Wendy Johnston

Correlates of suffering in amyotrophic lateral sclerosis.

Objectives: 1) To determine the prevalence of pain, suffering, poor quality of life, depression, and hopelessness in people with ALS, and the correlates of suffering and poor quality of life; 2) to analyze the relationship between pain, suffering, quality of life, and attitudes toward life-sustaining medical treatment and physician-assisted suicide; and 3) to determine concordance between patients with ALS and their caregivers in rating the patients’ pain, quality of life, and suffering. Methods: Subjects completed a single interview. We measured the subject’s pain, quality of life, suffering, hopelessness, depression, social support, perception of burden to others, level of disability, desire for life-sustaining medical treatment, and interest in assisted suicide. Caregivers also rated the patient’s quality of life, pain, and suffering. Results: A total of 100 subjects with ALS and 91 caregivers participated. Suffering was rated as 4 or greater on a six-point scale by 20% of subjects with ALS, and 19% rated their pain as 4 or greater on a six-point scale. Eleven percent had clinical depression. Physicians frequently failed to recognize and treat pain and depression. The correlates of suffering were increasing pain, hopelessness, and level of disability. The correlates of poor quality of life were poor social support and increasing hopelessness. The correlation between subjects’ and caregivers’ rating of the patient’s suffering was r = 0.47. There was no relationship between subjects’ ratings of pain, suffering, and quality of life, and their interest in life-sustaining treatment or physician-assisted suicide. Conclusion: Many patients with ALS suffer, and their suffering is correlated to pain and hopelessness. Physicians caring for patients with ALS frequently fail to recognize and treat their patients’ pain and depression.

Symptom factor analysis, clinical findings, and functional status in a population-based case control study of Gulf War unexplained illness.

Few epidemiological studies have been conducted that have incorporated clinical evaluations of Gulf War veterans with unexplained health symptoms and healthy controls. We conducted a mail survey of 2022 Gulf War veterans residing in the northwest United States and clinical examinations on a subset of 443 responders who seemed to have unexplained health symptoms or were healthy. Few clinical differences were found between cases and controls. The most frequent unexplained symptoms were cognitive/psychological, but significant overlap existed with musculoskeletal and fatigue symptoms. Over half of the veterans with unexplained musculoskeletal pain met the criteria for fibromyalgia, and a significant portion of the veterans with unexplained fatigue met the criteria for chronic fatigue syndrome. Similarities were found in the clinical interpretation of unexplained illness in this population and statistical factor analysis performed by this study group and others.

Combined structural and neurochemical evaluation of the corticospinal tract in amyotrophic lateral sclerosis.

Our objective was to characterize the structural and metabolic changes of the corticospinal tract (CST) in ALS patients using combined diffusion tensor imaging (DTI) and magnetic resonance spectroscopic imaging (MRSI). Fourteen patients (male:female, 6:8; mean age, 54 years) and 14 controls (male:female, 8:6; mean age, 53 years) underwent imaging. Four regions of the CST were evaluated: precentral gyrus, corona radiata, posterior limb of the internal capsule, and cerebral peduncle. DTI and MRSI indices tested included fractional anisotropy (FA), apparent diffusion coefficient (ADC), and the ratio of N-acetylaspartate to choline (NAA/Cho) and creatine (NAA/Cr). In the precentral gyrus, NAA/Cho was reduced 18% (p<0.001), NAA/Cr was reduced 9% (p=0.01), and FA was reduced 3% (p=0.02). NAA/Cho and NAA/Cr were reduced in the corona radiata (p<0.001). Reduced NAA/Cho in the precentral gyrus correlated with shorter symptom duration (r=0.66, p=0.02) and faster disease progression (r=−0.65, p=0.008). Increased spasticity correlated with higher ADC in the precentral gyrus (R=0.52, p=0.005). In conclusion, both MRSI and DTI provided in vivo evidence of intracranial degeneration of the CST in ALS that was most prominent rostrally in the precentral gyrus.

FK506-Induced Fulminant Leukoencephalopathy After Single-Lung Transplantation

FK506 is being used increasingly to prevent rejection after organ transplantation. Its use is associated with a wide spectrum of neurotoxicity, which has been described after most solid organ transplantations, but reports after lung transplantation are extremely rare. This is a report of the pathologic correlation of the clinical and radiologic features of delayed FK506-induced fulminant leukoencephalopathy after single-lung transplantation. The patient presented with neurologic symptoms that progressed to seizure activity. Neuroimaging showed diffuse changes in the brain, and results of a brain biopsy were consistent with leukoencephalopathy with microglial and astrocytic activation. The patient had a remarkable improvement in clinical status after discontinuation of FK506 administration, with resolution of the changes seen on neuroimaging.

U.S. Gulf War Veterans: Service periods in theater, differential exposures, and persistent unexplained illness

Approximately 80,000 of the 697,000 American men and women who were stationed in SW Asia during the Gulf War (GW) report unexplained illness consisting of symptoms of persistent fatigue, cognitive difficulties, such as mild memory loss, diffuse muscle and joint pain, gastrointestinal symptoms, skin lesions, and respiratory problems, among others. Associations between major symptom groups and periods of deployment in the theater of operations have been sought in a population-based, clinical case-control study of GW veterans resident in the north-western region of the United States. No statistically significant differences were evident in the proportion of cases with unexplained fatigue, cognitive/psychological or musculoskeletal symptoms among veterans present in SW Asia in 3 specific time periods: (a) 8/1/1990-12/31/1990 (which includes Desert Shield), (b) the period surrounding Desert Storm (1/1/1991-3/31/1991), and (c) the (post-combat) period immediately following hostilities (4/1/1991-7/31/1991). There was a trend for all 3 case symptoms to be more common among GW veterans who served in the post-combat period. As numbers in these deployment groups were small, and power to detect differences low, the apparent absence of significant differences in the frequency of major symptom groups among these veterans requires confirmation in a larger study. Deployment for discrete periods in SW Asia is a method to separate distinct constellations of environmental factors; these are useful for analyses of associations among symptoms and exposures given the near-total absence of objective data on chemical and other possible exposures in the theater of operations.

Can we eliminate placebo in ALS clinical trials

BACKGROUND Previous studies concluded that the decline in strength in patients with amyotrophic lateral sclerosis (ALS) is a linear function. If so, a patients natural history might serve as the control, instead of placebo, in a clinical trial. METHODS A placebo-controlled ALS clinical trial included a natural history phase, followed by a 6-month treatment phase. Each patients forced vital capacity (FVC) score and maximal voluntary isometric contraction (MVIC) raw scores were measured monthly, standardized, and averaged into megascores. For 138 patients, the arm, leg, FVC, arm+leg combination, and arm+leg+FVC combination megascore slopes during the natural history phase and during the placebo phase were compared. RESULTS The mean slope of megascores during the natural history phase and the mean slope during the placebo phase were not different for the arm, leg, and arm+leg megascores, but were different for the FVC and arm+leg+FVC combination megascores. CONCLUSIONS Natural history controls may be useful in ALS exploratory trials that use arm megascore slope as the primary outcome measure. However, there are distinct limitations to the use of natural history controls, so that Phase 3 ALS clinical trials require placebo controls.

An outbreak of acute hepatitis C among recipients of intravenous immunoglobulin

BACKGROUND An association between therapy with intravenous immunoglobulin (IVIG, Gammagard, Baxter Healthcare Corp) and acute hepatitis C (HCV) was reported by the manufacturer in 1994. OBJECTIVE We sought to describe those patients at risk at our institution who developed HCV infection after IVIG (Gammagard) treatment(s). MATERIALS An inception cohort study of patients with exposure to contaminated IVIG in a university tertiary care institution. Twenty-three patients received suspect IVIG and presented to be screened for HCV via ELISA II and polymerase chain reaction techniques. We describe the demographics and clinical characteristics of patients diagnosed with hepatitis C infection from IVIG. RESULTS Ten of 23 (44%) patients who had received immunoglobulin (2 g/kg) for neurologic or immunologic disorders and were tested for anti-HCV were positive. All were also HCV-RNA positive by polymerase chain reaction. None had other HCV risk factors; all but two had normal aminotransferases documented prior to therapy. The patients had received monthly therapy for periods ranging from 2 to 60 months. Four patients were asymptomatic and the others had mild symptoms. One patient spontaneously became PCR negative within 12 months after exposure. CONCLUSION Patients who received intravenous immunoglobulin (Gammagard, Baxter Healthcare Corp) between March, 1993, and February, 1994, are at risk for acute hepatitis C. The initial sequellae appear to be mild and spontaneous remission is possible.

Amyotrophic Lateral Sclerosis Ethical Challenges

The diagnosis of an incurable disease causing progressive disability unaffected by life-prolonging measures gives rise to many ethical challenges. The core elements of medical ethics can be applied to support decision-making in both common and unusual situations. In this fictional case, ethical dilemmas from several actual cases have been combined to illustrate ethical challenges that may be encountered in the care of a patient with amyotrophic lateral sclerosis (ALS). A 42-year-old man presents to the emergency room with depressed level of consciousness and arm weakness. He is intubated with a presumed stroke. The stroke team notes atrophy of the hand and arm muscles, generalized hyperreflexia, and bilateral Babinski responses, and refers the patient to the general neurology service. The patients wife, Anne Smith, reports that her husband Glen has suffered weakness of the hands and then arms gradually over the last year. Three months ago, he consulted a neurologist, who performed numerous investigations, then told Glen he had ALS or Lou Gehrigs disease. The neurologist told him that it was an incurable disease that caused gradual paralysis and resulted in death from respiratory failure in 18 months to 2 years. He gave Glen a brochure for the ALS Association. Anne had not attended these appointments; Glen told her much later that he had been given a “death sentence.” When Anne called to make a follow-up appointment, she was told that a referral to the ALS clinic was pending. Since the diagnosis, Glen has seemed increasingly tired. He has been napping after work, and for the past week he has had headaches in the mornings. Anne had assumed Glen was depressed by the diagnosis and became alarmed only when he could not be roused this morning. ALS ethics begins with breaking the news. Physicians should break the news in a manner …

Utility of the Addenbrooke’s Cognitive Examination in Amyotrophic Lateral Sclerosis

OBJECTIVE Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition that primarily affects motor neurons. Cognitive changes are reported in 25%-50% of patients, secondary to frontotemporal involvement. The objective of this study was to evaluate the utility of a screening tool, the Addenbrookes Cognitive Examination (ACE), in ALS patients. METHODS In this retrospective cross-sectional study, performance on the ACE was compared between 55 ALS patients and 49 healthy controls. The validation of the ACE in ALS patients was explored using a neuropsychometric battery. Correlations between the ACE and clinical variables such as the ALS Functional Rating Scale-Revised (ALSFRS-R) and forced vital capacity were computed. RESULTS A higher percentage of patients were below cut-off scores, although this remained non-significant between the patient and control groups. The ACE did not reveal significant differences between ALS patients and controls. The scores on the ACE displayed moderate correlations with our neuropsychometric battery for some domains, whereas others showed poor or no associations. Poor ACE Total was associated with lower ALSFRS-R and finger-tapping scores. CONCLUSIONS Performance on the ACE was comparable between patients and controls. Associations with motor function pose a challenge to accurate interpretation of ACE performance. It is likely that patients with poor cognition have greater disability, or that poor ACE performance reflects reduced motor ability to perform the task. This raises concern for the utility of the ACE as a screening tool in ALS patients, especially since recent versions of the ACE continue to include motor-based tasks.

Amyotrophic lateral sclerosis: Ethical challenges

# {#article-title-2} In the February 2011 issue of Neurology: Clinical Practice , Johnston et al.1 address the ethical issues amyotrophic lateral sclerosis (ALS) raises in a professional and compassionate manner. Nevertheless, some “unethical” thoughts come to mind. Doctors should not behave with an impersonal attitude, should be compassionate, and should not abandon patients even if faced with unacceptable requests. Is assisted suicide an unacceptable request? All of us have experienced assisting a dying patient with ALS and such a request should be addressed in a very thoughtful way. To withdraw a patient from a ventilator under a palliative sedation is more scientific and probably considered more ethical, while assisted suicide is seen as more sudden and dramatic but perhaps less devastating and less financially burdensome to the family. The economic issue sounds outrageous but insurance companies or private health care facilities are greedy. The patient had a previous tragic experience and instinctively asked for a rapid death to avoid a long-lasting agony. He knew that if he had deferred the issue to a surrogate decision-maker, it … Correspondence to: jableckimd{at}gmail.com Correspondence to: wendy.johnston{at}ualberta.ca