An exploratory study of serum creatinine levels in patients with amyotrophic lateral sclerosis

The etiology of amyotrophic lateral sclerosis (ALS) remains unknown, but existing data argue for a role of creatinine in ALS pathophysiology. Our aim is to clarify the correlation between serum creatinine and ALS in Chinese population. A total of 512 sporadic ALS (SALS) patients and 501 age- and gender-matched healthy controls were included. Revised ALS Functional Rating Scale (ALS-FRS-R) was used to assess the motor functional status of SALS patients. Survival analysis was performed using Kaplan–Meier method. Serum creatinine levels were significantly lower in SALS patients than in controls (p < 0.001). Patients with the second, the third and highest quartiles of creatinine levels had a significantly lower presence of ALS compared to those with the lowest quartile (p for trend <0.001). However, decreased presence of ALS was not found in the highest quartiles compared with the lowest quartiles in females. Sporadic ALS patients with different site of onset have similar serum creatinine levels, but underweight patients presented lower levels of serum creatinine. Patients with low serum creatinine levels are more likely to have severe motor impairment and low body mass index (BMI) values. This study demonstrates that SALS patients have lower serum creatinine levels than well-matched controls. Higher levels of serum creatinine are less likely to be associated with the presence of ALS in Chinese populations. Low serum creatinine levels may be related to severe motor impairment in SALS patients, after adjusting the confounding factor—BMI. However, serum creatinine has no deleterious impact on survival in ALS.     

EMMPRIN levels in serum of patients with amyotrophic lateral sclerosis

Iłżecka J. EMMPRIN levels in serum of patients with amyotrophic lateral sclerosis.
Acta Neurol Scand: 2011: 124: 424–428.
© 2011 John Wiley & Sons A/S. Objectives – There are evidence that extracellular matrix metalloproteinases (MMPs) may be implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS). The extracellular matrix metalloproteinase inducer (EMMPRIN) is said to increase the production of MMPs in cells. The aim of the study was to investigate serum EMMPRIN levels in patients with ALS. Materials and methods – The study included 50 patients with ALS and 50 patients from the control group. Serum EMMPRIN levels were measured using the enzyme‐linked immunosorbent method. Results – The study showed that EMMPRIN levels are significantly increased in the serum of the whole group of patients with ALS when compared to the control group and are significantly increased in patients with ALS with severe clinical state compared to patients with mild clinical state (P < 0.05). There was a significant correlation of serum EMMPRIN levels with severity of clinical state of patients with ALS (P < 0.05). Conclusion – The results indicate that EMMPRIN is implicated in pathophysiology of ALS and may be the marker of clinical state severity.     

Increased serum ferritin levels in amyotrophic lateral sclerosis (ALS) patients

Iron misregulation promotes oxidative stress, a proposed pathological mechanism in neurodegenerative disease. The aim of this study was to evaluate serum iron metabolism indicators in 60 amyotrophic lateral sclerosis (ALS) patients and 44 age matched controls. Serum ferritin levels were significantly increased in ALS patients compared to controls (p < 0.001), while no differences in the levels of serum iron, transferrin, iron saturation or total iron binding capacity were found. Likewise no differences in C reactive protein (CRP) or caeruloplasmin were detected, suggesting that the elevated ferritin levels in ALS did not merely indicate an acute phase response. The increased ferritin level may reflect a general increase in stored iron or be a consequence of ongoing muscle degeneration.     

Decreased serum-soluble TRAIL levels in patients with amyotrophic lateral sclerosis

Objectives –  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Previously, it was showed that apoptosis may play a role in the pathomechanisms of this disease. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with proapoptotic activity in the central nervous system. The aim of the study was to measure serum TRAIL levels in patients with ALS.
Materials and methods –  The study involved 25 patients with ALS and 20 controls. Serum TRAIL levels were performed by the enzyme-linked immunosorbent method.
Results –  Study showed that TRAIL levels were significantly decreased in the serum of patients with ALS compared with controls ( P  < 0.05). There was no significant correlation between serum TRAIL levels and clinical parameters of ALS ( P  > 0.05).
Conclusion –  A decrease in serum TRAIL levels in patients with ALS suggests that this cytokine may be implicated in the pathomechanisms of this disease.     

Elevation of serum heat-shock protein levels in amyotrophic lateral sclerosis

Heat-shock proteins (HSPs) have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). In this study, we aimed to examine whether the serum levels of HSPs (HSP27, HSP70, and HSP90) are altered in patients with ALS. We included 58 patients diagnosed with ALS and 85 control individuals. Serum HSP levels of patients and controls were determined using enzyme-linked immunosorbent assay. The serum levels of HSP70 and HSP90 were significantly higher in patients than in controls. In contrast, serum levels of HSP27 did not differ significantly between the patient and control groups. Moreover, serum levels of HSP70 and HSP90 in patients remained high throughout the duration of the disease. Taken together, our findings suggest that HSPs might have a role in ALS progression throughout the course of the disease. Further studies are needed to clarify the role of HSPs in the pathogenesis of ALS.     

Antineural antibodies in the serum of patients with amyotrophic lateral sclerosis

Sera from 12 patients with amyotrophic lateral sclerosis (ALS) and 18 controls were screened for antineural antibodies using immunoblotting. No consistent differences were detected between ALS patients and controls, although antibodies to 52,000- and 70,000-dalton proteins in mouse spinal cord were somewhat more common in ALS sera. Antibodies to a protein of approximately 150,000 to 200,000 daltons were also evident. The 70,000- and 52,000-dalton proteins were detected in brain, cerebellum, and liver as well as spinal cord. Immunohistochemistry suggested antibody activity was directed at least in part to neurofilaments. While the antibodies to the 52,000- and 70,000-dalton proteins were more common in ALS than control sera (p less than 0.02 and less than 0.05, respectively), it is not clear from this initial study that this difference is of clinical or etiologic significance.     

Plasma amino acid levels in patients with amyotrophic lateral sclerosis.

Evidence for a generalized defect in glutamate in patients with amyotrophic lateral sclerosis (ALS), associated with widespread alterations in the central nervous system level of this excitatory amino acid. We measured fasting plasma amino acid in 10 ALS patients and 10 controls matched for age and sex. ALS patients had statistically significant elevations in plasma level of aspartate, glutamate, and glycine. The plasma levels of other amino acids were not significantly different from those found in controls. No correlation between ALS severity or activity and degree of abnormality in amino acids was established.     

Effect of bromocriptine and metoclopramide on serum prolactin levels in patients with amyotrophic lateral sclerosis.

Secretion of prolactin in nine patients with amyotrophic lateral sclerosis and in seven healthy men was investigated with the use of metoclopramide stimulation and bromocriptine inhibition tests. Blood serum prolactin concentration was determined in the basal state and 30, 60 and 120 minutes after oral administration of 10 mg metoclopramide or 2.5 mg bromocriptine. A period of 3 days intervened between testing each drug in the same individual. It was shown that basal prolactin levels in amyotrophic lateral sclerosis patients and the controls did not differ significantly, whereas in the metoclopramide stimulation test seven amyotrophic lateral sclerosis patients showed a very exaggerated response. The mean value of maximal prolactin increment was 1609.90% (SD 456) in comparison with the control group 638.3% (SD 89.7) (p less than 0.01). In the bromocriptine inhibition test the mean value of maximal prolactin percentage decrement was 50.4% (SD 6.1) in amyotrophic lateral sclerosis and 66.5% (SD 5.3) in the controls and this difference was statistically insignificant. These data suggest that exaggerated prolactin response to metoclopramide in amyotrophic lateral sclerosis may be a result of a decreased activity of central dopaminergic neurons.     

Decreased cerebrospinal fluid cGMP levels in patients with amyotrophic lateral sclerosis

Summary. The role of cyclic guanosine 5 monophosphate (cGMP) in neurodegeneration of motor neurons in amyotrophic lateral sclerosis (ALS) is still controversial. The aim of this study was to measure levels of cGMP in cerebrospinal fluid (CSF) of patients with ALS, and to investigate whether there is a relationship between CSF cGMP levels and clinical parameters of the disease. The study involved 30 ALS and 20 control group patients. The CSF cGMP was measured by the enzyme-linked immunosorbent assay. The results showed that levels of CSF cGMP were significantly decreased in the group of ALS patients compared to controls and did not depend on clinical state of ALS patients, type of ALS onset, or the duration of the disease. Decreased levels of CSF cGMP observed in this study may suggest the role of cGMP in neurodegeneration in ALS. The CSF cGMP cannot be a marker of the disease activity.     

An exploratory study of the association between thyroid hormone and survival of amyotrophic lateral sclerosis

The objective of the study was to determine the correlation of thyroid hormones (THs) and survival in patients with amyotrophic lateral sclerosis (ALS). A total of 278 patients with ALS were enrolled and followed up prospectively every 3 months by face-to-face interviews or phone calls. Level of fasting serum TH was determined at the time of enrollment. Clinical data including age, onset age, onset body region, ALS Functional Rating Scale- Revised (ALS-FRS-R), and survival were collected. Patients were separated into four subgroups according to the quartile distribution of TH, and survival was compared among them. There was no significant difference in baseline characteristics, including onset age, gender, onset form as well as treatment with riluzole among different levels of TH subgroups. Chi-square test indicated that the lowest quartile of FT3 (<4.26 mg/L) might correlate with higher incidences of death (OR 0.374, 95 % CI 0.173–0.813), while second and third quartiles of FT4 (range 14.25–18.0 mg/L) with lower incidences of death in ALS. However, after correction for onset age and onset form using logistic regression analysis, no statistical difference was revealed in survival among patients with different TH levels. TH does not correlate with survival and is not a prognostic factor for ALS.     

Serum levels of coenzyme Q10 in patients with amyotrophic lateral sclerosis

Summary. To elucidate whether serum coenzyme Q₁₀ levels are related with the risk for amyotrophic lateral sclerosis (ALS), we compared serum levels of coenzyme Q₁₀ and the coenzyme Q₁₀/cholesterol ratio, in 30 patients with ALS and 42 matched controls using a high performance liquid chromatography technique. The mean serum coenzyme Q₁₀ levels and the coenzyme Q₁₀/cholesterol ratio did not differ significantly between the 2 study groups. These values were not influenced by the clinical form (spinal vs. bulbar) of ALS, and they did not correlate with age, age at onset, and duration of the disease. These results suggest that serum coenzyme Q₁₀ concentrations are unrelated with the risk for ALS. Received September 1, 1999; accepted January 4, 2000     

Sleep in patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis can be associated with profound sleep disturbances resulting from factors such as reduced mobility, muscle cramps, swallowing problems and anxiety. Although few studies have examined sleep patterns in ALS, disease-related symptoms such as restless legs and increased myoclonic activity can disturb both the initiation and maintenance of sleep. In addition, sleep-disordered breathing, exhibiting as hypoventilation, has been reported in patients with ALS. Interference with sleep patterns may produce daytime symptoms and activities of daily living can be further affected by an increased incidence of depression. Pharmacotherapy of sleep disturbance should be directed at the underlying cause and when hypnotics are required these should be short acting to minimise the carry-over effect into daytime.

     

An outcome study of riluzole in amyotrophic lateral sclerosis

Riluzole is the only therapy proven in clinical trials to prolong amyotrophic lateral sclerosis (ALS) survival (approximately three months). Questions remain concerning riluzole's effectiveness in everyday practice, the appropriate duration of treatment, which certain subtypes of ALS specifically benefit from the medication, and whether early administration prolongs survival in ALS patients. We report the results of a population-based outcome study of riluzole in the Irish ALS population over a five-year period. Using data from the Irish ALS Register, we examined the survival of patients diagnosed with ALS between 1 January 1996 and 31 December 2000 who attended a general neurology clinic (n = 264 patients, MD = 16). An intention to treat analysis is employed. 149 (61 %) patients were prescribed riluzole and the remaining 99 (39 %) were not. Riluzole therapy reduced mortality rate by 23 % and 15 % at 6 and 12 months respectively and prolonged survival by approximately four months. This beneficial effect was lost in prolonged follow-up. Suspected or possible ALS patients receiving riluzole experienced similar improvement in survival as the overall cohort. Survival benefit was more marked among patients with bulbar-onset disease. Multivariate analysis did not show riluzole to be an independent predictor of survival. We conclude that riluzole therapy improves ALS survival in everyday clinical practice by a short period of time. This beneficial effect is transient and stopping the medication in advanced ALS should be reconsidered. Bulbar-onset patients appear to particularly benefit from riluzole for unclear reasons. Our initial observations support riluzole use in early ALS. Received: 22 August 2002, Received in revised form: 7 November 2002, Accepted: 11 November 2002 Correspondence to Dr. Orla Hardiman     

Serum caspase-9 levels are increased in patients with amyotrophic lateral sclerosis

It is known that apoptosis may play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Moreover, caspase-9 is implicated in the apoptosis pathway. The aim of the study was to investigate caspase-9 levels in serum of patients with ALS. The study involved 30 patients with ALS and 30 patients from the control group. The serum caspase-9 levels were measured using the enzyme-linked immunosorbent method. The study showed that caspase-9 levels are significantly increased in serum of the patients with ALS comparing to the control group (p < 0.05). There was a significant correlation of serum caspase-9 levels with severity of clinical state of ALS patients and duration of the disease (p < 0.05). The results indicate that caspase-9 may be implicated in pathomechanism of neurodegeneration in ALS.