Centro Fisioterapia e Osteopatia Martinelli Gianluca

20/11/2025

📌Effects of physical exercise on neuromuscular junction degeneration during ageing: A systematic review

👉Physical exercise (or physical training) serves as a therapeutic strategy aimed at decelerating or potentially reversing age-related neuromuscular junction (NMJ) degeneration.
In brief, the effects of physical exercise on the NMJ, particularly in aged animals and humans, include:

🧩 General and Structural Remodeling

▪️ 🏋️ Exercise promotes NMJ hypertrophy and accelerates the remodeling process in the elderly, which may mitigate NMJ degradation and alleviate the progression of neuromuscular degeneration.

▪️ 🔄 Physical exercise can result in a partial reversal of structural alterations that have already occurred due to aging.

▪️ 🚴 Endurance training demonstrated a more pronounced effect on NMJ structural remodeling compared to resistance and voluntary exercise regimens, especially in fast twitch muscle fibers.

▪️ 💪 The adaptations of NMJ to resistance exercise appear to be independent of changes in muscle fiber profile.

👇

🧠 Presynaptic Compartment

▪️ 🔬 Some studies reported significantly smaller and more homogeneous nerve terminals in old animals following exercise.

▪️ 🌿 Exercise may lead to a greater number of nerve terminal branches and total branch length in young animals, although this effect was less observed in older animals.

▪️ 📌 Exercise training affects presynaptic proteins, such as Bassoon, which anchors active zones for presynaptic ACh vesicles.

▪️ 🦵 In one study, all physiological age-related changes were prevented in the extensor digitorum longus (EDL) NMJs by exercise, but not in the soleus NMJs.

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🎯 Postsynaptic Compartment (AChRs)

▪️ ✨ Exercise helps promote the formation and maintenance of acetylcholine receptor (AChR) clusters.

▪️ 🧩 It reduces postsynaptic receptor fragmentation.

▪️ 📐 Exercise improved the AChR perimeters and the overlap area of the NMJ in aged animals.

▪️ 📈 Resistance exercise has been shown to result in a 2-fold increase in the number of AChRs per field.

👇

🔬 Molecular and Functional Changes

▪️ 🛡️ Exercise stabilizes key regulatory proteins: Physical exercise promotes AChR cluster formation and maintenance by increasing recombinant docking protein 7 (Dok7) expression and stabilizing Agrin and lipoprotein receptor-related protein 4 (LRP4). Dok7 protein expression was found to be significantly higher in the exercise group than in sedentary mice.

▪️ ⚡ NMJ Transmission: Voluntary wheel running resulted in a significant improvement in NMJ transmission.

▪️ 🧬 Exercise influences gene expression: There is a significant upregulation of AChR α1 mRNA in the exercised leg in both elderly and young women. Genes encoding transporters and receptor components of glutaminergic transmission were significantly upregulated in exercised muscles in aged rodent models.

▪️ 💠 Physical exercise has been shown to improve the proportion of Type IIB muscle fibers and decrease Type IIA fibers in the gastrocnemius muscle of aged mice.

▪️ 🔋 Exercise may counteract age-related mitochondrial oxidative stress, which is implicated in metabolic impairment of NMJs. Physical exercise induces mitochondrial morphological adaptations and increases the capacity to produce ATP.

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⚠️Disclaimer: Sharing a study or a part of it is NOT an endorsement. Please read the original article and evaluate critically.⚠️

Link to Article 👇

12/11/2025

09/11/2025

ANATOMY OF TRIGEMINAL NERVE ✍️.

✅ The trigeminal nerve (CN V) is the fifth cranial nerve, originating in the brainstem from four nuclei (three sensory and one motor). It forms a sensory root and a motor root that merge before giving rise to the trigeminal ganglion, a cluster of nerve bodies. From the ganglion, it branches into three divisions: the purely sensory ophthalmic (V1), maxillary (V2), and mandibular (V3) nerves, with V3 also carrying the motor fibers.

✅ Core components
Nuclei: The nerve's nuclei are located in the brainstem (midbrain to medulla) and include:
Sensory nuclei: Mesencephalic, principal sensory, and spinal.
Motor nucleus: Controls chewing muscles.
Roots: The sensory and motor nuclei form the sensory and motor roots, respectively, which emerge from the pons.
Trigeminal Ganglion: Located in a dural cave in the middle cranial fossa, this is where the sensory neuron cell bodies reside. The motor root runs beneath the sensory root.

✅ The three branches
Ophthalmic (V1) (Sensory): Supplies the scalp, forehead, upper eyelid, and nose.
Maxillary (V2) (Sensory): Supplies the lower eyelid, cheeks, upper lip, and nasal cavity.
Mandibular (V3) (Mixed): Carries sensation from the lower lip, jaw, and chin, and is the only branch to contain motor fibers, which control the muscles of mastication (chewing).

09/11/2025

Just pubished 🔥

𝗔𝗲𝗿𝗼𝗯𝗶𝗰 𝗘𝘅𝗲𝗿𝗰𝗶𝘀𝗲 🚴‍♀️ 𝗮𝘀 𝗮 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰 𝗢𝗽𝘁𝗶𝗼𝗻 𝗳𝗼𝗿 𝗖𝗵𝗿𝗼𝗻𝗶𝗰 𝗟𝘂𝗺𝗯𝗮𝗿 𝗥𝗮𝗱𝗶𝗰𝘂𝗹𝗮𝗿 𝗣𝗮𝗶𝗻. 𝗔 𝗖𝗮𝘀𝗲 𝗦𝗲𝗿𝗶𝗲𝘀

Lumbar radicular pain (LRP), often termed sciatica, is a prevalent musculoskeletal condition with a lifetime incidence of up to 43% (https://pubmed.ncbi.nlm.nih.gov/18923325/). Patients with LRP typically experience more severe pain and disability compared to those with nonspecific low back pain (https://pubmed.ncbi.nlm.nih.gov/21358478/; https://pubmed.ncbi.nlm.nih.gov/23328336/). Conventional conservative management—including manual therapy, motor control training, or neurodynamic techniques—offers only modest benefits (https://pubmed.ncbi.nlm.nih.gov/36580149/).

🚴 Emerging preclinical evidence has highlighted the potential neuroprotective and analgesic benefits of aerobic exercise (AE) in animal models of sciatic nerve injury, showing reductions in hypersensitivity and neuroinflammation (https://pubmed.ncbi.nlm.nih.gov/36690283/; https://pubmed.ncbi.nlm.nih.gov/38137395/). Despite these promising findings, there is a substantial translational gap, as AE has been scarcely examined in clinical populations with radiculopathy (https://pubmed.ncbi.nlm.nih.gov/33490836/).

📘 In a brand-new study, Esposto, Arca, and Schmid (2025,👉 https://www.jospt.org/doi/10.2519/josptcases.2025.0171) conducted a case series to investigate whether aerobic exercise could be safely and feasibly integrated into a tele-rehabilitation program for patients with chronic lumbar radicular pain, and whether it may improve pain and functional outcomes.

✏️ This retrospective case series followed CARE guidelines (https://pubmed.ncbi.nlm.nih.gov/28529185/) and included five adult patients (aged 25–49 years) presenting with chronic lumbar radicular pain with or without radiculopathy treated in a telemedicine rehabilitation setting.

📋 The criteria for diagnosing lumbar radicular pain with or without radiculopathy followed published clinical recommendations: pins and needles or numbness in the involved lower limb; leg pain more severe than back pain; leg pain spreading below the knee; motor, sensory, or reflex deficits upon neurological examination; positive neurodynamic test (eg, straight-leg raise [SLR] or crossed SLR). The presence of a minimum sum score of 6 out of 10, representing 93% probability of sciatica according to Stynes et al. (https://pmc.ncbi.nlm.nih.gov/articles/PMC5886387/), was required for inclusion.

🚴 Intervention

Participants underwent a multicomponent tele-rehabilitation program combining:

💬 Patient education about pain mechanisms and active recovery. The aim was to help patients understand the difference between acute and persistent pain, the specifics of nerve pain, and the role of active recovery strategies such as AE.

💪 Graded strengthening to address strength deficits identified during the initial examination As patients’ tolerance and confidence improved, the program progressed to include more complex movements as well as specific activities that patients wanted to be able to perform again) and

💁‍♂️ neurodynamic exercises (eg, nerve sliders, performed daily within a pain-free range of motion).

🚴 Aerobic exercise (AE) was performed 3–5 times per week (cycling, walking, or interval running) with a duration of 20 to 30 minutes per session. AE was prescribed at 60–70% of maximum heart rate (HRmax), estimated by Fox’s formula (HRmax = 220 – age, https://pmc.ncbi.nlm.nih.gov/articles/PMC7523886/). Exercise intensity and duration were progressively adjusted based on tolerance. The specific modality was chosen based on the patient’s preference and symptoms tolerance, utilizing either a stationary bike, walking, or a combination of walking and running. For patients who chose running, a graded interval-based approach was used, starting with short running intervals (eg, 1 minute) alternating with longer walking periods (eg, 3 minutes).

📊 Outcome Measures

Primary outcomes were:

▶️ Pain intensity, measured by the Numeric Pain Rating Scale (NPRS)
▶️ Function, assessed by the Patient-Specific Functional Scale (PSFS)

Outcomes were measured monthly for 3–6 months. Adherence and adverse events were recorded at each session.

📊 Results

All five patients showed large, clinically meaningful improvements in both pain and disability:

✅ Mean leg pain decreased by 4–8 points on the NPRS.

✅ Functional scores on the PSFS improved by 3–6 points, surpassing minimal clinically important differences (https://pubmed.ncbi.nlm.nih.gov/24828475/).

✅ Average adherence was 87.6% for the full program and 86.2% for AE specifically.

✅ No major adverse events occurred; there were four minor and two moderate self-limiting flare-ups.

✅Notably, four patients reported immediate post-exercise hypoalgesia, consistent with the phenomenon of exercise-induced hypoalgesia described in pain research (https://pubmed.ncbi.nlm.nih.gov/30904519/; https://pubmed.ncbi.nlm.nih.gov/33062901/).

💡 Discussion

Aerobic exercise might be a feasible, safe, and potentially effective adjunct for patients with chronic lumbar radicular pain. These results provide preliminary clinical support for preclinical findings showing AE’s role in modulating neuroinflammation and promoting neural recovery (https://pubmed.ncbi.nlm.nih.gov/36690283/; https://pubmed.ncbi.nlm.nih.gov/38137395/).

While the multimodal design precludes causal attribution to AE alone, consistent improvement across all cases strengthens the hypothesis that AE contributes meaningfully to symptom relief and functional recovery. Moreover, the tele-rehabilitation approach demonstrated strong feasibility and adherence.

⭕ Key limitations include:

☑️ Small sample size (n=5) and lack of a control group
☑️ Retrospective design and absence of long-term follow-up
☑️ Possible inaccuracy in AE intensity estimation via HRmax formula

Illustration of SLR: https://www.magonlinelibrary.com/doi/abs/10.12968/pnur.2023.34.11.400?journalCode=pnur

08/11/2025

𝗘𝘅𝗮𝗺𝗶𝗻𝗶𝗻𝗴 𝘁𝗵𝗲 𝗔𝗻𝗮𝘁𝗼𝗺𝘆, 𝗣𝗮𝘁𝗵𝗼𝗽𝗵𝘆𝘀𝗶𝗼𝗹𝗼𝗴𝘆, 𝗮𝗻𝗱 𝗖𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝗣𝗿𝗲𝘀𝗲𝗻𝘁𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝗟𝗼𝘄𝗲𝗿 𝗘𝘅𝘁𝗿𝗲𝗺𝗶𝘁𝘆 𝗡𝗲𝘂𝗿𝗼𝗹𝗼𝗴𝗶𝗰 𝗗𝗲𝗳𝗶𝗰𝗶𝘁𝘀: 𝗔 𝗚𝘂𝗶𝗱𝗲 𝘁𝗼 𝗙𝗼𝗼𝘁 𝗗𝗿𝗼𝗽 🦶

🦶 Foot drop, defined as weakness or paralysis of the ankle dorsiflexor muscles, represents a frequent clinical challenge associated with considerable impairment in gait and quality of life. The underlying cause may occur anywhere along the motor pathway extending from the cerebral cortex to the peripheral nerves or the leg musculature itself. Foot drop is a multifactorial condition requiring a comprehensive diagnostic approach (https://pubmed.ncbi.nlm.nih.gov/18502948/, https://pubmed.ncbi.nlm.nih.gov/31288916/).

📘 In a brand-new review, Swiatek et al. (2025, https://pubmed.ncbi.nlm.nih.gov/40911727/) present an in-depth analysis of the anatomy, pathophysiology, and clinical manifestations of lower extremity neurologic deficits, offering a structured framework to improve evaluation and management.

💡 𝗔𝗽𝗽𝗹𝗶𝗲𝗱 𝗔𝗻𝗮𝘁𝗼𝗺𝘆 𝗮𝗻𝗱 𝗣𝗮𝘁𝗵𝗼𝗽𝗵𝘆𝘀𝗶𝗼𝗹𝗼𝗴𝘆

🩻 The authors emphasize that a precise understanding of the relevant neuroanatomy is fundamental to localizing the etiology of foot drop. At the spinal level, the L4 and L5 nerve roots join to form the lumbosacral trunk, which contributes to the sacral plexus (s. illustration). These roots are most often implicated in cases of foot drop due to degenerative spinal changes, disc herniation, iatrogenic surgical trauma, postoperative hematoma, infection, or tumor formation. Their anatomical course makes them particularly vulnerable during spinal procedures (https://pubmed.ncbi.nlm.nih.gov/17036418/; https://pubmed.ncbi.nlm.nih.gov/17445735/). The L5 nerve root is involved in ankle inversion, eversion, dorsiflexion, great toe extension, and hip abduction.

✅ As the sciatic nerve travels from the pelvis into the thigh, the peroneal division is more susceptible to injury than the tibial division, consistent with the law of Laplace, which relates fiber diameter to wall tension. Consequently, the peroneal fibers are at greater risk during total hip arthroplasty, especially with improper retractor placement, traction, or postoperative hematoma formation. Sciatic nerve palsy following hip replacement surgery may occur in up to three percent of cases and can cause isolated peroneal dysfunction (https://pubmed.ncbi.nlm.nih.gov/1123010/; https://pubmed.ncbi.nlm.nih.gov/1874771/).

✅ Below the knee, the common peroneal nerve—winding superficially around the fibular head—is the most frequent peripheral site of injury leading to foot drop. Compression during surgery, prolonged kneeling, leg crossing, or direct trauma are well-documented causes. Extraneural masses such as Baker’s cysts or schwannomas may also exert pressure on the nerve (https://pubmed.ncbi.nlm.nih.gov/26700629/). The common peroneal nerve divides into the superficial and deep branches, innervating the ankle evertors and dorsiflexors respectively. Selective lesions of these branches produce characteristic patterns:

▶️ isolated dorsiflexion weakness in deep peroneal neuropathy and

▶️isolated eversion weakness in superficial peroneal neuropathy.

🧠 Although peripheral lesions account for many cases, the review stresses that central causes must not be overlooked. Lesions affecting the pyramidal tract within the brain or spinal cord—such as those arising from tumors, stroke, multiple sclerosis, or thoracic disc herniation—may also result in foot drop (https://pubmed.ncbi.nlm.nih.gov/17385271/; https://books.google.de/books/about/Textbook_of_Clinical_Neurology.html?id=rU2mQgAACAAJ&redir_esc=y).

Such lesions produce upper motor neuron signs, including 👉hyperreflexia, 👉 clonus, and a 👉 positive Babinski reflex.

✅ Furthermore, several neuromuscular disorders, such as Charcot–Marie–Tooth disease, Lambert–Eaton syndrome, and myasthenia gravis, can produce distal weakness, generalized muscle atrophy, and diminished deep tendon reflexes (https://pubmed.ncbi.nlm.nih.gov/27704495/).

🩺 Clinical Examination

A comprehensive neurological examination remains central to accurate diagnosis.

𝗧𝗵𝗲 𝗺𝗼𝘁𝗼𝗿 𝗲𝘅𝗮𝗺𝗶𝗻𝗮𝘁𝗶𝗼𝗻 𝗲𝗻𝗮𝗯𝗹𝗲𝘀 𝗽𝗿𝗲𝗰𝗶𝘀𝗲 𝗹𝗲𝘀𝗶𝗼𝗻 𝗹𝗼𝗰𝗮𝗹𝗶𝘇𝗮𝘁𝗶𝗼𝗻

▶️ Weakness in hip abduction, mediated by the superior gluteal nerve, suggests L5 nerve root pathology,

▶️ while preserved hip abduction accompanied by dorsiflexion weakness indicates a more distal, peripheral lesion.

▶️ Weakness in the short head of the biceps femoris, uniquely innervated by the peroneal division of the sciatic nerve, points toward a lesion proximal to the common peroneal nerve.

▶️ The presence or absence of ankle inversion is equally significant: Normal inversion strength of the tibialis posterior implies intact tibial nerve and L5 function, ruling out isolated radiculopathy. Tibialis posterior strength can be accurately examined by asking the patient to invert the foot in full plantarflexion, whereas the clinician pushes laterally against the medial border of the foot.

𝗦𝗲𝗻𝘀𝗼𝗿𝘆 𝘁𝗲𝘀𝘁𝗶𝗻𝗴 𝗽𝗿𝗼𝘃𝗶𝗱𝗲𝘀 𝗮𝗱𝗱𝗶𝘁𝗶𝗼𝗻𝗮𝗹 𝗰𝗹𝘂𝗲𝘀

▶️ Dermatomal sensory deficits support a spinal root origin (but rememder…often, you can`t trust the dermatomes, https://www.youtube.com/watch?v=BZYtAR4zUpg),

▶️ whereas patchy or diffuse sensory loss without clear dermatomal correlation suggests peripheral neuropathy or systemic disease.

𝗥𝗲𝗳𝗹𝗲𝘅 𝘁𝗲𝘀𝘁𝗶𝗻𝗴 𝗿𝗲𝗳𝗶𝗻𝗲𝘀 𝘁𝗵𝗶𝘀 𝗹𝗼𝗰𝗮𝗹𝗶𝘇𝗮𝘁𝗶𝗼𝗻 𝗳𝘂𝗿𝘁𝗵𝗲𝗿

▶️ reduced ankle reflexes imply lower lumbar root compromise,

▶️ while an asymmetric medial hamstring reflex strongly correlates with L5 radiculopathy (sensitivity and specificity of 76% and 85%, https://pubmed.ncbi.nlm.nih.gov/23087820/).

▶️ By contrast, hyperreflexia, clonus, or bilateral presentation favor a central etiology.

🩻 Diagnostic Modalities

Swiatek et al. (2025) underscore the complementary roles of magnetic resonance imaging (MRI) and electrodiagnostic studies. MRI remains essential for detecting compressive lesions in the spine, knee, or brain, depending on the suspected level of pathology. Electromyography (EMG) and nerve conduction studies are invaluable for distinguishing radiculopathy from peripheral nerve injury and for assessing prognosis. EMG evidence of conduction block in the tibialis anterior without axonal loss predicts rapid recovery, whereas findings of extensive axonal degeneration portend a prolonged or incomplete recovery (https://pubmed.ncbi.nlm.nih.gov/36070242/).

👫Illustrative Case Studies

Two clinical cases in the review demonstrate the practical application of these principles.

1️⃣ In the first case, a woman developed left-sided foot drop following a fall onto her buttock. She exhibited preserved hip abduction and lacked spinal compression on MRI. EMG revealed L5 radiculopathy with concurrent peroneal neuropathy. These MRI and EMG findings, along with a physical examination demonstrating 5/5 hip abductor strength, led the clinician to believe that this patient’s foot drop was likely due to a peripheral lesion, potentially peroneal or sciatic nerve contusion from her injury. The symptoms resolved with conservative physical therapy and gait training.

2️⃣ The second case described an elderly man who developed postoperative left foot drop after lumbar fusion. Despite correct implant positioning, he displayed normal inversion and eversion strength, consistent with compressive peroneal neuropathy at the fibular head due to postoperative immobility. Non-surgical management led to full recovery. Both cases underscore the importance of considering peripheral and central etiologies alongside spinal causes.

Illustration: Nerves of the sacral plexus, https://books.google.de/books/about/Human_Anatomy_Media_Update_Books_a_la_Ca.html?id=Go0-XwAACAAJ&redir_esc=y

Summary (infographic) in comments!

06/11/2025

🩸 The Healing Process in Muscle Tissue

The healing process in muscle tissue generally follows the trajectory of wound healing, which consists of three interconnected phases. The outcome of this process determines whether the muscle recovers fully or if function is impaired by scar tissue.

⚙️ Phases of Muscle Healing

Muscle healing can be largely categorized into three major phases:
■ Inflammatory phase
■ Regenerative phase
■ Remodeling/repair phase

📝

🔥 1. Inflammatory Phase

This phase initiates immediately following trauma and focuses on clearing damaged tissue and preventing infection.

■ Initial Response:

Upon muscle injury, the site fills with blood, forming a scaffold-like hematoma which recruits immune cells and protects the tissue from infection.

Circulating, inactive enzymes activate the complement cascade and clotting pathways.

■ Signaling and Recruitment:

Activated platelets release immune mediators such as CXCL8, PDGF, and TNF-α, which promote inflammation and recruit immune cells.

Injured host cells release Danger Associated Molecular Patterns (DAMPs) and Alarmins, which are highly elevated following traumatic muscle injury and induce the recruitment of immune cells, particularly macrophages.

■ Cellular Activity:

Neutrophils are among the first immune cells to extravasate, responding to chemoattractants like CXCL8.

Monocytes are recruited and enter the injury site, polarizing into M1 “pro-inflammatory” macrophages.

M1 macrophages and other innate immune cells work to clear the site by phagocytosing dead tissue and apoptotic neutrophils.

Neutrophils also aid angiogenesis (via VEGF) and recruit other immune cells.

🧬 2. Regenerative Phase

The regenerative phase begins once the clot is formed and the threat of pathogens diminishes, allowing the immune system to shift focus from inflammation to repair.

■ Immune Shift:

Macrophages transition from the pro-inflammatory (M1) phenotype to the regenerative, immunosuppressive (M2) phenotype.

This M1-to-M2 transition provides critical cues for the differentiation and self-renewal of local stem cells.

■ Stem Cell Activation:

The adult muscle stem cell population, primarily satellite cells (the main myofiber precursors), rapidly proliferates and invades the margins of the wound site.

Perivascular stem cells (PVSCs) located near blood vessels can also differentiate into myoblasts.

M1 macrophages promote satellite cell replication, while M2 macrophages induce differentiation.

■ Tissue Reconstruction:

This phase is characterized by wound closure, angiogenesis (revascularization), and replacement of the initial hematoma scaffold.

Cytokines and growth factors recruit and activate fibroblasts, which secrete large volumes of Extracellular Matrix (ECM), mainly collagens, replacing the hematoma.

■ Adaptive Immunity Role:

Adaptive immune cells, particularly Th2 helper T cells, infiltrate the injury site.

Th2 cells secrete IL-4 and IL-13, which act as a brake on inflammation, promoting repair, M2 macrophage polarization, and fibroblast activation/ECM secretion.

Regulatory T cells (Tregs) also help suppress residual inflammation.

🧱 3. Remodeling/Repair Phase

The final phase involves the maturation of the regenerated tissue.

■ Functional Tissue Formation:

This phase involves the formation of functional tissue that is physiologically identical to the site prior to injury.

■ ECM Guidance:

Stem cells continue to differentiate, utilizing the deposited ECM to guide proper tissue formation.

The ECM deposition and modeling stabilize the wound site and promote proper myofiber growth to conform to the original tissue structure.

■ Resolution:

Eventually, inflammatory cells, fibroblasts, and blood vessels in the area either undergo cell death (apoptosis) or exit the tissue.

📃

🧩 Potential Outcomes of Muscle Healing

The result of the healing process can be largely categorized into two outcomes:
■ Full restoration of function (regeneration) or ■ Chronic failure to remodel

👇

💪 1. Full Regeneration

■ Definition:

Regeneration results in the full resolution of the injury, where the resulting tissue is conformationally and morphologically identical to the pre-trauma tissue.

■ Context:

Healthy muscle tissue possesses a regenerative nature that often allows it to heal successfully in response to minor trauma.

⚠️ 2. Failure to Regenerate (Fibrosis and Scarring)

■ Definition:

When a tissue is unable to fully regenerate, the outcome is characterized by a chronic fibrotic stage where the regenerative phase does not cease.

This results in the development of a scar that can severely affect tissue function.

■ Causes of Failure:

Failure occurs when the trauma exceeds the regenerative capacity of the muscle, triggering a dysregulated immune and regenerative response.

▪ Dysregulated ECM: Excess ECM secretion persists because immune cells fail to properly regulate ECM deposition and myoblast differentiation.
▪ Scar Formation: This excess deposition prevents satellite cells from forming proper myofibers, leading to scar tissue formation instead of muscle tissue.
▪ Tissue Invasion: Adipose tissue and fibroblasts invade the injured space to seal the wound.
▪ Severe Injuries: Traumas like Volumetric Muscle Loss (VML) injuries are immediately predisposed to this failure of resolution due to the massive immune cell influx resulting from the high elevation of immune mediators (DAMPs and Alarmins) released by the injured tissue.

⚠️Article 👇

01/11/2025

𝗛𝗼𝘄 𝗺𝘂𝗰𝗵 𝗮𝗲𝗿𝗼𝗯𝗶𝗰 𝗲𝘅𝗲𝗿𝗰𝗶𝘀𝗲 𝗶𝘀 𝗻𝗲𝗲𝗱𝗲𝗱 𝘁𝗼 𝗿𝗲𝗱𝘂𝗰𝗲 𝗺𝗶𝗴𝗿𝗮𝗶𝗻𝗲?

🤕 Migraine, a leading cause of disability affecting over 1.16 billion people worldwide (GBD Collaborators, 2024; Woldeamanuel & Cowan, 2017), contributes to an estimated $1.9 trillion economic burden in 2025 (Woldeamanuel et al., 2025). Given the limitations of pharmacologic therapy and access disparities in headache care (Bentivegna et al., 2023; Lanteri-Minet et al., 2024), scalable interventions like exercise are urgently needed.

📘 A brand-new dose-response meta-analysis by Ogrezeanu et al. (2025, https://pubmed.ncbi.nlm.nih.gov/41085000/) quantified, for the first time, a therapeutic dose of aerobic exercise for migraine and revealed a U-shaped dose–response curve.

🏃‍♀️Aerobic training significantly reduced both:

⬇️ Migraine pain intensity (SMD = –1.10),

⬇️ Attack frequency (SMD = –0.79),

✅ with optimal benefits achieved at 900–950 cumulative minutes of moderate-intensity aerobic exercise delivered over 10–11 weeks (equivalent to ~30 minutes, three sessions per week at 50–70% VO₂peak, infographic below).

👉 These findings build on earlier reviews supporting exercise efficacy (La Touche et al., 2020; Varangot-Reille et al., 2022; Reina-Varona et al., 2024) but are the first to define specific exercise dosing guidelines.

👉 Subgroup analyses suggest s*x differences and migraine chronicity modify treatment response:

▶️ Greater effects in episodic migraine than in chronic migraine (Ogrezeanu et al., 2025),

▶️ Larger reductions in attack frequency among women, consistent with s*x-based pain sensitivity and hormonal influences (Amin et al., 2018).

🏃‍♂️‍➡️ In an editorial, Woldeamanuel emphasizes a precision medicine approach, advocating graded exercise pacing to prevent overexertion cycles common in migraine patients (Andrews et al., 2012; Nielson et al., 2014). For sedentary individuals or those with kinesiophobia (fear of movement) (Benatto et al., 2019), exercise initiation at low intensity (40–50% VO₂peak) using time-contingent progression strategies is recommended (La Touche et al., 2023).

Importantly, exercise efficacy may be enhanced by addressing sleep and circadian regulation, as morning light exposure combined with exercise improves migraine stability (Youngstedt et al., 2016; Ong et al., 2018; Woldeamanuel et al., 2023).

💡 Practical tips:

☀️ Circadian Alignment: Encourage morning exercise with outdoor light exposure to stabilize sleep wake cycles.

😴 Lifestyle Integration: Advise consistent sleep (7-8 hoursnightly), strict meals at fixed daytimes, and hydration tracking.

⬆️ For complex cases with comorbid disorders—such as vestibular migraine, postural orthostatic tachycardia syndrome (POTS), or exercise intolerance—modifications including recumbent cycling, hydration strategies, compression garments, vestibular rehabilitation (gaze stabilization or balance training), and neck strengthening (Sun et al., 2022; Benatto et al., 2022) may improve tolerance.

🏋️‍♀️ Although promising, the review evidence is rated low to very low certainty due to heterogeneity and small sample sizes. In future studies, a comparison of aerobic vs. strength training is mandatory, as resistance training may be equally or more effective (Woldeamanuel & Oliveira, 2022; Wang et al., 2025; Sari Aslani et al., 2022).

✅ Conclusion

Exercise is positioned as a first-line behavioral intervention for migraine prevention. A personalized prescription of 900–950 cumulative minutes of moderate-intensity aerobic exercise over 10–11 weeks is supported by current evidence. Pharmacologic therapies should be used as bridge therapies to enable long-term lifestyle interventions that improve self-efficacy and disease control (Irby et al., 2016).

📚 References

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Benatto MT, Florencio LL, Bragatto MM, et al. (2022). BMC Neurol, 22:126.

Bentivegna E, Onan D, Martelletti P. (2023). Neurol Ther, 12:337–342.

GBD 2021 Diseases and Injuries Collaborators. (2024). Lancet, 403:2133–2161.

Irby MB, Bond DS, Lipton RB, et al. (2016). Headache, 56:357–369.

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La Touche R, Fierro-Marrero J, Sánchez-Ruiz I, et al. (2023). J Headache Pain, 24:68.

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01/11/2025

🧠 Fibromyalgia (FM)

▪ Characterized as a complex and enigmatic medical condition that challenges contemporary understanding.
▪ Fundamentally manifests as a profound neurological disorder rather than merely an inflammatory condition.
▪ Defined as a syndrome characterized by widespread, chronic pain in the muscles and skeletal system.
▪ Diagnosis and understanding rely heavily on identifying core persistent symptoms and systematically excluding alternative causes.

👇

⚠️ Fibromyalgia Symptoms

Fibromyalgia is defined by chronic and persistent symptoms that profoundly affect quality of life, often leading to significant functional limitations and chronic disability.

🔺 The Core Feature Triad

The three key features present in almost every fibromyalgia patient are:
▪ Widespread Pain
▪ Severe Fatigue
▪ Sleep Disturbance

💢 1. Widespread Musculoskeletal Pain

▪ The defining characteristic.
▪ The pain must be chronic and persistent.
▪ Often described as a deep, widespread, gnawing, or burning ache.
▪ The pain is variable in radiance.
▪ FM patients’ pain self-rating may exceed that of Rheumatoid Arthritis (RA).
▪ Historically, multiple tender points throughout the body upon physical examination were key features.

⚡ 2. Severe Fatigue

▪ Virtually all patients experience severe fatigue.
▪ Described as physically or emotionally draining.
▪ Often particularly severe in the morning, even following adequate sleep.
▪ Worsens by mid-afternoon and is chronic and persistent.

🌙 3. Sleep Disturbances

▪ Poor sleep patterns are consistently reported.

👉

🔄 Associated Symptoms and Comorbidities

The syndrome involves numerous additional features, suggesting it is a sophisticated neurological phenomenon with widespread systemic implications:
▪ Cognitive disturbances (impairments)
▪ Stiffness
▪ Skin tenderness
▪ Postexertional pain
▪ Mood disturbances such as anxiety and depression
▪ Irritable bowel syndrome (IBS)
▪ Irritable bladder syndrome
▪ Headaches, including tension or migraine headaches
▪ Dizziness
▪ Fluid retention
▪ Paresthesias
▪ Restless legs
▪ Raynaud’s phenomenon

▪ High rate of comorbidity with Chronic Fatigue Syndrome, with up to 80% of FM patients meeting criteria for both.
▪ Substantial overlap with temporomandibular disorders.

✨

🧩 Diagnosis of Fibromyalgia

Diagnosing fibromyalgia presents challenges because there are no suitable laboratory findings to confirm the condition.
Diagnosis relies on a comprehensive approach:
▪ Patient history
▪ Physical examination
▪ Laboratory assessments
▪ Systematic exclusion of alternative pathological explanations

📅 Diagnostic Requirements and Duration

▪ Duration: Symptoms must be chronic and persistent, existing for at least 3 months.
▪ Required Features: Patient must complain of widespread musculoskeletal pain accompanied by:
▪ Fatigue
▪ Sleep disturbances
▪ Other associated symptoms (e.g., headaches, cognitive disturbances, IBS).

📋 Traditional American College of Rheumatology (ACR) Criteria

▪ Criterion 1: History of widespread pain lasting at least 3 months.
▪ Criterion 2: Tenderness in at least 11 of 18 specified tender points when digitally palpated with ~4 kg per unit area of force.
▪ Diagnostic relevance of tender points was affirmed in the 1980s for differentiating FM from controls.

👇

🧭 Criticism and Modern Perspectives

▪ The ACR tender point criteria are accepted but have faced criticism.
▪ Critics argue that these criteria focus solely on pain, neglecting other vital symptoms.
▪ They may fail to capture the true “essence” of the syndrome.
▪ Modern perspectives advocate for more nuanced, holistic assessment methodologies.

🩺 Role of Physical and Laboratory Examinations

🔍 Physical Findings

▪ Clinicians find widespread tenderness on palpation in specified areas.
▪ Importantly, no signs of joint swelling or inflammation should be observed.

🧪 Laboratory Tests

▪ CBC, ESR, and CRP findings must be normal in range.

▪ The similarity between the cardinal symptoms of fibromyalgia and closely related diseases makes diagnosis and treatment assessment challenging due to substantial overlap with:
▪ Chronic Fatigue Syndrome
▪ Headaches
▪ Irritable Bowel Syndrome