The usefulness of neurolocalisation in the diagnosis and treatment of canine intervertebral disc herniation Neurolokalizacijos nustatymo nauda diagnozuojant ir gydant tarpslankstelinio disko išvaržą šunims

LITHUANIAN UNIVERSITY OF HEALTH SCIENCES VETERINARY ACADEMY

Faculty of Veterinary Medicine

Lisa Maria Ask Johansen

The usefulness of neurolocalisation in the diagnosis and

treatment of canine intervertebral disc herniation

Neurolokalizacijos nustatymo nauda diagnozuojant ir

gydant tarpslankstelinio disko išvaržą šunims

MASTER THESIS

of Integrated Studies of Veterinary Medicine

Supervisor: Assoc. Prof. Dr. Martinas Jankauskas

THE WORK WAS DONE IN THE DEPARTMENT OF SMALL ANIMAL CLINIC CONFIRMATION OF THE INDEPENDENCE OF DONE WORK

I confirm that the presented Master Thesis “The usefulness of neurolocalisation in the diagnosis and treatment of canine intervertebral disc herniation”.

1. has been done by me;

2. has not been used in any other Lithuanian or foreign university;

3. I have not used any other sources not indicated in the work and I present the complete list of the used literature.

Lisa Maria Ask Johansen

(date) (author’s name, surname) (signature)

CONFIRMATION ABOUT RESPONSIBILITY FOR CORRECTNESS OF THE ENGLISH LANGUAGE IN THE DONE WORK

I confirm the correctness of the English language in the done work. Lisa Maria Ask Johansen

(date) (editor’s name, surname) (signature)

CONCLUSION OF THE SUPERVISOR REGARDING DEFENCE OF THE MASTER THESIS

Martinas Jankauskas

(date) (supervisor’s name, surname) (signature)

THE MASTER THESIS HAVE BEEN APPROVED IN THE DEPARTMENT/CLINIC/INSTITUTE (date of approval) (name, surname of the head of

department/clinic/institute) (signature)

Reviewer of the Master Thesis

(name, surname) (signatures)

Evaluation of defence commission of the Master Thesis: (date) (name, surname of the secretary of the defence

TABLE OF CONTENTS

6. AIMS AND OBJECTIVES……….9

7. LITERATURE REVIEW………..…....10 – 15 7.1. The canine intervertebral disc………..…..……….10

7.2. Intervertebral disc herniation……….….……10 – 11 7.3. The canine spinal cord and its functional divisions………...….…11 – 12 7.4. Diagnostic imaging – CT and MRI ………....……....12

7.5. Treatment of canine intervertebral disc herniation……….…12 – 13 7.5.1. Conservative………...……..…12 – 13 7.5.2. Surgical………...……..………13 7.6. Neurolocalisation ………14 – 15 8. RESEARCH METHODOLOGY………...……..…..16 – 19 8.1. Neurological theory………...……..…..16 – 17 8.2. Collection of material………...…..………..18 8.3. Classification of data………...……..………..18

8.4. Calculations and data analysis………..…………...……..…..18 – 19 9. RESULTS………..………...……..…20 – 23 9.1. Occurrence of neurolocations and the sensitivity of neurolocalisation...20 – 21 9.2. Occurrence of non-neurolocalised patients and the specificity of neurolocalisation………...……..…21 – 22 9.3. The correlation between neurolocalisation, diagnostic method and treatment………...22 – 23 10. DISCUSSION OF RESULTS………...……..…………...24 – 25 11. CONCLUSIONS………...…...……..…26 12. ACKNOWLEDGEMENTS………....…………...….……27 13. LITERATURE LIST………...……..……...….…...28 – 30 14. ANNEXES………...…...……31

1.

SUMMARY

The usefulness of neurolocalisation in the diagnosis and treatment of canine intervertebral disc herniation

Lisa Maria Ask Johansen Master Thesis

This master’s thesis is performed as part of the department of Dr. L. Kriaučeliūno small animal clinic of Lithuanian University of Health Sciences in Kaunas. It aims to evaluate the usefulness of neurolocalisation and its effect on diagnostic method and treatment in canine patients with

intervertebral disc herniation.

The data was collected from the patient record of Fredrikstad Dyrehospital veterinary animal hospital in Norway between January and December 2020. The data was focused on patients with confirmed disc herniation by CT or MRI. The aim was achieved by evaluating the specificity and sensitivity of the neurolocalisation process, as well as calculating the dependence between

neurolocalisation and diagnostic method and treatment. The conclusion was made based on all the factors of the results of the study.

The results indicated a great specificity of neurolocalisation at 98.7%, however a notably low sensitivity at 40.7%. There was no indication of any significant correlation between the

neurolocalisation and the diagnostic method or treatment (p > 0.05).

2.

SANTRAUKA

Neurolokalizacijos nustatymo nauda diagnozuojant ir gydant tarpslankstelinio disko išvaržą šunims

Lisa Maria Ask Johansen Magistro baigiamasis darbas

Šis magistro darbas atliktas Lietuvos sveikatos mokslų, Veterinarijos akademijos, Dr. L. Kriaučeliūno smulkiųjų gyvūnų klinikos katedroje. Jo tikslas įvertinti neurolokalizacijos nustatymo naudą ir efektyvumą atliekant diagnostiką ir taikant gydymą šunims esant tarpslankstelinio disko išvaržai.

Duomenys buvo surinkti Fredrikstad Dyrehospital veterinarijos klinikoje Norvegijoje. Tyrimo laikotarpis nuo 2019 meų sausio mėnesio iki 2020 metų gruodžio mėnesio. Duomenys buvo atrinkti ir į tyrimą įtraukti, tik patvirtinus diagnozę kompiuterinės tomografijos ar magnetinio rezonanso tyrimo metodu. Buvo siekta įvertinti neurolokalizacijos tyrimo specifiškumą ir jautrumą taip pat patikrinti priklausomybę tarp neurolokalizacijos ir diganostikos metodų ir gydymo.

Rezultatai parodė didelį tyrimo specifiškumą - 98,7%, tačiau ypač mažą jautrumą - 40,7%. Reikšmingos koreliacijos tarp neurolokalizacijos ir diagnostikos bei gydymo nebuvo (p>0.05).

3. ABBREVIATIONS

CNS – Central Nervous System IVD – Intervertebral disc

IVDD – Intervertebral disc disease IVDH – Intervertebral disc herniation LMN – Lower Motor Neuron

4. TERMS

Functional division (of the spinal cord) – A group of caudally and cranially connected spinal segments which are classified together, which when compromised will produce similar clinical signs

Intervertebral space – The space between two adjacent vertebrae

Neurolocation – A functional division of the spinal cord which has been diagnosed on clinical examination by neurolocalisation

Neurolocalisation – The process of localising a neurological disorder to a specific area of the nervous system by clinical diagnosis

5. INTRODUCTION

Intervertebral disc herniation (IVDH), or slipped disc, is among the most frequently occurring spinal diseases in dogs. Although commonly associated with intervertebral disc degenerative disease, it is known as an acute acquired disorder and is usually seen following spinal trauma. Even minor impacts to the spine, such as jumping, can be a sufficient source of trauma. Intervertebral disc herniation causes clinical signs varying in degree and can present as severe neurological deficits and pain. It is considered to be a neurological disease of importance, the clinical effects arising from the mechanical pressure on the spinal cord.

In accordance with the widely acknowledged guidelines of common clinical neurology practice, these patients should receive thorough neurological examinations with the goal of an accurate diagnosis. In order to reach this diagnosis, neurolocalisation has been a part of common veterinary practice for many years and is often considered a gold standard for the clinical examination of neurological patients.

However, the diagnostic value of this categorization of patients in the relation to IVDH has been previously undocumented and unevaluated. Moreover, a major aspect of neurolocalisation of patients with spinal disorders is that not all patients will present with clinical signs sufficient to perform a proper neurolocalisation at all. These patients will commonly present with severe local pain of the neck and/or back.

6. AIMS AND OBJECTIVES

The aim of this study is to investigate the usefulness of neurolocalisation in canine patients with IVDH. The goal is to determine the value and significance of neurolocalisation in the diagnostic process, as well as to make an evaluation regarding the significance of neurolocalisation in the choice of treatment. The objectives are as listed, numbered according to their order of importance:

1. To determine the sensitivity of neurolocalisation in a group of 26 canine patients diagnosed with IVDH

2. To determine the specificity of neurolocalisation in a group of 26 canine patients diagnosed with IVDH

7. LITERATURE REVIEW

The general anatomy of the canine intervertebral disc has long been agreed upon. For the last 60 years approximately, articles and research work discussing the canine vertebrae and intervertebral discs have showed a general consensus regarding its structure and function. King et al., 1955, Bray et al., 1998, and later De Decker et al., 2010, Miller et al., 2013 and Dewey, 2016, all agree with Hansen in his distinguished article from 1952[1–6]. Existing between almost all vertebral bodies, the intervertebral disc (IVD) is an important part of the canine spinal anatomy. The canine intervertebral disc is divided into two anatomical structures and consists of a gelatinous core known as the nucleus pulposus, and the surrounding ring of fibrous tissue known as the anulus fibrosus. Resembling the structure of a round cushion, the intervertebral disc provides the spinal cord and surrounding vertebrae with protection against pressure, shock and trauma related with activity and impact. Only the intervertebral space between C1 and C2, the atlanto-axial joint, lacks the presence of an intervertebral disc[4]. The discs will vary in shape, size and thickness depending on their locations; the cervical discs being circular, the thoracic more of an oval shape, and the lumbar discs typically having a bean shape [1,7]. The cervical intervertebral discs are the thickest, reaching their thickest between the most caudal cervical vertebrae, and gradually decreasing in thickness and size caudally throughout the spine [4].

7.2. Intervertebral disc herniation

Having been described as common and presumed to be affecting a significant portion of the world’s canine population[2], intervertebral disc disease (IVDD) is of considerable relevance in the field of veterinary neurology. The chondrodystrophic breeds have been reported to be particularly predisposed to these pathologies, and the Dachshund showed a prevalence of 15,7% in a recent study published in 2016[8].

velocity – low, volume extrusion[9]. This herniation is however most commonly seen as non-compressive, which may explain why the Hansen type I and II are the most widely used in veterinary neurology[5,7,8].

The clinical effects of an intervertebral disc herniation are explained by the mechanical pressure to the spinal cord, causing neurological deficits of the spinal nerves affected. It is also believed to be partly due to the inflammatory chemokines present as a result of the local tissue trauma[10]. However, despite the severe clinical signs that have been related to this disease[11,12], it has also been reported in clinically normal patients [3]. Intervertebral disc herniation could therefore be considered to be an asymptomatic, accidental finding, as well as a symptomatic finding with clinical significance. It is accepted as both in the field of veterinary neurology.

7.3. The canine spinal cord and its functional divisions

Lesion localisation has been a highly recognised tool in veterinary neurology for a long time and is currently used in the diagnosis of neurological disorders. In order to accurately diagnose neurological pathologies in dogs, lesion localisation, or neurolocalisation, is a common practice by the veterinary neurologist. By evaluating mental status, nervous response and muscle condition, we can not only identify whether a problem is neurological in nature, but also localise what part of the nervous system is affected. Furthermore, by examining function and dysfunction of the spinal nerves specifically and evaluating their neurological deficits, the differential diagnosis can be limited to a smaller area of the spinal cord. These areas, known as spinal segment groups [4,5] or functional divisions [13], have been defined differently by various authors.

Although there is no disagreement regarding the number of canine vertebrae and their respective classifications [4,5,11,12], there have been some differences in the definitions of the spinal segments. The canine spine consists of 30 consistent vertebrae, divided into 7 cervical, 13 thoracic, 7 lumbar and 3 sacral vertebrae. In addition, caudal vertebrae are found caudally to the sacral vertebrae and will vary in number between 6 and 23 [4]. Notably, the 3 sacral vertebrae are fused.

not correspond to the anatomical division of vertebrae, and are defined by borders specific for the segments of the spinal cord[4,5].

7.4. Diagnostic imaging – CT and MRI

Diagnostic imaging is essential in the diagnosis of intervertebral disc herniations. Although traditional X-ray could be utilized to evaluate the distance between vertebrae and make an assumption regarding the diagnosis, computed tomography, with or without myelography, and magnetic resonance imaging are the diagnostic methods of choice in patients with suspected IVD herniation. Despite CT being both more convenient and therefore more widely used due to the specific requirements of MRI equipment, research has proven MRI to be more accurate in the diagnostic process.

In a study performed by Cooper et al. in 2013, MRI was reported to be superior to CT not only in the diagnosis of spinal cord compression associated with IVD herniation, but also to distinguish between protrusion and extrusion of the intervertebral disc [16]. A 10% difference in sensitivity was reported between CT and MRI in the diagnosis of intervertebral disc herniations. MRI was also favoured by Robertson et al. in 2011, in a study comparing CT and myelography to MRI as a diagnostic tool in patients with suspected IVD herniations.

One of the arguments made to support their claim was that CT myelography was inferior in patients with parenchymal lesions and circumferential reduction of the subarachnoid space, and that these lesions would only be apparent on CT if there was either swelling of the spinal cord or introduction of contrast medium into the spinal cord, both of which are uncommon. Their conclusion was that prior to MRI, a large number of patients probably received unnecessary decompressive surgery due to the uncertainty of the CT diagnosis [17]. Notably, a study was performed by Noyes et al. in 2017, investigating the differences in surgical plans formed with MRI as a diagnostic tool compared to CT. The results showed that in 57% of the cases, surgeons tended to plan larger laminectomy windows when using MRI compared to CT in the same patients [18]. Therefore, although MRI is a more accurate diagnostic tool, it may also motivate unnecessarily invasive procedures, and may even have an effect on clinical recovery.

7.5. Treatment of canine intervertebral disc herniation 7.5.1. Conservative

The goal of the conservative treatment is to indirectly decompress the spinal cord by decreasing the oedema surrounding the herniated disc created by the inflammatory process following the herniation [21]. This is usually accomplished directly by anti-inflammatories, and indirectly by decreasing the activity level and strain on the area, thus reducing further progression of the inflammatory process. In 2018, Nessler et al. performed a study comparing the outcome in patients receiving surgical treatment to those receiving conservative treatment, and concluded that the surgical intervention made an insignificant impact on the recovery period. Nessler et al. agreed with Borlace et al. and described their study from 2017 as the first study which clearly stated that surgical treatment was not superior to conservative in regards to recovery period [20].

However, in 1983, Davies et al. made a similar conclusion, stating that surgical fenestration offered no positive effect on the recovery rate of patients treated conservatively. Davies et al. also cited Funkquist from 1978, suggesting that this theory was already supported by similar research 40 years prior to the study performed by Nessler et al [22].

In regards to performance animals and canine athletes, an interesting comment was made by Lotsikas et al. in 2020, suggesting that for these patients, conservative treatment should only be considered in cases of very mild clinical signs, and surgery should be considered in all cases where the patient was unable to carry its own weight [19]. Whether this was aimed at paretic patients or completely non-ambulatory patients only is uncertain, however it does suggest a specific line separating the conservative from the surgical patients.

7.5.2. Surgical

The surgical treatment applied in cases of IVD herniations offers two different general techniques, the fenestration and the laminectomy, respectively. Of the two, the laminectomy is the surgical treatment of choice, although the fenestration is still performed [20,21]. As previously discussed, the benefits of surgical treatment in patients with less severe clinical signs are minor. However, in paralytic and non-ambulatory patients, surgical intervention is necessary and should be considered the only option [19,21].

7.6. Neurolocalisation

Neurolocalisation is the process of localising a neurological disorder to a specific area of the nervous or muscular system by clinical diagnosis. In practice, this is done by evaluating the function and dysfunction of different parts of the neuromuscular system, namely the cranial and spinal reflexes, mental status and motor and sensory functions [15]. Based on the previously established knowledge of neuroanatomy, agreed upon by authors such as LeCouteur, 2004, De Risio, 2005, Da Costa et al., 2010 and Dewey, 2016 [5,11,15,24], the results of these clinical tests will give an indication of where in the neuromuscular system the lesion is located. Another important aspect of neurolocalisation is of course to determine whether the lesion is located within the neuromuscular system at all [24].

The process of neurolocalisation is generally agreed upon by most recent authors, specifically considering what clinical tests should be performed and what aspect of the neuromuscular system they evaluate. However, the value of certain reflexes in clinical examination has been discussed by some authors such as Levine et al. Their research from 2002 evaluated the influence of age on the patellar tendon reflex and concluded that older dogs, although neurologically normal, showed a decrease in the patellar tendon reflex [25]. Similarly, Gutierrez-Quintana et al., 2012, evaluated the accuracy of the cutaneous trunci reflex. Their findings indicated that the results of clinical evaluation of the cutaneous trunci reflex can be used to identify a spinal cord lesion with a margin of 4 vertebrae [26]. Although this is impressively accurate for a clinical examination, the functional divisions of the spine are separated by adjacent borders of the spinal segments [5]. Therefore, a margin of error of 4 vertebrae can theoretically be enough to cause a mistake in neurolocalisation. As suggested by these authors, some parts of neurolocalisation may not be completely reliable.

Within the general neurolocation of the spinal cord, neurolocalisation also distinguish between the functional divisions mentioned in Chapter 6.3. There is a general consensus among authors regarding the neurolocalisation within the spinal cord, and most authors will separate them based on Upper Motor Neuron (UMN) and Lower Motor Neuron (LMN) deficits [5,13–15,24]. In a clinical examination, UMN deficits will present as paresis or paralysis, with normal or increased muscle tone and reflexes, and only mild muscle atrophy. Comparably, LMN deficits will also present as paresis or paralysis, but with reduced or completely absent reflexes, reduced muscle tone and severe muscle atrophy [5]. Applying this to the neurolocalisation of spinal cord lesions, the general consensus is that lesions within the functional division C1-C5 will show UMN deficits in both the thoracic and pelvic limbs, while lesions within C6-T2 will show LMN deficits in the thoracic limbs

and UMN deficits in the pelvic limbs. Lesions located within T3-L3 will show no deficits in the thoracic limbs, while presenting as UMN deficits in the pelvic limbs. Lastly, lesions located within L4-S3 will present as

Thoracic limb Pelvic limb

C1-C5 UMN UMN

C6-T2 UMN LMN

T3-L3 Normal UMN L4-S3 Normal LMN

8. METHODOLOGY

The canine neurological system consists of the central nervous system (CNS) and the peripheral nervous system (PNS). Neurological disorders can be classified into three main groups of spinal disorders, brain disorders and peripheral nervous system disorders, where the former two are located within the CNS. The latter can be further divided into nerve root disorders, neuromuscular disorders and synapse disorders. A basic classification of canine neurological disorders is presented in Figure 1, collected from Johansen, 2020 [27].

In practice, neurolocalisation is used to as a tool of clinical diagnosis to differentiate between these parts of the neuromuscular system. The common aspects of neurological examination and their corresponding evaluated parts of the neuromuscular system is presented in Figure 2. Because the suitable diagnostic method will change depending on where the lesion is localised, neurolocalisation is also used as an indication of how to further process the patient. In patients with suspected spinal cord disorders, both CT and MRI are suitable diagnostic methods, despite research favouring one over another, as mentioned in Chapter 7.4. A list of the parts of the neuromuscular system and their corresponding diagnostic methods is presented in Figure 3.

B

BRAIN STEM FOREBRAIN CEREBELLUM

CENTRAL

NERVOUS SYSTEM

BRAIN DISORDERS S_DISORDERSPINAL CORD

PERIPHERAL NERVOUS SYSTEM PNS DISORDERS NEUROMUSCULAR DISORDERS SYNAPSE DISORDERS NERVE ROOT DISORDERS SPINAL NERVE DISORDERS CRANIAL NERVE DISORDERS

Fig. 1: A basic classification of canine neurological disorders

Incorporating these theories into practice, neurolocalisation was used in the patients of this study to indicate the specific functional

division of the spinal cord in which the lesion was located. This was performed by veterinary neurologists at the clinic where the research material was collected.

Neurolocalisation may also indicate a treatment plan and expected prognosis early in the diagnostic process. This study will therefore evaluate the usefulness of neurolocalisation in canine patients with IVDH by comparing occurrence of neurolocalisation and neurolocations to the diagnostic methods and choice of treatment in 26 canine patients with diagnosed intervertebral disc herniation. •Brain CONSCIOUSNESS •Brain BEHAVIOR •Brain •Spinal cord •Neuromuscular POSTURE •Brain •Spinal cord •Neuromuscular •Synapse •Nerve root GAIT •Brain •Spinal cord •Neuromuscular •Synapse •Nerve root POSTURAL REACTIONS •Spinal cord •Neuromuscular •Synapse •Nerve root SPINAL REFLEXES •Spinal cord •Neuromuscular •Synapse •Nerve root CRANIAL NERVE REFLEXES •Brain •Spinal cord •Neuromuscular •Synapse •Nerve root SENSORY EVALUATION

Fig. 2: A basic classification of canine neurological disorders

[Johansen LMA, Myasthenia Gravis in dogs – clinical signs, diagnosis and treatment of canine neurological muscle weakness, 2020]

B

S

P

Fig. 3: A basic classification of canine neurological disorders

[Johansen LMA, Myasthenia Gravis in dogs – clinical signs, diagnosis and treatment of canine neurological muscle

8.2. Collection of research material

This is a retrospective study in which the patient histories of 26 canine patients were collected from the patient records of Fredrikstad Dyrehospital veterinary animal hospital in Norway between January and December 2020. All patients had been diagnosed with intervertebral disc herniation between 01.01.2019 and 01.01.2020 and had been examined with diagnostic imaging, which was either computed tomography (CT) or magnetic resonance imaging (MRI). The patients were categorised by age, breed, gender and Body Condition Score (BCS), presence or absence of neurolocalisation on initial clinical examination, diagnostic tool (CT/MRI), treatment type (conservative/surgical) and the location of the diagnosed herniation on diagnostic imaging. The latter was defined based on the anatomical intervertebral space and not the spinal segment affected.

8.3. Classification of data

The dogs were divided into two groups of Neurolocalised (NL) patients and Non-neurolocalised patients (NNL) based on the information from the neurological examination collected from the patient records. The neurolocalised patients were further categorised into four groups based on their neurolocations. These groups were defined using the functional divisions of the canine spine established by Richard A. LeCouteur in his lecture Localization of spinal cord lesions from 2004[15]. The neurolocations were defined as spinal segments C1-C5, C6-T2, T3-L3 and L4-S3, the last group also including the five cauda equina spinal segments and their corresponding nerve roots. The individual spinal segments were defined using the spinal segment borders described by Dewey in Practical guide to Canine and Feline Neurology from 2016[5].

Both groups NL and NNL were also categorised based on the exact location(s) of their diagnosed herniation(s) on diagnostic imaging. It should be noted that some patients had multiple diagnosed intervertebral disc herniations. In the NL group, these results were used to further divide the patients into two groups of Matching (M) and Non-Matching (NM), based on whether the location of the herniation was within the spinal segment borders of the neurolocation given on neurological examination. In the NNL group, the results were used to divide them into four groups of functional divisions corresponding to the neurolocations used in the NL group. These artificial neurolocalisations of the NNL patients were used to evaluate which functional divisions most frequently presented without clinical signs sufficient for a neurolocalisation.

8.4. Calculations and data analysis

𝑝 = $(𝑂 − 𝐸)!

𝐸

where

p = Chi square value O = observed values E = Expected values

Statistical dependence between two groups was defined as p > 0,05. The sensitivity of the neurolocalisation process was defined as

𝑆𝑒𝑛𝑠𝑖𝑡𝑖𝑣𝑖𝑡𝑦 = 𝑇𝑃

(𝑇𝑃 + 𝐹𝑁) 100

The specificity of the neurolocalisation process was defined as

𝑆𝑝𝑒𝑐𝑖𝑓𝑖𝑐𝑖𝑡𝑦 = 𝑇𝑁 (𝑇𝑁 + 𝐹𝑃) 100 where TP = true positives TN = true negatives FP = false positives FN = false negatives

It should be noted that out of all the patients in the studied group, only one patient had herniations located within two different functional divisions, whereas the rest had herniations located in only one functional division of the spinal cord.

The margin of error was calculated using the formula 𝑀 = 𝑡 𝑠

√𝑛 where

M = margin of error

9. RESULTS

9.1. Occurrence of neurolocations and the sensitivity of neurolocalisation

Out of 26 patients, only 46,2% ± 0.19 (=12 patients) were neurolocalised on clinical examination. Of these NL patients, 75% (=9 patients) were neurolocalised as a T3-L3 spinal cord deficit. Only 8,3% (=1 patient) was neurolocalised as a C1-C5 deficit, while the remaining 16,7% (=2 patients) were neurolocalised as L3-S4 spinal cord deficits. No NL patients were neurolocalised as C6-T2 spinal cord deficits. The occurrence of neurolocations in the NL group is presented in Figure 4.

Of the 12 neurolocalised patients, no patients had more than one neurolocation on clinical exam. Of the 12 neurolocations given on clinical

examination, 11 proved to be correct (M) and 1 proved to be incorrect (NM) when compared to the exact location of the herniation found on diagnostic imaging. These results are presented in Figure 5.

Artificial neurolocations were given to each of the 14 patients with no neurolocation on clinical examination. These added up to 15 neurolocations, as one of the patients had herniations within the spinal segment borders of two functional divisions. Adding these neurolocations to

1 14 11 0 1 2 3 4 5 6 7 8 9 10 P at ie nt s Neurolocation

Fig. 4: Occurrence of neurolocations in neurolocalised patients

C1-C5 T3-L3 L4-S3

9

53,8% 42,3%

3,8%

Fig. 5: The occurrence of correctly and incorrectly neurolocalised patients

Not neurolocalised Matched Not matched

1

those of the 12 neurolocalised patients, a total of 27 potential positive neurolocalisations were possible. Of these 27, 40,7% (=11 neurolocations) were diagnosed correctly, as presented in Figure 5. The sensitivity of neurolocalisation in this study, defined as the percentage of true positive occurrences, was 40,7% ± 0.11.

9.2. Occurrence of non-neurolocalised patients and the specificity of neurolocalisation Out of 26 patients, 53,8% ± 0.19 (=14 patients) were not neurolocalised on clinical examination. Some of these patients may have presented with neurological deficits, however these were insufficient for neurolocalisation. Each of the patients in the NNL group were given an artificial neurolocation based on the exact location(s) of their diagnosed herniation(s) and the spinal segment borders of the functional divisions of the spine. In one of the NNL patients, this corresponded to two functional divisions. In the rest, it corresponded to a single functional division. The frequency of each functional division in the NNL group is presented in Figure 6.

With 26 patients and four possible neurolocations, 104 possible neurolocations could be neurolocalised. Only one patient showed herniations in two different functional divisions on diagnostic imaging. Therefore, out of those 104 neurolocations, 27 neurolocations were potential positives. The remaining 77 neurolocations were potential negatives. These numbers are presented in Table 2.

Out of those 77 potential negatives, 41 negatives were correctly non-neurolocalised in the NNL group. One neurolocation was incorrectly non-neurolocalised in the NL group, which was the neurolocation of the Non-Matched patient. 35 neurolocations were correctly non-neurolocalised in the NL group. 76 true negatives out of 77 potential negatives were diagnosed using neurolocalisation. The

0 1 2 3 4 5 6 7 8 P at ie nt s Functional division

Fig. 6: Occurrence of functional divisions in non-neurolocalised patients

C1-C5 C6-T2 T3-L3 L4-S3

2

1

7

specificity of neurolocalisation, defined as the percentage of true negative occurrences, in this study was 98,7% ± 0.025. The specificity and sensitivity is presented in Figure 7.

Positive Negative Total

False 16 1 17

True 11 76 87

Total 27 77 104

9.3. The correlation between neurolocalisation, diagnostic method and treatment

In order to properly statistically evaluate the correlation between neurolocalisation and the choice of diagnostic method and treatment, the Chi square formula of independence was used as previously mentioned in Chapter 7, page 13. In the case of diagnostic methods, only diagnostic imaging was evaluated. This was either CT or MRI. In one case, both CT and MRI was used. The calculated frequencies of CT and MRI in the neurolocalised versus non-neurolocalised patients showed that 100% of the patients examined with only MRI were neurolocalised patients. The one patient which was examined with both CT and MRI was a non-neurolocalised patient. Of the 14 non-neurolocalised patients, CT based diagnosis was performed in 92,8%, while it only accounted for 75% of the 12 neurolocalised patients.

40,7%

59,3%

Sensitivity

True positive False negative

98,7% 1,3%

Specificity

True negative False positive

Fig. 7: Sensitivity and specificity of neurolocalisation in 26 canine patients with intervertebral disc herniation

The distribution of CT between the two groups was 40,9% and 59,1% in the NL and NNL group, respectively. The Chi Square test p value indicated no significant correlation between the neurolocalisation and the diagnostic method used, with p > 0.05 (p = 0,1).

10.

DISCUSSION OF RESULTS

Although the Chi Square test of independence showed no significant correlation between neurolocalisation and diagnostic method, it should be noted that due to the small sample size, further investigations should be performed with a larger sample size before a final conclusion is made. Most notably, the results of this study showed a tendency to rely solely on MRI for the diagnostic imaging in cases with neurolocalised patients. Taking into consideration the results found in the research performed by Noyes et al. in 2017 [18], this may indicate that neurolocalised patients typically receive more extensive surgeries.

In addition, although only one such case was seen in this study, the results suggest that neurolocalisation will eliminate the need to use both CT and MRI. The authors are however reluctant to make this conclusion based on this study alone, due to a limiting occurrence in the sample population.

When discussing the results of the correlation between neurolocalisation and treatment, it should be noted that despite the lack of neurolocalisation, all dogs in this study were examined using diagnostic imaging and the exact locations of intervertebral disc herniations were found. Therefore, although the results show a tendency to prefer conservative treatment or euthanasia in Non-neurolocalised patients only, this should not be due to a lack of diagnostic information. However, other factors such as owner’s wishes or the severity of clinical signs may be the explanation. These factors were not considered in this study.

The results showed no indication of a significant correlation between neurolocalisation and treatment method in this study, however as previously mentioned the authors recommend further investigations using a larger sample size for a more accurate evaluation. Comparing this to the results of Borlace et al, 2017 and Nessler et al., 2018 [20,28], the difference in recovery between patients treated surgically and those treated conservatively is inconsiderable in most patients, regardless of lesion location. Consequently, lesion location and therefore neurolocalisation may not be significant when deciding the treatment method in patients with IVDH.

However, Davies et al., 1983, investigated the outcome in patients with thoracolumbar intervertebral disc disease and found that recovery depended more on the severity of clinical signs than on the treatment method [22]. Although only thoracolumbar herniations were included in their research, when comparing their results to the ones found in this study, this may suggest that the severity of clinical signs has a more significant impact on diagnosis and treatment than the location of the lesion. Consequently, a grading system of clinical severity, such as the one used by Davies et al. [22], may be more valuable than neurolocalisation in patients with IVDH.

highly reliable positive neurolocalisation result. However, the sensitivity was notably low at 40.7%. In practice, this would mean that over half of the cases with a spinal cord injury arising from IVD herniation would not be neurolocalised on a clinical exam. This could potentially be true in cases of other spinal cord injuries as well, such as vertebral fractures. Consequently, it raises the question of whether the process of neurolocalisation of individual functional divisions of the spinal cord is useful in a clinical situation, or if it would be more beneficial to simply categorize these patients as spinal cord disorders. Notably, other authors have also previously reported a lack of reliability in certain aspects of the neurological examination, namely the patellar tendon reflex [25], the cutaneous trunci reflex [26] and the withdrawal reflex [29].

11.

CONCLUSIONS

This study aimed to investigate the usefulness of neurolocalisation in canine patients with intervertebral disc disease. The conclusions of this study are as follows, in no particular order of importance:

1. The sensitivity of the neurolocalisation process in dogs with intervertebral disc herniations is low. A negative neurolocalisation should therefore not be trusted as a negative diagnosis of intervertebral disc disease. This could potentially be applicable in cases involving other spinal cord disorders as well.

2. The specificity of the neurolocalisation process in dogs with intervertebral disc herniations is notably high and a positive neurolocalisation on clinical examination strongly suggests a positive diagnosis of intervertebral disc disease. As with the sensitivity, the conclusions regarding specificity could be applicable in cases involving other spinal cord disorders as well.

12.

ACKNOWLEDGEMENTS

13.

LITERATURE LIST

1. King AS, Smith RN. A Comparison of the Anatomy of the Intervertebral Disc in Dog and Man. Br Vet J. 1955 Apr;111(4):135–49.

2. Bray J, Burbidge H. The canine intervertebral disk: part one: structure and function. J Am Anim Hosp Assoc. 1998 Jan 1;34(1):55–63.

3. De Decker S, Gielen IMVL, Duchateau L, Van Soens I, Bavegems V, Bosmans T, et al. Low-field magnetic resonance imaging findings of the caudal portion of the cervical region in clinically normal Doberman Pinschers and Foxhounds. J Am Vet Med Assoc. 2010 Apr 15;236(8):886–886. 4. Evans HE, Miller ME. Miller’s anatomy of the dog. Fourth edition. St. Louis, Missouri: Elsevier; 2013. 850 p.

5. Dewey CW. Practical Guide to Canine and Feline Neurology. 3rd ed. Wiley Blackwell; 2016. 6. Hansen H-J. A Pathologic-Anatomical Study on Disc Degeneration in Dog: With Special Reference to the So-Called Enchondrosis Intervertebralis. Acta Orthop Scand. 1952 Dec;23(sup11):1– 130.

7. Brisson BA. Intervertebral Disc Disease in Dogs. Vet Clin North Am Small Anim Pract. 2010 Sep;40(5):829–58.

8. Packer RMA, Seath IJ, O’Neill DG, De Decker S, Volk HA. DachsLife 2015: an investigation of lifestyle associations with the risk of intervertebral disc disease in Dachshunds. Canine Genet Epidemiol. 2016 Dec;3(1):8.

9. De Risio L. A Review of Fibrocartilaginous Embolic Myelopathy and Different Types of Peracute Non-Compressive Intervertebral Disk Extrusions in Dogs and Cats. Front Vet Sci [Internet]. 2015 Aug 18 [cited 2020 Nov 20];2. Available from:

http://journal.frontiersin.org/Article/10.3389/fvets.2015.00024/abstract

10. Dydyk AM, Ngnitewe Massa R, Mesfin FB. Disc Herniation. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 [cited 2020 Nov 21]. Available from:

http://www.ncbi.nlm.nih.gov/books/NBK441822/

11. da Costa RC, Moore SA. Differential Diagnosis of Spinal Diseases. Vet Clin North Am Small Anim Pract. 2010 Sep;40(5):755–63.

12. Bergknut N, Smolders LA, Grinwis GCM, Hagman R, Lagerstedt A-S, Hazewinkel HAW, et al. Intervertebral disc degeneration in the dog. Part 1: Anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration. Vet J. 2013 Mar;195(3):282–91.

University, Palmerston North, New Zealand.

14. Wininger F. Neurolocalization Basics and “The Gait Game”. Presentation lecture presented at; 2017; Fetch DVM360 Conference.

15. Lecouteur RA. Localization of Spinal Cord Lesions. World Small Animal Veterinary Association World Congress Proceedings, 2004; 2004.

16. Cooper JJ, Young BD, Griffin JF, Fosgate GT, Levine JM. Comparison between noncontrast computed tomography and magnetic resonance imaging for detection and characterization of

thoracolumbar myelopathy caused by intervertebral disk herniation in dogs: MRI and CT for Diagnosing Thoracolumbar Disk Disease in Dogs. Vet Radiol Ultrasound. 2014 Mar;55(2):182–9. 17. Robertson I, Thrall DE. IMAGING DOGS WITH SUSPECTED DISC HERNIATION: PROS AND CONS OF MYELOGRAPHY, COMPUTED TOMOGRAPHY, AND MAGNETIC

RESONANCE: Imaging suspected disc herniation. Vet Radiol Ultrasound. 2011 Mar;52:S81–4. 18. Noyes JA, Thomovsky SA, Chen AV, Owen TJ, Fransson BA, Carbonneau KJ, et al. Magnetic resonance imaging versus computed tomography to plan hemilaminectomies in chondrodystrophic dogs with intervertebral disc extrusion. Vet Surg. 2017 Oct;46(7):1025–31.

19. Lotsikas PJ, Leasure C, Lotsikas FM. Intervertebral Disc Disease in the Canine Athlete. Vet Sports Med. 2020;

20. Nessler J, Flieshardt C, Tünsmeyer J, Dening R, Tipold A. Comparison of surgical and conservative treatment of hydrated nucleus pulposus extrusion in dogs. J Vet Intern Med. 2018 Nov;32(6):1989–95.

21. Berry W. Intervertebral Disc Disease - Medical or Surgical? World Small Animal Veterinary Association World Congress Proceedings, 2014; 2014.

22. Davies JV, Sharp NJH. A comparison of conservative treatment and fenestration for

thoracolumbar intervertebral disc disease in the dog. J Small Anim Pract. 1983 Dec;24(12):721–9. 23. Jeong I, Piao Z, Rahman M, Kim S, Kim N. Canine thoracolumbar intervertebral disk herniation and rehabilitation therapy after surgical decompression: A retrospective study. J Adv Vet Anim Res. 2019;6(3):394.

24. De Risio L. Neurologic Examination and Lesion Localization. 2005; World Small Animal Veterinary Association World Congress 2005.

25. Levine JM, Hillman RB, Erb HN, deLahunta A. The Influence of Age on Patellar Reflex Response in the Dog. J Vet Intern Med. 2002 May;16(3):244–6.

26. Gutierrez-Quintana R, Edgar J, Wessmann A, Cherubini GB, Penderis J. The cutaneous trunci reflex for localising and grading thoracolumbar spinal cord injuries in dogs. J Small Anim Pract. 2012 Aug;53(8):470–5.

neurological muscle weakness. 2020.

28. Borlace T, Gutierrez-Quintana R, Taylor-Brown FE, De Decker S. Comparison of medical and surgical treatment for acute cervical compressive hydrated nucleus pulposus extrusion in dogs. Vet Rec. 2017 Dec;181(23):625–625.

29. Forterre F, Konar M, Tomek A, Doherr M, Howard J, Spreng D, et al. Accuracy of the

14.

ANNEXES

Neurolocation code

Diagnostic method

Treatment Gender Breed Age Diagnose

code

NL01 CT Surgical Male Mixed breed 7 DL02

NL03 CT Surgical Female Mixed breed 10 DL03

NL03 CT Surgical Female Mixed breed 6 DL03

NL03 CT Surgical Female Dachshund 9 DL03

NL03 CT Surgical Male Dachshund 11 DL03

NL03 CT Surgical Male Dachshund 8 DL03

NL03 MRI Surgical Male Dachshund 8 DL03

NL03 MRI Surgical Female Mixed breed 3 DL03

NL03 MRI Surgical Male Dachshund 15 DL03

NL03 CT Surgical Male Dachshund 5 DL03

NL04 CT Surgical Female French Bulldog 5 DL04

NL04 CT Surgical Female Gordon Setter 6 DL04

NEG CT Surgical Female Japanese Spitz 11 DL01

NEG CT Surgical Danish-Swedish farm

dog 5 DL01

NEG CT, MRI Surgical Male Rottweiler 5 DL02

NEG CT Conservative Male Löwchen 8 DL03

NEG CT Surgical Female Coton de Tulear 7 DL03

NEG CT Surgical Female Miniature Dachshund 4 DL03

NEG CT Euthanasia Female Dachshund 4 DL03

NEG CT Surgical Female Miniature Dachshund 8 DL03

NEG CT Surgical Male Dachshund 3 DL03

NEG CT Conservative Female Cocker Spaniel 5 DL03,

DL04

NEG CT Surgical Male Mixed breed 5 DL04

NEG CT Surgical Male Jack Russel Terrier 6 DL04

NEG CT Surgical Male Mixed breed 6 DL04

NEG CT Surgical Female Parson Russel Terrier 8 DL04

Explanations: Neurolocation code: NL01 = C1 – C5 NL02 = C6 – T2 NL03 = T3 – L3 NL04 = L4 – S3

NEG = Not neurolocalised

Diagnose code:

DL01 = C1 – C5 DL02 = C6 – T2 DL03 = T3 – L3 DL04 = L4 – S3