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|NI FEATURE: THE EDITORIAL DEBATE-- PROS AND CONS
|Year : 2017 | Volume
| Issue : 1 | Page : 14-15
The death wish and motor neuron disease! The chameleons and new research optimism
Ashok Panagariya, Parul Dubey, Bhawna Sharma
Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India
|Date of Web Publication||12-Jan-2017|
7, Raj Niketan, Moti Dungari Road, Jaipur, Rajasthan
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Panagariya A, Dubey P, Sharma B. The death wish and motor neuron disease! The chameleons and new research optimism. Neurol India 2017;65:14-5
It is a million-dollar question whether “dying good” is as important as “living good.” The concept of “good death” in general may be considered as an act of cynicism. But the physicians are more and more confronted with the thoughts of death and the “wish to die” in individuals with chronic medical conditions with little hope of treatment, a poor quality of life, and in patients considering themselves of little value to the society.
While such a situation in the western world would more often arise when individuals are faced with incurable, life-threatening medical issues, which could prolong the phase of “badly living/dying,” in the Indian conditions, some of the religious belief systems have different perceptions about death. Death is not considered to be the end of life but a transition to next life or attainment of salvation or merger with the Almighty. Santhara, a concept in Jain philosophy means ascending to a higher level of personal evolution and merging into the divine.
Amyotrophic lateral sclerosis, a disease of rippling muscles, continues to be a serious therapeutic challenge. Dr. Gouri-Devi has elegantly presented the study on “death wish” in the patients suffering from amyotrophic lateral sclerosis in the Indian context.
Owing to the deep seated spiritual traditions in many religions, Indians are more prone to believe in karma and destiny. While clearly financial and socioeconomic conditions largely govern a person's assessment of his/her entire situation, depending upon the individual's educational and spiritual levels, some may be resigned to fate, while others with a stronger belief may accept such a condition as a part of the larger divine plan and as an integral component of the spiritual journey.
Having touched upon this abstract issue, it seems apt to discuss at this point, the clinical challenges involved in appropriately diagnosing amyotrophic lateral sclerosis, which is almost a death sentence owing to its degenerative and incurable nature; and, also in identifying the mimics and chameleons, which may either be treatable or have a much better prognosis with specific therapeutic interventions, often with a much brighter outlook.
Presence of fasciculations in grossly wasted muscles with upper motor neuron signs in the same territories is the clinical hallmark of the classical motor neuron disease, amyotrophic lateral sclerosis (ALS), which invariably harbours a poor prognosis. However, rippling of muscles is not always a harbinger of an untreatable neurological disorder. The chameleons, which could be potentially treatable include neuromyotonia, multifocal motor neuropathy (MMN) with conduction blocks, and the benign variants of motor neuron disease like Hirayama, Kennedy and rippling muscle disease, that have a relatively better prognosis.,
Most of these disorders of muscle rippling, despite having significant clinical similarities leading to bedside confusion, can be distinctly diagnosed and classified based on meticulous clinical, electrophysiological and immunologic evaluation.
The clinical overlap, in part, is attributable to an underlying motor unit hyperexcitability unifying the various entities. Associated central nervous involvement in some, may represent an extension of the same phenomenon of hyperexcitability due to shared ion channels between peripheral and central nervous systems, albeit at different locations. It is intriguing that the same phenomenon of motor unit or peripheral nerve hyperexcitability, which is initiated in ALS, neuromyotonia, benign fasciculation syndrome (BFS) or MMN, has differing etiological substrates, ranging from autoimmune to excitotoxic degeneration, and likewise, widely different outcomes in terms of therapeutic response and natural histories. A review of recent literature does indicate the possibility of common mechanisms being at the core of the pathophysiology of these varied disorders.
Evidence of autoimmunity in neuromyotonia and multifocal motor neuropathy with conduction block (MMNCB) has been well established by demonstration of autoantibodies and response to immunotherapy, while benign cramp fasciculation syndrome, at the border zones, remains intriguing.
Interestingly in a recent study by Turner et al., ALS was found to be significantly associated with a prior autoimmune disorder at least 1 year before the diagnosis of ALS. A case-control study in MMN showed that type 1 diabetes, Hashimoto thyroid disease, and celiac disease were all significantly more prevalent in family members of patients. Also, inherited ALS is being supposed a manifestation of a mitochondrial channelopathy due to a mutant superoxide dismutase 1 (SOD1), which binds and inhibits the mitochondrial channel, voltage dependent anion-selective channel 1 (VDAC1). Nosologic limits of continuous muscle fiber activity, however, are yet to be fully delineated and further clinicoelectrophysiological studies exploring the immunologic associations would further enhance our understanding of this group of disorders.,
The nervous system and the whole body is an orchestrated continuum of some basic physiologic phenomena like ionic functions, neurotransmitters and cellular mechanisms, which are finally determined at the genetic level. More research should be targeted towards deriving the common linkage between such seemingly diversified disorders which hint at a common association. Then we may hope to achieve cure by fixing the basic disordered mechanism.
| » References|| |
Panagariya A, Agarwal V, Agarwal N. All that ripples is not “motor neuron disease”. Ann Indian Acad Neurol 2007;10:88-91.
Turner MR, Talbot K. Mimics and chameleons in motor neuron disease. Pract Neurol 2013;13:153-64.
Sendtner, M. 2006. Motor neuron diseases: Molecular mechanism, pathophysiology, and treatments. Reviews in Cell Biology and Molecular Medicine. DOI: 10.1002/3527600906.mcb.200400146.
Küçükali CI, Kürtüncü M, Akçay Hİ, Tüzün E, Öge AE. Peripheral nerve hyperexcitability syndromes. Rev Neurosci. 2015;26:239-51.