38: Parkinsonism Relat Disord. 2006 Jun;12(5):327-9. Epub 2006 Feb 3.
Amyotrophic lateral sclerosis in an Italian professional soccer player.
Vanacore N, Binazzi A, Bottazzi M, Belli S.
National Centre of Epidemiology, Surveillance and Health Promotion, National
Institute of Health, Via Giano Della Bella, 34, 00161 Rome, Italy.
vanacore@iss.it
Amyotrophic lateral sclerosis (ALS) is a rare devastating neurodegenerative
disease of unknown etiology. Two recent epidemiological studies showed a high
risk for ALS among Italian male soccer players. We present the clinical and
occupational history of an Italian professional soccer player affected by
sporadic ALS. The early onset of ALS (45 years), the bulbar form, the playing
position (midfielder) and the duration of the job as professional soccer (17
years) are four characteristics of this patient that are in good agreement with
the findings in the previous epidemiological studies. This patient reports the
frequent consumption of fructose 1,6 biphosphate, extracts of suprarenal cortex,
crotetamide and cropropamide, and dietary supplements (branched chain amino
acids and creatine) during his playing career. Some hypotheses have been
proposed to explain this high excess of deaths for ALS among soccer players: (a)
vigorous physical activity; (b) soccer specific trauma or microtrauma; (c) use
of illegal toxic substances or chronic misuse of drugs (most often
anti-inflammatory) and dietary supplements; and (d) exposure to pesticides used
on playing fields. The overall available clinical and epidemiological evidence
supports the possible relation between the specific occupational environment
(soccer) and the occurrence of ALS in this patient.
Publication Types:
Case Reports
PMID: 16459125 [PubMed - indexed for MEDLINE]
37: Psychol Med. 2006 Jun;36(6):865-75. Epub 2006 Feb 21.
Predictors of psychological distress in carers of people with amyotrophic lateral sclerosis: a longitudinal study.
Goldstein LH, Atkins L, Landau S, Brown R, Leigh PN.
Department of Psychology, Institute of Psychiatry, King's College London, UK.
l.goldstein@iop.kcl.ac.uk
BACKGROUND: The majority of people providing informal care for people with
amyotrophic lateral sclerosis (ALS) are spouses. This prospective study set out
to examine changes in and predictors of psychological distress in spouse carers
of people with ALS. METHOD: Fifty spouse carers of people with ALS underwent an
initial interview and at least 21 underwent two further interviews, at median
intervals of approximately 5-6 months. They rated the functional impact of their
partner's ALS on everyday activities and everyday cognitive, emotional and
behavioural changes that might have occurred in the person with ALS. They also
rated their own social support and marital relationship, and completed measures
of mood, burden and strain. The ALS Severity Scale was also completed for their
partner with ALS. RESULTS: Over time, carers' psychological distress (a global
measure combining mood, burden and strain) increased significantly. Initially
carers' psychological distress was best predicted by the psychosocial impact of
their spouse/partners' ALS, the extent to which their partner demonstrated
emotional lability and how many other people were considered as dependents of
the carer. Subsequently, carer distress was best predicted by an initial measure
of negative social support and by their initial satisfaction with their social
relationships. CONCLUSIONS: Despite the significant physical impairment
associated with ALS, psychosocial factors appear important in determining short-
and longer-term psychological well-being in carers of people with ALS and may
help clinicians to predict which carers are likely to experience psychological
difficulties as part of their caring role.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16490122 [PubMed - indexed for MEDLINE]
36: Muscle Nerve. 2006 Jun;33(6):771-7.
Comment in:
Muscle Nerve. 2006 Jun;33(6):713-4.
Acute inflammatory demyelinating polyneuropathy: contribution of a dispersed
distal compound muscle action potential to electrodiagnosis.
Cleland JC, Malik K, Thaisetthawatkul P, Herrmann DN, Logigian EL.
Department of Neurology, University of Rochester Medical Center, 601 Elmwood
Avenue, Box 673, Rochester, New York 14642, USA.
James_Cleland@urmc.rochester.edu
Prolonged duration of the distal compound muscle action potential (DCMAP)
("DCMAP dispersion") is useful in the electrodiagnosis of chronic inflammatory
demyelinating polyneuropathy (CIDP) with good specificity in distinguishing CIDP
from amyotrophic lateral sclerosis (ALS) and diabetic polyneuropathy, but its
role in the electrodiagnosis of acute inflammatory demyelinating polyneuropathy
(AIDP) is unclear. This study addresses this issue by determining the optimal
cutoff for DCMAP duration using receiver operating characteristic (ROC) analysis
in 207 motor nerves from 53 clinically defined AIDP patients compared to 148
motor nerves from 55 ALS patients. We also determined whether the presence of
DCMAP dispersion improves the sensitivity of four of the most sensitive
published sets of electrodiagnostic criteria for AIDP. Using the ROC-derived
optimal DCMAP duration cutoff of 8.5 ms, DCMAP dispersion was found in at least
one motor nerve in 66% of subjects with AIDP compared to 9% of subjects with
ALS. DCMAP dispersion improved the sensitivity of the four tested criteria sets
to 76%-87% from 43%-77%. Moreover, of 13 AIDP patients who met none of the four
published criteria sets, 5 (38%) had at least one dispersed DCMAP. These
findings indicate that the presence of DCMAP dispersion adds electrodiagnostic
sensitivity to the currently published criteria sets, while maintaining
reasonably high specificity against a prototypical disorder of the primary motor
neuron with axon loss.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16523511 [PubMed - indexed for MEDLINE]
35: Neurosci Lett. 2006 Jun 19;401(1-2):25-9. Epub 2006 Mar 15.
Unilateral induction of progenitors in the spinal cord of hSOD1(G93A) transgenic
rats correlates with an asymmetrical hind limb paralysis.
de Hemptinne I, Boucherie C, Pochet R, Bantubungi K, Schiffmann SN, Maloteaux
JM, Hermans E.
Laboratoire de Pharmacologie Experimentale, Universite catholique de Louvain,
Av. Hippocrate 54.10, B-1200 Brussels, Belgium.
Transgenic rats expressing a mutated form of the human Cu/Zn superoxide
dismutase (hSOD1(G93A)) develop an amyotrophic lateral sclerosis (ALS)-like
phenotype, including motor neurone degeneration and reactive gliosis in the
spinal cord. This study aimed at examining the presence of endogenous neural
progenitors in the lumbar spinal cord of these rats at the end-stage of the
disease. Immunohistochemical data clearly demonstrated the induced expression of
the stem cell factor reported as a chemoattractant and survival factor for
neural stem cells as well as nestin (neuro-epithelial stem cell intermediate
filament) in the spinal cord sections. While the stem cell factor
immunolabelling appeared diffuse throughout the gray matter, nestin labelling
was restricted to clusters within the ventral horn. Interestingly, as paralysis
regularly develops asymmetrically, induction of nestin was only detected on the
ipsilateral side of the predominant symptoms. Finally, immunohistochemical
detection of the stem cell factor receptor (c-Kit) revealed its specific
induction which coincided with nestin immunolabelling. Together, these results
are indicative of endogenous recruitment of neural progenitors within lesioned
tissues and could support the development of treatments involving endogenous or
exogenous stem cells.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16540243 [PubMed - indexed for MEDLINE]
34: Exp Cell Res. 2006 Jun 10;312(10):1890-8. Epub 2006 Mar 29.
XIAP decreases caspase-12 cleavage and calpain activity in spinal cord of ALS
transgenic mice.
Wootz H, Hansson I, Korhonen L, Lindholm D.
Department of Neuroscience, Unit of Neurobiology, Uppsala University, Biomedical Centre, Box 587, S-751 23 Uppsala, Sweden.
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons. The cause for nerve cell demise is not clear but involves activation of the caspase family of cysteine proteases. We have shown that ER stress and caspase-12 activation occur in ALS transgenic mice carrying the mutant copper/zinc superoxide dismutase (SOD1) gene. In these mice, we found that the antiapoptotic proteins, X-linked Inhibitor of Apoptosis Protein (XIAP) and the related protein, MIAP2 were decreased. To study the role of this, we generated double transgenic mice expressing XIAP in ALS spinal cord neurons using the Thy1 promoter. Overexpression of XIAP inhibited caspase-12 cleavage and reduced calpain activity in the ALS mice. XIAP also reduced the breakdown of calpastatin that is an inhibitor of calpain. In the double transgenic mice, life span was increased by about 12%. These data support the view that XIAP has beneficial effects in ALS and extends survival. The neuroprotective effect of XIAP involves inhibition of caspases and the stabilization of the calpastatin/calpain system that is altered in the ALS mice.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16566922 [PubMed - indexed for MEDLINE]
33: Neurobiol Dis. 2006 Jun;22(3):599-610. Epub 2006 Apr 17.
Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal
cord pathology in the G93A SOD1 mouse model of ALS.
Browne SE, Yang L, DiMauro JP, Fuller SW, Licata SC, Beal MF.
Department of Neurology and Neuroscience, Weill Medical College of Cornell
University, 525 E. 68th Street, A-502, New York, NY 10021, USA.
sub2001@med.cornell.edu
Multiple cell death pathways are implicated in the etiology of amyotrophic lateral sclerosis (ALS), but the cause of the characteristic motor neuron degeneration remains unknown. To determine whether CNS metabolic defects are critical for ALS pathogenesis, we examined the temporal evolution of energetic defects in the G93A SOD1 mouse model of familial ALS. [14C]-2-deoxyglucose in vivo autoradiography in G93A mice showed that glucose utilization is impaired in components of the corticospinal and bulbospinal motor tracts prior to either pathologic or bioenergetic changes in the spinal cord. This was accompanied by significant depletions in cortical ATP content in presymptomatic mice, which was partially ameliorated by creatine administration. Findings suggest that
bioenergetic defects are involved in the initial stages of mSOD1-induced toxicity in G93A mice and imply that the selective dysfunction and degeneration of spinal cord motor neurons in this model may be secondary to dysfunction within cerebral motor pathways.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
PMID: 16616851 [PubMed - indexed for MEDLINE]
32: Ann Neurol. 2006 Jun;59(6):980-3.
Is prostaglandin E(2) a pathogenic factor in amyotrophic lateral sclerosis?
Almer G, Kikuchi H, Teismann P, Przedborski S.
Department of Neurology, Columbia University, New York, NY 10032, USA.
OBJECTIVE: To elucidate the role of cyclooxygenase-1 (Cox1) and prostaglandin
E(2) in ALS neurodegeneration. METHODS: Mutation in superoxide dismutase-1 is a
cause of the fatal paralytic disorder amyotrophic lateral sclerosis. Inhibition
of cyclooxygenase-2 (Cox-2) in transgenic mice expressing an amyotrophic lateral
sclerosis-linked superoxide dismutase-1 mutation led to the idea that prostaglandin E(2), the main synthetic product of Cox-2, is pathogenic in amyotrophic lateral sclerosis. RESULTS: Herein, we show by genetic intervention that prostaglandin E(2) in the spinal cord is mainly produced by Cox-1, and that ablation of Cox-1 fails to attenuate neurodegeneration. INTERPRETATION: The previously documented role of Cox-2 in ALS neurodegeneration in this particular mouse model occurs through a mechanism independent of prostaglandin E(2). Furthermore, plans to use selective Cox-1 inhibitors for neuroprotection in ALS are unlikely to be fruitful. Ann Neurol 2006.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
PMID: 16619237 [PubMed - indexed for MEDLINE]
31: Muscle Nerve. 2006 Jul;34(1):34-43.
The stimulus-response curve and motor unit variability in normal subjects and subjects with amyotrophic lateral sclerosis.
Henderson RD, Ridall GR, Pettitt AN, McCombe PA, Daube JR.
Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane,
Queensland 4029, Australia. robert_henderson@health.qld.gov.au
The behavior and stability of motor units (MUs) in response to electrical stimulation of different intensities can be assessed with the stimulus-response curve, which is a graphical representation of the size of the compound muscle action potential (CMAP) in relation to stimulus intensity. To examine MU characteristics across the whole stimulus range, the variability of CMAP responses to electrical stimulation, and the differences that occur between normal and disease states, the curve was studied in 11 normal subjects and 16 subjects with amyotrophic lateral sclerosis (ALS). In normal subjects, the curve
showed a gradual increase in CMAP size with increasing stimulus intensity,
although one or two discrete steps were sometimes observed in the upper half of
the curve, indicating the activation of large MUs at higher intensities. In ALS subjects, large discrete steps, due to loss of MUs and collateral sprouting, were frequently present. Variability of the CMAP responses was greater than baseline variability, indicating variability of MU responses, and at certain levels this variability was up to 100 microVms. The stimulus-response curve shows differences between normal and ALS subjects and provides information on MU activation and variability throughout the curve.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
PMID: 16634059 [PubMed - indexed for MEDLINE]
30: Neuropathol Appl Neurobiol. 2006 Jun;32(3):341-3.
Comment on:
Neuropathol Appl Neurobiol. 2005 Aug;31(4):345-53.
Commentary on: Return of the cycad hypothesis--does the amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) of Guam have new implications for global health?
Wilson J, Shaw CA.
Publication Types:
Comment
Letter
PMID: 16640652 [PubMed - indexed for MEDLINE]
29: Radiology. 2006 Jun;239(3):831-8. Epub 2006 Apr 26.
Amyotrophic lateral sclerosis: diffusion-tensor and chemical shift MR imaging at 3.0 T.
Wang S, Poptani H, Woo JH, Desiderio LM, Elman LB, McCluskey LF, Krejza J, Melhem ER.
Department of Radiology, Division of Neuroradiology, Hospital of the University of Pennsylvania, 3400 Spruce St, Dulles 2, Philadelphia, PA 19104, USA.
PURPOSE: To prospectively determine whether diffusion-tensor magnetic resonance (MR) imaging in conjunction with two-dimensional chemical shift imaging can assist in identifying upper motor neuron involvement and whether disease severity and duration can be predicted based on imaging parameters in patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Fifteen patients with ALS (12 men, three women; mean age, 57.3 years) with clinical evidence of upper motor neuron involvement and 10 healthy control subjects (five men and five women; mean age, 49.4 years) were studied. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured from the corticospinal tracts at the level of the internal capsule. Average N-acetylaspartate (NAA)/creatine-phosphocreatine (Cr) and NAA/choline-containing compounds (Cho) ratios were calculated from the precentral gyrus. Student t test, multiple linear regression analysis, and Spearman correlation coefficients were employed to quantify relationships between imaging and clinical parameters. RESULTS: Patients with ALS exhibited significantly reduced FA values and NAA/Cr and NAA/Cho ratios compared with values in control subjects (P<.05) for both affected and nonaffected sides of the brain. ADC was elevated significantly in the affected side (P<.05) and was an independent predictor of disease duration after adjusting for age; however, FA values and NAA/Cr ratios for the affected side were even stronger predictors of disease duration. Moderate but statistically significant correlation was found between the FA values for the affected side and the ALS Functional Rating Scale Revised (ALSFRS-R) score (r=0.51, P<.05). The NAA/Cr ratio also correlated with both the ALSFRS-R and upper motor neuron scores (r=0.50 and 0.54, respectively; P<.05). CONCLUSION: Diffusion-tensor and two-dimensional chemical shift MR imaging spectroscopy can be used to identify upper motor neuron involvement and predict disease duration in patients with ALS. Copyright (c) RSNA, 2006.
Publication Types:
Comparative Study
PMID: 16641339 [PubMed - indexed for MEDLINE]
27: Neurosci Lett. 2006 Jun 19;401(1-2):40-3. Epub 2006 May 2.
A TAT-modified fusion protein efficiently penetrates mouse hypoglossal nuclei from transduced ependyma.
Alisky JM, Xia H, Davidson BL.
Program in Gene Therapy, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA. alisky.joseph@marshfieldclinic.org
Future gene therapy for brainstem variant amyotrophic lateral sclerosis may be technically difficult if gene therapy vectors are injected near vital cardiorespiratory centers or if large portions of the tongue and pharyngeal muscles must be peripherally injected for retrograde transport of vectors to motor neurons. In this study we show that it is possible to deliver recombinant proteins to the hypoglossal nuclei without brainstem or muscle injections, by taking advantage of enhanced uptake of fusion proteins containing the protein transduction domain from the human immunodeficiency virus TAT protein.
Adenoviral vectors expressing either TAT-modified or native beta-glucuronidase
(beta-gluc) were injected into the lateral cerebral ventricles of mice, transducing ventricular epithelium down to the level of the obex in the brainstem. There was significant uptake into the hypoglossal nuclei of TAT-modified but not native beta-glucuronidase. The TAT-modified beta-gluc appeared to encompass half or more of the hypoglossal nuclei as visualized by retrograde labeling with cholera toxin subunit b in adjacent sections.
TAT-modification of gene products may allow a relatively non-invasive approach
to brainstem gene therapy via cerebroventricular injection.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16650576 [PubMed - indexed for MEDLINE]
26: Clin Neurophysiol. 2006 Jun;117(6):1260-5. Epub 2006 May 5.
F wave study in amyotrophic lateral sclerosis: assessment of balance between upper and lower motor neuron involvement.
Argyriou AA, Polychronopoulos P, Talelli P, Chroni E.
EMG Laboratory, Department of Neurology, The University of Patras Medical School, P.O. Box 1045, 26504 Rion-Patras, Greece.
OBJECTIVE: We sought to record significant F wave variable changes in ALS patients having no advanced disease. Furthermore, an interpretation of these F wave abnormalities in the context of upper (UMN) and lower motor neuron (LMN) dysfunction was attempted. METHODS: Standard motor and sensory conduction study was performed to the ulnar nerves of 23 patients with ALS (13 males and 10 females with mean age 67.2+/-5.3 years), having a clinically predominant LMN syndrome. A series of 40 electrical stimuli were also delivered to both their ulnar nerves in order to obtain F waves. The following F wave variables were estimated: F persistence, F wave latency, amplitude, duration and F chronodispersion. Twenty-three, age-and gender-matched healthy volunteers served as controls. RESULTS: Both the distal and proximal ulnar a-CMAPs (P=0.001) and the MCV (P=0.014) values were significantly decreased in patients, than the
controls. The sensory conduction study was normal. The ulnar F wave persistence
in the ALS patients was significantly lower than that of the controls (P=0.0007). The mean (P=0.0001), minimal (P=0.0001) and maximal (P=0.0001) F wave latencies were significantly prolonged, the F wave amplitudes (P=0.0001) were significantly higher and the F wave chronodispersion (P=0.014) was significantly increased in the patients than the controls. CONCLUSIONS: Significant F wave abnormalities occur in patients with ALS, even those patients having no advanced disease. Increased F wave amplitudes combined with low persistence is a pattern consistent with ALS. SIGNIFICANCE: Our results show that patients with ALS having predominantly LMN involvement also have
electrophysiological UMN dysfunction.
PMID: 16678483 [PubMed - indexed for MEDLINE]
25: Muscle Nerve. 2006 Jun;33(6):713-4.
Comment on:
Muscle Nerve. 2006 Jun;33(6):771-7.
Too many solutions for one problem.
van Dijk JG.
Publication Types:
Comment
Editorial
PMID: 16688723 [PubMed - indexed for MEDLINE]
24: J Geriatr Psychiatry Neurol. 2006 Jun;19(2):114-7.
IL-15 is elevated in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.
Rentzos M, Zoga M, Paraskevas GP, Kapaki E, Rombos A, Nikolaou C, Tsoutsou A,
Vassilopoulos D.
Department of Neurology, Aeginition Hospital-Athens Medical School. mrentzos@med.uoa.gr
Interleukin-15 is a novel proinflammatory cytokine. It is produced by activated blood monocytes, macrophages, and glial cells. The objective of our study was to assess the role of interleukin-15 as a marker of increased proinflammatory activity in patients with Alzheimer's disease and frontotemporal dementia. We measured cerebrospinal fluid interleukin-15 levels in 17 patients with Alzheimer's disease and 7 patients with frontotemporal dementia in comparison with 17 patients with amyotrophic lateral sclerosis and 15 patients with Parkinson's disease. Patients with Alzheimer's disease and frontotemporal dementia had significantly higher cerebrospinal fluid interleukin-15 levels compared with patients with noninflammatory neurological diseases (P < .05 and P
< .01, respectively). In Alzheimer's disease, a significant positive correlation was noted between interleukin-15 levels and age of onset (R = .48, P = .05). Our findings suggest that interleukin-15 may be implicated in the pathophysiology of Alzheimer's disease and frontotemporal dementia.
Publication Types:
Comparative Study
PMID: 16690997 [PubMed - indexed for MEDLINE]
23: J Comp Neurol. 2006 Jul 20;497(3):468-88.
The adult neural stem and progenitor cell niche is altered in amyotrophic lateral sclerosis mouse brain.
Liu Z, Martin LJ.
Department of Pathology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Amyotrophic lateral sclerosis (ALS) is a fatal adult human disease caused by motor neuron degeneration. Stem cell therapy might be a treatment for ALS. The adult mammalian forebrain has neural stem cells (NSCs) and neural progenito
cells (NPCs) in the anterior subventricular zone (SVZa), rostral migratory stream (RMS), olfactory bulb (OB) core, and dentate gyrus (DG). These cells could be used to rescue or replace degenerating upper and lower motor neurons through endogenous recruitment or autologous/allogenic transplantation. We evaluated the competency of forebrain NSCs and NPCs in transgenic (tg) mice harboring human mutant superoxide dismutase-1 (mSOD1), a model of ALS. Tg human wild-type SOD1 (wtSOD1) mice and non-tg mice were controls. Bromodeoxyuridine (BrdU) labeling of cells, a marker for cell proliferation and other events, was reduced in a niche-specific pattern in presymptomatic and symptomatic mice, with the SVZa having greater reductions than the RMS, OB, and DG. Different NSC and NPC complements were evaluated by localizing nestin, neural cell adhesion molecule, distalless-2 transcription factor, vimentin, and glial fibrillary
acidic protein. In symptomatic mice, NSC markers were reduced, whereas NPC
markers were unchanged or elevated. Neurogenesis was preserved in symptomatic
mSOD1 mice. NSC/NPC competence assessment in vitro revealed that mSOD1 SVZa
cells had the ability to proliferate and form neurospheres but had an impaired
response to mitogen stimulation. We conclude that adult mSOD1 ALS mice have
abnormalities in forebrain NSCs, but the essential features of NSC/NPCs remained
in presymptomatic and symptomatic mice. (c) 2006 Wiley-Liss, Inc.
Publication Types:
Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16736475 [PubMed - indexed for MEDLINE]
22: Brain Res. 2006 Jun 22;1096(1):180-95. Epub 2006 Jun 5.
Ascending neuropathology in the CNS of a mutant SOD1 mouse model of amyotrophic
lateral sclerosis.
Leichsenring A, Linnartz B, Zhu XR, Lubbert H, Stichel CC.
Department of Animal Physiology, Ruhr-University of Bochum, Germany.
Transgenic mice expressing a mutated human Cu/Zn superoxide dismutase (SOD1)
gene develop a motor neuron disease similar to familial amyotrophic lateral sclerosis (FALS). While the histopathology and the inflammatory reactions in the spinal cord of these mice are well described, their spatiotemporal extension into brain areas and the relationship between degenerative and inflammatory events remain obscure. In the present study, we investigated the time course and extent of degenerative changes and inflammatory reactions in the CNS during progression of the disease in a transgenic FALS model, the SOD1-G93A mouse with histological and immunohistochemical methods. Compared to non-transgenic littermates, the SOD1-G93A transgenics developed widespread degeneration in both motor and extra-motor regions up to telencephalic regions, including the cerebral cortex but sparing distinct regions like the striatum and hippocampus. We provide evidence that these degenerative processes are accompanied by intense inflammatory reactions in the brain, which spatiotemporally correlate with degeneration and comprise besides strong astro- and microgliotic reactions also an influx of peripheral immune cells such as T-lymphocytes and dendritic cells. Both degeneration and inflammatory reactions spread caudocranially, starting at
2 months in the spinal cord and reaching the telencephalon at 5 months of age.
Since the corticospinal tract lacked any signs of degeneration, we conclude that
the upper and the lower motor neurons degenerate independently of each other.
PMID: 16737688 [PubMed - indexed for MEDLINE]
21: Lancet Neurol. 2006 Jun;5(6):476.
Can ketogenic diet slow progression of ALS?
Siva N.
Publication Types:
News
PMID: 16739298 [PubMed - indexed for MEDLINE]
20: Amyotroph Lateral Scler. 2006 Jun;7(2):80-5.
Factors correlated with NPPV use in ALS.
Jackson CE, Lovitt S, Gowda N, Anderson F, Miller RG.
University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio,
TX 78229-3900, USA. jacksonce@uthscsa.edu
In spite of emerging evidence of therapeutic benefit from non-invasive positive
pressure ventilation (NPPV), only a minority of ALS patients use this therapy.
We examined factors which correlate with use of NPPV in ALS patients. Data were
analyzed from the ALS CARE Database on the use of NPPV in patients with FVC less
than 50% of predicted and probable or definite ALS based on modified El Escorial
criteria. Of the 403 eligible patients, 146 (36%) used NPPV. NPPV compliance was
strongly correlated with symptoms of dyspnea and orthopnea as well as with the
use of other therapies including PEG tubes, augmentative speech devices, and
riluzole. Male gender and household income >$80,000 were also associated with
higher NPPV use. There was no correlation between age, race, type of insurance,
forced vital capacity, duration of symptoms, ALSFRS-R, caregiver burden or
quality of life with the use of NPPV. These data suggest that the factors which
are most closely associated with NPPV utilization are symptomatic orthopnea and
dyspnea. The findings may be useful in designing prospective studies to examine
the factors which might explain the underutilization of NPPV and the optimal use
of this treatment.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16753971 [PubMed - indexed for MEDLINE]
19: Amyotroph Lateral Scler. 2006 Jun;7(2):86-95.
Predictors and course of elective long-term mechanical ventilation: A prospective study of ALS patients.
Rabkin JG, Albert SM, Tider T, Del Bene ML, O'Sullivan I, Rowland LP, Mitsumoto
H.
Department of Psychiatry, Columbia University Medical Center, and New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA. jgr1@columbia.edu
We sought to characterize ALS patients who opt for tracheostomy and long-term mechanical ventilation (LTMV) and compare them with respect to medical, psychiatric, and psychosocial measures to patients who declined tracheostomy and died. We studied 72 ALS patients who were identified as hospice-eligible. They were assessed monthly until the endpoint of death or tracheostomy. LTMV patients continued to be followed for up to 55 months. The spouse or other caregiver was similarly interviewed and followed. Medical and psychiatric evaluations were conducted, in addition to self-reported depressive symptoms, future orientation, attitudes about hastened death, religious beliefs, and quality of life. Global cognitive capacity was assessed by caregivers. Fourteen patients chose LTMV; 58 died without LTMV. At study entry, those who later chose LTMV were younger, more had young children, had more education, and higher household incomes on average. Although their physical conditions were similar, they reported higher levels of
optimism including belief in imminent cure, and more positive appraisals of their ability to function in daily life, their physical health and overall life satisfaction. At study entry, none who later chose LTMV were clinically depressed, compared to 26% of those who later refused LTMV, and their mean scores on the Beck Depression Inventory were in the "not depressed" range while the mean for patients who later died was in the "probable depression" range. Fourteen percent of patients who later chose LTMV were reported by caregivers to have had at least mild cognitive problems, compared to 49% of those who later died. After an average of 33 months on LTMV, only about half retained high levels of optimism and enjoyment of daily life, independent of residence (home vs. facility). Two patients expressed interest in hastening death but none had asked to terminate ventilation despite disease progression. However, half identified future circumstances that would render life intolerable. At last contact with caregivers, only one LTMV patient was reported to have major cognitive impairment. While reporting substantial emotional burden after LTMV, most but not all spousal caregivers continued to express satisfaction with care-giving. Our findings suggest that the choice of LTMV was not about desperation (although it may involve unrealistic expectations of cure by some), ignorance, or inability to make wishes clear during a chaotic dying period. Rather, LTMV choice was consistent with a sustained sense that life was worth living in any way possible, at least for some time and within certain boundaries. ALS clinicians will need to recognize this motivation and provide appropriate clinical education to both patient and family.
Publication Types:
Research Support, N.I.H., Extramural
PMID: 16753972 [PubMed - indexed for MEDLINE]
18: Amyotroph Lateral Scler. 2006 Jun;7(2):96-9.
Evaluation of sham non-invasive ventilation for randomized, controlled trials in ALS.
Gruis KL, Brown DL, Weatherwax KJ, Feldman EL, Chervin RD.
University of Michigan Health System, Department of Neurology, 1324 Taubman Center, 032221-500 E. Medical Center Drive, Ann Arbor, MI 48109, USA. kgruis@umich.edu
Non-invasive positive pressure ventilation (NIV) treatment of advanced respiratory insufficiency prolongs survival in ALS. To investigate the critical question of whether earlier initiation of NIV might provide additional benefit, a randomized trial with an appropriate placebo is needed. This study evaluated sub-therapeutic (sham) continuous positive airway pressure as a potential placebo. In a single-blind design, 40 ALS patients with forced vital capacity>50% were randomized to receive 30 seconds (s) of either active NIV,
with 8 cm H2O inspiratory and 4 cm H2O expiratory pressure, or sham NIV with<1
cm of H2O continuous positive airway pressure at the mask. A questionnaire was then used to assess whether subjects thought that they had received a "real" or "pretend" treatment trial. The subjects' median age was 60.5 years, and 38% were female. Twelve of 20 subjects (60%) who received active NIV and 7 (35%) of the 20 subjects who received sham thought that they had tried the active treatment (p = 0.11). Only 8 (20%) of all subjects were confident about their determination that they had received "real" or "pretend" NIV. Thus, sub-therapeutic (sham) continuous positive airway pressure is a promising
placebo control for NIV trials in ALS.
Publication Types:
Randomized Controlled Trial
PMID: 16753973 [PubMed - indexed for MEDLINE]
17: Amyotroph Lateral Scler. 2006 Jun;7(2):107-11.
A clinical pilot study: high frequency chest wall oscillation airway clearance in patients with amyotrophic lateral sclerosis.
Chaisson KM, Walsh S, Simmons Z, Vender RL.
Division of Pulmonary, Allergy and Critical Care Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Respiratory complications are common in patients with amyotrophic lateral sclerosis (ALS) with respiratory failure representing the most common cause of death. Ineffective airway clearance resultant from deficient cough frequently contributes to these abnormalities. We sought to evaluate the effectiveness of high frequency chest wall oscillation (HFCWO) administered through the Vest Airway Clearance System when added to standard care in preventing pulmonary complications and prolonging the time to death in patients with ALS. This is a single center study performed at the Penn State Milton S. Hershey Medical Center (HMC). Nine patients with a diagnosis of ALS and concurrently receiving non-invasive ventilatory support with bi-level positive airway pressure (BiPAP)
were recruited from the outpatient clinic at HMC. Four patients were randomized to receive standard care and five patients to receive standard care plus the addition of HFCWO administered twice-daily for 15 min duration. Longitudinal assessments of oxyhemoglobin saturation, forced vital capacity (FVC), and adverse events were obtained until time of death. Pulmonary complications of atelectasis, pneumonia, hospitalization for a respiratory-related abnormality, and tracheostomy with mechanical ventilation were monitored throughout the study duration. No differences were observed between treatment groups in relation to the rate of decline in FVC. The addition of HFCWO airway clearance failed to improve time to death compared to standard treatment alone (340 days +/- 247 vs. 470 days +/- 241; p = 0.26). The random allocation of HFCWO airway clearance to patients with ALS concomitantly receiving BiPAP failed to attain any significant clinical benefits in relation to either loss of lung function or mortality. This study does not exclude the potential benefit of HFCWO in select patients with ALS who have coexistent pulmonary diseases, pre-existent mucus-related pulmonary complications, or less severe levels of respiratory muscle weakness.
Publication Types:
Randomized Controlled Trial
PMID: 16753975 [PubMed - indexed for MEDLINE]
16: Amyotroph Lateral Scler. 2006 Jun;7(2):119-22.
VEGF C2578A polymorphism does not contribute to amyotrophic lateral sclerosis susceptibility in sporadic Chinese patients.
Zhang Y, Zhang H, Fu Y, Song H, Wang L, Zhang J, Fan D.
Department of Neurology, Peking University Third Hospital, 49 North Garden Road,
Haidian District, Beijing 100083, China.
A linkage and association of the VEGF (vascular endothelial growth factor) C2578A polymorphism and amyotrophic lateral sclerosis (ALS) has been found in some studies. We analysed the C2578A polymorphism in sporadic ALS patients from a Chinese population. The polymorphism was analysed in 115 patients and 200 healthy individuals by amplifying across position 2705 to 2494 of the promoter region of the VEGF gene. It was found that the frequency of the allele A was 24% in ALS patients and 28% in healthy individuals (p = 0.264). Comparing the background of this polymorphism in healthy individuals between Chinese and Caucasians, significant decreases were found in the frequencies of the A/A genotype and allele A (p(s)<0.001). We concluded that VEGF C2578A polymorphism did not confer a susceptibility to sporadic Chinese ALS patients, which was in disagreement with that reported previously in Caucasian populations and might be ascribed to the different genetic background between Chinese and Caucasians.
PMID: 16753977 [PubMed - indexed for MEDLINE]
15: Amyotroph Lateral Scler. 2006 Jun;7(2):123-5.
Monozygotic twins discordant for primary lateral sclerosis.
Sorenson EJ.
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
The genetics of the motor neuron diseases are becoming increasingly important. The relationship of primary lateral sclerosis and amyotrophic lateral sclerosis remains debated. Here a pair of monozygotic twins discordant for primary lateral sclerosis is presented. This monozygotic twin pair suggests that environmental factors were most relevant to this subject's development of primary lateral sclerosis. Their life history suggests very similar social and professional exposures without any apparent distinctions.
Publication Types:
Case Reports
PMID: 16753978 [PubMed - indexed for MEDLINE]
14: Amyotroph Lateral Scler. 2006 Jun;7(2):126-7; discussion 127.
Comment on:
Amyotroph Lateral Scler Other Motor Neuron Disord. 2005 Mar;6(1):3-4.
New ideas for therapy in ALS: critical considerations.
Beghi E, Bendotti C, Mennini T.
Publication Types:
Comment
Letter
PMID: 16753979 [PubMed - indexed for MEDLINE]
13: Clin Neurophysiol. 2006 Jul;117(7):1444-8. Epub 2006 Jun 9.
Distal excitability changes in motor axons in amyotrophic lateral sclerosis.
Nakata M, Kuwabara S, Kanai K, Misawa S, Tamura N, Sawai S, Hattori T, Bostock H.
Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1,
Inohana, Chuo-ku, Chiba, 260-8670, Japan. ellora@oak.dti.ne.jp
OBJECTIVE: Previous axonal excitability studies in amyotrophic lateral sclerosis (ALS) have suggested that impaired potassium channel function could be responsible for the generation of fasciculations, but the ectopic activity arises predominantly from the motor nerve terminals. This study tested the hypothesis that dysfunction of potassium channels is more pronounced in the more distal parts of axons. METHODS: Threshold electrotonus was used to compare accommodation at the motor point of abductor pollicis brevis, and at the wrist portion of the median nerve, between 22 patients with ALS and 19 normal
subjects. As target responses for motor point stimulation, movement-related potentials were recorded using an accelerometer. RESULTS: Compared to normal subjects, ALS patients showed greater threshold changes to depolarizing conditioning currents at both the motor point and wrist, suggesting less accommodation by potassium currents. Differences in the threshold electrotonus curves between the normal and ALS groups were much more prominent at the motor point than at the wrist. CONCLUSIONS: In ALS, axonal potassium channels are impaired more prominently in distal portions of axons than at the nerve trunk, and this is consistent with evidence that fasciculations mostly arise from the nerve terminals. SIGNIFICANCE: Excitability testing at the motor point provides additional information about the pathophysiology of ALS.
Publication Types:
Comparative Study
PMID: 16765084 [PubMed - indexed for MEDLINE]
12: Neurology. 2006 Jun 13;66(11):1770-1.
Tau protein hyperphosphorylation in sporadic ALS with cognitive impairment.
Strong MJ, Yang W, Strong WL, Leystra-Lantz C, Jaffe H, Pant HC.
Cell Biology Research Group, Robart's Research Institute, London, Ontario,
Canada. mstrong@uwo.ca
The authors have characterized frontal cortical tau protein in cognitively intact (4) and cognitively impaired (ALSci, 4) ALS patients and compared it with control (2) or Alzheimer disease (AD, 1)- derived tau. The authors observed expression of both 3R and 4R tau isoforms; increased insoluble tau protein; phosphatase resistance; and hyperphosphorylation at T175, S208, and S210. Soluble tau from both AD and ALSci was also phosphorylated at S237. Tau hyperphosphorylation is associated with ALS.
Publication Types:
Controlled Clinical Trial
Research Support, Non-U.S. Gov't
PMID: 16769962 [PubMed - indexed for MEDLINE]
11: Neurology. 2006 Jun 13;66(11):1786-7; author reply 1786-7.
Comment on:
Neurology. 2006 Jan 10;66(1):88-92.
Pentoxifylline in ALS: a double-blind, randomized, multicenter, placebo-controlled trial.
Levin BJ, Thompson G, Mitsumoto LH, Kaufmann P.
Publication Types:
Comment
Letter
Research Support, Non-U.S. Gov't
PMID: 16769973 [PubMed - indexed for MEDLINE]
10: Neurology. 2006 Jun 27;66(12):1929-31.
Possible gender-dependent association of vascular endothelial growth factor (VEGF) gene and ALS.
Fernandez-Santiago R, Sharma M, Mueller JC, Gohlke H, Illig T, Anneser J, Munch C, Ludolph A, Kamm C, Gasser T.
Department of Neurodegenerative Diseases, Hertie-Institute for Brain Research,
Eberhard-Karls University, Tuebingen, Germany.
Individuals homozygous for haplotypes -2578-A/-1154-A/-634-G or -2578-A/-1154-G/-634-G in the promoter/5'UTR of the VEGF gene have a 1.8-fold increased risk of ALS in several European populations. We did not observe any significant association with single markers, or haplotype pairs, in a German sample of 580 sporadic ALS patients and 628 controls. However, the promoter SNP-1154 (rs1570360) was associated with affection status in women (p = 0.036), suggesting that the VEGF effect may be dependent on the sex ratio of the sample.
Publication Types:
Controlled Clinical Trial
PMID: 16801663 [PubMed - indexed for MEDLINE]
9: Neuro Endocrinol Lett. 2006 Jun;27(3):355-8.
Reductions in plasma prolactin during acute erythropoietin administration.
Markianos M, Kosmidis ML, Sfagos C.
Athens University Medical School, Eginition Hospital, Department of Neurology,
Vas Sophias 74, Athens 11528, Greece. markian@otenet.gr
OBJECTIVES: The presence of erythropoietin (EPO) and its receptors in several central nervous system regions indicates additional functions beside its hematopoietic role. Preclinical data suggest that it may slow down the process of neuronal loss, and that EPO may cause dopamine release, and thus influence hormone release, especially prolactin. This possibility has not yet been studied in humans. METHODS: During a clinical trial on possible protective effects in patients with amyotrophic lateral sclerosis (ALS), we studied the acute effects of EPO administration on prolactin, the release of which is under tonic
inhibition of hypothalamic-pituitary dopaminergic activity. Prolactin as well as EPO levels were estimated in blood samples taken every 30 min over 2 hours after administration of 3000 IU EPO i.v. in seven male and four female patients with ALS. RESULTS: The baseline PRL levels of the 11 patients were all within normal range (4.5-10.5 ng/ml). EPO administration caused a significant reduction in prolactin levels, maximal at 60 min after administration. Reductions in PRL were not related to EPO dose (IU per kg body weight), or to duration of illness. CONCLUSIONS: The findings indicate that EPO promotes dopamine release in humans, and is consistent with preclinical data showing that EPO releases dopamine from rat striatal slices. Previous reports showed that dopaminergic neurons express EPO receptors, which exert a facilitating action on dopamine release, and the present data indicate that this may hold true in humans.
Publication Types:
Clinical Trial
PMID: 16816832 [PubMed - indexed for MEDLINE]
8: J Neurovirol. 2006 Jun;12(3):229-34.
Expression of Toll-like receptor 3 in the human cerebellar cortex in rabies,
herpes simplex encephalitis, and other neurological diseases.
Jackson AC, Rossiter JP, Lafon M.
Unite de Neuroimmunologie Virale, Departement de Neuroscience, Institut Pasteur,
Paris, France.
There is recent in vitro evidence that human neurons express the innate immune
response receptor, Toll-like receptor-3 (TLR-3), and that expression is enhanced
in viral infections. The authors examined the immunohistochemical expression of
TLR-3 in the cerebellar cortex of postmortem human brains. Purkinje cells were
found to express TLR-3 in all cases of rabies (4 of 4) and herpes simplex
encephalitis (2 of 2) as well as in cases of amyotrophic lateral sclerosis (1 of
2), stroke (1 of 2), and Alzheimer's disease (3 of 3). In cases of viral
infection, direct viral infection was not necessary for enhanced neuronal TLR-3
expression, suggesting that soluble factors likely play an important role in
inducing TLR-3 expression. In addition to neurons, occasional Bergmann glia
expressed TLR-3 in some cases. This study has provided evidence that human brain
neurons can express TLR-3 in vivo and suggests that neurons may play an
important role in initiating an inflammatory reaction in a variety of
neurological diseases.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16877304 [PubMed - indexed for MEDLINE]
7: Rinsho Shinkeigaku. 2006 Jun;46(6):390-4.
Inoue M, Kojima Y, Satoi H, Makino F, Kanda M, Shibasaki H.
Department of Neurology, Ijinkai Takeda General Hospital.
A 70-year-old Japanese male farmer, born and living in Kyoto prefecture, developed gait disturbance, with tendency to fall at age 68, and muscle atrophy and weakness of the right shoulder and arm a year and half later. All symptoms have been progressive ever since. The patient manifested marked dementia, parkinsonism associated with limitation of ocular movements in all directions with slow saccade, loss of startle reflex, asymmetric muscle atrophy and weakness in shoulder girdles and upper limbs with hyperreflexia, and positive Babinski reflexes. The needle electromyogram showed evidence of active denervation. Brain MRI showed cortical atrophy in the frontal and temporal lobes, and midbrain tegmentum. Cerebral blood flow image on SPECT suggested hypoperfusion in the frontal, temporal and parietal cortices and basal ganglia bilaterally. Thus, it is most likely that the present case suffered from clinical features of amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy at the same time. Relation to the ALS/Parkinsonism/Dementia complex reported from Kii peninsula and Guam was discussed.
Publication Types:
Case Reports
English Abstract
PMID: 16986699 [PubMed - indexed for MEDLINE]
6: Rinsho Shinkeigaku. 2006 Jun;46(6):381-9.
Terao S, Miura N, Osano Y, Adachi K, Sobue G.
Division of General Medicine, Department of Internal Medicine, Aichi Medical
University School of Medicine.
OBJECTIVE: To clarify the characteristics of elderly-onset amyotrophic lateral sclerosis (ALS). SUBJECTS AND METHODS: We analyzed the pattern of progression of clinical symptoms and respiratory dysfunction in 26 sporadic ALS patients (19 men, 7 women; mean age 73.2 +/- 6.0 years) with onset at age 65 years or older (E-ALS). We compared the results with those of 28 ALS patients (20 men, 8 women; 53.7 +/- 7.6 years) with younger onset ALS (Y-ALS). RESULTS: Among E-ALS patients, the bulbar palsy type (BP) was the most common (11 patients, 42%) followed by the respiratory failure type (RF) (7 patients, 27%). In contrast, upper extremity type (UE) was the most common (14 patients, 50%) in Y-ALS patients. Mean vital capacity percentage (%VC) at the initial examination was 71.1 +/- 20.4% (vital capacity (VC): 2.12 +/- 0.85 L) in all E-ALS patients, 64.5 +/- 14.5% in BP, 58.1 +/- 5.1% in RF, 94.4 +/- 11.1% in lower extremity type (LE), and 73.9 +/- 30.2% in UE. In all Y-ALS patients, %VC was 90.1 +/- 14.0% (2.94 +/- 0.57 L). The initial % VC value in E-ALS was significantly lower than that in Y-ALS (p < 0.01). VC was lower in RF and BP among E-ALS patients. It was also lower in BP E-ALS patients than in BP Y-ALS patients. Mean period from initial symptom until first examination was significantly shorter in RF in both groups, followed by BP. Twenty-two patients with E-ALS and 26 with Y-ALS
died from respiratory failure. Four patients with E-ALS and 2 with Y-ALS required a mechanical ventilator. The mean period until death or ventilation support was 20.9 +/- 10.4 months in E-ALS, and 38.8 +/- 21.1 months in Y-ALS. Significantly shorter survival was observed in E-ALS than Y-ALS (p<0.01). In E-ALS patients, the mean period until death or ventilation support was 21.4 +/- 9.1 months with BP, 10.3 +/- 7.6 months with RF, 29.8 +/- 4.0 months with LE, and 29.3 +/- 5.4 months with UE. This period was significantly shorter in RF patients in both groups, followed by BP patients (p< 0.05, 0.01). Time until death or ventilation support was significantly shorter in BP and UE patients with E-ALS than in those with Y-ALS (p< 0.05). CONCLUSION: In regard to the progression of respiratory function deterioration, early % VC was lower in E-ALS than in Y-ALS patients, and the period until VC fell below 1 L was shorter. The period until death was particularly short in elderly BP and RF patients, suggesting the possibility that the duration until death from respiratory failure is shorter in E-ALS, because of a decrease in respiratory reverse
capacity that accompanies age.
Publication Types:
Comparative Study
English Abstract
PMID: 16986698 [PubMed - indexed for MEDLINE]
5: Rinsho Shinkeigaku. 2006 Jun;46(6):377-80.
Shimohata T, Yanagawa K, Tanaka K, Nishizawa M.
Department of Neurology, Brain Research Institute, Niigata University.
To investigate the longitudinal changes in age at onset and the initial symptom of patients with sporadic amyotrophic lateral sclerosis (ALS), we performed a single hospital-based retrospective study over the past 38 years. A total of 280 sporadic ALS patients (169 men and 111 women) hospitalized in our department between 1965 and 2003 were investigated in this study. The clinical features including age at onset and the initial symptom of these patients were obtained from medical records. All the patients underwent an intensive diagnostic evaluation including electrophysiological examination, laboratory examinations of blood and cerebrospinal fluid, and neuroimagings of the brain and spinal cord to exclude other conditions similar to ALS. The mean age at onset was 58.3 +/- 11.3 years and age at onset significantly increased at the rate of 0.459 years
per year(r = 0.406, p< 0.001). The percentage of patients whose age at onset was > or = 70 years has increased from 3.0% (1980-1984) to 31.1% (2000-2003). To investigate the initial symptom of senile-onset ALS, patients whose age at onset was > or = 70 years were analyzed. The percentages of bulbar palsy-onset patients with onset in terms of age were 62.5% (30/48 patients; > or = 70 years) and 23.3% (54/232 patients; <70 years). The odd ratio for bulbar palsy was 5.40 (95% confidence interval, 2.79-10.44). Taken together, our study demonstrates that the ratio of senile-onset ALS has significantly increased, and that there were more bulbar palsy-onset patients among the patients.
Publication Types:
English Abstract
PMID: 16986697 [PubMed - indexed for MEDLINE]
4: No To Shinkei. 2006 Aug;58(8):709-13.
Takayasu N, Ito K, Kondo M, Muranishi M, Nagakane Y, Nakagawa M.
Department of Neurology, Research Institute for Neurological Diseases and
Geriatrics, Kyoto Prefectural University of Medicine, Japan.
A 76-year-old right-handed woman complained of speech disturbance and difficulity of singing was admitted to our hospital. Examination showed motor aphasia and mild cognitive impairment. After she was discharged, dementia and weakness of the extremities had rapidly progressed. She was readmitted eight month after the first visit, when she was almost abulic, her skeletal and bulbar muscles were remarkably atrophic, and hyperreflexia of the extremities were seen. Electromyographcal study showed neurogenic pattern. These findings suggest amyotrophic lateral sclerosis (ALS) with dementia. Pathological findings were atrophy at the anterior horn of the spinal cord. The brain was diffusely atrophic. The extent of degenerative change was not lateralized. This case is a discriminative type of ALS with dementia, that its first symptom is motor
aphasia.
Publication Types:
Case Reports
English Abstract
PMID: 16986678 [PubMed - indexed for MEDLINE]
3: Electromyogr Clin Neurophysiol. 2006 May-Jun;46(3):145-8.
Quantitative thermal sensory testing in patients with amyotrophic lateral
sclerosis using reaction time exclusive method of levels (MLE).
Deepika J, Manvir B, Sumit S, Vinay G, Trilochan S, Garima S, Padma MV, Madhuri B.
Department of Neurology, All India Institute of Medical Sciences, Neurosciences Centre, Ansari Nagar, New Delhi, India. d_joshi73@yahoo.co.in
OBJECTIVES: Quantitative thermal sensory testing (QST) systems are used for the noninvasive quantification of sensory nerve function including the small myelinated and unmyelinated fibres which is not provided by classical sensory nerve conduction studies. Although Amyotrophic Lateral Sclerosis (ALS) is a pure motor disorder, nevetheless involvement of the sensory fires has been reported occasionally by various techniques. In the present study Reaction Time Exclusive Method of Levels (MLE) was used to detect somatic small fibre involvement in ALS patients with no sensory abnomalities on routine NCS. MATERIAL & METHOD: Twenty patients of clinically definite ALS, were evaluated with QST using the reaction time exclusive method of Levels (MLE) for detecting the thresholds of cold sensation (CS) and warm sensation (WS). They were compared with 20 age matched controls. RESULTS: No abnormalities were detected in the thresholds for CS and WS in patients with ALS as compared to the controls. CONCLUSION: Thus ALS is essentially a pure motor disorder with normal thermal thresholds as revealed by QST.
Publication Types:
Comparative Study
PMID: 16918198 [PubMed - indexed for MEDLINE]
2: Eur J Neurosci. 2006 Jul;24(2):387-99.
Cell culture models to investigate the selective vulnerability of motoneuronal
mitochondria to familial ALS-linked G93ASOD1.
Raimondi A, Mangolini A, Rizzardini M, Tartari S, Massari S, Bendotti C, Francolini M, Borgese N, Cantoni L, Pietrini G.
Department of Pharmacology, School of Medicine, Center of Excellence on
Neurodegenerative Diseases, University of Milano, Consiglio Nazionale delle
Ricerche, CNR, Institute of Neuroscience, Milano, Italy.
Mitochondrial damage induced by superoxide dismutase (SOD1) mutants has been proposed to have a causative role in the selective degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). In order to investigate the basis of the tissue specificity of mutant SOD1 we compared the effect of the continuous expression of wild-type or mutant (G93A) human SOD1 on mitochondrial morphology in the NSC-34 motoneuronal-like, the N18TG2 neuroblastoma and the non-neuronal
Madin-Darby Canine Kidney (MDCK) cell lines. Morphological alterations of mitochondria were observed in NSC-34 expressing the G93A mutant (NSC-G93A) but not the wild-type SOD1, whereas a ten-fold greater level of total expression of the mutant had no effect on mitochondria of non-motoneuronal cell lines. Fragmented network, swelling and cristae remodelling but not vacuolization of mitochondria or other intracellular organelles were observed only in NSC-G93A cells. The mitochondrial alterations were not explained by a preferential localization of the mutant within NSC-G93A mitochondria, as a higher amount of the mutant SOD1 was found in mitochondria of MDCK-G93A cells. Our results
suggest that mitochondrial vulnerability of motoneurons to G93ASOD1 is recapitulated in NSC-34 cells, and that peculiar features in network dynamics may account for the selective alterations of motoneuronal mitochondria.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16903849 [PubMed - indexed for MEDLINE]
1: Palliat Support Care. 2006 Jun;4(2):135-43.
Artificial nutrition and hydration at the end of life: ethics and evidence.
Ganzini L.
Department of Psychiatry and Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA. linda.ganzini@med.va.gov
The case of Terri Schiavo resulted in substantial media attention about the use of artificial nutrition and hydration (ANH) especially by percutaneous endoscopic gastrostomy (PEG). In this article, I review ethical and legal principles governing decisions to choose or forgo ANH at the end of life,
including issues of autonomy and decision-making capacity, similarities and differences between ANH and other medical treatments, the role of proxies when patients lack decision-making capacity, and the equivalence of withholding and withdrawing treatment. Evidence for palliative or life-sustaining benefits for ANH are reviewed in three disease processes: amyotrophic lateral sclerosis (ALS), cancer, and dementias, including Alzheimer's disease. Although more recent studies suggest a possible palliative role for ANH in ALS and terminal cancer, feeding tubes do not appear to prolong survival or increase comfort in advanced dementia of the Alzheimer's type.
Publication Types:
Review
PMID: 16903584 [PubMed - indexed for MEDLINE]
