{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T05:34:11Z","timestamp":1763098451455,"version":"3.45.0"},"reference-count":109,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"home institutions of the investigators"},{"DOI":"10.13039\/100015539","name":"U.S. Federal Government","doi-asserted-by":"crossref","award":["IRS 48D","CFDA 21.013"],"award-info":[{"award-number":["IRS 48D","CFDA 21.013"]}],"id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Neurological disorders are the leading cause of disability, affecting over three billion people worldwide. Amyotrophic lateral sclerosis (ALS) is among the most feared and uniformly fatal neurodegenerative diseases, with no therapy capable of restoring lost function. Methods: We report the first application of therapeutic fever to ALS using Computerized Brain-Guided Intelligent Thermofebrile Therapy (CBIT2). This fully noninvasive treatment, delivered through an FDA-approved computerized platform, digitally reengineers the 1927 Nobel Prize-recognized malarial fever therapy into a modern treatment guided by the Brain\u2013Eyelid Thermoregulatory Tunnel. CBIT2 induces therapeutic fever through synchronized hypothalamic feedback, activating heat shock proteins, which are known to restore proteostasis and neuronal function. Case presentation: A 56-year-old woman was diagnosed with progressive ALS at the Mayo Clinic, with electromyography (EMG) demonstrating fibrillation and fasciculation indicative of denervation corroborated by neurological and MRI findings; the patient was informed that she had an expected survival of three to five years. A neurologist from Northwestern University confirmed the diagnosis and thus maintained the patient on FDA-approved ALS drugs (riluzole and edaravone). Her condition rapidly worsened despite pharmacological treatment, and she underwent CBIT2, resulting in (i) electrophysiological reversal with complete disappearance of denervation; (ii) biomarker correction, including reductions in neurofilament and homocysteine, IL-10 normalization (previously linked to mortality), and robust HSP70 induction; (iii) restoration of gait, swallowing, respiration, speech, and cognition; (iv) reconstitution of tongue structure; and (v) return to complex motor tasks, including golf, pickleball, and swimming. Discussion: This case provides the first documented evidence that ALS can be reversed through digitally reengineered fever therapy aligned with thermoregulation, which induces heat shock response and upregulates heat shock proteins, resulting in the patient no longer meeting diagnostic criteria for ALS and discontinuation of ALS-specific medications. Beyond ALS, shared protein-misfolding pathology suggests that CBIT2 may extend to Alzheimer\u2019s, Parkinson\u2019s, and related disorders. By modernizing this Nobel Prize-recognized therapeutic principle with computerized precision, CBIT2 establishes a framework for large-scale clinical trials. A century after fever therapy restored lost brain function and so decisively reversed dementia paralytica such that it earned the 1927 Nobel Prize in Medicine, CBIT2 now safely harnesses the therapeutic power of fever through noninvasive, intelligent, brain-guided thermal modulation. Amid a global brain health crisis, fever-based therapies may offer a path to preserve thought, memory, movement, and independence for the more than one-third of humanity currently affected by neurological disorders.<\/jats:p>","DOI":"10.3390\/diseases13110371","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:59:09Z","timestamp":1763027949000},"page":"371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Total Reversal of ALS Confirmed by EMG Normalization, Structural Reconstitution, and Neuromuscular\u2013Molecular Restoration Achieved Through Computerized Brain-Guided Reengineering of the 1927 Nobel Prize Fever Therapy: A Case Report"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8525-3274","authenticated-orcid":false,"given":"M. Marc","family":"Abreu","sequence":"first","affiliation":[{"name":"Clinical Sciences Division, BTT Medical Institute, Aventura, FL 33160, USA"},{"name":"Department of Biomedical Engineering and Medical Physics, BTT Medical Institute, Aventura, FL 33180, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9342-8644","authenticated-orcid":false,"given":"Mohammad","family":"Hosseine-Farid","sequence":"additional","affiliation":[{"name":"College of Computing and Engineering, Nova Southeastern University, Fort Lauderdale, FL 33314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9657-6412","authenticated-orcid":false,"given":"David G.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","unstructured":"Canada Brain Research Strategy (2025, August 19). 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