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Differentiation between musculoskeletal and neurologic causes of lameness in horses: 22 cases (1993–1995)
Refereed
DIFFERENTIATION BETWEEN MUSCULOSKELETAL AND NEUROLOGIC CAUSES OF LAMENESS IN HORSES: 22 CASES (1993-1995) D.P. Moore, DVM; N.A. White, DVM, MS
SUMMARY
Medical records of 78 horses tested for EPM via Western Blot and/or PCR tests on cerebrospinal fluid between January 1993 and September 1995 were examined. Twenty-two (Group 2) of the 78 horses in which the origin of gait abnormality (musculoskeletal vs neurologic system) could not be clearly determined on initial examination were compared to the rernalning 56 horses (Group 1). Horses in Group 2 were compared with respect to signalment, presenting problem, history, physical examination findings, results of diagnostic tests, and final diagnosis. Horses in Group 2 were more likely to be of warmblood breed and to be presented for lameness or for gait abnormality of uncertain origin (musculoskeletal vs neurologic). All horses presented for lameness or for gait abnormality of uncertain origin whose CSF samples subsequently tested positive for EPM were in Group 2. Horses in Group 2 tended to have multiple problems involving mild hind limb lameness and/or mild neurologic deficits. Some similarities of unusual movement were observed among cases where movement description was recorded. There was a marked increase in positive test results for EPM among Group 2 horses after introduction of the Polymerase Chain Reaction (PER) test.
INTRODUCTION
or spasm, mechanical dysfunction, or neurologic abnormality. While most cases of lameness are attributed to musculoskeletal pain, lesions of the nervous system can produce gait abnormalities that may be difficult to distinguish from musculoskeletal lameness, a Equine protozoal myeloencephalitis (EPM), caused by the protozoal parasite Sarcocystis neurona, a-7 can present with various combinations of neurologic signs, a'7-9 including gait abnormalities. Beginning in 1991, an antemortem diagnostic test a became available which could detect antibodies to the causative agent of EPM in blood or cerebrospinal fluid (CSF). s'6'1~ The presence of antibodies in serum only indicates exposure to the organismS,6'1~ a positive test result on CSF is required for diagnosis of disease. Consequently there has been an increase in the number of horses referred for collection of CSF for EPM testing. As EPM testing became available and was completed on suspicious cases, we noted that horses with subtle or difficult to diagnose gait deficits were frequently positive for EPM. This led us to question whether such horses might be affected by EPM more frequently than other horses tested for EPM. The purposes of the study reported here were to determine the prevalence of EPM in cases examined for gait abnormality in which the origin of the abnormality (musculoskeletal vs neurologic system) could not be clearly determined on initial examination, and to identify any characteristics unique to this group. C r i t e r i a for S e l e c t i o n of C a s e s
Authors' address: Marion duPont Scott Equine Medical Center, Virgima-Maryland Regional Collegeof VeterinaryMedmme, P.O. Box 1938,
The medical records of all horses tested for EPM at the Marion duPont Scott Equine Medical Center between January 1993 and September 1995 were reviewed. From these records, horses were separated into 2 groups: those in which the origin of gait abnormality (musculoskeletal vs neurologic
Leesburg, VA 22075
aWestern Immunoblot analysis,
Lameness in horses indicates either a structural or functional disorder, 1 and may be due to pain, muscular weakness
56
JOURNAL OF EQUINE VETERINARY SCIENCE
system) could not be clearly determined on initial examination comprised Group 2. The remaining horses comprised Group 1. Data recorded for each horse included signahnent, presenting problem, history, physical examination findings, results of diagnostic tests, and final diagnosis. Follow-up information was obtained from the owners by telephone or letter. Standard procedures were followed for lameness and neurologic examinations, as have been described in detail elsewhere.l,11 CSF samples were obtained via sterile collection through the lumbosacral space. 12 Throughout the rest of this report, the term "lameness" will be used to denote deviation from normal gait resulting from musculoskeletal dysfunction; abnormal gait resulting from neurologic dysfunction will be referred to as neurologic gait deficit. Deviation from normal gait which could not be clearly attributed to either the musculoskeletal or neurologic system will be referred to as gait abnormality of uncertain origin.
RESULTS
Seventy-eight cases were tested for EPM antibodies in CSF between January 1, 1993 and September 1, 1995. After initial examination at our hospital, the origin of gait abnormality (musculoskeletal vs neurologic) could not be clearly determined in 22 of these horses. These comprised Group 2, and consisted of nine Thoroughbreds, three Quarter Horses, three Crossbreds, five Warmbloods, and two horses of other breeds, with a mean age of 7.0 years (range, 2 - 12 years). Eight horses were female, one was a stallion, and 13 were geldings. Examination results in these 22 horses are reported in Table 1. The remaining 56 horses were assigned to Group 1, which consisted of 30 Thoroughbreds, six Quarter Horses, seven Crossbreds, three Warmbloods, five Arabians, and five horses of other breeds. Mean age was 8.7 years (range, three months to 28 years). Seventeen horses were female, eight were sexually intact males, and 31 were geldings. Presenting problems identified in the records for Group 1 horses were: ataxia (n = 30), other neurologic abnormalities (e.g., seizures) (n = 13), lameness (n = 5), gait abnormality of uncertain origin (n = 5), or other (e.g., colic, exercise intolerance) (n = 9 ). (These numbers add up to more than 56 because six cases presented with multiple problems.) Among the horses in which the origin of the gait deficit could not be determined at initial examination, four presented for ataxia, three for other neurologic problems, ten for lameness, seven for gait abnormality of uncertain origin, and one for other problems. (These numbers add up to more than 22 because three cases presented with multiple problems.) Positive western blot (WB) titers to Sarcocystis neurona in the CSF were detected in 13 Group 1 horses: nine of those presented with ataxia, one presented with other neurologic abnormalities, and three presented with other problems. In addition, suspect titers were detected in two horses presented Volume 18, Number 1, 1998
with ataxia and five presented with other neurologic problems. WB tests of CSF detected EPM in one of the Group 2 horses presented for ataxia, one presented for other neurologic problems, one presented for lameness, and one presented for gait abnormality of uncertain origin. In addition, suspect titers were detected in two horses presented for lameness, and two presented for gait abnormality of uncertain origin. Results were unavailable in one case, and in one horse CSF was not obtained. Beginning in 1995, some CSF samples were also analyzed via the recently- developed polymerase chain reaction (PCR) test, which detects the presence ofSarcocystis neurona DNA. la,14 Of the 11 WB suspect CSF samples in the group of all horses tested, four were subjected to further testing by the PCR test. In each of these cases (one Group 2 horse presented for lameness, two Group 2 and one Group 1 horse presented for gait abnormality of uncertain origin) the PCR test confirmed a diagnosis of EPM. In two Group 2 cases presented for lameness and one Group 1 case presented for ataxia, initial testing by WB analysis.was negative, but PCR testing confirmed a diagnosis of EPM. Overall, the number of Group 1 horses testing positive for EPM via WB and/or PCR tests on CSF was 10/30 presented for ataxia, 1/13 presented for other neurologic abnormalities, 1/5 presented for lameness, and 3/9 presented for other problems. None of the Group I horses presented for gait abnormality of uncertain origin tested positive for EPM via WB and/or PCR tests on CSF. Results were unavailable in eight cases, and in two horses, CSF could not be obtained (Table 2). Among Group 2 horses, 1/4 presented for ataxia, 1/ 3 presented for other neurologic problems, 3/10 presented for lameness, and 4/7 presented for gait abnormality of uncertain origin tested positive for EPM via WB and/or PCR tests on CSF. The overall incidence of EPM found in the horses in this study was 22% in Group 1 and 36% in Group 2. This compares with positive findings in 40% of 2000 CSF samples tested in 1994 by the laboratory which developed the test. e Final diagnosis of EPM was reached in 12 of the 56 Group 1 cases, other neurologic disease in 28, and other in three. No diagnosis was reached in 10 cases, and two horses were diagnosed with more than one problem (Table 3). Final diagnosis of EPM was reached in eight of the Group 2 cases, other neurologic disease in nine, and lameness in 13. Twelve of the Group 2 cases had final diagnosis of both a lameness and a neurologic gait defect. In three cases it was never determined whether the gait abnormalities were due to MS or neurologic causes (Table 3). In those cases in which a final diagnosis of lameness was reached (with or without concurrent neurologic disease), lameness was localized to one hind limb in seven cases, to both hind limbs in four cases, to one forelimb in one case, and to both fore and hind limbs in one case. Within Group 2, presenting gait abnormalities were observed in the hind limb(s) in 18 cases, forelimb(s) in 2 57
Table 1. Signalment, presenting problem, primary abnormalities, Equine Protozoal Myelitis (EPM) test results, and final diagnosis for 22 horses. For signalment, yr = years old, g = gelding, m = mare, f = filly, s = stallion; c o m m o n breed abbreviations are used. For presenting problem, A = ataxia, L= lameness, N-other = other neurologic problem, UO = gait abnormality of uncertain origin, O = other. For primary abnormalities and final diagnosis, R = right, L = left, F = fore, H = hind. EPM test results are given for Western Blot (WB) analysis on serum and cerebrospinal fluid (CSF), and polymerase chain reaction (PCR) analysis on CSF; nd = not done, unk = results unavailable.
Signalment
Presenting Problem
Assessment
WBSerum
9 yr TB g
UO
Gr 2 lame LH, responsive to flexion, blocked out high volar. Mild proprioceptive deficits, limited flexion of neck, enlarged cervical articular facets but myelogram WNL.
4 yr Trk m
UO
1 1/2 year history of RH lameness, unknown cause. Neurologic vs lameness cause not differentiated.
WBCSF
s
PCRCSF
Final Diagnosis
nd
1. Mild neurologic disease, unknown etiology. 2. LH fetlock lameness, unknown etiology.
nd
Not determmed whether neurologic or lame.
2 yr TB f
L
Stiff but not lame in RH. Limited flexion of unk neck, reluctant to circle left, mild propriocepttve deficits worsened by neck manipulation.
unk
unk
Cervical static stenosis.
9 yr Hol g
A initially L on 6 wk re-check
9 mo history of ataxia and tremors. 6 wk treat+ ment for EPM resolved neurologic abnormalities at re-check; however, lameness present at that time. One year later horse euthanatized due to persistent neurological deficits.
nd
nd
Neurologic defictts and lameness both present; not clear if problems were concurrent. Etiology unknown.
7 yr TB m
L and A
nd
1. RH and LH lameness, unknown etiology. 2. Possible concurrent neurologic deficit, unknown etiology.
nd
1. EPM. 2. Possible concurrent lameness, etiology unknown.
Lame RH, pos to flexion RH and LH. Questionable neurologic defictts.
s
12 yr TB/QH m L and muscle atrophy
Lame RF. BJlat shoulder muscle atrophy. Moderate to marked proprioceptive deficits, weakness.
+
7 yr Morg m
L
Gr 2/4 lame left hock. IA anesthesia caused RH lameness and ataxia to become apparent. Forelimbs gr 1 ataxia, hind hmbs gr 2 ataxia, spasticity, and paresis.
+
nd
1. Left hock lameness, etiology unknown. 2. Cervical spinal cord lesion, etiology unknown.
9 yr QH g
L
Acute onset severe lameness. Marked hypermetria in hmd limbs. Painful to hoof testers. Abaxial sesamoid block resolved lameness and hypermetria 90%. Normal after corrective shoeing and 5 wks rest.
+
nd
Sore feet.
5 yr TB/Conn m
A
Ataxia, waxing and waning head tilt, cranial nerve deficits. Also lame RH and LF, RF lame after LF blocked.
+
nd
1. Primary neurologtc disease strongly suspected but not confirmed. 2. LF lameness due to pastern DJD. 3. RF lameness due to suspensory desmitis. 4. RH lameness due to soft-tissue strain.
Gr 2/4 lame RH, not responsive to blocks. Neurologic deficits revealed with tests of proprioceptlon.
+
+
1. Cervical static stenosis. 2. EPM. 3. Possible concurrent RH lameness, etiology unknown.
3 yr TWH g
58
UO
+
JOURNAL OF EQUINE VETERINARY SCIENCE
Table 1. (Continued) Signalment
Presenting Problem
Assessment
WBSerum
WBCSF
PCRCSF
+
Final Diagnosis EPM.
4 yr~Hol s
L
History of RH lameness for 1 yr. Treated for EPM for 6 mos with no improvement. Gr 2/4 lame RH, not responsive to blocks. Abnormal response to tests of propfiocept]on; not clear how much due to pain.
3 yr TB f
L
Acute onset of severe lameness. Muscle atrophy + and cranial nerve deficits present. Not clear whether gait abnormality due to ataxia or upper limb injury.
11 y r T B g
L
Gait abnormalities attributed to gr 1 proprioceptive deficits, not lameness.
EPM.
Not determined whether neurologic or lame.
unk
Encephalomyelitis; histopathology consistent with viral origin.
4 yr DWB m
UO
Unable to distinguish neurologic vs lameness cause for long-standing RH abnormality.
7 yr QH g
UO
Very mild proprioceptJve deficits, with possible concurrent hmd limb lameness.
nd
1. EPM. 2. Possible concurrent hind lameness, etiology unknown.
5 yr TB g
UO
Gr 1/4 lameness and gr 1/4 proprioceptive deficits in RH.
nd
1. EPM. 2. Right hock lameness, etiology unknown. EPM.
10 yr TBX g
A
Gr I paresis and propnoceptive deficits in LH. Other 3 limbs neurologically normal. Lameness exam not done.
6 yr DWB g
N-other
Presented for 1 mo history of seizures. Gr 1 ataxia RF, gr 1 spasticity LH, also lame RH. Seizures not observed.
nd
Neurologic deficits and lameness both present. Cerebro-cortical lesion responsible for seizures.
6 yr TB g
L and A
1st Exam - Gr I proprioceptive deficits reportedly present since purchase 6 mos previous. Also lame LF (P1 chtp fracture) for 2.5 wks. 2nd Exam, 9 mos later - lame RF for 2 mos., no diagnosis. Nuclear scan neg. No neurologic abnormalities at this time.
nd
1st Exam-lameness due to P1 chip fracture,cause of neurologic abnormalities not determined. 2nd Exam - cause of lameness not deter mined, neurologically normal.
9 yr TB g
N-other
Referred for seizures/weakness. L side gluteal muscle atrophy. Lame LH, pos to flexion. No proprioceptive deficits. No seizures observed.
nd
None.
UO; also O
3 mo history of attitude change, reluctance to exercise, and lameness. Exam revealed no lameness and no neurologic abnormahtles.
15 yr QH g
7 yr TB g
L
Volume 18, Number 1, 1998
Shifting hmd leg lameness for 1 yr, mild gluteal muscle atrophy. Slight LH lameness and gr 1-2 ataxia observed.
EPM
nd
Neurologic deficits and lameness both present. Etiology unknown.
59
Table 2. Comparison of Groups 1 and 2 on the basis of positive EPM test results via Western Blot and/or PCR, by presenting problem. Presenting problems = A (ataxia), N-other (other neurologic problem), L (lameness), UO (cases in which it was unclear to the referring individual whether the origin of the gait abnormality was musculoskeletal or neurologic), and Other. Figures represent number of horses.
Group 1:
Group 2:
A 10/30 (33%)
N-Other L 1/13 1/5 (8%) (20%)
UO 0/5 (0%)
Other_ 3/9 (33%)
1/4 (25%)
1/3 (33%)
4/7 (57%)
0/1 (0%)
3/10 (30%)
cases, both fore and hind limbs in one case, and in neither in one case. Lameness grade was recorded for 11 horses - three were grade 0, one was grade 1, six were grade 2, and one was grade 4. Neurologic deficits were graded for 11 horses - two were grade 0, one was grade 0.5, six were grade 1, one was grade 1.5, and one was grade 2. Five of these horses had both lameness and neurologic deficits graded. The 3 horses with lameness grade 0 had neurologic deficits of grade 0, 0.5, and 1. The horse with grade 1 lameness also had a grade 1 neurologic deficit, and one of the horses with grade 2 lameness had a grade 1.5 neurologic deficit. Descriptions of the observed abnormal gait were recorded for 6 cases in Group 2. Dragging of the hind toe(s) was mentioned (3 horses); hyper-extension of the hind limb(s) (2 horses), a "slapping" motion of the lower hind leg(s) (2 horses), and excessive twisting of the hind feet were each mentioned (2 horses). The hyper-extension was described as affecting the hock in one horse, "as if flexion, and the initiation of the anterior phase of the stride, were delayed." In the other horse the limb was observed to undergo a period of very rapid extension from the fetlock distally as the limb approached ground contact, ending in a straight downward movement of the hoof which resulted in a flat-footed "slap" at ground contact. In the other horse for which a slapping motion was recorded, it was described as resulting in a shortened anterior phase of the stride, and was exacerbated by flexion. The excessive twisting of the hind feet was described as landing on the lateral hoof wall followed by a medial twisting of the hoof throughout the entire period of ground contact. In one horse the twisting motion was described as affecting the limb all the way up to the hock. Horses in Group 2 were reported to have had symptoms for an average of 7 months (range, 2 weeks to 30 months).
DISCUSSION
In our experience, neurologic problems that are most likely to produce gait deficits that might be confused with MS lameness include EPM and spinal cord compression. Consequently the introduction of the WB test on CSF, and subse60
Table 3. Comparison of Groups 1 and 2 on the basis of final diagnosis. Figures represent number of horses. Some horses appeared in multiple categories. Other Neurologic EPM Disease Lameness O t h e r None Multiple Group 1 12 28 0 3 10 2 (22%) (51%) (0%) (5.5%) (18%) (3.5%) Group 2
8 (36%)
9 (41%)
13 (59%)
0 (0%)
3 12 (14%) (54.5%)
quently the PCR test for antemortem diagnosis of EPM has greatly facilitated diagnosis of these challenging cases. Since the WB test detects the presence of antibodies to Sarcocystis neurona, a positive result on serum only indicates exposure to the organism. 5,6,t~ Recent reports estimate that 33-55% of horses have positive serum titers6; most of these show no signs of EPM. A positive result on CSF indicates that active disease is probable, s'l~ Low levels of antibody in the CSF will be reported as suspect; active disease is possible in these cases, or the low level of antibody may be due to contamination by serum antibody. Such contamination can occur in situ via blood brain barrier compromise, or iatrogenically via contamination of the sample with blood, s,10 None of the samples in our study were noted to be contaminated, although it is possible that a small amount of contamination might have gone undetected. The WB test is reported to detect antibody in 90% of active EPM cases. 5'1~ Affected horses which test negative may have a failure of antibody production, which could be due to immunosuppression or immuno-incompetence. 5'1~ Negative results can also occur in horses with acute EPM if they are tested before they have had time to mount a measurable immune response. 5,to Negative tests also tend to occur in chronic cases, 5,t~ and cases that have been treated for several weeks have been known to convert from positive to negative. 5 Falsely positive results are reported in approximately 6% of cases, b and are thought to be due to contamination of the CSF with serum antibody. 5,t~ Analysis of the CSF albumin quotient and IgG index at the time of sample collection may help to rule out false positives due to iatrogenic contamination 15; these tests were not performed on the samples in our study. The PCR test can be falsely negative if enzymes destroy the sarcocyst DNA. b This can occur in severe cases with marked inflammation, cases with a very strong immune response, or through improper sample handling, b Samples need to be chilled immediately after collection, and shipped chilled overnight in an EDTA tube. b In comparing Groups 1 and 2, some characteristics unique to Group 2 were identified. Breed distribution appeared to be similar between the two groups with the excepbGranstromDE: Personalcommunication.GluckEquineCenter,Department of VeterinarySciences,Unwers~tyof Kentucky,Lexington,Kentucky, 1995. JOURNAL OF EQUINE VETERINARY SCIENCE
tion of warmblood breeds, which were represented twice as frequently in Group 2. Further studies are needed in order to determine whether warmbloods are consistently over represented among cases which are difficult to diagnose, or whether this was a chance finding in our study. We suggest that any overrepresentation may be due not to any biological characteristic, but rather to the prevalence of their use as dressage horses. We think that dressage horses in our area are subjected to closer scrutiny of their gait during training, particularly in the hind limbs, than horses engaging in other activities; this may have resulted in them being referred for more subtle gait deficits. All of the horses presented for lameness or for gait abnormality of uncertain origin which subsequently tested positive on WB analysis of CSF were in Group 2. This suggests that horses presented for lameness which are found to have neurologic gait deficits, or horses presented with doubt as to whether the problem is MS or neurologic in origin, should be viewed as possible EPM cases. The additional information provided by the eight PCR tests which were submitted on horses in Group 2 was very helpful in establishing a diagnosis. Based on only WB results, 10% of the cases in Group 2 which presented for lameness and 14% of those presented for gait abnormality of uncertain origin would have been diagnosed with EPM. Addition of PCR test results increased these percentages to 45.5% and 32%, respectively. In Group 1, the additional information provided by the PCR test resulted in a change of diagnosis, from EPM negative to EPM positive, for one horse. All of the WB suspect cases which were tested via PCR (both groups) were confirmed to be positive for EPM. The WB suspect cases which were not tested via PCR received a diagnosis other than EPM in four out of six cases. This raises the question of whether these suspect cases might have been diagnosed differently had PCR results been available. The same question could be applied to the 34 WB negative cases which were not tested via PCR. The number of PCR test results available to us is too low to draw any conclusions about how frequently this information may change the outcome of a case; nevertheless it appears to be highly beneficial to run both tests on all CSF samples submitted. It was difficult to determine the cause of the gait abnormality in Group 2 horses for several reasons. Over half of the horses in this group had multiple problems. In addition lamenesses and neurologic deficits were mild. While the number of these cases is too low to conclude whether or not the descriptions of gait alterations represent characteristic movement, future attention to detailed record keeping, including descriptions of unusual gait, may help to identify signs indicative of EPM. Mild hind limb lameness and mild neurologic gait deficits may present a similar clinical appearance. Horses presenting with lameness which cannot be definitively localized or which is accompanied by unusual movement should receive a thorough neurologic examination; if neurologic deftVolume 18, Number 1, 1998
cits are suspected, EPM should be considered as one of the diagnostic rule outs.
REFERENCES 1. Stashak TS: Adams' Lameness in Horses. 4th ed. Philadelphia: Lea & Febiger, 1987;906 pp. 2. TurnerTA: Hindlimb lameness or neurologic disease?, Proc Am Coil Vet Int Med Annu Meet 1993;584-586. 3. Bowman DD: Equine protozoal myeloencephalitis: history and recent developments. Eq Pract 1991 ;13:28-33. 4. Davis SW, Daft BN, Dubey JP: Sarcocystis neurona cultured in vitro from a horse with equine protozoal myelitis. Eq Vet J 1991 ;23:315-317. 5. Granstrom DE: Diagnosis of equine protozoal myeloencephalitis:western blot analysis, in Pro Am Coil Vet Int Med Ann Meet 1993;587-590. 6. Granstrom DE: Equine protozoal myeloencephalitis. AAEP Report, July 1995;6-7. 7. MacKay RJ, Davis SW, Dubey JP: Equine protozoal myeloencephalitis. Compend Cent Educ Pract Vet 1992; 14:13591367. 8. Boy MG, Galligan DT, Divers T J: Protozoal encephalomyelitis in horses: 82 cases. J Amer Vet Med Assoc 1990; 196:632-634. 9. Yvorchuk K: Protozoal myeloencephalitis.In: Robinson, NE, ed. Current Therapy in Equine Medicine. 3rd ed. Philadelphia: W.B.Saunders Co., 1992;554-556. 10. Moore BR, Granstrom DE, Reed SM: Diagnosis of equine protozoal myeloencephalitis and cervical stenotic myelopathy. Compend Cont Educ Pract Vet 1995; 17:419-428. 11. Coyne CP, Cox J: Neurological examination. In: Robinson NE, ed. Current Therapy in Equine Medicine. 3rd ed. Philadelphia: W.B.Saunders Co., 1992;521-526. 12. Coyne CP: Cerebrospinal fluid collection and analysis. In: Robinson NE, ed. Current Therapy in Equine Medicine. 3rd ed. Philadelphia: W.B.Saunders Co., 1992; 527-530. 13. Fenger CK, Granstrom DE, Langemeier JL, et al.: Phylogenetic relationship of Sarcocystis neurona to other members of the family Sarcocystidae based on small subunit ribosomal RNA gene sequence. J Parasitol 1994;80:966- 975. 14. Granstrom DE, MacPherson JM, Gajadhar AA, et al.: Differentiataon of Sarcocystis neurona from eight related coccidia by random amplified polymorphic DNA assay. Mol Cell Probes 1994;8:353-356. 15. Andrews FM, Maddux JM, Faulk D: Total protein, albumin quotient, IgG and IgG index determtnatlons for horse cerebrospinal fluid. Prog Vet Neurol 1996; 1: 197-204.
61
DIFFERENTIATION BETWEEN MUSCULOSKELETAL AND NEUROLOGIC CAUSES OF LAMENESS IN HORSES: 22 CASES (1993-1995) D.P. Moore, DVM; N.A. White, DVM, MS
SUMMARY
Medical records of 78 horses tested for EPM via Western Blot and/or PCR tests on cerebrospinal fluid between January 1993 and September 1995 were examined. Twenty-two (Group 2) of the 78 horses in which the origin of gait abnormality (musculoskeletal vs neurologic system) could not be clearly determined on initial examination were compared to the rernalning 56 horses (Group 1). Horses in Group 2 were compared with respect to signalment, presenting problem, history, physical examination findings, results of diagnostic tests, and final diagnosis. Horses in Group 2 were more likely to be of warmblood breed and to be presented for lameness or for gait abnormality of uncertain origin (musculoskeletal vs neurologic). All horses presented for lameness or for gait abnormality of uncertain origin whose CSF samples subsequently tested positive for EPM were in Group 2. Horses in Group 2 tended to have multiple problems involving mild hind limb lameness and/or mild neurologic deficits. Some similarities of unusual movement were observed among cases where movement description was recorded. There was a marked increase in positive test results for EPM among Group 2 horses after introduction of the Polymerase Chain Reaction (PER) test.
INTRODUCTION
or spasm, mechanical dysfunction, or neurologic abnormality. While most cases of lameness are attributed to musculoskeletal pain, lesions of the nervous system can produce gait abnormalities that may be difficult to distinguish from musculoskeletal lameness, a Equine protozoal myeloencephalitis (EPM), caused by the protozoal parasite Sarcocystis neurona, a-7 can present with various combinations of neurologic signs, a'7-9 including gait abnormalities. Beginning in 1991, an antemortem diagnostic test a became available which could detect antibodies to the causative agent of EPM in blood or cerebrospinal fluid (CSF). s'6'1~ The presence of antibodies in serum only indicates exposure to the organismS,6'1~ a positive test result on CSF is required for diagnosis of disease. Consequently there has been an increase in the number of horses referred for collection of CSF for EPM testing. As EPM testing became available and was completed on suspicious cases, we noted that horses with subtle or difficult to diagnose gait deficits were frequently positive for EPM. This led us to question whether such horses might be affected by EPM more frequently than other horses tested for EPM. The purposes of the study reported here were to determine the prevalence of EPM in cases examined for gait abnormality in which the origin of the abnormality (musculoskeletal vs neurologic system) could not be clearly determined on initial examination, and to identify any characteristics unique to this group. C r i t e r i a for S e l e c t i o n of C a s e s
Authors' address: Marion duPont Scott Equine Medical Center, Virgima-Maryland Regional Collegeof VeterinaryMedmme, P.O. Box 1938,
The medical records of all horses tested for EPM at the Marion duPont Scott Equine Medical Center between January 1993 and September 1995 were reviewed. From these records, horses were separated into 2 groups: those in which the origin of gait abnormality (musculoskeletal vs neurologic
Leesburg, VA 22075
aWestern Immunoblot analysis,
Lameness in horses indicates either a structural or functional disorder, 1 and may be due to pain, muscular weakness
56
JOURNAL OF EQUINE VETERINARY SCIENCE
system) could not be clearly determined on initial examination comprised Group 2. The remaining horses comprised Group 1. Data recorded for each horse included signahnent, presenting problem, history, physical examination findings, results of diagnostic tests, and final diagnosis. Follow-up information was obtained from the owners by telephone or letter. Standard procedures were followed for lameness and neurologic examinations, as have been described in detail elsewhere.l,11 CSF samples were obtained via sterile collection through the lumbosacral space. 12 Throughout the rest of this report, the term "lameness" will be used to denote deviation from normal gait resulting from musculoskeletal dysfunction; abnormal gait resulting from neurologic dysfunction will be referred to as neurologic gait deficit. Deviation from normal gait which could not be clearly attributed to either the musculoskeletal or neurologic system will be referred to as gait abnormality of uncertain origin.
RESULTS
Seventy-eight cases were tested for EPM antibodies in CSF between January 1, 1993 and September 1, 1995. After initial examination at our hospital, the origin of gait abnormality (musculoskeletal vs neurologic) could not be clearly determined in 22 of these horses. These comprised Group 2, and consisted of nine Thoroughbreds, three Quarter Horses, three Crossbreds, five Warmbloods, and two horses of other breeds, with a mean age of 7.0 years (range, 2 - 12 years). Eight horses were female, one was a stallion, and 13 were geldings. Examination results in these 22 horses are reported in Table 1. The remaining 56 horses were assigned to Group 1, which consisted of 30 Thoroughbreds, six Quarter Horses, seven Crossbreds, three Warmbloods, five Arabians, and five horses of other breeds. Mean age was 8.7 years (range, three months to 28 years). Seventeen horses were female, eight were sexually intact males, and 31 were geldings. Presenting problems identified in the records for Group 1 horses were: ataxia (n = 30), other neurologic abnormalities (e.g., seizures) (n = 13), lameness (n = 5), gait abnormality of uncertain origin (n = 5), or other (e.g., colic, exercise intolerance) (n = 9 ). (These numbers add up to more than 56 because six cases presented with multiple problems.) Among the horses in which the origin of the gait deficit could not be determined at initial examination, four presented for ataxia, three for other neurologic problems, ten for lameness, seven for gait abnormality of uncertain origin, and one for other problems. (These numbers add up to more than 22 because three cases presented with multiple problems.) Positive western blot (WB) titers to Sarcocystis neurona in the CSF were detected in 13 Group 1 horses: nine of those presented with ataxia, one presented with other neurologic abnormalities, and three presented with other problems. In addition, suspect titers were detected in two horses presented Volume 18, Number 1, 1998
with ataxia and five presented with other neurologic problems. WB tests of CSF detected EPM in one of the Group 2 horses presented for ataxia, one presented for other neurologic problems, one presented for lameness, and one presented for gait abnormality of uncertain origin. In addition, suspect titers were detected in two horses presented for lameness, and two presented for gait abnormality of uncertain origin. Results were unavailable in one case, and in one horse CSF was not obtained. Beginning in 1995, some CSF samples were also analyzed via the recently- developed polymerase chain reaction (PCR) test, which detects the presence ofSarcocystis neurona DNA. la,14 Of the 11 WB suspect CSF samples in the group of all horses tested, four were subjected to further testing by the PCR test. In each of these cases (one Group 2 horse presented for lameness, two Group 2 and one Group 1 horse presented for gait abnormality of uncertain origin) the PCR test confirmed a diagnosis of EPM. In two Group 2 cases presented for lameness and one Group 1 case presented for ataxia, initial testing by WB analysis.was negative, but PCR testing confirmed a diagnosis of EPM. Overall, the number of Group 1 horses testing positive for EPM via WB and/or PCR tests on CSF was 10/30 presented for ataxia, 1/13 presented for other neurologic abnormalities, 1/5 presented for lameness, and 3/9 presented for other problems. None of the Group I horses presented for gait abnormality of uncertain origin tested positive for EPM via WB and/or PCR tests on CSF. Results were unavailable in eight cases, and in two horses, CSF could not be obtained (Table 2). Among Group 2 horses, 1/4 presented for ataxia, 1/ 3 presented for other neurologic problems, 3/10 presented for lameness, and 4/7 presented for gait abnormality of uncertain origin tested positive for EPM via WB and/or PCR tests on CSF. The overall incidence of EPM found in the horses in this study was 22% in Group 1 and 36% in Group 2. This compares with positive findings in 40% of 2000 CSF samples tested in 1994 by the laboratory which developed the test. e Final diagnosis of EPM was reached in 12 of the 56 Group 1 cases, other neurologic disease in 28, and other in three. No diagnosis was reached in 10 cases, and two horses were diagnosed with more than one problem (Table 3). Final diagnosis of EPM was reached in eight of the Group 2 cases, other neurologic disease in nine, and lameness in 13. Twelve of the Group 2 cases had final diagnosis of both a lameness and a neurologic gait defect. In three cases it was never determined whether the gait abnormalities were due to MS or neurologic causes (Table 3). In those cases in which a final diagnosis of lameness was reached (with or without concurrent neurologic disease), lameness was localized to one hind limb in seven cases, to both hind limbs in four cases, to one forelimb in one case, and to both fore and hind limbs in one case. Within Group 2, presenting gait abnormalities were observed in the hind limb(s) in 18 cases, forelimb(s) in 2 57
Table 1. Signalment, presenting problem, primary abnormalities, Equine Protozoal Myelitis (EPM) test results, and final diagnosis for 22 horses. For signalment, yr = years old, g = gelding, m = mare, f = filly, s = stallion; c o m m o n breed abbreviations are used. For presenting problem, A = ataxia, L= lameness, N-other = other neurologic problem, UO = gait abnormality of uncertain origin, O = other. For primary abnormalities and final diagnosis, R = right, L = left, F = fore, H = hind. EPM test results are given for Western Blot (WB) analysis on serum and cerebrospinal fluid (CSF), and polymerase chain reaction (PCR) analysis on CSF; nd = not done, unk = results unavailable.
Signalment
Presenting Problem
Assessment
WBSerum
9 yr TB g
UO
Gr 2 lame LH, responsive to flexion, blocked out high volar. Mild proprioceptive deficits, limited flexion of neck, enlarged cervical articular facets but myelogram WNL.
4 yr Trk m
UO
1 1/2 year history of RH lameness, unknown cause. Neurologic vs lameness cause not differentiated.
WBCSF
s
PCRCSF
Final Diagnosis
nd
1. Mild neurologic disease, unknown etiology. 2. LH fetlock lameness, unknown etiology.
nd
Not determmed whether neurologic or lame.
2 yr TB f
L
Stiff but not lame in RH. Limited flexion of unk neck, reluctant to circle left, mild propriocepttve deficits worsened by neck manipulation.
unk
unk
Cervical static stenosis.
9 yr Hol g
A initially L on 6 wk re-check
9 mo history of ataxia and tremors. 6 wk treat+ ment for EPM resolved neurologic abnormalities at re-check; however, lameness present at that time. One year later horse euthanatized due to persistent neurological deficits.
nd
nd
Neurologic defictts and lameness both present; not clear if problems were concurrent. Etiology unknown.
7 yr TB m
L and A
nd
1. RH and LH lameness, unknown etiology. 2. Possible concurrent neurologic deficit, unknown etiology.
nd
1. EPM. 2. Possible concurrent lameness, etiology unknown.
Lame RH, pos to flexion RH and LH. Questionable neurologic defictts.
s
12 yr TB/QH m L and muscle atrophy
Lame RF. BJlat shoulder muscle atrophy. Moderate to marked proprioceptive deficits, weakness.
+
7 yr Morg m
L
Gr 2/4 lame left hock. IA anesthesia caused RH lameness and ataxia to become apparent. Forelimbs gr 1 ataxia, hind hmbs gr 2 ataxia, spasticity, and paresis.
+
nd
1. Left hock lameness, etiology unknown. 2. Cervical spinal cord lesion, etiology unknown.
9 yr QH g
L
Acute onset severe lameness. Marked hypermetria in hmd limbs. Painful to hoof testers. Abaxial sesamoid block resolved lameness and hypermetria 90%. Normal after corrective shoeing and 5 wks rest.
+
nd
Sore feet.
5 yr TB/Conn m
A
Ataxia, waxing and waning head tilt, cranial nerve deficits. Also lame RH and LF, RF lame after LF blocked.
+
nd
1. Primary neurologtc disease strongly suspected but not confirmed. 2. LF lameness due to pastern DJD. 3. RF lameness due to suspensory desmitis. 4. RH lameness due to soft-tissue strain.
Gr 2/4 lame RH, not responsive to blocks. Neurologic deficits revealed with tests of proprioceptlon.
+
+
1. Cervical static stenosis. 2. EPM. 3. Possible concurrent RH lameness, etiology unknown.
3 yr TWH g
58
UO
+
JOURNAL OF EQUINE VETERINARY SCIENCE
Table 1. (Continued) Signalment
Presenting Problem
Assessment
WBSerum
WBCSF
PCRCSF
+
Final Diagnosis EPM.
4 yr~Hol s
L
History of RH lameness for 1 yr. Treated for EPM for 6 mos with no improvement. Gr 2/4 lame RH, not responsive to blocks. Abnormal response to tests of propfiocept]on; not clear how much due to pain.
3 yr TB f
L
Acute onset of severe lameness. Muscle atrophy + and cranial nerve deficits present. Not clear whether gait abnormality due to ataxia or upper limb injury.
11 y r T B g
L
Gait abnormalities attributed to gr 1 proprioceptive deficits, not lameness.
EPM.
Not determined whether neurologic or lame.
unk
Encephalomyelitis; histopathology consistent with viral origin.
4 yr DWB m
UO
Unable to distinguish neurologic vs lameness cause for long-standing RH abnormality.
7 yr QH g
UO
Very mild proprioceptJve deficits, with possible concurrent hmd limb lameness.
nd
1. EPM. 2. Possible concurrent hind lameness, etiology unknown.
5 yr TB g
UO
Gr 1/4 lameness and gr 1/4 proprioceptive deficits in RH.
nd
1. EPM. 2. Right hock lameness, etiology unknown. EPM.
10 yr TBX g
A
Gr I paresis and propnoceptive deficits in LH. Other 3 limbs neurologically normal. Lameness exam not done.
6 yr DWB g
N-other
Presented for 1 mo history of seizures. Gr 1 ataxia RF, gr 1 spasticity LH, also lame RH. Seizures not observed.
nd
Neurologic deficits and lameness both present. Cerebro-cortical lesion responsible for seizures.
6 yr TB g
L and A
1st Exam - Gr I proprioceptive deficits reportedly present since purchase 6 mos previous. Also lame LF (P1 chtp fracture) for 2.5 wks. 2nd Exam, 9 mos later - lame RF for 2 mos., no diagnosis. Nuclear scan neg. No neurologic abnormalities at this time.
nd
1st Exam-lameness due to P1 chip fracture,cause of neurologic abnormalities not determined. 2nd Exam - cause of lameness not deter mined, neurologically normal.
9 yr TB g
N-other
Referred for seizures/weakness. L side gluteal muscle atrophy. Lame LH, pos to flexion. No proprioceptive deficits. No seizures observed.
nd
None.
UO; also O
3 mo history of attitude change, reluctance to exercise, and lameness. Exam revealed no lameness and no neurologic abnormahtles.
15 yr QH g
7 yr TB g
L
Volume 18, Number 1, 1998
Shifting hmd leg lameness for 1 yr, mild gluteal muscle atrophy. Slight LH lameness and gr 1-2 ataxia observed.
EPM
nd
Neurologic deficits and lameness both present. Etiology unknown.
59
Table 2. Comparison of Groups 1 and 2 on the basis of positive EPM test results via Western Blot and/or PCR, by presenting problem. Presenting problems = A (ataxia), N-other (other neurologic problem), L (lameness), UO (cases in which it was unclear to the referring individual whether the origin of the gait abnormality was musculoskeletal or neurologic), and Other. Figures represent number of horses.
Group 1:
Group 2:
A 10/30 (33%)
N-Other L 1/13 1/5 (8%) (20%)
UO 0/5 (0%)
Other_ 3/9 (33%)
1/4 (25%)
1/3 (33%)
4/7 (57%)
0/1 (0%)
3/10 (30%)
cases, both fore and hind limbs in one case, and in neither in one case. Lameness grade was recorded for 11 horses - three were grade 0, one was grade 1, six were grade 2, and one was grade 4. Neurologic deficits were graded for 11 horses - two were grade 0, one was grade 0.5, six were grade 1, one was grade 1.5, and one was grade 2. Five of these horses had both lameness and neurologic deficits graded. The 3 horses with lameness grade 0 had neurologic deficits of grade 0, 0.5, and 1. The horse with grade 1 lameness also had a grade 1 neurologic deficit, and one of the horses with grade 2 lameness had a grade 1.5 neurologic deficit. Descriptions of the observed abnormal gait were recorded for 6 cases in Group 2. Dragging of the hind toe(s) was mentioned (3 horses); hyper-extension of the hind limb(s) (2 horses), a "slapping" motion of the lower hind leg(s) (2 horses), and excessive twisting of the hind feet were each mentioned (2 horses). The hyper-extension was described as affecting the hock in one horse, "as if flexion, and the initiation of the anterior phase of the stride, were delayed." In the other horse the limb was observed to undergo a period of very rapid extension from the fetlock distally as the limb approached ground contact, ending in a straight downward movement of the hoof which resulted in a flat-footed "slap" at ground contact. In the other horse for which a slapping motion was recorded, it was described as resulting in a shortened anterior phase of the stride, and was exacerbated by flexion. The excessive twisting of the hind feet was described as landing on the lateral hoof wall followed by a medial twisting of the hoof throughout the entire period of ground contact. In one horse the twisting motion was described as affecting the limb all the way up to the hock. Horses in Group 2 were reported to have had symptoms for an average of 7 months (range, 2 weeks to 30 months).
DISCUSSION
In our experience, neurologic problems that are most likely to produce gait deficits that might be confused with MS lameness include EPM and spinal cord compression. Consequently the introduction of the WB test on CSF, and subse60
Table 3. Comparison of Groups 1 and 2 on the basis of final diagnosis. Figures represent number of horses. Some horses appeared in multiple categories. Other Neurologic EPM Disease Lameness O t h e r None Multiple Group 1 12 28 0 3 10 2 (22%) (51%) (0%) (5.5%) (18%) (3.5%) Group 2
8 (36%)
9 (41%)
13 (59%)
0 (0%)
3 12 (14%) (54.5%)
quently the PCR test for antemortem diagnosis of EPM has greatly facilitated diagnosis of these challenging cases. Since the WB test detects the presence of antibodies to Sarcocystis neurona, a positive result on serum only indicates exposure to the organism. 5,6,t~ Recent reports estimate that 33-55% of horses have positive serum titers6; most of these show no signs of EPM. A positive result on CSF indicates that active disease is probable, s'l~ Low levels of antibody in the CSF will be reported as suspect; active disease is possible in these cases, or the low level of antibody may be due to contamination by serum antibody. Such contamination can occur in situ via blood brain barrier compromise, or iatrogenically via contamination of the sample with blood, s,10 None of the samples in our study were noted to be contaminated, although it is possible that a small amount of contamination might have gone undetected. The WB test is reported to detect antibody in 90% of active EPM cases. 5'1~ Affected horses which test negative may have a failure of antibody production, which could be due to immunosuppression or immuno-incompetence. 5'1~ Negative results can also occur in horses with acute EPM if they are tested before they have had time to mount a measurable immune response. 5,to Negative tests also tend to occur in chronic cases, 5,t~ and cases that have been treated for several weeks have been known to convert from positive to negative. 5 Falsely positive results are reported in approximately 6% of cases, b and are thought to be due to contamination of the CSF with serum antibody. 5,t~ Analysis of the CSF albumin quotient and IgG index at the time of sample collection may help to rule out false positives due to iatrogenic contamination 15; these tests were not performed on the samples in our study. The PCR test can be falsely negative if enzymes destroy the sarcocyst DNA. b This can occur in severe cases with marked inflammation, cases with a very strong immune response, or through improper sample handling, b Samples need to be chilled immediately after collection, and shipped chilled overnight in an EDTA tube. b In comparing Groups 1 and 2, some characteristics unique to Group 2 were identified. Breed distribution appeared to be similar between the two groups with the excepbGranstromDE: Personalcommunication.GluckEquineCenter,Department of VeterinarySciences,Unwers~tyof Kentucky,Lexington,Kentucky, 1995. JOURNAL OF EQUINE VETERINARY SCIENCE
tion of warmblood breeds, which were represented twice as frequently in Group 2. Further studies are needed in order to determine whether warmbloods are consistently over represented among cases which are difficult to diagnose, or whether this was a chance finding in our study. We suggest that any overrepresentation may be due not to any biological characteristic, but rather to the prevalence of their use as dressage horses. We think that dressage horses in our area are subjected to closer scrutiny of their gait during training, particularly in the hind limbs, than horses engaging in other activities; this may have resulted in them being referred for more subtle gait deficits. All of the horses presented for lameness or for gait abnormality of uncertain origin which subsequently tested positive on WB analysis of CSF were in Group 2. This suggests that horses presented for lameness which are found to have neurologic gait deficits, or horses presented with doubt as to whether the problem is MS or neurologic in origin, should be viewed as possible EPM cases. The additional information provided by the eight PCR tests which were submitted on horses in Group 2 was very helpful in establishing a diagnosis. Based on only WB results, 10% of the cases in Group 2 which presented for lameness and 14% of those presented for gait abnormality of uncertain origin would have been diagnosed with EPM. Addition of PCR test results increased these percentages to 45.5% and 32%, respectively. In Group 1, the additional information provided by the PCR test resulted in a change of diagnosis, from EPM negative to EPM positive, for one horse. All of the WB suspect cases which were tested via PCR (both groups) were confirmed to be positive for EPM. The WB suspect cases which were not tested via PCR received a diagnosis other than EPM in four out of six cases. This raises the question of whether these suspect cases might have been diagnosed differently had PCR results been available. The same question could be applied to the 34 WB negative cases which were not tested via PCR. The number of PCR test results available to us is too low to draw any conclusions about how frequently this information may change the outcome of a case; nevertheless it appears to be highly beneficial to run both tests on all CSF samples submitted. It was difficult to determine the cause of the gait abnormality in Group 2 horses for several reasons. Over half of the horses in this group had multiple problems. In addition lamenesses and neurologic deficits were mild. While the number of these cases is too low to conclude whether or not the descriptions of gait alterations represent characteristic movement, future attention to detailed record keeping, including descriptions of unusual gait, may help to identify signs indicative of EPM. Mild hind limb lameness and mild neurologic gait deficits may present a similar clinical appearance. Horses presenting with lameness which cannot be definitively localized or which is accompanied by unusual movement should receive a thorough neurologic examination; if neurologic deftVolume 18, Number 1, 1998
cits are suspected, EPM should be considered as one of the diagnostic rule outs.
REFERENCES 1. Stashak TS: Adams' Lameness in Horses. 4th ed. Philadelphia: Lea & Febiger, 1987;906 pp. 2. TurnerTA: Hindlimb lameness or neurologic disease?, Proc Am Coil Vet Int Med Annu Meet 1993;584-586. 3. Bowman DD: Equine protozoal myeloencephalitis: history and recent developments. Eq Pract 1991 ;13:28-33. 4. Davis SW, Daft BN, Dubey JP: Sarcocystis neurona cultured in vitro from a horse with equine protozoal myelitis. Eq Vet J 1991 ;23:315-317. 5. Granstrom DE: Diagnosis of equine protozoal myeloencephalitis:western blot analysis, in Pro Am Coil Vet Int Med Ann Meet 1993;587-590. 6. Granstrom DE: Equine protozoal myeloencephalitis. AAEP Report, July 1995;6-7. 7. MacKay RJ, Davis SW, Dubey JP: Equine protozoal myeloencephalitis. Compend Cent Educ Pract Vet 1992; 14:13591367. 8. Boy MG, Galligan DT, Divers T J: Protozoal encephalomyelitis in horses: 82 cases. J Amer Vet Med Assoc 1990; 196:632-634. 9. Yvorchuk K: Protozoal myeloencephalitis.In: Robinson, NE, ed. Current Therapy in Equine Medicine. 3rd ed. Philadelphia: W.B.Saunders Co., 1992;554-556. 10. Moore BR, Granstrom DE, Reed SM: Diagnosis of equine protozoal myeloencephalitis and cervical stenotic myelopathy. Compend Cont Educ Pract Vet 1995; 17:419-428. 11. Coyne CP, Cox J: Neurological examination. In: Robinson NE, ed. Current Therapy in Equine Medicine. 3rd ed. Philadelphia: W.B.Saunders Co., 1992;521-526. 12. Coyne CP: Cerebrospinal fluid collection and analysis. In: Robinson NE, ed. Current Therapy in Equine Medicine. 3rd ed. Philadelphia: W.B.Saunders Co., 1992; 527-530. 13. Fenger CK, Granstrom DE, Langemeier JL, et al.: Phylogenetic relationship of Sarcocystis neurona to other members of the family Sarcocystidae based on small subunit ribosomal RNA gene sequence. J Parasitol 1994;80:966- 975. 14. Granstrom DE, MacPherson JM, Gajadhar AA, et al.: Differentiataon of Sarcocystis neurona from eight related coccidia by random amplified polymorphic DNA assay. Mol Cell Probes 1994;8:353-356. 15. Andrews FM, Maddux JM, Faulk D: Total protein, albumin quotient, IgG and IgG index determtnatlons for horse cerebrospinal fluid. Prog Vet Neurol 1996; 1: 197-204.
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