Gian Domenico Borasio

EFNS guidelines on the clinical management of Amyotrophic Lateral Sclerosis (MALS) - revised report of an EFNS task force

Background:  The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak.

EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives

Despite being one of the most devastating diseases known, there is little evidence for diagnosing and managing patients with amyotrophic lateral sclerosis (ALS). Although specific therapy is lacking, correct early diagnosis and introduction of symptomatic and specific therapy can have a profound influence on the care and quality of life of the patient and may increase survival time. This document addresses the optimal clinical approach to ALS. The final literature search was performed in the spring of 2005. Consensus recommendations are given graded according to the EFNS guidance regulations. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. People affected with possible ALS should be examined as soon as possible by an experienced neurologist. Early diagnosis should be pursued and a number of investigations should be performed with high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. PEG is associated with improved nutrition and should be inserted early. The operation is hazardous in patients with vital capacity <50%. Non‐invasive positive pressure ventilation improves survival and quality of life but is underused. Maintaining the patients ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end of life care are important and should be fully discussed early with the patient and relatives respecting the patients social and cultural background.

Quality of life and psychosocial issues in ventilated patients with amyotrophic lateral sclerosis and their caregivers

Non-invasive ventilation (NIV) is an efficient palliative measure for symptoms of chronic hypoventilation in patients with amyotrophic lateral sclerosis (ALS), and can also lengthen survival. A subset of ALS patients undergoes tracheostomy ventilation (TV) for life prolongation. We investigated the quality of life (QOL) and psychosocial situation of 52 home ventilated ALS patients and their caregivers. The battery included sociodemographic, generic, and disease-specific variables, as well as the Profile of Mood States and the Munich Quality of Life Dimensions List. Data were compared between the NIV (n=32) and the TV (n=21) groups. Mean ventilation time was 14 months for NIV and 35 months for TV. Eighty-one percent of TV patients had been tracheotomized without informed consent. The data show a good overall QOL for both NIV and TV patients, but a very high burden of care for TV caregivers, 30% of whom rated their own QOL lower than their patients QOL. Sexuality was an important issue. Thus, any assessment of QOL in a home palliative care situation should include the primary caregivers.

The course of the terminal phase in patients with amyotrophic lateral sclerosis

Abstract The fear of “choking to death” is on the mind of most patients suffering from amyotrophic lateral sclerosis (ALS). So far, however, there have been no systematic surveys concerning the dying phase in a general ALS population. We therefore performed a structured telephone interview with the relatives of 121 patients who died from ALS and were followed by the Motor Neuron Outpatient Clinic of the Department of Neurology, University of Munich, Germany. These data are compared with those obtained by a retrospective analysis of medical records of 50 ALS patients who were followed by the Wisdom Hospice, Rochester, UK.The data show that most ALS patients (Germany 88 %, UK 98 %) died peacefully, and no patient “choked to death”. The symptoms most frequently reported for the last 24 hours were dyspnoea, coughing, anxiety and restlessness. Around half (G 55 %, UK 52 %) of the patients died at home. The main palliative measures in place during the terminal phase were: home mechanical ventilation (G 21 %, UK 0 %), percutaneous endoscopic gastrostomy (G 27 %, UK 14 %), morphine (G 27 %, UK 82 %) and benzodiazepines (G 32 %, UK 64 %). The use of these palliative measures was judged to be beneficial by almost all relatives. These data support the hypothesis of a peaceful death process in ALS and should be communicated to patients and their relatives, at the latest after the onset of dyspnoea, to relieve unwarranted fears.

Good practice in the management of amyotrophic lateral sclerosis : clinical guidelines. An evidence-based review with good practice points. EALSC Working Group.

The evidence base for diagnosis and management of ALS is still weak, and curative therapy is lacking. Nonetheless, early diagnosis and symptomatic therapy can profoundly influence care and quality of life of the patient and relatives, and may increase survival time. This review addresses the current optimal clinical approach to ALS. The literature search is complete to December 2006. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. We conclude that a diagnosis of ALS can be achieved by early examination by an experienced neurologist. The patient should be informed of the diagnosis by the consultant. Following diagnosis, a multi‐diciplinary care team should support the patient and relatives. Medication with riluzole should be initiated as early as possible. PEG is associated with improved nutrition and should be inserted early. The operation is hazardous in patients with VC <50%: RIG may be a better alternative. Non‐invasive positive pressure ventilation improves survival and quality of life but is underused in Europe. Maintaining the patients ability to communicate is essential. During the course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end of life care are important and should be discussed early with the patient and relatives if they so wish.

Palliative care in amyotrophic lateral sclerosis

The poor prognosis of amyotrophic lateral sclerosis (ALS) makes palliative care a challenge for the neurologist. Most disabilities associated with progressive disease can be ameliorated by symptomatic treatment. Prognosis and treatment options should be openly discussed with the patient and his/her relatives. Nutritional deficiency due to pronounced dysphagia can be efficiently relieved by a percutaneous enterogastrostomy. Respiratory insufficiency can be treated by non-invasive ventilation at home, provided the familial environment is supportive. Adequate assistance and palliative treatment in the terminal phase is of paramount importance.

Palliative therapy in the terminal stage of neurological disease

Abstract As recently pointed out by the American Academy of Neurology, providing adequate palliative care to dying patients is the duty of every neurologist. Because of a lack of relevant articles in the neurological literature, we have compiled current treatment recommendations for the most important symptoms arising in the endstage of neurological diseases. These recommendations include treatment of dyspnea, death rattle, restlessness, pain, thirst, depression, and others. A discussion of difficult decisions is included, e.g., the appropriate extent of fluid substitution or the ethical implications of sedation in the terminal phase. It is hoped that this compilation may provide a basis for future research in palliative therapy in neurology.

INHIBITORS OF P38 MITOGEN-ACTIVATED PROTEIN KINASE PROMOTE NEURONAL SURVIVAL IN VITRO

Mammalian mitogen‐activated protein kinases include the extracellular signal‐regulated protein kinase, the c‐Jun amino‐terminal kinase, and the p38 subgroups. Sustained activation of Jun kinase and p38 have been shown to precede apoptosis of PC12 pheochromocytoma cells induced by withdrawal of trophic factors. To investigate the possible role of p38 in neuronal apoptosis, we tested the effect of two selective p38 inhibitors, the pyridinyl imidazole compounds SB203580 and SB202190, on different populations of chick embryonic neurons in vitro. Both substances promoted the in vitro survival of sensory, sympathetic, ciliary and motor neurons in a dose‐dependent fashion. When assayed in nerve growth factor‐stimulated PC12 cells, SB203580 pretreatment inhibited the activation of both ribosomal S6 kinases‐1 and ‐2 with the same IC50 (approximately 30 μM) that inhibited apoptosis in primary neurons. Thus, p38 inhibitor‐sensitive pathways may be involved in apoptosis of neurotrophic factor‐deprived primary neurons, and in activation of ribosomal S6 kinases. J. Neurosci. Res. 52:483–490, 1998.

Effects of spiritual care training for palliative care professionals

Little is known about the effects of spiritual care training for professionals in palliative medicine. We therefore investigated prospectively the effects of such training over a six-month period. All 63 participants of the three and a half-day training were asked to fill out three questionnaires: before and after the training, as well as six months later. The questionnaires included demographic data, numeric rating scales about general attitudes towards the work in palliative care, the Self-Transcendence Scale (STS), the spiritual subscale of the Functional Assessment of Chronic Illness Therapy (FACIT-Sp) and the Idler Index of Religiosity (IIR). Forty-eight participants (76%) completed all three questionnaires (91% women, median age 49 years; 51% nurses, 16% hospice volunteers, 14% physicians). Significant and sustained improvements were found in self-perceived compassion for the dying (after the training: P =0.002; 6 months later: P=0.025), compassion for oneself (PB 0.001; P =0.013), attitude towards ones family (P =0.001; P =0.031), satisfaction with work (PB 0.001; P =0.039), reduction in work-related stress (PB 0.001; P =0.033), and attitude towards colleagues (P =0.039; P =0.040), as well as in the FACIT-Sp (PB 0.001; P =0.040). Our results suggest that the spiritual care training had a positive influence on the spiritual well-being and the attitudes of the participating palliative care professionals which was preserved over a six-month period.

Palliative care in amyotrophic lateral sclerosis.

Abstract The poor prognosis of amyotrophic lateral sclerosis (ALS) makes palliative care a challenge for the neurologist. Most disabilities associated with progressive disease can be ameliorated by symptomatic treatment. Prognosis and treatment options should be openly discussed with the patient and his/her relatives. Nutritional deficiency due to pronounced dysphagia can be efficiently relieved by a percutaneous enterogastrostomy. Respiratory insufficiency can be treated by non-invasive ventilation at home, provided the familial environment is supportive. Adequate assistance and palliative treatment in the terminal phase is of paramount importance.