"I'll take neurology for 500" (Proceedings)

Staphylococcus is a common cause of discospondylitis. Spinal epidural empyema (i.e. abcess) is most often associated with E. Coli, Bacteriodes spp and S. Intermedius.1 Thus, antibiotic choice should be targeted at these organisms when a bacterial infection is suspected. Cephalosporins and amoxicillin/clavulanic acid are both good choices. A fluoroquinolone may be used if a therapeutic response is not initially seen with the previous antibiotic choices. Fungal discospondylitis can be difficult to diagnosis, as a bacterial cause is typically suspected. Aspergillus tereus, Cladophialophora and Paecilomycosis may also cause discospondylitis. Coccidiomycosis can cause vertebral osteomyelitis. Fungal serology and often times biopsy and culture may be required to diagnose fungal infections of the spine. Itraconazole or voriconazole should be considered for fungal discospondylitis and osteomyelitis. While fluconazole is often used for CNS fungal infections because of its penetration in to CSF, it has little activity against Aspergillus.2

Thoracic limb lameness is often initially thought to be of orthopedic origin. Degenerative joint disease, tendon injury, neoplasia, trauma and less commonly osteomyelitis and joint infection encompass non neurological causes for lameness. Neurologic causes are commonly overlooked initially. Significant muscle atrophy, ataxia, horner's syndrome and CP deficits may suggest a neurologic cause for the lameness. Neoplasia (Peripheral nerve sheath tumor and lymphoma) not uncommonly affects the brachial plexus. Pain may or may not be present on palpation of the axilla. Lateralized disc herniations may cause thoracic limb lameness and are often painful. Radiographs of the affected limb and thorax can help identify neoplasia. Spinal MR imaging that includes the brachial plexus is helpful in differentiating disc disease from neoplasia. CSF analysis is important to evaluate for lymphoma and inflammatory CNS diseases. Amputation of the affected limb may be of benefit when peripheral nerve sheath tumors are present. However, good margins are often difficult to obtain in the brachial plexus. Thus, the high likelihood of recurrence makes amputation of questionable benefit when the tumor is quite proximal, at the level of the spinal canal. While radiation therapy is of benefit in peripheral nerve sheath tumors, anecdotally it is of limited benefit when the brachial plexus is involved. Loss of the ipsilateral cutaneous trunci reflex occurs with traumatic brachial plexus injuries, in which avulsion of the caudal brachial plexus occurs. The prognosis with brachial plexus injuries is poor. Traction injuries without avulsion may improve with time and rehabilitation therapy.

Horner's syndrome most commonly occurs with lesions of the middle ear or with a lesion from T1-T3. A partial horner's syndrome may be present with a lesion a T1. The occurrence of an acute C6-T2 myelopathy with concurrent horner's syndrome is commonly associated with fibrocartilaginous embolism and less commonly neoplasia.

Idiopathic cerebellitis (i.e. White Shaker Dog syndrome) occurs in small breed dogs of any coat color. Dogs classically present with tremors that worsen with movement. Cranial MR imaging is typically normal or may have very subtle changes in the cerebellum. CSF analysis typically identifies a mild pleocytosis. GME typically has a greater pleocytosis compared to idiopathic cerebellitis. However, at times GME can have a mild pleocytosis making differentiation difficult. The prognosis with idiopathic cerebellitis is typically good with immunosuppressive prednisone therapy. Dogs can often be tapered off of prednisone after a few months of therapy. Relapse can occur with premature withdrawal of prednisone therapy.

Anticonvulsant therapy for cats is often frustrating if phenobarbital is not successful. The use of potassium bromide is no longer recommended in cats due to the potential for asthma secondary to bromide therapy. Signs may resolve once bromide therapy is discontinued. The longer half life of diazepam in cats makes it a possible candidate for long term anticonvulsant therapy. However, the use of oral diazepam is limited due to the potential risk of severe liver disease in cats. Extensive studies regarding safety and efficacy of newer anticonvulsants in cats are lacking. Gabapentin may be used, however it has not been highly efficacious for seizures in small animals. Newer anticonvulsants such as levetiracetam 20 mg/kg PO TID and zonisamide 5-10 mg/kg PO SID in cats appear promising. Due to the limited number of studies and anecdotal experience (lower incidence of seizures in cats compared to dogs) care should be used when using these medications. Starting at the lower end of the dose range may be of benefit. Serial monitoring of the CBC and serum chemistry is recommended.

Serial evaluation of phenobarbital and bromide levels has historically been recommended. However, routine monitoring of levels often does not lead to a change in dosage and can become costly for clients. Furthermore, therapeutic levels and toxic levels are guidelines extrapolated from people, are based on population statistics and may not be accurate when extrapolated to an individual canine or feline patient. Determining anticonvulsant levels is most beneficial when: 1. A dose change is needed and toxicity is a concern. The formula (desired blood level /current blood level) x current dose = The newly recommended dose 2. A refractory patient becomes controlled. This allows the identification of a therapeutic level for that individual patient, provided the seizure disorder does not worsen. 3. The patient is sensitive to the toxic effects of the anticonvulsant (Bromide most common offender). Obtaining a blood level as soon as clinical signs of toxicity abate identifies the toxic level for that patient. Evaluation of blood levels may not be important when patients are currently and historically well controlled and free of adverse effects. Ideally, patients receiving phenobarbital should have a level obtained once they reach steady state given the risk of hepatoxicity at levels > 35 µg/ml. Therapeutic levels for levetiracetam, zonisamide and pregabalin are relatively unknown for dogs at this time. Thus, routine monitoring of levels is typically not done with usage of these drugs. It is important to be aware that bromide levels are affected by Cl-. Increased dietary Cl- or IV fluids containing Cl- will increase renal excretion of bromide and thus lower serum bromide levels. A patient receiving bromide therapy may lose seizure control as a result of a change in diet or IV fluids. Conversely, a decrease in dietary Cl- may lead to toxicity (sedation and ataxia) as renal bromide excretion is reduced and serum bromide levels subsequently increase. Thus, dietary changes should be minimized in patients receiving bromide therapy.

Recommendations against the use of acepromazine in dogs with a history of seizures are common. The reason has been a decrease in the seizure threshold with its use. However, evidence to warrant a contraindication for the use of acepromazine in seizure patients is lacking. The use of acepromazine in seizure patients is unlikely to result in seizures. A retrospective study evaluated 36 dogs with a history of seizures that were given acepromazine for sedation or as a pre-anesthetic. None of the 36 dogs seizured within 16 hours of use.3

Assessment of hypothyroidism is extremely difficult in dogs receiving phenobarbital. Total T4 (TT4) and freeT4 (FT4) values may be significantly decreased in dogs receiving phenobarbital. Total T3 changes minimally and TSH increases after several months of phenobarbital therapy. Serum cholesterol also increases after phenobarbital administration. It is unclear if the decrease in TT4 and FT4 is clinically significant. Increased thyroxinemonoiodination to T3 at the cellular level may occur, compensating for hypothyroxinemia. If so TT4, FT4 and TSH values are meaningless.4 TT4 values return to normal within 6 weeks of phenobarbital withdrawal. FT4 values may remain decreased for 10 weeks past cessation of phenobarbital therapy.5

The degree of hyperglycemia has been correlated to the severity of head trauma in dogs and cats. Hyperglycemia in patients with cerebral ischemia increases free radical production, excitatory amino acid release, cerebral edema and cerebral acidosis. Hyperglycemia is associated with increased mortality rates and neurologic outcomes in people and experimentally induced head trauma in animals. Thus the use of dextrose solutions and the use of corticosteroids should be avoided or minimized.6

Centronuclear myopathy (CNM), previously known as type II fiber deficiency, autosomal recessive muscular dystrophy of Labradors and hereditary Labrador retriever myopathy, affects young Labrador retrievers (typically 3-4 months of age) of both sexes. Affected puppies may exhibit signs of weakness, kyphosis, cervical ventroflexion, stiff gait and generalized muscle atrophy. Creatine kinase is typically normal to mildly increased. Clinical signs typically progress slowly and stabilize by 12 months of age, although rapid progression occurs sometimes.7 The disease is autosomal recessive with an insertional mutation within PTPLA exon 2.8 A commercial test is available for the mutation (www.labradorcnm.com). Muscle biopsy abnormalities are variable, but include angular atrophy, small and large group atrophy with a predominant loss of type II myofibers in some cases. Central nuclei are present in 74 % of cases.7 X linked myotubular myopathy has been reported in male Labrador retrievers. Clinical signs begin from 3 to 4 months of age and are similar to CNM. Serum CK is mildly increased. Genetic testing for CNM is negative. Biopsy changes include centrally placed nuclei resembling fetal myotubes and subsarcolemmal abnormalities. A missense mutation in the MTM1 gene has been identified in X linked myotubular myopathy.9 Canine X linked muscular dystrophy (CXMD) has typically affected golden retrievers, but has also been reported in the Labrador retriever. Dogs are affected at birth or <6 weeks of age and are male. Clinical signs include muscle weakness, bunny hopping gait, dysphagia, tongue enlargement and hypersalivation. An absence of membrane dystrophin on muscle biopsy confirms the diagnosis.7

Marijuana toxicity is associated with diffuse CNS signs such as obtundation, ataxia, CP deficits and tremors. Vomiting, hypersalivation, mydriasis, bradycardia or tachycardia may be seen. Urine dribbling consistent with a LMN bladder without complete localization to the cauda equina also suggests possible intoxication. Most animals develop clinical signs within 1 to 3 hours post ingestion.10 Human urine THC testing is negative in dogs due to metabolization to conjugated compounds. These compounds are larger and more delicate than THC metabolites in human urine. Most dogs with marijuana toxicity recover, although severe intoxication may lead to death. Treatment is supportive, with gastric lavage and activated charcoal limiting enterohepatic recirculation.11

Neurologic deficits with compressive myelopathies such as seen with intervertebral disc disease, proceed in a stereotypical fashion. CP deficits occur first followed by ambulatory paresis/ataxia → non ambulatory paresis/ataxia → paraplegia → loss of superficial pain sensation → loss of deep pain sensation. Urinary incontinence typically occurs between the stages of severe paresis to plegia. Thus, animals that have good motor function or are ambulatory do not typically need to be assessed for apparent pain sensation. However, some dogs that are paraplegic without apparent deep pain sensation can regain the ability to ambulate non voluntarily through the use of crossed extensor reflexes. These "spinal walkers" are urinary incontinent. Thus, deep pain should be tested for in ambulatory parapetic patients that are incontinent.

References

Lavely JA, Vernau KM, Vernau W, et al. Spinal epidural empyema in seven dogs. Vet Surg 2006; 35:176-185.

Lavely JA, Lipsitz D. Fungal infections of the central nervous system in the dog and cat. Clin Tech Small Anim Pract 2005;20:212-219.

Tobias KM, Marioni-Henry K, Wagner R. A retrospective study on the use of acepromazine maleate in dogs with seizures. J Am Anim Hosp Assoc 2006;42:283-289.

Müller PB, Wolfsheimer KJ, Taboada J, et al. Effects of long term phenobarbital treatment on the thyroid and adrenal axis andadrenal function tests in dogs. J Vet Intern Med 2000;14:157-164.

Gieger TL, Hosgood G, taboada J, et al. Thyroid function and serum hepatic enzyme activity in dogs after phenobarbital administration.

Syring RS, Otto CM, Drobatz KJ. Hyperglycemia in dogs and cats with head trauma:122 cases (1997-1999). J Am Vet Med Assoc 2001;218:1124-1129.

Cosford KL, Taylor SM, Thompson L et al. A possible new inherited myopathy in a young Labrador retriever. Can Vet J 2008;49:393-397.

Pelé M, Tiret L, Kessler JL, et al. SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronuclear myopathy in dogs. Human Molecular Genetics 2005;14:1417-1427.

Snead E, Böhm J, Kozlowski M, et al. A missense variant in the MTM1 gene associated with X-linked myotubular myopathy in Labrador retrievers. In ACVIM forum proceedings. Montreal, Canada. 2009

Janczyk P, Donaldson CW, Gwaltney S. Two hundred and thirteen clinical cases of marijuana toxicosis in dogs. Vet Human Toxicol 2004;46:19-21.

Teitler JB. Evaluation of a human on-site urine multidrug test for emergency use with dogs. J Am Anim Hosp Assoc 2009;45:59-66.