Journal of Neuro-Ophthalmology, September 1995, Volume 15, Issue 3

Intermittent Esotrophia Associated with Rippling Muscle Disease

PURPOSE: We report a rare myopathy known as rippling muscle disease, with the unique feature of extraocular muscle involvement, presenting as a variable esotropia. METHODS: Chart review with a review of the literature. RESULTS: Neurologic and neuro-ophthalmic examinations as well as electromyography and muscle biopsy confirm that this case closely resembles those described in the literature with the additional feature of a variable esotropia. CONCLUSION: Rippling muscle disease may be associated with intermittent esotropia. The pathophysiology of this disorder is unknown, but the intermittent esotropia is likely related to ""rippling"" of the medial recti.

journal of Niwo- Ojiftf/ mlmolosy ISO): 147- 151, 1995. CO 1995 Lippincott- Ravon Publishers, Philadelphia Intermittent Esotropia Associated with Rippling Muscle Disease Gregory S. Kosmorsky, D. O., Neal Mehta, M. D., Hiroshi Mitsumoto, M. D., and Richard Prayson, M. D. Abstract: Purpose: We report a rare myopathy known as rip­pling muscle disease, with the unique feature of extraoc­ular muscle involvement, presenting as a variable es­otropia. Methods: Chart review with a review of the literature. Results: Neurologic and neuro- ophthalmic examina­tions as well as electromyography and muscle biopsy confirm that this case closely resembles those described in the literature with the additional feature of a variable esotropia. Conclusion: Rippling muscle disease may be associ­ated with intermittent esotropia. The pathophysiology of this disorder is unknown, but the intermittent esotro­pia is likely related to " rippling" of the medial recti. Key Words: Rippling muscle- Esotropia. Torbergsen in 1975 ( 1) described a family with a disease resembling myotonia congenita but dis­tinct from it in significant respects. Since then, a number of authors have reported similar cases of a disorder whose essential features consist of muscle stiffness after periods of rest, a local mounding phenomenon on percussion of muscles, wave- like fasciculation of muscles on active contraction, stretching, on percussion that is electrically silent, and nonspecific findings on muscle biopsy. In all of the cases described, the process spared the cra­nial musculature except for occasional percussion myotonia of the tongue. Our patient had involve­ment of the extraocular muscles with intermittent, involuntary contraction of the medial recti, creat­ing an intermittent esotropia. Manuscript received June 27, 1994, From the Division of Ophthalmology ( G. S. K.), Department of Neurology ( G. S. K., H. M.), Division of Medicine ( N. M.), and Division of Pathology ( R. P.), Cleveland Clinic Foundation, Cleveland, Ohio, U. S. A. Presented at the 1994 Frank B. Walsh meeting, Chicago, Illi­nois Address correspondence and reprint requests to Dr. G. S. Kosmorsky, Department of Ophthalmology A- 31, Cleveland Clinic Foundation, 1 Clinic Center, Cleveland, OH 44195- 5024, U. S. A. CASE REPORT A 58- year- old white man was referred to the neuromuscular service of the Cleveland Clinic Foundation on February 2, 1992. He complained of a symmetrical weakness of his arms and legs. His problem started about a year before presentation when he dropped a ladder while at work because of weakness in his arms. Other symptoms con­sisted of a " rippling" phenomenon in his muscles when he tapped them. There was pain and stiff­ness in his thighs on prolonged sitting. Occasion­ally his tongue seemed to feel thickened, and his speech seemed to become slurred. During the course of the year, he had developed intermittent diplopia that progressively worsened. The diplo­pia was worse on awakening and when fatigued. His past medical history was significant for a myocardial infarction in 1980 and a coronary artery bypass graft in 1989. He drank about a case of beer a day until 2 months before presentation, when he abstained. He was employed as a metal plant in- 147 148 G, S. speetor where he was exposed to solvents used in titanium processing. However, all of the titanium was removed by the time he inspected the prod­uct. He had no knowledge of any relatives or co­workers with a similar disorder. General physical examination was unremark­able. The muscular disorder consisted of active vis­ible contractions that were associated with a pain­ful sensation. The muscle spasms were clinically obvious as a " rolling dimpling" of the skin. The typical wave- like rippling of the muscles was best observed on tapping his brachioradialis. On re­peated tapping of his muscles, the rippling phe­nomenon gradually became less prominent. Per­cussion of the large muscle bellies produced rapid contraction without dimpling. ( Fig. 1) Active con­traction produced giant dissipating fasciculations. Deep palpation of the muscles, especially the pec-toralis major, produced a mounding phenomenon that gradually dissipated. His hand- grip release was normal. Percussion myotonia of the tongue was noted. There was a mild diminution of vibra­tion of the toes bilaterally. Review of his outside laboratory investigations revealed an elevated creatinine phosphokinase ( 676 IU), mildly elevated Westergren sedimenta- F( G. 1. Demonstrating the dissipating fasciculation of the forearm muscles on percussion. In the lirst frame, the patient induces the contraction by sharply tapping his brachioradialis. The next two frames show the pro­gressive contraction of the brachioradialis. } Neuw- OfiiUlKlmol, Vol. 15. No. 3, 1995 ETAL. tion rate ( WSR) ( 30 mm/ h), negative antibody to nucleic acid ( ANA) and a negative rheumatoid fac­tor ( RF). The rapid plasma reagin ( RPR) was non-reactive, and a thyroid profile was normal. Mag­netic resonance imaging ( MRI) of the brain was normal. He was referred to the neuro- ophthalmology service for evaluation of his diplopia. His ocular examination revealed best corrected visual acuities of 20/ 15. The pupils were 4 mm in diameter, re­acted briskly, and there was no afferent pupillary defect. In the primary position, there was a 6- di-opter intermittent esotropia that increased to 20 diopters in right gaze and to 10 diopters in left gaze but was quite variable. At times he would be or-thophoric. He developed a medial rectus " spasm" with prolonged near gaze that he was not able to break easily when going from near to distance viewing ( Fig. 2). Coinciding with the spasm, he felt a " tugging" sensation around his eyes that was similar to the discomfort that he felt in his other muscles. These episodes could also be completely spontaneous but were most easily provoked by a near stimulus. The episodes were unassociated with pupillary miosis as seen in spasm of the near reflex. There was no evidence of ophthalmoplegia, FIG. 2. A: Orthophoria at distance. B: Convergence. C: Inability to relax the medial recti after convergence. nystagmus, or fatigable weakness. External, slit-lamp, and fundus examinations were unremark­able. Laboratory investigations revealed a creatine phosphokinase ( CPK) between 293 and 378 IU with a MM fraction of 95%. His thyroid profile was normal and the WSR was 20 mm/ h. The complete blood count and urinalysis were normal, and his liver enzymes had normalized except for mild ele­vation of alkaline phosphatase at 130 U ( normal, 20- 120 U). His electromyogram revealed normal nerve conduction and needle examinations with no evidence of electrical myotonia or membrane irritability. The rolling- muscle phenomenon was electrically silent. PATHOLOGY The 10% formalin- fixed and parafin- embedded tissue sections of the left vastus lateralis muscle were cut 4 p, m thick. Sections were stained with hematoxylin eosin. Frozen tissue segments of skel­etal muscle were cut and stained with H& E, NADH, cytochrome oxidase, Masson trichrome, periodic acid- Schiff ( PAS), adenosine triphos­phatase ( ATP- ase) ( pH 4.6 and 9.8), nonspecific esterase, oil- red- O, acid phosphatase, alkaline phosphatase, and sulfonated alcian blue stains. Rare focal interstitial and perivascular chronic in­flammation consisting primarily of lymphocytes was present ( Fig. 1). There was no evidence of vasculitis or granulomas. Acid phosphatase stain­ing showed rare regenerating muscle fibers. Scat­tered angular atrophic esterase- positive muscle fi­bers were present ( Fig. 2). Focal areas of small-group atrophy were also present. ATP- ase staining demonstrated that the atrophic muscle fibers were f ESOTROPIA 149 both type I and II. There appeared to be a promi­nent type IIB muscle fiber atrophy ( the patient never took corticosteroids). There was no evidence of fiber type grouping on the ATP- ase stains. Mild focal disruptions in the architecture were noted on the NADH and cytochrome oxidase stains. Rimmed vacuolar inclusions suggestive of inclu­sion body myositis were not seen on the trichrome stain. There was no evidence of amyloid on the sulfonated alcian blue stain. No abnormalities of glycogen or lipid were noted on the PAS and oil-red- O stains, respectively. Electron microscopy revealed " honeycomb- like" structures beneath the sarcolemma ( Fig. 3). These structures could not be identified as emanating from any particular muscular substructure. Their origin and function( s) are unknown. However, these identical structures have been reported in other cases of RMD. DISCUSSION Torbergsen ( 1) described a family of 32 mem­bers, five of whom had muscle stiffness, mound­ing of muscles on percussion ( myoedema), gener­alized muscular hypertrophy, rolling muscle con­tractions on mechanical stimuli, and myotonia- like reactions to percussion of the thenar eminence. The disorder had an autosomal dominant inheri­tance. Ricker et al. ( 2) described six patients from two families having the same autosomal dominant disorder. Alberca et al. ( 3) reported a sporadic case with similar features who also had some speech difficulties and what they thought was an inde­pendent cerebellar atrophy. Jusic ( 4) described a mother and son with a similar disorder who devel­oped progressive muscular contractures, begin- / Nmiv- Oi> hiktilniol, Vol. 15, No. 3, 1995 150 G. S. KOSMORSKY ET AL. FIG. 3. A: Skeletal muscle with peri-vascular chronic inflammation con­sisting mostly of lymphocytes ( ar­row). Scattered atrophic fibers are also present. ( Hematoxylin and eosin, x20.) B: Nonspecific esterase stain showing scattered angular atrophic positive- staining fibers in­dicative of acute neurogenic atro­phy. ( Esterase, xio.) C: Honeycomb­like subsarcotemrnal structures. ning with the fingers. They also had percussion myotonia of the tongue and chronic sensorimotor polyneuropathy. Sadeh et al. ( 5) described a father and son with the same findings, except for the absence of wave- like contractions. They found multiple vacuoles on electron microscopy that they thought represented dilations of the T- tubules. They hypothesized that the honeycomb structures described by Ricker ( 2) and Alberca ( 3) represented the same vacuoles. Rao et al. ( 6) described a similar sporadic case in a black teenager. The characteristic features described by Torberg-sen and subsequent authors, such as muscle stiff­ness, mounding phenomenon ( myoedema), elec­trically silent rippling of muscles, absence of myo­tonia on electromyogram ( EMG), moderately elevated CPK, and nonspecific findings of a my­opathy on muscle biopsy were all present in our patient. Recent genetic investigations performed by Stephan et al. ( 7) revealed a strong linkage of RMD to the lq41 locus. It appears that in at least one Oregon family, the genetic locus is within a 12- cM region between the D1S235 and D1S163 markers. These researchers were able to exclude the genes for the subsarcolemmal voltage- sensitive Ca2 + ( DHP- receptor), sarcoplasmic reticulum Ca2 + - induced release channel ( ryanodine receptor), my­otonic dystrophy kinase, and the voltage- sensitive muscle sodium channel as causes of this disorder. Further, they analyzed the German family re­ported by Ricker and were unable to identify the same genetic loci, thereby indicating genetic het­erogeneity in RMD. Symptom a tically, our patient's diplopia was the most troublesome feature. Ocular examination re­vealed a variable intermittent esotropia. Active, in­voluntary contraction of his medial recti, particu- | Nam- Oftlilhntnml, Vol, 15, No. 3, 1995 INTERMITTENT ESOTROPIA 151 larly with near viewing, resulted in spasms that he found difficult to break on subsequent distance viewing. He needed to blink once or twice to re­lieve his diplopia. He had a sense of discomfort with this esotropia. We believe that his ocular symptoms were due to involvement of his medial recti by the same pro­cess that affected his skeletal musculature. The parallel time course, clinical similarity of spasm on active contraction, and discomfort are all in favor of this supposition. Percussion myotonia of his tongue indicates involvement of other cranial mus­cles. An EMG of the medial recti to demonstrate electrical silence was considered to prove this phe­nomenon; however, in the absence of a definitive treatment, the patient declined. Given the variability of his esotropia, recessions of the medial recti could not be expected to im­prove his diplopia. Calcium channel blockers have been shown to have some efficacy in affected pa­tients. To date, this form of therapy has not im­proved our patient's intermittent diplopia. REFERENCES 1. Torbergsen T. A family with dominant hereditary myoto­nia, muscular hypertrophy, and increased muscle irritabil­ity, distinct from myotonia congenita. Thomsen. Acta Neu­rol Scand 1975; 51: 225- 32. 2. Ricker K, Moxley R, Robkamm R. Rippling muscle disease. Arch Neurol 1989; 46: 405- 8. 3. Alberca R, Rafel E, Castilla JM, Gil- Peralta A. Increased mechanical muscular irritability syndrome. Acta Neurol Seand 1980; 62: 250- 4. 4. Jusic A. Hereditary increased muscle mechanical irritability and progressive contracture with stretch- induced electro­myographic activity. Muscle Nerve 1989; 12: 103- 7. 5. Sadeh M, Berg M, Sandbank U. Familial my oedema, mus­cular hypertrophy and stiffness. Acta Neurol Seand 1990; 81: 70\- i. 6. Rao KR, Haf/ ord JM, Grunnet M, et al. Electrically silent muscle contractions, myoedema and myopathy. EEG Clin Neurophysio! 1987; 66: S85. 7. Stephan BS, Buist MB, Chittenden MS, Ricker K, Zhou J, Hoffman EP. A rippling muscle disease gene is localized to lq41: evidence for multiple genes. Neurology, 1994; 44: 1915- 20. / Neuro- Ofilillialmol, Vol. 15, Nu. 3, 1995