Shivam O Mittal | Cleveland Clinic (original) (raw)
Papers by Shivam O Mittal
Tremor and Other Hyperkinetic Movements, Jun 29, 2017
Background: Klinefelter's syndrome (KS) has been associated with tremor, but reports on tremo... more Background: Klinefelter's syndrome (KS) has been associated with tremor, but reports on tremor phenomenology and treatment are limited. Case Reports: Patient 1 is a 17‐year‐old male with a dystonic tremor treated with deep brain stimulation (DBS). Patient 2 is a 57‐year‐old male with a predominant left hand resting tremor and dystonic features. Discussion: Our cases suggest that the tremor in patients with KS may be dystonic in nature. Patient 1 is also the third reported case of successful treatment with DBS. These cases have implications for elucidating the underlying neurobiological mechanism of tremor and identifying treatment options.
Toxins, 2020
Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an ... more 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 ...
Parkinsonism & related disorders, Jan 12, 2018
To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for treatment of ess... more 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 followin...
Mayo Clinic proceedings, Sep 1, 2017
In essential tremor and Parkinson disease (PD) tremor, administration of onabotulinumtoxinA via a... more 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...
Journal of Neuro-Oncology, 2016
This comprehensive review provides information on epidemiology, size, grade, cerebral localizatio... more 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 & Rezvan Rostami
Seminars in Neurology, 2016
Neuropathic pain (NP), a common form of human pain, often poorly responds to analgesic medication... more 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.
Toxins, 2016
Cancer patients who undergo surgery or radiation can develop persistent focal pain at the site of... more 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.
Toxins, Jan 29, 2018
Restless Legs Syndrome (RLS) is a common movement disorder with an estimated prevalence of up to ... more 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. 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. Improvement from a severe (IRLS >21) to a mild/moderate (IRLS ≤20) score was significant at four weeks ( = 0.0036) and six weeks ( = 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 ( = 0.04) and the Johns Hopkins Quality of Life Questionnaire ( = 0.01) in the IncoA grou...
CNS & Neurological Disorders - Drug Targets, 2012
Parkinsonism and Related Disorders, 2018
To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for treatment of ess... more 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.
METHODS:
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.
RESULTS:
There was statistically significant improvement in clinical rating score of tremor at 4 and 8 weeks following the IncoA injection.
CONCLUSION:
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.
Toxins, 2018
Background: Restless Legs Syndrome (RLS) is a common movement disorder with an estimated prevalen... more 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.
Tremor and Other Hyperkinetic Movements, Jun 29, 2017
Background: Klinefelter's syndrome (KS) has been associated with tremor, but reports on tremo... more Background: Klinefelter's syndrome (KS) has been associated with tremor, but reports on tremor phenomenology and treatment are limited. Case Reports: Patient 1 is a 17‐year‐old male with a dystonic tremor treated with deep brain stimulation (DBS). Patient 2 is a 57‐year‐old male with a predominant left hand resting tremor and dystonic features. Discussion: Our cases suggest that the tremor in patients with KS may be dystonic in nature. Patient 1 is also the third reported case of successful treatment with DBS. These cases have implications for elucidating the underlying neurobiological mechanism of tremor and identifying treatment options.
Toxins, 2020
Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an ... more 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 ...
Parkinsonism & related disorders, Jan 12, 2018
To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for treatment of ess... more 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 followin...
Mayo Clinic proceedings, Sep 1, 2017
In essential tremor and Parkinson disease (PD) tremor, administration of onabotulinumtoxinA via a... more 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...
Journal of Neuro-Oncology, 2016
This comprehensive review provides information on epidemiology, size, grade, cerebral localizatio... more 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 & Rezvan Rostami
Seminars in Neurology, 2016
Neuropathic pain (NP), a common form of human pain, often poorly responds to analgesic medication... more 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.
Toxins, 2016
Cancer patients who undergo surgery or radiation can develop persistent focal pain at the site of... more 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.
Toxins, Jan 29, 2018
Restless Legs Syndrome (RLS) is a common movement disorder with an estimated prevalence of up to ... more 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. 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. Improvement from a severe (IRLS >21) to a mild/moderate (IRLS ≤20) score was significant at four weeks ( = 0.0036) and six weeks ( = 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 ( = 0.04) and the Johns Hopkins Quality of Life Questionnaire ( = 0.01) in the IncoA grou...
CNS & Neurological Disorders - Drug Targets, 2012
Parkinsonism and Related Disorders, 2018
To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for treatment of ess... more 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.
METHODS:
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.
RESULTS:
There was statistically significant improvement in clinical rating score of tremor at 4 and 8 weeks following the IncoA injection.
CONCLUSION:
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.
Toxins, 2018
Background: Restless Legs Syndrome (RLS) is a common movement disorder with an estimated prevalen... more 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.