Development and validation of Spasticity Index-Amyotrophic Lateral Sclerosis.

OBJECTIVES: Spasticity is a common and disabling feature of amyotrophic lateral sclerosis (ALS). There are currently no validated ALS-specific measures of spasticity. The aim of this study was to develop and use a self-report outcome measure for spasticity in ALS. METHODS: Following semi-structured interviews with 11 ALS patients, a draft scale was administered across ALS clinics in the UK. Internal validity of the scale was examined using the Rasch model. The numerical rating scale (NRS) for spasticity and Leeds Spasticity scale (LSS) were co-administered. The final scale was used in a path model of spasticity and quality of life. RESULTS: A total of 465 patients (mean age 64.7 years (SD 10), 59% male) with ALS participated. Spasticity was reported by 80% of subjects. A pool of 71 items representing main themes of physical symptoms, negative impact and modifying factors was subject to an iterative process of item reduction by Rasch analysis resulting in a 20-item scale-the Spasticity Index for ALS (SI-ALS)-which was unidimensional and free from differential item functioning. Moderate correlations were found with LSS and NRS-spasticity. Incorporating the latent estimate of spasticity into a path model, greater spasticity reduced quality of life and motor function; higher motor function was associated with better quality of life. CONCLUSIONS: The SI-ALS is a disease-specific self-report scale, which provides a robust interval-level measure of spasticity in ALS. Spasticity has a substantial impact on quality of life in ALS.

Prevalence of depression in amyotrophic lateral sclerosis/motor neuron disease: multi-attribute ascertainment and trajectories over 30 months.

Objective: Evidence is equivocal about the prevalence of depression in amyotrophic lateral sclerosis (ALS). This study uses a multi-attribute ascertainment of the prevalence of depression and examines this prevalence over time. Methods: Patients with ALS were recruited into the Trajectories of Outcome in Neurological Conditions (TONiC-ALS) study. Caseness was identified by the Modified-Hospital Anxiety and Depression Scale (M-HADS). In addition, participants provided data on co-morbidities and medication use. A combination of the three was used to derive the estimate for the prevalence of depression, treated or untreated. Longitudinal data were analyzed by trajectory analysis of interval level M-HADS-Depression data. Results: Among 1120 participants, the mean age was 65.0 years (SD 10.7), 60.4% male, and the median duration since diagnosis was 9 months (IQR 4-24). Caseness of probable depression at baseline, defined by M-HADS-Depression, was 6.45% (95%CI: 5.1-8.0). Taken together with antidepressant medication and co-morbidity data, the prevalence of depression was 23.1% (95%CI: 20.7-25.6). Of those with depression, 17.8% were untreated. Trajectory analysis identified three groups, one of which contained the most cases; the level of depression for each group remained almost constant over time. Conclusion: Depression affects almost a quarter of those with ALS, largely confined to a single trajectory group. Prevalence estimates based on screening for current depressive symptoms substantially under-estimate the population experiencing depression. Future prevalence studies should differentiate data based on current symptoms from those including treated patients. Both have their place in assessing depression and the response by the health care system, including medication, depending upon the hypothesis under test.

'Ball valve' small bowel obstruction caused by a large caecal faecolith.

Small bowel obstruction is a common surgical presentation, but intestinal faecoliths are rarely reported as a cause. A 75-year-old woman presented with small bowel obstruction from a large faecolith lodged in the caecum. This required removal at laparoscopy-assisted surgery. This case highlights the need to deal promptly with symptomatic intestinal faecoliths as they are unlikely to pass spontaneously and are prone to cause acute obstruction.

Measuring coping in people with amyotrophic lateral sclerosis using the Coping Index-ALS: A patient derived, Rasch compliant scale.

OBJECTIVE: The progressively disabling and terminal nature of ALS/MND imposes major coping demands on patients. We wished to improve the psychometric properties of our previously published MND-Coping Scale, so that parametric analyses were valid, and to make it simpler for patients to complete and clinicians to score. METHODS: After a new qualitative analysis of 26 patients with ALS/MND, the draft Coping Index-ALS (CI-ALS) was administered to 465 additional patients, alongside COPE-60, General Perceived Self Efficacy scale, and WHOQOL-BREF. Validity of the CI-ALS was assessed using the Rasch model. External validity was checked against comparator measures. RESULTS: Thirteen centres contributed 465 patients, mean age 64.9 years (SD 10.8), mean disease duration 28.4 months (SD 37.5). The CI-ALS-Self and CI-ALS-Others both satisfied Rasch model expectations and showed invariance across age, gender, marital status and type of onset. Expected correlations were observed with comparator scales. A nomogram is available to convert the raw scores to interval level measures suitable for parametric analysis. CONCLUSIONS: Coping abilities in ALS/MND can now be measured using a simple 21 item self-report measure, offering two subscales with a focus of 'coping by self ' and 'coping with others'. This allows clinicians to identify individuals with poor coping and facilitates research on interventions that may improve coping skills.

Prognostic factors in patients with acute liver failure undergoing live donor liver transplantation.

Mortality from acute liver failure (ALF) is high. Live donor liver transplantation (LDLT) is the treatment of choice for ALF in Asia, because cadaveric donors are rare. We sought to review our results in ALF patients with undergoing LDLT at our center. One hundred two LDLTs were performed at our center from April 2002 to November 2007, 15 (14%) because of ALF. Mean (SEM; median, range) follow-up was 1,065 (189; 1400; 3-2046) days. Nine patients (60%) had acute exacerbation of chronic hepatitis B; and 6 (40%) had drug-induced liver injury. Age was 47 (3; 50; 27-65) years. Ten patients (67%) were men. At transplantation, laboratory values were included bilirubin, 449 (35) micromol/L; creatinine concentration, 182 (32) mmol/L. The international normalized ratio was 2.4 (0.2). The Model for End-Stage Liver Disease (MELD) score was 34 (2). Both inpatient and long-term mortality was 20% 3 of 15 patients died. The 5-year survival was 80%. Compared with survivors, patients who died had a significantly higher creatinine concentration 289 vs 155 micromol/L, international normalized ratio (3.4 vs 2.1), MELD score (47 vs 32). We conclude that despite being sick with median and mean MELD scores of 32 and 34, 80% of patients with ALF can achieve good long-term survival after LDLT.

Experience of the transplant team is an important factor for posttransplant survival in patients with hepatocellular carcinoma undergoing living-donor liver transplantation.

Living-donor liver transplantation (LDLT) is an effective treatment for patients with unresectable hepatocellular carcinoma (HCC). However, it remains controversial whether expanded listing criteria can be used for LDLT. We aimed to review results of LDLT for patients with HCC at our center. Patients with HCC were accepted for LDLT if there was no extrahepatic spread on computed tomography (CT) and positron emission tomography CT scan. Transarterial chemoembolization was performed before LDLT to control the tumors. Sirolimus or everolimus was used as part of the immunosuppressive protocol for all patients. Over the last 6 years, 35 of the 102 (34%) LDLT were performed at our center for HCC. Age (mean +/- SEM) was 55.3 +/- 1.3 years; 28 patients (80%) were men. Eight (23%) had LDLT performed in 2002 or 2003 (period 1), and 27 (77%) in 2004 to 2007 (period 2). Eleven (31%) were within and 23 (69%) were outside the Milan criteria. After 583 +/- 76 days follow-up, nine (25%) died, three of recurrent HCC. Three-year survival was significantly better in period 2 than in period 1 (90% vs 13%; P < .001). Although the 3-year survival for those within Milan criteria was better than those outside Milan criteria, the difference did not reach statistical significance (86% vs 57%; P = .26). Six (17%) had HCC recurrence, of whom five died. We concluded that reasonable medium-term survival can be obtained for patients with HCC. The experience level of the transplant team seemed to be the most important predictor of patient outcome.

An Overlapping Case of Miller Fisher Syndrome, Bickerstaff's Encephalitis, and the ASMAN Variant of Guillain-Barre Syndrome.

A 56-year-old man presented with a 3-day history of progressive tingling of the hands, unsteadiness, and diplopia. He was initially diagnosed clinically with Miller Fisher Syndrome (MFS) but later developed limb weakness consistent with Guillain-Barre Syndrome (GBS) and subsequently reduced consciousness consistent with Bickerstaff's brainstem encephalitis (BBE). Neurophysiology revealed an axonal motor and sensory neuropathy, in keeping with the Acute Motor and Sensory Axonal Neuropathy (AMSAN) variant of GBS. We believe that our patient had an MFS-AMSAN-BBE overlap syndrome. This is supported by his glycolipid antibody profile with high titres of anti-GQ1b IgG antibody and anti-GD1a IgG antibody. Anti-GQ1b antibodies are frequently found in both MFS and BBE and the anti-GD1a antibody is associated with axonal forms of GBS. Overlapping cases of MFS and BBE are well described, and because the same antibody is often found in both conditions, it is thought that they share a common autoimmune mechanism. BBE has also been previously reported in association with GBS lending support that it also lies on the same spectrum. This overlapping case of ASMAN variant of GBS, MFS, and BBE provides further support that these conditions are part of the same spectrum.

Follicular dendritic cell tumour of tonsil - is it an under-diagnosed entity?

Neoplasms of follicular dendritic cells are uncommon and while majority of them occur in lymph nodes, they are increasingly recognized at varied sites such as abdominal viscera. Tonsil is the most common extra nodal site for occurrence of FDCT in the head and neck region. We describe three cases of follicular dendritic cell tumour occurring in the tonsil.

Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome.

We examined 5HT1a-mediated ACTH release in patients with chronic fatigue syndrome (CFS) using a between-subjects design. Patients attending a specialist outpatient clinic for CFS, who fulfilled CDC criteria, together with age- and sex-matched healthy comparison subjects, were recruited. Subjects had a cannula inserted in a forearm vein at 0830 h and were allowed to relax until 0900 h, when baseline bloods for ACTH and cortisol were drawn. They were then given ipsapirone 20 mg PO and further blood for hormone estimation was taken at +30, +60, +90, +120 and +180 min. Baseline ACTH and cortisol levels did not differ between the two groups. Release of ACTH (but not cortisol) in response to ipsapirone challenge was significantly blunted in patients with CFS. We conclude that serotonergic activation of the hypothalamic-pituitary-adrenal axis is defective in CFS. This defect may be of pathophysiological significance.

Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome.

Seven patients with chronic fatigue syndrome (CFS) were matched with ten healthy control subjects of similar age. Hippocampal volume, obtained from magnetic resonance images using an unbiased method, showed no difference between the two groups, whereas proton magnetic resonance spectroscopy showed a significantly reduced concentration of N-acetylaspartate in the right hippocampus of CFS patients (p = 0.005).

Effect of oral and injectable contraceptives on serum electrolytes, weight and blood pressure.

BACKGROUND: Since the introduction of oral and injectable contraceptives, many metabolic side effects have been reported. The use of oral contraceptive has been shown to be associated with increased level of serum electrolytes, but decrease in levels of serum electrolytes has been reported in women using injectable contraceptives. This study evaluated serum electrolytes, weight and blood pressure in women taking oral and injectable contraceptives because these changes have adverse effects on the health and economy of the subject. METHODS: Serum electrolytes, weight and blood pressure were measured in 50 women taking oral contraceptive (Lofeminal) and 50 women taking injectable contraceptives (Depomedroxy progesterone acetate and Norigest). The same women served as control before starting these contraceptives. RESULTS: There was a significant increase in serum sodium and chloride but significant decrease in serum potassium and bicarbonate level in women taking oral contraceptive. There was non-significant decrease in serum electrolytes in women taking injectable contraceptives. There was significant increase in weight and blood pressure of women taking these contraceptives.

Effect of oral and injectable contraceptives on serum calcium, magnesium and phosphorus in women.

BACKGROUND: This study aims at evaluating serum calcium, magnesium and phosphorus levels in women taking oral and injectable contraceptives. METHODS: Serum calcium, magnesium and phosphorus were measured in 50 women taking oral contraceptives (Lofeminal) and 50 women taking injectable contraceptive (Depo-medroxy progesterone acetate and Norigest). These women were used as controls before starting these contraceptives. RESULTS: There was significant decrease in serum levels of calcium, magnesium and phosphorus in women taking oral contraceptives but there was significant increase in these minerals in women taking injectable contraceptives. CONCLUSIONS: It is suggested that these contraceptives should be used with due care and with proper investigations of the women before and during the therapy.

Abnormalities of carnitine metabolism in chronic fatigue syndrome.

Carnitine may be involved in the pathogenesis of the chronic fatigue syndrome (CFS). However, no information about the cellular metabolism of carnitine in CFS patients is currently available. Therefore, we aimed to measure the levels of carnitine (total, free and short-chain) in both peripheral blood lymphocytes (PBLs) and sera from patients with CFS. The serum levels of total, free and short-chain were comparable in CFS patients, considered as the whole group, to those in healthy control subjects, even though a trend indicating slightly reduced serum concentrations of free carnitine was observed in male patients with CFS. In contrast, the concentrations of total, free and short-chain carnitine in PBLs from patients with CFS were significantly lower than in cells from healthy controls. Our study indicates that patients with CFS require exogenous carnitine supplementation. The low carnitine concentrations in PBLs from patients with CFS probably reflect the carnitine deficiency occurring in other tissues, including the skeletal muscles. The low cellular concentrations of carnitines may help to explain both the immunological abnormalities and the impaired energy metabolism in skeletal muscles.

A comparative study of serum F protein and other liver function tests as an index of hepatocellular damage in epileptic patients.

Gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) may not be sensitive indicators of hepatocellular damage in patients taking anticonvulsant drugs as raised levels may only reflect enzyme induction. Aspartate aminotransferase (AST) is a specific, but relatively insensitive marker of liver damage and has a poor correlation with liver histology. Serum F protein is found in high concentration in the liver and levels are not influenced by enzyme induction. We measured serum F protein levels in patients taking carbamazepine (CBZ) and phenytoin (PHT) as monotherapy and in patients receiving multiple drugs. We compared the results with patients taking sodium valproate (VPA). Serum F protein levels were elevated in 6%, 22% and 13% of patients receiving CBZ, PHT and VPA, respectively. Raised GGT levels were reported for both the CBZ (26%) and PHT (78%) groups. Raised ALP levels were observed in 16%, 25% and 4% of the CBZ, PHT and VPA groups, respectively. Raised levels of serum F protein in the VPA group and the absence of any associated increases in either GGT or AST may further support the suggestion that serum F protein is an indicator of hepatocellular dysfunction associated with anticonvulsant therapy. However, further correlation with liver histology is required.

A pulsating auroral X-ray hot spot on Jupiter.

Jupiter's X-ray aurora has been thought to be excited by energetic sulphur and oxygen ions precipitating from the inner magnetosphere into the planet's polar regions. Here we report high-spatial-resolution observations that demonstrate that most of Jupiter's northern auroral X-rays come from a 'hot spot' located significantly poleward of the latitudes connected to the inner magnetosphere. The hot spot seems to be fixed in magnetic latitude and longitude and occurs in a region where anomalous infrared and ultraviolet emissions have also been observed. We infer from the data that the particles that excite the aurora originate in the outer magnetosphere. The hot spot X-rays pulsate with an approximately 45-min period, a period similar to that reported for high-latitude radio and energetic electron bursts observed by near-Jupiter spacecraft. These results invalidate the idea that jovian auroral X-ray emissions are mainly excited by steady precipitation of energetic heavy ions from the inner magnetosphere. Instead, the X-rays seem to result from currently unexplained processes in the outer magnetosphere that produce highly localized and highly variable emissions over an extremely wide range of wavelengths.

Validity of vision screening by school nurses in seven regions of Oman

We tested the validity of vision screening in schools in 7 regions of Oman in 2003.Two researchers tested 1719 randomly selected students in 4 school grades using the Snellen E acuity test. Trained school nurses had previously screened 182 233 students. The visual status recorded in the 2 screenings was compared. Sensitivity of screening by nurses was 68.34% [95% CI: 67.30-69.38] and specificity 99.23% [95% CI: 99.19-99.27]. The positive predictive value was 85.42% [95% CI: 84.63-86.21] and negative predictive value was 97.93% [95% CI: 97.87-98.00].The sensitivity of the vision test was significantly higher in females, older students and in North Sharqiya region. In general, the vision screening of school students in Oman has satisfactory validity. Periodic training of nurses and supervision of the screening procedures could improve its sensitivity. Underlying causes of the high numbers of false negative cases should be further investigated