When is enough, enough? Avoiding Trans-neuronal Degeneration (TND)

When is enough, enough? Avoiding Trans-neuronal Degeneration (TND)
Pedro Luis Rivera, DVM, FACFN, DACVSMR, FCoAC
Program Director, Healing Oasis Wellness Center

Starting with a Good History

Every case intake starts not only with good observational skills but with a thorough history. A good history and complete physical examination (cranial nerve and peripheral nerve evaluation included) will provide the clinician with several differential diagnoses (Ddx). The Ddx is what determines if further diagnostics or referral to a specialist is indicated. It is recommended that the clinician attain at least 4 Ddx before the patient receives any treatment.

Clinically, we are routinely presented with cases that have been diagnosed correctly, provided with an optimal standard of care, and yet get re-injured several weeks after returning to function. Several reasons for re-injury are discussed below.

Reasons for Re-injury

• Wrong diagnosis
• Undiagnosed metabolic or medical condition
• Unrealistic treatment protocol expectations (from the client or clinician)
• Treatment protocol conducted too fast, without considering whether the patient was undergoing transneuronal degeneration (TND) or neuronal degeneration (ND)
• Patient conditioning not attained before protocol intensity was changed
• Poor client compliance
• Patient nutrition not addressed
• Patient fatigue leading to TND
• Dysafferentation
• Alpha-gamma sensitivity changes to the locomotor system
• Decreased input to the cerebellum
• Underlying nociception or pain affecting concentration during performance
• Condition of the surface on which the patient is being exercised or trained
• Others

Fatigue and Cellular Metabolic Rate

As with any athlete, fatigue is a primary reason for injury. Clinicians must keep in mind that fatigability begins at the cellular level. By the time outward clinical changes are visible, the patient is already behind, leaving them more prone to injury.

Changes that occur at a cellular level without exceeding the patient's metabolic rate will provide an excellent central integrative state (CIS) of not only the cell, but the system to which the cell is linked.

All licensed health care practitioners providing receptor-based therapy must understand what happens at the cellular level secondary to any receptor stimulation. Stimulating a receptor can improve individual, local, segmental, and supra-segmental connections, but can also be counterproductive if not stimulated correctly.

Cellular changes are crucial to maintaining the active and constant CIS of neuronal connections. These changes should be accepted only when inadequate responses such as dysafferentation and TND/ND are NOT created or caused.

Basic Neuronal Requirements

When discussing functional neurology as it applies to any manual therapy, clinicians must consider the CIS of neuronal pathways and individual neuronal systems. Neurons need several things to stay healthy and viable:

• Oxygen
• Glucose (nutrition)
• Neurotrophic factors
• Correct and healthy stimulation by its pre-synaptic pool

The basic end-result of adequate cellular stimulation is the production of adenosine triphosphate (ATP) and protein. These byproducts maintain an adequate negative gradient so the cell stays within its resting membrane potential, and provide the protein required to replenish, replace, and maintain daily cellular requirements.

Protein and ATP production are also required for replenishing cytoskeletal structures (microfilaments or microtubules), membrane channels, axoplasmic tubules, and neurotransmitters, among others.

Exceeding Metabolic Rate

When practitioners treat patients, they often fail to assess parameters that can quantitatively determine whether the patient is exceeding the metabolic rate of the receptors, as well as those of the post-synaptic cells and their connections. When the metabolic rate of any neuronal connection is exceeded, nutrient and oxygen supply will decrease, leading to downregulation of ATP and protein production.

If not reversed, this can lead to TND/ND. Cells that begin exceeding their metabolic rate will become more sensitive to external stimuli in an attempt to maintain adequate protein and ATP concentration, starting a vicious degenerative cycle of less nutrition, less oxygen, and further cellular deterioration.

Cellular Immediate Early Gene Response (CIEGR)

Good cellular CIS leads to healthy connections, with the ultimate goal of enhancing plasticity. Plasticity can be a double-edged sword, depending on which receptors are being stimulated. Would you prefer to create plasticity on small-diameter fibers (A-delta and C fibers) or large-diameter fibers (A-alpha, A-beta, Ia, Ib, or II)? The latter is preferred.

Cellular changes proceed on a step-by-step basis:

1. A cell is stimulated by its presynaptic pool (chemical or electrical).
2. The cell membrane releases products (Ca+2 or cAMP) secondary to primary stimulation. Ca+2 and cAMP are the most well-known cellular first messengers.
3. The excited cell activates specific immediate early genes (IEG), described as cellular immediate early gene response (CIEGR), either Type I or Type II:
   • Type I addresses the cell's nucleus. This cascade activates a third-order messenger that modulates the expression of nuclear DNA.
   • Type II addresses the expression of mitochondrial DNA, with the ultimate goal of ATP production.
4. Third-order messengers activated in the cell's nucleus (by Type I IEG) also activate reverse transcriptase and messenger ribonucleic acid (mRNA) expression. This nuclear expression carries instructions for producing specific proteins necessary for maintaining the cell's CIS.
5. Of the third messengers, "c-fos" is the most well-known, as it stimulates the cAMP response element binding protein (CREB).

With proper receptor stimulation, the expected cellular outcomes are:

• Adequate ATP production
• Adequate protein synthesis
• Proper maintenance of all cellular needs
• Adequate function of the Na:K pump
• Maintenance of cellular CIS

Assessing Metabolic Rate in Practice

How can practitioners ensure, or at least assess, that a treatment protocol does not exceed the patient's metabolic rate or energy resources for a positive recovery? The answer is to use parameters that can be quantified: heart rate, respiratory rate, and blood pressure, among others.

Phrases like "it has to get worse before it gets better" or "your dog/cat/horse felt off for 36 hours because it is in a healing mode" should not be used.

Persistent downregulation can lead to TND/ND. Cells exceeding their metabolic rate will become increasingly sensitive to external stimuli in an attempt to maintain adequate protein and ATP concentration, starting a degenerative cycle of less nutrition, less oxygen, and further cellular deterioration that will ultimately lead to apoptosis.

Assessment of heart rate, respiratory rate, blood pressure, and pupillary light reflex provides a window into the patient's CIS and autonomic balance, helping clinicians determine when it is prudent to stop or reconsider a treatment protocol.

Correct stimulation is the beginning of recovery. Over-stimulation stops recovery and makes the patient more prone to re-injury and worsening clinical symptoms.

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