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CT afferents, affective touch and interoception
e162
British Society for Clinical Neurophysiology / Clinical Neurophysiology 118 (2007) e161–e164
X-linked form of CMT is mainly caused by coding mutations in the GJB1 gene, encoding Connexin 32 (Cx32). Two non-coding mutations have been previously identified in the promoter region. We identified a large family from Essex in the UK with typical Xlinked CMT. Sequencing of the Cx32 coding region was negative but sequencing the promoter region revealed a novel mutation at position 526 bp in the P2 region which segregated with the disease. Genetic linkage studies showed the family were tightly linked to the Cx32 (Xq13.1) region. We carried out detailed clinical and neurophysiological studies on 16 affected individuals from this family. Mean ulnar motor velocity in affected males was 32 ± SD 4.0 (range 28–36) m/s and in affected females was 46 ± SD 2.9 (range 34–55) m/s. The Cx32 P2 promoter region mutation was at a SOX10 S2 binding site and highly conserved in a number of different species. Functional studies carried out suggested that mutations in this region of the Cx32 promoter are part of a complex process of Schwann cell dysfunction, involving SOX10 and EGR2 and leading to demyelination. Progress in the understanding of how mutant genes lead to the development of different types of neuropathy is likely to be critical to an understanding of the pathogenesis of CMT and the neurophysiological expression of this disorder. doi:10.1016/j.clinph.2006.07.252
CT afferents, affective touch and interoception—H. Olausson 1, J. Cole 2, F. McGlone 3, H. Kramer 1, K. Rylander 1, G. Stark 1, B.G. Wallin 1 (1 University of Goteborg, Sweden, 2 Poole Hospital and University of Bournemouth, UK, 3 Unilever Ltd and University of Nottingham, UK) Microneurography has revealed a dual tactile innervation from human hairy skin. In addition to the well-known large myelinated A-b fibres, small C-fibre tactile afferents (CT afferents) have been found. The latters’ role has been uncertain since their activation is always accompanied by simultaneous A-b fibre activation. Recently Olausson and co-workers studied subject GL, without A-b but with intact CT fibres. She experienced a pleasurable sensation with brushing and was shown to have activation in posterior insula rather than somatosensory cortices (S1 and S2). They suggested CT afferents underpin affective touch (Olausson et al., Nature Neuroscience, 2002, 5, 900–904). We have repeated these experiments with subject IW, also without A-b but with CT afferents. He also showed activation of insula cortex, though with less pleasurable sensation, possibly due to partial loss of CT fibres. In addition stimulation of CT afferents on the arm evoked transient skin resistance reductions, indicating activation of a sympathetic reflex, even when he was not aware of stimulation. Thus CT afferents may also be involved in an interoceptive system affecting homeostasis. This work was supported by the Swedish Research Council. doi:10.1016/j.clinph.2006.07.253
Outcome after epilepsy surgery in patients with normal neuroimaging—G. Alarco´n 1, A. Valentı´n 1, R. Selway 2, R.C. Elwes 1, J. Jarosz 3, N. Mullatti 1, F. Brunhuber 1,
C.D. Binnie 1, C.E. Polkey 2 (1 Department of Clinical Neurophysiology, King’s College Hospital, London, UK, 2 Department of Neurosurgery, King’s College Hospital, London, UK, 3 Department of Neuroradiology, King’s College Hospital, London, UK) Presurgical assessment of epileptic patients with normal neuroimaging poses a particularly difficult problem. Whereas some centres abandon surgery in patients with normal neuroimaging, others report favourable results after assessment with intracranial electrodes (IE). We report results from 105 consecutive patients assessed with IE between September 1999 and May 2004 at King’s College Hospital. Thirty-nine patients (37%) had normal neuroimaging whereas 66 (63%) showed lesion(s). Twenty-one of the 39 patients with normal neuroimaging (54%) and 40 of the 66 lesional patients (61%) had surgery. All operated patients with normal neuroimaging had IE. We report surgical outcome on the 40 operated patients who presently have a follow up longer than one year. Eleven of the 17 patients with normal neuroimaging (65%) had favourable outcome (Engel grades 1–2), and 17 of the 23 lesional patients (74%) had favourable outcome. It is concluded that: (a) A significant proportion of patients assessed for epilepsy surgery can have normal neuroimaging; (b) Over 50% of patients with normal neuroimaging are suitable for surgery after assessment with IE; (c) The proportion of patients with favourable postsurgical seizure control is only slightly lower among patients with normal neuroimaging (65% in our series) than among patients with lesions (74%). doi:10.1016/j.clinph.2006.07.254
An audit of neurophysiological investigation for narcolepsy—C.A. Scott, S.J.M. Smith, M.C. Walker (Telemetry Unit, The National Hospital for Neurology and Neurosurgery, London, UK) This audit was undertaken to examine the current practice for investigating narcolepsy at the National Hospital for Neurology and Neurosurgery with specific reference to the yield from polysomnographic records (PSG) over two nights compared with the yield from PSG for a single night. We reviewed 25 patients investigated for narcolepsy between December 2002 and November 2003. From the original investigation, six had a definite diagnosis of narcolepsy and seven had an equivocal diagnosis. The factual reports, with all information relating to the second night removed, were reviewed independently by two neurophysiology consultants. These results were then compared with the original findings to see whether the same clinical conclusion was obtained with the second night included. There was agreement in 22/25 cases with the original diagnosis. There was disagreement between the two consultants in the other 3 cases, suggesting that this was due to difficulty in diagnosis (none were given an original diagnosis of definite narcolepsy). These data suggest that including a second night probably adds little additional information. doi:10.1016/j.clinph.2006.07.255
British Society for Clinical Neurophysiology / Clinical Neurophysiology 118 (2007) e161–e164
X-linked form of CMT is mainly caused by coding mutations in the GJB1 gene, encoding Connexin 32 (Cx32). Two non-coding mutations have been previously identified in the promoter region. We identified a large family from Essex in the UK with typical Xlinked CMT. Sequencing of the Cx32 coding region was negative but sequencing the promoter region revealed a novel mutation at position 526 bp in the P2 region which segregated with the disease. Genetic linkage studies showed the family were tightly linked to the Cx32 (Xq13.1) region. We carried out detailed clinical and neurophysiological studies on 16 affected individuals from this family. Mean ulnar motor velocity in affected males was 32 ± SD 4.0 (range 28–36) m/s and in affected females was 46 ± SD 2.9 (range 34–55) m/s. The Cx32 P2 promoter region mutation was at a SOX10 S2 binding site and highly conserved in a number of different species. Functional studies carried out suggested that mutations in this region of the Cx32 promoter are part of a complex process of Schwann cell dysfunction, involving SOX10 and EGR2 and leading to demyelination. Progress in the understanding of how mutant genes lead to the development of different types of neuropathy is likely to be critical to an understanding of the pathogenesis of CMT and the neurophysiological expression of this disorder. doi:10.1016/j.clinph.2006.07.252
CT afferents, affective touch and interoception—H. Olausson 1, J. Cole 2, F. McGlone 3, H. Kramer 1, K. Rylander 1, G. Stark 1, B.G. Wallin 1 (1 University of Goteborg, Sweden, 2 Poole Hospital and University of Bournemouth, UK, 3 Unilever Ltd and University of Nottingham, UK) Microneurography has revealed a dual tactile innervation from human hairy skin. In addition to the well-known large myelinated A-b fibres, small C-fibre tactile afferents (CT afferents) have been found. The latters’ role has been uncertain since their activation is always accompanied by simultaneous A-b fibre activation. Recently Olausson and co-workers studied subject GL, without A-b but with intact CT fibres. She experienced a pleasurable sensation with brushing and was shown to have activation in posterior insula rather than somatosensory cortices (S1 and S2). They suggested CT afferents underpin affective touch (Olausson et al., Nature Neuroscience, 2002, 5, 900–904). We have repeated these experiments with subject IW, also without A-b but with CT afferents. He also showed activation of insula cortex, though with less pleasurable sensation, possibly due to partial loss of CT fibres. In addition stimulation of CT afferents on the arm evoked transient skin resistance reductions, indicating activation of a sympathetic reflex, even when he was not aware of stimulation. Thus CT afferents may also be involved in an interoceptive system affecting homeostasis. This work was supported by the Swedish Research Council. doi:10.1016/j.clinph.2006.07.253
Outcome after epilepsy surgery in patients with normal neuroimaging—G. Alarco´n 1, A. Valentı´n 1, R. Selway 2, R.C. Elwes 1, J. Jarosz 3, N. Mullatti 1, F. Brunhuber 1,
C.D. Binnie 1, C.E. Polkey 2 (1 Department of Clinical Neurophysiology, King’s College Hospital, London, UK, 2 Department of Neurosurgery, King’s College Hospital, London, UK, 3 Department of Neuroradiology, King’s College Hospital, London, UK) Presurgical assessment of epileptic patients with normal neuroimaging poses a particularly difficult problem. Whereas some centres abandon surgery in patients with normal neuroimaging, others report favourable results after assessment with intracranial electrodes (IE). We report results from 105 consecutive patients assessed with IE between September 1999 and May 2004 at King’s College Hospital. Thirty-nine patients (37%) had normal neuroimaging whereas 66 (63%) showed lesion(s). Twenty-one of the 39 patients with normal neuroimaging (54%) and 40 of the 66 lesional patients (61%) had surgery. All operated patients with normal neuroimaging had IE. We report surgical outcome on the 40 operated patients who presently have a follow up longer than one year. Eleven of the 17 patients with normal neuroimaging (65%) had favourable outcome (Engel grades 1–2), and 17 of the 23 lesional patients (74%) had favourable outcome. It is concluded that: (a) A significant proportion of patients assessed for epilepsy surgery can have normal neuroimaging; (b) Over 50% of patients with normal neuroimaging are suitable for surgery after assessment with IE; (c) The proportion of patients with favourable postsurgical seizure control is only slightly lower among patients with normal neuroimaging (65% in our series) than among patients with lesions (74%). doi:10.1016/j.clinph.2006.07.254
An audit of neurophysiological investigation for narcolepsy—C.A. Scott, S.J.M. Smith, M.C. Walker (Telemetry Unit, The National Hospital for Neurology and Neurosurgery, London, UK) This audit was undertaken to examine the current practice for investigating narcolepsy at the National Hospital for Neurology and Neurosurgery with specific reference to the yield from polysomnographic records (PSG) over two nights compared with the yield from PSG for a single night. We reviewed 25 patients investigated for narcolepsy between December 2002 and November 2003. From the original investigation, six had a definite diagnosis of narcolepsy and seven had an equivocal diagnosis. The factual reports, with all information relating to the second night removed, were reviewed independently by two neurophysiology consultants. These results were then compared with the original findings to see whether the same clinical conclusion was obtained with the second night included. There was agreement in 22/25 cases with the original diagnosis. There was disagreement between the two consultants in the other 3 cases, suggesting that this was due to difficulty in diagnosis (none were given an original diagnosis of definite narcolepsy). These data suggest that including a second night probably adds little additional information. doi:10.1016/j.clinph.2006.07.255