Sensory Tracts Research Articles

Neuropathic Pain Medication Use Does Not Alter Outcomes of Spinal Cord Stimulation for Lower Extremity Pain

Spinal cord stimulation (SCS) for the treatment of lower extremity pain is believed to the result of increased activity in the descending inhibitory and decreased activity in the ascending excitatory tracts. Evidence suggests that the analgesia afforded by SCS may be altered using certain neuropathic pain medications that also modulate neurotransmitters in these sensory tracts. We hypothesize that neuropathic pain medications may alter the response to SCS therapy. One hundred and fifteen subjects undergoing SCS therapy for lower extremity pain were retrospectively examined. The pharmacologic profile, including stable use of neuropathic and opioid medications, were recorded. Three separate logistic regression models examined the odds ratio of primary outcomes; a successful SCS trial, a 50% decrease in pain or a 50% reduction in opioid use one year after implant. Neither the use of opioids or neuropathic pain medications were associated with changes in the odds of a successful SCS trial or a 50% pain reduction. A higher dose of chronic opioids use prior to a trial was associated with greater odds of having a 50% reduction in opioid use following implant. OR 1.02, 95% CI 1.01-1.02, p-value < 0.01). The use of neuropathic pain medications did not change the odds of either a successful SCS trial, or of experiencing a 50% reduction in pain at one year. The association between higher opioid doses and greater odds of a 50% reduction in opioid use may be the reflective of SCS's ability to reduce opioid reliance in chronic pain patients.

The Spectrum of &amp;lt;i&amp;gt;ROBO&amp;lt;/i&amp;gt;3 Mutations in Horizontal Gaze Palsy with Progressive Scoliosis: An Update

Horizontal Gaze Palsy with Progressive Scoliosis is a rare, congenital autosomal recessive disorder caused by mutations in the ROBO3 gene. It is characterized by the absence of conjugate horizontal eye movements with preserved vertical gaze, variable convergence, and progressive scoliosis, developing in childhood and adolescence. ROBO3 gene mutations are causative of the lack, or at least reduction, of crossing of the descending corticospinal and ascending lemniscal sensory tracts in the medulla. To date, 39 different mutations, including missense, nonsense, frameshift, and splice site mutations have been described in the ROBO3 gene and related to Horizontal Gaze Palsy With Progressive Scoliosis. In addition, a lot of variants of uncertain pathological significance have been reported for the first time by Illumina Clinical Services. Here we report an update on mutations of the ROBO3 gene and some information on the pathogenesis but much remains to be investigated on the consequences of mutations on ROBO3 expression and function. Therefore, further detailed functional analyses are necessary to clarify a possible role of the variants of uncertain pathological significance as the cause of the disease. In conclusion, we hope that this article will help in molecular screening for the ROBO3 gene and will contribute to enlargement of the ROBO3 gene variation database.

Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter.

Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected. Astrocyte pathology starts postnatally in the sensory tracts, followed by changes in the astrocytic populations in the motor tracts. Studies in post‐mortem tissue of two VWM patients, a 13‐year‐old boy and a 6‐year‐old girl, confirmed astrocyte abnormalities in the spinal cord. For proper development of new treatment options for VWM and, possibly, other leukodystrophies, future studies should investigate spinal cord involvement.

Suppression of Inflammatory Demyelinaton and Axon Degeneration through Inhibiting Kv3 Channels.

The development of neuroprotective and repair strategies for treating progressive multiple sclerosis (MS) requires new insights into axonal injury. 4-aminopyridine (4-AP), a blocker of voltage-gated K+ (Kv) channels, is used in symptomatic treatment of progressive MS, but the underlying mechanism remains unclear. Here we report that deleting Kv3.1—the channel with the highest 4-AP sensitivity—reduces clinical signs in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. In Kv3.1 knockout (KO) mice, EAE lesions in sensory and motor tracts of spinal cord were markedly reduced, and radial astroglia were activated with increased expression of brain derived neurotrophic factor (BDNF). Kv3.3/Kv3.1 and activated BDNF receptors were upregulated in demyelinating axons in EAE and MS lesions. In spinal cord myelin coculture, BDNF treatment promoted myelination, and neuronal firing via altering channel expression. Therefore, suppressing Kv3.1 alters neural circuit activity, which may enhance BNDF signaling and hence protect axons from inflammatory insults.

Reorganization of the somatosensory cortex in hemiplegic cerebral palsy associated with impaired sensory tracts.

Functional neuroimaging studies argue that sensory deficits in hemiplegic cerebral palsy (HCP) are related to deviant somatosensory processing in the ipsilesional primary somatosensory cortex (S1). A separate body of structural neuroimaging literature argues that these deficits are due to structural damage of the ascending sensory tracts (AST). The relationship between the functional and structural integrity of the somatosensory system and the sensory performance is largely unknown in HCP. To address this relationship, we combined findings from magnetoencephalography (MEG) and probabilistic diffusion tractography (PDT) in 10 children with HCP and 13 typically developing (TD) children. With MEG, we mapped the functionally active regions in the contralateral S1 during tactile stimulation of the thumb, middle, and little fingers of both hands. Using these MEG-defined functional active regions as regions of interest for PDT, we estimated the diffusion parameters of the AST. Somatosensory function was assessed via two-point discrimination tests. Our MEG data showed: (i) an abnormal somatotopic organization in all children with HCP in either one or both of their hemispheres; (ii) longer Euclidean distances between the digit maps in the S1 of children with HCP compared to TD children; (iii) suppressed gamma responses at early latencies for both hemispheres of children with HCP; and (iv) a positive correlation between the Euclidean distances and the sensory tests for the more affected hemisphere of children with HCP. Our MEG-guided PDT data showed: (i) higher mean and radian diffusivity of the AST in children with HCP; (ii) a positive correlation between the axial diffusivity of the AST with the sensory tests for the more affected hemisphere; and (iii) a negative correlation between the gamma power change and the AD of the AST for the MA hemisphere. Our findings associate for the first time bilateral cortical functional reorganization in the S1 of HCP children with abnormalities in the structural integrity of the AST, and correlate these abnormalities with behaviorally-assessed sensory deficits.

Region-specific impairment of the cervical spinal cord (SC) in amyotrophic lateral sclerosis: A preliminary study using SC templates and quantitative MRI (diffusion tensor imaging/inhomogeneous magnetization transfer).

In this preliminary study, our objective was to investigate the potential of high-resolution anatomical imaging, diffusion tensor imaging (DTI) and conventional/inhomogeneous magnetization transfer imaging [magnetization transfer (MT)/inhomogeneous magnetization transfer (ihMT)] at 3T, analyzed with template-extracted regions of interest, to measure the atrophy and structural changes of white (WM) and gray (GM) matter spinal cord (SC) occurring in patients with amyotrophic lateral sclerosis (ALS). Ten patients with ALS and 20 age-matched healthy controls were recruited. SC GM and WM areas were automatically segmented using dedicated templates. Atrophy indices were evaluated from T2 *-weighted images at each vertebral level from cervical C1 to C6. DTI and ihMT metrics were quantified within the corticospinal tract (CST), posterior sensory tract (PST) and anterior GM (aGM) horns at the C2 and C5 levels. Clinical disabilities of patients with ALS were evaluated using the Revised ALS Functional Rating Scale, upper motor neuron (UMN) and Medical Research Council scorings, and correlated with MR metrics. Compared with healthy controls, GM and WM atrophy was observed in patients with ALS, especially at lower cervical levels, where a strong correlation was also observed between GM atrophy and the UMN score (R=-0.75, p=0.05 at C6). Interestingly, a significant decrease in ihMT ratio was found in all regions of interest (p<0.0008), fractional anisotropy (FA) and MT ratios decreased significantly in CST, especially at C5 (p<0.005), and λ// (axial diffusivity) decreased significantly in CST (p=0.0004) and PST (p=0.003) at C2. Strong correlations between MRI metrics and clinical scores were also found (0.47<|R|<0.87, p<0.05). Altogether, these preliminary results suggest that high-resolution anatomical imaging and ihMT imaging, in addition to DTI, are valuable for the characterization of SC tissue impairment in ALS. In this study, in addition to an important SC WM demyelination, we also observed, for the first time in ALS, impairments of cervical aGM.

Early trigeminal nerve involvement in Listeria monocytogenes rhombencephalitis: case series and systematic review.

Listeria monocytogenes is associated with rhombencephalitis. However, the exact mechanisms of brainstem invasion remains poorly understood. Here, we demonstrate clinical and radiological data suggesting that Listeria may invade the brainstem via the trigeminal nerve. Three females (41, 64 and 70years) with culture proven L. monocytogenes bacteremia and rhombencephalitis were investigated in the period of 2014-16. T2-weighted and contrast-enhanced T1-weighted MRI revealed a cerebellopontine abscess in all three patients, including the involvement of the trigeminal nerve root. In two patients, MRI also revealed selective contrast enhancement of the sensory trigeminal tract in the pons and medulla oblongata. Prior to any other neurological symptoms, two patients complained of hypoesthesia and a tingling sensation in the ipsilateral half of the face, consistent with sensory trigeminal nerve dysfunction on that side. In addition, we identified another 120 cases of Listeria rhombencephalitis following a systematic review. Cranial nerves VII, V, IX, and X, respectively, medulla oblongata, cerebellum and pons, were the most frequently involved brain structures. The present clinical and radiological findings corroborate earlier data from animal experiments, indicating that L. monocytogenes may be capable of retrograde intra-axonal migration along the cranial nerves. We suggest that in a subset of patients with rhombencephalitis L. monocytogenes enters the cerebellopontine angle through the trigeminal nerve, invading the brainstem via the sensory trigeminal nuclei.

Afferent input and sensory function after human spinal cord injury.

Spinal cord injury (SCI) often disrupts the integrity of afferent (sensory) axons projecting through the spinal cord dorsal columns to the brain. Examinations of ascending sensory tracts, therefore, are critical for monitoring the extent of SCI and recovery processes. In this review, we discuss the most common electrophysiological techniques used to assess transmission of afferent inputs to the primary motor cortex (i.e., afferent input-induced facilitation and inhibition) and the somatosensory cortex [i.e., somatosensory evoked potentials (SSEPs), dermatomal SSEPs, and electrical perceptual thresholds] following human SCI. We discuss how afferent input modulates corticospinal excitability by involving cortical and spinal mechanisms depending on the timing of the effects, which need to be considered separately for upper and lower limb muscles. We argue that the time of arrival of afferent input onto the sensory and motor cortex is critical to consider in plasticity-induced protocols in humans with SCI. We also discuss how current sensory exams have been used to detect differences between control and SCI participants but might be less optimal to characterize the level and severity of injury. There is a need to conduct some of these electrophysiological examinations during functionally relevant behaviors to understand the contribution of impaired afferent inputs to the control, or lack of control, of movement. Thus the effects of transmission of afferent inputs to the brain need to be considered on multiple functions following human SCI.

Regulatory Forum Opinion Piece*: Effective Sectioning of Spinal Cord during Regulatory-type Nonclinical Toxicity Studies.

Regulatory guidelines for nonclinical neurotoxicity testing require spinal cord evaluation but do not specify a trimming scheme. The Society of Toxicologic Pathology (STP) "best practices" for nervous system sampling during nonclinical general toxicity studies recommend that spinal cord be assessed in both longitudinal/oblique and transverse sections. This article defines possible longitudinal/oblique orientations, describes their benefits and challenges, and provides an expert recommendation regarding suitable trimming planes. Longitudinal parasagittal (LP) sections follow a vertical plane just lateral to the midline, revealing sensory and motor tracts but little gray matter. Longitudinal horizontal sections transect only sensory or motor tracts and variable quantities of gray matter. Oblique vertical (OV) sections angle across the spinal cord from side to side. Oblique transverse (OT) sections slant through from top (dorsal [posterior]) to bottom (ventral [anterior]). Compared to longitudinal planes, oblique orientations demonstrate considerably more gray matter and white matter. Current STP "best practices" explicitly recommend the LP and OV options; the OT orientation also will yield suitable sections while permitting assessment of anatomic symmetry. Selection among the LP, OT, and OV planes should be at the discretion of the study pathologist. The bilaterally symmetrical OT sections likely will be analyzed most easily by nonneuropathologists.

The Relationship between Trans-Lesional Conduction, Motor Neuron Pool Excitability, and Motor Function in Dogs with Incomplete Recovery from Severe Spinal Cord Injury.

Spontaneous, acute, complete thoracolumbar spinal cord injury (TL-SCI) in dogs frequently results in permanent deficits modeling chronic paralysis in people. Recovery of walking without recovery of sensation has been interpreted in dogs as reflexive spinal walking. To evaluate this assumption, this study characterized the electrophysiological status of motor and sensory long tracts and local reflex circuitry in dogs with absent recovery of sensation after acute TL-SCI and correlated findings to gait scores. Twenty dogs with permanent deficits after acute, clinically complete TL-SCI and 6 normal dogs were prospectively enrolled. Transcranial magnetic motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), H-reflex, and F-waves were evaluated. Gait was quantified using an ordinal, open field scale (OFS) and treadmill-based stepping and coordination scores (SS, RI). MEP latency and H-reflex variables were compared between cases and controls. Associations between presence of MEPs, SSEPs, F-waves or H-reflex variables, and gait scores were determined. Pelvic limb MEPs were detected in 4 cases; no case had trans-lesional sensory conduction. Latency was longer and conduction velocity slower in cases than controls (pa = 0.0064, 0.0023, respectively). Three of 4 cases with pelvic limb MEPs were ambulatory, and gait scores (OFS, SS, RI) were each associated with presence of trans-lesional conduction (pa = 0.006, 0.006, 0.003, respectively). H threshold in cases (mean, 3.2mA ±2.5) was lower than controls (mean, 7.9mA ±3.1; pa = 0.011) and was inversely associated with treadmill-based scores, SS, and RI (pa = 0.042, 0.043, respectively). The association between pelvic limb MEPs and gait scores supports the importance of descending influence on regaining walking after severe TL-SCI in dogs rather than just activation of spinal walking. The inverse association between H-reflex threshold and gait scores implies that increases in motor neuron pool excitability might also contribute to motor recovery.

Cervical spinal cord and motor unit pathology in a canine model of SOD1-associated amyotrophic lateral sclerosis

Development of effective treatments for amyotrophic lateral sclerosis (ALS) would be facilitated by identification of early events in the pathological cascade of disease progression. Degenerative myelopathy (DM), a naturally occurring disease in dogs, is quite similar to forms of ALS associated with SOD1 mutations and is likely to be a good model for these forms of the human disease. The sequence of histopathological changes that occur in DM was characterized by analyzing tissue samples obtained from affected dogs euthanized at various stages of disease progression. Cervical spinal cord and the associated spinal nerve roots, ulnar nerve, and the extensor carpi radialis (ECR) muscle were obtained from Pembroke Welsh Corgi dogs (PWCs) with early and late stage DM and from age-matched unaffected PWCs. In early stage disease there was a substantial change in the ratio of the two main muscle fiber types and an increase in mean muscle fiber area in the ECR. DM, even in late stage disease, was not accompanied by changes in the number of motor neuron cell bodies, in the number of axons in the motor or sensory nerve roots, or in the ulnar nerve. In addition, no disease-related denervation of the acetylcholine receptors of the ECR was observed at any stage of the disease. On the other hand, axon densities in both motor and sensory nerve tracts in the cervical cord were reduced in affected dogs. SOD1-immunoreactive aggregates were observed in spinal cord motor neuron cell bodies only in late stage disease. These findings suggest that some of the earliest pathological changes in DM occur in the muscle fibers and upper motor and sensory neuron tracts in the spinal cord. Targeting therapeutic interventions to these early events in the disease are most likely to be effective in slowing disease progression for DM and may translate to therapy of SOD1-related forms of ALS.

Susac Syndrome: A differential diagnosis of white matter lesions

IntroductionSusac Syndrome is an autoimmune endotheliopathy affecting capillaries and precapillary arterioles of the brain, inner ear and retina. The classic symptom triad includes visual disturbances, hypoacusia, and encephalopathy, but is rarely fully manifest at onset. The syndrome typically follows an active fluctuating monophasic course. Typical imaging findings on brain magnetic resonance show central fiber microischemias/microinfarctions of the corpus callosum known as “snow balls”, as well as lineal infarcts and upper callosal fiber involvement. Fluorescein angiography and tonal audiometry are important tools to confirm diagnosis, even in patients who are asymptomatic for visual or auditory disturbances. We describe 8 patients with Susac Syndrome treated at our center and compare findings to those of other published case series. MethodsEight adults with Susac Syndrome diagnosed between January 2007 and August 2016 at our center, in Buenos Aires, Argentina are described. Magnetic Brain Resonance, fluorescein angiography, tonal audiometry, a complete serologic battery and lumbar puncture were performed to all patients. ResultsThe majority of patients were males, and average age at diagnosis was 37.5 years (range: 22–52 yrs). Two patients presented full clinical triad at onset, while the remaining developed visual and/or auditory disturbances later during the course of disease. All cases manifested varied neurological symptoms including pyramidal and/or sensory tract symptoms, amnesic disorders, ataxia and vertigo. Psychiatric manifestations such as disinhibition, aggressive behavior, paranoid ideation and hallucinations were also present. Seven patients suffered at least one relapse. Typical central corpus callosum fiber ischemias/infarcts, also known as snowball lesions were visible in all patients. Spokes, icicles, periventricular lesions and internal capsule “string of beads” patterns were observed on diffusion weighted images. Four cases presented fornix microischemias/microinfarctions, 5 juxtacortical involvement and 3 infratentorial infarcts. Leptomeningeal involvement was evident in only 1 patient after rabies vaccination. Fluorescein angiography was abnormal in 7 cases. Tonal audiometry revealed unilateral hypoacusia in 5 patients, 3 with low frequency hearing loss. Immunosuppressive treatment was indicated in all cases. Patient follow up ranged between 6 months and 9 years, only 1 patient was lost to follow up after three years. ConclusionSusac Syndrome is probably both underdiagnosed and misdiagnosed. Early and aggressive immunosuppressive treatment is indicated in order to prevent potential disabilities.

Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia.

Despite extensive efforts, half of patients with rare movement disorders such as hereditary spastic paraplegias and cerebellar ataxias remain genetically unexplained, implicating novel genes and unrecognized mutations in known genes. Non-coding DNA variants are suspected to account for a substantial part of undiscovered causes of rare diseases. Here we identified mutations located deep in introns of POLR3A to be a frequent cause of hereditary spastic paraplegia and cerebellar ataxia. First, whole-exome sequencing findings in a recessive spastic ataxia family turned our attention to intronic variants in POLR3A, a gene previously associated with hypomyelinating leukodystrophy type 7. Next, we screened a cohort of hereditary spastic paraplegia and cerebellar ataxia cases (n = 618) for mutations in POLR3A and identified compound heterozygous POLR3A mutations in ∼3.1% of index cases. Interestingly, >80% of POLR3A mutation carriers presented the same deep-intronic mutation (c.1909+22G>A), which activates a cryptic splice site in a tissue and stage of development-specific manner and leads to a novel distinct and uniform phenotype. The phenotype is characterized by adolescent-onset progressive spastic ataxia with frequent occurrence of tremor, involvement of the central sensory tracts and dental problems (hypodontia, early onset of severe and aggressive periodontal disease). Instead of the typical hypomyelination magnetic resonance imaging pattern associated with classical POLR3A mutations, cases carrying c.1909+22G>A demonstrated hyperintensities along the superior cerebellar peduncles. These hyperintensities may represent the structural correlate to the cerebellar symptoms observed in these patients. The associated c.1909+22G>A variant was significantly enriched in 1139 cases with spastic ataxia-related phenotypes as compared to unrelated neurological and non-neurological phenotypes and healthy controls (P = 1.3 × 10-4). In this study we demonstrate that (i) autosomal-recessive mutations in POLR3A are a frequent cause of hereditary spastic ataxias, accounting for about 3% of hitherto genetically unclassified autosomal recessive and sporadic cases; and (ii) hypomyelination is frequently absent in POLR3A-related syndromes, especially when intronic mutations are present, and thus can no longer be considered as the unifying feature of POLR3A disease. Furthermore, our results demonstrate that substantial progress in revealing the causes of Mendelian diseases can be made by exploring the non-coding sequences of the human genome.

Constructing 3 Dimensional Models of Sensory and Motor Tracts of the Spinal Cord as an Active Learning Technique

The aim of this study was to measure the effectiveness of making 3 dimensional models as a method to enhance student understanding, enthusiasm and retention of the anatomy and physiology of pathways of the spinal cord. A total of 20 students participated in this study and were enrolled in a two semester undergraduate Human Anatomy and Physiology course taught at American University.Students worked in self‐selected groups of between 5–7 students. Following a lecture on the motor and sensory tracts of the spinal cord as part of the nervous system module, students were given the task of constructing 3 dimensional models of a number of pathways in order to visualize the different neural pathways in relation to each other in a hands‐on manner. Students were responsible for constructing models of a list of pathways of the spinal cord from colored card and ribbon. Pieces of card represented cerebrum, cerebellum, medulla and spinal cord and ribbon was used to trace the pathways. Students constructed and labelled multiple pathways on each model. The students were able to use their notes and text book as reference material while constructing the models. Upon completion of the task we reviewed the models as a class for 5–10 minutes and students had the opportunity to correct any errors and misunderstandings. Students completed an anonymous questionnaire in order to obtain feedback on the effectiveness of the model making exercise and the students experience.Of the 20 students polled 60% agreed or strongly agreed with the statement that the exercise increased their learning of the topic. At least 85% of participants agreed or strongly agreed that working as part of a group was beneficial in this exercise. More than 60% of the students polled reported that the time spent on the exercise was sufficient. However, in the written feedback from students 50% requested more time for discussion after the exercise. Other comments included preferring smaller working groups and more discussion time before the exercise.One drawback from this study was the absence of a control group of students that didn't participate in the model making exercise. This therefore prevented comparison of how the model making task affected student learning.In conclusion the results indicate that the students reported a perceived benefit from the model making exercise however adjustments such as increasing discussion time afterwards and using smaller working groups of students may improve the outcomes of this exercise.

Sensory tractography and robot-quantified proprioception in hemiparetic children with perinatal stroke.

Perinatal stroke causes most hemiparetic cerebral palsy, resulting in lifelong disability. We have demonstrated the ability of robots to quantify sensory dysfunction in hemiparetic children but the relationship between such deficits and sensory tract structural connectivity has not been explored. It was aimed to characterize the relationship between the dorsal column medial lemniscus (DCML) pathway connectivity and proprioceptive dysfunction in children with perinatal stroke. Twenty-nine participants (6-19 years old) with MRI-classified, unilateral perinatal ischemic stroke (14 arterial, 15 venous), and upper extremity deficits were recruited from a population-based cohort and compared with 21 healthy controls. Diffusion tensor imaging (DTI) defined DCML tracts and five diffusion properties were quantified: fractional anisotropy (FA), mean, radial, and axial diffusivities (MD, RD, AD), and fiber count. A robotic exoskeleton (KINARM) tested upper limb proprioception in an augmented reality environment. Correlations between robotic measures and sensory tract diffusion parameters were evaluated. Lesioned hemisphere sensory tracts demonstrated lower FA and higher MD, RD, and AD compared with the non-dominant hemisphere of controls. Dominant (contralesional) hemisphere tracts were not different from controls. Both arterial and venous stroke groups demonstrated impairments in proprioception that correlated with lesioned hemisphere DCML tract diffusion properties. Sensory tract connectivity is altered in the lesioned hemisphere of hemiparetic children with perinatal stroke. A correlation between lesioned DCML tract diffusion properties and robotic proprioceptive measures suggests clinical relevance and a possible target for therapeutic intervention. Hum Brain Mapp 38:2424-2440, 2017. © 2017 Wiley Periodicals, Inc.

Effects of Combined Transcranial Direct Current Stimulation (tDCS) And Robotic-Assisted Arm Training (RAT) on the Main Motor, Sensory and Cerebellar Tracts in Spinal Cord Injury

Effects of Combined Transcranial Direct Current Stimulation (tDCS) And Robotic-Assisted Arm Training (RAT) on the Main Motor, Sensory and Cerebellar Tracts in Spinal Cord Injury

Hirayama Disease-A Case Study

Hirayama disease is a type of cervical myelopathy related to flexion movements of the neck. It is considered to be a benign motor neuron disorder with a stationary stage after a progressive course. Chronic microcirculatory changes in the territory of the anterior spinal artery induced by repeated or sustained flexion account for the necrosis of the anterior horns of the lower cervical cord, which is the hallmark of pathology. It typically occurs mainly in young males between the age of 15–25 years. It is often of insidious onset presenting with a predominantly unilateral upper extremity weakness and atrophy, cold paresis and no sensory or pyramidal tract involvement. It is also characterized by muscle weakness and atrophy in the hand and forearm with sparing of the brachioradialis, giving the characteristic appearance of oblique amyotrophy that affects the C7, C8 and T1 myotomes. The amyotrophy is unilateral in most patients, asymmetrically bilateral in some and rarely symmetric.1

Posterior Spinal Tuberculosis: A Review

Natural history of posterior spinal tuberculosis has been described. Classifications of the posterior spinal tuberculosis disease process and principles of management based upon the clinical behavior of the disease has been highlighted and emphasized. A thorough review of literature was conducted with the aim to provide the clinicoradiological correlation of the natural history of posterior spinal tuberculosis in described. Management strategy is developed based upon the severity of the clinical behavior of the disease. In anterior spinal tuberculosis, motor fibers are compressed first as they are placed anterior to the sensory tracts in the spinal cord. The sensory fibers are therefore involved in late stages. Ironically, in posterior spinal tuberculosis when compression is predominantly from the posterior aspect of the cord, we again find that motor fibers are involved prior to the sensory fibers. This is in contradiction to the general belief. It is difficult to offer any simple explanation to this apparent paradox. In general, motor fibers are considered more susceptible to pressure effect, whereas sensory fibers are more susceptible to ischemia. That is why in compression paraplegia, signs and symptoms of motor loss appear prior to the sensory loss, as collaterals prevent ischemia for quite some times. In posterior spinal tuberculosis when compression is from the posterior aspect of the cord, at first pressure is exerted on the column of cerebrospinal fluid (CSF) surrounding the cord and gets transmitted to the ligamentum denticulatum. Motor fibers in the close vicinity, get pulled and show early involvement. Secondly, in compression from the posterior aspect of the cord, the cord is displaced anteriorly and anteriorly placed motor fibers are compressed against the anterior wall of the bony spinal canal causing early motor fiber functional loss. Therefore similar classification of paraplegia predominantly based upon the progressive motor weakness is valid for paraplegia noted following posterior spinal tuberculosis. Neurological deficit grading based management is developed. Grade 1 and 2, conservative treatment, grade 3, gray zone and grade 4, operative treatment is emphasized. The five stages of natural history of tuberculosis of spine have been developed from the clinician’s point of view. However, indications of surgery are different than what are described for the anterior spinal tuberculosis. Principles of management with role of rest, braces, chemotherapy and surgery are discussed. Management of posterior spinal tuberculosis of spine, in general, it is no different than management of soft tissue tuberculosis, in HIV negative or positive patients. Role of surgery is very different than anterior spinal tubercolosis. Management of posterior spinal tubercular paraplegia, is simple, logical, efficient and easy to understand and remember by any orthopedic/treating surgeon.

Pathological lesions in the central nervous system and peripheral tissues of ddY mice with street rabies virus (1088 strain).

Most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. Therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 106 focus forming units were inoculated into the right hindlimb of ddY mice (6 weeks, female). At 3 days postinoculation (DPI), mild inflammation was observed in the hindlimb muscle. At 5 DPI, ganglion cells in the right lumbosacral spinal dorsal root ganglia showed chromatolysis. Axonal degeneration and inflammatory cells increased with infection progress in the spinal dorsal horn and dorsal root ganglia. Right hindlimb paralysis was observed from 7 DPI, which progressed to quadriparalysis. However, no pathological changes were observed in the ventral horn and root fibers of the spinal cord. Viral antigen was first detected in the right hindlimb muscle at 3 DPI, followed by the right lumbosacral dorsal root ganglia, dorsal horn of spinal cord, left red nuclei, medulla oblongata and cerebral cortex (M1 area) at 5 DPI. These results suggested that the 1088 virus ascended the lumbosacral spinal cord via mainly afferent fibers at early stage of infection and moved to cerebral cortex (M1 area) using descending spinal tract. Additionally, we concluded that significant pathological changes in mice infected with 1088 strain occur in the sensory tract of the spinal cord; this selective susceptibility results in clinical features of the disease.

Restoring axonal localization and transport of transmembrane receptors to promote repair within the injured CNS: a critical step in CNS regeneration.

Each neuronal subtype is distinct in how it develops, responds to environmental cues, and whether it is capable of mounting a regenerative response following injury. Although the adult central nervous system (CNS) does not regenerate, several experimental interventions have been trialled with successful albeit limited instances of axonal repair. We highlight here some of these approaches including extracellular matrix (ECM) modification, cellular grafting, gene therapy-induced replacement of proteins, as well as application of biomaterials. We also review the recent report demonstrating the failure of axonal localization and transport of growth-promoting receptors within certain classes of mature neurons. More specifically, we discuss an inability of integrin receptors to localize within the axonal compartment of mature motor neurons such as in the corticospinal and rubrospinal tracts, whereas in immature neurons of those pathways and in mature sensory tracts such as in the optic nerve and dorsal column pathways these receptors readily localize within axons. Furthermore we assert that this failure of axonal localization contributes to the intrinsic inability of axonal regeneration. We conclude by highlighting the necessity for both combined therapies as well as a targeted approach specific to both age and neuronal subtype will be required to induce substantial CNS repair.