- Email: [email protected]
1-01-06 Proton magnetic resonance spectroscopy in patients with AIDS dementia: A longitudinal study
ALS & Related Disorders
s4
1l-01 -06 1 Proton magnetic resonance spectroscopy in patients with AIDS dementia: A longitudinal study B. Stankoff 1,2, A. Tourbah ‘t314, S. Suarez5, J.L. Stievenart3, L. Conqui5, 0. Rosenblum 5, E. Turell ’ , F. Bricaire !j, V. Calvez ‘, 0. Lyon-Caen ‘, EA. Cabanis3, C. Lubetzki 1,2. ’ FBderafion de Neurologie, 2/nserm U-734, Hopital de /a Sa/p&ri&re, Paris, 3Service de Neuroradiobgia, C.H.N.O. des Quinze-Vingts, Paris, 5Laboratoire de Neuropathologie et Association Claude Bemanl, B Service de Maladies Infectieuses, ‘Service de Virologie, 4 CJF Pathobgie de /a Myeline, Hcpital de /a Salp&triere, Paris, France AIDS associated cognitive changes are mainly reported in advanced HIV disease, and symptoms are dominated by attention and memory impairment. Neuropathological changes range from microglial nodules, gliosis, myelin alteration and neuronal suffering, but correlation between neuropathological features and clinical or virological status remains controversial. Furthermore, mechanisms underlying neuronal changes are not well understood since neuronal HIV infection has never been observed, neither in post-mortem examination, nor in in-vitro experimentation, and the existence of additional indirect mechanism of neurotoxicity has been put foreward. Proton magnetic resonance spectroscopy (1-H MRS) allows in vivo neurochemical study which may be correlated to pathological changes in the brain. It gives insight into early changes in patients with HIV encephalopathy. To determine the relationship between chemical pathological changes and clinical disability or virological status, we performed 1-H MRS longitudinal study in HIV patients with advanced disease. During the follow-up period, each patient had serial neurological and neuropsychological (quantified using the Mattis dementia rating scale) assessment, as well as standard MRI and 1-H MRS, blood and cerebra-spinal fluid HIV load measurement. Demented and non-demented patients were compared. Results will be presented and their relevance to earfy diagnosis and pathophysiological understanding of AIDS dementia will be discussed.
02
ALS & Related Disorders
muscle action potential (CMAP) and at least ten unitary muscle action potentials (uMAPs) of the abductor digiti minimi (ADM) and extensor digitorum brevis (EDB) muscles. We then averaged uMAPs digitally to obtain the mean uMAP. MUNEs were calculated by dividing the area of the negative portion of the CMAP area by that of the mean uMAP. MUNEs of ADM and EDB muscles in the headache patient group were 95 f 23 and 121 f 49, respectively, whereas those in the ALS patient group were 26 f 15 and 37 f 21, respectively (P -Z 0.005). We have concluded that our method can be appiied in a clinical setting as easily as in the basic research.
l-02-03
1 Expression of Bcl-2, Bax and ICH-1 L in ALS spinal cord motor neurons
T. Ekegren ‘, E. Grundstrom ‘, D. Lindholm 2, S.-M. Aquilonius’ ‘Department of Neurology Univekty Hospital, Uppsala, Sweden, 2 Department of Developmental Neuroscience, Biomedical Center Uppsala, Sweden The etiology of motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is still unknown, as well as the characteristics of the degenerative process. Recent studies suggest that programmed cell death (apoptosis) might be a mechanism behind the degeneration. Bcl-2, Bax and ICH-1L are a few of many factors that regulate the apoptotic pathway. Bcl-2 blocks apoptosis, while both Bax and ICH-1L induces apoptosis. The aim of this study was to compare expression of Bcl-2, Bax and ICH-IL in motor neurons in ALS- and control postmortal spinal cords. Spinal cord sections, thoracic level, from ALS cases and from non-neurological controls were treated immuno-histochemically wfth antibodies to choline acetyltransferase (ChAT) and to Bcl-2, Bax and ICH-IL. Some sections were stained with cresyl violet only. The secondary antibodies were labelled with fluorescent dyes and the treated sections examined in a confocal microscope. The results demonstrate significantly fewer cholinergic motor neurons in ALS spinal cords as compared to control sections. Bcl-2 was the least expressed factor in ALS motor neurons while it’s antagonist Bax was the most expressed factor. These apoptosis regulating factors were quite evenly expressed in the control group. ICH-1~ was equally expressed in both ALS- and control spinal cord motor neurons.
1 02 L-l
02
A new, reliable method to obtain motor unit number estimates and its application to patients with amyotrophic lateral sclerosis (ALS)
K. Arasaki, M. Tamaki. Tokyo, Japan
Department
of Neurolog)!
N77Kanto
Teishin Hospital,
Using our new, reliable method to obtain motor unit number estimates (MUNEs) (K. Arasaki et al., Muscle Nerve, in press), we obtained MUNEs in seven patients with ALS, who had been symptomatic for 11-13 months, and ten agematched patients with headaches. In each patient we stimulated the ulnar and peroneal nerves by needle electrodes and recorded the maximal compound
lateral sclerosis
Limoges database
Objective: Todevelop astandardized database of amyotrophic lateral sclerosis (ALS). Methods: This database was set up whose objectives were: to improve the follow-up of patients suffering from ALS; to ensure that all the data were recorded; to allow and facilitate large epidemiological studies. The database was developed on a micro-computer with Microsoft Access 2.0 (or 7.0), based on a relational model. For an easy use, it needs the following minimal system requirements: PC with 466 processor (66 MHz); 16 MO RAM. Results: The database includes 6 tables: identification; past medical history; onset of the disease; follow-up; clinical findings; biological findings; other paraclinical examinations; post-mortem findings. The links between the tables are based on an automatic number given by the software and on the dates of the follow-up examinations (for clinical, biological and other paraclinical examinations). Clinical findings include Norris, ALSFRS scales, and muscular testing. Data entry is facilitated by scrolling menus. Retrieval procedures and automatic generated graphs of clinical scales and respiratory function results were implemented. Confidentiality is ensured by a password. The easy use of this database allows data entry by non-medical personal. Conclusion: The use of this database by several ALS centers in France could improve the knowledge on natural history, prognostic factors and therapeutic follow-up in ALS.
l-02-04 1 l-02-01
Amyotrophic
P.M. Preux, H. Boutonnat, M. Druet-Cabanac, M. Dumas, J. M. Vallat, Ph. Couratier. Department of Neurology, institute of Neurobgical Epidemiology and Department of Biostatistics and Medical Informatics, University of Limoges, France
The clinical assessment
A. Goonetilleke, R.J. Guiloff, N. Nikhar, Hospital, London, UK
of muscle force
R.W. Orrell, S.V. Tan. Chafing
Cross
We study the accuracy, reliability and variability of the Medical Research Council (MRC) clinical muscle force’ scales, and provide guidelines for their use in natural history studies and therapeutic trials. Hand-held dynamometry was performed on 16 muscle groups in 75 normals and 43 motor neuron disease patients. The patients were also assessed using 6 and 6 graded traditional MRC scales; 12 of them were assessed by each of five neurologists. 4042 combined dynamometry and MRC grades assessments were analysed. Patients’ dynamometry readings were expressed as percentage force of sex and age matched controls. The MRC-estimate (MRCest) was defined as the mean % normal force corresponding to each MRC grade. Upper limb, lower limb and global composite scores formed with MRC grades, MRC estimates and dynamometry were compared. The normal controls showed a linear decline in force starting at the age of 40 in males and 50 in females. MRC grades O-3 in patients represented 10% total normal force; 44, 4 and 4+ represented 32.5, 60 and 60% of normal force respectively. lntra and interrater reliability of 6 and 6 graded scales was fair to good, with median kappa coefficients of over 0.23 (unweighted) or over 0.59 (weighted). Composite scores based on MRC grades overestimated force by 20-30% normal force, but those based on MRC estimates by only 5-10%. The latter were more accurate, less variable and had a linear relationship to dynamometry. The slopes of scores obtained by dynamometry were similar to those obtained using MRC grades and MRC estimates; when using change from baseline slopes, only those using MRC estimates for an 6 graded scale remained similar to dynamometry. Sample sizes for clinical trials were smallest with dynamometry derived composite scores expressed as change from baseline. For non-dynamometry scores they were smaller if using MRC estimates rather than MRC grades, and on an 6 rather than a 6 graded scale. The sample sizes when using multiple raters were minimised if serial assessments from individual patients were by the same rater throughout. Force scores and change from baseline slopes using traditional MRC grades are inaccurate and require large sample sizes; conversion to MRC estimates improve these. Optimal longitudinal assessments are obtained with a single rater, using composite scores derived from MRC estimates if dynamometry is not used. If multiple raters are used sample sizes can be minimised assessing individual patients by the same rater throughout.
s4
1l-01 -06 1 Proton magnetic resonance spectroscopy in patients with AIDS dementia: A longitudinal study B. Stankoff 1,2, A. Tourbah ‘t314, S. Suarez5, J.L. Stievenart3, L. Conqui5, 0. Rosenblum 5, E. Turell ’ , F. Bricaire !j, V. Calvez ‘, 0. Lyon-Caen ‘, EA. Cabanis3, C. Lubetzki 1,2. ’ FBderafion de Neurologie, 2/nserm U-734, Hopital de /a Sa/p&ri&re, Paris, 3Service de Neuroradiobgia, C.H.N.O. des Quinze-Vingts, Paris, 5Laboratoire de Neuropathologie et Association Claude Bemanl, B Service de Maladies Infectieuses, ‘Service de Virologie, 4 CJF Pathobgie de /a Myeline, Hcpital de /a Salp&triere, Paris, France AIDS associated cognitive changes are mainly reported in advanced HIV disease, and symptoms are dominated by attention and memory impairment. Neuropathological changes range from microglial nodules, gliosis, myelin alteration and neuronal suffering, but correlation between neuropathological features and clinical or virological status remains controversial. Furthermore, mechanisms underlying neuronal changes are not well understood since neuronal HIV infection has never been observed, neither in post-mortem examination, nor in in-vitro experimentation, and the existence of additional indirect mechanism of neurotoxicity has been put foreward. Proton magnetic resonance spectroscopy (1-H MRS) allows in vivo neurochemical study which may be correlated to pathological changes in the brain. It gives insight into early changes in patients with HIV encephalopathy. To determine the relationship between chemical pathological changes and clinical disability or virological status, we performed 1-H MRS longitudinal study in HIV patients with advanced disease. During the follow-up period, each patient had serial neurological and neuropsychological (quantified using the Mattis dementia rating scale) assessment, as well as standard MRI and 1-H MRS, blood and cerebra-spinal fluid HIV load measurement. Demented and non-demented patients were compared. Results will be presented and their relevance to earfy diagnosis and pathophysiological understanding of AIDS dementia will be discussed.
02
ALS & Related Disorders
muscle action potential (CMAP) and at least ten unitary muscle action potentials (uMAPs) of the abductor digiti minimi (ADM) and extensor digitorum brevis (EDB) muscles. We then averaged uMAPs digitally to obtain the mean uMAP. MUNEs were calculated by dividing the area of the negative portion of the CMAP area by that of the mean uMAP. MUNEs of ADM and EDB muscles in the headache patient group were 95 f 23 and 121 f 49, respectively, whereas those in the ALS patient group were 26 f 15 and 37 f 21, respectively (P -Z 0.005). We have concluded that our method can be appiied in a clinical setting as easily as in the basic research.
l-02-03
1 Expression of Bcl-2, Bax and ICH-1 L in ALS spinal cord motor neurons
T. Ekegren ‘, E. Grundstrom ‘, D. Lindholm 2, S.-M. Aquilonius’ ‘Department of Neurology Univekty Hospital, Uppsala, Sweden, 2 Department of Developmental Neuroscience, Biomedical Center Uppsala, Sweden The etiology of motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is still unknown, as well as the characteristics of the degenerative process. Recent studies suggest that programmed cell death (apoptosis) might be a mechanism behind the degeneration. Bcl-2, Bax and ICH-1L are a few of many factors that regulate the apoptotic pathway. Bcl-2 blocks apoptosis, while both Bax and ICH-1L induces apoptosis. The aim of this study was to compare expression of Bcl-2, Bax and ICH-IL in motor neurons in ALS- and control postmortal spinal cords. Spinal cord sections, thoracic level, from ALS cases and from non-neurological controls were treated immuno-histochemically wfth antibodies to choline acetyltransferase (ChAT) and to Bcl-2, Bax and ICH-IL. Some sections were stained with cresyl violet only. The secondary antibodies were labelled with fluorescent dyes and the treated sections examined in a confocal microscope. The results demonstrate significantly fewer cholinergic motor neurons in ALS spinal cords as compared to control sections. Bcl-2 was the least expressed factor in ALS motor neurons while it’s antagonist Bax was the most expressed factor. These apoptosis regulating factors were quite evenly expressed in the control group. ICH-1~ was equally expressed in both ALS- and control spinal cord motor neurons.
1 02 L-l
02
A new, reliable method to obtain motor unit number estimates and its application to patients with amyotrophic lateral sclerosis (ALS)
K. Arasaki, M. Tamaki. Tokyo, Japan
Department
of Neurolog)!
N77Kanto
Teishin Hospital,
Using our new, reliable method to obtain motor unit number estimates (MUNEs) (K. Arasaki et al., Muscle Nerve, in press), we obtained MUNEs in seven patients with ALS, who had been symptomatic for 11-13 months, and ten agematched patients with headaches. In each patient we stimulated the ulnar and peroneal nerves by needle electrodes and recorded the maximal compound
lateral sclerosis
Limoges database
Objective: Todevelop astandardized database of amyotrophic lateral sclerosis (ALS). Methods: This database was set up whose objectives were: to improve the follow-up of patients suffering from ALS; to ensure that all the data were recorded; to allow and facilitate large epidemiological studies. The database was developed on a micro-computer with Microsoft Access 2.0 (or 7.0), based on a relational model. For an easy use, it needs the following minimal system requirements: PC with 466 processor (66 MHz); 16 MO RAM. Results: The database includes 6 tables: identification; past medical history; onset of the disease; follow-up; clinical findings; biological findings; other paraclinical examinations; post-mortem findings. The links between the tables are based on an automatic number given by the software and on the dates of the follow-up examinations (for clinical, biological and other paraclinical examinations). Clinical findings include Norris, ALSFRS scales, and muscular testing. Data entry is facilitated by scrolling menus. Retrieval procedures and automatic generated graphs of clinical scales and respiratory function results were implemented. Confidentiality is ensured by a password. The easy use of this database allows data entry by non-medical personal. Conclusion: The use of this database by several ALS centers in France could improve the knowledge on natural history, prognostic factors and therapeutic follow-up in ALS.
l-02-04 1 l-02-01
Amyotrophic
P.M. Preux, H. Boutonnat, M. Druet-Cabanac, M. Dumas, J. M. Vallat, Ph. Couratier. Department of Neurology, institute of Neurobgical Epidemiology and Department of Biostatistics and Medical Informatics, University of Limoges, France
The clinical assessment
A. Goonetilleke, R.J. Guiloff, N. Nikhar, Hospital, London, UK
of muscle force
R.W. Orrell, S.V. Tan. Chafing
Cross
We study the accuracy, reliability and variability of the Medical Research Council (MRC) clinical muscle force’ scales, and provide guidelines for their use in natural history studies and therapeutic trials. Hand-held dynamometry was performed on 16 muscle groups in 75 normals and 43 motor neuron disease patients. The patients were also assessed using 6 and 6 graded traditional MRC scales; 12 of them were assessed by each of five neurologists. 4042 combined dynamometry and MRC grades assessments were analysed. Patients’ dynamometry readings were expressed as percentage force of sex and age matched controls. The MRC-estimate (MRCest) was defined as the mean % normal force corresponding to each MRC grade. Upper limb, lower limb and global composite scores formed with MRC grades, MRC estimates and dynamometry were compared. The normal controls showed a linear decline in force starting at the age of 40 in males and 50 in females. MRC grades O-3 in patients represented 10% total normal force; 44, 4 and 4+ represented 32.5, 60 and 60% of normal force respectively. lntra and interrater reliability of 6 and 6 graded scales was fair to good, with median kappa coefficients of over 0.23 (unweighted) or over 0.59 (weighted). Composite scores based on MRC grades overestimated force by 20-30% normal force, but those based on MRC estimates by only 5-10%. The latter were more accurate, less variable and had a linear relationship to dynamometry. The slopes of scores obtained by dynamometry were similar to those obtained using MRC grades and MRC estimates; when using change from baseline slopes, only those using MRC estimates for an 6 graded scale remained similar to dynamometry. Sample sizes for clinical trials were smallest with dynamometry derived composite scores expressed as change from baseline. For non-dynamometry scores they were smaller if using MRC estimates rather than MRC grades, and on an 6 rather than a 6 graded scale. The sample sizes when using multiple raters were minimised if serial assessments from individual patients were by the same rater throughout. Force scores and change from baseline slopes using traditional MRC grades are inaccurate and require large sample sizes; conversion to MRC estimates improve these. Optimal longitudinal assessments are obtained with a single rater, using composite scores derived from MRC estimates if dynamometry is not used. If multiple raters are used sample sizes can be minimised assessing individual patients by the same rater throughout.