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S. Mittal
From the Department of Neurology (A.H., K.A.J., E.J.S., J.E.A.), Mayo Clinic, Rochester, MN; Department of Neurology (S.O.M.), Cleveland Clinic Abu Dhabi, United Arab Emirates; and Department of Neurology (W.T.H.), Emory University, Atlanta, GA

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Journal article
Published: 26 February 2021 in Neurology
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Objective To assess whether primary lateral sclerosis (PLS), classified as pure when the EMG is normal, converts to amyotrophic lateral sclerosis (ALS) after longitudinal follow-up. Methods Retrospective chart review was performed of patients with pure PLS at Mayo Clinic in Rochester, MN (1990–2016). Inclusion criteria required a normal EMG during the first 4 years of symptoms. Results Forty-three patients had pure PLS (25 female, 58%) with a median onset age of 50 years (range 38–78 years) and median follow-up at 9 years’ disease duration (range 4–36 years). The ascending paraparesis phenotype (n = 30, 70%) was most common, followed by hemiparetic onset (n = 9, 21%) and bulbar onset (n = 4, 9%). Among the 30 paraparetic-onset cases, bladder symptoms (n = 18, 60%) and dysarthria (n = 15, 50%) were more common than pseudobulbar affect (n = 9, 30%) and dysphagia (n = 8, 27%). By the last follow-up, 17 of 30 (56%) used a cane and 6 (20%) required a wheelchair. The paraparetic variant, compared with hemiparetic and bulbar onset, had the youngest onset (48 vs 56 vs 60 years, respectively; p = 0.02). Five patients died; 1 patient required a feeding tube; and none required permanent noninvasive ventilation. Two patients developed an idiopathic multisystem neurodegenerative disorder, which surfaced after 19 and 20 years. Two patients developed minor EMG abnormalities. The remainder 39 had persistently normal EMGs. Conclusions Pure PLS did not convert to ALS after a median of 9 years’ disease duration follow-up in our study population. The ascending paraparetic phenotype was most common, with earlier onset and frequent bladder involvement. After years of pure PLS, <5% develop a more pervasive neurodegenerative disorder.

ACS Style

Anhar Hassan; Shivam Om Mittal; William T. Hu; Keith A. Josephs; Eric J. Sorenson; J. Eric Ahlskog. Natural History of “Pure” Primary Lateral Sclerosis. Neurology 2021, 96, e2231 -e2238.

AMA Style

Anhar Hassan, Shivam Om Mittal, William T. Hu, Keith A. Josephs, Eric J. Sorenson, J. Eric Ahlskog. Natural History of “Pure” Primary Lateral Sclerosis. Neurology. 2021; 96 (17):e2231-e2238.

Chicago/Turabian Style

Anhar Hassan; Shivam Om Mittal; William T. Hu; Keith A. Josephs; Eric J. Sorenson; J. Eric Ahlskog. 2021. "Natural History of “Pure” Primary Lateral Sclerosis." Neurology 96, no. 17: e2231-e2238.

Review
Published: 31 December 2020 in Tremor and Other Hyperkinetic Movements
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Hand tremor associated with Parkinson disease (PD) and essential tremor (ET) can often become challenging to treat in clinical practice. Local injections of botulinum toxin-A (BoNT-A) for hand tremor is an evolving field with newer injection techniques being utilized in clinical studies. The utility of BoNT-A therapy for ET and PD-tremor however, has been questioned based on the high incidence of finger and hand weakness after treatment. The study includes detailed analysis of the techniques utilized in BoNT injection in ET and PD tremor. There were 4 high-quality investigations which consisted of Class I or II double-blind placebo-controlled trials and one medium-quality study that was a prospective, open label, class III investigation. This paper discusses two recently developed technology-based injection methods for BoNT-A therapy of ET and PD tremor, which includes comprehensive EMG screening of forearm and arm muscles with selective injections (Yale method) and the whole arm kinematic tremor assessment developed by Jog et al. In recent years, controlled, blinded studies of these two methods have shown significant post-injection reduction of finger, hand and whole limb tremor compared to the previously published controlled clinical trials not using these methodologies.

ACS Style

Shivam Om Mittal; Mandar Jog; Jack Lee; Bahman Jabbari. Novel Botulinum Toxin Injection Protocols for Parkinson Tremor and Essential Tremor – the Yale Technique and Sensor-Based Kinematics Procedure for Safe and Effective Treatment. Tremor and Other Hyperkinetic Movements 2020, 10, 1 .

AMA Style

Shivam Om Mittal, Mandar Jog, Jack Lee, Bahman Jabbari. Novel Botulinum Toxin Injection Protocols for Parkinson Tremor and Essential Tremor – the Yale Technique and Sensor-Based Kinematics Procedure for Safe and Effective Treatment. Tremor and Other Hyperkinetic Movements. 2020; 10 (1):1.

Chicago/Turabian Style

Shivam Om Mittal; Mandar Jog; Jack Lee; Bahman Jabbari. 2020. "Novel Botulinum Toxin Injection Protocols for Parkinson Tremor and Essential Tremor – the Yale Technique and Sensor-Based Kinematics Procedure for Safe and Effective Treatment." Tremor and Other Hyperkinetic Movements 10, no. 1: 1.

Correspondence
Published: 04 November 2020 in Parkinsonism & Related Disorders
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This is a case of young man who has severe generalized dystonic spells with moaning with severe parkinsonism, which improves with dopaminergic medications. Patient was found to be DNAJC6 related juvenile Parkinson's disease. This case adds to the phenotypic variability of the DNAJC6 juvenile Parkinson's disease as severe dystonic spells and moaning has not been reported previously. Early diagnosis and symptomatic treatment with dopaminergic medications helps significantly to improve the quality of life.

ACS Style

Shivam Om Mittal. Levodopa responsive-generalized dystonic spells and moaning in DNAJC6 related Juvenile Parkinson’s disease. Parkinsonism & Related Disorders 2020, 81, 188 -189.

AMA Style

Shivam Om Mittal. Levodopa responsive-generalized dystonic spells and moaning in DNAJC6 related Juvenile Parkinson’s disease. Parkinsonism & Related Disorders. 2020; 81 ():188-189.

Chicago/Turabian Style

Shivam Om Mittal. 2020. "Levodopa responsive-generalized dystonic spells and moaning in DNAJC6 related Juvenile Parkinson’s disease." Parkinsonism & Related Disorders 81, no. : 188-189.

Review
Published: 30 March 2020 in Drugs in Context
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Tics and Tourette's syndrome are common hyperkinetic movement disorders seen mostly in the pediatric age group. Tics are defined as sudden, rapid, recurrent, nonrhythmic motor movements or vocalization, generally preceded by urge. Tourette's syndrome is defined as the presence of both motor and phonic tics for more than 1 year in patients with onset less than 18 years old. Most of these hyperkinetic movement disorders improve in adulthood. This review emphasizes the clinical pearls in the diagnosis and distinguishing it from other movement disorders. The treatment ranges from behavioral therapies, medical management, and also surgical treatment such as deep brain stimulation that is limited to refractory patients.

ACS Style

Shivam Om Mittal. Tics and Tourette's syndrome. Drugs in Context 2020, 9, 1 -7.

AMA Style

Shivam Om Mittal. Tics and Tourette's syndrome. Drugs in Context. 2020; 9 ():1-7.

Chicago/Turabian Style

Shivam Om Mittal. 2020. "Tics and Tourette's syndrome." Drugs in Context 9, no. : 1-7.

Review
Published: 05 January 2020 in Toxins
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Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the release of major pain transmitters such as substance P, calcitonin gene related peptide (CGRP) and glutamate from peripheral nerve endings as well as peripheral and central neurons (dorsal root ganglia and spinal cord). These effects lead to pain relief via the reduction of peripheral and central sensitization both of which reflect important mechanisms of pain chronicity. This review provides updated information about the effect of botulinum toxin injection on local pain caused by cancer, painful muscle spasms from a remote cancer, and pain at the site of cancer surgery and radiation. The data from the literature suggests that the local injection of BoNTs improves muscle spasms caused by cancerous mass lesions and alleviates the post-operative neuropathic pain at the site of surgery and radiation. It also helps repair the parotid damage (fistula, sialocele) caused by facial surgery and radiation and improves post-parotidectomy gustatory hyperhidrosis. The limited literature that suggests adding botulinum toxins to cell culture slows/halts the growth of certain cancer cells is also reviewed and discussed.

ACS Style

Shivam O. Mittal; Bahman Jabbari. Botulinum Neurotoxins and Cancer—A Review of the Literature. Toxins 2020, 12, 32 .

AMA Style

Shivam O. Mittal, Bahman Jabbari. Botulinum Neurotoxins and Cancer—A Review of the Literature. Toxins. 2020; 12 (1):32.

Chicago/Turabian Style

Shivam O. Mittal; Bahman Jabbari. 2020. "Botulinum Neurotoxins and Cancer—A Review of the Literature." Toxins 12, no. 1: 32.

Review
Published: 18 June 2019 in Movement Disorders Clinical Practice
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Background West Nile virus (WNV) is a flavivirus that is recognized as one of the common causes of arboviral neurological disease in the world. WNV infections usually manifest with constitutional symptoms such as fever, fatigue, myalgia, rash, arthralgia, and headache. Neuroinvasive WNV infections are characterized by signs and symptoms suggestive of meningitis, encephalitis, meningoencephalitis, and acute flaccid paralysis. In addition, many patients with neuroinvasive WNV infection develop a wide range of movement disorders. This article aims to comprehensively review the spectrum and natural course of the movement disorders observed in patients with neuroinvasive WNV infections. Methods A literature search was performed in March 2019 (in PubMed and EMBASE) to identify articles for this review. Results Movement disorders observed in the context of WNV infections include tremor, opsoclonus–myoclonus, parkinsonism, myoclonus, ataxia, and chorea. Most often, these movement disorders resolve within a few weeks to months with an indolent course. The commonly observed tremor phenotypes include action tremor of the upper extremities (bilateral > unilateral). Tremor in patients with West Nile meningitis subsides earlier than that in patients with West Nile encephalitis/acute flaccid paralysis. Opsoclonus–myoclonus in WNV infections responds well to intravenous immunoglobulins/plasmapheresis/corticosteroids. Parkinsonism has been reported to be mild in nature and usually lasts for a few weeks to months in the majority of the patients. Conclusion A wide spectrum of movement disorders is observed in neuroinvasive WNV infections. Longitudinal studies are warranted to obtain better insights into the natural course of these movement disorders.

ACS Style

Abhishek Lenka Md; Anuja Kamat; Shivam Om Mittal. Spectrum of Movement Disorders in Patients With Neuroinvasive West Nile Virus Infection. Movement Disorders Clinical Practice 2019, 6, 426 -433.

AMA Style

Abhishek Lenka Md, Anuja Kamat, Shivam Om Mittal. Spectrum of Movement Disorders in Patients With Neuroinvasive West Nile Virus Infection. Movement Disorders Clinical Practice. 2019; 6 (6):426-433.

Chicago/Turabian Style

Abhishek Lenka Md; Anuja Kamat; Shivam Om Mittal. 2019. "Spectrum of Movement Disorders in Patients With Neuroinvasive West Nile Virus Infection." Movement Disorders Clinical Practice 6, no. 6: 426-433.

Review
Published: 25 January 2019 in Parkinsonism & Related Disorders
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Tremor is a key clinical feature of several common neurological disorders. Adequate management of tremor has been an unmet need in clinical practice. Most of the anti-tremor medications have limited efficacy and are associated with undesirable adverse effects, especially in elderly patients. Several studies have reported good outcomes with the use of botulinum neurotoxin (BoNT) for the treatment of tremor. This article aims to systematically review these studies and to highlight the role of BoNT in the management of tremor. A PubMed search was performed in August 2018 to identify articles pertinent to this review. Majority of the studies that have assessed the efficacy of BoNT in tremor, enrolled patients with essential tremor (ET), Parkinson's disease (PD), and dystonic tremor. Results of these studies suggest clinically meaningful improvement in hand tremor in both ET and PD and vocal tremor in ET after BoNT therapy. Additionally, BoNT has been reported to be efficacious in alleviating head and palatal tremor, tremor in multiple sclerosis, and proximal positional tremor. It is apparent that BoNT injections tailored to the needs of individual patients yield better efficacy and lower adverse effects compared to fixed-muscle-fixed-dose approach. BoNT individualized approach adds to the armamentarium for patients who have medically refractory tremors or those who are unable to tolerate the anti-tremor medications. The studies are limited and mostly open-label; thus, randomized placebo-controlled studies are needed to prove the efficacy of BoNT in various tremor conditions.

ACS Style

Shivam Om Mittal; Abhishek Lenka; Joseph Jankovic. Botulinum toxin for the treatment of tremor. Parkinsonism & Related Disorders 2019, 63, 31 -41.

AMA Style

Shivam Om Mittal, Abhishek Lenka, Joseph Jankovic. Botulinum toxin for the treatment of tremor. Parkinsonism & Related Disorders. 2019; 63 ():31-41.

Chicago/Turabian Style

Shivam Om Mittal; Abhishek Lenka; Joseph Jankovic. 2019. "Botulinum toxin for the treatment of tremor." Parkinsonism & Related Disorders 63, no. : 31-41.

Randomized controlled trial
Published: 29 September 2018 in Toxins
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Background: Restless Legs Syndrome (RLS) is a common movement disorder with an estimated prevalence of up to 12%. Previous small studies with onabotulinumtoxin A (OnaA) for RLS have shown inconsistent results. Methods: Twenty-four patients with an International RLS score (IRLS) of >11 (moderate-severe) were enrolled in this blinded, placebo-controlled crossover study. Twenty-one patients completed the evaluations at 4, 6, and 8 weeks after each injection. One-hundred units of Incobotulinumtoxin A (IncoA) or normal saline were injected into tibialis anterior, gastrocnemius, and biceps femoris muscles each side. Results: Improvement from a severe (IRLS >21) to a mild/moderate (IRLS ≤20) score was significant at four weeks (p = 0.0036) and six weeks (p = 0.0325) following IncoA administration compared to placebo. Additionally, there was significant improvement in pain score at six weeks as measured by Visual Analogue Scale (p = 0.04) and the Johns Hopkins Quality of Life Questionnaire (p = 0.01) in the IncoA group. Definite or marked improvement on Patient Global Impression of Change was seen in 7 out of 21 patients in the IncoA group vs. 1 out of 21 patients in the placebo group at 4 weeks (p = 0.012). Conclusion: IncoA injection lead to a reduction in severity of RLS symptoms, pain score, and quality of life, without any adverse effects.

ACS Style

Shivam Om Mittal; Duarte Machado; Diana Richardson; Divyanshu Dubey; Bahman Jabbari. Botulinum Toxin in Restless Legs Syndrome—A Randomized Double-Blind Placebo-Controlled Crossover Study. Toxins 2018, 10, 401 .

AMA Style

Shivam Om Mittal, Duarte Machado, Diana Richardson, Divyanshu Dubey, Bahman Jabbari. Botulinum Toxin in Restless Legs Syndrome—A Randomized Double-Blind Placebo-Controlled Crossover Study. Toxins. 2018; 10 (10):401.

Chicago/Turabian Style

Shivam Om Mittal; Duarte Machado; Diana Richardson; Divyanshu Dubey; Bahman Jabbari. 2018. "Botulinum Toxin in Restless Legs Syndrome—A Randomized Double-Blind Placebo-Controlled Crossover Study." Toxins 10, no. 10: 401.

Randomized controlled trial
Published: 12 June 2018 in Parkinsonism & Related Disorders
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To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for treatment of essential hand tremor. In essential tremor and Parkinson's disease tremor, administration of onabotulinumtoxinA via a fixed injection approach improves the tremor but a high percentage of patients (30–70%) develop moderate to severe hand weakness which has limited its use in clinical practice. This study was performed from July 2013 to July 2016 on 33 subjects. This is a double-blind, placebo-controlled, crossover trial injecting 80–120 units of IncoA into 8–14 hand and forearm muscles using a customized approach. The subjects were followed for 28 weeks. The treatment efficacy was evaluated by the Fahn Tolosa Marin tremor rating score and NIH genetic criteria for tremor severity at 4 and 8 weeks after each of the two sets of treatments. Hand strength was assessed by an ergometer. There was statistically significant improvement in clinical rating score of tremor at 4 and 8 weeks following the IncoA injection. In this study, injection of IncoA treatment via a customized approach improved essential tremor on the clinical scales and patient's perception with a low occurrence of significant hand weakness.

ACS Style

Shivam Om Mittal; Duarte Machado; Diana Richardson; Divyanshu Dubey; Bahman Jabbari. Botulinum toxin in essential hand tremor - A randomized double-blind placebo-controlled study with customized injection approach. Parkinsonism & Related Disorders 2018, 56, 65 -69.

AMA Style

Shivam Om Mittal, Duarte Machado, Diana Richardson, Divyanshu Dubey, Bahman Jabbari. Botulinum toxin in essential hand tremor - A randomized double-blind placebo-controlled study with customized injection approach. Parkinsonism & Related Disorders. 2018; 56 ():65-69.

Chicago/Turabian Style

Shivam Om Mittal; Duarte Machado; Diana Richardson; Divyanshu Dubey; Bahman Jabbari. 2018. "Botulinum toxin in essential hand tremor - A randomized double-blind placebo-controlled study with customized injection approach." Parkinsonism & Related Disorders 56, no. : 65-69.

Randomized controlled trial
Published: 01 September 2017 in Mayo Clinic Proceedings
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In essential tremor and Parkinson disease (PD) tremor, administration of onabotulinumtoxinA via a fixed injection approach improves the tremor, but many patients (30%-70%) develop moderate to severe hand weakness, limiting the use of onabotulinumtoxinA in clinical practice.To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for the treatment of tremor in PD.In this double-blind, placebo-controlled, crossover trial, 30 patients each received 7 to 12 (mean, 9) IncoA injections into hand and forearm muscles using a customized approach. The study was performed from June 1, 2012, through June 30, 2015, and participants were followed for 24 weeks. Treatment efficacy was evaluated by the tremor subsets of the Unified Parkinson's Disease Rating Scale and the Patient Global Impression of Change 4 and 8 weeks after each of the 2 sets of treatments. Hand strength was assessed using an ergometer.There was a statistically significant improvement in clinical rating scores of rest tremor and tremor severity 4 and 8 weeks after the IncoA injection and of action/postural tremor at 8 weeks. There was a significant improvement in patient perception of improvement at 4 and 8 weeks in the IncoA group. There was no statistically significant difference in grip strength at 4 weeks between the 2 groups.Injection of IncoA via a customized approach improved PD tremor on a clinical scale and patient perception, with a low occurrence of significant hand weakness.clinicaltrials.gov Identifier: NCT02419313.

ACS Style

Shivam Om Mittal; Duarte Machado; Diana Richardson; Divyanshu Dubey; Bahman Jabbari. Botulinum Toxin in Parkinson Disease Tremor. Mayo Clinic Proceedings 2017, 92, 1359 -1367.

AMA Style

Shivam Om Mittal, Duarte Machado, Diana Richardson, Divyanshu Dubey, Bahman Jabbari. Botulinum Toxin in Parkinson Disease Tremor. Mayo Clinic Proceedings. 2017; 92 (9):1359-1367.

Chicago/Turabian Style

Shivam Om Mittal; Duarte Machado; Diana Richardson; Divyanshu Dubey; Bahman Jabbari. 2017. "Botulinum Toxin in Parkinson Disease Tremor." Mayo Clinic Proceedings 92, no. 9: 1359-1367.

Case reports
Published: 01 September 2017 in Clinical Neuropharmacology
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The aim of this study was to report worsening of Tourette syndrome (TS) in 2 patients treated with varenicline. Abnormal dopaminergic signaling is likely involved in the pathophysiology of TS. Varenicline is a partial α4β2 nicotinic acetylcholine agonist that enhances dopamine release. Therefore, the use of varenicline may influence tics in patients with TS. We analyzed and described 2 case studies on patients with significant worsening of tics after treatment with varenicline. Patient 1 had motor tics in childhood, which completely resolved by the age of 20 years. At the age of 25 years, he started varenicline and stopped smoking. Within 2 weeks, he developed motor followed by vocal tics that persisted despite stopping varenicline and restarting smoking. The tics were complex, medically refractory, and caused severe disability at work and school (Yale Global Tic Severity Scale score, 86). Patient 2 developed motor and vocal tics in adolescence that persisted into her 20s and caused significant disability in association with psychiatric comorbidities. At the age of 31 years, she started varenicline to quit smoking, which led to a marked increase in tic frequency and severity. Varenicline was discontinued after 3 weeks with improvement to baseline tic severity (Yale Global Tic Severity Scale score, 94). Ultimately, both patients successfully underwent deep brain stimulation to bilateral centromedian/parafascicular complex thalamic nuclei for medically refractory TS. We report 2 patients with motor and/or vocal tics that had severe worsening of tics after varenicline use. This may be due to varenicline-induced increased striatal dopamine in conjunction with nicotine cessation, influencing dopamine receptor sensitivity in TS. Providers should be cautious in prescribing varenicline to patients with TS.

ACS Style

Shivam Om Mittal; Bryan T. Klassen; Anhar Hassan; James H. Bower; Elizabeth A. Coon. Acute Worsening of Tics on Varenicline. Clinical Neuropharmacology 2017, 40, 231 -232.

AMA Style

Shivam Om Mittal, Bryan T. Klassen, Anhar Hassan, James H. Bower, Elizabeth A. Coon. Acute Worsening of Tics on Varenicline. Clinical Neuropharmacology. 2017; 40 (5):231-232.

Chicago/Turabian Style

Shivam Om Mittal; Bryan T. Klassen; Anhar Hassan; James H. Bower; Elizabeth A. Coon. 2017. "Acute Worsening of Tics on Varenicline." Clinical Neuropharmacology 40, no. 5: 231-232.

Chapter
Published: 24 August 2017 in Botulinum Toxin Treatment in Clinical Medicine
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Neuropathic pain (NP) results from damage to or a lesion in the peripheral or central nervous system. It is a common form of human pain, often with poor response to analgesic medications. In this chapter, we discuss our current knowledge of the pathophysiology of NP followed by its conventional treatment and provide evidence-based comments on the efficacy of botulinum neurotoxins (BoNTs) in the management of NP. The published guidelines of the American Academy of Neurology are used as determinants of the level of efficacy of BoNT therapy in different NP categories. Available data indicate that BoNT therapy is effective (level A evidence) in post-herpetic, post-traumatic, and trigeminal neuralgias. It is probably effective (Level B) in painful diabetic neuropathy, plantar fasciitis, and central (spinal cord) neuropathic pain. The data available on the use of BoNTs in complex regional pain syndrome, carpal tunnel syndrome, occipital neuralgia, and phantom limb pain are of low quality and controversial; hence, conduction of clinical trials of higher quality is required to determine if there is a therapeutic role for BoNTs in these conditions. The dosage and technique of injection, dilutions, and differences among BoNTs in the treatment of neuropathic pain remains to be established.

ACS Style

Shivam Om Mittal; Bahman Jabbari. Botulinum Toxin Treatment of Neuropathic Pain. Botulinum Toxin Treatment in Clinical Medicine 2017, 167 -191.

AMA Style

Shivam Om Mittal, Bahman Jabbari. Botulinum Toxin Treatment of Neuropathic Pain. Botulinum Toxin Treatment in Clinical Medicine. 2017; ():167-191.

Chicago/Turabian Style

Shivam Om Mittal; Bahman Jabbari. 2017. "Botulinum Toxin Treatment of Neuropathic Pain." Botulinum Toxin Treatment in Clinical Medicine , no. : 167-191.

Journal article
Published: 07 August 2017 in Neurology: Clinical Practice
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ACS Style

Shivam Om Mittal; Anhar Hassan; Joyce Sanchez; Carrie Robertson. Powassan virus postencephalitic parkinsonism. Neurology: Clinical Practice 2017, 7, 527 -530.

AMA Style

Shivam Om Mittal, Anhar Hassan, Joyce Sanchez, Carrie Robertson. Powassan virus postencephalitic parkinsonism. Neurology: Clinical Practice. 2017; 7 (6):527-530.

Chicago/Turabian Style

Shivam Om Mittal; Anhar Hassan; Joyce Sanchez; Carrie Robertson. 2017. "Powassan virus postencephalitic parkinsonism." Neurology: Clinical Practice 7, no. 6: 527-530.

Case report
Published: 27 June 2017 in Movement Disorders Clinical Practice
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Fragile X–Associated Tremor/Ataxia Syndrome (FXTAS) is caused by a small expansion with 55-200 CGG repeats, termed as “premutation”, in the promoter region of the fragile X mental retardation 1 (FMR1) gene. The elevated CGG repeat mRNA has deleterious consequences causing the phenotypic features of FXTAS.1 After the initial description of FXTAS in five patients2, Jacquemont et al described FXTAS in 26 male patients, all over 50 years of age who had intention tremor and/or cerebellar ataxia with MRI brain showing T2 hyper intensity in the bilateral middle cerebellar peduncles.3 Since then several females with FXTAS have been reported. We report the youngest case of FXTAS in an adolescent girl.This article is protected by copyright. All rights reserved.

ACS Style

Shivam Om Mittal; Kenneth Mack; James H. Bower. Fragile X-associated Tremor/Ataxia Syndrome in an Adolescent Female. Movement Disorders Clinical Practice 2017, 4, 778 -780.

AMA Style

Shivam Om Mittal, Kenneth Mack, James H. Bower. Fragile X-associated Tremor/Ataxia Syndrome in an Adolescent Female. Movement Disorders Clinical Practice. 2017; 4 (5):778-780.

Chicago/Turabian Style

Shivam Om Mittal; Kenneth Mack; James H. Bower. 2017. "Fragile X-associated Tremor/Ataxia Syndrome in an Adolescent Female." Movement Disorders Clinical Practice 4, no. 5: 778-780.

Case reports
Published: 01 May 2017 in Neurology
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A 32-year-old immunocompetent man presented with new-onset generalized tonic-clonic seizures. On examination, he had mild right hand weakness, with right-sided Hoffman sign, ankle clonus, and Babinski reflex present. MRI of the brain demonstrated vasogenic edema surrounding a ring-enhancing lesion in the left parietal lobe (figure, A). Repeat brain MRIs showed rapid progression of the lesion, with new lesions appearing in the contralateral hemisphere (figure, B and C). Pathology showed necrotizing meningoencephalitis with organisms consistent with ameba (figure, D). Indirect immunofluorescence and PCR was positive for Balamuthia mandrillaris . About 200 cases of Balamuthia infection have been reported worldwide, and it has a very high mortality rate of 95%. 1

ACS Style

Shivam Om Mittal; Omar Alsinaidi. Teaching NeuroImages: Balamuthia mandrillaris amebic encephalitis. Neurology 2017, 88, e183 -e183.

AMA Style

Shivam Om Mittal, Omar Alsinaidi. Teaching NeuroImages: Balamuthia mandrillaris amebic encephalitis. Neurology. 2017; 88 (18):e183-e183.

Chicago/Turabian Style

Shivam Om Mittal; Omar Alsinaidi. 2017. "Teaching NeuroImages: Balamuthia mandrillaris amebic encephalitis." Neurology 88, no. 18: e183-e183.

Case reports
Published: 24 February 2017 in Journal of Clinical Neuroscience
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Isolated unilateral abducens nerve palsy is usually due to ischemia, trauma or neoplasm. Dorello's canal is the space between the petrous apex and superolateral portion of the clivus, bound superiorly by Gruber's ligament. The abducens nerve travels with inferior petrosal sinus (IPS) though the Dorello's canal before entering the cavernous sinus. A 31-year-old man presented with neck pain, and binocular horizontal diplopia, worse looking towards left and at distance. He had a history of intravenous drug abuse but no history of hypertension or diabetes. On examination, he had complete left 6th nerve palsy with normal fundi, pupils, and other cranial nerves. Methicillin-resistant Staphylococcus aureus bacteremia was detected with naïve tricuspid valve endocarditis and multiple septic emboli to lungs with infarcts. His cerebrospinal fluid was normal. MRI of the brain was normal. MRV of head and neck showed thrombosis of the left internal jugular vein, left sigmoid sinus and left inferior petrosal sinus with normal cavernous sinus and no evidence of mastoiditis. He was treated with broad spectrum antibiotics. He was not anticoagulated for fear of pulmonary hemorrhage from pulmonary infarcts. Although cerebral venous sinus thrombosis commonly presents with elevated intracranial pressure, isolated ipsilateral 6th nerve palsy from its compression in Dorello's canal due to thrombosis of the ipsilateral inferior petrosal sinus is extremely rare. To our knowledge, only two patients have been reported with isolated abducens palsy due to IPS thrombosis; one caused by septic emboli and the other developed it during IPS cortisol level sampling.

ACS Style

Shivam Om Mittal; Junaid Siddiqui; Bashar Katirji. Abducens nerve palsy due to inferior petrosal sinus thrombosis. Journal of Clinical Neuroscience 2017, 40, 69 -71.

AMA Style

Shivam Om Mittal, Junaid Siddiqui, Bashar Katirji. Abducens nerve palsy due to inferior petrosal sinus thrombosis. Journal of Clinical Neuroscience. 2017; 40 ():69-71.

Chicago/Turabian Style

Shivam Om Mittal; Junaid Siddiqui; Bashar Katirji. 2017. "Abducens nerve palsy due to inferior petrosal sinus thrombosis." Journal of Clinical Neuroscience 40, no. : 69-71.

Image of the moment
Published: 10 January 2017 in Practical Neurology
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ACS Style

Shivam Om Mittal; Bashar Katirji. Parascapular muscle atrophy as a delayed effect of radiation treatment. Practical Neurology 2017, 17, 127 -127.

AMA Style

Shivam Om Mittal, Bashar Katirji. Parascapular muscle atrophy as a delayed effect of radiation treatment. Practical Neurology. 2017; 17 (2):127-127.

Chicago/Turabian Style

Shivam Om Mittal; Bashar Katirji. 2017. "Parascapular muscle atrophy as a delayed effect of radiation treatment." Practical Neurology 17, no. 2: 127-127.

Review
Published: 24 February 2016 in Journal of Neuro-Oncology
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This comprehensive review provides information on epidemiology, size, grade, cerebral localization, clinical symptoms, treatments, and factors associated with longer survival in 14,599 patients with brain metastasis from breast cancer; the molecular features of breast cancers most likely to develop brain metastases and the potential use of these predictive molecular alterations for patient management and future therapeutic targets are also addressed. The review covers the data from 106 articles representing this subject in the era of modern neuroimaging (past 35 years). The incidence of brain metastasis from breast cancer (24 % in this review) is increasing due to advances in both imaging technologies leading to earlier detection of the brain metastases and introduction of novel therapies resulting in longer survival from the primary breast cancer. The mean age at the time of breast cancer and brain metastasis diagnoses was 50.3 and 48.8 years respectively. Axillary node metastasis was noted in 32.8 % of the patients who developed brain metastasis. The median time intervals between the diagnosis of breast cancer to identification of brain metastasis and from identification of brain metastasis to death were 34 and 15 months, respectively. The most common symptoms experienced in patients with brain metastasis consisted of headache (35 %), vomiting (26 %), nausea (23 %), hemiparesis (22 %), visual changes (13 %) and seizures (12 %). A majority of the patients had multiple metastases (54.2 %). Cerebellum and frontal lobes were the most common sites of metastasis (33 and 16 %, respectively). Of the primary tumors for which biomarkers were recorded, 37 % were estrogen receptor (ER)+, 41 % ER-, 36 % progesterone receptor (PR)+, 34 % PR-, 35 % human epithelial growth factor receptor 2 (HER2)+, 41 % HER2-, 27 % triple negative and 18 % triple positive (TP). Treatment in most patients consisted of a multimodality approach often with two or more of the following: whole brain radiation therapy (52 %), chemotherapy (51 %), stereotactic radiosurgery (20 %), surgical resection (14 %), trastuzumab (39 %) for HER2 positive tumors, and hormonal therapy (34 %) for ER and/or PR positive tumors. Factors that had an impact on prognosis included grade and size of the tumor, multiple metastases, presence of extra-cranial metastasis, triple negative or HER2+ biomarker status, and high Karnovsky score. Novel therapies such as application of agents to reduce tumor angiogenesis or alter permeability of the blood brain barrier are being explored with preliminary results suggesting a potential to improve survival after brain metastasis. Other potential therapies based on genetic alterations in the tumor and the microenvironment in the brain are being investigated; these are briefly discussed.

ACS Style

Rezvan Rostami; Shivam Mittal; Pooya Rostami; Fattaneh Tavassoli; Bahman Jabbari. Brain metastasis in breast cancer: a comprehensive literature review. Journal of Neuro-Oncology 2016, 127, 407 -414.

AMA Style

Rezvan Rostami, Shivam Mittal, Pooya Rostami, Fattaneh Tavassoli, Bahman Jabbari. Brain metastasis in breast cancer: a comprehensive literature review. Journal of Neuro-Oncology. 2016; 127 (3):407-414.

Chicago/Turabian Style

Rezvan Rostami; Shivam Mittal; Pooya Rostami; Fattaneh Tavassoli; Bahman Jabbari. 2016. "Brain metastasis in breast cancer: a comprehensive literature review." Journal of Neuro-Oncology 127, no. 3: 407-414.

Case reports
Published: 11 February 2016 in Seminars in Neurology
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Neuropathic pain (NP), a common form of human pain, often poorly responds to analgesic medications. In this review the authors discuss the pathophysiology and conventional treatment of neuropathic pain and provide evidenced-based statements on the efficacy of botulinum neurotoxins (BoNTs) in this form of pain. The level of efficacy for BoNT treatment in each category of NP is defined according to the published guidelines of the American Academy of Neurology. The data indicate that BoNT treatment (most of the literature is with onabotulinumtoxinA) is effective (level A evidence) in postherpetic neuralgia and trigeminal neuralgia. It is probably effective (level B) in posttraumatic neuralgia and painful diabetic neuropathy. The data on complex regional pain syndrome, carpal tunnel syndrome, occipital neuralgia, and phantom limb pain are preliminary and await conduction of randomized, blinded clinical trials. Much remains to be learned about the most-effective dosage and technique of injection, optimum dilutions, and differences among BoNTs in the treatment of neuropathic pain.

ACS Style

Shivam Om Mittal; Delaram Safarpour; Bahman Jabbari. Botulinum Toxin Treatment of Neuropathic Pain. Seminars in Neurology 2016, 36, 073 -083.

AMA Style

Shivam Om Mittal, Delaram Safarpour, Bahman Jabbari. Botulinum Toxin Treatment of Neuropathic Pain. Seminars in Neurology. 2016; 36 (1):073-083.

Chicago/Turabian Style

Shivam Om Mittal; Delaram Safarpour; Bahman Jabbari. 2016. "Botulinum Toxin Treatment of Neuropathic Pain." Seminars in Neurology 36, no. 1: 073-083.

Clinical trial
Published: 13 January 2016 in Toxins
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Cancer patients who undergo surgery or radiation can develop persistent focal pain at the site of radiation or surgery. Twelve patients who had surgery or radiation for local cancer and failed at least two analgesic medications for pain control were prospectively enrolled in a research protocol. Patients were injected up to 100 units of incobotulinum toxin A (IncoA) intramuscularly or subcutaneously depending on the type and location of pain (muscle cramp or neuropathic pain). Two patients passed away, one dropped out due to a skin reaction and another patient could not return for the follow up due to his poor general condition. All remaining 8 subjects (Age 31–70, 4 female) demonstrated significant improvement of Visual Analog Scale (VAS) (3 to 9 degrees, average 3.9 degrees) and reported significant satisfaction in Patients’ Global Impression of Change scale (PGIC) (7 out of 8 reported the pain as much improved). Three of the 8 patients reported significant improvement of quality of life.

ACS Style

Rezvan Rostami; Shivam Om Mittal; Reza Radmand; Bahman Jabbari. Incobotulinum Toxin-A Improves Post-Surgical and Post-Radiation Pain in Cancer Patients. Toxins 2016, 8, 22 .

AMA Style

Rezvan Rostami, Shivam Om Mittal, Reza Radmand, Bahman Jabbari. Incobotulinum Toxin-A Improves Post-Surgical and Post-Radiation Pain in Cancer Patients. Toxins. 2016; 8 (1):22.

Chicago/Turabian Style

Rezvan Rostami; Shivam Om Mittal; Reza Radmand; Bahman Jabbari. 2016. "Incobotulinum Toxin-A Improves Post-Surgical and Post-Radiation Pain in Cancer Patients." Toxins 8, no. 1: 22.