Introduction
Specific laboratory testing is required for the diagnosis of neuromuscular diseases.  Results of these tests, in combination with signalment, clinical examinations and ancillary testing should facilitate reaching an accurate diagnosis followed by implementation of appropriate therapies.  For neuromuscular diseases in particular, where a delay in reaching a correct diagnosis or in institution of appropriate therapy could result in irreversible muscle damage, joint contractures or even death, early testing is critical. 

Minimum Database (MDB) for Neuromuscular Diseases
In addition to the standard MDB (complete blood count, serum biochemistry panel and urinalysis), a MDB for neuromuscular diseases should also include measurement of serum creatine kinase activity and electrolytes, blood or plasma lactate concentration, urine testing for myoglobinuria, thyroid screening and the serum assay for acetylcholine receptor antibody.   

Creatine kinase (CK) - Unfortunately CK activity is not included on many serum biochemistry panels but should be.  CK is a sensitive and specific indicator of skeletal muscle damage and even mild elevations, if persistently elevated, should not be ignored. Marked elevations of CK (>10,000 IU/L) are usually found in muscular dystrophies (Go to March 2007 and June 2008 Cases of the Month) and necrotizing myopathies (Go to February 2009 Case of the Month), and occasionally in inflammatory myopathies.  Mild to moderate elevations of CK (<10,000 IU/L) may be found in inflammatory (Go to July 2006 Case of the Month) and some degenerative myopathies.  A normal CK activity does not rule out an inflammatory muscle disease.  Anorexia in cats may result in moderate to marked elevations in CK resulting from increased skeletal muscle catabolism (Fascetti et al. J Vet Int Med 1997;11:9-13).

Electrolytes (Na+, K+, Ca++, Mg++) – Electrolyte alterations can result in muscle weakness and may be found in endocrine and metabolic diseases, and inherited genetic diseases, including hyperkalemic and hypokalemic periodic paralysis (For a review see Platt SR. Vet Clin North Am 32;1:125-146)

Blood or plasma lactate – Lactic acidosis and exercise intolerance syndromes are known to be associated with inborn metabolic errors  (i.e.: pyruvate dehydrogenase phosphatase 1 deficiency in Clumber and Sussex spaniels; Cameron JM et al. Mol Genet Metabol 2007;90:15-23). Lactate concentration should be measured at rest and following 10 minutes of exercise (intensity determined by clinical status of the patient).  Lactate concentration should also be evaluated from an age and size matched control dog exercised at a similar intensity. In addition to metabolic myopathies, lactic acidosis may occur with excitement during venipuncture or with abnormalities of ventilation and perfusion.

Myoglobinuria – Following significant muscle injury (i.e.: rhabdomyolysis, Go to February 2009 Case of the Month), myoglobinuria may be observed as “coca-cola” colored urine. Once hematuria has been excluded by examination of the urine sediment,  pigmenturia due to myoglobin may be distinguished from that due to hemoglobin by an ammonium sulfate precipitation test which is available through most commercial laboratories.

Thyroid screening – Hypothyroidism may be associated with muscle weakness in dogs (Go to January 2009 Case of the Month). Of clinical significance,  marked myopathic features of hypothyroidism can be found in muscle biopsies of hypothyroid dogs without clinical signs of weakness, suggesting that hypothyroid  myopathy may be an under-recognized complication (Rossmeisl JH et al. Am J Vet Res 2009;70:in press).  Such dogs may escape clinical detection if not subjected to vigorous exercise regimens as the myopathy may exist in the absence of weakness or abnormal biochemical markers of muscle damage commonly used in the clinical setting.  Weakness may be a clinical feature of hyperthyroidism in cats and can be easily diagnosed by appropriate clinical signs and evaluation of thyroid function (i.e.: total T4). 

Acetylcholine receptor antibody – Autoimmune (acquired) myasthenia gravis (MG) may occur in many clinical forms (For a review see Shelton GD. Vet Clin North Am 2002;32:189-206).  As the spectrum of clinical presentations is broad and variable, autoimmune MG should be high on the list of differential diagnoses for any dog or cat presenting with focal or generalized neuromuscular weakness, megaesophagus, or dysphagia. The acetylcholine receptor antibody test remains the “gold-standard” for the diagnosis of acquired MG and is available through the Comparative Neuromuscular Laboratory, University of California, San Diego (http://vetneuromuscular.ucsd.edu).

Ancillary Testing – Additional laboratory testing may be indicated based on results of the neuromuscular MDB and pathologic changes in the muscle biopsy (Go to December 2006 Case of the Month). Further laboratory diagnostics could include testing for infectious agents such as Toxoplasma gondii, Neospora caninum or tick-related diseases, evaluation of a metabolic panel including quantitative plasma amino acids and urinary organic acids (Go to September 2008 Case of the Month), blood gas and anion-gap analysis, quantification of muscle, plasma and urine carnitine concentrations,  and determination of cardiac troponin I concentration (For use of this test in a neuromuscular disease see Wells RJ et al. J Am Vet Med Assoc 2009;234:1049-1054).