38: Biochim Biophys Acta. 2006 Mar;1760(3):404-14. Epub 2006 Jan 4.
Intracellular conformational alterations of mutant SOD1 and the implications for
fALS-associated SOD1 mutant induced motor neuron cell death.
Zhang F, Zhu H.
Department of Molecular and Cellular Biochemistry, College of Medicine
University of Kentucky, 741 South Limestone, Lexington, KY 40536, USA.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective death of motor neurons. Approximately 10% of ALS cases are familial (fALS) and about 25% of fALS patients inherit autosomal dominant mutations in the gene encoding copper-zinc superoxide dismutase (SOD1).
Over 90 different SOD1 mutations have been identified in fALS patients. It has been established that the ALS-linked SOD1 mutations provoke a new toxic function, the nature of which remains unclear. In vitro studies using various biophysical techniques have demonstrated that the SOD1 mutants share a reduced conformational stability. However, conformational alterations of the ALS mutants have not been directly demonstrated in vivo. We employed an SOD1-GFP fusion protein system in this study to monitor the intracellular protein conformation. We demonstrate that the ALS-linked SOD1 mutants adopt different conformations from the wild-type (WT) protein in living cells. Moreover, the conformational alterations of mutant SOD1 render the mutants susceptible to the formation of high-molecular-weight complexes prior to the appearance of detergent-resistant aggregates. Finally, we show that the motor neuron-like cells expressing mutant SOD1 are more susceptible to H2O2 induced cell death compared to the cells expressing WT SOD1. This study provides direct evidence of in vivo conformational differences between WT and mutant SOD1. In addition, the SOD1-GFP system can be exploited in future studies to investigate how conformational alterations of mutant SOD1 lead to protein aggregation and to study the potential toxicity of such aggregates in familial ALS.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16431026 [PubMed - indexed for MEDLINE]
37: Neurochem Int. 2006 Mar;48(4):306-11. Epub 2006 Jan 19.
Increased glutamine synthetase but normal EAAT2 expression in platelets of ALS patients.
Bos IW, Hoogland G, Meine Jansen CF, Willigen G, Spierenburg HA, van den Berg
LH, de Graan PN.
Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy,
University Medical Center, Utrecht, The Netherlands.
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease and glutamate
excitotoxicity has been implicated in its pathogenesis. Platelets contain a glutamate uptake system and express components of the glutamate-glutamine cycle, such as the predominant glial excitatory amino acid transporter 2 (EAAT2). In several neurological diseases platelets have proven to be systemic markers for the disease. We compared properties of key components of the glutamate-glutamine cycle in blood platelets of ALS patients and healthy controls. Platelets were analyzed for (3)H-glutamate uptake in the presence or absence of thrombin and for EAAT2 and glutamine synthetase protein expression by Western blotting. Platelets of ALS patients showed a 37% increase in expression of glutamine synthetase, but normal expression of glutamate transporter EAAT2. Glutamate uptake in resting or thrombin-stimulated platelets did not differ significantly between platelets from ALS patients and controls. Thrombin-stimulation resulted in about a seven-fold increase in glutamate uptake. Our data suggest that
glutamine synthetase may be a peripheral marker of ALS and encourage further
investigation into the role of this enzyme in ALS.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16426705 [PubMed - indexed for MEDLINE]
36: J Neurochem. 2006 Mar;96(5):1277-88. Epub 2006 Jan 25.
Mapping superoxide dismutase 1 domains of non-native interaction: roles of
intra- and intermolecular disulfide bonding in aggregation.
Wang J, Xu G, Borchelt DR.
Department of Pathology, The Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA.
Superoxide dismutase 1 (SOD1) proteins harboring mutations linked to familial
amyotrophic lateral sclerosis (FALS) uniformly show heightened potential to form
high molecular weight structures. Here, we examine the domains of SOD1 that are
involved in forming these structures (aggregates) and study the role of intra-
and intermolecular disulfide bonds. An analysis of disease mutations identified
to date reveals a non-random distribution with predominant occurrence at
residues within highly conserved beta-strands or at highly conserved residues in
loop domains. Using a cell transfection assay for aggregation, we determined
that no single domain in SOD1 is indispensable in the formation of sedimentable
aggregates, suggesting multiple potential motifs in the protein mediate
non-native interactions. By a cell-free aggregation assay, analysis of
transgenic mouse tissues, and mutagenesis approaches, we found evidence that
redox conditions may modulate SOD1 aggregation; reduction of the native
intramolecular disulfide bonds may predispose SOD1 to unfolding and aggregation,
whereas non-native intermolecular disulfide linkages may help stabilize
aggregates in vivo. The results suggest a possible mechanism for diversity in
the structures formed by different SOD1 mutants, and define a potential
contribution of redox conditions to SOD1 aggregation.
Publication Types:
Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16441516 [PubMed - indexed for MEDLINE]
35: Zh Nevrol Psikhiatr Im S S Korsakova. 2006;106(1):14-20.
Stuchevskaia TR, Kazakov VM, Rudenko DI, Posokhina OV, Skoromets AA.
We carried out an analysis of 5 sporadic cases of lower motor neuron disease
with predominant affection of the proximal parts of arms in 2 patients and
distal parts in 3 patients. From clinical point of view, our own observations,
along with similar cases reported in the literature with predominantly affected
upper limbs, different progression of the disease and denervation changes during
needle EMG, can argue for clinical heterogeneity of lower motor neuron disease.
There were some difficulties in establishment of a differential diagnosis
between atypical variants of amyotrophic lateral sclerosis ("flail arm"
syndrome) and primary muscular atrophy of adults at the early stages of the
disease. We suppose that atypical variants of amyotrophic lateral sclerosis
resultant from affection of lower motor neuron only ("flail arm" syndrome and
distal amyotrophy), could be distinguished from amyotrophic lateral sclerosis
and considered as an independent entity.
Publication Types:
Comparative Study
English Abstract
PMID: 16457128 [PubMed - indexed for MEDLINE]
34: Exp Neurol. 2006 Mar;198(1):1-3. Epub 2006 Feb 3.
Is ALS a systemic disorder? Evidence from muscle mitochondria.
Appel SH.
Department of Neurology, Methodist Neurological Institute, Houston, TX 77030,
USA. sappel@tmh.tmc.edu
PMID: 16458887 [PubMed - indexed for MEDLINE]
33: Clin Neurophysiol. 2006 Mar;117(3):538-48. Epub 2006 Feb 7.
Comment in:
Clin Neurophysiol. 2006 Mar;117(3):479-83.
A P300-based brain-computer interface: initial tests by ALS patients.
Sellers EW, Donchin E.
New York State Department of Health, Wadsworth Center, E1001 Empire State Plaza,
Albany, NY 12201, USA. esellers@wadsworth.org
OBJECTIVE: The current study evaluates the effectiveness of a brain-computer
interface (BCI) system that operates by detecting a P300 elicited by one of four
randomly presented stimuli (i.e. YES, NO, PASS, END). METHODS: Two groups of
participants were tested. The first group included three amyotrophic lateral
sclerosis (ALS) patients that varied in degree of disability, but all retained
the ability to communicate; the second group included three non-ALS controls.
Each participant participated in ten experimental sessions during a period of
approximately 6 weeks. During each run the participant's task was to attend to
one stimulus and disregard the other three. Stimuli were presented auditorily,
visually, or in both modes. RESULTS: Two of the 3 ALS patient's classification
rates were equal to those achieved by the non-ALS participants. Waveform
morphology varied as a function of the presentation mode, but not in a similar
pattern for each participant. CONCLUSIONS: The event-related potentials elicited
by the target stimuli could be discriminated from the non-target stimuli for the
non-ALS and the ALS groups. Future studies will begin to examine online
classification. SIGNIFICANCE: The results of offline classification suggest that
a P300-based BCI can serve as a non-muscular communication device in both ALS,
and non-ALS control groups.
Publication Types:
Comparative Study
Research Support, N.I.H., Extramural
PMID: 16461003 [PubMed - indexed for MEDLINE]
32: Neuromuscul Disord. 2006 Mar;16(3):204-7. Epub 2006 Feb 17.
Wheelchair economy class syndrome in amyotrophic lateral sclerosis.
Kimura F, Ishida S, Furutama D, Hirata Y, Sato T, Hosokawa T, Hanafusa T.
Division of Neurology, The First Department of Internal Medicine, Osaka Medical
College, Daigaku-machi 2-7, Takatsukishi, Osaka 569-8686, Japan.
in1110@poh.osaka-med.ac.jp
A wheelchair-bound 61-year-old diabetic man with amyotrophic lateral sclerosis
(ALS) developed sudden respiratory failure. Specific findings for hypoxemia and
hypocapnia were incompatible with type II respiratory failure seen in the
terminal stages of ALS. 'Economy class syndrome' was diagnosed, with massive
thrombosis in the pulmonary arteries and deep vein thrombosis. This case offers
a warning for long-term wheelchair users, particularly hypoxemic ALS patients,
regarding the risks of treatable pulmonary thromboembolism.
Publication Types:
Case Reports
PMID: 16487707 [PubMed - indexed for MEDLINE]
31: Lancet Neurol. 2006 Mar;5(3):203.
Comment on:
Lancet Neurol. 2006 Feb;5(2):105-6.
Correction to our comment.
Piepers S, van den Berg L.
Publication Types:
Comment
Letter
PMID: 16488375 [PubMed - indexed for MEDLINE]
30: Med Hypotheses. 2006;66(6):1222-6. Epub 2006 Feb 20.
Cycad toxins, Helicobacter pylori and parkinsonism: cholesterol glucosides as
the common denomenator.
Schulz JD, Hawkes EL, Shaw CA.
Department of Ophthalmology, University of British Columbia, Vancouver, Canada.
Understanding sporadic cases of age-dependent neurodegenerative diseases such as
parkinsonism requires the evaluation of potential environmental factors.
Amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC), a
neurological disorder in which features of parkinsonism are present and for
which no consistent genetic explanation has been found, has been linked to the
consumption of cycad (Cycas micronesica). Similarly, epidemiological evidence
suggests an association between parkinsonism and gastric ulcer caused by
Helicobacter pylori infection. While common immunological and inflammatory
changes have been proposed to account for the link between parkinsonism and H.
pylori infection, we propose an alternate explanation based on our work on the
"cycad theory" of ALS-PDC. Recent experiments in our laboratory have identified
several sterol glucosides in cycad that have neurotoxic properties in vitro and
that appear to be linked to the development of neurodegenerative disease in
vivo. Specifically, mice fed cycad display behavioural symptoms of parkinsonism
such as reduced gait length, as well as neuropathological signs such as a loss
of striatal dopaminergic (DAergic) terminals and an upregulation of the dopamine
D2 receptor. These cycad-derived sterol glucosides are structurally similar to
cholesterol glucosides that account for a significant part pf the lipid profile
of H. pylori. We hypothesize that cholesterol glucosides arising from H. pylori
infection may act as neurotoxins, promoting the degeneration of the DAergic
neurons affected in parkinsonism, in a similar reaction to that which is thought
to link cycad consumption and ALS-PDC. This hypothesis will be tested in future
studies that will include exposing mice to purified sterol or cholestorol
glucosides derived from cycad and comparing these mice behaviourally and
neuropathologically to ones chronically infected with H. pylori.
PMID: 16488551 [PubMed - indexed for MEDLINE]
29: Nat Rev Neurosci. 2006 Mar;7(3):194-206.
Astrocyte dysfunction in neurological disorders: a molecular perspective.
Seifert G, Schilling K, Steinhauser C.
Department of Experimental Neurobiology, Clinic of Neurosurgery, University of
Bonn, Germany.
Recent work on glial cell physiology has revealed that glial cells, and
astrocytes in particular, are much more actively involved in brain information
processing than previously thought. This finding has stimulated the view that
the active brain should no longer be regarded solely as a network of neuronal
contacts, but instead as a circuit of integrated, interactive neurons and glial
cells. Consequently, glial cells could also have as yet unexpected roles in the
diseased brain. An improved understanding of astrocyte biology and heterogeneity
and the involvement of these cells in pathogenesis offers the potential for
developing novel strategies to treat neurological disorders.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 16495941 [PubMed - indexed for MEDLINE]
28: Nat Neurosci. 2006 Mar;9(3):304.
Quantifying motor neuron loss in ALS.
Narasimhan K.
Publication Types:
News
PMID: 16498424 [PubMed - indexed for MEDLINE]
27: FASEB J. 2006 Mar;20(3):583-5. Epub 2006 Jan 17.
Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a
reduction in Akt and an increase in atrogin-1.
Leger B, Vergani L, Soraru G, Hespel P, Derave W, Gobelet C, D'Ascenzio C,
Angelini C, Russell AP.
Clinique romande de readaptation, SuvaCare, Sion, Switzerland.
The molecular mechanisms influencing muscle atrophy in humans are poorly
understood. Atrogin-1 and MuRF1, two ubiquitin E3-ligases, mediate rodent and
cell muscle atrophy and are suggested to be regulated by an Akt/Forkhead (FKHR)
signaling pathway. Here we investigated the expression of atrogin-1, MuRF1, and
the activity of Akt and its catabolic (FKHR and FKHRL1) and anabolic (p70(s6k)
and GSK-3beta) targets in human skeletal muscle atrophy. The muscle atrophy
model used was amyotrophic lateral sclerosis (ALS). All measurements were
performed in biopsies from 22 ALS patients and 16 healthy controls as well as in
G93A ALS mice. ALS patients had a significant increase in atrogin-1 mRNA and
protein content, which was associated with a decrease in Akt activity. There was
no difference in the mRNA and protein content of FKHR, FKHRL1, p70(s6k), and
GSK-3beta. Similar observations were made in the G93A ALS mice. Human skeletal
muscle atrophy, as seen in the ALS model, is associated with an increase in
atrogin-1 and a decrease in Akt. The transcriptional regulation of human
atrogin-1 may be controlled by an Akt-mediated transcription factor other than
FKHR or via another signaling pathway.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16507768 [PubMed - indexed for MEDLINE]
26: J Neurosci. 2006 Mar 1;26(9):2467-73.
Thalidomide and lenalidomide extend survival in a transgenic mouse model of
amyotrophic lateral sclerosis.
Kiaei M, Petri S, Kipiani K, Gardian G, Choi DK, Chen J, Calingasan NY, Schafer
P, Muller GW, Stewart C, Hensley K, Beal MF.
Department of Neurology and Neuroscience, Weill Medical College, Cornell
University, New York-Presbyterian Hospital, New York, New York 10021, USA.
mak2026@med.cornell.edu
Accumulating evidence suggests that inflammation plays a major role in the
pathogenesis of motor neuron death in amyotrophic lateral sclerosis (ALS).
Important mediators of inflammation such as the cytokine tumor necrosis
factor-alpha (TNF-alpha) and its superfamily member fibroblast-associated
cell-surface ligand (FasL) have been implicated in apoptosis. We found increased
TNF-alpha and FasL immunoreactivity in lumbar spinal cord sections of ALS
patients and G93A transgenic mice. Both increased TNF-alpha and FasL
immunostaining in the lumbar spinal cord of the G93A SOD1 transgenic mice
occurred at 40-60 d, well before the onset of symptoms and loss of motor
neurons. We tested the neuroprotective effect of thalidomide and its analog
lenalidomide, pharmacological agents that inhibit the expression of TNF-alpha
and other cytokines by destabilizing their mRNA. Treatment with either
thalidomide or lenalidomide attenuated weight loss, enhanced motor performance,
decreased motor neuron cell death, and significantly increased the life span in
G93A transgenic mice. Treated G93A mice showed a reduction in TNF-alpha and FasL
immunoreactivity as well as their mRNA in the lumbar spinal cord. Both compounds
also reduced interleukin (IL)-12p40, IL-1alpha, and IL-1beta and increased IL-RA
and TGF-beta1 mRNA. Therefore, both thalidomide and lenalidomide bear promise as
therapeutic interventions for the treatment of ALS.
Publication Types:
Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16510725 [PubMed - indexed for MEDLINE]
25: BMC Neurol. 2006 Mar 2;6:12.
COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial
cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal
cord.
Yiangou Y, Facer P, Durrenberger P, Chessell IP, Naylor A, Bountra C, Banati RR,
Anand P.
Peripheral Neuropathy Unit, Imperial College, Hammersmith Hospital, London, UK.
Yiangou@imperial.ac.uk
BACKGROUND: While multiple sclerosis (MS) and amyotrophic lateral sclerosis
(ALS) are primarily inflammatory and degenerative disorders respectively, there
is increasing evidence for shared cellular mechanisms that may affect disease
progression, particularly glial responses. Cyclooxygenase 2 (COX-2) inhibition
prolongs survival and cannabinoids ameliorate progression of clinical disease in
animal models of ALS and MS respectively, but the mechanism is uncertain.
Therefore, three key molecules known to be expressed in activated microglial
cells/macrophages, COX-2, CB2 and P2X7, which plays a role in inflammatory
cascades, were studied in MS and ALS post-mortem human spinal cord. METHODS:
Frozen human post mortem spinal cord specimens, controls (n = 12), ALS (n = 9)
and MS (n = 19), were available for study by immunocytochemistry and Western
blotting, using specific antibodies to COX-2, CB2 and P2X7, and markers of
microglial cells/macrophages (CD 68, ferritin). In addition, autoradiography for
peripheral benzodiazepine binding sites was performed on some spinal cord
sections using [3H] (R)-PK11195, a marker of activated microglial
cells/macrophages. Results of immunostaining and Western blotting were
quantified by computerized image and optical density analysis respectively.
RESULTS: In control spinal cord, few small microglial cells/macrophages-like
COX-2-immunoreactive cells, mostly bipolar with short processes, were scattered
throughout the tissue, whilst MS and ALS specimens had significantly greater
density of such cells with longer processes in affected regions, by image
analysis. Inflammatory cell marker CD68-immunoreactivity, [3H] (R)-PK11195
autoradiography, and double-staining against ferritin confirmed increased
production of COX-2 by activated microglial cells/macrophages. An expected
70-kDa band was seen by Western blotting which was significantly increased in MS
spinal cord. There was good correlation between the COX-2 immunostaining and
optical density of the COX-2 70-kDa band in the MS group (r = 0.89, P = 0.0011,
n = 10). MS and ALS specimens also had significantly greater density of P2X7 and
CB2-immunoreactive microglial cells/macrophages in affected regions. CONCLUSION:
It is hypothesized that the known increase of lesion-associated extracellular
ATP contributes via P2X7 activation to release IL-1 beta which in turn induces
COX-2 and downstream pathogenic mediators. Selective CNS-penetrant COX-2 and
P2X7 inhibitors and CB2 specific agonists deserve evaluation in the progression
of MS and ALS.
Publication Types:
Comparative Study
PMID: 16512913 [PubMed - indexed for MEDLINE]
24: Glia. 2006 May;53(7):744-53.
Origin and distribution of bone marrow-derived cells in the central nervous
system in a mouse model of amyotrophic lateral sclerosis.
Solomon JN, Lewis CA, Ajami B, Corbel SY, Rossi FM, Krieger C.
Department of Molecular Biology and Biochemistry, Simon Fraser University,
Burnaby, British Columbia V5A 1S6, Canada.
Amyotrophic lateral sclerosis (ALS) is associated with increased numbers of
microglia within the central nervous system (CNS). However, it is unknown
whether the microgliosis results from proliferation of CNS resident microglia,
or recruitment of bone marrow (BM)-derived microglial precursors. Here we assess
the distribution and number of BM-derived cells in spinal cord using
transplantation of green fluorescent protein (GFP)-labeled BM cells into
myelo-ablated mice over-expressing human mutant superoxide dismutase 1 (mSOD), a
murine model of ALS. Transplantation of GFP+ BM did not affect the rate of
disease progression in mSOD mice. Mean numbers of microglia and GFP+ cells in
spinal cords of control mice were not significantly different from those in
asymptomatic mSOD mice and showed no change with animal age. The number of GFP+
cells and microglia (F4/80+ and CD11b+ cells) within the spinal cord of mSOD
mice increased compared to age-matched controls at a time when mSOD mice
exhibited disease symptoms, continuing up to disease end-stage. Although we
observed an increase in the number of GFP+ cells in spinal cords of mSOD mice
with disease symptoms, mean numbers of GFP+ F4/80+ cells comprised less than 20%
of all F4/80+ cells and did not increase with disease progression. Furthermore,
the relative rates of proliferation in CD45+GFP- and CD45+GFP+ cells were
comparable. Thus, we demonstrate that the microgliosis present in spinal cord
tissue of mSOD mice is primarily due to an expansion of resident microglia and
not to the recruitment of microglial precursors from the circulation. Copyright
2006 Wiley-Liss, Inc.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16518833 [PubMed - indexed for MEDLINE]
23: J Peripher Nerv Syst. 2006 Mar;11(1):67-71.
Circulating levels of cytokines and their modulation by intravenous
immunoglobulin in multifocal motor neuropathy.
Terenghi F, Allaria S, Nobile-Orazio E.
Department of Neurological Sciences, 'Giorgio Spagnol' Neuroimmunology Service,
Dino Ferrari Center and Center for Neurodegenerative Diseases, Milan University,
Milan, Italy.
We found comparable levels of tumor necrosis factor (TNF)-alpha,
interferon-gamma, interleukin (IL)-2, IL-4, IL-10, and IL-12 in the sera of 22
patients with multifocal motor neuropathy (MMN), 12 with amyotrophic lateral
sclerosis (ALS), 12 multiple sclerosis, seven chronic inflammatory demyelinating
polyneuropathy, five myasthenia gravis, and 13 healthy controls (NS). TNF-alpha
levels, however, were higher in 15 (68%) MMN patients than in any NS. In all but
one MMN patient tested, TNF-alpha levels repeatedly, albeit slightly, increased
after each intravenous immunoglobulin infusion in parallel with clinical
improvement and decreased 3-4 weeks after therapy, while in both ALS patients
tested, they decreased or remained unchanged. The possible pathogenetic
relevance of serum TNF-alpha modification in MMN remains to be clarified.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
PMID: 16519784 [PubMed - indexed for MEDLINE]
22: J Neurosci. 2006 Mar 8;26(10):2661-72.
Calcium signaling pathways mediating synaptic potentiation triggered by
amyotrophic lateral sclerosis IgG in motor nerve terminals.
Pagani MR, Reisin RC, Uchitel OD.
Laboratorio de Fisiologia y Biologia Molecular, Instituto de Fisiologia Biologia
Molecular y Neurociencias UBA-CONICET, Facultad de Ciencias Exactas y Naturales,
Universidad de Buenos Aires, Ciudad Universitaria, C1428EHA Buenos Aires,
Argentina.
Sporadic amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that
affects particularly motoneurons. Several pieces of evidence suggested the
involvement of autoimmune mechanisms mediated by antibodies in ALS. However, the
significance of those antibodies in the disease and the underlying mechanisms
are unknown. Here we showed that IgG purified from a group of sporadic ALS
patients, but not familial ALS patients, specifically interact with the
presynaptic membrane of motoneurons through an antigen-antibody interaction and
modulated synaptic transmission. Immunoreactivity against nerve terminals showed
strong correlation with synaptic modulation ability. In addition, several
controls have ruled out the possibility for this synaptic modulation to be
mediated through proteases or nonspecific effects. Effective IgG potentiated
both spontaneous and asynchronous transmitter release. Application of
pharmacological inhibitors suggested that activation of this increased release
required a nonconstitutive Ca2+ influx through N-type (Cav2.2) channels and
phospholipase C activity and that activation of IP3 and ryanodine receptors were
necessary to both activate and sustain the increased release. Consistent with
the notion that ALS is heterogeneous disorder, our results reveal that, in
approximately 50% of ALS patients, motor nerve terminals constitutes a target
for autoimmune response.
Publication Types:
Comparative Study
In Vitro
Research Support, Non-U.S. Gov't
PMID: 16525045 [PubMed - indexed for MEDLINE]
21: Med Arh. 2006;60(2):108-9.
Ibrahimagic OC, Sinanovic O, Zonic L, Hudic J.
Klinika za Neurologiju, Univerzitetski Klinicki Centar Tuzla.
Amyotrophic lateral sclerosis is a progressive degenerative neuromuscular
disease in adults that occurs in familial and sporadic forms. The mean age of
onset of symptoms is 56 years and the mean duration of disease is 3 years. One
of the theories on the pathogenesis suggests on mutation in gene that encodes
superoxide dismutase, which is involved in metabolism of free radicals (copper,
zinc). In this article we showed patient with early onset of disease associated
with abnormality of copper level. Co morbidity with Wilson disease has not been
proved. According to this case it is possible to think about changes in cuprum
level at ALS patients.
Publication Types:
Case Reports
English Abstract
PMID: 16528929 [PubMed - indexed for MEDLINE]
20: Expert Rev Neurother. 2006 Mar;6(3):417-28.
Therapeutic targets for amyotrophic lateral sclerosis: current treatments and
prospects for more effective therapies.
Bruijn LI, Cudkowicz M.
The ALS Association, Palm Harbor, FL 34685, USA. lucie@alsa-national.org
Although amyotrophic lateral sclerosis (ALS) was described more than 130 years
ago, the cause(s) of most cases of this adult motor neuron disease remains a
mystery. With the discovery of mutations in one gene (Cu/Zn superoxide
dismutase) as a primary cause of some forms of ALS, model systems have been
developed that have helped us begin to understand mechanisms involved in motor
neuron death and enabled testing of potential new therapies. Several other genes
have been implicated as risk factors in motor neuron diseases, including
neurofilaments, cytoplasmic dynein and dynactin, vascular endothelial growth
factor, and angiogenin. With advances in the basic research of the disease, many
hypotheses accounting for motor neuron death are being explored, including loss
of trophic support, protein mishandling, mitochondrial dysfunction,
excitotoxicity, axonal abnormalities and inflammation. Many of these mechanisms
are the focus of research in other neurodegenerative disorders, such as
Parkinson's, Alzheimer's and Huntington's disease.
Publication Types:
Review
PMID: 16533145 [PubMed - indexed for MEDLINE]
19: Arch Neurol. 2006 Mar;63(3):319-20.
Comment on:
Arch Neurol. 2006 Mar;63(3):345-52.
ALS--not what we thought.
Strong MJ.
Publication Types:
Comment
Editorial
PMID: 16533957 [PubMed - indexed for MEDLINE]
18: Arch Neurol. 2006 Mar;63(3):345-52.
Comment in:
Arch Neurol. 2006 Mar;63(3):319-20.
An observational study of cognitive impairment in amyotrophic lateral sclerosis.
Rippon GA, Scarmeas N, Gordon PH, Murphy PL, Albert SM, Mitsumoto H, Marder K,
Rowland LP, Stern Y.
Department of Neurology, Gertrude H. Sergievsky Center, Taub Institute for
Research on Alzheimer's Disease and the Aging Brain, Eleanor and Lou Gehrig
MDA/ALS Research Center, New York, NY, USA.
BACKGROUND: Cognitive impairment is increasingly recognized in patients with
amyotrophic lateral sclerosis (ALS). Clinical and pathologic features overlap in
frontotemporal lobar dementia and ALS. Demographics, respiratory status, bulbar
site of onset, and disease severity are potential risk factors for cognitive
impairment in ALS. OBJECTIVES: To further delineate the frequency, nature, and
implications of cognitive impairment in ALS and to assess previously identified
risk factors. DESIGN: Case-control and retrospective cohort study. SETTING:
Academic referral center. PARTICIPANTS: Forty consecutive patients with ALS
underwent baseline neurologic and neuropsychologic examinations. Cognitive test
performance was compared in patients with ALS and matched controls. An
exploratory analysis of the relationship between cognitive performance and ALS
survival was performed. MAIN OUTCOME MEASURES: Neuropsychologic test
performance, ALS severity, and survival. RESULTS: Twelve patients (30%) showed
evidence of cognitive impairment, including 9 (23%) who met the neuropsychologic
criteria for dementia. No statistically significant differences were found
between demented and nondemented ALS groups regarding demographics, family
history, site of onset, bulbar dysfunction, or ALS severity. Only 1 patient with
dementia had bulbar-onset disease. An association was observed between
increasing ALS severity and declining verbal fluency performance. Demented
patients with ALS showed predominant impairment in free recall, executive
function, and naming, with relative preservation of attention, psychomotor
speed, and visuospatial function. No association was observed between cognition
and survival, controlling for ALS severity. CONCLUSIONS: Nearly a third of the
patients with ALS showed evidence of cognitive impairment in a pattern
consistent with frontotemporal lobar dementia. Cognitive performance was not
related to site of onset or survival.
Publication Types:
Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16533961 [PubMed - indexed for MEDLINE]
17: Neurology. 2006 Mar 14;66(5):624-5.
Comment on:
Neurology. 2006 Mar 14;66(5):647-53.
What's in a name? Lumping or splitting ALS, PLS, PMA, and the other motor neuron
diseases.
Rosenfeld J, Swash M.
Publication Types:
Comment
Editorial
PMID: 16534097 [PubMed - indexed for MEDLINE]
16: Neurology. 2006 Mar 14;66(5):647-53.
Comment in:
Neurology. 2006 Mar 14;66(5):624-5.
The natural history of primary lateral sclerosis.
Gordon PH, Cheng B, Katz IB, Pinto M, Hays AP, Mitsumoto H, Rowland LP.
Department of Neurology, Columbia University, New York, NY, USA.
PHG8@columbia.edu
OBJECTIVE: To define the syndrome of primary lateral sclerosis (PLS) and
disorders that contain features of both ALS and PLS, to determine the time
beyond which PLS is less likely to become ALS clinically, and to determine the
outcome of people with PLS and those who develop lower motor neuron (LMN) signs.
METHODS: The authors reviewed the records of all 39 patients initially diagnosed
with PLS in 1984 to 2004. Diagnostic subgroups were defined based on clinical
features. The authors used Kaplan-Meier methods to estimate the time to
diagnosis, linear regression analyses to assess function, and a Cox proportional
hazard model to assess survival in subgroups. RESULTS: Of the 39 patients, 29
had only upper motor neuron (UMN) signs on initial evaluation. Thirteen of the
29 were later classified as having UMN-dominant ALS (UMN-D) because they
acquired evidence of denervation by EMG (3.17 years) or examination (3.67
years). Sixteen of the 29 patients, classified as clinically pure PLS, retained
only UMN signs and a normal EMG (mean follow-up 8.7 years). Ten patients who met
criteria for ALS at the initial visit were used as controls. The UMN-dominant
ALS group had lower functional scores (p = 0.033) than the PLS group, and
similar scores to those with ALS. Survival was longer in both the PLS group (p =
0.027) and the UMN-D group (p = 0.067) than the ALS group. CONCLUSIONS:
Clinically pure PLS can be defined by isolated UMN signs 4 years after symptom
onset, and is a syndrome of slow progression with high levels of function. Prior
to the fourth year, the diagnosis of PLS cannot be made with certainty because
many patients develop LMN signs. UMN-dominant ALS, defined by predominantly UMN
disease with minor LMN signs, has disability similar to ALS, but slower
progression.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16534101 [PubMed - indexed for MEDLINE]
15: Neurology. 2006 Mar 14;66(5):660-3.
Comment in:
Neurology. 2006 Mar 14;66(5):626-7.
A two-stage design for a phase II clinical trial of coenzyme Q10 in ALS.
Levy G, Kaufmann P, Buchsbaum R, Montes J, Barsdorf A, Arbing R, Battista V,
Zhou X, Mitsumoto H, Levin B, Thompson JL.
Department of Biostatistics, Mailman School of Public Health, Columbia
University, New York, NY 10032, USA. GL227@columbia.edu
BACKGROUND: The combination of a small pool of patients at any given time with
the availability of many potential neuroprotective agents to be tested in ALS
requires efficient phase II trial designs. OBJECTIVE: To describe the design of
the Clinical Trial of High Dose Coenzyme Q10 (CoQ10) in ALS (QALS study)--a
phase II, randomized, placebo-controlled, double-blind, multicenter clinical
trial. METHODS: The study design features two stages. The first stage (dose
selection) identifies which of two doses of CoQ10 (1800 mg or 2700 mg) is
preferred using a selection procedure rather than a formal hypothesis test. The
second stage (early efficacy test) compares the preferred dose of CoQ10 against
placebo using a non-superiority or futility design. Data from patients assigned
to the preferred dose of CoQ10 in the first stage are also used in the second
stage. The primary outcome measure is the decline in Amyotrophic Lateral
Sclerosis Functional Rating Scale-revised (ALSFRSr) score from baseline to 9
months. RESULTS: The total sample size required is 185 patients, as compared to
a much larger sample size estimated to be necessary using a conventional
superiority design (total: 852 patients). The authors report a bias correction
made necessary by the inclusion of patient data from the first stage in the
second stage. CONCLUSIONS: Several features of the Clinical Trial of High Dose
Coenzyme Q10 in ALS study design promote efficiency. These features may be
beneficial in phase II trials in amyotrophic lateral sclerosis and other fields.
Publication Types:
Clinical Trial, Phase II
Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16534103 [PubMed - indexed for MEDLINE]
14: Neurology. 2006 Mar 14;66(5):783-4; author reply 783-4.
Comment on:
Neurology. 2005 Jul 12;65(1):68-74.
Wish to die in end-stage ALS.
Kennedy PR.
Publication Types:
Comment
Letter
PMID: 16534137 [PubMed - indexed for MEDLINE]
13: Amyotroph Lateral Scler. 2006 Mar;7(1):3-4.
Comment on:
Amyotroph Lateral Scler. 2006 Mar;7(1):5-15.
Ventilation in ALS.
de Carvalho M, Pinto A.
Publication Types:
Comment
Editorial
PMID: 16546752 [PubMed - indexed for MEDLINE]
12: Amyotroph Lateral Scler. 2006 Mar;7(1):5-15.
Comment in:
Amyotroph Lateral Scler. 2006 Mar;7(1):3-4.
Management of respiration in MND/ALS patients: an evidence based review.
Heffernan C, Jenkinson C, Holmes T, Macleod H, Kinnear W, Oliver D, Leigh N,
Ampong MA.
Department of Public Health, University of Oxford, UK.
This systematic review comprises an objective appraisal of the evidence in
regard to the management of respiration in patients with motor neuron disease
(MND/ALS). Studies were identified through computerised searches of 32
databases. Internet searches of websites of drug companies and MND/ALS research
web sites, 'snow balling' and hand searches were also employed to locate any
unpublished study or other 'grey literature' on respiration and MND/ALS. Since
management of MND/ALS involves a number of health professionals and care
workers, searches were made across multiple disciplines. No time frame was
imposed on the search in order to increase the probability of identifying all
relevant studies, although there was a final limit of March 2005.
Recommendations for patient and carer-based guidelines for the clinical
management of respiration for MND/ALS patients are suggested on the basis of
qualitative analyses of the available evidence. However, these recommendations
are based on current evidence of best practice, which largely comprises
observational research and clinical opinion. There is a clear need for further
evidence, in particular randomised and non-randomised controlled trials on the
effects of non-invasive ventilation and additional larger scale cohort studies
on the issues of initial assessment of respiratory symptoms, and management and
timing of interventions.
Publication Types:
Review
PMID: 16546753 [PubMed - indexed for MEDLINE]
11: Amyotroph Lateral Scler. 2006 Mar;7(1):16-21.
Survival of patients with ALS following institution of enteral feeding is
related to pre-procedure oximetry: a retrospective review of 98 patients in a
single centre.
Shaw AS, Ampong MA, Rio A, Al-Chalabi A, Sellars ME, Ellis C, Shaw CE, Leigh NP,
Sidhu PS.
Department of Radiology, King's College Hospital, London, UK.
A retrospective review was carried out on the influence of pre-procedure
respiratory assessment on survival of patients with amyotrophic lateral
sclerosis (ALS) requiring nutritional support with either a gastrostomy or a
nasogastric feeding tube. Over a five-year period 98 patients (49 male, 49
female; median age 61 years, range 26-86 years) with ALS were referred for
enteral feeding with either radiological inserted gastrostomy (RIG),
percutaneous endoscopic gastrostomy (PEG) or nasogastric tube (NG). Case notes
review was performed to record patient age, sex, pre-procedure respiratory
assessment, method of enteral feeding and survival post-procedure. Kaplan-Meier
survival curves were constructed for each group, with Cox regression analyses
performed in order to establish the effect of each variable on outcome. Median
survival (with 95% confidence intervals) following RIG, PEG and NG was 6.31
months (4.58-8.04 months), 7.13 months (4.81-9.45 months) and 0.95 months
(0.00-2.77 months), respectively. The survival advantage between RIG and PEG was
not statistically significant (p = 0.50), but for NG versus RIG and PEG groups
combined, there was a significant difference (p = 0.03). For patients with
normal overnight oximetry, median survival was 8.54 months (3.88-13.21 months),
compared to 4.80 months (1.20-8.39 months) in the abnormal oximetry group (p =
0.03; relative risk 1.97). It is concluded that RIG and PEG are equivalent in
terms of post-procedure survival. Abnormal oximetry prior to the procedure is a
significant indicator of post-procedure survival.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16546754 [PubMed - indexed for MEDLINE]
10: Amyotroph Lateral Scler. 2006 Mar;7(1):22-6.
Association between metallothionein genes polymorphisms and sporadic amyotrophic
lateral sclerosis in a Japanese population.
Hayashi Y, Hashizume T, Wakida K, Satoh M, Uchida Y, Watabe K, Matsuyama Z,
Kimura A, Inuzuka T, Hozumi I.
Department of Neurology and Geriatrics, Gifu University Graduate School of
Medicine, Gifu, Japan.
Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative
disease that selectively affects motor neurons. Reactive oxygen species (ROS)
are assumed to be involved in the pathogenesis of ALS. Metallothioneins (MTs)
are self-protective, multifunctional proteins that scavenge ROS. In particular,
metallothionein-III (MT-III) has a strong scavenging effect on hydroxyl
radicals. MTs have been suggested to have important roles in the pathophysiology
of ALS. Therefore we investigated single nucleotide polymorphisms (SNPs) of the
MT-III and the metallothionein-IIA (MT-IIA) promoter region in 37 Japanese SALS
cases and 206 sex-matched healthy controls using polymerase chain reaction
(PCR)-direct sequencing or PCR-temporal temperature gradient gel electrophoresis
(TTGE). We detected no SNPs of the MT-III gene in SALS cases and controls, and
no detectable association between SALS phenotypes and a SNP of the MT-IIA
promoter region. We conclude that gene polymorphisms of MT-IIA promoter region
and MT-III gene are not associated with SALS phenotypes in a Japanese
population.
Publication Types:
Controlled Clinical Trial
Research Support, Non-U.S. Gov't
PMID: 16546755 [PubMed - indexed for MEDLINE]
9: Amyotroph Lateral Scler. 2006 Mar;7(1):27-31.
Premorbid personality characteristics of patients with ALS.
Grossman AB, Levin BE, Bradley WG.
Department of Neurology, Miller School of Medicine, University of Miami,
Florida, USA. agrossman@med.miami.edu
Experienced neurologists caring for patients with amyotrophic lateral sclerosis
(ALS) have commented that these patients commonly exhibit similar personality
features. Previous research studies on the premorbid personality characteristics
of ALS patients have however not clearly substantiated this observation. In the
present study, caregivers of newly diagnosed ALS patients provided ratings of
patients' premorbid personality traits, and these ratings were compared with
those of caregivers of patients newly diagnosed with other chronic, progressive
diseases. Results indicated that ALS patients were rated as significantly lower
than the other medical patients in the Openness trait on the NEO-Personality
Inventory. This finding is discussed in relation to past research findings,
prevailing clinical characterizations of ALS patients, and current research on
cognitive and behavioral changes in ALS.
Publication Types:
Comparative Study
Controlled Clinical Trial
Research Support, Non-U.S. Gov't
PMID: 16546756 [PubMed - indexed for MEDLINE]
8: Amyotroph Lateral Scler. 2006 Mar;7(1):32-7.
Benefit of tianeptine and morphine in a transgenic model of familial amyotrophic
lateral sclerosis.
Chritin M, Savasta M, Besson G.
Service de Neurologie, CHU de Grenoble, Grenoble, France.
The familial form of amyotrophic lateral sclerosis (FALS) has been linked in
some cases to dominant mutations in the gene encoding the Cu/Zn superoxide
dismutase (SOD1) mutation. Transgenic mice bearing the G93A SOD1 mutation
develop clinical symptoms and pathological features similar to those described
in the human disease and represent a good model to explore the potential benefit
of therapeutic agents. Using this animal model, we tested the efficacy of
morphine and tianeptine treatments, separately and in association, on both
disease progression and survival. Acute injection of either of them,
administered daily and before the onset of the disease, significantly prolonged
the survival of the transgenic mice.
PMID: 16546757 [PubMed - indexed for MEDLINE]
7: Amyotroph Lateral Scler. 2006 Mar;7(1):46-56.
No association of DYNC1H1 with sporadic ALS in a case-control study of a
northern European derived population: a tagging SNP approach.
Shah PR, Ahmad-Annuar A, Ahmadi KR, Russ C, Sapp PC, Horvitz HR, Brown RH Jr,
Goldstein DB, Fisher EM.
Department of Neurodegenerative Disease, Institute of Neurology, London, UK.
The cytoplasmic dynein-dynactin complex has been implicated in the aetiology of
motor neuron degeneration in both mouse models and human forms of motor neuron
disease. We have previously shown that mutations in the cytoplasmic dynein 1
heavy chain 1 gene (Dync1h1) are causal in a mouse model of late-onset motor
neuron degeneration but have found no association of the homologous sites in
human DYNC1H1 with human motor neuron disease. Here we extend these analyses to
investigate the DYNC1H1 genomic locus to determine if it is associated with
sporadic amyotrophic lateral sclerosis (ALS) in a northern European-derived
population. Among the 16 single nucleotide polymorphisms (SNPs) we examined,
just two SNPs (rs2251644 and rs941793) were sufficient to tag the majority of
haplotypic variation (r2 > or = 0.85) and these were tested in a case-control
association study with 266 North American sporadic ALS patients and 225 matched
controls. We found no association between genetic variation at DYNC1H1 and
sporadic ALS (rs2251644; p = 0.538, rs941793; p = 0.204, haplotype; p = 0.956).
In addition we investigated patterns of diversity at DYNC1H1 in Japanese and
Cameroonian populations to establish the evolutionary history for this gene and
observed reduced genetic diversity in the northern Europeans suggestive of
selection at this locus.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
PMID: 16546759 [PubMed - indexed for MEDLINE]
6: Amyotroph Lateral Scler. 2006 Mar;7(1):61-3.
A4V superoxide dismutase mutation in apparently sporadic ALS resembling
neuralgic amyotrophy.
Weiss MD, Ravits JM, Schuman N, Carter GT.
Department of Neurology, University of Washington Medical Center, Seattle 98195,
USA. mdweiss@u.washington.edu
We report a case of apparently sporadic amyotrophic lateral sclerosis (ALS) in a
young pregnant woman presenting subacutely with severe left shoulder pain
followed by progressive weakness and wasting of the left arm, mimicking
neuralgic amyotrophy. She was later found electrophysiologically to have
widespread denervation involving more than just the arm and an alanine for
valine substitution in codon 4 (A4V) in the gene for Cu/Zn superoxide dismutase
1 (SOD1). Her case illustrates that pain on initial presentation, though
uncommon, does not exclude a diagnosis of ALS.
Publication Types:
Case Reports
PMID: 16546761 [PubMed - indexed for MEDLINE]
5: Neurology. 2006 Mar 28;66(6):852-6.
Axonal damage markers in cerebrospinal fluid are increased in ALS.
Brettschneider J, Petzold A, Sussmuth SD, Ludolph AC, Tumani H.
Department of Neurology, University of Ulm, Ulm, Germany.
OBJECTIVE: To test whether biomarkers for axonal degeneration correlated with
clinical subtypes and were of use in predicting progression of ALS. METHODS:
Patients with ALS (n = 69), patients with Alzheimer disease (AD; n = 73), and
age-matched controls (n = 33) were included in this prospective study. CSF
levels of tau protein and neurofilaments (NfHSMI35) were measured using ELISA.
In 49 patients with ALS, follow-up data were available (median follow-up 7
months). RESULTS: CSF levels of NfHSMI35 were five times higher in patients with
ALS (1.7 ng/mL) than in controls (0.3 ng/mL, p < 0.001) and 10 times higher than
in patients with AD (0.14 ng/mL, p < 0.001). NfHSMI35 values were also higher in
patients with upper motor neuron-dominant ALS than in patients with typical ALS
(upper motor neuron + lower motor neuron) at p = 0.02. Values of NfHSMI35 were
higher in ALS of more rapid progression. The values of NfH and tau did not
correlate with CSF protein content. CONCLUSIONS: The authors propose that axonal
damage markers in CSF may discriminate between subtypes of ALS and that they
could be used as markers for therapeutic trials. CSF NfH was superior to tau in
these discriminations.
Publication Types:
Comparative Study
PMID: 16567701 [PubMed - indexed for MEDLINE]
4: Indian J Pediatr. 2006 Mar;73(3):225-6.
Juvenile amyotrophic lateral sclerosis.
Aggarwal A, Shashiraj.
Department of Pediatrics, University College of Medical Sciences, Guru Tegh
Bahadur Hospital, Delhi, India. aanju@bol.net.in.
Juvenile amytrophic lateral sclerosis (JALS) is a type of motor neuron disease
presenting before 25 years of age. It is characterized by a combination of upper
and lower motor signs. It may be familial or sporadic. We are reporting a
sporadic case of JALS with onset of symptoms at 4 years of age. Diagnostic
criteria and a brief review of literature are presented.
Publication Types:
Case Reports
PMID: 16567917 [PubMed - indexed for MEDLINE]
3: Rinsho Shinkeigaku. 2006 Mar;46(3):193-8.
[The most probable clinical diagnosis to the applicants for the intractable
disease registration of Parkinson's disease, spinocerebellar degeneration and
amyotrophic lateral sclerosis]
Narita Y, Taniguchi A, Kuzuhara S.
Medical Care Networking Center, Mie University Hospital.
Amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and
spinocerebellar degeneration (SCD) are included in the 45 intractable diseases"
acknowledged by the Ministry of Health, Labour and Welfare of Japan. The
registration of applicants is based on the attending doctors' diagnosis, and
medical costs of registered patients are covered by the government. However, the
accuracy of the diagnoses has not been investigated previously. The aim of the
present study is to investigate the accuracy of the diagnoses of patients
registered as PD, SCD and ALS in Mie prefecture of Japan. The study design was
cross-sectional and the survey was carried out using an anonymous questionnaire.
We asked the attending doctors the most probable clinical diagnosis in each
applicant for PD, SCD or ALS at the annual renewal of application form of the
specified diseases by the Ministry. The questionnaires were sent to the 57
neurologists in 20 general hospitals and 2 neurology clinics in Mie prefecture,
Japan. The survey was carried out from July to September, 2003. For each
disorder (PD, ALS, SCD), the accuracy rates were calculated as the ratio of the
number of patients with the most probable diagnosis of the consistent disease to
the number of all patients registered each disease. Questionnaires on 678
patients replied from 31 neurologists, 27 of whom were the neurology specialists
approved by the Japanese Society of Neurology, were retrieved and analyzed. They
covered 41.1% of the total registered PD cases, 45.4% of total SCD cases, and
54.0% of total ALS cases in Mie prefecture. The final clinical diagnosis were
made by such specialists in 641 cases (94.5%). The accuracy rate of PD was 97.3%
for all degenerative parkinsonisms and 90.2% for idiopathic PD, 96.0% for SCD,
and 77.8% for typical ALS and 81.5% for ALS and Kennedy-Alter-Sung syndrome.
Although the most probable diagnoses were performed by the attending physicians
without verification by other raters, the accuracy rates were excellently high
in these diseases, partly because most of the attending physicians were
neurology specialists. The relatively low accuracy rate in ALS may be caused
partly by the difficulty in differentiating it from spine diseases, neuropathies
or myopathies at the early stage of the disease when the patients had been
registered, or by inclusion of other motor neuron diseases such as
Kennedy-Alter-Sung syndrome.
Publication Types:
English Abstract
PMID: 16642929 [PubMed - indexed for MEDLINE]
2: Neurochem Res. 2006 Mar;31(3):321-31. Epub 2006 May 3.
Implementation of X-ray fluorescence microscopy for investigation of elemental
abnormalities in amyotrophic lateral sclerosis.
Tomik B, Chwiej J, Szczerbowska-Boruchowska M, Lankosz M, Wojcik S, Adamek D,
Falkenberg G, Bohic S, Simionovici A, Stegowski Z, Szczudlik A.
Institute of Neurology, Jagiellonian University Medical College, Krakow, Poland.
The abnormalities of metallochemical reactions may contribute to the
pathogenesis of Amyotrophic Lateral Sclerosis (ALS). In the present work, an
investigation of the elemental composition of the gray matter, nerve cells and
white matter from spinal cord tissues representing three ALS cases and five
non-ALS controls was performed. This was done with the use of the synchrotron
microbeam X-ray fluorescence technique (micro-SRXRF). The following elements
were detected in the tissue sections: P, S, Cl, K, Ca, Fe, Cu, Zn and Br. A
higher accumulation of Cl, K, Ca, Zn and Br was observed in the nerve cell
bodies than in the surrounding tissue. Contrary to all other elements, Zn
accumulation was lower in the white matter areas than in the gray matter ones.
The results of quantitative analysis showed that there were no general
abnormalities in the elemental accumulation between the ALS and the control
group. However, for individual ALS cases such abnormalities were observed for
the nerve cells. We also demonstrated differences in the elemental accumulation
between the analyzed ALS cases.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16733809 [PubMed - indexed for MEDLINE]
1: P R Health Sci J. 2006 Mar;25(1):51-66.
Are there causal relationships between the development of the inflammatory diseases amyotrophic lateral sclerosis and asthma?
Menendez A, Kuffler D.
Dept of Pediatrics, University of Puerto Rico.
Amyotrophic lateral sclerosis (ALS) and asthma are inflammatory diseases. ALS is a fatal progressive, neurodegenerative disease with inflammation around the upper and lower motor neurons leading to their degeneration, muscle atrophy, paralysis, and death. Asthma is a chronic inflammatory disease with reversible airway obstruction and nonspecific airway hyper-reactivity. The local release of sensory neuropeptides from capsaicin-sensitive primary afferents causes motor neuron pathophysiology and airway inflammation and hyper-reactivity. While there is no cure for ALS, asthma is managed according to its symptoms and severity, to decrease the symptoms, improve pulmonary function, and reduce morbidity. To determine whether understanding asthma may provide insights into how to clinically deal with ALS, the authors examined the etiologies of ALS and asthma, and the factors that exacerbate the symptoms. Although no direct correlations were found, the similar multifactorial triggers, and the critical roles of neuronal inflammation, suggest that one or more exists.
Publication Types:
Review
PMID: 16883679 [PubMed - indexed for MEDLINE]
