NEUROMUSCULAR CASE OF THE MONTH - MARCH 2000

Shifting, multifocal weakness in a
9 year old female spayed German Shorthaired Pointer
Contributed by Drs. Brian Cellio and Dennis O'Brien
University of Missouri
Columbia, Missouri


Clinical History
The dog presented for evaluation of weakness of approximately 5 weeks duration. Weakness initially involved only the right forelimb but progressed over several weeks to involve the right hind limb with inability to stand. Cage rest and anti-inflammatory doses of corticosteroids instituted by the referring veterinarian did not result in improvement. A myelogram performed at a specialty clinic was unremarkable. Bloodwork performed by the referring veterinarian (CBC, biochemical analysis, and T4/TSH) 10 days prior to presentation was unremarkable. Appetite and attitude remained normal. No prior medical problems were identified. Vaccination history was good and the dog was not currently receiving any medications. The owner reported the condition had substantially improved within the week prior to presentation.

Physical and Neurological Examination
Examination revealed pronounced muscle atrophy over the scapula of the right forelimb and mild/moderate atrophy of the gluteal muscles bilaterally. The dog was visibly weak but ambulatory with minimal assistance. Postural reactions revealed deficits in conscious proprioception (CP) in the right forelimb and right hind limb. There was severe weakness of the right forelimb and mild/moderate weakness of the hind limbs. Myotactic reflexes were present but diminished in the right forelimb (ECR, extensor carpi radialis) and both hind limbs (sciatic and femoral distribution), with the right more severely affected than the left. Significant and repeatable pain was elicited upon extension of the right forelimb. The remainder of the neurological examination, including the cranial nerve exam, was normal.

With the exception of thoracic radiographs (normal) and titers for infectious disease (normal), the owner initially declined diagnostics and scheduled a re-check examination in one week. Evaluation at this time showed that the previous right forelimb weakness had clinically resolved. However, the gait was now significantly altered by the development of left forelimb weakness. The muscle atrophy evident at the initial visit was improving and previous CP deficits were inconsistent. CP deficits were obvious in the left forelimb. In addition, the ECR reflex was diminished in the newly affected limb. Previously described reflex abnormalities were now considered normal. Pain was still present in the right forelimb but diminished in severity.

Diagnostic Tests
Routine Laboratory Tests:
CBC and biochemical analysis (including CK) - no abnormalities

CSF analysis (cisternal):
Normal cell count and differential with mildly increased protein (36 mg/dl; Reference <30 mg/dl)

Spinal MRI: Within normal limits

Electrodiagnostics:
Electromyography revealed fibrillations and positive sharp waves (Fig. 1A) in all appendicular and axial muscles tested (all major muscle groups were evaluated) with the exception of the muscles of the head. Motor nerve conduction velocity (right tibial nerve) was normal with temporal dispersion (Fig. 1B).

Figure 1A. Electromyogram showing fibrillations and
positive sharp waves


Figure 1B. Temporal dispersion
was present within
the right tibial nerve

Muscle and Nerve Biopsies:
Biopsies were examined from the cranial tibial, triceps, and biceps muscles of the left limbs. Variable degrees of myofiber atrophy were present within all three muscles with the cranial tibial muscle showing generalized atrophy (Fig. 2A). The normal mosaic pattern of muscle fiber types was present without fiber type grouping. This indicates that the muscle fibers atrophied at a similar point in time and reinnervation had not yet occurred (no fiber type grouping). Several medium caliber arteries and small arterioles showed very dark labeling with the immunoreagent SPA-HRPO (Fig. 2B) suggesting localization of immune complexes.

A fixed biopsy from the left peroneal nerve was plastic embedded and evaluated in 1 µm sections. There was marked depletion of nerve fibers (Fig. 3A)  with scattered myelin ovoids. Remaining nerve fibers were undergoing active axonal degeneration. Numerous small, thinly myelinated nerve fibers were present (Fig. 3B) demonstrating significant nerve regeneration.


Figure 2A. Frozen biopsy
section from the cranial tibial muscle showing generalized myofiber atrophy (H&E)


Figure 2B. Frozen biopsy
section from the cranial tibial muscle showing peroxidase localization within a darkly
stained medium caliber artery (SPA-HRPO)


Figure 3A. Biopsy from the peroneal nerve showing marked nerve fiber depletion. (Toluidine blue-acid fuschin)


Figure 3B. Arrowheads demonstrate small thinly myelinated regenerating fibers (Toluidine blue-acid fuschin)
Conclusion
The dog was discharged without medication pending biopsy results. Upon communication with the owner 10 days after discharge, the dog had begun to display signs of improvement. Complete recovery was described by 1.5 months after discharge. The referring veterinarian could not detect any residual deficits. The clinical findings of weakness, severe muscle atrophy, and segmental hyporeflexia were compatible with a polyneuropathy. Although they can also be seen in myopathies, the fibrillations and positive sharp waves on the EMG suggested axonal loss which was supported by the histopathological findings. The normal NCV suggested that the fastest conducting fibers were still functioning normally, but the temporal dispersion supported unequal conduction in some motor units. The pathological changes within the nerve biopsy were marked and it is surprising that the NCV was not slowed. Since there was such a multifocal distribution to the clinical presentation, it is possible that the fascicles available for evaluation were severely affected ones and other nerve fascicles were affected to a lesser degree. The numerous small, thinly myelinated fibers indicated vigorous regeneration making the prognosis for recovery favorable. Although the etiology was not determined, differentials include infectious/inflammatory, toxic, metabolic, vascular, neopalstic/paraneoplastic, and immune-mediated causes. The shifting, multifocal character of the clinical signs and spontaneous remission would make an inflammatory/vasculitic condition most likely. The presence of the darkly staining vessels following incubation of muscle biopsy sections with the immunoreagent SPA-HRPO would support this hypothesis.

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