Padma Srivastava

Current status of intravenous thrombolysis for acute ischemic stroke in Asia

Background Data regarding thrombolysis for acute ischemic stroke in Asia are scarce and only a small percentage of patients are thrombolysed. The dose of intravenous tissue plasminogen activator (IV-tPA) in Asia remains controversial. Case-controlled observation studies in Asia included only Japanese patients and suggested the clinical efficacy and safety of low-dose IV-tPA (0·6 mg/kg body weight; max 60 mg) comparable to standard dose (0·9 mg/kg body weight; max. 90 mg). Reduced treatment cost, lower symptomatic intracerebral hemorrhage risk and comparable efficacy encouraged many Asian centers to adopt low-dose or even variable-dose IV-tPA regimens. We evaluated various Asian thrombolysis studies and compared with SITS-MOST registry and NINDS trial. Methods We included the published studies on acute ischemic stroke thrombolysis in Asia. Unadjusted relative risks and 95% Confidence intervals were calculated for each study. Pooled estimates from random effects models were used because the tests for heterogeneity were significant. Results We found only 18 publications regarding acute ischemic stroke thrombolysis in Asia that included total of 9300 patients. Owing to ethnic differences, stroke severity, small number of cases in individual reports, outcome measures and tPA dose regimes, it is difficult to compare these studies. Functional outcomes were almost similar (to Japanese studies) when lower-dose IV-tPA was used in non-Japanese populations across Asia. Interestingly, with standard dose IV-tPA, considerably better functional outcomes were observed, without increasing symptomatic intracerebral hemorrhage rates. Conclusions Variable dose regimens of IV-tPA are used across Asia without any reliable or established evidence. Establishing a uniform IV-tPA regimen is essential since the rapid improvements in health-care facilities and public awareness are expected to increase the rates of thrombolysis in Asia.

Telestroke a viable option to improve stroke care in India.

In India, stroke care services are not well developed. There is a need to explore alternative options to tackle the rising burden of stroke. Telemedicine has been used by the Indian Space Research Organization (ISRO) to meet the needs of remote hospitals in India. The telemedicine network implemented by ISRO in 2001 presently stretches to around 100 hospitals all over the country, with 78 remote/rural/district health centers connected to 22 specialty hospitals in major cities, thus providing treatment to more than 25 000 patients, which includes stroke patients. Telemedicine is currently used in India for diagnosing stroke patients, subtyping stroke as ischemic or hemorrhagic, and treating accordingly. However, a dedicated telestroke system for providing acute stroke care is needed. Keeping in mind Indias flourishing technology sector and leading communication networks, the hub-and-spoke model could work out really well in the upcoming years. Until then, simpler alternatives like smartphones, online data transfer, and new mobile applications like WhatsApp could be used. Telestroke facilities could increase the pool of patients eligible for thrombolysis. But this primary aim of telestroke can be achieved in India only if thrombolysis and imaging techniques are made available at all levels of health care.

The First Indian-Origin Family with Genetically Proven Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)

We report the first family of Indian origin known to be affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Seventeen members of the family spanning 3 generations had neurologic syndromes compatible with CADASIL, of whom 5 were genetically confirmed carriers of the Notch3 gene R141C mutation in exon 4 (421(C→T) and 141(Cys→Arg)). Our report highlights that CADASIL not only occurs sporadically in South Asians, but also may account for stroke in South Asians with a strong family history. Furthermore, the similarity of clinical presentations described here to those typical for Caucasian case series suggests that the CADASIL phenotype is preserved across racial groups.

Advances and potential new treatments in stroke management.

The last 3 decades have brought more advances in stroke management than any other era before. This special issue is an attempt to highlight some of these areas ranging from stroke prevention to stroke rehabilitation. The validation of tPA in improving outcome in 1995 is perhaps one of the most important milestones achieved in acute stroke management [1]. However, there is a small but significant risk of symptomatic hemorrhagic conversion with such treatment. Dr. D. J. Blacker and his group describe some novel strategies to reduce the risk of hemorrhagic transformation after thrombolysis with minocycline as well as other strategies. Recurrent stroke prevention is highly linked to identification of the underlying mechanism2. This still remains a problem in 25–30% of incident cases. Drs. M. Khan and D. J. Miller review the existing literature and discuss the current approaches to improve detection of mechanisms underlying these cryptogenic stroke cases in “Detection of paroxysmal atrial fibrillation in stroke/TIA patients.” Drs. V. Singh and N. J. Edwards, in their review article “Advances in the critical care management of ischemic stroke,” discuss the advances in acute stroke management including advances in critical care and endovascular treatment. Drs. P. B. Gorelick and U. Farooq in their review article “Advances in our understanding of “resistance” to antiplatelet agents for prevention of ischemic stroke,” provide an in-depth review of the current antiplatelet therapy and explore the concept of platelet resistance to antiplatelet agents, its place in clinical testing, and impact on outcomes. Imaging techniques in acute stroke management continue to grow [2] and are addressed in context by Dr. P. Dubey and her colleagues in their review article “Acute stroke imaging: recent updates.” This includes the controversy of CT versus MRI based imaging and the current controversies and consensus. Stroke recovery besides the natural history is impacted by several additional factors including comorbid conditions, the hospital course, and subsequent rehabilitation. In this context, Dr. B. Husaini and his group investigated the impact of comorbid depression in a large Medicaid group from Tennessee. They explored this often ignored, poorly understood factor and demonstrated its impact on length of hospital stay and outcome broken down by race and gender in “Depression increases stroke hospitalization cost: an analysis of 17,010 stroke patients in 2008 by race and gender.” The subsequent two articles on stroke rehabilitation explore the concept of recovery and neural plasticity (Drs. N. Takeuchi and S.-I. Izumi) and the intriguing role of piano playing in improving fine motor control (Drs. M. Villeneuve and A. Lamontagne). Fine motor control in the upper extremities is often the last modality to recover and a cause of persistent disability for many stroke patients. We hope that highlighting these ongoing multifaceted efforts in our endless pursuits to improve stroke care will provide new insights to trigger more active research and to bring about new treatment strategies for ischemic stroke. Majaz Moonis Padma Srivastava Magdy Selim Marc Fisher

Chronic Inflammatory Demyelinating Polyneuropathy: A Case Series

To the Editor: Pediatric chronic inflammatory demyelinating polyneuropathy (PCIDP) is uncommon. There are no randomized controlled trials (RCTs) and choice of treatment is empirical based on that in adult CIDP and experience of treating physician [1]. Intravenous immunoglobulin (IVIG) and corticosteroids are the first line drugs. Plasmapheresis, azathioprine, mycophenolate mofetil, cyclophosphamide and rituximab are started if the case is refractory to IVIG or steroid dependent [2]. The course may be monophasic, acute onset resembling acute inflammatory demyelinating polyneuropathy (AIDP), subacute onset over 4–8 wk, chronic (>8 wk), multiphasic with infrequent relapses or progressive and refractory [2]. We discuss the course and management of one patient and summarize the rest of the patients in Table 1. An 8 y old boy presented with rapidly ascending quadriparesis, progressed over 2 wk with areflexia. Nerve conduction study (NCS) showed demyelinating neuropathy. AIDP was diagnosed; IVIg 2 g/kg was given with >80% improvement in 2 mo, though he was not able keep up to his peers in sports. After 3 mo, he relapsed over 2 wk, with similar disability. He received IVIg and prednisolone 2 mg/kg (45 mg/d) and improved in 1 mo to baseline disability. Gradual prednisolone tapering was started and when on 10 mg/d, he relapsed. IVIG was given, prednisolone stepped upto 1 mg/ kg (25 mg/d). Due to cushingoid features, slow tapering was started but he had a relapse 2 mo later. IVIg was given and prednisolone was increased to 30 mg/d. Azathioprine was started (2 mg/kg/d) and prednisolone tapered. Currently he is stable and is being followed up closely. PCIDP is an uncommon disease. ENMC International Workshop developed criterion for PCIDP diagnosis [3] which helps differentiate CIDP from hereditary polyneuropathy. Cerebrospinal fluid (CSF) examination was done in one patient which was normal. Nerve biopsy was not done in view of clinical profile, electrophysiology being consistent with CIDP as well as the good response to treatment. Investigations including viral markers and anti ganglioside antibodies were negative. Treatment was planned based on evidence from case series in children [4, 5]. PCIDP is different from adult CIDP: 1) Rapid onset with peak in about 2 wk, 2) facial sparing 3) requirement of longer immunomodulation, and 4) frequently relapsing on early steroid withdrawal. Our series of PCIDP illustrates variable presentation and remarkable recovery with immunomodulation. In view of frequent recurrence, early and effective treatment prevents axonal loss and disability and provides a good outcome. * Vinay Goyal drvinaygoyal@gmail.com

Effect of providing sudden unexpected death in epilepsy (SUDEP) information to persons with epilepsy (PWE) and their caregivers-Experience from a tertiary care hospital

The primary objective of present study was to observe the effect of providing SUDEP (Sudden Unexpected Death in Epilepsy) information on drug adherence in persons with epilepsy (PWE). We also looked at impact of disclosing SUDEP information on patients quality of life and mood.

The cerebellum: Learning movement, language, and social skills

This monograph on the cerebellum written by Dianne M. Broussard is an in-depth revelation of what the cerebellum is and can be. This often neglected part of brain has been given its due respect. The book, divided into four sections, starts with a thorough description of macro and micro anatomy along with a histological perspective as well as physiological correlations of the cerebellum. The second chapter describes cerebellar operations as either a linear system versus a discrete timing system. Paralleled to the functioning of a super computer hard drive, the crerbellum is described to function in learning, identifying patterns and recoding information. Synaptic plasticity gives it the capacity to learn accurately-timed responses to particular patterns of input activity. It can also optimize adaptive fitters that determine how time varying signals are transmitted by the cerebellum and pattern recognition devices that encode patterns as pauses in P-cell discharge. Using all its tools, the cerebellum can learn to recognize situations and to generate optimized behavioural responses to them. Thus, the cerebellum helps to perfect and speed up the motor activity and behavioural repertoire. Chapters 3 and 4 deal with cerebellar long-term depression (LTD) and describe how plasticity works at the cellular level and how the different mechanisms may interact to cause learning between synaptic long term potentiation (LTP) and LTD at excitatory and inhibitory synapses and intrinsic plasticity. The cerebellar cortex has a large toolbox at its disposal. The cortical circuitry may carry out expansion recoding by generating a variety of temporal patterns in the granular layer.