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Complementary and alternative medicine for neurologic disorders
Complementary and Alternative Medicine for Neurologic Disorders Karen L. Kline, DVM, MS, CVA, Diplomate ACVIM, Neurology
The use of complementary and alternative veterinary medicine in treating neurologic disorders has increased in popularity in response to advances in human alternative and integrative therapies. Neurolocalization of lesions to the brain, spinal cord, and neuromuscular systems is discussed, as well as the diagnostics and therapeutics used to treat such disorders. Emphasis is placed on integrative and alternative treatments for such neurologic diseases as seizures, cerebrovascular accidents, canine cognitive disorder, meningitis, intervertebral disc disease, fibrocartilagenous embolism, degenerative myelopathy, and myopathies. Thorough physical and neurologic examinations, establishment of a correct diagnosis, and integrative therapeutics are aimed at improving the overall quality of life of the veterinary patient. Copyright 2002, Elsevier Science (USA). All rights reserved.
omplementary and alternative veterinary medmine (CAVM) has become more popular with the advent of more accepted practices in the human medical sciences. National Institutes of Health (NIH) grants on alternative medicine and its benefits have been numerous and are lending credibility to a field of veterinary medicine that is both progressive and has its roots in ancient practice and philosophies. Complementary medicine implies the use of alternative techniques coupled with conventional medicine. As the field of veterinary medicine expands and envelops more modalities of therapy, owners are increasingly looking for other means to enhance their animal's quality of life and health. The use of complementary techniques in the treatment of veterinary neurologic diseases has increased in popularity over the last two decades. This popularity is due to a number of factors and undoubtedly stems from a crossover from human medicine. The use of CAM in human neurologic disease has been well studied. Indications for the use of CAVM in the treatment of neurologic diseases are numerous, but patient and individual case selection, as well as correct diagnosis, are of utmost importance. Knowing when to offer complementary and alternative medical intervention to an animal with neurologic disease is as important as the physical examination, correct interpretation of blood work, and diagnostic imaging. Without an adequate di-
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From the Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA. Address reprint requests to Karen L. Khne, DVM, Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250. Copyright 2002, Elsevier Science (USA). All rights reserved. 1096-2867/02/1701-0005535.00/0 dol:10.1053/svms.2002.29075
agnosis, some treatments will undoubtedly fail and thus lead to the decline of the patient and lack of owner confidence. CAVM for the treatment of neurologic diseases has been most useful in the treatment of geriatric patients, patients who are an anesthetic risk, patients with nonsurgical neurologic lesions, and those patients whose neurologic deficits have become refractory to conventional management and need further interventional therapy. CAVM may prove to be a helpful adjunctive therapy in many cases of neurologic disease if used wisely and integratively. The evaluation of the neurologic veterinary patient encompasses a thorough history, in-depth physical and neurologic examinations, and appropriate diagnostics aimed at pinpointing not only the location of the neurologic lesion, but also its rectification and prognosis for recovery. The most important question to ask is: "Does this patient have disease of the nervous system?" (Table 1). Many metabolic and orthopedic diseases can mimic or cause neurologic dysfuncuon and make diagnoses difficult and unrewarding. Such examples include syncope or other cardiac-related abnormalities; hepatic encephalopathy; renal disease; and underlying orthopedic diseases such as bilateral cruciate rupture, coxofemoral degenerative joint disease, and patellar luxations. Once we have determined that the patient truly has neurologic dysfunction, the next goal is to determine if the disease is located in the brain, spinal cord, or neuromuscular system. Brain disease can involve the forebrain (cerebral cortex), the brain stem, or the cerebellum. Signs of forebrain disease include behavior changes, visual changes, seizures, circling, changes in sleep-wake patterns, and urmation/defecation habits. The neurologic examination can show content of consciousness changes and contralateral partial cranial-nerve deficits, conscious proprioceptive loss, and weakness (hemiparesis). x,2 Brainstem disease usually presents with a history of changes in level of consciousness (progressing from alertness to dullness to stupor). The neurologic examination reveals a change in the level of consciousness, and ipsilateral complete cranial nerve deficits, _+ head tilt (if the central vestibular structures are involved), weakness (hemiparesis), and conscious proprioceptive loss. Cerebellar disease manifests itself as an inability to regulate the range, rate, and force of a movement. Thus, signs may include head tremors and dysmetria (goose-stepping gait), but normal mentation and strength. The neurologic examination reveals normal mentation, strength, and proprioception with normal CNN function, except for an absent menace reflex either unilaterally or bilaterally. Spinal-cord signs vary with location of the lesion. The spinal cord can be divided into 4 segments: C1-C5, C6-T2, T3-L3, and L4-$2. Signs of a C1-C5 lesion may include: upper motor neuron (UMN) hyperreflexia to all limbs, tetraparesis or tetraple-
Clinical Techniques in Small Animal Practice, Vol 17, No 1 (February), 2002: pp 25-33
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gia, and unilateral or bilateral proprioceptive loss. Signs of a C6-T2 myelopathy can include: ipsilateral or bilateral tetraparesis or tetraplegia, front- or hindlimb proprioceptive loss, decreased withdrawal or hyporeflexic front limbs, and UMN signs to the hindlimbs. Lower motor neuron (LMN) muscle atrophy of the front limbs may also be observed. Signs of a T3-L3 myelopathy may include hindlimb paraparesis or plegia, either unilaterally or bilaterally. In most cases, the front limbs will have normal tone, but can have increased tone due to injury to the border cells located within the spinal cord at Tt2-L2. The border cells are inhibitory to increased extensor tone in the front limbs. 1.2 Signs of an L4-$2 lesion include: normal front limbs; LMN hyporeflexia in the hindlimbs (unilateral or bilateral); hindlimb weakness (paresis) or paralysis; poor withdrawal (if an L7-$2 lesion); and signs of decreased tail tone, or urinary or fecal incontinence. Neuromuscular disease involves a lesion affecting one or more areas: (1) the nerve root, (2) the peripheral nerve, (3) the neuromuscular junction, and (4) the muscle. Neuromuscular diseases are characterized by either continual or episodic weakness, with normal proprioception. Nerve-root lesions may manifest as either sensory or motor dysfunction. Examples include polyradiculoneuritis or brachial plexus avulsion. Peripheral neuropathies can be associated with traumatic injuries, degenerative processes, or endocrine disturbances such as diabetes mellitus and hypothyroidism. Junctionopathies include such diseases as myasthenia gravis (congenital or acquired), tick paralysis, or botulism. Myopathies can be related to traumatic injury; metabolic disease (hypokalemia, hypoglycemia), endocrinopathies such as hypothyroidism, hyperadrenocorticism, immune-mediated disease (polymyositis alone or associated with systemic lupus erythmatosus), and infectious agents such as Toxoplasmagondii or Neospora caninum. If a lesion cannot be localized to one area of the nervous system, it should be considered multifocal. Infectious agents and metabolic disturbances, most commonly, cause such signs and should be investigated more thoroughly. Specific categories of neurologic disease will be discussed in terms of a pathophysiology, diagnostics, and proposed treatment. An emphasis will be placed on the use of complementary and alternative medicine in the treatment of these disorders and how conventional therapy can be used integratively with CAVM
Vascular Disease Vascular disease involving the brain can be observed in veterinary patients with underlying metabolic and cardiovascular dysfunction. The central nervous system (CNS) is the most common portion of the nervous system (brain and spinal cord) affected by vascular disease. Signs are usually lateralizing and have an acute nonprogressive course. Pain usually is not a feature of these diseases except for ischemic myoneuropathy. Neurologic signs correspond to the location of the lesion. Animals with Cushing's disease (hyperadrenocorticism), cardiovascular disease, immune-mediated thrombocytopenia and anemia, hypertension, hyperthyroidism, hypothyroidism, sepsis, and glomerular disease have an increased risk for thrombosis and/or vascular compromise due to a number of underlying mechanisms that have been described pathophysiologically. Diagnosis of these disorders is key to treatment of the patient 26
and is essential if complementary therapy is to be used. Complete blood counts; serum chemistry; urinalysis; diagnostic imaging such as radiographs, ultrasound, magnetic resonance imaging (MRI) or computed tomography (CT) scans; bloodpressure measurements; and endocrine testing can be used to determine the cause of the illness. Prognosis for animals with vascular disease involving the nervous system depends on the underlying cause and the neurolocalization of the injury. Treatment of CNS vascular disease involves addressing the underlying cause, and using conventional drugs and treatment designed control the underlying disease. CNS vascular diseases often can improve remarkably over time (dependent on location of injury), and complementary therapy has been shown to be effective in hastening that recovery. The goal of integrative therapy in these patients is to speed recovery and improve quality of life. Holistic therapies include acupuncture, use of herbs, and nutritional supplements. Acupuncture therapy for vascular disease is aimed at increasing regional blood flow to the area affected, and to relieve the anxiety and stress of the patient. Traditional Chinese medicine (TCM) treatment principles involve pacifying the liver, extinguishing wind, resolving phlegm, clearing the senses, and nourishing the Yin. 3-5 In multiple studies of human patients with cerebrovascular accidents, recovery was faster in the acupuncture group who had an acute onset of clinical signs, and underwent 20 treatments (Fig 1).6 In addition, vascular disease due to trauma has been shown to be responsive to AP treatment. Decreases in fibrinogen levels, fibrin degradation products, and serum triglycerides have been shown to occur with acupuncture treatment. AP treatment is most effective in these cases when used with physical therapy. 6-15 Herbal and nutritional supplementation for CNS vascular disease includes those compounds mentioned under Cognitive disorder (CCD). 16,17
Seizures Seizures are classified as abnormal bursts of electrical activity that occur primarily in the forebrain. When evaluating a patient with seizures, it is important to determine if the episode the animal is having is actually a seizure and not a syncopal, vestibular, or pain-related event. Seizures are composed ofpreictal, ictal, and postictal periods that last variable amounts of time. Seizures can be focal (whisker, ear twitching, pupil dilation, temperature elevation); partial (one of more limb motor activities or body jerking); or tonic-clonic (grand real):loss of consciousness, autonomic release, purposeless limb movements, or involuntary urination and/or defecation. Animals with psychomotor or temporal-lobe seizures may fly-bite, chase their tails, vomit, or manifest other stereotypical behaviors. The causes of seizures are numerous and can be divided into categories that are dependent on the patient's signalment and/or history. Metabolic causes of seizures can include hepatic encephalopathy, electrolytic disturbances, hypoglycemia, endocrine diseases, and severe azotemia. Structural causes include infection, inflammation, traumatic injury, vascular changes, and congenital causes such as hydrocephalus. Toxins such as lead, molds, and strychnine can also be problematic. The terms "idiopathic" or "cryptogenic" epilepsy can be applied to an animal whose neurologic and physical examination are normal, has a normal intenctal period, normal findings on KAREN L. KLINE
TABLE 1. Neurolocalization of Lesions in the Nervous System, Differentials and Treatment Options
./
Does this animal have disease of the Nervous system? Yes
No Evaluate other causes Metabolic Cardiac Orthopedic Soft Tissue Injury
Localize and Prognosticate
Brain
J
\ Spinal Cord
1
1
Nerve root Peripheral nerve Neuromuscular Junction (NMJ) Muscle
Cerebral cortex Brain stem Cerebellum
/ Metabolic: -Hypoglycemia -HE -Electrolyte disturbances -Endocrine Imbalance
Neuromuscular
C1-C5 C6-T2 T3-L3 L4-$2
l
\
IVDD -Type1 -Type 2 Traumatic FCE Inflammatory Infectious
Structural -Vascular -Inflammatory -Infectious -Congenital -Traumatic
Metabolic Traumatic ImmuneMediated Infectious Inflammatory
\
Medical vs. Surgical Management \ Treat underlying cause
Complementary and/or Alternative Treatment
Complementary and/or Alternative Therapies
routine and advanced hemotaologic and biochemical screening at the time of evaluation, and whose seizures are nonprogressive. In cats, a structural cause--either quiescent or progress i v e - i s usually more common, is The animal may have had either a traumatic toxic or infectious process occur previously that has since resolved, but has left "scarring" in the cerebral cortex that can become a focus of seizure activity. This category is often a diagnosis of exclusion. The initial evaluation of all animals with seizures includes an accurate history, physical and neurologic exams, routine blood work, advanced endocrine studies, routine radiography, spinalCAVM AND NEUROLOGIC DISORDERS
fluid evaluation, and advanced diagnostic imaging such as CT scan or MRI, depending on the initial evaluation. Treatment is dependent on finding the underlying etiology of the seizures and its accurate diagnosis. Once a seizure focus is established, there is always a chance that the area may remain active. Conventional therapies, such as the anticonvulsants, phenobarbital and potassium bromide (KBr), can be very helpful in the control of seizure activity, especially in cases of idiopathic epilepsy. Some animals are less tolerant of their side effects, which include polyuria/polydipsia, polyphagia; weight gain (phenobarbital) and sedation, vomiting, and very rarely 27
\
Fig 1. Electroacupuncture unit. Electroacupuncture is most helpful in the treatment of painful, acute syndromes once a definitive diagnosis has been made.
pancreatitis (KBr). In addition, some animals may become refractory to these current medications, despite normal or high blood levels, or using one or both together. After reassessing the patient thoroughly to rule out a missed diagnosis and finding no abnormalities on further imaging, alternative therapies can be used to help complement the current medications. Indications for alternative or complementary therapies include several side effects to routine anticonvulsants, rising blood levels of these drugs with refractory seizures, and no new neurologic findings or owner decisions in terms of quality of life of the patient. Such therapies include needle acupuncture (Figs 2 and 3); cold laser therapy; massage therapy; and the use of nutriceuticals, herbs, and dietary changes to aid in improving seizure management. Acupuncture treatment of idiopathic epilepsy has been studied extensively in the veterinary and human literature. The TCM diagnosis of epilepsy is internal Wind invading the channels of Liver Wind due to Liver Yang rising, r Needle acupuncture has been used in seizure management, although electrical stimulation using needling can, at times, exacerbate seizures. Gold-bead implantation in points over the calvarium has also been cited as helpful in one study, while other studies cite the use of auricular acupuncture as very promising in the dog (Fig 4). 19-26 Stainless-steel auricular needles also can be implanted in the Shen Men points of the ear to aid in seizure control. 24 The use of nutriceuticals and herbs has been advocated as an
Fig 2. Acupuncture needles are available in a variety of sizes and types. Selection is dependent on the syndrome being treated. ~)8
Fig 3. "Cold" LASER unit. This therapy is especially useful for patients who do not tolerate needling and for the treatment of lymphedema and nonhealing wounds,
adjunctive therapy in epilepsy control. Suggested nutritional therapy in humans includes dimethylglycine (DMG), taurine, betaine HC1, proanthocyanidin complex, vitamin B6, folic acid, pyridoxine, magnesium, manganese, zinc, and choline. 23 DMG is a metabolic enhancer used both in human and veterinary medicine and has been theorized to enhance oxygen usage, improve muscle metabolism, and prevent lactic-acid buildup. It is considered an "antistress" nutrient that improves the cardiovascular system and the immune system by potentiating both B- and T-cell function when given orally. DMG has been cited as being of benefit in the treatment of seizures in human and veterinary medicine. Ketogenic diets have also been recommended based on the human literature, although more studies must be completed. Dietary management with hypoallergenic recipes has also been recommended. Efficacy of hypoallergenic diets is theorized to be due to alterations in neurovascular immunology. 2r,28 Components of this system are theorized to be potent, short-lived, vasoactive neurotransmitter and neuromodulator molecules most commonly identified in the Type 1 hypersensitivity reaction. Examples include amino acids such as aspartate, glutamate, and glycine; amines (decarboxylated amino acids) such as histamine and 5-hydroxytryptamine (serotonin); peptides such as substance P and neurotensin; and short-carbon chain
Fig 4. Other traditional acupuncture therapies include goldbead implants and moxabustion. KAREN L. KLINE
lipids such as prostaglandins and thromboxane. Receptors for these are found on neurons and on immune response ceils. It is theorized that due to the complex nature of neurovascular immunology, alterations in neurotransmitters, their metabolism, and their receptors may lead to more seizure activity than previously thought. As far back as 1931, one author reported the associations between food allergy and neurologic signs in humans, while other reports are noted in human and veterinary medicine. 29 One case report by Collins involved a Bernese mountain dog with fly-chasing seizure activity, viciousness, and a concurrent, recurrent staphylococcal pyoderma. With a dietary change instituted to help with the dermatologic condition, the seizure activity ceased and began anew when the original diet was reinstituted. 28 There is concern over the cyclic nature of food allergies and their symptoms due to a number of digestive and manufacturing variations. Due to this cyclic change, it is theorized that antigen gradually builds up until a threshold is exceeded and causes a "violent" reaction, then drops off again; as such, the cycles continue. This effect may be due to multiple foods (summation) or to just one food type. Idiopathic-epilepsy seizure complex has been theorized to be part of an immunoglobulin E or mast-cell response, although this is yet to be proven. 28 One plan is to institute a diet of 2 parts carbohydrate and 1 part protein, ie, potato and turkey or rabbit (that the patient has not been fed before), and to feed for 2 months without a change or providing treats. Proanthocyanidins (also known as the flavonoids) are part of the naturally occurring plant polyphenolic compounds that are thought to have antioxidant effects against lipid peroxidation, and a role in the inhibition of the arachadonic acid cascade through the blocking of lipoxygenase and their freeradical scavenging properties. They also inhibit cyclic adenosine monophosphate, transport adenosine triphosphatases (ATPases), and may play a role in the tight regulation of CNS function and dysfunction, including seizures, w,23 More research is being done to uncover further nutritional supplements and herbs that may be useful in adjunctive seizure control.
Canine Cognitive Dysfunction Syndrome Senile dementia (age-related deterioration of cognitive abilities) in the dog has been termed "canine cognitive dysfunction syndrome" and has been linked to cerebral vascular changes, ventricular dilatation, neurotransmitter dysfunction, and imbalances in the cerebral cortex resulting in reduced blood flow. Dysfunctional syndrome (CDS) has also implicated clinical signs occurring in the geriatric patient and is consistent with forebrain dysfunction (pacing, wandering, inappropriate elimination, behavior changes). Diagnosis of this syndrome is by exclusion. Metabolic encephalopathies can be ruled out by normal hematology, serum chemistries, bile acids, and endocrine testing. The absence of intracranial structural lesions can be confirmed by the use of MRI or CT scan. Treatment for canine cognitive dysfunction has had variable success once a definitive diagnosis is made. Selegiline hydrochloride as Selegiline (Anipryl) has been used with some success. It is theorized to enhance catecholaminergic nerve function and increased CNS dopamine levels. CAVM techniques for the treatment of CDS have not been discussed at great length in the literature. Acupuncture may prove to be a useful modality CAVM AND NEUROLOGIC DISORDERS
when used to stimulate Qi flow and Kidney Jlng, as well as immune function. 3 Nutriceuticals and herbs may also have a place in the treatment of this disorder. Compounds of particular interest include antioxidants like vitamin E, ginkgo biloba, acetyl-L-carnitine, S-adenosyl-methionine and phosphatidylserine, which is being advocated in human medicine as an enhancer of mental alertness and memory. Phytotherapies like ginkgo biloba have been theorized to aid in humans in the treatment of stroke, senile dementia, and cerebral vascular insufficiencies. It is theorized to improve cognitive dysfunction by altering arterial and vascular elasticity, and acting as an antiplatelet activating factor, lr Melatonin, a hormone produced by the pineal gland, is theorized to have an inhibitory effect on free radical production, antitoxidant properties, and may exert a depressive influence on CNS excitability, lr It may also play a role in the T-aminobutyric acid or benzodiazepine receptor complex as a potentiate of inhibitory neurotransmission. It may show promise in sleep disorders and other cognitive dysfunctions. Further studies in veterinary medicine on these treatments must be performed to evaluate their efficacy.
Meningitis The terms "meningitis" and ~'encephalitis" imply inflammation of the lining of the brain and spinal cord, the meninges, and the brain parenchyma, respectively. The causes of meningitis/encephalitis in the canine are numerous and include a theorized immune-mediated basis granulomatous meningoencephalomyelitis (GME); pug encephalitis and the encephalitis of Yorkshire terriers and Maltese breeds; and infectious agents (viral, protozoal, rickettsial, and bacterial). In the cat, feline infectious peritonitis is the main cause of meningitis as well as cryptococcosis. Diagnosis is based on findings on cerebrospinal-fluid analysis. Once a causative agent has been identified, treatment should be instituted accordingly. Unfortunately, in many cases of canine meningitis, causative agents are difficult to isolate, and these agents may actually induce secondary immune-mediated lesions that are sometimes more difficult to treat than the underlying, inciting agent. Examples of such disease include GME and sterile suppurative meningitis (SSM). Conventional therapies include immunosuppressive doses of corticosteroids. The goal in treating these diseases with CAVM is to palliate the pain associated with the inflammation and to normalize immune system function, as well as to decrease the need for large quantities of corticosteroids. Acupuncture can be effective in some cases, especially of cervical GME and SSM, to alleviate cervical pain, but should be used integrattvely with other medications, r The bladder meridian points (BL10, 11, 12) can be quite helpful in these instances, as well as points used to enhance immune function (SP6). Other immunomodulators such as interferon and vitamins E and B12 may help in beneficially altering immune function and decreasing lipid peroxidation. Chinese herbs may be helpful when prescribed according to traditional principles.
Spinal-Cord Disease The main spinal-cord diseases to be discussed will be intervertebral disc disease (IVDD), fibrocartilagenous embolism (FCE), and degenerative myelopathy. The pathophysiology of IVDD has been discussed at length in
29
the literature.i, 2 Type I and type 2 IVDD involve either an acute onset of clinical signs due to abrupt rupture of the calcified nucleus pulposus (type 1) or to chronic fibrinoid degeneration of the annulus fibrosis (type 2), which causes a slowly progressive onset of clinical signs. Diagnosis of both depends on patient signalment, history, neurologic examination, and neurolocalization. Myelography and other diagnostic imaging techniques such as MRI or CT scan are the diagnostics of choice. Treatment options depend on severity of the signs, progression, and patient signalment. Surgery is warranted if the patient has pain that is refractory to medical management, has progressively worsening clinical signs, or presents with worsening paresis or paralysis. Complementary and alternative therapies in the patient with IVDD are most useful when a definitive diagnosis is made or when surgical intervention is not an option due to patient concerns (ie, geriatric, other underlying disease). These therapies can be used in the postoperative period to help alleviate postoperative pain due to soft-tissue and bone manipulation, as well as to enhance regional blood flow to the affected area and to improve strength. Acupuncture has been shown to decrease the need for postoperative medication in surgical patients, and can be performed once daily in the immediate postoperative period, r Needle acupuncture and electrical stimulation are most helpful, as well as the use of therapeutic ultrasound, applied electrical fields, and cold laser therapy, r,25-34 The cold laser can be used to stimulate wound healing through the activation of fibroblast migration, 35 while also promoting soft-tissue perfusion, lymphatic drainage, and lessening soft-tissue/muscle edema. Nutriceuticals for IVDD can be used as an adjunctive therapy. One such dietary nutritional supplement is a product that contains bovine tracheal cartilage, a source of chondroitin 4 and 6 sulfates (Vetri-disc), that is theorized to lubricate and support connective tissue regeneration and lubrication of the spine and disk, although this has not been proven. Chiropractic has been suggested as an effective adjunct in preventing recurrences of disk prolapse, but care must be taken not to damage unstable or abnormal segments. Consultation with a practitioner trained in veterinary chiropractic is essential. Chinese herbs may also be helpful when prescribed according to traditional principles.
FCE Another spinal-cord disease that may be helped by the use of CAVM is FCE. FCE is theorized to be caused by a sudden occlusion of arterial blood supply to the spinal cord by a small portion of nucleus pulposus that escapes from the degenerating intervertebral disk annulus that has been neovascularized. Clinical signs are dependent on location of the embolization. Key features of FCE include a young/middle-aged, medium- to large-breed signalment (although schnauzers are overrepresented), and on acute onset of lateralizing signs after strenuous activity. These animals may first appear to be in pain, but then become nonpainful, within minutes to hours after the incident. Diagnosis is by exclusion. No spinal-cord compression is visualized on myelogram or MRI/CT scan, and no to minimal inflammation is found on cerebrospinal-fluid evaluation. Conventional therapy includes physical therapy and time. Prognosis is dependent on location of the lesion (ie, LMN signs have a graver prognosis than UMN signs). CAVM therapies 30
include electrical stimulation using acupuncture, therapeutic ultrasound, intensive physical therapy, and the use of nutriceuticals and herbs.7,17,22,31,32 Degenerative myelopathy (DM) is a degenerative condition that preferentially affects the white matter of the spinal cord. Although German shepherds (GSD) are over represented, other breeds such as the boxer may also be affected. This disease affects middle- to older-aged dogs and presents with a history of progressive, nonpainful, hindlimb weakness and proprioceprive ataxia most consistent with a T3-L3 myelopathy. Other differentials include intramednllary neoplasia or type 2 intervertebral disc protrusion. Diagnosis is based on findings on physical and neurological exams (some dogs have depressed or absent patellar reflexes), normal blood work, CSF analysis, myelography, and/or MRI. The underlying pathogenesis of DM in the German shepherd has been extensively studied, and several theories have been proposed. 36-44Three studies cite depressed lymphocyte blastogenesis to plant mitogens, thus causing a depressed or aberrant cell-mediated immune response) °,43,44 This suppression may be linked to genesis of a circulating suppressor cell, whereas some dogs possess antigen-binding cells directed against myelin basic protein. Immune complex deposition leading to inflammatory lesions is also theorized. 37 Other studies have cited genetic factors and possible dysfunctions in vitamin and oxidative metabolism pathways. 42 Active research in these areas is ongoing, but the true pathogenesis remains elusive and is most likely multifactorial. Treatment of DM is aimed at decreasing the theorized inflammatory onslaught of the disease and at slowing its progression. Clemmons et a141 advocated an integrative approach to treatment that included a 4-step program: (1) exercise and physical therapy, (2) dietary supplementation, (3) medication, and (4) other support. Exercise such as walking and swimming helps to build strength and improve muscle oxidative metabolism. Dietary supplementation and a change to a more natural diet may prove to slow the disease process, but not reverse it. Vitamins such as B-complex (thought to enhance neural regeneration), vitamin E (an antioxidant), and vitamin C may help to inhibit the inflammatory cascade stimulated by the prostaglandins and cytokines released from the influx of inflammatory cells; membrane stabilizers (omega-3 fatty acids, gamma-linoleic acid, soybean lecithin, and coenzyme Q10) can act as anti-inflammatories. Herbs and supplements such as gingko leaves, ginseng (males only), Dong quai (females only), green tea, grape-seed extract, hydergine (derived from ergot), bromelain/curcumin, and feverfew may be helpful. Medications such as aminocaproic acid (EACA) and N-acetylcysteine (NAC) are advocated. EACA is an amino acid and is thought to inhibit degradation of fibrin elicited by immune-complex formation, which decreases inflammatory cell migration. NAC is a potent antioxidant that is theorized to block activation of tissue enzymes and the formation of oxygen free radicals. The author has had very mixed results with the above protocols. It is important to note that the above treatments are based on the theories of one group researching this disease. 41 Other studies are being conducted to further our knowledge of etiology and treatment options. Acupuncture, although not effective in slowing the degenerative process of DM itself, may be helpful in those cases in which degenerative joint disease (DJD) is a complicating factor. This therapy can provide pain relief, tendon and muscle KAREN L. KLINE
TABLE 2. Specific Neurologic Disorders and Their Complementary and Alternative Therapies
Neurolocalization/Disease Process
CAM Treatment
BRAIN Cerebrovascular accident
Acupuncture Phytotherapy (Herbal medicine)
Seizures
Acupuncture Nutriceuticals Phytotherapy Dietary modifications
Cognitive Disorder
Acupuncture Phytotherapy
Meningitis
Acupuncture Interferon?
SPINAL CORD IVDD (Intewertebral Disk Disease) Type 1 Type 2
FCE (Fibrocartilagenous Embolism)
Degenerative Myelopathy
NEUROMUSCULAR
1 Masticatory myositis
Metabolic myopathies
CAVM AND NEUROLOGIC DISORDERS
r
Electroacupuncture (EAP) Needle acupuncture Laser acupuncture Nutriceuticals Physical Therapy - Massage therapy, hydrotherapy Therapeutic ultrasound Electroacupuncture Needle Acupuncture Physical Therapy Hydrotherapy Nutriceuticals Coenzyme Q10 Omega 3 Fatty acids Gammalinoleic acid Vitamins - B complex, E, C Physical Therapy AP (if associated orthopedic disease) Herbs - Gingko leaves Ginseng (males only) Dong quail (females only) Electroacupuncture (EAP) Nutriceuticals L-carnitine (650 mg/kg BID) Coenzyme Q10 (1 mg/kg/day) Vitamins Riboflavin 100 mg daily Vitamin C 50 mg/kg daily 31
strengthening, as well as improve immune function, r As of this writing, however, a direct link to its efficacy in the treatment of degenerative myelopathy is unknown. Other nutriceuticals such as glycosaminoglycans and chondrotin sulfate may also help in cases of DJD, and Chinese herbs such as Zhui Feng Tou Gu Wan (Chase Wind Penetrate Bone) are also used for arthritis and DJD. 45 Other classical Chinese formulas used to treat arthritis and DJD include: Du Huo Ji Sheng Tang (Du Huo and Loranthus formula), Yi Yi Ren Tang (Coix combination), Jia Wei Bai Hu Tang, and Guan Ji Yan Wan.
Neuromuscular Disorders Masticatory myositis in the canine is an immune-mediated inflammation of the type 2 M muscle fibers that comprise the muscles of mastication. No other muscle fiber types are affected in this disease. There is no breed predilection, and the primary presenting complaint is an inability to fully open the mouth. The dog may be quite painful, and signs can worsen with chronicity. Diagnosis is based on demonstration of inflammatory cells in a muscle biopsy (temporal or masseter muscles) and/or a positive type 2M muscle antibody titer. Conventional therapy is with immunosuppressive doses of corticosteroids. In some cases, other immunosuppressives such as azothioprine can be used. CAVM techniques for this syndrome can include acupuncture (electroacupuncture is theorized to be most helpful) and Chinese herbs. .6 The concomitant use of steroids with acupuncture may decrease the efficacy of the acupuncture treatment, although this has been a subject of debate.
Metabolic Myopathies The myopathies observed in the canine species can be specific to breed and genetic predisposition. (The same can be observed in the feline, although much less prevalently.) The breed in which this is most commonly recognized is the Labrador retriever. This myopathy is characterized by a heritable (autosomal recessive) depletion of type 2 muscle fibers. Dogs with this disease have a characteristic short, choppy gait and congenital muscle atrophy. Signs are exacerbated by cold weather and usually do not progress afterl to 2 years of age, but do not improve. Diagnosis is by electromyelogrpahy and muscle biopsy. Therapy is aimed at limiting overexercise and stress. Nutriceuticals such as coenzyme QI0, carnitine, and vitamin B complex and E may be helpful in palliating signs, although this is not proven. Acupuncture may be helpful in overall enhancement of muscle strength. The other metabolic myopathies involve select breakdowns in the molecular metabolic pathways found in the muscle, which leads to exercise intolerance and muscle cramping. Defects in mitochondrial function, ATP availability, and vital substrate availability can lead to signs of exercise intolerance secondary to resultant defects in muscle-oxidative metabolism. Diagnosis of these diseases can be difficult and include submission of muscle and nerve samples to experienced scientists to rule out any other underlying diseases such as polymyositis, polyneuropathy, or myasthenia gravis. Electron microscopy and other specific muscle-enzyme studies may be necessary to quantitate the disease process. Treatment consists of determining the genetic origin of the disease and moderation of strenuous exercise, which can, at times, be life-threatening (hyperthermia). The use of nutriceu32
ticals and vitamins such as coenzyme Q10, vitamin B complex, vitamin C, and vitamin E, as well as carnitine, has been attempted in some studies 4r to help decrease or alleviate clinical signs. Further cases must be evaluated to determine the effectiveness of these regimes. As of this writing, acupuncture has not been used extensively in the treatment of this syndrome, although it may have its application in helping to alleviate pain. The need for evidence-based research in the study of CAVM is paralleling that observed in the human sector. Multiple NIH grants for studies involving the efficacy of CAM in human medical disorders should help to lend credibility to the alternative therapies offered in the treatment of our veterinary patients. The treatment of neurologic disorders in the veterinary field with complementary and alternative therapies is aimed at integrating accepted conventional treatments with noninvasive techniques such as acupuncture; massage therapy; and chiropractic, therapeutic, ultrasound, and phytotherapy methods for the betterment of animal health and quality of life (Table 2).
References 1. Oliver JE, Lorenz MD, Kornegay JN: Handbook of Veterinary Neurology (ed 3). Philadelphia, PA, Saunders, 1993, pp 1-46 2. Oliver JE, Hoerlein BF, Mayhew IG: Veterinary Neurology. Philadelphia, PA, Saunders, 1987, pp 15-46 3. IVAS Course Proceedings, 1998-1999, pp 10.1.1-10.7.11 4. Jirui C, Wang N: Acupuncture Case Histories from China. Seattle, WA, Eastland Press, 1988, pp 110-168 5. National Institutes of Health: Acupuncture 1970-1997, current bibliographies in medicine, NIH National Library of medicine No. 97(6), 1977, pp 72-78 6. Naeser MA: Acupuncture in the treatment of paralysis due to central nervous system damage. J AItern Complement Med 2:211-248, 1996 7. Kline KL, Caplan ER, Joseph RJ: Acupuncture for Neurologic Disorders, in Shoen AM (ed): Veterinary Acupuncture; Ancient Art to Modern Medicine, Vol 2 (ed 2). St. Louis, MO, Mosby, 2001, pp 179-192 8. Chen GS, Erdman W: Effects of acupuncture on tissue oxygenation of the rat brain. Comp Med East West 5:147-154, 1977 9. Hu HH, et al: A randomized controlled trial on the treatment for acute atrial ischemic stroke with acupuncture. Neuroepidemiology 12:106, 1993 10. Kjendahl A: A one year follow-up study on the effects of acupuncture in the treatment of stroke patients in the subacute stage: A randomized, controlled study. Clin Rehabil 11:192, 1997 11. Li Y, Wang X, Li T: Acupuncture therapy for 12 cases of cranial trauma. J Tradit Chin Med 13(1):5-10, 1993 12. Naeser MA: Real vs sham acupuncture in the treatment of paralysis in acute stroke patients: ACT scan lesion site study. J Neurol Rehabll 6:163, 1992 13. Naeser MA: Acupuncture in the treatment of paralysis in chronic and acute stroke patients: Improvement correlated with specific CT scan lesion sites. Acupunct Electrother Res 19:227, 1994 14. Naeser MA: Acupuncture in the treatment of paralysis in chronic and acute stroke patients: Improvement observed in all cases. Clin Rehab 8:127, 1994 15. Zhao C. Treatment of acute cerebrovascular diseases and sequelae with acupuncture. J Tradit Chin Med 10(1):70-73, 1990 16. Freeman LW, Lawlis FG: Complementary Alternative Medicine: A Research-Based Approach, Vol 1 (edl). St. Louis, MO, Mosby, 2001, pp 329-332 17. Diamond BJ, Shiflett SC, Schoenberger NE, et al: Complementary/ alternative therapies in the treatment of neurolgic disorders, in Spencer JW, Jacobs JJ (eds): Complementary/Alternative Medicine: An Evidence-Based Approach, Vol 1. St. Louis, MO, Mosby, 1999, pp 170 18. Kline KL. Feline epilepsy. CIm Tech Small Anim Pract 13:152-158, 1998 19. Klide AM, Farnbach GC, Gallagher SM: Acupuncture therapy for the KAREN L. KLINE
20. 21. 22. 23.
24. 2S.
26.
27.
28. 29. 30. 31.
32. 33.
treatment of intractable idiopathic epilepsy in five dogs. Acupunct Electrother Res 12:71, 1987 Van Niekerk J, Eckersley GN: The use of acupuncture in canine epilepsy. Vet Acupunct Newsletter 15:15, 1989 Ross J: Acupuncture Point Combinations: The Key to Clinical Success. Edinburgh, Scotland, Churchill Livingstone, 1995, pp 424-427 Still J: Research in Veterinary Acupuncture. Brussels, Belgium. Belgian Veterinary Acupuncture Society, 1991, pp 31-41 Wynn SG, Schoen AM: Complementary and Alternative Veterinary Medicine: Principles and Practice, Vol 1 (ed 1). St. Louis, MO, Mosby, 1998, pp 159-163 Partington M: Auricular Shermen implant for the treatment of idiopathic epilepsy in a dog. Vet Acupunct Newsletter 15:4-5, 1989 Duysens J: Basic neurophysiotogical mechanisms underlying acupuncture. Proceedtngs of the Thirteenth Annual Congress on Veterinary Acupuncture, Belgium, 1987 Lorenz KY: Auricular acupuncture in animal: Effects of optate withdrawal and involvement of endorphin, J Altern Complement Med 2:61-63, 1996 Bell IR: Effects of food allergy in the central nervous system. In Barostaff J, Challacombe SJ (eds): Food Allergy and Intolerance. Philadelphia, PA, Bailliere Tindall, 1987, p 709 Collins JR: Seizures and other neurologic manifestations of allergy. Vet Clin North Am Small Anim Pract 24:735-748, 1994 Rowe AH: Food allergy: Its manifestattons, diagnosis and treatment. Philadelphia, PA, Lea & Febiger, 1931, p 476 Ding-Zong W: Acupuncture and neurophysiology. Clin Neurol Neurosurg 92(1):13-25, 1990 Politis MJ, Korchinski MS: Beneficial effects of acupuncture treatment following experimental spinal cord injury: A behavioral, morphological, and biochemical study. Acupunct Electrother Res J Int J 15:37-49, 1990 Suzuki K: Successful electrotherapy for severe hind limb paralysis caused by spinal cord injury in dogs. Int Vet Acupunct 7:10-12, 1998 Zonakis MF: Regeneration in mammalian nervous system using
CAVM AND NEUROLOGIC DISORDERS
34. 35. 36.
37.
38. 39. 40. 41. 42. 43.
44.
45. 46.
47.
applied electrical fields: A literature review. Acupunct Electrother Res Int J 13:47-57, 1988 Politis MJ: Facilitated regeneration in the rat peripheral nervous system suing applied electrical fields. J Trauma 28:1375-1381, 1988 Lucroy MD: Low-intensity laser light-induced closure of a chronic wound in a dog. Vet Surg 28:292-295, 1999 Averill DR: Degenerative myelopathy in the aging German shepherd dog: Clinical and pathologtc findings. J Am Med Assoc 162:1045, 1973 Barclay JB, Haines DM: Immunohistochemical evidence for immunoglobulin and complement deposition in spinal cord lesions in degenerative myelopathy in German shepherd dogs. Can J Vet Res 58(1):20-24, 1994 Braund KG, Vandevelde M: German shepherd dog myelopathy--A morphologic and morphometric study. Am J Vet Res 39:1309, 1978 Braund KG: Hip dysplasia and degenerative myelopathy: Making the distinction in dogs. Vet Med 82:782-789, 1987 Clemmons RM: Vet Clin North Am Small Anim Pract 22:965-971, 1992 Clemmons R: Degenerative Myopathy. University of Florida VTH Web page Coates JR: Canine Degenerative Myelopathy. Proceedings of the 19th ACVlM Forum, Denver, CO, 2001, pp 405-407 Waxman FJ, Clemmons RM, Johnson G, et al: Progressive myelopathy in older German shepherd dogs I. Depressed response to thymus-dependent mitogens. J Immunol 124:1209, 1980 Waxman FJ, Clemmons RM, Hendrichs DJ: Progressive myelopathy in older German Shepherd dogs. II. Presence of circulating suppressor cells. J Immunol 124:1216, 1980 Monda L: Golden Flower Chinese Herbs Product Guide. Jin Hua Press, 1997, p 5 Loo WC: Symptom association with impaired transmission of nerve impulses to different muscle areas and their treatment with acupuncture. Am J Acupunct 13;319-330, 1985 Cuddon P: Clinical Presentation of Some Newer Myopathies. ACVIM Proceedings, San Diego, CA, 1998, pp 298-300
33
The use of complementary and alternative veterinary medicine in treating neurologic disorders has increased in popularity in response to advances in human alternative and integrative therapies. Neurolocalization of lesions to the brain, spinal cord, and neuromuscular systems is discussed, as well as the diagnostics and therapeutics used to treat such disorders. Emphasis is placed on integrative and alternative treatments for such neurologic diseases as seizures, cerebrovascular accidents, canine cognitive disorder, meningitis, intervertebral disc disease, fibrocartilagenous embolism, degenerative myelopathy, and myopathies. Thorough physical and neurologic examinations, establishment of a correct diagnosis, and integrative therapeutics are aimed at improving the overall quality of life of the veterinary patient. Copyright 2002, Elsevier Science (USA). All rights reserved.
omplementary and alternative veterinary medmine (CAVM) has become more popular with the advent of more accepted practices in the human medical sciences. National Institutes of Health (NIH) grants on alternative medicine and its benefits have been numerous and are lending credibility to a field of veterinary medicine that is both progressive and has its roots in ancient practice and philosophies. Complementary medicine implies the use of alternative techniques coupled with conventional medicine. As the field of veterinary medicine expands and envelops more modalities of therapy, owners are increasingly looking for other means to enhance their animal's quality of life and health. The use of complementary techniques in the treatment of veterinary neurologic diseases has increased in popularity over the last two decades. This popularity is due to a number of factors and undoubtedly stems from a crossover from human medicine. The use of CAM in human neurologic disease has been well studied. Indications for the use of CAVM in the treatment of neurologic diseases are numerous, but patient and individual case selection, as well as correct diagnosis, are of utmost importance. Knowing when to offer complementary and alternative medical intervention to an animal with neurologic disease is as important as the physical examination, correct interpretation of blood work, and diagnostic imaging. Without an adequate di-
C
From the Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA. Address reprint requests to Karen L. Khne, DVM, Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250. Copyright 2002, Elsevier Science (USA). All rights reserved. 1096-2867/02/1701-0005535.00/0 dol:10.1053/svms.2002.29075
agnosis, some treatments will undoubtedly fail and thus lead to the decline of the patient and lack of owner confidence. CAVM for the treatment of neurologic diseases has been most useful in the treatment of geriatric patients, patients who are an anesthetic risk, patients with nonsurgical neurologic lesions, and those patients whose neurologic deficits have become refractory to conventional management and need further interventional therapy. CAVM may prove to be a helpful adjunctive therapy in many cases of neurologic disease if used wisely and integratively. The evaluation of the neurologic veterinary patient encompasses a thorough history, in-depth physical and neurologic examinations, and appropriate diagnostics aimed at pinpointing not only the location of the neurologic lesion, but also its rectification and prognosis for recovery. The most important question to ask is: "Does this patient have disease of the nervous system?" (Table 1). Many metabolic and orthopedic diseases can mimic or cause neurologic dysfuncuon and make diagnoses difficult and unrewarding. Such examples include syncope or other cardiac-related abnormalities; hepatic encephalopathy; renal disease; and underlying orthopedic diseases such as bilateral cruciate rupture, coxofemoral degenerative joint disease, and patellar luxations. Once we have determined that the patient truly has neurologic dysfunction, the next goal is to determine if the disease is located in the brain, spinal cord, or neuromuscular system. Brain disease can involve the forebrain (cerebral cortex), the brain stem, or the cerebellum. Signs of forebrain disease include behavior changes, visual changes, seizures, circling, changes in sleep-wake patterns, and urmation/defecation habits. The neurologic examination can show content of consciousness changes and contralateral partial cranial-nerve deficits, conscious proprioceptive loss, and weakness (hemiparesis). x,2 Brainstem disease usually presents with a history of changes in level of consciousness (progressing from alertness to dullness to stupor). The neurologic examination reveals a change in the level of consciousness, and ipsilateral complete cranial nerve deficits, _+ head tilt (if the central vestibular structures are involved), weakness (hemiparesis), and conscious proprioceptive loss. Cerebellar disease manifests itself as an inability to regulate the range, rate, and force of a movement. Thus, signs may include head tremors and dysmetria (goose-stepping gait), but normal mentation and strength. The neurologic examination reveals normal mentation, strength, and proprioception with normal CNN function, except for an absent menace reflex either unilaterally or bilaterally. Spinal-cord signs vary with location of the lesion. The spinal cord can be divided into 4 segments: C1-C5, C6-T2, T3-L3, and L4-$2. Signs of a C1-C5 lesion may include: upper motor neuron (UMN) hyperreflexia to all limbs, tetraparesis or tetraple-
Clinical Techniques in Small Animal Practice, Vol 17, No 1 (February), 2002: pp 25-33
25
gia, and unilateral or bilateral proprioceptive loss. Signs of a C6-T2 myelopathy can include: ipsilateral or bilateral tetraparesis or tetraplegia, front- or hindlimb proprioceptive loss, decreased withdrawal or hyporeflexic front limbs, and UMN signs to the hindlimbs. Lower motor neuron (LMN) muscle atrophy of the front limbs may also be observed. Signs of a T3-L3 myelopathy may include hindlimb paraparesis or plegia, either unilaterally or bilaterally. In most cases, the front limbs will have normal tone, but can have increased tone due to injury to the border cells located within the spinal cord at Tt2-L2. The border cells are inhibitory to increased extensor tone in the front limbs. 1.2 Signs of an L4-$2 lesion include: normal front limbs; LMN hyporeflexia in the hindlimbs (unilateral or bilateral); hindlimb weakness (paresis) or paralysis; poor withdrawal (if an L7-$2 lesion); and signs of decreased tail tone, or urinary or fecal incontinence. Neuromuscular disease involves a lesion affecting one or more areas: (1) the nerve root, (2) the peripheral nerve, (3) the neuromuscular junction, and (4) the muscle. Neuromuscular diseases are characterized by either continual or episodic weakness, with normal proprioception. Nerve-root lesions may manifest as either sensory or motor dysfunction. Examples include polyradiculoneuritis or brachial plexus avulsion. Peripheral neuropathies can be associated with traumatic injuries, degenerative processes, or endocrine disturbances such as diabetes mellitus and hypothyroidism. Junctionopathies include such diseases as myasthenia gravis (congenital or acquired), tick paralysis, or botulism. Myopathies can be related to traumatic injury; metabolic disease (hypokalemia, hypoglycemia), endocrinopathies such as hypothyroidism, hyperadrenocorticism, immune-mediated disease (polymyositis alone or associated with systemic lupus erythmatosus), and infectious agents such as Toxoplasmagondii or Neospora caninum. If a lesion cannot be localized to one area of the nervous system, it should be considered multifocal. Infectious agents and metabolic disturbances, most commonly, cause such signs and should be investigated more thoroughly. Specific categories of neurologic disease will be discussed in terms of a pathophysiology, diagnostics, and proposed treatment. An emphasis will be placed on the use of complementary and alternative medicine in the treatment of these disorders and how conventional therapy can be used integratively with CAVM
Vascular Disease Vascular disease involving the brain can be observed in veterinary patients with underlying metabolic and cardiovascular dysfunction. The central nervous system (CNS) is the most common portion of the nervous system (brain and spinal cord) affected by vascular disease. Signs are usually lateralizing and have an acute nonprogressive course. Pain usually is not a feature of these diseases except for ischemic myoneuropathy. Neurologic signs correspond to the location of the lesion. Animals with Cushing's disease (hyperadrenocorticism), cardiovascular disease, immune-mediated thrombocytopenia and anemia, hypertension, hyperthyroidism, hypothyroidism, sepsis, and glomerular disease have an increased risk for thrombosis and/or vascular compromise due to a number of underlying mechanisms that have been described pathophysiologically. Diagnosis of these disorders is key to treatment of the patient 26
and is essential if complementary therapy is to be used. Complete blood counts; serum chemistry; urinalysis; diagnostic imaging such as radiographs, ultrasound, magnetic resonance imaging (MRI) or computed tomography (CT) scans; bloodpressure measurements; and endocrine testing can be used to determine the cause of the illness. Prognosis for animals with vascular disease involving the nervous system depends on the underlying cause and the neurolocalization of the injury. Treatment of CNS vascular disease involves addressing the underlying cause, and using conventional drugs and treatment designed control the underlying disease. CNS vascular diseases often can improve remarkably over time (dependent on location of injury), and complementary therapy has been shown to be effective in hastening that recovery. The goal of integrative therapy in these patients is to speed recovery and improve quality of life. Holistic therapies include acupuncture, use of herbs, and nutritional supplements. Acupuncture therapy for vascular disease is aimed at increasing regional blood flow to the area affected, and to relieve the anxiety and stress of the patient. Traditional Chinese medicine (TCM) treatment principles involve pacifying the liver, extinguishing wind, resolving phlegm, clearing the senses, and nourishing the Yin. 3-5 In multiple studies of human patients with cerebrovascular accidents, recovery was faster in the acupuncture group who had an acute onset of clinical signs, and underwent 20 treatments (Fig 1).6 In addition, vascular disease due to trauma has been shown to be responsive to AP treatment. Decreases in fibrinogen levels, fibrin degradation products, and serum triglycerides have been shown to occur with acupuncture treatment. AP treatment is most effective in these cases when used with physical therapy. 6-15 Herbal and nutritional supplementation for CNS vascular disease includes those compounds mentioned under Cognitive disorder (CCD). 16,17
Seizures Seizures are classified as abnormal bursts of electrical activity that occur primarily in the forebrain. When evaluating a patient with seizures, it is important to determine if the episode the animal is having is actually a seizure and not a syncopal, vestibular, or pain-related event. Seizures are composed ofpreictal, ictal, and postictal periods that last variable amounts of time. Seizures can be focal (whisker, ear twitching, pupil dilation, temperature elevation); partial (one of more limb motor activities or body jerking); or tonic-clonic (grand real):loss of consciousness, autonomic release, purposeless limb movements, or involuntary urination and/or defecation. Animals with psychomotor or temporal-lobe seizures may fly-bite, chase their tails, vomit, or manifest other stereotypical behaviors. The causes of seizures are numerous and can be divided into categories that are dependent on the patient's signalment and/or history. Metabolic causes of seizures can include hepatic encephalopathy, electrolytic disturbances, hypoglycemia, endocrine diseases, and severe azotemia. Structural causes include infection, inflammation, traumatic injury, vascular changes, and congenital causes such as hydrocephalus. Toxins such as lead, molds, and strychnine can also be problematic. The terms "idiopathic" or "cryptogenic" epilepsy can be applied to an animal whose neurologic and physical examination are normal, has a normal intenctal period, normal findings on KAREN L. KLINE
TABLE 1. Neurolocalization of Lesions in the Nervous System, Differentials and Treatment Options
./
Does this animal have disease of the Nervous system? Yes
No Evaluate other causes Metabolic Cardiac Orthopedic Soft Tissue Injury
Localize and Prognosticate
Brain
J
\ Spinal Cord
1
1
Nerve root Peripheral nerve Neuromuscular Junction (NMJ) Muscle
Cerebral cortex Brain stem Cerebellum
/ Metabolic: -Hypoglycemia -HE -Electrolyte disturbances -Endocrine Imbalance
Neuromuscular
C1-C5 C6-T2 T3-L3 L4-$2
l
\
IVDD -Type1 -Type 2 Traumatic FCE Inflammatory Infectious
Structural -Vascular -Inflammatory -Infectious -Congenital -Traumatic
Metabolic Traumatic ImmuneMediated Infectious Inflammatory
\
Medical vs. Surgical Management \ Treat underlying cause
Complementary and/or Alternative Treatment
Complementary and/or Alternative Therapies
routine and advanced hemotaologic and biochemical screening at the time of evaluation, and whose seizures are nonprogressive. In cats, a structural cause--either quiescent or progress i v e - i s usually more common, is The animal may have had either a traumatic toxic or infectious process occur previously that has since resolved, but has left "scarring" in the cerebral cortex that can become a focus of seizure activity. This category is often a diagnosis of exclusion. The initial evaluation of all animals with seizures includes an accurate history, physical and neurologic exams, routine blood work, advanced endocrine studies, routine radiography, spinalCAVM AND NEUROLOGIC DISORDERS
fluid evaluation, and advanced diagnostic imaging such as CT scan or MRI, depending on the initial evaluation. Treatment is dependent on finding the underlying etiology of the seizures and its accurate diagnosis. Once a seizure focus is established, there is always a chance that the area may remain active. Conventional therapies, such as the anticonvulsants, phenobarbital and potassium bromide (KBr), can be very helpful in the control of seizure activity, especially in cases of idiopathic epilepsy. Some animals are less tolerant of their side effects, which include polyuria/polydipsia, polyphagia; weight gain (phenobarbital) and sedation, vomiting, and very rarely 27
\
Fig 1. Electroacupuncture unit. Electroacupuncture is most helpful in the treatment of painful, acute syndromes once a definitive diagnosis has been made.
pancreatitis (KBr). In addition, some animals may become refractory to these current medications, despite normal or high blood levels, or using one or both together. After reassessing the patient thoroughly to rule out a missed diagnosis and finding no abnormalities on further imaging, alternative therapies can be used to help complement the current medications. Indications for alternative or complementary therapies include several side effects to routine anticonvulsants, rising blood levels of these drugs with refractory seizures, and no new neurologic findings or owner decisions in terms of quality of life of the patient. Such therapies include needle acupuncture (Figs 2 and 3); cold laser therapy; massage therapy; and the use of nutriceuticals, herbs, and dietary changes to aid in improving seizure management. Acupuncture treatment of idiopathic epilepsy has been studied extensively in the veterinary and human literature. The TCM diagnosis of epilepsy is internal Wind invading the channels of Liver Wind due to Liver Yang rising, r Needle acupuncture has been used in seizure management, although electrical stimulation using needling can, at times, exacerbate seizures. Gold-bead implantation in points over the calvarium has also been cited as helpful in one study, while other studies cite the use of auricular acupuncture as very promising in the dog (Fig 4). 19-26 Stainless-steel auricular needles also can be implanted in the Shen Men points of the ear to aid in seizure control. 24 The use of nutriceuticals and herbs has been advocated as an
Fig 2. Acupuncture needles are available in a variety of sizes and types. Selection is dependent on the syndrome being treated. ~)8
Fig 3. "Cold" LASER unit. This therapy is especially useful for patients who do not tolerate needling and for the treatment of lymphedema and nonhealing wounds,
adjunctive therapy in epilepsy control. Suggested nutritional therapy in humans includes dimethylglycine (DMG), taurine, betaine HC1, proanthocyanidin complex, vitamin B6, folic acid, pyridoxine, magnesium, manganese, zinc, and choline. 23 DMG is a metabolic enhancer used both in human and veterinary medicine and has been theorized to enhance oxygen usage, improve muscle metabolism, and prevent lactic-acid buildup. It is considered an "antistress" nutrient that improves the cardiovascular system and the immune system by potentiating both B- and T-cell function when given orally. DMG has been cited as being of benefit in the treatment of seizures in human and veterinary medicine. Ketogenic diets have also been recommended based on the human literature, although more studies must be completed. Dietary management with hypoallergenic recipes has also been recommended. Efficacy of hypoallergenic diets is theorized to be due to alterations in neurovascular immunology. 2r,28 Components of this system are theorized to be potent, short-lived, vasoactive neurotransmitter and neuromodulator molecules most commonly identified in the Type 1 hypersensitivity reaction. Examples include amino acids such as aspartate, glutamate, and glycine; amines (decarboxylated amino acids) such as histamine and 5-hydroxytryptamine (serotonin); peptides such as substance P and neurotensin; and short-carbon chain
Fig 4. Other traditional acupuncture therapies include goldbead implants and moxabustion. KAREN L. KLINE
lipids such as prostaglandins and thromboxane. Receptors for these are found on neurons and on immune response ceils. It is theorized that due to the complex nature of neurovascular immunology, alterations in neurotransmitters, their metabolism, and their receptors may lead to more seizure activity than previously thought. As far back as 1931, one author reported the associations between food allergy and neurologic signs in humans, while other reports are noted in human and veterinary medicine. 29 One case report by Collins involved a Bernese mountain dog with fly-chasing seizure activity, viciousness, and a concurrent, recurrent staphylococcal pyoderma. With a dietary change instituted to help with the dermatologic condition, the seizure activity ceased and began anew when the original diet was reinstituted. 28 There is concern over the cyclic nature of food allergies and their symptoms due to a number of digestive and manufacturing variations. Due to this cyclic change, it is theorized that antigen gradually builds up until a threshold is exceeded and causes a "violent" reaction, then drops off again; as such, the cycles continue. This effect may be due to multiple foods (summation) or to just one food type. Idiopathic-epilepsy seizure complex has been theorized to be part of an immunoglobulin E or mast-cell response, although this is yet to be proven. 28 One plan is to institute a diet of 2 parts carbohydrate and 1 part protein, ie, potato and turkey or rabbit (that the patient has not been fed before), and to feed for 2 months without a change or providing treats. Proanthocyanidins (also known as the flavonoids) are part of the naturally occurring plant polyphenolic compounds that are thought to have antioxidant effects against lipid peroxidation, and a role in the inhibition of the arachadonic acid cascade through the blocking of lipoxygenase and their freeradical scavenging properties. They also inhibit cyclic adenosine monophosphate, transport adenosine triphosphatases (ATPases), and may play a role in the tight regulation of CNS function and dysfunction, including seizures, w,23 More research is being done to uncover further nutritional supplements and herbs that may be useful in adjunctive seizure control.
Canine Cognitive Dysfunction Syndrome Senile dementia (age-related deterioration of cognitive abilities) in the dog has been termed "canine cognitive dysfunction syndrome" and has been linked to cerebral vascular changes, ventricular dilatation, neurotransmitter dysfunction, and imbalances in the cerebral cortex resulting in reduced blood flow. Dysfunctional syndrome (CDS) has also implicated clinical signs occurring in the geriatric patient and is consistent with forebrain dysfunction (pacing, wandering, inappropriate elimination, behavior changes). Diagnosis of this syndrome is by exclusion. Metabolic encephalopathies can be ruled out by normal hematology, serum chemistries, bile acids, and endocrine testing. The absence of intracranial structural lesions can be confirmed by the use of MRI or CT scan. Treatment for canine cognitive dysfunction has had variable success once a definitive diagnosis is made. Selegiline hydrochloride as Selegiline (Anipryl) has been used with some success. It is theorized to enhance catecholaminergic nerve function and increased CNS dopamine levels. CAVM techniques for the treatment of CDS have not been discussed at great length in the literature. Acupuncture may prove to be a useful modality CAVM AND NEUROLOGIC DISORDERS
when used to stimulate Qi flow and Kidney Jlng, as well as immune function. 3 Nutriceuticals and herbs may also have a place in the treatment of this disorder. Compounds of particular interest include antioxidants like vitamin E, ginkgo biloba, acetyl-L-carnitine, S-adenosyl-methionine and phosphatidylserine, which is being advocated in human medicine as an enhancer of mental alertness and memory. Phytotherapies like ginkgo biloba have been theorized to aid in humans in the treatment of stroke, senile dementia, and cerebral vascular insufficiencies. It is theorized to improve cognitive dysfunction by altering arterial and vascular elasticity, and acting as an antiplatelet activating factor, lr Melatonin, a hormone produced by the pineal gland, is theorized to have an inhibitory effect on free radical production, antitoxidant properties, and may exert a depressive influence on CNS excitability, lr It may also play a role in the T-aminobutyric acid or benzodiazepine receptor complex as a potentiate of inhibitory neurotransmission. It may show promise in sleep disorders and other cognitive dysfunctions. Further studies in veterinary medicine on these treatments must be performed to evaluate their efficacy.
Meningitis The terms "meningitis" and ~'encephalitis" imply inflammation of the lining of the brain and spinal cord, the meninges, and the brain parenchyma, respectively. The causes of meningitis/encephalitis in the canine are numerous and include a theorized immune-mediated basis granulomatous meningoencephalomyelitis (GME); pug encephalitis and the encephalitis of Yorkshire terriers and Maltese breeds; and infectious agents (viral, protozoal, rickettsial, and bacterial). In the cat, feline infectious peritonitis is the main cause of meningitis as well as cryptococcosis. Diagnosis is based on findings on cerebrospinal-fluid analysis. Once a causative agent has been identified, treatment should be instituted accordingly. Unfortunately, in many cases of canine meningitis, causative agents are difficult to isolate, and these agents may actually induce secondary immune-mediated lesions that are sometimes more difficult to treat than the underlying, inciting agent. Examples of such disease include GME and sterile suppurative meningitis (SSM). Conventional therapies include immunosuppressive doses of corticosteroids. The goal in treating these diseases with CAVM is to palliate the pain associated with the inflammation and to normalize immune system function, as well as to decrease the need for large quantities of corticosteroids. Acupuncture can be effective in some cases, especially of cervical GME and SSM, to alleviate cervical pain, but should be used integrattvely with other medications, r The bladder meridian points (BL10, 11, 12) can be quite helpful in these instances, as well as points used to enhance immune function (SP6). Other immunomodulators such as interferon and vitamins E and B12 may help in beneficially altering immune function and decreasing lipid peroxidation. Chinese herbs may be helpful when prescribed according to traditional principles.
Spinal-Cord Disease The main spinal-cord diseases to be discussed will be intervertebral disc disease (IVDD), fibrocartilagenous embolism (FCE), and degenerative myelopathy. The pathophysiology of IVDD has been discussed at length in
29
the literature.i, 2 Type I and type 2 IVDD involve either an acute onset of clinical signs due to abrupt rupture of the calcified nucleus pulposus (type 1) or to chronic fibrinoid degeneration of the annulus fibrosis (type 2), which causes a slowly progressive onset of clinical signs. Diagnosis of both depends on patient signalment, history, neurologic examination, and neurolocalization. Myelography and other diagnostic imaging techniques such as MRI or CT scan are the diagnostics of choice. Treatment options depend on severity of the signs, progression, and patient signalment. Surgery is warranted if the patient has pain that is refractory to medical management, has progressively worsening clinical signs, or presents with worsening paresis or paralysis. Complementary and alternative therapies in the patient with IVDD are most useful when a definitive diagnosis is made or when surgical intervention is not an option due to patient concerns (ie, geriatric, other underlying disease). These therapies can be used in the postoperative period to help alleviate postoperative pain due to soft-tissue and bone manipulation, as well as to enhance regional blood flow to the affected area and to improve strength. Acupuncture has been shown to decrease the need for postoperative medication in surgical patients, and can be performed once daily in the immediate postoperative period, r Needle acupuncture and electrical stimulation are most helpful, as well as the use of therapeutic ultrasound, applied electrical fields, and cold laser therapy, r,25-34 The cold laser can be used to stimulate wound healing through the activation of fibroblast migration, 35 while also promoting soft-tissue perfusion, lymphatic drainage, and lessening soft-tissue/muscle edema. Nutriceuticals for IVDD can be used as an adjunctive therapy. One such dietary nutritional supplement is a product that contains bovine tracheal cartilage, a source of chondroitin 4 and 6 sulfates (Vetri-disc), that is theorized to lubricate and support connective tissue regeneration and lubrication of the spine and disk, although this has not been proven. Chiropractic has been suggested as an effective adjunct in preventing recurrences of disk prolapse, but care must be taken not to damage unstable or abnormal segments. Consultation with a practitioner trained in veterinary chiropractic is essential. Chinese herbs may also be helpful when prescribed according to traditional principles.
FCE Another spinal-cord disease that may be helped by the use of CAVM is FCE. FCE is theorized to be caused by a sudden occlusion of arterial blood supply to the spinal cord by a small portion of nucleus pulposus that escapes from the degenerating intervertebral disk annulus that has been neovascularized. Clinical signs are dependent on location of the embolization. Key features of FCE include a young/middle-aged, medium- to large-breed signalment (although schnauzers are overrepresented), and on acute onset of lateralizing signs after strenuous activity. These animals may first appear to be in pain, but then become nonpainful, within minutes to hours after the incident. Diagnosis is by exclusion. No spinal-cord compression is visualized on myelogram or MRI/CT scan, and no to minimal inflammation is found on cerebrospinal-fluid evaluation. Conventional therapy includes physical therapy and time. Prognosis is dependent on location of the lesion (ie, LMN signs have a graver prognosis than UMN signs). CAVM therapies 30
include electrical stimulation using acupuncture, therapeutic ultrasound, intensive physical therapy, and the use of nutriceuticals and herbs.7,17,22,31,32 Degenerative myelopathy (DM) is a degenerative condition that preferentially affects the white matter of the spinal cord. Although German shepherds (GSD) are over represented, other breeds such as the boxer may also be affected. This disease affects middle- to older-aged dogs and presents with a history of progressive, nonpainful, hindlimb weakness and proprioceprive ataxia most consistent with a T3-L3 myelopathy. Other differentials include intramednllary neoplasia or type 2 intervertebral disc protrusion. Diagnosis is based on findings on physical and neurological exams (some dogs have depressed or absent patellar reflexes), normal blood work, CSF analysis, myelography, and/or MRI. The underlying pathogenesis of DM in the German shepherd has been extensively studied, and several theories have been proposed. 36-44Three studies cite depressed lymphocyte blastogenesis to plant mitogens, thus causing a depressed or aberrant cell-mediated immune response) °,43,44 This suppression may be linked to genesis of a circulating suppressor cell, whereas some dogs possess antigen-binding cells directed against myelin basic protein. Immune complex deposition leading to inflammatory lesions is also theorized. 37 Other studies have cited genetic factors and possible dysfunctions in vitamin and oxidative metabolism pathways. 42 Active research in these areas is ongoing, but the true pathogenesis remains elusive and is most likely multifactorial. Treatment of DM is aimed at decreasing the theorized inflammatory onslaught of the disease and at slowing its progression. Clemmons et a141 advocated an integrative approach to treatment that included a 4-step program: (1) exercise and physical therapy, (2) dietary supplementation, (3) medication, and (4) other support. Exercise such as walking and swimming helps to build strength and improve muscle oxidative metabolism. Dietary supplementation and a change to a more natural diet may prove to slow the disease process, but not reverse it. Vitamins such as B-complex (thought to enhance neural regeneration), vitamin E (an antioxidant), and vitamin C may help to inhibit the inflammatory cascade stimulated by the prostaglandins and cytokines released from the influx of inflammatory cells; membrane stabilizers (omega-3 fatty acids, gamma-linoleic acid, soybean lecithin, and coenzyme Q10) can act as anti-inflammatories. Herbs and supplements such as gingko leaves, ginseng (males only), Dong quai (females only), green tea, grape-seed extract, hydergine (derived from ergot), bromelain/curcumin, and feverfew may be helpful. Medications such as aminocaproic acid (EACA) and N-acetylcysteine (NAC) are advocated. EACA is an amino acid and is thought to inhibit degradation of fibrin elicited by immune-complex formation, which decreases inflammatory cell migration. NAC is a potent antioxidant that is theorized to block activation of tissue enzymes and the formation of oxygen free radicals. The author has had very mixed results with the above protocols. It is important to note that the above treatments are based on the theories of one group researching this disease. 41 Other studies are being conducted to further our knowledge of etiology and treatment options. Acupuncture, although not effective in slowing the degenerative process of DM itself, may be helpful in those cases in which degenerative joint disease (DJD) is a complicating factor. This therapy can provide pain relief, tendon and muscle KAREN L. KLINE
TABLE 2. Specific Neurologic Disorders and Their Complementary and Alternative Therapies
Neurolocalization/Disease Process
CAM Treatment
BRAIN Cerebrovascular accident
Acupuncture Phytotherapy (Herbal medicine)
Seizures
Acupuncture Nutriceuticals Phytotherapy Dietary modifications
Cognitive Disorder
Acupuncture Phytotherapy
Meningitis
Acupuncture Interferon?
SPINAL CORD IVDD (Intewertebral Disk Disease) Type 1 Type 2
FCE (Fibrocartilagenous Embolism)
Degenerative Myelopathy
NEUROMUSCULAR
1 Masticatory myositis
Metabolic myopathies
CAVM AND NEUROLOGIC DISORDERS
r
Electroacupuncture (EAP) Needle acupuncture Laser acupuncture Nutriceuticals Physical Therapy - Massage therapy, hydrotherapy Therapeutic ultrasound Electroacupuncture Needle Acupuncture Physical Therapy Hydrotherapy Nutriceuticals Coenzyme Q10 Omega 3 Fatty acids Gammalinoleic acid Vitamins - B complex, E, C Physical Therapy AP (if associated orthopedic disease) Herbs - Gingko leaves Ginseng (males only) Dong quail (females only) Electroacupuncture (EAP) Nutriceuticals L-carnitine (650 mg/kg BID) Coenzyme Q10 (1 mg/kg/day) Vitamins Riboflavin 100 mg daily Vitamin C 50 mg/kg daily 31
strengthening, as well as improve immune function, r As of this writing, however, a direct link to its efficacy in the treatment of degenerative myelopathy is unknown. Other nutriceuticals such as glycosaminoglycans and chondrotin sulfate may also help in cases of DJD, and Chinese herbs such as Zhui Feng Tou Gu Wan (Chase Wind Penetrate Bone) are also used for arthritis and DJD. 45 Other classical Chinese formulas used to treat arthritis and DJD include: Du Huo Ji Sheng Tang (Du Huo and Loranthus formula), Yi Yi Ren Tang (Coix combination), Jia Wei Bai Hu Tang, and Guan Ji Yan Wan.
Neuromuscular Disorders Masticatory myositis in the canine is an immune-mediated inflammation of the type 2 M muscle fibers that comprise the muscles of mastication. No other muscle fiber types are affected in this disease. There is no breed predilection, and the primary presenting complaint is an inability to fully open the mouth. The dog may be quite painful, and signs can worsen with chronicity. Diagnosis is based on demonstration of inflammatory cells in a muscle biopsy (temporal or masseter muscles) and/or a positive type 2M muscle antibody titer. Conventional therapy is with immunosuppressive doses of corticosteroids. In some cases, other immunosuppressives such as azothioprine can be used. CAVM techniques for this syndrome can include acupuncture (electroacupuncture is theorized to be most helpful) and Chinese herbs. .6 The concomitant use of steroids with acupuncture may decrease the efficacy of the acupuncture treatment, although this has been a subject of debate.
Metabolic Myopathies The myopathies observed in the canine species can be specific to breed and genetic predisposition. (The same can be observed in the feline, although much less prevalently.) The breed in which this is most commonly recognized is the Labrador retriever. This myopathy is characterized by a heritable (autosomal recessive) depletion of type 2 muscle fibers. Dogs with this disease have a characteristic short, choppy gait and congenital muscle atrophy. Signs are exacerbated by cold weather and usually do not progress afterl to 2 years of age, but do not improve. Diagnosis is by electromyelogrpahy and muscle biopsy. Therapy is aimed at limiting overexercise and stress. Nutriceuticals such as coenzyme QI0, carnitine, and vitamin B complex and E may be helpful in palliating signs, although this is not proven. Acupuncture may be helpful in overall enhancement of muscle strength. The other metabolic myopathies involve select breakdowns in the molecular metabolic pathways found in the muscle, which leads to exercise intolerance and muscle cramping. Defects in mitochondrial function, ATP availability, and vital substrate availability can lead to signs of exercise intolerance secondary to resultant defects in muscle-oxidative metabolism. Diagnosis of these diseases can be difficult and include submission of muscle and nerve samples to experienced scientists to rule out any other underlying diseases such as polymyositis, polyneuropathy, or myasthenia gravis. Electron microscopy and other specific muscle-enzyme studies may be necessary to quantitate the disease process. Treatment consists of determining the genetic origin of the disease and moderation of strenuous exercise, which can, at times, be life-threatening (hyperthermia). The use of nutriceu32
ticals and vitamins such as coenzyme Q10, vitamin B complex, vitamin C, and vitamin E, as well as carnitine, has been attempted in some studies 4r to help decrease or alleviate clinical signs. Further cases must be evaluated to determine the effectiveness of these regimes. As of this writing, acupuncture has not been used extensively in the treatment of this syndrome, although it may have its application in helping to alleviate pain. The need for evidence-based research in the study of CAVM is paralleling that observed in the human sector. Multiple NIH grants for studies involving the efficacy of CAM in human medical disorders should help to lend credibility to the alternative therapies offered in the treatment of our veterinary patients. The treatment of neurologic disorders in the veterinary field with complementary and alternative therapies is aimed at integrating accepted conventional treatments with noninvasive techniques such as acupuncture; massage therapy; and chiropractic, therapeutic, ultrasound, and phytotherapy methods for the betterment of animal health and quality of life (Table 2).
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