- Email: [email protected]
205: Prognostic accuracy of clinical signs, somatosensory evoked potentials and electroencephalography in hypoxic coma in adults
338
Abstracts / Journal of Clinical Neuroscience 15 (2008) 337–369
1.2 ± 0.6%; SALS 0.7 ± 0.3%;pre-symptomatic SOD-1 mutation carriers 8.3 ± 1.8%; controls 8.5 ± 1.0%, P < 0.00001) and was accompanied by an increase in intracortical facilitation, motor evoked potential amplitude and magnetic stimulus-response curve gradient, all indicative of cortical hyperexcitability. In 14 asymptomatic SOD-1 carriers cortical excitability was normal. In two pre-symptomatic SOD-1 mutation carriers SICI was markedly reduced (SICI patient 1, 3.2%; patients 2, 1.3%). These two individuals subsequently developed clinical features of ALS within 3 months of neurophysiological testing. Conclusions: Simultaneous investigation of central and peripheral excitability has established that cortical hyperexcitability precedes the development of clinical symptoms in pre-symptomatic carriers of the SOD1 mutation, suggesting that cortical hyperexcitability appears to drive neurodegeneration in FALS. doi:10.1016/j.jocn.2007.07.007
204: Fluoromisonidazole (FMISO) in stroke – identifies ischaemic penumbra and early infarct core Neil J. Spratt a, Geoffrey A. Donnan b, David W. b Howells ; a University of Newcastle & John Hunter Hospital, Australia; b National Stroke Research Institute, University of Melbourne & Austin Health, Australia Purpose: Human [18F]FMISO-PET studies have demonstrated binding of FMISO with timing and distribution consistent with ischemic penumbra (the threatened but potentially salvageable tissue soon after stroke). A drawback of some penumbral imaging methods has been that mildly ischaemic tissue not at-risk of infarction (‘oligaemic’ tissue), or already irreversibly injured tissue (infarct core) is identified as penumbra. We conducted experiments to determine whether FMISO binds only tissue at risk of infarction. Methods: A rat middle cerebral artery occlusion (MCAo) model was used. [3H]FMISO autoradiography was performed 24 h after onset of MCAo, enabling correlation of histological outcome from the same tissue sections. [3H]FMISO was administered immediately postMCAo in rats subject to 2 h temporary MCAo. Autoradiographs and corresponding histological sections were overlayed to determine whether any FMISO-bound tissue was salvageable by reperfusion. Comparison cohorts with permanent MCAo and 24 h or 6 day survival were used to determine final infarct size in the absence of reperfusion. To determine whether irreversibly injured tissues exhibit FMISO binding, tracer was administered 4–6 hours postonset of 24 h permanent MCAo (n = 9). Striatal regions (infarct core) of autoradiographs and histology were examined. Results: In the 2 h temporary MCAo animals, the FMISO-bound volume was significantly greater than infarct volume (P < 0.05, Table), but was not different to
the infarct volumes in the permanent occlusion animals (24 h or 6 day survival, Table). All animals with tracer administration 4–6 h post MCAo demonstrated avid [3H]FMISO binding within striatum, corresponding to areas of greatest histological injury. Conclusions: These experiments demonstrate that FMISO binding occurs in ischaemic penumbra without significant binding in mildly ischaemic unthreatened (‘oligaemic’) tissue. However, avid binding was demonstrated in the infarct core relatively early in stroke evolution. 2 hour tMCAo 24 hour FMISO (n = 6) 140 ±31 Volume (mean ± sem, mm3 *
2 hour pMCAo pMCAo tMCAo, Infarct, 24 Infarct, 24 hour hour (n = 24) 6 day Infarct (n = 4) 88 ± 27*
140 ± 16
142 ± 47
Significantly different from 2h tMCAo FMISO (p < 0.05).
doi:10.1016/j.jocn.2007.07.008
205: Prognostic accuracy of clinical signs, somatosensory evoked potentials and electroencephalography in hypoxic coma in adults Yong Chern Lee a, David A. Ingram a, Thanh G. Phan b, David C. Reutens b; a Barts and The London NHS Trust, London, United Kingdom; b Monash Medical Centre, Southern Health, Australia Introduction: Hypoxic coma is a serious medical condition with a mortality of approximately 70% and overall survival of 30%. Previous attempts to identify the prognostic value of early clinical signs, somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) have yielded a range of sensitivities and specificities. We have therefore performed a meta-analysis of 32 publications in the world literature using summary receiver operating characteristic curves (SROC) in order to compare the diagnostic accuracy of these clinical and neurophysiological markers and thus derive an index of overall performance for each parameter. Methods: PubMed (1966–2005), Medline (1966–2005) and Embase (1966-2005) were searched for reports in English, German and French. Raw data was extracted to obtain positive and negative test results and the eventual clinical outcome. A SROC curve was constructed for each test using sensitivity and specificity values, thus permitting comparison of different tests using area under curve (AUC) calculations. Results: The AUC of SROCs (indicative of the overall performance of each test) for absent pupil response and graded motor responses (M1, M < 2, M < 3) for each of the 3 days post-coma showed an incremental pattern with optimal results on day 3. AUC of SROCs for clinical mea-
Abstracts / Journal of Clinical Neuroscience 15 (2008) 337–369
339
sures were generally larger than for bilaterally absent SSEPs and for abnormal EEG findings. Conclusion: Prognostic accuracy of coma outcome improves with time after the onset of coma, being optimal on day 3. The overall diagnostic performance of absent pupillary response and motor responses (M1, M < 2, M < 3) are at least equal, if not superior, to that of bilaterally absent SSEPs or abnormal EEG findings throughout the first three days post-coma onset. SSEP studies are especially helpful when clinical signs are unreliable (e.g. in the presence of sedative medications or muscle relaxants). Of the markers examined, EEG is the least helpful in predicting coma outcome. doi:10.1016/j.jocn.2007.07.009
206: Isolated ataxia and infarction of the precentral knob Annabelle N. Sellbach, Andrew A. Wong, Richard S. Boyle; Department of Neurology, Princess Alexandra Hospital, Australia Introduction: We describe two cases of precentral knob infarction causing isolated upper limb ataxia. Functional imaging has localized motor hand activation to a part of the primary motor cortex known as the precentral knob. Several cases of hand weakness from small cortical infarcts of this region have been reported. Only two other case reports refer to isolated upper limb ataxia and infarction of the precentral knob. The mechanism for this remains unclear. Cases: Both patients presented acutely with signs suggestive of upper limb cerebellar ataxia (bilateral and right sided respectively). There were no motor or sensory deficits. MRI confirmed recent infarction of the precentral knobs bilaterally in patient 1 and on the contralateral side to the ataxia in patient 2 (See Fig. 1). There were no other lesions on MRI to explain the ataxia. Discussion: Ataxia caused by lesions distant to the cerebellum has been well established in the ataxic hemiparesis stroke syndrome. This is typically due to lacunar infarction of the pons, thalamus, internal capsule or corona radiata where corticopontocerebellar or dentatorubrothalamocortical pathways are thought to be interrupted. Cortical lesions in ataxic hemiparesis are rare and typically take the form of leg weakness with brachial ataxia. A recent single-photon emission computed tomography (SPECT) study has demonstrated the presence of crossed cerebellar diaschisis (CCD) in three patients with ataxic hemiparesis due to infarcts of the corona radiata. Whilst traditionally associated with large infarcts, emerging evidence suggests that infarct location rather than size or severity is critical for the development of CCD. The ataxia in our cases may represent direct interruption of corticopontocerebellar or dentatorubrothalamocortical pathways or indirect functional deafferentation and CCD.
Fig. 1. Axial FLAIR (A,C) and diffusion-weighted (B,D) MRI of patient 1 (A,B) and patient 2 (C,D) shearing precentral knob infarction.
Conclusion: We propose that the precentral knob localizes important cortico-cerebellar pathways and may be critical for the development of CCD.
doi:10.1016/j.jocn.2007.07.010
207: Myophosphorylase deficiency (McArdle disease): Clinical and laboratory features in seven cases Ferdinand Miteff, David Hutchinson; Auckland City Hospital, New Zealand Purpose: To demonstrate the typical clinical and laboratory features of myophosphorylase deficiency and review our experience with the molecular analysis of the PYGM gene. Methods: Hospital notes, laboratory results and muscle biopsies were reviewed. Patients were included if they had been seen by one of the authors (DH) and had myophosphorylase deficiency demonstrated by muscle histochemistry. Muscle biopsies were obtained under local anaesthesia and cryostat sections from flash-frozen muscle were examined histologically, which included myophosphorylase histochemistry. DNA was prepared from blood or frozen muscle by a guanidine thiocyanate method and 33 exons amplified by PCR. Results: Symptoms were present since early childhood in the seven patients and consisted of muscle discomfort provoked by moderate exercise, usually forcing patients
Abstracts / Journal of Clinical Neuroscience 15 (2008) 337–369
1.2 ± 0.6%; SALS 0.7 ± 0.3%;pre-symptomatic SOD-1 mutation carriers 8.3 ± 1.8%; controls 8.5 ± 1.0%, P < 0.00001) and was accompanied by an increase in intracortical facilitation, motor evoked potential amplitude and magnetic stimulus-response curve gradient, all indicative of cortical hyperexcitability. In 14 asymptomatic SOD-1 carriers cortical excitability was normal. In two pre-symptomatic SOD-1 mutation carriers SICI was markedly reduced (SICI patient 1, 3.2%; patients 2, 1.3%). These two individuals subsequently developed clinical features of ALS within 3 months of neurophysiological testing. Conclusions: Simultaneous investigation of central and peripheral excitability has established that cortical hyperexcitability precedes the development of clinical symptoms in pre-symptomatic carriers of the SOD1 mutation, suggesting that cortical hyperexcitability appears to drive neurodegeneration in FALS. doi:10.1016/j.jocn.2007.07.007
204: Fluoromisonidazole (FMISO) in stroke – identifies ischaemic penumbra and early infarct core Neil J. Spratt a, Geoffrey A. Donnan b, David W. b Howells ; a University of Newcastle & John Hunter Hospital, Australia; b National Stroke Research Institute, University of Melbourne & Austin Health, Australia Purpose: Human [18F]FMISO-PET studies have demonstrated binding of FMISO with timing and distribution consistent with ischemic penumbra (the threatened but potentially salvageable tissue soon after stroke). A drawback of some penumbral imaging methods has been that mildly ischaemic tissue not at-risk of infarction (‘oligaemic’ tissue), or already irreversibly injured tissue (infarct core) is identified as penumbra. We conducted experiments to determine whether FMISO binds only tissue at risk of infarction. Methods: A rat middle cerebral artery occlusion (MCAo) model was used. [3H]FMISO autoradiography was performed 24 h after onset of MCAo, enabling correlation of histological outcome from the same tissue sections. [3H]FMISO was administered immediately postMCAo in rats subject to 2 h temporary MCAo. Autoradiographs and corresponding histological sections were overlayed to determine whether any FMISO-bound tissue was salvageable by reperfusion. Comparison cohorts with permanent MCAo and 24 h or 6 day survival were used to determine final infarct size in the absence of reperfusion. To determine whether irreversibly injured tissues exhibit FMISO binding, tracer was administered 4–6 hours postonset of 24 h permanent MCAo (n = 9). Striatal regions (infarct core) of autoradiographs and histology were examined. Results: In the 2 h temporary MCAo animals, the FMISO-bound volume was significantly greater than infarct volume (P < 0.05, Table), but was not different to
the infarct volumes in the permanent occlusion animals (24 h or 6 day survival, Table). All animals with tracer administration 4–6 h post MCAo demonstrated avid [3H]FMISO binding within striatum, corresponding to areas of greatest histological injury. Conclusions: These experiments demonstrate that FMISO binding occurs in ischaemic penumbra without significant binding in mildly ischaemic unthreatened (‘oligaemic’) tissue. However, avid binding was demonstrated in the infarct core relatively early in stroke evolution. 2 hour tMCAo 24 hour FMISO (n = 6) 140 ±31 Volume (mean ± sem, mm3 *
2 hour pMCAo pMCAo tMCAo, Infarct, 24 Infarct, 24 hour hour (n = 24) 6 day Infarct (n = 4) 88 ± 27*
140 ± 16
142 ± 47
Significantly different from 2h tMCAo FMISO (p < 0.05).
doi:10.1016/j.jocn.2007.07.008
205: Prognostic accuracy of clinical signs, somatosensory evoked potentials and electroencephalography in hypoxic coma in adults Yong Chern Lee a, David A. Ingram a, Thanh G. Phan b, David C. Reutens b; a Barts and The London NHS Trust, London, United Kingdom; b Monash Medical Centre, Southern Health, Australia Introduction: Hypoxic coma is a serious medical condition with a mortality of approximately 70% and overall survival of 30%. Previous attempts to identify the prognostic value of early clinical signs, somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) have yielded a range of sensitivities and specificities. We have therefore performed a meta-analysis of 32 publications in the world literature using summary receiver operating characteristic curves (SROC) in order to compare the diagnostic accuracy of these clinical and neurophysiological markers and thus derive an index of overall performance for each parameter. Methods: PubMed (1966–2005), Medline (1966–2005) and Embase (1966-2005) were searched for reports in English, German and French. Raw data was extracted to obtain positive and negative test results and the eventual clinical outcome. A SROC curve was constructed for each test using sensitivity and specificity values, thus permitting comparison of different tests using area under curve (AUC) calculations. Results: The AUC of SROCs (indicative of the overall performance of each test) for absent pupil response and graded motor responses (M1, M < 2, M < 3) for each of the 3 days post-coma showed an incremental pattern with optimal results on day 3. AUC of SROCs for clinical mea-
Abstracts / Journal of Clinical Neuroscience 15 (2008) 337–369
339
sures were generally larger than for bilaterally absent SSEPs and for abnormal EEG findings. Conclusion: Prognostic accuracy of coma outcome improves with time after the onset of coma, being optimal on day 3. The overall diagnostic performance of absent pupillary response and motor responses (M1, M < 2, M < 3) are at least equal, if not superior, to that of bilaterally absent SSEPs or abnormal EEG findings throughout the first three days post-coma onset. SSEP studies are especially helpful when clinical signs are unreliable (e.g. in the presence of sedative medications or muscle relaxants). Of the markers examined, EEG is the least helpful in predicting coma outcome. doi:10.1016/j.jocn.2007.07.009
206: Isolated ataxia and infarction of the precentral knob Annabelle N. Sellbach, Andrew A. Wong, Richard S. Boyle; Department of Neurology, Princess Alexandra Hospital, Australia Introduction: We describe two cases of precentral knob infarction causing isolated upper limb ataxia. Functional imaging has localized motor hand activation to a part of the primary motor cortex known as the precentral knob. Several cases of hand weakness from small cortical infarcts of this region have been reported. Only two other case reports refer to isolated upper limb ataxia and infarction of the precentral knob. The mechanism for this remains unclear. Cases: Both patients presented acutely with signs suggestive of upper limb cerebellar ataxia (bilateral and right sided respectively). There were no motor or sensory deficits. MRI confirmed recent infarction of the precentral knobs bilaterally in patient 1 and on the contralateral side to the ataxia in patient 2 (See Fig. 1). There were no other lesions on MRI to explain the ataxia. Discussion: Ataxia caused by lesions distant to the cerebellum has been well established in the ataxic hemiparesis stroke syndrome. This is typically due to lacunar infarction of the pons, thalamus, internal capsule or corona radiata where corticopontocerebellar or dentatorubrothalamocortical pathways are thought to be interrupted. Cortical lesions in ataxic hemiparesis are rare and typically take the form of leg weakness with brachial ataxia. A recent single-photon emission computed tomography (SPECT) study has demonstrated the presence of crossed cerebellar diaschisis (CCD) in three patients with ataxic hemiparesis due to infarcts of the corona radiata. Whilst traditionally associated with large infarcts, emerging evidence suggests that infarct location rather than size or severity is critical for the development of CCD. The ataxia in our cases may represent direct interruption of corticopontocerebellar or dentatorubrothalamocortical pathways or indirect functional deafferentation and CCD.
Fig. 1. Axial FLAIR (A,C) and diffusion-weighted (B,D) MRI of patient 1 (A,B) and patient 2 (C,D) shearing precentral knob infarction.
Conclusion: We propose that the precentral knob localizes important cortico-cerebellar pathways and may be critical for the development of CCD.
doi:10.1016/j.jocn.2007.07.010
207: Myophosphorylase deficiency (McArdle disease): Clinical and laboratory features in seven cases Ferdinand Miteff, David Hutchinson; Auckland City Hospital, New Zealand Purpose: To demonstrate the typical clinical and laboratory features of myophosphorylase deficiency and review our experience with the molecular analysis of the PYGM gene. Methods: Hospital notes, laboratory results and muscle biopsies were reviewed. Patients were included if they had been seen by one of the authors (DH) and had myophosphorylase deficiency demonstrated by muscle histochemistry. Muscle biopsies were obtained under local anaesthesia and cryostat sections from flash-frozen muscle were examined histologically, which included myophosphorylase histochemistry. DNA was prepared from blood or frozen muscle by a guanidine thiocyanate method and 33 exons amplified by PCR. Results: Symptoms were present since early childhood in the seven patients and consisted of muscle discomfort provoked by moderate exercise, usually forcing patients