Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ALS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMed1998

Kinetic studies with iodine-123-labeled serum amyloid P component in patients with systemic AA and AL amyloidosis and assessment of clinical value.

UNLABELLED: In systemic amyloidosis, widespread amyloid deposition interferes with organ function, frequently with fatal consequences. Diagnosis rests on demonstrating amyloid deposits in the tissues, traditionally with histology although scintigraphic imaging with radiolabeled serum amyloid P component (SAP) has lately been developed as a specific noninvasive alternative. We report a detailed analysis of the abnormal turnover of SAP in patients with systemic amyloidosis and an assessment of its clinical value. METHODS: Iodine-123-labeled human SAP (200 MBq) SAP was injected intravenously into 49 patients with histologically proven systemic AA- or AL- amyloidosis and in 7 control subjects. Plasma clearance and whole-body retention of labeled SAP were analyzed over 48 hr using plasma sampling, whole-body gamma camera imaging and measurement of radioactivity in the urine. The rate of SAP synthesis and interstitial exchange were determined, and the size of the amyloid compartment was compared with clinical estimates of whole-body amyloid load and patient survival. RESULTS: All plasma time-activity curves were biphasic. In comparison with control subjects, patients with amyloidosis showed significantly faster plasma disappearance [4-hr value: AA 48% +/- 18%, AL 45% +/- 15% versus 65% +/- 8% (p < 0.05)], higher total-body retention 48 hr p.i. [AA 74% +/- 14%, AL 73% +/- 17% versus 46% +/- 15% (p < 0.01)] and especially higher extravascular retention 48 hr p.i. [AA 59% +/- 16%, AL 58% +/- 19% versus 30% +/- 14% (p < 0.01)]. Extravascular retention correlated with clinical estimation of the amyloid load. If extravascular retention values in patients with AL amyloidosis were over 60%, survival was decreased (median 4 versus 23 mo, p < 0.001). Markedly increased interstitial exchange rates were present in amyloidosis (AA 64 +/- 61, AL 50 +/- 37 versus 18 +/- 8 mg/hr), whereas the SAP synthesis rate did not differ from the control values (AA 5.0 +/- 3.0, AL 5.5 +/- 3.2 versus 4.5 +/- 1.4 mg/hr). CONCLUSION: The presence of systemic amyloidosis is characterized by accelerated initial clearance of 123I-SAP from the plasma and increased interstitial exchange rate and extravascular retention. These findings reflect reversible binding of radiolabeled SAP to amyloid deposits and provide clinically useful information for diagnosis, monitoring of therapy and prognosis in patients with systemic amyloidosis.

Adult↗
PubMed2003

Percutaneous endoscopic gastrostomy (PEG) in patients with ALS and bulbar dysfunction.

OBJECTIVE: To compare characteristics of ALS patients with and without percutaneous endoscopic gastrostomy (PEG). METHODS: Using the ALS Patient Care Database, data from patients with and without PEG with ALS Functional Rating Scale-bulbar subscale (ALSFRSb) scores < or = 5 were analyzed; follow-up data were also collected. RESULTS: PEG use was markedly increased with declining ALSFRSb scores. Demographics did not differ, but ALSFRS composite scores and bulbar and arm subscale scores were lower (P<0.0001). PEG patients used significantly more assistive devices, multidisciplinary care, home care nurses and aides, had more frequent physician and emergency department visits and hospital admissions (P<0.0001), and had lower health status based on the mini-SIP scale (P=0.0047). PEG use varied greatly between ALS centers. In the follow-up study, positive impact of PEG was noted in 79 % of PEG patients but in only 37.5% of patients who received PEG later, based on a small number of patients. PEG use showed no survival benefit. CONCLUSION: Patients did not receive PEG until bulbar function was severely reduced and overall ALS had markedly progressed. PEG may have been performed too late to demonstrate survival benefits. Aggressive proactive nutritional management appears essential in patients with ALS. To determine whether PEG provides benefits, it must be performed at earlier stages of the disease and prospectively studied.

Amyotrophic Lateral Sclerosis↗
PubMed2005

Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS: studies with [11C]flumazenil PET.

Five to ten percent of amyotrophic lateral sclerosis (ALS) cases are associated with mutations of the superoxide dismutase-1 (SOD1) gene, and the 'D90A' mutation is associated with a unique phenotype and markedly slower disease progression (mean survival time 14 years). Relative sparing of inhibitory cortical neuronal circuits might be one mechanism contributing to the slower progression in patients homozygous for the D90A mutation (homD90A). The GABA(A) receptor PET ligand [11C]flumazenil has demonstrated motor and extra-motor cortical changes in sporadic ALS. In this study, we used [11C]flumazenil PET to explore differences in the pattern of cortical involvement between sporadic and genetically homogeneous ALS groups. Twenty-four sporadic ALS (sALS) and 10 homD90A patients underwent [11C]flumazenil PET of the brain. In addition, two subjects homozygous for the D90A mutation, but without symptoms or signs ('pre-symptomatic', psD90A), also underwent imaging. Results for each group were compared with those for 24 healthy controls of similar age. Decreases in the binding of [11C]flumazenil in the sALS group were found within premotor regions, motor cortex and posterior motor association areas. In the homD90A group of ALS patients, however, decreases were concentrated in the left fronto-temporal junction and anterior cingulate gyrus. In the two psD90A subjects, a small focus of reduced [11C]flumazenil binding at the left fronto-temporal junction was seen, similar to the pattern seen in the clinically affected patients. Within the sALS group, there was no statistically significant association between decreases in cortical [11C]flumazenil binding and revised ALS functional rating scale (ALSFRS-R score), whereas the upper motor neuron (UMN) score correlated with widespread and marked cortical decreases over the dominant hemisphere. In the homD90A group, there was a stronger statistical association between reduced cortical [11C]flumazenil binding and the ALSFRS-R, rather than the UMN, score, and also with disease duration. This study provides evidence for differences in the distribution of reduced cortical [11C]flumazenil binding in homD90A compared with sALS patients. We hypothesize that this might reflect differences in cortical neuronal vulnerability.

Adult↗
PubMed2006

A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia.

OBJECTIVE: To perform genetic linkage analysis in a family affected with ALS and frontotemporal dementia (FTD). METHODS: The authors performed a genome-wide linkage analysis of a four-generation, 50-member Scandinavian family in which five individuals were diagnosed with ALS and nine with FTD. Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed. Further analyses for ALS alone and FTD alone were performed. A parametric logarithm of odds (lod) score of 2.0 or greater was required for further study of a potential locus and crossover (haplotype) analysis. RESULTS: A new ALS-FTD locus was identified between markers D9s1870 and D9s1791 on human chromosome 9p21.3-p13.3. A maximum multipoint lod score of 3.00 was obtained between markers D9s1121 and D9s2154. Crossover analysis indicates this region covers approximately 21.8 cM, or 14Mb. CONCLUSIONS: A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD.

Aged↗
PubMed2026

Preclinical evaluation of AL-001, a gene therapy for wet age-related macular degeneration.

BACKGROUND: Frequent intravitreal administration of antivascular endothelial growth factor Vascular endothelial growth factor agents remains a major limitation in the management of wet age-related macular degeneration (wAMD). This study evaluated whether suprachoroidal delivery of an engineered recombinant adeno-associated viral (rAAV)-aflibercept vector could achieve sustained, targeted expression with improved efficacy and safety compared with intravitreal administration. METHODS: AL-001, an engineered rAAV vector expressing aflibercept, was developed and characterized. Its expression profile was first assessed in New Zealand white rabbits following suprachoroidal space (SCS) injection. Efficacy, pharmacokinetics, and safety were then evaluated in a nonhuman primate model of laser-induced choroidal neovascularization (CNV), comparing SCS and intravitreal (IVT) administration routes. RESULTS: AL-001 efficiently expressed aflibercept in relevant ocular cells in vitro. In rabbits, SCS administration produced sustained aflibercept levels in ocular tissues. In the nonhuman primate CNV model, a single SCS injection of AL-001 showed favorable efficacy to IVT injection and a notable mild inflammatory response. At week 4, grade IV lesion incidence was 0% (0/48) after SCS administration versus 14.3% (6/42) after IVT administration (absolute difference, -14.3 percentage points; 95% CI, 3.7%-27.8%; P = 0.0258). Throughout follow-up, mean leakage area and grade IV lesion incidence remained 0 with SCS, versus IVT peaks of approximately 0.3&#xa0;mm2 and 33.0%, respectively, declining to 0.03&#xa0;mm2 and 2.0% by day 100. Both the medium and high doses decreased pathological vascular leakage and subretinal hyperreflective material. Vector administration preceded laser-induced CNV modeling, demonstrating that sustained intraocular aflibercept expression in the retina and choroid provided durable antiangiogenic protection. Pharmacokinetic analysis confirmed distinct ocular exposure profiles between routes, with viral genomes confined predominantly to the injected eye and no significant systemic accumulation. AL-001 was well tolerated, without sustained intraocular pressure elevation or severe ocular inflammation, and only mild-to-moderate treatment-emergent adverse events. Low pre-existing anti-AAV2 immunity and time-dependent neutralizing antibody responses postdosing, informing a translational model for patient stratification and redosing feasibility. CONCLUSION: Suprachoroidal administration of AL-001 is well tolerated and provides durable, targeted aflibercept expression with pronounced antiangiogenic efficacy. These results support AL-001 as a promising, long-acting therapeutic candidate for wAMD.

AAV↗
PubMed2003

Endothelial dysfunction precedes C-fiber abnormalities in primary (AL) amyloidosis.

Primary (AL; immunoglobulin light-chain associated) amyloidosis is characterized by the deposition of pathological proteins in the extracellular matrix of tissues and organs. Autonomic and sensory peripheral neuropathy is a common feature of this disorder. The pathogenesis of the neuropathy is poorly defined. The aims of this study were to investigate vascular and neural function in the cutaneous microcirculation of AL amyloidosis patients. Seven patients with AL amyloidosis and controls were studied. Acetylcholine and sodium nitroprusside were iontophoresed into the forearm skin. Endothelial, smooth muscle, and C-fiber-mediated cutaneous blood flow (CuBF) were recorded by laser Doppler flowmetry. Endothelial vasodilation in the forearm skin was attenuated in AL amyloidosis patients (p = 0.007). Maximum endothelium-mediated CuBF in the patient group was reduced (p = 0.047). No group differences could be detected in the C-fiber response or smooth muscle vasodilation (p value not significant). Maximum C-fiber and endothelium-independent CuBF did not differ between the two groups (p value not significant). Early in the disease, AL amyloidosis patients present with impaired endothelial function. At this stage, C-fiber and smooth muscle function are still preserved. These data suggest that endothelial abnormalities precede and may contribute to the pathogenesis of the neuropathy associated with AL amyloidosis.

Adult↗
PubMed2002

Characteristics and porcelain bond strength of (Ti,Al)N coating on dental alloys.

The effect of a novel titanium-aluminum nitride film, or (Ti,Al)N film, on the bond strength between a dental porcelain and two nickel-based dental alloy substrates was investigated. A thin layer of (Ti,Al)N film was deposited on flat metal samples using a reactive radio-frequency sputtering method. A uniform thickness of porcelain was applied to the film- coated metal samples. Metal-ceramic specimens were subjected to three-point bending, and failure loads were recorded. Bond strengths between the porcelain and (Ti,Al)N-coated metal alloys ranged from 159.0 +/- 11.7 N to 278.0 +/- 12.3 N. These values were significantly greater (p< 0.05) than bond strengths recorded for control samples that did not incorporate the (Ti,Al)N film. An electron probe microanalyzer with a line profile mode was used to characterize the interface between the (Ti,Al)N film and the porcelain. Results of this investigation suggest that the (Ti,Al)N film (1) increases the flexural bond strength between dental porcelain and nickel-based alloy substrates by permitting elemental diffusion, (2) interferes with the surface oxide formation that characteristically originates from the nickel-based metal alloy substrate, and (3) provides an appropriate oxide layer for porcelain application.

Alloys↗
PubMed1993

An analytical electron microscopic investigation of precipitation in an Al-Cu-Zn-Mg-Ag alloy.

The distribution, morphology, chemistry, and crystallography of the precipitates formed during aging of an Al-Cu-Zn-Mg-Ag alloy have been studied using analytical transmission electron microscopy. The first precipitates to appear during aging at 150 degrees C were thin hexagonal-shaped plate-like precipitates which formed on the (111)Al planes. These precipitates had a face-centred orthorhombic crystal structure and their composition was essentially CuAl2 although they contained a trace of silver. At peak hardness the microstructure consisted of the plate-like precipitates on (111)Al planes and theta' precipitates on (100)Al planes. Overaging resulted in the precipitation of equilibrium theta, CuAl2, which exhibited a lath morphology and an orientation-relationship with the matrix (210)Al magnitude of (110)gamma; (001)Al misoriented from (001)gamma by approximately 6 degrees. Prolonged overaging at 250 degrees C resulted in the formation of cuboid-shaped Al5(Cu,Zn)6Mg2 precipitates which had a cubic crystal structure and a cube:cube orientation-relationship with the matrix.

Alloys↗
PubMed1993

Motor unit estimation: reproducibility of the spike-triggered averaging technique in normal and ALS subjects.

Reproducibility of the spike-triggered averaging technique of motor unit estimation (MUE) was assessed in biceps-brachialis muscle in 10 normal subjects and 15 subjects with amyotrophic lateral sclerosis (ALS). MUE was calculated by dividing the compound muscle action potential by the mean amplitude of 15 surface motor unit potentials (S-MUPs) of low recruitment threshold. Averaged MUE values in normal subjects were higher than in ALS subjects, with few values overlapping. Differences between test and retest MUE values were not significant for either subject group. The relative differences between test-retest values were 45.3% for normal subjects and 32.6% for ALS subjects. Correlation coefficients between test and retest values were low (r = 0.07) for normal subjects when influential outlying points were removed, and higher (r = 0.65) for ALS subjects when individuals with MUE values within the normal range were removed. The higher correlation of test-retest MUE values in ALS subjects compared to normal subjects may be due to a greater probability of resampling among the smaller number of motor units in ALS subjects. In summary, the reproducibility and technical aspects of the spike-triggered averaging technique are similar to those reported for other MUE techniques.

Action Potentials↗
PubMed1995

Thenar motor unit number estimates using the multiple point stimulation technique: reproducibility studies in ALS patients and normal subjects.

Thenar motor unit number estimate (MUNE) reproducibility was assessed in 20 patients with amyotrophic lateral sclerosis (ALS) and 16 normal subjects using the multiple point stimulation (MPS) technique. The MUNE was calculated by dividing the thenar compound muscle action potential negative-peak (n-p) area by the mean n-p area of 10 lowest threshold, all-or-nothing, surface-recorded motor unit action potentials. Two trials (test-retest) were performed by the same examiner either on separate days or on the same day with new electrode placements. The mean test MUNE was 43.4 (SD: 35.9, range: 6-145) for ALS patients and 219.4 (SD: 80.8, range: 122-368) for normal subjects. Test-retest MUNE differences were not significant for ALS patients or normal subjects. The test-retest correlation coefficient (r) was 0.99 for ALS patients and 0.85 for normal subjects. The mean difference between test-retest values was 10% for ALS patients and 17% for normal subjects. Test-retest reproducibility of the thenar MUNE using the MPS technique is high in both ALS patients and normal subjects. The reliability of the MPS technique in estimating motor unit numbers may make it a useful outcome measure in following the course of patients with progressive lower motor neuron disease, especially those enrolled in experimental drug trials.

Action Potentials↗
PubMed2000

Effects of Al(3+) and related metals on membrane phase state and hydration: correlation with lipid oxidation.

The aim of the present study was to further understand how changes in membrane organization can lead to higher rates of lipid oxidation. We previously demonstrated that Al(3+), Sc(3+), Ga(3+), Be(2+), Y(3+), and La(3+) promote lipid packing and lateral phase separation. Using the probe Laurdan, we evaluated in liposomes if the higher rigidity of the membrane caused by Al(3+) can alter membrane phase state and/or hydration, and the relation of this effect to Al(3+)-stimulated lipid oxidation. In liposomes of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylserine, Al(3+) (10-100 microM) induced phase coexistence and displacement of T(m). In contrast, in liposomes of brain phosphatidylcholine and brain phosphatidylserine, Al(3+) (10-200 microM) did not affect membrane phase state but increased Laurdan generalized polarization (GP = -0. 04 and 0.09 in the absence and presence of 200 microM Al(3+), respectively). Sc(3+), Ga(3+), Be(2+), Y(3+), and La(3+) also increased GP values, with an effect equivalent to a decrease in membrane temperature between 10 and 20 degrees C. GP values in the presence of the cations were significantly correlated (r(2) = 0.98, P < 0.001) with their capacity to stimulate Fe(2+)-initiated lipid oxidation. Metal-promoted membrane dehydration did not correlate with ability to enhance lipid oxidation, indicating that dehydration of the phospholipid polar headgroup is not a mechanism involved in cation-mediated enhancement of Fe(2+)-initiated lipid oxidation. Results indicate that changes in membrane phospholipid phase state favoring the displacement to gel state can facilitate the propagation of lipid oxidation.

2-Naphthylamine↗
PubMed2000

Genetic mapping of a mouse modifier gene that can prevent ALS onset.

Mutations in the cytoplasmic Cu/Zn superoxide dismutase (SOD1) gene on human chromosome 21q22.1 cause 10-20% of familial amyotrophic lateral sclerosis (ALS) cases. The expression of the ALS phenotype in mice carrying the murine G86R SOD1 mutation is highly dependent upon the mouse genetic background. This is similar to the phenotypic variation observed in ALS patients containing identical SOD1 mutations. In the FVB/N background, mice expressing mG86R SOD1 develop an ALS phenotype at approximately 100 days. However, when these mice were bred into a mixed background of C57Bl6/129Sv, the onset of the ALS phenotype was delayed (143 days to >2 years). Using 129 polymorphic autosomal markers in a whole genome scan, we have identified a major genetic modifier locus with a maximum lod score of 5.07 on mouse chromosome 13 between D13mit36 and D13mit76. This 5- to 8-cM interval contains the spinal muscular atrophy (SMA)-associated gene Smn (survival motor neuron) and seven copies of Naip (neuronal apoptosis inhibitory protein), suggesting a potential link between SMA and ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Surface Acidity and Hydrophilicity of Coprecipitated Al(2)O(3)-SiO(2) Xerogels Prepared from Aluminium Nitrate Nonahydrate and Tetraethylorthosilicate.

Amorphous aluminosilicate xerogels with various chemical compositions were prepared by coprecipitation, and their surface acidity and hydrophilicity were investigated by NH(3) gas temperature programed desorption (TPD), water vapor adsorption-desorption isotherms, and (27)Al magic angle spinning nuclear magnetic resonance (MAS NMR). The xerogels were synthesized by adding conc. NH(4)OH to an ethanol solution of calculated amounts of aluminium nitrate nonahydrate and tetraethylorthosilicate, and calcined at 300 degrees C for 4 h. All the NH(3) TPD spectra of the xerogels showed similar asymmetric peak profiles at around 200 degrees C tailing to the higher temperature side. The amount of acidity evaluated from the peak area of the TPD spectra showed a maximum at around 10 mol% Al(2)O(3) composition. The change as a function of composition showed a good correlation with the total amount of four and five coordinated Al atoms in the xerogels deduced from the (27)Al MAS NMR spectra. The water vapor adsorption isotherms of the xerogels were all of type IV irrespective of the composition. The maximum amounts of water vapor adsorbed by these xerogels were about 600-700 ml(STP)/g and were relatively high compared with those for various other adsorbents reported so far. Since the thickness of the adsorbed water vapor layer of the xerogels in the low relative pressure region increased with increasing Al(2)O(3) content, the surface of the xerogels is considered to become more hydrophilic with increasing Al(2)O(3) content of the xerogels. Copyright 1999 Academic Press.

Journal Article↗
PubMed2000

Covalent Grafting of Ethylene Glycol into the Zn-Al-CO(3) Layered Double Hydroxide.

Zn-Al-CO(3) layered double hydroxide was synthesized at room temperature using a procedure reported elsewhere. After characterization, 0.5 g of the Zn-Al-CO(3) layered compound was reacted under air with 15 cm(3) of ethylene glycol at 80 degrees C for a period of 5 days. After washing with acetone and drying at 50 degrees C, the resulting white powder was characterized by X-ray powder diffraction, thermal analysis (simultaneous TG/DSC), elemental analysis (C, H, N, Al, and Zn content), and FTIR spectroscopy. All of the experimental data were consistent with the bidentade grafting of ethylene glycol into the interlayer surface of the Al-Zn double hydroxide. The stoichiometry obtained [Zn(0.66)Al(0.34)(OCH(2)CH(2)O)](OH)(0.34).0.4H(2)O] showed that all of the surface hydroxide groups were replaced by ethylene glycol through Al-(Zn)-O-C bonds. Carbonate could not be detected by FTIR, proving that OH(-) was probably the actual intercalated counteranion. Copyright 2000 Academic Press.

Journal Article↗
PubMed1997

Abnormal dephosphorylation effect on NMDA receptor regulation in ALS spinal cord.

Previous studies have demonstrated a significant reduction of N-methyl-D-aspartate (NMDA) receptor binding in spinal cord sections from patients who died with amyotrophic lateral sclerosis (ALS) compared to that in control patients. The reduction in NMDA receptor binding in ALS could be increased toward control values by treatment with phorbol ester, suggesting a role for receptor protein phosphorylation in this disorder. In the present study we have evaluated the time course of recovery of [3H]MK-801 binding following phorbol ester treatment to assess protein phosphatase activity in spinal cord sections from ALS and control subjects. Phorbol ester-stimulated changes in [3H]MK-801 binding returned to untreated values significantly faster in ALS tissue compared to control and could not be blocked by the coapplication of the protein phosphatase inhibitors sodium vanadate or sodium beta-D-glycerol phosphate. Okadaic acid coapplication blocked recovery in both ALS and control tissue at a concentration range at which phosphatase 2B (calcineurin) would likely be inhibited. The results suggest that abnormal levels or activity of protein phosphatases, including calcineurin, may be involved in the abnormal levels of NMDA receptors in ALS and may play some role in the pathogenesis of the disease.

Aged↗
PubMed1994

Effect of aluminium (Al) on brain mitochondrial monoamine oxidase-A (MAO-A) activity--an in vitro kinetic study.

Effect of aluminium (Al) on rat brain mitochondrial monoamine oxidase-A (MAO-A) was studied in vitro at three different pH (4.0, 7.4 and 9.0) values. The results have shown that Al is a non-competitive inhibitor for MAO-A. The data also showed that MAO-A inhibition by Al varies with free Al3+ concentration and different forms of Al under different pH conditions. Al altered the maximum velocity (Vmax) of MAO-A but did not affect substrate-enzyme affinity (Km). Al formed a strong chelation with the substrate (Kynuramine) (1:1).

Aluminum Compounds↗
PubMed1994

The effects of Al on the calcium currents in Helix neurons.

1. The effects of aluminium (Al) on calcium (Ca) currents were investigated by using the conventional two-electrode voltage clamp technique in Helix pomatia neurons. The peak amplitude, kinetics, and voltage dependence of activation and inactivation of the Ca currents were studied in the presence of 10(-5)-10(-3) M AlCl3, at pH 6. 2. Al prolonged the rising phase of the Ca currents and therefore increased the time to peak at each command voltage step used. 3. There was no significant influence of Al on the peak amplitude of the Ca currents, but the voltage dependence of the time to peak, activation, and inactivation of the Ca currents shifted to more positive potentials as a consequence of Al treatment. 4. The leak currents were not influenced by Al up to 1 mM, which was the maximal dose applied. 5. The results support the suggestion that Al may modify the Ca homeostasis and that it exerts a neurotoxic effect, at least in part, by modulation of the Ca current of the neuronal membrane.

Aluminum↗
PubMed1991

Involvement of Onuf's nucleus in ALS. Demonstration of intraneuronal conglomerate inclusions and Bunina bodies.

Onuf's nucleus of 3 ALS cases was examined histologically, morphometrically and for metal content. Case 1 showed conglomerate inclusions (CIs), cases 2 and 3 showed Bunina bodies in Onuf's nucleus. Electron microscopy showed that CIs were intracytoplasmic accumulations of 10 nm neurofilaments with discrete borders. Onuf's neurons in ALS showed a significant decrease (P less than 0.001) in the cytoplasmic, nuclear and nucleolar areas in comparison with neurons of age-matched controls and elderly controls. Metal analysis of the sacral spinal cords by alpha particle-excited X-ray fluorescence analysis (PIXE) showed relatively high Al levels in the ALS cases compared with controls. Morin staining revealed intense green fluorescence (indicating Al) in the nucleoli and cytoplasm of the CI-containing neurons, but not in the CIs themselves. The appearance of CIs or Bunina bodies and neuronal atrophy in Onuf's nucleus seems to indicate that this structure is also involved in the disease process of ALS, although it is less vulnerable than most other motor ganglia.

Adult↗