Metronidazole toxicity typically occurs with dosages greater than 60 mg/kg/day. Cerebellar Purkinje cell loss and axonal degeneration may occur. Thus, cerebellar and vestibular signs such as ataxia, hypermetria and nystagmus may be seen with toxicity.
Metronidazole toxicity typically occurs with dosages greater than 60 mg/kg/day. Cerebellar Purkinje cell loss and axonal degeneration may occur. Thus, cerebellar and vestibular signs such as ataxia, hypermetria and nystagmus may be seen with toxicity. Toxicity may be seen at lower dosages, particularly with treatment of longer duration. Diazepam treatment q 8 hours may speed recovery by competitive binding at the GABA receptor. Dogs treated with an average dose of 0.43 mg/kg diazepam q 8 hours for 3 days significantly improved at an average of 13.4 hours compared to 4.25 days for dogs not given diazepam.1
Cerebellar abiotrophy is a premature degeneration of cerebellar tissue, most typically purkinje cells. Animals are typically normal at birth and develop cerebellar signs as they age. Cerebellar abiotrophy has been reported in several breeds with a variable age of onset depending upon the breed.2 In animals affected by cerebellar hypoplasia the cerebellum develops abnormally. Cerebellar hyoplasia is typically inherited. Cerebellar hypoplasia most commonly affects kittens infected in utero with the feline panleukopenia virus3
Central vestibular disease results from lesions affecting the brainstem or cerebellum. Paradoxical vestibular disease, a form of central vestibular disease may occur with lesions affecting the caudal cerebelar peduncle, the fastigial nucleus, vestibular nuclei or the floculonodular lobes. On MRI, lesions affecting the cerebellar pontine angle often result in paradoxical vestibular disease. Lesions affecting the vestibulocochear nerve or the receptor organs of the inner ear result in peripheral vestibular disease.4 Head tilt, falling, rolling, ataxia, nystagmus, strabismus and nausea are often signs of vestibular disease. Differentiating central vestibular disease from peripheral vestibular may change the order of differential diagnoses. For instance otitis media/interna in dogs and cats and inflammatory polyps in cats may cause peripheral vestibular disease while neoplasia and vascular events are more often associated with central vestibular disease. Idiopathic vestibular disease may affect either the central or peripheral vestibular systems. With central vestibular disease decreased mentation, cranial nerve deficits and ipsilateral conscious proprioceptive deficits may be present. In paradoxical vestibular disease the head tilt is contralateral to the lesion. Animals with vestibular disease will often have decreased tone in the ipsilateral limbs and increased tone in the contralateral limbs. MRI is the imaging test of choice to evaluate the vestibular system. CSF analysis is important as inflammatory brain diseases such as GME have a predilection for the brainstem. CSF may also help identify central extension of otitis media/interna, lymphoma and infectious diseases such as Cryptococcus and FIP.
Feline neurology can often be frustrating. Common feline neurological diseases include lymphoma, cryptococcosis, FIP and toxoplasmosis. These diseases can affect any location within the CNS and thus should be considered regardless of lesion localization. Meningiomas are common in cats and typically affect the cerebrum, although other locations within the CNS may also be affected. Vascular events may occur, particularly in cats with cardiac disease or systemic hypertension. Blood pressure evaluation, thoracic radiographs and echocardiography may be useful to non-invasively assess the possibility of a vascular event. Evidence of spontaneous contrast (i.e. "smoke") or an intracardiac thrombus on echocardiography indicates a high risk of arterial thromboembolism. Cranial MRI may also be helpful in identifying a lesion consistent with infarction. Cryptococcus antigen testing is highly sensitive and may be useful in assessing cats with neurological disease. Toxoplasma serology identifies antibodies and thus exposure, but does not necessarily indicate causation of neurological disease. However, a positive IgM titer suggests recent infection. Serum globulins are often elevated in FIP. MRI may identify ependymal lesions, periventricular lesions or secondary hydrocephalus consistent with FIP. CSF analysis may be very helpful in differentiating between the various feline neurological diseases. Lymphoma as well as cryptococcal organisms can be directly identified in CSF. FIP often yields a neutrophilic pleocytosis with increased protein. Toxoplasma may yield a mixed pleocytosis with increased CSF protein.
Degenerative disc disease is common in cats. However, it is uncommon for cats to exhibit myelopathic signs secondary to intervertebral disc protrusion.5
Cervical ventroflexion in cats is an indicator of muscle weakness and thus neuromuscular disease. When cervical ventroflexion is identified myasthenia gravis and hypokalemia should be ruled out. Myasthenia gravis is uncommon in cats, however is more common in Abyssinian and Somali cats. Most commonly feline myasthenia gravis presents with generalized weakness without a megaesophagus (28.6 %) or generalized weakness associated with a cranial mediastinal mass (25.7 %). Less commonly focal myasthenia gravis occurs with megaesophagus and dysphagia (14.3%).6 Megaesophagus is more commonly seen in the dog due to the presence of striated muscle throughout the length of the esophagus whereas in the cat the distal 1/3 is smooth muscle. Methimazole therapy has been associated with myasthenia gravis in cats. Acetylcholine receptor antibody testing is highly sensitive with seronegative generalized myasthenia gravis occurring in about 2 % of dogs. Resolution of weakness immediately following Intravenous injection of edrophonium "Tensilon test" (0.1-0.2 mg/kg IV in dogs and 0.25-0.5 mg total dose in cats) is highly suggestive of myasthenia gravis. Atropine should be given prior to edrophonium injection in cats as they are more sensitive than dogs to edrophonium. Atropine sulfate (0.02 – 0.04 mg/kg) should be readily available at the time of Tensilon testing as adverse effects such as salivation, lacrimation, diarrhea and vomiting may occur. The standard treatment of myasthenia gravis has been pyridostigmine bromide1-3 mg/kg PO BID to TID. In animals unable to swallow medications safely, pyridostigmine bromide (0.01-0.03 mg/kg/h) may be administered via constant rate infusion.7 Immunosuppressive therapy has also been used to treat myasthenia gravis. Various immunosuppressive medications have been used such as azathioprine, cyclosporine, mycophenylate and corticosteroid therapy. The high incidence of aspiration pneumonia in myasthenic patients should be considered when choosing either immunosuppressive therapy or anticholinesterase therapy. The prognosis for myasthenia gravis is variable. A significant number of dogs, 87%, go into spontaneous remission.7 However, one study indicated that the one year survival rate was 40.4 %.8
Hypokalemia in cats may cause a polymyopathy. Cats present with generalized weakness, and cervical ventroflexion. Serum CK may be elevated. Clinical signs may resolve once potassium levels are re-established. A lag time between normalization of serum potassium levels and resolution of clinical signs may occur. Potassium loss with chronic renal disease is the most important cause. Congenital hypokalemia is a consideration in Burmese kittens.9
Degenerative myelopathy typically presents as a progressive, non painful T3-L3 myelopathy. With progression decreased patellar reflexes may be seen and even clinical signs of a cervical myelopathy. Affected dogs are typically over 5 years old. Histopathologically, axonal loss is primarily seen, especially in the lateral funiculi. Average time to euthanasia was reportedly 19 months in the Pembroke Welsh Corgi.10 A study of dogs with suspected degenerative myelopathy indicated that dogs with intense physiotherapy had a longer survival time (8.5 months) than dogs with moderate (4.3 months) and dogs without physiotherapy (1.8 months).11 Degenerative myelopathy was recently identified as an E40K missense mutation through resequencing of the SOD1 gene in the Pembroke Welsh Corgi, German Shepherd dog, Rhodesian ridgeback, Boxer and Chesapeake Bay retriever. Affected dogs are homozygous for the A allele.12
Incomplete closure of the developing neural tube results in spinal dysraphism and congenital syringohydromyelia. Ataxia, a bunny hopping pelvic limb gait and pelvic limb spinal reflex deficits may be seen. Spinal dysraphism is heritable in Weimaraners. Affected Weimaraners may lack a central canal, a ventral median fissure or have incomplete separation of the ventral horns.13,14
Diagnosis of tetanus is based on clinical signs. In the initial stages clear signs of tetanus may not be apparent. Ocular changes initially may be subtle. Lethargy, anorexia and vomiting are also common initial signs. As the disease progresses protrusion of the third eyelid and enophthalmos may be seen. The ears may become erect and the lips drawn back, known as Risus sardonicus. Contraction of the masticatory muscles may lead to trismus. Dysphagia may result. A generalized stiff gait is apparent with generalized tetanus and may progress to the extreme rigidity of a sawhorse type posture.15
A stiff gait may also be caused by other generalized neuromuscular diseases, degenerative joint disease, polyarthritis and meningitis. Serum CK may be elevated in dogs with polymyopathies and thus inclusion of CK evaluation on serum chemistry testing is essential. Polyarthritis may occur concurrently with meningitis. A study evaluating dogs with immune mediated polyarthritis and spinal pain identified concurrent meningitis in 5 of 11 dogs that had CSF collected. None of the 5 dogs were lame or had palpably swollen joints. Only 1 dog exhibited apparent joint pain. Cervical pain and thoracolumbar pain were common. Despite similar treatment for polyarthritis and meningitis identification of CNS involvement is considered important.16 Thus, both CSF evaluation and joint fluid evaluation are considered important with in dogs with apparent spinal pain.
Acute polyradiculoneuritis, botulism and tick paralysis all may cause acute generalized lower motor neuron disease. Differentiation can be difficult. Identification of embedded ticks with rapid resolution of signs supports the diagnosis of tick paralysis. A salivary neurotoxin secreted by Dermatocentor and Ixodes tick species impairs presynaptic neuromuscular transmission. Botulism is caused by ingestion of type C neurotoxin of Clostridium botulinum and results in inhibition of presynaptic Ach release from cholinergic fiber nerve terminals. Complete recovery should occur with supportive care within 1-3 weeks.7 Acute polyradiculoneuritis is of unknown etiology, but is likely immune mediated. Exposure to raccoon saliva may be the immune stimulus in many, but not all cases. The ventral nerve roots are affected with varying degrees of axonal degeneration, demyelination and infiltration of inflammatory cells. Lumbar CSF may have increased CSF protein. EMG evaluation may be abnormal after about 5 days. Nerve conduction studies typically show slowed F wave latencies and prolonged F ratios. Hyperesthesia may arise. Recovery typically occurs within several weeks to 6 months with supportive care. Corticosteroids are not recommended and have been associated with reduced survival rate in people with the human equivalent of an acute neuropathy called Guillain–Barré syndrome.17
Neuroanatomic localization is very important in developing a list of differential diagnoses and is essential in imaging the appropriate area. Decreased reflexes indicate lower motor neuron involvement. A myelopathic patient with decreased patellar reflexes traditionally indicates a L4-L6 myelopathy. A T3-L3 lesion should also be considered, as neurologically normal dogs may lack a patellar reflex response. The absent reflex may be unilateral or bilateral. It is more commonly identified in dogs at 10 years of age or older. 18 The lack of a thoracic limb withdrawal reflex in a tetraparetic dog traditionally indicates a C6-T2 myelopathy. However, a recent study indicated that the withdrawal reflex deficit led to incorrect neuroanatomic localization in 11/14 dogs when judged by comparison to MRI. Cranial cervical disk herniations (C2-C3 andC3-C4) were most often associated with incorrect neuroanatomic localizations due to decreased withdrawal reflexes. Resolution of the withdrawal reflex deficit occurred in 13 of 19 dogs evaluated 6 weeks post operatively.19
Assessment of deep pain sensation can sometimes be difficult. Testing of deep pain is done by clamping/pinching hemostats across the digits and compressing the bone/periosteum. Vocalization, turning sharply or attempting to bite are clear signs that the dog or cat retains pain sensation. Withdrawal of the limb may be a reflex and not necessarily an indicator of true pain sensation and thus is not reliable in determining prognosis. More subtle indications of deep pain sensation may include an increase in respiration. At times agitation and excitement may mask the appearance of pain sensation. Thus testing in a relaxed atmosphere with or without the owner present may be of benefit. With compressive myelopathies deep pain sensation is present when voluntary motor function is present. Thus it is not typically assessed unless severe paresis or plegia is present.
Evans J, Levesque D, Knowles K, et al. Diazepam as a treatment for metronidazole toxicosis in dogs: a retrospective study of 21 cases. J Vet Intern Med 2003; 17:304-310
Jokinen TS, Rusbridge C, Steffen F, et al. Cerebellar cortical abiotrophy in Lagotto Romagnolo dogs. Journal of Small Animal Practice. 2007; 48:470-473
Coates JR, O'Brien DP, Kline KL, et al. Neonatal cerebellar ataxia in cotton de tulear dogs. J Vet Intern Med. 2002; 16:680-689.
Garosi LS, Dennis R, Penderis J, et al. Results of magnetic resonance imaging in dogs with vestibular disorders: 85 cases (1996-1999). J Am Vet Med Assoc 2001; 218:385-391
Lu D, Lamb CR, Wesselingh K, et al. Acute intervertebral disc extrusion in a cat: clinical and MRI findings. J Fel Med & Surg 2002; 4:65-68.
Shelton GD, HO M, Kass PH. Risk factors for acquired myasthenia gravis in cats: 105 cases (1986-1998). J Am Vet Med Assoc 2000; 216:55-57.
Shelton GD. Myasthenia gravis and disorders of neuromuscular transmission. Vet Clinics NA Small Animal Pract 2002; 32:189-206.
Dewey CW, Bailey CS, Shelton GD, et al. Clinical forms of acquired myasthenia gravis in dogs: 25 cases (1988-1995). J Vet Intern Med 1997; 11:50-57.
Platt SR. Neuromuscular complications in endocrine and metabolic disorders. Vet Clinics NA Small Animal Pract 2002; 32:125-146.
Coates JR, March PA, Oglesbee M et al. Clinical characterization of a familial degenerative myelopathy in Pembroke welsh corgi dogs. J Vet Intern Med 2007; 21:1323-1331.
Kathmann I, Cizinauska S, Doherr MG, et al. Daily controlled physiotherapy increases survival time in dogs with suspected degenerative myelopathy. J Vet Intern Med 2006; 20:927-932.
Awano T, Johnson GS, Wade CM, et al Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. PNAS 2009; 106:2794-2799.
Lavely JA. Pediatric Neurology of the dog and cat. Vet Clin NA Small Anim Pract 2006; 36:475-501.
Summers BA, Cummings JF, De Lahunta A. Malformations of the central nervous system. In: Veterinary neuropathology. St Louis (MO): Mosby; 1995. p. 68–94.
Greene CE. Tetanus. In: Greene CE, editor. Infectious diseases of the dog and cat. 3rd edition. St. Louis: Elsevier; 2006. p. 395- 402.
Webb AA, Taylor SM, Muir GD. Steroid-Responsive Meningitis-Arteritis in Dogs with Noninfectious, Nonerosive, Idiopathic, Immune-Mediated Polyarthritis. J Vet Intern Med 2002; 16:269-273.
Cuddon PA. Acquired canine peripheral neuropathies. Vet Clin NA Small Anim Pract 2002; 32:207-249.
Levine JM, Hillman RB, Erb HN et al. The influence of age on patellar reflex response in dogs. J Vet Intern Med 2002; 16:244-246.
Forterre F, Konar M, Tomek A, et al. Accuracy of the withdrawal reflex for localization of the site of cervical disk herniation in dogs: 35 cases (2004–2007). J Am Vet Med Assoc 2008; 232:559-563.