Emerging Neurological Syndromes

Emerging Neurologic Syndromes Discussed at World Equine Vet Meeting

“The more we look for neurologic signs, the more we discover new syndromes,” said I.G. Joe Mayhew, BVSc, FRCVS, PhD, Dipl ACVIM, ECVN, head of Equine Massey and professor of Equine Studies at Massey University in New Zealand, at the 2009 WEVA Congress. Mayhew gave several presentations, including an update on emerging neurologic syndromes.

“Over the last five years or so, we have learned much about existing and new (neurologic) disorders in horses from documentation of careful clinical observations and interventions, and from painstaking pathologic studies with special emphasis on clinicopathologic correlates,” he noted. “This paper will highlight a few of these disorders through which we have added to our understanding of anatomy, physiology, and clinicopathologic correlates–the building blocks for advancing equine neurology.”

Unintentional Parasite

Some nematode parasites that cause neurologic disease in wild and domestic ruminants have now been found to cause problems in horses.

Parelaphostrongylus tenuis is a lungworm that’s life cycle includes cervids (horned animals, such as deer) worldwide, including some in North America. This parasite passes through the host’s central nervous system (CNS) as part of its life cycle. In horses (although not a normal host for the parasite), it has been found to cause acquired cervical torticollis (“wry neck”) due to contraction of the cervical muscles that produce a twisting of the neck and an unnatural posture of the head.

“The scoliosis (curvature of the spine) was clearly argued to be due to loss of afferent cervical proprioceptive inputs because of the dorsal gray column lesions with some white matter involvement accounting for ataxia and weakness,” Mayhew said.

“These nematodes appear to be sensitive to various anthelmintics, such as fenbendazole and ivermectin, and such therapy has been successful when the cases have been treated soon after onset of clinical signs,” he continued.

Cervical Vertebrae Problems

Injury to the cervical vertebrae can affect the horse’s balance. “Special proprioceptive inputs from the cranial cervical vertebral ligaments and muscles pass via at least the C1-3 dorsal spinal nerve roots to ascend the spinal cord via the spinovestibular tract to the caudal vestibular nuclei,” said Mayhew. “These nuclei receive no other afferent inputs. Lesions involving these cranial cervical nerves or the vestibulospinal input to the vestibular apparatus can result in signs of vestibular disease (such as incoordination or loss of balance).”

He said confirmation that apparent neck stiffness and pain, or thoracic limb lameness, is emanating from specific arthritic vertebral articulations “requires radiographic and possibly scintigraphic (on bone scan) evidence of active arthritis and positive relief being achieved from intra- and peri-articular injection of local anesthetic agent.”


Mayhew reported on a “very sensitive and quite specific electrophysiologic test for disruption of somatic motor pathways in disease states” for horses with neurologic problems such as wobbler syndrome. “When used with the more elaborate, but error-prone, quantitative EMG investigations, this should allow more accurate identification of the presence and location of conduction blocks (electrical impulses to muscles), and, thus, functional lesions, in neurologic disease states such as wobblers and unusual hind limb gait abnormalities,” he explained.

Scandinavian Knuckling Horses

There have been reports of several individual cases and at least five “outbreaks” in groups of horses of a hind-limb knuckling syndrome. In one outbreak 24 cases occurred in a population of 75 animals. Only three of the 24 survived, and one of those three recovered fully.

Veterinarians have described another 75 cases of idiopathic (unknown origin) knuckling in horses in Norway, with no cause determined, but a frequent finding in the cases was poor feed in the form of low-quality baled silage. “Peripheral neurotoxins of plant or nonbiologic origin would be the most likely cause of these crippling syndromes,” said Mayhew.

Equine Motor Neuron Disease

“Acquired equine motor neuron disease (EMND) is a fascinating neuromuscular disorder of horses that does not appear to have existed prior to 1982 and was first described by the late John Cummings (DVM, PhD) and co-workers from Cornell University in 1993,” noted Mayhew. “Hundreds, if not thousands, of horses now have been definitively diagnosed with EMND in North America and from around the world.”

Clinical signs of EMND in horses depend on the stage of the disease, he said. Those signs in early cases often include weight loss in the face of a good to increased appetite, increased recumbency (inability to rise), and slight muscle tremors at rest. “The weight loss often precedes the onset of trembling by several weeks,” he noted. “Many animals display an extended tailhead position that appears to be due to selective involvement of dorsal sacrococcygeal (pertaining to both the sacrum and the coccyx, or the tailbone) muscles that are postural muscles containing a high proportion of Type 1 (slow-contracting muscle) fibers. Atrophy is followed by fibrous contracture leading to an elevated tail position.

“A short-strided gait is commonly seen that can show a rapid placement of the foot at the end of the protraction phase akin to that seen with fibrotic myopathy,” he described. “This also may well be due to fibrous contracture of affected muscles that in this case are caudal thigh muscles involved in stifle flexion and/or hip extension.

“Ophthalmic examination reveals varying degrees of a mosaic pattern with dark brown to yellow brown pigment deposited in the tapetal zone (the tapetum being the iridescent membrane of the choroid of the eye), coupled with a horizontal band of pigment at the junction of the tapetum and nontapetum,” Mayhew said. “A clinical truism for the syndrome is that affected horses move better than they stand.

“Overall study of this disease has given us a better understanding of syndromes of diffuse weakness in horses and particularly weakness involving Type 1 postural, slow-twitch muscles,” he said.

Equine Polysaccharide Storage Myopathy

Equine polysaccharide storage myopathy (EPSM) is an autosomal recessive disorder in Quarter Horse and related breeds and can result in rather exceptional susceptibility to recurrent exertional rhabdomyolysis, reviewed Mayhew.

“The disease EPSM thus refers to the clinical syndrome of muscle disease, particularly rhabdomyolysis, with amylase-resistant, sarcolemmal inclusions of acid mucopolysaccharides evident on muscle biopsy sample,” he said. However, to differentiate EPSM from other diseases of this type, “where there are clinical signs of myopathy (muscle disease or disorder), but histologic evidence of no or mild myopathic changes with excess aggregates or cores of sarcoplasmic (material in which the fibrillae of the muscle fiber are embedded), mostly amylase-sensitive polysaccharide (glycogen), then a distinguishing term such as polysaccharide-associated myopathy should be used.”

EPSM is seen particularly as a likely autosomal recessive trait in Quarter Horses and related breeds and in several other breeds including draft horses.

EPSM is one cause of exertional rhabdomyolysis, and glycogen-associated myopathy probably is also.

“Signs of a hypometric (short-strided) gait, reluctance to move, thoracolumbar lordotic (swayback), and kyphotic (hunchback) postures, and several movement disorders can be seen in association with these disorders,” Mayhew said. He added that “glycogen-associated myopathy is not the cause of most cases of the common postural and movement disorder known as shivers in draft horse and many other breeds.”

Hyperkalemic Periodic Paralysis

Veterinarians have reported the autosomal dominant disease known as hyperkalemic periodic paralysis (HYPP) in Quarter Horse and Quarter Horse-related breeds. Most affected animals are 2 to 3 years old and are male. Homozygous animals (having identical alleles on the paired chromosome) are more severely affected than heterozygotes (those having only one allele).

“The owner notices intermittent episodes of muscle trembling over the body or face, sometimes with intermittent projection of the nictitating membrane (third eyelid), that may lead to involuntary recumbency,” said Mayhew. “Other warning signs include yawning, lowering of the neck, swaying, and disinterest in food and water. During a mild episode the horse is alert, appears distracted and reluctant to move, and may stumble as if weak.” He said that in a full-blown episode, fasciculations (muscle tremors), particularly involving the flank, shoulders, neck, and sometimes the face, progress to staggering, buckling, marked muscle spasms, and paralysis of the limbs might precede involuntary recumbency.

“A severe episode, perhaps following forced exercise, results in severe tremor and tetany (spasming) of many muscles with recumbency and sweating,” he described. “This is followed by a state of flaccidity, possibly with depressed spinal reflexes. Attempts to move the patient result in further tremor and tetany, although the horse remains alert. An episode may last several minutes to hours, typically less than an hour, with full and usually rapid recovery occurring. Between episodes, affected, well-muscled Quarter Horses appear essentially normal.

He said most owners notice stridor (high-pitched respiratory noise) at some time in affected horses. Exercise and rest following exercise might precipitate episodes, which can occur daily or monthly. Stressors such as transportation, weaning, and anesthesia also can trigger episodes.

Stiff Horse Syndrome

Mayhew said a stiff horse syndrome–similar to stiff person syndrome–has been reported. Clinical signs appear to wax and wane and range from mild muscle stiffness to sudden and often violent muscle contractions. Generally, the onset is insidious.

“Between episodes the horse may appear normal, although generalized muscle stiffness may persist,” said Mayhew. “Stiff person syndrome (SPS) has been recognized in humans for some time. It is characterized by muscle rigidity and episodic and often violent muscle cramps.”

In horses, Mayhew described, “Exercise intolerance associated with mild to moderate muscle stiffness may be the only initial clinical sign. This may easily be attributed to a primary myopathy, with pain on muscle palpation, although serum muscle enzyme concentrations remain in the normal range. Components of the syndrome bear resemblance to such disorders as tetanus, equine motor neuron disease, hyperkalemic periodic paralysis, exertional myopathies, and especially the acquired channelopathies associated with the mycotoxicoses, such as perennial ryegrass staggers.

“The most useful diagnostic test is detection of antibodies against the enzyme glutamic acid decarboxylase (GAD) in serum and cerebrospinal fluid, and although some cases have had high anti-GAD titers, several strongly suspected cases have been negative on this test,” Mayhew noted. “It may be necessary to liaise with a human hospital for analyzing for GAD antibodies in the obtained samples. The test relies on cross-reaction with human antigens.

“The overall message really is that with the array of enigmatic movement and postural disorders encountered in equine neurology that appear to be variations on the themes of stringhalt, shivering, and claudication (cramping), a broad approach to delving into possible etiologic mechanisms should be taken that includes the possibility of immune-associated neurotransmitter derangements, such as SPS.”

Grass Sickness

Grass sickness (equine dysautonomia) has been described since the early 20th century, said Mayhew. “Since then it has had quite a devastating effect on equine populations in parts of Western Europe,” he added. “Horses of all breeds, as well as nondomestic equidae and camelids, can be affected, and dogs, cats, rabbits, and hares are affected by similar dysautonomias.”

Mayhew said this disease usually occurs in 3- to 8-year-old horses that are kept outside during late spring and summer, although cases occur year-round. The problem rarely is seen in stalled animals.

“The disease occurs commonly in Northern and Western Europe, particularly in Scotland and England,” he said. “More recently it has been recorded as an epizootic (a disease that appears as new cases in a given animal population, during a given period, at a rate that substantially exceeds what is “expected” based on recent experience) in Hungary, where 15 out of 55 1- to 3-year-old horses in one group succumbed to the disease over one summer, with only three surviving.

“An identical equine dysautonomia known as mal seco occurs in at least Argentina and Chile in South America, and grass sickness appears to now occur in the horse in North America,” stated Mayhew.

Clinical signs can range from acute colic with gastrointestinal stasis (slowing/stopping) and rupture, to anorexia with mild signs of colic and ileus, to chronic intestinal disorder.

“Moderate tachycardia (rapid heart rate), indifference to food, difficulty swallowing, excessive salivation, depressed gastrointestinal sounds, abdominal distension, and usually mild colic are very often present to varying degrees,” noted Mayhew. “Muscular tremor and patchy sweating may be primary signs or may reflect the dehydration, electrolyte imbalances, and colic that occur. Posturing with all feet close together as a weak patient does, ptosis (drooping eyelid), and especially rhinitis sicca (wasting of the mucous membranes and glands with no secretions) are very distinctive signs when present. No definitive clinical diagnostic test exists.”

Atypical Myopathy

Mayhew said several hundred cases of highly fatal, atypical myopathy or myoglobinuria (myoglobin in urine, causing it to appear red-tinged) have been reported in young adult grazing horses. Most of these have been reported in Europe, but they’ve also been detected in North America and Australasia.

“Horses may be found dead or more often showing various signs of reluctance to move, stiff and short strides, apparent sedation, and fine muscle tremors,” he noted. “They quickly become laterally recumbent and urine becomes dark with myoglobin staining, although more subacute cases do occur.”

Symptomatic fluid and analgesic therapy (given as clinical signs dictate) with attentive nursing care for severely ill and often recumbent patients is called for, but the mortality rate of the disease is around 90%.

“Outbreaks do occur, usually in the colder months, and can occur repeatedly on a property,” noted Mayhew. “Access to trees and inclement weather appear to be risk factors for the disease. Plant, bacterial, and fungal toxins have all been considered as possibilities, but the cause or causes remain completely unknown.”

He said preliminary results from one group of investigators suggested thatClostridium sordellii and Clostridium bifermentans toxins might play a role in what they term “pasture myodystrophy.”

Veterinarians with suspected cases are urged to log on to the atypical myopathy alert site (ivis.org) and complete the appropriate forms. This might help in the effort to unravel the epidemiology of this disease.

Lateral Digital Myotenectomy to Treat Stringhalt

Mayhew said stringhalt, also known as springhalt and Hahnentritt (“rooster kick”), is an anciently recorded disease that is characterized by a sudden, apparently involuntary, exaggerated flexion of one or both hind limbs during attempted movement.

“The hind limb motion may be as mild as a slightly excessive flexion to violent movements during which the fetlock or toe will contact the abdomen, thorax, and occasionally the elbow with attempted strides leading to a peculiar bunny hopping and plunging gait,” he described. “The form that usually occurs as outbreaks is seen in Australia, New Zealand, United States, Chile, and Japan, and will be referred to as bilateral, plant-associated stringhalt.”

Usually there is symmetrical or slightly asymmetrical involvement of the pelvic limbs in this syndrome, with prominent distal (farther away from the horse’s core) muscle atrophy in severe cases. The thoracic limbs are also affected in severe cases, with knuckling of the forelimb fetlocks, prominent extension of more proximal joints (those closer to the horse’s body), and atrophy of the distal musculature in association with prominent stringhalt in both hind limbs.

Bilateral stringhalt has been associated with exposure to several plants, notably related species of flat weeds: Hypochoeris radicata, Taraxacum officinale (the common dandelion), and Malva parviflora (mallow weed).

“It is interesting that size and age may be predisposing factors in at least bilateral stringhalt, in so far as older and taller horses tend to become affected in preference to smaller horses, such as ponies and native Chilean breeds,” noted Mayhew. “Although palliative, removing a section of the myotendinous region of the lateral digital extensor muscle relieves the syndrome quite spectacularly in many cases.”

Temporohyoid Osteoarthropathy

Temporohyoid osteoarthropathy (THO) with proliferative osteopathy (bone disease) involving the temporal bone, temporohyoid joint, and hyoid bone in the head, is reported only in adult horses, said Mayhew. It might be subclinical (undetectable) or can result in difficulty chewing or, more often, neurologic syndromes, notably various combinations of facial and vestibulochoclear (ear) nerve dysfunction. (The horse’s tongue lies on the floor of the mouth and is composed of a mass of muscle anchored by the hyoid bone and the bodies of the left and right mandibles–lower jaw.)

“Some of the cases have bilateral disease as determined by endoscopic and radio imaging studies, although the clinical signs are most often unilateral (on one side),” said Mayhew. “The cause of temporohyoid osteoarthropathy is unclear, although to this author a traumatic origin is most plausible in most cases with chronic otitis (ear) media/interna (inflammation of middle/inner ear structures) accounting for a select few cases.

“Regardless of the etiology of the osteoarthritis, clinical signs can occur from either the osteoarthritis itself or from fractures of the adjacent temporal bone and, rarely, basilar bones, due to partial or complete fusion of the joint,” he said. “Physical examination findings may include difficulty chewing, pain on external palpation of the parotid area, headshaking, and behavioral problems–especially when being ridden.

“Once the joint is partly fused, sudden forced head jerking, falling, teeth floating, nasogastric intubation, and sudden prolonged vocalization can cause periarticular fractures of the petrous temporal bone, resulting in combinations of an abrupt onset of facial and vestibular nerve dysfunction,” he noted. “Endoscopic examination of the guttural pouch is probably superior to plain radiographic imaging in confirming the presence of the disease by revealing enlargement of the proximal stylohyoid bone due to osteoarthritis when compared to the opposite side. “In acute or progressive cases having ill-defined endoscopic and plain radiographic imaging findings, gamma scintigraphy should be considered as a diagnostic aid.”

Mayhew said he was aware of several cases that improved over time, only to show further signs relative to facial and vestibular nerve dysfunction in weeks to months time. “These would seem to be ideal candidates for unilateral surgical disunion of the hyoid apparatus,” he noted. “Initial surgical disunion of the hyoid apparatus was performed by removal of a midshaft portion of the stylohyoid bone. To reduce the temporary difficulties in swallowing encountered and to reduce the possibility of other real and potential complications of this surgery, the technique of ceratohyoidectomy was proposed and used with success.”

He said that except for major cranial fractures and residual eye problems, the outlook for survival with residual neurologic deficits is quite good. “Of 33 cases of temporohyoid osteoarthropathy, 20 cases survived for which there were longer term follow-up details,” he reported. “Of these, 70% returned to previous level of use, although more than 50% of the 20 horses still had evidence of facial nerve deficits and/or vestibular dysfunction.

“Thus, in spite of some optimistic suggestions, if full athletic performance without neurologic dysfunction is required, then the prognosis with or without surgical intervention has to be fair to guarded for these cases,” he said. “Cases of THO have given us a better insight into the ability of horses to accommodate to vestibular dysfunction and to survive with degrees of facial paralysis.”

Post-Anesthetic Cerebral Necrosis

A newly defined, unexpected complication of apparently routine general anesthesia in some mature horses is diffuse and severe cerebral necrosis, resulting in signs of diffuse (not concentrated or localized) encephalopathy immediately or some hours to days after recovery from anesthesia, reported Mayhew.

There is cerebral edema (fluid swelling) and laminar neuronal cortical necrosis associated with generalized signs that predominantly consist of somnolence (drowsiness) to dementia, central blindness, wandering compulsively, pushing against objects, and ataxia.

“One patient with this tentative diagnosis that recovered showed prominent muzzle and ear twitching, very reminiscent of patients suffering from bacterial meningitis and from West Nile viral meningoencephalitis (inflammation of the brain and the meninges–the membranes that cover the brain),” he said.

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