Integrative Approach to Neurology


21
Integrative Approach to Neurology


Patrick Roynard


Introduction


Neurological disorders are common among companion animals, and some of the most frequently encountered are myelopathies (e.g. intervertebral disc disease [IVDD]) and seizure disorders. Clinical neurology has markedly changed in the past few decades with the spread of advanced imaging, often pre-requisite to an accurate diagnosis for disorders of the central nervous system (CNS). Conventional treatments for neurological disorders can be broadly divided into medical and surgical interventions, with decompression of the CNS being a frequent surgical goal. Various “alternative or complimentary” treatment modalities have been described in the management of small animal neurological disorders, often as an adjunct to standard medical care. Some of these modalities, such as acupuncture and physical rehabilitation for spinal cord injuries (SCIs), have already been investigated in several clinical studies and are relatively well-established practice at this time. This text does not aim at being exhaustive but rather presenting the integrative modalities most used and documented in small animal neurological disorders, along with suggestions for their implementation. The modalities are presented per neurolocalization (i.e. myelopathies, encephalopathies, neuropathies), with emphasis on the most reported indications for integrative therapies first (e.g. acupuncture and physical rehabilitation for IVDD). For more specific discussion regarding each therapeutic modality, the reader is referred to the corresponding sections and chapters of this textbook.


Myelopathies


Acupuncture for Myelopathies


Spinal Cord Injury (SCI)


Following initial spinal cord trauma, neuroscience has established an important secondary neurodegenerative process that occurs, which causes significant cord injury. Calcium entry into neurons and glial cells results in a cytokine and free radical cascade released by activated microglia and damaged mitochondrial membranes [1, 2]. Tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), matrix metalloprotease-9 (MMP-9), and nitric oxide (NO) promote the inflammatory-cascade, creating neuronal and oligodendrocyte damage. Demyelination of axons, neuronal inflammation and progressive disruption of nervous tissue follows with long-term consequences that impair SCI recovery [2, 3]. No proven pharmacological protocol providing protection from these secondary changes is currently available; however, research suggests acupuncture may inhibit this process. An experimental study of SCI in rats with sham/placebo control demonstrated acupuncture improved functional recovery after SCI compared to controls (P < 0.01). Acupuncture attenuated microglial activation (P < 0.01) and reduced expression of TNF-α (P < 0.01), IL-1β (P < 0.01), IL-6 (P < 0.01), MMP-9 (P < 0.05), NO synthase (P < 0.001), and cyclooxygenase-2 (P < 0.001). Reduced apoptotic cell death of both neurons and oligodendrocytes (P < 0.001) along with axonal loss and lesion size reduction on immune-histochemical staining (P < 0.05) demonstrated acupuncture provided neuroprotection [4].


Neuroplasticity defines the ability of nervous tissue to change structurally, resulting in functional changes. Trauma and neurologic disease alter plasticity-factors. Specific neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurotrophic factor-3 (NT-3) are endogenous plasticity promoters that may be key to recovery from SCI. These neurotrophins are downregulated in SCI [5] and SCI rodent-model studies suggest a positive correlation of BDNF and NT-3 levels with optimum functional neurologic recovery [6, 7] and reduction in neuropathic pain [8]. An SCI murine model study reported a positive correlation between electro-acupuncture’s neuro-protective effects and improved locomotor function recovery with the up-regulation of BDNF and NT-3 (P < 0.05) [9].


Intervertebral Disc Disease (IVDD)


In the traditional Chinese veterinary medicine (TCVM) paradigm, SCIs are due to Qi and Blood Stagnation, and acupuncture has long been used for various myelopathies. Multiple studies document the use of acupuncture for canine IVDD, as adjunct or alternative to standard management. While several studies present methodological flaws and researcher bias (groups not matched, evaluator not blinded), a trend toward faster, more complete recovery appears to be associated with electro-acupuncture (EA), and some authors have concluded EA may have a canine thoracolumbar (TL) IVDD treatment success rate up to 83–95% [10, 11]. In one study on 50 dogs with TL-IVDD, a significantly shorter time to recover ambulation was reported with conventional treatment + EA (10.10 ± 6.49 days) versus conventional treatment alone (20.83 ± 11.99 days; P = 0.0341) for non-ambulatory dogs with intact nociception (grades 3 and 4). The ability to walk without assistance for grades 3 or 4 and overall success rate were also significantly higher with EA (respectively P = 0.047 and 0.015) [12]. In a retrospective study (80 dogs) with paraplegia and intact nociception from TL-IVDD (grade 4), the combination of EA with prednisone was significantly (P = 0.01) more effective than prednisone alone to recover ambulation; allowed faster return to ambulatory status (P = 0.011), relieved back pain (P = 0.001) and decreased relapse rate (P = 0.031) [13]. Another study compared EA, hemilaminectomy and hemilaminectomy + EA in 40 dogs with more than 48 hours of severe neurologic deficits due to IVDD (only grades 4 and 5) confirmed by diagnostic imaging (MRI, CT, myelography). “Clinical success,” defined as a patient initially classified grade 4 or 5 then classified as grade 1 or 2 within 6 months of treatment, was significantly (P < 0.05) higher for dogs that received EA alone (15/19, 79%) or EA and surgery (8/11, 73%) than dogs with surgery alone (4/10, 40%) [14]. Refer to Table 21.1 for grading of neurological deficits.


Table 21.1  Grading scale for neurological deficits commonly used in canine IVDD and suggested recommendation for use of TCVM and integrative modalities.






































0 Normal
1 Cervical or thoracolumbar pain, hyperesthesia with no neurological deficits:
TCVM and other modalities (e.g. laser) as an adjunct, or alternative to standard management (activity restriction still recommended in acute/painful stage)
2 Ataxia, paresis, decreased proprioception, ambulatory:
TCVM and other modalities (e.g. laser) ideally used as adjunct to standard management including rehabilitation (activity restriction still recommended in acute/painful stage)
3 Paresis with absent proprioception, non-ambulatory:
TCVM and other modalities (e.g. laser), as an adjunct to standard management with recommendation for advanced imaging +/– decompressive surgery and rehabilitation
4 Paralysis, nociception present:
TCVM as adjunct to standard management with recommendation for advanced imaging +/– decompressive surgery and intensive neuro-rehabilitation post-operatively (e.g. NMES, therapeutic exercises including land treadmill, laser)
5 Paralysis, absent nociception:
Both TCVM, decompressive surgery and intensive neuro-rehabilitation post-operatively (e.g. NMES, therapeutic exercises including land treadmill, laser)

Besides benefiting the spinal cord itself, EA has also shown effects on vertebrae and intervertebral discs likely to be beneficial in cases of IVDD. In a randomized controlled murine study, EA inhibited Wnt-βcatenin, which may delay the degenerative process of cervical intervertebral discs [15]. Acupuncture can also improve the ability of degenerated discs to repair by reducing the amount of type I collagen in the nucleus pulposus while promoting type II collagen, necessary for proper hydration of proteoglycans leading to compression resistance [16, 17]. In an IVDD rat model, EA also increased vertebral blood flow, micro-vessel density, and number of normal spinal cord neurons. [18]


TCVM can be used for cervical IVDD and, in the author’s opinion, may be one of the most rewarding conditions to treat with EA. A retrospective study (19 dogs, cervical myelopathy), used three different acupuncture protocols: dry needle acupuncture (DN) +/– EA, and Chinese herbal medicine (CHM).1,2 All 19 dogs, which had previously failed conventional medical/surgical management (18 with IVDD, 1 with fibro-cartilaginous embolic myelopathy), reported both pain and neurological function improvement [19]. A case report also describes successful use of EA and herbals for IVDD at C3-C4 in a miniature Pinscher [20].


While the author still recommends advanced imaging and decompressive surgery when indicated for cases of presumptive IVDD, these results justify offering EA as an adjunct to the “gold standard,” whether the conventional management pursued is surgical or conservative. Suggested recommendations for TCVM use based on neurological deficit grade is included in Table 21.1.


Cervical Spondylomyelopathy (CSM)


A clinical trial of 40 dogs with presumptive or diagnosed CSM comparing standard treatment (medical and surgical) vs standard treatment + EA reported an overall EA efficacy of 85% versus 20% standard treatment only (noticeably lower than classically reported) [21]. A retrospective study of 19 animals (13 dogs, 6 horses) with presumptive or diagnosed CSM reported results obtained with the following TCVM treatments: DN, EA, aqua-acupuncture (1000 μcg/ml Vitamin B-12), CHM1 for all patients, CHM2 in grades 2 or higher, CHM3 in patients with cervical pain, and additional Chinese herbal medicines based on the Chinese pattern diagnosis. All animals showed improvement, except for one horse with poor tolerance of acupuncture, precluding completion of treatment [22].


As for IVDD, the author still recommends advanced imaging and surgery (if indicated) for presumptive cases of CSM, but also recommends integrating TCVM and neurological rehabilitation for ideal pain management and functional recovery.


Selection of Acupuncture Points Based on Neuroanatomical Function


For a more in-depth review of the anatomy and physiology relevant to acupuncture, the reader is referred to Section II, Chapters 4 and 6 of this textbook.


Recent studies have allowed identification of criteria associated with higher likelihood of effect when considering acupuncture points. Up to 70% of acupuncture points have been identified as motor entry points, which are locations where the motor branch of a nerve enters the muscle belly of an innervated muscle [23]. These points can be identified with neuromuscular electrical stimulation (NMES) as the point that will elicit maximal contraction of a muscle belly if stimulated. Recently, acupuncture points have also been identified as neurogenic inflammatory spots, which are areas of local tissue response caused by cutaneous neurogenic inflammation encountered in visceral disorders. They are located in the dermatome overlapping the visceral afferent innervation [24]. Features of neurogenic spots include: plasma extravasation, vasodilation in postcapillary venules of the skin, wheal-and-flare reaction and substance P from activated small diameter sensory afferents. Neurogenic spots also show hypersensitivity, high electrical conductance and small diameter nerve fiber-mediated sensation (C fibers, Aδ). Features which are classically associated with acupuncture points [25]. Overall approximately 70% of neurogenic spots were found to match acupoints. More importantly, in murine models of colitis and hypertension, acupuncture was effective when performed at acupoints that were also neurogenic spots, and ineffective at non-neurogenic spot acupoints [24].


Although it has been reported that acupuncture is more efficient when practiced according to patient TCVM Pattern diagnosis (See Section II, Chapter 5), based on these studies and personal observations, the author suggests including local points (e.g. Jing-jia-ji for cervical IVDD) and distal points (including specific acupoints identified as motor entry points and/or neurogenic spots) when using EA for neurological disorders (Table 21.2).


Table 21.2  Acupuncture points for neurological disorders and indication.





























































Location Acupuncture point* Suggested indications (emphasis on neurological disorders)

Thoracic limbs


(from proximal to distal)

LI-11 (Large Intestine 11) Thoracic limbs paresis, radial nerve disorders, elbow pain, diarrhea, clearing heat
LI-10 (Large Intestine 10) Thoracic limbs paresis (and paraparesis), musculocutaneous and radial nerve disorders, contralateral motor cortex disorders, elbow pain, immune regulation, diarrhea
LI-4 (Large Intestine 4) Thoracic limb paresis, master point for face and mouth
PC-8 (Pericardium 8) Thoracic limb paresis, median nerve disorders, oral disorders (e.g. stomatitis); bilateral PC-8 form the “4 roots” with bilateral KID-1
Pelvic limbs (from proximal to distal) SP-10 (Spleen-10) Paraparesis and paralysis, femoral nerve disorders, blood deficiency
BL-40 (Bladder 40) Paraparesis, sciatic nerve disorders, spinal and pelvic pain, pyelonephritis, urinary pain, coxofemoral joint pain, master point for lower back
GB-34 (Gallbladder 34) Paraparesis, sciatic nerve disorders, tendon and ligament pain, stifle pain
ST-36 (Stomach 36) Paraparesis, sciatic nerve disorders, contralateral motor cortex disorders, gastrointestinal or abdominal pain, nausea, vomiting, gastric ulcers
BL-60 (Bladder 60) Paraparesis, sciatic nerve disorders, spinal pain, tarsal pain, headache, cervical pain, hypertension
LIV-3 (Liver 3) Paraparesis, generalized pain, anxiety, pelvic limb lameness
KID-1 (Kidney 1) Paraparesis and paralysis, heel pain; bilateral KID-1 form the “4 roots” with bilateral PC-8
Truncal (paraspinal) Jing-jia-ji (cervical Hua-tuo-jia-ji) Cervical pain and stiffness (e.g. IVDD, cervical spondylomyelopathy)
Hua-tuo-jia-ji IVDD, spinal pain
BL-23 (Bladder 23) Spinal pain, paraparesis, urinary tract pain, pyelonephritis
Bai-hui IVDD, lumbosacral (LS) disease, pelvic limb pain

* acupoints that are motor entry points are bolded.


Electro-acupuncture Treatment Timing and Parameters


The author recommends acupuncture early after injury/surgery (ideally within 24–72 hours), in order to maximize benefits. Very low frequency EA (2–10Hz) is helpful in treating neuropathic pain and is, like low frequency EA (20–40Hz), associated with endorphins and enkephalins release. High frequency (80–120Hz) and very high frequency (200Hz) are associated, respectively, with dynorphin and serotonin release. Suggested protocol includes 10 minutes at low frequencies (20/40 Hz), followed by 5–10 minutes at higher (80/120 Hz) and very high frequencies (0/200 Hz), with added very low frequency (2–5Hz) for 5–15 minutes in case of neuropathic pain, based on severity and patient’s tolerance. The author suggests starting each session with “permission points” (e.g. GV-20 and bilateral An-Shen) to help patient compliance, and recommends EA 1–2 times/week for the first 3 weeks prior to considering progressive reduction of frequency.


Another benefit is that, acupuncture as a “passive” modality, is acceptable therapy in acute inflammation when the patient may not be a candidate for other interventions (e.g., pain preventing active treadmill work or unstable vertebral fractures) or early post-operative period (Figures 21.1 and 21.2).


Figure 21.1 10 YO FS Italian Greyhound receiving EA for multifocal IVDD. Note the multiple leads with both truncal/local points (e.g. Jing-jia-ji, Hua-tuo-jia-ji, Bladder acupoints) and appendicular/distal points (e.g. LI-4, LI-10, ST-36, GB-34).


Figure 21.2 (A) T2 weighted fat-sat MR image (sagittal view) showing protrusion of the meninges and spinal cord/ nervous tissue (myelomeningocele) through bifidous spinous process at the last lumbar vertebra (spina bifida) in a six-month-old French Bulldog with congenital urinary/fecal incontinence. The spinal cord is deviated dorsally, consistent with tethered cord syndrome.



Figure 21.2 (B, C) Intra-operative images of surgical correction. After identification of the myelomeningocele (B), it is dissected down to the vertebral canal and the nervous structures (visible through the durotomy incision) are being dissected from adhesions (C) to restore normal anatomy.


Figure 21.2 (D) Patient one-day post-operative receiving electro-acupuncture at GV-1, CV-1, ST-36, and BL-40.


Rehabilitation/Physical Therapy for Myelopathies


For a more in-depth review of the anatomy and treatment modalities involved in physical rehabilitation, the reader is referred to Section VI, Chapters 13, 14, and 15 of this textbook.


Physical activity increases levels of neurotrophins and exercise has been suggested the best method to increase BDNF levels [6, 26]. Early initiation after SCI, [5, 27] type of exercise, timing and duration of session(s) have been reported to influence effects; with early treadmill training (repetitive, sustained locomotor work), increasing BDNF boosting functional recoveries in SCI [8, 28], and stroke murine models [2931]. It is noticeable that static standing and swimming did not exhibit similar benefits [32]. NT-3 is also up-regulated in the spinal cord and skeletal muscle with treadmill exercise [6, 33, 34]. Studies have shown benefits (albeit sometimes minimal) in neuroplasticity, motor and sensory recovery (allodynia) when exercise is initiated early after neurologic injury [8, 32, 35], with stronger improvements noted with comprehensive, multimodal rehabilitation [36]. This suggests that exercise such as sustained gait training modulates neuro-inflammation and stimulates neurotrophins, which is potentiated when combined with other modalities, NMES, laser, and acupuncture [3640].


Canine Models of Spinal Cord Injury


Studies in canine models of SCI support the positive association between BDNF and functional recovery [41, 42], with higher levels of BDNF being associated with improved recovery, which can be stimulated with sustained exercise in dogs [43]. However, MMP-9, a pro-inflammatory metalloproteinase, may dampen the benefits of treadmill training in promoting BDNF and NT-3 [35], highlighting the possible synergistic effect of using treatment modalities diminishing neuro-inflammation (e.g. acupuncture, laser) concomitantly to locomotor training. Hence, locomotor training (e.g. land treadmill) appears as a cornerstone for a neuro-rehabilitation program in dogs. In clinical practice, treadmill training is routinely used to initiate rhythmic locomotor movements and is relatively easy to implement (Figure 21.3). In the authors’ experience, patients with a remaining degree of motor function (whether ambulatory or not) benefit most from treadmill training. Animals with severe deficits and paralysis may show limited benefits, or even detrimental in stimulating negative neuroplasticity and/or compensation.


Figure 21.3 (A, B, C) 5YO MN Dachshund recovering from TL IVDD surgery and undergoing physical therapy with land treadmill (A) and balance exercises to help improve proprioception (B). (C) Dog receiving neuromuscular electrical stimulation (NMES) on quadriceps and hamstrings while engaged in an assisted standing exercise (fNMES).


Intervertebral Disc Disease (IVDD)


Several studies report the use of physical rehabilitation in dogs recovering from TL-IVDD surgery, with conflicting findings regarding results, but an overall trend toward improved recovery. Many studies are retrospective, address patients that were non-ambulatory at presentation, involve some rehabilitation even in the control group and all involve multimodal therapy in the protocols including physical exercise (e.g. land treadmill once patients can stand, NMES, balance board, laser therapy) [4450].


A randomized, blinded, prospective clinical trial on 30 non-ambulatory paraparetic or paraplegic dogs (with pain perception) after surgery for TL-IVDD found that early initiation of intensive postoperative rehabilitation was safe and well-tolerated. No significant improvement in outcome, however, was found when comparing early intensive post-operative rehabilitation [supported standing, NMES, weight shifting/balance board exercises, underwater treadmill] to less intensive post-operative treatment (ice/hot packs, passive ROM, sling walks) [44]. The lack of significant benefits of intense neurologic rehabilitation program(s) in outcome is limited to this study, as all other published studies, albeit retrospective concluded some benefits. A retrospective study on 248 non-ambulatory dogs reported multimodal post-operative rehabilitation did not accelerate recovery, but improved functional outcome with higher chance of complete recovery and lower chance of complications [45]. Another similar retrospective study (186 dogs) reported faster and significantly higher successful outcome with multimodal rehabilitation than without, for all neurological grades (86%, 83/96 vs 52%, 47/90; P < 0.01) [46].


A larger retrospective controlled clinical study (367 paraplegic dogs) also reported significant improvement in recovery of ambulation with intensive neurorehabilitation (P < 0.001) [47]. Finally, another retrospective study of 113 dogs treated with comprehensive rehabilitation post-operatively reported that more time in formal rehabilitation (P < 0.001) and more underwater treadmill sessions (P < 0.001) increased the chances of improvement [50]. This trend is also reported in cervical IVDD, with a retrospective study (58 dogs) reporting significantly higher success with multimodal rehabilitation post-operatively (27/34 vs 15/24; P < 0.05) [51].


Degenerative Myelopathy


A retrospective study reported on the effects of varying intensities of physical rehabilitative therapy on survival and length of ambulatory status in 50 dogs with presumptive degenerative myelopathy (DM) [52]. Survival time was positively associated with the degree of physical rehabilitation therapy. Dogs that received intensive physical rehabilitation (n = 59) had longer survival time (mean 255 days) than dogs with moderate (n = 56, mean 130 days) or no (n = 57, mean 55 days) rehabilitation (P = 0.05). The authors reported that, compared to the group with intensive physiotherapy, the risk of death was 5.8 times higher (P = 0.046) for dogs with moderate physical rehabilitation and 112 times higher (P = 0.001) for dogs without physical rehabilitation [52]. Another retrospective study on 20 dogs with presumptive degenerative myelopathy (DM) receiving a combination of rehabilitation therapy and either one of two different PBMT therapy protocols showed no difference in survival time compared to historical controls for one of the groups, but there was significantly longer time to reach non-ambulatory paraparesis along with longer survival time for the group receiving intense laser therapy treatment (p < 0.05) [53]. Despite study limitations (e.g. few dogs with confirmed DM), this and physical rehabilitation are the only clinical therapies documented that suggest slower disease progression.


Botanical Medicine


A comprehensive review of all herbal indications in small animal neurology is beyond the spectrum of this chapter. For a more in-depth review of herbal medicine with actions and indications, the reader is referred to Section IV, Chapters 9–10 and Section VIII, Chapter 24 of this textbook as well as other texts published on the topic [54].


Research has shown multiple benefits of herbal formulas, such as promoting neural regeneration, seizure control, alleviating pain, reducing hemorrhage, and treating peripheral nerve injuries [5562

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Jul 30, 2023 | Posted by in ANIMAL RADIOLOGY | Comments Off on Integrative Approach to Neurology

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