The Biochemical Changes in Parkinsonism-Dementia-Exploring Theamyotrophic Lateral Sclerosis Complex: A Clinical Case Study and Implications for Diagnosis and Treatment

Authors

  • Ahmed Kareem Thamer Assistant Lecturer Pharmacy College, University of Al-Qadisiyah, Al-Diwaniya, Iraq
  • Bahaulddin Jafar Seger Assistant Lecturer Pharmacy College, University of Al-Qadisiyah, Al-Diwaniya, Iraq
  • Gufran Abbas Isewid Assistant Lecturer Pharmacy College, University of Al-Qadisiyah, Al-Diwaniya, Iraq
  • Nahid Sabah Aldin Saber Assistant Lecturer Pharmacy College, University of Al-Qadisiyah, Al-Diwaniya, Iraq

Keywords:

Parkinsonism, Dementia, Amyotrophic Lateral Sclerosis, Neurodegenerative Disease

Abstract

The Parkinsonism-Dementia-Amyotrophic Lateral Sclerosis (PD-ALS) complex, initially identified in Guam, poses diagnostic challenges due to its rarity. This study presents a clinical case to elucidate the nosological and pathogenetic implications of this neurodegenerative disease, particularly in populations where this association is unexpected. A patient of Iraqi origin manifested systemic symptoms evolving over 5 years, followed by cognitive alterations and subsequently developing gait disturbances and motor symptoms suggestive of parkinsonism with atypical features. Motor neuron disease signs were also observed, confirmed by extension studies revealing the involvement of both upper and lower motor neurons. A mutation in the POLG gene associated with mitochondrial depletion syndrome was identified. Diagnosing the PD-ALS complex remains clinically challenging, with molecular mechanisms yet to be fully understood. Common genes associated with parkinsonism and amyotrophic lateral sclerosis have been ruled out, and attempts to localize the locus have yielded inconclusive results. Unfortunately, the prognosis remains fatal, and there are no disease-modifying treatments available. This case underscores the importance of further research into this complex neurodegenerative disease and the need for improved diagnostic and therapeutic strategies. The association between parkinsonism-dementia and ALS is an infrequent entity and difficult to diagnose clinically for inexperienced doctors, for whom it represents a diagnostic challenge. Due to the unfavorable prognosis of the disease and the functional limitation it confers, many times, it is not possible to conclude the diagnosis or provide adequate follow-up. The importance of knowing the clinical data of motor neuron disease and the warning of Parkinsonism has made it possible to standardize the diagnostic conduct from the first evaluation.

Downloads

Download data is not yet available.

References

E. Candeias, D. Nunes-Costa, A. R. Pereira-Santos, and ..., “Neurotoxicity induced by the microbial metabolite β-methylamino-L-alanine: pathways and mechanisms,” Natural Molecules in …, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/B9780443237638000683

A. L. Young, N. P. Oxtoby, S. Garbarino, N. C. Fox, and ..., “Data-driven modelling of neurodegenerative disease progression: thinking outside the black box,” Nature Reviews …, 2024, [Online]. Available: https://www.nature.com/articles/s41583-023-00779-6

Á. Bartók and L. Csanády, “TRPM2-An adjustable thermostat,” Cell Calcium, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/S0143416024000083

F. Sofyantoro, A. Frediansyah, W. A. Putri, and ..., “10 Herbal Medicines,” … for Brain Drug …, 2024, [Online]. Available: https://books.google.com/books?hl=en&lr=&id=MNrrEAAAQBAJ&oi=fnd&pg=PA210&dq=10+herbal+medicines&ots=9SzAZe9OLB&sig=f7vGbDuD7OjHDtK8d-GJr-SJGJ0

N. Bhatt, N. Puangmalai, U. Sengupta, C. Jerez, and ..., “C9orf72-associated dipeptide protein repeats form A11-positive oligomers in amyotrophic lateral sclerosis and frontotemporal dementia,” Journal of Biological …, 2024, [Online]. Available: https://www.jbc.org/article/S0021-9258(24)00004-8/abstract

A. Goswami and S. Carra, “PML nuclear bodies: new players in familial amyotrophic lateral sclerosis-frontotemporal dementia?,” Neural Regen Res, 2024, [Online]. Available: https://journals.lww.com/nrronline/fulltext/2024/09000/pml_nuclear_bodies__new_players_in_familial.8.aspx?context=latestarticles

N. Hartopp, A. Markovinovic, C. C. J. Miller, and ..., “Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis,” Neural Regeneration …, 2024, [Online]. Available: https://journals.lww.com/nrronline/fulltext/2024/07000/insight_into_endoplasmic_reticulum_mitochondria.6.aspx?context=latestarticles

W. Yu et al., “Quantitative association between lead exposure and amyotrophic lateral sclerosis: a Bayesian network-based predictive study,” Environmental …, 2024, doi: 10.1186/s12940-023-01041-3.

V. Baskerville, S. Rapuri, E. Mehlhop, and A. N. Coyne, “SUN1 facilitates CHMP7 nuclear influx and injury cascades in sporadic amyotrophic lateral sclerosis,” Brain, 2024, [Online]. Available: https://academic.oup.com/brain/article-abstract/147/1/109/7252804

C. B. Morrow, “Geriatric Psychiatry and the Future of Dementia Care: Diagnosing TDP-43 Neurodegenerative Disease,” The American Journal of Geriatric Psychiatry, 2024, [Online]. Available: https://www.ajgponline.org/article/S1064-7481(23)00406-2/abstract

H. Wang, Y. T. Liu, Y. L. Ren, X. Y. Guo, and Y. Wang, “Association of peripheral immune activation with amyotrophic lateral sclerosis and Parkinson’s disease: A systematic review and meta-analysis,” J Neuroimmunol, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/S0165572824000080

Y. Wang, L. Liu, H. Chen, Y. Yang, C. Mu, and ..., “Disrupted phase behavior of FUS underlies poly-PR-induced DNA damage in amyotrophic lateral sclerosis,” Human Molecular …, 2024, [Online]. Available: https://academic.oup.com/hmg/article-abstract/33/1/64/7282670

L. D. Aubrey, N. Ninkina, S. M. Ulamec, and ..., “Substitution of Met-38 to Ile in γ-synuclein found in two patients with amyotrophic lateral sclerosis induces aggregation into amyloid,” Proceedings of the …, 2024, doi: 10.1073/pnas.2309700120.

I. S. da Silva, A. R. Cardoso, and M. G. F. Sales, “Electrochemical biosensor-based detection assays for early diagnosis of neurodegenerative disorders,” Smart Diagnostics for …, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/B9780323955393000107

J. T. Alshaikh, A. Paul, E. Moukheiber, and ..., “VCP mutations and parkinsonism: An emerging link,” … & Related Disorders, 2024, [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10746554/

A. Mahin, S. P. Soman, P. K. Modi, R. Raju, and ..., “Meta-analysis of the serum/plasma proteome identifies significant associations between COVID-19 with Alzheimer’s/Parkinson’s diseases,” Journal of …, 2024, doi: 10.1007/s13365-023-01191-7.

I. Martinelli, E. Zucchi, C. Simonini, and ..., “SerpinA1 levels in amyotrophic lateral sclerosis patients: An exploratory study,” European Journal of …, 2024, doi: 10.1111/ene.16054.

Y. Xiang et al., “Estimating the sequence of biomarker changes in Parkinson’s disease,” Parkinsonism &Related …, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/S1353802023010180

I. Y. Iskusnykh, A. A. Zakharova, E. D. Kryl’skii, and ..., “Aging, Neurodegenerative Disorders, and Cerebellum,” International Journal of …, 2024, [Online]. Available: https://www.mdpi.com/1422-0067/25/2/1018

S. Gallo, F. Vignaroli, E. Contaldi, D. Vecchio, and ..., “Parkinson’s disease and chronic inflammatory demyelinating polyneuropathy: Broadening the clinical spectrum of VCP mutations,” … & Related Disorders, 2024, [Online]. Available: https://www.prd-journal.com/article/S1353-8020(23)01032-5/abstract

S. Liu et al., “Glymphatic dysfunction in patients with early-stage amyotrophic lateral sclerosis,” Brain, 2024, [Online]. Available: https://academic.oup.com/brain/article-abstract/147/1/100/7242943

U. Manera, E. Matteoni, A. Canosa, and ..., “Mycotoxins and Amyotrophic Lateral Sclerosis: food exposure, nutritional implications and dietary solutions,” CNS &Neurological …, 2024, [Online]. Available: https://www.ingentaconnect.com/content/ben/cnsnddt/2024/00000023/00000005/art00005

D. Huo et al., “Roflupram alleviates autophagy defects and reduces mutant hSOD1-induced motor neuron damage in cell and mouse models of amyotrophic lateral sclerosis,” …, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/S0028390823004021

T. Payne, T. Burgess, S. Bradley, S. Roscoe, M. Sassani, and ..., “Multimodal assessment of mitochondrial function in Parkinson’s disease,” Brain, 2024, [Online]. Available: https://academic.oup.com/brain/article-abstract/147/1/267/7459758

K. Tsuji, Y. Nakayama, J. Taruya, and ..., “Persistence of Kii amyotrophic lateral sclerosis after the 2000s and its characteristic aging-related tau astrogliopathy,” Journal of Neuropathology …, 2024, [Online]. Available: https://academic.oup.com/jnen/article-abstract/83/2/79/7513119

F. Wu, A. M. Malek, J. M. Buchanich, V. C. Arena, and ..., “Exposure to ambient air toxicants and the risk of amyotrophic lateral sclerosis (ALS): A matched case control study,” Environmental …, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/S0013935123025239

Y. Kwon, M. Kang, Y. M. Jeon, S. Lee, H. W. Lee, and ..., “Identification and characterization of novel ERBB4 variant associated with sporadic amyotrophic lateral sclerosis (ALS),” Journal of the …, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/S0022510X24000200

F. Jia et al., “Exploring the cuproptosis-related molecular clusters in the peripheral blood of patients with amyotrophic lateral sclerosis,” Computers in Biology …, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/S0010482523012416

H. Leonard, C. Jonson, K. Levine, J. Lake, L. Hertslet, and ..., “Assessing the lack of diversity in genetics research across neurodegenerative diseases: a systematic review of the GWAS Catalog and literature,” medRxiv, 2024, doi: 10.1101/2024.01.08.24301007.abstract.

F. De Marchi, S. Venkatesan, M. Saraceno, and ..., “Acetyl-L-carnitine and Amyotrophic Lateral Sclerosis: Current evidence and potential use,” CNS &Neurological …, 2024, [Online]. Available: https://www.ingentaconnect.com/content/ben/cnsnddt/pre-prints/content-36998125

S. H. Jeong, J. Cha, H. S. Yoo, S. J. Chung, J. H. Jung, and ..., “Different effect of hypo-and hypermetabolism on cognition in dementia with Lewy bodies: are they coupled or independent?,” npj Parkinson’s …, 2024, [Online]. Available: https://www.nature.com/articles/s41531-023-00622-w

V. E. Neubrand, M. R. Sepúlveda, C. Dias, and ..., “1421 A dysregulated calcium homeostasis as the earliest pathological sign in stem cell-derived Parkinson’s disease neurons?,” NEURAL …, 2024, [Online]. Available: https://www.researchgate.net/profile/Ruitian-Liu/publication/374654847_Neuronal_conversion_from_glia_to_replenish_the_lost_neurons/links/657812376610947889bb2a05/Neuronal-conversion-from-glia-to-replenish-the-lost-neurons.pdf

K. Chen, T. Gao, Y. Liu, K. Zhu, T. Wang, and P. Zeng, “Identifying risk loci for FTD and shared genetic component with ALS: A large-scale multitrait association analysis,” Neurobiol Aging, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/S0197458023002361

X. Xuan et al., “Alterations in regional homogeneity and functional connectivity in the cerebellum of patients with sporadic amyotrophic lateral sclerosis,” Behavioural Brain …, 2024, [Online]. Available: https://www.sciencedirect.com/science/article/pii/S0166432823004679

K. Klíčová, J. Mareš, K. Menšíková, M. Kaiserová, and ..., “Utilizing neurodegenerative markers for the diagnostic evaluation of amyotrophic lateral sclerosis,” European Journal of …, 2024, doi: 10.1186/s40001-023-01596-4.

A. Carmona, E. Carboni, L. C. Gomes, and ..., “Metal dyshomeostasis in the substantia nigra of patients with Parkinson’s disease or multiple sclerosis,” Journal of …, 2024, doi: 10.1111/jnc.16040.

Downloads

Published

2024-04-25

How to Cite

Thamer, A. K. ., Seger, B. J., Isewid, G. A., & Saber, N. S. A. (2024). The Biochemical Changes in Parkinsonism-Dementia-Exploring Theamyotrophic Lateral Sclerosis Complex: A Clinical Case Study and Implications for Diagnosis and Treatment. INTERNATIONAL JOURNAL OF HEALTH SYSTEMS AND MEDICAL SCIENCES, 3(2), 104–114. Retrieved from https://inter-publishing.com/index.php/IJHSMS/article/view/3500

Issue

Section

Articles