DIFFERENTIAL DIAGNOSIS

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1 NEUROGENIC LAMENESS Ronaldo C. da Costa, DMV, MSc, PhD, Dipl. ACVIM Neurology Professor and Service Head, Neurology and Neurosurgery College of Veterinary Medicine, The Ohio State University Key points Neurogenic lameness should be suspected in any patient with lameness in which no cause can be identified Neurogenic muscle atrophy is the most common clinical sign The main cause of neurogenic lameness is primary nerve sheath tumor, most commonly affecting the thoracic limbs Lameness is a common problem in small animal practice. The majority of cases of lameness are caused by orthopedic diseases. However, neurological diseases also cause lameness. It is important to always consider neurological causes, especially in patients with chronic and/or recurrent episodes of lameness. The goal of this overview is to present the clinical approach, ancillary tests and the main characteristics of the primary differential diagnosis of neurogenic lameness. Emphasis will be placed on the clinical presentations and diseases where lameness can be the main clinical sign. CLINICAL APPROACH The diagnostic approach should initially involve thorough physical and orthopedic examinations to clearly establish the absence of orthopedic disease. Neurogenic lameness should be strongly considered in chronically lame patients with no evidence of musculoskeletal disease that respond to neither conservative treatment nor rest. A complete neurological examination (evaluation of mental status, gait and posture, cranial nerves, postural reactions, spinal reflexes and pain perception) should be always carried out to assess the extent, if any, of neurological involvement. In a patient with lameness, neurological signs that are highly suggestive of nervous system disease are ataxia, weakness, postural reaction deficits and obvious spinal pain. If any of these signs are associated with lameness, the index of suspicion for an underlying neurogenic cause is raised; however, many, and perhaps the majority of patients with neurogenic lameness do not present with clear neurological signs associated with lameness. These are the challenging cases. In these patients, clinical signs suggestive of neurogenic involvement are: severe muscle atrophy, Horner s syndrome (miosis, ptosis, third eyelid protrusion and enophtalmus), decreased or absent cutaneous trunci (formerly panniculus) reflex, decreased muscle tone and spinal reflexes (lower motor neuron signs), signs of weakness/hypertonicity in the ipsilateral pelvic limb in cases of lameness involving a thoracic limb, and pain on spinal, axillary or limb palpation/manipulation. Clinical signs that may be seen and are highly suggestive of neurogenic involvement are monoparesis or monoplegia and self-mutilation. It is important to emphasize that any dog with chronic lameness is expected to develop some degree of muscle atrophy from disuse alone. However, neurogenic muscle muscle atrophy is almost always much more severe than disuse atrophy. Severe muscle atrophy, either affecting one, or several muscle groups is, in this author s opinion, the most important feature of neurogenic lameness in patients lacking other neurological signs and by itself warrants pursuit of additional diagnostic testing.

2 DIFFERENTIAL DIAGNOSIS The primary differential diagnoses of neurogenic lameness are: malignant peripheral nerve sheath tumor (MPNST), intervertebral disk disease, spinal neoplasia, brachial plexus avulsion, traumatic neuropathy, degenerative lumbosacral stenosis, cervical spondylomyelopathy and diskospondylitis. 1,2 Not all of these differentials affect the thoracic and pelvic limbs equally and their clinical presentation in relation to lameness and other neurological signs may be quite different. ANCILLARY TESTS Several ancillary tests can be used to aid the diagnosis of neurogenic lameness. The selection of the each test should be guided by the differential diagnosis being considered. Electrodiagnostic tests 3 Electromyography (EMG) EMG is commonly used to differentiate neurogenic from disuse muscle atrophy. It is a highly sensitive technique. Fibrillation potential and positive sharp waves are suggestive of neurogenic muscle atrophy. Electrodiagnostic techniques are invaluable to confirm neurogenic involvement and are very sensitive. However, they are not specific to any of the differential diagnosis, and require specialized equipment and the use of general anesthesia. Imaging Survey radiographs Radiographs can demonstrate evidence of intervertebral disk disease, osteolytic/osteoproliferative lesions, and occasionally may allow visualization of an enlarged intervertebral foramen in cases of proximal peripheral nerve sheath tumors. Radiographs are usually utilized as a screening test to rule out major abnormalities. Ultrasonography (US) Axillary ultrasonography is an extremely useful technique due to its simplicity and sensitivity in cases of distal nerve sheath tumors. If a mass is identified, US guided fine needle aspiration biopsy should be attempted. One limitation of US is that it only identifies neoplasms at the level of the brachial/lumbosacral plexus or distal to it, therefore a normal US exam can not rule out primary or secondary nerve tumors. Myelography Can establish a definitive diagnosis if the disease causes compression of the subarachnoid space surrounding the spinal cord. Most diseases that cause neurogenic lameness involve the nerve roots, the spinal nerves or peripheral nerves, thus myelography may be nondiagnostic. Computed tomography (CT) and magnetic resonance imaging (MRI) these advanced imaging modalities allow visualization of the vertebral canal, plexus area and distal nerve regions. Therefore they offer significant advantages over radiographs, myelography or ultrasonography. It is important to select a field of view large enough to allow visualization of the plexus area. MRI is the diagnostic modality of choice because it provides the greatest soft tissue characterization. Laboratory analysis Cerebrospinal fluid analysis Usually only shows albuminocytologic dissociation, which is a non-specific finding. Cytology Cytology is extremely useful in the diagnosis of neoplastic masses because the treatment of primary nerve sheath tumors is very different from that of secondary nerve tumors such as lymphoma.

3 CAUSES OF NEUROGENIC LAMENESS Malignant peripheral nerve sheath tumor Malignant peripheral nerve sheath tumors, previously called schwannomas or neurofibromas, are the main causes of chronic neurogenic lameness in dogs. 5 The clinical presentation of MPNST is indistinguishable from other causes of lameness in the early stages of the disease. The majority of MPNSTs (80%) occur in the thoracic limbs. Approximately 55% of MPNSTs are located in the plexus or peripheral nerve regions (distal tumors), while 45% are located in the nerve root region (proximal tumors). 6 The most common sign is chronic progressive thoracic limb lameness; however, acute cases have been reported. Muscle atrophy (neurogenic) is often present and is more severe than that observed with orthopedic disorders. Diagnosis of MPNST is established by imaging accompanied by cytology or histopathology. Ultrasonography can be used as an initial test because it can be readily performed and does not require general anesthesia. 7, 4 Axillary ultrasonography should allow detection of at least 50% of tumors. Proximal tumors will not be visible with US, therefore myelography, CT or MRI would be required (MRI is preferred). The treatment of choice for MPNSTs is surgical resection. Local resection has been shown recently to yield very long-term survival times when complete resection is achieved. Nerve sheath tumors are locally invasive and rarely metastasize; however, postoperative local recurrence is common (up to 72% of cases). A post-operatory chemotherapy protocol using metronomic therapy with cyclophosphamide and piroxicam was shown to significantly delay tumor recurrence in dogs with incompletely resected soft tissue sarcomas, including MPNSTs. 9 Radiation therapy has also been shown to yield long survival times. Oral corticosteroids and gabapentin (or pregabalin) are used as a palliative measure in nonsurgical cases. Intervertebral disk disease (IVDD) Both intervertebral disk protrusion and extrusion can cause neurogenic lameness. The direction of the disk herniation is usually lateralized, causing compression of the nerve roots. Intervertebral disk herniation tends to causes lameness when the herniation occurs in the regions of the cervicothoracic (C4-5, C5-6, C6-C7, C7-T1) or lumbosacral (L4-5, L5-6, L-6-7) intumescences. 10 However, cranial cervical disk herniations (C2-3, C3-4) have also been reported to cause lameness. 11, 12 Usually the lameness in these cases is associated with spinal pain and it is called nerve root signature. It is much more common to see this presentation with cervical disk herniations, compared to caudal lumbar disk herniations. Pain is an important feature of lateral or foraminal disk extrusions. Dogs may vocalize periodically or cry as if they were experiencing sharp pain. Pain may be elicited by limb manipulation or spinal palpation. 10 Diagnosis of lateral or foraminal disk extrusions is easily achieved by advanced imaging with CT or MRI. Oblique radiographs may be able to show asymmetric opacity in the foraminal region. 12 In cases of lateral and foraminal extrusions, myelography is often unrewarding. Surgical and medical treatment options exist for the management of IVDD. Surgical treatment is usually recommended because the pain often does not subside until the offending disk is removed and the nerve freed from entrapment. 10 Brachial Plexus Avulsion (BPA) This is a common sequel of major traumas, usually traffic accidents. The majority of dogs have avulsion of all roots of the brachial plexus (C6-T2) causing dysfunction of the suprascapular, musculocutaneous, radial, median, ulnar, lateral thoracic nerve and sympathetic

4 nerves. The second most common type of avulsion involves only the caudal roots (C8-T1-T2) affecting radial, median, ulnar, lateral thoracic nerve and sympathetic nerves. In both instances, dogs present with thoracic limb monoparesis or monoplegia. Other signs commonly seen are analgesia of the limb and absence of flexor reflex. Horner s syndrome and unilateral absence of the cutaneous trunci reflex are seen in approximately 70% of cases. Less commonly, dogs with BPA can have avulsion of only one or two nerve roots. In these cases of focal brachial plexus avulsion, instead of monoparesis or monoplegia, the clinical picture is dominated by a nonweight bearing lameness. Diagnosis of BPA is based on a history of trauma and electrodiagnostic abnormalities. CT and MRI may delineate the areas of avulsion. Unfortunately the only specific treatment is reimplantation of the avulsed nerve roots and it has only been done experimentally in dogs. 13 Physical therapy and limb protection are recommended for at least 2-3 months to allow resolution of edema, and remyelination of partially affected axons. The only reliable negative prognostic indicator is complete analgesia distal to the elbow. 14 Spinal Neoplasia Spinal neoplasias can be extradural, intradural/extramedullary or intramedullary. Extradural tumors (e.g. osteosarcoma, chondrosarcoma) are the most common. The osseous proliferation associated with some of these tumors can cause nerve root compression or entrapment, and lead to lameness. Spinal pain is often present. Spinal radiographs may show osteolytic and/or osteoproliferative changes. Computed tomography, CT myelography and MRI allow assessment of spinal cord involvement. 15,16 Biopsy and histopathology is often necessary to select the most appropriate treatment. Cervical spondylomyelopathy Some dogs with cervical spondylomyelopathy (CSM) have an asymmetric tetraparesis with more severe weakness of one of the thoracic limbs and difficulty bearing weight with frequent collapse. This is sometimes interpreted as lameness by owners, but a careful examination readily reveals other neurological signs. This presentation can be observed with either disk-associated asymmetric compressions, or osseous compressions causing pedicular malformation and foraminal stenosis. The compressions are often located at C5-6 and C6-7 regions. MRI is the diagnostic modality of choice. Treatment can be surgical or non-surgical. Degenerative lumbosacral stenosis (DLS) This is a disease typical of older large breed dogs. Male dogs and German Shepherds are over-represented. DLS is often caused by a combination of intervertebral disk protrusion with vertebral canal stenosis. Compression of the nerve roots or spinal nerves is often caused by lateralized disk protrusion and/or foraminal stenosis at the L6-L7 or L7-S1 regions. Lameness is usually associated with other historical findings, such as reluctance to jump, difficulty in rising and climbing stairs. 2 Caudal lumbar and lumbosacral pain is a very consistent finding in dogs with DLS. Pain can be elicited by digital pressure over the L6-L7 or L7-S1 regions, or by lifting the tail and pushing it dorsally. Proper support in the pelvic region is important when applying digital pressure during palpation because many patients have concomitant hip dysplasia. Diagnosis is best established by advanced imaging, preferably by MRI. 17 Treatment of DLS can be surgical or non-surgical. Recently, descriptions of surgical techniques using a lateral approach have been reported to allow more direct decompression of foraminal stenosis. 18,19 References

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