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NI Feature: The Fourth Dimension COMMENTRY
A summary of some of the recently-published, seminal papers in Neuroscience K. Sridhar Department of Neuro and Spine Surgery, Institute of Neurosciences and Spinal Disorders, Global Health City, Perumbakkam, Chennai, Tamil Nadu, India
McKelvey R, et al: Neuropathic pain is constitutively suppressed in early life by anti-inflammatory neuroimmune regulation. J. Neurosci., 35:457–466, 2015 Neuropathic pain is rare in infants, and only very few reports exist of it presenting before the age of 5–6 years. It is also rare prior to adolescence. McKelvey et al. showed that the lack of neuropathic pain in children and infants is due to an active immune suppression of the dorsal horn pain pathway. Infant peripheral nerve injury evokes an anti-inflammatory response in the dorsal horn cells. Using infant mice, they show that the pain response in the dorsal horn is anti-inflammatory with increases in levels of interleukin (IL)-4 and IL-10. Neuropathic pain in infants can be unmasked by intrathecal injections of anti-IL-10 showing that the phenomenon is due to an active suppression of neuropathic pain in young children. As adolescence is reached, there is a switch from anti-inflammatory to a pro-inflammatory response allowing for development of delayed neuropathic pain in older and adult mice. McKelvey et al. have shown that the neuroimmune profile changes from infancy to adulthood and that the absence of neuropathic pain in infants is not due to an absence of the pathway, but an active suppression, which can get activated later in life. These findings are corroborated by the clinical findings in humans of the absence of neuropathic Access this article online Website: www.neurologyindia.com DOI: 10.4103/0028-3886.152668 PMID: xxxxx
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pain in infants and young children following nerve injury; and, the peak age of onset of complex pain syndromes following an early injury in adolescence and later in life. These findings may have therapeutic relevance in the management of these difficult-to-treat pain syndromes.
Penzo M et al: The paraventricular thalamus controls a central amygdala fear circuit. Nature, January, 2015. 10.1038/nature13978 Fear is learnt and expressed at the lateral division of the central nucleus of the amygdala (CeL). The differences in fear generation and its expression in different individuals are perhaps due to the modulation of this “fear center”. The paraventricular nucleus of the thalamus (PVT) is known to be activated by stress. The authors have attempted to study the role of PVT in the regulation of fear expression by CeL. They studied the role of PVT-CeL in mice and showed that the PVT projections to the CeL regulate the fear processing and expression. This study shows the presence of a probable new circuit involved in fear expression that is modulated by the activation of brain-derived neurotrophic factor (BDNF) receptor tropomyosin-related kinase B. This is a unique circuit both for memory and responses related to fear and helps to construct appropriate responses and adaptive behavior to an eminent threat.
Kim H et al.: Validation of the supplemented SpetzlerMartin grading system for brain arteriovenous malformations in a multicenter cohort of 1009 surgical patients. Neurosurgery 76:25–33, 2015 The Spetzler–Martin (SM) grading system has been used to grade arteriovenous malformations (AVMs) to determine the management plan. It has also withstood the test of
Address for correspondence: Prof. K. Sridhar, Head Department of Neuro and Spine Surgery, Director, Institute of Neurosciences and Spinal Disorders, Global Health City, 439, Cheran Nagar, Perumbakkam, Off OMR, Sholinganallur-Tambaram Highway, Chennai - 600 100, Tamil Nadu, India. E-mail: [email protected]
Neurology India / January 2015 / Volume 63 / Issue 1
101
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time unlike many other classifications and grading systems. However, it is relatively crude and still has many drawbacks. Kim et al., in their paper have performed a multi-institutional analysis of a large number of patients operated for AVMs to study the accuracy and usefulness of the “Supplemental” SM grading System (SM-Supp) versus the traditional SM grading system. The elements that are looked at in the SM-Supp also called the Lawton–Young grading system are A for age of the patient, B for the presence of bleeding, and C for a compact nidus. The authors found that the SM-supplemental grading provided a higher predictive accuracy than the SM system and stratified the surgical risk better. The combined SM and SM-Supp systems provided a clear cutoff for operability when the grade was 6 or greater. One of the problems with the study is that there is a preexistent bias in that the patients have already been selected for surgery. Another problem with the SM-Supp is the definition of a “diffuse” AVM as opposed to a compact one. The cut-off of 6 may not be acceptable to all. Nonetheless, it is a relatively easy grading system to determine operability of an AVM.
Tawk RG et al: Influence of body mass index and age on functional outcomes in patients with subarachnoid hemorrhage, Neurosurgery 76:136–141, 2015 This article studies the paradox of patients with chronic obesity having apparently a greater chance of survival following subarachnoid hemorrhage (SAH) than patients with normal weight. Tawk et al., retrospectively reviewed the case records of patients with SAH and studied the association between body mass index (BMI) and both the severity of SAH as well as the functional outcome. They concluded that obesity is not associated with the severity of SAH, once the multivariate analysis was done adjusting for age, where older age had a worse severity and outcome.
Popescu BFG et al: Diagnostic utility of aquaporin-4 in the analysis of active demyelinating lesions. Neurology 84:148–158, 2015 Fujihara K et al: AQP4 in biopsied demyelinating lesions as a diagnostic clue to NMOSD and MS: Final answer? Neurology 84:110–111, 2015 Demyelinating disease may present as a tumefactive spaceoccupying lesion both in the brain and the spinal cord. Till date, it has been necessary to perform a biopsy to prove the pathology. Popescu et al., assessed in a surgical cohort of patients, the utility of aquaporin-4 (AQP4) in the diagnosis of neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD). They concluded that it is important to consider 102
NMOSD in the differential diagnosis of tumefactive brain or spinal cord lesions; and, that AQP4-IgG testing may help in avoiding a biopsy and in avoiding ineffective therapies if these patients are erroneously treated for multiple sclerosis. Fujihara et al inform us that there is an international panel now proposing a new diagnostic criteria of NMOSDs, a unifying term to encompass the entire disease spectrum (optic neuritis, acute longitudinally extensive transverse myelitis (LETM), some brain syndromes, and combinations including the typical NMO). They conclude that some brain lesions, as well as LETM in NMOSD, are tumefactive. Thus, NMOSD has joined the list of clinical entities manifesting with tumefactive demyelinating lesions.
Devanand DP et al: Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community. Neurology 84: 182–189, 2015 Devanand et al., looked at baseline odor identification deficits in a multiethnic cohort of over 1,000 patients without dementia and followed them for cognitive decline between 2 and 4 years. Impairment in odor identification was found to be superior to deficits in verbal episodic memory in predicting cognitive decline in a cognitively intact population. The use of a relatively inexpensive odor identification test may serve as an early biomarker of cognitive decline and dementia.
Peng KP et al: Increased risk of Bell palsy in patients with migraine: A nationwide cohort study. Neurology 84: 116-124, 2015 If you have migraine, there is an increased risk of developing Bell’s palsy. Peng et al., performed a nationwide cohort study using the data from national insurance to look at the association between migraine and Bell’s palsy. They found that migraine was a significant independent risk factor in the development of Bell’s palsy. They suggest that the association between the two may be a linked disease mechanism that needs further study.
Burt R et al: Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsingremitting multiple sclerosis. JAMA 313:275–284, 2015 The authors investigate the role for nonmyeloablative hematopoietic stem cell transplantation in relapsing–remitting multiple sclerosis. A case series of patients with multiple sclerosis underwent treatment with cyclophosphamide and alemtuzumab (22 patients) or cyclophosphamide
Neurology India / January 2015 / Volume 63 / Issue 1
[Downloaded free from http://www.neurologyindia.com on Thursday, March 05, 2015, IP: 202.177.173.189] || Click here to download free Android application for this journal Sridhar: The Fourth Dimension
and thymoglobulin (129 patients) followed by infusion of unmanipulated peripheral blood stem cells. The patients were followed-up for a mean duration of 2.5 years. The primary end-point of the follow-up was either progression or reversal of neurological deficit, where as secondary outcomes were measured using Numeric Rating Scale (NRS) scores, Short Form (SF)-36 scores and volume lesions on T2-weighted magnetic resonance imaging (MRI). The authors found an improvement in neurological disability and other scores and recommend a randomized trial for confirmation of their findings.
Arima H et al.: Optimal achieved blood pressure in acute intracerebral hemorrhage INTERACT2. Neurology 8:464–471, 2015 INTERACT2 was an open, blinded endpoint, randomized
controlled trial in 2,839 patients with intracerebral hemorrhage (ICH) within 6 h of onset and elevated systolic blood pressure (SBP; 150–220 mmHg) who were allocated to receive intensive (target SBP
NI Feature: The Fourth Dimension COMMENTRY
A summary of some of the recently-published, seminal papers in Neuroscience K. Sridhar Department of Neuro and Spine Surgery, Institute of Neurosciences and Spinal Disorders, Global Health City, Perumbakkam, Chennai, Tamil Nadu, India
McKelvey R, et al: Neuropathic pain is constitutively suppressed in early life by anti-inflammatory neuroimmune regulation. J. Neurosci., 35:457–466, 2015 Neuropathic pain is rare in infants, and only very few reports exist of it presenting before the age of 5–6 years. It is also rare prior to adolescence. McKelvey et al. showed that the lack of neuropathic pain in children and infants is due to an active immune suppression of the dorsal horn pain pathway. Infant peripheral nerve injury evokes an anti-inflammatory response in the dorsal horn cells. Using infant mice, they show that the pain response in the dorsal horn is anti-inflammatory with increases in levels of interleukin (IL)-4 and IL-10. Neuropathic pain in infants can be unmasked by intrathecal injections of anti-IL-10 showing that the phenomenon is due to an active suppression of neuropathic pain in young children. As adolescence is reached, there is a switch from anti-inflammatory to a pro-inflammatory response allowing for development of delayed neuropathic pain in older and adult mice. McKelvey et al. have shown that the neuroimmune profile changes from infancy to adulthood and that the absence of neuropathic pain in infants is not due to an absence of the pathway, but an active suppression, which can get activated later in life. These findings are corroborated by the clinical findings in humans of the absence of neuropathic Access this article online Website: www.neurologyindia.com DOI: 10.4103/0028-3886.152668 PMID: xxxxx
Quick Response Code
pain in infants and young children following nerve injury; and, the peak age of onset of complex pain syndromes following an early injury in adolescence and later in life. These findings may have therapeutic relevance in the management of these difficult-to-treat pain syndromes.
Penzo M et al: The paraventricular thalamus controls a central amygdala fear circuit. Nature, January, 2015. 10.1038/nature13978 Fear is learnt and expressed at the lateral division of the central nucleus of the amygdala (CeL). The differences in fear generation and its expression in different individuals are perhaps due to the modulation of this “fear center”. The paraventricular nucleus of the thalamus (PVT) is known to be activated by stress. The authors have attempted to study the role of PVT in the regulation of fear expression by CeL. They studied the role of PVT-CeL in mice and showed that the PVT projections to the CeL regulate the fear processing and expression. This study shows the presence of a probable new circuit involved in fear expression that is modulated by the activation of brain-derived neurotrophic factor (BDNF) receptor tropomyosin-related kinase B. This is a unique circuit both for memory and responses related to fear and helps to construct appropriate responses and adaptive behavior to an eminent threat.
Kim H et al.: Validation of the supplemented SpetzlerMartin grading system for brain arteriovenous malformations in a multicenter cohort of 1009 surgical patients. Neurosurgery 76:25–33, 2015 The Spetzler–Martin (SM) grading system has been used to grade arteriovenous malformations (AVMs) to determine the management plan. It has also withstood the test of
Address for correspondence: Prof. K. Sridhar, Head Department of Neuro and Spine Surgery, Director, Institute of Neurosciences and Spinal Disorders, Global Health City, 439, Cheran Nagar, Perumbakkam, Off OMR, Sholinganallur-Tambaram Highway, Chennai - 600 100, Tamil Nadu, India. E-mail: [email protected]
Neurology India / January 2015 / Volume 63 / Issue 1
101
[Downloaded free from http://www.neurologyindia.com on Thursday, March 05, 2015, IP: 202.177.173.189] || Click here to download free Android application for th journal Sridhar: The Fourth Dimension
time unlike many other classifications and grading systems. However, it is relatively crude and still has many drawbacks. Kim et al., in their paper have performed a multi-institutional analysis of a large number of patients operated for AVMs to study the accuracy and usefulness of the “Supplemental” SM grading System (SM-Supp) versus the traditional SM grading system. The elements that are looked at in the SM-Supp also called the Lawton–Young grading system are A for age of the patient, B for the presence of bleeding, and C for a compact nidus. The authors found that the SM-supplemental grading provided a higher predictive accuracy than the SM system and stratified the surgical risk better. The combined SM and SM-Supp systems provided a clear cutoff for operability when the grade was 6 or greater. One of the problems with the study is that there is a preexistent bias in that the patients have already been selected for surgery. Another problem with the SM-Supp is the definition of a “diffuse” AVM as opposed to a compact one. The cut-off of 6 may not be acceptable to all. Nonetheless, it is a relatively easy grading system to determine operability of an AVM.
Tawk RG et al: Influence of body mass index and age on functional outcomes in patients with subarachnoid hemorrhage, Neurosurgery 76:136–141, 2015 This article studies the paradox of patients with chronic obesity having apparently a greater chance of survival following subarachnoid hemorrhage (SAH) than patients with normal weight. Tawk et al., retrospectively reviewed the case records of patients with SAH and studied the association between body mass index (BMI) and both the severity of SAH as well as the functional outcome. They concluded that obesity is not associated with the severity of SAH, once the multivariate analysis was done adjusting for age, where older age had a worse severity and outcome.
Popescu BFG et al: Diagnostic utility of aquaporin-4 in the analysis of active demyelinating lesions. Neurology 84:148–158, 2015 Fujihara K et al: AQP4 in biopsied demyelinating lesions as a diagnostic clue to NMOSD and MS: Final answer? Neurology 84:110–111, 2015 Demyelinating disease may present as a tumefactive spaceoccupying lesion both in the brain and the spinal cord. Till date, it has been necessary to perform a biopsy to prove the pathology. Popescu et al., assessed in a surgical cohort of patients, the utility of aquaporin-4 (AQP4) in the diagnosis of neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD). They concluded that it is important to consider 102
NMOSD in the differential diagnosis of tumefactive brain or spinal cord lesions; and, that AQP4-IgG testing may help in avoiding a biopsy and in avoiding ineffective therapies if these patients are erroneously treated for multiple sclerosis. Fujihara et al inform us that there is an international panel now proposing a new diagnostic criteria of NMOSDs, a unifying term to encompass the entire disease spectrum (optic neuritis, acute longitudinally extensive transverse myelitis (LETM), some brain syndromes, and combinations including the typical NMO). They conclude that some brain lesions, as well as LETM in NMOSD, are tumefactive. Thus, NMOSD has joined the list of clinical entities manifesting with tumefactive demyelinating lesions.
Devanand DP et al: Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community. Neurology 84: 182–189, 2015 Devanand et al., looked at baseline odor identification deficits in a multiethnic cohort of over 1,000 patients without dementia and followed them for cognitive decline between 2 and 4 years. Impairment in odor identification was found to be superior to deficits in verbal episodic memory in predicting cognitive decline in a cognitively intact population. The use of a relatively inexpensive odor identification test may serve as an early biomarker of cognitive decline and dementia.
Peng KP et al: Increased risk of Bell palsy in patients with migraine: A nationwide cohort study. Neurology 84: 116-124, 2015 If you have migraine, there is an increased risk of developing Bell’s palsy. Peng et al., performed a nationwide cohort study using the data from national insurance to look at the association between migraine and Bell’s palsy. They found that migraine was a significant independent risk factor in the development of Bell’s palsy. They suggest that the association between the two may be a linked disease mechanism that needs further study.
Burt R et al: Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsingremitting multiple sclerosis. JAMA 313:275–284, 2015 The authors investigate the role for nonmyeloablative hematopoietic stem cell transplantation in relapsing–remitting multiple sclerosis. A case series of patients with multiple sclerosis underwent treatment with cyclophosphamide and alemtuzumab (22 patients) or cyclophosphamide
Neurology India / January 2015 / Volume 63 / Issue 1
[Downloaded free from http://www.neurologyindia.com on Thursday, March 05, 2015, IP: 202.177.173.189] || Click here to download free Android application for this journal Sridhar: The Fourth Dimension
and thymoglobulin (129 patients) followed by infusion of unmanipulated peripheral blood stem cells. The patients were followed-up for a mean duration of 2.5 years. The primary end-point of the follow-up was either progression or reversal of neurological deficit, where as secondary outcomes were measured using Numeric Rating Scale (NRS) scores, Short Form (SF)-36 scores and volume lesions on T2-weighted magnetic resonance imaging (MRI). The authors found an improvement in neurological disability and other scores and recommend a randomized trial for confirmation of their findings.
Arima H et al.: Optimal achieved blood pressure in acute intracerebral hemorrhage INTERACT2. Neurology 8:464–471, 2015 INTERACT2 was an open, blinded endpoint, randomized
controlled trial in 2,839 patients with intracerebral hemorrhage (ICH) within 6 h of onset and elevated systolic blood pressure (SBP; 150–220 mmHg) who were allocated to receive intensive (target SBP
