Resurgo Protocol: Non-surgical Rehabilitation for Compression-Ischemic Neuropathy (Radial Nerve Injury)

"Resurgo" Protocol: Comprehensive Conservative Rehabilitation for Compression-Ischemic Radial Neuropathy (Retrospective Case Series, n=11) Article type: Case Series (Retrospective, Descriptive Study) Disclaimer: The research concept has been tested on a limited number of patients and requires further validation. This document does not contain clinical instructions and is not a medical recommendation. Informed Consent: Written or verbal informed consent for treatment was obtained from all patients at the time of their enrollment in the treatment program. Ethics Statement: This study is a retrospective analysis of clinical data obtained during standard care. Therefore, the requirement for formal prior ethical approval from an Institutional Review Board (IRB) or Ethics Committee was waived, according to established local guidelines for retrospective reviews. All patient data presented are anonymized and de-identified to ensure privacy and adhere to the ethical principles of the Declaration of Helsinki Funding support: This research did not receive any specific grant from fundingagencies in the public, commercial, or not-for-profit sectors. Attachments: The manuscript includes 2 figures and 1 table. Murad Novruzov - corresponding author (ORCID: 0009-0007-2386-6332) E-mail: [email protected] Affiliation: 1. Independent Biomedical Researcher - Azerbaijan, Baku Role: Primary Author & Concept Originator. Marziyya Mammadova, MD (ORCID: 0000-0001-5976-6551) Affiliation: 1. Azerbaijan State Advanced Training Institute for Doctors named after Aziz Aliyev - Azerbaijan, Baku; 2. Assistant of Neurology and Clinical Neurophysiology department - Azerbaijan, Baku; 3. Ministry of Health of Azerbaijan - Azerbaijan, Baku;; 4. Azerbaijan Science and Health Initiatives (ASHI) - Azerbaijan, Baku. Role: Provided specialized medical knowledge, data, and contributed to the conceptual and editorial development of the manuscript. Abstract (Structured Abstract) Objective: To present and evaluate the clinical results of the comprehensive conservative protocol “Resurgo” in 11 patients diagnosed with compression-ischemic radial neuropathy, paying particular attention to the dynamics of pain, muscle tone, and restoration of active motor function. Methods: A multicomponent conservative regimen was applied, combining: 1) A strictly regulated 5-day local cycle of alternating gels and compresses; 2) Weekly subcutaneous injections of hyaluronidase with novocaine in the area of the suspected fibrous scar; 3) A course of systemic neuroprotective pharmacotherapy (ipidacrine, cerebrovin, liposom forte) and muscle relaxants (tolperisone); 4) Cyclical functional rehabilitation program (therapeutic physical training/TPT and stimulation). Monitoring was performed weekly with assessment of pain (VAS) [30], range of motion (ROM), and muscle tone. Results: In the index case (n1), the pain level on the visual analog scale (VAS) decreased from 10/10 to ~1/10 by the 25th day of treatment. By weeks 7–12, there was a reduction in spasticity and the appearance of minimal active extension. In an additional cohort (n=10), comparable positive trends were observed in pain relief (VAS\↓ by 50–80% within 4–6 weeks) and normalization of tone. The rate of active recovery of motor functions varied, but was progressive in cases of earlier initiation of therapy. Side effects were limited to rare cases of local dermatitis at the site of application of the compress. Conclusion: The Resurgo protocol demonstrated a clinically significant effect in alleviating pain, eliminating contractures, and stimulating motor function in this series of cases. Prospective randomized controlled trials are needed for further confirmation [3]. Keywords: radial nerve, compression-ischemic neuropathy, contracture, conservative therapy, Hyaluronidase, Dimexide, Ipidacrine, rehabilitation, series of cases. Introduction (Introduction) Background and Rationale Compression-ischemic radial neuropathy (CIRN) is one of the most common tunnel syndromes of the upper extremity, often resulting from traumatic injury or prolonged compression [1, 10]. The clinical picture, often described as “wrist drop,” usually includes motor deficit in the extensor compartment and loss of sensation [4]. The pathogenesis of CIRN involves ischemic damage to the nerve trunk, perineural edema, and, most importantly, the development of localized fibrosis and scarring, especially in chronic forms [12]. Knowledge Gap Conservative treatment, including activity modification and splinting, remains the first-line treatment for radial nerve entrapment syndrome [2, 9]. However, conservative treatment is often tried for at least six weeks before moving on to other treatments, and there is limited evidence of the high effectiveness of these standard treatments in severe chronic cases [9, 6]. The main limitation to achieving functional recovery, especially in cases of prolonged axonotmesis, is mechanical resistance caused by perineural scarring and chronic inflammation [13]. Therefore, there is a need for comprehensive, multi-stage conservative protocols that aggressively target the fibro-adhesive component while promoting neurotrophic support and functional rehabilitation [3, 19]. Study Objective The aim of this study is to provide a detailed description of the new Resurgo protocol and a retrospective analysis of its clinical results in a cohort of 11 patients, demonstrating its potential for achieving regression of chronic symptoms and functional recovery without the need for invasive surgical neurolysis [6]. Methods (Methods) Study Design and Patient Cohort Design: Retrospective descriptive case series. Sample: The study included 11 patients (1 index case, 10 additional observations) with clinically and, in some cases, instrumentally (electroneuromyography—ENMG) confirmed diagnosis of CIRN. Inclusion criteria: clinical picture of radial nerve neuropathy, absence of signs of anatomical nerve rupture, duration of disease from 1 month to 3 years, and informed consent to the described conservative therapy. The "Resurgo" Treatment Protocol The protocol is structured around three synergistic blocks: I. Local Defibrosing Therapy, II. Systemic Neuroprotection, and III. Functional Rehabilitation. I. Local Defibrosing and Anti-Inflammatory Therapy A. Cyclical 5-Day External Course: A 7-day cycle with 5 days of active treatment was implemented to facilitate local drug delivery and minimize skin irritation [19]. Day 1 (Troxerutin): Application of gel to stabilize the vascular wall and reduce perineural edema [1]. Day 2 (The "Troika" Compress): A key element combining three agents: Lidaza (Hyaluronidase) - a spreading enzyme that hydrolyzes hyaluronic acid, essential for reducing the structural density of connective and scar tissue [11, 12]; Dimexide (DMSO) - utilized as a highly effective penetration enhancer for transdermal drug delivery [16] and for its inherent anti-inflammatory, local analgesic, and anti-edematous effects [15, 17]; Novocaine - for local pain blockade and potential vasodilating effects [20]. Day 3 (Contractubex): Topical application for scar tissue management [14]. Day 4 (Menovazin): A combined local irritant/analgesic. Days 5, 6, 7: Rest (recovery). B. Subcutaneous Injections: Composition: Hyaluronidase + Novocaine. Regimen: 1 time every 7 days into the area of maximal tenderness/induration, targeting the suspected fibrotic zone [14]. This direct local delivery minimizes systemic effects and focuses the defibrosing action [19, 18]. II. Systemic Neuroprotective Pharmacotherapy (Course-Based) Neuromuscular Conduction: IIpidacrine (Neurromidine) — taken orally in courses. As a cholinesterase inhibitor, it improves nerve impulse conduction [23] and has been shown to activate axonal transport and trigger recovery processes in traumatic neuropathies [21, 22]. Neurotrophics and Metabolism: Cerebrovin and Liposom Forte - used to enhance neurotrophism and regeneration of the injured nerve tissue [28]. Muscle Tone Correction: Tolperisone (a centrally acting muscle relaxant) is prescribed for the treatment of pathological hypertonicity and spasticity [25]. Tolperisone inhibits pathological reflex activity at the spinal cord level [26] and has an analgesic effect due to its membrane-stabilizing, lidocaine-like activity [27, 24]. III. Functional Rehabilitation (Microcycle) A cyclical program implemented in the strictly pain-free range [5, 29] to prevent contractures (Passive ROM is critical [5]) and stimulate re-innervating muscles [7]. Day 1: Electrostimulation (spot massager) + Therapeutic Exercise (passive and light active stretching, nerve glides [8]). Day 3: Hand and finger exerciser + LFK. Day 5: Intensive LFK session. Days 2, 4, 6: Rest. Day 7: Light massage (anti-edema, drainage). Outcome Assessment and Monitoring Primary Endpoints: Reduction of pain syndrome (by VAS) by more than 50% from the baseline level [30]. Emergence or significant gain in active extension of the wrist and fingers (Active ROM). Secondary Endpoints: Dynamics of muscle tone/spasticity (Ashworth scale equivalent). Frequency and nature of adverse events. Gain in passive Range of Motion (Passive ROM). Monitoring was conducted by a physician weekly. Results (Results) 1. Cohort Characteristics and Baseline Data The series included 11 patients. The time from trauma to the start of treatment varied from 1 month to 3 years. Baseline pain levels on the VAS ranged from 2/10 to 10/10. 2. Dynamics of Primary Endpoints 2.1. Detailed Analysis of the Index Case (Case n1) Patient n1 (trauma duration\sim 1.5 years) represented a severe, chronic case. Pain Relief: The VAS score decreased from 10/10 to a moderate level by the 3rd week. By the 5th week (25 days), pain decreased to\sim 1/10, meeting the primary endpoint for pain relief. Motor Function: Minimal active movements (Active ROM) in wrist extension were first observed between weeks 7 and 12, a significant finding given the chronicity of the injury. Further functional gain was noted by the 19th week. Tone: Significant reduction in pathological rigid tone and increase in Passive ROM were observed beginning at the 3rd week, following the initiation of the local injection therapy. 2.2. Summary Results of the Cohort (n=11) Pain Relief: Pain reduction of\ge 50\% (VAS) was achieved in 9 out of 11 cases within the first 6 weeks of treatment. Motor Function: The appearance or clear improvement of active extension was recorded in most cases where active movement was initially absent or severely limited. It was particularly effective in cases where the period since the injury was generally shorter (1–5 months), confirming the prognosis for milder injuries (neurapraxia or early axonolysis) [4]. Case Time since injury Baseline pain (VAS) Baseline extension ROM Spasticity/tone # of 5‑day cycles Subcutaneous Hyaluronidase+Novocaine (1/7) Adverse events Outcome at 4–6 weeks n1 (index) ~1.5 years 10/10 absent pronounced 19 yes minimal See case card n1 n2 3 months 4/10 limited moderate 3–4 as indicated none/minimal ↓pain over 3– 4 wks; partial ↑ROM n3 3 years 6/10 absent pronounced 12 yes mild local reaction (rare) ↓pain; minimal ROM dynamics n4 1 month 9/10 absent/limited pronounced 14 yes none ↓pain; partial emergence of active movements n5 3.5 months 7/10 limited moderate 6 as indicated pronounced local reaction ↓pain; tone stabilized n6 2.5 years 7/10 limited moderate–pronounced 16 yes none/minimal ↓pain; ↑ROM; ↓hypertonus n7 5 months 5/10 limited moderate 6 as indicated none ↓pain; gain in active movements variable n8 2 months 9/10 absent/limited moderate 4–5 yes none ↓pain; onset of active extension (individual) n9 1 year 3/10 limited moderate 8 as indicated single mild skin reaction ↓pain; gradual ↑ROM n10 8 months 9/10 absent pronounced 14 yes none ↓pain; gradual ↑ROM n11 2.5 months 2/10 markedly limited moderate 3–4 as indicated none/minimal ↓pain; onset of active extension (individual) Table 1. Summary Registry of Patients: Select Baseline Data and Primary Clinical Outcomes Figure 1. Pain Dynamics (VAS) in Patients with Compression-Ischemic Radial Neuropathy Treated with the “Resurgo” Protocol Figure 2. Recovery of Active Range of Motion (ROM) Following the “Resurgo” Protocol 3. Adverse Events Local skin reactions (redness, irritation) to the application of compresses with Dimexide were the most common side effects (n3, n5, n9). In one case (n5), the reaction was severe, leading to discontinuation of the local cycle, which correlated with slower motor recovery, emphasizing the importance of local therapy [18]. Discussion (Discussion) Pathophysiological Rationale of the Protocol The efficacy of the "Resurgo" protocol stems from its multipronged attack on the key pathological factors of CIRN: Defibrosis: Subcutaneous and topical Hyaluronidase directly targets the fibro-adhesive matrix, reducing mechanical compression and improving the local environment for axonal regrowth [13, 22]. Neurotransmission and Protection: Ipidacrine ensures that existing or newly regenerated axons function optimally by enhancing neuromuscular conduction [21]. Tonal Control and Rehabilitation: Tolperisone reduces pathological tone and reflex activity of antagonist muscles [26], which is a necessary condition for restoring active movements, while a strict, painless exercise therapy program maintains passive range of motion and promotes neuroplasticity [5, 8]. The use of local drug delivery (DMSO carrier) further maximizes the local concentration of therapeutic agents, reducing the systemic risks associated with oral administration [19, 16]. Interpretation of Results The rapid pain relief achieved in most patients indicates an effective combined analgesic mechanism involving C-fiber blockade by DMSO [17], local application of novocaine, and systemic application of tolperisone [27]. In addition, the observation of active recovery of movement in a chronic index case (n1) highlights the potential of the defibrosing component (hyaluronidase injections) to relieve prolonged mechanical compression of the nerve, which is often cited as the cause of unresolved chronic CIRN [14]. Although this was expected, the improvement in outcomes in cases with a shorter time since injury confirms the importance of early intervention combining neuromobilization [5, 8] with aggressive local treatment. Limitations This study is limited by its retrospective design and lack of a true control group, which is standard for preliminary case series but limits definitive conclusions about causality. In addition, heterogeneity in patient adherence and variability in the severity of the underlying nerve injury (neurapraxia versus axonotmesis) [4] contribute to variability in results. Future studies should include electrophysiological validation (ENMG) and standardized measurements of functional outcomes (e.g., DASH or QuickDASH) [29]. Conclusion and Recommendation The Resurgo protocol, combining targeted local defibrosing agents, neuroprotective pharmacology, and active functional rehabilitation, demonstrated significant clinical improvement in pain, tone, and functional status in this series of 11 patients with CIRN, including patients with chronic disease. This protocol warrants further investigation. 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