Disk Herniation
H.-L. Amendt1*, N. Steffensen1, U. Kordass1, K. Rohn2, A. Tipold1, V.M. Stein1
1Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany.
2Department of Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Hannover, Germany.
* Corresponding author: Hanna-Luise Amendt
Department of Small Animal Medicine and Surgery University of Veterinary Medicine Hannover Bünteweg 9
D-30559 Hannover Germany
Tel. 0049-511-953-6200
e-mail: hlamendt@tiho-hannover.de
Abstract
Transcranial Magnetic Stimulation (TMS) is a non-invasive method to determine the functional integrity of the spinal cord descending motor pathways. In dogs with intervertebral disk herniation (IVDH) these pathways are compromised to a different degree which is reflected by the severity of their neurological deficits. Therefore, the hypothesis of this study are (1) TMS results of healthy dogs are different to TMS results of dogs with IVDH and (2) TMS can reflect different severities of neurological signs caused by IVDH. Furthermore, (3) TMS can document functional motor improvement and therefore aid in monitoring regeneration during therapy progression.
Magnetic Motor Evoked Potentials (MMEPs) were recorded under sedation (Magstim 200², Carmarthenshire, UK) in the extensor carpi radialis and cranial tibial muscles in 50 dogs suffering from IVDH in the thoracolumbar spinal cord region. Of these, 19 dogs showed clinical signs ranging from spinal hyperesthesia to severe paraparesis and 31 dogs displayed a paraplegia with or without deep pain sensation. The dogs were classified on the basis of the severity of their neurological signs according to Sharp and Wheeler (2005). In 33/50 dogs TMS was repeated during follow-up examinations. Ten healthy Beagle dogs served as controls.
A significant increase in onset latency and decrease in peak-to-peak amplitude were detected in the pelvic limb MMEPs of dogs with clinical signs of IVDH compared to the control dogs. The waveform of MMEPs was polyphasic in contrast to the biphasic waveform of the controls. No MMEPs could be generated in paraplegic dogs. However, MMEPs with increased onset latencies and decreased peak-to-peak amplitudes could be recorded in the pelvic limb in 15/18 dogs with functional motor improvement after therapy.
In conclusion, severity of neurological deficits is reflected by TMS findings and can document functional motor recovery in surgically treated dogs with IVDH. TMS can therefore be used as an ancillary test for therapy monitoring in dogs during rehabilitation.
Keywords: Intervertebral Disk Herniation; Magnetic Motor Evoked Potentials; Transcranial Magnetic Stimulation
Introduction
Intervertebral Disk Herniation (IVDH) is a common disease in veterinary medicine mainly seen in chondrodystrophic dogs that are predisposed to Hansen-Type-I thoracolumbar disk herniation (Hansen, 1951, Ferreira et al., 2002, Olby et al., 2003 Bull et al., 2008). The ruptured annulus fibrosus releases the degenerated nucleus pulposus which induces spinal cord injury with loss of functional integrity (Jeffery et al., 2013). Clinical signs are variable from back pain to severe neurological deficits (Aikawa et al., 2012). For long-term outcome of functional motor recovery after treatment different prognostic values are available in which the key indicator is the presence or absence of deep pain sensation (Olby et al., 2003).
Magnetic resonance imaging (MRI) is the imaging modality of choice to diagnose IVDH and illustrate details of spinal cord parenchyma and severity of injury resulting from disk herniation. However, MRI does not provide information about the functionality of the spinal cord (da Costa et al., 2006). Decompressive surgical intervention provides a good chance for rapid functional motor recovery in dogs suffering from IVDH (Bull et al., 2008).
Furthermore, it is difficult for the clinician to provide the owner of an affected dog with a definite prognosis.
Transcranial magnetic stimulation (TMS) has been used in previous studies in human and veterinary medicine to evaluate descending motor tracts (Sylvestre et al., 1993; Di Lazzaro et al., 1999; Nollet et al., 2003; Van Soens and Van Ham 2011; Martin-Vaquero and da Costa;
2014). Barker (1991) could show that the motor cortex can be stimulated by TMS non-invasively and painless with the conduction of the stimulus to nervous tissue (Van Soens and Van Ham, 2011). The evolved Magnetic Motor Evoked Potentials (MMEPs) are measured in the periphery (Di Lazzaro et al., 1999). TMS is considered to be a safe technique to evaluate the functional integrity of the spinal cord and has been used in previous studies to illustrate MMEPs in dogs suffering from different neurological diseases under sedation (Van Ham et al., 1994; da Costa et al., 2006; De Decker et al., 2011; Van Soens and Van Ham, 2011;
Martin-Vaquero and da Costa, 2014).
The purpose of this prospective study was (1) to compare the findings of MMEPs at TMS in dogs suffering from IVDH with the findings in healthy control dogs and (2) whether TMS findings can reflect different severities of neurological deficits, and (3) to evaluate whether
TMS can document functional motor recovery to use it as an ancillary test for monitoring functional improvement during therapy progression.
Material and Methods Dogs
Fifty client-owned dogs were recruited from the patients of the Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Germany. The study was conducted in accordance with the guidelines of the Animal Care Committee and national regulations for animal welfare (animal experiment number 33.14-42502-04-13/1277). Written owner consent was obtained prior to study enrollment.
The patients were prospectively enrolled between May 2013 and May 2014. All dogs underwent a general physical and blood examination. As an inclusion criterion the neurological examination had to reveal deficits in the pelvic limbs of different severity localized to the T3-L3 spinal cord segment. Intervertebral disk herniation was diagnosed using MRI (n = 50) and confirmed with surgery (n = 47). In 2/50 dogs a conservative treatment was chosen and 1 dog was euthanized on request of the owner due to severity of MRI findings. The severity of the neurological deficits was graduated according to Sharp and Wheeler (2005): Grade I was defined as spinal hyperesthesia without neurological deficits, grade II as ambulatory paraparesis and ataxia, grade III as non-ambulatory paraparesis. Dogs with paraplegia with and without nociception were defined as grade IV and grade V, respectively. Ten healthy Beagle dogs, nine male and one female, from the colony of the Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Germany, served as controls (Amendt et al., submitted 2014). These dogs had no abnormal findings in physical and neurological examination. Their mean of age was 32 months (range: 27 - 73 months) and mean bodyweight of 16.7 kg (range: 10.2 - 20.6 kg).
Sedation
TMS was performed before imaging. An intravenous (IV) catheter (B. Braun Melsungen AG, Melsungen; Germany) was placed in the V. saphena lateralis or the V. cevalica antebrachii of the right or left thoracic or pelvic limb. The dogs were sedated with acepromazine (0.02 - 0.05 mg/kg, Vetranquil®, CEVA Tiergesundheit GmbH, Düsseldorf, Germany) combined with levomethadone/fenpipramide (0.2 - 0.4 mg/kg L-Polamivet®,
Intervet Deutschland GmbH, Unterschleißheim, Germany) given slowly IV while monitoring heartbeat. Body temperature was measured every ten minutes. As soon as deep sedation was achieved the dogs were placed in lateral recumbency or in ventral position.
TMS
The TMS was performed as described in previous studies with minor modifications (Sylvestre et al., 1993; Van Ham et al., 1994; da Costa et al., 2006; Granger et al., 2012;
Amendt et al., submitted 2014). The MMEPs were provoked by a Magstim 200² (Magstim, Carmarthenshire, UK) with a 50 mm circular coil and a peak magnetic field capacity of 4.0 Tesla, which complies with a 100 % intensity. This monophasic, single pulse stimulator is used for peripheral and cortical stimulation (0.25 Hz frequency maximum, maximum frequency burst 0.5 Hz) with a minimal pulse interval of two seconds. Sensitivity ranged from 2 to 20 mV for all recordings in the non-affected thoracic limbs as well as in the affected pelvic limbs. The total recording time including all measurements ranged between 10 to 40 minutes. A ring coil was bonded to the magnetic stimulator and was held tangentially to the skull with the center of the coil lateral to the vertex and in close contact to the skin to stimulate the motor cortex (Fig. 1). The magnetic field induced from TMS resulted in synchronized excitatory stimuli of descending spinal cord pathways and can be recorded as MMEPs on an electromyograph (Nicolet™ NicVue 2.9.1, Natus Medical Incorporated, Planegg, Germany).
Figure 1: For the Transcranial Magnetic Stimulation (TMS) the ring coil (50 mm) was placed tangentially to the skull directly over the vertex in contact to the skin and connected to the magnetic stimulator.
Four measurements were performed in the extensor carpi radialis (MECR) and the cranial tibial muscles (MTC) for the thoracic and pelvic limbs, respectively with different intensities of the magnetic field. TMS was performed at stimulation intensities ranging from 70 % up to 100 % in all four limbs. In the cases in which no MMEP was generated only two measurements were processed with a stimulation intensity of 100 % (4.0 Tesla) in the right and left pelvic limbs. Monopolar 23 mm non-insulated stainless steel needle electrodes (Natus Medical Incorporated, Planegg, Germany) were placed with the tip of the recording electrode directly into the middle of the muscle belly. It was positioned cranial to the lateral humeral epicondyle into the muscle belly for the extensor carpi radialis muscle. The placement of the recording needle for the tibialis cranialis muscle was lateral to the distal end of the tibial crest into the muscle belly. A reference electrode (CareFusion, Hoechberg, Germany) was placed subcutaneously 1 cm distal to the recording needle at the level of the carpal joint for the evaluation of the MECR and at the tarsal joint for the recordings of the MTC. A ground electrode (CareFusion, Hoechberg, Germany) was positioned axially at the level of Th1-Th3 for the evaluation of the MECR or at the level of L4-L6 to evaluate the MTC. Each electrode was connected to the electromyograph Nicolet™ NicVue 2.9.1 (Natus Medical Incorporated, Planegg, Germany) to obtain the recordings. The VikingSelect-Software Version 11.0 (Viasys healthcare, CareFusion, Höchberg, Germany) was used to evaluate the measurements.
Magnetic motor evoked potential recordings (MMEPs)
The variables to asses MMEPs were onset latency, defined as the interval from the onset of the stimulus to the start of the muscle response measured in milliseconds (ms), and peak-to-peak amplitude evaluated in millivolt (mV) defining the distance from the lowest to the highest peak (Fig. 2A). The path from the transcranial magnetic stimulation to the recording electrode within the extensor carpi radialis (MECR) or cranial tibial (MTC) muscles were documented as the neuronal path length.
Statistical methods
In dogs with IVDH or presumed IVDH the data collected from the right and left MECR and MTC were averaged to obtain a single value for the thoracic and pelvic limbs, respectively.
Age, weight, and neuronal path length were also averaged to obtain single data.
Non-parametric methods were used because the data were not normally distributed. Tukey´s range test was performed to compare the data of the groups. No data of the pelvic limbs could be collected from dogs with grade IV and V of their neurological signs due to the absent MMEPs and are consequently not included in the statistics. Wilcoxon rang test was used to compare the values of dogs graded from I to III before treatment with values of the follow-up dogs for therapy monitoring. The statistical analyses of data were performed with commercial software program (SAS 9.3 Enterprise, Cary, North Carolina, USA). Statistical difference was considered if P < 0.05.
Results
Fifty dogs, 22 females (10 neutered) and 28 males (10 neutered), suffering from IVDH or presumed IVDH were included in this study between May 2013 and May 2014. The most common breed was the dachshund (n = 20) followed by mixed breed dogs (n = 14). Other included breeds were French bulldog (5/50), Jack Russell Terrier (3/50), Shih Tzu (2/50), Chihuahua (2/50), Pekingese (1/50), Pug dog (1/50), West Highland White Terrier (1/50), and English Cocker Spaniel (1/50). The age varied from 34 to 159 months with a mean of 65 months. Their mean bodyweight was 9.6 kg (range: 2.5 - 19.6 kg). Neuronal path length was evaluated in means for the thoracic limbs (373.8 mm; range: 220 – 530 mm), and for the pelvic limbs (548.7 mm; range: 370 – 910 mm). The dogs with T3-L3 lesions had clinical signs of different severity that were furthermore categorized in grade I (n = 6), grade II (n = 7), grade III (n = 6), grade IV (n = 14), and grade V (n = 17).
For the follow-up studies 33/50 dogs could be recruited. Of these dogs 15/33 were still paraplegic after decompressive surgery. Ten of these had a history of chronic IVDH ( > 28 days) and were presented to our referral hospital after decompressive surgery at the referring veterinarian (n = 8) or conservative treatment (n = 2) resulting in no neurological improvement. In these paraplegic dogs no MMEPs could be evoked in the follow-up period.
In contrast, 18/33 dogs with follow-up TMS showed a neurological improvement. TMS was performed at the day of functional motor improvement after decompressive surgery (n = 4), three months after surgery (n = 10), and six months after surgery (n = 4). The group of ten healthy Beagle dogs served as controls.
MMEPs findings and correlation to severity of clinical signs of IVDH
The collected data of this study were averaged for the right and left thoracic and pelvic limbs, respectively. Reproducible MMEPs of the non-affected MECR could be generated in 50 of 50 dogs suffering from IVDH with stimulation intensities ranging from 70 % to 100 % (4.0 Tesla). The waveform of the MMEPs recorded from the MECR was mostly biphasic such as in the healthy controls (Fig. 2A). In contrast, the waveforms generated in the MTC obtained from dogs with clinical signs of IVDH were strikingly polyphasic (Fig. 2B) at stimulation intensities ranging from 80 % to 100 %. Polyphasic waveforms could be found in the MTC of all dogs with IVDH in their pelvic limbs irrespectively of the severity of clinical signs (grade I, II or III). In dogs with neurological deficits of grade IV and V no MMEPs could be generated in the MTCs (Fig. 2C). In 10/50 dogs with paraparesis (grade II: 4/10;
grade III: 6/10) MMEPs could only be generated in one pelvic limb. However, in one dog with spinal hyperesthesia without neurological deficits (group I: 1/6) MMEPs could also only be evaluated in one pelvic limb.
(A) healthy dog (B) dog with clinical signs of IVDH
(C) paraplegic dog (D) dog with functional motor improvement
Figure 2: Onset latency (horizontal bar) was evaluated as the time of distance between stimulus artefact and deflection from the baseline. Peak-to-peak amplitude (vertical bars) was recorded from deepest and highest peak of adverse polarity. The waveform of Magnetic Motor Evoked Potentials (MMEPs) in the controls (A) was mainly biphasic. In contrast, dogs with clinical signs of Interverteral Disk Herniation (IVDH; B) and dogs measured during therapy progression (D) had polyphasic waves. No data could be evaluated in paraplegic dogs (C) as they only showed a stimulus artefact but no subsequent MMEP was generated.
In dogs with IVDH and clinical signs grade I-III onset latencies of the MMEP measured in the cranial tibial muscle were significantly longer (P < 0.0005) and the peak-to-peak amplitude was significantly smaller (P < 0.0004) compared to the healthy controls (Table 1;
Fig. 3).
-Table 1: Mean onset latencies and peak-to-peak amplitudes of Magnetic Motor Evoked Potentials (MMEPs) at Transcranial Magnetic Stimulation (TMS) recorded from the cranial tibial muscle in ten healthy Beagle dogs (controls) and 50 dogs suffering from intervertebral disk herniation (IVDH) with different severity of neurological deficits.
The severity of the neurological deficits was graduated according to Sharp and Wheeler (2005):
Grade I = spinal hyperesthesia; no neurological deficits.
Grade II = ambulatory paraparesis.
Grade III = non-ambulatory paraparesis.
Grade IV = Paraplegia with deep pain sensation.
Grade V = Paraplegia with loss of deep pain sensation.
- = No MMEPs were measurable in paraplegic dogs (grade IV–V)
No significant difference was detected between MMEPs of dogs with different severity of neurological signs (groups I-III; Table 2).
Controls vs.
Grade I, II, III
Grade I vs.
Grade II
Grade I vs.
III
Grade II vs.
Grade III
Grade IV Grade V
P–Value onset latency
< 0.0005* 0.93 0.28 0.56 -
-P–Value peak-to-peak
amplitude
< 0.0004* 0.69 0.31 0.89 -
-Table 2: Comparison of Magnetic Motor Evoked Potentials (MMEPs) findings obtained in the right and left cranial tibial muscle from ten healthy Beagle dogs (controls) and 50 dogs suffering from intervertebral disk herniation (IVDH) with different severity of neurological deficits. The P-values are given for the hypothesis that a difference between the groups exists.
95% Confidence interval.
* significant difference was detected if P < 0.05
In dogs with no voluntary movement in the pelvic limbs (groups IV and V) only the stimulus artefact was obtained and no MMEPs could be generated with stimulation intensities of 80 % to 100 % (Fig. 2C). Therefore, no data concerning onset latency and peak-to-peak amplitude could be assessed (Fig. 3).
Figure 3: In dogs with intervertebral disk herniation (IVDH) with different severity of neurological signs significantly higher onset latencies (P < 0.0005) and smaller peak-to-peak amplitudes (P < 0.0004) were evaluated compared to healthy dogs (controls). Neurological signs were graded according to Sharp and Wheeler (2005) with Grade I: spinal hyperesthesia without neurological deficits; Grade II: ambulatory paraparesis; Grade III: non-ambulatory paraparesis; Grade IV: paraplegia with nociception; Grade V: paraplegia with loss of nociception. No MMEPs could be generated in paraplegic dogs. The boxes contain 95 % of the sample values and the bar is illustrating the median.
Thirtythree dogs were available for the follow-up studies of which 18 showed improvement of their neurological signs. TMS was performed in 4 dogs at the time of functional motor recovery. Only in one of these dogs MMEPs could be generated (Table 3). Ten dogs were available for the TMS three months after decompressive surgery. MMEPs could be evoked in all of these dogs. Four dogs were available for repeated TMS six months following decompressive surgery in all of which MMEPs could be recorded (Table 3). The MMEP waveforms were small and polyphasic in all dogs with prolonged onset latencies and small peak-to-peak amplitudes during the period of functional motor recovery (Table 3). No
MMEPs could be evoked in dogs that did not show improvement of motor function in their Evoked Potentials (MMEPs) at Transcranial Magnetic Stimulation (TMS) in dogs suffering from intervertebral disk herniation (IVDH) in the follow-up examination after decompressive surgery.
No significant differences in onset latencies (P > 0.29) and peak-to-peak amplitudes (P >
0.69) were found in dogs with IVDH and clinical signs grade I-III (n = 15; Fig. 2B) assessed at inital presentation before treatment compared to the findings in dogs with improvement of motor function during the follow-up (Fig. 2D; Fig. 4). The mean of onset latency of the dogs graded I-III at initial presentation was 64.06 ms ± 46.67 and the mean of dogs at therapy monitoring was 67.60 ms ± 34.43 (Fig. 4).
Figure 4: Eighteen of 31 dogs that initially were paraplegic (grade IV + V) showed a functional motor improvement after decompressive surgery. The onset latency of these dogs (therapy-monitoring) was slightly longer (mean 67.6 ms) compared to dogs that were grade I-III before treatment (mean 64.1 ms). However, there was no significant difference in onset latencies (P > 0.29) and peak-to-peak amplitudes (P > 0.69) between these groups. The boxes contain 95 % of the sample values with the bar showing the median.
Discussion
In this study the data of MMEPs generated by TMS in dogs with different severity of neurological signs due to IVDH are presented and compared with data from healthy controls.
Similarly to other studies the dachshund was overrepresented in our study (Aikawa et al., 2012) and also the majority of other dogs were chondrodystrophic or mixed breed dogs. The body dimension of the chondrodystrophic dachshund is associated with a higher risk for a thoracolumbar lesion in the spinal cord and severity of neurological deficits (Levine et al., 2006).
TMS is fast and easy to perform, but unpleasant due to the generalized muscle twitches and the auditory stimulus of the clicking sound from the magnetic stimulator. This necessitated a deep sedation of the patients. MMEPs are known to show individual variability, however in our data, onset latency and peak-to-peak amplitude demonstrated more variability in dogs suffering from IVDH compared to controls, consistent with other studies (Sylvestre et al., 1993; Martin-Vaquero and da Costa, 2014) leading to the conclusion that a high individual variability may correlate with neurological signs. No adverse effects of TMS were seen,
which underlines the reported safety of this method to determine functional integrity of the spinal cord (Nollet et al., 2003).
TMS is a fast technique to assess the descending spinal cord tracts and MMEPs were easily elicited in the non-affected thoracic limbs with mainly biphasic waveforms comparable to the results in other unaffected animals (Van Ham et al., 1994, Nollet et al., 2003, da Costa et al.,
TMS is a fast technique to assess the descending spinal cord tracts and MMEPs were easily elicited in the non-affected thoracic limbs with mainly biphasic waveforms comparable to the results in other unaffected animals (Van Ham et al., 1994, Nollet et al., 2003, da Costa et al.,