Somatosensory findings in patients with spinal cord injury and central dysaesthesia pain.

OBJECTIVE: To determine whether central pain in patients with spinal cord injury is only dependent on the lesioning of spinothalamic pathways. METHODS: In sixteen patients with spinal cord injury and central dysaesthesia pain, somatosensory abnormalities in painful denervated skin areas were compared with somatosensory findings in normal skin areas as well as in non-painful denervated skin areas. RESULTS: The threshold values for detection of thermal (heat, cold, heat pain, or cold pain) and tactile stimulation were significantly changed in denervated skin areas although there were no significant differences in the threshold values between painful and non-painful denervated skin areas. The reductions of sensations of touch, vibration, joint position, and two point discrimination in painful and non-painful denervated skin areas were not significantly different. Allodynia (pain caused by non-noxious stimulation) and wind up-like pain (pain caused by repeatedly pricking the skin) were significantly more common in painful than non-painful denervated skin areas. CONCLUSIONS: Because pain and thermal sensory perception are primarily mediated to the brain via spinothalamic pathways, whereas the sensations of touch, vibration and joint position are primarily mediated by dorsal column-medial lemniscal pathways, the results indicate that central pain is not only dependent on the lesioning of either dorsal column-medial lemniscal pathways or spinothalamic pathways. The findings of abnormal evoked pain (allodynia and wind up-like pain) may be consistent with the experimental findings of hyperexcitability in nociceptive spinothalamic tract neurons, that may be involved in the pathogenesis of central pain.     

Non-painful phantom limb phenomena in amputees: incidence, clinical characterstics and temporal course

58 patients undergoing limb amputation mainly because of peripheral vascular disease were interviewed by means of a standard questionnaire and examined 8 days, 6 months and 2 years after limb amputation regarding non-painful phantom limb phenomena. During the follow-up period, 41% of patients died. The incidence of phantom limb 8 days, 6 months and 2 years after limb loss was 84%, 90% and 71%, respectively. Phantom limb phenomena changed within the first half year after amputation from a mainly proximal and distal distribution to a mainly distal localized sensation. While approximately 3/4 of patients with phantom limb had kinaesthetic sensations in the limb (i.e. feeling of length, volume or other spatial sensation) during the first 6 months after amputation, less than 50% of patients had this later in the course; 30% of patients noticed a clear shortening of the phantom limb during the follow-up period. While the incidence of phantom limb did not decrease during the follow-up period, both the duration and frequency of phantom limb phenomena declined significantly. The distribution of non-painful and painful phantom limb did not differ significantly from each other. The present findings suggest that mechanisms both in periphery, spinal cord and brain participate in generating the phantom limb percept.     

Spinal injuries in Canadian ice hockey: documentation of injuries sustained from 1943-1999

OBJECTIVES: Study objectives were: (a) to examine the causes and incidence of major spinal cord injuries sustained by ice hockey players; and (b) to add recently reported Canadian cases to the Canadian Ice Hockey Spinal Injury Registry to determine the effectiveness of prevention efforts. METHODS: The study was a review of questionnaires returned retrospectively by physicians and other sources reporting ice hockey related spinal injuries in Canada. Physicians reported on the mechanism of injury, vertebral level of injury, presence of neurologic deficit, type of event, and type of fracture. RESULTS: Between 1943 and 1999, 271 major spinal injuries were reported in Canadian ice hockey players, of which 49.0% occurred to players 16-20 years of age. Ontario has had a disproportionately large number of injuries compared to some provinces, especially Quebec. Of the spinal cord injuries, 65.8% resulted from colliding with the boards, and 36.6% were due to players being pushed or checked from behind. The recent survey shows that there has been a decline in the number of major spinal cord injuries in Canadian ice hockey, especially those causing paralysis due to checking or pushing from behind. CONCLUSIONS: Impact of the head with the boards after being checked or pushed from behind was the most common mechanism of spinal cord injury. Injury prevention programs are becoming effective in reducing the overall number of injuries, especially those due to checking from behind. Greater awareness of the occurrence and mechanisms of injury through educational programs and rules changes by organized hockey have reduced the annual incidence of catastrophic spinal injuries in Canadian ice hockey.     

A neural substrate for nonpainful phantom limb phenomena

Activity in the cerebral cortex associated with non-painful phantom limb sensation was studied in 14 upper extremity amputees. In four subjects, repetitive tactile stimulation of the digits or the lower corner of the mouth elicited non-painful phantom sensation in the amputated limb, in the remaining 10 patients no sensation could be evoked. Neuroelectric source imaging revealed significantly elevated activity in SI and posterior parietal cortex, and significantly decreased activity in ipsilateral SII cortex when referred sensations were present. However, nonpainful referred phantom sensations were not associated with a shift of the cortical representation of the mouth into the hand region, as previously suggested. Nonpainful phantom limb experiences seem to have widely distributed neural networks in multiple cortical regions.     

Reorganization of sensory processing below the level of spinal cord injury as revealed by fMRI

The adult mammalian CNS undergoes plastic changes in response to injury. To investigate such changes in spinal cord, functional magnetic resonance imaging (fMRI) was applied in rats subjected to complete transection of the mid-thoracic spinal cord. Blood oxygenation level-dependent (BOLD) contrasts were recorded in the distal spinal cord different times after injury (3, 7, and 14 days, and 1, 3, and 6 months) in response to electrical hind limb stimulation. Functional MRI demonstrated a substantial increase of neuronal activation in the ipsilateral dorsal horn after injury. Notably, 0.5 mA, which did not evoke activation in the normal spinal cord and was considered a non-painful stimulus, induced significant BOLD responses in the dorsal horn after injury. Increased sensitivity was also seen in response to 1.0 mA stimulation. Our results suggest exaggerated responsiveness of spinal neurons after spinal cord injury. Reorganization in the injured spinal cord has been shown to involve the amplification of peripheral inputs and implicated as one underlying mechanism causing neuropathic pain and autonomic dysreflexia. Since BOLD signals can demonstrate such plastic changes in spinal cord parenchyma, we propose fMRI as a method to monitor functional reorganization in the spinal cord after injury. Combining brain and spinal cord fMRI allows the visualization of neuronal activities along the entire neuroaxis and thereby an evaluation of the different plastic responses to CNS injuries that occur in the brain and the spinal cord.     

Psychophysical correlates of phantom limb experience.

Phantom limb phenomena were correlated with psychophysiological measures of peripheral sympathetic nervous system activity measured at the amputation stump and contralateral limb. Amputees were assigned to one of three groups depending on whether they reported phantom limb pain, non-painful phantom limb sensations, or no phantom limb at all. Skin conductance and skin temperature were recorded continuously during two 30 minute sessions while subjects continuously monitored and rated the intensity of any phantom limb sensation or pain they experienced. The results from both sessions showed that mean skin temperature was significantly lower at the stump than the contralateral limb in the groups with phantom limb pain and non-painful phantom limb sensations, but not among subjects with no phantom limb at all. In addition, stump skin conductance responses correlated significantly with the intensity of non-painful phantom limb paresthesiae but not other qualities of sensation or pain. Between-limb measures of pressure sensitivity were not significantly different in any group. The results suggest that the presence of a phantom limb, whether painful or painless, is related to the sympathetic-efferent outflow of cutaneous vasoconstrictor fibres in the stump and stump neuromas. The hypothesis of a sympathetic-efferent somatic-afferent mechanism involving both sudomotor and vasoconstrictor fibres is proposed to explain the relationship between stump skin conductance responses and non-painful phantom limb paresthesiae. It is suggested that increases in the intensity of phantom limb paresthesiae follow bursts of sympathetic activity due to neurotransmitter release onto apposing sprouts of large diameter primary afferents located in stump neuromas, and decreases correspond to periods of relative sympathetic inactivity. The results of the study agree with recent suggestions that phantom limb pain is not a unitary syndrome, but a symptom class with each class subserved by different aetiological mechanisms.     

The utility of testing tactile perception of direction of scratch as a sensitive clinical sign of posterior column dysfunction in spinal cord disorders.

Classical beliefs about the functions of the dorsal columns of the spinal cord have been attacked following recent evidence that position and vibration sensations may be carried in the dorsal spinocerebellar tracts. There is evidence that the one specific function of the dorsal columns is for the transmission of information concerning the direction of tactile cutaneous movement. Thirty normal controls, 43 patients with spinal cord disorders and 10 patients with functional disorders were examined prospectively using an easily administered "direction of scratch" protocol. Interpretation of the direction of a 2 cm vertical tactile cutaneous movement over the lower limbs was found to be accurate in normal controls and grossly inaccurate in patients with functional disorders, exceeding the error rate of guessing. Detection of direction of 2 cm scratch was moderately impaired in 11 of 13 patients with spastic paraparesis and preserved sensation to all other modalities and 23 of 24 patients with spastic paraparesis and impaired proprioception and/or vibration sensations. Direction of 2 cm scratch, proprioception and vibration sensations were preserved in the three cases with anterior spinal cord syndromes. It is proposed that tactile perception of direction of 2 cm scratch over the lower limbs is a sensitive sign of posterior column function which can be usefully incorporated into the clinical sensory examination in the evaluation of spinal cord disorders.     

Barostat testing of rectal sensation and compliance in humans: comparison of results across two centres and overall reproducibility

We assessed reproducibility of measurements of rectal compliance and sensation in health in studies conducted at two centres. We estimated samples size necessary to show clinically meaningful changes in future studies. We performed rectal barostat tests three times (day 1, day 1 after 4 h and 14-17 days later) in 34 healthy participants. We measured compliance and pressure thresholds for first sensation, urgency, discomfort and pain using ascending method of limits and symptom ratings for gas, urgency, discomfort and pain during four phasic distensions (12, 24, 36 and 48 mmHg) in random order. Results obtained at the two centres differed minimally. Reproducibility of sensory end points varies with type of sensation, pressure level and method of distension. Pressure threshold for pain and sensory ratings for non-painful sensations at 36 and 48 mmHg distension were most reproducible in the two centres. Sample size calculations suggested that crossover design is preferable in therapeutic trials: for each dose of medication tested, a sample of 21 should be sufficient to demonstrate 30% changes in all sensory thresholds and almost all sensory ratings. We conclude that reproducibility varies with sensation type, pressure level and distension method, but in a two-centre study, differences in observed results of sensation are minimal and pressure threshold for pain and sensory ratings at 36-48 mmHg of distension are reproducible.     

Diagnostic spinal anaesthesia in chronic spinal cord injury pain.

In a double blind study, 21 patients with chronic spinal cord injury (SCI) pain underwent placement of a lumbar subarachnoid catheter and injection of placebo and lidocaine. The effects on pain intensity, distribution, altered sensations and sensory level of anaesthesia were monitored. Four patients responded briefly to placebo, while 13 demonstrated a mean reduction of pain intensity of 37.8 +/- 37% for a mean duration of 123.1 +/- 95.3 minutes in response to lidocaine. The pain response to subarachnoid lidocaine differed significantly (p less than 0.01) from placebo. Spinal anaesthesia was also associated with changes in pain distribution and altered sensation. A spinal anaesthetic-induced sensory level could not be achieved cephalad to the sensory level of neurological injury in 5 patients who presented with spinal canal obstruction. This study has demonstrated that response to diagnostic spinal anaesthesia in chronic SCI pain is complex, requiring individual interpretation in each patient and consideration of the following factors; symptomatology, etiology, pain perception, spinal canal anatomy, CSF chemistry and local anaesthetic pharmacology.     

Cortical processing of residual ano-rectal sensation in patients with spinal cord injury: an fMRI study

Abstract  Eleven paraplegic patients with complete traumatic spinal cord injuries (SCI) [according to American Spinal Injury Association (ASIA) criteria] at different levels (Th3–L3) were investigated during non-painful stimulation of the distal rectum and anal canal, using event related functional magnetic resonance imaging. Although a complete lesion was clinically diagnosed in all, four of them experienced reproducible sensations during anal and/or rectal stimulation. In six patients, individual data analysis revealed significant activation in the right secondary somatosensory cortex SII, the posterior cingular gyrus, the prefrontal cortex, and the left posterior cerebellar lobe during either anal or rectal stimulation or both. A Region of interest analysis using a data mask from healthy controls confirmed that SCI patients demonstrate cortical activation in areas similar to those activated in healthy volunteers, but to a less extensive degree. This supports the notion that the diagnosis of complete spinal cord transsection by ASIA criteria alone may be insufficient for assessment of 'completeness' of cord lesions, and that visceral sensitivity testing may be required in addition.     

Chronic and predominantly sensory polyneuropathy in Toroku Valley where a mining company produced arsenic]

We report 9 patients (5 males, 4 females, ages 63-77) with chronic polyneuropathy. They were exposed to arsenic for about 15-40 years in Toroku Valley, Takachiho-Town, Miyazaki Prefecture, Japan, where a mining company produced arsenic from 1920-1962. Predominantly sensory polyneuropathy was the most significant neurological finding. In 5 of them, superficial and deep sensation was equally affected over the entire body, including head, face, and mucous membranes of the mouth. The corneal reflexes were absent or sluggish. Pin-prick and light-touch perception was absent in their hands and legs. Another sensory disorder such as glove and stocking-type was seen in 4 of them. All 9 patients were comfortable with extremely hot water in their beverages, their baths, and their wash basins compared with controls. But these patients felt that their temperature sensation was normal. Motor involvement was minimal. Although motor-nerve conduction velocities were normal or reduced minimally, sensory-nerve conduction velocities were moderately reduced. Sural-nerve biopsy revealed reduction of both small myelinated and unmyelinated fibers, which occurs with axonal degeneration of peripheral nerves. Other main symptoms and signs were tension-type headaches, non-painful tonic spasms of limbs, and losses or significantly decreased sensations of taste and smell. Dantrolene-sodium was effective for the treatment of their non-painful tonic spasms of limbs. As for the general medical condition of these patients, all of them had suffered from chronic bronchitis and skin eruption during childhood or in their early life or in their young adulthood when the mine was producing arsenic. At the time of this study only four of them suffered from chronic bronchitis and none of them had skin eruptions or discoloration of the skin, 37 years after closure of the mine. These 9 patients were diagnosed as having chronic arsenic poisoning and arsenic polyneuropathy. The multiplicity of symptoms found in these patients--anosmia, ageusia, chronic bronchitis, tension-type headaches, and non-painful tonic spasms of limbs--differs from the symptoms previously reported cases with arsenic poisoning. This may be due to combined overexposure to environmentally hazardous arsenic by effluent gas, dust, and drinking water in Toroku Valley. As concerns the sensory disorders described above, it is necessary to investigate sensory conduction pathways, including cerebral sensory cortex, spinal cord, and skin sensory receptors such as Pacini corpuscles, and Meissner corpuscles. Unfortunately, no information has been obtained about this problem because there were no autopsy cases.     

Sensory perception in complete spinal cord injury

OBJECTIVES: To describe sensations evoked by painful or repetitive stimulation below injury level in patients with a clinically complete (American Spinal Injury Association, ASIA Grade A) spinal cord injury (SCI). MATERIAL AND METHODS: Twenty-four patients (11 with central neuropathic pain and 13 without pain) with a traumatic SCI above the tenth thoracic vertebra were examined using quantitative sensory testing, MR imaging, and somatosensory evoked potentials (SEP). RESULTS: Painful (pressure, pinch, heat or cold) or repetitive (pinprick) stimuli elicited vague localized sensations in 12 patients (50%). Pain, spasticity, and spasms were equally seen in SCI patients with or without localized sensations. SEP and MRI did not differentiate between these two groups. CONCLUSION: The present study suggests retained sensory communication across the injury in complete SCI, i.e. 'sensory discomplete' SCI.     

Spinal cord repair: bridging the divide

The normal spinal cord coordinates movement and sensation in the body. It is a complex organ containing nerve cells, supporting cells, and nerve fibers to and from the brain. The spinal cord is arranged in segments, with higher segments controlling movement and sensation in the upper parts of the body and lower segments controlling the lower parts of the body. Recent notable discoveries in the fields of neuroscience and cell biology have ensured that many more people survive injuries to the brain and spinal cord. The consequences of injury reflect this organization. Although these developments have been mirrored by significant strides in our understanding of the evolution and pathology of spinal injuries, complete repair of structure and hence function remain elusive. Most spinal cord injuries still cause lifelong disability, and continued research is critically needed. Here we review the molecular and cellular processes that occur during the evolution of an injury to the central nervous system. Throughout, we highlight several promising therapies aimed to restore the disrupted connections in the brain and spinal cord. These, used in combination with supportive care and rehabilitation strategies, may help patients to achieve significant long-term recovery.     

Temporal course of motor recovery after Brown-Sequard spinal cord injuries

Recovery of voluntary motor function after incomplete spinal cord injuries is attributed to a variety of physiological mechanisms, such as resolution of conduction block in injured axons, and neuroplasticity mechanisms in spared axons. To better understand these recovery mechanisms, we have examined motor recovery in one type of incomplete cord injury, the Brown-Sequard Syndrome. This syndrome is observed in patients with unilateral injury of the spinal cord and is manifested as asymmetric weakness and pain/temperature sensory loss contralateral to the weakest extremity. We have followed the course of motor recovery in two patients and reviewed the literature in an additional 59. Common features of this motor recovery include: 1) recovery of ipsilateral proximal extensor muscles before ipsilateral distal flexors, 2) recovery of any weakness in the extremity with pain/temperature sensory loss before the opposite extremity, and 3) recovery of voluntary motor strength and a functional gait by 1 to 6 months. We discuss these observations with respect to three hypotheses to explain motor recovery and suggest that neuroplasticity mechanisms functioning in spared descending axons may mediate much of the observed recovery after Brown-Sequard cord lesions.     

Fire and phantoms after spinal cord injury: Na+ channels and central pain

Neuropathic pain and phantom phenomena occur commonly after spinal cord injury (SCI) but their molecular basis is not yet fully understood. Recent findings demonstrate abnormal expression of the Nav1.3 Na(+) channel within second-order spinal cord dorsal horn neurons and third-order thalamic neurons along the pain pathway after SCI, and suggest that this change makes these neurons hyperexcitable so that they act as pain amplifiers and generators. Delineation of molecular changes that contribute to hyperexcitability of pain-signaling neurons might lead to identification of molecular targets that will be useful in the treatment of neuropathic pain after SCI and related nervous system injuries.     

Post-surgical ischaemic myelopathy

Ischaemic myelopathy is an infrequent but well-known cause of spinal cord injury. While the overall incidence of neurological injury following thoraco-abdominal aortic surgery is low (1-14%), procedures requiring surgical cross-clamping of the aorta have been reported as the major cause of ischaemic cord injury (31%). Little has been reported regarding the clinical and functional outcomes of these injuries. Three patients with a non-penetrating aortic injury who showed evidence of ischaemic cord injury within 72 hours of surgical cross-clamping of the aorta are presented. Data includes functional assessments, muscle strength testing and electromyographic findings. All three patients showed lower thoracic incomplete motor and sensory spinal cord injuries. These findings suggest that, after a period of neurological improvement, a plateau phase is reached at approximately 3 months post injury after which no significant gain in muscle strength is made. All patients were functionally independent and able to ambulate using a straight cane.     

Motor and somatosensory evoked potentials in a primate model of experimental spinal cord injury

Motor and somatosensory evoked potentials (MEP and SSEP) were compared after experimental spinal cord injury in Bonnet monkeys (macaca radiata). The MEP and SSEP changes following graded injuries were related to clinical outcome. Eight healthy mature monkeys with a mean weight of 4.2 + 0.9 Kg were chosen for the study. Graded spinal cord injury was caused using 50, 100, 200, 300 gm-cm force by modified Allens' weight drop device. MEP and SSEP recordings were done before injury and at 0, 2, 4 and 6 hours after injury and on the 7th postoperative day. Neurological assessment was done at 24 hours and on the 7th day following injury. 50, 100, 200 gm-cm force caused partial injuries and 300 gm-cm force caused severe spinal cord injury. The predictive value of MEP and SSEP following partial injuries was 80% and 66.67% respectively. Both MEP and SSEP were 100% predictive in severe injury. MEP and SSEP monitoring can therefore be complementary to each other in predicting the neurological outcome in partial injuries to the spinal cord.     

Generating artificial sensations with spinal cord stimulation in primates and rodents

For patients who have lost sensory function due to a neurological injury such as spinal cord injury (SCI), stroke, or amputation, spinal cord stimulation (SCS) may provide a mechanism for restoring somatic sensations via an intuitive, non-visual pathway. Inspired by this vision, here we trained rhesus monkeys and rats to detect and discriminate patterns of epidural SCS. Thereafter, we constructed psychometric curves describing the relationship between different SCS parameters and the animal's ability to detect SCS and/or changes in its characteristics. We found that the stimulus detection threshold decreased with higher frequency, longer pulse-width, and increasing duration of SCS. Moreover, we found that monkeys were able to discriminate temporally- and spatially-varying patterns (i.e. variations in frequency and location) of SCS delivered through multiple electrodes. Additionally, sensory discrimination of SCS-induced sensations in rats obeyed Weber's law of just-noticeable differences. These findings suggest that by varying SCS intensity, temporal pattern, and location different sensory experiences can be evoked. As such, we posit that SCS can provide intuitive sensory feedback in neuroprosthetic devices.     

Relationships between the changes in compound muscle action potentials and selective injuries to the spinal cord and spinal nerve roots.

OBJECTIVE: Compound muscle action potentials (CMAPs) evoked by transcranial electrical stimulation have been widely introduced to monitor motor function during spinal surgery. They may reflect segmental injuries as well as injuries to motor-related tracts in the spinal cord. However, we have experience with some patients who developed postoperative segmental motor weakness without any potential changes during surgery. To evaluate the efficacy of this method, we used a cat model to observe the relationships between potential changes and selective injuries to the white and gray matters of the spinal cord and spinal nerve roots. METHODS: Ten CMAPs were obtained before and after injury to the spinal cord and spinal nerve roots in 20 cats. Changes in the amplitude, latency, and duration of CMAPs were analyzed. RESULTS: CMAPs decreased in amplitude significantly after the insult to the motor-related tracts in the spinal cord in all cats, while the potentials did not always change when the insult was restricted to a limited area in the anterior horn of the spinal cord or to the single spinal nerve root. CONCLUSIONS: CMAPs may not exactly reflect segmental injury, and careful attention should be paid to the interpretation of CMAPs.     

Targeting axon guidance cues for neural circuit repair after spinal cord injury

At least two-thirds of spinal cord injury cases are anatomically incomplete, without complete spinal cord transection, although the initial injuries cause complete loss of sensory and motor functions. The malleability of neural circuits and networks allows varied extend of functional restoration in some individuals after successful rehabilitative training. However, in most cases, the efficiency and extent are both limited and uncertain, largely due to the many obstacles of repair. The restoration of function after anatomically incomplete injury is in part made possible by the growth of new axons or new axon branches through the spared spinal cord tissue and the new synaptic connections they make, either along the areas they grow through or in the areas they terminate. This review will discuss new progress on the understanding of the role of axon guidance molecules, particularly the Wnt family proteins, in spinal cord injury and how the knowledge and tools of axon guidance can be applied to increase the potential of recovery. These strategies, combined with others, such as neuroprotection and rehabilitation, may bring new promises. The recovery strategies for anatomically incomplete spinal cord injuries are relevant and may be applicable to traumatic brain injury and stroke.