Back
40: Muscle Nerve. 2006 Sep;34(3):359-60.
Inappropriate surgeries resulting from misdiagnosis of early amyotrophic lateral
sclerosis.
Srinivasan J, Scala S, Jones HR, Saleh F, Russell JA.
Department of Neurology, Lahey Clinic, 41 Mall Road, Burlington, Massachusetts
01805, USA. jayashri_srinivasan@lahey.org
Initial symptoms of amyotrophic lateral sclerosis (ALS) may mimic radiculopathy, myelopathy, mononeuropathy, or arthropathy. A retrospective review of 260 consecutive patients with ALS evaluated between 1996 and 2004 revealed that 55 (21%) had had surgery within the 5 years prior to ALS diagnosis. Thirty-four of these 55 (61%) had surgery for symptoms and signs that retrospectively were attributable to early manifestations of ALS. Misdiagnosis of early ALS may lead to unnecessary surgeries with their attendant potential complications.
PMID: 16609978 [PubMed - indexed for MEDLINE]
39: Adv Exp Med Biol. 2006;576:241-62; discussion 361-3.
N-acetylaspartate as a marker of neuronal injury in neurodegenerative disease.
Schuff N, Meyerhoff DJ, Mueller S, Chao L, Sacrey DT, Laxer K, Weiner MW.
Magnetic Resonance Unit VA Medical Center, Department of Radiology, University of California, San Francisco, CA 94121, USA.
Publication Types:
Review
PMID: 16802717 [PubMed - indexed for MEDLINE]
38: Adv Exp Med Biol. 2006;576:275-82; discussion 361-3.
Magnetic resonance spectroscopy for monitoring neuronal integrity in amyotrophic lateral sclerosis.
Kalra S, Arnold DL.
Division of Neurology, Department of Medicine, University of Alberta, 2E3.18 WMC, 8440-112 Street, Edmonton, Alberta, T6G 2B7, Canada. sanjay.kalra@ualberta.ca
Publication Types:
Review
PMID: 16802719 [PubMed - indexed for MEDLINE]
37: Exp Neurol. 2006 Sep;201(1):15-23. Epub 2006 Jun 27.
Comment on:
Exp Neurol. 2006 Jun;199(2):281-90.
Does excitotoxic cell death of motor neurons in ALS arise from glutamate transporter and glutamate receptor abnormalities?
Rattray M, Bendotti C.
King's College London, Wolfson Centre for Age-Related Diseases, Guy's HospitalCampus, London SE1 1UL, UK.
Publication Types:
Comment
Research Support, Non-U.S. Gov't
PMID: 16806177 [PubMed - indexed for MEDLINE]
36: Neurosci Lett. 2006 Sep 1;404(3):315-9. Epub 2006 Jun 27.
Expression of ubiquitin and proteasome in motorneurons and astrocytes of spinal cords from patients with amyotrophic lateral sclerosis.
Mendonca DM, Chimelli L, Martinez AM.
Departamento de Histologia e Embriologia, Instituto de Ciencias Biomedicas, Centro de Ciencias da Saude, Universidade Federal do Rio de Janeiro, Av. Brig. Trompowsky, s/n, Bl. F, 21941-540 Rio de Janeiro, RJ, Brasil.
Proteasome, ubiquitin, GFAP and neurofilament were evaluated in motorneurons and
astrocytes of spinal cords of ALS and control cases. ALS neurons exhibited ubiquitin positive inclusions and areas of strong immunoreaction for proteasome. Areas of proteasome stain were observed close to neurofilament positive proximal process enlargement. The percentage of neurons strongly immunoreacted, for proteasome was higher in ALS cases than in controls. Many astrocytes were positive for ubiquitin and proteasome. These results suggest that the ubiquitin-proteasome pathway is involved in the ALS pathogenesis and agree with the view that ALS is a disorder of protein aggregation that affects neurons and nonneuronal cells.
PMID: 16806703 [PubMed - indexed for MEDLINE]
35: Neurology. 2006 Sep 26;67(6):1074-7. Epub 2006 Jun 28.
ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).
Parkinson N, Ince PG, Smith MO, Highley R, Skibinski G, Andersen PM, Morrison KE, Pall HS, Hardiman O, Collinge J, Shaw PJ, Fisher EM; MRC Proteomics in ALS Study; FReJA Consortium.
MRC Prion Unit, Institute of Neurology, University College London, London, UK.
Mutation in the CHMP2B gene has been implicated in frontotemporal dementia. The authors screened CHMP2B in patients with ALS and several cohorts of control samples. They identified mutations (Q206H; I29V) in two patients with non-SOD1 ALS. Neuropathology of the Q206H case showed lower motor neuron predominant disease with ubiquitylated inclusions in motor neurons. Antibodies to p62 (sequestosome 1) showed novel oligodendroglial inclusions in the motor cortex.
Publication Types:
Case Reports
Comparative Study
Research Support, Non-U.S. Gov't
PMID: 16807408 [PubMed - indexed for MEDLINE]
34: Neurosci Lett. 2006 Sep 1;404(3):347-51. Epub 2006 Jul 3.
Erythropoietin in the cerebrospinal fluid in neurodegenerative diseases.
Brettschneider J, Widl K, Ehrenreich H, Riepe M, Tumani H.
Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
Erythropoietin (EPO) and its specific receptor (EPOR) have been proposed to act as an endogenous system protecting against neuronal injury and neurodegeneration. We measured EPO in cerebrospinal fluid (CSF) of patients with neurodegenerative diseases, and tested for a correlation with an established biomarker of neuro-axonal damage, tau protein. Patients with Alzheimer's disease (AD, N=40), vascular dementia (VD, N=19), frontotemporal lobe dementia (FTLD, N=5), ALS (N=30) and controls (N=49) were included. Cerebrospinal fluid and serum levels of EPO and tau were measured using ELISA techniques. We found CSF EPO in ALS to be lower than in controls (p=0.04), while no difference between patients with AD, VD, FTLD and controls was detectable. CSF EPO correlated with age (p<0.001) as well as with tau protein (p=0.002) in all patients pooled. In contrast to the upregulation of the EPO/EPOR system in brain tissue upon various
conditions of neuronal distress, CSF EPO concentrations in neurodegenerative disease were found in the same range or even reduced as compared to controls. This may be due to a relative deficiency of endogenous CNS EPO in these conditions and/or to a more efficient extraction of free EPO molecules from brain intercellular fluid by increased numbers of EPOR.
PMID: 16815630 [PubMed - indexed for MEDLINE]
33: Neuroscience. 2006 Sep 15;141(4):1879-86. Epub 2006 Jul 3.
Protective effect of metabotropic glutamate receptor inhibition on amyotrophic lateral sclerosis-cerebrospinal fluid toxicity in vitro.
Anneser JM, Chahli C, Borasio GD.
Department of Neurology, University of Munich, Klinikum Grosshadern, D-81366 Munchen, Germany. Johanna.Anneser@med.uni-muenchen.de
Conflicting results have been reported concerning the toxicity of cerebrospinal fluid from patients with amyotrophic lateral sclerosis (ALS-CSF) when added to neuronal cultures. The possible toxic factor(s) and the exact mode of action (e.g. requirement of glial cells) have not been identified so far. Glutamate is a potential candidate for this toxic effect, since antagonists of ionotropic glutamate receptors have been shown to attenuate ALS-CSF toxicity. We studied the effects of ALS-CSF on mixed and motoneuron-enriched chick embryonic spinal cord cultures. We found a toxic action of ALS-CSF in both culture types which could not be attenuated by 5 kDa-filtration or 15 min 90 degrees C heating. Nevertheless, the metabotropic glutamate receptor (mGluR) group I antagonist 1-aminoindan-1,5-dicarboxylic acid, but also the group I agonist (s)-3,5 dihydroxyphenylglycine (DHPG) exerted protective effects against ALS-CSF toxicity. In this experimental setting, DHPG may functionally act via a receptor blockade due to sustained activation. No protective effect was seen with the mGluR group III inhibitor (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG). Addition of DHPG did not increase the protective action of the AMPA inhibitor 6-chloro-4-hydroxyquinoline-2-carboxylic acid (6-CKU). Addition of l-glutamate did not mimic these toxic ALS-CSF effects in motoneuron-enriched cultures. Our experiments demonstrate that ALS-CSF toxicity is mediated by a small heat-resistant molecule which may act directly on neurons. Since blockade of group I mGluRs exerts a protective effect, the possibility of targeting these mGluRs pharmacologically in motoneuron disease should be kept in mind.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
PMID: 16820266 [PubMed - indexed for MEDLINE]
32: Neurology. 2006 Sep 12;67(5):771-6. Epub 2006 Jul 5.
Comment in:
Neurology. 2006 Sep 12;67(5):736-7.
Neurology. 2006 Sep 12;67(5):738-9.
Paraoxonase cluster polymorphisms are associated with sporadic ALS.
Saeed M, Siddique N, Hung WY, Usacheva E, Liu E, Sufit RL, Heller SL, Haines JL,
Pericak-Vance M, Siddique T.
Davee Department of Neurology and Clinical Neurosciences, Feinberg School of
Medicine, Northwestern University, Chicago, IL 60611, USA.
BACKGROUND: Paraoxonases (PONs) are involved in the detoxification of organophosphate pesticides and chemical nerve agents. Due to a reported possible twofold increased risk of ALS in Gulf War veterans and the associations of PON1 polymorphisms with the neurologic symptom complex of the Gulf War syndrome, the authors investigated the association between sporadic ALS (SALS) and PON gene
cluster variants in a large North American Caucasian family-based and case-control cohort (N = 1,891). METHODS: Clinically definite and probable ALS was diagnosed according to the revised El Escorial criteria, exclusion of family history of ALS, and SOD1 mutation analysis. Single nucleotide polymorphism (SNP) genotyping was done using TaqMan assays on ABI7900HT. Data were analyzed using SPSS, Haploview, FBAT, and THESIAS. RESULTS: A haploblock of high linkage disequilibrium (LD) spanning PON2 and PON3 was associated with SALS. The SNPs rs10487132 and rs11981433 were in strong LD and associated with SALS in the trio (parents-affected child triad) model. The association of rs10487132 was replicated in 450 nuclear pedigrees comprising trios and discordant sibpairs. No association was found in case-control models, and their haplostructure was different from that of the trios with overall reduced LD. Resequencing identified an intronic variant (rs17876088) that differentiated between
detrimental and protective SALS haplotypes. CONCLUSION: This study demonstrates evidence of significant association of variants in the Paraoxonase gene cluster with sporadic ALS and is compatible with the hypothesis that environmental toxicity in a susceptible host may precipitate ALS.
Publication Types:
Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16822964 [PubMed - indexed for MEDLINE]
31: Neurology. 2006 Sep 12;67(5):766-70. Epub 2006 Jul 5.
Comment in:
Neurology. 2006 Sep 12;67(5):738-9.
Paraoxonase gene polymorphisms and sporadic ALS.
Slowik A, Tomik B, Wolkow PP, Partyka D, Turaj W, Malecki MT, Pera J, Dziedzic T, Szczudlik A, Figlewicz DA.
Department of Neurology, Jagiellonian University, Botaniczna 3, 31-503 Krakow, Poland. slowik@cm-uj.krakow.pl
BACKGROUND: The human paraoxonase (PON) gene family consists of three members, PON1, PON2, and PON3, located adjacent to each other on chromosome 7. PON catalytic activity may be influenced by frequent amino acid variants. Chronic exposure to certain chemicals or to environmental factors causing enhanced lipid peroxidation metabolized by paraoxonases may be a risk factor for sporadic ALS (sALS). OBJECTIVE: The aim of this study was to examine the association between PON1 Q192R, PON1 L55M, and PON2 C311S functional polymorphisms and the risk of sALS in a Polish population. METHODS: The authors included 185 patients with a definite or probable diagnosis of sALS (El Escorial Criteria) and 437 healthy controls of similar age and gender. The paraoxonase polymorphisms were studied by PCR and restriction enzyme digestion. RESULTS: Using logistic regression analyses, the C allele of the C311S polymorphism was associated with sALS in dominant and additive models, whereas the R allele of the Q192R polymorphism was associated with sALS in recessive, additive, and dominant models. The authors compared the distribution of haplotypes between cases and controls. The R-C haplotype was overrepresented among cases (odds ratio 3.44, 95% CI: 1.55 to
7.62, p = 0.002). CONCLUSIONS: Frequent amino acid variants in the paraoxonase 1
and paraoxonase 2 genes are associated with sporadic ALS in a Polish population.
Publication Types:
Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16822965 [PubMed - indexed for MEDLINE]
30: Neurobiol Dis. 2006 Sep;23(3):697-707. Epub 2006 Jul 11.
Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis.
Holzbaur EL, Howland DS, Weber N, Wallace K, She Y, Kwak S, Tchistiakova LA, Murphy E, Hinson J, Karim R, Tan XY, Kelley P, McGill KC, Williams G, Hobbs C, Doherty P, Zaleska MM, Pangalos MN, Walsh FS.
Department of Physiology, University of Pennsylvania School of Medicine, D400 Richards Building, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA. holzbaur@mail.med.upenn.edu
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease leading to motor neuron cell death, but recent studies suggest that non-neuronal cells may contribute to the pathological mechanisms involved. Myostatin is a negative regulator of muscle growth whose function can be inhibited using neutralizing antibodies. In this study, we used transgenic mouse and rat models
of ALS to test whether treatment with anti-myostatin antibody slows muscle atrophy, motor neuron loss, or disease onset and progression. Significant increases in muscle mass and strength were observed in
myostatin-antibody-treated SOD1(G93A) mice and rats prior to disease onset and during early-stage disease. By late stage disease, only diaphragm muscle remained significantly different in treated animals in comparison to untreated controls. Myostatin inhibition did not delay disease onset nor extend survival in either the SOD1(G93A) mouse or rat. Together, these results indicate that inhibition of myostatin does not protect against the onset and progression of motor neuron degenerative disease. However, the preservation of skeletal muscle during early-stage disease and improved diaphragm morphology and function maintained through late stage disease suggest that anti-myostatin therapy may promote some improved muscle function in ALS.
PMID: 16837207 [PubMed - indexed for MEDLINE]
29: Neurobiol Dis. 2006 Sep;23(3):578-86. Epub 2006 Jul 20.
Allele-specific RNAi selectively silences mutant SOD1 and achieves significant therapeutic benefit in vivo.
Xia X, Zhou H, Huang Y, Xu Z.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, 817 LRB, Worcester, MA 01605, USA. xugang.xia@umassmed.edu
RNA interference (RNAi) has the potential to treat diseases caused by dominant, gain-of-function type of gene mutations. In these diseases, one allele is mutated and produces a toxic protein, whereas the other allele is normal and performs vital functions. One challenge in the treatment is to specifically inhibit the mutant allele toxicity while maintaining the normal allele function. To test allele-specific silencing in vivo, we made transgenic mice that express an shRNA against mutant Cu, Zn superoxide dismutase gene (SOD1(G93A)), which causes amyotrophic lateral sclerosis (ALS) by a gain of an unknown toxic property. By crossing this transgenic line with mice that express SOD1(G93A) and mice that express wild-type human SOD1, we found that this shRNA specifically silences the mutant, but not the wild-type SOD1. The silencing of the mutant
significantly delayed ALS onset and extended survival. Thus, RNAi can achieve allele-specific silencing and therapeutic benefit in vivo.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16857362 [PubMed - indexed for MEDLINE]
28: Augment Altern Commun. 2006 Sep;22(3):209-21.
Purposes of AAC device use for persons with ALS as reported by caregivers.
Fried-Oken M, Fox L, Rau MT, Tullman J, Baker G, Hindal M, Wile N, Lou JS.
Oregon Health & Science University, Oregon Institute on Disability and
Development, P.O. Box 574, Portland, OR 97207, USA. friedm@ohsu.edu
Thirty-four informal caregivers who support 26 persons with ALS reported on AAC technology use. Each caregiver completed the Communication Device Use Checklist, a survey tool developed for this study based on Light's (1988) classification of the purposes of social interaction (Augmentative and Alternative Communication, 4, 66-82). The checklist includes 17 purposes of communication and asks participants to judge importance, mode, and frequency of use for each purpose. Results show that the three communication purposes used most frequently and valued as important by caregivers involve regulating the behavior of others for basic needs and wants (getting needs met; giving instructions or directions to others; and clarifying needs). Consistent reports of use and frequency for the purposes of staying connected (social closeness) and discussing important issues (information transfer) indicate that AAC technology can assist the dyad in maintaining previous relationships. The face-to-face spontaneous conversation mode is used most frequently, despite the slow rate of production, the lack of permanence, and the demands on conversational partners during message generation. Clinical and research implications are discussed.
Publication Types:
Research Support, N.I.H., Extramural
PMID: 17114164 [PubMed - indexed for MEDLINE]
27: No To Shinkei. 2006 Sep;58(9):779-84.
[Amyotrophic lateral sclerosis associated with extrapyramidal symptoms or signs]
[Article in Japanese]
Hama K, Kihira T, Okawa M, Kajimoto Y, Hiwatani Y, Morita S, Nakanishi I, Miwa
H, Kondo T.
Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama
641 8510, Japan.
This investigation was conducted to clarify the frequency and characteristics of
ALS associated with extrapyramidal symptoms or signs in Wakayama prefecture. The
questionnaires to survey ALS cases were mailed to all medical centers in
Wakayama prefecture. A total of 252 cases were found to have motor neuron
diseases. Among them, 204 cases fulfilled probable or definite according to El
Escorial Criteria. In 10 of them, extrapyramidal signs were identified as follows: rigidity 50%, tremor 40% and akinesia 10%. Family history of ALS in these cases (20%) is higher than expected in usual ALS, and all of them are negative for SOD-1 mutation. Dementia and autonomic nervous symptoms were observed in several cases. Incidence of extrapyramidal signs in ALS resulted in 4.8%. The incidence of extrapyramidal signs is more frequent than expected by chance, suggesting that the degeneration of basal ganglia and/or substantia nigra may not be so rare in ALS.
Publication Types:
Case Reports
English Abstract
PMID: 17052005 [PubMed - indexed for MEDLINE]
26: Int J Immunopathol Pharmacol. 2006 Jul-Sep;19(3):489-98.
A study of the purine derivative AIT-082 in G93A SOD1 transgenic mice.
Jiang F, Li WP, Kwiecien J, Turnbull J.
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
AIT-082 is a purine derivative with neuroprotective and neurotrophic activity that is desirable in a candidate therapy for Amyotrophic Lateral Sclerosis. Consequently, we investigated the effect of AIT-082 in a transgenic mouse model of ALS. AIT-082 (0, 1, 3, 10, 30, 60, 100 mg/kg) was given to TgN(SOD1-G93A)1Gur transgenic mice from age 30 days until death. The age at onset of clinical signs of disease and the age at death were recorded for each animal. Disease progression was measured by the weekly average distance run in a running wheel. Analysis was made by the Kaplan Meier method with log rank statistics, log rank for trend and Cox regression. Neuropathological study of the brain, spinal cord, muscles and other organs was undertaken at death. In a second experiment we studied the effect of AIT-082 (30 mg/kg) at the onset of disease and during survival of transgenic G93A SOD1 mice, beginning dosing at different ages (20, 30, 40, 60, 80 days). Disease onset was mildly earlier (i.e. worse) at 1 and 10 mg/kg AIT-082 and mildly delayed at 30 mg/kg. This improvement did not reach the usual statistical significance. There was no difference in the age at death for any treatment dose. There was no difference in the neuropathology of treated and untreated G93A mice. However, there was an early improvement in the running wheel function at all tested doses. Using Cox regression, after adjustment for sex, the mice in the running wheels had slightly delayed onset of disease without change in survival and, after adjustment for exercise, the female mice had slightly improved survival. Consequently, AIT-082 would not be an attractive candidate for ALS clinical trials as monotherapy and justification for its use in combination therapy would require additional laboratory support. There was dissociation between the endpoints of disease progression (as judged by running wheel performance) and disease onset and survival. AIT-082 improved early running wheel performance yet led to accelerated late decline and had no impact on survival. It is possible that the drug facilitates early sprouting that leads to accelerated late decline.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 17026833 [PubMed - indexed for MEDLINE]
25: Curr Alzheimer Res. 2006 Sep;3(4):397-401.
A commentary on neuronal degeneration and cell death in Guam ALS and PD: an
evolutionary process of understanding.
Garruto RM.
Laboratory of Biomedical Anthropology and Neurosciences, State University of New
York at Binghamton, Binghamton, New York 13902-6000, USA.
rgarruto@binghamton.edu
The Twentieth Century witnessed tremendous advances in our understanding of
neurodegenerative diseases. Not least among them were the contributions from
hyperendemic foci of neurodegenerative disorders in isolated human groups
worldwide, with the knowledge gained applicable to our understanding of related
neurodegenerative diseases globally.
Publication Types:
Review
PMID: 17017870 [PubMed - indexed for MEDLINE]
24: Neurology. 2006 Sep 26;67(6):1078-9.
The challenge of diagnosing ALS in patients with prior poliomyelitis.
Salajegheh M, Bryan WW, Dalakas MC.
NDS/NINDS/NIH, Bethesda, MD 20892, USA.
Four patients with postpolio syndrome (PPS) developed ALS. Weakness and atrophy
started from previously unaffected extremities but, contrary to PPS, spread to
all muscles leading to death within 0.4 to 8 (mean 3.9) years. Upper motor
neuron signs were absent in the atrophic limbs. Abundant spontaneous activity
and group atrophy in newly affected muscles were prominent. ALS can rarely occur
in the postpolio population starting de novo rather than as evolution of PPS.
Publication Types:
Comparative Study
Research Support, N.I.H., Intramural
PMID: 17000983 [PubMed - indexed for MEDLINE]
23: Neurology. 2006 Sep 26;67(6):991-7.
High-frequency chest wall oscillation in ALS: an exploratory randomized,
controlled trial.
Lange DJ, Lechtzin N, Davey C, David W, Heiman-Patterson T, Gelinas D, Becker B,
Mitsumoto H; HFCWO Study Group.
Department of Neurology, Mt. Sinai School of Medicine, One Gustave L. Levy
Place, Box 1052, New York, NY 10029, USA. dale.lange@mssm.edu
OBJECTIVES: To evaluate changes in respiratory function in patients with ALS after using high-frequency chest wall oscillation (HFCWO). METHODS: This was a 12-week randomized, controlled trial of HFCWO in patients with probable or definite ALS, an Amyotrophic Lateral Sclerosis Functional Rating Scale
respiratory subscale score < or = 11 and > or = 5, and forced vital capacity (FVC) > or = 40% predicted. RESULTS: We enrolled 46 patients (58.0 +/- 9.8 years; 21 men, 25 women); 22 used HFCWO and 24 were untreated. Thirty-five completed the trial: 19 used HFCWO and 16 untreated. HFCWO users had less breathlessness (p = 0.021) and coughed more at night (p = 0.048) at 12 weeks compared to baseline. At 12 weeks, HFCWO users reported a decline in breathlessness (p = 0.048); nonusers reported more noise when breathing (p = 0.027). There were no significant differences in FVC change, peak expiratory flow, capnography, oxygen saturation, fatigue, or transitional dyspnea index.
When patients with FVC between 40 and 70% predicted were analyzed, FVC showed a significant mean decrease in untreated patients but not in HFCWO patients; HFCWO patients had significantly less increased fatigue and breathlessness. Satisfaction with HFCWO was 79%. CONCLUSION: High-frequency chest wall oscillation was well tolerated, considered helpful by a majority of patients,
and decreased symptoms of breathlessness. In patients with impaired breathing, high-frequency chest wall oscillation decreased fatigue and showed a trend toward slowing the decline of forced vital capacity.
Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
PMID: 17000967 [PubMed - indexed for MEDLINE]
22: Science. 2006 Sep 22;313(5794):1737.
Comment in:
Science. 2006 Nov 24;314(5803):1242.
Comment on:
Science. 2006 Jul 28;313(5786):428-31.
Debating the cause of a neurological disorder.
Duncan MW, Marini AM.
Publication Types: Comment, Letter.
PMID: 16990532 [PubMed - indexed for MEDLINE]
21: Neurology. 2006 Sep 12;67(5):902-4.
Caregiver time use in ALS.
Chio A, Gauthier A, Vignola A, Calvo A, Ghiglione P, Cavallo E, Terreni AA,
Mutani R.
Department of Neuroscience, University of Turin, Torino, Italy. achio@usa.net
The authors evaluated the caregiver time for 70 patients with ALS. The mean number of caregivers per patient was 2.0 (SD 1.3). Caregiver time increased with worsening of disability (p = 0.0001). The most time-consuming duties were housekeeping, feeding, and toileting. With worsening of patients' disability, families relied increasingly on paid caregivers. Caregiver time is a hidden cost of ALS care and is a major burden for caregivers.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
PMID: 16966565 [PubMed - indexed for MEDLINE]
20: Neurology. 2006 Sep 12;67(5):777-80.
Trends in hospital utilization and outcome for patients with ALS: analysis of a
large U.S. cohort.
Dubinsky R, Chen J, Lai SM.
Department of Neurology, University of Kansas Medical Center, Mail Stop 2012,
3599 Rainbow Blvd., Kansas City, KS 66160, USA. rdubinsky@safetyresearch.com
OBJECTIVE: To examine hospital mortality, utilization, and trends in care of
patients with ALS in a large U.S. cohort. METHODS: The authors performed a
retrospective cohort comparison, using the Nationwide Inpatient Sample for 1988
to 2002. They identified admissions, comorbidities, and procedures using ICD-9
codes. Outcomes included reason for admission, cost (adjusted to 2002 dollars),
length of stay, discharge disposition, and utilization of hospice care.
Significance was set a priori at p < 0.001. RESULTS: They identified 17,249
records. The significant findings were that common morbidities increased over
time (pneumonia [38.1% to 47.3%], respiratory failure [26.9% to 35.5%], and
nutritional deficiency [43.0% to 56.3%]); the median length of stay dropped from
6 to 4 days; mean hospital charges increased from 21,574 dollars to 24,314
dollars; the proportion of hospital deaths decreased over time (17.6% to 14.6%),
whereas the proportion discharged to home health/hospice care (14.0% to 18.2%)
and to long-term care facilities (13.2% to 27.9%) increased. The odds ratio (OR)
of death was 5.03 (95% CI: 4.57 to 5.54) for those admitted with respiratory
failure, 1.36 (1.24 to 1.50) for those with pneumonia, and 0.84 (0.77 to 0.92)
for those with nutritional deficiency. CONCLUSION: The high OR of death in
patients admitted for pneumonia or respiratory failure is likely associated with
more advanced disease, whereas the protective effect of admission for
nutritional deficiency is consistent with the predominance of bulbar symptoms
and admission earlier in the disease. The trends during the 15 years of this
administrative data set were for increasing comorbidities and higher utilization
of end-of-life care.
Publication Types:
Comparative Study
PMID: 16966536 [PubMed - indexed for MEDLINE]
19: Neurology. 2006 Sep 12;67(5):738-9.
Comment on:
Neurology. 2006 Sep 12;67(5):766-70.
Neurology. 2006 Sep 12;67(5):771-6.
Susceptibility genes in sporadic ALS: separating the wheat from the chaff by
international collaboration.
Shaw CE, Al-Chalabi A.
Publication Types:
Comment
Editorial
PMID: 16966531 [PubMed - indexed for MEDLINE]
18: Neurology. 2006 Sep 12;67(5):736-7.
Comment on:
Neurology. 2006 Sep 12;67(5):771-6.
NIPPV: a treatment for ALS whose time has come.
Heiman-Patterson TD, Miller RG.
Publication Types:
Comment
Editorial
PMID: 16966530 [PubMed - indexed for MEDLINE]
17: Amyotroph Lateral Scler. 2006 Sep;7(3):183-6.
ALS: cytokine profile in cerebrospinal fluid T-cell clones.
Holmoy T, Roos PM, Kvale EO.
Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway.
trygve.holmoy@medisin.uio.no
T -cells are present in the spinal cord from patients with amyotrophic lateral
sclerosis (ALS), and could attack neurons or activate microglia through
secretion of cytokines. We report that interferon (IFN)-gamma, tumour necrosis
factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5 and IL-10 could not be
detected in cerebrospinal fluid (CSF) samples from 15 ALS patients and 23 out of
25 controls with a multiplexed cytometric bead assay. In vivo activated T-cell
clones were established from CSF (n = 26) and blood (n = 21) of one ALS patient.
The proliferative capacity of CSF T-cell clones was lower than that of T-cell
clones from blood (p = 0.0007). All CD4+ CSF T-cell clones produced IFN-gamma,
compatible with a predominant T helper (h) 1 phenotype, but several T-cell
clones also produced Th2 cytokines. These data suggest that in vivo activated
intrathecal T-cells can be induced to secrete cytokines which may play a role in
ALS.
Publication Types:
Comparative Study
PMID: 16963408 [PubMed - indexed for MEDLINE]
16: Amyotroph Lateral Scler. 2006 Sep;7(3):173-82.
Analysis of factors that modify susceptibility and rate of progression in
amyotrophic lateral sclerosis (ALS).
Qureshi MM, Hayden D, Urbinelli L, Ferrante K, Newhall K, Myers D, Hilgenberg S,
Smart R, Brown RH, Cudkowicz ME.
Neurology Clinical Trials Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA.
We conducted case-control and prospective longitudinal studies to examine risk
factors and predictors of disease progression for ALS. Ninety-five subjects with
ALS and 106 healthy control subjects were enrolled. All subjects completed a
risk factor questionnaire at enrollment. The ALS subjects were prospectively
followed for one year to define factors that influence the rate of disease
progression, measured by rate of change in percent predicted forced vital
capacity (%FVC) and the ALS functional rating scale (ALSFRS) score. The
association of each potential risk factor with ALS was determined using
univariate logistic regression. A random slope model was used to determine the
association of each risk factor with disease progression. The demographic
characteristics of ALS subjects and controls at enrollment did not differ.
Significant risk factors for ALS included reported exposure to lead (p = 0.02)
and pesticides (p = 0.03). Disease progression was faster in the ALS subjects
having bulbar onset and a shorter time period between onset of symptoms and
diagnosis. Pertinent variables not associated with either causation or
progression of ALS included physical activity, cigarette smoking and a history
of physical trauma or other clinical disorders.
Publication Types:
Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16963407 [PubMed - indexed for MEDLINE]
15: Amyotroph Lateral Scler. 2006 Sep;7(3):167-72.
Measurement of decline of functioning in persons with amyotrophic lateral
sclerosis: responsiveness and possible applications of the Functional
Independence Measure, Barthel Index, Rehabilitation Activities Profile and
Frenchay Activities Index.
De Groot IJ, Post MW, Van Heuveln T, Van Den Berg LH, Lindeman E.
Rehabilitation Centre, De Hoogstraat, Utrecht, The Netherlands.
It is important not only to monitor the functional change during the course of
ALS, but also to determine whether or not the available help is sufficient. This
study was performed to determine which generic assessment instrument is most
appropriate. A multicentre cohort of patients with ALS was followed for one
year. At baseline, six months, and 1 year four instruments were used: Functional
Independence Measure (FIM), Rehabilitation Activities Profile (RAP), Barthel
Index (BI), and Frenchay Activities Index (FAI). The responsiveness of the
measures was examined using effect sizes and standardized response mean
statistics. Seventy-three patients at baseline, 63 after six months and 43 after
one year were assessed. If calculated on the group that completed all three
assessments, the FIM, BI, and RAP showed moderate effect sizes and standardized
response means over a period of six months and large effect sizes over 12
months. Based on their responsiveness FIM, BI, and RAP can be used to evaluate
limitations in activities and care needs of persons with ALS and to evaluate
treatment results in trials. The FIM was the most responsive instrument,
although the BI might be easier to use in clinical practice.
Publication Types:
Comparative Study
Multicenter Study
PMID: 16963406 [PubMed - indexed for MEDLINE]
14: Amyotroph Lateral Scler. 2006 Sep;7(3):142-9.
Clinical phenotypes of a large Chinese multigenerational kindred with autosomal
dominant familial ALS due to Ile149Thr SOD1 gene mutation.
Fong GC, Kwok KH, Song YQ, Cheng TS, Ho PW, Chu AC, Kung MH, Chan KH, Mak W,
Cheung RT, Ramsden DB, Ho SL.
Division of Neurology, University Department of Medicine, University of Hong
Kong, Hong Kong.
About 10% of amyotrophic lateral sclerosis (ALS) cases are familial. We identified a five-generation Chinese family with autosomal dominant familial ALS (FALS). We performed a detailed family study, clinical and electromyographic validation, and SOD1, VEGF and CNTF mutation analyses. Forty-five living members (16 affected) were studied and DNA samples collected. Genealogical data were collected for deceased members. Based on the duration between symptom onset to ventilator dependence, they were divided into rapidly progressive (range 1-18 months, mean (SD) duration = 12.08 (+/-6.10) months, mean (SD) age of symptom onset = 39.75 (+/-9.84) years) and slowly progressive groups (>18 months; mean (SD) age of onset = 37.25 (+/-5.32) years old). We identified a heterozygous mutation of ATT to ACT of SOD1 gene at codon 149 in exon 5 resulting in
substitution of isoleucine to threonine. It co-segregated with all affected members and 11 non-symptomatic members. We report a large multigenerational Chinese FALS kindred with I149T mutation in SOD1. No polymorphisms or mutations were found to date in two known modifier genes, namely, VEGF and CNTF, which were associated with heterogeneity in the phenotype within this kindred. Follow-up of the family will be helpful to explore any potential disease markers.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
PMID: 16963403 [PubMed - indexed for MEDLINE]
13: Amyotroph Lateral Scler. 2006 Sep;7(3):132-41.
Comment in:
Amyotroph Lateral Scler. 2006 Sep;7(3):131.
A Review: carers, MND and service provision.
Mockford C, Jenkinson C, Fitzpatrick R.
Health Services Research Unit, Department of Public Health, University of
Oxford, UK.
Carers of people with MND may experience changes to their health and lifestyle.
Statutory and voluntary organizations are able to support the carer in various ways. This review investigates the personal impact on carers and their experiences of service provision. A systematic search of online and grey literature was made for the period 1994-2004. Thirty-two key texts were retrieved and a narrative synthesis conducted. The main themes were: 1) Impact on carer: general health, emotional state, life satisfaction, socio-economic concerns, relationships, and protective factors; 2) Experience of service
provision: primary care, health professionals, social care, written information, and voluntary organizations. There is a paucity of written documentation on the experience of assisting someone with MND. Data collected are diverse and sometimes contradictory. Sample sizes are often small and generalization difficult. Main findings show that maintenance of social support, activities, and a positive outlook may lessen the chance of ill health arising from long hours spent caring, and having a named coordinator may assist with access to resources, and provide practical and emotional support during and after the caring role. Carers may become ill themselves unless adequate support is given
to them throughout the course of the disease.
Publication Types:
Review
PMID: 16963402 [PubMed - indexed for MEDLINE]
12: Amyotroph Lateral Scler. 2006 Sep;7(3):131.
Comment on:
Amyotroph Lateral Scler. 2006 Sep;7(3):132-41.
Who cares for the carers?
Armon C.
Publication Types:
Comment
Editorial
PMID: 16963401 [PubMed - indexed for MEDLINE]
11: J Neurosci. 2006 Sep 6;26(36):9250-63.
Erratum in:
J Neurosci. 2006 Oct 4;26(40):10079. Russell, David.
Protecting motor neurons from toxic insult by antagonism of adenosine A2a and Trk receptors.
Mojsilovic-Petrovic J, Jeong GB, Crocker A, Arneja A, David S, Russell DS, Kalb RG.
Department of Neurology, Children's Hospital of Philadelphia, Joseph Stokes Jr.
Research Institute, Philadelphia, Pennsylvania 19104, USA.
The death of motor neurons in amyotrophic lateral sclerosis (ALS) is thought to result from the interaction of a variety of factors including excitotoxicity, accumulation of toxic proteins, and abnormal axonal transport. Previously, we found that the susceptibility of motor neurons to excitotoxic insults can be
limited by inhibiting signals evoked by brain-derived neurotrophic factor (BDNF) activation of the receptor tyrosine kinase B (TrkB). Here we show that this can be achieved by direct kinase inhibition or by blockade of a transactivation pathway that uses adenosine A2a receptors and src-family kinases (SFKs).
Downstream signaling cascades (such as mitogen-activated protein kinase and phosphatidylinositol-3 kinase) are inhibited by these blockers. In addition to protecting motor neurons from excitotoxic insult, these agents also prevent toxicity that follows from the expression of mutant proteins (G85R superoxide
dismutase 1; G59S p150(glued)) that cause familial motor neuron disease. TrkB, adenosine A2a receptors, and SFKs associate into complexes in lipid raft and nonlipid raft membranes and the signaling from lipids rafts may be particularly important because their disruption by cholesterol depletion blocks the ability of BDNF to render motor neurons vulnerable to insult. The neuroprotective versatility of Trk antagonism suggests that it may have broad utility in the treatment of ALS patients.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16957081 [PubMed - indexed for MEDLINE]
10: Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13860-5. Epub 2006 Aug 30.
Familial ALS-superoxide dismutases associate with mitochondria and shift their
redox potentials.
Ferri A, Cozzolino M, Crosio C, Nencini M, Casciati A, Gralla EB, Rotilio G,
Valentine JS, Carri MT.
Institute of Neuroscience, Department of Psychobiology and Psychopharmacology,
Consiglio Nazionale delle Ricerche, 00100 Rome, Italy.
Recent studies suggest that the toxicity of familial amyotrophic lateral
sclerosis mutant Cu, Zn superoxide dismutase (SOD1) arises from its selective
recruitment to mitochondria. Here we demonstrate that each of 12 different
familial ALS-mutant SOD1s with widely differing biophysical properties are
associated with mitochondria of motoneuronal cells to a much greater extent than
wild-type SOD1, and that this effect may depend on the oxidation of Cys
residues. We demonstrate further that mutant SOD1 proteins associated with the
mitochondria tend to form cross-linked oligomers and that their presence causes
a shift in the redox state of these organelles and results in impairment of
respiratory complexes. The observation that such a diverse set of mutant SOD1
proteins behave so similarly in mitochondria of motoneuronal cells and so
differently from wild-type SOD1 suggests that this behavior may explain the
toxicity of ALS-mutant SOD1 proteins, which causes motor neurons to die.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16945901 [PubMed - indexed for MEDLINE]
9: J Proteome Res. 2006 Sep;5(9):2364-71.
Focused proteomics in post-mortem human spinal cord.
Ekegren T, Hanrieder J, Aquilonius SM, Bergquist J.
Department of Physical and Analytical Chemistry, Analytical Chemistry, Uppsala
University, Uppsala, Sweden.
With a highly sensitive electrospray ionization-Fourier transform ion cyclotron
resonance mass spectrometry (ESI-FTICR MS) system, proteins were identified in
minimal amounts of spinal cord from patients with the neurodegenerative disease
amyotrophic lateral sclerosis (ALS) and compared to proteins in spinal cord from
control subjects. The results show 18 versus 16 significantly identified (p < 0.05) proteins, respectively, all known to be found in the central nervous system. The most abundant protein in both groups was the glial fibrillary acidic protein, GFAP. Other proteins were, for example, hemoglobin alpha- and beta chain, myelin basic protein, thioredoxin, alpha enolase, and choline acetyltransferase. This study also includes the technique of laser
microdissection in combination with pressure catapulting (LMPC) for the dissection of samples and specific neurons. Furthermore, complementary experiments with nanoLC-matrix assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS) confirmed the results of the ESI-FTICR MS screening and provided additional results of further identified proteins.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
PMID: 16944948 [PubMed - indexed for MEDLINE]
8: Neurol India. 2006 Sep;54(3):304-5.
Familial amyotrophic lateral sclerosis: first report from India.
Nalini A, Yeshraj G, Veerendrakumar M.
Department of Neurology, National Institute of Mental Health and Neurosciences,
Bangalore, India. nalini@nimhans.kar.nic.in
We report two patients diagnosed to have familial amyotrophic lateral sclerosis
(FALS). A 40 year old lady had progressive weakness and atrophy of the limbs and
bulbar palsy from the age of 39 years and with electrophysiological evaluation
was confirmed as definite ALS. Her mother had presented in 1978 at the age of 42
years with symptoms and signs of ALS. The other patient was a 43 year old male
with rapidly progressive weakness, wasting and spasticity of the limbs and
bulbar palsy of 4 months duration and with electrophysiological evidence of
diffuse anterior horn cell involvement. His father also had onset of illness at
43 years of age with gradually progressive spasticity and atrophy of the
extremities followed by bulbar palsy. In the first instance the mother had a
duration of illness of 8 years while in the second the father lived for 15 years
after the onset of illness.
Publication Types:
Case Reports
PMID: 16936397 [PubMed - indexed for MEDLINE]
7: Nat Clin Pract Neurol. 2006 Sep;2(9):462-3.
Amyotrophic lateral sclerosis and gene therapy.
Miller TM, Smith RA, Cleveland DW.
Department of Neurosciences, Ludwig Institute for Cancer Research, University of
California, San Diego, La Jolla, CA 92093-0670, USA.
Publication Types:
Review
PMID: 16932606 [PubMed - indexed for MEDLINE]
6: Curr Neurol Neurosci Rep. 2006 Sep;6(5):423-31.
Genetics of motor neuron disease.
Van Den Bosch L, Timmerman V.
Neurobiology, Campus Gasthuisberg O&N2 PB1022,Herestraat 49, B-3000 Leuven,
Belgium. ludo.vandenbosch@med.kuleuven.be
The number of genes associated with motor neuron degeneration has increased considerably over the past few years. As more gene mutations are identified, the
hope arises that certain common themes and/or pathways become clear. In this overview, we focus on recent discoveries related to amyotrophic lateral sclerosis (ALS), spinal muscular atrophies (SMA), and distal hereditary motor neuropathies (dHMN). It is striking that many of the mutated genes that were linked to these diseases encode proteins that are either directly or indirectly involved in axonal transport or play a role in RNA metabolism. We hypothesize that both phenomena are not only crucial for the normal functioning of motor neurons, but that they could also be interconnected. In analogy with the situation after acute stress, axonal mRNA translation followed by retrograde
transport of the signal back to the nucleus could play an important role in chronic motor neuron diseases. We hope that information on the genetic causes of these diseases and the insight into the pathologic processes involved could ultimately lead to therapeutic strategies that prevent or at least slow this degenerative process.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 16928353 [PubMed - indexed for MEDLINE]
5: Curr Neurol Neurosci Rep. 2006 Sep;6(5):387-92.
The relationship between amyotrophic lateral sclerosis and frontotemporal dementia.
Ringholz GM, Greene SR.
Department of Neurology, Emory University,1841 Clifton Road, Room 442, Atlanta, GA 30329, USA. george.ringholz@emory.edu
Despite the traditional view of amyotrophic lateral sclerosis (ALS) as an isolated motor neuron disorder, recent evidence suggests that ALS is, in fact, a multisystem disorder with a varying presentation and with widespread extramotor neuropathologic involvement. Support for a concept of ALS as a multisystem
disorder has some basis in historical clinical reports that have highlighted the existence of a frank dementia in at least a small percentage of ALS patients. More recent evidence of extramotor involvement in ALS, derived from neurocognitive, neuropathologic, genetic, proteomic, and neuroradiologic
perspectives, provides further support for these early observations and has drawn considerable attention to a possible association between ALS and frontotemporal dementia (FTD). Literature from these diverse clinical and basic scientific disciplines, when integrated, demonstrates commonalities between ALS and FTD and suggests that these disorders not only affect the same general neuroanatomic substrate, but also may represent two points on the same neuropathologic continuum. This review discusses this putative association between ALS and FTD and provides possible directions for future research in this area.
Publication Types:
Review
PMID: 16928348 [PubMed - indexed for MEDLINE]
4: Nat Rev Neurosci. 2006 Sep;7(9):710-23.
Molecular biology of amyotrophic lateral sclerosis: insights from genetics.
Pasinelli P, Brown RH.
Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Room
3125, Building 114, 16th Street, Navy Yard, Charlestown, Massachusetts 02429, USA.
Amyotrophic lateral sclerosis (ALS) is a paralytic disorder caused by motor
neuron degeneration. Mutations in more than 50 human genes cause diverse types
of motor neuron pathology. Moreover, defects in five Mendelian genes lead to
motor neuron disease, with two mutations reproducing the ALS phenotype. Analyses
of these genetic effects have generated new insights into the diverse molecular
pathways involved in ALS pathogenesis. Here, we present an overview of the
mechanisms for motor neuron death and of the role of non-neuronal cells in ALS.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
PMID: 16924260 [PubMed - indexed for MEDLINE]
3: Clin Endocrinol (Oxf). 2006 Sep;65(3):385-8.
Growth hormone secretion is impaired in amyotrophic lateral sclerosis.
Morselli LL, Bongioanni P, Genovesi M, Licitra R, Rossi B, Murri L, Rossi G,
Martino E, Gasperi M.
Department of Endocrinology, University of Pisa, Pisa, Italy.
OBJECTIVE: ALS is the most common motor neurone disorder in human adults. Scanty
data on endocrine abnormalities have been reported. The aim of the present study
was to investigate the GH-IGF-I axis in ALS patients. PATIENTS: Twenty-two ALS
patients (12 men, 10 women), mean age 61 years, and 25 normal age- and sex-matched subjects. No patient was under riluzole therapy. MEASUREMENTS: Patients and controls underwent a GHRH plus arginine test. IGF-I was determined at baseline. A complete evaluation of pituitary function was also performed. RESULTS: Mean (+/- SD) basal GH levels were significantly reduced compared with normal controls (0.2 +/- 0.3 vs 1.6 +/- 1.8 ng/ml, P < 0.01), as well as peak GH concentrations after GHRH + arginine administration (12.6 +/- 8.9 vs 39.9 +/- 18.7 ng/ml, P < 0.001). Six (27%) patients showed a normal GH response to stimulus; 7 (32%) patients displayed a moderate GH deficiency; in 9 (40%)
patients GH response was markedly deficient. IGF-I levels were normal in the majority of patients (mean +/- SD: 143.6 +/- 63.8 ng/ml). No significant correlation was observed between peak GH concentrations and age, BMI, disease duration, severity or clinical form. A higher incidence of GH deficiency was observed in male compared to female patients (83%vs 60%), with a peak GH response in males significantly lower than in females (8.9 +/- 6.6 vs 17 +/- 9.6 ng/ml, P = 0.03). Eighteen patients repeated the test after 5 months and similar results were obtained. CONCLUSIONS: The present data indicate a reduction of GH secretion in ALS patients.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16918961 [PubMed - indexed for MEDLINE]
2: Acta Neurol Scand. 2006 Sep;114(3):205-9.
Cerebrospinal fluid Flt3 ligand level in patients with amyotrophic lateral
sclerosis.
Ilzecka J.
Department of Neurology, Medical University, Lublin, Poland. ilzecka@onet.pl
OBJECTIVES: The Flt3 ligand (FL) is a cytokine with a neurotrophic and antiapoptotic activity in the central nervous system that induces the survival of neurons. The aim of the study was to measure levels of FL in amyotrophic lateral sclerosis (ALS) patients. MATERIALS AND METHODS: The study involved 23 ALS patients and 23 people in the control group. The measurement of FL in the cerebrospinal fluid (CSF) and serum was performed by the enzyme-linked immunosorbent method. RESULTS: Results showed that CSF FL levels were significantly increased in ALS patients compared with the controls (P < 0.05) but the serum levels of this cytokine did not differ from the controls (P > 0.05). There was no significant correlation between CSF and serum FL levels and clinical parameters of ALS (P > 0.05). The difference in CSF/serum ratio of FL between ALS patients and controls was not statistically significant (P > 0.05). CONCLUSION: An increase in CSF FL levels in ALS patients, observed in this study, could be a compensative response for neurodegeneration but may also reflect increased diffusion of this cytokine into the central nervous system caused by blood-CSF barrier dysfunction.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16911350 [PubMed - indexed for MEDLINE]
1: Neurology. 2006 Sep 12;67(5):761-5. Epub 2006 Aug 9.
Noninvasive positive-pressure ventilation in ALS: predictors of tolerance and survival.
Lo Coco D, Marchese S, Pesco MC, La Bella V, Piccoli F, Lo Coco A.
ALS Research Center, Department of Neurology, Ophthalmology, Otorhinolaryngology, and Psychiatry, Universita di Palermo, Via G La Loggia, 1, 90129 Palermo, Italy. danielelococo@yahoo.com
OBJECTIVE: To identify factors associated with tolerance and survival after noninvasive positive-pressure ventilation (NIPPV) and to investigate the influence of NIPPV on lung function in patients with ALS. METHODS: NIPPV was offered to 71 patients with ALS in accordance with currently published
guidelines. Effects of NIPPV on lung function and factors influencing tolerance and survival after NIPPV were studied. RESULTS: Forty-four patients (61.9%; 95% CI: 50.6 to 73.2) tolerated NIPPV (NIPPV use >or=4 h/day) and 27 (38.1%; 95% CI: 26.8 to 49.4) were intolerant (NIPPV use <4 h/day). Patients with mild or moderate bulbar symptoms were more likely to tolerate NIPPV than those with severe impairment (odds ratio = 6.09, 95% CI: 1.18 to 31.52, p = 0.031). After NIPPV introduction, a slower decline in forced vital capacity (FVC) was observed in tolerant vs intolerant patients (p = 0.002). The slope of FVC decline after NIPPV initiation (risk ratio [RR]: 0.78, 95% CI: 0.65 to 0.94, p = 0.01)
together with NIPPV tolerance (RR: 0.32, 95% CI: 0.13 to 0.78, p = 0.013) were the only independent predictors of survival in the overall group of patients. In multivariate analysis, body mass index was the most powerful predictor of longer survival after NIPPV in tolerant patients (RR: 0.77, 95% CI: 0.61 to 0.96, p = 0.022). CONCLUSION: Survival after noninvasive ventilation was independently related to ventilatory use (>or=4 h/day) and to the modifications of forced vital capacity decline after treatment initiation. The severity of bulbar impairment and the nutritional status of the ALS patients at the introduction of ventilation may predict tolerance and survival.
Publication Types:
Clinical Trial
Comparative Study
PMID: 16899545 [PubMed - indexed for MEDLINE]
