Case Report by Julie Blossom, DVM, cVMA (Graduate of the Medical Acupuncture for Veterinarians Program by CuraCore)
DOWNLOAD HANDOUT ON ANTI-NGF MONOCLONAL ANTIBODY DRUGS HERE.
Abstract:
A geriatric male cat with diabetes mellitus was treated for suspected osteoarthritis and significantly impaired mobility. Our main goals in treating this cat were to enhance comfort and quality of life, as well as to reduce dependence on oral pharmaceuticals. Prior to integrative treatment, he was treated unsuccessfully with Solensia. During this case study, in addition to medications relating to managing his diabetes, the patient was treated with robenacoxib, gabapentin, acupuncture, LED phototherapy, massage and pulsed electromagnetic field therapy. Within three weeks, he showed a positive response to integrative treatment: faster and greater mobility, fewer proprioceptive problems, and the ability to maintain good comfort and mobility after discontinuation of robenacoxib. He maintained fair to good regulation of his diabetes mellitus throughout treatment.
History of Present Illness(es):
Misha is a 16-year-old male neutered domestic shorthair cat. He was diagnosed with diabetes mellitus in 2017. His owner first noticed impaired mobility beginning in 2020 when he started having trouble jumping. In late 2022 he started to have more noticeable trouble using his back legs. He also has a history of pruritis (related to ingesting chicken), chronic kidney disease, and suspected chronic pancreatitis and/or early inflammatory bowel disease.
Current medications include Levemir (insulin detemir, 3 units subcutaneously twice daily), maropitant (8-12mg by mouth once daily), chlorpheniramine (2mg by mouth twice daily), gabapentin (25mg by mouth twice daily) and robenacoxib (3mg by mouth every other day). He had previously required treatment with low dose meloxicam to help manage his stiffness but was switched to robenacoxib to see if a new non-steroidal anti-inflammatory would improve his stiffness.
Current supplements include vitamin B12 (2500 micrograms subcutaneously once weekly), and feline Antinol (2 capsules daily – proprietary blend of green-lipped mussel extract, vitamin E and essential fatty acids).
A series of three Solensia injections (frunevetmab,1mL subcutaneously), 3 weeks apart had been tried 3 months prior to integrative evaluation. The owner noted the following response to Solensia: the initial injection was unsuccessful at reducing symptoms of stiffness, there was a mild improvement in symptoms after the second injection, and the third injection seemed to cause him to feel worse and his clinical symptoms to deteriorate more rapidly. Solensia was discontinued at that time.
Physical Examination and Clinical Assessments:
Misha is friendly, alert and hydrated on initial examination. His body condition score is 7/9. He has a continuous glucose monitor (FreeStyle Libre 3) adhered to a shaved area on his left caudal thorax. His thoracic auscultation and abdominal palpation are normal. There is mild dental plaque found on both upper and lower teeth arcades. The palmar aspects of his forepaws are pruritic, slightly moist, and erythematous.
Haircoat evaluation: Misha has a slightly rougher and less kempt haircoat around the elbows, shoulders, lumbosacral region, stifles, and length of the spine. Misha’s hair is semi-erect generally.
Gait assessment: Misha exhibits moderate to severe trouble ambulating, despite flooring type. His thoracic limbs are held in abduction at the elbow both when walking and sitting. His pelvic limbs demonstrate moderate proprioceptive deficits and ataxia, as well as stiffness and circumduction during forward stride. When he navigates a small step, his pelvic limbs stumble before he catches his balance. When walking, due to the proprioceptive deficits in his hind end, he sometimes deviates involuntarily from a straight line.
Myofascial examination: Dramatic generalized muscle tension is present in Misha’s neck, dorsum, thoracic limbs, and pelvic limbs. Lumbar spine kyphosis is present with heat. There are multiple painful trigger points located throughout the major muscle groups, especially noted in the triceps, lumbar muscles, biceps femoris, and cranial tibialis. Misha is averse to skin and muscular palpation prior to beginning treatment.
Neurological examination: Cranial nerves are intact. Patellar reflexes were normal. Withdrawal reflexes were normal. Proprioceptive placement of limbs is normal in both thoracic limbs and is slightly delayed to inexact in both pelvic limbs.
Laboratory findings: Complete blood count iss unremarkable. Chemistry shows a slightly high albumin 4.2 g/dL, slightly high BUN at 57 mg/dL, creatinine of 2.0 mg/dL, and a slightly elevated blood glucose of 215 mg/dl. He has an elevated fructosamine of 445 umol/L, indicating fair regulation of diabetes mellitus. He has a normal cobalamin level but a low folate level (7.9 ng/mL) possibly indicating diffuse disease of the proximal small intestine.
Problem List:
-Generalized myofascial restriction
-Hyperglycemia / slightly elevated fructosamine
-Chronic kidney disease – Stage 2
-Low folate and suspected proximal small intestinal disease
-Over conditioned body score
-Palmar pruritis and erythema
-Mild dental plaque
Differential Diagnoses for generalized myofascial restriction:
- Vascular – ischemic neuropathy, hypertension, aortic or other thromboembolism, endothelial cell damage
- Infectious/Inflammatory – osteoarthritis, myositis, inflammatory bowel disease, dental disease, Toxoplasmosis
- Neoplastic – lymphoma, osteosarcoma, fibrosarcoma
- Degenerative – osteoarthritis, spondylosis deformans, chronic kidney disease
- Iatrogenic / Intoxication – dietary excess leading to obesity, repeated placement of FreeStyle Libre continuous glucose monitor, repeated subcutaneous injections
- Congenital – genetic predisposition to development of arthritis, breed-related conformational abnormalities
- Autoimmune – immune-mediated polyarthritis
- Traumatic – injuries from feline housemate
- Endocrine/Metabolic – diabetic neuropathy, acromegaly
- Myofascial – compensatory muscle and fascial strain from osteoarthritis
Differential Diagnoses for hyperglycemia:
- Vascular – hypertensive stress relating to neuromuscular injury or chronic kidney disease
- Infectious/Inflammatory – acute episode of pancreatitis, acute sepsis
- Neoplastic – somatotrophic adenoma of the pituitary gland (acromegaly), exocrine pancreatic neoplasia, lymphoma
- Degenerative – none
- Iatrogenic / Intoxication – postprandial, imbalanced nutritional intake, stress hyperglycemia, medication administration (no history of steroid or hormone administration)
- Congenital – none
- Autoimmune – none
- Traumatic – stressful interactions with housemate, stress relating to visiting the vet, fall trauma (no history)
- Endocrine/Metabolic – diabetes mellitus, acromegaly
- Myofascia – stress relating to compensatory muscle tension from osteoarthritis
Definitive Diagnoses:
1) Generalized myofascial restriction secondary to osteoarthritis. Radiographs of the elbows show medial epicondylitis of the left humeral condyle. There is ventral bridging spondylosis at T9/T10 and at the lumbosacral joint.
2) Hyperglycemia –diabetes mellitus (DM), managed on insulin and monitored with a continuous glucose monitor and periodic fructosamine levels.
Medical Decision-Making:
An integrative treatment plan including acupuncture, photo biomodulation (PBM), massage and pulsed electromagnetic therapy (PEMF) was formulated with the chief goal of enhancing Misha’s general comfort and mobility and the secondary goal of reducing oral pharmaceutical dependence. All treatments were carried out in the owner’s home to minimize Misha’s sympathetic nervous system activation during car trips to the veterinarian’s office. Misha’s owner was a willing and committed partner in his osteoarthritis management. She was already very attentive to making environmental modifications for him, including a ramp to the bed, area- rugs and carpeting to cover smooth flooring, padded resting choices, daily outdoor walks, and a secure outdoor “catio” for exercise. Misha was allowed to experience treatment voluntarily for the most part, meaning we allowed him to find a comfortable location to rest in, placed acupuncture needles only after he indicated that he was ready, and attended to his body language and posture as indications of when he was ready to be finished with his integrative sessions.
Acupuncture Treatments:
DATE: 3/4/23 – Introductory Visit
Treatment began gently and voluntarily when Misha was in a comfortable resting position on the rug. Two introductory needles were placed at Bai Hui and GV 14 (Seirin 0.16mm x 30mm). I chose GV 14 as an easily accessible cervicothoracic convergence point, as well as a parasympathomimetic point. Bai Hui was selected as another easily accessible point relevant to the lumbosacral nerve roots with respect to his pelvic limb ataxia. Misha rested on the rug and tolerated these needles well. I removed them after 20 minutes. The 30 mm length needles seemed to cause a bit of pruritis, so shorter needles were selected for subsequent treatments.
DATE: 3/11/23 – Second Visit
Misha was still having significant trouble ambulating per the owner’s report. His clinical symptoms of diabetes were well-controlled, however. He was treated in a sleeping position on the owner’s footstool. I used Seirin 0.16mm x 15mm needles in the following locations: GV 20, GV 14, BL 17.5 (L), BL 18 (L), Bai Hui, ST 36 (L), GB 29 (L) and GB 30 (R). Points were needled as Misha presented them and when they were accessible depending on resting position. I chose BL 17.5 as the back Shu point for the pancreas, and BL 18 as the back Shu point for the liver, as well as a neuromodulatory point for mid-thoracic spinal nerves.
GV 14, GV 20 and ST 36 were chosen for parasympathomimetic effect. ST 36 was chosen for local effect on his left pelvic limb. Bai Hui, GB 29 and 30 were chosen for local effect on confirmed osteoarthritis in the lumbosacral joint, as well as for suspected OA in the coxofemoral joints. Misha tolerated this treatment astoundingly well, laying perfectly still in a sleeping position the entire time. Needles were removed around 20 minutes.
DATE: 3/18/23 – Third Visit
Misha was noted as beginning to walk better by his owner on 3/12/23, just after the last visit. He was still experiencing ataxia in his hind end. He was treated with Seirin 0.16mm x 15mm needles in the following locations: GV 14, BL 17.5 (R/L), BL 23 (R/L), BL 25 (R/L), GB 29 (L), GB 30 (L) and ST 36 (L). BL 25 was added for assistance with thoracolumbar fascial pain and BL 23 as the back Shu point for the kidneys. He was very wiggly for this treatment; however we were still able to leave most needles in for about 10 minutes.
DATE: 3/25/23 – Fourth Visit
Misha is now starting to enjoy his daily outdoor walks with greater vigor. He is jumping up on uneven surfaces (rocks) with greater accuracy and the owner notes he seems to be more comfortable sleeping. A recheck of myofascial palpation was performed at this visit and I found that Misha had less overall myofascial restriction and was notably more comfortable for the examination. He was still slightly tender in his major muscle groups, but with an improvement in his level of ataxia in the pelvic limbs. He continued to have a slightly kyphotic lumbar region. He was treated using Seirin 0.16mm x 15mm needles in the following locations: GV 14, BL 17.5 (R/L), BL 23 (R/L), BL 25 (R/L), GB 29 (L), GB 30 (L) and ST 36 (L). Misha sat still for his treatment on the rug for 15 minutes. He did not allow treatment of his right side today due to his preferred resting position.
DATE: 4/1/23 – Fifth Visit
The owner notes Misha is not “wobbling” as much when walking and is eager to go for his daily walk. The owner discontinued robenacoxib on 3/28/23 due to an episode of vomiting and has not needed to restart it because he has remained comfortable. He is walking better than the owner has ever noticed before. He was treated using Seirin 0.14mm x 15mm needles at the following points: GV 14, BL 17-21 (R/L), Bai Hui and GB 29. The bladder line was used from 17-21 today because of myofascial restrictions noted in the thoracic and thoracolumbar areas. Smaller needles were chosen as Misha was wiggly and a bit intolerant to needles today.
April 2023 Follow-up: Misha continues to enjoy weekly treatments with acupuncture using similar points to the above-described visits. On days when he seems to want to walk around more, we use Carbo 0.18 x 15mm needles, as these seem to stay in for a longer period with movement. He will regularly accept treatment for 30 or more minutes, typically settling after needle placement and sleeping comfortably in his bed. His owner reports continued good daily averages for his blood glucose values on the FreeStyle Libre without any changes to insulin therapy.
Photobiomodulation Treatments:
At my guidance, the owner purchased a therapeutic LED device (Shine model by TendLite, combined 660nm red and 850nm infrared LED cluster, 1500 mW output). We agreed on a one-minute treatment protocol of every other day for 10 days (3/18/23 to 3/28/23) to the following areas: cervicothoracic spine, lumbosacral spine, elbows, and shoulders. Misha was not a huge fan of treatments with this device, likely because of the heat it generated after about 30 seconds of use, and so it was used for the 10-day period and then stopped.
Massage Treatments:
The owner was instructed on gentle petrissage and effleurage to the following areas: hip and lower lumbar areas. He seemed to enjoy both areas being massaged, and so was treated for 5 minutes daily by his owner starting on 3/11/23. Misha also allowed me to massage him for several minutes after acupuncture treatments.
Pulsed Electromagnetic Field Therapy Treatments: An Assisi loop was used by the owner on the pelvis (1 treatment for 15 minutes per day). Due to frustrations using the large and uncomfortable Assisi loop, it was discontinued in favor of a smaller more comfortable pulsed shortwave therapy device (Acti-Patch – Bioelectronic Corp., Frederick MD, USA) which has proven clinical efficacy in humans with arthritis, back pain, knee pain and fibromyalgia. Acti-Patch shows promising research in dogs with neck pain and is lighter and better tolerated in small patients.
Outcome and Discussion:
As indicated by the above visit details, Misha had a positive response to integrative treatment, particularly acupuncture, after about three treatments. Not only did his gait and ataxia improve noticeably, but the owner was able to discontinue NSAID treatment without noticing regression. My initial assessment of Misha’s extensive myofascial restriction and aversion to even light palpation caused me to wonder whether diabetic neuropathy might be partly to blame. Diabetic neuropathy is best described in humans who experience degeneration of the nervi vasorum relating to chronic hyperglycemia and can develop subsequent debilitating neuropathic pain, peripheral vasculitis, and skin ulcerations. After treating Misha, I think that this still could play a role, however most of the compensatory myofascial restriction and pain present is probably simply due to multifocal osteoarthritis.
It is also interesting to note that Misha was a poor responder to Solensia, a relatively new, anti-nerve growth factor (NGF) monoclonal antibody (mAb). While this drug has been marketed as a panacea for osteoarthritis in cats, Misha is evidence that the story is more complicated. NGF is required for the survival and proliferation of sensory neurons as well as sympathetic neurons. By taking away too much of this neuronal cell signal, we may potentially be limiting the capacity of the nervous system to regulate itself and regenerate. In one review article I located, Freeman et al describe how neurons undergo apoptosis in the absence of NGF. Due to ongoing, long-term unknowns about targeting NGF with antibodies, perhaps it is best to evaluate each patient individually, and use Solensia judiciously in conjunction with other multi-modal therapies.
Lastly, I think that getting to know Misha on his terms, in his environment increased the success of our treatments. I was able to spend considerable time observing him navigate his actual home, and thus able to target treatment according to what I observed directly. He remained comfortable, calm, and was able to avoid spikes in cortisol related to travelling to the veterinarian. The ability to treat him at home, and the success of acupuncture in treating his osteoarthritis likely contributed to the stability in his diabetes regulation over the 5-week treatment period.
Veterinary acupuncture induces relaxation and reduces pain; it often requires little to no restraint.
References:
- Freeman, RS et al. NGF deprivation-induced gene expression: after ten years, where do we stand? Progress in Brain Research, 2004;146:111-26.
- Heiskanen V. and Hamblin MR. Photobiomodulation: Lasers vs Light Emitting Diodes? Photochem Photobiol Sci. 2018; 17(8): 1003-1017.
- Anju, M et al. Low level laser therapy for patients with painful diabetic neuropathy – A systematic review. Diabetes and Metabolic Syndrome, 2019; 13: 2667-2670.
- https://acti-patch.co.za/clinical-evidence – Acti-Patch Research Reference Collection
- Sprunks, T et al. Pulsed shortwave electromagnetic field therapy increases passive range of motion and reduces behaviors associated with osteoarthritis in canines. 2023 pending publication. Manuscript can be found at: http://www.bielcorp.com/veterinary