly administered KPPS in Hindi/English to all consecutive bilingual persons with PD. The results were appropriately analyzed. Results: A total of 119 PD patients were enrolled with a mean age of 64.34 (± 9.57) years. Median Hoehn and Yahr stage was 2 (42.85%). Pain was present in 62 (52.1%) PD patients. The most common type was musculoskeletal (74.19%). The mean total KPPS score was 16.02 ± 10.57. KPPS score was significantly higher in women and correlated positively with unified Parkinson's disease rating scale (UPDRS) part 2 and 4 scores (r = 0.27 and r = 0.25). Risk factors for pain were female gender, higher H and Y stage, total UPDRS score, and individual UPDRS part 3 and 4 scores. Difficulty falling asleep (P = 0.01), frequent awakenings (P = 0.01), diminished smell sensation (P = 0.003), diminished speech volume (P = 0.02), gait freezing (P = 0.03), and falls (P = 0.001) correlated with the presence of pain. The interclass correlation coefficient between the Hindi and English versions of KPPS was 0.835, while Bland–Altman analysis showed 96.7% agreement suggesting excellent correlation and validation. Conclusions: KPPS is an easy tool for characterization, scoring, and follow-up of pain in PD patients. The Hindi version has good agreement with the original English version.
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Clinical profile of migraine in a rural population presenting to Tertiary Care Hospital in North India p. 781
Sulena , Monika Singla, Jaisal Brar, Richa Kale, Sandesh Kale
DOI:10.4103/aian.AIAN_671_19  
Background and Objective: Migraine is one of the most common types of headache leading to significant disability; still people do not seek early help in developing countries. Therefore, we planned to conduct a study to assess the clinical profile of migraine, its triggers, comorbidities, and related disability in rural India. Design: An observational study in which 1,245 men and women suffering from migraine were recruited at a tertiary care hospital and were asked to complete a questionnaire related to migraine, its triggers, comorbidities, and disability. Results: Out of 1245 patients, females constituted 75% (937) of the patient pool and rest 25% were males (308). Fatigability (52.7%), nausea/vomiting (42.7%), phonophobia (33.57%), numbness (28.2%), and vertiginous sensation (20.8%) were accompanying features. Stress was the most common trigger impacting 44.9% of the patient population, followed by noise in 44.3% of cases. Exertion and sleep disturbance acted as triggers in 36.1%, smells in 20.5%, hormonal factors in 11.5%, and visual stimuli in 5.1% of patients. Anxiety was identified as the most common comorbidity affecting 542 patients (43.5%), followed by depression in 25.7%of patients. Around 103 patients (8.2%) had other psychiatric illnesses such as panic disorder and bipolar mood disorder. Conclusion: The migraine-related disability is high; therefore we conducted a study to understand its triggers and clinical profile. This was the first observational study conducted in a tertiary care hospital on migraine in north India catering to a sizeable rural population however, larger population studies are required to understand migraine more exhaustively.
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The serum prolidase enzyme activity as a biomarker for evaluation of the subclinical vascular damage in children with epilepsy p. 787
Nurettin Karacan, Mustafa Çalik, Halil Kazanasmaz, Özlem Ethemoğlu, Ahmet Güzelçiçek, Sedat Yaşin, Hasan Kandemir, Emre Çeçen
DOI:10.4103/aian.AIAN_640_19  
Backgroud: Epilepsy is a chronic medical condition requiring long term or even lifelong therapy. Various researches have shown that epilepsy patients have vascular risk factors such as abnormal lipids, insulin, elevated oxidative stress, chronic inflammation, and subclinical atherosclerosis. Objectives: The purpose of the present study was to determine serum prolidase enzyme activity as a biomarker in children taking antiepileptic drug treatment through comparison with control cases. Materials and Methods: The present study group consists of 61 children (20 females, 41 males) with epilepsy and a control group was formed of 32 healthy individuals (14 females, 18 males). Aspectrophotometric method was used to measure serum prolidase enzyme activity. Results: The epilepsy group demonstrated statistically significantly higher prolidase enzyme activity values when compared with the control group (P = 0.003). It was measured that the serum TOS and OSI values were significantly elevated in patients with epilepsy compared to controls (P < 0.001). However, serum TAS values were significantly lower in the epilepsy group than in the control group (P = 0.032). Conclusions: These results supported that epileptic patients taking the antiepileptic treatment had increased serum prolidase enzyme activity, suggesting that it may show an increased risk of subclinical vascular damage related to both chronic inflammation and fibrotic process associated with degenerated collagen turnover. Therefore, serum prolidase enzyme activity could be considered a useful biomarker for evaluation of the subclinical vascular damage in children with epilepsy on some antiepileptic drugs.
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Erectile dysfunction in migraine in Indian patients p. 792
SC Nemichandra, R Pradeep, S Harsha, K Radhika, Roshan Iqbal
DOI:10.4103/aian.AIAN_554_19  
Background: Migraine is one of the common causes of primary headache worldwide. Migraine headaches significantly affect family and social activities. Migraine also impacts the sexual function of the sufferers. There are no published studies in India so far where they have studied the erectile function in male migrainers. This study is done to look for erectile dysfunction in male migrainers. Materials and Methods: This case-control study was done to look for presence of erectile dysfunction in male migrainers and the factors affecting it. Thirty age matched males with migraine and without migraine were studied. The International Headache Society's International Classification of Headache Disorders, 3rd Edition, was used to diagnose migraine with or without aura. Migraine disability assessment scale was used to assess migraine-related disability, Numerical Rating Scale was used assess to the severity of headaches, Migraine-Specific Quality of Life Questionnaire to assess the quality of life, and International Index of Erectile Function score was used to assess the erectile function. Results: The mean age of the cases was 38.83 ± 5.7 years and that of the controls was 38.63 ± 5.3 years. The erectile dysfunction was seen in 80% of migrainers and none in the control group had erectile dysfunction. Those with erectile dysfunction had more severe headache which were severely disabling. Conclusion: Erectile dysfunction is common in migraine. There is a significant negative correlation of erectile dysfunction with severe disabling migraine.
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Clinical experience of nusinersen in a broad spectrum of spinal muscular atrophy: A retrospective study p. 796
Ae Ryoung Kim, Jong-Mok Lee, Yu-Sun Min, Hoseok Lee, Dongsub Kim, Su-Kyeong Hwang, Soonhak Kwon, Yun Jeong Lee
DOI:10.4103/aian.AIAN_524_20  
Background: Nusinersen has recently been approved and more widely used as first-line treatment of spinal muscular atrophy (SMA). This study aimed to evaluate the real-world experience of nusinersen use for patients with a broad spectrum of SMA. Methods: We reviewed consecutive patients with SMA treated with nusinersen from April 2018 to April 2020. Data collected included clinical and diagnostic characteristics, molecular genetics, functional motor outcomes, and adverse events. Results: Seven patients including four with SMA type 1 and three with SMA type 2 were treated with nusinersen. The median disease duration at the time of the first dose and the median follow-up duration were 37 months (range: 0.5–254 months) and 6.1 months (range: 2.1–22.1 months), respectively. Of the 41 lumbar punctures (LPs), seven fluoroscopy-guided LPs were successfully performed for two patients without sedation. All patients showed improvement in motor function even though the current tools for motor assessment seemed unable to detect subtle subjective improvement. All patients maintained a stable respiratory status. No patient has experienced a severe adverse event or discontinued treatment so far. Conclusion: Although the number of patients in this study was small, our results suggest that nusinersen is effective even in patients with a later stage of the disease. Additional long-term prospective studies with more number of patients having a broad spectrum of diseases are needed to identify meaningful improvement in the motor function and quality of life after nusinersen treatment.
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CASE REPORTS Top

Mitochondrial membrane protein–associated neurodegeneration: A case series of six children Highly accessed article p. 802
Faruk Incecik, Ozlem M Herguner, Atil Bisgin
DOI:10.4103/aian.AIAN_268_19  
Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic disorders with a progressive extrapyramidal syndrome and excessive iron deposition in the brain, particularly in the globus pallidus and substantia nigra. Mitochondrial membrane protein–associated neurodegeneration (MPAN), a subtype of NBIA, is caused by mutation in the orphan gene C19orf12. A slowly progressive gait disorder from generalized dystonia and spasticity and cognitive impairment constitute the main features of MPAN. The C19orf12 p.Thr11Met mutation is frequent among Turkish patients with MPAN. Here, we report the clinical manifestations and genetic study results of six Turkish patients with MPAN due to different mutations from previous.
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Zoster brachial plexopathy as a presenting manifestation of human immunodeficiency virus infection p. 804
Rajesh Verma, Soumik Sarkar, Chetan Shettigar
DOI:10.4103/aian.AIAN_158_19  
Brachial plexopathy is an uncommon neurologic complication of varicella-zoster virus (VZV) infection. VZV is not an acquired immunodeficiency syndrome-defining illness, but human immunodeficiency virus (HIV) infection is a risk factor for atypical and severe complications of VZV reactivation. Here, we present a 70-year-old male, who presented with left upper-limb weakness, preceded by painful dermatomal vesicular eruption, and was diagnosed to have zoster brachial plexopathy. This severe and atypical manifestation of VZV prompted HIV infection testing, leading to a new diagnosis of HIV infection.
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Neurological manifestations of scrub typhus: A case series from Tertiary Care Hospital in Southern East Rajasthan Highly accessed article p. 808
Vijay Sardana, Prashant Shringi
DOI:10.4103/aian.AIAN_97_19  
Scrub typhus is an acute febrile infectious illness caused by rickettsia species Orientia tsutsugamushi. In recent years, scrub typhus has reemerged as a life-threatening disease in India Scrub typhus has diverse clinical manifestations ranging from a nonspecific febrile illness to severe multiorgan dysfunction, and neurological complications are also common. Spectrum of neurological complications varies from common complications such as aseptic meningitis, meningoencephalitis and cerebellitis to rare complications such as myelitis, cerebral hemorrhage, acute disseminated encephalomyelitis (ADEM), and cerebral infarction. Scrub typhus is not a common cause of acute febrile illness in state like Rajasthan, but has emerged as a life-threatening disease in recent years along with dreaded neurological complications. This case series highlights various neurological manifestations of scrub typhus as early diagnosis and treatment of neurological complications have good prognosis.
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Calcified pseudoneoplasm of the neuraxis (CAPNON)–A rare cause for temporal lobe epilepsy: Not all warrant a surgical intervention Highly accessed article p. 811
Prashanth Raghu, Balaji Jeevanandham, Rajoo Ramachandran, Jeffrey Ralph, Pranesh Paneerselvam
DOI:10.4103/aian.AIAN_462_19  
Epilepsy is a common neurological condition with varied etiological causes, with temporal lobe epilepsy being the most common. Among the varied etiologies of temporal lobe epilepsy, mesial temporal sclerosis is an important one and it presents as intractable epilepsy. However, we describe here a case of intractable temporal lobe epilepsy with a rather rare etiology, calcifying pseudo neoplasm of neuraxis (CAPNON) syndrome. CAPNON is a rare benign lesion that can occur anywhere in the central nervous system. The thought process till date is to excise any intracranial space occupying lesion to relieve pressure and for a better prognosis, which is not questionable. However, we feel in case of CAPNON, wait and watch protocol can be used to a better effect with radiological and clinical follow-up. Above all surgical excision was primarily done due to imaging confusion over CAPNON and this article comes up with few key findings to clinch the radiological diagnosis of CAPNON.
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SECTION: LIGHTER MOMENTS-ARTWORK Top

Cocooned in Covid p. 814
KP Divya
DOI:10.4103/aian.AIAN_617_20  
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LIGHTER MOMENTS (ARTWORK OR PHOTOGRAPHY) Top

Master of the symphony p. 815
Madhusudan Samprathi
DOI:10.4103/aian.AIAN_677_20  
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LETTERS TO THE EDITOR Top

Fatal cerebral events following insect stings may be due to inappropriate mast cell activation p. 816
Sujoy Khan
DOI:10.4103/aian.AIAN_50_20  
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Congenital absence of internal carotid artery and complex cerebral vascular abnormalities with thalassemia intermedia: A novel association? p. 817
Poonam Sherwani, Manali Arora, Indar Kumar Sharawat, Prateek Kumar Panda, Raksha Ranjan, Sudhir Saxena
DOI:10.4103/aian.AIAN_60_20  
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Guillain barre syndrome: A rare cause of floppy neonate p. 819
Rajkumar M Meshram, Swapnil D Bhongade, Vishal S Gajimwar
DOI:10.4103/aian.AIAN_368_19  
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“Motor band sign” in susceptibility-weighted imaging in motor neuron Disease p. 821
Arvind N Prabhu, Lakshmi Manasa Sajja
DOI:10.4103/aian.AIAN_259_19  
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Visual loss in biotinidase deficiency Highly accessed article p. 821
Nataraja P Venugopal
DOI:10.4103/aian.AIAN_503_19  
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Amnesia following hot water bath from gas geyser p. 823
Pradhan Sunil, Das Animesh
DOI:10.4103/aian.AIAN_310_19  
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Two clinical cases of LBSL: Diagnostic problems and possible therapeutic approaches p. 825
Mariia A Bedova, Aleksandr G Ilves, Lidia N Prakhova, Zhanna I Savintseva, Elena M Chernysheva
DOI:10.4103/aian.AIAN_430_19  
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Isolated cerebellar involvement in X-linked adrenoleukodystrophy p. 827
CA Mansoor
DOI:10.4103/aian.AIAN_48_20  
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Kabuki syndrome: A rare clinical presentation p. 828
Abhishek D Wankar
DOI:10.4103/aian.AIAN_541_19  
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Understanding demyelination in leprosy neuropathy: A nerve biopsy analysis p. 829
Rubina Hassan, Monalisa Hui, Yareeda Sireesha, Jabeen Afshan, AK Meena, Megha S Uppin
DOI:10.4103/aian.AIAN_553_19  
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Novel heterozygous HTRA1 pathogenic variant found in a Chinese family with autosomal dominant cerebral small vessel Disease p. 832
Changzhu Wu, Long Chen, Shaofa Ke
DOI:10.4103/aian.AIAN_74_20  
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Application of internal auditory canal MRI in ramsay hunt syndrome involving multiple cranial nerves p. 835
Changqing Li, Jian Li, Lichun Zhou
DOI:10.4103/aian.AIAN_20_20  
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Paroxysmal exercise-induced dyskinesia in siblings due to ECHS1 gene mutation – First Indian case report p. 837
Vajramanickam Senthilkumar, Kiruthika Sivaraj
DOI:10.4103/aian.AIAN_89_20  
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Spontaneous subarachnoid haemorrhage in an obstetric patient post spinal anaesthesia p. 838
Abhishek Yadav, Avishkar Agrawal, Roopa Sharma
DOI:10.4103/aian.AIAN_97_20  
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BOOK REVIEW Top

100 interesting case studies in neurointervention: Tips and tricks p. 841
Blaise Baxter
DOI:10.4103/aian.AIAN_497_20  
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