Spinal Cord Research 2015-Q2&3: Top 5 Articles

The first quarter of 2015 provided us with exciting new technologies and procedures in spinal cord research. Likewise, the following five articles from the second and third quarters of 2015 outline further progress in spinal cord research 2015-Q2&3. They touch on neurological and psychological relationships to spinal cord injuries, and track trends in spinal cord injuries in the U.S. over a period of about twenty years.

Spinal Cord Research 2015-Q2&3: #1

Traumatic Spinal Cord Injury in the United States, 1993-2012

Journal: JAMA • Authors: Nitin B. Jain and Colleagues • Head Institution: Department of Physical Medicine and Rehabilitation, Vanderbilt University School of Medicine [1]

Spinal Cord Research 2015-Q2&3: #1

Traumatic Spinal Cord Injury in the United States, 1993-2012

Journal: JAMA • Authors: Nitin B. Jain and Colleagues • Head Institution: Department of Physical Medicine and Rehabilitation, Vanderbilt University School of Medicine [1]

Spinal Cord Research 2015-Q2&3: #1

Traumatic Spinal Cord Injury in the United States, 1993-2012
Journal: JAMA • Authors: Nitin B. Jain and Colleagues • Head Institution: Department of Physical Medicine and Rehabilitation, Vanderbilt University School of Medicine [1]

Spinal Cord Research 2015-Q2&3: #1

Traumatic Spinal Cord Injury in the United States, 1993-2012
Journal: JAMA • Authors: Nitin B. Jain and Colleagues • Head Institution: Department of Physical Medicine and Rehabilitation, Vanderbilt University School of Medicine [1]

Traumatic spinal cord injury can result in chronic impairment and disability, often leading to a lower quality of life. Unfortunately, contemporary trends in incidences of traumatic spinal cord injury in the United States have typically remained unmonitored.

Dr. Jain and colleagues at the Vanderbilt University School of Medicine recently analyzed survey data from the Department of Health and Human Services’ Agency for Healthcare Research, and Quality Nationwide Inpatient Sample Databases from 1993-2013—including 63,109 patients with traumatic spinal cord Injury. This study illustrates the relative stability in occurrences of traumatic spinal cord injury, with an estimated 53 and 54 cases per 1 million persons in 1993 and 2012 respectively.

The team investigated the association of unintentional falls, motor vehicle crashes, or firearms with the occurrence of traumatic spinal cord injuries; they found a significant increase in the incidence of these injuries associated with unintentional falls from 19.3% in 1997 to 40.4% in 2012. These findings on the relationship between traumatic spinal cord injury and falls raise a major public health issue and must be further evaluated in additional studies.

The authors point out some limitations of their study including missing patient cases from federal facilities, errors in reporting patient cases, changes in the classification of unintentional falls, and variations in clinical symptoms and outcomes.

  1. Traumatic Spinal Cord Injury in the United States, 1993-2012 [2015-06-09. Nitin B. Jain and Colleagues. JAMA]
Spinal Cord Research 2015-Q2&3 — (Fig.1) Temporal Trends in Acute Traumatic Spinal Cord Injury Incidence Rate per 1 Million Persons in the United States, 1993–2012

(Fig.1) Temporal Trends in Acute Traumatic Spinal Cord Injury Incidence Rate per 1 Million Persons in the United States, 1993-2012. Primary diagnosis indicates primary spinal cord injury diagnosis or secondary spinal cord injury diagnosis with a primary trauma diagnosis. All diagnoses indicate any diagnosis code for spinal cord injury with or without a trauma code. [1]

Spinal Cord Research 2015-Q2&3: #2

Function of the nucleus accumbens in motor control during recovery after spinal cord injury

Journal: Science • Authors: Yukio Nishimura and Colleagues • Head Institution: Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki [2]

Spinal Cord Research 2015-Q2&3: #2

Function of the nucleus accumbens in motor control during recovery after spinal cord injury

Journal: Science • Authors: Yukio Nishimura and Colleagues • Head Institution: Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki [2]

Spinal Cord Research 2015-Q2&3: #2

Function of the nucleus accumbens in motor control during recovery after spinal cord injury
Journal: Science • Authors: Yukio Nishimura and Colleagues • Head Institution: Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki [2]

Spinal Cord Research 2015-Q2&3: #2

Function of the nucleus accumbens in motor control during recovery after spinal cord injury
Journal: Science • Authors: Yukio Nishimura and Colleagues • Head Institution: Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki [2]

Motivational enhancement can promote recovery from spinal cord injury, but specific psychological effects on recovery remain unclear.

Dr. Nishimura and colleagues at the National Institute for Physiological Sciences in Japan studied a motivation-related brain region, the nucleus accumbens, and its possible relationship to the activity of a movement-related brain region, the sensorimotor cortex. It is possible that the interactions between the two regions promotes recovery after a spinal cord injury. The team employed a potent psychoactive compound, muscimol, to (reversibly) inactivated nucleus accumbens in a monkey model of spinal cord injury. The study shows that a muscimol injection during the early recovery period reduces movement-related, high-frequency oscillatory activity in the sensorimotor cortex, leading to severe deficits in finger movement. These results suggest that the nucleus accumbens is involved in the control of finger movement during early recovery. Further research could identify if targeting the nucleus accumbens might be useful for promoting recovery from spinal cord injury.

The authors of this study point out its limitations including the limited number of only 4 monkeys, and the intrinsic variability of experimental data.

  1. Function of the nucleus accumbens in motor control during recovery after spinal cord injury [2015-10-02. Yukio Nishimura and Colleagues. Science]

(Fig.2) Time course of recovery of finger dexterity and brain activity.

[2]


Spinal Cord Research 2015-Q2&3 — (Fig.2 A/B) Time course of recovery of finger dexterity and brain activity

(A) Reach and grasp.

(B) The time course of precision grip success rate in monkey R. Black arrowheads indicate the days corresponding to the recordings shown in (D). The black area in the inset indicates the site of the spinal cord lesion. The percentage value beside the spinal cord illustration shows the proportion of the tissue that was lesioned.


Spinal Cord Research 2015-Q2&3 — (Fig.2 C/D) Time course of recovery of finger dexterity and brain activity

(C) Schematic drawing of simultaneous recording of SMC-ECoG and NAc-LFP.

(D) Timefrequencygram of M1 (upper panels) and NAc (lower panels) activities in monkey R. Time 0, grasp onset; green arrowheads, reach onset; red arrowheads, grasp end. Each panel is the average of 30 trials.


Spinal Cord Research 2015-Q2&3 — (Fig.2 E/F) Time course of recovery of finger dexterity and brain activity

(E) Population data of mean power change compared with baseline period (–1.5 to –1.0 s from grasp onset) in M1 while the monkeys were grasping (0 to 0.5 s from grasp onset). n: The number of simultaneous recording sessions consisted of 30 trials across two monkeys (Tand R) at each stage. Shading indicates the standard error of the mean (SEM). Blue points at the top of the graph: P < 0.05, one-way analysis of variance.

(F) Same as (E) but in the NAc.

Spinal Cord Research 2015-Q2&3: #3

Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord

Journal: Science • Authors: Hiroyuki Kamiguchi and Colleagues • Head Institution: RIKEN Brain Science Institute [3]

Spinal Cord Research 2015-Q2&3: #3

Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord

Journal: Science • Authors: Hiroyuki Kamiguchi and Colleagues • Head Institution: RIKEN Brain Science Institute [3]

Spinal Cord Research 2015-Q2&3: #3

Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord
Journal: Science • Authors: Hiroyuki Kamiguchi and Colleagues • Head Institution: RIKEN Brain Science Institute [3]

Spinal Cord Research 2015-Q2&3: #3

Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord
Journal: Science • Authors: Hiroyuki Kamiguchi and Colleagues • Head Institution: RIKEN Brain Science Institute [3]

The development of the nervous system requires the precise formation of neuron networks, but it remains unclear exactly which mechanisms are involved in guiding neurons to reach different places in the brain and spinal cord.

Scientists at the RIKEN Brain Science Institute have discovered that lipids, in addition to proteins, can guide neurons in the proper direction. The authors of this study found (by using a chick experimental system) that a water soluble glycerophospholipid, LysoPtdGlc, is released by radical glia; it then accumulates in the spinal cord and rejects nociceptive, but not proprioceptive, central axon projections.

In vivo function-blocking antibody experiments confirm that LysoPtdGlc selectively repels nociceptive central axon projections. By utilizing a knockout mouse experimental system, the researchers found that this repellent effect of LysoPtdGlc is partially mediated by the G protein-coupled receptor 55. The data suggests that LysoPtdGlc regulates nociceptive central axon projections in the spinal cord. Further research could investigate whether developing a targeting LysoPtdGlc-based signaling system could be useful in treating spinal cord injury.

It is worth noting that this study is based on experimental, animal modeled evidence, and that the role of LysoPtdGlc in human nervous system development remains unclear.

  1. Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord [2015-08-28. Hiroyuki Kamiguchi and Colleagues. Science]

(Fig.3) Directionality of activity interactions.

[3]


(A) Representative time-frequencygram of GCA during the task in monkey R. Time alignment is the same as in Fig. 1D. Causal information flow from the NAc to M1 of each stage (upper panels) and from M1 to the NAc (lower panels) is shown.


(B) GCA population data from the NAc to M1 (left panel) and from M1 to the NAc (right panel) during the task, obtained across all recordings in two monkeys (T and R). The number means the total number of experimental days across the two monkeys. Shading indicates the SEM.


(C) GCA networks. The x and y axes are the source and sink of information, respectively.


Spinal Cord Research 2015-Q2&3 | (Fig.3) Directionality of activity interactions. (A) Representative time-frequencygram of GCA during the task in monkey R. Time alignment is the same as in Fig. 1D. Causal information flow from the NAc to M1 of each stage (upper panels) and from M1 to the NAc (lower panels) is shown. (B) GCA population data from the NAc to M1 (left panel) and from M1 to the NAc (right panel) during the task, obtained across all recordings in two monkeys (T and R). The number means the total number of experimental days across the two monkeys. Shading indicates the SEM. (C) GCA networks. The x and y axes are the source and sink of information, respectively.

Spinal Cord Research 2015-Q2&3: #4

Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates

Journal: Science Translational Medicine • Authors: Grégoire Courtine and Colleagues • Head Institution: Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology [4]

Spinal Cord Research 2015-Q2&3: #4

Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates

Journal: Science Translational Medicine • Authors: Grégoire Courtine and Colleagues • Head Institution: Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology [4]

Spinal Cord Research 2015-Q2&3: #4

Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates
Journal: Science Translational Medicine • Authors: Grégoire Courtine and Colleagues • Head Institution: Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology [4]

Spinal Cord Research 2015-Q2&3: #4

Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates
Journal: Science Translational Medicine • Authors: Grégoire Courtine and Colleagues • Head Institution: Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology [4]

The animal model is a potent tool in the study of spinal cord injury, but encouraging recovery across species (e.g. primates or rodents) requires further research.

Dr. Courtine and colleagues at the Swiss Federal Institute of Technology have attempted to do just this through monitoring more than 400 quadriplegic patients, and then testing correlations against other species. They found that lateralized, but not symmetrical, spinal cord injuries are correlated with anatomical remodeling of corticospinal tract and functional recovery from those injuries.

To test this potential connection in other species, the authors modeled lateralized injuries in monkeys and rats. Their research found that monkeys and humans exhibit greater recovery rates than rats. Additionally, monkeys are similar to human patients in that they also show the anatomical reorganization of corticospinal tract—this is nearly absent in rats. This study highlights the difference between monkeys and rats in the recovery process, and reinforces the necessity of primate models in studying human spinal cord injury.

This study focuses on lateralized spinal cord injuries, so the general application of its findings to other incomplete injuries is uncertain.

  1. Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates [2015-08-26. Grégoire Courtine and Colleagues. Science Translational Medicine]

(Fig.4) Humans, but not rats, recover the ability to traverse a horizontal ladder after lateralized Spinal Cord Injury (SCI).

[4]


Spinal Cord Research 2015-Q2&3 — (Fig.4A) Humans, but not rats, recover the ability to traverse a horizontal ladder after lateralized SCI.

Differences in gait recovery were particularly striking during challenging conditions, such as traversing a horizontal ladder. The four patients executed this task with 100% success (Fig. 4A).

(A and B) Decomposition of lower limbmotion during locomotion along the equally spaced rungs of a horizontal ladder. Foot placement was measured as the relative positioning of the ipsilesional foot with respect to two successive rung positions (red dots). The number of occurrences per 5% bin is reported together with the percentage of accurate, slipped, and missed placements.


Spinal Cord Research 2015-Q2&3 — (Fig.4 B) Humans, but not rats, recover the ability to traverse a horizontal ladder after lateralized SCI.

In contrast, rats failed to position their ipsilesional hindpawonto the rungs of the ladder (Fig. 4B). This failure was not due to deficits in forelimb placement because rodents with a thoracic hemisection also display permanent loss of hindpaw placements during locomotion along ladders.

(A and B) Decomposition of lower limbmotion during locomotion along the equally spaced rungs of a horizontal ladder. Foot placement was measured as the relative positioning of the ipsilesional foot with respect to two successive rung positions (red dots). The number of occurrences per 5% bin is reported together with the percentage of accurate, slipped, and missed placements.


Spinal Cord Research 2015-Q2&3 — (Fig.4 C/D) Humans, but not rats, recover the ability to traverse a horizontal ladder after lateralized SCI.

The patients performed well on the horizontal ladder despite the use of distinct gait strategies and slight postural instability compared to healthy subjects (Fig. 4 C/D). Notwithstanding differences in the execution of bipedal versus quadrupedal locomotion along ladders, there was a strong disparity between rats and humans in the recovery of legmotor skills. For safety reasons, monkeys were not tested on this task.

(C) Principal component (PC) analysis was applied on dimensionless parameters (n = 101): 101 kinematic parameters measured for the ipsilesional leg before the injury (or healthy) and at the chronic stage of SCI. Individual (lines) and averaged 3D distance between noninjured data points and those measured at late time points. ***P<0.001, ANOVA. Data are means ± SEM (n = 4 humans, 15 rats).

(D) Differences in recovery of skilled locomotion between Humans and Rats.

Spinal Cord Research 2015-Q2&3: #5

MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis

Journal: Lancet Neurology • Authors: Achim Gass and Colleagues • Head Institution: Department of Neurology, Universit.tsmedizin Mannheim, University of Heidelberg [5]

Spinal Cord Research 2015-Q2&3: #5

MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis

Journal: Lancet Neurology • Authors: Achim Gass and Colleagues • Head Institution: Department of Neurology, Universit.tsmedizin Mannheim, University of Heidelberg [5]

Spinal Cord Research 2015-Q2&3: #5

MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis
Journal: Lancet Neurology • Authors: Achim Gass and Colleagues • Head Institution: Department of Neurology, Universit.tsmedizin Mannheim, University of Heidelberg [5]

Spinal Cord Research 2015-Q2&3: #5

MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis
Journal: Lancet Neurology • Authors: Achim Gass and Colleagues • Head Institution: Department of Neurology, Universit.tsmedizin Mannheim, University of Heidelberg [5]

In a recent study, Dr. Achim Gass and his colleagues at the University of Heidelberg examined the progress of magnetic resonance imaging (MRI) analysis in monitoring pathological changes in spinal cord patients with multiple sclerosis.

The authors indicate that technological developments in MRI instrumentation promote spinal cord imaging with a better signal-to-noise ratio, and improved spatial resolution. These developments provide new and important insights into the progression of multiple sclerosis. For example, grey matter demyelination in the spinal cord, the importance of diffuse tissue injury in the spinal cord, and small effect of focal lesions on diffuse changes in the spinal cord.

Functional MRI can reveal changes in the response pattern to sensory stimulation in patients with multiple sclerosis. Through use of these techniques, findings of cord atrophy, intrinsic cord damage, and adaptation are shown to occur largely independently of focal spinal cord lesion load, which emphasises their relevance in depiction of the true burden of disease. Combinations of magnetisation transfer ratio or diffusion tension imaging indices with cord atrophy markers seem to be the most robust and meaningful biomarkers to monitor disease evolution in early multiple sclerosis.

The study discusses the application of several new techniques for spinal cord imaging; including magnetization transfer imaging, diffusion tensor imaging, functional MRI of the spinal cord, and proton magnetic resonance spectroscopy. The researchers conclude that further technical developments of spinal cord imaging would not only help improve the accuracy of disease diagnosis, but the evaluation of disease prognosis as well.

It is worth noting that this study does not consider the cost-effectiveness of new techniques compared to conventional ones.

  1. MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis [2015-04. Achim Gass and Colleagues. Lancet Neurology]
Spinal Cord Research 2015-Q2&3 — (Fig.5) Biplanar conventional MRI of a 41-year-old female patient with relapsing remitting multiple sclerosis

(Fig.5) Biplanar conventional MRI of a 41-year-old female patient with relapsing remitting multiple sclerosis: (A) Sagittal proton-density weighted MRI of the whole spinal cord, with lesions seen as hyperintense areas. (B) The axial images confirm the location of the pathology; lesions are marked with green arrow heads. [5]

Credit: English Text curated by Jinnah Griffin

Wanqiu Hou is the Founder of Scientific HealthSense, a website based application in mining health data for a consumer service. He received his PhD from the Chinese Academy of Sciences. Dr. Hou has more than 10 years of experience in medical research, writing and communications.

Wanqiu Hou is the Founder of Scientific HealthSense, a website based application in mining health data for a consumer service. He received his PhD from the Chinese Academy of Sciences. Dr. Hou has more than 10 years of experience in medical research, writing and communications.

Wanqiu Hou is the Founder of Scientific HealthSense, a website based application in mining health data for a consumer service. He received his PhD from the Chinese Academy of Sciences. Dr. Hou has more than 10 years of experience in medical research, writing and communications.

Wanqiu Hou is the Founder of Scientific HealthSense, a website based application in mining health data for a consumer service. He received his PhD from the Chinese Academy of Sciences. Dr. Hou has more than 10 years of experience in medical research, writing and communications.


The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.