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Cannabinoids in multiple sclerosis: do they have a therapeutic role?

This is an exciting time for cannabinoid research. Evidence suggests that cannabis (marijuana) can alleviate symptoms like muscle spasticity and pain in patients with multiple sclerosis (MS). Interest in the field of cannabinoids has been strengthened by the identification and cloning of cannabinoid receptors located in the central nervous system and the peripheral immune organs, and by the discovery of the endogenous cannabinoid ligands. Cannabinoids are also efficacious in animal models of MS. However, there have been only ten published clinical reports on the use of cannabis in MS, involving 78 individuals worldwide, and the results have been equivocal. Researchers encounter a number of difficulties in designing clinical studies that use cannabinoids. From the studies reporting the use of cannabinoids in MS patients with spasticity, the somewhat better designed studies failed to demonstrate objective improvement. Therefore, convincing evidence that cannabinoids are effective in MS is still lacking.

Animals↗

Motor control in the human spinal cord and the repair of cord function.

In this review we describe clinical and neurophysiological features of motor control in human spinal cord injury based on two models. First, motor control is considered in subjects with injury-induced complete division of the spinal cord from brain and brainstem structures, and second, in those in which the division is partial. We describe motor control in terms of segmental and plurisegmental reflex activity that dominates motor unit output to the muscles following complete separation from the brain motor structures by accidental injury. With incomplete separation of the spinal cord from brain structures, motor control is defined as the voluntary manipulation of reflex and automatic activity integrated with internal and external feedback signals. We review here motor control found after complete spinal cord injury with paradigm of single and regular-repeating stimuli applied to elicit cutaneous and muscle stretch reflex responses. We argue, that isolated spinal cord neural circuitry is capable of organizing characteristic reflex events that depend on the characteristics of the stimulus. Also, the profile of residual brain and brainstem, modified by the reduction in descending long spinal tract fibers arriving at their targets in the spinal gray matter, produces characteristic changes in motor output to the muscles that leads to the development of new neural strategies for control of segmental and plurisegmental neural circuitry. In the second part of this review, we discuss available treatment modalities for impaired cord function and briefly outline neurobiological interventions under development for repair of spinal cord injury.

Humans↗

An experimental study of reflex variability in selective dorsal rhizotomy.

Significant problems regarding the measurement technique currently used to choose nerve roots for sectioning in the selective dorsal rhizotomy procedure have recently been reported. To better understand the source of these problems, a series of six experiments was performed in which the selective rhizotomy technique was applied to cats that were either intact, decerebrate, or spinalized. Measurements were made before and after partial rhizotomy. In decerebrate preparations, large, spontaneous changes in reflex threshold were observed over short periods of time, especially after partial rhizotomy was performed, and threshold changes greater than 1000% could be observed over 10-minute periods. Using constant-current stimulation of the dorsal root at threshold, the response of each ipsilateral leg muscle demonstrated frequent changes, and changes coincided with the variability in threshold estimation. In addition, very low thresholds were measured (0.1 to 0.25 mA) in half (3 of 6) of these experiments, these measurements being well below the currents customarily used for intraoperative decision making. Stimulation at twice threshold was found to consistently increase the pathological quality of the responses observed. Although intact animals never displayed contralateral responses when stimulated at threshold, such contralateral responses could readily be elicited at twice threshold. These laboratory results raise further doubts regarding the reliability of the measurement techniques now widely used for selective dorsal rhizotomy.

Animals↗

Effect of selective dorsal rhizotomy in the treatment of children with cerebral palsy.

OBJECT: In this investigation the authors compared impairment and functional outcomes between two groups of children with cerebral palsy (CP): one group underwent selective dorsal rhizotomy (SDR) followed by intensive physical therapy (PT), and the other group underwent the latter only (PT group). Data from an age-matched group of children without disability (nondisabled [ND] group) were also collected. METHODS: Data pertaining to the 68 children with CP were collected before any intervention and again 8 and 20 months afterwards. Data regarding the 40 children in the ND group were collected in a single session. CONCLUSIONS: Although patients in both groups with CP were weaker than those in the ND group, they did have strength gains. Gait speed in the SDR-PT group was slower than that in the ND group preoperatively but not at 20 months postoperatively. Gait speed in the PT group remained slower than that in the ND group. The pre- to postoperative change in the Gross Motor Abilities Estimate score was significantly greater in the SDR-PT group than in the PT-only group. An effective treatment for children with CP, SDR offers gains in strength, gait speed, and overall gross motor function.

Adolescent↗

Calcifying pseudoneoplasms of the spine with myelopathy. Report of two cases.

The authors describe two cases of calcifying pseudoneoplasms, rare degenerative lesions that mimic tumor or infection. One case involved the cervical spine and the second the thoracic spine. Both patients experienced progressive myelopathy from extradural compression of the spinal cord. The radiological evaluation, pathological findings in the lesions, treatment, and follow up are described. Total or subtotal excision can relieve symptoms and prevent recurrence of this lesion.

Calcinosis↗

"Myelodysplasia," myeloneuropathy, and copper deficiency.

We describe a patient with a suspected myelodysplastic syndrome that developed in association with a neurologic disorder resembling subacute combined degeneration but without vitamin B12 deficiency. Ultimately, the hematologic manifestations and the neurologic syndrome were linked to severe copper deficiency. Prompt and complete reversal of the hematologic abnormalities occurred with copper replacement. Serum copper determination should be included in the work-up of patients with anemia and leukopenia of unclear etiology who have associated myeloneuropathy. The hematologic picture can resemble sideroblastic anemia or myelodysplastic syndrome. Hyperzincemia can be an accompanying abnormality even without exogenous zinc ingestion. The reason for the copper deficiency may not be evident.

Biopsy, Needle↗

Calcaneonavicular bar resection. A retrospective review.

The authors present a retrospective study evaluating the results of calcaneonavicular bar resection with interposition of the extensor digitorum brevis in ten patients with painful calcaneonavicular coalition. All operative procedures were supervised by one of the authors to ensure consistency in preoperative evaluation, surgical technique, and postoperative care. Results obtained from questionnaires showed significant improvement of preoperative symptoms with increased activity levels noted in all patients.

Adolescent↗

Measuring muscle tone and movement.

Abnormal or altered muscle tone in the neurologically damaged patient presents major problems for restoring motor function. Many nursing interventions, such as passive limb exercises and correct limb positioning, attempt to normalise muscle tone. The effect of abnormal tone on movement can be clearly seen, therefore it may be more appropriate to measure the 'quality' of movement. This article describes various methods of measuring muscle tone, such as video analysis, and examines the reliability of these techniques.

Humans↗

Role of exercise testing in the functional assessment of cerebral palsy children after botulinum A toxin injection.

The purpose of this clinical prospective study was to assess the effect of intramuscular injections of botulinum toxin A on energy cost of movement and walking endurance in 15 children with cerebral palsy, aged 4 to 13 years, by using incremental walking treadmill protocol to voluntary exhaustion. Oxygen-uptake response to exercise stress and endurance time were analyzed before and 2 and 6 months after botulinum toxin A injection. Endurance time was significantly improved 2 months after botulinum toxin A injection in 13 patients, and a residual improvement was still present 6 months after injection in some of them. The effect of botulinum toxin A on energy cost of movement was very variable. This study provides clinical evidence of the efficacy of botulinum toxin A in reducing the energy cost of movement and in improving the endurance of spastic muscles in children with cerebral palsy.

Adolescent↗

Botulism-like syndrome after injections of botulinum toxin.

Botulinum type A toxin (BTA) is an orphan drug used to treat several disorders of muscle spasticity. We report the first known case of systemic botulism-like syndrome induced by BTA therapy which resulted in respiratory arrest. Clinicians should be aware that systemic effects may occur with localized BTA therapy and may be life-threatening.

Adult↗

[Potential therapeutic usefulness of cannabis and cannabinoids].

Diseases in which Cannabis and cannabinoids have demonstrated some medicinal putative properties are: nausea and vomiting associated with cancer chemotherapy, muscle spasticity (multiple sclerosis, movement disorders), pain, anorexia, epilepsy, glaucoma, bronchial asthma, neuroegenerative diseases, cancer, etc. Although some of the current data comes from clinical controlled essays, the majority are based on anecdotic reports. Basic pharmacokinetic and pharmacodynamic studies and more extensive controlled clinical essays with higher number of patients and long term studies are necessary to consider these compounds useful since a therapeutical point of view.

Cannabinoids↗

[Acrocyanosis: changing concepts and nosological limitations].

Acrocyanosis is undoubtedly the most commonplace acrosyndrome, both in terms of pathogenesis and prognosis. Patients experience functional impairment and an esthetic prejudice that must not be neglected. Adopting the nosological classifications described for Raynaud's syndrome, primary acrocyanosis must be distinguished from exceptional secondary phenomena that have a radically different clinical course. Primary acrocyanosis is generally observed in a young woman who appears thin or has recently lost weight. No paroxysmal episode (syncope, cyanosis, suspicious event involving the fingers) is found. The physical examination is negative and no complementary explorations are needed. Current pathophysiological hypotheses remain insufficient but suggest that vasospasticity rather than hemorheology is involved. The hypothesis that a thermoregulation disorder could be associated with weight loss deserves further study. Symptomatic care relies on dietary and hygiene counseling, emphasizing the importance of warm clothing. The psychological element must also be considered even in the most common forms.

Adult↗