A prospective study of quality of life in amyotrophic lateral sclerosis patients.

OBJECTS: The aim of this prospective and longitudinal study was to describe individual quality of life in patients with amyotrophic lateral sclerosis (ALS) and its correlations with physical function and emotional well-being from diagnosis and over time. MATERIALS AND METHODS: Thirty-six patients were included in the study. Individual quality of life was measured with the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), illness severity was assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS FRS-R), and emotional distress was measured using the Hospital Anxiety and Depression Scale (HADS). Data were collected from diagnosis and thereafter, every six months for a period of two years. Twelve patients completed the 24-month follow-up. RESULTS: Family, friends and own physical health were important for overall quality of life, from diagnosis and during the disease progression. Most patients had good quality of life, which remained stable, despite changed physical functions. Several patients scored above the cut-off score for doubtful and clinical anxiety and depression early on after diagnosis, and there was a significant decrease in anxiety over time. Soon after diagnosis, there was a correlation between depression and quality of life. CONCLUSION: The family, social relations and own physical health are important for overall quality of life in patients with ALS. Thus, supporting the family and facilitating so that patients can continue to stay in contact with friends are important aspects during the disease. Conducting an early screening for depression can be important for preventing decreased quality of life.

Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D3: a pilot study.

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder. Vitamin D has important roles both in the autoimmune response and in skeletal muscles. We determined the levels of 25-hydroxy vitamin D [25(OH)D] in patients with MG and in healthy subjects to determine whether vitamin D deficiency is present in MG and whether vitamin D supplementation has beneficial effects on fatigue. METHODS: Plasma levels of 25(OH)D were analyzed in 33 patients with MG (22 males; mean age, 58 years) and in 50 healthy age- and sex-matched blood donors, without vitamin D3 medication. MG composite (MGC) score assessed fatigue. Thirteen patients with MG without previous vitamin D3 supplementation were started on vitamin D3 supplementation (cholecalciferol) 800 IU/day, with a follow-up examination after 2.5-10 months (mean, 6 months). RESULTS: Patients with MG without pre-existing vitamin D3 supplementation (N = 16) had a mean MGC of 4.5 and lower plasma 25(OH)D levels (mean, 51 ± 19 nM) than healthy controls (69 ± 21 nM) (P = 0.017). Seventeen patients had pre-existing vitamin D3 supplementation, because of corticosteroid treatment, and their mean 25(OH)D was 79 ± 22 nM and mean MGC was 5.5. In the 13 patients who received cholecalciferol, 25(OH)D was overall increased at follow-up with 22% (P = 0.033) and MGC score improved by 38% (P = 0.05). CONCLUSIONS: Plasma 25(OH)D levels are significantly lower in patients with MG compared with healthy controls. As vitamin D has beneficial effects on the autoimmune response and on fatigue score in patients with MG, we suggest monitoring this parameter in patients with MG and supplementation with vitamin D3 when 25(OH)D levels are low.

Nurse or surgeon follow-up after rectal cancer: a randomized trial.

AIM: Follow-up programmes consume a large amount of resources with less time for the surgeon to take on new patients. The aim of this randomized study was to compare patient satisfaction, resource utilization and medical safety in patients curatively operated for rectal cancer who were followed up by either a surgeon or a nurse. METHOD: The nurse was trained by the colorectal surgeon before the start of the study. Curatively operated patients were asked to give their consent to participate. Randomization was performed by the stoma therapist. After each consultation, the patient completed a questionnaire. RESULTS: A total of 110 patients (58 men) age 68 (range 41-87) years were included between 2002 and 2005. Only three patients refused participation. Patient satisfaction was high according to the Visual Analogue Scale (VAS): 9.4 for the surgeon and 9.5 for the nurse (NS). Consultation time was longer for the nurse: 24 vs 15 min (P = 0.001), with more blood samples being taken (29%vs 7%, P = 0.002). Radiological investigations exceeding the routine were made in 11%vs 4% (NS) cases. Surgical assistance was needed in 13 of 182 consultations with the nurse [mean 6 (1-15) min, total 75 min]. Distant metastases were detected in seven patients in the surgeon group and eight in the nurse group (P = 0.953). Total costs of follow-up did not differ. CONCLUSION: Patient satisfaction was equally high for the specialist nurse as for the colorectal surgeon. On only a few occasions was surgical assistance necessary and total costs for the follow-up showed no difference. Medical safety appeared uncompromised. Nurse-led follow-up is encouraged.

Quality assurance using a photodiode array.

Improved treatment techniques in radiation therapy provide incentive to reduce treatment margins, thereby increasing the necessity for more accurate geometrical setup of the linear accelerator and accompanying components. In the present paper, we describe the development of a novel device that enables precise and automated measurement of geometric parameters for the purpose of improving initial setup accuracy, and for standardizing repeated quality control activities. The device consists of a silicon photodiode array, an evaluation board, a data acquisition card, and a laptop. Measurements that demonstrate the utility of the device are also presented. Using the device, we show that the radiation light field congruence for both 6 and 15 MV beams is within 1.3 mm. The maximum measured disagreement between radiation field edges and light field edges was 1.290 ± 0.002 mm, while the smallest disagreement between the light field and radiation field edge was 0.016 ± 0.003 mm. Because measurements are automated, ambiguities resulting from interobserver variability are removed, greatly improving the reproducibility of measurements across observers. We expect the device to find use in consistency measurements on linear accelerators used for stereotactic radiosurgery, during the commissioning of new linear accelerators, or as an alternative to film or other commercially available devices for performing monthly or annual quality control checks.

Monozygous twins with neuromuscular transmission defects at opposite sides of the motor endplate.

Disorders affecting the postsynaptic side of the neuromuscular junction include autoimmune myasthenia gravis (MG) as well as some of the congenital myasthenic syndromes (CMS). Lambert-Eaton myasthenic syndrome (LEMS) is an acquired autoimmune neuromuscular disorder in which autoantibodies are directed against the presynaptic calcium channels. Here we describe two monozygous twin brothers: case 1 was diagnosed with an indeterminate form of acquired postsynaptic neuromuscular junction defect at age 32 and case 2 with LEMS at age 47. Case 1 presented clinically with mild generalized myasthenic weakness, neurophysiological examination revealed disturbed neuromuscular transmission along with probable myositis and serum analysis regarding antibodies against the acetylcholine receptor and muscle-specific tyrosine kinase was negative. Case 2 presented with proximal muscle fatigue accompanied by areflexia at rest and antibodies against the P/Q-type voltage-gated calcium channels were present. Neurophysiologically, case 2 had reduced baseline compound motor action potential amplitudes on neurography, decrement on low-frequency repetitive nerve stimulation (RNS) and pathological increment on high frequency RNS. To our knowledge this is the first case report of its kind and adds an intriguing contrast to the more common diagnosis of CMS in monozygous twins.

Increased expression of glial cell line-derived neurotrophic factor mRNA in muscle biopsies from patients with amyotrophic lateral sclerosis.

The expression of glial cell line-derived neurotrophic factor (GDNF) mRNA and brain-derived neurotrophic factor (BDNF) mRNA were studied in muscle biopsies from five patients with amyotrophic lateral sclerosis (ALS), six patients with other neuromuscular diseases and eight healthy control persons. All five patients with ALS had higher GDNF mRNA expressions in their biopsies than the healthy control group (almost a three fold increase). Among the other patients only one, who had a rapidly progressing toxic polyneuropathy, showed a GDNF mRNA expression above those of the controls. The BDNF mRNA expressions in the biopsies from the ALS patients were in the same range as those from the healthy controls, although the mean value of the ALS patients was higher. The only biopsy that showed a markedly higher BDNF mRNA expression was taken from one patient with progressive muscular atrophy. These results suggest that increased GDNF mRNA expression in muscle is an unspecific response to ongoing denervation and that this response is maintained in ALS, at least temporarily. If increased GDNF mRNA in muscle proves to be a constant finding in ALS the rationale for the use of GDNF as a therapeutic agent in ALS must be questioned.

Sci-Thur AM: Planning - 09: Assessing dynamic IMRT field modulation in prostate plans.

In a previous study, the variogram fractal dimension (FD) method was found to be very accurate at identifying planned head and neck IMRT fields that are overly-modulated. In the current study, the authors used MATLAB® to develop FracMod, a graphical user interface (GUI) and variogram FD analysis tool to assess modulation complexity of dynamic IMRT fields designed for treatments of the prostate alone and prostate plus pelvic nodes. A set of 5 prostate plans (25 fields) and 5 prostate plus pelvic node plans (35 fields) were used to choose FD cut-points that ensure no false positives (100% specificity) in distinguishing between moderate field modulation (typical modulation used clinically at the authors' institution) and high modulation. Field modulation was controlled by adjusting fluence smoothing parameters in the Eclipse™ treatment planning system. The area under the curve (AUC) from receiver operating characteristic (ROC) analysis was used to quantitatively compare the ability of FD and the number of monitor units (MUs) for distinguishing between the moderate and high modulation fields. The variogram FD method gave AUCs of 0.96 (almost perfect classification) and 1.00 (perfect classification) for the prostate alone and the prostate plus pelvic node fields, respectively. The variogram FD method is an accurate metric; performing better than the number of MUs at identifying high modulation IMRT fields planned for the treatment of prostatic carcinoma. Hence, FracMod will enable Radiotherapy Physicists to easily and accurately quantify the degree of modulation of IMRT fields and adjust overly-modulated fields at the treatment planning stage.

The ALS/MND prevalence in Sweden estimated by riluzole sales statistics.

OBJECTIVES: To determine whether sales statistics for riluzole can be used as a marker for the prevalence of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) in Sweden. MATERIALS AND METHODS: A questionnaire was sent to all neurological units in Sweden asking about the numbers of patients with ALS/MND and whether these patients were treated with riluzole. Sales statistics for riluzole were obtained from the 906 public pharmacies and 89 hospital pharmacies in Sweden. RESULTS: Eighty percent of the neurological units answered the questionnaire. The estimated prevalence in September 2003 from the questionnaire was 5.4/100,000 inhabitants. The sales expressed in defined daily dose/100,000 inhabitants/day was 3.8. For the counties the correlation between these two parameters was 0.83. CONCLUSION: Estimated prevalence is highly correlated with sales statistics for riluzole. Riluzole sales statistics could be used as a crude marker for the prevalence of ALS/MND in Sweden.

Increased red blood cell polyamines in ALS and Parkinson's disease.

The polyamines spermidine (SPD) and spermine (SPM) are implicated in nerve cell degeneration and regeneration. Over 70% of circulating polyamines are associated with red blood cells (RBC). Against this background we have analysed RBC polyamines in two neurodegenerative disorders, amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Twenty patients with the sporadic form of ALS, 20 patients with PD, and 20 healthy controls were studied. The highest levels of SPD and SPM were found in the PD group where the mean values were 134 and 115%, respectively, above those of the controls. The patients with PD also presented the lowest levels of the SPD precursor, putrescine (PUTR). In the patients suffering from ALS the SPD and SPM mean levels were increased by 46 and 112%, respectively. The RBC SPD/SPM ratio in the patients suffering from PD was significantly elevated in comparison with that of ALS patient group, suggesting a different involvement of the polyamine system in these disorders. It is at present unknown if raised polyamine levels may contribute to induce the degeneration of susceptible neurons or if the increase represents a compensatory protective reaction, or simply an unspecific epiphenomenon.