12th International Symposium on ALS/MND November 18-20, 2001

Oakland California Highlights and Summary of Clinical Sessions

The International Symposium on ALS/MND is a unique annual event that brings together leading international scientific and clinical researchers and clinicians to present and debate key innovations in their respective fields. The clinical track features research and
advances in the care and management for people with ALS.

Preceding the Symposium, an Ask the Experts educational program addressed the latest in ALS research and clinical treatments for patients and their families. Included in the presentations were discussions of the role genetics plays in ALS - and what additional influence we may yet have to learn, stem cell research, immune/ inflammatory considerations, viruses and ALS, glutamate, Rilutek and anti-oxidants and nutritional supplements. Different leaders in the ALS field presented an overview of the current status of each topic.

This year's clinical sessions were exciting and offered new information and interesting ideas to improve clinical care for people living with ALS.

Having a number of international presentations pointed out some of the striking differences in clinical care throughout the world. Two examples are issues of patient autonomy and empowerment which, along with the quest for information about ALS, are clearly prevalent in the U.S., but are much less common in other countries. The percentage of people with ALS living with long term mechanical ventilation is 56% in Japan where the government pays for the necessary supportive care. Whereas, data from the ALS CARE database suggest that as few as <2% of people with ALS in the U.S. have chosen mechanical ventilation.

Knowing when and how to evaluate a patient's respiratory status in the ways that will reliably identify the earliest signs of impaired respiratory function are important. Non-invasive ventilation is a treatment for the respiratory weakness ALS can cause. This therapy is probably the most significant treatment available to prolong life in ALS. There were a number of presentations on how best to analyze when non-invasive ventilation should be offered. Various tests of prognostic value were discussed recognizing that many patients with bulbar symptoms have trouble with ventilation tests. Nocturnal pulse oximetry measuring oxygen desaturation at night is emerging as an important indicator of respiratory status. The value of monitoring symptoms such as sleep disturbances, sleeping with the head raised, daytime yawning and sleepiness, and morning headaches as early indicators of respiratory impairment were stressed. There is broad variation among ALS clinics as to the numbers and percentages of ALS patients with feeding tubes - Percutaneous Endoscopic tubes (PEG). Despite the recommendation from the ALS Practice Parameter that PEG should be considered early in the course of ALS and begun before breathing function declines below 50% of predicted, the numbers of patients with PEGs vary from 0 to 50% of patients, depending on the clinic. Although it has been demonstrated that PEG can make a significant improvement in a person's nutritional and fluid status as well as quality of life, data to suggest an increase in survival are less clear. One study reported at this conference included data showing a slight trend to decreasing mortality with PEG.

Reports from three separate patient databases described long range experience with riluzole. All three reports suggest a trend of increasing survival with riluzole over time. More studies that are double blind and controlled are needed to confirm these database observations. The trend appears to indicate that longer periods of time than those used in the riluzole clinical trials may be needed to see the long-term survival advantage of the drug. An interesting observation was that despite the fact that the Irish government provides riluzole free of charge to people in Ireland with ALS, only two-thirds of the patients registered in the Ireland national ALS database reported taking riluzole.

Preliminary results of a small study (31 patients at three ALS clinics) of ultrapure creatine were encouraging in demonstrating a short-term trend of improvement in muscle strength. There was no change in scores on the ALS Functional Rating Scale that asks about level and independence in several activities of daily living. Findings from the initial study have led to a larger study that is now enrolling patients. The evaluation of the safety of Creatine showed no significant adverse drug effects. An overview of a project to improve end of life care for people with ALS and their families stressed the need for better communication with patients from the time of diagnosis through the end of life, more research in this area and policy changes to improve hospice accessibility and other important care. The project is sponsored by the Robert Wood Johnson Foundation and is led by The ALS Association. Suggestions related to improving the efficiency of clinical trials were discussed including using the patient as his/her own control. While this design would ensure that each person in the clinical trial received the treatment, it is not totally blinded and the Food and Drug Administration has not supported this design. Although a single-arm trial design with the patient serving as his/her own control would require a longer study period than the conventional two-arm trial, up to eight times fewer patients would be required for this design than the placebo-controlled design. In the one-arm design, there is a period of no treatment that measures the patient's natural progression and a second period where the treatment is administered. Preliminary data from one German survey of 33 ALS patients and their partners suggest that the meaning and importance of sexuality does decline during the course of ALS, but its importance is still significantly underestimated by health care professionals. ALS clinicians should inquire about possible problems with sexuality and provide information, counseling and support as necessary.

Deep Vein Thrombosis (DVT) - blood clot in the blood vessels of the legs - and pulmonary embolism (PE) - blood clot in the blood vessels of the lungs - are especially difficult to detect in people with ALS who have other reasons for limb swelling and difficulty breathing. As the consequences of these conditions can be life threatening, ALS clinicians may want to routinely include an assessment of these two conditions for their ALS patients - especially those who are elderly and/or have become immobile.

Caregiving for people with ALS was a continuing theme throughout many presentations recognizing the critical role families play in this disease. It was acknowledged that further analysis of ALS caregivers and support for this staggeringly difficult role must be a future emphasis.

Two reports of U.S. epidemiological studies in ALS emphasized the difficulty in conducting population-based research and in the contributions well conducted epidemiological studies can make to understanding possible risks for the disease and, potentially, a better understanding of the cause. A review of 22 years of deaths from ALS in Texas revealed that there is a suggestion of a slight increase in the number of people dying from the disease. The increase was seen in the 6th and 7th decades of life in this retrospective review of death certificates. Over the 22-year period, 55% of the ALS deaths were in men and the median age at death for all people in the study was 68 years. The study did not find any evidence of an increasing incidence of ALS in younger people. There were several reports of ALS patients with various cognitive impairments - perhaps as many as 3-15% of all ALS patients. Clinician observance of cognitive changes in their ALS patients has been reported increasingly over the past few years. Examples of the types of changes that are described include memory loss, behavior changes, problems with both judgment and performing multiple tasks.