Acquired equine polyneuropathy in Norway and Sweden: A clinical and epidemiological study



Reasons for performing study

Acquired equine polyneuropathy (AEP, also known as ‘Scandinavian knuckling syndrome’), is a serious disease of unknown aetiology, which emerged clustering in horse farms in Sweden, Norway and Finland in the 1990s. Clinical and epidemiological data regarding the syndrome are scarce.


To describe the clinical and epidemiological findings and outcome in outbreaks of AEP and compare risk factors in affected and unaffected horses on affected farms in Norway and Sweden during 2007–2009.


Neurological examinations were performed and data collected regarding demography, usage, turning-out, feeding, prophylactic strategies and long-term outcome.


Thirteen affected farms with 157 horses of various breeds, of which 42 were AEP cases, were studied. Typical digital extensor dysfunction and knuckling of pelvic limbs were noted in 34 definitive cases. Eight additional plausible cases had a severe, acute course of neurological disease. There were no signs of brain or cranial nerve dysfunction. Cases occurred from December to April, with new cases emerging within 100 days of the index case. Affected and unaffected horses were fed wrapped forage. Prevalence for AEP was 27% and case fatality 29%. The median duration of AEP in survivors was 4.4 months (1–17 months). Survivors returned to full work within 19 months (median 6.6 months). Acquired equine polyneuropathy was less prevalent in horses aged >12 years and young horses had a higher chance of survival than older horses. Management factors did not differ between affected and unaffected horses.


Acquired equine polyneuropathy is a potentially fatal neurological disease characterised by pelvic limb knuckling. Surviving horses returned to normal function after a long period of rest. Cases were clustered in farms during the winter/spring season. Wrapped forage was used in all farms.

Potential relevance

The results provide valuable insights into the clinical examination, handling and prognosis of cases of AEP, an emerging neurological disease of unknown aetiology in horses.


An equine disease characterised by bilateral pelvic limb knuckling has been observed in Sweden [1], Norway [2] and Finland [3] and is sometimes referred to as ‘Scandinavian knuckling syndrome’ [3]. Polyneuropathy with inflammatory demyelination and Schwann cell inclusions has been reported in affected horses [2, 3]. The term ‘acquired equine polyneuropathy (AEP)’ is hereafter used, as suggested by an international workshop on the disease in Helsinki in 2009 (R. Tulamo, personal communication). The aetiology of this disease is unclear. Clinical signs appear mainly in late winter to spring and almost all affected horses have been fed wrapped forage (haylage/silage). Affected horses in Sweden and Norway have clustered within farms [1, 2]. To the authors' knowledge, no outbreaks of AEP have occurred in Sweden since 2009, whereas several outbreaks every year have occurred in Norway.

The clinical and epidemiological pattern of AEP does not readily fit into other characterised diseases in the horse, other animal species or man. Polyneuropathy with knuckling has been described also in 3 horses in Japan, but with different clinical and pathological features (e.g. fore- vs. hindlimb knuckling and primary axonal changes vs. primary Schwann cell lesions) [4, 5].

Polyneuropathy may develop due to toxicological, metabolic or immune-mediated causes, vitamin deficiencies, genetic traits or compression. Inherited polyneuropathies have been previously described in man and dogs [6-9]. Neither compression nor genetic aetiologies have been considered likely in AEP. Acquired polyneuropathies in man are often immune-mediated, e.g. Guillain–Barré syndrome [10]. A forage-related toxicity has been suggested for the aetiology of AEP [1-3]. Similar to AEP, some other neurological diseases in horses that cluster within herds have been hypothesised to be of toxic and toxicoinfectious origin, such as Australian stringhalt [11] and equine grass sickness syndrome [12]. In contrast, equine motor neuron disease has been related to nutritional deficiencies in forage [13, 14].

The aim of this study was to describe the clinical findings and outcome for AEP and compare potential risk factors between affected and unaffected horses on farms where the disease has occurred. Data regarding neurological signs, demography, usage, stabling and turning-out practices, feeding and recent deworming and vaccination strategies in affected and unaffected horses were compared. The long-term survival in horses with AEP and the time before survivors returned to full work was determined.

Materials and methods

Definition of definitive and plausible cases

A case was defined either as a ‘definitive’ or a ‘plausible’ case. ‘Definitive’ cases had digital extensor dysfunction in the pelvic limbs with consistent repeated knuckling. Inclusion criteria were normal behaviour, appetite and alertness. Exclusion criteria were ataxia or neurological signs indicative of brain involvement or a recent history of infectious disease. Most AEP cases were clearly identified when the investigators performed the neurological examination. In addition, horses were classified as definitive cases if they fulfilled the definition earlier or later during the same season according to information collected from the owners or attending veterinarians.

‘Plausible’ cases were horses with severe neurological signs appearing within 2 months prior to the onset of the first definitive AEP case, according to attending veterinarians. These horses were already dead at the time of the examination by the investigators.

Controls were all horses in participating farms deemed unaffected by AEP.

Design of the prospective part of the study

A prospective documentation of neurological signs and potential epidemiological risk factors for horses on farms with AEP in Norway and Sweden was carried out during 2007–2009. Recruitment of cases was encouraged using different types of media. It was estimated that approximately 3 affected farms each year for a period of 3 years could be recruited. Ignoring clustering, between-horse level risk factors with an odds ratio ≥3.5 could be detected, given a power of 80%, confidence of 95%, ratio of controls/cases of 4, an exposure in the controls of 35% and a total sample size of 130 ( Inclusion criteria for farms in the study were availability of affected horses, informed consent of the owners and researchers within a feasible travel distance.


A questionnaire was completed by horse owners at the visit or by telephone. Variables on demography, management (Table 1) and history of lameness or neurological signs of each case and control horse were included. Data for plausible cases were collected as far as possible. Details on grouping of horses in paddocks were documented.

Table 1. Questions on epidemiological attributes for each horse at farms with cases of acquired equine polyneuropathy
CategoryVariableUnit or category
  1. aIf given in interval, mid-interval was used in calculations. bCategorised from free text for analysis. cCombined in the analysis.
I. HorsesAgeYears
Time of residence on farmYears
Bodyweightkg, exact or intervala
BreedFree text, post categorisedb
Pregnant (if mare)Yes/No
Body conditionBelow optimal/optimal/above optimal
Weight changeLost weight/no weight change/gained weight
Lameness reported by owner during last 2 monthsYes/No (diagnosis if Yes)
II. UsageWork frequencyDays in usage/week, exact or interval
Most common type of usageFree text, post categorised
Work intensityLow/medium/high
III. Outdoor/indoorHours spent in paddockHours
Hours spent in stableHours
StablingLoose (group) housing outdoors/individual box housing indoors
Surface in paddockFree text, post categorised
Alone in paddockYes/No
IV. FeedingWrapped forage rationkg/day
Feeds/dayNumber of times
Pellets rationl/day
Oats rationkg/day (converted if given in volume units)
Ad libitum wrapped silageYes/portioned wrapped forage
Molassed sugar beet pulpYes/No
Mineral supplementsYes/No
Vitamin supplementsYes/No
V. Vaccination/dewormingDeworming 1 (most recent)Date
Deworming 2Date
Type of deworming (1 and 2)Product name, post categorised
Most recent influenza vaccinationDate
Most recent tetanus vaccinationDate
Botulism vaccination within 1 yearYes/No; if Yes, date

Clinical and neurological examinations and follow-up

The clinical and neurological examination followed a 2-part protocol (A and B; available on request). Body temperature, mental status, general muscle atrophy and gait were examined in all horses in the initial screening (Part A). Horses were examined at walk, straight trot, trot and abrupt stop, backing-up and, when available, walking up and down a slope. Lungeing was added in some cases. For the gait, the following observations were noted: recumbency; knuckling; toe dragging; circumduction; lameness; inability or unwillingness to back-up and ‘other findings’. ‘Other findings’ observed were described in free text. Knuckling (abnormal position with dorsal side of one or both hooves or fetlocks touching the ground) was graded as follows: tendency for knuckling; knuckling but instantaneously replaced in the correct position; knuckling 1–3 s; knuckling >3 s. For each subtest in Part B, signs of weakness were noted for each limb. Horses with signs suggestive of AEP in Part A were subjected to further examinations (Part B).

Part B included evaluation of general appearance, pulse frequency, mucous membranes, cardiac auscultation and general body posture. Gait and posture evaluation in Part B included the following subtests as described by Mayhew (2009) [15]: serpentine walking, walking in tight circles in both directions as well as sway reactions (tested while standing, walking in straight lines and in circles). Functions of the cranial nerves were evaluated with menace responses, direct and indirect pupillary reflexes, sensitivity in different areas of the head, tone and activity of facial muscles, size, tone and activity of masticatory muscles, vestibular and spontaneous nystagmus, tongue tone, abnormal respiratory noise and swallowing reflexes. A slap-test was performed to evaluate the laryngeal adductory reflex [16]. In addition, the cutaneous trunci reflex, the cervico-facial reflex, tail tone and anal reflex were examined. Each coronary band was pricked with a sharp instrument to test for nociception and flexor reflexes. Also, the skin next to the tail was pricked and, if decreased nociception was observed, it was tested whether a border could be determined for the decreased nociception.

All Norwegian horses in 10 farms were examined by S.H.O. and by S.H.O. and either C.F.I., K.H.J. or A.E. in 6 farms. All Swedish horses in 3 farms were examined by G.G., together with 2 other authors (J.B. and A.E.) in 2 farms. Video recordings were performed at most farms and were reviewed mainly in cases of ambiguity of interpretations. Local veterinarians assisted the farms during the follow-up period. The general progression of the horses was monitored with 2–3 owner interviews within 25 months after the farm visit.

Data analysis

Data were entered into spreadsheets (MS Excel)1. The SAS statistical package2 was used with PROC GLIMMIX for logistic regression and PROC LIFETEST for survival.

Potential risk factors were analysed comparing cases with controls in a case-control design. Frequencies in cases and controls were first compared using the Chi-square or Fisher's exact test and continuous variables compared using the nonparametric Wilcoxon's test. The variables with a univariable P value <0.2 and with nonmissing observations on at least 110 horses were considered for multivariable logistic regression analysis, including farm as random effect. Collinearity of continuous variables was checked. When Spearman's correlation coefficient was >0.8, the variable with the fewest missing observations was selected. The continuous variables were further checked subjectively for linearity using 4 equidistant dummies and if not considered linear kept as dummy variables (categories were further amalgamated if deemed suitable). Each of these variables was first checked together with the random effect and kept in a primary model if the type 3 criterion P value was <0.2, then 2-way interactions between remaining fixed-effect variables were also tried, after which only effects at P<0.05 were kept.

Survival curves and median survival times, where applicable, were created for 4 outcomes calculated relative to day of onset in each case. The first 2 were for mortality: ‘death’ (in all cases) and ‘death’ (in definitive cases, excluding plausible cases). Euthanasia was included in ‘death’. A third survival probability was estimated for ‘the last time knuckling was observed’ (in surviving cases) and the fourth for ‘return to work’, the last only calculated for surviving case horses used for work, i.e. excluding brood mares and unbroken horses. The survival was tested for statistical significant difference relative to age, divided at the median age in the cases; <5.5 or ≥5.5 years of age, using the Log Rank test.


Farms and dates of disease

Suspected cases of AEP were reported during 2007–2009 from 35 Norwegian and 7 Swedish farms, of which 13 farms were included in this study. Geographic location, availability of investigators, late notice in the disease progression, lack of enough surviving horses, or negative consent from owners precluded examinations on other farms. None of the farms had observed AEP before 2007. Cases only occurred for a limited period in each farm. Table 2 shows the number of cases, definitive and plausible and controls per farm. The overall prevalence of AEP was 27%. At the farm level, the prevalence varied from 11–71% (mean 24%), based on 9 farms with 7–40 horses (excluding 4 farms with only 2 or 3 horses; Table 2). Studied farms were located within 100 km of Oslo in Norway and in the south or central parts of Sweden. By farm, the usage of horses was for pleasure (n = 5), breeding/pleasure (n = 3), breeding/harness race training (n = 3), endurance/pleasure (n = 1) and endurance (n = 1). The outbreaks commenced in mid-winter to spring, i.e. December to April. The median time between the onsets of the first and the last cases in farms with several cases was 56 days (3–100; n = 11 farms) including plausible cases, or 28 days (12–82; n = 8 farms), excluding plausible cases.

Table 2. The distribution of 157 horses on 13 case farms with acquired equine polyneuropathy during 2007–2009, relative to country, case status and time parameters
FarmCountryaTotal No. horsesTotal No. AEP casesPlausible casesbDefinitive casescCase fatalities within 3 months from onsetdOnset of index casee relative to onset of first definitive case (days)Day of examination relative to onset of first definitive case
  1. aNO = Norway; SE = Sweden. bPlausible cases were deceased before the visit. cDefinitive cases were examined at the visit. dAll plausible cases died within 0–21 days (median 1 day) of onset, 4 definitive cases were subjected to euthanasia 12–84 days after onset. eIndex case = first neurological case at farm.
 3NO930300 (same)17
 4NO320200 (same)19
 7NO310100 (same)38
 8NO210100 (same)69
11NO1820200 (same)68
12SE1030310 (same)12
13SE4081710 (same)71
All farms1574283412 (29%)  

Cases and control horses

This study includes 157 horses, of which 42 were cases and 115 unaffected controls. Of the 42 affected horses, 34 were identified as definitive cases and 8 as plausible cases. Twenty-eight of the 34 definitive cases had typical clinical signs identified during the neurological examination. One additional definitive case had knuckled frequently for 3 months but improved and did not knuckle during the neurological examination or afterwards. Five other definitive cases presented with typical signs within 1–8 weeks of the farm visit. Seven of 8 plausible cases had acutely become recumbent and were then subjected to euthanasia within 21 days (median one day) of onset of neurological signs. One plausible case died by an accident, possibly related to the weakness, the same day as signs appeared. Knuckling was observed in 2 plausible cases before recumbency and another horse had contusion wounds on the fetlocks, suggesting previous knuckling. The median onset of signs in plausible cases was 24 days before the first definitive case appeared (Table 2).

Neurological examination of controls

Ninety of 115 controls underwent Part A of the neurological examination. In one stable with 40 horses, 25 horses were instead categorised as unaffected by AEP as per trainer's observations at their daily trotting training. However, all controls that shared paddocks with case horses at the time of the visit were examined on that farm. None of the controls had any recent history of neurological signs.

The mental status and body temperature were normal in all examined controls. Mild asymmetrical muscle atrophy was noted in the gluteal and shoulder muscles in 2 controls. Mild lameness, unrelated to neurological problems, was noted in 3 controls (thoracic limb, n = 1; pelvic, n = 2). Another control had signs of shivering. Minor signs, which may relate to weakness, occurred once each in 5 controls, e.g. a tendency to knuckle in a single step. These signs were not repeated during the examination.

Neurological examination of cases

Tendencies for knuckling in the pelvic limbs and knuckling with instant replacement were frequently observed during the examination of 28 cases and sometimes knuckling persisted for up to several seconds (Table 3). Six additional cases (not included in Table 3) had consistent knuckling before (n = 1) or after (n = 5) the day of the visit. Knuckling was generally bilateral, sometimes slightly asymmetric. Signs were most effectively provoked by circling with and without tail pull and at sudden halt from trot (Table 3). Mild to moderate pelvic limb weakness was noted in 16 cases. One horse fell when walking uphill and became recumbent. In 7 cases with severe signs, some gait tests were excluded due to the risk of falling. Dorsal pelvic limb fetlock abrasions, unwillingness or stiffness in movements (often observed when backing-up) and hypermetric or hypometric strides were noted in several cases. One case had upward patellar fixation and another had right pelvic limb lameness (grade 2/5). Three cases had mild and inconsistent signs in the thoracic limbs, i.e. stumbling (n = 2) and a tendency to knuckle (n = 1).

Table 3. Pelvic limb gait abnormalities at the neurological examination of 28 horses with acquired equine polyneuropathy during years 2007–2009 in Norway and Sweden. More than one type of gait abnormality noted in several horses in some subtests. Only the most severe category of knuckling observed was noted for each test
 SubtestCases examined 1Knuckling (any degree)Tendency for knucklingKnuckling but instantaneously placed in the correct positionKnuckling 1–3sKnuckling > 3sToe draggingCircumductionOther remarks 2Total no. of horses with gait abnormalities (any)
  1. 1Seven cases with severe signs were omitted from some tests. A slope was not available for 3 horses. 2Other remarks are further described in the text. 3Six horses showed marked reluctance and stiffness at backing. 4Two horses stumbled on their front limbs when walking downhill. 5One horse stumbled and fell when walking uphill.
Abrupt stop from trot261973%774100%00%00%1973%
Back up327622%3300415%00%14%1037%
Walk downhill418950%621000%00%16%1056%
Walk uphill518633%311116%00%16%739%
BWalk in serpents271348%561114%519%27%1763%
Walk in circles251872%693028%728%28%2288%
Sway reaction straight walk241250%732000%00%00%1250%
Sway reaction at circling231983%667029%730%14%2191%

The mental status and body temperature were unremarkable in all cases. Evaluation of the cranial nerves, spinal reflexes and the nociception resulted in normal findings in almost all case horses. Pupillary reflexes were normal in all tested cases (n = 20). The slap test was performed in 16 cases and a decreased reflex on the left side was noted in 2. Reduced cervico-facial responses were noted in 4 cases, 2 of which had reduced cutaneous trunci reflexes. Two cases had no reaction to the skin pricking test in the thoracic limbs but normal reactions in the pelvic limbs.

Mild local muscle atrophy was noted in 7 cases (gluteal muscles, n = 5 of which one had slight asymmetry; thigh muscles, n = 1; back muscles, n = 1). On average these cases had shown signs of AEP for 49 days (s.d. 21, n = 7), compared with 27 days (s.d. 27, n = 21) for cases without muscle atrophy. The heights of the tubera coxae were asymmetric in one horse.

Epidemiological attributes and risk factor analyses

Tables 4 and 5 summarise the distribution of the continuous and categorical epidemiological risk factor variables by cases and controls. All cases and controls were fed wrapped forage (haylage, ≥500 g DM/kg bwt; or silage, <500 g DM/kg bwt), and some also received hay. In farms No. 12 and 13 (Table 2), 2 different batches of wrapped forages were used in each farm and AEP was only found among horses fed one of the batches. All horses were turned out daily in paddocks with 1–11 other horses or were kept in outdoor loose-housing systems. No horses had access to growing pasture due to the season. Cases shared paddocks with healthy horses, except for 3 cases that were kept alone. Some paddocks contained only nonaffected horses. Few individuals had changed group recently. No cases or controls had been vaccinated against botulism. Reported causes for previous lameness in 5 cases and 5 controls (Table 5) were similar and not related to neurological disease.

Table 4. Continuous risk factor variables on horses, usage, stabling, feeding, vaccination and deworming by cases (n = 42) and controls (n = 115) in a study of acquired equine polyneuropathy during years 2007–2009 in Norway and Sweden
nMeans.d.MedianMinMaxnMeans.d.MedianMins.d.P value
I. HorsesAge (years)406461161129681290.017
Residence on farm (years)363320111033420160.63
Bodyweight (kg)26416111413225700744431194501507000.12
II. UsageWork frequency (days/week)313230688324070.13
III. Outdoor/indoorHours spent in paddock/pasture4019724724113167136240.06
IV. FeedingWrapped forage ration (kg bwt/day)12123118203293112150.046
Feeds/day (n)273131770323170.36
Pellets ration (l/day)172220847222080.61
Oats ration (converted to kg bwt/day)131111221111030.47
V. Vaccination/dewormingMost recent deworming (days)3981577272517297679803430.26
Most recent influenza vaccination (days)35158113121243796316314111305050.50
Most recent tetanus vaccination (days)252371592682470854250280194013660.31
Table 5. Categorical risk factor variables on horses, usage, stabling, feeding, vaccination and deworming by cases (n = 42) and controls (n = 115) in a study of acquired equine polyneuropathy during years 2007–2009 in Norway and Sweden
GeneralVariableCategoryCasesControlsP value
  1. *Not counted in statistical analysis.
I. HorsesGenderMare276460540.48
 Missing*0 4  
 Arabian and English Thoroughbreds92198 
 Icelandic horses2576 
 Standardbred trotter13315247 
 Missing0 5  
Pregnant (if mare)Yes3117121.00
Body conditionBelow optimal722350.055
 Above optimal9282342 
 Missing10 60  
Weight changeLost weight819330.0008
 No weight change327611096 
 Gained weight2522 
Lameness previous 2 monthsYes515560.11
II. UsageMost common usageHack/hobby103431410.43
 Arena riding4141114 
 Trot training6211216 
 Endurance training31011 
 Young horse3101114 
 Brood mare3101013 
 Missing13 39  
Work intensityLow156517260.003
 Missing19 50  
III. Outdoor and stablingStablingLoose (group) housing outdoors245747410.07
 Box (individual) indoors18436859 
Surface in paddockBare ground, no plant growth184759540.79
 Snow, no plant growth19504844 
 Bare ground or snow in forest1333 
 Missing4 5  
Alone in paddock/at pastureYes410440.21
 Missing2 2  
IV. FeedingAd libitum wrapped silageYes256073630.65
 Portioned wrapped forage17404237 
Bran or barleyYes3721180.087
Molassed sugar beet pulpYes71723200.64
 Mineral supplementsYes133139340.73
Vitamin supplementsYes81927230.55
V. Prophylactic treatmentsLast influenza vaccination<6 months226335560.62
 6–12 months12342337 
 >12 months1358 
 Missing7 52  
Last tetanus vaccination<6 months114426480.26
 6–12 months11441528 
 >12 months3121324 
Last deworming<6 months389769961.00
 6–12 months1334 
 >12 months0000 
 Missing3 43  
Type of dewormingBenzimidazoles560.79
 Pyrantel8 16  
 Ivermectin/moxidectin26 45  

Primary random-effects models were made for the continuous variables age and number of hours spent at pasture (both modelled as dummies) and the categorical variables weight change, stabling and whether given bran or barley. Age (P = 0.03) and weight change (P = 0.004) remained in the final model (n = 148). Age was modelled as <4 years (baseline); 4–11 years, odds ratio 0.7 and 95% confidence interval (CI) (0.4–1.0); and ≥12 years, odds ratio 0.1; 95% CI (0.1–0.3). Compared with no weight change (baseline), the odds ratio for weight gain was 6.3 (95% CI 0.6–68), and odds ratio for weight loss 13 (95% CI 2.7–59). The stabling variable left the model at P = 0.06, where ‘box’ had an odds ratio of 0.4. If the dataset was used without the plausible cases, the significant variables remained and stabling did not enter the model.


The case fatality rate for AEP was 29% (Table 2). Within 3 months of diagnosis, one case horse was found dead and 11 were subjected to euthanasia. All 8 plausible cases (100%) were dead within 0–21 days, median one day. Four of the 34 definitive cases (12%) were subjected to euthanasia within 12–84 days. The remaining cases and all controls remained alive throughout the follow-up period (Fig 1), which was 10–25 months (median 21.4 months) after the farm visit. The survival rate was higher in cases younger than 5.5 years (86%) than in older cases (55%; P = 0.02). Six of 8 acute, severely affected plausible cases were >5.5 years of age.

Figure 1.

Survival to death in definitive and plausible cases of acquired equine polyneuropathy (solid line; n = 42), as well as omitting the plausible cases (dashed line; n = 34) in 2007–2009 in Norway and Sweden.

The reasons for euthanasia in 4 definitive cases were recumbency in 2 horses (Days 12 and 24) and persistent severe signs of AEP in one horse (Day 84). The fourth horse was slowly recovering from AEP but was accidently injured and subjected to euthanasia after 49 days. Post mortem examination of a definitive case subjected to euthanasia on Day 12 revealed evidence of demyelination and axonal degeneration in peripheral nerves. Necropsy in 3 plausible cases revealed no gross pathological changes and there was no histological evidence of equine herpesvirus myeloencephalopathy, cerebral or spinal cord lesions but post mortem autolysis prohibited adequate histopathology of the peripheral nerves.

To ensure there was no relapse of AEP, the 30 surviving cases were followed after their recovery, from 2.5 months up to 2.1 years (median 1.9 years) after onset of signs and all horses recovered fully. Knuckling ceased 9 days to 17 months after onset in the survivors, median 4.4 months (95% CI 3.2–5.1; n = 30, one censored). Most surviving cases were simply confined to box rest or a small paddock during recovery. However, intensive efforts were made in one severely affected pony that eventually recovered fully. The pony was lifted repeatedly with slings for 6 weeks each time it laid down but otherwise was kept without slings in a large box stall. All horses previously used for work returned to full work within 19 months, median 6.6 months (95% CI 5.1–8.8) (n = 21, one censored). The median times for return to full work in young horses (<5.5 years of age) and older horses were 6.2 and 10 months, respectively, which were not significantly different (P = 0.053).


Clinical signs and follow-up

Knuckling was used as an inclusion criterion for definitive cases of AEP while obvious ataxia was an exclusion criterion, according to earlier observations in Sweden and Norway [1, 2]. In equines, the combination of pelvic limb knuckling and no obvious ataxia is rather unusual. In a report from Finland on this disease, one knuckling horse also had a moderate to severe ataxia potentially referable to a cervical spinal cord lesion [3]. Such ataxia was not observed in any of the horses from our AEP-affected farms. Eight plausible cases in the present study were acutely and severely affected, some without registration of knuckling before recumbency. Because they appeared temporally close to more typical knuckling cases on the farms, they were likely AEP-affected; however, autolysis prohibited final diagnosis at necropsy. Hanche-Olsen et al. (2008) also reported paraplegia and recumbency within hours of onset in some cases [2].

The tests that most consistently produced typical pelvic limb gait deficits in cases were walking in circles, with and without tail pull (sway reaction test) and abrupt stop from trot. Caution is advocated regarding provoking movement in horses with severe AEP, as they may fall, as occurred in one case. On the other hand, mild cases were identified and 6 cases had no signs on the day of neurological examination, which demonstrates that systematic and repeated examinations are of value in an affected yard. In our experience, physical exercise on deep or uneven surfaces is sometimes necessary to elicit neurological deficits (knuckling) in mild cases or early stages of AEP. Our results indicate that the severity of the neurological signs observed is partly related to when in the disease process the horse is examined. Whether or not the variability also reflects a dose-related toxic aetiology remains to be investigated.

The lesion found in AEP has been described as a demyelinating polyneuropathy [1, 3] and neurological signs other than knuckling are theoretically possible but other signs were uncommon and inconsistent. Hanche-Olsen et al. [2] described decreased sensory perception of skin distal to the hock in a few cases but this was not typical for AEP in the present study. The decreased response to skin pricking in the front limbs in 2 cases might have been due to the stoic nature of these individuals. Repeated examination at another time would have been valuable. Seven case horses and 2 controls had mild focal atrophy of muscles, which is a possible feature of neuropathies. The mild deficit of muscle mass in the croup and back in these cases could also well be an effect of lack of activity during their convalescence. There were no signs of atrophy of digital extensor muscles in the pelvic limbs, which would be the expected location of a possible neurogenic atrophy in a motor neuropathy causing knuckling. Since the 2 controls were not showing any other signs attributable to neuromuscular disease, the mild muscle loss noted was not interpreted as an effect of polyneuropathy. Muscle biopsies may have elucidated this further.

The 29% mortality rate in horses with AEP and loss of horses in 8 of 13 farms in this study demonstrate that the condition often becomes severe and life-threatening. Including plausible cases, mortality was greater in horses older than 5.5 years. The most severely affected pony that survived in the present study was salvaged by repeated lifting with slings. This can be contrasted to a previously reported grave case, similarly supported for 8 weeks and then subjected to euthanasia due to recumbency [2]. In severe and rapidly progressing cases, the prognosis must be guarded, whereas nonrecumbent cases have a good long-term prognosis. The times to cessation of knuckling (median 4.4 months) and to return to work (median 6.6 months) can only be considered an approximate measure of return to health because of the variable ability and keenness of owners for observations of knuckling.

Epidemiology and risk factors

The observed uneven geographical dispersion of AEP remains enigmatic. Only Nordic countries have reported AEP and Norway has most cases both in absolute and relative numbers. During 2007–2009, several-fold higher number of farms and horses were reported with AEP in Norway (10 included farms and 25 other farms) compared with Sweden (3 included farms and 4 other farms), despite the fact that the Swedish horse population is estimated to be 6 times larger than the Norwegian population (Sweden, n = 362,700 in 2010 [17]; Norway, n = 60,000. K. Hustad, personal communication).

The demography as well as the broad spectrum of breeds and usages affected with AEP in the literature infer that AEP is not caused by a genetic trait nor linked to gender and not related to a specific usage of horses. The clinical examination did not detect signs of general infection nor any localised signs from other than the locomotor system, specifically, signs of brain or cranial nerve dysfunction were not present. The clinical and epidemiological findings may fit with a toxic or toxicoinfectious aetiology of AEP involving exposure of several horses on a farm to a common factor, possibly in the forage [1-3]. Immune-mediated reactions may be involved in the pathogenesis in conjunction with a microbial or chemically derived toxin. Further studies on the pathogenesis are needed.

Coincidence of feeding wrapped forage and AEP was demonstrated in the present study, in accordance with most earlier reported cases in Norway and Sweden [1, 2]. The first outbreaks of the knuckling syndrome appeared in Norway and Sweden in the 1990s, concurrent with a shift from hay to wrapped forage on many horse farms. Wrapped forage is now used in over 50% of all horse farms in Sweden and the features of this type of forage have been previously described [18]. An interesting finding in the present study was that cases appeared only among horses fed certain batches of forage on 2 of the studied farms. Temporal and spatial coincidence does not prove a causal relationship and despite the feeding of wrapped forage to all horses in the affected farms in the present study, all were not affected with signs. The earliest cases on the studied premises were often the most severe in this case series. One may speculate on the possibility that there may have been only a short exposure to the putative toxin in some farms, with the horses receiving the highest doses appearing affected first and most severely and the horses with lower exposures taking longer to show up and often presenting milder signs. However, putative toxic factors in forage may be unevenly distributed and sensitivity may differ among individuals, which complicates the interpretation. In contrast to our findings, there are also a few historical observations of AEP cases occurring in late summer–autumn [1, 2], also in Finland with different feeding management [3]. Thus, the hypothesis of a toxic factor in forage remains unproven at this stage. A potential coupling between food poisoning and polyneuropathy exists in man, where the immune-mediated Guillain–Barré syndrome has been associated with exposure to pathogens such as Campylobacter jejuni [10]. The authors are currently carrying out further evaluation of features and management of wrapped forage as risk factors for AEP, as well as neuropathological studies to elucidate the role of the immune system in AEP.

Horses 12 years or older were less associated with AEP than were younger horses. On the other hand, young cases (<5.5 years) had a higher survival rate than older horses and a tendency to return to work in a shorter time. Box stabling at night, compared with loose-housing tended to be less associated with AEP in the multivariable analysis. The interpretation of these findings is unclear, but may be facilitated by increased knowledge on aetiology and pathogenesis. Weight loss before the farm visit was associated with AEP cases. In retrospect, as bodyweight was subjectively estimated by the owner without weighing the horses regularly, we suggest that little emphasis should be put on this finding. Low work intensity was associated with AEP cases in the univariable analysis but due to many missing observations, it was not formally tested in the final multivariable analysis. Thus, correlation to other variables cannot be analysed.

The farms included in the present study represented around 30% of the farms that reported having AEP during the period. Inclusion of more farms would have strengthened the study but the sampled farms (type, size, time of year) seem to be representative of the typical affected population. The power in the case–control part was low and inherent was that nonaffected horses were part of affected herds. Compared with the power calculation if a reasonable design effect of 2 would prevail, then a sample size twice the current size would be needed to find significant differences.

Considering the prospective approach used in the present study, there was a relatively large amount of missing data; however, data on missing variables were actively sought and updated to a large degree. In the multivariable analyses there were varying numbers of observations for each variable and in the final model 148 of 157 horses were included. The approach made it possible to use most of the data in the final conclusions. This means that all models in the analysis were not done on the same dataset, i.e. during model reduction the models were not truly hierarchical. Reduced datasets did not alter the conclusions (data not shown).


Acquired equine polyneuropathy, an emerging peripheral neurological disease in horses, is characterised by pelvic limb knuckling without other signs of general disease. Signs progressed to recumbency in one-third of the cases, which led to euthanasia. Surviving horses returned to health and work after months of rest. Cases clustered in farms during winter/spring season and all cases and controls were fed wrapped forage. Horses of a younger age were more often affected than older horses, but tended to recover more rapidly. A forage-related aetiology for this disease is a possibililty, but has not been proven. Other management risk factors for cases within affected stables were not identified.

Authors' declaration of interests

No competing interests have been declared.

Sources of funding

This study was funded by the Swedish-Norwegian Foundation for Equine Research, Grant no. V0747001.


Horse owners and local veterinarians are gratefully acknowledged for their cooperation.


All authors contributed to the design of the study, the clinical examinations and approved the final version of the manuscript. Data collection and study execution including analysis and interpretation of the data and preparation of the manuscript were done by G.G., S.H.O., K.H.J. and A.E. Statistics were performed by A.E.

Manufacturers' addresses

  1. 1

    Microsoft Corporation, Redmond, Washington, USA.

  2. 2

    SAS Institute Inc., Cary, North Carolina, USA.