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Manual therapeutic plasma exchange for treatment of a dog with suspected acute canine polyradiculoneuritis

Manual therapeutic plasma exchange for treatment of a dog with suspected acute canine... Background Acute canine polyradiculoneuritis is one of the most common polyneuropathies occurring in dogs. The disease is very similar to the Guillain–Barré syndrome in humans. In veterinary medicine, there is no established treatment for this disease, while in human medicine, therapeutic plasma exchange and intravenous immunoglobulin administration are two main immunotherapy treatments of this syndrome. Case presentation A 12-year-old male Jack Russel Terrier was presented with a history of acute weakness of the pelvic limbs progressing to flaccid tetraplegia with respiratory compromise. Complete diagnostic workup was performed including blood work, diagnostic imaging (radiographs of the thorax as well as ultrasound of the abdomen) and echocardiography. Based on the clinical course, neurological localisation and the results of electrodiagnostic examination acute canine polyradiculoneuritis was suspected. During the hospitalization, the dog deteriorated and was admitted to the intensive care unit for respiratory support via tracheostomy tube. In addition to symptomatic treatment, immunotherapy via single treatment of manual therapeutic plasma exchange was administered. This procedure was safe, and the dog showed improvement of clinical signs 3 days after therapy was initiated, as well as improvement of neurological signs (from grade 4 tetraplegia to grade 3) within 5 days. However, the dog was euthanized 3 weeks later due to complications related to the tracheostomy. Conclusions This is the first case report of a manual therapeutic plasma exchange in a dog with suspected acute canine polyradiculoneuritis suggesting that this method is safe and well tolerated in dogs with this disease. It may be a reasonable adjunctive treatment to supportive therapy in severe cases. Keywords Canine, Guillain-Barré syndrome, Neuromuscular disease, Therapeutic plasma exchange *Correspondence: Adriana Czerwik adriana.czerwik@vetmed.uni-giessen.de Department of Veterinary Clinical Sciences, Neuroradiology and Clinical Neurology, Small Animal Clinic, Justus-Liebig-University, Frankfurter Str.114, 35392 Neurosurgery, Giessen, Germany Department of Veterinary Clinical Sciences, Internal Medicine, Small Animal Clinic, Justus- Liebig-University, Frankfurter Str.114, 35392 Giessen, Germany Department of Emergency and Critical Care Service, Vetklinikum LS, Laxenburger Str. 252a, 1230, Vienna, Austria © The Author(s) 2023. 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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 2 of 9 Background withdrawal reflex, the dog showed hyperesthesia. Neck Acute canine polyradiculoneuritis (ACP) is one of the movements were weak, and the dog could not lift his most common polyneuropathies occurring in dogs head. The perineal reflex and cranial nerves were intact. [1]. The disease is very similar to Guillain–Barré Syn - The patient maintained the ability to move its tail and to drome (GBS) in humans, caused by the immune-system urinate and defecate. Moderate, generalized muscle atro- inflicted damage of the peripheral nervous system. In phy was visible. The clinical signs were localized to the veterinary literature, the disorder is also known as coon- peripheral nervous system involving the motor nerve hound paralysis or idiopathic polyradiculoneuritis [1, 2]. roots. Although the pathogenesis of ACP is uncertain, an auto- The neurological examination was followed by labo - immune process affecting both axons and myelin of the ratory analysis including complete blood count, serum ventral nerve roots is suspected. The proposed patho - biochemical profile (glucose, total protein, albumin, urea genesis includes molecular mimicry or the production nitrogen, creatinine, total bilirubin, alanine and aspartate of autoantibodies against axolemmal components such transferase, alkaline phosphatase, creatine kinase, lipase, + − + + + a anti-ganglioside antibodies (Abs)[1, 3]. The first clini - cholesterol, Na , PO , iCa , K , iMg and c-reactive-pro- cal signs in affected dogs usually develop in the pelvic tein), thyroid hormones (TSH, T4) and antibody levels limbs and eventually progress to the thoracic limbs, caus- against Neospora caninum and Toxoplasma gondii. The ing generalized lower motor neuron paresis/plegia. Most dog underwent radiographic examination of the thorax affected patients develop non-ambulatory tetraparesis/ as well as ultrasound examination of the abdomen and tetraplegia within 10 days of the onset of clinical signs echocardiography. [4]. The prognosis for full recovery is usually favourable, The CBC, serum chemical and electrolyte analyses if adequate supportive treatment is applied, except in were within reference ranges, except for a decreased cases with life-threatening respiratory impairment [5], T4 level (0.7  µg/dl with the reference 1.5-4  µg/dl) with where full recovery is prolonged, taking several weeks to a normal TSH level (0.09ng/ml with the reference up to several months or it may even lead to death. There is no 0,30bg/ml), which was attributed to the euthyroid sick known disease-specific therapy described in veterinary syndrome. The antibody results for N. caninum and T. medicine. Hence, treatment options for ACP are war- gondii were negative with IgG titer 1:80, IgM titer < 1:40 ranted. A recent study showed that dogs suffering from (reference < 1:40) and IgG titer < 1:64, IgM titer < 1:16 ACP treated with intravenous immunoglobulin (IVIg) [5] (reference < 1:64) respectively. The results of the radio - recovered faster compared with dogs without immuno- logical examinations (radiographs as well as ultrasound) therapy. Dogs suffering from myasthenia gravis, another showed no clinically relevant abnormalities. The cardio - neuromuscular, autoimmune disease treated with thera- logical examination revealed a mitral valve insufficiency peutic plasma exchange (TPE), recovered faster com- with a moderate enlargement of the left atrium, indicat- pared with dogs without immunotherapy [6]. In human ing a stage B2 myxomatous mitral valve degeneration medicine, plasma exchange as well as IVIg have become (MMVD). All results from imaging diagnostics including the gold standard treatment for GBS [7]. echocardiography were reviewed by board certified radi - This case report describes the clinical and neurologi - ologist and cardiologist. cal presentation, electrodiagnostic findings and manual The dog was admitted to the hospital for supportive therapeutic plasma exchange treatment in a small breed care and began to show signs of mild dyspnoea, loss of dog with suspected ACP. appetite and apathy on the second day of hospitaliza- tion. At this stage, respiratory movements were shallow Case presentation and primarily abdominal. On the following day, the dog A 12-year-old male Jack Russel terrier was referred to the was hypoventilating and was assigned to the intensive Department of Veterinary Clinical Sciences in the Small care unit for ventilatory support (mechanical ventilation) Animal Clinic of the Justus-Liebig-University Giessen, (Fig. 1). Ventilatory support was achieved using pressure- Germany with a history of symmetrical weakness which controlled ventilation allowing the patient to trigger began in the hindlimbs, evolved to the forelimbs, and each respiratory cycle with use of the respirator software progressed to a non-ambulatory flaccid tetraplegia within (Servo-S, Maquet Getinge Group, Rastatt, Germany). A 4 days. The medical history revealed no information tracheostomy tube was placed to improve care and regu- about possible trauma, concomitant illnesses, or expo- late the dog’s condition with minimal sedation. The dog’s sure to neurotoxins. Apart from a left apical systolic heart condition did not change during the first three days of murmur grade 5, there were no abnormalities present intensive care. on the physical examination. The neurological examina - Seven days after clinical onset, electrophysiological tion revealed lack of postural reactions and absent spi- tests were performed under general anaesthesia with the nal reflexes (flaccid tetraplegia). On examination of the dog in lateral recumbency, using a Nicolet VikingQuest Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 3 of 9 Fig. 1 The dog during a stay in the intensive care unit System (Electrodiagnostic Software, USA). The elec - After three day of ventilatory support, single manual tromyographic examination (EMG) revealed moder- TPE was performed. A commercial autotransfusion set ate insertional activity and fibrillation potentials in the used for orthopedic procedures and described elsewhere quadriceps, cranial tibial and plantar interosseus mus- [9] was applied to the existing peripheral central venous cles. Motor nerve conduction velocity (MNCV) of the catheter (3  F 200  mm Careflow One Lumen catheter, tibial nerve was measured following proximal (trochan- Merit medical Ireland Ldt, Galway, Ireland) in the left ter), middle (caudal stifle) and distal (hock) stimulation cephalic vein. A second peripheral central venous cath- using monopolar needle electrodes. Compound action eter was placed into the right saphenous vein. Although potentials (CMAPs) were recorded from the plantar use of some commercially available TPE systems is interosseus muscle. The distal latency and amplitude of described in small sized dogs with corresponding blood the CAMPs were measured. MNCV was calculated from priming related to the large extracorporal needed [10– the trochanter to the stifle and the stifle to the hock seg - 12], those systems were not available in the presented ment of the tibial nerve and revealed a moderate reduc- case. A therapeutic plasma exchange system was built tion in the MNCV of the tibial nerve (proximal 26  m/ between the two catheters consisting of a set of infu- sec, distal 63 m/sec, with the reference 60–70 m/sec and sion lines, a modified autotransfusion system (Orthopat, 70–80 m/sec respectively) [8]. The tibial residual latency Haemonetics inc, Boston, MA, USA) and a bag of donor was normal (1.72 m/sec, with the reference 1.6-2 m/sec) plasma. Fifty ml of blood was manually drawn and antico- [8]. F-waves were measured using the same electrode agulated with sodium citrate (sodium citrate 3.13%, Eifel- configuration and were recorded at the plantar interossei fango) taken from the peripheral central venous catheter muscles. An increased F-wave latency of 16.4 m/sec was and transferred to the reservoir of the system (Fig. 2). The detected (minimal expected F-wave latency was 13  m/ blood was aspirated and centrifuged, the plasma sepa- sec). The calculated F-ratio was higher than the reference rated, and the blood additionally washed with 0.9% saline values for the stifle (1.67 vs. 0.8), which indicated more (isotonic sodium chloride ad us vet., B. Braun Vet Care) severe involvement of the proximal part of the nerve. according to the manufacturer’s instructions. Following Neuromuscular transmission was assessed using repeti- the centrifugation process, the blood was automatically tive nerve stimulation (RNS) at the hock at 2 and 3  Hz transferred as an erythrocyte concentrate into a sterile recorded at the plantar interosseous muscles, to exclude 50 mL syringe. Subsequently, these washed cells were a neuromuscular junction disease. RNS was normal with administered to the dog through the other catheter with no decrement. a corresponding amount of a donor plasma. Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 4 of 9 Fig. 2 Scheme of the approach to the plasma exchange (1) Aspiration of dog’s blood into a syringe and injection of this blood into the autotransfusion system; (2) Anticoagulation of the aspirated blood with sodium citrate; (3) separation of dog’s blood into plasma and red blood cells in the autotransfusion system; (4) collecting bag for dog’s plasma; (5) donor plasma; (6) aspiration of the erythrocyte concentrate from the autotransfusion system in exange with aspiration of donor plasma, injection of the erythrocytes or plasma into the dog; (7) substitution of calcium as required This cycle was repeated until as much as 1.16 of total other complications were observed. Clinical signs related plasma volume was replaced. The amount of exchanged to hypocalcaemia such as cardiac arrhythmias or tetanic plasma volume in our case was comparable to exchanged muscle contractions were not observed. plasma volume in another study [13], which used 1.0 Over the following two days, the clinical signs were times total plasma volume. This number was extrapoli - slowly improving, and the dog gradually required less ated from human medicine, where usually in a single TPE mechanical support compared to previous days. On day 3 procedure 1–1.5 of total plasma volume is replaced [14]. after TPE, the dog was completely weaned off the ventila - Exchange of larger volumes is not reported to be more tor and was able to breath independently without signs efficient and the risk of side-effects is increased [ 15]. of dyspnoea or hypoventilation. An increase of alertness The total plasma volume was assumed according to and responsiveness to its environment was also noticed the following formula: 0.09 x BW [4.7] x (1-haematocrit and the dog´s appetite improved. The tracheal tube was [0.4]) and calculated to 250 mL. The exchanged plasma removed on day 3 post TPE. On day 5, the dog returned volume was 290 mL and the procedure of the exchange to the neurological department and showed a mild neu- took approximately 3 h. Because of the risk of an immu- rological improvement. The dog was able to hold its nologic reaction and haemodynamic complications, the head when placed in sternal recumbency while eating dog was connected to a medical monitor (Carescape and showed voluntary movement of the limbs. The dog B650, GE HealthCare, Chicago, IL, USA) and the vital was discharged the following day with recommended functions (ECG, respiratory rate and pattern, body tem- intensive and regular physiotherapy as well as post-tra- perature, NIBP, SpO ) were continuously monitored dur- cheostomy wound care (bandage change). No pharmaco- ing the whole procedure. Due to the administration of a logical therapy was needed other than pimobendane for large volume of donor plasma containing calcium citrate the MMVD Stage B2. to prevent blood-clotting, there was a risk of develop- One week following discharge, the dog returned to ing a clinically relevant hypocalcaemia. Hence, blood the hospital for a follow-up examination. The own - gas analyses were repeatedly performed (after exchange ers reported that the dog had been doing well at home of half of the calculated plasma volume, immediately and tried to crawl. Apart from generalized, advanced after the procedure and 10  h thereafter). Calcium defi - muscle atrophy and persistent heart murmur at the ciency was substituted with calcium gluconate(calcium level of the mitral valve, the general physical examina- gluconate B. Braun 10%) as required (Additional file 1). tion was unremarkable. During the neurological exami- Except gradual decrease of ionized calcium (1.16 mmol/L nation the dog was able to lift its head and to keep it in before TPE to 0.708 mmol/L) during the procedure, no an upward position without assistance. The dog showed Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 5 of 9 voluntary movement in all limbs but was not able to plasma from cells using membrane filtration or centrifu - ambulate. The muscle tone was improved but remained gation. While plasma is removed from the patient, cells mildly decreased. Postural reactions were decreased and are reinfused. TPE aims to remove the antibodies from the absence of the patellar, tibialis cranialis and extensor the blood stream and replace them by plasma products carpi radialis reflexes remained. The withdrawal reflex (plasma exchange) or a combination of crystalloids, fresh was reduced in the pelvic limbs and absent in the tho- frozen plasma and colloids (synthetic or albumin). IVIg racic limbs. The dog maintained the ability to move its was shown to be equally effective [ 18–21] and now both tail and to urinate and defecate. techniques are commonly used as first-line treatment for The dog returned to the emergency service 5 days after GBS. However, there are reports suggesting that patients the first clinical check-up with severe inspiratory and with severe GBS may benefit from TPE after immu - expiratory dyspnoea and cyanosis. Radiographs of the noglobulin treatment in refractory cases [16, 17]. TPE neck and chest revealed an advanced soft tissue tracheal should be considered in GBS cases with early axonal stenosis in the area where the tracheostomy was initially involvement and in the recurrent or familial GBS forms. performed (Fig.  3). The prognosis was guarded, the only Humans treated with TPE or IVIg had significantly faster possible treatment was insertion of the tracheal stent. motor function recovery and required less frequent ven- Due to the high cost of further treatment, the own- tilatory support compared to untreated patients [7, 16]. ers decided to have the dog euthanized and the owners It is worth mentioning that in GBS, anti-ganglioside declined further necropsy . Abs are considered important inflammatory mediators. Serum anti-ganglioside Abs were previously reported in Discussion and conclusions ACP in dogs suggesting that the disorder is the canine Acute canine polyradiculoneuritis is an acquired periph- equivalent to GBS in humans and may share a similar eral neuropathy primarily involving the ventral nerve pathophysiology [2]. However, this measurement is not roots characterized by the rapid development of a non- commercially available, yet. ambulatory, lower motor neuron tetraparesis/tetraplegia The diagnosis of ACP in dogs is based particularly on [4]. GBS is considered the human counterpart of ACP. history provided by the owners and characteristic clini- Its exact pathogenesis remains unknown. Potential trig- cal signs. Additionally, routine blood tests including thy- gers, which activate the immune system, are thought roid hormones (TSH, T4), the antibody levels against N. to include exposure to bacteria such as Campylobacter caninum and T. gondii as well as thoracic radiographs jejuni, Mycoplasma pneumonia, and Haemophilus influ - and abdominal ultrasound should be performed to rule enzae and viruses such as cytomegalovirus and Epstein- out metabolic and infectious as well as para-neoplastic Barr virus, acting as a kind of molecular mimicry [7]. causes, respectively [4]. An electrophysiological exami- Autoimmune factors such as antibodies are thought to nation should be carried out in dogs suspected of ACP cause the disease. Therefore, TPE may be used to treat as some findings are reliable indicators of the disease. GBS in humans. TPE was first reported in the treatment EMG typically reveals denervation potentials such as of GBS between 1978 and 1981 and it was the first GBS fibrillations and positive sharp waves in the affected treatment proven to be superior to supportive treat- muscles, however electromyographic abnormalities ment alone [16, 17]. The technique works by separating may not be detectable for five to seven days following Fig. 3 Radiographic features of the trachea (A: neck) and (B: chest) in laterolateral view, showing its advanced stenosis at the height of the entrance in the chest Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 6 of 9 denervation [1]. MNC velocity values remain normal or medical treatment with anticholinesterase and immu- mildly decreased. The minimum F-wave latencies are nosuppressive drugs [6]. In the presented case, the dog prolonged, and the F-ratios are increased. The RNS with developed clinical complications resulting from paraly- a loss of amplitude within 10% is considered physiologi- sis of the respiratory muscles. We decided to treat the cal, pointing to no disturbance in neuromuscular trans- dog with TPE which, as mentioned above, is reported to mission. Such findings indicate a motor axonopathy and, be superior to IVIg in humans with severe or recurrent with concurrent prolonged F-wave latencies as well as forms of GBS. F-ratios, indicate more severe involvement of the proxi- There are three possible systems or principles which mal portions of motor nerves, ventral roots, or both [4, can be used for the TPE procedure. According to litera- 22]. The results of the electrodiagnostic examination of ture, membrane based TPE using commercial extracor- the presented dog corresponded to the described results poreal sets consisting of a membrane filter that separates suggesting a simultaneous impairment of ventral roots. the plasma and blood cells while adding donor plasma Neuromuscular junctions were intact excluding a myas- before retransfusing the blood, is the most used system thenic syndrome or botulism. The histopathological [24]. Alternatively, centrifugation-based systems with results of a nerve biopsy can also support the diagnosis single-use sets are available, separating the blood cells [1]. They may contain perivascular and interstitial lym - from the plasma via centrifugation and adding donor phocytic infiltrations, demyelination, and axonal necrosis plasma before retransfusion. There have been reports of of motor nerves, but are usually nonspecific because the manual TPE procedures [26]. As previously mentioned, primary non-suppurative inflammation is most prevalent we used a modified commercial autotransfusion set com - in the ventral roots and spares the more peripheral parts mon in orthopaedic procedures, via the existing periph- of the nerves [2, 23]. Therefore, biopsies were not taken eral central venous catheter. in the described case. The dog in this report showed daily improvement of It is worth mentioning that in GBS, anti-ganglioside the clinical status after treatment with TPE. After the first Abs are considered important inflammatory mediators. day, the dog showed a more stable breathing pattern and Serum anti-ganglioside Abs were previously reported in was able to breath independently on the third day. There ACP in dogs suggesting that the disorder is the canine was an improvement of the dog´s general condition, equivalent to GBS in humans and may share a similar activity, and appetite. On the fifth day, the dog returned pathophysiology [2]. However, this measurement is not to the neurological department from the intensive care commercially available, yet. unit with a mild improvement of the neurological status In veterinary medicine, there is no specific treatment showing voluntary movements of the pelvic limbs with- for ACP. The reported treatment of ACP is limited to out ambulation and ability to breath unassisted. On the physical rehabilitation, supportive care, and proper first control, 11 days after treatment with TPE, the neu - nutrition. Despite it being an immune-mediated disor- rological condition of the dog, including muscle tone as der, treatment with corticosteroids does not improve the well as spinal reflexes, improved, and the owner reported condition of the dogs [1, 5]. Similarly, steroids are not daily improvement of his status after the discharge. This effective for the treatment of GBS and prolonged corti - indicated that the dog tolerated the TPE well, and there costeroid therapy may slow recovery [7]. Dogs receiv- were no complications following the therapy. ing supportive treatment recover within 4–8 weeks [5]. In humans, approximately one third of patients with However, prolonged recovery of up to 3 months or lack GBS develop respiratory compromise requiring ICU of improvement are also reported [1, 4, 5]. Although admission. About half of them need to be intubated and TPE has been used for immune-mediated diseases (such mechanically ventilated (MV). The median duration of as immune-mediated haemolytic anaemia = AIHA and MV in humans is 21–27 days, although a subset of them thrombocytopenia = ITP) other than myasthenia gravis requires prolonged ventilation over several weeks till [6, 24, 25], there is no information of its use as a treat- months [27–29]. There is only limited information about ment for dogs with ACP. In dogs with ACP, one study the median time of MV required in neurological disease reports a clear trend towards faster recovery in dogs in veterinary literature. However, one study focused on treated with IVIg (a median of 27.5 days, range 15–127 the outcome of peripheral neurological diseases that days) in comparison to the control group (a median 75.5 required MV where median time of ventilation was 109 h days, range 5–220 days). These results indicate a possible and 4 dogs with ACP were included requiring 55 to 253 h beneficial use of IVIg treatment in dogs with ACP [ 5]. In of MV [30]. The clinical condition of the dog started to another study with immune-mediated myasthenia gravis, improve after the first day of TPE which resulted in an three dogs were treated with TPE [6]. TPE was well toler- early discontinuation (after 3 days) of MV. We speculate ated in those dogs and was regarded as a safe adjunctive that manual TPE therapy might have contributed to the therapy in patients that did not respond to conventional Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 7 of 9 rapid clinical improvement and resulted in an earlier dis- Unfortunately there is no commercial test available continuation of MV. to measure serum anti-ganglioside Abs concentration The death of the dog was not related to the primary in dogs with ACP thus a comparison between Abs titer disease and the treatment with TPE. The dog showed before and after treatment was not possible. We can only progressive neurological improvement and no signs of state, that manual TPE procedure performed in this case respiratory disease. Development of respiratory distress report was safe for the patient. Another limitation was was a complication to tracheostomy, which was diag- the single treatment with TPE. Consecutive treatments nosed more than 2 weeks after completed treatment with should be performed at 24–48  h intervals for greater TPE. Tracheostomy is a commonly performed intensive reduction of antibody load. Two or three TPE procedures care unit procedure. Traditionally, its use was restricted are routinely used in dogs with other immune-mediated to the emergency management of upper airway obstruc- diseases like IMHA, ITP and myasthenia gravis [6, 24, tion but has recently been also indicated in prolonged 25]. Using a single procedure might remove intravascu- mechanical ventilation [29]. The advantages of trache - lar antibodies but without influence on the extravascu - ostomy include the animal’s comfort, safety, no need lar distribution. Furthermore, a rebound from ongoing to keep the animal under general anaesthesia as well as antibody production and redistribution from the extra- better oral and airway care. Moreover, animals with tra- vascular to intravascular space might occur after a single cheostomy may have shorter intensive care unit stays treatment with TPE instead of using multiple procedures. and shorter periods of mechanical ventilation and hos- In this dog, the single TPE procedure was performed, pital stays as this procedure facilitates care outside the because he started to improve after 24 h of the treatment. ICU [29]. In our case, the dog developed life-threatening The improvement was seen every day that allowed him respiratory paralysis due to ACP, which required MV. We to be weaned off the mechanical ventilator on day 3 and decided to perform tracheostomy because of the indica- return to neurological department on day 5. Another rea- tions described above and to enable the regular evalua- son for single TPE procedure was the financial limitation tion of the dog’s clinical and neurological condition with of the owners. minimal use of sedation. During the hospitalization, In summary, the use of TPE for the treatment of ACP there were no observed complications following trache- in the presented case was well tolerated. This is the first ostomy. During the first control, the wound was healing case report presenting manual TPE in a dog with pre- well, and the dog had no signs of respiratory compro- sumed acute canine polyradiculoneuritis. The goal of a mise. Five days after the first control, the dog returned single manual TPE to rapidly improve the neurological to the clinic during emergency hours because of acute, condition of the dog was achieved without significant severe inspiratory and expiratory dyspnoea and cyanosis. complication. Due to complications of the tracheostomy A soft tissue tracheal stenosis at the level of the previ- and euthanasia of the dog, the effectiveness of the treat - ous tracheostomy site was diagnosed on radiographs. In ment with respect to the recovery time could not be eval- humans, the most significant long-term complication of uated, but it can be assumed that the therapy contributed tracheostomy is tracheal stenosis, which affects 11-17.8% to faster wean off from MV. This case report confirms of patients. It is thought that increased pressure against that TPE is a safe method and should be considered as an the tracheal rings causes cartilage erosion and results in additional therapy in dogs with ACP especially with more activation of inflammatory processes, producing a gener - severe signs of life threating paralysis of the respiratory ous stoma [31, 32]. Complications in the form of narrow- muscles. A larger prospective study is warranted to assess ing of the tracheal lumen due to granulation tissue have the effectiveness of TPE in the treatment of ACP. been described in about 18–24% of canines [32]. Severe Abbreviations lesions require intraluminal stent placement or surgical AIHA immune-mediated haemolytic anaemia resection and end-to-end anastomosis [32]. Due to high ACP acute canine polyradiculoneuritis CMAP compound action potentials costs of such treatment, the owner opted for euthanasia. GBS Guillain–Barré Syndrome The presented case report has a few limitations. It is IVIg intravenous immunoglobulin a single case report and not a case control study which ITP immune-mediated thrombocytopenia purpura MMVD Myxomatous mitral valve degeneration affects the validity of our hypothesis. Nevertheless, we MNCV motor neve conduction velocity suspect, that manual TPE improved the neurological MV mechanically ventilated status of the dog, as it started to constantly improve the RNS repetitive nerve stimulation TPE therapeutic plasma exchange day after initiated treatment. However, it is unknown, whether manual TPE resulted in the dog’s clinical improvement or if similar clinical outcome would have Supplementary Information The online version contains supplementary material available at https://doi. been seen with ongoing supportive care only. org/10.1186/s13028-023-00675-0. Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 8 of 9 8. Cuddon PA. Electrodiagnosis in veterinary neurology: Supplementary Material 1 Electromyography,Nerve conduction studies and evoked potentials 9. Ipe TS, Davis AR, Raval JS. Therapeutic plasma exchange in myasthenia gravis: a systemic literature review and meta-analysis of comparative evidence. Front Acknowledgements Neurol. 2021;12:1–17. The support of the Faculty of Veterinary Medicine of the Justus-Liebig- 10. Hofbauer N, Windberger U, Schwendenwein I, Tichy A, Eberspächer E. Evalua- University Giessen, Germany is gratefully acknowledged. 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Pilot trial of immuno- Declarations globulin versus plasma exchange in patients with Guillain-Barré syndrome. Neurology. 1996;46:100–3. Competing interests 20. Randomized trial of. Plasma exchange, intravenous immunoglobulin, and The authors declare that they have no competing interests. combined treatments in Guillain-Barré syndrome. Plasma Exchange/Sando- globulin Guillain-Barré Syndrome Trial Group. The Lancet. 1997;349:225–30. Consent for publication 21. Diener H-C, Haupt WF, Kloss TM, Rosenow F, Philipp T, Koeppen S, et al. A A permission of the owner to include an image of the dog in the article was preliminary, randomized, multicenter study comparing intravenous immu- given. noglobulin, plasma exchange, and immune adsorption in Guillain-Barré syndrome. Eur Neurol. 2001;46:107–9. Ethics approval 22. Stanciu GD, Musteata M, Armasu M, Saftencu PM, Solcan G. Electrophysi- The dog was handled according to good veterinary practice and German ological aspects in idiopathic acute canine polyradiculoneuritis. Bull UASVM veterinary regulations. Veterinary Med. 2014;71:292–7. 23. Vandevelde M, Higgins JR, Oevermann A. Veterinary neuropathology. Essen- Prior publication tials of theory and practice. Wiley Blackwell; 2012. p. 78. Data have not been published previously. 24. Francey T, Etter M, Schweighauser A. Evaluation of membrane-based thera- peutic plasma exchange as adjunctive treatment for immune‐mediated Received: 9 August 2022 / Accepted: 15 March 2023 hematologic disorders in dogs. J Vet Intern Med. 2021;35:925–35. 25. Kopecny L, Palm CA, Naylor S, Kirny J, Cowgill LD. Application of therapeutic plasma exchange in dogs with immune-mediated thrombocytopenia. J Vet Intern Med. 2020;34:4. 26. Culler CA, Reinhardt A, Vigani A. Successful management of clinical signs associated with hepatic encephalopathy with manual therapeutic plasma exchange in a dog. J Vet Emerg Crit Care. 2020;30:312–7. References 27. Shang P, Zhu M, Baker M, Feng J, Zhou Ch, Hong-Liang Z. Mechanical ventila- 1. Dewey CW, Da Costa RC. Practical guide to canine and feline neurology. 3rd tion in Guillain- Barré syndrome. Expert Rev Clin Immunol. 2020;16:1053–64. ed. Oxford: Wiley BlackWell; 2016. pp. 463–5. 28. Berg B, Storm EF, Garssen MJP, Blomkwist-Markens PH, Jacobs BC. Clinical 2. De Lahunta A, Glass E, Kent M. Veterinary neuroanatomy and clinical neurol- outcome of Guillain- Barré syndrome after prolonged mechanical ventilation. ogy. 4th ed. St. Louis, MO: Elsevier; 2015. p. 271. J Neurol Neurosurg Psychiatry. 2018;89:949–54. 3. Rupp A, Galban-Horcajo F, Bianchi E, Dondi M, Penderis J, Cappell J. Anti-GM2 29. Kalita J, Ranjan A, Misra UK. Outcome of Guillain- Barré syndrome patients ganglioside antibodies are a biomarker for acute canine poliradiculoneuritis. with respiratory paralysis. QJM. 2016;109:319–23. J Peripher Nerv Syst. 2013;18:75–88. 30. Rutter ChR, Rozanski EA, Sharp CR, Powell LL, Kent M. Outcome and 4. Anor S. Acute lower motor neuron tetraparesis. Vet Clin North Am Small Anim medical management in dogs with lower motor neuron disease undergo- Pract. 2014;44:1201–22. ing mechanical ventilation: 14 cases (2003–2009). J Vet Emerg Crit Care. 5. Hirschvogel K, Jurina K, Steinberg TA, Matiasek LA, Matiasek K, Beltran E, et al. 2011;21:531–41. Clinical course of acute canine polyradiculoneuritis following treatment with 31. Regan K, Hunt K. Tracheostomy management. Continuing Educ Anaesth Crit human IV immunoglobulin. J Am Animal Hosp Assoc. 2012;48:299–309. Care Pain. 2008;8:31–5. 6. Vitalo A, Buckley G, Londono L. Therapeutic plasma exchange as adjunct 32. Johnson SA, Tobias KM. Veterinary surgery small animal. 2nd ed. Elsevier; therapy in 3 dogs with myasthenia gravis and myasthenia-like syndrome. J 2018. 4574 – 5.25. Vet Emerg Crit Care. 2021;31:106–11. 7. Hughes RAC, Cornblath DR. Guillain- Barré syndrome. Lancet. 2005;366:1653–66. Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 9 of 9 Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Acta Veterinaria Scandinavica Springer Journals

Manual therapeutic plasma exchange for treatment of a dog with suspected acute canine polyradiculoneuritis

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Abstract

Background Acute canine polyradiculoneuritis is one of the most common polyneuropathies occurring in dogs. The disease is very similar to the Guillain–Barré syndrome in humans. In veterinary medicine, there is no established treatment for this disease, while in human medicine, therapeutic plasma exchange and intravenous immunoglobulin administration are two main immunotherapy treatments of this syndrome. Case presentation A 12-year-old male Jack Russel Terrier was presented with a history of acute weakness of the pelvic limbs progressing to flaccid tetraplegia with respiratory compromise. Complete diagnostic workup was performed including blood work, diagnostic imaging (radiographs of the thorax as well as ultrasound of the abdomen) and echocardiography. Based on the clinical course, neurological localisation and the results of electrodiagnostic examination acute canine polyradiculoneuritis was suspected. During the hospitalization, the dog deteriorated and was admitted to the intensive care unit for respiratory support via tracheostomy tube. In addition to symptomatic treatment, immunotherapy via single treatment of manual therapeutic plasma exchange was administered. This procedure was safe, and the dog showed improvement of clinical signs 3 days after therapy was initiated, as well as improvement of neurological signs (from grade 4 tetraplegia to grade 3) within 5 days. However, the dog was euthanized 3 weeks later due to complications related to the tracheostomy. Conclusions This is the first case report of a manual therapeutic plasma exchange in a dog with suspected acute canine polyradiculoneuritis suggesting that this method is safe and well tolerated in dogs with this disease. It may be a reasonable adjunctive treatment to supportive therapy in severe cases. Keywords Canine, Guillain-Barré syndrome, Neuromuscular disease, Therapeutic plasma exchange *Correspondence: Adriana Czerwik adriana.czerwik@vetmed.uni-giessen.de Department of Veterinary Clinical Sciences, Neuroradiology and Clinical Neurology, Small Animal Clinic, Justus-Liebig-University, Frankfurter Str.114, 35392 Neurosurgery, Giessen, Germany Department of Veterinary Clinical Sciences, Internal Medicine, Small Animal Clinic, Justus- Liebig-University, Frankfurter Str.114, 35392 Giessen, Germany Department of Emergency and Critical Care Service, Vetklinikum LS, Laxenburger Str. 252a, 1230, Vienna, Austria © The Author(s) 2023. 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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 2 of 9 Background withdrawal reflex, the dog showed hyperesthesia. Neck Acute canine polyradiculoneuritis (ACP) is one of the movements were weak, and the dog could not lift his most common polyneuropathies occurring in dogs head. The perineal reflex and cranial nerves were intact. [1]. The disease is very similar to Guillain–Barré Syn - The patient maintained the ability to move its tail and to drome (GBS) in humans, caused by the immune-system urinate and defecate. Moderate, generalized muscle atro- inflicted damage of the peripheral nervous system. In phy was visible. The clinical signs were localized to the veterinary literature, the disorder is also known as coon- peripheral nervous system involving the motor nerve hound paralysis or idiopathic polyradiculoneuritis [1, 2]. roots. Although the pathogenesis of ACP is uncertain, an auto- The neurological examination was followed by labo - immune process affecting both axons and myelin of the ratory analysis including complete blood count, serum ventral nerve roots is suspected. The proposed patho - biochemical profile (glucose, total protein, albumin, urea genesis includes molecular mimicry or the production nitrogen, creatinine, total bilirubin, alanine and aspartate of autoantibodies against axolemmal components such transferase, alkaline phosphatase, creatine kinase, lipase, + − + + + a anti-ganglioside antibodies (Abs)[1, 3]. The first clini - cholesterol, Na , PO , iCa , K , iMg and c-reactive-pro- cal signs in affected dogs usually develop in the pelvic tein), thyroid hormones (TSH, T4) and antibody levels limbs and eventually progress to the thoracic limbs, caus- against Neospora caninum and Toxoplasma gondii. The ing generalized lower motor neuron paresis/plegia. Most dog underwent radiographic examination of the thorax affected patients develop non-ambulatory tetraparesis/ as well as ultrasound examination of the abdomen and tetraplegia within 10 days of the onset of clinical signs echocardiography. [4]. The prognosis for full recovery is usually favourable, The CBC, serum chemical and electrolyte analyses if adequate supportive treatment is applied, except in were within reference ranges, except for a decreased cases with life-threatening respiratory impairment [5], T4 level (0.7  µg/dl with the reference 1.5-4  µg/dl) with where full recovery is prolonged, taking several weeks to a normal TSH level (0.09ng/ml with the reference up to several months or it may even lead to death. There is no 0,30bg/ml), which was attributed to the euthyroid sick known disease-specific therapy described in veterinary syndrome. The antibody results for N. caninum and T. medicine. Hence, treatment options for ACP are war- gondii were negative with IgG titer 1:80, IgM titer < 1:40 ranted. A recent study showed that dogs suffering from (reference < 1:40) and IgG titer < 1:64, IgM titer < 1:16 ACP treated with intravenous immunoglobulin (IVIg) [5] (reference < 1:64) respectively. The results of the radio - recovered faster compared with dogs without immuno- logical examinations (radiographs as well as ultrasound) therapy. Dogs suffering from myasthenia gravis, another showed no clinically relevant abnormalities. The cardio - neuromuscular, autoimmune disease treated with thera- logical examination revealed a mitral valve insufficiency peutic plasma exchange (TPE), recovered faster com- with a moderate enlargement of the left atrium, indicat- pared with dogs without immunotherapy [6]. In human ing a stage B2 myxomatous mitral valve degeneration medicine, plasma exchange as well as IVIg have become (MMVD). All results from imaging diagnostics including the gold standard treatment for GBS [7]. echocardiography were reviewed by board certified radi - This case report describes the clinical and neurologi - ologist and cardiologist. cal presentation, electrodiagnostic findings and manual The dog was admitted to the hospital for supportive therapeutic plasma exchange treatment in a small breed care and began to show signs of mild dyspnoea, loss of dog with suspected ACP. appetite and apathy on the second day of hospitaliza- tion. At this stage, respiratory movements were shallow Case presentation and primarily abdominal. On the following day, the dog A 12-year-old male Jack Russel terrier was referred to the was hypoventilating and was assigned to the intensive Department of Veterinary Clinical Sciences in the Small care unit for ventilatory support (mechanical ventilation) Animal Clinic of the Justus-Liebig-University Giessen, (Fig. 1). Ventilatory support was achieved using pressure- Germany with a history of symmetrical weakness which controlled ventilation allowing the patient to trigger began in the hindlimbs, evolved to the forelimbs, and each respiratory cycle with use of the respirator software progressed to a non-ambulatory flaccid tetraplegia within (Servo-S, Maquet Getinge Group, Rastatt, Germany). A 4 days. The medical history revealed no information tracheostomy tube was placed to improve care and regu- about possible trauma, concomitant illnesses, or expo- late the dog’s condition with minimal sedation. The dog’s sure to neurotoxins. Apart from a left apical systolic heart condition did not change during the first three days of murmur grade 5, there were no abnormalities present intensive care. on the physical examination. The neurological examina - Seven days after clinical onset, electrophysiological tion revealed lack of postural reactions and absent spi- tests were performed under general anaesthesia with the nal reflexes (flaccid tetraplegia). On examination of the dog in lateral recumbency, using a Nicolet VikingQuest Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 3 of 9 Fig. 1 The dog during a stay in the intensive care unit System (Electrodiagnostic Software, USA). The elec - After three day of ventilatory support, single manual tromyographic examination (EMG) revealed moder- TPE was performed. A commercial autotransfusion set ate insertional activity and fibrillation potentials in the used for orthopedic procedures and described elsewhere quadriceps, cranial tibial and plantar interosseus mus- [9] was applied to the existing peripheral central venous cles. Motor nerve conduction velocity (MNCV) of the catheter (3  F 200  mm Careflow One Lumen catheter, tibial nerve was measured following proximal (trochan- Merit medical Ireland Ldt, Galway, Ireland) in the left ter), middle (caudal stifle) and distal (hock) stimulation cephalic vein. A second peripheral central venous cath- using monopolar needle electrodes. Compound action eter was placed into the right saphenous vein. Although potentials (CMAPs) were recorded from the plantar use of some commercially available TPE systems is interosseus muscle. The distal latency and amplitude of described in small sized dogs with corresponding blood the CAMPs were measured. MNCV was calculated from priming related to the large extracorporal needed [10– the trochanter to the stifle and the stifle to the hock seg - 12], those systems were not available in the presented ment of the tibial nerve and revealed a moderate reduc- case. A therapeutic plasma exchange system was built tion in the MNCV of the tibial nerve (proximal 26  m/ between the two catheters consisting of a set of infu- sec, distal 63 m/sec, with the reference 60–70 m/sec and sion lines, a modified autotransfusion system (Orthopat, 70–80 m/sec respectively) [8]. The tibial residual latency Haemonetics inc, Boston, MA, USA) and a bag of donor was normal (1.72 m/sec, with the reference 1.6-2 m/sec) plasma. Fifty ml of blood was manually drawn and antico- [8]. F-waves were measured using the same electrode agulated with sodium citrate (sodium citrate 3.13%, Eifel- configuration and were recorded at the plantar interossei fango) taken from the peripheral central venous catheter muscles. An increased F-wave latency of 16.4 m/sec was and transferred to the reservoir of the system (Fig. 2). The detected (minimal expected F-wave latency was 13  m/ blood was aspirated and centrifuged, the plasma sepa- sec). The calculated F-ratio was higher than the reference rated, and the blood additionally washed with 0.9% saline values for the stifle (1.67 vs. 0.8), which indicated more (isotonic sodium chloride ad us vet., B. Braun Vet Care) severe involvement of the proximal part of the nerve. according to the manufacturer’s instructions. Following Neuromuscular transmission was assessed using repeti- the centrifugation process, the blood was automatically tive nerve stimulation (RNS) at the hock at 2 and 3  Hz transferred as an erythrocyte concentrate into a sterile recorded at the plantar interosseous muscles, to exclude 50 mL syringe. Subsequently, these washed cells were a neuromuscular junction disease. RNS was normal with administered to the dog through the other catheter with no decrement. a corresponding amount of a donor plasma. Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 4 of 9 Fig. 2 Scheme of the approach to the plasma exchange (1) Aspiration of dog’s blood into a syringe and injection of this blood into the autotransfusion system; (2) Anticoagulation of the aspirated blood with sodium citrate; (3) separation of dog’s blood into plasma and red blood cells in the autotransfusion system; (4) collecting bag for dog’s plasma; (5) donor plasma; (6) aspiration of the erythrocyte concentrate from the autotransfusion system in exange with aspiration of donor plasma, injection of the erythrocytes or plasma into the dog; (7) substitution of calcium as required This cycle was repeated until as much as 1.16 of total other complications were observed. Clinical signs related plasma volume was replaced. The amount of exchanged to hypocalcaemia such as cardiac arrhythmias or tetanic plasma volume in our case was comparable to exchanged muscle contractions were not observed. plasma volume in another study [13], which used 1.0 Over the following two days, the clinical signs were times total plasma volume. This number was extrapoli - slowly improving, and the dog gradually required less ated from human medicine, where usually in a single TPE mechanical support compared to previous days. On day 3 procedure 1–1.5 of total plasma volume is replaced [14]. after TPE, the dog was completely weaned off the ventila - Exchange of larger volumes is not reported to be more tor and was able to breath independently without signs efficient and the risk of side-effects is increased [ 15]. of dyspnoea or hypoventilation. An increase of alertness The total plasma volume was assumed according to and responsiveness to its environment was also noticed the following formula: 0.09 x BW [4.7] x (1-haematocrit and the dog´s appetite improved. The tracheal tube was [0.4]) and calculated to 250 mL. The exchanged plasma removed on day 3 post TPE. On day 5, the dog returned volume was 290 mL and the procedure of the exchange to the neurological department and showed a mild neu- took approximately 3 h. Because of the risk of an immu- rological improvement. The dog was able to hold its nologic reaction and haemodynamic complications, the head when placed in sternal recumbency while eating dog was connected to a medical monitor (Carescape and showed voluntary movement of the limbs. The dog B650, GE HealthCare, Chicago, IL, USA) and the vital was discharged the following day with recommended functions (ECG, respiratory rate and pattern, body tem- intensive and regular physiotherapy as well as post-tra- perature, NIBP, SpO ) were continuously monitored dur- cheostomy wound care (bandage change). No pharmaco- ing the whole procedure. Due to the administration of a logical therapy was needed other than pimobendane for large volume of donor plasma containing calcium citrate the MMVD Stage B2. to prevent blood-clotting, there was a risk of develop- One week following discharge, the dog returned to ing a clinically relevant hypocalcaemia. Hence, blood the hospital for a follow-up examination. The own - gas analyses were repeatedly performed (after exchange ers reported that the dog had been doing well at home of half of the calculated plasma volume, immediately and tried to crawl. Apart from generalized, advanced after the procedure and 10  h thereafter). Calcium defi - muscle atrophy and persistent heart murmur at the ciency was substituted with calcium gluconate(calcium level of the mitral valve, the general physical examina- gluconate B. Braun 10%) as required (Additional file 1). tion was unremarkable. During the neurological exami- Except gradual decrease of ionized calcium (1.16 mmol/L nation the dog was able to lift its head and to keep it in before TPE to 0.708 mmol/L) during the procedure, no an upward position without assistance. The dog showed Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 5 of 9 voluntary movement in all limbs but was not able to plasma from cells using membrane filtration or centrifu - ambulate. The muscle tone was improved but remained gation. While plasma is removed from the patient, cells mildly decreased. Postural reactions were decreased and are reinfused. TPE aims to remove the antibodies from the absence of the patellar, tibialis cranialis and extensor the blood stream and replace them by plasma products carpi radialis reflexes remained. The withdrawal reflex (plasma exchange) or a combination of crystalloids, fresh was reduced in the pelvic limbs and absent in the tho- frozen plasma and colloids (synthetic or albumin). IVIg racic limbs. The dog maintained the ability to move its was shown to be equally effective [ 18–21] and now both tail and to urinate and defecate. techniques are commonly used as first-line treatment for The dog returned to the emergency service 5 days after GBS. However, there are reports suggesting that patients the first clinical check-up with severe inspiratory and with severe GBS may benefit from TPE after immu - expiratory dyspnoea and cyanosis. Radiographs of the noglobulin treatment in refractory cases [16, 17]. TPE neck and chest revealed an advanced soft tissue tracheal should be considered in GBS cases with early axonal stenosis in the area where the tracheostomy was initially involvement and in the recurrent or familial GBS forms. performed (Fig.  3). The prognosis was guarded, the only Humans treated with TPE or IVIg had significantly faster possible treatment was insertion of the tracheal stent. motor function recovery and required less frequent ven- Due to the high cost of further treatment, the own- tilatory support compared to untreated patients [7, 16]. ers decided to have the dog euthanized and the owners It is worth mentioning that in GBS, anti-ganglioside declined further necropsy . Abs are considered important inflammatory mediators. Serum anti-ganglioside Abs were previously reported in Discussion and conclusions ACP in dogs suggesting that the disorder is the canine Acute canine polyradiculoneuritis is an acquired periph- equivalent to GBS in humans and may share a similar eral neuropathy primarily involving the ventral nerve pathophysiology [2]. However, this measurement is not roots characterized by the rapid development of a non- commercially available, yet. ambulatory, lower motor neuron tetraparesis/tetraplegia The diagnosis of ACP in dogs is based particularly on [4]. GBS is considered the human counterpart of ACP. history provided by the owners and characteristic clini- Its exact pathogenesis remains unknown. Potential trig- cal signs. Additionally, routine blood tests including thy- gers, which activate the immune system, are thought roid hormones (TSH, T4), the antibody levels against N. to include exposure to bacteria such as Campylobacter caninum and T. gondii as well as thoracic radiographs jejuni, Mycoplasma pneumonia, and Haemophilus influ - and abdominal ultrasound should be performed to rule enzae and viruses such as cytomegalovirus and Epstein- out metabolic and infectious as well as para-neoplastic Barr virus, acting as a kind of molecular mimicry [7]. causes, respectively [4]. An electrophysiological exami- Autoimmune factors such as antibodies are thought to nation should be carried out in dogs suspected of ACP cause the disease. Therefore, TPE may be used to treat as some findings are reliable indicators of the disease. GBS in humans. TPE was first reported in the treatment EMG typically reveals denervation potentials such as of GBS between 1978 and 1981 and it was the first GBS fibrillations and positive sharp waves in the affected treatment proven to be superior to supportive treat- muscles, however electromyographic abnormalities ment alone [16, 17]. The technique works by separating may not be detectable for five to seven days following Fig. 3 Radiographic features of the trachea (A: neck) and (B: chest) in laterolateral view, showing its advanced stenosis at the height of the entrance in the chest Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 6 of 9 denervation [1]. MNC velocity values remain normal or medical treatment with anticholinesterase and immu- mildly decreased. The minimum F-wave latencies are nosuppressive drugs [6]. In the presented case, the dog prolonged, and the F-ratios are increased. The RNS with developed clinical complications resulting from paraly- a loss of amplitude within 10% is considered physiologi- sis of the respiratory muscles. We decided to treat the cal, pointing to no disturbance in neuromuscular trans- dog with TPE which, as mentioned above, is reported to mission. Such findings indicate a motor axonopathy and, be superior to IVIg in humans with severe or recurrent with concurrent prolonged F-wave latencies as well as forms of GBS. F-ratios, indicate more severe involvement of the proxi- There are three possible systems or principles which mal portions of motor nerves, ventral roots, or both [4, can be used for the TPE procedure. According to litera- 22]. The results of the electrodiagnostic examination of ture, membrane based TPE using commercial extracor- the presented dog corresponded to the described results poreal sets consisting of a membrane filter that separates suggesting a simultaneous impairment of ventral roots. the plasma and blood cells while adding donor plasma Neuromuscular junctions were intact excluding a myas- before retransfusing the blood, is the most used system thenic syndrome or botulism. The histopathological [24]. Alternatively, centrifugation-based systems with results of a nerve biopsy can also support the diagnosis single-use sets are available, separating the blood cells [1]. They may contain perivascular and interstitial lym - from the plasma via centrifugation and adding donor phocytic infiltrations, demyelination, and axonal necrosis plasma before retransfusion. There have been reports of of motor nerves, but are usually nonspecific because the manual TPE procedures [26]. As previously mentioned, primary non-suppurative inflammation is most prevalent we used a modified commercial autotransfusion set com - in the ventral roots and spares the more peripheral parts mon in orthopaedic procedures, via the existing periph- of the nerves [2, 23]. Therefore, biopsies were not taken eral central venous catheter. in the described case. The dog in this report showed daily improvement of It is worth mentioning that in GBS, anti-ganglioside the clinical status after treatment with TPE. After the first Abs are considered important inflammatory mediators. day, the dog showed a more stable breathing pattern and Serum anti-ganglioside Abs were previously reported in was able to breath independently on the third day. There ACP in dogs suggesting that the disorder is the canine was an improvement of the dog´s general condition, equivalent to GBS in humans and may share a similar activity, and appetite. On the fifth day, the dog returned pathophysiology [2]. However, this measurement is not to the neurological department from the intensive care commercially available, yet. unit with a mild improvement of the neurological status In veterinary medicine, there is no specific treatment showing voluntary movements of the pelvic limbs with- for ACP. The reported treatment of ACP is limited to out ambulation and ability to breath unassisted. On the physical rehabilitation, supportive care, and proper first control, 11 days after treatment with TPE, the neu - nutrition. Despite it being an immune-mediated disor- rological condition of the dog, including muscle tone as der, treatment with corticosteroids does not improve the well as spinal reflexes, improved, and the owner reported condition of the dogs [1, 5]. Similarly, steroids are not daily improvement of his status after the discharge. This effective for the treatment of GBS and prolonged corti - indicated that the dog tolerated the TPE well, and there costeroid therapy may slow recovery [7]. Dogs receiv- were no complications following the therapy. ing supportive treatment recover within 4–8 weeks [5]. In humans, approximately one third of patients with However, prolonged recovery of up to 3 months or lack GBS develop respiratory compromise requiring ICU of improvement are also reported [1, 4, 5]. Although admission. About half of them need to be intubated and TPE has been used for immune-mediated diseases (such mechanically ventilated (MV). The median duration of as immune-mediated haemolytic anaemia = AIHA and MV in humans is 21–27 days, although a subset of them thrombocytopenia = ITP) other than myasthenia gravis requires prolonged ventilation over several weeks till [6, 24, 25], there is no information of its use as a treat- months [27–29]. There is only limited information about ment for dogs with ACP. In dogs with ACP, one study the median time of MV required in neurological disease reports a clear trend towards faster recovery in dogs in veterinary literature. However, one study focused on treated with IVIg (a median of 27.5 days, range 15–127 the outcome of peripheral neurological diseases that days) in comparison to the control group (a median 75.5 required MV where median time of ventilation was 109 h days, range 5–220 days). These results indicate a possible and 4 dogs with ACP were included requiring 55 to 253 h beneficial use of IVIg treatment in dogs with ACP [ 5]. In of MV [30]. The clinical condition of the dog started to another study with immune-mediated myasthenia gravis, improve after the first day of TPE which resulted in an three dogs were treated with TPE [6]. TPE was well toler- early discontinuation (after 3 days) of MV. We speculate ated in those dogs and was regarded as a safe adjunctive that manual TPE therapy might have contributed to the therapy in patients that did not respond to conventional Czerwik et al. Acta Veterinaria Scandinavica (2023) 65:14 Page 7 of 9 rapid clinical improvement and resulted in an earlier dis- Unfortunately there is no commercial test available continuation of MV. to measure serum anti-ganglioside Abs concentration The death of the dog was not related to the primary in dogs with ACP thus a comparison between Abs titer disease and the treatment with TPE. The dog showed before and after treatment was not possible. We can only progressive neurological improvement and no signs of state, that manual TPE procedure performed in this case respiratory disease. Development of respiratory distress report was safe for the patient. Another limitation was was a complication to tracheostomy, which was diag- the single treatment with TPE. Consecutive treatments nosed more than 2 weeks after completed treatment with should be performed at 24–48  h intervals for greater TPE. Tracheostomy is a commonly performed intensive reduction of antibody load. Two or three TPE procedures care unit procedure. Traditionally, its use was restricted are routinely used in dogs with other immune-mediated to the emergency management of upper airway obstruc- diseases like IMHA, ITP and myasthenia gravis [6, 24, tion but has recently been also indicated in prolonged 25]. Using a single procedure might remove intravascu- mechanical ventilation [29]. The advantages of trache - lar antibodies but without influence on the extravascu - ostomy include the animal’s comfort, safety, no need lar distribution. Furthermore, a rebound from ongoing to keep the animal under general anaesthesia as well as antibody production and redistribution from the extra- better oral and airway care. Moreover, animals with tra- vascular to intravascular space might occur after a single cheostomy may have shorter intensive care unit stays treatment with TPE instead of using multiple procedures. and shorter periods of mechanical ventilation and hos- In this dog, the single TPE procedure was performed, pital stays as this procedure facilitates care outside the because he started to improve after 24 h of the treatment. ICU [29]. In our case, the dog developed life-threatening The improvement was seen every day that allowed him respiratory paralysis due to ACP, which required MV. We to be weaned off the mechanical ventilator on day 3 and decided to perform tracheostomy because of the indica- return to neurological department on day 5. Another rea- tions described above and to enable the regular evalua- son for single TPE procedure was the financial limitation tion of the dog’s clinical and neurological condition with of the owners. minimal use of sedation. During the hospitalization, In summary, the use of TPE for the treatment of ACP there were no observed complications following trache- in the presented case was well tolerated. This is the first ostomy. During the first control, the wound was healing case report presenting manual TPE in a dog with pre- well, and the dog had no signs of respiratory compro- sumed acute canine polyradiculoneuritis. The goal of a mise. Five days after the first control, the dog returned single manual TPE to rapidly improve the neurological to the clinic during emergency hours because of acute, condition of the dog was achieved without significant severe inspiratory and expiratory dyspnoea and cyanosis. complication. Due to complications of the tracheostomy A soft tissue tracheal stenosis at the level of the previ- and euthanasia of the dog, the effectiveness of the treat - ous tracheostomy site was diagnosed on radiographs. In ment with respect to the recovery time could not be eval- humans, the most significant long-term complication of uated, but it can be assumed that the therapy contributed tracheostomy is tracheal stenosis, which affects 11-17.8% to faster wean off from MV. This case report confirms of patients. It is thought that increased pressure against that TPE is a safe method and should be considered as an the tracheal rings causes cartilage erosion and results in additional therapy in dogs with ACP especially with more activation of inflammatory processes, producing a gener - severe signs of life threating paralysis of the respiratory ous stoma [31, 32]. Complications in the form of narrow- muscles. A larger prospective study is warranted to assess ing of the tracheal lumen due to granulation tissue have the effectiveness of TPE in the treatment of ACP. been described in about 18–24% of canines [32]. Severe Abbreviations lesions require intraluminal stent placement or surgical AIHA immune-mediated haemolytic anaemia resection and end-to-end anastomosis [32]. Due to high ACP acute canine polyradiculoneuritis CMAP compound action potentials costs of such treatment, the owner opted for euthanasia. GBS Guillain–Barré Syndrome The presented case report has a few limitations. It is IVIg intravenous immunoglobulin a single case report and not a case control study which ITP immune-mediated thrombocytopenia purpura MMVD Myxomatous mitral valve degeneration affects the validity of our hypothesis. Nevertheless, we MNCV motor neve conduction velocity suspect, that manual TPE improved the neurological MV mechanically ventilated status of the dog, as it started to constantly improve the RNS repetitive nerve stimulation TPE therapeutic plasma exchange day after initiated treatment. 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Journal

Acta Veterinaria ScandinavicaSpringer Journals

Published: Mar 27, 2023

Keywords: Canine; Guillain-Barré syndrome; Neuromuscular disease; Therapeutic plasma exchange

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