Central nervous system regeneration does not occur.

STUDY DESIGN: Review. OBJECTIVES: To examine the state of research in central nervous system (CNS) regeneration and to suggest an alternative to the sterile research at the lesion site. SETTING: Worldwide. METHODS: A search of publications using 'PubMed' and a search of the historical literature relevant to CNS regeneration, biological models, the neurone theory, collateral sprouting, spinal shock and the central pattern generator. RESULTS: There is no evidence for CNS regeneration. CONCLUSION: A century of research focussed on the lesion site has been unproductive. An alternative field of research must be developed and the best candidate is the undamaged CNS.

The case for specialist units.

There is considerable evidence that management in a specialist unit is beneficial both for the individual patient and for the economy. A specialised unit provides a focus for a campaign for prevention, for the improvement in care in areas such as orthopaedic, bladder, bowel, skin, etc and for the promotion of interdisciplinary work, combining the needs of public health, low-cost technology, and high quality. Strategy and training is dictated by the specific problems that occur in patients with spinal injuries, particularly the multisystem impairment, which is a feature of such injuries and can only be comprehensively dealt with in a specialised unit. For developing countries, training may be either on-site or in centres abroad, or a combination of both, and rather than training on an individual basis, it is preferable for a team to be trained together. The likely cost depends on local circumstances. However, even the cost of a purpose-built centre of 44 beds serving 3000 paralysed people in the UK is only the equivalent of the lifetime costs of about 12 people with SCI.

Herpes simplex encephalitis: long term magnetic resonance imaging and neuropsychological profile.

The first comprehensive in vivo documentation of the long term profile of pathological and spared tissue is described in a group of 10 patients with a diagnosis of herpes simplex encephalitis, who were left with memory difficulties as a major residual sequel of their condition. With a dedicated MRI protocol, which included high resolution images of temporal lobe and limbic system areas, data are provided on structures that have recently gained importance as anatomical substrates for amnesia. The major features of the lesion profile were: (1) unilateral or bilateral hippocampal damage never occurred in isolation, and was often accompanied by damage to the parahippocampus, the amygdala, specific temporal lobe gyri, and the temporal poles; (2) the insula was always abnormal; (3) neocortical temporal lobe damage was usually unilateral or asymmetric. It never occurred in isolation, and was invariably associated with more medial pathological changes; (4) anterior and inferior temporal lobe gyri were damaged more often and more severely than posterior and superior temporal lobe gyri; (5) pronounced abnormality was often present in the substantia innominata (region of the basal forebrain/anterior perforated substance); (6) there was evidence of significant abnormality in the fornix; (7) there was evidence of damage to the mammillary bodies; (8) thalamic nuclei were affected in around 50% of cases, with damage usually unilateral; (9) frontal lobe damage was present in a few patients, and affected medial areas more than dorsolateral areas; (10) there was some involvement of the striatum, although this was usually unilateral and mild; (11) there was usually limited involvement of the cingulate gyrus and of the parietal and occipital lobes; (12) the cerebellum and brain stem were never damaged. Lesion covariance analysis indicated a close relation between the presence of abnormalities in temporal lobe and limbic-diencephalic regions. Unlike severe head injury, lesions in the temporal pole were not associated with the presence of lesions in the orbitofrontal cortex. Long term neuropsychological impairments were characterised by a dense amnesia in 60% of cases, and a less serve but noticeable anterograde memory impairment in the others. Naming and problem solving deficits were found in a small number of cases. Only two patients were able to return to open employment. Severity of amnesia showed a significant relation with severity of damage to medical limbic system structures such as the hippocampus, with bilateral damage being particularly important. By contrast, there was a minimal relation between memory loss and severity of damage to the thalamus, to lateral temporal lobe areas, or to the frontal lobes.

Reversible motor and sensory neurophysiological abnormalities in cauda equina claudication.

A case of cauda equina claudication with canal stenosis is presented. Neurophysiological studies show reversible changes during symptomatic and asymptomatic phases. The somatosensory evoked potential from the tibial nerve was reduced in amplitude. Central motor conduction time (CMCT) after transcranial magnetic stimulation of the brain was reversibly prolonged in the symptomatic phase. Reversible CMCT changes have not been previously shown. The findings are discussed in the light of the pathophysiology of ischaemic nerve.

Monoclonal IgM cold agglutinins with anti-Pr1d specificity in a patient with peripheral neuropathy.

A patient with a demyelinating sensory motor polyneuropathy secondary to IgM paraproteinaemia is reported. The paraprotein binds to the gangliosides GD1b, GT1b, GQ1b and GD3, all of which contain disialosyl groups with the sequence NeuAc alpha 2-8NeuAc alpha 2-3Gal. The paraprotein also acts as a cold agglutinin recognising the sialic-acid-dependent Pr1d antigenic determinant of the red cell membrane glycophorins. In this and in similar cases that have been reported, the coexistence of anti-Pr cold agglutinins and peripheral neuropathy suggest that they might be the causative agents of the disease.

Spinal shock: possible role of receptor plasticity and non synaptic transmission.

Spinal shock remains an enigma. To date there has been no convincing explanation of the recovery of reflexes following their complete abolition. Volume transmission includes both the activation of extrasynaptic receptors, and activity induced by substances diffusing into synaptic clefts via the extracellular fluid. A brief review of non synaptic transmission is given, and a review of spinal shock. We suggest that the recovery of reflexes in spinal shock may be related to the up regulation of receptors, resulting in increased sensitivity to neurotransmitters and other neuroactive substances released at the surviving synapses, or elsewhere, and transported in the extracellular fluid. Further understanding of spinal shock would give both practical help for the patient and have academic implications for the scientific basis of neurological rehabilitation.

On the late failure of spinal cord stimulation for deafferentation pain.

Two cases are described in which spinal cord stimulation was effective in abolishing previously intractable deafferentation pain for a number of years, but in which late failure occurred for non-technical reasons. A possible explanation for this is advanced; namely that the dorsal column fibres have altered electrical properties due to a form of transganglionic degeneration.

Spinal cord stimulation for the control of spasticity in patients with chronic spinal cord injury: I. Clinical observations.

The effectiveness of spinal cord stimulation for control of spasticity was studied in 59 spinal cord injury patients. SCS was markedly or moderately effective in reducing spasticity in 63% of the patients. We found that control of spasticity by SCS was not correlated with the severity of spasticity, the type of spasticity (flexor or extensor), or the ability to ambulate. However, stimulation was more effective in patients with incomplete cervical lesions than in complete cervical lesions. Stimulation below the lesion was more effective than above. We conclude that SCS was effective when electrodes were properly positioned below the lesion over the posterior aspect of the spinal cord in patients with some residual spinal cord function. We hypothesize that SCS controls spasticity by modification of activity of spinal-brainstem-spinal loops and by suppression of segmental excitation through antidromic activation of propriospinal pathways.

Spinal cord stimulation for the control of spasticity in patients with chronic spinal cord injury: II. Neurophysiologic observations.

We sought neurophysiologic evidence that spinal cord stimulation could modify the behavior of spinal reflexes in 15 chronic SCI patients who showed the beneficial effect of SCS on spasticity. We studied the behavior of passive stretch, clonus, cutaneous touch, plantar reflex irradiation, and the response to the neck flexion reinforcement maneuver during spinal cord stimulation by use of surface PEMG recordings. Fifty-five percent of the responses were changed during spinal cord stimulation, but with widely varying patterns of response in individual patients. Exceptional patients showed changes in most or all responses; most showed changes in two or three. Thirty of seventy-five responses showed a reduction in motor unit activity in the recordings. Eleven of seventy-five responses were increased. Excessive stimulation strength enhanced spasticity in patients in whom another stimulus setting suppressed spasticity. We conclude that spinal cord stimulation could modify segmental reflexes but that the effects were selective, probably dependent on the preserved segmental structures and ascending and descending pathways.